A Selected Chronological Bibliography of Biology and Medicine — Part II

1857 — 1924

Compiled by James Southworth Steen, Ph.D.
Delta State University

Dedicated to my loving family

This document celebrates those secondary authors and laboratory technicians
without whom most of this great labor of discovery would have proved impossible.


Please forward any editorial comments to:

John D. Tiftickjian, Jr., Ph.D., Professor of Biology
Delta State University
Box 3262, Cleveland, MS 38733
e-mail: jtift@deltastate.edu




1857

“Disease is from of old and nothing about it has changed. It is we who change, as we learn to recognize what was formerly imperceptible.” Jean-Martin Charcot(1).

“It may be considered as a general fact, very likely to be more fully illustrated as investigations cover a wider ground, that the phases of development of all living animals correspond to the order of succession of their extinct representatives in past geological times. As far as this goes, the oldest representatives of every class may then be considered as embryonic types of their respective orders or families among the living.” Jean Louis Rodolphe Agassiz(2).

Claude-Félix-Abel Niepce de Saint-Victor (FR) noticed a fogging of silver chloride emulsions by uranium salts. He reported that the blackening of the emulsions occurred even when they were separated from the uranium salts by thin sheets of paper. He did not appreciate the true nature of the phenomenon but this probably represents the first observation of radioactivity(3-6).

Eduard Schweizer (CH) developed a solution of cupric oxide in ammonia which would dissolve cellulose without decomposing it(7).

Franz Leybig (DE) was the first person who stated in unequivocal terms that the cell-wall is not a necessary constituent of the cell. “. . . not all cells are of bladder-like nature; a membrane separable from the contents is not always distinguishable. For the morphological idea of a cell one requires a more or less soft substance, primitively approaching a sphere in shape, and containing a central body called a kernel (nucleus). The cell-substance often hardens to a more or less independent boundary-layer or membrane, and the cell then resolves itself, according to the terminology of scholars, into membrane, cell contents, and kernel”(8).

Charles Edward Isaacs (US) discovered that, “….the Malpighian tuft or coil is covered by oval, nucleated cells, which are differently affected by chemical reagents from those which line the capsule, and consequently have a different organization. The Malpighian tuft is evidently, then, a glandular structure, every way adapted for the separation of the proximate elements of the urine…”(9). (Malpighian tuft or coil = glomerulus).

Georg Meissner (DE) discovered the submucosal nervous plexus consisting of small aggregations of ganglion cells, innervating the submucosa of the alimentary tract(10). These became known as Meissner’s plexus.

Karl Wilhelm von Nägeli (CH) introduced the term Schizomycetes (fission fungi) as a collective designation for the bacteria(11).

Louis Pasteur (FR) produced fermentation in a solution which did not contain gluten (albumin). He showed that in a solution of pure sugar with a small quantity of ammonium phosphate and chalk, a cloudiness appears and gas was evolved. As the fermentation proceeded the ammonia disappeared, phosphates and calcium salts were dissolved, lactate of calcium was formed, and lactic yeast settled to the bottom. He showed that in all probability the lactic ferment came from the air, for when he used sterile solutions of the various ingredients and allowed only heated air to enter, neither lactic fermentation nor lactic acid nor infusoria appeared; the fluid remained barren. He also showed that some of the sugar was incorporated into cellular material(12, 13).

Jean Baptiste Payer (FR) wrote an outstanding treatise on floral anatomy(14). This work along with that of Van Tieghem below represents the origin of the scholarly treatment of floral anatomy.

Philippe Edouard Léon Van Tieghem (FR) defined the plant as having three distinct parts, the stem, the root, and the leaf. He studied the origin and differentiation of each type of plant tissue. He studied the gross anatomy of the phanerogams (plants with reproductive organs) and the cryptogams (plants without reproductive organs), such as mosses and ferns. Van Tieghem created a plant anatomy founded on the homologies of tissues and on their origin from the initial cells(15-20).

Franz von Leydig (DE) described a large secretory cell, found in the epidermis of fishes and larval amphibians. This mucous cell is peculiar in that it does not pour its secretion over the surface of the epithelium. Leydig believed that its function was to lubricate the skin; the cell now bears his name(21).

Karl Wilhelm von Nägeli (CH) described spores which were probably Nosma bombycis, a microsporidian, when he investigated an outbreak of a disease called pébrine in the silkworm, Bombyx mori(22).

Édouard-Gérard Balbiani (FR) placed Nosema bombysis, the causative agent of pébrine a disease of silkworms, in the class Sporozoa(23).

Claude Bernard (FR) found that glucose production continued in diabetic cases where glycogen stores had been depleted. This was the first recognition of the process of gluconeogenesis(24).

Friedrich August Brauell (DE), a professor of veterinary medicine, carried out a number of inoculations to demonstrate the transmissibility of anthrax to sheep by means of human or horse anthrax blood. Dogs and fowl were found to resist infection. He found rod shaped objects in the anthrax bloods but did not regard them as unique to anthrax(25, 26).

Carl Theodor Ernst von Siebold (DE) discovered parthenogenesis in moths and the honeybee, Apis mellifera Linn(27). He is commemorated by Ergasilus sieboldi von Nordmann, 1832; Lineola sieboldii Kölliker, 1845; and Pegantha sieboldi Haeckel, 1879.

Friedrich Wilhelm Ernst Albrecht von Graefe (DE) justified iridectomy for glaucoma as follows: “It seemed to me that all the characteristic symptoms [of glaucoma] tended to one point—increase of the intra-ocular pressure…. Supported by these facts and considerations, I considered myself perfectly justified in performing iridectomy in glaucoma; for I knew the favorable action of the operation on the condition of the choroid in regard to its circulation”(28). In his short career von Graefe performed more than 10,000 eye operations. He died at 42. He was undoubtedly the most important ophthalmologist of the 19th century.

Nikolaus Friedreich (DE) gave the first description of acute leukaemia(29).

Thomas Henry Huxley (GB) insisted that as suggestive as they are, comparisons of adult structures are insufficient for the demonstration of homology in animals. Only by studying the embryonic development of the various structures from their earliest stages and determining that they follow the same path of development can we say with certainty that they are homologous(30).

Per Henrik Malmsten (SE) described the parasitic ciliated protozoan Balantidium coli which was later named by F. Stein ()(31, 32).

Robert Bentley Todd (IE-GB) was the first to describe hypertrophic cirrhosis of the liver accurately, sometimes called Todd’s Disease(33).

Rocco Gritti (IT) described knee disarticulation using the patella as a protective flap(34).

The journal Jahrbücher für Wissenschaftliche Botanik was founded.

1858

Stanislao Cannizzaro (IT) demonstrated the validity of Avogadro's number(35).

Friedrich August Kekulé von Stradonitz (DE) was the first to suggest that carbon is tetravalent, with the ability to bond with up to three other elements and possessing the ability to bond with one, two, three, or even four other carbon atoms. Kekulé also allowed for double and triple bonds(36). 

Archibald Scott Couper (GB), contributed significantly when he suggested that the chemical bonds could be represented as dashes, assumed carbon to have a combining power of four, and the ability to combine with itself(37, 38).

Kekulé structures quickly became the most popular way of representing molecules. Kekulé along with Johann Friedrich Wilhelm Adolf von Baeyer (DE) pioneered the concepts of structural organic chemistry.

Karl Friedrich Wilhelm Ludwig (DE) defined what would come to be known as molecular biology. “Whenever the body of an animal is subdivided to its ultimate parts, one always finally arrives at a limited number of chemical atoms…. One draws the conclusion in harmony with this observation, that all forms of activity arising in the animal body must be a result of the simple attractions and repulsions which would be observed in the coming together of those elementary objects”(39).

Johann Peter Griess (DE) discovered the diazo compounds which are so important in the chemistry of dyestuffs(40). 

Joseph von Gerlach (DE) is regarded as the originator of controlled and standardized methods of staining in histology(41).

Johann Florian Heller (AT) developed the caustic potash test for blood in the urine(42).

O. Maschke (DE) succeeded in extracting the reserve protein of the Brazil nut and crystallizing it in his laboratory. Later this protein was called excelsin(43, 44).

Moritz Traube (PL) proposed that catalytic power in tissues resides in proteins and that biological oxidations are based on the activation of molecular oxygen by intracellular enzymes(45-48).

Hermann Welcher (DE) was the first to determine the total blood volume and the volume of the normal blood cells(49, 50).

Louis Pasteur (FR) reported that during the tartaric acid fermentation he had observed an organism (probably Penicillium) to use only the dextrorotatory ammonium tartrate when grown in a mixture of dextrorotatory and levorotatory ammonium tartrate. Thus he developed a practical method for separating compounds which are identical except for the spatial arrangement of the substituent group(51, 52).

Félix Archimède Pouchet (FR) began the presentation of a series of papers to the Academy of Sciences of Paris in which he claimed that he had proven the existence of spontaneous generation or heterogenesis. He was not of the opinion that life springs de novo from a fortuitous arrangement of molecules. He believed in the necessary existence of a vital force coming from pre-existing living matter. Like previous experimenters on the question of spontaneous generation, Pouchet admitted that the real point at issue was whether there are germs in the air or not(53-59).

Robert Remak (PL-DE) concluded that cells with more than one nucleus arose by failure of the cell to complete its division(60).

Karl Wilhelm von Nägeli (CH), coined the term meristem, described the function of the apical cell, explained the significance of primary meristem, and identified starch grains. He developed the distinction between meristematic tissue (bildungsgewebe) and structural parts (dauergewebe) whose cells do not multiply(61).

Spencer Fullerton Baird (US), John Cassin (US), and George Newbold Lawrence (US) authored the most important treatise on the systematics and nomenclature of North American birds up to that time(62).

Louis Xavier Édouard Léopold Ollier (FR) described the inner layer of the periosteum, closest to the bone. The osteoblasts are in this layer(63).

Heinrich Müller (DE) performed histological examinations of bone growth including a comparison of normal to abnormal bone structure. He described the healing of a ricketic lesion(64).

Gustav Pommer (DE) carefully described the distinguishing histologic features of bone structure in rickets, osteomalacia, and osteoporosis(65).

Heinrich Müller (DE) published descriptions of three eye muscles: the superior and inferior muscles of the tarsal plate, the muscle that bridges the inferior orbital fissure, and the innermost fibers of the circular portion of the ciliary muscle(66, 67).

Wilhelm Max Wundt (DE) described the isotonic curves produced by muscle under continuous and constant excitation(68).

Rudolph Ludwig Carl Virchow (DE) confirmed Remak’s conclusion that the cells of diseased tissue descended from normal cells of ordinary tissue. There was no sudden break or discontinuity signifying the disease, but a smooth development of abnormality. Thus he helped bring disease down to the cellular level(69, 70). The medical historian Ralph Herman Major states that for this and his other great works Virchow, “…was unquestionably the outstanding physician of his generation, a man who stands aloof in the select company of Hippocrates, Galen, Morgagni, Auenbrugger, and Laënnec. He was the creator of the modern science of pathology, in which subject he had among his precursors only one rival, Morgagni, and among his successors none”(71).

Rudolph Ludwig Carl Virchow (DE) confirmed that syphilis is a disease which involves all organs and tissues of the body and showed that the causal organism is transferred through the blood to the various organs and tissues(72).

Casimir Joseph Davaine (FR) and Giovanni Battista Grassi (IT) determined that humans become infected with Ascaris lumbricoides by ingesting the eggs(73, 74).

Ernst Leberecht Wagner (DE) presented the first important contribution to the knowledge of the gross pathology of uterine cancer(75).

Robert Remak (PL-DE) having treated some 70 patients with galvanic current, believed that it was superior to faradic current for electrotherapy(76).

Henry Gray (GB) and Henry Vandyke Carter (GB) produced the first edition of Anatomy, Descriptive and Surgical. This would become known simply as Gray’s Anatomy, the most influential human anatomy book in history, going through many editions(77). Gray died of smallpox at thirty-four years of age.

Johannes Hubertus van den Broek (NL) pioneered work demonstrating that many normal tissues such as blood, urine, and vegetable matter are free of microorganisms. He aseptically cut open grapes then squeezed the juice into sterile containers. Even after months the juice showed no signs of fermentation. When he introduced sterile oxygen no fermentation occurred. When he introduced yeast cells the grape juice underwent fermentation (78, 79).

Guillaume Benjamin Amand Duchenne de Boulogne (FR) delineated tabetic locomotor ataxia as a degeneration of the posterior roots and column of the spinal cord and the brain stem. Characterized by attacks of pain, progressive ataxia, loss of reflexes, functional disorders of the bladder, larynx, and gastrointestinal system, and impotence. It develops in conjunction with syphilis and most frequently affects middle aged men(80, 81).

John Murray Carnochan (US) excised the superior maxillary nerve (including Meckel’s ganglion) for facial neuralgia(82).

Alfred Russel Wallace (GB), while ill in Borneo, had a brilliant insight into how natural selection works. He quickly wrote to Charles Robert Darwin (GB) expressing these thoughts. Darwin had for many years been working on the same theory. The two jointly published a paper, On the tendency of species to form varieties; and On the perpetuation of varieties and species by natural selection, in the Journal of the Proceedings of the Linnean Society expressing their thoughts on the subject. This article included Wallace's paper and excerpts from Darwin's unpublished book, as well as a letter Darwin had written to Asa Grey on the subject in 1857(83). Darwin's monograph was published the following year(84).

Philip Lutley Sclater (GB) produced studies of the geographical distribution of birds which resulted in the classification of the zoological regions of the world into six major categories. This was the first serious attempt to study geographical distribution of organisms(85).

Philip and William Lutley Sclater (GB) later extended these studies to mammals, and it is still the basis for work in zoogeography(86).

Alfred Russel Wallace (GB) gave an accounting of "what animals live where and why" which helped provide a firm foundation for the subsequent development of the field of zoogeography. Wallace’s Line separates the predominately Australian fauna from that of Asia(87, 88). 

Henry Darwin Rogers (US) named the Pennsylvanian period, and Alexander Winchell (US), named the Mississippian period; both these divisions were given system/period status in Geology by Thomas Chrowder Chamberlin (US) and Rollin Daniel Salisbury (US)(89-91).

Joseph Leidy (US) reported the finding by William Parker Foulke (US) of the first relatively complete dinosaur skeleton. Leidy named this creature found in New Jersey, Hadrosaurus foulkii(92).

Ibis, journal of the British Ornithological Union, was founded.

1859

“At last gleams of light have come, and I am almost convinced that species are not (it is like confessing a murder) immutable.” Charles Robert Darwin(93).

“You would be surprised at the number of years it took me to see clearly what some of the problems were which had to be solved…. Looking back, I think it was more difficult to see what the problems were than to solve them.” Letter from Charles Robert Darwin to Charles Lyell(94).

John William Dawson (CA) discovered fossil plant remains (Psilophyton princeps) in Middle and Lower Devonian rocks from the Gaspé Peninsula in Eastern Canada(95, 96).

Thore Gustaf Halle (SE), Robert Kidston (GB), and William H. Lang (GB) later found similar confirming fossils and established the order Psilophytes(97, 98).

Harlan Parker Banks (US) subsequently split the Psilophytes into three divisions: Rhyniophytina (Rhyniophyta), Zosterophyllophyta, and Trimerophytina (Trimerophytophyta)(99).

Jean Baptiste Joseph Dieudonné Boussingault (FR) demonstrated a spontaneous increase of nitrates in plant-free soil(100).

Charles Hanson Greville Williams (GB) made the dye safranin(101).

O. Maschke (DE) introduced the use of indigo to histology(102).

Wilhelm Friedrich Kühne (DE) used strong salt solutions to extract then characterize the protein he called myosin from muscle(103-105).

Carl H.D. Boedeker (DE) established the biochemical basis for alcaptonuria by isolating the chemical cause for the darkening seen in the patients urine. The chemical is 2,5-dihydroxyphenylacetic acid or homogentisic acid, he named it alcapton then later alkapton(106, 107).

Edward Smith (GB) made many observations on the relationship of human activity to energy requirements. He noted that the amount of urea in the urine was determined by the amount of nitrogenous substance in the diet and not by level of activity. He observed that output of exhaled carbon dioxide rose with the level of activity(108).

Claude Bernard (FR) reported that he was unsuccessful when he tried to acidify blood by injecting dilute solutions of acetic or lactic acid intravenously. The animal always died before the blood reached neutrality. Here he also describes some organs as secreting substances outside the blood, others as secreting substances directly into the blood, while others secrete substances both outside and into the blood(109).

Moritz Schiff (DE-FR-CH) proved that removal of the thyroid gland in dogs is fatal(110). He later discovered that death could be prevented by grafts or injections of thyroid extracts(111). Schiff used ground sheep thyroid to successfully treat patients operated on for struma, i.e., goiter. They received injections of the extract twice a week, and after a few months were cured. See, Albucasis, c. 1000.

Sir William Withey Gull (GB) was the first to describe the idiopathic form of hypothyroidism, called Gull’s disease, and associate it with atrophy of the thyroid gland—which he regarded correctly as the adult form of cretinism(112, 113).

William M. Ord (GB), who worked with Gull, is credited with coining the name myxoedema for the non-pitting edema he observed in patients(114).

R. Bettencourt (PT) and J-A. Serrano (PT) reported success in implanting a sheep thyroid gland under the skin of the infra-mammary area of a woman suffering from myxedema. The operation was followed by immediate improvement(115, 116).

George Redmayne Murray (GB) postulated that extracts of thyroid glands should be effective in hypothyroidism. He presented in July 1891, at the Annual Meeting of the British Medical Association, his observation of a female patient with hypothyroidism (myxedema) treated successfully with hypodermic injections of extract from the thyroid glands of sheep(117).

Hector W.G. MacKenzie (GB) and Edward L. Fox (GB) reported respectively that oral administration of fresh sheep thyroid glands and thyroid extract were effective in reversing the signs and symptoms of hypothyroidism in a female patient(118, 119).

Thomas Henry Huxley (GB) compared the serous and mucous layers characterized by Christian Heinrich Pander with the ectoderm and endoderm of the Coelonterata(120). See, Pander, 1817.

Charles Robert Darwin (GB) published his book, On the Origin of Species by Natural Selection. In this book Darwin gave strong support for the new paradigm that life has had a complex, ever-changing history, i.e., evolution. He also put forward natural selection as the force propelling evolution.

Since this was such a seminal work I offer this excerpt: “A struggle for existence inevitably follows from the high rate at which all organic beings tend to increase. Every thing, which during its natural lifetime produces several eggs or seeds, must suffer destruction during some period of its life, and during some season or occasional year, otherwise, on the principle of geometrical increase, its numbers would quickly become so inordinately great that no country could support the product. Hence, as more individuals are produced than can possibly survive, there must in every case be a struggle for existence, either one individual with another of the same species, or with individuals of distinct species, or with the physical conditions of life. It is the doctrine of Malthus applied with manifold force to the whole animal and vegetable kingdoms… There is no exception to the rule that every organic being naturally increases at so high a rate, that if not destroyed, the earth would soon be covered by the progeny of a single pair.

Owing to this struggle for life, any variation, however slight and from whatever cause proceeding, if it be in any degree profitable to an individual of any species, in its infinitely complex relations to other organic beings and to external nature, will tend to the preservation of that individual, and will generally be inherited by its offspring. The offspring, also, will thus have a better chance of surviving, for, of the many individuals of any species which are periodically born, but a small number can survive. I have called this principle, by which each slight variation, if useful is preserved, by the term of Natural Selection, in order to mark its relation to man’s power of selection. We have seen that man by selection can produce great results, and can adapt organic beings to his own uses, through the accumulation of slight but useful variations, given to him by the hand of nature. But Natural Selection… is a power incessantly ready for action, and is as immeasurably superior to man’s feeble efforts, as the works of Nature are to those of Art”(84). See Anaximander, c.580 B.C.E. and Patrick Matthew, 1831.

Karl Gegenbaur (DE) emphasized that structural similarities among various animals provide clues to their evolutionary history(121).

Charles Robert Darwin (GB) performed the first experiment to strongly suggest dispersal of aquatic invasive species by movement of waterfowl(84). This phenomenon is known as epizoochory.

Baron Jules de Guerne (FR) reported dispersal of algae by waterfowl(122). This informatin came by way of a report by Zacharias.

Baron Jules de Guerne (FR) reported disperal of leeches by duck(123).

Florence Nightingale (GB) by training, example, will, and strength of character changed nursing forever; becoming the founder of modern nursing(71, 124, 125). The first edition of her book, Notes on Nursing: What it is, and What it is Not, was published in 1859.

Starting with her service in the Crimean War in 1885 Nightingale probably suffered from not one but four disorders. She likely had an underlying bipolar personality disorder, which both magnified the post-traumatic effects of her Crimean experience and enabled her to carry on in spite of them. She very likely contracted brucellosis in the Crimea, and, almost certainly, it was the post-traumatic-stress-disorder (PTSD) that sent her to bed for thirty years after the war. She recovered from the latter only to develop a form of dementia; possibly Alzheimer's(126). 

Charles Marie Édouard Chassaignac (FR) was not the inventor of surgical drainage, but he was the first to apply india-rubber tubes to drain abscesses(127).

Iwan Michajlowitsch Setschenow; Iwan Michajlowitsch Sechenov; Iwan Michajlowitsch Secenov (RU), working with Karl Friedrich Wilhelm Ludwig (DE), described the mercurial blood-gas pump, which enabled them to separate gases from a given quantity of blood(128). This opened the way for studying the relationships between gases and the blood.

François Leuret (FR) and Louis Pierre Gratiolet (FR) pointed out that the two hemispheres of the brain develop asymmetrically: the frontal gyri are formed faster, i.e., earlier in fetal life, on the left than on the right, whereas in the occipital-sphenoidal, i.e., parietal area, the reverse occurs(129).

1860

Stanislao Cannizzaro (IT), at a meeting of chemists in Karlsruhe, Germany, spoke so convincingly in support of Charles Frédéric Gerhardt’s system of atomic and molecular weights that most chemists in Western Europe quickly accepted it(130, 131).

Gustav Robert Kirchhoff (DE) and Robert Wilhelm Eberhard Bunsen (DE) introduced the technique of spectroscopy into chemical analyses(132). 

Pierre Eugène Marcellin Berthelot (FR) prepared invertase (beta-fructofuranosidase) in dry form from yeast cells by alcoholic precipitation. Invertase converts cane sugar into glucose and fructose. Berthelot named it, ferment inversif. This ferment’s (enzyme’s) hydrolysis of sucrose contradicts the notion that fermentation requires an intrinsic vital force present only in living cells(133). Bèchamp (FR) called this enzyme zymase.

Victor Paschutin (DE) and Claude Bernard (FR) independently discovered that invertase is secreted by the epithelial cells of the mucosa of the small intestine(134, 135).

Horace T. Brown (BR) and John Heron (BR) discovered invertase in the leaves of higher plants(136).

Alvan Wentworth Chapman (US) while living in virtual isolation from academic support, first in Georgia, then in Florida, produced his Flora of the Southern United States. A remarkable feat(137).

Light trap development started for insect control; chiefly for cotton leafworm(138).

Thomas Henry Huxley (GB) debated Bishop Samuel Wilberforce (GB) and Sir Richard Owen (GB) under the auspices of the British Association for the Advancement of Science at Oxford, England on June 30, 1860. Their subject was the zoological position of man, i.e., Darwin’s theory of evolution. The audience numbered over one thousand. Although the debate was somewhat superficial it is one of the great turning-points of human thought. The attitude of most educated people respecting our place in nature was permanently affected. Note: The debate was not recorded.

Wilhelm Krause (DE) described specialized cutaneous nerve endings which were later named Krause end bulbs(139-141).

Louis Pasteur (FR) wrote that he is a staunch upholder of the view that yeast are a living organism which, in the course of its life, splits sugar not only into alcohol and carbon dioxide but also into other substances(142, 143).

He demonstrated that germs are not uniformly distributed in air by using a number of sterile sealed glass bulbs filled with infusion. He would break the sealed tips then re-seal them with flame a few minutes later. Flasks were opened and then re-sealed at a number of locations including: the cellars of the Paris Observatory, the road to Dole, Mount Poupet (850 meters), Mount Montanvert (1,910 meters), and the Mer de Glace (1400-2140 meters). In general, he found that the air in rural and elevated locations contained fewer germs than air from urban and low altitudes(144-146).

Robert Caspary (DE) discovered that light promotes the germination of certain seeds(147).

Adolph Cieslar (DE) found that some colors stimulate germination while others inhibit(148).

Lewis H. Flint (US) and Edward D. McAlister (US), using Arlington Fancy lettuce seeds, revealed that light in the violet-blue-green region is inhibitory to seed germination with 760 nm being the most inhibitory. They found that yellow-orange-red light stimulates seed germination with 670 nm being the most effective. Flint and McAlister suggested that chlorophyll, the green pigment that harnesses light energy during photosynthesis, might be the photoreceptor in seed germination(149-152). 

Francois Jules Lemaire (FR), on the basis of the germ theory of putrefaction, suggested that carbolic acid (phenol) be used to treat wounds. His work precedes that of Joseph Lister. Lister later applied this knowledge and organized a system of antiseptic treatment(153, 154).

Karl Georg Friedrich Rudolf Leuckart (DE) demonstrated that the worm-like parasite known as Linguatulidae (Pentasoma) found in the body cavity of serpents and other vertebrates are degenerate Arthropoda, probably related to the Arachnida(155).

Theodor Ludwig Wilhelm von Bischoff (DE) and Karl von Voit (DE) developed a test for studying nitrogen intake and output. By matching the nitrogen contained in the urea excreted with that contained in the protein ingested, they could tell the state of the nitrogen balance; that is whether the body was storing nitrogen, losing nitrogen, or keeping the balance even. They found that if animals were fed pure proteins such as gelatin they would waste away and die. This line of investigation led to the discovery of essential amino acids(156).

Adolph Eugen Fick (DE) proposed his method for measuring cardiac output. It is based on the principle that the total uptake of oxygen by an organ is the product of blood flow to the organ and the arteriovenous concentration difference of oxygen across the organ. Cardiac output is measured as the product of oxygen consumption of the lungs per minute and the arteriovenous oxygen difference across the lungs. If there is no intracardiac shunt, then pulmonary blood flow is nearly equivalent to systemic blood flow or cardiac output. Oxygen consumption is measured as the oxygen extracted by the lungs per minute by the polarographic method or the Douglas bag. His calculations are the basis for today's procedures of cardiac catheterization(157).

Casimir Joseph Davaine (FR) wrote, Traité des Entozoaires et des Maladies Vermineuses de L'Homme et des Animaux Domestiques, a classic book in parasitology(158).

Rudolf Ludwig Karl Virchow (DE) noted the plasma origin of fibrin and named its precursor form fibrinogen(159, 160). See, Babington, 1830.

Gustav Theodor Fechner (DE) developed Fechner's law (the intensity of a sensation produced by a varying stimulus varies directly as the logarithm of that stimulus)(161).

Friedrich Wilhelm Ernst Albrecht von Graefe (DE) pointed out that most cases of blindness and impaired vision connected with cerebral disorders are traceable to optic neuritis rather than to paralysis of the optic nerve(162).

Guillaume Benjamin Amand Duchenne de Boulogne (FR) described a condition he called primary labioglossolaryngeal paralysis. The onset is typically between 50 and 60 years of age and characterized by gradually increasing dysphagia, i.e., difficulty swallowing, progressive speech defect, from minor defect in articulation to the production of incomprehensible sound (laryngeal). Weakness and spasticity of the muscles of the pharynx, larynx, and tongue, spasticity of extremity muscles; hyper-reflexia. Loss of emotional control with episodes of sudden laughing and crying(163). Duchenne’s syndrome is a synonym.

Adolph Wachsmuth (EE) suggested the name progressive bulbar paralysis(164).

Jean Martin Charcot (FR) and Alexis Joffroy (FR) contributed the description of its characteristic pathology(165). 

Bénédict Augustin Morel (FR) introduced the term démence-precoce (dementia praecox) to refer to a mental and emotional deterioration beginning at the time of puberty(166). 

Emil Wilhelm Magnus Georg Kraepelin (DE) was the first to clinically distinguish manic-depressive psychoses and dementia praecox. He described dementia praecox as a “tangible affection of the brain, probably damage or destruction of cortical cells…which was the result of chemical disturbances”(167, 168).

Eugen Bleuler (CH) later introduced the term schizophrenia as synonymous with dementia praecox(169).“I call dementia praecox schizophrenia because (as I hope to demonstrate) the splitting of the different psychic functions is one of its most important characteristics. For the sake of convenience, I use the word in the singular although it is apparent that the group includes several diseases”(170). See, Willis, 1664

Auguste Ambroise Tardieu (FR) first described battered-child syndrome(171).

C. Henry Kempe (US), Frederic N. Silverman (US), Brandt F. Steele (US), William Droegemueller (US), Henry K. Silver (US), and John Patrick Caffey (US) defined the battered-child syndrome, resulting in a dramatic increase in public awareness of the impact of overt physical abuse on children(172, 173). Also called Tardieu's syndrome or Caffey-Kempe syndrome.

John Phillips (GB) diagramed the progressive but fluctuating diversity of life on earth based on the fossil record, publishing the first Phanerozoic diversity curve (Great Britain). His work evidences massive extinctions at the end of the Paleozoic and Mesozoic, and increased diversity in each subsequent age(174).

David M. Raup (US) showed that global records of the Phanerozoic sedimentary rock record exhibits a pattern that is nearly the reverse of Britain by itself(175).

Berliner Medicinische Gesellschaft was founded.

1861-1865

The U.S. Civil War brought epidemics of dysentery, typhoid fever, hepatitis, malaria, smallpox, measles, and venereal diseases. More than three times as many soldiers died of infectious disease than died of battle wounds(176).

1861

"The only satisfactory method of explaining our perception of colors is to suppose that we have in our eyes several different sets of nerves, one set being most affected by one kind of light and another set by a different kind of light." James Clark Maxwell(177).

Hermann von Meyer (DE) gave the name Archaeopteryx (Archeopteryx) to a fossil discovered in fine sandstone Jurassic strata of a quarry near Solenhofen in Bavaria. It appeared to be intermediate in character between reptiles and birds. The Natural History Section of the British Museum purchased the specimen which was described by Sir Richard Owen (GB)(178). In 1876 another fossil Archaeopteryx was discovered. This fossil, which now resides in the Humboldt Museum für Naturkunde in Berlin, is of such rare quality and importance that Dr. Alan Feduccia says it, “may well be the most important natural history specimen in existence, comparable perhaps in scientific and even monetary value to the Rosetta stone”(179, 180).

Alexander Mikhailovich Butlerov (RU) introduced the term chemical structure in the following context: “there will be possible only one such rational formula for each substance. If then the general laws will have been derived which govern the dependence of the chemical characteristics of the substances on their structure, such a formula will express all these characteristics … Time and experience will teach us best how the new formulas will have to appear if they are to express chemical structure”(181).

Ernst Wilhelm Ritter von Brücke (DE) was the first to use adsorption methods for enzyme purification(182). 

Friedrich Goppelsröder (CH) undoubtedly originated chromatography as a analytical laboratory tool. His work employed paper chromatography to separate individual dyes from complex mixtures(183, 184).

Thomas Graham (GB) developed the concept of dialysis as a means of removing solute from a solution. Using parchment as the semipermeable membrane he demonstrated removal of urea from urine(185, 186).

Thomas Graham (GB) worked on understanding the colloidal state of matter and thus advanced the understanding of protoplasmic systems(187).

False hellebore (Veratrum californicum ) was first recommended as a bioicide for control of imported cabbage worm(138). It contains the alkaloid veratrine and is also a good parasiticide. The inventor is unknown. 

Adolf Friedrich Ludwig Strecker (DE) characterized a nitrogen containing substance in bile and named it choline(188).

Gabriel Gustav Valentin (DE-CH) was the first to use polarized light in the study of plant and animal tissues(189).

Maximillian Johann Sigismund Schultze (DE) defined a cell as, “a cell is a little lump of protoplasm, in the interior of which lies a nucleus.” The actual words are: “Eine zelle ist ein kliimpchen protoplasma, in dessen innerem ein kern liegt.” In this paper he declares that the likeness between animal and vegetable protoplasm is not only structural and chemical, but also physiologic(190).

Louis Pasteur (FR) demonstrated that air really contains germs by creating an aspirator to draw outside air through a glass tube and pass it over a plug of gun-cotton acting as a filter. After aspiration was complete the gun-cotton was placed in a mixture of alcohol and ether to dissolve the gun-cotton. The dust being insoluble collected at the bottom of the tube and was examined under the microscope. It showed, in addition to inorganic matter, a considerable number of small, round, or oval bodies, indistinguishable from the spores of minute plants or the ova of animalcules. The number of the bodies varied according to the temperature, moisture, and movement of the air, and the distance above the soil at which the gun-cotton had been placed.

He showed that infusions can be sterilized in an open flask provided that the neck of the latter is drawn out and bent down in such a way that the germs cannot descend into the infusion. This type of experiment, previously used by H. Hoffmann, removed all criticism on the question of air, as such, activating into life an organic infusion. If the bent neck of an open flask which had long remained sterile was cut off the infusion rapidly teemed with living things (191-193). See, Spallanzani, 1776.

Louis Pasteur (FR) discovered anaerobes when he studied and reported on the butyric acid fermentation. Examining a drop of fluid containing the butyric vibrio under a cover-glass on a slide, he was astonished to see on the margin of the drop where it was in contact with air that the vibrios had ceased to move although they were actively motile in the center. The question immediately arose as to whether the air or oxygen was necessary to their movement and vitality. He tested this by passing a stream of oxygen through an active butyric fermenting liquid with the result that the fermentation was inhibited. He discovered other anaerobes and coined the term anaérobies (anaerobes) in 1863 (194-196).

Louis Pasteur (FR) showed that acidic infusions can be sterilized with temperatures around 100°C., but alkaline infusions require temperatures above 100°C (191).

Louis Pasteur (FR) formulated a medium for growing bacteria which became known as Pasteur fluid. It consisted of water 100 parts, pure candy sugar 10 parts, ammonium tartrate 1 part, and 1 part of ash of yeast (194, 195).

Louis Pasteur (FR) demonstrated that yeast can grow and ferment in the absence of gaseous oxygen and discovered that per gram of glucose more yeast is formed in the presence of air than in its absence. It was the first demonstration that aerobic metabolism is more efficient than anaerobic metabolism and the first clue to the difference in efficiency of glycolysis and oxidative phosphorylation. Pasteur also observed that in the presence of air, glucose disappeared more slowly than in the absence of air, which pointed to the operation of a control mechanism that was later called the Pasteur effect(194, 197, 198).

Otto Fritz Meyerhof (DE-US) showed that in the presence of oxygen, only one-fifth to one-fourth of the lactic acid produced during anaerobic contraction of the muscle is subsequently oxidized to carbon dioxide and water. Thus, he tied the release of energy during this particular oxidation to the reconversion of the remaining four fifths of the lactic acid back to glycogen. This confirmed Pasteur’s theory. The depression of glycolysis by respiration is sometimes referred to as the Pasteur-Meyerhof effect. This conversion of glycogen to lactic acid then back again to glycogen was the first evidence of the cyclical character of energy transformations in living cells(199-211).

Sir John Bennett Lawes (GB), Joseph Henry Gilbert (GB), and Evan Pugh (GB) firmly established that green plants alone are incapable of using atmospheric nitrogen (212).

Moritz Traube (PL) supported the idea that most respiratory activity occurs in the tissues outside the circulatory system when he wrote … “The released oxygen passes in a dissolved state through the capillary walls and forms with the muscle fiber a loose combination that is able to transfer the oxygen to other substances, dissolved in the muscle fluid, and [the muscle fiber] can then take up new oxygen. … the fact that all organs of the animal body require arterial blood indicates that not only the blood, but all organs of the body respire … What we call respiration is therefore a very complex process. It represents the sum of the consumption of all those quantities of oxygen needed by each organ, either for its nutrition or for its maintenance. Thus, there can be an increase in the respiration of the brain, or liver and spleen, or indeed individual groups of muscle, without an accelerated respiration in other organs of the body … The motive forces, however, which oxygen elicits in the muscles, nerves, spinal cord, and brain are a consequence of the characteristic construction and chemical nature of the apparatus in which the oxidative processes proceed, so that these forces do not appear in the form of heat, but in the form of their specific, as yet inexplicable, vital functions”(48).

Max Joseph von Pettenkofer (DE) designed a respiratory machine large enough to accommodate a man. He and Karl von Voit (DE) accurately determined the respiratory quotients of protein, carbohydrate, and fat when metabolized in the body. They were able to study man’s overall metabolic rate under various conditions and were the first to establish the basal metabolic rate. This would later help diagnose diseases like abnormal thyroid(213).

Rudolf Albert von Kölliker (CH) authored the first work of comparative embryology which includes the relationship of the notochord to the development of the spine skull in the adult. He was the first to interpret the development of the embryo in terms of the cell theory(214).

Jean Louis René Antoine Édouard Claparéde (CH) discovered giant axons in annelid worms(215).

Thomas Henry Huxley (GB) wrote an essay which was instrumental in man’s being considered in zoological terms and his origin as a result of the evolutionary process(216). He also revised much of the information concerning fishes from the Devonian Epoch(217).

Étienne Jules Marey (FR) and Jean Baptiste Auguste Chauveau (FR) elucidated the nature of the apex beat of the heart. They simultaneously recorded the apex beat movement and pressures in the right atrium and right ventricle in an awake horse using elastic balloons attached to catheters as motion and pressure transducers. Access to the right heart chambers was by way of the external jugular vein. Each movement or pressure change generated a pulsation within the air-filled catheters and was, in turn, transmitted to a rotating smoked-drum sphygmograph. Their finding that the apical impulse is caused by early forceful ventricular contraction was the first graphic recording of intracardiac events(218, 219).

Jeffrey Allen Marston (GB) provided the first modern clinical description of brucellosis, which he termed Mediterranean gastric remittent fever(220).

Major-General Sir David Bruce (AU-GB) was assigned by the British military to find the cause of Malta Fever, a debilitating disease long-known from the Central Mediterranean and the cause of British soldiers dying on the island of Malta. He and his wife— Mary Elizabeth Steele Bruce (GB) — did so by discovering that a bacterium they named Micrococcus melitensis (later named Brucella melitensis) is the cause of this infection (later called brucellosis). This is an undulant fever like malaria, but unlike malaria it is transmitted by contaminated goat’s milk(221-223).

Bernhard Laurits Frederik Bang (DK) and Valdemar Stribolt (DK) isolated Brucella abortus and determined the etiology of contagious abortion (Bang’s disease) in cattle(224).

M. Louis Hughes (GB) suggested the name undulant fever(225, 226).

Themistocles Zammit (MT) discovered that the Brucellae are transmitted to man chiefly through the consumption of raw goat’s or cow’s milk(227-229). For this achievement he was knighted.

Bruce was an avid collector of marine copepods and is commemorated by Botrynema brucei Browne, 1908; Nicothoe brucei Kabata; Pseudomesochra brucei T. & A. Scott, 1901; and Paramphiascella brucei, T. & A. Scott, 1901.

Maybelle L. Feusier (US) and Karl Friedrich Meyer (CH-US) suggested the generic name Brucella in honor of Sir David Bruce (AU-GB)(230).

Hubert von Luschka (DE) provided the first authentic description of polyposis of the colon(231).

Prosper Ménière (FR) was the first to attribute the sudden onset of vertigo, tinnitus (ringing or sounds in the ears), hearing loss, nausea and vomiting to an abnormality within the inner ear. This became known as Ménière’s disease or endolymphatic hydrops (glaucoma of the ear)(232-234). This syndrome is easily confused with cerebral congestion of the apoplectic type.

Thomas Henry Huxley (GB) coined the term calcarine sulcus in referring to the spur shaped hippocampus minor in the black spider monkey, Ateles paniscus(235).

Paul Louis Duroziez (FR) described the double intermittent murmur over the femoral arteries as a sign of aortic insufficiency(236).

Erastus Bradley Wolcott (US) performed the first nephrectomy. It was for renal tumor(237).

Henri Dunant (CH) wrote, Un Souvenir de Solférino, which was inspired by his having witnessed the suffering at the Battle of Solférino in 1859(238). The impact of his book led directly to the founding of the Red Cross by the Geneva Convention of 1864.

1862

Max Joseph von Pettenkofer (DE) devised a quantitative test for free carbonic acid. The gaseous mixture is shaken up with baryta or lime water of known strength and the change in alkalinity ascertained by means of oxalic acid. He also devised a qualitative test for strophanthin. refs

Friedrich Wilhelm Benecke (DE) introduced the use of the aniline dyes to histology(239). Verify name

Alexander Jakovlevich Danilevsky; Danielewski (RU) was the first to use preparative enzyme separation. He used selective adsorption onto collodion to subdivide a complex mixture of enzymes into purified fractions. His starting material was pancreatin(240).

Ernst Heinrich Philipp August Haeckel (DE) described the ability of molluscan leucocytes to ingest India ink particles(241). 

Ferdinand Gustav Julius von Sachs (DE) showed that plants like animals respond to their environments and documented plant tropisms; worked out plant transpiration and proved that chlorophyll in plant cells is confined to certain discrete green plastid bodies within the cell and produced experimental evidence that starch is a product of photosynthesis. He originated the simple iodine test for the presence of starch(242-244).

Andreas Franz Wilhelm Schimper (DE) later named these green plastids chloroplasts(245). See, von Mohl, 1837, concerning chloroplasts.

Louis Pasteur (FR) discovered that the acetic acid fermentation is due to the activity of microorganisms in the genus Mycoderma(246).

George Bentham (GB) and Sir Joseph Dalton Hooker (GB) undertook the ambitious task of compiling an unambiguous descriptive classification of all seed plants. They produced the monumental Genera Plantarum covering 200 "orders" (analogous to what are now known as families) with 7,569 genera, which included more than 97,200 species. The families recognized in this work are, in general, those recognized today(247).

The Congress of the United States created the Department of Agriculture and included within it a Division of Chemistry(248-250).

Henry Walter Bates (GB) observed mimicry of distasteful or poisonous species by harmless, palatable species in the lepidoptera and suggested that the mimics enjoy protection from predation because of their resemblance(251). This phenomenon is called Batesian mimicry in his honor.

Sir Thomas Richard Fraser (GB), in 1862, discovered that when extracts of Calabar bean (Physostigma venenosum) are introduced into the eye they cause the contraction of the pupil(252). 

Douglas Moray Cooper Lamb Argyll Robertson (GB) discovered its ability to stimulate the ciliary nerves and cause contraction of the sphincter pupillae by instilling an extract of the bean into his own eye(253).

Douglas Moray Cooper Lamb Argyll Robertson (GB) introduced Calabar bean extract (physostigmine) as an agent to constrict the pupil. From his examinations of 5 tabetic patients he described what is known as Argyll Robertson pupil. “I could not observe any contraction of either pupil under the influence of light, but, on accommodating the eyes for a near object, both pupils contracted.” He also studied miosis (excessive contractions of the pupil) caused by various drugs, and wrote on the tonic pupil(254).

Thomas Richard Fraser (GB) was able to counteract the effect of Calabar extract by use of atropine(252).

Adolf Weber (DE) reported the positive therapeutic value of Calabar bean extracts in treating glaucoma(255). 

Herman Snellen (NL) invented the eye chart with black block shaped letters to test vision(256).

Ernst Kohlschütter (DE) performed the first experiments to determine the depth of sleep throughout the night(257).

Jean Baptiste Edouard Gélineau (FR) coined the term narcolepsy, defining it as an ailment characterized by a compelling need to sleep for short durations at close intervals(258).

George Thomas White Patrick (US) and J. Allen Gilbert (US) performed the first “controlled” sleep-deprivation study on human subjects(259).

Marie Mikhailovna de Manacéïne (RU) deprived 10 puppies of sleep for four or five days and found that it proved fatal despite the presence of food and water. The younger the puppy the more quickly it died(260, 261).

Ludwig Mauthner (HU-AT) deduced that normal sleep could be due to “fatigue” of the cells in the gray mater of the midbrain near the aqueduct of Sylvius. This fatigue could cause a functional break in the sensory pathways between the brainstem and the cerebral cortex, effectively deafferenting the cortex(262).

Walter Hess (CH) showed that stimulation of the gray matter surrounding the third ventricle of the brainstem caused animals to go to sleep. The animals could then be roused normally(263, 264).

Maurice Raynaud (FR) described local asphyxia and symmetrical gangrene of the extremities, i.e., Raynaud phenomenon(265).

Claude Bernard (FR) and Johann Friedrich Horner (CH) independently described the effects of paralysis of the human cervical sympathetic nerves, a condition later called Bernard-Horner syndrome. Quoting Horner, “The pupil of the right eye is considerably more constricted than that of the left, but reacts to light; the globe has sunk inward very slightly…. Both eyes…have normal visual acuity. During the clinical discussion of the case, the right side of her face became red and warm…while the left side remained pale and cool. The right side seemed turgid and rounded, the left more sunken and angular; the one perfectly dry, the other moist. The boundary of the redness and warmth was exactly in the midline”(266, 267).

Claude Bernard (FR) discovered that if he severed the cervical sympathetic nerve there was an accompanying rise in local skin temperature(266).

Friedrich Albert von Zenker (DE) was the first to describe pulmonary fat embolism in man(268).

Aldred Scott Warthin (US) provided a classic description of fat embolism(269).

Sir Richard Owen (GB) discovered the parathyroid glands while performing necropsy on a rhinoceros which had died at the London zoo(270). The necropsy took place in 1850. 

Ivor Sandström (SE) described human parathyroid glands(271).

Austin Flint (US) described a type of heart murmur which is called Flint’s Murmur or Austin Flint Murmur in his honor. It is a presystolic or late diastolic (mitral) heart murmur present in some cases of aortic insufficiency and best heard at the apex of the heart(272).

William Withey Gull (GB) described the clinical signs of syringomyelia (abnormal liquid filled cavities within the spinal cord)(273).

Hans Chiari (AT) coined the term syringomyelia(274).

1863-1879

The fourth cholera pandemic of the 19th century appeared in Bengal, India then spread to the Middle-East where it killed 30,000 pilgrims to Mecca. From there it spread by way of Suez to Mediterranean ports then on to Africa, Western Europe, North America, and Russia. It arrived in New York on a ship coming from France in October 1865, and spread rapidly. Public health reform kept the death toll lower than in previous epidemics, but there were tens of thousands of deaths nonetheless. Another wave swept through the South and Midwest in 1873, hitting particularly hard in the Mississippi and Ohio valleys. It claimed 90,000 lives in Russia during 1866. In Zanzibar 70,000 people were reported to have died in 1869–70(176, 275-277).

1863

“I propose with all kinds of misgivings these new words aerobic and anaerobic, to indicate the existence of two classes [of microbe]... those which survive only in the presence of free oxygen gas, and those which can multiply without contact with free oxygen.” Louis Pasteur(196).

Carl A. Martius (DE-GB), John Dale (GB) and Heinrich Caro (DE-GB-DE) synthesized Manchester brown (“Bismarck brown“), and Manchester yellow 

(“Martius yellow“). The patent for Bismarck brown being (English Patent 3307 of 1863).

Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) introduced the use of logwood extract (hematoxylin) to histology(278).

Franz Böhmer (DE) introduced the use of crystalline hematoxylin (from logwood) to histology and dramatically increased its staining power by using it in the presence of alum as a mordant. He also used hematoxylin in the presence of chromium and in the presence of copper sulfate(279). Hematoxylin is the most widely used natural dye in histotechnology. It will stain tissue components such as myelin, elastic and collagenic fibers, muscle striations, mitochondria and so on, but its most common application is as a nuclear dye in the standard hematoxylin and eosin stain, the primary staining method for tissue section analysis. Hematoxylin is obtained from the logwood, Hematoxylon campechianum, a tree of the order Leguminosae (Genus Eucaesalpinieae) and so named because of the reddish color of its heartwood (from the Greek hemato, blood, and xylo, wood) and young leaves.

Pierre Alain Bitot (FR) concluded that night blindness and xerophthalmia are manifestations of the same condition(280).

M. Mori (JP) discovered that both night blindness and xerophthalmia could be cured by cod-liver oil(281). Hippocrates, ca. 400 B.C.E.,  recommended eating raw liver as a treatment of night blindness(282).

Elmer Verner McCollum (US), Marguerite Davis (US), Thomas Burr Osborne (US), and Lafayette Benedict Mendel (US) showed that rats developed xerophthalmia on diets in which lard supplied the fat; the condition was cured by substitution of butterfat. This was an early indicator of fat-soluble vitamin A (retinol)(283-287).

E. Freise (DE), M. Goldschmidt (DE), and A. Frank (DE) were the first to analyze the histology of vitamin A (retinol) dietary depletion. In young rats they found that eyelashes fell out, the sclerotic coat became dry with keratomalacia, the cornea clouded and ulcerated, and their coats became rough(288).

Carl E. Bloch (DK) was the first to study what was later identified as vitamin A (retinol) deficiency in humans. He carried out nutritional experiments with malnourished children during World War I and realized that both xerophthalmia and night blindness could be reversed by a diet including whole milk or butter(289).

Sir Edward Mellanby (GB), Elmer Verner McCollum (US), Nina Simmonds (US), J. Ernestine Becker (US), and Paul Galpin Shipley (US) demonstrated that rickets results from a deficiency in the human diet. The deficiency is in what was called fat soluble A common in cod-liver oil, butter, and suet(290-295). Later it was found that fat soluble A is complex; containing among other things vitamin A (retinol) and vitamin D(295). Vitamin D proved to be the antirachitic factor.

Alarik Frithjof Holmgren (SE) reported that the uptake of oxygen by blood in the lungs assists the release of carbon dioxide by blood in the lungs(296).

Maximillian Johann Sigismund Schultze (DE) established the protoplasm concept and, after noting the essential similarity between the cell contents of protozoa, plants and animals, concluded that "the cell is an accumulation of living substance or protoplasm definitely delimited in space and possessing a cell membrane and nucleus”(297).

Albert von Recklinghausen (DE) described granular cells in the frog mesentery; later named mast cells by Paul Ehrlich. He noted translocational locomotion of leucocytes for the first time and observed ingestion of particles by mammalian blood cells(298).

Maximillian Johann Sigismund Schultze (DE) also observed ingestion of particles by mammalian blood cells(297).

Paul Ehrlich (DE) rediscovered the mast cell, and named it such, in his medical thesis entitled, Contributions to the Theory and Practice of Histological Staining(299).

Wilhelm Friedrich Kühne (DE) saw a nematode swimming freely within muscle fiber. In its movements, the parasite clearly passed through the striated part of the muscle which closed again behind the nematode’s tail. He concluded that the fiber was not as solid as most people thought and reasoned that they consisted of a concentrated solution of albumins(300).

Karl Remigius Fresenius (DE) was among the first to use a solid culture medium (potato) for culture of microorganisms. ref See, Pier’ Antonio Micheli, 1729. 

Louis Pasteur (FR) observed the bacterial fermentation of ammonium tartrate under oil in the absence of gaseous oxygen. He used the terms aerobic and anaerobic to indicate microorganisms which live with or without free oxygen (196).

Louis Pasteur (FR) was one of the first to realize the indispensability of decay for the maintenance of life on earth, and to state explicitly that microbes are the driving force in the process. He stated that putrefaction was definitely produced by organized ferments of the genus Vibrio, and he described the appearances in point of time of the different bacteria, aerobic and anaerobic, which bring about the putrefactive changes in organic matter. These observations stimulated many investigators to look into the role of microorganisms in putrefaction, putrid intoxication, wound infections, pyemia, and septicemia (196).

John William Draper (GB-US) showed that plants grown in solutions of sodium bicarbonate can liberate oxygen in the light(301).

Carl Claus (DE) wrote a monograph on the marine free-living copepods. It represents a major starting point of our knowledge of these organisms(302).

Karl Georg Friedrich Rudolf Leuckart (DE) published a study on the parasites of man in which he worked out the complicated life histories of many tapeworms and flukes. He created the subphylum Sporozoa for the spore-forming parasitic protozoa. They are characterized by alternations of the asexual (schizogony) and sexual (sporogony) generations. He created the subclass Coccidia for those sporozoans requiring only one host(303-305). Rudolf Ludwig Karl Virchow (DE) recorded the first instance of coccidiosis in the small intestine of man(306).

Henry Walter Bates (GB) wrote The Naturalist on the River Amazons, perhaps the best natural history written during the nineteenth century(307).

Hermann Ludwig Ferdinand von Helmholtz (DE) proposed the resonance theory of hearing(308).

Leopold Auerbach (DE) discovered the myenteric plexus. A plexus of sympathetic nerve fibers situated between the longitudinal (outer muscle layer) and circular (inner) muscular coat of the stomach and intestines. It is one of the nerve networks controlling intestinal movement(309).

Rudolph Ludwig Carl Virchow (DE) wrote, Die Krankhaften Geschwülste, a book on tumors in which many tumor types were named and described for the first time(310).

Alfred Baring Garrod (GB) determined that gout results from the failure to excrete excess uric acid(311).

John Hilton (GB) recognized how to detect a blockage in the flow of cerebrospinal fluid(312). 

Hans Heinrich George Queckenstedt (DE) had a special interest in the physics of cerebrospinal fluid pressure which led to his development of the Queckenstedt test for spinal subarachnoid block(313).

Nikolaus Friedreich (DE) performed outstanding work on hereditary spinal ataxia (Friedreich's ataxia)(314-317).

Jean-Nicolas Demarquay (FR) found parasitic microfilaria of what would later be called Wuchereria bancrofti (elephantiasis) in the hydrocele (watery fluid around the testicle) fluid from a Cuban patient(318).

Otto Henry Wucherer (BR) found the microfilaria in urine(319).

Timothy Richards Lewis (GB) was the first to find the microfilaria of Wuchereria bancrofti in human blood; he named it Filaria sanguini(320, 321).

Joseph Bancroft (GB-AU), in 1876, discovered a microfilarial worm in blood and tissues of a patient with elephantiasis and also described the adult worm in various patients(322-324).

Thomas Spencer Cobbold (GB) named these nematodes Filaria bancrofti in honor of Joseph Bancroft(325).

Sir Patrick Manson (GB) discovered that the Culex pipiens quinquefasciatus mosquito is the intermediate host of Filaria bancrofti(326).

Sir Patrick Manson (GB) elucidated the life cycle of Filaria bancrofti (Wuchereria bancrofti) in the mosquito and demonstrated that filariasis (elephantiasis) is transmitted to man by the bite of a mosquito(327). This was the first time that an insect was shown to be a vector of human disease.

Thomas Lane Bancroft (AU) reported the metamorphosis of the young form of Filaria bancrofti in the body of Culex ciliaris(328).

Christian Albert Theodor Billroth (DE) wrote Die Allgemeine Chirurgische Pathologie und Therapie in Fünfzig Vorlesungen: ein Handbuch für Studirende und Ärzte, a landmark in the development of modern surgery which was translated into ten languages(329).

Thomas Henry Huxley (GB) wrote Evidence as to Man’s Place in Nature, which was the first attempt to apply evolution explicitly to the human race(330).

Archiv fur Mikroskopische Anatomie was founded.

Berliner Klinische Wochenschrift was founded.

The National Academy of Sciences of the United States of America was established as a private institution under a congressional charter.

1864

Sir William Thomson; Lord Kelvin (GB) computed the age of the Earth at between 25 million years and 400 million years(331).

Peter Waage (NO) and Cato Maximilian Guldberg (NO) put forward the idea that the direction taken by a chemical reaction is dependent not merely on the mass of the various components of the reaction, but rather the mass per unit volume (concentration). The Law of Mass Action(332).

Hugo Josef Schiff; Ugo Josef Schiff (DE) discovered the condensation products of aldehydes and amines, later known as Schiff bases. In 1866, he introduced the fuchsine test for aldehydes which distinguishes aldehydes from ketones(333, 334). This test is used to detect polysaccharides, DNA and proteins. It is variously called the aldehyde reaction and the nucleal reaction.

Maximillian Johann Sigismund Schultze (DE) stained the luminous organs of the male of  the European glow-worm (Lampyris splendidula) using osmic acid(335).

George Gabriel Stokes (GB) suggested that venous blood must be oxidized during its time course in the lungs(336).

George Gabriel Stokes (GB) made the observation that green leaves contain both chlorophyll a and chlorophyll b; the pigments were separated using partition methods(337).

Louis Pasteur (FR) published papers detailing his studies of the acetic acid fermentation (338).

Heinrich Anton de Bary (DE) wrote the first important book on the slime molds (myxomycetes) in which he reported the actual formation of multinucleate cells by fusion of single cells(339).

Jean Baptiste Joseph Dieudonné Boussingault (FR) determined the ratio of oxygen evolved to carbon dioxide taken up (the photosynthetic quotient) to be close to 1.0(340). 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) created and named the taxon Gastrotricha, separating them from the rotifers(341).

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) discovered alternation of generations in the nematodes(342).

Édouard Placide Duchassaing de Fonbressin (FR) and Giovanni Michelotti (IT) produced Spongiaires de la Mer Caraibe, the first work containing water colors of sponges made from specimens fresh from the water(343).

Alexander Ecker (DE) and Robert Wiedersheim (DE) produced Die Anatomie des Frosches [The Anatomy of the Frog], one of the most outstanding descriptive works of its time(344, 345).

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) outlined the essential elements of modern zoological classification and coined many words commonly used by biologists today, such as phylum, phylogeny, gastrula, coelom and ecology. In his book of 1866 he designated the third living kingdom, the Protista, the first living creatures. They included the “Protozoa” and “Protophyta” as well as “Protista Neutralia,” those ancestral to neither plant nor animal. Haeckel placed the bacteria in the order Moneres (later Monera) at “the lowest stage of the protist kingdom.” Bacteria were unique, he argued, because unlike other protists, they possessed no nucleus. Haeckel believed that the term ecology was needed to refer to the study of the multifaceted struggle for existence that Darwin had discussed in his 1859 treatise On the Origin of Species(346-348).

Organisms named in Haeckel’s honor include: Haeckelia Carus, 1863, [Ctenophora]; Asteropus haeckeli Dendy, 1905, [Porifera]; Leucetta haeckeliana Polejaeff, 1883, [Porifera]; Pilochrota haeckeli Sollas, 1886, [Porifera]; Margelopsis haeckeli Hartlaub, 1897, [Cnidaria: Hydrozoa]; Pantachogon haeckeli Maas, 1893, [Cnidaria: Hydrozoa]; Lucernaria haeckeli Antipa, 1892, [Cnidaria: Scyphozoa]; Protiara haeckeli Hargitt, 1902, [Cnidaria: Hydrozoa]; Pseudorhiza haeckeli Haacke, 1884, [Cnidaria: Scyphozoa]; Colobomatus haeckeli Richiardi, 1877, [Arthropoda]; Actinostephanus haeckeli Kwietniewski C. R., 1897, [Cnidaria].

August Friedrich Leopold Weismann (DE) was the first to fully recognize the function and significance of the imaginal discs(349). See, Lyonet, 1762.

Friedrich Leopold Goltz (DE) showed that paralysis of the abdominal sympathetic plexus causes widespread venodilatation, which in turn induces syncope owing to the accompanying failure in venus return(350).

Rudolf Peter Heinrich Heidenhain (DE) found that the total energy output (heat and mechanical work) of muscle increases with increasing load (increasing active tension), an unexpected result. It showed that muscle liberates more energy when the resistance to its contraction is greater—that there is a kind of self-regulation of the energy expenditure in the working muscle—and thus that the muscle’s work is very economical(351).

Silas Weir Mitchell (US), William Williams Keen, Jr. (US), and George R. Morehouse (US) wrote, Gunshot Wounds and Other Injuries of Nerves, an important work on nerve and related injuries and causalgia(352). Mitchell did research and reporting on post-paralytic chorea, and described for the first time causalgia (a neuralgia characterized by intense local sensation as of burning pain) and erythromelalgia (acromelalgia or Weir Mitchell’s disease), and cerebellar function(353, 354). William Williams Keen, Jr. was the first brain surgeon in the United States.

Sir James Young Simpson (GB) introduced acupressure, a new method of arresting surgical hemorrhage and of accelerating the healing of wounds(355).

Andrew Woods Smyth (US) performed, on 15 May, 1864, the first recorded operation of successfully tying the arteria innominata for subclavian aneurism. His success was attributed to ligating—where secondary hemorrhage had occurred—the vertebral artery, which prevented regurgitant hemorrhage(356).

Herbert Spencer (GB) formulated Social Darwinism, the idea that poverty and wealth are inevitable as they represent the biological rules which govern society. He also coined the phrase the survival of the fittest and the word evolution in its biological sense(357-360).

George Perkins Marsh (US) wrote a book which was an important influence on the conservation movement in America(361).

Edouard Lartet (FR) and Henry Christy (GB), in 1864, discovered an engraved mammoth tusk at La Madeleine, France showing a drawing of a woolly mammoth. This piece gave strong evidence that man coexisted with Pleistocene animals(362).

Zoological Record was founded.

Archiv für Mikroskopische Anatomie was founded.

Berliner Klinische Wochenschrift was founded.

Journal de l’Anatomie et de la Physiologie Normales et Pathologiques de l’Homme et des Animaux was founded.

ca. 1865

“Destiny has conferred upon us professors the favor of helping the responsive heart of youth to find the right path. In the seemingly insignificant vocation of the Schoolmaster there is enclosed a high, blessed calling. I know no higher.” Karl Friedrich Wilhelm Ludwig (DE) in a letter to Warren P. Lombard(363).

1865

The Mendel paper "is one of the triumphs of the human mind…it presents facts in a conceptual scheme which gives them general meanings…it is a supreme example of scientific experimentation and profound penetration of data." Kurt Guenter Stern and Eva R. Sherwood(364).

“When the observed evidence is opposed to a theory prevailing at the moment, one must accept the data and give up the theory, even when it is supported by famous names and widely accepted.” Claude Bernard(365).

“The application of mathematics to natural phenomena is the aim of all science.” Claude Bernard(365).

“Liebig first recognized the importance of chemical transformation in the body. Thanks to the interaction between the organic components, foodstuffs, and oxygen, a series of chemical permutations took place with the formation of metabolic products. Thus, as a result of these activities and motions, there was life. Liebig clearly recognized the relationship between chemical decomposition and its effects, ascribing all animal motion and heat to such chemically induced breakdowns. …Thus Liebig came to the momentous separation between the nitrogenous and non-nitrogenous nutrients and their role in organic functions. Nitrogen-containing products replaced the used bodily matter and allowed motions, while the materials without nitrogen served for the production of animal heat.” Carl Voit (DE) speaking of Johann Justus Freiherr von Liebig (DE)(366).

“The theory is confirmed that the pea hybrids form egg and pollen cells which, in their constitution, represent in equal numbers all constant forms which result from the combination of the characters united in fertilization.…The constant characters which appear in the several varieties of a group of plants may be obtained in all the associations which are possible according to the [mathematical] laws of combinations, by means of repeated artificial fertilization.” Johann Gregor Mendel(367).

Alarik Frithiof Holmgren (SE) reported that the resting current between electrodes at the front and the back of the eye swing in a cornea-positive direction at both onset and cessation of illumination of the (frog) eye and thus discovered the retina’s electrical response to light, i.e., today’s electroretinogram. This begins the use of electrophysiological methods for studying visual systems(368, 369).

Friedrich August Kekulé von Stradonitz (DE) indicated the correct structure of benzene in a paper communicated to the Paris Chemical Society in 1865. In doing so, he presented the idea that carbon atoms can join in rings thus explaining the structure of such chemicals(370).

Karl Wilhelm von Kupffer (DE) described macrophages lining the walls of the hepatic sinusoids(371, 372). To honor him these are called Kupffer cells.

Emil Cramer (DE) isolated the amino acid hydroxylalanine from hydrolyzed silk thinking it was serikos (serine)(373).

Franz Schweigger-Seidel (DE) and Baron Adolf Johann Hubert von La Valette St. George (DE) proved that a spermatozoon is a cell possessing a nucleus and cytoplasm(374, 375).

Claude Bernard (FR) discovered that certain nerves govern dilatation of blood vessels and others their constriction, i.e., vasomotor system. In this way the body is able to control the distribution of heat within itself. He found by performing cardiac catheterism that blood within the right ventricle always proved to be warmer than that in the left. He also showed that it is the erythrocytes of the blood which transport oxygen from lungs to tissues. He was the first to advance the idea that the body mechanisms act as though they are striving to maintain a constant inner environment despite the outer environment. To do so, the various organs had to be under a tight and integrated central control. He called this concept milieu intérieur and Walter Bradford Cannon was later to name it homeostasis. Bernard also did important work on the physiology of smooth muscle. In 1865, Bernard authored Introduction to the Study of Experimental Medicine, one of the greatest medical books in history(365, 376, 377). “…we must therefore seek the true foundation of animal physics and chemistry in the physical-chemical properties of the inner environment. The life of an organism is simply the result of all its innermost workings. All of the vital mechanisms, however varied they may be, have always but one goal, to maintain the uniformity of the conditions of life in the internal environment. The living organism does not really exist in the milieu extérieur (the atmosphere, if it breathes air; salt or fresh water, if that is its element), but in the liquid milieu intérieur formed by the circulating organic liquid which surrounds and bathes all the tissue elements; this is the lymph or plasma, the liquid part of the blood, which in the higher animals is diffused through the tissues and forms the ensemble of the intracellular liquids and is the basis of all local nutrition and the common factor of all elementary exchanges.

The stability of the milieu intérieur is the primary condition for freedom and independence of existence; the mechanism which allows of this is that which ensures in the milieu intérieur the maintenance of all the conditions necessary to the life of the elements”(377). See, isonomy of Alcmaèon, 520 B.C.E. and homeostasis of Walter Bradford Cannon, 1926.

Karl Friedrich Wilhelm Ludwig (DE) developed perfusion techniques for keeping animal organs alive while they were separated from the general circulation. They did this to study the metabolism of an isolated organ while keeping it alive by artificially circulating defibrinated blood through it(378). Scelkow () was a helper during these studies.

Louis Pasteur (FR) interrupted his fermentation studies to study the diseases of silk worms which, at that time, were dying at a rate sufficient to threaten the French silk industry (379).

Christian Herman Ludwig Stieda (DE) described sporogony of the coccidia in the rabbit(380).

Johann Gregor Mendel (Moravian-CZ) initiated the science of genetics when he published his experiments in plant hybridization. Most of his experiments started with true-breeding varieties of garden peas which were then used to generate hybrids. The hybrids themselves and the offspring resulting from selfing these hybrids were analyzed for the frequency of expression of various traits. Mendel established that seed contain two factors or elemente as he called them. These elemente were inherited in such a way as to produce predictable patterns among the offspring. He noted that some of these elemente behaved in a dominant fashion, others in a recessive fashion(367, 381-383). See, Knight 1799 and Colladon, 1821.

Madan K. Bhattacharyya (GB), Allison M. Smith (GB), T.H. Noel Ellis (GB), Cliff Hedley (GB), and Cathie Martin (GB) identified the protein difference that distinguishes round (RR or Rr) from wrinkled (rr) peas. The functional R allele encodes a form of starch-branching enzyme, which normally links sugars into longer carbohydrates. Developing seeds (peas) of rr plants lack this enzyme, so they contain many free sugars. This draws water into the cells, which swells the seeds. When the pea matures, the water exits the cells, and the seeds wrinkle. Peas of genotype rr also have less protein and more lipid than Rr or RR peas(384).

Diane R. Lester (AU), John J. Ross (AU), Peter J. Davies (AU), and James B. Reid (AU) identified the product of the Le gene, which determines stem length, and therefore whether a pea plant is short or tall. The functional allele encodes an enzyme necessary for synthesis of gibberellin, a plant hormone that causes stems to elongate between nodes. A change in the gene (a mutation) replaces one amino acid with another in the encoded enzyme product at its active site, impairing its function. With the enzyme disabled, gibberellin is in short supply, and the plant is stunted(385).

Wilhelm His (CH) presented a new classification of tissues based on histogenesis. He put forth the basic concepts of tissue embryology. Using serial sections and three-dimensional models to illustrate his theories, he showed that the serous spaces in the embryo are mesodermal in origin and that they are lined by the special layer which he was the first to term endothelial(386).

Claude Bernard (FR) found that herbivores, which normally void a turbid alkaline urine, if fasted would void a clear acidic urine. He interpreted this to mean that a fasting herbivore was consuming its own flesh and metabolizing like a carnivore(365).

Otto Friedrich Karl Deiters (DE) differentiated dendrites from axons and described the lateral vestibular nucleus (Deiter's nucleus)(387). The names axon and dendrite would be coined at a later date, dendrite by Wilhelm His (CH)(388); neuron by Heinrich Wilhelm Gottfried von Waldeyer-Hartz(389) and axon by Rudolf Albert von Kölliker(390).

Vladimir Mikhailovich Bekhterev (RU) distinguished between the anterior and posterior roots of the eighth cranial nerve(391, 392).

Enrico Sertoli (IT) described supporting elongated cells of seminiferous tubules (tubuli seminiferi contorti). They provide nourishment to the sperm cells for the duration of spermatogenesis until the mature spermatozoa are formed. These Sertoli cells form the blood-testis barrier(393).

Max Joseph von Pettenkofer (DE) was the first professor of hygiene at any university(394).

Elizabeth Garrett Anderson (GB) was the first English woman to qualify in medicine. Unable to attend medical school she studied privately and was licensed by the Society of Apothecaries in London in 1865.

Sydney Ringer (GB) studied the use of body temperature as a diagnostic indicator(395).

Karl Thiersch (DE) reported that there is a relationship between skin carcinomas and exposure to sunlight(396).

Jules Bernard Luys (FR), Bernard von Gudden (DE), and Constantin von Monakow (RU-CH) established the identity and independence of the brain’s thalamic nuclei, thus laying the foundation on which rests the specificity of thalamic projections to the cortex(397-399).

George Harley (GB) described paroxysmal hematuria(400).

Armand Trousseau (FR) gave the first description of hemochromatosis(401). 

Friedrich Daniel von Recklinghausen (DE) coined the term hemochromatosis(402).

William Howship Dickinson (GB) described paroxysmal hemoglobinuria(403).

Friedrich Wilhelm Ernst Albrecht von Graefe (DE) improved the treatment of cataract by the modified linear extraction, which dramatically reduced the loss of the eye(404-406).

Significant numbers of cases of yellow fever and Russian cattle plague occur in England.

Zeitschrift für Biologie was founded.

1866

Karl Heinrich Leopold Ritthausen (DE) was the first to isolate glutamic acid which he named. The source was the acid hydrolysate of wheat gluten(407). Glutamic acid is also called aminoglutaric acid.

Ferdinand Julius Cohn (DE) was the first to stress the importance of microorganisms in transforming organic and inorganic substances on earth, with the result that these may be used over and over again to sustain life of other organisms. He discussed the role of bacteria in the cycling of elements in nature and modified Mayer’s fluid medium for culture of bacteria. Cohn’s fluid did not contain sugar but was rather a salt solution to which various carbon sources could be added. The formula was as follows: potassium phosphate, 0.5 gm.; magnesium sulfate, 0.5 gm.; calcium phosphate, 0.05 gm.; ammonium tartrate, 1 gm.; and distilled water, 100 gm(408).

Sir John Bennet Lawes (GB) and Joseph Henry Gilbert (GB) demonstrated that animals can convert both sugar and protein into fat. They also concluded that during exercise of ordinary and extraordinary muscular force, an animal requires non-nitrogenous rather than nitrogenous food(409).

Emerich Meissl (DE) and Fritz Strohmer (DE) provided definite proof that carbohydrates can be converted into fat within the animal body(410).

Adolf Eugen Fick (DE), Johannes Adolf Wislicenus (DE), and Sir Edward Frankland (GB) independently concluded that muscular energy comes principally from the oxidation of non-nitrogenous materials(411, 412).

Sir Edward Frankland (GB) was the first to use a combustion calorimeter to study foods for the quantitative energy values which they yielded on combustion(412).

Max Josef von Pettenkofer (DE), Karl von Voit (DE), and Hermann Lossen (DE) performed experiments which led them to the conclusion that foodstuffs do not combine directly with oxygen to form carbon dioxide and water. Rather, they undergo a long chain of reactions during which a succession of intermediate products are evanescently formed with carbon dioxide and water being formed along the way(413-415).

Julius Friedrich Cohnheim (DE) stained peripheral nerve endings with gold salts and thus introduced their use in histology(416).

Elie de Cyon (LT-DE-RU-FR) and Karl Friedrich Wilhelm Ludwig (DE) discovered the nervus depressor when they stimulated the central end of the depressor nerve and found a reflexive fall of blood pressure and bradycardia. They suggested that the afferent depressor nerves serve to brake the cardiac rate and to lower the peripheral resistance when the blood pressure is unduly high(417).

Louis Pasteur (FR) published work which dealt with diseases of wines due to wild yeasts and bacteria which invade the wine and alter its chemical and physical properties. He pointed out that heating wine at 50 to 60°C (pasteurization) solved the spoilage problem (418).

Leon Coze (DE) and Victor Feltz (DE) were the first to purify bacteria by inoculating a healthy animal with a mixture containing the pathogen desired, removing some of its blood and subsequently using it to inoculate another healthy animal and so on through a series of animals (419). Davaine was to later call this ‘passing’ through the animal (‘en passant si je puis ains dire dans l’économie d’un animal vivant’) (420).

Heinrich Hermann Robert Koch (DE), in 1876, used this "passing" technique to purify anthrax material (421).

Heinrich Anton de Bary (DE) discovered that the pustules on barberry (Aecidium berberidis) and the rust on wheat (Triticum spp.) are both caused by the same organism. He even recognized that the pycnospores are sperm. He worked out the complex life cycle of Puccina graminis and was the first to recognize the Pyrenomycetes as a coherent group(422).

August Heinrich Rudolf Grisebach (DE) coined the term geobotanik (geobotany) and extended the system of physiognomic plant types (vegetative forms) founded by Friedrich Wilhelm Heinrich Alexander von Humboldt (DE) to comprise fifty-four forms(423). 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU) and Karl Georg Friedrich Rudolf Leuckart (1865) found, in diptera, that cellular descendants of germ-cell segregation during the early cleavage stage migrate into the body cavity of the embryo to become the sex cell(424).   

Aleksandr Onufriyevich Kovalevsky; Alexander Kowalewski; Alexander Kovalevski; Alexander Kowalewsky (RU) extended the germ layer concept of Christian Heinrich Pander (LV) and Karl Ernst von Baer (EE-DE-RU) to include the invertebrates, establishing an important embryologic unity in the animal kingdom. He demonstrated the similarity between Amphioxus and the larval stages of tunicates and established the chordate status of the tunicates (425-428).

William Bateson (GB) would show that the acorn-worm, Balanoglossus, possesses a notochord, gill-slits, and a dorsal nerve chord. Based on his knowledge that vertebrates also contain a notochord during embryonic development he proposed that hemichordates are so like chordates that they should be included in the chordate phylum(429). Later the hemichordates were placed in their own phylum(430).

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) published Generelle Morphologie der Organismen (General Morphology of Organisms), the first detailed genealogical tree relating all known organisms, incorporating the principles of Darwinian evolution. This work contains Haeckel’s first expression of his law of organic development (biogenetic law). This law proposes that ontogeny recapitulates phylogeny. It is here that he formulated the kingdom Protista to represent one of the three primary lines of descent (the others being the Plantae and the Animalia) and hypothesizes that the nucleus of a cell transmits its heredity information(347). See, Meckel, 1821.

Karl Ernst von Baer (EE-DE-RU) suggested that embryos of higher and lower forms resemble each other more the earlier they are compared in their development, and not that embryos of higher forms resemble the adults of lower organisms; a more conservative and sounder statement of the biogenetic law(431). 

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) in his book, Riddle of the Universe at the Close of the Nineteenth Century, writes "I established the opposite view, that this history of the embryo (ontogeny) must be completed by a second, equally valuable, and closely connected branch of thought - the history of race (phylogeny). Both of these branches of evolutionary science, are, in my opinion, in the closest causal connection; this arises from the reciprocal action of the laws of heredity and adaptation... 'ontogenesis is a brief and rapid recapitulation of phylogenesis, determined by the physiological functions of heredity (generation) and adaptation (maintenance),” i.e., an organism, in developing from the ovum, goes through the same changes as did the species in developing from the lower to the higher forms of animal life. This is often referred to as the law of recapitulation and is usually abbreviated as ontogeny recapitulates phylogeny. Although a strict form of recapitulation is not correct, phylogeny and ontogeny are intertwined, and many biologists are beginning to both explore and understand the basis for this connection(347, 432-434).

James Marion Sims (US) reported important and pioneering work on the treatment of infertility, including analysis of the conditions essential to conception, and the record of a successful artificial insemination(435).

Ivan Mikhailovich Sechenov (RU) wrote a major classic, Refleksy Golovnogo Mozga (Reflexes of the Brain). He contended that all actions, conscious and unconscious alike, originate as reflexes, and the mental or psychic reflexes are based on physiologic phenomena and provide evidence of a hierarchic organization of brain function(436-438). This work was to have a profound effect on the thinking of Pavlov.

John Hughlings Jackson (GB) postulated that seizures are caused by "occasional, sudden, excessive, rapid, local discharges of grey matter". He described a seizure pattern, Jacksonian Epilepsy, and formulated concepts, even principles, that explain paroxysmal seizures of all types. He also postulated truly evolutionary levels of the sensori-motor-mechanisms: the lowest being the spinal cord, medulla and pons, the middle, being the rolandic region, and the highest level being the prefrontal lobes. As a neurologist, he published some 300 papers mostly in obscure journals(439-447).

1867

“When it had been shown by… Pasteur that the septic property of the atmosphere depended…on minute organisms suspended in it…it occurred to me that decomposition in the injured part might be avoided…by applying as a dressing some material capable of destroying the life of the floating particles…. The material which I have employed is carbolic…acid…. Since the antiseptic treatment has been brought into full operation…my wards…have completely changed…so that during the last nine months not a single instance of pyemia, hospital gangrene, or erysipelas has occurred.” Joseph Lister(448).

Henry Clifton Sorby (GB) invented the microspectroscope(449).

Moritz Traube (PL) developed artificial semipermeable membranes by precipitating ferrocyanide in a thin-layer over porous porcelain(450). 

Charles Lauth (FR) made the dye methyl violet(451). Note: Crystal violet is one of the components of methyl violet. 

An impure copper acetoarsenite, [(CH3COO)2Cu.3Cu(AsO2)2], called Paris Green was introduced for control of Colorado potato beetle, Leptinotarsa deecemlineata (Say) in the state of Mississippi. This is the first general use of an insecticide. Paris Green was used so successfully as a plant protectant that orchardists next adopted it in their fight against the codling moth. Paris Green became so popular that by 1900 its use became widespread in the US and Europe(138, 452). 

By 1872, Paris green was recommended for the control of cankerworms and cotton leafworm. Petroleum was first recommended in U. S. for insect bites and stings(138).

In 1878, Paris green was discovered to be effective for control of codling moth(138).

Carl Huber (DE) crystallized salts of an organic acid he named nicotinic acid (niacin; vitamin B3). He also determined its elemental composition(453).

Friedrich Wilhelm Adolf von Baeyer (DE) synthesized acetylcholine(454).

Eduard Schwarz (AT) introduced differentiation to histology by using the double stain technique. He stained with ammonium carminate followed by picric acid(455).

Louis-Antoine Ranvier (FR) simplified the double stain technique by combining the two stains in one solution(456). 

Rudolf Albert von Kölliker (CH) described yellowish pigmented granules inside neurons located beside the nucleus(457).

H. Rosin (DE) in 1896 suggested that they contain fatty substance and called them lipofuscin(458).

Ernst Sehrt (DE), in 1906, proved that lipofuscin is of a fatty nature because of the way it reacts when stained with Sudan III. Ref

Wilhelm Friedrich Benedikt Hofmeister (DE) established the regularity of the “dissolution” of the nucleus prior to division of the maternal cell, and the appearance of new nuclei in daughter cells(459).

Federigo Delpino (IT) was a botanist who made early studies on pollination(460). He is commemorated by the genus Delphinium.

Thomas Henry Huxley (GB) wrote what is probably the first comprehensive, comparative study of a single avian organ system (skeleton)(461).

Albert Charles Lewis Gotthilf Günther (DE-GB) discovered that the New Zealand tuatara is not a lizard but a living representative of an otherwise extinct order of reptiles, the Rhynchocephalia(462).

Paul Bert (FR) observed that the blood of cuttlefish turned from colorless to blue when exposed to air(463).

Léon Frédéricq (BE) was the first to realize the functional relationship between the hemocyanins of invertebrates and the hemoglobins. He coined the words hemocyanin and oxyhemocyanin and proposed that copper is a normal constituent of hemocyanin(464).

Ludimar Hermann (CH), in 1867, proposed that digestion consists of a series of hydrolytic breakdowns which facilitated resorption. In turn, the products of these chemical separations enabled the body to make new and multiple syntheses, in a fashion ‘like letters of dissolving sentences in a book could be reassembled in order to make new ones’(465).

Albert von Bezold (DE) and Ludwig Hirt (DE) injected rabbits with veratrine causing bradycardia, hypotension, and apnea(466). This represents the discovery of a cardiovascular decompressor reflex involving a marked increase in vagal (parasympathetic) efferent discharge to the heart, elicited by stimulation of chemoreceptors, primarily in the left ventricle. This causes a slowing of the heart beat (bradycardia) and dilatation of the peripheral blood vessels with resulting lowering of the blood pressure.

Adolf Jarisch, Jr. (DE) rediscovered this effect after which it was named the Bezold-Jarisch reflex(467).

Corneille Jean Francois Heymans (BE) and Eric Neil (BE) investigated the Bezold-Jarisch reflex and discovered both chemoreceptors and pressoreceptors in the region of the internal carotid artery(468).

Domingo M. Aviado, Jr. (US) reported that nicotine has the same effect on the Bezold-Jarisch reflex as veratine(469).

Thomas Lauder Brunton (GB) discovered that amyl nitrite is useful in the relief of angina pectoris(470).

Joseph Lister (GB), on 12 August 1865, for the first time used carbolic acid in the treatment of an 11 year old boy with a compound fracture of his tibia. In 1867, Lister presented to the British Medical Association that the use of carbolic acid had prevented wound infections and in 1869 he first described the use of a carbolic spray to the wound and the atmosphere around an operation. At this time most physicians felt that copious suppuration of wounds was a desirable effect. Lister showed that measures to prevent the development of microbes in wounds and surgical procedures in general prevented suppuration and likewise permitted healing with a minimum of scarring and distress and danger to the life of the patient. From this start came our modern aseptic surgery(448, 471-473). In 1883 he was made a baronet and in 1897 became Baron Lister of Lyme Regis. He was the first physician to sit in the House of Lords and succeeded Sir William Thomson, Lord Kelvin as president of the Royal Society.

Richard Payne Cotton (GB) published on observations of unusually rapid action of the heart(474).

Léon Bouveret (FR) observed patients with paroxysmal supraventricular tachycardias (paroxysmal tachycardia), naming the condition tachycardie essentielle paroxystique(475).

August Hoffmann (DE) described observations of paroxysmal tachycardia over a period of many years(476).

Louis-Benedict Gallavardin (FR) differentiated the following: Paroxysmal tachycardia (maladie de Bouveret); tachycardie paroxystique a center excitable; extrasystoles a paroxysmes tachycardiques; and terminal tachycardia(477-479). 

Louis Xavier Édouard Léopold Ollier (FR) used experimental animals to show that the periosteum and the subperiosteal osteogenetic layer allowed joint excision to be performed underneath the periosteum or underneath the capsule and periosteum, in cases of severe inflammation of the joints, which, in those days, would either be fatal or require amputation to save the patient's life(480).

John Eric Erichsen (GB) defined postconcussion syndrome or railway spine (shell-shocked)(481, 482).

Ferdinand Julius Cohn (DE) proposed that Phycochromaceae (Cyanophyceae) were early inhabitants of the earth because of their ability to adapt to extreme habitats, their simple way of reproduction, and the fossil records(483).

The Canadian Medical Association was organized.

1868-1875

Smallpox outbreaks hit New York, Philadelphia and other cities, and it was discovered that many children had not been vaccinated. The New York City Board of Health recommended that all residents be vaccinated in 1870, but there was widespread public resistance, since the vaccine itself was not without risk, and people perceived the campaign as creating a panic situation and allowing doctors to profit from it(176).

ca. 1868

Thomas Jonathan Burrill (US) offered a course in bacteriology at Illinois Industrial University (later to become the University of Illinois). This very likely was the first offering of a bacteriology course in America(484).

1868

Gustavus Detlef Hinrichs (US) and Julius Lothar Meyer (DE) were the first to conceive the so called law of octaves, which later was explained fully by Dimitri Ivanovich Mendeléev under the title of the periodic law(485, 486).

Climent Arkad´evitch Timiriazeff; Climent Arkad´evitch Timiryazev; Climent Arkad´evitch Timirjazeff (RU) established the red maximum of the absorption spectrum of chlorophyll and showed that this absorbed red light is the most efficient in promoting photosynthesis. He proposed that this absorbed light causes chemical transformations leading to photosynthesis(487-490).

Theodor Wilhelm Engelmann (DE), at roughly this same time, also discovered that red light is absorbed by plants and promotes photosynthesis(491-494).

Carl Bernhard Wilhelm Scheibler (DE) was the first to isolate arabinose. He obtained it by acid hydrolysis of beet pulp and believed it to be an isomer of glucose(495, 496).

Heinrich Kiliani (DE) proved arabinose to be a pentose(497).

Thomas Henry Huxley (GB) was the first to propose that birds originated from dinosaurs. All dinosaurs he examined had strong ornithic characteristics in the tetraradiate arrangement of the ilium, ischium, pubis, and femur. He combined the reptiles and birds into Sauropsida(498-500).

John Harold Ostrom (US) proposed that birds descended from theropods (dinosaurs)(501).

Robert T. Bakker (US) proclaims that birds are descendants of the dinosaurs(502).

Casimir Joseph Davaine (FR) demonstrated that anthrax could result from the inoculation of as little as one-millionth of a drop of anthrax blood into a healthy animal(503).

Michael Sars (NO) and Georg Ossian Sars (NO) collected living stalked crinoids (sea lilies) off the coast of Norway. These organisms were believed to have become extinct during the Mesozoic(504, 505).

Sir Edwin Ray Lankester (GB) made clear morphological distinctions between the different orders of invertebrates. He distinguished between the hemocoel (blood containing cavity) in Mollusca and Arthropoda and the coelom (fluid-filled cavity) in worms and vertebrates for the first time, showing that while functionally similar they have different origins. He coined the words homoplasy and blastopore(506-510).

Thomas Henry Huxley (GB) incorporated geographical distribution into his taxonomy while considering the gallinaceous birds (grouse, quail, and turkey)(511).

Johann Bernard Theodor Altum (DE) originated the concept of territory among birds. He concluded that territory reduced competition for food among members of the same species and the function of song was to threaten other males and to invite females(512).

H. Eliot Howard (GB) rediscovered this concept in 1920(513).

Franz Ernest Christian Neumann (DE) described the presence of nucleated erythrocytes in the bone marrow of humans and rabbits. On the basis of this observation, he was the first to conclude that during postembryonic life, erythropoiesis and leukopoiesis is taking place in the bone marrow(514-516).

Giulio Bizzozero (IT) made the same discovery about the same time(517, 518). 

Heinrich Irenaeus Quincke (DE) noted that there is a capillary and venous pulse observable in the fingernails, hand, forearm, and foot. It is best seen in one's own fingernails at the juncture between the white, anemic area and the redder region(519).

Carl Reinhold August Wunderlich (DE) was the first to recognize that fever is not a disease in itself but merely a sign. He was the first to insist on careful records of the fever’s progress and took such records himself. It was Wunderlich who established that 98.6°F [37°C] is the normal temperature of the human body. Wunderlich’s curve is the typical typhoid fever curve. He is considered the founder of modern clinical thermometry(520, 521).

Phillip A. Mackowiak (US), Steven S. Wasserman (US), and Myron M. Levine (US) took a critical look at Wunderlich’s long established 98.6°F normal body temperature of humans and concluded that normal orally measured temperature fluctuates between 96.1°F and 100.8°F [35.6°C and 38.2°C](522).

Paul Langerhans, Jr. (DE) described the dendritic cells in the skin which now bear his name and which from their morphology he believed to be nerve cells(523).

Gustave Albert Schwalbe (DE) and Otto Christian Lovén (SE) independently discovered taste buds in rabbits, hares, man, horse, dog, pig, squirrel, and guinea pig(524, 525).

Guillaume Benjamin Amand Duchenne (FR) described the Duchenne-Erb palsy caused by upper brachial plexus injury during childbirth(526).

Ewald Hering (DE) and Josef Breuer (AT) showed that the mechanism of breathing is automatic and self-regulating, the distention and contraction of the lungs being, in themselves, a normal stimulus of the vagus nerve(527, 528).

Armand Trousseau (FR) described a type of hand contraction which became known as Trousseau sign(529). This type of contraction is common to tetany.

Theodore Hermann Meynert (FR-AT) performed histologic analysis of the cerebral cortex; dividing the cerebrum into anterior, motor quarters and posterior, sensory quarters. He also found that over most of brain the cortex was stratified into five layers: an outer neurological layer containing a few angular nerve cells, a second layer of small pyramidal cells, a third of large pyramidal cells, a fourth of multiform or granular cells, and a fifth layer composed of large, squat pyramids and more deeply lying spindle-shape cells(530).

Jean-Martin Charcot (FR) described what became known as Charcot’s Joints, a degenerative disease with progressive destruction of the bones and joints within the foot, resulting from neurological disorders(531).

Jean-Martin Charcot (FR) and Paul Marie Louis Pierre Richer (FR) were perhaps the first to describe syphilitic sclerosis(532, 533).

Jean Antoine Villemin (FR) in his book, Studies on Tuberculosis, writes: “There is no other affection which has been the object of as many studies as tuberculosis…. Constant and numerous efforts having been made to throw light on this dangerous affection, one has tried to analyze it, to divide it into distinct species, in the hope that this might permit the capturing of truth by fragments. But these attempts, far from simplifying the question, have only complicated it even more and have thrown the whole history of tuberculosis into hopeless confusion.… The inoculation of tuberculous material does not act by virtue of the visible and tangible matter, but because it contains a more subtle principle which escapes our senses…. Tuberculosis is inoculable, this is an uncontestable fact. From now on this affection must be classified as a virulent disease, such as morve-farcin [glanders], which is its closest relative, nosologically speaking…. We would be wrong to think that the affected organism has made the virus, sense if we transfer from one organism to another a drop of vaccinal serosity, a drop of variolar or syphilitic pus, a fragment of tuberculous matter, etc., one reproduces in the inoculated subject a multitude of lesions which are similar to those found in the subject from which the inoculated material had been taken…. But the organism plays only the role of a medium in which the virus multiplies as a parasite…. We must establish a fundamental distinction between the virus and the substance that contains it. The latter is made by the organism under the prodding of the virus. The variolar virus is contained in the pus of the pustule but the pus is not the virus”(534).

Jean Antoine Villemin (FR) was the first to demonstrate that tuberculosis is a communicable disease. He induced the disease by using material from human tuberculous lesions and injecting it into rabbits(534).

Johann Dogiel (LT) and Karl Friedrich Wilhelm Ludwig (DE) concluded that the first cardiac sound is chiefly due to contraction of the muscular fibres of the ventricles assisted by closure of the auriculo-ventricular valves(535).

Franciscus Cornelis Donders (NL) proposed a general method to measure thought processes based on a simple logic. He subtracted the time course needed to respond to a light (say, by pressing a key) from the time course needed to respond to a particular color of light. He found that discriminating color required about 50 milliseconds. In this way, Donders isolated and measured a mental process for the first time by subtracting a control state (i.e., responding to a light) from a task state (i.e., discriminating the color of the light)(536, 537).

Jules Emile Péan (FR) and Eugène Koeberlé (Alsation) both claimed to have invented the operative hemostat. Ref

John Stough Bobbs (US) was the first to perform cholecystotomy for gall-stones(538, 539).

Louis Lartet (FR), in 1868, was the first to find fossil remains of Homo sapiens sapiens (Cro-Magnon man). These were located in a rock shelter site near the village of Les Eyzies in Southwestern France(540). The remains were dated to ca. 28,000 B.C.E. The name: Cro-Magnon comes from Abri Cro-Magnon, Les Eyzies, France where the remains were found. Though spelled magnon the correct pronunciation is "man yon." Louis Lartet was a geologist and son of solicitor and prehistorian Edouard Lartet (FR).

Discarded bones at their ancient campsites testify that Cro-Magnon often fed on vertebrates such as horses and reindeer(541).

The journal Archives de Physiologie Normale et Pathologique was founded.

The journal Archiv für die Gesamte Physiologie was founded.

The journal Archiv für Psychiatrie und Nervenkrankheiten was founded.

1869

Dmitrii Ivanovich Mendeleev; Dmitrii Ivanovich Mendelejeff (RU) published his discovery of the periodic table showing the chemical elements and their relationships to one another. Based on this table he predicted that there were elements yet to be discovered and intentionally left gaps in the table to accommodate them(542-544).

Johannes Adolf Wislicenus (DE) discovered that the two forms of lactic acid, muscle and fermentation, differed only in the rather subtle way in which they behaved with respect to polarized light. Muscle acid is dextrorotatory, whereas the fermentation acid is optically inactive. He decided that there must be some subtle differences in their formulas, one that could not be displayed in the ordinary method then used to write formulas. O. Meister quotes him, “Facts like these will force us to explain the difference of isomeric molecules of equivalent structure by different positions of their atoms in space, and to look for possible ideas about these positions. Possibly an exact determination of the density of the modifications of lactic acid will bring to light a difference in the spatial materialization of molecules [molekülare Raumerfüllung], perhaps such that the optically active meat lactic acid, which the lecturer considers a modification of ethylidene lactic acid…does not contain the atoms arranged together in the smallest possible space”(545, 546).

Jakob Ernst Arthur Böttcher (DE) introduced the method of regressive staining—over-staining followed by de-staining, or differentiation, with alcohol(547).

Jules Raulin (FR) identified zinc as an essential trace metal in plants and animals(548).

Gabriel Émile Bertrand (FR) and Boje Benzon (FR) were the first to determine that zinc is essential to animal nutrition(549, 550).

Giulio Bizzozero (IT), in 1869, was the first to describe giant cells of the bone marrow(551).

William Henry Howell (US) named Bizzozero’s giant bone marrow cells megakaryocytes(552). See, Wright 1906 for their role in platelet formation.

Sebastiano Rivolta (IT) and Pietro Delprato (IT), in 1869, observed the inclusion bodies associated with a fowlpox infection(553).

Amédée Borrel (FR) observed minute bodies in enormous numbers in scrapings from fowlpox lesions and thought them to be the causative agent of the disease(554). These would later be named Bollinger bodies in honor of Otto Ritter von Bollinger (DE).

Hermann Hoffmann (DE), in 1869, used fuchsin and carmine to stain bacteria and thus improve viewing. This is one of the earliest examples of staining bacteria(555).

Theodor Albrecht Edwin Klebs (DE) introduced paraffin imbedding to microtechnology(556).

Karl Ludwig Wilhelm Otto Schultzen (DE) and Marceli Nencki; Marcellus von Nencki (PL) fed glycine and leucine to a dog and observed an increase in its urea excretion. Since urea contains two nitrogen atoms and these particular amino acids possess only one nitrogen each they concluded that some type of biosynthesis must be occurring(557).

Sir Francis Galton (GB) wrote Hereditary Genius: An Inquiry into its Laws and Consequences in which he claimed that intelligence is hereditary. This led the way to eugenics(558).

Sir Francis Galton (GB) argued that ‘inferiority’ and ‘superiority’ could be objectively measured(559). 

Paul Thenard (FR), in 1869, proposed injecting carbon disulfide into the soil around grape vines as a means of controlling Phylloxera and then conducted experiments near Bordeaux to demonstrate its effectiveness. This is the first use of a soil fumigant and these experiments inaugurated the era of scientific agriculture(560).

Hermann Hoffmann (DE), professor of botany in Giessen, was the first person to attempt to stain bacteria. He used aqueous tinctures of both carmine and fuchsin(555, 561).

Adolf Eduard Mayer (DE) improved the Pasteur fluid for growing bacteria by using chemically pure solutions of the salts found in ash of yeast(562).

Simon Schwendener (CH-DE) proposed that the green cells in lichens are themselves true algae parasitized and imprisoned by fungal hyphae, and that the two separate and unrelated organisms live together by obligate symbiosis(563, 564). This was proven to be true by Max Ferdinand Friedrich Rees (GB) in 1871, [Jean-Baptiste] Édouard Bornet (FR) in 1872, and Heinrich Anton De Bary (DE) in 1873.

Hinrich Nitsche (DE) proposed to divide the Bryozoa into two groups, Entoprocta, and Ectoprocta with Entoprocta used as a phylum name(565, 566).

Hermann Beigel (DE) described white piedra, i.e., Beigel's disease; Tinea blanca; Trichosporon beigelii, a fungus infection of the hair shafts of the human scalp or beard(567).

Pedro Severiano de Magalhaes (BR) discovered a very similar disease called black piedra in 1901. Ref It is caused by Piedra hortae named for Paulo Parreiras Horta (BR).

Paulo Parreiras Horta (BR) classified piedra into 2 types. The first is black piedra, which is caused by Piedraia hortae. The second is white piedra(568). The etiological agents of white piedra, originally named Pleurococcus beigelii and later Trichosporon beigelii, are now called Trichosporon asahii and 5 other species: Trichosporon ovoides, Trichosporon inkin, Trichosporon mucoides, Trichosporon asteroides, and Trichosporon cutaneum.

Paul Langerhans, Jr. (DE), while studying the structure of the pancreas, noted specialized groups or islands of cells that are well supplied with microscopic blood vessels(569, 570). These would later be named the Islets of Langerhans in his honor.

Langerhans was also an avid zoologist with a keen interest in the polychaetes. He is commemorated by Langerhansia, Autolytus langerhansi Gidholm, 1967; Demonax langerhansi P. Knight-Jones, 1983; and Hyalopomatus langerhansi Ehlers, 1887.

Jean-Martin Charcot (FR) and Alexis Joffroy (FR) described amyotrophic lateral sclerosis (ALS). It is also called motor neuron disease (MND), Charcot’s disease or Lou Gehrig’s disease(571-573). ALS is an age-dependent and fatal paralytic disorder, caused by degeneration of motor neurons in the motor cortex, brain stem, and spinal cord.

Alexis Yakovlievich Kozhevnikov (RU) demonstrated that in amyotrophic lateral sclerosis the nerve degeneration in the form of corps granuleux could be followed up to the motor cortex(574).

Teepu Siddique (US) identified mutations in the superoxide dismutase gene SOD1 as a cause of familial amyotrophic lateral sclerosis(575).

Adolf Kussmaul (DE) performed gastric intubations, “Often when I observed the patient in the wretched prodromal stage of vomiting, the thought occurred to me that I might relieve her suffering by the employment of the stomach-pump, as the removal of large masses of decomposed acid gastric contents should cause relief from agonizing burning and retching at once”(576). Although his advocacy of gastric lavage established this method of treatment in medical practice, the instrument had already been used many years previously.

Alexander Muirhead (GB) performed the first successful recording of electrical rhythm in the human heart. He used a Thomson siphon recorder at St. Bartholomew’s Hospital, London. This equipment was originally devised to record signals passing through the transatlantic cable, which had been laid in 1866. Not published.

George Miller Beard (US) and Edward H. Van Deusen (US) independently made observations on a form of nervous prostration which they named neurasthenia. It had been called nervous prostration and would later be called chronic fatigue syndrome(577, 578).

Thomas Henry Huxley (GB) founded Nature magazine, which has become one of the world’s most important journals for scientific papers. 

Joseph Leidy (US) authored The Extinct Mammalian Fauna of Dakota and Nebraska which included a synopsis of the mammalian remains of North America(579).

Marcelino de Santuola (ES), in 1869, discovered the Altamira Caves near Santillana del Mar, Spain. These caves contain important Paleolithic art 14,000-16,000 years old(580).

American Journal of Obstetrics was founded.

1870

“The tragedy of science—the slaying of a beautiful hypothesis by an ugly fact.” Thomas Henry Huxley(581). 

Paul Bert (FR) was the first to clearly view the organism as a gas exchange system(582).

Johann Friedrich Wilhelm Adolf von Baeyer (DE) was the first to suggest a scheme [pathway] of chemical reactions to explain the chemical changes brought about by living organisms. He formulated the changes characteristic of the alcoholic and lactic fermentations with the intermediate stages being derived from the hydrated aldehyde formula of glucose by the successive removal and addition of the elements of water. This was an important conceptual breakthrough(583).

Johann Friedrich Wilhelm Adolf von Baeyer (DE) and Rudolf Fittig (DE) determined the molecular formula for glucose(583, 584).

Pyrethrum production started in California about this time. The first experiments conducted with crude carbolic acid emulsion as insecticide took place. Garden engine force pump appeared on U.S. market. Potash solution was recommended for the control of scale insects on shade trees and moist heat first demonstrated as means of insect control(138).

Johannes Ludwig Emil Robert von Hanstein (DE) was the first to describe the sequence of cell divisions in the development of the plant embryo(585).

Nathanael Lieberkühn (DE) showed that leucocytes can ingest erythrocytes(586).

William Osler (CA), in 1882, found erythrocyte-containing leucocytes in the blood of humans with various diseases(587).

Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) discovered the germinal epithelium(588).

Timothy Richards Lewis (GB) was the first to describe amoebas in the stools of humans although his descriptions do not allow identification(321, 589).

Gustav Heinrich Theodor Eimer (DE) established the pathogenicity of trophozoites from his work on Cyclospora in the intestine of the mole(590).

Sir Thomas Clifford Allbutt (GB) designed the medical thermometer, a short thermometer no more than six inches long which reaches equilibrium in only five minutes. Then, and only then, did it become possible to make temperature measurements as a matter of routine and to follow the course of fever(591).

Theodor Albrecht Edwin Klebs (DE) gave the classic description of glomerulonephritis(592).

Franz Ernest Christian Neumann (DE) was the first to note changes in the bone marrow in leukemia, and he proposed the term myelogenous leukaemia(593).

Gustav Simon (DE) reported the first successful planned nephrectomy (kidney removal). It was prompted by a urinary tract fistula(594).

Theodore Gaillard Thomas (US) was the first to perform vaginal ovariotomy(595). 

Edward Drinker Cope (US) was America's greatest herpetologist. He was perhaps best-known for the dinosaur wars with his rival Othniel Charles Marsh of Yale. They were paleontologists and colorful rivals in the collecting of dinosaur skeletons which had been discovered in abundance in the Garden Park area of Colorado and at Como Bluff, Wyoming, in the late 1870s. These specimens initiated the first great dinosaur rush in North America. Cope published nearly 1,400 papers, including large monographs. The journal Copeia from the American Society of Ichthyology and Herpetology since 1913, is named for him. He is also commemorated by Xenodermichthys copei Gill, 1884.

Beiträge zur Biologie der Pflanzen was founded.

Archiv für Gynäkologie was founded.

Sammlung Klinischer Vorträge was founded.

1871

“False facts are highly injurious to the progress of science, for they often endure long; but false views, if supported by some evidence, do little harm, for everyone takes a salutary pleasure in proving their falseness.” Charles Robert Darwin(596).

“I have recovered by treating [pus] cells…with diluted hydrochloric acid…. a fine powder…. consisting of completely clean nuclei…. I believe that from the analyses [of them] presented…the conclusion can be drawn that we are…dealing…with a chemical entity…. In favor of this is the approximate agreement in the N-context of the soluble nuclein and of the whole nuclei….” Johann Friedrich Miescher, Jr. regarding the isolation of DNA(597).

“No, a thousand times no; there does not exist a category of science to which one can give the name applied science. There are science and the applications of science, bound together as the fruit to the tree which bears it”(598).

Dimitri Ivanovich Mendeléev; Dimitri Ivanovich Mendeléeff (RU) predicted that the gaps in his periodic table represented elements as yet undiscovered(599).

Heinrich Hlasiwetz (CZ) and Josef Habermann (CZ) predicted that asparagine and glutamine are constituents of proteins which are normally hydrolyzed to the corresponding acids (aspartic acid and glutamic acid) in the course of protein breakdown(600, 601).

Ernst Felix Immanuel Hoppe-Seyler (DE) discovered that yeast extract contains invertase, an enzyme which catalyzes the conversion of sucrose to glucose and fructose(602).

Johann Friedrich Miescher, Jr. (CH) in his investigations to uncover the chemical nature of the nucleus used the nuclei of pus cells, the yolk of hen’s eggs, and spermatozoa of the Rhine salmon. He isolated what he called nuclein. Miescher determined that it was rich in phosphorus (phosphoric acid), soluble in alkali solution, and insoluble in dilute acids. He concluded that the unknown substance was not a protein(597, 603-606).

Richard Altmann (DE), a biochemist and a student of Johann Friedrich Miescher, developed a method for producing nuclein preparations which he considered to be free of protein; he named such protein-free nucleins nucleic acids(607).

Carl Weigert (DE) was the first to stain bacteria. While studying smallpox pustules he showed that the nuclear dye carmine will stain cocci(608).

Ernst Tiegel (DE) used a porous unburnt clay filter to separate anthrax from fluids containing it. This was the first successful filtration of bacteria from a liquid medium(609).

David Douglas Cunningham (GB) described what was probably Endamoeba coli in the stools of humans(610).

Henry Pickering Bowditch (US), using the isolated frog heart preparation, discovered the staircase, Treppe, phenomenon which is a gradual increase in the extent of muscular contraction following rapidly repeated stimulation. Furthermore, from the experiments in this study, three important phenomena were observed: the all-or-none-law, the absolute refractory period, and the origin of cardiac automaticity, which is located in the atrium and the atrioventricular area(611, 612).

Francis Gotch (GB) determined that the nerve action potential is an all-or none phenomenon(613).

Frederick Haven Pratt (US) would later demonstrate that skeletal muscles also follow the all-or-none principle of contraction(614).

Wilhelm Max Wundt (DE) described reaction time course and reflex time course through the spinal cord and ganglia, and muscle sense(615).

Nathan Zuntz (DE) and Armin Rohrig (DE) found that curarized rabbits lost the power of maintaining body temperature and that the metabolic rate decreased by half. Thus it was deduced that there was a reflex connection between skin and skeletal muscle and that one of the skin reactions to cold was to increase muscle activity to increase metabolism. A further deduction was that maintenance of muscular tonus accounted for a large part of the total maintenance energy requirement. This is the basis of what was later called chemical heat regulation(616).

Johann Ernst Oswald Schmiedeberg (RU-DE) and Karl Friedrich Wilhelm Ludwig (DE) traced the accelerator fibers of the vagus nerve in the dog(617).

Karl Friedrich Wilhelm Ludwig (DE), Phillip Owsjannikow (DE) and Carl Dittmar (DE) performed precise, histologically controlled lesioning experiments into the question of the location of the vasomotor center in the medulla oblongata. A small area in the ventrolateral parts of the medulla with its caudal border 3 mm cranial to the obex and an extension of 3-4 mm in cranial direction was described as the vasomotor area which has to be left intact for normal vasomotor tone and reflexes(618-620). Although not explicit, it is very likely that Dittmar presented a guiding device for spatial localization of intracranial structures for the positioning of electrodes in the medulla oblongata in rats.

Jean Baptiste André Dumas (FR) was the first scientist to objectively report on dietary conditions which clearly indicated that a human diet consisting only of protein, carbohydrate, fat and salts was inadequate(621).

C. Hilton Fagge (GB) concluded that degeneration, atrophy, or loss of the thyroid gland resulted in cretinism(622).

Charles Emile Troisier (FR) described diabetes mellitus associated with hypertrophic cirrhosis of the liver and dark brownish skin pigmentation caused by deposition of excess of melanin or iron pigment, or both, in tissues(623).

Friedrich Daniel von Recklinghausen (DE) named the condition hemochromatosis(402). Troisier-Hanot-Chauffard syndrome.

Gustav Simon (DE), in 1871, performed a nephrectomy for stone disease. He carried this out on an American woman who had traveled from America to Heidelberg to undergo the procedure(624).

Sir Jonathan Hutchinson (GB), in 1871, was the first to successfully operate on a case of intussusception, in a two year-old infant. Intussusception is the invagination or indigitation of a portion of the intestine into an adjacent portion(625).

Karl Friedrich Otto Westphal (DE) first described agoraphobia (fear of open places)(626).

Silas Weir Mitchell (US) provided a detailed account of phantom limb syndrome(627, 628).

Theodor Albrecht Edwin Klebs (DE), over a two month period, autopsied 115 men who died of gun shot wounds. Of this number, 73% showed the occurrence of septicemia and pyemia. He carried out microscopic examinations in fresh and preserved specimens and found bacteria of different forms in nearly every case(629, 630).

William Alexander Hammond (US) and Graeme Monroe Hammond (US) was the first to distinguish athetosis or choreo-athetosis from other choreic disorders. They predicted that the responsible lesion would be found in the striatum of the brain(631).

Hugo Mella (US) offered experimental confirmation of the importance of the striatum in athetosis(632).

Charles Robert Darwin (GB) published The Descent of Man which cast doubt on the idea that the universe was created for man. The role of sexual selection in evolution was described for the first time(596).

Spencer Fullerton Baird (US), zoologist and ornithologist: organized expeditions aboard the Albatross; founded the U.S. National Museum (Smithsonian Institution); and the U.S. Commission of Fisheries with its first Laboratory at Woods Hole in 1871. This started the tradition at Woods Hole and in 1888 the Marine Biological Laboratory was established, followed in 1931 by Woods Hole Oceanographic Institute (WHOI)(633).

1872

“Perhaps few persons who are not physicians can realize the influence which long-continued and unendurable pain may have on body and mind . . . Under such torments the temper changes, the most amiable grow irritable, the bravest soldier becomes a coward, and the strongest man is scarcely less nervous than the most hysterical girl. Nothing can better illustrate the extent to which these statements may be true than the cases of burning pain, or, as I prefer to term it, causalgia, the most terrible of all tortures which a nerve wound may inflict.” Silas Weir Mitchell (US)(628).

Otto Nasse (DE) measured the ammonia evolved when proteins were boiled with alkali (he gives R. Thiele (?) credit for originating this technique). He worked out a method to determine the “loosely bound nitrogen” of proteins with accuracy. He compared a number of proteins in terms of the ratio of ammonia nitrogen to the total nitrogen(634-636).

Charles Lauth (FR) and H. Baubigny (FR), in 1872, made the dye methyl green(101). In biology methyl green is used for staining a great variety of microscopic specimens including normal and infected plant tissues, bacteria, yeasts, etc. It is also used, principally in conjunction with pyronine Y, as a histochemical procedure for differential demonstration of DNA and RNA.

Nathaniel B. Kurnick (US) and Marilee Foster (US) discovered that methyl green combines with highly polymerized DNA at pH 7.5(637).

L. Jullien (FR) was the first to develop a stain for connective tissue. It consisted of saturated aqueous indigo carmine acidified with oxalic acid added to saturated picric acid(638).

Gustav Albert Schwalbe (DE) discovered Paneth cells of the duodenum(639).

Joseph Paneth (AT) described "cellules etroites" (Paneth’s cell) of the mucosa lining the small intestine and the appendix, at the base of tube-like depressions known as Lieberkühn glands(640). They are functionally similar to neutrophils. When exposed to bacteria or bacterial antigens, Paneth cells secrete a number of antimicrobial molecules (alpha-defensins, also known as cryptones) into the lumen of the crypt.

Theodor Albrecht Edwin Klebs (DE), in 1872, employed as culture medium sturgeon’s glue—one of the first uses of a solid medium in bacteriology. ref See Pier’ Antonio Micheli, 1729 and Karl Remigius Fresenius, 1863. 

Henry Charlton Bastian (GB) published his book, entitled The Beginnings of Life, in which he staunchly supports the doctrine of heterogenesis. The effect of his book was beneficial although its conclusions were incorrect. Bastian (GB) forced Louis Pasteur (FR) and others to refine their experiments to meet his objections and thereby ultimately added to their credibility. It was through Bastian’s (GB) experiments with alkalized urine that it came to be known that germs may be much more thermo-resistant than had been supposed. The practice of heating to 115°-120°C. all liquids to be sterilized dates from the repetition of Bastain’s (GB) experiments by Louis Pasteur (FR) and Charles Édouard Chamberland (FR)(641-643).

Ferdinand Julius Cohn (DE) published his classic paper Untersuchungen über Bacterien and launched our modern ideas in bacteriology. Cohn raised the fundamental question whether, like plants or animals, bacteria can be arranged in genera and species. His researches convinced him that they can. This is based on studies of the larger, and especially the spiral, forms of bacteria which in his judgment and experience showed a marked constancy of form irrespective of external conditions. He clearly pointed out, however, that a purely morphological classification is insufficient, as he recognized that bacteria similar or identical in form may differ from each other in their physiological characteristics, and in their products. In this paper he coined the genus name Bacillus(644).

Ferdinand Julius Cohn (DE) suggested the division of bacteria into four groups (Tribus), each of which contained one or more genera. His classification was as follows:

Tribus I. Sphaerobacteria

Genus 1. Micrococcus

Tribus II. Microbacteria

Genus 2. Bacterium

Tribus III. Desmobacteria

Genus 3. Bacillus

Genus 4. Vibrio

Tribus IV. Spirobacteria

Genus 5. Spirillum

Genus 6. Spirochaete

Among the round or Sphaerobacteria he described chromogenic, zymogenic, and pathogenic species. Among the zymogenic species he placed Micrococcus ureae, which had become known from Pasteur’s (FR) work. His pathogenic Sphaerobacteria included Micrococcus vaccinae, discovered by Cohn (DE) himself in 1872, and cocci in diphtheritis and sepsis. The Microbacteria differed from the Sphaerobacteria in shape and motility and he recognized one genus—Bacterium.

The Desmobacteria or filamentous forms contained two genera, viz., Bacillus and Vibrio. For the straight filaments he reserved the name Bacillus, and for the wavy forms, Vibrio. In the genus Bacillus he gave a detailed description of Bacillus subtilis and recognized and figured the spore which he correctly interpreted as the persisting form. He placed Devaine’s anthrax bacillus in the Genus Bacillus. Of the genus Vibrio he described Vibrio rugula and Vibrio serpens.

Among the spiral bacteria (Spirobacteria) Cohn placed Spirochaete with flexible screw forms and Spirillum with inflexible screw forms. Spirillum volutans was described in great detail.

Ferdinand Julius Cohn (DE) independently discovered the extremely heat resistant form of the hay bacillus, Bacillus subtilis. He worked out the life cycle of the organism including germination, vegetative phase, and light refractive spores, which he called endospores. It is in Cohn’s work where we see the beginning of bacteriological techniques such as cotton plug closures. He also discussed the relation of bacteria with allied groups of plants and concluded that they constitute a pretty close group of organisms which show no relation to yeasts or molds, but have close affinities with certain blue-green algae, i.e., cyanobacteria(644-646).

Joseph Lister (GB), in 1872, made clinical use of Penicillium saying, "Should a suitable case present, I shall endeavor to employ Penicillium glaucum and observe if the growth of the organisms be inhibited in the human tissues." Such an opportunity did arise and he reported using Penicillium to great effect on a patient injured in a road accident. ref

John Tyndall (GB), in 1875, described to the Royal Society in London how a species of Penicillium had made several bacteria burst open and die(647).

Ernest Duchesne (FR) described in his dissertation the effectiveness of Penicillium glaucum in animals injected with normally fatal doses of pathogenic bacteria. In a subsequent article he emphasized the therapeutic value of Penicillium(648, 649).

André Gratia (BE) and Sara Dath (BE) mentioned that a Penicillium strain exerted a highly bacteriolytic activity against anthrax-causing bacteria(650).

Georges Papacostas (FR) and Jean Gaté (FR) used the term antibiotic and reported clinical applications of antibiotic substances(651).

Sir Alexander Fleming (GB) observed that some mold contaminants of his plates of Staphylococcus aureus exerted a specific antagonism toward the bacteria. He postulated that the mold Penicillium produced a potent antibacterial agent. He named the agent penicillin and noted that it killed gram-positive bacteria more effectively than gram-negative bacteria(652).

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) established the taxonomic position of the Chordata, and proposed the Gastraea as the hypothetical ancestor to all metazoa saying, “From these identical gastrulae of representatives of the most different animal phyla, from poriferans to vertebrates, I conclude, according to the biogenetic law, that the animal phyla have a common descent from one unique unknown ancestor, which in essence was identical to the gastrula: Gastraea”(348, 653).

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) proposed the gastrea hypothesis of Metazoan ancestry. He speculated that the ancestor of all the Metazoa consisted of two layers (ectoderm and endoderm) similar to the gastrula stage in embryonic development, and endoderm arose as an invagination of the blastula. Thus the diploblastic stage of ontogeny is considered a repetition of this ancestral form(653). 

Casimir Joseph Davaine (FR) found that the blood of animals suffering or dead from putrid injections is capable of inducing a similar condition when introduced into a normal animal, and it can produce a lethal effect from incredibly minute doses. He found that the virulence of such blood disappears on keeping. He also found that the minimal lethal dose varies not with the size but with the species of the animal injected. Inside a particular species, young were more susceptible than older animals(420).

Joseph Schroeter (DE) used solid media to isolate pigmented bacteria in axenic culture. His solid medias included potato (Solanum tuberosum), potato paste, flour paste, egg albumin, bread, and meat. He obtained bacteria which were red, blue, green, orange, yellow, brown, and violet (654).

Karl Joseph Eberth (DE) took anthrax blood and diluted it with water. After allowing the mixture to settle he demonstrated that the supernatant fraction was non-infectious, whereas, the sediment was capable of producing anthrax in a healthy animal(655).

Julius Oscar Brefeld (DE) laid down the principles which must be followed for obtaining pure fungal cultures. These principles apply equally to bacteria although with bacteria their implementation is difficult. They were: (1) that the inoculum must be as small as is practically possible, (2) the culture medium should be clear and transparent and yield optimum growth for the organism being cultivated, and (3) the culture should throughout the growth period be protected from external contamination. He was also the first to suggest the addition of gelatin or carragheen to liquid media to produce gelled media(656).

August Heinrich Rudolf Grisebach (DE) wrote one of the first comprehensive reviews of knowledge of the Earth’s vegetation(657).

John Thomas Gulick (US) and Alfred Russel Wallace (GB) discovered that variation in the shells of several species of self-fertilizing land snails (family Achatinellinae) occurred randomly with chance leading to the preservation of certain patterns which became fixed into races by reproductive isolation(658-660).

Sewall Wright (US) would later popularize Gulick’s discovery as random genetic drift (the Sewall-Wright effect)(661-665).

Elliott Coues (US) authored Key to North American Birds in which he adopted the viewpoint that geographically complementary forms which were clearly closely related were subspecies of one species, regardless of the degree of difference between the extremes. Coues used the abbreviation var. to indicate geographical races(666).

H.M.S. Challenger , 7 December 1872 sailed from Sheerness, England on what can be characterized as the first serious attempt to study life beneath the surface of the sea. It returned to Spithead, England on 24 May 1876. Aboard were six civilian staff/scientists under the direction of Sir Charles Wyville Thomson (GB). They included the 'naturalists' Sir John Murray (GB), Henry N. Mosely (GB), Rudolph von Willemoes-Suhm (DE), the 'chemist/physicist' John Buchanan (GB) and the official artist J.J. Wild (GB). Challenger traversed 68,890 nautical miles, in the course of which she sampled in the North and South Atlantic and Pacific Oceans and traveled north of the limits of drift ice in the North Atlantic polar seas and south of the Antarctic Circle. Wyville Thomson reported the Challenger to have made 362 sample/observation stations "at intervals as nearly uniform as possible". 

Back at home, the scientific findings of the cruise were examined by over 100 scientists, primarily under the guidance of John Murray, who should receive the highest praise for the work's eventual publication in The Report of the Scientific Results of the Exploring Voyage of H.M.S. Challenger during the years 1873-76 occupying 50 volumes, each measuring about 13 by 10 inches and as thick as a family Bible. They appeared between 1885 and 1895. At its completion, The Report discussed with full detail of text and illustrations the currents, temperatures, depths and constituents of the oceans, the topography of the sea bottom, the geology and biology of its covering and the animal life of the abyssal waters. The Challenger cruise had lain the cornerstone of scientific oceanography and begun its introduction to the wider scientific and lay community. The findings of the cruise were correctly described by Sir John Murray in 1895 as "the greatest advance in the knowledge of our planet since the celebrated discoveries of the fifteenth and sixteenth centuries"(667).

Felix Victor Birch-Hirschfeld (DE) found that bacterial cocci injected into the blood stream may be taken up by leucocytes (668).

Morrill Wyman (US) stressed family predispositions to hay cold due to pollens(669).

Daae-Finsen Krankheit (NO) first described epidemic pleurodynia. He reported it as acute muscular rheumatism. It is also known by other names including: epidemic myalgia, Bornholm disease, epidemic muscular rheumatism, acute benign dry pleurisy, epidemic pleuritic pain, Bamble disease, and devil’s grip. The disease is acute, febrile, specific, infectious, and of limited duration. It has an affinity for children and young adults(670). It is usually caused by one of the group B coxsackieviruses and is less often caused by a group A coxsackievirus or an echovirus

Hjalmar Heiberg (NO) quoted Øjvind Winge (DK) as having detected microorganisms in vegetations of endocarditis(671). 

Rudolf Ludwig Karl Virchow (DE) detected microbes in endocarditis vegetations(672).

Anton Weichselbaum (AT), in 1883, cultivated both streptococci and staphylococci from endocardial vegetations(673).

Vladimir Wyssokowitch (DE), Johannas Orth (DE) and Moritz Wilhelm Hugo Ribbert (DE) demonstrated that various bacteria introduced into the bloodstream could cause endocarditis on heart valves previously damaged(674-677).

Hugo Schottmüller (DE) presented proof of the bacterial nature of malignant endocarditis (acute and subacute endocarditis)(678).

Frederick John Poynton (GB), Alexander Paine (GB), Carey Franklin Coombs (GB) and Alvin Franklin Coburn (US) found that reaction to hemolytic streptococci is responsible for much if not all of rheumatic heart disease(679-681).

Charles S.F. Easmon (GB) and Janusz Jeljaszewicz (PL) state that perhaps the archetype of a cryptic and persistent bacterial infection, in which the pathogens adhere to a tissue in large microcolonies, is bacterial endocarditis. These adherent pathogens routinely produce macroscopic vegetations on the endocardium and the cells within these huge dextran-enclosed microcolonies are inherently resistant to conventional therapy even though they are fully and directly exposed to circulating blood levels of these agents(682).

When a plastic or metal prosthesis is introduced into an animal body its biologically inert surface offers a unique substratum for colonization by bacteria, whose preferential mode of growth is the formation of adherent biofilms. Once established, adherent microcolonies of bacteria are much less susceptible than their planktonic counterparts to surfactants, antiseptics, antibiotics, opsonizing antibodies, and phagocytosis(683).

The normal biofilm of microorganisms on human tissues often excludes would be pathogens from gaining a foothold(684).

Adherent microorganisms in a thick glycocalyx are significantly more resistant to chemical biocides than are their otherwise equivalent planktonic counterparts(685).

Adhesion of bacteria to phagocytes is essential to the successful function of the phagocytic defense system(686). 

Ferdinand Ritter von Hebra (AT) and Moriz Kohn Kaposi (HU) wrote Lehrbuch der Hautkrankheiten (Textbook on Skin Diseases) and On Diseases of the Skin, Including the Exanthemata; important books on human skin diseases. They were the first to give a clinical description of scleroderma and the then rare Kaposi’s sarcoma which would years later receive much attention as one of the signs of acquired immune deficiency syndrome (AIDS)(687-690).

Ferdinand Ritter von Hebra (AT) was the first to describe impetigo herpetiformis(691).

Moriz Kohn Kaposi (HU) completed and refined the description of impetigo herpetiformis(692).

Ludwig Traube (DE) coined the name of Pulsus alternans. “ …it has to do with a succession of high and low pulses, in such a manner that a low pulse follows regularly a high pulse and this low pulse is separated from the following high pulse by a shorter pause than that between it and the preceding high pulse”(693).

Emil Jacob Noeggerath (US) described the effects of latent gonorrhea in women(694, 695).

Christian Albert Theodor Billroth (DE-AT) performed the first resection of the esophagus in laboratory animals(696).

Vincenz Czerny (CZ-DE) performed the first successful resection of the thoracic region of the esophagus in humans (esophagectomy)(697, 698).

Franz Torek (DE-US) performed the first successful transthoracic resection of the esophagus for carcinoma(699).

Marc B. Orringer (US) and Herbert Sloan (US) presented their surgical technique of esophagectomy without thoracotomy(700). This was a revival of an incidental technique carried out by George Grey-Turner (GB) in 1933(701).

John Harry Garlock (US) showed that it is possible to excise the esophagus and to bring the stomach up through the chest and join it to the pharynx. Lengths of colon are also used as grafts to bridge the gap(702-704).

Robert Battey (US) was the first to perform oöphorectomy, the excision of uterine appendages, for such non-ovarian conditions as painful menstruation and neuroses(705).

Frank Eastman Bundy (US) and William Ingalls (US), on October 8, 1872, carried out the first nephrolithotomy. A surgical procedure in which the kidney is cut to remove a stone(706).

Douglas Alexander Spalding (GB), James Mark Baldwin (US), Conwy Lloyd Morgan (US) and Henry Fairfield Osborn (US), proposed a mechanism by which learned traits could make their way into the genome: organisms that are capable of learning an advantageous behavior will survive better; the capacity to learn will thereby spread through the population; the learned behavior will pave the way for an even more advantageous heritable version of the behavior to arise; and natural selection will thus push the congenital trait to fixation(707-713).

Felix Anton Dohrn (DE) was a major figure in early phylogenetics. He studied the phylogenetics of arthropods using embryological and comparative anatomical data and advocated the annelid theory of vertebrate origins. At Naples, Italy he established Statzione Zoologica de Napoli which was among the first marine biology laboratories to routinely accept visiting scientists from other countries.

1873

Johannes Diderik van der Waals (NL) described the weakest of the electrostatic attractions between atoms of opposite charge(714). Today these forces of attraction are named van der Waals’ forces in his honor.

Ernst Karl Abbé (DE) published his formula for calculating the resolving power of a light microscope. This immediately led to an understanding that there is a finite limit to resolving power(715). 

Casimir Joseph Davaine (FR) discovered the antimicrobial properties of iodine(716).

Kerosene, applied by paint brush to tree limbs, was advocated for the control of woolly apple aphid. By 1875 a kerosene emulsion spray had been developed(138).

Heinrich Hermann Hlasiwetz (HU-AT) and Josef Habermann (CZ) made the first serious attempt to account for the composition of a protein (casein) in terms of the products of the complete hydrolysis. They hydrolyzed protein using hydrochloric acid in the presence of stannous chloride to eliminate humin formation. This was a first. It also describes for the first time the isolation of glutamic acid hydrochloride directly from a concentrated hydrolysate(717, 718). 

Bartolomeo Camillo Emilio Golgi (IT) and N. Manfredi (IT) used potassium dichromate with silver nitrate to form silver chromate which penetrates and stains nonmyelinated nerve fibers revealing nerve cell details never before seen. This staining technique was called the "black reaction." With this new stain they observed two types of cerebral cortical cells—those with long processes that travel to the white matter and subcortex (type 1) and others with processes confined within the cortex (type 2). They determined that axons are invested with co-lateral branches(719-723).

Alfred Wilhelm Volkmann (DE) described the canals in bone carrying blood vessels from the periosteum (Volkmann's canals)(724).

David Luginbühl (DE), Carl Weigert (DE) and Eduard Krauss (DE) were the first to report multinucleate cells in lesions that can with certainty be identified as of viral origin(725-727).

Theodor Wilhelm Engelmann (DE) discovered that I (isotropic) bands shorten during contraction of striated muscle(728, 729).

Sebastiano Rivolta (IT) determined that epizootic lymphangitis (African glanders) is caused by the yeast Cryptococcus farciminosus(730). In 1934 it would be renamed Histoplasma farciminosum.

Otto Hugo Franz Obermeier (DE) while examining the blood of patients with European relapsing fever discovered Borrelia recurrentis, the bacterial cause of relapsing fever(731). This organism has been called Obermeier’s spirillum.

Gregor Münch (DE) suggested that relapsing fever may be transmitted by the bite of blood-sucking arthropods such as lice, fleas, and bugs. ref

Henry Foley (FR) and Edmond Sergent (FR) suspected and later demonstrated the exclusive role played by the louse (Pediculus corporis, P. vestimenti, or P. humanus) in the transmission of relapsing fever of which they studied an important epidemic occurring at the Algerian-Moroccan border between 1907-1910(732).

Theodor Albrecht Edwin Klebs (DE) was the first to attempt the isolation of pathogenic bacteria in axenic culture. His technique was to inoculate liquid medium with a small inoculum. As soon as growth was obvious a small quantity was transferred to fresh medium. The process was repeated a number of times. It was hoped that any contamination would in time be eliminated, and that the organism present in the greatest quantity in the original inoculum would ultimately dominate the situation and show itself as an axenic cultivation. We do not know much about his successes(733).

Theodor Albrecht Edwin Klebs (DE) produced tuberculosis in cattle by feeding them infected milk(734).

Louis-Antoine Ranvier (FR) found that dark (red) muscles contract slowly, develop tetanus (lock in full contraction) at lower rates of stimulation, have relatively more sarcoplasm, have more distinct longitudinal striations, and are more resistant to fatigue(735).

Physicians in the United States are documented, during these years 1873-1880, to have transfused milk (from cows and goats), as a blood substitute, to humans(736).

Charles Harrison Blackley (GB) reported that the symptoms described in 1819 by John Bostock under the term of catarrhus aestivus (hay-fever or hay-asthma) are due to the grains of pollens. To investigate his own hay-fever, he performed the first skin test, doing so by applying pollen through a small break in his skin. His experiment introduced the concept that pollen sensitivity caused hay-fever. Today's skin testing methods vary in the way in which the allergen extract is introduced into the skin; however, the principle remains the same. As Blakely found, a positive reaction to a specific allergen becomes evident in about twenty minutes by the appearance of a hive like response at the tested skin site(737). 

Pierre Cyprien Oré (FR) was the first to use an intravenous anesthetic in humans. He sedated a 52 year old man with an acute phase of tetanus using intravenous chloral hydrate injections(738-740).

James Paget (GB) described eczema of the nipple with subsequent mammary carcinoma, i.e., Paget’s disease of the nipple(741).

Christian Albert Theodor Billroth (DE-AT) and Carl Gussenbauer (DE), in 1873, performed the first total laryngectomy(698, 742, 743).

Nikolaus Friedreich (DE) wrote a monograph on progressive muscular atrophy(744).

Jean Joseph Emile Letievant (FR) was the first to describe cranial and peripheral neurectomy to alleviate pain(745).

Robert Waldo Abbe (US) performed the first spinal dorsal rhizotomy, i.e., division of the roots of the spinal nerves for pain or paralysis. He describes surgery on a patient suffering from intractable brachial neuralgia. He tried nerve stretching, amputation, and finally, division of posterior roots of the sixth, seventh, and eighth cervical. The patient improved(746).

William H. Bennett (US) completely removed acute spasmodic pain in the left lower extremity by subdural division of the posterior roots of certain spinal nerves(747).

Sir Victor Alexander Haden Horsley (GB), James Taylor (GB), and Walter S. Colman (GB) described an operation for the treatment of trigeminal neuralgia in which the trigeminal ganglion was removed through a temporal approach(748). This type of operation is typically performed to give patients relief from very painful facial neuralgia.

Frank Hartley (US) performed an intracranial neurectomy of the second and third divisions of the fifth nerve(749).

Fedor Krause (DE) performed an intracranial neurectomy in the fifth nerve(750).

Sir Henry Head (GB), Alfred Walter Campbell (GB), and Theodore Thompson (GB) showed herpes zoster to be a hemorrhagic inflammation of the posterior nerve roots and the homologous spinal ganglia. They made a map of human dermatomes. Patients with herpes zoster provided valuable information to the development of this map(751, 752). 

Harvey Williams Cushing (US) reported a method of total extirpation of the Gasserian ganglion for trigeminal neuralgia, by a route through the temporal fossa and beneath the middle meningeal artery(753).

William Gibson Spiller (US) and Charles Harrison Frazier (US), using a modification of Horsley’s approach, divided a sensory root of the fifth cranial nerve, accomplished through a subtemporal approach, to relieve tic douloureux(754).

William Gibson Spiller (US) believed that intractable lower-body pain could be cured by section of the anterolateral column of the spinal cord. He provided understanding of the location of the pain fibers and Edward Martin (US) was the first to successfully perform this operation(755).

Charles Harrison Frazier (US) perfected the operation for the radical cure of trigeminal neuralgia(756).

Otfrid Foerster (DE) made a thorough study of the human dermatomes, including overlap in nerve distributions. This overlapping is correct and conflicts with some of Henry Head’s conclusions. Foerster suggested the concept of gate control. This theory asserts that large nerve fibers can inhibit small nerve fibers during a painful experience. He also introduced topographical localization of function, suggesting that pain fibers are in different locations from temperature and touch fibers(757).

Egas Moniz (FR) reported successful control of intractable pain after frontal lobotomy(758).

Sir David Ferrier (GB) and William Aldren Turner (GB) began reporting their neurological studies which according to Sir Charles Scott Sherrington (GB) in 1928, “….established the localization of the ‘motor’ cortex very much as we now know it. He located it as a region accompanying the Rolandic fissure across the lateral aspect of the hemisphere and extending thence over and upon the hemisphere’s median aspect. He pointed out that its extent was greater and its character more detailed in the ape than in any of the types less near to man. He showed that its focal movements were obtainable with such definition and precision that ‘the experimenter can predict with certainty the result of stimulation of a given region.’ He went on to determine the effects of destruction of limited portions of the cerebral cortex. He allocated regions specially concerned with vision (occipital cortex) and with hearing (superior temporal gyrus) respectively. He showed that the hemiplegias, ensuing on injuries within the motor region of the ape, were characteristically greater than those produced by similar cerebral lesions in the dog. The symptoms in the ape he stressed as being strikingly akin to those familiar in the clinic”(759-770). 

Douglas Alexander Spalding (GB) discovered stamping-in (imprinting)(713).

Konrad Zacharias Lorenz (AT), one of the founders of ethology, carried out studies which led to a deeper understanding of behavior patterns in animals, notably the releaser concept and imprinting in young birds(771-774). In the 1937 paper Lorenz defined releaser as, “The means evolved for the sending out of key-stimuli may lie in a bodily character, as a special color design or structure, or in an instinctive action, such as posturing, dance movements and the like. In most cases they are to be found in both, that is, in some instinctive acts which display color schemes or structure that were evolved exclusively for this end. All such devices for the issuing of releasing stimuli, I have termed releasers (Auslöser), regardless of whether the releasing factor be optical or acoustical, whether an act, a structure or a color.” The 1935 and 1937 papers are the classics on imprinting.

Oscar Heinroth (DE) and his wife Magdalena also discovered imprinting (prägung): an especially rapid and relatively irreversible learning process that occurs early in the individual's life where auditory and visual stimuli from an animal's parents are needed to induce the young to follow their parents. They conducted 'deprivation experiments', raising a variety of central European bird species in isolation, deprived of all influence of their natural parents. They did so in order to discover which instinctive acts are innate in birds and which are supplemented in their development through experience or through learning. They along with their correspondent Konrad Zacharias Lorenz (AT) founded comparative ethology (study of the immediate causes of behavior in animals, including external stimulation and physiological mechanisms and states)(775, 776).

Charles O. Whitman (US), like Oskar Heinroth (DE) and Konrad Zacharias Lorenz (AT), was a founding father of comparative ethology. His posthumous work The Behavior of Pigeons is a particular example(777).

Archives for Experimental Pathology and Pharmacology was founded.

1874

Jacobus Hendricus van’t Hoff (NL) and Joseph Achille Le Bel (FR) independently advanced a three dimensional stereochemical representation of organic molecules such as lactic acid and proposed that the carbon atom bonds in a tetrahedral fashion. This image of the carbon atom led them to propose that it can form asymmetric relationships which would explain optical activity of organic compounds. Their description of isomerism in terms of differences in the arrangement of atoms in space (stereoisomerism) provided a convincing argument for considering structural formulas as representations of reality(778-781). 

Heinrich Caro (DE) synthesized the dye eosin in 1874. It is a phthalein product consisting of brominated fluorescein(782). Eosin would later prove useful for selectively staining cytoplasmic proteins. 

Max Jaffé (DE) isolated and named urocanic acid (Greek ouro, urine + Latin canis, dog) from dog’s urine(783, 784).

Andrew Hunter (US) determined that urocanic acid is an imidazole derivative, and a product of the deamination of the amino acid histidine(785).

J. Piccard (DE) discovered that the hydrolysis of nucleoproteins yields the purines, guanine, and xanthine(786).

Walther Flemming (DE) used carmine to stain the eggs of Anodonta (freshwater muscle)(787).

Frédéric Alphonse Musculus (FR) obtained an enzyme (urease) from putrid urine, which he found capable of decomposing urea in aqueous solutions(788, 789).

Albert Wojciech Adamkiewicz (PL) presented his reagent which gives a color reaction with proteins. It was later found to give a positive reaction with tryptophane(790, 791).

Richard Neumeister (DE) coined the name tryptophane for that substance which gives a color reaction with chlorine water following extensive degradation of a protein (the Adamkiewicz test)(792).

Sir Frederick Gowland Hopkins (GB) and Sydney William Cole (GB) isolated tryptophane from a trypsin digest of casein and showed that some proteins did not contain it, e.g. gelatin(793).

Alexander Ellinger (DE) and Max Geutzen (DE) found that tryptophane can act as a precursor to indole production in the intestine(794, 795).

Edith G. Willcock (GB) and Sir Frederick Gowland Hopkins (GB) carried out feeding experiments with mice which represent the earliest animal experiments in which a decisive test proved the indispensability of a specific amino acid (tryptophane) in nutrition. Willcock and Hopkins thus originated the concept that some amino acids are essential in the diet(796). Others had shown that rats could not survive when gelatin was their sole source of amino acids.

Thomas Burr Osborne (US) and Lafayette Benedict Mendel (US) demonstrated that rats can not survive on zein of corn as their sole dietary protein unless tryptophane and lysine are added. This was also an early indicator that individual amino acids might be required by animals(797).

Otto Folin (SE-US) and Vintila Ciocalteu (US) developed a method of determining the tyrosine and tryptophane in proteins(798).

Henry D. Schmidt (US) described intersegmental clefts in the myelin sheath of peripheral nerves(799). To honor him these are called Schmidt's Clefts.

William Roberts (GB) found that when infusions of hay are carefully neutralized they can withstand three hours boiling before they are rendered sterile. He drew attention to the fact that the degree of heat required to produce sterility varies greatly according to the nature of the materials tested.

He confirmed Johannes Hubertus Van den Broek’s work suggesting that the interiors of plant tissues are sterile. Roberts tested the interior of grapes, oranges, tomatoes, turnips, and potatoes (Solanum tuberosum). His methodology consisted of heating a spot on the surface of the tissue then puncturing it with a sterile Pasteur pipette. Plant fluids were draw into the pipette after which it was sealed with a flame.

He commented that when Penicillium glaucum was growing on a medium it was very difficult to also get bacteria to grow on the same medium. This he interpreted in Darwinian terms of the drive to survive. He was the first to use antagonism in this context(800).

William Gilson Farlow (GB) and Heinrich Anton de Bary (DE) discovered that the asexual phase can arise directly (that is, vegetatively) from the sexual phase, i.e., apogamy, in the Pteridophyta (ferns, horsetails, and club-mosses)(801, 802).

Christian Albert Theodor Billroth (DE-AT) reported on a five year study of the bacteria associated with putrefaction and infectious disease. He concluded (incorrectly) that all the round and rod shaped bacterial forms were but stages of a plant—he regarded it as an algae—which he called Coccobacteria septica. He did introduce many names such as micrococcus, diplococcus, streptococcus, gliacoccus, petalococcus, mesacoccus, megacoccus, ascococcus, gliabacteria, petalobacteria, and streptobacteria, some of which persist today (803).

Wilhelm Kurz (DE) was among the first to point out that environmental conditions may trigger parthenogenesis. He found that increased salt concentrations in evaporating watery media brought it about in Daphnia. Kurz was apparently the first to document the existence of sex intermediates in the Cladocera(804).

Wilhelm His (CH) presented the hypothesis of germinal localization based on what he called the principle of organ-forming primordial-regions. This hypothesis suggests that in the course of normal embryonic development identifiable regions of the early embryo develop into specific structures of the older embryo(805, 806).

Pierre-Joseph van Bénéden (BE) was able to show through his studies of the digestive tracts of many fishes that organisms known as cysticerci are larvae of intestinal worms then called taeniae (adult tapeworms). His work covered a wide range of parasites in diverse animals(807). About 1859 he began a study of fossil and recent whales, which resulted in a major work, written in collaboration with Paul Gervais (BE)(808). He is commemorated by Tubificoides benedii d'Udekem, 1855, Vanbenedenia Malm, 1860, Nematobothrium benedeni Monticelli, 1893, Haploporus benedenii Stossich, 1887, Benedenia Diesing, 1858, Allometabenedeniella Velasquez, 1982, Metabenedeniella Yamaguti, 1958, Neobenedenia, Acanthobothrium benedenii Lönnberg, 1889, Echinobothrium benedeni Ruszkowski, 1928, Benedenipora Pergens, 1889, Barentia benedeni Foettinger, 1886, Actigia vanbenedeni Hincks, 1869, and Bougainvillia vanbenedeni Bonnevie, 1898.

Carl Erhardt (DE) recommended the administration of potassium fluoride to pregnant women and to children during the period of tooth development. His views of the relationship between sound teeth and dietary fluoride rested on meager experimental evidence from dogs(809, 810).

Alvaro Francisco Carlos Reynoso (CU) filed a patent, Improvement in Medical Compounds, on Elixir and Sirup containing fluoride of potassium, sodium or ammonium. His "elixir", he says, is "invigorating, nutritious, and complemental to food", "fluorated sirup" is "... for infants at the period when the bones and teeth are in process of formation(811).

Gerhard Henrik Armauer Hansen (NO) described the rod shaped bacterium of leprosy (Mycobacterium leprae) in association with leprous lesions. This organism is sometimes called Hansen’s bacillus(812-814). This was the first bacterium to be implicated as the probable cause of an infectious disease.

Albert Ludwig Siegmund Neisser (DE) used aniline dyes to convincingly demonstrate that Mycobacterium leprae is the etiological agent of leprosy(815).

H. Böttcher (DE) and Maurice Letulle (FR) discovered bacteria in the floor and margins of gastric ulcers. They were the first to propose that bacteria can cause ulcer disease(816, 817).

Walery Jaworski (PL) isolated a spiral bacterium characteristically present in stomach cancer and ulcer. He called the bacterium Vibrio rugula(818).

Giulio Bizzozero (IT) noted spirochetes in the gastric mucosa infiltrating gastric glands and found them within the cytoplasm and vacuoles of parietal cells of dogs(819).These organisms were named Helicobacter bizzozeronii in 1996.

Sir Berkely George Andrew Moynihan (GB) stated, “I believe that a further search should be made for an organism thriving in hydrochloric acid medium (and variations of hydrochloric acid are normal in all stomachs) as a possible factor of chronicity, if not an etiologic factor, in peptic ulcer”(820).

John Robin Warren (AU) and Barry J. Marshall (AU) reported that there is a strong association of a Campylobacter-like organism with gastritis and peptic ulceration(821, 822).

Charles Stewart Goodwin (AU), John A. Armstrong (AU), Terry Chilvers (AU), Michelle Peters (AU), M. David Collins (GB), Lindsay I. Sly (AU), William Mc Connell (AU), and William E.S. Harper (AU) presented compelling evidence that this organism should be placed in a new genus as Helicobacter pylori(823).

David Y. Graham (US), Ginger M. Lew (US), Peter D. Klein (US), Dolores G. Evans (US), Doyle J. Evans, Jr. (US), Zahid A. Saeed (PK-US), Hoda M. Malaty (US), International Agency for Research on Cancer (IARC), Barry J. Marshall (AU), John A. Armstrong (AU), David B. McGechie (AU), Ross J. Glancy (AU), Julie Parsonnet (US), Svein Hansen (NO), Larissa Rodriguez (US), Arnold B. Gelb (US), Roger A. Warnke (US), Egil Jellum (NO), Norman Orentreich (US), Joseph H. Vogelman (US), Gary D. Friedman (US), and Walter L. Peterson (US) proved that Helicobacter pylori, a bacterium, is the etiological agent of acute or chronic gastritis, and a predisposing factor in peptic ulcer disease, gastric carcinoma and B cell mucosa-associated lymphoid tissue (MALT) lymphoma(824-828).

Massimo Marignani (IT), Stefano Angeletti IT), Cesare Bordi (IT), F. Malagnino (IT), C. Mancino (IT), Gianfranco Della Fave (IT), and Bruno Annibale (IT) reported that Helicobacter pylori infection can be involved in unexplained cases of iron deficiency anaemia in adults, and its cure can normalize the hematologic picture(829).

Emil Heinrich du Bois-Reymond (DE) hypothesized that the transmission of the excitatory process from nerves to effector cells could take place either electrically via currents or chemically using excitatory substances liberated by nerve endings(830).

Michael Foster (GB) and Charles Scott Sherrington (GB) deduced the existence of and named the nerve cell synapse (a name suggested by the Euripidean scholar Verrall, then at Cambridge) by showing that individual nerve cells can exert integrative influences on other nerve cells by graded excitatory or inhibitory synaptic actions(831). Absolute proof of the existence of the synapse came in 1959 with the electron micrographs of Edward George Gray (GB)(832).

Rudolf Peter Heinrich Heidenhain (DE) and Albert Ludwig Siegmund Neisser (DE), on the basis of carefully controlled dye injection studies, provided experimental proof for the existence of proximal tubular secretion as a principal transport process involved in urine formation(833).

Sir William Osler (CA) was doubtless describing platelets (thrombocytes) when he reported that they exist as, “pale granular masses, which on closer inspection present a corpuscular appearance. In size they vary greatly from half or quarter that of a white blood-corpuscle, to enormous masses…. They have a compact solid look…while in specimens examined without any reagents the filaments of fibrin adhere to them”(834).

Vladimir Alekseyevich Betz; Vladimir Aleksandrovich Betz (RU) published work on giant pyramidal cells (later named for him) of the brain’s central cortex. He also put forward the important concept that motor functions are represented anterior to the central sulcus (of Rolando) and sensory functions posterior to it(835).

W. Bevan Lewis (GB) and Henry Clarke (GB) published work on the giant pyramidal cells of human pre-central gyrus(836, 837).

Karl Gegenbaur (DE) stressed the higher value of comparative anatomy as the basis of the study of homologies, i.e., of the relations between corresponding parts in different animals, as, for example, the arm of man, with the foreleg of a horse, and with the wing of a fowl. He showed how embryonic structures which in fish eventually come to form gills, form other organs, from Eustachian tubes to the thymus gland, in land vertebrates. He also extended the work of Rudolf Albert von Kölliker (CH) to show that not only mammalian eggs and sperm but all eggs and sperm, even the giant eggs of birds and reptiles, are single cells. Gegenbaur applied the term syncytium to striated muscle(838).

Francis Galton (GB) used the phrase nature and nuture to explain heredity and environment(839).

Hugo Kronecker (DE) and William Stirling (GB) showed that the heart muscle cannot be tetanized(840).

Roberts Bartholow (US) was the first to electrically stimulate the human cortical tissue(841).

Carl Wernicke (PL-DE) published a small volume on aphasia which vaulted him into international fame. In it is precise pathoanatomic analysis paralleling the clinical picture. He is best known for his work on sensory aphasia and poliomyelitis hemorrhagia superior. Both of these descriptions bear his name. Further, his books on the disorders of the internal capsule and his textbooks on diseases of the nervous system perpetuate him. In this work he also relates damage to the left temporoparietal junction of the brain to loss of language comprehension(842, 843). See Broca, 1856. Sensory aphasia is due to cortical lesions in the posterior portion of the left first temporal convolution.

Karl Thiersch (DE) introduced a method of split skin grafting using epidermis and a portion of the dermis. It consists of shaving thin strips of healthy skin so that the true skin is divided and then implanting these strips on granulating tissue(844).

Abraham Groves (CA) may have been the first to sterilize surgical instruments by boiling. He removed an ovarian cancer from a 40-year-old woman with a tumor filling the whole abdomen. Careful examination of its location and physical characteristics led him to conclude that the tumor was ovarian and monocystic. Tapping yielded about 25 pints of clear fluid, but the fluid rapidly accumulated, two further aspirations bringing only transient relief. Groves operated on her on 5 May 1874. The operation, which was successful, featured the rigorous application of antiseptic principles. Groves boiled all the water, used carbolized cat-gut to tie the pedicle, and dressed the wound with cotton saturated with a solution of carbolic acid. To his knowledge instruments and dressings had never been sterilized by boiling before that time. This became his surgical practice from then on(845).

Andrew Taylor Still (US) began discussing changes in medical practice which would lead to his establishment of osteopathic medicine. In 1892, he opened the American School of Osteopathy in Kirksville, MO.

Wilhelm Philipp Schimper (DE), in 1874, recognized and named the Paleocene Epoch (65 Ma B.P.—54.9 Ma B.P.) of the Cenozoic Era based on a study of floral samples from the Paris Basin(846).

The Botanischer Jahresbericht was founded.

ca. 1875

Georg Meissner (DE) was successful in preserving unchanged many organs and tissues aseptically removed from cats and rabbits. Whole kidneys, spleens, pancreas, and pieces of liver from these animals as well as frogs’ thighs were removed immediately after death and preserved in a dust-free atmosphere for two or three years. The exact technique employed is not given, but it is known that everything had been sterilized by heat. All glassware was plugged with cotton-wool and heated to 160° C. All the water was boiled. No sponges were used, but only sterile cotton-wool swabs. The operations were carried out in a dust-proof room, and the number of assistants was reduced to a minimum. The skin of the animal was generally stripped off completely. Meissner had developed high-class aseptic surgical techniques long before they were in vogue in human surgery. His experiments showed that tissues are sterile and will not autonomously decay and putrify(847).

1875

Wilbur Olin Atwater (US) was instrumental in persuading the Connecticut Legislature to set up the first state agricultural research station in the United States, at Middletown. In 1887, again at his prodding, The U.S. Congress passed the Hatch Act, providing funds for agricultural experiment stations in all the states. He was the first director of the Office of Experiment Stations (1888).

Hermann Emil Fischer (DE) discovered phenylhydrazine in 1875, then found that it reacts with simple sugars to produce crystalline substances called osazones. Osazone crystals are often characteristic of the sugar from which they were derived.

Hermann Emil Fischer (DE), Joseph Hirschberger (DE), and Julius Tafel (CH-DE) developed an extensive work on the chemical synthesis of sugars, on their isomeric forms and stereochemistry, and on the selective transformation of some of them by yeast. They were able to synthesize 5, 6, 7, 8, and 9 carbon monosaccharides, produce their phenylhydrazine derivatives, then determine the molecular structures of fructose, glucose, and many other sugars(848-861). 

Hermann Emil Fischer (DE) applied the Le Bel-Van’t Hoff theory to the sugar series and showed how to distinguish the formulas of the 16 stereoisometric glucoses (Fischer projections). He states, “All previous observations in the sugar group are in such complete agreement with the theory of the asymmetric carbon atom that the use of this theory as a basis for the classification of these substances seems justifiable”(861-863). In the course of his stereochemical research, Fischer discovered that there are two series of sugars, the D sugars and the L sugars, that are mirror images of each other. The D & L forms of mannoic acid were the first pair of enantiomorphs to be discovered in this group of sugars(856, 861). 

Hermann Emil Fischer (DE) related the optical activity of sugars to that of tartaric acid(864).

Wilhelm Friedrich Kühne (DE) showed that indole appears after proteinaceous material putrifies. The protein will give a violet color when nitric acid is added(865).

Whale oil, soap, and kerosene were advocated as insecticidal spray for numerous insect pests(138).

André Victor Cornil (FR), using methyl aniline violet, was probably the first to stain tissue and observe a metachromatic effect. He observed that hyaline cartilage was stained in such a manner that the cells and their capsules were violet, the intracellular material red; connective tissue fibrils and elastin fibers as well as the cells and fibers of elastic cartilage stained violet(866).

Paul Ehrlich (DE) is often given credit for discovering metachromasy and explaining that it is due to certain basic dyes staining acidic cell constituents one color and other cell components another color(867).

Rudolf Arndt (DE) was the first to demonstrate chromophilic granules within cells. These are granules which certain dyes color more intensely than the surrounding cytoplasm(868). See Franz Nissl, 1890.

Ferdinand Julius Cohn (DE) studied a group of peach-colored sulfur bacteria isolated from contaminated waters. Although they looked alike, he concluded, based on their physiology that they were separate species. He also described Cladothrix dichotoma in 1873 and Streptothrix foersteri in 1875(645).

Jules Emile Planchon (FR) discovered the fungus Phylloxera which causes a severe disease of grapevines(869).

Otto Bütschli (DE) was the first to identify and order sequentially the stages of nuclear division in several types of animal cells, simultaneously with Strassburger’s work on the division of plant cells and several years prior to Flemming’s studies on mitosis. Bütschli demonstorated that the polar bodies of eggs arise through atypical cell division, and in studying fertilization he was the first to describe the fertilization cone and to prove that normally only one sperm enters the egg. He clearly illustrated the fusion of male and female pronuclei in the eggs of snails. His illustrations of the zygotene “bouquet” stage and of diakinesis during the first meiotic division of spermatogonia in the roach were excellent. He suggested that in the ciliates reproduction and the sexual processes are not closely associated. Bütschli was the first to recognize this and to demonstrate that conjugation was not a reproductive process per se, but a sexual reorganization of the cell similar to fertilization(870-872).

Wilhelm August Oskar Hertwig (DE) concluded that the physical basis of inheritance must be the chromosomes. He described the intracellular events following fertilization as they occur within the egg of the roundworm Ascaris. Hertwig was one of the discoverers of meiosis(873).

Giulio Bizzozero (IT) produced images of mitosis in the spleen of the triton (1883).

Édouard Joseph Louis Marie van Beneden (BE) using the horse roundworm, Ascaris megalocephala, observed that in fertilization, as in cell division, continuity depends on chromosomes: the sperm’s contribution to fertilization is a set of chromosomes homologous with those present in the egg. Rather than fusing with one another the maternal and paternal chromosomes retain their identity through subsequent cell divisions. He noted that the number of chromosomes is constant for a given species and that this number is reduced in half in reproductive cells or gametes(874). Édouard Joseph Louis Marie van Beneden (BE) is also one of those who discovered meiosis.

Emil Heuser (DE) described in the microsporocytes of Tradescantia a transverse fission of bivalent chromosomes in the first division. He thus made the important discovery that the chromatids (spalthälften) of each chromosome were exactly separated and distributed to the two opposite spindle poles(875).

August Friedrich Leopold Weismann (DE) wrote an article which emphasized meiosis as an exact mechanism of chromosome distribution(876).

Walther Flemming (DE) provided the first cytological evidence that the cell divisions involved in the production of sperm differed from the normal type of mitosis. Spermatogenesis, he reported, involved two types of cell division. The first type differed little from normal mitosis, but the second, or heterotypic mitosis, seemed to be unique in two ways. First, the chromosomes appeared as knots or rings. Second, and more significantly, the number of such ringed chromosomes was half the number that appeared in tissue cells, twelve rather than twenty-four in the salamander(877).

Theodor Boveri (DE), working with Ascaris megalocephala and Ascaris univalens, established that chromosomal individuality is stably maintained from one generation to the next. He also presented the first description of chromosome tetrads (Vierergruppen) and their behavior during reduction division. In Ascaris megalocephala var. bivalens, where the normal diploid number is four, Boveri observed two groups of chromosomes with four chromosomes in each group. The first division of the egg separated the tetrads into two dyads, one of which remained in the egg, the second of which entered the first polar body. The second division of the egg separated the two elements of each dyad, leaving a total of two chromosomes in the egg cell and two chromosomes in the second polar body. Meanwhile, the first polar body divided once. Thus the divisions produced a total of three polar bodies, each containing two chromosomes(878-880).

August Friedrich Leopold Weismann (DE) elaborated an all-encompassing theory of chromosome behavior during cell division and fertilization and predicted the occurrence of meiosis(881).

Édouard Joseph Louis Marie van Beneden (BE) and Adolphe Neyt (BE) demonstrated chromosome reduction in gamete maturation and discovered that each species has a fixed number of chromosomes, thereby confirming August Friedrich Leopold Weismann’s predictions. They along with Theodor Boveri (DE) described the role of the centrosome in cell division and established the independent inheritance of this organelle. It was Boveri who named it centromere in 1888(878, 879, 882-884).

August Friedrich Leopold Weismann (DE) made the very significant remark that since it was unlikely that the polar bodies would remove the same ids (ancestral germ plasms) each time, those retained in the germ cells also would be different. In other words, the germ nuclei were probably different from each other(885).

August Brauer (DE) described meiosis (spermatogenesis) in Ascaris megalocephala males. The diploid chromosome number in Ascaris is 4. The cells of the testis that will later form the sperm are diploid. The 4 chromosomes undergoing synapsis. As meiosis continues each chromosome becomes shortened until it forms a tiny sphere. During this process each chromosome splits. As a result each of the 2 pairs of synapsed chromosomes forms a tetrad. At the first meiotic division the 2 tetrads enter the spindle and are divided, half of each tetrad (a dyad) going to each pole. As a result of the first meiotic division 2 cells are formed. Each of these contains 2 dyads. In the second meiotic division the dyads of the 2 cells are pulled apart. At the end of this division there are 4 cells. Each of these contains 2 chromosomes, the haploid number. There is no further division of these 4 cells and they develop directly into sperm(886).

Eduard Adolf Strasburger (PL-DE) recognized the cytological significance of an alternation of a diploid, spore-producing generation with a haploid, gamete-producing generation in the bryophytes (liverworts and mosses) and other organisms(887).

William Austin Cannon (US), Edmund Beecher Wilson (US), and Walter Stanborough Sutton (US) pointed out the precise equivalence between the patterns of inheritance of genes and chromosomes in organisms that reproduce sexually, that is, by the union of eggs and sperm. Cannon was the first to recognize that Mendel’s results could be explained by meiosis(888, 889).

Thomas Harrison Montgomery, Jr. (US) published his classic paper detailing sperm formation and egg formation in many species of Hemiptera (true bugs). He concluded that chromosomes are permanent structures; that they occur in homologous pairs consisting of one originally inherited from the mother and the other from the father; that synapsis during meiosis consists of the coming together of these homologous chromosomes; that in meiosis each spermatid receives one chromosome of each type. He described accessory chromosomes that later investigators were to associate with sex determination(890, 891).

Walter Stanborough Sutton (US), Theodor Boveri (DE), and Carl Franz Joseph Erich Correns (DE) were independently the first to relate genetics to the study of chromosome behavior and provide the basis of the chromosomal theory of heredity. Sutton analyzed chromosome movements during meiosis in the grasshopper Brachystola, and stated, “I may finally call attention to the probability that the association of paternal and maternal chromosomes in pairs and their subsequent separation during the reducing division…may constitute the physical basis of the Mendelian law of heredity. To this subject I hope to return in another place.” Boveri analyzed chromosome movements during meiosis in the roundworm Ascaris. Correns stated clearly the hypothesis of the physical mechanism of segregation of alleles which underlies the chromosome theory of heredity, stating “Each tetrad contains bodies of both kinds, those with A as well as those with a, accordingly segregation must be carried out by nuclear division, in fact by the first division of the pollen mother cells.” They all provided strong evidence that there is an exact parallel in the behavior of Mendelian hereditary units and of the chromosomes in meiosis and fertilization. The most obvious conclusion was, therefore, that the hereditary units are parts of chromosomes(892-899).

Walter Stanborough Sutton (US) proposed the hypothesis that Johann Gregor Mendel’s results could be explained if hereditary units were parts of chromosomes. He predicted that if he were correct some non-Mendelian results could be expected because all genes on the same chromosome would have a tendency to be inherited as a unit (linkage). Sutton summarized what was known as follows:

(1) The diploid chromosome group consists of two morphologically similar chromosome sets. Each chromosome type is represented twice or, as we say today, chromosomes are in homologous pairs. Strong grounds exist for the belief that one set is derived from the father and one set from the mother at the time of fertilization.

(2) Synapsis is the pairing of homologous chromosomes.

(3) Meiosis results in a gamete receiving only one chromosome from each homologous pair.

(4) The chromosomes retain their individuality throughout mitosis and meiosis in spite of great changes in appearance.

(5) The distribution in meiosis of the members of each homologous pair of chromosomes is independent of that of each other pair. While each gamete receives one of each pair, which one is a matter of chance(898). See Boveri, 1904. Sutton was a 26 year old graduate student at Columbia University when he wrote his brilliant insightful paper of 1903.

Eduard Adolf Strasburger (PL-DE) introduced the terms haploid and diploid for the gametic and somatic chromosome numbers respectively(900).

Sir John Bretland Farmer (GB), and John Edmund Shorec Moore (GB) showed that during reductive division half of the chromosomes are lost within the polar bodies - a process they named maiosis (meiosis)(901). Strasburger had described meiosis in pollen mother cells and the embryo sac(902).

Charles E. Allen (US) was the first to observe meiosis in the algae; his material was Coleochaete(903).

Estrella Eleanor Carothers (US) used differences between members of homologous pairs of chromosomes to give direct proof of the independent assortment of members of different pairs—which Sutton had assumed as a consequence of the location of Mendelian factors in chromosomes. The evidence became overwhelming that chromosome pairs behave in meiosis like pairs of alleles(904). 

August Wilhelm Eichler (DE) produced Bluthendiagramme, a book containing analytical drawings of the flower and inflorescence structure of all Angiosperm families then known(905).

Alexander Goette (DE) authored Die Entwickelungsgeschichte der Unke (Bombinator igneus) als Grundlage Einer Vergleichenden Morphologie der Wirbelthiere which was to become the model for all later descriptive work on frog embryology(906).

Louis-Antoine Ranvier (FR) observed that a frog’s leucocytes can engulf (phagocytize) particles of carmine which remain visible within the leucocytes as they pass through the walls of the capillaries(907).

Bartolomeo Camillo Emilio Golgi (IT), in 1875, showed that some brain tumors contain distinctive star-shaped neuroglial cells of the brain, and he distinguished soft and hard forms of tumors(908).

Leon Semenowitj Cienkowski (PL-RU) was the first to observe the formation of multinucleated cells from single cells in invertebrates(909).

Oscar Lange (DE) was the first to observe the actual formation of multinucleate cells in vertebrates by fusion of single cells. He was studying blood-borne amoeboid cells in the frog(910).

Carl Weigert (DE) considered the logic of whether the objects called bacteria, associated with many morbid conditions, were really such or whether they were by-products of tissue degeneration. He also asked the important question of what is it about a bacterium that makes it pathogenic if it is indeed pathogenic? Is it something secreted by the bacterium, or something attached to it? He attempted to show that bacteria stain differently from degenerative products. He showed that the areas of tissue damage often coincided with the area where the bacteria were concentrated. He though it unlikely that harmless bacteria would migrate to an area damaged by some other force or agent. He argued that there is no reason to suppose that because bacteria are microscopic they are necessarily all alike(911).

Carl Weigert (DE) found during his studies of umbilical cord ulcerations in newborns that methyl violet, a product of the new aniline dye industry in Germany, was excellent for staining bacteria (probably micrococci)(911).

Moritz Traube (PL) and Richard Gscheidlen (DE) pointed out that fresh blood resisted putrefaction. They observed that the anti-putrefactive power of the blood has limits(46).

Thomas Henry Huxley (GB) put forward the idea that according to their embryonic development three kinds of body-cavity ought to be distinguished: (1) the enterocoelic which arises from enteric diverticula, (2) the schizocoelic which develops as a split in the embryonic mesoblast, and (3) the epicoelic which was enclosed by folds of skin and lined by ectoderm, e.g., atrial cavity of Tunicates. He proposed the group Deuterostomata for all the coelomate Bilateria, basing the name on the lack of relationship of the mouth to the blastopore. Deuterostomata was divided into three categories: Enterocoela for echinoderms, chaetognaths, and enteropneusts; Schizocoela for mollusks, polychaetes, and arthropods; and Epicoela for tunicates and Amphioxus(912-915).

James F.P. McConnell (GB) was the first to describe the Chinese liver fluke, Clonorchis sinensis(916).

Harujiro Kobayashi (JP) discovered that an important food fish is the second intermediate host of Clonorchis sinensis. This is the source by which human infections are acquired(917).

Masatomo Muto (JP) recognized the snail host of Clonorchis sinensis(918).

John O’Neill (IE) gave the first description of human onchocerciasis (caused by the filarial worm Onchocerca volvulus) when he demonstrated the presence of the microfilaria in skin biopsies of an African suffering from a cutaneous disease known as craw-craw or kru kru(919).

Alexandre Joseph Émile Brumpt (FR), in 1890, recognized that the infection occurs most commonly along river banks, and that the microfilariae in the skin come from deeper cutaneous nodules where adult filariae reside(920).

Sir Patrick Manson (GB) described adult Onchocerca from material given him by Karl Georg Friedrich Rudolf Leuckart (DE)(921).

Louis Joseph Alcide Railliet (FR) and A. Henry (FR) named it Onchocerca volvulus(922).

Rodolfo Robles (GT), in 1915, proved that onchocerciasis is caused by a species of filaria, Onchocerca caecutiens(923).

Jean Montpellier () and A. Lacroix () established the role of the microfilaria in causing the skin lesions(924).

Breadablane Blacklock (GB), working in Sierra Leone, determined that Onchocerca volvulus is transmitted by black flies (Simulium damnosum)(925).

Jean Hissette (BE) discovered the part played by microfilaria in blindness(926).

Leonard Landois (DE) reviewed 478 blood transfusions between humans and 129 transfusions between animals. Of 129 animal-to-human blood transfusions - 62 had shown no improvement or had died, 25 had dubious reports of temporary "improvement", 42 had, according to their authors, shown signs of recovery of improvement; of 347 human-to-human blood transfusions - 150 "improved", 12 had dubious reports of temporary "improvement", 180 were "unfavorable", two died, and the results for the remaining three were unknown. He showed that, if the erythrocytes of an animal belonging to one species were mixed with serum taken from an animal of another species, the red cells usually clumped and that sometimes the red cells burst, i.e., hemolyzed. Thus, the danger of transfusing blood of another species to humans was established scientifically(927).

Richard von Volkmann (DE) gave the first description of industrial tar and paraffin cancer(928).

Karl Freiherr von Rokitansky (CZ-AT) wrote his great memoir on defects in the septum of the heart(929).

Apollinaire Bouchardat (FR) wrote what is probably the first textbook on diabetes, associating clinical observations, experimental steps and proposals for a treatment based on the patients' way of life: mainly diet and exercise. He defined urinary sugar concentration as an indication of the patient's clinical condition(930).

Claude Bernard (FR) was one of the first to advocate an adequate oxygen supply during anesthesia, as well as the first to suggest pre-anesthetic medication with morphine and other central nervous system depressants(931).

Johannes von Kries (DE) was the first to measure capillary pressure(932).

Josef Breuer (AT), Ernst Waldfried Josef Wenzel Mach (CZ), and Alexander Crum-Brown (US), independently reached the conclusion that the semi-circular canal apparatus is a sensory organ for the perception of rotary motion and that the phenomena of rotatory vertigo is the result of abnormally strong stimulation of this sensory organ(933-935).

Wilhelm Heinrich Erb (DE) and Karl Friedrich Otto Westphal (DE) described the knee jerk reflex, the most important reflex anomaly seen in tabes dorsalis. Absence of the knee jerk is found in central nervous system syphilis. This reflex anomaly is most pronounced in tabes dorsalis, but also occurs in other disturbances(936, 937).

Hugh Owen Thomas (GB) developed a way to immobilize a fractured thigh and hip(Thomas hip-splint)(938).

A particularly bad epidemic of scarlet fever swept Australia, with high mortality rates(176).

Moritz Litten (DE) reported that acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) leads to abdominal catastrophe and death(939).

Karl Wilhelm Ernst Joachim Schönborn (DE), in 1875, described the first true pharyngeal flap surgery, an inferiorly based flap surgery for velopharyngeal insufficiency (cleft palate). In 1886 he  switched to a superiorly based flap operation(940, 941).

Madeleine Brès (FR) was the first woman in France to become a doctor of medicine.

Deutsche Medicinische Wochenschrift was founded.

1876

“…we have now recognized that the most significant occurrence in fertilization is the fusion of the two cell nuclei”(873).

Josiah Willard Gibbs (US) published, between 1876 and 1878, his concepts of thermodynamics as they apply to chemical reactions. In doing this he evolved the concepts of free energy and chemical potential as the driving force behind chemical reactions(942).

Ernst Fischer (DE) introduced the use of eosin to histology(943).

Otto Nikolaus Witt (CH-DE) proposed the Chromophore-auxochrome theory for colored organic compounds and in the process coined the terms chromophore and auxochrome. He theorized that dyes consist of conjugated systems, called chromophores, and salt-forming groups, or auxochromes, polar substituents that modify their colors(944).

Otto Nikolaus Witt (CH-DE), in 1876, was the first to prepare the dyestuff chrysoidine (diamino-azo-benzene)(945).

Johann Friedrich Wilhelm Adolf von Baeyer (DE) synthesized fluorescein by the condensation of phthalic anhydride with resorcin(946).

Heinrich Caro (DE) made the dye methylene blue(101).

Charles Lauth (FR) made the dye thionin (Lauth’s violet)( 3,7-diamino-5-phenothiazinium chloride )(101).

Johann Friedrich Miescher, Jr. (CH) was probably the first protein chemist to recognize the amphoteric properties of proteins(606).

Louis Pasteur (FR) published his book Études sur la Bière in which he stated that fermentations are essentially the result of life without oxygen(947).

Louis Pasteur (FR) described methods to demonstrate fermentation under anaerobic conditions(947).

John Tyndall (GB) began publishing his studies on floating matter of the air in relation to putrefaction and infection. He had been studying radiant heat and its relation to gases, and in his experiments on air he had been impressed with the difficulty of removing particles suspended in the air. It was found that although these particles are invisible to the naked eye they could be made visible by passing a strong beam of light through the air containing them. Tyndall found that he could render air within a closed container free of these particles by burning them with the flame of an alcohol lamp. This black space free of particles Tyndall pronounced to be optically inactive.

By chance he noticed one day that a flask which had been standing for a long time was optically inactive. The dust particles had settled on the bottom and sides of the flask. This led him to construct a chamber suitable for experiments on optically inactive air. This chamber or case had a glass front, and the top, bottom, back, and sides were of wood. At the back was a small door, while two panes of glass were let in like windows in the sides. The top was perforated in the middle by a hole, two inches in diameter, closed air-tight by a sheet of rubber, which was pierced through the middle by a pin-hole through which was pushed a long pipette ending externally in a thistle tube. A circular tin collar two inches in diameter and one and one-half inches deep surrounded the pipette, the space between being well packed with cotton-wool moistened with glycerin. Into two other small openings in the top of the chamber were inserted air-tight the open ends of two narrow tubes connecting the interior of the box with the outside air. The tubes were bent up and down several times so as to trap any particles carried in the air by changes in temperature. The bottom of the chamber was pierced with holes to take a number of test tubes intended to hold the infusions which were to be exposed to the optically inactive air. The method of experimentation was as follows. The chamber, being closed, was left untouched for several days and until a beam of light passed through the lateral windows showed that the air was optically inactive and that particles were trapped on the interior surfaces, where they were retained by a layer of glycerin with which these surfaces had previously been coated. The pipette in the top of the box being moved into position, the infusion was poured into the thistle funnel and allowed to enter the test-tubes until they were nearly filled. The tubes were then lowered into a bath of brine raised to the boiling point, and allowed to boil for five minutes. The fluids tested were urine, infusions of mutton, beef, liver, haddock, sole, cod, turbot, herring, hare, rabbit, pheasant, grouse, and vegetable infusions of turnip or hay. Tubes filled with similar infusions but exposed to air outside the box acted as controls. After some refining of his techniques Tyndall (GB) found that the protected infusions in the chambers remained unaffected even for months, and it was thereby established that the power of developing bacterial life by the atmosphere and its power of scattering light go hand in hand. He also studied the geographical distribution of aerial germs by exposing trays containing 100 tubes filled with infusions, and was able to show that the distribution of bacteria is not uniform.

Tyndall found that infusions made from old, dried hay were more difficult to sterilize than those made with new fresh hay. Following prolonged and exhaustive experimentation he reached the conclusion that bacteria have phases, one being relatively thermolabile in that it was destroyed at 100°C. in 5 minutes, whereas the other, which he regarded as the germ of the bacterium, is thermoresistant to an almost incredible extent(647, 948-952).

Carl Julius Salomonsen (DK) purified bacteria of putrid blood by forcing the blood into capillary tubes (50-60 cm. X 0.5-1.0 mm.) which he was able to place under the microscope for further observation. Breaking the tubes where isolated spots occurred, he found that each spot contained only one sort of bacterium. No spots occurred in blood taken aseptically from vessels of healthy living animals(953, 954).

Anton Kerner von Marilaun (AT) discovered parthenogenesis in the plant Antennaria alpina(955).

Hans Oscar Juel (SE) and Svante Murbeck (SE) confirmed this in Antennaria and Alchemilla(956-959).

Philippe Edouard Léon Van Tieghem (FR), in 1876, was the first to describe blastomycosis (called Gilchrist's Disease for Thomas Caspar Gilchrist. It is also known as North American blastomycosis). Ref He described Aspergillus niger. ref

Édouard Joseph Louis Marie van Beneden (BE) coined the term Mesozoa to include animals intermediate in structure between Protozoa and Metazoa(960).

David Starr Jordan (US), while a high school teacher in Wisconsin, authored Manual of the Vertebrates of the Northern United States. This is a remarkable book which became the bible of many an early naturalist(961).

Joseph Marie Jules Parrot (FR) was the first to describe the primary lesion in pulmonary tuberculosis in children (Gohn’s primary focus)(962).

Charles Murchison (GB), in 1876, stated that to prevent endemic typhus one must protect the individual from lice. ref

Osip Moczutkowski (RU) proved that the etiological agent of endemic typhus is present in the blood during the febrile period by inoculating himself with such blood(963).

Louis Alexis Normand (FR) found a novel minute worm (Strongyloides stercoralis) about 0.25 mm in length in the feces of troops who had been repatriated from Cochin-China (Vietnam) with diarrhea. He was the first to describe this parasitic nematode(964, 965).

Arthur Réné Jean Baptiste Bavay (FR) realized that some specimens sent to him by Normand were the adult worms of the larvae that were found in the feces(966).

Karl Georg Friedrich Rudolf Leuckart (DE) discovered the alternation of generations involving parasitic and free-living phases of Strongyloides(967).

Paul Van Durme (BE) discovered that infection occurs through the skin(968).

Arthur Looss (DE) purposely infected himself by putting larvae of Strongyloide stercoralis on his skin and finding larvae in his feces 64 days later(969).

Friedrich Fülleborn (DE), working with dogs, described the phenomenon of autoinfection and discovered how Strongyloides stercoralis (and also Ancylostoma spp.) migrates around the body before ending up in the intestine(970).

Paul Emil Flechsig (DE) discovered unequal degree of crossing of the pyramidal tracts in the brain. This supported the idea that the brain possesses asymmetry in some of its internal arrangements(971).

Étienne Jules Marey (FR)  explored the nature of cardiac excitability and, in 1876, determined that the heart could be excited by an electrical stimulus only during diastole(972). In 1896, he described the unexcitable phase of the cardiac cycle as the 'refractory period'. See, Fontana, 1780.

Thomas John MacLagan (GB) was the first European physician to treat acute rheumatism with salicin (salicylates)(973).

Ernst Viktor von Leyden (DE) gave the first description of myotonia congenita(974).

George Armstrong Custer (US), 36 year old general and military commander at the battle of the Little Bighorn, in 1876, probably suffered from histrionic personality disorder(975).

Karl Alfred von Zittel (DE) created a systematics of the organic fossil record in his monumental work, Handbuch der Palaeontologie. In it he discussed fossil animals from protozoa to mammals. He was the first to investigate fossil sponges by zoological methods. Zittel later wrote Geschichte der Geologie und Paläontologie, an encyclopedic historical survey of geology and paleontology(976, 977).

Wilhelm His (CH) and Christian Ludwig Braune (CH), established the journal Zeitschrift für Anatomie und Entwicklungsgeschichte. It later became the anatomical part of the Archiv für Anatomie und Physiologie.

1877

“I recall my student days and the impression made upon us by a man like Johannes Müller, the physiologist. When one feels himself in contact with a man of the first order, the entire scale of his intellectual conception is modified for life; contact with such a man is perhaps the most interesting thing life has to offer.” Hermann Ludwig Ferdinand von Helmholtz (DE), probably from Das Denken in der Medizin [On Thought in Medicine], a lecture delivered in 1877(978).

“Perhaps one must have witnessed the eyes of a dying patient as well as the grief and desperation which befalls the affected families in order to ask oneself the crucial question: was everything possible done to avoid the tragedy? Did, indeed, science furnish all the possible knowledge and aid in such a situation? Therefore, the theoretical questions can acquire dimensions and practical implications which go far beyond the merely methodological issues. The theoretical investigator may smile glibly and remain detached, his imagination and pride may even flourish for a time in the isolation of his untroubled laboratory. He may even find the older prejudices interesting and excusable, labeling them as mere reflections of poetical romanticism and youthful ecstasy. Those, however, who have to struggle with the real adverse powers, cannot be indifferent nor romantic. They always have to test critically what they know and are able to do, and use only the harsh light of facts, rather than entertaining pleasant illusions.” Hermann Ludwig Ferdinand von Helmholtz (DE)(978).

Paul Ehrlich (DE) made the first systematic study of the biological staining properties of the new synthetic aniline dyes following William Henry Perkin’s discovery of mauve in 1856(979). Ehrlich realized that the nuclear region of cells had an affinity for basic dyes therefore he referred to them as basophilic.

Pierre Émile Duclaux (FR) introduced the custom of designating an enzyme by the name of the substrate on which its action was first reported and adding the suffix - ase(980).

Carbon bisulfide was first recommended in the U. S. as a fumigant for insect control(138).

Max Jaffé (DE) discovered that when he fed birds benzoic acid they detoxified it by conjugating it with ornithine (diaminovaleric acid) (Greek ornithos, bird) which they excreted as ornithuric acid from which he prepared ornithine chloride(981).

Nathanael Pringsheim (DE) discovered asexual reproduction and alternation of generation in the bryophytes (liverworts and mosses)(982).

Arthur Downes (GB) and Thomas P. Blunt (GB) reported that sunlight kills bacteria, and showed that this effect is chiefly associated with the short wavelength component of the radiation(983).

Niels Ryberg Finsen (DK) discovered that light in the ultraviolet range kills bacteria. He called these waves from the blue and ultraviolet area chemical waves(984).

Niels Ryberg Finsen (DK) used light to successfully treat certain skin diseases such as lupus vulgaris (cutaneous tuberculosis)(985-987).

Frederick L. Gates (US) related the effective wavelengths of ultraviolet radiation for killing bacteria to its observed absorption by nucleic acids(988-990).

Alexander Hollaender (US) and Chester W. Emmons (US) determined that radiation with a wavelength of 2650 angstroms appears to be the most mutagenic and fungicidal within the ultraviolet range. They noted that 2650 angstroms coincides with the high absorption coefficient of nucleic acids near this wavelength(991). 

Carl Weigert (DE), in 1877, at a scientific meeting in Munich, showed stained sections of dog spleen, lung, and kidney infected with anthrax. The anthrax organism could be distinctly seen in contrast to the tissues(992).

John Tyndall (GB) developed a method for heat killing endospores without having to resort to extremely high temperatures. This involved heating at 100°C. on successive days until the medium was sterile. Temperatures of 100°C. kills all cells other than endospores which are stimulated to germinate by the heat and nutrients present. Once they have germinated the second round of heating will kill them. Three or more rounds may be necessary to render the sample sterile. The process is today called Tyndallization(993).

Louis Pasteur (FR) and John Tyndall (GB), the one a chemist, the other a physicist, neither of them medical but both trained in the most exact methods of experimentation, jointly accomplished the final downfall of the doctrine of spontaneous generation (994).

Heinrich Hermann Robert Koch (DE) was the first to prepare and stain thin films of bacteria on cover-glass. In his early staining methods he used methyl violet 5B, fuchsin, and aniline brown. He was the first to stain bacterial flagella. For this he employed logwood extract (hematoxylin) followed by chromic acid (995).

Richard Caton (GB) reported finding nerve action potentials picked up from the frontal lobe of the brain of an anesthetized rabbit when, for example, light was directed to the contra lateral retina. These were later called evoked potentials. He was thus the first to record spontaneous electrical activity from the brain(996).

Francis Gotch (GB) and Sir Victor Haden Alexander Horsley (GB) showed that electric currents are produced in the mammalian brain, and they recorded them with a string galvanometer of the capillary electrometer(997).

Hans Berger (DE), while studying brain generated action potentials in animals discovered that the brain develops a low-level subaudio-frequency electrical activity. This discovery led to the establishment of a neurophysiological specialty known as electroencephalography (EEGy). In 1924, he made the first elektrenkephalogram (electro-encephalogram) (EEG) of a human and reported the discovery of rhythmic 10Kz waves (which he termed 'alpha waves') in subjects with eyes closed. In addition, he observed smaller amplitude faster frequency activity which he called 'beta waves'. This work was reported in 1929(998, 999). Alpha waves occur in adults who have their eyes closed or who are relaxed. Beta waves mainly occur in adults who are awake, alert or focused.

Lord Edgar Douglas Adrian (GB) and Bryan Harold Cabot Matthews (GB), in 1934, confirmed Hans Berger’s findings of alpha and beta waves then discovered delta waves. Delta waves occur mainly in infants, sleeping adults or adults with brain tumors(1000).

William Grey Walter (GB) proved that, by using a larger number of electrodes pasted to the scalp, each one having a small size, it was possible to identify abnormal electrical activity in the brain areas around a tumor, and diminished activity inside it(1001, 1002).

William Grey Walter (GB) and Vivian J. Dovey (GB), in 1943, discovered theta brain waves. Theta waves occur mainly in children ages 2–5 years old(1003). 

Louis Pasteur (FR) and Jules Francois Joubert (FR) were the first to identify a pathogenic species of Clostridium, Clostridium septicum or Vibrion septique(1004).

Louis Pasteur (FR) and Jules Francois Joubert (FR) were probably the first to recognize antagonism (antibiosis) between microorganisms (Bacillus anthracis and other bacteria in culture)(1005). See, William Roberts, 1874.

Jean Jacques Theophile Schloesing (FR) and Achille Muntz (FR) proved that nitrification is a biological process in the soil by using chloroform vapors to inhibit the production of nitrate. One of the greatest practical applications of this knowledge was in the treatment of sewage(1006).

Theodor Wilhelm Engelmann (DE) proposed intercellular current flow(1007, 1008).

Howard J. Curtis (US) and David M. Travis (US) gave the first direct evidence for intercellular current flow(1009).

Charles Sedgwick Minot (US) and Theodor Boveri (DE) realized that parthenogenesis is due to some failure or modification of cell division during the maturation of the egg(1010, 1011).

Leonard Doncaster (GB) found that in the parthenogenetic ova of certain insects, e.g. Rhodites rosae (Henking) and Nematus lacteus, reductive division does not occur, although two polar bodies are formed(1012).

Gualtherus Carel Jacob Vosmaer (NL) separated the sponges from the coelenterates. Ref A number of sea creatures were given genus and species names in his honor.

George Engelmann (DE-US) was a plant explorer and systematist centered in St.Louis. His collections formed the basis for the Missouri Botanical Garden begun by Henry Shaw(GB-US) in 1859(1013).

Claude Bernard (FR) found that one of the primary signs of diabetes is an excess of sugar in the blood and usually in the urine, i.e., in diabetes there is primarily glycaemia followed by glycosuria(134).

Claude Bernard (FR) found evidence for a diastase (amylase) in the liver(1014). When he purified this liver diastase he found that it could convert starch and glycogen to sugars. Bernard then concluded that sugar is formed identically in animals and plants. The complicated starch he reasoned is also decomposed to the simpler sugars which are soluble, and can be circulated and assimilated(377).

Gabriel Madeleine Camille Dareste (FR) described the successful production of developmental monstrosities by experimental means(1015).

Emil Heinrich du Bois-Reymond (DE), Thomas Renton Elliott (GB), and John Newport Langley (GB) expressed the concept that the nerve impulse should not pass from nerve to muscle by an electrical discharge but by the secretion of a special substance at the end of the nerve that we presently designate as a neurotransmitter. This is the idea of chemical synaptic transmission(1016-1019).

John Newport Langley (GB) was the first to suggest the presence of receptive substances on cells(1020).

Masaharu Noda (JP), Hideo Takahashi (JP), Tsutomu Tanabe (JP), Mitsuyoshi Toyosato (JP), Yasuji Furutani (JP), Tadaaki Hirose (JP), Michiko Asai (JP), Seiichi Inayama (JP), Takashi Miyata (JP), Shosaku Numa (JP), Sho Kikyotani (JP), Hideaki Takashima (JP), Toni Claudio (US), Marc C. Ballivet (CH), James W. Patrick (US), Stephen F. Heinemann (US), L. Boas (), John Forrest (US), Holly A. Ingraham (US), Pam Mason (US), Siegfried Stengelin (US), Satashi Ueno (US), N. Davis Hershey (US), Dan J. Noonan (US), Katharine S. Mixter (US), and Norman Ralph Davidson (US) would later contribute to the nicotine receptor being the first to be sequenced, cloned, and gene-sequenced(1021-1026). This can be considered the origin of neuroendocrinology.

Richard Felix Marchand (DE) and Theodor Wilhelm Engelmann (DE) were the first to present graphically the time course of the variations in electric potential of the heart of lower animals, i.e., an electrocardiogram(1027, 1028).

Augustus Désiré Waller (FR-GB) confirmed that the human heart produces an electric current on contraction. “If a pair of electrodes (zinc covered by chamois leather and moistened with brine) are strapped to the front and back of the chest, and connected with a Lippmann's capillary electrometer, the mercury in the latter will be seen to move slightly but sharply at each beat of the heart…. The electrical variation precedes the heart's beat”(1029, 1030).

Gabriel Lippmann (FR) invented the capillary electrometer used by Waller in his studies(1031).

J.W. Gordon (GB) introduced the concept of ballistocardiography(1032). A ballistocardiograph is an instrument that records the motions of the body imparted to it by the heart beat.

Yandell Henderson (US) eloquently described ballistocardiography as follows: “Under the influence of the mass-movements of the circulation, the body recoils at each heart beat feetward, headward, and again feetward. By means of a "swinging table" these movements can be magnified one hundred times and recorded in the form of a "recoil curve." The amplitude of these recoil movements…is held to be proportional to the volume of the systolic discharge of the heart”(1033).

Isaac Starr (US), Arthur Joy Rawson (US), Henry A. Schroeder (US), and Norman Ross Joseph (US) coined the term ballistocardiogram(1034).

Julius Friedrich Cohnheim (DE) and Carl Julius Salomonsen (DK) confirmed Jean Antoine Villemin’s earlier claim that tuberculosis is infectious by inoculating tuberculous material into the anterior chamber of a rabbit’s eye, where the development of the lesion could be watched from day to day(1035).

Friedrich Bezold (DE) provided the first clear description of mastoiditis(1036, 1037).

Jean-Martin Charcot (FR) wrote Lectures on the Diseases of the Nervous System, a very important book in the history of the neurosciences. In this book he described multiple sclerosis noting that the nerves are abnormally demyelinated, yet he did not appreciate the significance of this demyelination(1038).

Derek Ernest Denny-Brown (NZ-GB-US) and Charles L. Brenner (US) observed that when a damaged nerve is stimulated, it fails to pass the impulse to the connected muscle. They concluded that it is the demyelination associated with lesions on the nerve that is responsible for the block in conduction and thus the symptoms of multiple sclerosis(1039).

Francis Maitland Balfour (GB) observed that the medullary region of the adrenal gland is derived from ectodermal rudiments that also give rise to parts of the sympathetic nervous system, while the cortex arises from mesodermal buds(1040).

Francis Maitland Balfour (GB) wrote his monograph on the development of elasmobranch fishes(1041). This was the most important addition to vertebrate embryology since Johannes Muller.

James Paget (GB) described Paget’s disease of the bone (osteitis deformans)(1042).

Reginald Southey (GB) introduced Southey tubes as a means of removing large amounts of dependent edema -- up to 40lbs of fluid in 2 days. These tiny tubes (each 1 inch long) were inserted subcutaneously by means of a trocar in the dorsum of the foot and the lateral aspect of the lower leg. The trocar was then removed and the Southey tubes were connected to tubing which emptied into a bucket(1043). These tubes are helpful in treating congestive heart failure.

Adolf Kussmaul (DE) characterized agnosia as “They were neither inarticulate (incapable of speech) nor illiterate (incapable of writing); but despite an acute sense of hearing they could no longer comprehend words they heard or, despite good vision, they could no longer read the words they saw”(1044).

Carl Nicoladoni (AT) performed the first operation for an esophagus diverticulum(1045). He also is the originator of the concept of a gastroenterostomy.

Anton Wölfler (AT), in 1881, was the first to perform a gastroenterostomy. He by-passed a pyloric stenosis using anastomosis of the anterior surface of the stomach with the jejunum(1046, 1047).

Ernst Felix Immanual Hoppe-Seyler (DE) founded the journal Zeitschrift für Physiologische Chemie.

Othniel Charles Marsh (US) introduced and briefly described Apatosaurus ajax, (now known to be synonymous with Brontosaurus)(1048, 1049). Two years later he described and introduced Brontosaurus, thinking they were different animals(1050). Apatosaurus means “deceptive lizard”; Brontosaurus means “thunder lizard”.

1878

"I beseech you to take interest in these sacred domains so expressively called laboratories. Ask that there be more and that they be adorned for these are the temples of the future, wealth and well-being. It is here that humanity will grow, strengthen and improve. Here, humanity will learn to read progress and individual harmony in the works of nature, while humanity's own works are all to often those of barbarism, fanaticism, and destruction." Louis Pasteur(1051).

“Now that he has departed from us, he has left us a rich heritage, but inestimable good has sunk into the grave with him. The one on whom his soulful eyes rested, who listened to the flow of his thoughtful words, who felt the pressure of his hand, will always long for him. Yet not only the friend, each one who in life and in science came in contact with his power, will mourn the death of  a man, in whom were mingled in complete harmony a spirit as clear as his and a nature of such richness.”  Karl Friedrich Wilhelm Ludwig’s remarks at the Gedachtnissrede (memorial service) for Ernst Heinrich Weber(363).

“There is a true interior environment that serves as an intermediary between the external world and life itself…. It is the internal environment that provides the physical needs for life." Claude Bernard(377). In volume 1 of this work on pages 273, 278-279, Bernard performed experiments demonstrating that respiration is common to all higher life forms, both plants and animals.

"I have, on many occasions, examined normal blood and normal tissues using methods that ensure that such organisms are not overlooked, and I have never, in a single instance, found bacteria. I therefore conclude that bacteria do not occur in the blood or tissues of healthy animals or humans." Heinrich Hermann Robert Koch(1052, 1053).

Carl Gustaf Patrik de Laval (SE) patened a continuously operating, high-speed turbine driven, centrifugal, cream separator. This machine was a precursor to the modern centrifuge.

H. Baum (?) synthesized the dye orange GG (acid orange 10). The main use of Orange G is in the OG-6 Papanicolaou stain, to stain keratin, however it is also a major component of the Alexander test for pollen staining. It is often combined with other yellow dyes and used to stain erythrocytes in the trichrome methods. Orange G can be used as a color marker to monitor the process of agarose gel electrophoresis, running approximately at the size of a 50 base pair (bp) DNA molecule, and polyacrylamide gel electrophoresis. ref

Baron Adolf Johann Hubert von La Valette St. George (DE), in 1878, was the first to describe the Golgi apparatus (dictyosome). He found it in the head cap of the acrosome "samenkörper"(1054).

Bartolomeo Camillo Emilio Golgi (IT) discovered the cell organelle which bears his name, Golgi apparatus or Golgi body, in the cytoplasm of the Purkinje cells of the cerebellar cortex of the owl's brain. He called it apparato reticulare interno(721, 722, 1055).

Gustaf Platner (DE) also gave an early description of the "nebenkern" (Golgi apparatus) in snail spermatocytes(1056).

Emil Algot Holmgren (SE) described this organelle as canaliculi and observed it in a number of cell types(1057, 1058).

Santiago Ramón y Cajal (ES) coined the name Golgi-Holmgren canals(1059).

London purple was introduced in 1878. It was used for control of the Colorado potato beetle(138).

Wilhelm Friedrich Kühne (DE) and Carl Anton Ewald (DE) isolated rhodopsin from retinas(1060-1063).

Arthur Gamgee GB), ca. 1878, began spectral analysis leading to the conclusion that spectroscopy can distinguish unambiguously between the various forms of hemoglobin: the reduced form; the oxygenated form bound to oxygen; the form binding carbon monoxide; and methemoglobin in which the iron of the heme group is irreversibly oxidized to the ferric state. These results occurred regardless of the species of origin(1064).

Camille Jean Marie Méhu (FR) discovered that proteins are quantitatively precipitated from their aqueous solutions upon saturation with ammonium sulfate, and that they are not coagulated by this treatment. Once precipitated the proteins could be redissolved in water or in neutral salt solution remaining unaltered from their native state(1065, 1066).

Charles Otis Whitman (US) was the first to use the term cytokinesis to denote the cytoplasmic changes occurring during cell division(1067, 1068).

Edoardo Perroncito (IT) described and isolated the bacterial agent of fowl cholera (Pasteurella multocida), a serious disease of chickens in Italy(1069, 1070). 

Jean-Joseph-Henri Toussaint (FR) also isolated the bacterial agent of fowl cholera(1071, 1072). The agent was eventually named Pasteurella multocda.

Paul Bert (FR) laid the foundation of knowledge of the physiological effects of air-pressure, both above and below atmospheric pressure. From his experiments he concluded that pressure does not effect man physically, but rather chemically by changing the proportions of oxygen in the blood. Too little creates oxygen deprivation and too much creates oxygen poisoning. He showed that pure oxygen under high pressure can be deadly and to this day Central Nervous System (CNS) oxygen toxicity is known as the ‘Paul Bert Effect’. He established the principle that it is the partial pressure of a gas-not its percentage in the atmosphere that has physiological importance. Bert reasoned that divers and caisson workers should decompress slowly and at a constant rate “for they must not only allow time for the nitrogen of the blood to escape but also to allow the nitrogen of the tissues time to pass into the blood.” When the pressure is released quickly, nitrogen boils-off producing pain (the bends). (1073, 1074).

Arthur E. Boycott (GB), Guybon C. Damant (GB), and John Scott Haldane (GB) were the first to apply a scientific approach to predicting decompression and their methods form the basis of the majority of modern decompression theories. They developed practical dive tables based on research that included slower ascent rates as the diver approached the surface(1075).

Karl Brandt (DE), M.A. Certes (FR) and Paul Ehrlich (DE) introduced true vital staining to biology. Brandt, in 1878, used bismarck brown to color granules in living Actinosphärium. Certes recommended a weak solution of cyanin for staining live infusoria, and Ehrlich used methylene blue to stain the nervelets in the intestine of the mouse. Certes also introduced the vital staining of leucocytes, using cyanine and quinolene blue for the differential staining of frog's leucocytes and noticed that they retained their motility for a short time course while taking up the dye(1076-1080).

Louis-Antoine Ranvier (FR) discovered myelin and the short specialized interruptions in the myelin sheath occurring along myelinated nerve fibers(1081). These interruptions, called the nodes of Ranvier, permit saltatory conduction.

Charles Emmanuel Sédillot (FR) coined the word microbe to refer to all living things which cannot be seen with the unaided eye(1082, 1083).

Joseph Lister (GB), while studying the lactic acid fermentation, succeeded in obtaining an axenic culture of bacteria by diluting to the point that growth took its origin from one cell, often called dilution to extinction. He named the organism Bacterium lactis(1084). This dilution technique is also the principle underlying the Most Probable Number method for estimating the number of bacteria in a liquid. See, Theodor Albrecht Edwin Klebs, 1873.

Heinrich Hermann Robert Koch (DE) introduced the logical steps for relating a specific microorganism with a specific disease. We now habitually refer to these steps as Koch’s postulates. The 1884 paper was the first time they appeared in print (1053, 1085). He also identified staphylococci in human pus .

Louis Pasteur (FR), Jules Francois Joubert (FR), and Charles Édouard Chamberland (FR) present their germ theory of disease(1086).

Louis Pasteur (FR), Joubert (FR), and Charles Édouard Chamberland (FR), in 1878, credited Schwann as the real founder of the germ theory of fermentation(1087).

Timothy Richards Lewis (GB) reported that microscopic organisms found in the blood of man and other animals could cause disease(1088).

Heinrich Hermann Robert Koch (DE) isolated Erysipelothrix muriseptica from mice which had been injected with putrefying blood(1053).

Anton Julius Friedrich Rosenbach (DE) isolated the sam organism as above from erysipeloid infections in man and named it Erysipelothrix rhusiopathiae. The patient exhibited localized cutaneous lesions, thus establishing this organism as a human pathogen(1089, 1090). Erysipelothrix rhusiopathiae causes a disease known as erysipelas in animals and erysipeloid in humans. The human disease called erysipelas is not caused by E. rhusiopathiae, but by various members of the genus Streptococcus.

George Francis (AU) reported the first documented case of lethal intoxication of livestock by drinking water. The water came from an Lake Alexandrina in South Australia which heavily infested with blue-green algal (cyanobacterial) blooms(1091, 1092).

Michael Stephanovitch Woronin (DE) was the first to describe the fungus Olpidium brassicae(1093).

Patrick Geddes (FR) found that certain green planaria were in fact green because they contained symbiotic algae(1094).

Berthold Hatschek (CZ-AT) proposed the trochophore theory which states that the trochophore is the larva of an ancestral form, the trochozoon, which was the common ancestor of most, if not all, the bilateral phyla, and which, of living forms, most nearly resembled a rotifer(1095).

Coenraad Kerbert (NL) described the lung fluke, Distoma westermanii, from the lungs of a tiger in the Amsterdam Zoo(1096). 

B. Sydney Ringer (GB), in 1879, was the first to report a clinical case of lung-fluke infection (human paragonimiasis, pulmonary distomiasis, endemic hemoptysis). It was from a postmortem examination of a Portuguese patient, who had died of a ruptured aortic aneurysm. At autopsy, Ringer found, in addition to the aneurysm, a parasite in the lungs(1097). Need Ringer article

Maximillian Gustav Christian Carl Braun (DE) suggested the name Paragonimus westermani for the fluke(1098).

Erwin Otto Eduard von Baelz (DE) and Patrick Manson (GB) independently recognized the eggs of Paragonimus westermani in the sputum of man. Manson also suggested that a snail might act as an intermediate host(1099, 1100).

Koan Nakagawa (JP), Sadamu Yokogawa (JP), Harujiro Kobayashi (JP), and Keinosuke Miyairi (JP) reported on the whole life cycle of the lung fluke in the snail Semisulcospira(1101-1114).

Fritz Müller; Johann Friedrich Theodor Müller (DE) in discussing mimicry explained that predators must learn through warning characteristics which species are palatable, and that in the process some of the prey population must be sacrificed(1115-1117). 

Adam Politzer (AT) wrote Lehrbuch der Ohrenheilkunde, the most outstanding textbook on the ear in the 19th and 20th centuries(1118).

Rudolf Peter Heinrich Heidenhain (DE) described a new technique, which he had developed to study secretion of digestive juices in dogs. The technique was named after him. Heidenhain’s pouch is a procedure in which part of the stomach is isolated from the main body of the organ(1119). One common use of the Heidenhain pouch in dogs or its equivalent in the rat, over the past fifty or so years, has been the development of drugs which reduce stomach-acid secretion . These drugs include those acting upon the histamine system such as cimetidine, or the ‘proton pump inhibitors’ like omeprazole which act upon another stomach enzyme.

Sir William Richard Gowers (GB) found that unilateral lesions of the spinal cord, which cause loss of sensibility of the skin, do so on the side opposite to the lesion. Painful sensations are conducted in the lateral column, those of touch in the posterior column(1120). 

Richard von Volkmann (DE) performed the first excision of carcinoma of the rectum(1121).

Wilhelm Alexander Freund (DE) undertook the first ever abdominal extirpation of a cancerous uterus. It was not reported until 1885(1122).

Pierre Paul Broca (FR) described and named the great limbic lobe of the brain(1123). Limbic implies no function or theory, and has no definite shape.

Yellow fever again swept through New Orleans, Memphis, and the Mississippi and Ohio River valleys(176).

Journal of Physiology (London) was founded.

1879

Sir William Crookes (GB) was the first person to confirm the existence of cathode rays (x-rays) by displaying them, with his invention of the Crookes tube, a crude prototype for all future cathode ray tubes(1124).

Pierre Eugène Marcellin Berthelot (FR) coined the terms endothermic and exothermic(1125).

Otto Nasse (DE) discovered that a positive Millon test is not confined to proteids and to tyrosine, but is a general reaction to all aromatic bodies in which a hydroxyl group is connected with the benzol ring(1126, 1127).

Paul Ehrlich (DE) showed that all dyes can be described as possessing either basic, acidic, or neutral character and introduced the use of aniline dyes to stain specific granulations in white blood cells which he clearly recognized fell into three categories: acidophilic, basophilic, and neutral. He was the first to classify the blood granulocytes into the three types we know today(867, 1128, 1129).

Paul Ehrlich (DE) discovered the eosinophil when he stained fixed blood smears with aniline dyes(1130).

Heinrich Ferdinand Edmund Drechsel (DE) and Georg Grübler (DE) crystallized protein from Bertholletia (Brazil nuts), pumpkin seed (Cucurbita) and squash seed respectively. They allowed a warm sodium chloride solution saturated with the protein to cool slowly, whereupon crystals appeared(1131, 1132).

Albrecht Karl Ludwig Martin Leonard Kossel (DE), Albert Neumann (DE), and Henry Drysdale Dakin (US) showed that the nuclein first isolated by Johann Friedrich Miescher (CH) contains a protein and a nonprotein portion. The protein portion was much like other proteins, but the nonprotein portion was unlike any other natural product known until that time. When he broke down the nonprotein part Kossel found that it contained purines and pyrimidines. He isolated two different purines (a name coined by Hermann Emil Fischer): adenine and guanine, and a total of three different pyrimidines: thymine, uracil, and cytosine. He obtained from goose erythrocytes a peptone-like substance (he named it histone) that readily combined with nuclein to form a nucleohistone. He also recognized that the nonprotein part contained a carbohydrate, but he failed to identify it(1133-1139).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) discovered that DNA contains guanine(1140, 1141).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Albert Neumann (DE) discovered that DNA contains adenine and thymine(1142-1149).

Alberto Ascoli (IT) described uracil(1150).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Hermann Z. Steudel (DE) discovered that DNA contains cytosine(1151).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Hermann Z. Steudel (DE) discovered that DNA contains uracil(1152).

Bartolomeo Camillo Emilio Golgi (IT) and R. Rezzonico (IT) reported on the histological structure of myelin(1153, 1154).

Heinrich Anton de Bary (DE) coined the word symbiosis, using it to mean living together of unlike organisms regardless of what might be the result of such an association(1155).

Fredrick Schmitz (DE) reported syngamy, the fusion of the male and female gametes in plants(1156)

T. Arnold (DE) made drawings of human chromosomes in cancer cells (sarcoma)(1157).

Timothy Richards Lewis (GB) found parasitic trypanosomes in the blood of healthy rats (Trypanosoma lewisi) in India(1158).

George Evans (GB) found parasitic trypanosomes (Trypanosoma evansi) in horses and camels in India(1159). 

Albert Ludwig Siegmund Neisser (DE) discovered that “If gonorrheal pus is spread out in…a layer, allowed to dry, stained by…methyl violet…a number of…masses of micrococci are seen…. They have a…characteristic, typical form…. These characteristic micrococci…appear to be a constant mark of all gonorrheal affections…”(1160). The organism was later named Neisseria gonorrhoeae. Neisser may have been the first to attribute a chronic human disease to a microorganism.

Frédéric Weiss, (FR) isolated Neisseria gonorrhoeae(1161).

Leo Leistikow (DE) isolated Neisseria gonorrhoeae(1162, 1163). 

Ernst von Bumm (DE) grew axenic cultures of Neisser’s gonococcus, Neisseria gonorrhoeae, and proved by inoculations of humans that it causes gonorrhea(1164, 1165).

Ernst Wertheim (AT) demonstrated the existence of gonococcus in tissue of the Fallopian tubes in 1890. By 1892 he had established his theory that gonococci can ascend the female reproductive tract(1166).

Ernst Wertheim (AT) demonstrated the gonococcus in acute cystitis(1167).

Ernst Wertheim (AT) emphasized the importance of latent uterine gonorrhea(1168).

Theodor Albrecht Edwin Klebs (DE) successfully inoculated monkeys with syphilis(1169).

Pierre Victor Galtier (FR) became the first to successfully pass rabies from dogs to rabbits and then from rabbits back to dogs, confirming that rabies is some sort of infectious disease(1170).

Louis Pasteur (FR) found anthrax endospores in the soil above an anthrax carcass buried ten months previously. He and his assistants, Charles Édouard Chamberland (FR) and Pierre Paul Émile Roux (FR) concluded that the endospores in the buried anthrax carcass had been gradually brought to the surface of the soil by earthworms(1171-1174).

Erwin Otto Eduard von Baelz (DE) and K. Kawakami (JP) were the first to recognize the disease known as tsutsugamushi in certain isolated river valleys in Japan(1175). The etiological agent was later determined to be rickettsial.

Heinrich Gustav Adolf Engler (DE) and Karl Prantl (DE), in Das Pflanzenfamilien, worked out a plant classification scheme which became the most influential systematic authority since Linnaeus. This system, covering the plant kingdom to the generic level, held authority until the 1970s(1176, 1177). His multi-authored Syllabus der Pflanzenfamilien was published at intervals to keep the scheme updated.

Engler founded and edited (from 1881) the periodical Botanische Jahrbücher.

Charles Edwin Bessey (US), in his The Phylogenetic Taxonomy of Flowering Plants, asserted that plants with bisexual flowers with numerous petals, sepals, etc., were the basic types from which the reduced kinds, for example, willows, oaks, and birches, representing several unrelated but superficially similar lines, were derived(1178-1180). This contradicted one of Engler and Prantl's basic tenants.

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) wrote Das System der Medusen which was largely responsible for the medusa classification that we still use today(1181).

Giovanni Battista Grassi (IT), Corrado Parona (IT), and Ernesto Parona (IT) described the life cycle of Strongyloides stercoralis (a parasitic nematode)(1182). The organism was first described in 1876 in French soldiers returning from Cochin China (now Vietnam) who were suffering from intractable diarrhea.

Jean Henri Casimir Fabre (FR) wrote Souvenirs Entomologiques, a ten volume work which includes studies on the anatomy and behavior of wasps, bees, and many other insects(1183).

Sigmund Exner (DE) stated that reaction time course (time between stimulus and response) is often devoid of free will(1184).

Wilhelm August Oskar Hertwig (DE) and Richard Karl Wilhelm Theodor von Hertwig (DE) developed the germ theory proposed by Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE); that all organs and tissues are derived variously from three basic tissue layers. What Haeckel called Gastraea-Theorie the Hertwigs would call Coelomtheorie. The Coelomtheorie suggests that development of all germ layers can be explained by the simple principle of epithelium folding(1185-1192).

Ivar Victor Sandström (SE) discovered the parathyroid glands and named them glandulae parathyreoideae(1193). See, Owen, 1862.

Gerhard Engel (DE) and Friedrich Daniel Recklinghausen (DE) described osteitis cystica (primary hyperparathyroidism syndrome)(1194, 1195).

Max Askanazy (DE) was the first to associate osteitis fibrosa cystica with tumors of the parathyroid gland(1196).

Jakob Erdheim (AT) demonstrated that the four parathyroid glands are enlarged in osteomalacia and in rickets, concluding correctly that this was a compensatory phenomenon. He showed that when he removed the parathyroid glands in rats, their teeth lost calcium(1197).

William George MacCallum (US) and Carl Voegtlin (US) showed that administration of calcium salts relieved the symptoms of tetany and that the parathyroid glands control calcium metabolism. They determined that an animal deprived of the parathyroids developed a calcium diabetes with loss of large amounts of calcium in the urine(1198, 1199).

William Stewart Halsted (US) successfully treated patients with tetany by the administration of beef parathyroids, thus establishing the strong possibility that these glands helped regulate the blood content of calcium(1200, 1201).

James Bertram Collip (CA) isolated parathormone, the active ingredient of the parathyroid glands. It acts to prevent or control parathyroid tetany and regulate the level of blood calcium(1202).

Douglas Harold Copp (CA), E. Cuthbert Cameron (CA), Barbara A. Cheney (CA), A. George F. Davidson (CA), and Kurt G. Henze (CA) discovered a hypocalcemic factor released only from the parathyroids as a result of hypercalcemia. They suggested that it be named calcitonin(1203).

Camillo Bozzolo (IT) introduced thymol as a treatment for hookworm infestation(1204).

Henri-Louis Roger (FR) described a form of congenital heart disease which would later bear his name (Roger disease) as follows: “A developmental defect of the heart occurs from which cyanosis does not ensue in spite of the fact that a communication exists between the cavities of the two ventricles and in spite of the fact that admixture of venous blood and arterial blood occurs. This congenital defect…is even compatible with a long life”(1205).

William Murrell (GB) introduced nitroglycerin to treat angina pectoris(1206).

Heinrich Obersteiner (AT) described concussion of the spinal cord and status epilepticus(1207). He wrote an important volume on general paresis and tabes dorsalis, also a neurology text on the anatomy of the nervous system(1208). He published much on nerve fibers, granular cells of the cerebellum, and on pigment in nerve cells. With Emil Redlich (AT) he demonstrated that tabes dorsalis is a disease of the posterior roots(1209).

Pierre Paul Broca (FR) was interested in the circulatory changes associated with mental activities as manifest by changes in brain temperature. He studied the effect of various mental activities, especially language, on the localized temperature of the scalp of medical students. Although such measurements might seem unlikely to yield any useful information, the reported observations, unbiased by preconceived notions of the functional anatomy of the cortex, were remarkably perceptive(1210).

Angelo Mosso (IT) recorded the pulsation of the human cortex in patients with skull defects following neurosurgical procedures. Mosso showed that these pulsations increased regionally during mental activity and concluded, correctly we now know, that brain circulation changes selectively with neuronal activity(1211).

Vincenz Czerny (CZ-DE) performed the first total hysterectomy by the vaginal route(1212).

Jules Émile Péan (FR) performed the first resection of the stomach for cancer(1213). The operation was unsuccessful.

Ludwik Rydygier (PL) was the second to perform partial stomach resection. It was to relieve a carcinomatous pylorus associated with peptic ulcer disease. His patient survived for 12 hours(1214). Rydygier introduced the technique of resection better known as the Billroth I procedure.

Christian Albert Theodor Billroth (AT) performed the first successful resection of the stomach. It was performed on a 43 year old woman with pyloric cancer. A 14 cm portion of stomach was excised and an anastomosis of the remaining stomach to the duodenum was fashioned with about 50 carbolised silk sutures. Using chloroform anesthesia he took an hour and a half to remove the cancer(1215, 1216).

Walter Hermann Heineke (DE) first described a pyelotomy (surgical incision into the renal pelvis of a kidney) for the extraction of calculi from the renal pelvis. in 1879. ref

Charles Lapworth (GB) defined the Ordovician System of strata to resolve the Murchison-Sedgwick conflict over their overlapping claims for their Silurian and Cambrian systems(1217). The Ordovician Period of the Paleozoic Era (from the name of an ancient British tribe, the Ordovices) extended from 505 Ma until 438 Ma. At the end of the Cambrian, sea levels fell, causing extinctions. It was in the Ordovician that the first animals with backbones arose, the Agnatha, these jawless fishes were the first animals with true bony skeletons. The Ordovician is best known for the presence of its diverse marine invertebrates, including graptolites, trilobites, brachiopods, and the conodonts (early vertebrates). A typical marine community consisted of these animals, plus red and green algae, primitive fish, cephalopods, corals, crinoids, and gastropods. More recently, there has been found evidence of tetrahedral spores that are similar to those of primitive land plants, suggesting that plants invaded the land at this time. 

The Ordovician Period ended with a mass extinction. About 25% of all families did not make it into the Silurian.

Classic Fossil-Bearing Sites include: Whiterock Formation, Utah; and the Nevada Cincinattian Series, Ohio/Indiana/ Kentucky.

Leo Lesquereux (CH-US), America’s first paleobotanist, wrote the book which became the standard coverage of fossil flora of the carboniferous formation(1218).

Index Medicus was founded.

1880

“Life should be made into a dream and a dream into a reality.” Pierre Curie, ca. 1880 from his diary.

"My delight may be conceived when there were revealed to me beautiful tangles, tufts 

and chains of round organisms in great numbers, which stood out clear and distinct 

among the pus cells and debris... Alexander Ogston(1219). Here Ogston is discussing his discovery of the major cause of pus.

Pierre Curie (FR) and his brother Jacques Curie (FR) discovered the piezoelectric effect in certain crystals. This became the basis for many instruments, among them ultrasound(1220).

Johann Friedrich Wilhelm Adolf von Baeyer (DE) synthesized indigo.

London purple (a mixture of arsenic trioxide, aniline, lime, and ferrous oxide) was first reported effective in codling moth control as the result of the first official experiments with arsenical insecticides. The presence of poisonous residues on sprayed fruit was considered at this time: the conclusion was that the quantity of poison carried over to harvest as the result of spraying was insignificant--a correct reasoning at the time when few applications were required to keep pest under control.

Lime-sulfur was first used in U. S. for the control of San Jose scale(138).

Zdenko Hans Skraup (CZ) synthesized quinoline which can be used as an antimalarial(1221).

Emile Clément Jungfleisch (FR) and Lefranc (FR) were the first to crystallize levulose (fructose)(1222). 

Ernst Felix Immanuel Hoppe-Seyler (DE) found that heme or iron-protoporphyrin and the magnesium containing chlorophyll are structurally related(1223).

Bronislaus Radziszewski (PL) made pioneering studies of the chemiluminescence of various organic compounds and the establishment of the enzyme theory of biological oxidations(1224).

Charles Adolphe Würtz (FR) demonstrated the formation of an enzyme-substrate complex when he found that the enzyme papain (which he named) is completely removed from solution by fibrin and that the enzyme cannot be detached from the insoluble material by thorough washing(1225).

Cornelius O’Sullivan (GB) and Frederick William Tompson (GB) also presented one of the first papers concluding that an enzyme-substrate complex formed. Their evidence for this conclusion is based on the observation that invertase is more heat stable in the presence than in the absence of cane sugar, its substrate(1226).

Johannes Ludwig Emil Robert von Hanstein (DE) coined the name protoplast for the protoplasmic part of a single cell. He applied the name to the vital units of both plants and animals. The unit might secrete a wall, but he recognized that this was far from being necessary(1227).

Louis Pasteur (FR) was the first to show the presence of staphylococci in pus(1228).

Louis Pasteur (FR) examined cases of furunculosis, osteomyelitis, and puerperal fever, all of which he attributed to the development of microorganisms infecting the pus of these inflammatory conditions(1229).

Jean Joseph Henri Toussaint (FR), in July 1880, reported to the French Academy of Sciences that he had successfully protected four dogs against anthrax using a preparation of heat-killed bacilli(1230).

Louis Pasteur (FR) confirmed that fowl cholera is caused by a bacterium. He found that if the organism was grown in series in cultures the virulence for fowls was maintained, but that there were conditions in which the virulence for fowls diminished. This enfeeblement of the bacterium Pasteur called attenuation. In the same year he announced the fundamental fact that if the fowls are first inoculated with the living attenuated bacterium of chicken cholera they withstand a subsequent inoculation which kills unprotected animals acutely. He was led to this discovery by a number of observations. He noted, for example, that the effect of chicken-cholera cultures is not always constant with fluctuations in virulence occurring. He observed that chicken cholera is not likely to reoccur if the fowl has once recovered from an attack of the disease, and that where relapses do occur they are in the inverse ratio to the severity of the first attack. In some cases inoculation produces a chronic form of the disease in certain fowls, but the transfer of the bacterium from such cases usually causes the acute form of the disease in other fowls. He noted, however, that the virulence of the culture depends on the time course which elapses between successive cultures. As the period of time increases there are signs of progressive attenuation of the bacterium as shown by the lessened case mortality and by the delay in the development of the symptoms. If the infectious agent is transplanted from medium to medium at intervals varying from days to a month or two no change is observed when the cultures are tested for virulence. If the interval between two successive transfers is carried to 3,4,5, or 8 months the scene changes. Instead of being active as judged by the mortality the latter becomes less and may disappear altogether.

It was apparently an inspiration which led Louis Pasteur (FR) to apply a virulent cholera bacterium to fowls which had come safely through an inoculation of the attenuated bacterium, and this led to his establishment of the principle of prophylaxis following the inoculation of the attenuated bacterium—a principle which he established almost at once for anthrax, swine erysipelas, and rabies. Attenuation of the fowl cholera bacterium was believed by Louis Pasteur (FR) to reside in the deleterious effect of air and particularly oxygen. Cultures in closed tubes of broth were found to maintain their virulence up to ten months(1231, 1232).

Karl Joseph Eberth (DE) was the first to describe the typhoid bacillus. This organism was later named Salmonella typhi(1233, 1234).

Sir James Kingston Fowler (GB) drew attention to the association of throat infection with acute rheumatism(1235).

John H. Bell (GB) gave a clinical description of cutaneous anthrax infections in man, heifers, and sheep. In man it is commonly called wool sorter’s disease(1236).

George Miller Sternberg (US) published his translation of The Bacteria by Antoine Magnin (FR). This was the first textbook of bacteriology printed within the U.S.A(1237).

Charles Louis Alphonse Laveran (FR), a military surgeon working in Algiers, discovered the parasitic malarial protozoan (Plasmodium spp.) in the blood of man and associated it with the disease(1238-1240). Laveran named the parasite, Oscillaria malariae.

Ettore Marchiafava (IT), Angelo Celli (IT), and Amico Bignami (IT) gave the first accurate description of the malaria plasmodium discovered by Laveran, and named it Plasmodium malariae. They determined that malaria is transmitted by way of the blood and differentiated the malarial parasites into the three types recognized today— tertian, quartan, and aestivo-autumnal(1241-1244).

Bartolomeo Camillo Emilio Golgi (IT) described in detail the life history of the sporozoan parasites of various forms of malaria (quartan fever caused by Plasmodium malariae, tertian fever caused by Plasmodium vivax, and aestivo-autumnal fever caused by Plasmodium falciparum) and concluded that they could be distinguished morphologically. He also showed that the malarial fever always coincides with the release of merozoites into the blood. In addition, Golgi developed effective and adequate dosages of quinine for the treatment of malaria in its various stages(1245-1255).

Bartolomeo Camillo Emilio Golgi (IT) identified the parasite which causes malignant tertain fever(1256, 1257).

Cheslav Ivanovich Khentsinsky (RU) presented thorough descriptions and drawings of various forms and stages of malarial parasites in the blood. The exflagellation of P. falciparum gametocytes and his findings of P. falciparum in the liver(1258, 1259). 

Nikolai A. Sakharov (RU), in 1889, published the first comprehensive description of Plasmodium falciparum, the pathogen of aestivo-autumnal malaria, and in 1893 he described the flagellate bodies as phases in the development of plasmodia outside the human body. Ref

Nikolai A. Sakharov (RU) injected himself with intestinal contents of a leech which had fed on a patient with malaria. The result was that he developed malaria, confirming that the malarial plasmodium can survive outside the human body(1260).

Friedrich Siegmund Merkel (DE) described one form of sensory "tactile" nerve ending(1261, 1262). They are designated by the eponym Merkel’s corpuscles.

Bartolomeo Camillo Emilio Golgi (IT) described the musculo-tendineous organs (later to be know as the Golgi tendon organs). These are proprioceptive sense organs that are located at the insertion of skeletal muscle fibers into the tendon. This was a major contribution to the histology of proprioception(723, 1263).

Edmund Beecher Wilson (US) examined the embryonic development of Lumbricus (earthworm) and Nereis (polychaete marine worm) where he found that the mesoderm is formed in a spiral (mosaic) manner—that is certain cells are set aside quite early to form the mesodermal tissues. These cells begin to proliferate at the gastrula stage and all mesodermal tissues originate from them. His work suggested that spiral cleavage was probably a characteristic of all annelids(1264-1266).

Francis Maitland Balfour (GB) wrote, A Treatise on Comparative Embryology, a book which some consider the beginning of modern embryology. He suggested that all creatures possessing a notochord at some time in their life be grouped in the phylum Chordata; that suggestion was accepted(1267).

Thomas Henry Huxley (GB) subdivided the Mammalia into three groups. Prototheria (monotremes), Metatheria (marsupials), and Eutheria (placentals)(1268).

Etienne Lancereaux (FR) made the distinction between fat and thin diabetes: diabete gras and diabete maigre(1269). In the preinsulin era, most children and some adults died of diabetes within months, whereas overweight older patients often survived for years.

Wilhelm His (CH) presented the first accurate and exhaustive study of the development of the human embryo. He was the first to study the human embryo as a whole(1270).

Maximilian Ritter von Vintschgau (AT) limited the qualities of taste to: sour, sweet, salty, and bitter(1271).

Hjalmar Öhrwall (SE) supported the idea of four basic tastes. He concluded that the more basic unit of function had to be the taste bud and that while a papilla may contain a number of different types of taste buds, the taste buds themselves were probably specific to the primaries(1272, 1273). 

Henry Morris (GB) performed a complete operative cure for nephrolithiasis (kidney stone disease) on a 31-year-old woman by lumbar incision and removal of the stone through the kidney parenchyma(1274).

Vincenz Czerny (CZ-DE), in 1880, performed a complete operative cure (pyelolithotomy) for a nephrolithiasis (kidney stone disease). Pyelolithotomy is the removal of a stone through the pelvic wall of the kidney. ref

Moritz Litten (DE) found that if the abdominal aorta in rabbits is compressed for one hour a permanent paralysis of the lower limbs and incontinence of urine are common. Ref

Paul Ehrlich (DE) and Ludwig Brieger (DE) determined that in fact anterior horn cells of the spinal cord are killed by this compression(1275).

Jean Baptiste Edouard Gélineau (FR) introduced the word narcolepsy (Gk. narkosis = benumbing, lepsis = to overtake) to signify the uncontrollable desire to sleep, occurring at frequent intervals(258).

Stephen Alfred Forbes (US) did pioneering work in his analyses of food webs. He undertook detailed analyses of the food relations of insects, insects, birds, and fish within the community, believing that exact information was needed before the value of a species to society could be assessed(1276).

The Zoologischer Jahresbericht was founded.

Zeitschrift für Klinische Medizin was founded.

Science was founded by New York journalist John Michaels with financial support from Thomas Edison and later from Alexander Graham Bell. Science became the journal of the American Association for the Advancement of Science in 1900.

1881-1896

A fifth cholera pandemic was notable for the discovery of its cause, by the German physician Heinrich Hermann Robert Koch. Like its predecessors, this epidemic began in India, and spread both east and west from there. By this time improvements in sanitation kept it from affecting many European cities, and improved diagnosis and quarantine measures kept it out of the United States. A sixth pandemic began in 1899, and continued to spread through Asia over the next ten years. The United States was not affected, nor were most western European cities(176).

1881

Pierre Eugène Marcellin Berthelot (FR), in 1881, introduced the bomb calorimeter for measuring heat liberated during combustions in oxygen and proposed that chemical reactions be characterized as either exothermic or endothermic, depending on whether they were accompanied by the release or uptake of heat(1277). See, Berthelot, 1879.

Kerosene emulsion, the first practical contact insecticide, was recommended for control of insects affecting fruits. Pyrethrum was first advocated for control of grape leafhopper(138).

Ernst August Schulze (CH) and Johann Barbieri (DE) identified the amino acid phenylalanine as a constituent of plant proteins from lupine (Lupinus luteus)(1278, 1279).

Friedrich Gustav Carl Emil Erlenmeyer (DE) and A. Lipp (DE) determined the constitution of phenylalanine which they synthesized from phenylacetaldehyde, hydrogen cyanide, and ammonia(1280).

It was later determined by others that phenylalanine is the source of the benzoic acid which forms when proteins are oxidized with agents like potassium permanganate.

Eduard Zacharias (DE) showed that the characteristic material of chromosomes was either nuclein or was intimately associated with it. He demonstrated that nuclein (nucleic acid) and chromatin are the same material. This lead to the conclusion that chromatin, chromosomes, and nuclein comprised one and the same substance(1281).

Édouard-Gérard Balbiani (FR) was the first to describe what later became known as polytene chromosomes. He did not understand their nature. The dipteran Chironomus was his experimental material(1282). Later it was found that all diptera have these chromosomes. 

Johann Heinrich Emil Heitz (DE) and Hans Bauer (DE) described the large strands found in the nuclei of dipteran salivary gland cells as giant chromosomes(1283).

Theophilus Shickel Painter (US) discovered that the giant chromosomes found in the salivary gland cells of Drosophila are in fact composed of closely paired homologous chromosomes (polytene). In this article he introduced the acetocarmine chromosome squash technique which became so closely identified with Drosophila genetics(1284-1287). Painter quickly identified each chromosome then began to map gene loci because he found that the succession of stained bands in the salivary X chromosome of Drosophila correspond to the linear sequence of gene loci as determined by crossing over experiments.

Milislav L. Demerec (AT/HU-US) and Margaret E. Hoover (US) pointed out the correspondence between giant salivary gland chromosome bands and gene maps(1288).

Nikolai Konstantinovich Koltzoff (RU) and Calvin Blackman Bridges (US) independently suggested that the giant chromosomes of Diptera are polytenic(1289, 1290).

Johann Heinrich Emil Heitz (DE) reported that the banding pattern of polytene chromosomes is consistent(1291).

Gunther Hertwig (DE) noted that the gigantic dimensions of polytene chromosomes are achieved by real growth, i.e., by multiple doubling of the genome(1292).

Gustaf Magnus Retzius (SE) gave a detailed description of the reticular system of muscle and suggested that the T-system plays a role in the conduction of the excitation into the interior of the muscle cell. This is possibly the first definitive description of the sarcoplasmic reticulum(1293, 1294).

Gunnar Nyström (SE) provided experimental evidence for the opening of the transverse network to the extracellular space. After injection of India ink into heart muscle he observed the formation of dark lines crossing the myofibrils at spacings equal to that of the striations(1295).

Emilio Veratti (IT) used the "black reaction" of Golgi to observe a complex, delicate network of longitudinal and transverse filaments in a wide variety of muscles at different stages of development and illustrated them in beautiful drawings, that accurately represent their distribution in the longitudinal and transverse plane of the muscle fiber. Veratti’s paper is a classic description and discovery of the sarcoplasmic reticulum in skeletal muscle fibers(1296, 1297).

Ebba Andersson-Cedergren (SE) described a part of the muscle cell reticulum having the form of transversely oriented tubules (T tubules)(1298). These are instrumental in conducting the signal for contraction inward from the surface membrane.

Bartolomeo Camillo Emilio Golgi (IT) used histological examination to show that many nerve cells originate centrally from the spinal cord(720, 1299-1301). 

Charles Darwin (GB) and his son Francis Darwin (GB) discovered that the phototropic stimulus is detected at the tip of the plant. They found that the tip of the coleoptile is necessary for phototropism but that the bending takes place in the region below the tip. If they placed an opaque cover over the tip, phototropism failed to occur even though the rest of the coleoptile was illuminated from one side. However, when they buried the plant in fine black sand so that only its tip was exposed, there was no interference with the tropism - the buried coleoptile bent in the direction of the light(1302).

Nicholas Ivanovich Lunin (RU) studied the effect of milk on the survival rate of mice feed artificial diets and concluded that milk contained some, as yet unknown, substance necessary to sustain life. That substance was not protein, fat, sugar, salts or water(1303).

Moritz Wilhelm Hugo Ribbert (DE) was the first to report inclusion bodies of cytomegalovirus. He observed these in the kidneys of a stillborn infant with syphilis in 1881. The results were not published until years later(1304).

Karl Brandt (DE) described the zusammenleben (life in common: symbiosis, in modern terms) of algae and animals, and coined the word Zoochlorella to describe the algae found in the body of Hydrae and Zooxanthella for those (yellow) living in Radiolariae(1305).

Theodor Wilhelm Engelmann (DE) described the accumulation of Bacterium termo, a small, rod-shaped, polarly flagellated putrefactive bacterium, in regions of high oxygen tension surrounding cells of higher and lower plants undergoing photosynthesis. This is one of the earliest recorded examples of chemotaxis(1306).

Wilhelm Friedrich Philipp Pfeffer (DE) also discovered chemotaxis and determined that motile bacteria can exhibit a positive as well as a negative chemotaxis(1307-1309).

Julius Adler (US) proved that bacteria possess sensory devices, chemoreceptors, that measure changes in concentration of certain chemicals and report the changes to the flagella(1310).

Heinrich Hermann Robert Koch (DE) presented the streak plate method of isolating microorganisms in axenic culture on solid media (gelatin) in a shallow dish. This is without doubt one of the most significant papers in the history of microbiology. In this paper Koch discusses using potato slices as a medium for culturing bacteria. He prepared them by soaking the raw potato (Solanum tuberosum) in a solution of corrosive sublimate (1:1000) then sterilizing it with steam. It was split in half using a sterile knife and allowed to fall open inside a sterile covered glass vessel. The cut surface was then inoculated with the bacterial material. Here he also reports that high dilutions of mercury bichloride are bacteriostatic and bactericidal for endospores and vegetative cells of the most resistant microorganisms(1311).

Heinrich Hermann Robert Koch (DE) introduced the use of heat as a method of fixing bacterial smears (1311).

Paul Ehrlich (DE) introduced the use of methylene blue as a bacterial stain(1312).

Heinrich Hermann Robert Koch (DE) and Gustav Wolffhügel (DE) determined the exact value of hot air as a sterilizing agent (1313).

Albert Ludwig Siegmund Neisser (DE) while staining the leprosy microorganism noted what would later be appreciated as its acid-fast nature(1314).

Heinrich Hermann Robert Koch (DE), Georg Theodor August Gaffky (DE), and Friederich August Johannes Löffler (DE) determined the limitations of steam at 100°C. as a sterilizing agent(1315).

Louis Pasteur (FR) observed that superheated steam is an excellent sterilizing agent. He first accomplished this by immersing sealed vials in a bath of calcium chloride heated above 100°C. Later he used Denis Papin’s (FR) digester (steam under pressure).

Heinrich Hermann Robert Koch (DE) used axenic cultures of certain bacteria to compare the antiseptic capacity of a number of chemicals. Axenic cultures were dried on small pieces of silk thread then immersed in the test chemical. After various intervals of time the impregnated threads were removed from the test chemical, washed in sterile water or sterile broth, and implanted in a medium to determine whether the bacteria had been killed or not. He was soon able to draw a distinction between the concentration of an agent which prevents a microorganism from growing (bacteriostatic) and that concentration which kills the microorganism (bactericidal). He found that these limits may be, and usually are, far apart. Of over 70 chemicals tested, Koch found mercuric dichloride to be the most antibacterial. Koch showed that mercuric chloride was superior to carbolic acid, and that live steam surpassed hot air in sterilizing power(1316).

Wilhelm Olbers Focke (DE) coined the term xenia to denote the immediate effect of pollen on the endosperm in the maize seed(1317).

Wilhelm August Oskar Hertwig (DE) and Richard Wilhelm Karl Theodor von Hertwig (DE) originated the term mesenchyme, a protoplasmic network filled with a fluid intercellular substance. It may be derived from all three germ layers, but is primarily mesodermal in origin, and gives rise to a variety of tissues: primarily connective tissue(1188).

Joseph Leidy (US) described his discovery of microorganisms in the hindgut of termites as follows: “In watching the Termites from time to time wandering along their passages beneath stones, I have often wondered as to what might be the exact nature of their food in these situations. Observing some brownish matter within the translucent abdomen of the insects, I was led to examine it with the object of ascertaining its character. On removing the intestinal canal of an individual I observed the brownish matter was contained within the small intestine, which is comparatively large and capacious. The brownish matter proved to be the semi-liquid food; but my astonishment was great to find it swarming with myriad parasites, which indeed actually predominated over the real food in quantity. Repeated examination showed that all individuals harbored the same world of parasites wonderful in number, variety and form.

If the intestine is ruptured, myriad living occupants escape, reminding one of the turning out of a multitude of persons from the door of a crowded meeting-house. So numerous are the parasites and so varied their form, movement, and activity, that their distinctive characters cannot be seen until they become more or less widely diffused and separated”(1318).

Charles Robert Darwin (GB) was the first to report how important worms are to soil fertility(1319).

Louis Pasteur (FR), Charles Édouard Chamberland (FR), Pierre Paul Émile Roux (FR), and Louis Thuillier (FR) demonstrated that rabies has an affinity for brain tissue. They discovered that the incubation period could be shortened to one or two weeks by inoculating the virus directly under the dura mater of dogs(1320, 1321).

Joseph Marie Jules Parrot (FR) mentions a pneumococcus associated with human infection(1322).

Louis Pasteur (FR), Charles Édouard Chamberland (FR), Pierre Paul Emile Roux, (FR), and Louis Thuillier (FR) isolated Streptococcus pneumoniae, or pneumococcus, from the saliva of a patient with rabies(1320).

George Miller Sternberg (US) almost simultaneously announced the discovery of the pneumococcus(1323).

Albert Fraenkel (DE) and Anton Weichselbaum (AT) grew pneumococcus (Streptococcus pneumoniae) in a pure state and established its relationship to lobar pneumonia(1324-1330).

Friederich August Johannes Löffler (DE) introduced the use of common broth or bouillon for culturing bacteria during his studies of the bacillus causing mouse septicemia. He grew this organism in a medium consisting of meat infusion, to which was added 1 percent of peptone, and 0.6 percent of common salt. The solution was made slightly alkaline with sodium monohydrogen phosphate (1331).

Karl Joseph Eberth (DE) isolated the typhoid bacillus from the mesenteric glands and the spleen of persons dying from typhoid fever(1234).

Georg Theodor August Gaffky (DE) isolated Gaffkya tetragena from the pulmonary cavities of patients with phthisis (pulmonary tuberculosis)(1332).

Louis Pasteur (FR), Pierre Paul Émile Roux (FR), and Charles Édouard Chamberland (FR) developed a vaccine for anthrax. This was a difficult task because of the presence of endospores in the cultures. They found that anthrax would not grow above 45°C. but yielded abundant growth at 42-43°C. At the latter temperatures no endospores were formed. The culture had indeed become asporogenous, and in a month had ceased to grow. When a virulent anthrax culture in broth was kept at 42-43°C. for eight days it had lost a considerable part of its virulence and was innocuous when injected into guinea-pigs, rabbits, or sheep. By longer cultivation at the above temperature it became still more attenuated. They recommended this method as an anthrax prophylactic or vaccine. Louis Pasteur (FR) coined the term vaccine to honor Edward Jenner and the cowpox prophylactic treatment Jenner developed for smallpox(1174, 1333-1335).

John W. Ezzell (US), Perry Mikesell (US), Bruce E. Ivins (US), and Stephen H. Leppla (US) noted that avirulent cultures of anthrax lack a critical virulence plasmid. They point out, ironically, that Pasteur’s nonchalance about pure clone cultures, so much criticized by Koch, was the key to the success of his anthrax vaccine, which was a mixture of plasmid-deprived and still toxic (and immunogenic) plasmid-positive cells(1336). 

Alexander Ogston (GB), assistant-surgeon to the Aberdeen Royal Infirmary examined 100 abscesses, some acute and some inactive, for bacteria. No microorganisms could be found in the inactive abscesses, whereas the active ones were found to contain many micrococci. Sometimes the cocci were clumped like the roe of fish (staphylococci) and other times appeared in chains (streptococci). He showed that the difference in appearance was due to a difference in mode of fission. Using a hemocytometer he determined that the average number of cocci per cubic milliliter of pus was nearly 3 million, although in individual samples it varied between a minimum of 900 and a maximum of 45 million. He found spirilla and fusiform bacteria in alveolar abscesses. Injection of inactive abscess material into mice was without pathogenic effect. When he injected mice with material from active abscesses the results were dramatically different. Abscesses invariably developed and he traced with great clearness the symptoms and lesions, and showed by the process of counting that the cocci in the experimental lesion must have increased greatly in numbers, and that the experimental inflammatory disease with abscess formation could be propagated in series. Ogston examined lesions other than abscesses. Among them gonorrhea, soft chancre, sycosis, sputa from phthisis (pulmonary tuberculosis), discharges from wounds and ulcers. Micrococci were found in all. He cultured the cocci outside the body of animals by using fresh eggs. Using cocci from these fresh egg cultures he was able to experimentally produce typical abscesses by inoculation into mice. 

Ogston concluded that micrococci produced inflammation and suppuration. There was microscopic evidence of their proliferation locally; the cocci invaded peripherally and might pass into the blood. In abscesses they were finally excluded by the formation of a delimiting wall of granulation tissue which arrested their invasion and led to their final extrusion among the pus corpuscles (1337-1340).

Friedrich Fehleisen (DE) and Anton Julius Friedrich Rosenbach (DE) obtained axenic cultures of these microorganisms and reached similar conclusions. Anton Julius Friedrich Rosenbach (DE), adopting the term streptococcus (previously introduced by Billroth) to name Streptococcus pyogenes; the variety of organism isolated by him from suppurative lesions. Rosenbach also isolated Staphylococcus  in axenic culture. He named them for the pigmented appearance of their colonies: Staphylococcus aureus, from the Latin aurum for gold, and Staphylococcus albus (now called epidermidis), from the Latin albus for white. Rosenbach was the first to show a causal relationship between the micrococci and the suppuration of wounds and osteomyelitis(1341, 1342).

W. Reinhard (DE) created the class Kinorhyncha (Gr. kīneō 'move' + rhynchos 'snout') for the genus Echinoderes. Commonly called "mud dragon" it is in the phylum Aschelminthes (or Nemathelminthes)(1343, 1344). These are pseudocoelomate invertebrates that are widespread in mud or sand at all depths.

Carlos Juan Finlay (CU) presented a paper at the International Sanitary Conference in Washington in which he suggested that mosquitoes of the genus Stegomyia (Aedes) might be transmitters of the unknown germ causing yellow fever(1345, 1346). While not the first to make this suggestion, he was perhaps the most zealous and enthusiastic proponent of this point of view. Finlay, an unassuming man with an international background, a Scottish father and a French mother, had much of his early training in France and other European countries, and received his medical degree at Jefferson Medical School in 1855.

Walter Reed (US) was to say, “To Dr. Carlos Juan Finlay of Havana must be given, however, full credit for the theory of the propagation of yellow fever by means of the mosquito, which he proposed in a paper read before the Royal Academy in that session of the 14th day of August, 1881(1347). From that date to the present time, Finlay has made a number of valuable contributions to the origin and mode of transmission and the prevention of yellow fever.”

Henry Rose Carter (US) studied an outbreak of yellow fever in Mississippi and defined the limits of the extrinsic incubation period, i.e., the period of time course necessary before the surroundings of a case become infectious, as 10-15 days(1348).

W.T. Milles (GB) and Arthur Swayne Underwood (GB) consider that dental caries, as well as suppuration of the pulp and alveolar abscess, depends upon the presence and proliferation of micro-organisms. These organisms attack first the organic material, and feeding upon it create an acid, which removes the lime-salts(1349).

Ernst Ziegler (DE) described a decrease in bone mass which would later be called osteoporosis(1350).

Carroll A. Pfeiffer (US) and William U. Gardner (US) found that injection of estrogen into pigeons is followed by a rise in the serum calcium level and hypercalcification of the bone(1351).

Stanley Wallach (US) and Philip H. Henneman (US) conducted a 25-year retrospective study of the results of prolonged estrogen therapy in 292 post-menopausal women which showed excellent results in the treatment of post-menopausal osteoporosis(1352).

Alexander Crombil (GB) suggested the injection of morphine prior to the administration of chloroform to patients. This was probably the first type of preanesthetic medication(1353).

Karl Siegmund Franz Credé (DE) was the first to recognize the antimicrobial properties of silver when he introduced the use of silver nitrate as a prophylactic agent against gonorrheal ophthalmia neonatorum(1354, 1355).

Albert Coombs Barnes (US) and Hermann Hille (DE), in 1899, developed a mild silver nitrate antiseptic solution, marketed as Argyrol, and used in the treatment of gonorrhea and as a preventative of gonorrheal blindness in newborn infants. Argyrol was first sold in 1902(1356).

Richard von Volkmann (DE) discovered that relaxation and contractures of limbs following application of tight bandages are caused by the rapid and massive deterioration of contractile substance and by…reactive and regenerative processes(1357). These are now called Volkmann ischemic contractures.

Hermann Munk (DE) placed the cerebral center for hearing in the temporal lobes of the brain(1358, 1359).

Théodule Ribot (FR) cited a number of cases from the literature to illustrate the occasional separation of procedural (ways of doing things) from declarative (factual) memory(1360).

Sanger Brown (GB) and Sir Edward Albert Schäfer (GB) reported that damage to the temporal lobes and the underlying hippocampus may affect memory(1361).

William B. Scoville (US) and Brenda Milner (US) reported on a patient in which lesions destroyed the anterior two-thirds of the hippocampus, in addition to the parahippocampal gyrus, anterior temporal cortex, uncus, and amygdala. Declarative (factual) memory seemed to depend more upon the integrity of the hippocampus than did procedural (ways of doing things) memory(1362). 

Moritz Litten (DE) was the first physician to describe vitreous bleeding in correlation with subarachnoid hemorrhage(SAH)(1363).

William MacEwen (GB) and Joseph Lister (GB) independently found that if incisions or wounds were kept aseptic and closed with sterile catgut (sterilized with hot wax) whose loose ends had been clipped close to the tie that the catgut would be absorbed as infection free healing took place. To make the absorbable catgut antimicrobial, Lister treated it with a mixture of one part chromic acid, 4000 parts distilled water and 200 parts carbolic acid(1364, 1365).

William Holbrook Gaskell (GB) presented the results of his studies, in which he defined the five properties of cardiac muscle, viz., excitability, conductivity, tonicity, rhythmicity, and automatic contractile power(1366).

Sir William Richard Gowers (GB) gave a classic description of epilepsy(1367).

Waren Tay (US) and Bernard Sachs (US) described amaurotic family idiocy (Tay-Sachs disease), a fatal autosomal recessive genetic disorder in which harmful quantities of a fatty substance later called ganglioside GM2 accumulate in the nerve cells in the brain(1368, 1369). Patients and carriers of Tay-Sachs disease can be identified by a simple blood test that measures hexosaminidase.

Ernest-Charles Lasègue (FR) discovered a sign frequently seen in lumbar root or sciatic nerve irritation: when patient is supine with hip flexed, dorsiflexion of ankle causes pain or muscle spasm in the posterior thigh. It was reported years later by J.J. Forst, one of his pupils(1370).

Friedrich Trendelenburg (DE) introduced the head-down tilt with pelvic elevation for abdominal surgery in 1881. This position is also favored for patients in shock. One of his students was first to report this innovation. In the 1890 paper he identified saphenofemoral incompetence in patients with varicose veins(1371-1373).

Vincenz Czerny (CZ-DE) introduced the operation of enucleation of subperitoneal uterine fibroids by the vaginal route(1374).

Anton Wölfler (PL) perfected the operation of gastro-enterostomy (creation of an artificial passage between the stomach and intestines)(1375).

Nikolaus Friedreich (DE) was the first to describe paramyoclonus multiplex(1376).

Emil Wilhelm Magnus Georg Kraepelin (DE) wrote about the influence of infectious diseases on the onset of mental illness(1377, 1378).

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) was the first to use the electric esophagoscope invented by Josef Leiter (PL) in 1880, and the first gastroscope in 1881(1379).

Sir William Alvin Macewen (GB) reported the successful removal of a left frontal meningioma in a 14-year-old girl(1380). The operation was performed in 1879.

Francesco Durante (IT) successfully removed a cranial base meningioma. Durante performed a large left frontal craniotomy and removed an "applesized sarcoma." The patient recovered from the surgery without incident(1381). The operation was performed in 1884.

Alexander Hughes Bennett (GB) and Rickman John Godlee (GB) diagnosed then surgically removed a cerebral tumor. The patient was a farmer, 25, who applied for advice to the Hospital for Epilepsy and Paralysis, Regent's Park, on November 3rd, 1884. His chief complaint was paralysis of the left hand and arm, which incapacitated him from work. Following surgery the patient lived only one month, dying from what was undoubtedly an infection(1382, 1383).

Max Schüller (DE) performed the first successful operation for non-descending testicle(1384).

Jean-Francois-Auguste Le Dentu (FR) carried out the a successful nephrolithotomy (removal of kidney stones). (1385).

Karl Semper (US) was one of the first to point out the modern ecological point of view and laid the basis for many ecological concepts of existence(1386).

The Congress of the United States passed an agricultural appropriation act establishing a divisional organization for the United States Department of Agriculture, at which time the divisions of Seed, Gardens and Grounds, and of Botany were founded. The Division of Pomology was established in 1886; the Division of Vegetable Pathology achieved independence from the Division of Botany in 1891, and became the Division of Vegetable Physiology and Pathology in 1895; in that year, the Division of Agrostology was also founded. The Section Foreign Seed and Plant Introduction was established in 1897(1387).

Caesar Peter Møller Boeck (NO) with Skjelderup and Stabell established the journal Tidsskrift for Praktisk Medicin.

Gesellschaft für Innere Medizin was founded.

Botanische Jahrbücher was founded.

1882

August Von Freund (AT) discovered and described cyclopropane (trimethylene)(1388).

George H. W. Lucas (CA) and Vilyien E. Henderson (CA) showed that cyclopropane has anesthetizing properties(1389).

John A. Stiles (US), William B. Neff (US), Emery A. Rovenstine (US), and Ralph M. Waters (US) began to use cyclopropane clinically(1390).

Ferdinand Gustav Julius von Sachs (DE) suggested that nuclein carrys hereditary information by pointing out that the nucleins of egg and sperm could hardly be identical—that the nuclein brought into the egg by the sperm must be different from the nuclein already there(1391, 1392).

Ferdinand Gustav Julius von Sachs (DE), in 1882, noted that plants synthesize organ-forming substances that are polarly distributed(1393).

Theodor Wilhelm Engelmann (DE) discovered that during illumination oxygen requiring motile bacteria are attracted to the surface of the eukaryotic alga Spirogyra near the chloroplast; in the absence of light they are not attracted. This provided the first direct evidence that the chloroplast is the site of oxygen production in eukaryotic organisms(1394-1396).

White arsenic is first used to control codling moth. Napthalene is first used for insect control purposes. It is used in a cone form(138).

Eduard Adolf Strasburger (PL-DE) coined the terms cytoplasm and nucleoplasm to describe the cell body and nucleus, respectively. ref 

Johannes Ludwig Emil Robert von Hanstein (DE) coined the name microsome for some small granules common in the cytoplasm(1397).

Édouard-Gérard Balbiani (FR) found that the formation of the sexual organs of the Chironomus (Diptera: Chironomidae) demonstrated that the sexual cells derive directly from the egg and are differentiated before the blastoderm appears - and that consequently they precede the individual itself. This essential fact was later observed in other species and eventually was responsible for the general theory of the autonomy of the germ cell(1398).

Paul Ehrlich (DE) introduced the use of aniline water, and either methyl violet or fuchsin as a dye superior to methylene blue for staining tubercle bacilli. Aniline was shaken in water then filtered to yield aniline water. This was then saturated with either methyl violet or fuchsin in alcoholic solution. By this means the tubercle bacillus was stained deeply and the color was acid fast in that it could not be discharged by even nitric acid in a concentration of 30% in water. He counterstained with dilute blue or yellow dye. This was the first staining procedure to take advantage of the acid-fast quality of tubercle bacilli (1399).

Franz Ziehl (DE) described a method for staining the tubercle bacilli. His technique did not employ a counterstain(1400).

Friedrich Carl Neelsen (DE) introduced what we may call the classic procedure for staining acid-fast bacteria(1401). Today it is referred to as the Ziehl-Neelsen method. It was first mentioned in a paper by A. Johne (DE)(1402).

Sydney Ringer (GB) introduced the use of a salt solution which enhanced the survival rate and function of excised animal body parts. The solution contained sodium chloride, potassium chloride, and calcium chloride. He and Dudley W. Buxton (GB) concluded that extracellular calcium ion is required to preserve the contractility of the heart but calcium, potassium, and sodium must be present in correct proportions (as in the Ringer’s solution) for normal heart activity(1403-1412). Harrington Sainsbury (GB) and Arthur G. Phear (GB) were among Ringer’s research colleagues.

Frank Spiller Locke (GB) optimized the various salt concentrations at NaCl 0.9-1.0 percent, CaCl2 0.02-0.024 percent, KCl 0.02-0.04 percent, and NaHCO3 0.01-0.03 percent. He also discovered that while each of these chlorine salts, if used individually, might be toxic to the heart they could be given together with no ill effect. The concept of antagonistic salt action was thus introduced to physiology(1413, 1414).

Percy G. Stiles (US) found that rhythmic contractions of smooth muscle in frog esophagus strips showed similar dependence on extracellular calcium ions and potassium, as did the frog heart(1415).

Hermann von Tappeiner (DE) observed that although ruminants did not secrete enzymes which digested cellulose it nevertheless disappeared from their digestive tract. The inescapable conclusion was that microorganisms of the digestive tract were responsible for the enzymatic attack of cellulose and therefore they were absolutely necessary if the ruminant was to lead a normal life(1416, 1417).

Wilhelm Friedrich Kühne (DE), Carl Anton Ewald (DE), William C. Ayres (US), and J. Steiner (DE), in 22 articles beginning in 1877, determined that the retina (with its epithelium) acts not as a photographic plate, but actually more like a complete photographic laboratory, in which workers continuously supply new highly photosensitive material to the plate, erasing the older images. Using an alum solution as a fixative they were able to actually fix the image of a rabbit on the retina. Kühne called these optogramms. They summarized, 1) It is the function of rhodopsin to be decomposed by light; 2) the products of this photochemical reaction then stimulate the nerve impulse to the brain(1418, 1419).

Bartolomeo Camillo Emilio Golgi (IT) used his "black reaction" staining technique to trace the olfactory nerves in man and other mammals(720, 1420, 1421).

Waldemar von Schroeder (DE) perfused the liver of dogs with ammonium carbonate or ammonium formate and observed that the liver produced a significant amount of urea. This was additional evidence that urea is biosynthesized(1422).

Pier’ Andrea Saccardo (IT) with the aid of Alessandro Trotter (IT), Domenico Saccardo (IT), Giovanni Battista Traverso (IT), Paul Sydow (GB) and others produced a 25 volume work on the fungi entitled Sylloge Fungorum. This exhaustive work was begun in 1882 and ended in 1931(1423). It spurred renewed interest around the world in describing new fungi.

Karl Wilhelm von Nägeli (CH) studied the effect on bacterial growth of various carbohydrates and proteins. He found that sugars were generally the best carbon sources and peptones were generally the best nitrogen sources(1424).

Heinrich Hermann Robert Koch (DE) introduced the use of blood-serum stiffened by heat as a solid medium of great nutritive value. He used it to cultivate the tubercle bacillus (1425).

Thomas Jonathan Burrill (US) discovered and described the bacillus which causes fire blight in pears and twig blight in apples. He never grew it in axenic culture or strictly followed Koch’s postulates. Some consider this, along with Jan Hendrik Wakker’s work in 1883, to be the birth of the science of bacterial phytopathology. Burrill named the bacterium Bacillus amylovorus(1426-1429). See, Wakker in 1883.

Ludwig von Graff (AT) proposed the planuloid-acoeloid theory to explain how the bilateral animals evolved from the radiates(1430).

Libbie Henrietta Hyman (US) has vigorously promoted the planuloid-acoeloid theory(1431). 

George Albert Boulenger (BE-GB) was invited in 1880 to come to the British Museum to undertake a new edition of the catalogues of amphibians and reptiles. While there he oversaw the production of nine volumes which constituted a summary of the world fauna for the classes Amphibia and Reptilia to the year 1896. He also catalogued the fishes of Africa. Notwithstanding the presence of errors this body of work represented a fundamental reform of the classification of the two great classes of vertebrates, the Amphibia and Reptilia, and was to shape zoological thinking in Europe for many years(1432-1436).

Harry Marshall Ward (GB) stressed the relationship of environment to the epidemiology of coffee rust in Ceylon(1437).

Joseph Jules François Félix Babinski (PL-FR) published a treatise on typhoid fever(1438). 

Heinrich Hermann Robert Koch (DE) discovered that tuberculosis is caused by a specific bacterium, Mycobacterium tuberculosis. In publishing his results he laid down the laws since considered fundamental to the science, viz., that before recognition as the cause of a disease a germ (1) must be found constantly associated with that disease, (2) must be isolated from a lesion of that disease apart from other germs, (3) must reproduce the disease in a suitable animal on inoculation with axenic culture, and finally (4) be found again in the lesions of this artificially produced disease(1425).

He described how alkaline methylene blue penetrates the tubercle bacillus and remains there despite subsequent treatment with vesuvin or Bismarck brown. He used this technique to show the tubercle bacillus when he first worked with it (1425). Note: Tuberculosis has been called phthisis, consumption, scrofula, and the white plague.

Charles Clemens von Baumgarten (DE) independently and almost simultaneously with Heinrich Hermann Robert Koch (DE) described the tubercle bacillus(1439).

Carl Friedländer (DE) discovered a bacterium which causes pneumonia in humans and named it Bacillus pneumoniae(1440, 1441). Today it is referred to as Klebsiella pneumoniae. Occasionally it is called Freidländer’s bacillus in his honor. Friedländer contracted pulmonary tuberculosis at the age of 35 and died 5 years later(1442).

Carle Gessard (FR) discovered that the blue or blue-green stains that sometimes appeared on surgical dressings is caused by the presence of Pseudomonas pyocyanea (Pseudomonas aeruginosa)(1443, 1444).

Alexander Ogston (GB) gave a general statement of his views on ‘micrococcus poisoning’. He considered that micrococci were of two kinds, the one arranged in chains (Streptococcus, Billroth) and the other in masses, which he named Staphylococcus (a bunch of grapes). He opposed the view that pyemia and septicemia were blood diseases, and showed that the blood was merely the vehicle which may generalize in the body what, without its aid, would be only a local process(1339).

Rudolf von Jaksch; Rudolf Jaksch Ritter von Wartenhorst (AT) identified acetoacetic acid in the urine of diabetics. It would, with the loss of carbon dioxide, break down into acetone(1445, 1446).

Heinrich Irenaeus Quincke (DE) described angioneurotic edema(1447). He also  studied the mechanism of body temperature control, wrote on anosmia, traumatic brain lesions, and on hyperthermia in cord lesions.

Friedrich Daniel von Recklinghausen (DE) wrote a classic article on neurofibromatosis, Recklinghausen’s disease(1448).

Kanehiro Takaki (JP) reduced the incidence of beriberi in the Japanese navy by dietary improvements. To test his dietary theory, Takaki gave the crew of the training ship, Ryujo, a white-rice diet and gave the crew of another training ship, Tsukuba, an enriched diet of his own devising. Leaving Japan in December 1882 and in February 1884 Ryujo and Tsukuba sailed to New Zealand, along the coast of South America from Santiago to Lima, to Honolulu, and back to Japan in voyages lasting some 9 months. Of the 376 crewmen of Ryujo, all of whom were eating the white-rice diet, 161 contracted beriberi and 25 died. However, only 14 of the crew of Tsukuba, who ate Takaki's enriched diet, contracted beriberi and none died. He supplemented the rice diet with milk and vegetables(1449). Takaki's success came 10 years before that of Dutch hygienist Christian Eijkman.

Philippe Charles Ernest Gaucher (FR) described a case of the disease which would later bear his name(1450).

Hans Lieb (DE) and Emil Epstein (DE) isolated a fatty substance (the cerebroside, kerasin) from the spleens of patients with Gaucher Disease(1451, 1452). 

Henriette Aghion (FR) identified this fatty substance as glucocerebroside(Aghion 1934).

William Bloom (US) described the histopathology of Gaucher’s and Niemann’s diseases(1453).

Roscoe O. Brady (US), Andrew E. Gal (US), Julian N. Kanfer (US), and Roy M. Bradley (US) proved that glucocerebroside collects in Gaucher cells due to the lack of an enzyme known as glucocerebrosidase(1454-1456).

Wilhelm August Balser (DE) and Reginald Heber Fitz (US) described acute hemorrhagic pancreatitis and some of its attendant problems(1457-1459).

Paul Bruns (DE) formulated the general pattern of the age and the sex specific incidence of various types of human bone fractures in an impressive review of fracture epidemiology(1460).

Ernst Viktor von Leyden (DE) described fatty infiltration of the heart for the first time(1461).

Eduard Albert (AT) introduced the concept of joint arthrodesis (fixation of a joint by fusion of the joint surfaces) into orthopedic surgery. This is the first description of arthrodesis of an ankle for paralytic foot(1462).

Alexander von Winiwarter (AT-BE) was the first to successfully perform a cholecystoenterostomy in man(1463, 1464).

From 1882-1924 the U.S.S. Albatross, under the direction of the U. S. Fish Commission, further extended knowledge of the extent and variety of marine life.

Simon Schwendener (CH-DE) was one of the founders of the journal Deutsche Botanische Gesellschaft.

1883

Johan Gustav Christoffer Thorsager Kjeldahl (DK) described his method for determination of nitrogen in organic materials(1465, 1466).

Jacques Louis Soret (FR) discovered an intense absorption band in the blue region of the spectrum of porphyrins and their derivatives. It became known as the Soret band(1467).

Heinrich August Bernthsen (DE) made the dye azure B(1468, 1469). 

Franz Hundeshagen (DE) synthesized lecithin(1470).

Max Rubner (DE) discovered that the energy supplied to the human body by foodstuffs is precisely the same in quantity as it would have been if those same foodstuffs had been consumed in a fire (once the energy content of urea was subtracted). The laws of thermodynamics, in other words, hold for living tissue. He perfected the methods of computation used in modern animal calorimetry and demonstrated that living bodies obey the law of the conservation of energy. He also established the relationship between the skin surface area of an animal and its food requirements. He showed that the heat value of metabolism in a resting animal is proportional to the area of the body surface(1471-1474).

Karl James Peter Graebe (DE) and Heinrich Caro (DE) discovered acridine orange(1475).

L. Benda (DE) synthesized acridine orange and proflavine(1476).

Carl Hamilton Browning (GB) and Walter Gilmour (GB) recognized the antimicrobial properties of acriflavine(1477).

Ernst August Schulze (CH) and E. Bosshard (CH) isolated the amino acid glutamine from beet juice(1478).

Ernst August Schulze (CH) established that asparagine and glutamine are important in plant metabolism(1479).

Edmund J. Mills (GB), James Snodgrass (GB), and Thomas Akitt (GB) suggested that absorption of halogen might be used to measure the degree of saturation of a fat or fatty acid(1480, 1481).

Marceli Nencki; Marcellus von Nencki (PL) and B. Lachowicz (PL) observed putrefaction under conditions in which no free oxygen could be detected even by the most sensitive tests(1482, 1483).

Hikorokuro Yoshida (JP) was the first to clearly identify an oxidative enzyme as such. The enzyme was diastatic matter which promoted the darkening and hardening of the latex of the Japanese lacquer tree. It catalyzes the oxidation of a plant constituent (urushiol) by atmospheric oxygen(1484).

Sydney Ringer (GB) reported that calcium ions are required in the bathing medium to maintain the contraction of an isolated frog heart(1404).

Arthur Meyer (DE) described the chloroplast as consisting of a colorless, homogeneous matrix in which grana are embedded(Meyer 1883).

S. Jenny Doutreligne (NL) and Johann Heinrich Emil Heitz (DE) described chloroplasts as consisting of a lighter-colored stroma impregnated with a number of darker grana(1485-1487).

Bert Hubert (NL) and Albert Frey-Wyssling (CH) postulated that grana contain alternate proteidic and lipoidic layers with chlorophyll molecules attached(1488-1490).

Theodor Wilhelm Engelmann (DE) discovered that Bacterium photometricum, a motile purple bacterium which metabolizes sulfur compounds is phototaxic, inhibited from motion by carbon dioxide, and does not liberate oxygen. When he illuminated the culture with a spectrum, the cells accumulated in bands at the wavelengths at which they could respond. This led to the discovery of bacteriochlorophyll a, a pigment absorbing in the near infrared, 850 nm(1491).

Heinrich Hermann Robert Koch (DE) decided that it is impossible to develop a universal medium with equal nutritional value for all bacteria. He developed an artificial solid medium by adding 2 and one-half to 5 percent gelatin to well-tried fluid medias. The sterile gelatin medium was poured onto sterile slides under a bell jar and allowed to harden. The slides were inoculated by means of a sterilized needle or platinum wire which was drawn lightly across the surface of the gel. When growth appeared it was transferred to test tubes plugged with cotton and containing sterile nutrient gelatin which had been set in an upright or slanted position. This technique was to revolutionize microbiology(1492).

Heinrich Hermann Robert Koch (DE) developed the pour plate method of isolating bacteria in axenic culture. A mixture of organisms was inoculated into molten nutrient gelatin, mixed thoroughly, then poured onto cold sterile glass plates. This method for obtaining axenic cultures soon became the method of choice(1492).

Ulysse Gayon (FR) and Gabriel Dupetit (FR) isolated two strains of denitrifying bacteria in axenic culture. They found that a variety of simple and complex organics could serve as carbon sources and as reductants of nitrate(1493).

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) reported that natural immunity depends on a cellular rather than a humoral mechanism. The cells which possess this property were named phagocytes by Mechnikov, and the process phagocytosis. This phagocytic activity was first observed by him in starfish larvae which he purposely irritated with rose thorns. Later he observed that the crustacean Daphnia magna used phagocytosis to defend against the parasite, Monospora bicuspidata(1494-1496).

Christian Gottfried Ehrenberg (DE) described the first observations of wave-shaped flagella, which he thought were probably necessary for motility(1497).

Emil Christian Hansen (DK) was the first to provide scientific evidence of the various strains of yeast. His greatly improved dilution technique allowed him to produce axenic cultures of yeast and by doing so revolutionized this aspect of the brewing industry(1498-1501).

Alphonse de Candolle (FR) wrote Origine des Plantes Cultivée which identified the geographic origin of most agronomic, horticultural, and fruit crop plants(1502).

Moriz Loewit (AT) described the development of the erythrocyte from a non-haemoglobiniferous small round cell(1503).

Jan Hendrik Wakker (NL) discovered and described the microorganism causing “yellows” disease of hyacinths. Some consider this and Thomas Jonathan Burrill’s work of a year earlier to represent the birth of the science of bacterial phytopathology(1504). See, Burrill in 1882.

Theodor Albrecht Edwin Klebs (DE) announced that one type of diphtheria is caused by a bacillus which when stained with methylene blue appears to have a knob at either end of the cell. He observed that it was always present on the surface of the membranes formed in the throat, but never could be found in other tissues of diphtheria victims(1505).

Friedrich Fehleisen (DE-US) gave the first detailed account of Streptococcus erysipelatis. He induced typical erysipelas in human volunteers with streptococci from lesions of patients with the same disease(1341). In the Middle Ages erysipelas and acute ergot poisoning were both called St. Anthony’s fire.

Louis Pasteur (FR) and Louis Thuillier (FR) successfully produced a vaccine against swine erysipelas by passing the bacterium through the bodies of rabbits. Thuiller was to die later that year, at the age of 27, from cholera he was studying in Alexandria Egypt(1506).

Albert Freeman Africanus King (US) wrote a paper in which he gave 19 reasons why mosquitoes were likely to be the vector of malaria(1507).

Paul Gerson Unna (DE) recognized human transmission of herpes simplex virus infections between individuals(1508).

Sir Victor Alexander Haden Horsley (GB) described the effects of nitrous oxide anesthesia(1509).

Wilhelm Roux (DE) worked out the timing of the determination of the main axes of the frog’s embryo and developed the first important hypothesis to explain differentiation—mosaic or determinant development—during embryonic development(1510, 1511).

Wilhelm Roux (DE) was the first to cultue somatic cells outside the body of the organism. His objective was to observe embryonic development. He demonstrated that closure of the frog neural tube could take place without the pressure that was thought to be exerted by the surrounding tissues(1512).

Wilhelm Roux (DE) founded what he called entwickelungsmechanik (developmental mechanics) which became experimental embryology then analytical embryology(1513).

Emil Theodor Kocher (CH) showed the relationship of goiter to activity of the thyroid gland(1514). He was the first to find a way to tie off all the thyroid’s blood vessels, allowing surgery. During his professional life he performed over 2,000 thyroidectomies. In 1878, he described his early experiences with thyroidectomy for thyrotoxicosis which he performed with a mortality of 13%. By the time he published more detailed descriptions in 1883 his operative mortality had fallen to less than 1%. He recognized myxedema after thyroidectomy which he described as cachexia strumipriva. This occurred after 30% of thyroidectomies at that time.

His other significant contributions to surgery were descriptions of a maneuver to reduce a subluxed shoulder (1870), radical surgery for carcinoma of the tongue (1880) and an operation for inguinal hernias (1892)(1515-1517). He introduced the use of sterilized silk sutures into his surgical practice in 1882. His name is associated with a toothed surgical clamp, an atraumatic bowel clamp and a curved director. A sub-costal incision for an open cholecystectomy, a percondylar humeral fracture and a maneuver to mobilize the duodenum are also named after him.

Sir Algernon Phillips Withiel Thomas (GB-NZ) and Karl Georg Friedrich Rudolf Leuckart (DE) independently established the life cycle of Fasciola hepatica, the liver-fluke. This was the first time that a trematode life cycle was described(1518-1524). Note: at this point it was still uncertain how the encysted cercaria infected the second host.

Adolfo Lutz (BR) proved that infection of the second host is acquired by ingestion of cysts containing metacercaria(1525).

Dimitry F. Sinitsin (RU), in 1911, demonstrated the pathway of migration taken by the metacercaria in the second host. They penetrate the intestinal wall and pass into the peritoneal cavity, then attach to the liver and penetrate into biliary passages where they mature(1526).

Jaime Ferrán (ES) in a letter of 3 April, 1883 to the French Academy of Sciences in Paris described how he had protected guinea pigs from an otherwise lethal dose of Vibrio cholera by previously giving them a subcutaneous injection of Vibrio cholera(1527).

Waldemar Mordecai Wolff Haffkine (RU-CH-FR) developed a vaccine for cholera which he and his colleagues used to treat many people in India. He founded the Government Research Laboratory (now Haffkine Institute) in Bombay. Haffkine first inoculated himself to prove the safety of the vaccine before inoculating others(994, 1528). 

Sir Francis Galton (GB) coined the term eugenic (well-born) to refer to the breeding of members of a species in such a way as to concentrate desirable traits within offspring(1529).

Paul Albert Grawitz (DE) described renal hypernephroma, i.e., adenocarcinoma of kidney, hypernephroid tumor, clear cell carcinoma, hypernephroma, kidney adenocarcinoma, renal adenocarcinoma, renal cell carcinoma, strumasuprarenalis cystica hemorrhagicarenal cell carcinoma(1530, 1531).

Robert Lawson Tait (GB) was the first surgeon to successfully remove a ruptured ectopic pregnancy. The operation took place on March 1, 1883, in Birmingham England(1532).

H. Leyden (DE) performed the first percutaneous needle biopsy of the lung. It consisted of the examinnation of the consolidated right lower lobe of a moribund 48-year-old man. The specimen was stained, and bacteria and WBCs were identified. Pneumonia was diagnosed(1533).

Lloyd F. Craver (US) performed transthoracic needle biopsy of the lung at Memorial Hospital in New York city as early as 1927(1534).

Emil Wilhelm Magnus Georg Kraepelin (DE) attributed mental illnesses to either exogenous treatable causes or endogenous untreatable causes. In the sixth edition of his Compendium der Psychiatrie, manic-depressive psychoses were called such for the first time. He coined the terms neuroses and psychoses(1535).

Sir William Henry Flower (GB) was the first to show that lemurs are primates. He re-implanted Homo within Linnaeus’ Primates. In the almost 150 years of systematics that followed the first edition of the Systema Naturae, this was just the second time that humans were classified with the animals. Prior to Flower, only the mid-nineteenth-century French systematist Isidore Geoffroy Saint-Hilaire had been so bold(1536).

Karl August Möbius (DE) expressed the concept of community (he called it biocoenosis), however, his essay lacked the detail and impact of later papers(1537).

Stephen Alfred Forbes (US) put forth his classic description of community in its ecological context and characterized the main goal of ecological research: to analyze how harmony is maintained through the complex predatory and competitive relations of the community. This essay drew attention to the way species are bound up with others within the community(1538-1540). 

The Journal of the American Medical Association was founded(71).

Charles Doolittle Walcott (US) identified pillar shaped masses of thinly layered limestone rock in Precambrian strata from the Grand Canyon in western North America. Although he did not understand their significance as fossils he later interpreted these and pillar like structures of limestone as fossilized reefs laid down by algae (cyanobacteria)(1541). These pillar like structures called Cryptozoon (hidden life) are now called stromatolites.

Max Joseph von Pettenkofer (DE) founded the journal Archiv für Hygiene, which became Zentralblatt für Hygiene und Umweltmedizin, Journal of Hygiene and Environmental Medicine, then International Journal of Hygiene and Environmental Health.

The journal Science was founded.

1884

“After all it is the quest after perfect truth, not its possession, that falls our lot, that gladdens us, fills up the measure of our life, nay! hallows it.” August Friedrich Leopold Weismann(1542).

Svante August Arrhenius (SE), in 1884, proposed in his doctoral dissertation that some substances when dissolved in water will behave as electrolytes and thus carry a current because they exist as charged ions in solution. Substances which can not behave as electrolytes are non-ionic. He defined acids as substances which release hydrogen ions when dissolved in water to become negatively charged ions highly capable of reacting with other compounds(1543-1545).

Wilhelm Friedrich Ostwald (LV-DE) proffered his dissolution law(1546).

Paul Böttiger (PL-DE), in 1883, synthesized congo red then patented it in 1884. Congo red was the first dyestuff capable of directly staining cotton without a mordant(1547).

H. Griesbach (DE) in 1886, was the first to report using Congo red to stain tissue(1548).

H. Bennhold (DE), in1922, reported that Congo red was found to bind avidly to amyloid protein(1549).

Paul Divry (BE) and Marcel Florkin (BE), studying degenerative changes in aging brains, first noted the characteristic green birefringence of amyloid substance when stained with Congo red and viewed under polarized light(1550-1552).

Hans-Peter Missmahl (DE), Marga Hartwig (DE), Mordechai Ravid (IL), Joseph Gafni (IL), and Ezra Sohar (IL) described the “congophilic” staining of amyloid in fixed tissue with the associated apple-green birefringence when viewed under polarized light(1553, 1554). This methodology remains essential for the diagnosis of amyloidosis.

Hermann Emil Fischer (DE) began research on the purines in 1881, coined the word purine in 1884, and synthesized a purine in 1898(1555, 1556).

Carl Weigert (DE) introduced hematoxylin stain for myelin(1557).

Hugo Marie de Vries (NL) demonstrated that solutions of substances with very similar molecular structure and at the same concentrations exert the same osmotic pressure.

He introduced a new method, that of determining the osmotic value of plant cells by immersion in solutions of known concentrations of cane sugar or potassium nitrate. He determined the concentration of each solute which would bring about plasmolysis or the withdrawal of the protoplasm from the walls of the cells. He reasoned that all solutions inducing the same minimum degree of visible plasmolysis of cells must be of equal strength(1558, 1559).

Oscar Minkowski; Oskar Minkowsky (DE) identified b-hydroxybutyric acid in the urine of diabetics along with a decrease in blood bicarbonate leading to diabetic acidosis(1560). Minkowski also proved that diabetic coma is accompanied by a decrease in the amount of carbon dioxide dissolved in the blood, and he introduced alkali therapy to counteract it.

Johannes Ludwig Wilhelm Thudichum (DE-GB) discovered hematoporphyria and worked on the chemical constitution of the brain in which he discovered, galactose, glucose, lactic acid, cerebranic sulfatides, kephalin, and the lipoid nature of myelin (present on some CNS cells); distinguished kephalin from lecithin; introduced the terms phosphotide and sphingolipid, discovered the sphingomyelin and cerebrosides in the brain—isolating phrenosin and kerasin—and proposed that “the great diseases of the brain and spine, such as general paralysis, acute and chronic mania, melancholy and others will be shown to be connected with specific chemical changes in the neuroplasm”(1561). Thudichum is considered to be the founder of neruochemistry.

Wilhelm August Oskar Hertwig (DE) presented his kernideoplasma theory saying, “I believe that I have at least made it highly probable that nuclein is the substance that is responsible not only for fertilization but also for transmission of hereditary characteristics... Furthermore, nuclein is in an organized state before, during and after fertilization, so that fertilization is at the same time both a morphological and a physiochemical event”(1191, 1192, 1562).

Heinrich Anton de Bary (DE) called for the blue-green algae (cyanobacteria) to be considered bacteria and not algae(1563).

Charles T. Druery (GB) and Frederick Orpen Bower (GB) discovered apospory in the Pteridophyta (ferns, horsetails, and club-mosses)(1564, 1565).

Theodor Wilhelm Engelmann (DE) concluded that all plastid pigments, and not merely chlorophyll, can mediate photosynthetic oxygen evolution(1566).

Hans Christian Joachim Gram (DK) found that if bacteria are stained by Ehrlich’s aniline-water-gentian-violet, then treated with Lugol’s iodine in potassium iodide, and finally placed in alcohol, the color is discharged from certain bacteria but is retained in other bacteria. He devised this method to display bacteria in tissue sections. Gram did not use any counterstains. He actually considered the iodine as a counterstain. Neither did he appreciate the significance of the fact that some bacteria did not stain by this method. The idea of gram-positive and gram-negative bacteria was not appreciated until later. Although modified, the essence of the Gram procedure remains the differential stain most widely used in bacteriology(1567, 1568).

Agar-agar replaced gelatin as the solidifying agent of choice in bacteriological media. It was introduced by Angelina Fannie Hesse, the wife of Walther Hesse, one of Heinrich Hermann Robert Koch’s early co-workers. She had obtained samples, through Dutch friends, from Batavia, where it was well known for culinary purposes and especially in the making of jam. The peculiar virtue which has established its dominance in bacteriological culture technique is that a high temperature is required to melt it, but once melted it can be cooled down to about 40°C. before it sets into a stiff and relatively transparent gel. No formal article was written describing this discovery(1569).

The Parisian engineering firm of Weisnegg produced an instrument for generating steam under pressure. It was called Chamberland’s autoclave (for Charles Édouard Chamberland) and found to be very useful in sterilizing various objects(1570).

Louis Théophile Joseph Landouzy (FR) was the first to suggest the infectious nature of herpes(1571).

Émile Julien Armand Gautier (FR) introduced a bacterial filtering device made of borax, silica, and red lead. Charles Édouard Chamberland (FR) modified Gautier’s filter so that it had a candle shape with a porcelain nipple (1570, 1572).

Eduard Friedrich Wilhelm Pflüger (DE), by allowing frog eggs to cleave under pressure between two panes of glass, showed that the planes of cleavage are modified, nevertheless, abnormal cleavage patterns do not preclude formation of a normal embryo(1573).

Ettore Marchiafava (IT), and Angelo Celli (IT) stained diplococci in meningeal exudates from patients with meningitis(1574).

Friederich August Johannes Löffler (DE) and Theodor Albrecht Edwin Klebs (DE) stained and described Corynebacterium diphtheriae, the bacterium which causes diphtheria. They used an alkaline version of methylene blue which is today the most popular version of this dye. This organism is sometimes called the Klebs-Löffler bacillus.

The following are excerpts from Friedrich August Löffler’s report to the German Imperial Health Office which beautifully describe his methodology in defining his discovery that Corynebacterium diphtheriae is the etiological agent of diphtheria (Gr. coryne, club).

“Sixty years have elapsed since Bretonneau presented his classic description of diphtheria. Despite many studies, no universally acceptable explanation of the etiology of this disease has been reached. The divergence of opinions arises from the characteristics of the disease. The appearance of individual cases varies with the age of the patient, the severity and the stage of the disease. Especially significant is the frequent difficulty in deciding whether the observed lesions are due to the frequent complications or to the disease proper. Furthermore, many inflammatory diseases other than those caused by the virus of diphtheria produce pharyngeal lesions which cannot be differentiated from diphtheria. The only significant pathognomonic differential factor is the etiological agent.

This disease is localized on a mucous membrane which is exposed to the extensive bacterial flora of the exterior world. The numerous organisms from food and drink reaching the rugose mucous membrane of the upper respiratory tract find there a favorable medium for growth. These favorable conditions are further improved by the protein-rich inflammatory exudate induced by diphtheria. It will therefore be difficult to differentiate the primary etiological agent from the proliferating multitude of saprophytes present in the normal mouth and pharynx. The failure to define the etiological agent of diphtheria has been due to the difficulty in recognizing the essential organism in the presence of many others and to the inadequacy of methods previously available for differentiation and isolation. The inadequacies of the experimental methods have been overcome by Koch.

Earlier investigators sought the specific agent in the mucous exudate of the pharynx rather than the internal organs. Experience from accidental infections justified this choice in source material, since physicians and nurses aspirating exudate by mouth suction through tracheal cannulae would acquire the disease if they came in contact with it, but the disease was not acquired by contact with material from other organs and body fluids….

If, then, diphtheria is a disease caused by microorganism, three postulates must be fulfilled:

1. The organism typical in form and arrangement must be consistently demonstrated in the diseased area.

2. The organism which by its behavior appears responsible for the pathological process, must be isolated and grown in axenic culture.

3. A specific experimental disease must be produced with the axenic culture….

An evaluation of the results of the past investigations reveals that these postulates have not been fulfilled. Previous investigators saw bacteria in pseudomembranes, but few gave detailed data regarding the types of bacteria present. The earliest investigators stated merely that molds were present. The status of bacteriology at the time did not permit more precise differentiation, technique being limited to smear preparations. Subsequently, sections were prepared which demonstrated the relationship of molds to tissue. Molds were more frequent in the upper layers of pseudomembranes. Micrococci predominated and were located in the lymph vessels. The demonstration of bacteria in internal organs was uncertain and depended upon resistance of tissue structures to the types of reagents used, acetic acid, alkali, ether, etc. Reliable investigations, utilizing stains, Abbe condensers and oil immersion, revealed the absence of bacteria in internal organs and their presence in pseudomembranes. Attempts to culture the micrococci resulted in mixed growth, since the source material was tonsillar overlay in which other bacteria were always present. Cultures of tissue from internal organs were negative.

Attempts to transmit diphtheria to animals, using a variety of infecting procedures did not lead to a truly typical diphtheria. Intramuscular injection of diphtheritic material produced a hemorrhagic inflammation. Corneal injection led to keratitis and intratrachael injection led frequently to a pseudomembranous tracheitis. Most investigators could not produce these reactions with disrupted organic materials that were used as controls, but some investigators could produce identical changes with non-diphtheritic material….

It seemed indicated, using Koch’s recently developed methods for isolation and cultivation of bacteria on solidified culture media, to reinvestigate types of bacteria associated with diphtherial tissue, to determine which might be of etiological significance, to grow these in axenic culture, and finally to perform inoculation experiments with axenic cultures in the largest possible number of animal species….

In most instances the source specimens at my disposal were not accompanied by comprehensive clinical data; acquisition of such data would have required full attendance in the hospital. However, I attempted to determine the clinical course, and especially the duration of illness, of source cases. Even though scarlatinal diphtheria was differentiated from diphtheria, the frequency of the combined disease led me to include such cases in the scope of this study.

For examining microscopic sections it was necessary to use a staining method which would be applicable to a wide variety of bacteria. None of the available methods, namely the Weigert nuclear stain, the pico-carmine gentian-violet differential stain and the Koch-Ehrlich differential stain for tubercle bacilli were satisfactory. While studying sections of syphilitic sclerae, I found a more intense and rapid staining was achieved with a mixture of 1 cc. of concentrated alcoholic methylene blue in 200 cc. of water when 0.2 cc. of 10% potassium hydroxide was added than when such a mixture lacked potassium hydroxide. Since this weak methylene blue solution did not stain some types of bacteria adequately, I raised its concentration, and the most rapid and intense staining was achieved with 300 cc. of concentrated alcoholic methylene blue in 100 cc. of a 1-10,000 dilution of potassium hydroxide in water. The sections were immersed in the stain for several minutes and then rinsed in 0.5% acetic acid to remove excess stain and achieve differentiation of nuclei. They were then dehydrated in alcohol, treated with cedar oil and finally mounted in Canada balsam. Anthrax, rabbit and mouse septicemia bacilli, typhoid and glanders bacilli, erysipelas micrococci, Micrococcus tetragenus, spirochetes of relapsing fever, fungal mycelia, etc., were all equally well stained. This technique thus approached a universal staining method….” 

Löffler examined clinical materials from twenty-seven patients. Anatomical diagnosis were followed by a description of sections from various tissues and organs.

“ A consideration of the case material reveals that 3 types of cases may be recognized. In one type, chain-forming micrococci appear to play a major role. The mucosal surfaces are completely denuded of epithelium are greyish yellow in color and there has been a loss of tissue as a result of necrosis. Pseudomembranes are absent. The micrococci are present on the surface and penetrate into the tissues forming wedge- or tongue-like areas of necrosis marginated by a narrow unstained border followed by a layer of proliferating cells. The micrococci may thus penetrate into the lymph vessels and then spread to other organs of the body where they form plugs in the capillaries. A similar picture is seen accompanying other diseases such as smallpox, typhus fever, puerperal fever, etc., where chain-forming micrococci are known to produce complications accompanying the primary disease. Similarly these organisms are most likely a complication of primary diphtheria, thus the frequency of the occurrence of micrococci on and in mucous membrane in diphtheria should not lead to confusion regarding the true primary agent….

Another type of case offers more direct evidence of the secondary invasive role of the micrococci. True pseudomembranes are present and in addition to micrococci, a second type off organism is seen. Too few micrococci are present to account for the observed damage, but the other organism may readily account for the pseudomembrane formation. The second type of organism is Kleb’s bacillus. Unlike the micrococcus, the Kleb’s bacillus alone may be present in typical cases that are characterized by the presence of a thick pseudomembrane in the pharynx, larynx and trachea. A variety of bacteria are irregularly distributed on the surface of the pseudomembrane. Below the surface are small masses of bacilli which stain intensely with methylene blue….

The third type of case strongly supports the hypothesis that the bacilli occurring just below the surface are the etiological agents. It can be illustrated by the case of a child who died on the third day of the disease. The pseudomembrane in the trachea, which undoubtedly was the last such element to be formed, was a thick membrane containing masses of the characteristic bacillus alone. Another child who also died on the third day of the disease with dyspnea and symptoms of lung inflammation had not only a pseudomembrane in the trachea but also masses of rods in the alveoli as well….

From the pathologico-anatomical studies it could not be determined whether the micrococci or the bacillus was the etiological agent. The only remaining course was to obtain axenic cultures of each of the two types of organisms and, by animal inoculation, to determine which could produce a disease analogous to human diphtheria.

The cases chosen for the cultural study of the coccus were those showing chain-forming micrococci either solely or in overwhelming proportion in microscopic smear preparations of tonsils and internal organs. Meat broth-peptone-gelatin was used as culture medium. Fragments from infected tonsils were incorporated into the liquified medium on slides, and the mixtures were covered with glass cover slips. The gelatin was then allowed to solidify, permitting the development of isolated colonies. The preparation of axenic cultures from internal organs was simpler. To eliminate surface contaminants, the organs were washed in 5% phenol for 10 minutes to kill vegetative forms of bacteria and in 1% bichloride of mercury for 5 minutes, to kill spores. The organs were dried on blotting paper. After the surfaces were dried, the organs were cut with a hot glowing knife and hot glowing forceps were used to tease portions of tissue for culture study. With these methods axenic cultures of chain-forming micrococci were obtained from five cases: 2 of scarlatinal diphtheria and 3 of typical diphtheria.

The chain-forming micrococci grew slowly in gelatin. After three days of growth, examination with direct light revealed small, round, grayish translucent colonies…. In reflected light the colonies were white and granular, indistinguishable from erysipelas cultures. The micrococci grew luxuriantly in meat infusion medium (meat infused with 1% peptone, 0.5% NaCl and 1% dextrose). After 24 hours of incubation at 37°C. finely threaded floccules appeared. These floccules were formed by long interweaving chains comprising up to 100 cocci. The organism grew on meat infusion broth solidified with 1% agar, but growth was more luxuriant when serum was used as gel. Pure coagulated serum was inferior to a mixture of 1 part meat infusion medium and 4 parts serum.…. Growth on cooked potato (Solanum tuberosum), was slow. In the various culture media, bacterial cell division was observed in both the horizontal and longitudinal plane.

Animal passage studies were performed with four axenic cultures of chain-forming cocci….”

After extensive animal experimentations with mice, guinea pigs, rabbits, birds, dogs, and apes, Löffler was finally convinced that the micrococcus could not produce a diphtherial disease in animals. He concluded:

“Since, (1) the chain-forming cocci did not produce a diphtheria-like disease in any experimental animal species, (2) the cocci were see in only a limited proportion of diphtheric cases in man, (3) they occurred in diphtherial lesions only in association with a type of bacillus to be described more fully below, and finally, (4) they were also found in internal organs in other diseases, we are justified in concluding that the chain-forming cocci are only accidental secondary invaders in diphtheria. The chain-forming micrococci may, however, produce a diphtheria-like disease when the pharynx is invaded and the organisms spread through the lymphatics to the trachea and lungs. Such was the case of an infant who had a nasal discharge and a slight pseudomembrane in the throat. After several days the infant became hoarse and a dyspnea of increasing severity set in followed by death. At autopsy the pharynx was clear, but there was a thin grey pseudomembrane on the epiglottis, trachea, and bronchi, and areas of hemorrhagic bronchopneumonia in the lungs. In sections the epithelium of the epiglottis was still intact, but the lymph vessels in the mucous membrane below were filled with micrococci. The trachea was denuded of epithelium and covered with an exudate of inflammatory cells and micrococci. Micrococci were also seen in the mucous membrane of the lungs. All other organs were normal. The disease could be interpreted as a diphtheria-like mucous membrane erysipelas.

The characteristic rods, which [had been observed previously by Klebs] were slightly bent and enlarged at the poles, and were frequently seen in smears and sections, could not be cultured on meat infusion-peptone-gelatin…. It was therefore decided to culture the material on coagulated blood serum with incubation at body temperature. Despite the possibility of rapid overgrowth with putrefying contaminants, the very first trial using this technique met with success.

Segments of organs from a dead patient were sent to me in a glass jar. The organs lay for several hours in blood that had seeped from the cut surfaces of the organs. Liver, heart, and kidney which in smears yielded only micrococci, were washed in 5% phenol followed by 1% mercuric bichloride. Fragments of these organs were cultured on meat infusion-peptone-gelatin incubated at room temperature, coagulated beef serum incubated at 37°C. In addition, scrapings from areas of pseudomembrane of the pharynx, showing both micrococci and Kleb’s bacilli in smear preparations, were cultured on coagulated sheep serum incubated at 37°C. On the following day discrete translucent colonies were seen in all serum cultures. Most of these colonies consisted of micrococci, but occasional ones were of rods identical with the ones in the pseudomembranes. After three days of incubation the colonies of micrococci were small, yellowish and translucent, whereas the colonies of rods were large, whitish and opaque. No Kleb’s bacilli were recovered from gelatin cultures. Occasional colonies of rods were now seen in cultures of liver and kidney, which until then had revealed only micrococci. However, the presence of the rods on the peripheral areas of the internal organs is, in my estimation, a post-mortem change caused by the organs and pharynx being held in the same fluid.

For animal passage experiments loopfuls of growth from colonies of characteristic rods were suspended in 10 cc. amounts of sterile water and loopfuls of those suspensions were cultured on fresh serum slants. The organisms grew as isolated colonies. Third passage cultures prepared from isolated colonies, were used for animal inoculation. Such axenic cultures were certainly free of original tissue. The medium consisted of three parts calf or sheep serum and one part veal bouillon containing 1% peptone, 1% dextrose and 0.5% NaCl. Growth on this medium was luxuriant; in 2 days a 1 mm. thickness of culture was evident and isolated colonies attained a diameter of 0.5 cm. This medium was used for subsequent cultures. Another axenic culture of rods was obtained from the tracheal pseudomembrane from another case, which in smear preparations revealed many rods.

Following the isolation of rods from autopsy material, recovery of axenic cultures of rods from living patients presented no difficulties. Axenic cultures were obtained from 4 successive living cases. Portions of membrane were removed for microscopic section and for axenic culture isolation as described above. In sections, micrococci predominated on the surface, but rods were abundant in the cellular layer immediately below the surface. The fibrinous layer was free of bacteria.

In culture, the rods appeared first followed by the micrococci. Axenic cultures of rods were obtained as before. The rods were non-motile and stained intensely with methylene blue. They were straight, or slightly bent, about as long as and twice as thick as tubercle bacilli. The larger ones were segmented with thickening at their points of junction. The ends were sometimes enlarged. Barred staining and intensified polar staining were frequent.

Treatment of methylene blue smears with dilute iodine intensified the stain in the polar granules and decolorized the remaining areas of the cells. The polar granules did not appear to be spores. They did not glisten in reflected light, they stained readily, and rods with polar granules were destroyed by heating for 30 minutes at 60°C. Cultures were viable for 3 months. The rods required temperatures above 20°C. for growth and cooked potato (Solanum tuberosum) medium did not support their growth.

Of major interest was the effect of axenic cultures of the rods in various animal species. Six axenic cultures were tested in mice, rats, guinea pigs, rabbits, apes, small birds, pigeons, and chickens. The animals were inoculated by subcutaneous route, application to traumatized and intact mucous membranes, and by inhalation.”

After having shown that mice and rats were refractory to any pernicious effect of the rods, Löffler found that the bacillus was highly pathogenic for guinea pigs. He performed pathogenicity trials, both with tube culture inocula and tissue from infected animals. Twenty-eight guinea pigs were used and all were injected by subcutaneous route. He presented the observations and results in considerable detail, and summed up as follows:

“Pairs of guinea pigs were inoculated subcutaneously with each of a series of cultures. All guinea pigs were sick on the day following injection; they were listless, coats were ruffled, and there was swelling at the site of injection. The animals died within two to seven days. There were grayish white membranes at the sites of injection, edema in the surrounding subcutaneous tissue, bloody serous exudate in the pleural cavities, and brownish red dense and atelectatic areas in the lungs. The remaining internal organs were normal. Bacilli were recoverable only at the site of injection.

I have presented the results with this series of guinea pigs in detail, first because they demonstrate that bacilli isolated from the various human cases produced the same pathology, second because they demonstrated conclusively that death resulted not from a generalized dissemination of bacilli, but from an effect induced by the bacilli at the site of injection. The hemorrhagic edema, the pleural exudate, the brownish red areas of consolidation in the lungs, where bacilli could not be demonstrated, were conclusive indications that a toxin generated at the site of injection and transmitted through the blood stream, induced severe damage to vessel walls. The toxin generated by the bacilli in the guinea pig is undoubtedly similar to the toxin of human diphtheria. The toxin in man, like that in the guinea pig, appears to act primarily on blood vessels. 

Other noteworthy observations in the guinea pig were the formation of grayish white pseudomembranes at the sites of inoculation, and the disappearance of bacilli in lesions after several days, despite the lethal outcome in the animals.

The canary, finch, siskin, etc., were more susceptible than the guinea pig, when inoculated intramuscularly…. All birds died by the third day following infection with the symptoms described above. Bacilli were recovered only from the site of inoculation and all cultures from internal organs were sterile. When birds were inoculated with nutrient broth-peptone-gelatin cultures, survival rates could be prolonged up to 5 days, but the pathological changes were the same as those obtained after injection with cultures on coagulated serum and all cultures from internal organs were sterile. As in guinea pigs, the animals died from the effects of the localized infection.

The responses of rabbits were more variable than those of guinea pigs and small birds. Cultures of the bacillus were applied on the scarified cornea or conjunctiva, injected intramuscularly in the thigh or applied on the trachea by means of a tracheotomy. Where tracheotomies were performed, both the muscle and skin wounds were closed with sutures. A small number of intravenous inoculations were also performed.”

Löffler performed an extensive series of rabbit inoculations. Twenty-five rabbits were injected with three different strains.

“The various isolates of the bacillus induced the formation of dense fibrinous membrane on the conjunctival and tracheal mucous membranes of a high proportion of the test rabbits. The pseudomembrane formation must be attributed to the bacilli because the operative procedure alone and other bacteria isolated from diphtheric material injected in the same manner did not produce these effects.

The bacilli induced the formation of pseudomembranes in experimental animals, but the bacilli in the experimental pseudomembranes were not as numerous as in human cases and were distributed differently. The membranes in animals were essentially limited to the site of inoculation and contained few bacilli. Despite the limited site of membrane formation, as in guinea pigs, the infections could lead to death. Where death occurred followed intratracheal inoculation, the mechanical obstruction caused by the intratracheal pseudomembrane possibly could be implicated as the primary cause of death but deaths following conjunctival or intramuscular inoculation must be attributed to the formation of toxin at the site of inoculation and its subsequent dissemination through the blood stream; intravenous inoculation of large numbers of bacilli in rabbits did not lead to death. The organisms seen in rabbit tissues stained poorly and showed aberrant giant forms. These forms and staining reactions were encountered in the unfavorable nutrient gelatin cultures and imply that the rabbit body is not a favorable environment for the development of the bacilli.

Since there are reports of many cases of transmission of diphtheria from man to larger birds and vice versa, it appears especially interesting to study the effect of the bacilli on pigeons and chickens.

The third serial transfer of bacilli strain No. 1 was injected under the tongue and into the gums of three pigeons; one of the three pigeons was also injected in the breast muscle. A yellowish exudate developed at the sites of injection and spread over the beak cavity. The infiltration in one animal interfered with food intake and led to death on the 11th day. In both other animals, the exudates were resorbed and the animals recovered.

Pigeons are useful for such studies because the laryngeal and tracheal mucosa are easily injected without traumatization. These areas are exposed when the beak is opened. It was thus possible to see if introduction of the rods into the untraumatized respiratory tract could induce pseudomembrane formation.

The trachea of a pigeon was streaked with the 13th serial transfer of strain No. 1 and remained well. The fifteenth passage of the same bacillus was then applied to the trachea through tracheotomy. The soft tissues of the throat became edematous on the following day and a pseudomembrane was formed on the larynx. The animal died of respiratory failure on the 7th day. At autopsy there was a yellowish fibrinous pseudomembrane at the tracheotomal wound, larynx and buccal cavity, containing a variety of bacteria including the characteristic rod.”

He then repeated the experiment with some variations, using various strains that had gone through five to twenty-three serial transfers in vitro. The variations in the route of infection involved intratracheal application through the beak cavity and through tracheotomy, injection into multiple sites in the beak cavity, and intramuscular injection. Application of the cultures through tracheotomy led to death. Injection into beak cavity or muscle was not fatal; a local lesion developed but healed in approximately two weeks. Löffler then demonstrated a similar range of pathogenic reactions in chickens with six cultures injected in a total of eleven animals. Summarizing:

“In general, these experiments demonstrated that pigeons and chicks are not nearly so susceptible as small birds, namely finches, sparrows, and canaries.

It is important at this point to discuss observations on two pigeons and one rooster. In one of the pigeons injected with strain No. 1, a weakness in the limbs and the inability to fly was evident after 4 weeks. This progressed to severe paralysis and then to eventual recovery. This animal, which had been injected in the beak cavity with a axenic culture of rods isolated from a fatal human case, had developed a pseudomembrane that regressed. The paralytic episode in the bird was reminiscent of the transitory paralysis that occurs sometimes in human diphtheria, and might be attributed to the specific organism.

This conclusion was strengthened by a similar observation on a rooster that had been infected by tracheal application on the 25th serial transfer of the same strain. After transitory pseudo membrane formation, the animal developed paralysis of the legs and wings beginning 4 weeks after injection. The paralysis did not regress. Since such a symptomatology for chickens is not described in the literature, I believed that the paralysis was due to diphtherial infection. Paralysis was also encountered in a rabbit that had received the very same inoculum.

The pigeon that had been paralyzed and had recovered was reinjected in the beak cavity and breast with the 30th transfer of strain No. 1. A transitory pseudomembrane formation was again followed by paralysis. The animal died 23 days after the second injection. Autopsy revealed pneumonia to be the cause of death and there were masses of uric acid crystals around the joints and connecting tendons. This paralytic episode therefore was not of diphtherial origin but due to a uratic arthritis. 

The rooster was then sacrificed. The entire rump musculature was atrophic, the sternum and ribs were distorted, the junctions of the ribs with the sternum were swollen, and the vertebra softened. Thus the animal was suffering from a rachitis of the rump, bones and muscles, that accounted for the paralysis. Again diphtheria did not seem to be directly involved.”

Similarly, for the second pigeon in this group of three large birds that developed paralysis, the symptoms were nondiphtheritic in origin. At autopsy a myxoma was found in the lower spinal cord.

“I considered it necessary to present the information in these three birds in order to spare subsequent investigators the possibility of being misled by such observations.

There remains to be described two experiments in an ape. A long-tailed Java ape was infected by streaking and traumatizing the pharynx with a stiff brush infected with the 9th serial transfer of strain No. 3. A small transitory ulcer resulted. The animal was then injected in the conjunctiva and subcutaneously in the axilla. A transitory swelling occurred in the conjunctiva and an edematous infiltration followed by ulceration and healing occurred in the axilla. These experiments indicated that apes are not susceptible to diphtheria.

In the experiments so far discussed natural modes of infection were not used. A more natural method of infection was then tried. Three chickens, 3 pigeons, 3 rabbits and 3 guinea pigs were placed in a chamber 1 meter X 0.5 m. X 0.5 m. Three hundred cc. of a densely turbid suspension of the 6th serial transfer of bacillar strain No. 3 were then atomized into the chamber. An ape was placed in a cylindrical chamber 0.75 meters high and 0.5 meters in diameter. The cylinder was equipped with the necessary food, water and bedding. One hundred and fifty cc. of the same bacterial suspension were sprayed into the cylinder. Even though the animals were exposed to infection both by inhalation and ingestion of contaminated food, none became sick. Similarly repeated attempts to infect rabbits and guinea pigs by application of cultures to undamaged mucous membranes were unsuccessful.”

Löffler decided to try one more route of infection, the vaginal inoculation of guinea pigs. He noted that: “Recovery occurred in most animals despite severe initial symptoms of intoxication.” This recovery was due, he thought, to the fact that the animals could remove the inoculum and the membranes that might form by licking. He continued:

“Such rapid removal and subsequent recovery could not be expected to occur following subcutaneous injection of organisms.

Before further discussing the evidence regarding the implication of the bacillus as the etiological agent of diphtheria we should determine whether or not the bacillus can be found in the oral and pharyngeal secretions of healthy individuals. Children were used for this study because they are the most susceptible age group. Cultures on broth peptone sugar serum medium were taken from the oral mucous of 20 children, ages 1 to 8, and cultures from 10 adults served as controls. The cultures were examined after three days of incubation and methylene blue smears were prepared from all grayish white or white colonies. These colonies were found to consist either of micrococci or of short ovoid bacilli that were not even remotely similar to our specific rod. Axenic cultures isolated from three colonies of the short bacilli were each injected into two guinea pigs and were found to be avirulent.

In one culture from a child, bacilli morphologically similar to the diphtheric rods were observed. They were slender, the size of tubercle bacilli, showed intense polar staining and polar clubbing. After four in vitro transfers, the culture of this organism was injected subcutaneously into two guinea pigs. Both animals were sick on the day following injection and died on the third day. In one there was a grayish pseudomembrane at the site of inoculation and edema in the surrounding area. The axillary glands were swollen and hemorrhagic, the kidneys and adrenals were engorged with blood. The specific bacilli were only observed at the site of inoculation. The findings in the other guinea pig were complicated by tuberculosis. Fifth passage culture of the same organism was then injected subcutaneously into three guinea pigs. All three animals died after two days with the typical diphtheric syndrome. There could be no doubt that this organism isolated from a healthy child was the same as the bacillus isolated from cases of diphtheria.

The following facts favor designating the bacillus as the etiological agent of diphtheria: The rods were found in thirteen of twenty-seven typical cases of diphtheria with fibrinous pharyngeal exudate. The rods were present in the oldest areas of the pseudomembranes and were deeper than other organisms. Cultures of the rods were lethal when inoculated subcutaneously into guinea pigs and small birds. Whitish and hemorrhagic exudates developed at the sites of injection with diffuse edema in the surrounding tissues. As in humans, the internal organs were free of lesions. The bacilli produced pseudomembranes on the exposed tracheae of rabbits, chickens and pigeons, on the scarified conjunctivae of rabbits and on the vaginal vulvae of young guinea pigs. Another characteristic effect was severe lesions of the blood vessels as evidenced by the bloody edema, hemorrhagic lymph glands and pleural exudate. As in humans, younger animals were more susceptible than older ones.

The following points may be made against the conclusion that the bacillus is the etiological agent of diphtheria:

1. The bacilli were absent in a number of typical cases of diphtheria.

2. The bacilli in the pseudomembranes of rabbits and chickens were not arranged as in the pseudomembranes of man.

3. The bacilli did not produce disease on the untraumatized pharyngeal mucous membranes of animal species which were susceptible when the mucous membranes were traumatized.

4. Animals surviving experimental infection did not become paralyzed.

5. Finally, a typical virulent bacillus was found in the throat of a healthy child.

The proof that the bacillus is the etiological agent of diphtheria is thus not complete. However in typical human cases where the bacilli were not found, they might have been recently eliminated, as was indicated in the experiments on vulval infection in guinea pigs. The third objection may not be important since it has been frequently observed in man that diphtheria is preceded by catarrh of the throat and air passages. The effect of sharp north or northeast winds on the incidence of such catarrhs is well known. In addition one should note that the experimental animals used in these studies did not possess an organ comparable to the human tonsil. The tonsil with its many crypts and folds offers a favorable site for growth of the organism. Paralysis was not observed in the susceptible animal species because few survived infection and, in addition, its frequency even in human diphtheria is relatively low. A maximum incidence of 11% has been reported. As far as the last objection is concerned, it is conceivable that agents which are rarely infectious could occasionally be found in healthy subjects.

In my estimation, the noted objections are not major ones. The future lines of study seem clear. Special emphasis should be put on the characterization of the toxin. It should be possible, in view of our knowledge of the nutritional requirements of the organism, to produce large amounts of the chemical substances that it forms. If the same specific compound occurs in the culture medium, the infected guinea pig and the diphtheria patient, it would be an important argument in support of the bacillary etiology of the disease”(1575, 1576).

Georg Theodor August Gaffky (DE) isolated the bacterial cause of typhoid, Salmonella typhosa, in axenic culture(1577).

Louis Pasteur (FR), Charles Édouard Chamberland (FR) and Pierre Paul Émile Roux (FR) demonstrated that the virulence of the rabies virus increased up to a fixed maximum by successive passage through a host animal. It was shown that the rabies virus is attenuated for the dog, rabbit, and guinea-pig, by passage through a series of monkeys(1578, 1579).

Louis Pasteur (FR), Charles Édouard Chamberland (FR), and Pierre Paul Émile Roux (FR) demonstrated that a dog can be protected from an injection of virulent rabies by first inoculating it with spinal cords of rabies infected rabbits which were dried for two weeks and ground-up in a broth (1579).

Vasili Yakovlevich Danilevskii; Vasili Yakovlevich Danilewsky (RU) discovered many of the blood parasites of birds including the parasitic malarial protozoan (Plasmodium spp.) which he associated with the disease(1580-1583). 

Antonio Carle (IT) and Giorgio Rattone (IT) were the first to produce tetanus in experimental animals (rabbits). They injected them with pus from a fatal human tetanus case(1584). This strongly suggested that an infectious agent might be the cause.

Arthur Nicolaier (DE) was the first to describe Clostridium tetani, the etiological agent of tetanus. He did not purify it nor prove that it causes tetanus(1585). This organism is sometimes referred to as Nicolaier’s bacillus.

Shibasaburo Kitasato (JP) successfully cultivated the tetanus bacillus, Clostridium tetani , and demonstrated that it causes lockjaw. He showed that culture media in which the organism had been grown were still highly toxic for animals after the bacilli had been removed by filtration(1586). He also proved the inability of the tetanus bacillus to invade the blood stream and showed the disease to be an intoxication(1587).

Edmond Isidore Étienne Nocard (FR) demonstrated the protective effect of passively transferred tetanus antitoxin in horses. The Pasteur Institute supplied the antitoxin(1588). Passive immunization in humans was used during World War I. 

Pierre A. Descombey (CA) prepared tetanus toxoid(1589). The effectiveness of active immunization with tetanus toxoid was demonstrated in World War II.

Adam Sedgwick (GB), grandnephew of Adam Sedgwick (GB) the geologist, proposed the enterocoel theory which states that the coelom is of enterocoelous origin having formed as the result of the pinching off of outpouchings of the gastric cavity(1590). His researches on the wormlike organism Peripatus, which he recognized as the zoologically important connecting link between the Annelida, or segmented worms, and the Arthropoda, such as crabs, spiders, and insects are also very important(1591, 1592).

William Bateson (GB) showed that Balanoglossus (the acorn-worm), with a larval stage resembling that of echinoderms, possesses gill-slits, a notochord, and a dorsal nerve chord. This established this creature as a chordate. This was the first indication that chordates are offshoots of a primitive echinoderm stock, a theory now widely accepted. Bateson also described how in Enteropneusta the coelom arises from sacs formed from a portion or portions of the primitive enteron(1593, 1594).

Angelo Mosso (IT), a gifted investigator, invented the ergograph for measuring muscular work, the ponometer to measure pain, a sphygmomanometer for measuring blood pressure in the finger, a plethysmograph to measure the volume of organs. He showed that fatigue is due to the buildup of a toxic substance in muscle tissue(1595, 1596).

Issac Ott (US) discovered that the center for temperature regulation is located in the corpora striata region of the brain(1597). 

Greene Vardiman Black (US) was the first to routinely employ nitrous oxide for extracting teeth without pain and in 1870 invented the cord-driven dental engine. Black wrote important books on dental care such as: The Technical Procedures in Filling Teeth; The Formation of Poisons by Microorganisms; A Biological Study of the Germ Theory of Disease; A Study of the Histological Characters of the Periosteum and Peridental Membrane; Descriptive Anatomy of the Human Teeth; and A Work on Operative Dentistry. Black also perfected the use of the amalgam for filling teeth(1598-1602).

Ernest Charles Lasègue (FR) wrote a classic work on the cerebrum dealing with vascular disturbances of the brain. The Laségue sign is ascribed to him although there is some dispute that others preceded him in their descriptions(1603, 1604).

Carl Koller (CZ-US) was the first physician to use a local anesthetic during surgery. He used cocaine for an operation on the eye(1605). Anesthesia in the form of eye drops (cocaine) obviated the hazards of general anesthesia and its post-operative complications.

Alfred Einhorn (DE) and Emil Uhlfelder (DE) produced an alkamin ester of para-aminobenzoic acid which they named procaine(1606, 1607). Procaine would later be renamed Novocaine. Einhorn was issued a U.S. patent for procaine in 1906.

Nils Löfgren (SE), in 1943, synthesized Lidocaine under the name Xylocaine. His colleague Bengt Lundqvist (SE) made the first injection anesthesia experiments on himself(1608). In addition to being a local anesthetic xylocaine has been used to prevent tachycardia, treat arrhythmias arising during heart surgery, treat post-operative arrhythmias, and treat arrhythmias resulting from myocardial infarction. It is derived from gramine which is an alkaloid found in a reed plant (Hordeum vulgare) of Central Asia. Lidocaine has now largely replaced Novocaine.

Ludwig Wilhelm Carl Rehn (DE) performed the first thyroidectomy for exophthalmic goiter. The operation reported was performed in 1880(1609).

Louis A. Duhring (US) provided a description of dermatitis herpetiformis which has remained valid to this day(1610). It is also called Duhring’s disease

William Stewart Halsted (US), in 1884, performed the first documented case of brachial plexus anesthesia when he injected the brachial plexus in the supraclavicular region under direct vision. He injected exposed roots of the brachial plexus with cocaine(1611). This is sometimes called conduction anesthesia.

K. Mulley (DE) developed the interscalene approach to brachial plexus block in order to avoid pneumothorax(1612).

Alon P. Winnie (US), Lennart Häkansson (SE), and Poul Buckhöj (SE) developed the modern interscalene approach using the level of the sixth cervical transverse process as the reference point for needle insertion(1613).

Magnus Blix (SE), Alfred Goldscheider (DE), and Henry Herbert Donaldson (US) described spots on the skin associated with different sensations(1614-1616).

Moses Allen Starr (US) reported that lesions in the region of the Rolandic fissure can cause sensory disturbances in humans. Typically somatosensory disturbances involved lesions posterior to the fissure of Rolando, most often in the post-central gyrus or parietal region. He noted that some cases of frontal lobe injury show deficiences in self-control, lack of self-restraint, and undue excitability. These changes result in a change of character, which he attributed to a loss of inhibition and good judgement(1617, 1618).

Henri Verger (FR), Joseph Jules Déjérine (CH-FR), and J. Mouzon (FR) were the first to demonstrate convincingly that damage to the human parietal lobe may result in relatively minor disturbances of pain and temperature sensitivity, but clear deficits in tactile localization, postural sensitivity, and fine tactile discrimination(1619, 1620).

Mieczyslaw Minkowski (CH), using monkeys, concluded that cutaneous discriminative ability is chiefly, but not exclusively, represented in the post-central gyrus of the brain(1621).

Johannes Gregorius Dusser de Barenne (NL-US) treated specific areas of the monkey cortex with strychnine and, like Minkowski, concluded that the precentral cortex has some sensory functions, but that the parietal cortex is the major projection area for cutaneous sensation(1622-1624).

Lord Edgar Douglas Adrian (GB) discovered a second somatosensory cortex, just above the Sylvian fissure in the brain of the cat(1625).

Joannes Gregarius Dusser De Barenne (NL-US), Clyde Marshall (US), Leslie F. Nims (US), and William E. Stone (US) found that strychnine placed on either side of the brain’s central (Rolandic) sulcus greatly exacerbated sensitivity to somatic sensory stimulation. They described the activity of the brain after strychnine application(1626). 

Sir Victor Alexander Haden Horsley (GB) induced both cretinism and myxedema in monkeys by experimentally removing the thyroid gland. He came to the conclusion that the cretinous symptoms following thyroidectomy are due to the arrest of a function of the thyroid gland(1627, 1628).

1885

“The death of this child appearing to be inevitable, I decided, not without lively and sore anxiety, as may well be believed, to try upon Joseph Meister the method which I had found constantly successful with dogs…. I thus made thirteen inoculations, and prolonged the treatment to ten days…. On the last days, therefore, I had inoculated Joseph Meister with the most virulent virus of rabies… Three months and three weeks have elapsed since the accident, his state of health leaves nothing to be desired.” Louis Pasteur(1629).

"Science meets with two obstacles, the deficiencies of our senses to discover facts and the insufficiency of our language to describe them. The object of the graphic methods is to get around these two obstacles; to grasp fine details which would be otherwise unobserved; and to transcribe them with a clarity superior to that of our words." Étienne Jules Marey(1630).

Baits containing poisons (bran-arsenic) were developed for insect control purposes. The first insecticide (arsenic) was recommended for use in soil to control insects damaging plant roots(138).

Paul Ehrlich (DE) observed that certain vital dyes administered intravenously to small animals stained all of the organs except the brain. He interpreted this to mean that the brain had a lower affinity for the dye than the other tissues(1631).

Max Lewandowsky (DE) coined the phrase blood-brain barrier (Bluthirnschranke)(1632).

Edwin Ellen Goldmann (DE) injected dye into the spinal fluid of the brain directly. He found that in this case the brain would become dyed, but the rest of the body would not. In light of Ehrlich’s finding this clearly demonstrated the existence of some sort of barrier between the two(1633, 1634). These experiments demonstrated that the central nervous system is separated from the blood by a barrier of some kind, i.e., the blood-brain barrier.

Lina Salomonovna Stern (LT-CH-RU) and Raymond Gautier (CH) proposed the existence of a blood-brain barrier (hemato-encephalic barrier)(1635). 

Thomas S. Reese (US) and Morris J. Karnovsky (US), and Milton W. Brightman (US), Yngve Olsson (SE), and Igor Klatzo (RU-LT-PL-CA-US) identified the site of the blood-brain barrier as the vascular endothelial cells of the brain of all vertebrates with the exception of the elasmobranch fishes. In elasmobranchs glial cells form the blood-brain barrier(1636-1638).

Michael W.B. Bradbury (GB) reported that the blood-brain-barrier is formed by a complex cellular system of endothelial cells, astroglia, pericytes, perivascular macrophages, and a basal lamina with lipid soluble substances easily penetrating the cerebral endothelial plasma membranes and readily attaining equilibrium between blood and brain tissue(1639).

Robert Behrend (DE) and Adolf Pinner (DE) coined the words uracil and pyrimidine respectively(1640, 1641).

Thomas Richard Fraser (GB) was the first to isolate strophanthinic acid, a cardioactive glycoside, from the strophanthus plant(1642).

Albert Fraenkel (DE) produced an injectable form of strophanthinic acid(1643).

Raphael Horace DuBois (FR) reported the first definitive experiments regarding the nature of the chemical components necessary for light production by organisms. He found that the luminous organs of a beetle would cease to emit light if immersed in hot water. He also noted, however, that a cold water extract which ceased to luminesce could be stimulated to emit light by adding the hot-water extract. He proposed that the hot water extract contained a substance stable to heat, luciferin, which was destroyed during its luminescent oxidation by a catalyst, luciferase, present in the cold-water extract(1644).

E. Newton Harvey (US) found that certain fish possess light organs which contain luminous bacteria as the source of their luminescence(1645).

William David McElroy (US), and Bernard L. Strehler (US) found that ATP can phosphorylate luciferin(1646). In fireflies when luciferan-phosphate is split, light is emitted.

Shimon Ulitzur (IL) and J. Woodland Hastings (US) reported that the light-emitting reaction of luminous bacteria involves a luciferase-catalyzed oxidation of reduced flavin mononucleotide (FMNH2) by molecular oxygen, with the concomitant oxidation of a long-chain aliphatic aldehyde, probably tetradecanal(1647).

Ludwig Edinger (DE) and Paul Emil Flechsig (DE) discovered that many dorsal root fibers, after ascending in the dorsal column, effect synapses in the bulbar nuclei with secondary neurons which pass to the thalamus(1648, 1649).

Henry Pickering Bowditch (US) demonstrated the indefatigability of nerves. This was accomplished by paralyzing the motor nerve-endings in the muscle with curare, the first experiment in producing a functional nerve-block with a drug(1650).

Johann Friedrich Miescher-Rüsch (CH), in a paper that is one of the masterpieces of physiology, summarized all the evidence available and reached the conclusion that it is the variations in the amount of carbon dioxide which principally induce the immediate adjustments of respiration. In a classic phrase inspired by the insight of genius he wrote: “Over the oxygen supply of the body carbon dioxide spreads its protecting wings”(1651).

Theodor Boveri (DE) followed the embryonic development of enucleated eggs of one species of sea urchin, Sphaerechinus, when they were fertilized with the spermatozoa of other species of sea urchin, Psammechinus or Paracentrotus. The results indicated that before gastrulation the chromosomes exert only general effects; after gastrulation, the factors for species-specific characters come into play, in interaction between nucleus and cytoplasm. This was the first expression of the concept of phase-specific and time-bound action of genes during development. It attributed to the cytoplasm a more specialized significance than had heretofore been acknowledged. Boveri referred to the development of sperm fertilized enucleated ova as merogony(1652-1655).

Sydney Ringer (GB) postulated the existence of an endogenousdigitalis” in mammals(1406).

Albert Imre Szent-Györgyi (HU-US) later revived Ringer’s idea(1656).

Vittorio Marchi (IT) and G. Aligeri (IT) discovered that the initial products of degeneration in myelinated nerve fibers can be stained selectively by osmic acid after preliminary mordanting with potassium bichromate. This method is still used to trace the origin, course, and destination of fiber connections in both experimental and clinicopathological material(1657).

Gustav Hauser (DE) was the first to describe the bacterial genus Proteus, named for the Greek sea god Proteus because it is pleomorphic and appears in many different sizes and shapes(1658).

Paul Clemens von Baumgarten (DE) clarified what is taking place at the tissue level during the tuberculous processes(1659).

David Douglas Cunningham (GB), in 1885, and Peter F. Borovsky (RU), in 1898, described Leishmania(1660-1662). Borovsky is also referred to as Alfred Borovsky.

James Homer Wright (US) accurately described Leishmania tropica, the causative agent of oriental sore, also known as Delhi boil, or tropical ulcer(1663).

Sir William Boog Leishman (GB) and Charles Donovan (GB) discovered the protozoan which causes kala-azar (Hindu for black fever), also known as dum-dum fever, tropical splenomegaly, and leishmaniasis, in the spleens of a patients who died of the disease(1664, 1665). The causative agent was later named Leishmania donovani in their honor.

Frederick George Novy (US) and Rudolph E. Knapp (US) discovered, identified, and cultured the spirochete of American relapsing fever, Spirochaeta novyi(1666).

Frederick George Novy (US) produced the first case of experimental infection with Leishmania(1667).

Antonio Carini (IT), Ulysses Paranhos (BR), and Adolph Lindenberg (BR) described Leishmania in the New World(1668, 1669).

Gaspar de Oliveira Vianna (BR) found that the parasites of New World, cutaneous and mucocutaneous leishmaniasis in South America differed from those in Africa and India and created a new species, Leishmania braziliensis(1670).

Gaspar de Oliveira Vianna (BR) introduced the use of the tartar emetic (potassium antimony tartrate) for the treatment of parasitic Leishmaniasis by intravenous injection(1671). Antimonal compounds are still the main drugs for therapy in human and canine leishmaniasis.

Edmond Sergent (FR), Etienne Sergent (FR), Louis Parrott (FR), André Donatien (FR), Maurice Beguet (FR), Robert Knowles (GB), Lionel Everard Napier (GB), R.O.A. Smith (GB), Sir Samuel Rickard Christophers (GB), Henry Edward Shortt (GB), and Philip James Barraud (GB) proved that the sandfly Phlebotomus is the vector of kala-azar(1672-1674).

Henrique de Beaurepaire Aragão (BR) discovered that the genus involved in transmission of New World leishmaniasis is actually Lutzomyia, a genus of sandfly(1675).

Saul P. Adler (RU-GB-IL) and M. Ber (IL) determined the precise mode of infection of Leishmania donovani is through the bite of the sandfly(1676).

Ralph Lainson (GB) elaborated the complex life pattern of species of the Leishmania parasite, its vector, reservoir host, and disease(1677).

Albert B. Frank (DE) was the first to report that a symbiotic relationship can exist between tree roots and fungi. He introduced the term mycorrhiza (fungus root) to describe this phenomenon(1678).

Julius Kollmann (CH) described and named the phenomenon of neoteny (the process of transformation whereby newts and similar creatures mature sexually while they are still in larval form) as observed in the axolotl form of Ambystoma tigrinum(1679).

Pierre Marie Alexis Millardet (FR) observed that the Bordeaux mixture (also called Médoc Mixture) used to prevent pilferage of grapes along roadsides also protected them from infection by the downy mildew, Plasmopara viticola. This mixture became the primary fungicide on grapes for some sixty years. The formula for treatment consists of the following: In 100 liters of water one dissolves 8 kg of commercial copper sulfate. Separately, one prepares milk of lime by mixing 30 liters of water and 15 kg of lime. Both solutions are mixed together forming a blueish paste. The mixture is sprinkled on the leaves with a little broom, being careful not to touch the grapes. Although organic fungicides and antibiotics introduced during the 1940’s are today’s major fungicides, the old reliable Bordeaux mixture is still used(1680).

Frank R. Cheshire (GB) and W. Watson Cheyne (GB) reported Bacillus alvei (Paenibacillus alvei) as the etiological agent of European foulbrood(1681).

Friederich August Johannes Löffler (DE) discovered the cause of swine erysipelas, Erysipelothrix rhusiopathiae(1682, 1683). 

Edmond Isidore Étienne Nocard (FR) recognized a weakly acid-fast bacillus which causes avian tuberculosis(1684). 

Daniel Elmer Salmon (US) and Theobald Smith (US) isolated and described a motile, gram-negative, easily cultivable bacillus from a number of cases of hog cholera. They applied Koch’s postulates to prove that it was the causative agent of hog cholera(1685).

Emil Alexander de Schweinitz (US) and Marion Dorset (US) found that hog cholera is caused by a virus, and that the bacillus is present as a secondary invader(1686).

In honor of Salmon, the bacterium is today called Salmonella cholera suis(1687, 1688). The genus name Salmonella was coined by José Lignières (AR) in 1900 to honor Daniel Elmer Salmon an American pathologist. 

Arnold Paltauf (AT) reported a fatal fungal infection in a patient with involvement of the central nervous system; including dissemination to the brain. He thought the etiological agent was the fungus Mucor because of its appearance in the tissues(1689). These mucormycoses (phycomycoses) are known to be caused by species from Mucor, Absidia, and Rhizopus. Compromised patients such as those with diabetes mellitus are at greatest risk.

Paul Ehrlich (DE) put forward a general theory of immunity, the side-chain or receptor theory(1631). Robert Joseph Lefkowitz (US) says this is “perhaps the earliest progenitor of the modern concept of receptors(1690).”

Ludwig Brieger (DE) found excess phenol, indigo, paraoxyphenylpropionic acid, paraoxyphenlacetic acid, and ethereal sulfates in the urine of many of his patients suffering from various disorders. He believed these represented by-products, in the colon, of microbial putrefactive action on proteins. Brieger named them ptomaines. He was also convinced that their absorption by the digestive tract was harmful(1691).

H. Senator (DE) had originated this idea of self-intoxication(1692).

Hermann Sahli (CH) developed a mixture of borax and methylene blue to stain bacteria of central nervous system infections(1693).

Augusta Marie Dejerine-Klumpke (US-FR) studied medicine in Paris and become the first woman to be named interne des hopitaux. She is known as a clinician and a neuropathologist. In 1885 she described the symptomatology of lower brachial plexus lesions(1694).

Carl Garré (CH) inoculated himself by rubbing a axenic culture of Staphylococcus upon the uninjured skin of his forearm, with the result that a series of carbuncles was produced, seventeen scars remaining to testify to the success of the experiment(1695).

Theodor Escherich (DE), a pediatrician and bacteriologist, isolated Bacterium coli commune from the excrement of a breast-fed infant. This organism was later to bear his name as Escherichia coli(1696, 1697).

Louis Pasteur (FR) described a way to protect (by vaccination) a dog from rabies even after it had received the virus from a bite of a rabid dog (1629).

On July 6, 1885 Louis Pasteur (FR) and his colleagues treated Joseph Meister, aged 9, who was suffering from bites on the hand, legs, and thighs from a dog certainly rabid. Sixty hours after the bites had been inflicted, Meister, the first human being treated by Pasteur’s method, was injected with attenuated rabbit marrow, fourteen days old. In a further twelve inoculations he received virus stronger and stronger until on 16 July he received an inoculation of virulent marrow only one day after it had left the body of a rabbit dead from rabies.

The virulence of the material used in the whole of Meister’s thirteen inoculations was controlled on rabbits, and it was shown that the boy in his last two inoculations had withstood a living virus which in rabbits was shown to be of maximal virulence with a seven-day incubation period. The boy recovered completely (994).

Sir William Osler (CA) wrote the first comprehensive description of subacute bacterial endocarditis(1698).

Franklin Paine Mall (US) working with Karl Friedrich Wilhelm Ludwig (DE), in 1885, showed that the veins as well as the arteries of the portal system are under the control of nerves(1699, 1700).

J. Leonard Corning (US) thought he had performed the first spinal block for anesthesia. He injected cocaine between the spinous processes of the lower dorsal vertebrae, first in a young dog and then in a generally healthy man(1701). Later it was determined that Corning's injection was extradural, and that Bier deserves the laurels for introducing spinal anesthesia.

August Karl Gustav Bier (DE) and J. Friedrich A. von Esmarch (DE) reported the injection of cocaine by lumbar puncture into a 34-year-old patient for excision of a tuberculous capsule at the ankle joint. Bier and his assistant, a Dr. Hilderbrandt, also injected one another to personally experience and record the signs and symptoms(1702). This represents the first successful intradural spinal block to induce anesthesia.

Heinrich Irenaeus Quincke (DE) and August Karl Gustav Bier (DE), popularized the technique in Europe. Rudolph Matas (US) wrote extensively about his experience in the US. 

Jan Mikulicz-Radecki; Johannes Freiherr von Mikulicz-Radecki (PL-AT) was the first to successfully suture a perforated gastric ulcer(1703).

Max von Frey (DE) and Max von Gruber (AT) described the artificial extrapulmonary oxygenation of blood. They used a blood pump in which gas exchange occurred as blood flowed onto a thin film over the inner surface of a slanted rotating cylinder(1704).

Thomas Annandale (GB) performed the first deliberate and planned operation for the relief of internal derangement of the knee-joint caused by a displaced cartilage(1705).

Louis Xavier Édouard Léopold Ollier (FR) dedicated himself to surgical work in human subjects, using an especially designed elevator to perform subperiosteal bone resections and subcapsulo-subperiosteal joint excisions(1706).

Ludwig Edinger (DE) identified the accessory nucleus of the 3rd oculomotor nerve (Edinger-Westphal nucleus) in the fetus(1707-1709).

Karl Friedrich Otto Westphal (DE) did the same in the adult brain(1710). This nucleus supplies pre-ganglionic parasympathetics to the eye, which constrict the pupil and accommodate the lens.

Hermann Ebbinghaus (DE) was the first to experimentally measure acquisition, recall, and recognition, i.e., memory(1711).

Richard Llewellyn Jones Llewellyn (GB) in writing of biorhythms said, “The tendency to rhythm is deep ingrained in protoplasm--write as plain in the systole and diastole of the heart, the inspiratory and expiratory phases of respiration as in the recurrence of the menstrual cycle. Do not our body cells, too, like the "laughing soil," respond to the call of the seasons, the biologic action of light, heat, and electrical stakes or disturbances?”(1712).

Liberty Hyde Bailey, Jr. (US) established at Michigan State (Agricultural) College the department of horticulture and landscape gardening, the first of its kind in the United States.

1886

…curious to a vice, investigators to the point of cruelty, with uninhibited fingers for the unfathomable, with teeth and stomachs for the most indigestible, … arrangers and collectors from morning till late, misers of our riches and our crammed drawers, economical in learning and forgetting, inventive in schemes, occasionally proud of tables of categories, occasionally pedants, occasionally night owls of work even in broad daylight.” Friedrich Wilhelm Nietzsche(1713, 1714).

Sir Francis Galton (GB) devised a new useful statistical tool, the correlation table. It is an excellent tool in applying statistical methods to many biological problems(1715).

Ernst Karl Abbé (DE) working at Zeiss Optical Works made a series of lenses that enabled microscopists to resolve structures at the theoritical limits of the light microscope. This included the apochromatic objective lens which he invented. Apochromatic lenses eliminate both primary and secondary color distortions. He improved the resolution his apochromatic oil-immersion objective microscope lenses by using oils which match the refractive index of the lens(1716).

Ernst August Schulze (CH) and E. Steiger (DE) isolated and named arginine in a precipitate resulting from mixing phosphotungstic acid with extract of germinating lupine seeds (Lupinus luteus)(1717, 1718).

Sven G. Hedin (SE) isolated arginine from horn(1719, 1720).

Friedrich Koch (DE) discovered xylose when he treated wood gum by acid hydrolysis(1721). 

Karl Peters (DE) was the first to describe the diene structure of linoleic acid(1722).

Paul Ehrlich (DE) introduced the acid haematoxylin stain, stabilizing the stain and the mordant (alum) with acid(1080).

The first notice was made of a tobacco-soapsuds mixture advocated for aphid control. Lime-sulphur-salt spray was first noted as useful against scale insects. Hydrocyanic acid gas (HCN), one of most deadliest gases known, was discovered as a fumigant for insect control purposes. Rosin fish-oil soap was first used as an insecticide for scale control in California(138).

Friedrich Hermann Hellriegel (DE) and Hermann Wilfarth (DE) demonstrated the bacterial nature of the root nodules of leguminous plants and showed that without these nodules the plants were unable to fix nitrogen. A preliminary report came out in 1886 with the full article following in 1888(1723-1726).

Wilhelm His (CH) proposed, “that every nerve-fiber arises as an offshoot from one single cell. This cell is its embryonic (genetisches), nutritive, and functional center, and other connexions of the fiber are either only indirect, or have originated secondarily(1727).” He went on to describe the outgrowth of the axon from the neuroblast in various vertebrates. This was essential to the development of the neuron theory, which states that the neuron, or nerve cell, is the basic unit of the nervous system.

Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) wrote a highly influential review in which he stated that nerve cells terminate freely with end arborizations and that the neuron is the anatomical and physiological unit of the nervous system. This is the coining of the term neuron(389). 

Ludwig Brieger (DE) discovered that some microbes produce and secrete poisonous substances called toxins(1728).

Silas Weir Mitchell (US) and Edward Tyson Reichert (US) established that snake venom is protein in nature, and demonstrated the presence of toxic albumins(1729).

Leonard Charles Wooldridge (GB) proposed for the first time that the prothrombin activator is a protein/phospholipid complex derived from damaged tissue(1730).

Charles Alexander MacMunn (GB) observed myohematins and histohematins in representatives of almost all orders of the animal world. He proposed that these pigments are concerned with internal respiration of the tissues and organs(1731, 1732).

Otto Heinrich Warburg (DE) worked with charcoals of blood, and later of hemin and impure aniline dyes contaminated with iron salts in his attempt to understand intracellular respiration. He concluded that “… molecular oxygen reacts with divalent iron, whereby there results a higher oxidation state of iron. The higher oxidation state reacts with the organic substance with the regeneration of divalent iron …. Molecular oxygen never reacts directly with the organic substance.” He defined the respiratory enzyme (atmungsferment) as “… the sum of all catalytically-active iron compounds present in the cell.” Then went on to say, “The catalytically active substance in hemin-charcoal is therefore iron, but not iron in any form whatever, but iron bound to nitrogen”(1733-1735).

David Keilin (PL-GB) made spectral analysis of pigments he found in the muscles of horse bot-flies (Gasterophilus intestinalis) and in yeast. He realized that they exhibited a four-banded absorption spectrum just like the myohematins and histohematins observed by Charles Alexander MacMunn (GB). Keilin concluded that the four-banded spectrum was associated with three separate hemochromogens which he named cytochromes a, b, and c and assigned them a significant role as oxidation catalysts in intracellular respiration(1736, 1737). The 1925 article by Keilin marked the beginning of studies of what Warburg later called the respiratory chain (atmungskette), many called the electron transfer chain,  and David Green, the electron transport chain.

Otto Heinrich Warburg (DE) demonstrated that the oxygen uptake associated with respiration in yeast is inhibited by carbon monoxide and is a reversible reaction. He concluded that “… the Atmungsferment (equivalent to Keilin’s cytochrome) is an iron-pyrrole compound in which the iron is bound to nitrogen, as in hemoglobin.” Warburg did not believe cytochrome and his atmungsferment to be equivalent(1738).

Otto Heinrich Warburg (DE) and Erwin Paul Negelein (DE) in a brilliant set of experiments used indirect determination of light absorption spectra to demonstrate that atmungsferment (Keilin’s cytochrome) is a porphyrin with a protein component(1739, 1740). This enzyme is now called cytochrome oxidase.

David Keilin (PL-GB) realizing that the cytochromes are not auto-oxidizable considered indophenol oxidase to be an enzyme capable of catalyzing the oxidation of cytochrome by oxygen. Later, at the suggestion of Malcolm Dixon (GB)(1741), he used the term cytochrome oxidase to denote this enzyme which he viewed as being equivalent to Warburg’s atmungsferment(1742).

David Keilin (GB) and Edward Francis Hartree (GB) demonstrated the existence of the auto-oxidizable cytochrome a3 which Keilin had previously thought was indophenol oxidase. They noted that it combines with cyanide and carbon monoxide. Its spectroscopic properties agree with those of Warburg’s atmungsferment(1743).

Eijiro Yakushiji (JP) and Kazuo Okunuki (JP) discovered cytochrome c1(1744). In 1941, they placed c1 in the cytochrome chain in the order b-c1-c-a-a3.

Bernard Leonard Horecker (US) and Arthur J. Kornberg (US) found that cyanide reacts with cytochrome c(1745).

Frederick L. Crane (US), Youssef Hatefi (IR-US), Robert L. Lester (US), and Christine Widmer (CH) discovered ubiquinone (coenzyme Q) as a new hydrogen carrier between the dehydrogenases and the electron transfer chain in beef heart mitochondria(1746).

Richard Alan Morton (GB), G.M. Wilson (GB), J.S. Lowe (GB), and W.M.F. Leat (GB) defined a compound obtained from vitamin A deficient rat liver to be the same as CoQ10. In their 1957 paper they named it ubiquinone; meaning the ubiquitous quinone(1747-1749).

Donald E. Wolf (US), Carl H. Hoffman (US), Nelson R. Trenner (US), Byron H. Arison (US), Clifford H. Shunk, (US) Bruce O. Linn (US), James F. McPherson (US), and Karl August Folkers (US) determined the precise chemical structure of CoQ10 to be 2,3 dimethoxy-5 methyl-6 decaprenyl benzoquinone, synthesized it, and were the first to produce it by fermentation(1750). 

Frederick L. Crane (US) reported the presence of two coenzyme Q type molecules and Norman I. Bishop (US) reported a quinone molecule, all reactive in the light driven electron transport process of isolated chloroplasts. One of the coenzyme Q molecules and the quinone molecule would prove to be plastoquinone(1751, 1752). 

Helmut Beinert (US) and Graham Palmer (US) used paramagnetic resonance (EPR) spectrometry to establish that copper, as well as, iron is involved in the oxidation of cytochrome c(1753).

Bob F. van Gelder (NL) showed that cytochrome c oxidase takes up four electrons per molecule, one each into the hemes of cytochrome a and a3 and two into the copper atoms(1754).

St. Szez. Zaleski (DE) and Gustav von Bunge (DE) discovered that the fetal liver in animals is used as a storage organ for iron(1755, 1756).

Carl Benda (DE) introduced the use of the iron-hematoxylin dye to histology(1757).

Bartolomeo Camillo Emilio Golgi (IT), August H. Forel (CH) and Fridtjof Nansen (NO) concluded but could not prove that “transmission of a stimulus without direct continuity is possible” in the sensory organs. They favored contiguity, not continuity of nerve cells(720, 1758, 1759).

Bartolomeo Camillo Emilio Golgi (IT) gave a precise description of the nerve cell. He distinguished between axons and dendrites and noted that nerve cells can have extensive protoplasmic branches. He describes the "fine anatomy" of the convolutions front center and top of the occipital cortex (the structures to which contemporary research had attributed, respectively, motor and sensory function), the cerebellum, the foot d ' hippocampus, corpus callosum, olfactory lobes. In addition, after a first chapter of a general nature on the nerve cell, contains a chapter on neuroglia and one on methods of the "black reaction"(720, 1760).

Santiago Ramón y Cajal (ES) improved Golgi’s silver-chromate stain for nerve tissue. Using his reduced silver nitrate technique he worked out the connections of the cells in the grey matter of the brain and spinal cord and the complexity of the system. His introduction of a gold chloride-mercury bichloride technique to demonstrate astrocytes was a monumental contribution as was his work on degeneration and regeneration of the nervous system later. He also worked out the structure of the retina of the eye, describing in detail the major cell types in all three retinal layers and proclaimed that the nervous system consisted entirely of neurons and their processes. He concluded: “(1) Nervous cells are independent units, they never anastomose either through their dendritic branches or through nerve fibers emanating from their axons. (2) Every axis cylinder terminates freely in varicose and flexuous arborisations…(3) These arborisations are applied either to the body or to the dendritic branches of other nervous cells establishing connexion by contiguity…which is just as efficacious in transmitting impulses as if there were real connexion of substance between the neurons. (4) The cell body of the dendritic branches are as much concerned with conduction of impulses as with neuronal nutrition. The dendrites carry impulses to the cell body, while axonal transmission is away from the cell body.” He emphasized that the direction of conduction is from the receptors in the retina, through the horizontal, bipolar, and amacrine cells of the inner nuclear layer, ultimately to the ganglion cells, whose axons constitute the optic nerve(1761-1766).

Max Bielschowsky (DE) began his fundamental studies on the silver impregnation of nerve fibers. He truly replaced Santiago Ramon y Cajal’s method on which his was based(1767). He is known as a superior neuropathologist with his contributions in the study of tuberous sclerosis, amaurotic family idiocy (late infantile type), herpes zoster, paralysis agitans, Huntington’s chorea, and myotonia congenita

Philippe Edouard Léon Van Tieghem (FR) and Henri Douliot (FR) introduced the concept of the stele to the anatomy of the Pteridophyta (ferns, horsetails, and club-mosses)(18). 

Nathan Zuntz (DE) and August Julius Geppert (DE) created the Zuntz-Geppert respiratory apparatus for indirect calorimetry(1768).

Wilbur Olin Atwater (US) and Edward Bennett Rosa (US) constructed the Atwater-Rosa calorimeter with which they, along with Francis Gano Benedict (US) and Thorne Martin Carpenter (US), proved the law of conservation of energy in human beings and made it possible to calculate the caloric values of different foods(1769-1771).

William Holbrook Gaskell (GB), in studies of the autonomic nervous system, concluded that the “involuntary system” is composed of two antagonistic subsystems(1772).

Franz von Soxhlet (DE) reasoned that summer diarrhea in children might be caused by bacteria growing in the milk they consumed. When he sterilized the milk, a dramatic decrease in the frequency of summer diarrhea occurred(1773). 

Adolf Eduard Mayer (DE) demonstrated an infectious agent (virus) to be the most likely cause of tobacco mosaic disease in plants(1774, 1775).

James Brown Buist (GB) was probably the first to perform a laboratory-based diagnosis of a viral disease when he stained the lymph obtained from the skin lesions of patients with smallpox and saw elementary bodies, which he took to be the cause of the disease(1776, 1777). Note that this was six years before viruses were discovered.

Adolf Weil (DE) was the first to describe infectious jaundice or what was later called Weil’s disease(1778). The etiological agent is a spirochete. See Inada, 1916.

Daniel Elmer Salmon (US) and Theobald Smith (US) showed that dead swine plague bacilli can be used as a vaccine(1779, 1780). Although Smith made the discovery on his own, his supervisor, Daniel Elmer Salmon, usurped credit.

Josef von Fodor (HU) and Vladimir Wyssokowitch (DE) emphasized that the anti-putrefactive quality of circulating blood is part of the body’s defense mechanism. They demonstrated that bacteria introduced into the blood-stream rapidly disappear and apparently do not leave the body by any of the channels of secretion or excretion(1781-1784).

Josef von Fodor (HU) found that blood mixed in vitro with anthrax bacilli at 38°C caused a rapid decrease in the number of cells capable of growing on gelatin plates (1783).

George Henry Falkiner Nuttall (US-GB) confirmed observations by von Fodor and Wyssokowitch then discovered that the bacterial killing power of the blood was lost on aging, and destroyed by heating to 52°C for 10 to 30 minutes(1785, 1786). This represents the discovery of the complement system.

Jean Alfred Fournier (FR) described congenital syphilis and emphasized that syphilis could cause degenerative diseases(1787).

Frantisek Vejdovsky (CZ), in 1886, separated the gordiaceans from the nematodes and hence his name, Nematomorpha for the gordiaceans. They are a class within the phylum Aschelminthes (Nemathelminthes)(1788).

Daniel Alcides Carrión (PE) inoculated himself (fatally) and proved that Oroya fever and verruga peruana are stages of a single disease now commonly known as Carrión’s disease(1789).

Ernest Ordiozola (PE) introduced the term Carrión’s disease(1790).

Alberto Leopoldo Barton (PE) discovered that Carrión’s disease is caused by the rickettsium Bartonella bacilliformis(1791). 

Charles H. T. Townsend (US) found a species of Phlebotomus (sandfly) whose bite caused the outbreak of the disease. He named the sandfly Phlebotomus verrucarum(Lutzomyia verrucarum )(1792).

Charles H.T. Townsend (US) provided evidence that lizzards act as a reservoir for Bartonella bacilliformis(1793).

The rickettsial microorganism was named by Strong and others in honor of Barton(1794). 

Hideyo Noguchi (JP-US), also demonstrated that Oroya fever and verruga peruana are both caused by the parasite Bartonella bacilliformis and are actually two different stages of the same infection called Carrion's disease, or bartonellosis(1795).

Marshall Hertig (US) definitely established the role of the sandfly(1796). Note: Cosme Bueno (ES-PE), in 1764, wrote that Andean peoples of Peru attributed the diseases now known as leishmaniasis and bartonellosis to the bite of the uta or sand fly(1797).

Felix Fränkel (DE) reported the first case of a tumor of the adrenal medulla(1798), a type of tumor that has become known as pheochromocytoma. The patient in this case was an 18 year-old girl who had died suddenly of collapse. Her clinical history and autopsy findings pointed to a severe hypertensive crisis. This, combined with the discovery of an adrenal medullary tumor, presented what appears to be the first evidence, seer-, only in retrospect, of the relationship between the adrenal medulla and blood pressure.

Pierre Marie (FR) fully described and named the constellation of symptoms termed acromegaly: excessive growth of the viscera and the bones of the face, hands, and feet, and the thickening of soft tissues like the tongue, lips, and nose, which made the features of acromegalic patients gradually become strikingly coarse and elongated. Other signs and symptoms that Marie noted as characteristic of the chronic condition included severe headaches, intense thirst and appetite, cessation of menstruation, changes in the thyroid, and damaged vision. Then, in 1890 and 1891, Marie reported that enlarged pituitaries were always found in postmortern examinations of persons with acromegaly, and he hypothesized that the abnormal growth of the pituitary caused a glandular deficiency and hence toxemia. He was the first to correlate the clinical and pathological findings(1799, 1800).

Jean-Martin Charcot (FR), Pierre Marie (FR), Howard Henry Tooth (GB), and Johann Hoffmann (DE) described what became known as Charcot-Marie-Tooth-Hoffmann syndrome. It is characterized by slowly progressive wasting and weakness of distal muscle of the arms and feet, caused by degeneration of the peripheral nerves, nerve roots, and even the spinal cord, with loss of reflexes, loss of cutaneous sensations and development of foot drop. Optic atrophy is sometimes present(1801-1803). The disease had been described previously, but its neuropathic basis was not appreciated.

Benjamin B. Roa (US), Carlos A. Garcia (US), Ueli Suter (CH), Deanna A. Kulpa (US), Carol A. Wise (US), Jane Mueller (US), Andrew A. Welcher (US), G. Jackson Snipes (US), Eric M. Shooter (GB-US), Pragna I. Patel (IN-US), and James R. Lupski (US) determined that Charcot-Marie-Tooth disease type 1A (CMT1A), the most common form, is caused by a defect in the gene for myelin protein PMP22(1804).

JoAnn Bergoffen (US), James A. Trofatter (US), Margaret A. Pericak-Vance (US), Jonathan L. Haines (US), Phillip F. Chance (US), and Kenneth H. Fischbeck (US) determined that the X-linked form of Charcot-Marie-Tooth disease (CMTX) is caused by mutations in the gap junction protein, connexin 32(1805).

Phileppe Latour (FR), Fransoise Blanquet (FR), Eva Nelis (BE), Christine Bonnebouche (FR), Frangoise Chapon (FR), Philippe Diraison (FR), Elizabeth Ollagnon (FR), Andre Dautigny (FR), Danielle Pham-Dinh (FR), Guy Chazot (FR), Michel Boucherat (FR), Christine Van Broeckhoven (FR), and Antoon Vandenberghe (FR) determined that Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by a defect in the gene for myelin protein Po(1806).

Sir Victor Alexander Haden Horsley (GB), using dogs, performed the first successful experimental hypophysectomy. Two dogs survived five and six months respectively after this operation(1807).

Sir Victor Alexander Haden Horsley (GB) successfully operated on several cases of pituitary tumors in man(1808, 1809). The first of these operations was performed in 1889.

Hermann Schloffer (AT) reported the first successful resection of a pituitary tumor via a transphenoidal approach. Local anesthesia was provided by cocaine(1810).

Anton Freiherr von Eiselsberg (AT) and Lothar von Frankl-Hochwart (AT) successfully drained a cystic tumor of the pituitary gland by way of a superior transnasal approach. The patient died 2 days later of purulent meningitis(1811, 1812).

Julius von Hochenegg (AT) and I. Head (AT), in 1908, used the same superior transnasal approach to successfully treat a case of acromegaly(1813).

Sir William MacCormac (GB) introduced an operation for the treatment of intraperitoneal rupture of the bladder(1814).

Jan Mikulicz-Radecki; Johannes Freiherr von Mikulicz-Radecki (PL-AT) was the first to make a plastic reconstruction of the esophagus after the resection of its cervical portion for carcinoma(1815).

Hermann Kümmell (DE), in 1886, attempted the first choledochotomy (surgical incision into the common bile duct)(1816).

The world's first Ph.D. in psychology was awarded to Joseph Jastrow at Johns Hopkins University.

1887

“It was from these dissections, from an elaborate course of reading, and from numerous visits to the pork and slaughter houses of Cincinnati, that I derived the knowledge upon which I founded my work on Pathological Anatomy.” Samuel David Gross(1817).

Albert Abraham Michelson (PL-US) and Edward Williams Morley (US) determined that the speed of light is constant regardless of whether it is emitted from a moving or a stationary object(1818). Michelson, in 1907, was the first American to receive a Nobel Prize in the sciences (physics).

Jacobus Hendricus van’t Hoff (NL) realized that the osmotic pressure generated by molecules (or later, ions) in solution was exactly the same as they would exert at the same concentration in a gas, thus linking solution theory to the long established laws describing the behavior of gases. Subsequently, he formulated the osmotic pressure equation, and the theory of solutions that connected osmotic pressure, freezing-point depression, and the lowering of vapor pressure as thermodynamic properties(1819).

Ernst August Schulze (CH) and E. Steiger (DE) developed a solution of zinc chloride-iodine-potassium iodide in water useful for testing for cellulose, which it colors blue(1820). Verify ref

Friedrich W. Semmler (DE) prepared divinyl ether(1821). 

Chauncey Depew Leake (US) and Mei-Yü Chen (US) first observed the anesthetic properties of divinyl ether(1822).

Chauncey Depew Leake (US), Peter K. Knoefel (US), and Arthur E. Guedel (US) introduced divinyl oxide as an anesthetic(1823). 

Julius Richard Petri (DE), one of Heinrich Hermann Robert Koch’s assistants, invented a dish now routinely used in microbiology; the petri dish(1824).

André Victor Cornil (FR), Victor Babès (FR), William Nicati (FR), and Maximillien Rietsch (FR) described very similar dishes a couple of years earlier(1825, 1826).

Ernst Salkowski (DE) discovered phytosterol (phytosterin), the nucleus of vegetable fats(1827). Phytosterols act as a structural component in the cell membrane of plants, analogous to the cholesterol in the cell of animals.

William Dobinson Halliburton (GB) gave the first credible experimental descriptions of actin's properties(1828).

Harunori Ishikawa (US), Richard Bischoff (US), and Howard Holtzer (US) detected actin filaments not just in muscle cells, but in a wide variety of mammalian cell types(1829).

Klaus Weber (PL-DE-US) and Ute Groeschel-Stewart (DE) specifically visualized myosin containing filaments in non-muscle cells(1830).

Elias Lazarides (US) identified tropomyosin in non-muscle cells(1831).

Elias Lazarides (US) and Keith Burridge (GB-US) identified alpha-actinin as a normal component of non-muscle cells(1832).

Sergei Nikolaevich Winogradsky (RU) discovered chemoautotrophic bacteria that oxidize hydrogen sulfide to sulfur and others which oxidize sulfur to sulfuric acid while using carbon dioxide as a carbon source. These studies of sulfur bacteria eventually led to the concept of the sulfur cycle(1833, 1834).

Sergei Nikolaevich Winogradsky (RU) discovered. Beggiatoa minima, Clostridium pasteurianum, Cytophaga hutchinsonii, Nitrosococcus nitrosus, Nitrosocystis javaensis, N. coccoides, Nitrosomonas europaea, Nitrosospira briensis, N. antarctica, and Nitrobacter.

In his book Soil Microbiology, published in 1949, he wrote: “I started my work in 1885… impressed by the incomparable glitter of Pasteur’s discoveries, as a young student I entered this field of investigation and have remained faithful to it to the end… My first investigations dealt with filamentous bacteria found in sulfur and iron-containing springs; these were the first known autotrophs…”(1835).

Viktor Hensen (DE) introduced the term plankton to mean all particles and material which floats in a water column, regardless of whether it occurs in the upper or lower layers of the water column, or whether it is alive or dead. It is derived from the Greek planktos, to wander or drift. Hensen credits his colleague Professor Foerster with suggesting this term(1836).

Emile Maupas (FR) and Richard Karl Wilhelm Theodor von Hertwig (DE) independently demonstrated exchange of micronuclei during conjugation by Paramecium(1837, 1838).

Jules Héricourt (FR) and Charles Robert Richet (FR) were the first to conceive the notion of producing an immune serum; that is, of injecting into an animal a particular substance to which it could then produce an antidote. (The injected material is an antigen; the countermaterial produced is an antibody). If the antigen is a bacterium or a bacterial toxin, then an antibody will exist that will prevent future infections. If serum containing this antibody is then injected into a human being, it may lend him immunity to a particular disease(1839). Richet tried to produce such an immune serum for tuberculosis but failed(1840). Later, Emil Adolf von Behring working along similar lines, succeeded with tetanus and diphtheria. Note: Richet was the first to injection serum into a human in 1890. 

Maurice Kaufmann (FR) used European viper (Vipera berus) venom and guinea pigs while Henry Sewall (US) used rattlesnake venom and pigeons to independently discover that anti-venoms are produced in the blood of animals inoculated with small doses of venom, and that the degree of immunity can be built up by slowly increasing the dosage of venom in successive inoculations(1841, 1842).

John Brown Buist (GB) discovered very minute elementary bodies in the cells of epithelial tissues infected with variola or vaccinia. These appear as cytoplasmic inclusions(1777, 1843).

Enrique Paschen (DE) rediscovered these elementary bodies(1844). They were later named Paschen bodies in his honor. These elementary bodies or Paschen bodies are now recognized as collections of the virus.

Theodor Boveri (DE), while studying Ascaris megalocephala, was the first to recognize narurally occurring polyploidy(884).

Fridtjof Nansen (NO) was the first to point out that the posterior root nerve fibers divide on entering the spinal cord into ascending and descending branches(1759).

Wilhelm Roux (DE) demonstrated that shortly after fertilization of an amphibian egg a broad crescent develops in the lower hemisphere, opposite the point of sperm entry, loses some of its dark pigment and becomes the gray crescent. The gray cresent persists at most for a few cleavages. He found that the dorsal lip of the blastopore appears where the gray crescent had been and he deduced that the plane of the first cleavage (median plane) bisects the blastopore dividing the embryo into a right and left half. The three axes of the future embryo are thus fixed before segregation of the egg begins(1845, 1846).

Luigi Salvatore Savastano (IT) determined the bacterial cause of galling on olives (Olea europaea ) to be Pseudomonas savastanoi(1847). This disease, called olive knot, was discovered in France.

Nil Feodorovich Filatov (RU) and Emil Pfeiffer (DE) independently gave early clinical descriptions of infectious mononucleosis(1848, 1849).

Thomas Peck Sprunt (US) and Frank Alexander Evans (US) are responsible for coining the phrase infectious mononucleosis(1850).

Howard A. Kelly (US) performed a hysterorrhaphy (suturing of a lacerated uterus)(1851).

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE), after studying the radiolaria brought back by the Challenger expedition elaborated the concept of organic form and symmetry. Symmetry referring to the spatial relations and arrangements of parts in such a way as to form geometrical designs(1852). 

Harry Marshall Ward (GB) wrote the first English translation of Ferdinand Gustav Julius von Sach’s Lectures on the Physiology of Plants; The Oak; A Popular Introduction to Forest-Botany; Text-book of the Diseases of Trees, with Robert Hartig; and Grasses; A Handbook for the Use in the Field and Laboratory(1392, 1853-1855).

Henry Seebohm (GB) was the first ornithologist to recognize the importance of isolation in species formation(1856).

Saturnin Arloing (FR), Charles Cornevin (FR), and Onésine Thomas (FR) cultured Clostridium chauvoei and established its etiological relationship to blackleg, also known as quarter evil, and symptomatic anthrax (not to be confused with anthrax) and developed a method of prophylactic inoculation called the Lyon vaccine(1857). This is an acute disease affecting cattle. The bacterium was named in honor of Auguste Chauveau (FR).

Paralytic polio was described as epidemic in Sweden(176).

Heinrich Hermann Robert Koch (DE) observed a small bacillus, later identified as Hemophilus aegyptius, while examining a series of eye inflammations in Egypt(1858). 

John Elmer Weeks (US) was the first to cultivate Hemophilus aegypticus(1859). It is now recognized as the cause of a highly contagious form of conjunctivitis known as pink-eye. This organism is sometimes referred to as the Koch-Weeks bacillus.

Margaret Pittman (US) and Dorland J. Davis (US) were the first to identify this organism as Hemophilus aegypticus(1860).

Anton Weichselbaum (AT) isolated the causative agent of septic meningitis, Neisseria meningitidis, and associated it with six cases of acute cerebrospinal meningitis(1861).

Johann Otto Leonhard Heubner (DE) was the first to isolate meningococci from the cerebrospinal fluid of living beings(1862).

Guido Banti (IT) pointed out that typhoid fever is caused by a bacterium(1863).

Johan Frederik Eykman (NL) and Maurits Greshoff (NL) independently described how the natives of India used snakeroot (Rauwolfia serpentina) to treat snake bites and the mentally ill. The Indian word for mental is chandrá meaning moon, e.g., moon disease or lunacy(1864, 1865).

Edward Hartley Angle (US) developed the Angle system of regulation and retention of the teeth, and treatment of fractures of the maxillae. This rapidly became the most popular orthodontic method in the world(1866-1868).

Paul Gerson Unna (DE) described seborrheic dermatitis and distinguished it from chronic eczema and psoriasis(1869).

Joseph Jules Déjérine (CH-FR) described Déjérine’s neuro-tabes (multiple peripheral neuritis with symptoms like those of locomotor ataxia)(1870).

Oscar Minkowski; Oskar Minkowsky (DE) associated acromegaly with a hyperfunctional pituitary gland(1871).

Julius Wagner-Jauregg (AT) induced fevers in the mentally ill, using at turns tuberculin, typhus vaccine, and tertian malaria. In 1917, nine patients with general paresis (neurosyphilis) were treated by injecting blood from patients experiencing active malaria; three recovered, three showed temporary relief, and three showed no improvement(1872-1874). 

George Washington Crile (US) was the first to perform major operations with intraneural injections of cocaine. His first such operation was in 1887(1875, 1876).

Jan Mikulicz-Radecki; Johannes Freiherr von Mikulicz-Radecki (PL-AT) developed an operation for the treatment of disease of the accessory nasal sinuses(1877).

Jan Mikulicz-Radecki; Johannes Freiherr von Mikulicz-Radecki (PL-AT) introduced the folded gauze pad for packing off the viscera in abdominal operations and used as sponge in general(1878).

Walter Hermann Heineke (DE) and Jan Mikulicz-Radecki; Johannes Freiherr von Mikulicz-Radecki (PL-AT) independently and almost simultaneously performed the first pyloroplasty. This was done to eliminate pyloric stenosis. A short longitudinal incision is made through all layers of the pylorus and closed transversely. Used after truncal vagotomy. F. Fronmüller described Heineke’s operation(1879, 1880).

Henry L. Coit (US) began as early as 1887 to work to ensure a safe milk supply for infants, by educating the public, lawmakers, and the medical community. He coined the term "Certified Milk" and established the first Medical Milk Commission in New Jersey(1881).

Abraham Jacobi (US) collaborated with the philanthropist Nathan Straus (US) to establish pasteurization plants and milk stations for poor infants in New York beginning in 1893. A reduction in infant mortality of 65% was observed in just one year in the foundling hospital on Randall’s Island after a pasteurization plant was established there by Straus(1881, 1882).

In1908, Chicago became the first city in the world to require pasteurization of milk(1881).

John Langdon Down (GB) coined the term idiots savants to apply to children who, while feeble-minded, exhibit special faculties which are capable of being cultivated to a very great extent(1883).

The Canadian Geological Survey found rich fossil beds containing Upper Cretaceous dinosaur fauna along the Red Deer River in Alberta(1884).

The National Institutes of Health was established in the United States of America.

Annales de l’Institut Pasteur was founded.

Annals of Botany was founded.

Zeitschrift fur Physikalische Chemie was founded.

1888

“Put forward nothing that cannot be proved simply and conclusively. Venerate the critical spirit…. Without it all else is nothing. It always has the last word.” Louis Pasteur. Remarks at the dedication of the Pasteur Institute of Paris, November 14(1885).

The Pasteur Institute was erected in Paris and dedicated on November 14. It was paid for by public donations from all over the world(994) .

Johann August Ludwig Friedrich Kehrmann (CH), Viktor Meyer; Victor Meyer (DE) and John Joseph Sudborough (GB) found that while atom groupings ordinarily can rotate freely about a single bond attaching them to the rest of the molecule, the bulk of nearby groups of atoms sometimes prevents this rotation. This they called steric hindrance(1886-1888).

Erwin Frink Smith (US) postulated some sort of a virus as the cause of peach yellows(1889).

Auguste Fernbach (FR) tested for the presence of bacteria in 555 samples taken from the interiors of various plant tissues. Bacteria were found in only 6.3% of the samples. Fernbach considered that these growths were the result of accidental contaminations (1890).

Sergei Nikolaevich Winogradsky (RU) described photosynthetic purple sulfur bacteria; including Chromatium(1891).

Nikolai Fedorovich Gamaléia (RU) discovered Vibrio metchnikovii in the intestinal tract and blood of fowls suffering from an epidemic disease resembling fowl cholera(1892).

August Gärtner (DE) isolated a bacterium from contaminated beef responsible for an outbreak of gastroenteritis, and named it Bacillus enteritidis. Today we recognize it as Salmonella enteritidis(1893). This was possibly the first clear indication that microorganisms could cause food poisoning.

André Chantemesse (FR) and Georges Fernand Isidore Widal (FR) made the first observations of immunity conferred on experimental animals following injection with heat killed typhoid bacilli(1894, 1895).

Sir Almoth Edward Wright (GB), Richard Friedrich Johannes Pfeiffer (DE) and Wilhelm Kolle (DE) prepared and recommended a heat inactivated vaccine for typhoid fever which could be prepared from killed typhoid bacilli(1896-1898).

Pierre Paul Émile Roux (FR) and Alexandre Émile Jean Yersin (CH) proved that Corynebacterium diphtheriae produces a soluble toxin responsible for the characteristic symptoms and lesions of diphtheria and thus demonstrated its etiological relationship to the disease(1899-1901).

Victor Babès (RO) and Paul Ernst (DE) discovered and described the metachromatic granules seen in the protoplasm of various gram-positive bacteria, algae, and protozoa. These granules stain deeply with aniline dyes and are now known as Babes-Ernst granules or bodies(1902-1904).

Victor Babès (RO) discovered a group of small protozoan parasites that invade the blood of various animals and are now placed in the genus Babesia, named to honor him(1905, 1906).

Auguste Trillat (FR), in 1888, discovered the germicidal value of formalin (40% formaldehyde in water)(1907, 1908). In 1891, Trillat patented the solution as Formolin.

Theodor Geuther (DE) discovered that formalin (Formolin) destroys the germinating power of smut spores(1909). 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) extended his theory of cellular immunity by showing that anthrax bacteria are actively phagocytized and destroyed by phagocytes from animals previous exposed to the bacterium(1910).

Wilhelm Roux (DE) experimentally produced a half-embryo by killing one blastomere of the two-celled frog embryo(1911).

William Johnson Sollas (GB), geologist, paleontologist, and spongiologist wrote Report on the Tetractinellida Collected by H.M.S. Challenger During the Years 1873-1876; still considered a benchmark publication. In this monograph all tetractinellids known at that time are treated, including the many dredged by H.M.S. Challenger. Many of the genera and families erected by Sollas are still recognized as valid(1912). He is commemorated by Amphius sollasi Burton & Rao, 1932; Callipelta sollasi Lévi&Lévi, 1989; Erylus sollasi Von Lendenfeld,1910; Isops sollasi Lendenfeld, 1910; Pachastrella sollasi Topsent, 1890; Penares sollasi Thiele, 1900; Proteleia sollasi Dendy & Ridley , 1886; Sollasella Lendenfeld, 1888; Sollasellidae Lendenfeld, 1888; Tethya sollasi Bergquist & Kelly-Borges, 1991, and Alcyonium sollasi.

Samuel Wendell Williston (US), in 1888, wrote the 1st edition of a very important and influential book on the North American diptera(1913).

Maximilian Fürbringer (DE) authored Untersuchungen zur Morphologie und Systematik der Vogel, one of the great classics in bird anatomy(1914).

Edmond Isidore Étienne Nocard (FR) first described an infection in cattle called farcy which is caused by an aerobic, partially acid-fast, branching type of actinomycete, Streptothrix farcinica(1915). Vittore Benedetto Trevisan (IT) erected the genus Nocardia in honor of Nocard(1916); the etiological agent became Nocardia farcinica.

Sir Victor Alexander Haden Horsley (GB) and Edward Albert Schäfer (GB) published a somatotopic map of the monkey motor cortex(1917).

Hugo Schulz (DE) noted that many chemicals are able to stimulate growth and respiration of yeast at low doses but are inhibitory at higher levels(1918). This concept of a generalized low-dose stimulation-high-dose inhibition was gradually supported by similar observations with other chemicals and eventually became known as the Arndt-Schulz law—Rudolf Arndt (DE). Although Schulz ushered in the so-called modern concept of hormesis, i.e., to set in motion, Paracelsus writing in the 16th century, likewise noted that various toxic substances may be beneficial in small quantities. See, Paracelsus, c.1526.

The two phases (biphasic) of a drug's action are dose-dependent. For instance, it is widely recognized that normal medical doses of atropine block the parasympathetic nerves, causing mucous membranes to dry up, while exceedingly small doses of atropine cause increased secretions of mucous membranes.

William Williams Keen, Jr. (US) was the first American to remove an intracranial meningioma(1919).

Arnaldo Cantani (CZ-IT) proposed the concept of the neural spread of rabies: in laboratory animals the transection of limb nerves following peripheral inoculation prevented the evolution of the disease(1920).

Alfonso Di Vestea (IT) and Giuseppe Zagari (IT) used laboratory animals to provide convincing evidence to support Cantani’s proposal(1921).

Karl Schaffer (HU) produced evidence for the neural spread of rabies in humans(1922).

Sir Byrom Bramwell (GB) recognized a connection between pituitary tumors and body fat and polyuria(1923).

Ètienne-Louis-Arthur Fallot (FR) described a congenital form of heart disease which would later bear his name (tetralogy of Fallot) as follows: “Cyanosis, especially in the adult, is the result of a small number of cardiac malformations well determined…. One…is much more frequent than the others…. This malformation consists of a true anatomopathologic type represented by the following tetralogy: (1) Stenosis of the pulmonary artery; (2) Interventricular communication; (3) Deviation of the origin of the aorta to the right; and (4) Hypertrophy, almost always concentric in type, of the right ventricle. Failure of obliteration of the foramen ovale may occasionally be added in a wholly accessory manner”(1924). 

Niels Stensen (DK) had described this condition in 1671(1925).

Thomas Bevill Peacock (GB) had described this disease in 1846(1926).

Harald Hirschsprung (DK) described megacolon, a disease in which nerve ganglia are absent in the myenteric plexus of the rectosigmoid area of the large intestine, leading to improper development. The colon above the inactive area of the sigmoid dilates and there is chronic constipation, abdominal distension, and fecal impaction. The condition would later be named Hirschsprung’s disease(1927).

Caleb Hillier Parry (GB) had been the first to report this disease(1928).

Samuel Jones Gee (GB), Christian Archibald Herter (US), Johann Otto Leonhard Heubner (DE), and Thorvald Einar Hess Thaysen (DK) described and defined a gastrointestinal disease resulting from defective fat and calcium absorption, with deficient capacity for metabolizing the gluten fraction gliadin(1929-1932).

J.H. Van De Kamer (NL), H. Ten Bookkel Huinink (NL), and H.A. Weijers (NL) developed the first accurate method of quantitating stool fat. They thereby proved that diets containing wheat, barley, and rye worsened fecal fat excretion and clinical symptoms in celiac patients(1933).

Willem-Karel Dicke (NL), in the food scarce days of WWII, noticed his hospitalized I toddlers, who existed on “gruel” (porridge) improved when rice or potato flour replaced wheat flour. When Swedish planes dropped bread in The Netherlands, his patients, who had improved on wheat-free diets, all relapsed(1934).

Willem-Karel Dicke (NL), H.A. Weijers (NL), and J.H. Van De Kamer (NL) discovered that celiac disease is cured when wheat is banished from the diet, and rice flour, maize starch, and peeled, boiled potatoes are given instead(1935).

Cyrus E. Rubin (US), Lloyd L. Brandborg (US), Arnold L. Flick (US), Cherill M. Parmentier (US), and Sally Van Niel (US) observed acute small intestine changes brought about by wheat, barley, and rye in celiac disease(1936).

Walburga Dieterich (DE), Eberhardt Laag (DE), Heike Schöpper (DE), 

Umberto Volta (IT), Anne Ferguson (GB), Helen Gillett (GB), Ernst Otto Riecken (DE), and Detlef Schuppen (DE) identified tissue transglutaminase (tTG) as the major if not sole endomysial autoantigen in celiac sprue. IgA anti-tTG and IgA endomysium (EMA) show an excellent correlation, further confirming the enzyme as the celiac disease autoantigen(1937).

Lu Shan (US), Øyvind Molberg (NO), Isabelle Parrot (US), Felix Hausch (US), Ferda Filiz (US), Gary M. Gray (US), Ludvig M. Sollid (NO), and Chaltan Khosla (US) identified a 33-mer peptide that has several characteristics suggesting it is the primary initiator of the inflammatory response to gluten in celiac sprue patients. This peptide is resistant to attack by all gastric, pancreatic, and intestinal brush-border membrane proteases in these genetically predisposed patients. The peptide reacted with tissue transglutaminase (tTG), the major autoantigen in celiac sprue, with substantially greater selectivity than known natural substrates of this extracellular enzyme. It was a potent inducer of gut-derived human T cell lines from 14 of 14 celiac sprue patients. Homologs of this peptide were found in all food grains that are toxic to celiac sprue patients but are absent from all nontoxic food grains. The peptide could be detoxified in in vitro and in vivo assays by exposure to a bacterial prolyl endopeptidase, suggesting a strategy for oral peptidase supplement therapy for celiac sprue(1938).  

Paul Ehrlich (DE) was the first to distinguish the aplastic type of anemia(1939).

Sir William Richard Gowers (GB) and Sir Victor Alexander Haden Horsley (GB) reported the first successful operation for the removal of an extramedullary tumor of the spinal cord(1940).

Joseph Jules Francoise Felix Babinski (PL-FR), Paul Lècene (FR), F. Bourlot (FR), Thierry de Martel (FR), and Joseph Jumentié (FR) successfully removed spinal meningiomas(1941, 1942).

Rudolph Matas (US) reported the first known endoaneurysmorrhaphy, which he performed by opening the aneurysmal sac and narrowing the internal lumen by suture(1943, 1944).

Rudolph Matas (US), in 1888, was the first to use intravenous fluids in a surgical patient. He amputated the leg of a young man and while the blood loss of the patient was “comparatively slight” according to Dr. Matas, the patient was in a state of shock with a “small, shallow, and rapid” pulse. Dr. Matas injected two pints of a warm saline solution into the patient, resulting in a strengthening and slowing of the pulse(1945, 1946).

Jan Mikulicz-Radecki; Johannes Freiherr von Mikulicz-Radecki (PL-AT) developed an operation to repair complete prolapse of the rectum(1947).

Ian Greaves (US) and Norbert Hirschhorn (US) proposed that Louisa May Alcott (US), famous Ameican author, whose immediate cause of death in 1888 was a stroke, suffered a multi-system disease, possibly originating from effects of mercury on the immune system. A portrait of Alcott at the Alcott museum, Orchard House, in Concord, Mass exhibiting a distinctive "butterfly-rash," a pinkish hue across Alcott's cheeks and nose, that often accompanies lupus raises the possibility that she had systemic lupus erythematosus (SLE)(1948).

Sir William Osler (CA) was the primary force behind bringing the best teaching methods from Europe to Johns Hopkins Medical School and making it the leading medical center in America. He wrote Principles and Practice of Medicine, the greatest textbook of medicine in its time(1949).

Harry Govier Seeley (GB) determined that dinosaurs consist of lizard-hipped (saurischian) and bird-hipped (ornithischian) branches(1950). He named Agrosaurus (1891), Anoplosaurus (1878), Aristosuchus (1887), Craterosaurus (1874), Macrurosaurus (1876), Orthomerus (1883), Priodontognathus (1875), Rhadionsaurus (1881), and Thecospondylus (1882).

The Marine Biological Station at Woods Hole, MA in the United States was established.

1889

Svante August Arrhenius (SE) presented his equation for temperature dependence of the rate of a chemical reaction and suggested the existence of an energy of activation, an amount of energy that must be supplied to molecules before they will react(1951).

Walther Hermann Nernst (DE) discovered the energetic equivalence of Faraday's constant F to PV/n of the gas laws, thereby mathematically linking electrometric ion activity to the behavior of gases(1952).

Martinus Willum Beijerinck (NL), in 1889, is generally credited with the first thin-layer chromatography (TLC). He diffused a drop of hydrochloric and sulfuric acid mix through a gelatin thin-layer and found that the hydrochloric acid traveled faster than the sulfuric acid, separating into concentric rings. He also pioneered the use of visualization reagents. The HCl was visualized with silver nitrate, and the sulfuric acid with barium chloride. Ref 

Hendrik Paulus Wijsman, Jr. (NL) used Beijerinck's (TLC) technique to identify the active enzyme in malt diastase which splits off maltose from soluble starch. He invented the first fluorescent indicator for (TLC) visualization by preparing a gelatin layer containing starch and a marine fluorescent bacterium, he diffused the amylase mixture through the gelatin, obtaining a fluorescent band only where the beta-amylase reacted with the starch(1953).

Nikolai A. Izmailov (RU) and Maria S. Shraiber (RU) developed the "drop-chromatographic method" which later became known as thin-layer chromatography. To separate a mixture of organic plant extracts they used microscope slides coated with a suspension of various adsorbents (calcium, magnesium, aluminum oxide), then deposited one drop of the mixture on this layer, followed by one drop of the same solvent which would be used in a column separation. The separated components appeared as concentric rings that fluoresced in various colors under a UV lamp(1954).

James E. Meinhard (US) and Norris F. Hall (US) used thin-layer chromatography (TLC) to separate terpenes found in essential oils(1955).

Justus G. Kirchner (US), John M. Miller (US), George J. Keller (US), Randall G. Rice (US), Leslie S. Ettre (US), and Albert Zlatkis (US) at the US Department of Agriculture's Fruit and Vegetable Laboratory in California perfected thin-layer chromatography (TLC) by modifying the Meinhard & Hall technique, substituting silica gel as the adsorbent after investigation of over a dozen candidates and settling on gypsum as the least reactive binder(1956-1959).

Heinrich Ferdinand Edmund Drechsel (DE) isolated the amino acid lysine from hydrolyzed casein. He called it lysatine from the Greek meaning loosing(1960).

Charles Tanret (FR) isolated ergosterol from plant tissue (rye)(1961, 1962).

Gerhard Lange (DE) isolated lignic acid from wood(1963, 1964).

Gerhard Lange (DE) determined the quantitative cellulose content within woods(1965).

Franz Hofmeister (CZ-DE) crystallized ovalbumin from a half-saturated solution of ammonium sulfate. This was one of the first proteins to be isolated in pure form(1966, 1967). 

Jean-Paul Vuillemin (FR) coined the term antibiosis(1968).

Selman Abraham Waksman (RU-US ), in 1942, recoined the term as antibiotic in its modern incarnation to mean chemical substances, including compounds and preparations that are produced by microbes and have antimicrobial properties(1969).

Rudolf Emmerich (DE) and Oscar Löw (DE) introduced an antibacterial agent from aged cultures of Pseudomonas. They named their material pyocyanase, thinking it was an enzyme. Although a potent antibiotic it proved to be so toxic that it was not clinically usable(1970).

Martinus Willem Beijerinck (NL) invented the technique of auxanography. Its application underlies the disk diffusion antibiotic assay and vitamin assays based on diffusion of the vitamin within a gel(1971).

Theodor Boveri (DE) demonstrated the role of the nucleus in heredity by fertilizing nonnucleated fragments of uncleaved sea urchin eggs and found that in some cases, at least, normal larvae developed, as they did also on occasion from unfertilized egg fragments containing only the egg nucleus. This was a clear demonstration of the equivalence, for development, of the maternal and paternal nuclei(1972).

August Julius Geppert (DE) demonstrated that while mercuric dichloride appears to be a potent antibacterial agent, its effect must be qualified. He found that on adding ammonium sulfide to precipitate all the mercury at the end of an experiment many of the cells which appeared to be dead by Koch’s technique were in fact still alive. They had been unable to develop because of the traces of mercuric chloride surrounding them. Without ammonium sulfide treatment, mercuric dichloride in a concentration of 1:1000 apparently killed all the anthrax spores in from 3 to 7 minutes, but if the mercury was precipitated as sulfide many of the spores were shown to have survived. Even after exposure to a concentration of 1:100 mercuric dichloride, anthrax spores were not destroyed with certainty when treated for 6 to 12 minutes(1973).

Hans Ernst August Buchner (DE) confirmed the work of Josef von Fodor (HU) and George Henry Falkiner Nuttall (US-GB) by showing that antibacterial substances occur in the serum. He went on to show that this bactericidal quality of blood can be demonstrated in vivo. The carotid artery of a dog was exposed and connected with a cannula. The animal was then injected with a culture of typhoid bacilli, and 50 c.c. of blood allowed to flow from the cannula to ensure that the artery was filled with blood. A small quantity of blood was again run out and tested for the presence of typhoid bacilli. The artery above was then ligated in two places and the contents of the isolated segment was examined five hours later, when it was found that a profound reduction in the number of bacilli had ensued. In the course of his prolonged researches Hans Buchner gradually elaborated the view of the existence of substances in the serum inimical to bacteria. He named the substances alexines (I defend) for their protective and defensive properties(1974-1976). This work is part of the discovery of the complement system. See, von Fodor 1887.

Otto Bütschli (DE) and Conrad Schwager (DE) wrote one of the first and most important monographs on the protozoa. The scale and range of this three volume work is remarkable(1977). 

During 1889 and in 1892, there occurred among the caterpillars of the nun moth, Lymantria monacha Linn., which was destroying large spruce forests in Europe, a peculiar disease which killed off enormous numbers of the insect. The disease, later found to be a virus-induced polyhedrosis called Wipfelkrankheit, is one of the first known examples of natural insect pest control(1978).

Edward Klein (DE) reported that Bacillus gallinarum was the cause of an outbreak of fowl cholera and reported as an infectious enteritis(1979).

Veranus A. Moore (US) described the disease as infectious leukaemia and named the organism Bacillus sanguinarum(1980, 1981).

Leo F. Rettger (US) (1899) was the first to isolate Salmonella pullorum and describe it as the cause of a fatal septicemia of young chicks(1982).

Leo F. Rettger (US) designated the disease as white diarrhoea(1983).

Frederick Cooper Curtice (1902) studied the disease in Rhode Island and named it fowl typhoid(1984).

Leo F. Rettger (US) and Frederick H. Stoneburn (US) expanded the term to bacillary white diarrhea to distinguish it from other diseases that might be classified under a common term of white diarrhea(1985).

Theobald Smith (US) and Carl TenBroeck (US) recorded that Salmonella gallinarum and Salmonella pullorum are serologically identical(1986).

Albert Charrin (FR) and Henri Louis Roger (FR) found that when Bacillus pyocyaneus is grown in the serum of an animal previously injected with B. pyocyaneus it does not grow diffusely through the medium, as it does in broth or normal serum, but in small masses which sink to the bottom of the tubes and the bacilli are found stuck together. The clumping of particulate matter, e.g., bacteria, due to immune serum is now called agglutination (1987).

Max von Gruber (AT) and Herbert Edward Durham (GB) extended this observation by showing that the agglutination of bacteria by serum is specific(1988-1992). This was quickly seized upon as a new diagnostic tool.

Georges Fernand Isidore Widal (FR), Arthur Sicard (FR) and Albert Sidney Frankau Grünbaum (GB)— Grünbaum later changed his name to Albert Sidney Frankau Leyton— showed that the agglutination of enteric bacteria can be used as an aid to identifying the infectious agent. This reaction is brought about by the addition of a patient’s serum to a uniform suspension of a known bacterium. The Widal test is used for diagnosis of typhoid fever by mixing the patients serum with a 24-hour Salmonella typhi culture on a glass slide or other appropriate surface. Clumping of the cells after a 30 to 60 minute incubation is a positive reaction(1993-1996).

Theobald Smith (US) and Frederick Lucius Kilbourne (US), assisted by Frederick Cooper Curtice (US) discovered that the infectious agent of Texas cattle fever, also known as tick fever, or bovine fever, is Pirosoma bigeminum (Babesia bigemina) (a protozoan) which is transmitted by the cattle tick, Boophilus bovis (Boophilus annulatus). Their 1893 paper is a masterpiece of orderly reasoning, experiments to answer specific questions, and complete details of each animal used; it is a recognized classic in medical literature. Quoting from a summary in the 1893 monograph,

“(1) Texas cattle fever is a disease of the blood, characterized by the destruction of red corpuscles. The symptoms are partly due to the anemia produced; partly to the large amount of debris in the blood, which is excreted with difficulty, and which causes derangement of the organs occupied with its removal.

(2) The destruction of the red corpuscles is due to a microorganism or micro-parasite which lives within them. It belongs to the protozoa and passes through several distinct phases in the blood.

(3) Cattle from the permanently infected territory, though otherwise healthy, carry the micro-parasite of Texas fever in their blood.

(4) Texas fever may be produced in susceptible cattle as a direct inoculation of blood containing the micro-parasite.

(5) Texas fever in nature is transmitted from cattle which come from the permanently infected territory to cattle outside of this territory by the cattle tick (Boophilus bovis).

(6) The infection is carried by the transovarian passage through the progeny of the ticks that matured on infected cattle, and the organisms inoculated by them directly into the blood of susceptible cattle.

(7) Sick natives may be a source of infection (when ticks are present).

(8) Texas fever is more fatal to adult than to young cattle.

(9) Two mild attacks or one severe attack will probably prevent a subsequent fatal attack in every case.

(10) Sheep, rabbits, guinea pigs, and pigeons are susceptible to direct inoculation. (Other animals have not been tested.)

(11) In the diagnosis of Texas fever in the living animal the blood should always be examined microscopically if possible"(1997, 1998).

Heinrich Hermann Robert Koch (DE) described the stages of Babesia bigemina developing in the tick's gut within the first 20 hours after repletion(1999).

Henri Parinaud (BE) discovered cat-scratch-fever(2000).

M. Petzetakis (GR) described cat-scratch- fever, an acute infectious disease, occurring most commonly in children and young adults, in patients who have been scratched or bitten by cats or exposed to a penetrating wound (thorn, splinters, hooks)(2001).

Robert Anselme Debré (FR), Maurice Larny (FR), and Marie-Louise Jammet (FR) discovered that the cat is the natural reservoir of cat-scratch-fever(2002).

Charles K. English (US), Douglas J. Wear (US), Andrew M. Margileth (US), Christopher R. Lissner (US), and Gerald P. Walsh (US), isolated the etiological agent of cat-scratch-fever(2003). Bartonella henselae or Bartonella clarridgeiae are known to cause this disease.

Ira Van Gieson (US) introduced the first triple staining technique to histology. He used hematoxylin, acid fuchsin, and picric acid to stain nerve tissue(2004).

Walther Flemming (DE) introduced his triple stain to histology. It consisted of safranin, followed by gentian violet, and decolorization in orange G. It is a favorite with botanical cytologists and is valued for staining cells in mitosis(2005).

Wilhelm His (CH) proved that the origins of neural parts of the nervous system are ectodermal and the vascular parts mesodermal. He further suggested that embryonal neuroglial fibers may guide the migration of early neuronal cells(388).

Carlo Giovanni Martinotti (IT) described a cortical neuron with an ascending axon (this neuron now bears his name, Martinotti cell)(2006).

Franz C. Müller-Lyer (DE) discovered the Müller-Lyer illusion (an optical illusion in which the orientation of arrowheads makes one line segment look longer than another)(2007).

Sir Francis Galton (GB) formulated the law of ancestral inheritance, a statistical description of the relative contributions to heredity made by one's ancestors(2008). This book is considered the beginning of modern biometry.

Sir Henry Head (GB) demonstrated the action of the vagus nerve in respiration(2009).

Ludwig Edinger (DE), in 1889, discovered the direct connection of the spinal cord and thalamus in fish, frogs and cat embryos. He found that cells in the dorsal horn give rise to axons which pass through the ventral commissure, ascend in the opposite anterolateral funiculus and seemingly end in the thalamus. ref

Leopold Auerbach (DE) confirmed this(2010).

Eliza Dalgleish Ewart (GB) gave the first comprehensive description of the anatomy of the human lung(2011).

Charles-Édouard Brown-Séquard (FR) reported that he had “rejuvenated” himself with subcutaneous injections of a testicular extract from freshly killed guinea pigs and dogs(2012, 2013).

Berthold Hatschek (CZ-AT) removed the ctenophores as a separate group recognizing that the coelonterata should be subdivided into Spongiara, Cnidaria, and Ctenophora. He gave a distinct name to the group as Phylum Ctenophora(2014).

Ernst Fuchs (DE) described an outbreak of epidemic keratoconjunctivitis (EKC)(2015).

Ernest Jawetz (US), Samuel J. Kimura (US), Lavelle Hanna (US), Virginia R. Coleman (US), Phillips Thygeson (US), and A.N. Nicholas (US) discovered that this clinical picture of epidemic keratoconjunctivitis (EKC) is associated with adenovirus type 8(2016, 2017).

Stephen Paget (GB) analyzed 735 case histories of fatal breast cancer, he found that metastases formed in the liver far more often than in any other organ — even those such as the spleen that could be considered to have the same exposure to the cancer cells because of similar blood flows. Paget reasoned that sites of secondary growths are not a matter of chance, and that some organs provide a more fertile environment than others for the growth of certain metastases. "The best work in the pathology of cancer is now done by those who... are studying the nature of the seed," he noted. "They are like scientific botanists; and he who turns over the records of cases of cancer is only a ploughman, but his observation of the properties of the soil may also be useful." This is referred to as the seed and soil hypothesis of cancer(2018).

Ian Hart (GB) and Isaiah Fidler (US) performed experiments in mice which verified Paget’s hypothesis(2019).

Joseph von Mering (DE) and Oskar Minkowski (DE) discovered the role of the pancreas in glucoregulation when they surgically removed the pancreas of dogs and found that their blood sugar and urine sugar would rise causing hyperglycemia and glycosuria (diabetes mellitus)(2020-2022). See Thomas Cawley, 1788.

William Stewart Halsted (US) pioneered the radical mastectomy operation that entailed removal of the breast and underlying muscles, and lymph nodes under the arm. This was in response to the high rate of cancer recurrence experienced at the time(2023). He eventually achieved an unprecedented 72 percent five-year cure rate for patients whose disease had not spread to adjoining glands. Halsted first performed this operation in 1889.

Jan Mikulicz-Radecki; Johannes Freiherr von Mikulicz-Radecki (PL-AT) performed the first enterocystoplasty(2024).

Edoardo Bassini (IT) and William Stewart Halsted (US) independently developed a surgical procedure for the radical repair of inguinal hernia (Bassini's operation) (Halsted’s operation 1). Bassini used cocaine as a local anesthetic in these operations(2025-2027). This is called herniorrhaphy.

Wilhelm Wagner (DE) used a scalpel, hammer, and chisel to resect a flap of scalp and skull hinged upon muscle so that it could be replaced. With such a large osteoplastic flap, the surgeon could cut the dura mater about an attached tumor or reflect the dura mater to explore much of the lateral cortex. This method could expose a much larger area of the brain’s surface than a trephine(2028).

Ernst Gustav Benjamin von Bergmann (LV-DE) wrote a classic textbook on cranial surgery which was later incorporated into the five volume work on surgery by von Bergmann and Paul von Bruns (DE)(2029, 2030).

Paul Loye (FR) concluded that the loss of complete consciousness and brain death occurred immediately after decapitation, but various parts of the body, such as the heart, continued to work for several minutes as a reflex action(2031).

Pierre Marie Félix Janet (FR) argued that "hysterical symptoms are due to subconscious fixed ideas that have been isolated and usually forgotten. Split off from consciousness – 'dissociated' – they embody painful experiences, but become autonomous by virtue of their segregation from the main stream of consciousness(2032). This predated Freud's announcement of virtually, an identical discovery, by four years.

Sir Jonathan Hutchinson (GB) originated the naming of clinical disorders after patients—Hilliard’s lupus—as opposed to naming them for the describing physician(2033).

A worldwide epidemic of influenza, the most devastating to that time, began in central Asia in the summer of 1889, spread north into Russia, east to China and west to Europe. By December it had struck the major U.S. cities, and continued to spread through North America the following year. Parts of Africa and the Middle East were infected early in 1890; and India, Southeast Asia, Australia and New Zealand were reached between February and May. Completing the circle, Eastern China had the last major outbreak of this pandemic, in September and October of 1890(176).

1890

“When you have eliminated the impossible, whatever remains, however improbable, must be the truth.” Sherlock Holmes from the Sign of the Four by Sir Arthur Conan Doyle(2034).

"The immunity of rabbits and mice which have been immunized against tetanus rests on the capability of cell-free blood serum to render harmless the toxic substances which the tetanus bacilli produce." Emil Adolf von Behring, Shibasaburo Kitasato(2035).

Jakob Stilling (DE) reported the bacteriostatic action of the triphenylmethane dyes. Methyl violet and auramine were recommended as useful antiseptics(2036, 2037). The bacteriostatic property of malachite green was reported later.

John W. Churchman (US) showed that derivatives of triphenylmethane such as gentian violet and brilliant green dyes are inhibitory to bacteria, particularly Gram positives; and crystal violet causes some inhibition of fungi(2038).

Friederich August Johannes Löffler (DE) made a thorough investigation of and perfected the technique of staining bacterial flagella. He discovered that quite often the method had to be varied slightly with each different species of bacterium being stained. He discovered that the reaction in its relation to H-ion concentration is critical and that no one H-ion concentration is best for all bacteria(2039).

Richard Altmann (DE) introduced the technique of freeze-drying to preserve tissue(2040).

Leon F. Shackell (US) reported on the principle of vacuum desiccation from the frozen state, a process essential to the production of a highly soluble product which would retain its original biological properties(2041).

Pierre Miquel (FR) obtained urease from bacteria(2042).

Theodor Boveri (DE) and Jean-Louis-Léon Guignard (FR) established that the nuclei of egg and spermatozoon furnish to the zygote equivalent complements of chromosomes(2043, 2044).

Wilhelm August Oskar Hertwig (DE) reached the same conclusion as Boveri and Guignard above and concluded that, the polar body does not represent a part of the germ plasm removed from the egg but has, in fact, ''the morphological value of rudimentary egg cells"(2045).

Knud Helge Faber (DK), Ludwig Brieger (DE), and Carl Fraenkel (DE) showed that the symptoms of tetanus lockjaw are due to a toxin produced by the bacterium Clostridium tetani(2046-2048).

Willoughby Dayton Miller (US) elucidated the bacteriology of dental caries(2049).

Christiaan Eijkman (NL), Gerrit Grijns (NL), Adolphe Guillaume Vorderman (NL), Henry Fraser (GB), and Ambroise Thomas Stanton (GB) discovered that a constituent of rice (Oryza sativa) husks (thiamine, vitamin B1) cured a neurological disease of birds (polyneuritis gallinarum) that resembles the human disease known as beriberi. They knew it was a dietary-deficiency-disease, although they did not know what was missing from a diet to cause it. They discovered that beriberi could be cured by adding rice shavings (outer layer) to the diet(2050-2057).

Christiaan Eijkman (NL) and Gerrit Grijns (NL) described the properties of their antineuritic dietary factor (thiamine, vitamin B1) as soluble in water or dilute alcohol, and diffusable through a semi-permeable membrane(2058).

Umetaro Suzuki (JP), Torai Shimamura (JP), and Seizaburo Okada (JP) isolated the antineuritic, anti-beriberi factor (thiamine, vitamin B1) as a crystalline picrate(2059).

Juan Antonio Collazo (UY) and Casimir Funk (PL-GB-FR-US) noted that pigeons placed on a diet deficient in the antineuritic, anti-beriberi factor (thiamine, vitamin B1) then fed a diet high in carbohydrates exhibited a toxic (beriberi) effect. He concluded that in this vitamin deficiency, normal carbohydrate metabolism cannot function properly(2060).

Barend Coenraad Petrus Jansen (NL) and Willem Frederik Donath (NL) crystallized thiamine (vitamin B1)(2061).

Louis Sigurd Fridericia (DK), P. Freudenthal (DK), Skúli V. Gudjónnson (DK), G. Johansen (DK), and N. Schoubye (DK) demonstrated that rats are capable of adjusting their digestion to accommodate a diet deficient in thiamine (vitamin B1). They called this phenomenon refection. The microbiota of the cecum of refected rats differs significantly from that of rats on a diet containing thiamine(2062).

Carl Arthur Scheunert (DE), Martin Schieblich (DE), and Johannes Rodenkirchen (DE) associated this synthesis of thiamine (vitamin B1) in refected rats with the presence of intestinal vibrios(2063).

R. Inawashiro (JP), E. Hayasaka (JP), Henry Wulff Kinnersley (GB), Nicolai Gavrilescu (HU), and Sir Rudolph Albert Peters (GB) demonstrated that vitamin B1 (thiamine) and pyrophosphate are associated with the breakdown and removal of pyruvic acid from animal tissue, since lactic acid disappeared more slowly from the blood of beriberi patients after exercise and lactic acid accumulated in the brain tissue of B1-deficient pigeons, and the addition of vitamin B1 and pyrophosphate to the minced tissue caused the rapid disappearance of pyruvic acid without the accumulation of lactic acid. They determined that the head retraction and opisthotonus of pigeons fed on polished rice (Oryza sativa) were of central and not peripheral nerve origin, and that vitamin B1 (thiamine) played a special part in tissue oxidations(2064-2070).

Adolf Otto Rheinhold Windaus (DE), Rudolf Tschesche (DE), Hans Ruhkopf (DE), Fritz Laquer (DE), and Fritz Schultz (DE) isolated the pure vitamin B1 from yeast and established its empirical formula(2071).

Adolf Otto Rheinhold Windaus (DE), Rudolf Tschesche (DE), and Hans Ruhkopf (DE) discovered that vitamin B1 (thiamine) contains sulfur(2072).

Ernst Auhagen (DE) discovered that yeast carboxylase, the enzyme which decarboxylates pyruvic acid to acetylaldehyde, requires a heat-stable dialyzable coenzyme(2073). It was first called co-carboxylase, then later named thiamine (vitamin B1).

Robert Rampathnam Williams (US), Robert E. Waterman (US), and John C. Keresztesy (US) isolated the antineuritic, anti-beriberi factor (thiamine, vitamin B1) in highly purified form on a large scale(2074).

Robert Rampathnam Williams (US), Joseph K. Cline (US), Jacob Finkelstein (US), Alexander Robertus Todd (GB), Franz Bergel (GB), Hans Andersag (DE), Kurt Westphal (DE), Kurt Guenter Stern (GB-US), and Jesse W. Hofer (US) synthesized and determined the structure of the co-carboxylase (a pyrophosphoric ester of vitamin B1) discovered by Ernst Auhagen (DE). They characterized it as a pyrimidine ring linked by a methyl group to a thiazole ring and named it thiamine (vitamin B1)(2075-2080).

Karl Lohmann (DE) and Philipp Schuster (DE) determined that thiamine pyrophosphate chloride (vitamin B1) functions as a coenzyme (co-carboxylase) which is necessary for the enzyme carboxylase active in the decarboxylation of many alpha-keto acids(2081).

Wilhelm Friedrich Ostwald (LV-DE) laid the theoretical groundwork for the membrane theory of nerve conduction. He suggested that the electrical potential at artificial semipermeable membranes was due to their selective permeability to ions ("ion sieve")(2082).

Julius Bernstein (DE), in 1902, stated his membrane theory as follows, “The electrical currents observed in many living organs of animals and plants have been the objects of much research. We detect such currents in muscles, nerves, secretory glands, and electric organs of fish as well as in plant tissue. It seems likely that all these currents have a similar, if not the same basis, and that their strength and potency depends on the structural conditions and chemical composition of the cells making up each organ.” He postulated that the membrane of the nerve cell is able to selectively pass certain kinds of ions. Bernstein made the suggestion that nerves are normally polarized with positive ions on the outside and negative ions inside and that the current he measured was the change in this polarization. Obviously when equilibrium is reached an electrical potential exists across the membrane - the transmembrane potential. The nerve impulse is simply a localized region of depolarization, or loss of this transmembrane potential, that travels down the nerve fiber with the membrane potential being immediately restored behind it(2083, 2084). This is remarkably close to what is currently accepted as how a nerve impulse is generated.

Ralph Stayner Lillie (US) started experiments in 1909 which supported the membrane theory of nerve conduction(2085).

Sir Alan Lloyd Hodgkin (GB) supported this theory with experiment(2086, 2087).

Francois-Gilbert Viault (FR) found that following 23 days at 4392 meters of altitude his red cell count rose from 5 to 8 million per cubic millimeter(2088). He later confirmed that hemoglobin concentrations rise on ascent to higher altitudes.

Carl Fraenkel (DE) found that he could immunize guinea pigs against living Corynebacterium diphtheriae by giving an injection of a three week old heat killed (60-70°C for one hour) culture of the same species(2089).

Emil Adolf von Behring (DE) and Shibasaburo Kitasato (JP) discovered antitoxin while working on immunity to tetanus and diphtheria. They reported that when rabbits and mice were immunized to tetanus a protective element was present in the cell-free serum which neutralized the effect of the toxin. This capacity was so durable that it still exhibited its activity when the immune serum was transferred to the bodies of other animals. They referred to the serum as possessing an antitoxic quality(2035, 2090).

Augosto Ducrey (IT) described the infection and isolated the bacterium which now bears his name, Hemophilus ducreyi, from a lesion of the venereal disease called soft chancre or chancroid(2091-2094).

F. Bezancon (FR), V. Griffon (FR), and L.C. Le Sourd (FR) obtained the organism in axenic culture(2095).

F. Bezancon (FR), V. Griffon (FR), and L.C. Le Sourd (FR) inoculated the forearms of human volunteers with culture purified organisms and produced characteristic soft chancres from which the same organism was re-isolated(2096).

Hans Eppinger (DE) was the first to describe an infection in humans caused by Nocardia spp. He called it Cladothrix which was changed to Nocardia in 1895 by Blanchard. The fungus-like organism caused lesions in pulmonary and central nervous system tissues (nocardiosis)(2097).

Johann Gottfried Hallier; Hans Gottfried Hallier (DE) insisted that only the broadest possible basis was sufficient for establishing the taxonomy of plants. He included not only the morphology of reproductive structures, but added comparative morphology of the vegetative organs; comparative anatomy, ontogeny and embryology; phytochemistry, physiology and ecology; structure of pollen and seed coat; relation to climate, seasons and the surrounding organic world, plant geography, paleophytology, etc(2098-2104). See, page 154 of the 1905 reference for articles going back to 1890. 

Douglas Houghton Campbell (US) discovered the precise manner of formation of the archegonia and antheridia in the eusporangiate ferns. He also linked the ferns with the liverworts by way of Anthoceros(2105-2114).

Jacques Loeb (DE-US) introduced the concepts of forced movements, tropisms and animal conduct. He vehemently opposed any anthropomorphic or teleological interpretations of animal behavior(2115, 2116).

Thomas Henry Huxley (GB) and Theodor Wilhelm Engelmann (DE) suggested that muscle fibrils are the likely location for the contractile mechanism(2117, 2118).

Charles Smart Roy (GB) and Charles Scott Sherrington (GB) concluded that, “The chemical products of cerebral metabolism contained in the lymph which bathes the walls of the arterioles of the brain can cause variations of the caliber of the cerebral vessels; … in this reaction the brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with local variations of functional activity”(2119).

Henry S. Forbes (US) and Stanley Cobb (US) supported them and concluded that carbon dioxide is a major regulator of vasomotor activity in the brain(2120).

Vittorio Mibelli (IT) described and named angiokeratoma as, “The presence of small red spots could be seen, which resembled telangiectases and were covered already by a slightly elevated and horny epidermis…. The external appearance of the small tumors suggested the diagnosis of keratoma”(2121).

Franz König (DE) gave a detailed description of joint involvement in hemophilia(2122).

Allvar Gullstrand (SE) presented his theory of astigmatism and elucidated how the eye accomplishes intracapsular accommodation(2123-2127).

Pierre Marie (FR) described hypertrophic osteoarthropathy (digital Hippocratism) as follows: “The volume of all the phalanges of the fingers are increased, but above all in the case of the phalangette. The nail is enlarged; it has the Hippocratic appearance of a parrot's beak”(2128).

Odilon Marc Lannelongue (FR) performed the first thyroid transplantation, for treatment of cretinism(2129).

William Rose (GB) performed a Gasserian ganglionectomy for trigeminal neuralgia; the patient lived for at least two years(2130).

Ludwig Courvoisier (CH) did important work concerned surgery to the biliary tract. It was he who developed the operation of cholecystectomy and he was one of the first surgeons to remove a stone from the common bile duct. The well known Courvoisier's law is named after him stating that 'if in the presence of jaundice the gallbladder is palpable, then the jaundice is unlikely to be due a stone.' This was first proposed by him in his book The Pathology and Surgery of the Gallbladder(2131).

Sir Charles Alfred Ballance (GB) popularized the operation of radical mastoidectomy for advanced middle ear infection in 1890(2132). Ballance also demonstrated cranial base approaches to treat infectious thrombophlebitis of the petrosal, lateral, and cavernous sinus.

Themistocles Gluck (DE), during the 1880s, performed 14 total joint replacements; five of them were still in function in 1891: three total knee replacements, one elbow, and one wrist total replacement. All total joints were made from ivory. For their fixation inside the marrow cavity Gluck often used a special form of very hot "bone cement" that hardened within one minute(2133, 2134).

Hermann Oppenheim (DE) and R. Köhler (DE) performed the first successful removal of a brain tumor(2135). verify

Friedrich Trendelenburg (DE) described the Trendelenburg position for surgery as, “If one places the body of a patient on the operating table in such a way that the symphysis pubis forms the highest point of the trunk and the long axis of the trunk forms an angle of at least 45 degrees with the horizontal”(1373).

Sergei Sergeievich Korsakoff (RU) described a special form of psychic disorder which occurs in conjunction with multiple neuritis. This disorder is now known as Korsakoff's psychosis(2136, 2137).

The Brooklyn Institute of Arts and Science in New York established the Biological Laboratory at the southwest corner of Cold Spring Harbor, Long Island, NY. Charles B. Davenport (US) became its first director. In 1904, he persuaded Andrew Carnegie to found for him the Station for Experimental Evolution on the same site as the Biological Laboratory. Davenport became the director of both. The two were formally joined in 1962 as the Cold Spring Harbor Laboratory.

The journal Zentralblatt für Allgemeine Pathologie und Pathologische Anatomie was founded.

1891

Johannes Diderik van der Waals (NL) presented his equation of state for gases and liquids which explains molecular behavior when a substance is composed of two species(2138).

Hermann Nordtmeyer (DE) introduced a new filtering medium made of the compressed infusorial (diatomaceous) earth known as Kieselguhr(2139).

Alfred Werner (DE) formulated a new approach to inorganic chemistry that allowed the formulation of atomic groups about a metal ion. As applied to heme, the theory led to the recognition that the ferrous iron is hexacoordinate, with four valencies satisfied by the nitrogens of the pyrroles of the porphyrin ring and the other two available for other interactions (e.g., with O2, CO, imidazole, pyridine)(2140).

Lead arsenate insecticide was first used as an insecticide for control of the gypsy moth. Carbon bisulfide was first tested for control of wireworms. Creosote oil was discovered as an ovicide for gypsy moth(138).

Ernst August Schulze (CH) discovered that the woody substances of plants contain polysaccharides (hemicelluloses and pentosans) which are much more readily hydrolyzed to sugars by very dilute mineral acids than is cellulose. Among the sugars formed in this way he detected galactose, mannose, and the pentose sugars, arabinose and xylose. He coined the term hemicellulose(2141).

Isidor Traube (DE) discovered that many organic solutes are adsorbed at a water/air interface, with the polar ends of molecules in the water and non-polar parts sticking out into the air(2142).

Karl von Voit (DE) showed that fasting hens stored glycogen in their livers not only when they were supplied with glucose but also when sucrose, fructose, or maltose were in their diet in place of glucose(2143).

Hermann Henking (DE) observed an unpaired chromatin-element in spermatogenesis of Pyrrhocoris apterus (Hemiptera) so that sperms of two different types were produced, half with and half without this element. Henking did not realize that the element was a chromosome nor did he associate it with sex. He called it x. He also demonstrated that reductive division begins with conjugation of chromosomes, two by two (2144). This is the first indication for a connection between chromosomes and sex.

Johannes Ruckert (DE) suggested that the conjugants had come one from each parent, and that they could exchange material(2145).

Ernst Malachowski (PL) stained malarial parasites using borax methylene blue which had polychromed because of its age (2-3 years). The plasmodial chromatin took on a red-purple color(2146).

Dimitri Leonidovich Romanowsky; Dimitri Leonidovich Romanovsk (RU) developed a stain which allowed for differential identification of blood parasites, including malaria(2147).

Paul Ehrlich (DE) selectively stained mast cells using a dye called dahlia(2148).

Liberty Hyde Bailey, Jr. (US) published the first detailed study of the growth of plants under artificial light(2149, 2150).

Joseph F. Payne (GB) remarked on the infectious nature of warts(2151).

Merton B. Waite (US) discovered that bees and wasps are vectors of fire blight, a bacterial disease of pears and other orchard fruits(2152).

Pierre-Jean Achalme (FR) was the first to cultivate Clostridium perfringens. He incorrectly supposed it to cause articular rheumatism(2153).

William Henry Welch (US) and George Henry Falkiner Nuttall (US-GB) isolated and characterized the same organism from the foamy organs of a cadaver, naming it Bacillus aerogenes capsalatus(2154).

Adolf Schenkl (CZ), R.R. von Limbeck (CZ), Emanuel Zaufal (CZ), et al. used animal studies to verify that a gram-positive spore-forming rod shaped microorganism that grew only under anaerobic conditions, was the etiologic agent of gas gangrene(2155). Note, this clinical entity is also called clostridial myonecrosis.

Eugen Fraenkel (DE) isolated this organism and designated it Bacillus phlegmonis emphysematosae(2156). It has been called by various names including: Clostridium welchii, Clostridium perfringens (L. perfringens, breakthrough), and Fraenkel’s bacillus.

Clostridium perfringens is the common leavening agent in salt rising bread(2157).

Paul Ehrlich (DE) during his studies of ricin from the castor bean and abrin from the Indian licorice seed showed that each of these vegetable poisons induces the production of an antitoxin which is specific. He also discovered that there is always a delay (latent period) in the production of antitoxin following the administration of toxin. In mice this production did not begin to appear until the fifth day post-inoculation(2158).

Paul Ehrlich (DE) pointed out that there is a difference between active and passive immunization. He injected mice with abrin, ricin, robin (a phytotoxin from locust tree bark), or tetanus poisons and showed that males highly immunized with abrin are incapable, when paired with normal females, of transmitting their immunity to their offspring, in other words the immunizing principle is not carried in the genes of the sperma. Female mice immunized before conception bore immune young, but the immunity was of a passive type in that it disappeared in a relatively short space of time. Further, the immunity was not transmitted in the next generation and was not truly hereditary. Investigating the matter still further, Ehrlich observed that immunity in the offspring of mice actively immunized against ricin lasted longer than the immunity of adult mice passively immunized with antitoxin. To test this further he took the young of the non-immunized mother and put them to the breast of an immunized mother and the young of the immunized mother and put them to the breast of a non-immunized mother. The result was conclusive. The young of the immunized mother lost their immunity while sucking the normal mother, whereas the young of the non-immune mother put to the breast of an immunized mouse rapidly developed an immunity which must have been lactogenic(2159).

Heinrich Hermann Robert Koch (DE) made his much awaited announcement of the composition of his remedy for tuberculosis. It was a simple culture extract which was soon referred to as Koch’s Lymph and later became known as tuberculin(2160).

Emil Adolf von Behring (DE) and Shibasaburo Kitasato (JP) used their anti-diphtheria toxin to treat humans for the first time on Christmas night, 1891(2161). The results were disappointing.

Alexander T. Glenny (GB), Barbara Hopkins (GB) and Gaston Ramon (FR) produced an effective toxoid vaccine to diphtheria. With subsequent improvements this became one of the most effective vaccines available in medicine. See, Glenny, Hopkins, and Ramon, 1923.

Hans Driesch (DE) separated a developing sea urchin embryo at the two cell stage and found that each of the cells would form a complete, though small larva. He realized that if each half-egg forms a whole rather than a half-embryo, then an interaction must occur between the two cells to restrict their potentials in normal development. Dreisch's theory of totipotency contradicted Wilhelm Roux's mosaic theory (2162). Driesch went on to show that up to the four cell stage separated blastomeres would develop into perfect embryos, each of reduced size(2163).

Walter Heape (GB) was the first to achieve normal embryonic development and birth following the transfer of a fertilized ovum (zygote) from one female to the uterus of another variety of the same animal (rabbits)(2164).

Gregory Goodwin Pincus (US) and Ernst Vincenz Enzmann (US) isolated a rabbit ovum, fertilized it in a watch glass then reimplanted it in a rabbit doe other than the one which furnished the oocyte. A successful pregnancy was thus inaugurated in the unmated recipient(2165).

Min Chueh Chang (CN-US) demonstrated that ova from a black rabbit fertilized in vitro by capacitated sperm from a black male and transferred to a white female resulted in the birth of a litter of black young. This represents the first verified in vitro fertilization in which the resulting zygotes were brought to term(2166).

Robert G. Edwards (GB), Barry D. Bavister (GB), Patrick Christopher Steptoe (GB), and Jean M. Purdy (GB) achieved in vitro fertilization of a human ovum, a technological advance that has revolutionized the treatment of human infertility(2167-2172).

Yves Menezo (FR)  developed the world's first B2 culture medium, known as "the French medium" it reflected the follicular, tubal, and uterine environments of sheep, rabbits and humans. 

Louise Joy Brown (GB) the world’s first test tube baby (in vitro fertilization) was born in Oldham, Northern England, on July 25, 1978. Patrick Christopher Steptoe (GB) and Robert G. Edwards (GB) performed the operation(2169). 

Mark E. Cohen (US) discussed some of the legal aspects attendant to the first successful human in vitro fertilization (IVF) and subsequent live birth of Louise Joy Brown(2173).

Elizabeth Jordan Carr (US) was born December, 1981, the first baby in the United States to be conceived using in vitro fertilization (IVF) and the 15th in the world. Howard Jones (US) and Georgeanna Seegar Jones (US) directed the process. Mason Andrews (US) delivered her(2174).

Andrea Laws-King (AU), Alan Trounson (AU), A. Henry Sathananthan (AU), and Ismail  Kola (ZA) reported a technique that would revolutionize assisted reproductive technology and offer hope to couples where other infertility treatments had failed. The technique — referred to as SUZI (sub-zonal insertion)— involved the microinjection of sperm under the zona pellucida of human oocytes. Using preovulatory oocytes and spermatozoa that had undergone capacitation through chemical exposure, a single spermatozoon was microinjected into the perivitelline space. Of five out of seven oocytes fertilized, three went on to cleave and one reached the six-cell stage of cleavage(2175).

The SUZI technique had profound implications for the treatment of severe male infertility, and offered hope to men with completely immotile, immature or abnormal spermatozoa. However, there were drawbacks. When the technique was used for treating infertility, multiple sperm were injected under the zona pellucida to increase the chance of fertilization. This increased the risk of polyspermy, a lethal condition when more than one sperm enters the oocyte.

Gianpiero Palermo (BE), Hubert Joris (BE), Paul Devroey (BE), and André C. Van Steirteghem (BE) obtained successful human pregnancies in three out of four couples that had previously been unsuccessful with SUZI and other in vitro techniques. Successful fertilization using the ICSI (intracytoplasmic sperm injection) method required the microinjection of just a single spermatozoon into the ooplasm of an oocyte, thereby bypassing spermatozoa binding and penetration into the zona pellucida and the fusion of sperm by the acrosome reaction(2176). 

Trasaburo Araki (JP) and Hermann Zillessen (DE) found that if they interrupted oxygen supply to muscles in mammals and birds, lactic acid was formed and increased. This was the first demonstration of the relationship between tissue hypoxia and the formation of lactate(2177-2181).

Sir William Maddock Bayliss (GB) and Ernest Henry Starling (GB) demonstrated a delay of about 0.13 seconds between atrial stimulation and ventricular depolarization (later called the PR interval)(2182).

Paul Guttmann (DE) and Paul Ehrlich (DE) were the first to report the antimalarial properties of a synthetic, rather than a natural, material when they described the clinical cure of two patients after oral administration of a thiazine dye, methylene blue(2183).

Luigi Luciani (IT) distinguished three stages of starvation in man - hunger, physiological inanition (exhaustion), and pathological inanition(2184).

John Benjamin Murphy (US) invented Murphy’s button, used to rapidly join the ends of a divided intestine. This devise revolutionized abdominal surgery(2185).

Luigi Luciani (IT-DE) proposed that the cerebellar region of the brain functions as a regulator of tonic and static motor activity. From his experimental results he assigned a generalized (unitary) refining role to the cerebellum such that it acts on voluntary movements initiated by higher centers(2186).

Friedrich Maass (DE) was the first to clinically describe closed-chest cardiopulmonary resuscitation (CPR). He resuscitated a teenager for 60 minutes with closed-chest cardiac massage in 1891 (with return of mental function), and described that the optimal technique was to apply forceful pressure and to do so at a rapid rate(2187).

William Bennett Kouwenhoven (US), William R. Milnor (US), G. Guy Knickerbocker (US), and W.R. Chesnut (US) performed extensive closed chest defibrillation experiments in dogs(2188).

Henry T. Bahnson (US), in 1958, resuscitated a two year old child whose heart was in ventricular fibrillation with the combined method of external cardiac compression and closed chest defibrillation(2189).

Otto Ritter von Bollinger (DE) described a delayed traumatic apoplexy he called traumatische Spät-Apoplexie. Today this condition is called delayed traumatic intracerebral hematoma or (DTICH)(2190).

Heinrich Irenaeus Quincke (DE) introduced the lumbar puncture as a diagnostic and therapeutic technique; using it to accurately measure pressure at the beginning and the end of the procedure, measure protein and sugar values, and describe the low sugar occurring in the cerebrospinal fluid (CSF) in purulent meningitis. He diagnosed tuberculous meningitis by demonstrating tubercle bacilli in the CSF and was the first person to puncture the lateral ventricle to obtain CSF in infants with hydrocephalus(2191, 2192).

Walter Essex Wynter (GB) performed lumbar puncture to relieve spinal fluid pressure in four cases of tubercular meningitis(2193).

Berthold Earnest Hadra (US) introduced spine wiring to treat instability(2194).

Marin-Théodore Tuffier (FR) used inhalational anesthesia administered under pressure to successfully remove the apex of a tuberculous lung; he even added an inflatable cuff around the tube inserted in the trachea to ensure a gas-tight fit(2195). Tuffier was ahead of his time.

Ivan Magill (GB) and E. Stanley Rowbotham (GB), working at Gillies' plastic-surgery unit, found their way back to the simplicity of the endotracheal tube and positive pressure(2196, 2197).

Ralph M. Waters (US), in 1931, showed that respiration can be controlled either by squeezing the anesthetic bag by hand or by using a small motor. Refs

Alexandr Petrovich Karpinsky (RU) was trained as a geologist and became an expert paleontologist. From fossil remains of ammonids he was able to relate ontogenesis and phylogenesis of these animals to their historical development. He constructed a genealogical tree of the ammonids and thus determined their phylogenetic relationships(2198, 2199).

Deutsche Zeitschrift für Nervenheilkunde was founded.

Skandinavische Archiv fur Physiologie was founded. It became Acta Physiologica Scandinavica in 1939.

1892

“Even if I erred and the experiment threatened my life, I would look Death calmly in the eye, for it would not have been a frivolous suicide; I would die in the service of science like a soldier on the field of honor. Health and life are indeed very high earthly goods, but not after all the highest for human goods. Man, who wants to stand in a higher position than the animal, must be willing to sacrifice even life and health for higher, ideal goods.” Max Joseph von Pettenkofer (DE) referring to a famous experiment in which he drank a diluted culture of the cholera vibrio(2200).

K. Bratuscheck () was the first to study phase relations within the microscope(2201).

Julius Rheinberg (GB) and A.E. Conrady (GB) obtained photographs of a fine grating with a phase-contrast microscope(2202-2204).

Fritz Zernicke (NL) explained the physical principles of phase-contrast microscopy(2205-2207). The 1934 article announced Fritz Zernicke's discovery of the phase contrast principle.

Lead arsenate was first proposed as an insecticidal spray for codling moth control. The first published results of the use of kerosene as means of mosquito control was made. This was the result of the accidental discovery made in 1867 following spilling of kerosene into a mosquito-infested watering trough while filling a lantern. The first record of dinitrophenols as insecticides was made in Germany(138).

Harold Picton (GB) and S. Ernest Linder (GB) were the first to demonstrate electric charge directly when they measured the movement of collloidal particles, including hemoglobin molecules in solution, under the influence of an electric field. This was the origin of moving boundary electrophoresis(2208, 2209).

William Bate Hardy (GB) studied the migration of egg white in an electrical field and found that under the influence of a constant current the albumin moves with the negative stream if the reaction of the fluid is alkaline; with the positive stream if the reaction is acid(2210). A year later he discovered that proteins have an isoelectric point, a pH at which they have no net charge and therefore will not migrate. He therefore appreciated that pH could have a profound effect on the net charge of a protein further noting that at the isoelectric point a protein tends to coagulate or precipitate(2211).

Arne Vilhelm Kaurin Tiselius (SE), Stig Claesson (SE) and Paul König (AT) developed apparatus which can effectively separate mixtures of proteins based on their electrophoretic mobility. Tiselius used a special tube arranged like a rectangular U within which the proteins could move and separate. Lenses were designed to detect changes in the index of refraction as protein concentration changed in the developing bands. It was by this method that blood proteins were first separated into albumin and globulin fractions. This technique is referred to as moving-boundry electrophoresis. König used filter paper as a stabilizing matrix for electrophoresis(2212-2214). See, Hardy, 1899.

Arne Vilhelm Kaurin Tiselius (SE) and Elvin Abraham Kabat (US) used electrophoresis to show that antibodies make up part of the gamma globulin fraction of serum. They also found that antibodies are not uniform in electrical charge or sedimentation characteristics. This was the first clue that antibodies are physically heterogeneous. The alpha, beta, and gamma notation was coined by Tiselius and first used in the 1937b article(2215, 2216).

Johann Friedrich Miescher, Jr. (CH), with remarkable insight, wrote his uncle and expressed his thoughts that nuclein might convey the hereditary message, “just as the words and concepts of all languages can find expression in 24-30 letters of the alphabet”(2217).

Leo Lilienfeld (AT) coined the word nucleohistone to apply to material extractable with distilled water from leucocytes or minced thymus and precipitatable from the aqueous extracts with acetic acid(2218, 2219).

Martinus Willem Beijerinck (NL) published his work on tobacco mosaic disease, showing that the causal agent had many of the qualities associated with a living organism. He hypothesized that the agent must be incorporated into host cells before it could reproduce and that its reproduction was linked to the reproduction of the host cell. These papers along with those of Adolf Eduard Mayer (DE) in 1886 and Dimitri Ivanowsky; Dimitri Iwanowski; Dimitri Ivanovski (RU) in 1892 and Erwin Baur (DE), in 1904, are considered the co-discoveries of plant diseases caused by filterable agents (viruses)(1774, 1775, 2220-2225).

Friederich August Johannes Löffler (DE) and Paul Frosch (DE) demonstrated that the causative agent of foot-and-mouth disease of cattle can pass through a bacteriological filter. This paper represents the first evidence for the presence of animal pathogens which we now call filterable viruses. They concluded “that the activity of the filtrate is not due to the presence in it of a soluble substance, but due to the presence of a causal agent capable of reproducing. This agent must then be obviously so small that the pores of a filter which will hold back the smallest bacterium will still allow it to pass.… If it is confirmed by further studies … that the action of the filtrate … is actually due to the presence of such a minute living being, this brings up the thought that the causal agents of a large number of other infectious diseases … which up to now have been sought in vain, may also belong to this smallest group of organisms”(2226, 2227).

Eugenio Centanni (IT), Ezio Savonuzzi (IT), Arnaldo Maggiora (IT), Gian Luoa Valenti (IT), Alois Lode (AT), and J. Gruber (AT) demonstrated the filterability (viral nature) of the etiological agent of fowl plague(2228-2231).

Arnaldo Maggiora (IT) and Gian Luoa Valenti (IT) concluded that the etiological agent of fowl plague behaved as a true virus(2232).

Émile Marchoux (FR) reported successful in vitro culture of the fowl plague virus(2233).

Werner Schafer (DE) determined that fowl plague (FP) virus is actually one of the influenza A viruses(2234).

Frederick Cooper Curtice (US) was widely scorned by his peers when he proposed the vector theory: that ticks could transmit a disease-causing agent to animals, including humans(2235-2237).

Bulletin No. 1 of the Bureau of Animal Industry, issued in 1893, announced the momentous discovery that infection can be carried from one animal to another through the agency of an intermediate host the tick. The disease was Texas cattle fever also known as tick fever and southern cattle fever. Note, this was the first demonstration of arthropod transmission of disease. See, Theobald Smith, 1893.

Sir Joseph Barcroft (GB) and John Scott Haldane (GB) designed a blood-gas manometric apparatus which was modified by Thomas Gregor Brodie in 1910 and became known as the Warburg apparatus in honor of Otto Heinrich Warburg (DE). Warburg had devised a method for preparing thin slices of still-respiring tissue and measuring the uptake of oxygen by the decrease in pressure in a small flask, this decrease being determined by the change in level of a fluid in a thin U-shaped tube attached to the flask. Carbon dioxide was absorbed by a small well of alkaline solution within the flask. Such a Warburg manometer to which Warburg flasks were attached proved a powerful tool for studying respiration(2238-2242).

Curt Herbst (DE) observed that the blastomeres of the cleaving sea urchin egg spontaneously separate from each other after a brief exposure to calcium-free sea water. This produced an elegant method for isolating undamaged blastomeres and for following their development independently(2243).

Ludwig Edinger (DE) introduced the concept of centrally arising pains(2244).

Lewis Erle Shore (GB) found that the tip of the human tongue is more sensitive to sweet, whereas the edges are more sensitive to sour, and the base of the tongue is most sensitive to bitter. The mid-dorsum was found to be insensitive to all tastes. All but the mid-dorsum are sensitive to salty(2245).

George Miller Sternberg (US) found that calves infected with vaccinia virus produced specific antibody which could neutralization the virus(2246). 

Dmitrii Iosifovich Ivanowski; Dmitrii Iosifovich Iwanowsky; Dmitrii Iosifovich Ivanovski (RU) demonstrated that the mosaic disease of tobacco (Nicotiana tabacum) could be transmitted by the juice of infected plants which had been passed through a filter that would stop bacteria(1775, 2223-2225, 2247). This is considered to be one of the co-discoveries of viruses.

Guiseppe Guarnieri (IT) observed homogenous acidophilic inclusion bodies, 2 to 10 millimicrons in size, in the cytoplasm of epithelial cells from patients with variola (smallpox)(2248). These structures are frequently referred to in the literature as Guarnieri bodies.

Richard Friedrich Johannes Pfeiffer (DE) isolated Hemophilus influenzae during the influenza pandemic of 1889 and erroneously thought that it was the causative agent of influenza, hence its name. This organism may have behaved synergistically with the virus to produce a more severe disease. It is sometimes called Pfeiffer’s bacillus(2249, 2250).

Richard Friedrich Johannes Pfeiffer (DE) and August Paul von Wassermann (DE) concluded from their studies that wall material from young cultures of Vibrio cholerae contains a potent heat-stable toxic substance which they named endotoxin(2251, 2252).

William Thompson Sedgwick (US) and John L. Batchelder (US) demonstrated the relationship of the bacterial count of milk to its sanitary quality(2253, 2254).

Roland Thaxter (US) first described the Myxobacteria(2255-2257).

Konstantin Wingradoff (RU) was the first to describe infections of Opisthorchis in humans(2258).

Hans Vogel (DE) discovered the snail and fish hosts and their roles in the life cycle of Opisthorchi(2259).

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) presented his theory of cellular immunity. He noted that phagocytic cells protected invertebrates from some fungus infections and not from others. He predicted that abnormalities of the phagocytic cells would compromise host defenses(2260, 2261).

Joseph Marcos Malbran (AR), in Argentina during 1892,  discovered the first case of rhinosporidiosis when he examined a polyp from the nose. He regarded the infectious agent as a sporozoon(2262).

Guillermo Seeber (AR) thought it was a protozoon when he described it(2263).

Roberto Johann Wernicke (AR) named it Coccidium seeberia after the protozoal subdivision Coccidia and his pupil, Guillermo Seeber (AR)(2264).

Guillermo Seeber (AR) then renamed it Rhinosporidium seeberi(2263).

Roger A. Herr (US), Libero Ajello (US), John W. Taylor (US), Sarath N. Arseculeratne (LK) and Leonel Mendoza (CR-US) performed nucleic acid analysis on R. seeberi and found it to be the only microorganism that is classified in the class Mesomycetozoea and is pathogenic to mammals and birds(2265). The class Mesomycetozoea includes a heterogeneous group of microorganisms that are at the animal-fungal boundary and consists of two orders; Dermocystida and Ichthyophonida.

Alejandro Posadas (AR) and Roberto Johann Wernicke (AR) found the tissue form of coccidioidomycosis in a patient in Argentina(2266-2268).

William Ophüls (US) and Herbert C. Moffitt (US) demonstrated the mycotic nature of the infection(2269, 2270). The etiological agent was named Coccidioides immitis under the mistaken impression that it was a protozoan. The disease is usually an acute, benign, self-limiting, respiratory infection which may occasionally become systemic and life threatening. 

Sir Francis Galton (GB), a cousin to Charles Robert Darwin, was the first to suggest that fingerprints would be useful in tracing criminals(2271, 2272).

Julius Wolff (DE) stated that “the external form and internal architecture of a bone are related to the forces which act upon it.” This is known as Wolff’s Law(2273).

Gheorghe Marinescu (RO) and Paul Oscar Blocq (FR) were the first to describe plaques in brain tissue of senile patients(2274).

Carl Ludwig Schleich (DE) was the first to demonstrate infiltration anesthesia (local anesthesia) on humans. He used dilute cocaine(2275).

Arnold Pick (CZ) did work on lobar cortical atrophy which made him famous (Pick’s disease)(2276). This is a rare and fatal degenerative disease of the nervous system. Clinically there are major overlaps with Alzheimer's presenile dementia.

Josef Albert Amann (DE) and Gotthard Schubert (DE) independently developed an operation used in cases of congenital absence of vagina. Amann making an artificial vagina from the ampulla recti. Schubert creating an artificial vagina using transplants from anus and rectum(2277, 2278).

William Stewart Halsted (US) performed the first successful ligation of the left subclavian artery(2279).

Sir William Arbuthnot Lane (GB) introduced mastoid drainage in purulent otitis media with specially designed chisels and gouges(2280).

Clinton Hart Merriam (US) hypothesized that animals and plants are restricted in their northward distribution by the total quantity of heat during the season of growth and reproduction, and their southward distribution is restricted by the mean temperature during the hottest part of the year. This established life zones(2281, 2282).


Marie Eugène François Thomas Dubois (NL) found a fossil skullcap, teeth, and femur in the Javan town of Trinil. He insisted that these fossils belonged to the same type individual, a missing link between humans and apes. These finds were reported in the quarterly and annual reports to the Dutch East Indies government but not to the scientific community at large until 1920(2283-2285). Opposition to his claim remained widespread and many doubted that the bones all belonged to the same individual. He adopted the name Anthropithecus erectus then changed it to Pithecanthropus, which had been coined earlier by the German zoologist Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel, calling his discoveries Pithecanthropus erectus (upright ape-man)(2286). This specimen of Homo erectus is commonly called Java man.

Davidson Black (CA) coined the name Sinanthropus pekinensis, for what was popularly called Peking man(2287, 2288).

Franz Weidenreich (DE-US) and Lucile Swan (DE) prepared the original reconstruction from the fossil remains of several different individuals found in the caves at Zhoukoudian, China(2289, 2290).

Pierre Teilhard de Chardin (FR), a Jesuit priest, also did early work on Peking man, a Homo erectus, also known as Pithecanthropus pekinenses and Sinanthropus pekinensis(2291, 2292). 

Towikromo (ID) discovered another Homo erectus, Sangiran 17, in 1969 in Java, Indonesia. It was first described in 1971 by Sastrohamidjojo Sartono (ID) as Pithecanthropus erectus(2293). Modern paleontologists consider this Java man to be Homo erectus.

Andrew Taylor Still (US) founded the first school of osteopathy – the American School of Osteopathy (now A.T. Still University of the Health Sciences) in Kirksville, Missouri in 1892(2294).

The American Psychological Association was formed.

1893

“The mother has supplied a hundred or thousand-fold more protoplasm to the fertilized egg-cell, competent for development, yet no greater portion of the hereditary properties than the father.” Joseph Gottlieb Kölreuter(2295).

August Karl Johann Valentin Köhler (DE) discovered the technique which became known as "Köhler illumination"(2296).

Adolf Pinner (DE) determined the structure of nicotine as known today(2297).

Karl Wilhelm von Nägeli (CH) coined the phrase oligodynamic action to describe the antimicrobial activity of microgram quantities of silver ions(2298).

Ferdinand Blum (DE) originated tissue fixation with formaldehyde(2299). 

Wilhelm August Oskar Hertwig (DE) centrifuged frog eggs and demonstrated the effect of yolk distribution on cleavage(2300). 

Francisco Sanfelice (IT) found that nontoxic “pseudotetanus” clostridia when inoculated into filtrates of the anaerobic sporeforming Clostridium tetani became toxicogenic, the acquired toxicity persisting for several transfers(2301). This change could possibly be attributed to the transforming factor (DNA) or the presence of lysogenic phage.

Wilhelm His, Jr. (CH-DE) researched the development of the embryonic heart during which he discovered the auriculo-ventricular bundle (bundle of His), also called the fasciculus atrioventricularis. He demonstrated that there is a muscular AV connection, and was the first to describe the function of this AV conduction system(2302).

Albert Frank Stanley Kent (GB) discovered a similar bundle which runs from the posterior wall of the right atrium to the ventricular septum, permitting premature excitation of the ventricles by the sinus node(2303).

Wilhelm His, Jr. (CH-DE) showed that following section of the A-V bundle, the auricular and ventricular beats became dissociated(2304). It would later be realized that this observation explained the Adams-Stokes syndrome (slow pulse, vertigo, and epileptoid seizures).

Sunao Tawara (JP) and Karl Albert Ludwig Aschoff (DE) discovered the auriculoventricular (AV) node of the heart, a small node of modified cardiac muscle that transmits the impulses originating in the sinus node down to the ventricles. It is the beginning of the auricular-ventricular bundle of His(2305). Today it is called the Aschoff-Tawara node or the AV node.

Sir Arthur Berridale Keith (GB), and Martin William Flack (GB) discovered the sinoauricular node (SA) of the heart, often called the pacemaker of the heart and noted that the auriculo-ventricular system discovered by His and Kent is but part of a system of fibers which extend to the whole heart and determine its rhythm(2306). It is also called the Keith-Flack node or sinus node.

Jean George Bachmann (FR-US) described the interatrial bundle (Bachmann’s bundle) as an interatrial link allowing conduction from the right to the left atrium(2307).

Thomas Naum James (US) identified bypass fibers of an internodal connection. This represents a circumvention of the AV node, originating in the atrial conduction system and running below the AV node and extending to the bundle of His and to the fascicles(2308).

Ralph Stockman (GB) refuted the idea that only organic iron is useful in treating anemia. He demonstrated that inorganic iron has great value as a nutrient(2309).

Jean Baptiste Emile Vidal (FR) was likely the first to successfully transmit herpes fibrilis from one human to another(2310).

Jean Baptiste Emile Vidal (FR) reported human-to-human transmission of herpes simplex virus infections, identifying the necessity of intimate human contact for spread of infection(2311, 2312).

A. Lowenstein (DE) performed experimental transmission of herpes simplex virus type 1 (HSV-1) from human lesions to rabbit corneas(2313). This work supported the proposal put forth in 1893 by Jean Baptiste Emile Vidal (FR) that person-to-person transmission could result in the spread of cold sores caused by HSV. 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR), Pierre Paul Emile Roux (FR), Alexandre Taurelli-Salimbeni (IT), and Brau et Denier (FR) concluded from their experiments that the cholera vibrio produces a soluble exotoxin which, by injection, can be used to produce an antitoxin(2314-2319).

Hans Lohmann (DE) wrote a report about plankton from the German Plankton Expedition. He discovered the existence of nanoplankton(2320). He is commemorated by the genus Lohmannella, Trouessart, 1901.

Friedrich August Ferdinand Christian Went (NL) was the first to describe the fungal infection of sugar-cane which became known as Red Rot of the Stem(2321). He was also the first to describe the fungus that produced the disease, Colletotrichum falcatum

Heinrich Irenaeus Quincke (DE) and Ernst Roos (DE) distinguished Entamoeba histolytica from Enatamoeba coli(2322).

August Paul von Wassermann (DE) was able to vaccinate guinea pigs against the intraperitoneal infection with living cholera bacilli. In order to achieve this, he found that cholera vibrios or their body substance must be injected in such doses that a mild specific illness, a general reaction, follows(2323).

Pierre Paul Émile Roux (FR) and Louis Vaillard (FR) demonstrated that antitoxin is something created or newly produced in the body as a result of the injection of toxin. The antitoxin (antibody) was found not to appear immediately after the injection of the toxin (antigen) (2324).

Wilhelm August Oskar Hertwig (DE) obtained twin embryos in the newt by constricting the egg by means of fine ligatures(2325).

Hermann Endres (DE), Amedeo Herlitzka (IT) and Hans Spemann (DE) confirmed and extended his results with very similar experiments(2326-2333).

Wilhelm August Oskar Hertwig (DE) proposed that all cells in an animal embryo receive the same number of chromosomes(2334).

Wilhelm August Oskar Hertwig (DE) wrote Die Zelle und die Gewebe in which he clearly distinguished histology as the science of tissues from cytology as the science of cell structure and function. Cytology as a field of study dates from this work(2335). 

Charles Reid Barnes (US) proposed that the biological process for synthesis of complex carbon compounds out of carbonic acid, in the presence of chlorophyll, under the influence of light should be designated as either photosyntax or photosynthesis. He preferred the word photosyntax, but photosynthesis came into common usage as the term of choice(2336).

Edmund Beecher Wilson (US) and Albert Prescott Mathews (US) were able to show that triploblastic animals (those having three germ layers) fall into two large groups in terms of the mode of mesodermal formation. One group, including annelids, arthropods, and molluscs, shows the spiral or mosaic pattern he had observed in the earthworm. See Edmund Beecher Wilson, 1880. The other group, including the echinoderms, primitive chordates, and invertebrates, shows a pattern called radial in which the mesoderm originates from pouches in the endoderm of the gastrula(2337-2340).

Edouard Brissaud (FR) produced an atlas of the human brain drawn completely by hand(2341).

John Newport Langley (GB) introduced the terms pre-ganglionic and post-ganglionic in 1893 and gave the autonomic nervous system its name in 1898. He named the cranial and sacral divisions of the autonomic nervous system, which seemed to be involved with the restoration and conservation of bodily resources, parasympathetic(2342).

Joseph Jules Déjérine (CH-FR) and Jules Sottas (FR) described Déjérine-Sottas disease (hypertrophic progressive interstitial neuritis)(2343). It is believed to be an autosomal dominant trait. 

Luigi Luciani (IT) succeeded in keeping dogs alive after total extirpation of the cerebellum, and initiated the modern study of cerebellar function(2344).

Pierre Marie (FR) described hereditary cerebellar ataxia(2345).

Heinrich Irenaeus Quincke (DE) recognized the syndrome of meningitis serosa(2346).

Paul Emil Flechsig (DE), in 1893, embarked on the study of myelogenesis in the brain hemispheres and supplemented his myelogenetic findings with clinical observations and data from degeneration experiments. He very precisely traced neuronal projections to the visual cortex from areas such as the lateral geniculate nucleus, then reported that the fibers from the medial geniculate body to the temporal lobe are concerned with hearing (2347-2354).

Paul Emil Flechsig (DE) outlined the auditory radiation(2355) and could list twelve cortical areas that are myelinated – and therefore functional before birth – as well as twenty-four in which myelinization occurs after birth; these he arranged chronologically according to the time course of myelinization. 

Sir William Alvin Macewen (GB) recorded 25 cases of brain abscess. Nineteen of these patients came to his attention in time to undergo surgery, resulting in 18 recoveries. All five of his patients with extradural abscess recovered; at that time most other surgeons had 100 percent mortality rates for the condition(2356).

Willem Einthoven (NL) initiated electrocardiology when he began to explore the use of the capillary electrometer to record minute electrical currents. In 1895, he was able to detect recognizable waves, which he labeled “P, Q, R, S, and T.” The limitations of capillary electrometers led Einthoven to develop the first string galvanometer. This consisted of a delicate conducting string stretched across a magnetic field. A current flowing through the thread would cause it to deviate at right angles to the magnetic lines of force, the extent of deviation being proportional to the strength of the current. The sensitivity of this instrument meant that it could be used to detect and measure the varying electrical potentials of the heart, i.e., an electrocardiograph. It was subsequently applied to the taking of electroencephalograms (graphs). With his new technique, he standardized the tracings and formulated the concept of “Einthoven’s triangle” by mathematically relating the 3 leads (Lead III = Lead II – Lead I). He described bigeminy, complete heart block, “P mitrale,” right and left and ventricular hypertrophy, atrial fibrillation and flutter, the U wave, and examples of various heart diseases. It was Einthoven who introduced the term electrocardiogram and used the abbreviation ‘EKG’(2357-2365). See, Waller, 1887.

Willem Einthoven (NL) documented his clinical use of the electrocardiogram(2366).

Why PQRST and not ABCDE? The four deflections prior to the correction formula were labeled ABCD and the 5 derived deflections were labeled PQRST. The choice of P is a mathematical convention by using letters from the second half of the alphabet. N has other meanings in mathematics and O is used for the origin of the Cartesian coordinates. In fact Einthoven used O ..... X to mark the timeline on his diagrams. P is simply the next letter. A lot of work had been undertaken to reveal the true electrical waveform of the ECG by eliminating the damping effect of the moving parts in the amplifiers and using correction formulae. If you look at the diagram in Einthoven's 1895 paper you will see how close it is to the string galvanometer recordings and the electrocardiograms we see today. The image of the PQRST diagram may have been striking enough to have been adopted by the researchers as a true representation of the underlying form. It would have then been logical to continue the same naming convention when the more advanced string galvanometer started creating electrocardiograms a few years later.

Willem Einthoven (NL), George Fahr (NL), and Alfred de Waart (NL) described the Einthoven triangle as the basis for calculations of electrocardiograms(2367, 2368).

Max Cremer (DE) introduced esophageal electrocardiography when he passed an electrode down the throat of a professional sword swallower. This technique allows for analysis of atrial stress, ectopic impulse formation, and conduction abnormalities(2369).

Charles C. Wolferth (US) and Francis Clark Wood (US) introduced the use of chest leads to electrocardiography(2370).

Frank N. Wilson (US), Franklin D. Johnston (US), A. Garrard MacLeod (US), and Paul S. Barker (US) introduced unipolar chest wall leads for the electrocardiogram(2371).

Fritz Schellong (DE), S. Heller (DE), and E. Schwingel (DE) introduced vector electrocardiography(2372).

H. Frank Macinnis (CA) and Norman Jefferis Holter (US) independently applied bioelectrical signal telemetry to continuous ECG recording(2373-2375). Norman Jefferis Holter (US) and Joseph Anthony Gengerelli (US) had invented bioelectrical signal telemetry(2376).

Emanuel Goldberger (US) introduced the unipolar extremity electrode system(2377).

Ernest Frank (US) designed the corrected orthogonal lead system(2378).

Paul Puech (FR), in 1957, was he first to demonstrate electrical potentials coming from the bundle of His. This occurred during a catheterization of a patient with tetralogy of Fallot(2379).

Gaston Giraud (FR), Paul Puech (FR), Hugues Latour (FR), and Jean Hertault (FR) developed intracardiac leads(2380).

Dirk Durrer (NL), Leo Schoo (NL), Reinier M. Schuilenburg (NL), Hein Joan Joost Wellens (NL) and Jan P. Roos (NL) introduced electrical stimulation of the heart as a diagnostic tool in cardiology. Their epicardial mapping allowed intraoperative identification of accessory pathways in the human heart(2381-2383).

Benjamin J. Scherlag (US), Sun H. Lau (US), Richard H. Helfant (US), Walter D. Berkowitz (US), Emmanuel Stein (US), and Anthony N. Damato (US) developed a catheter technique for recording His bundle activity in man(2384).

Hein Joan Joost Wellens (NL), Reinier M. Schuilenburg (NL), and Dirk Durrer (NL) described the mechanism of reentry tachycardia. They founded the modern era of tachycardia management concerning atrial and ventricular arrhythmias(2385).

Guy Fontaine (FR), Robert Frank (FR), Gerard Guiraudon (FR), Jacques Vedel (FR), Yves Grosgogeat (FR), and Christian Cabrol (FR) devised a method of depicting ventricular late potentials in patients with ventricular tachycardia. It is believed that late potentials arise in the peripheral zones of old myocardial infarcts and can be demonstrated in patients with a tendency toward ventricular tachycardia originating in the area immediately surrounding the old infarct location(2386).  

Friedrich von Müller (DE) demonstrated that exophthalmic goitre is accompanied by an increased metabolism(2387).

Alexis Yakovlievich Kozhevnikov (RU) reported a mild continuous epilepsia characterized by almost continuous, rhythmic muscular contractions affecting a limited part of the body for a period of hours, days, or even years(2388, 2389). It is called Kozhevnikov’s syndrome I.

Adam Politzer (AT) was the first to describe otosclerosis as a specific disease fixating the stapes(2390, 2391).

George Ryerson Fowler (US) performed the first known thoracoplasty(2392). Thoracoplasty is the surgical removal of ribs to gain access during surgery or to collapse the chest wall.

Charles Barrett Lockwood (GB) devised an operation for radical repair of femoral and inguinal hernia(2393).

The first large recorded outbreak of polio in the U.S. began in Boston, and spread into New England, particularly Vermont. Of 132 cases documented in Vermont, there were 18 deaths and 30 victims left with permanent paralysis(176).

Louis Antoine Marie Joseph Dollo (FR-BE) proposed that evolution never repeats itself, i.e., is irreversible. This became known as Dollo’s law. Darwin's natural selection does not necessarily prescribe progress or regression, does not imply a direction of evolution in time, it only states an environmental constraint. Indirectly, Dollo's law does: it prescribes a trend towards more and more complex, and more and more ordered, living structures. Dollo's law expresses the visible fact that reproduction, ontogeny and phylogeny are biological organizations whose behavior is irreversible: both during growth and during evolution, entropy of biological information constantly increases. We evolved from bacteria to humans, we grew from children to adults(2394-2397).

Rachel Collin (US), Roberto Cipriani (VE), Michael F. Whiting (US), Sven Bradler (DE), and Taylor Maxwell (US) presented evidence that there may be exceptions to Dollo’s law(2398, 2399).

The Index Kewensis was founded. It is a publication that aims to register all botanical names for seed plants at the rank of species and genera. It later came to include names of taxonomic families and ranks below that of species. The Index is maintained by the Royal Botanic Gardens at Kew in London, England.

1894

“The restricted action of the enzymes on glucosides could be explained by the assumption that only in the case of similar geometrical structure can the molecules approach each other sufficiently closely to initiate a chemical action. To use a metaphor, I would like to say that enzyme and glucoside have to fit together like lock and key in order to exert a chemical effect on each other.” Hermann Emil Fischer(2400).

“The students of adaptation forget that even on the strictest application of the theory of selection it is unnecessary to suppose that every part of an animal has, and every thing which it does, is useful and for its good. We, animals, live not only by virtue of, but in spite of what we are.” William Bateson(2401).

Arvid Gustaf Högbom (SE) suggested an internal source for our atmosphere as a result of gradual, episodic, or rapid volcanic outgassing and weathering(2402).

Steffen L. Thomsen (DE), Claude J. Allègre (FR), Thomas Staudacher (FR), and Philippe Sarda (FR) determined that early catastrophic outgassing occurred on the young Earth(2403, 2404). This would have released significant amounts of nitrogen, carbon dioxide, carbon monoxide, methane, water, hydrogen, sulfur dioxide, and hydrogen sulfide.

Georg Bredig (DE) described what he called an inner salt because it existed as a molecule containing both positive and negative charges(2405).

Friedrich Wilhelm Küster (DE), while working with methyl orange, coined the name zwitterion for molecules carrying opposite charges(2406). Bredig accepted this name and pointed out that amino acids also form zwitterions(2407).

Karl Ludwig Winkelblech (DE) proposed that simple amino acids in their state of neutrality are dipolar ions(2408).

Elliot Quincy Adams (US) suggested that amino acids are zwitterions at their isoelectric pH(2409).

Niels Janniksen Bjerrum (DK) used the strength constants of acids and bases to study the dissociation of other compounds. He also demonstrated that amino acids in their isoelectric state are not uncharged molecules but are zwitterionen (dipolar ions)(Bjerrum 1923)(2410).

Hans Hermann Weber (DE) was the first to show by direct demonstration that isoelectric proteins are zwitterions truly bristling with charges (+ and – in equal number)(2411, 2412). 

Wilhelm Friedrich Ostwald (LV-DE) postulated that enzymes acting as catalysts speed up both directions of reversible reactions. He pointed out that the theories of Josiah Willard Gibbs (US) made it necessary to assume that catalysts hasten a reaction without altering the energy relationships of the substances involved(2413). Ostwald is generally believed to be the first to understand the nature of catalytic reactions.

Hermann Emil Fischer (DE) and Paul Lindner (DE) found that cane sugar, alpha-methylglucoside, is hydrolyzed by invertin (alpha-glycosidase), extracted from dried yeast, but not by emulsin, whereas beta-methylglucoside is cleaved by emulsin but not invertin. He concluded, “…I will say that the enzyme and the glucoside have to adapt with each other like a key in a lock ('Schloss und Schlüssel') to carry out a chemical action one on the other…. The finding that the activity of enzymes is limited by molecular geometry to so marked a degree should be of some use for physiological research.” This is Fischer’s famous lock-and-key hypothesis explaining enzyme specificity(2400, 2414).

Olaf Hammarsten (SE) isolated beta-nucleoprotein from ox pancreatic nucleoprotein(2415).

Ivar Christian Bang (SE) prepared guanylic acid from Hammarsten’s beta-nucleoprotein, then elucidated its structure as a compound of guanine, pentose, and phosphoric acid in equimolar proportions(2416).  

August Gürber (DE) crystallized horse serum albumin(2417).

Franz Nissl (DE) developed a staining procedure which shows Nissl's substance (extranuclear RNA) in the nerve cells. These Nissl’s granules or Nissl’s bodies are found in the cell bodies and dendrites of neurons, but absent from axons. They are concerned with protein synthesis and metabolism; their condition varies with physiological and pathological conditions(2418, 2419).

Arsenite of copper was discovered to be an insecticide(138).

Giulio Bizzozero (IT) noticed a link between mitosis and regenerative capacity. He divided mitotic cells into three catagories: 1) labile cells which demonstrate mitosis throughout life, e.g., bone marrow, 2) stable cells in which spontaneous mitotic activity is uncommon following birth, e.g., connective tissue, and 3) permanent cells which are mitotic in adulthood but do not regenerate, e.g., striated muscle(2420).

Carl Ludwig Schleich (DE) suggested that neuroglia moderate neuronal activity through an inhibitory action(2421).

Gustav Born (DE) originated heteroplastic transplantation by joining together parts of embryos belonging to different species such as frog and toad, i.e., chimeras. He obtained individuals which continued to develop(2422, 2423). Hans Winkler (DE) was the first to produce plant chimeras by grafting tomato and nightshade(2424).

Max Rubner (DE) painstakingly tested the energy consumption of dogs using large calorimeters. He measured the nitrogen content of urine and feces, and carefully estimated the quantity of the various foodstuffs in the diet he fed his subjects. He found that the heat produced by the animal equaled the heats of combustion of the fats, carbohydrates, and protein minus that of the urinary matter. He concluded, that no one particular type of foodstuff supplied all the energy. The body made use of fats, carbohydrates, and proteins with equal readiness. The nitrogen portion of the proteins was split away before it was used as a fuel, he maintained, and in this he was correct(2425).

William Bateson (GB) emphasized the importance of discontinuous variations, foreshadowing the rediscovery of Mendel's work. In this work he conjectured that all organisms are made from an orderly series of parts or segments, and coined the term homeosis for it(2401, 2426).

Martin Heidenhain (DE) coined the term telophase as it applies to cell division(2427).

Hans Driesch (DE) theorized that all cell nuclei of an organism are equipotential but vary in their activity in accordance with the differentiation of tissues(2428). 

Emil Friedrich August Walter Migula (DE) described bacteria as belonging to two major divisions, the Eubacteria (true bacteria) and the Thiobacteria (sulfur bacteria). The first group contained bacteria that were nonnucleated and colorless; the second group contained nonnucleated cells that had granules of sulfur or a bacterial pigment(2429).

Martinus Willem Beijerinck (NL) was the first to isolate a bacterium capable of reducing sulfates, Spirillum desulfuricans (Desulfovibrio desulfuricans)(2430).

Shibasaburo Kitasato (JP) and Alexandre Émile Jean Yersin (CH) independently discovered the plague bacillus, later named Yersinia pestis(2431-2435).

Joseph Denys (BE) and Jules Havet (BE) found that dogs’ serum is less bactericidal than dogs’ whole blood. Working with Bacillus coli, Bacillus subtilis, and Staphylococcus they found that the leucocytes play a fundamental part, for when they are removed the plasma is found to be robbed of a considerable part of its bactericidal properties. Microscopic examination of the blood showed all stages of phagocytosis. This was the first demonstration that phagocytosis was enhanced by the presence of immune serum(2436).

Angelo Ruffini (IT), using gold chloride as a stain, described encapsulated nerve endings that respond to warmth. These later became known as Ruffini corpuscles(2437).

Edmund Faustyn Biernacki (PL) noted the increased sedimentation rate of blood from ill individuals and realized that it was due to the presence of fibrinogen(2438).

Robert Sanno Fåhraeus (SE) furthered Biernacki's work. His initial motivation to study the erythrocyte sedimentation rate (ESR) was as a pregnancy test but his interest expanded to the study of the ESR in disease states(2439-2441).

Alf Vilhelm Albertsson Westergren (SE) refined the technique of performing the erythrocyte sedimentation rate (ESR) and reported its usefulness in determining the prognosis of patients with tuberculosis(2442).

Frederick George Novy (US) isolated the bacterium he called Bacillus oedematis maligni during his study of malignant edema in guinea pigs(2443). It was named Bacillus novyi by Walter Migula in 1900. It now bears the name Clostridium novyi. and is one of the important causes of gas gangrene.

Richard Friedrich Johannes Pfeiffer (DE) and Vasily Isayevich Isayev; Vassilii Issaevicj Issaev (last name also spelled Issaeff) (RU) began their classic researches which showed that the destruction of the cholera vibrio takes place by a kind of dissolution which they called bacteriolysis. Cholera vibrios were destroyed in vitro in the serum of animals immunized against cholera, and the same effect took place in the peritoneal cavity of the living animal. By an ingenious and simple technique they showed that in the normal peritoneal cavity vibrios multiply rapidly, whereas in the immunized animal they disappear. They removed drops of peritoneal fluid by means of capillary pipettes and found in the case of the immune animal that cholera vibrios which had been injected were almost instantly rendered motionless and swollen. They then changed into micrococcus like bodies which became more and more difficult to see and ultimately they disappeared from view altogether. This process of lysis occupied about 20 minutes and was apparently independent of any cellular intervention. They showed that the serum also acts in vitro but its activity is abolished by dilution or heat at 60°C. The solution or lysis of vibrios in the peritoneal cavity of an immunized animal is spoken of as Pfeiffer’s phenomenon, and is, as they showed, highly specific in that vibrios closely related to Vibrio cholerae are not destroyed by cholera serum. They also observed that cholera immunity could be passively transmitted, for when anti-cholera serum from an immunized guinea-pig was injected into the peritoneum of a normal guinea-pig cholera vibrios subsequently introduced into the latter underwent the characteristic bacteriolysis(2444-2446).

Otto Busse (DE) and Abraham Buschke (DE) described a generalized fatal infection apparently caused by a yeast. This was most likely what is today called cryptococcosis, caused by Cryptococcus neoformans(2447-2449).

David Paul von Hansemann (DE) was the first to describe a case of meningitis caused by the fungus Torula histolytica later it was realized that the etiological agent was the yeast Cryptococcus neoformans(2450).

Jakob Eriksson (DE) was the first to describe physiological races of fungal rusts(2451).

Pierre-Augustin Dangeard (FR) discovered sexual reproduction in the Basidiomycetes and Ascomycetes(2452-2455).

Henry Horatio Dixon (IE) and John Joly (IE) proposed the cohesion or tension-cohesion theory as an explanation for how water (sap) rises in a tree(2456-2460).

Eugen Askenasy (DE) made a very similar proposal only one year later(2461). The most important common feature to both sets of papers was the identification of the cell walls of parenchyma cells, whether living or dead, as the sites where surface tensions develop due to the transpiration of water. Both papers emphasized that a moist cell wall is impermeable to air, so that even at negative pressures air cannot be sucked into conducting elements.

Raymond Jacques Adrien Sabouraud (FR) made thorough mycological and clinical studies of fungi which attack the hair, in man and other animals—the so-called tineas, ringworms, favus, and so on(2462-2464).

Theodor Wilhelm Engelmann (DE) was able to prove that oxygen is generated by chloroplasts by varying the points of illumination and recording the distribution of bacteria near the chloroplasts(2465).

Ramón y Cajal (ES) discovered a nerve-fiber bundle between the hypothalamus and the pituitary gland in the rat(2466).

George Oliver (GB) and Sir Edward Albert Schäfer (GB) were the first to extract a hormone from an endocrine organ when they showed that a preparation from the adrenal medulla of sheep and calves increases blood pressure, accelerates the heart beat, and depresses kidney function. They also demonstrated that an extract of the pituitary gland raises blood pressure(2467, 2468). The words "endocrine" and "endocrinology," (from the Greek, I separate within)

Ladislaus Szymonowicz (PL) and Napoleon Cybulski (PL) independently performed experiments quite similar to those of Oliver and Schäfer in 1894(2469).

Karl Pearson (GB) published the first in a long series of contributions to the mathematical theory of evolution. Here he introduces the method of moments and applies it to estimating a mixture of normal distributions(2470).

Karl Pearson (GB) developed normal correlation and regression and applied them to heredity(2471).

Karl Pearson (GB) introduced the chi-square goodness of fit test(2472).

Walter Garstang (DE) theorized that primitive chordates were sessile, filter-feeding marine organisms very similar to present day ascidians. The tadpole ascidian larvae, with its basic organization of a vertebrate, which had evolved within the group by progressive evolution and by neoteny became sexually mature, ceased to metamorphose into a sessile, mature ascidian, and became the ancestral vertebrate(2473, 2474).

Harris Hawthorne Wilder (US) discovered that certain salamanders do not possess lungs(2475).

Conwy Lloyd Morgan (GB) established the basic principles in the study of animal behavior including his famous canon that the actions of an animal should be interpreted in terms of the simplest mental processes(2476).

Arthur König (DE), Edward Nevill Willmer (GB), and W. David Wright (GB) provided psychophysical evidence that the center of the human fovea is tritanopic (blind to blue) for very small objects(2477, 2478).

W. David Wright (GB) found that blue-blindness is very rare in man, not sex-linked, and affecting only about 1 in 2000 persons, about 40 percent are women(2479).

Léon Charles Albert Calmette (FR) prepared horse anti-cobra anti-venom which he used to protect chickens(2480-2482). He later  became the first to prepare a commercial anti-venom for medical use.

Paul Gerson Unna (DE) was convinced that UV and, possibly, the violet-blue rays of sunlight were responsible for increased skin thickness, pigmentation, and skin cancer in sailors(2483).

Guido Banti (IT) described Banti’s syndrome (splenic anemia attended with cirrhosis of the liver, hypertrophy of the spleen, and ascites)(2484, 2485).

Pierre Paul Émile Roux (FR), Louis M. Martin (FR), and M. Auguste Chaillou (FR) treated diphtheritic children with antiserum they produced in horses(2486, 2487). No mention of serum sickness accompanies these reports.

Johannes Andreas Grib Fibiger (DK) investigated the effect of serum treatment on diphtheria. It was the first clinical trial in which random allocation was used and emphasized as a pivotal methodological principle. This pioneering improvement in methodology, combined with a large number of patients and rigorous planning, conduct, and reporting, makes this trial a milestone in the history of clinical trials(2488).

Gustav Mann (GB-US) discovered a relationship between Nissl Granules or Bodies and nervous activity when he demonstrated that these bodies disappear from the spinal anterior horn cells of dogs after excessive muscular exercise and likewise they are diminished within pyramidal cells in the occipital cortex after exposure of the eye to light. He concluded that the chromatic material within these bodies builds up during rest and diminishes during function(2489).

Hans Held (DE) determined that the intraneuronal Nissl Granules or Bodies are composed of nucleoalbumine (nucleoprotein). This represents the first time nucleoprotein was located within the cytoplasm(2490).

Jean Louis Brachet (FR) proved that Nissl bodies contain ribonucleic acid(2491).

Siegmund Exner (AT) first formulated the concept of a neural network, a concept later used in computer design(2492).

William B. Coley (US) found that he could  cure people of inoperable sarcoma by using repeated injections of the toxins of erysipelas (Streptococcus erysipelas, the causative agent of erysipelas) and those of Bacillus prodigiosus(2493).  

Simplacio Del Vecchio (IT), in 1894, exhibited a dog with a sutured cardiac wound before the 11th International Medical Congress in Rome. Del Vecchio described to the Congress how the suturing is possible and proved that the heart is more resilient than previously believed(2494).

Edmond Delorme (FR) performed the first decortication (removal of pleura) of the lung for treatment of chronic empyema(2495).

Jules Emile Péan (FR) is widely credited with having performed the first total shoulder replacement on March 11, 1893(2496).

Mathieu Jaboulay (FR) is credited with the first interilio-abdominal amputation (amputation of a lower limb through the sacroiliac joint). It is also called a hemipelvectomy(2497).

Otto Binswanger (CH) described a new clinical and neuropathological picture that he termed "encephalitis subcorticalis chronica progressiva"(2498). It is this disease that is named after him, Binswanger’s disease. It is also known as ischemic periventricular leukoencephalopathy and subcortical dementia. This dementia is characterized by damage to small penetrating blood vessels in the subcortical regions of the brain. These cerebrovascular lesions are deep in the white matter of the brain.

In 1894, five men and two women with Hansen's disease, then called leprosy, were brought by barge to an abandoned sugar plantation, known only as Indian Camp, on a bend of the Mississippi River between Baton Rouge and New Orleans. Named the Gillis W. Long Hansen's Disease Center, it is now known as the National Hansen's Disease Programs.

William Crawford Williamson (GB) and Dunkinfield Henry Scott (GB) sent three memoirs to the Royal Society of London which included a description of the evolutionary links between ferns and cycads. This led to the development of phylogenetic theories of plants(2499-2502).

The journal Wilhelm Roux' Archiv fur Entwicklungsmechanik der Organismen was founded. This was the first journal of experimental embryology.

ca. 1895

Josef Albert Amann (DE) introduced his original abdominal seem, the transperitoneal method of extirpation of carcinoma of the uterus, his suggestion for limiting the risk of infections, during surgery of the uterus. Ref 

1895

Philipp Lenard Wilhelm Konrad von Roentgen; Philipp Lenard Wilhelm Konrad von Röntgen (DE) observed that a new form of penetrating radiation, which he named x-rays, was produced when cathode rays (electrons) hit a metal target(2503-2506).

John William Strutt (Lord Rayleigh) (GB) and Sir William Ramsay (GB) collaborated to discover argon, the first of the “inert” or Noble gases(2507). Ramsay went on to discover helium, neon, krypton, and xenon.

Sven G. Hedin (SE) and Albrecht Karl Ludwig Martin Leonard Kossel (DE), working independently, isolated the amino acid histidine. Kossel isolated it from sturgeon sperm and called it histidin from the greek word meaning tissue. Hedin isolated it from animal horn(2508, 2509).

Charles Frederick Cross (GB), Edward John Bevan (GB), and Clayton Beadle (GB) were the first to purify cellulose from wood(2510).

Henry Edward Schunck (DE) and Leon Paul Theodor Marchlewski (DE) prepared pure phylloporphyrin from chlorophyll and later discovered how similar its absorption spectrum is to that of hematoporphyrin(2511, 2512).

Gabriel Émile Bertrand (FR) isolated the enzyme laccase from latex(2513). Note: This was the first isolated enzyme of the oxidation-reduction type. Up to this point all isolated enzymes had been of the hydrolytic type.

Gabriel Émile Bertrand (FR) coined the term oxidases to describe a number of plant enzymes which catalyzed oxidation reactions. He also discovered that some oxidases were likely to require metals, which he named coferments or coenzymes, and were therefore catalytic metalloproteins(2514).

Charles Ernest Overton (GB) analyzed how substances pass into cells from outside through the boundary layer. He discovered that non-polar solutes pass though more easily than polar solutes and concluded that the boundary layer has the dissolving qualities of a fatty oil. He guessed that it must contain lipids calling the layers surrounding cells “lipoids” made from lipids and cholesterol. He reported active transport of solutes across a cell membrane against a concentration gradient(2515-2517).

Tamás von Marschalkó (HU) was the first to describe the characteristics of plasma cells, including blocked chromatin, eccentric position of the nucleus, aperinuclear pale area (hof) and a spherical or irregular cytoplasm(2518).

Paul Gerson Unna (DE) used the term plasma cell but it is not known precisely what type of cell he was viewing(2519).

Paul Gerson Unna (DE) defined the plasma cell as a protoplasm poor cell which is frequently an important component of the infiltration of the skin in a number of diseases(2520).

Frank Spiller Locke (GB) recognized that calcium ions are necessary for effective neuromuscular transmission(2521).

Sergei Nikolaevich Winogradsky (RU) discovered chemoautotrophic bacteria that oxidize ammonia to nitrite (Nitrosococcus), and other chemoautotrophs which oxidize nitrite to nitrate (Nitrobacter). These organisms contain no chlorophyll, yet they could assimilate carbon dioxide and make organic material in the dark. This work provided a firm foundation for his concept of the chemoautotrophic life style(2522).

Sergei Nikolaevich Winogradsky (RU) isolated a free living anaerobic nitrogen fixing bacterium and named it Clostridium pasteurianum(2522). Martinus Willum Beijerinck (NL) later isolated and identified it as Azotobacter chroococcum(2523).

Frederick Frost Blackman (GB) proved that most of the gaseous exchange between the leaves of a plant and the surrounding atmosphere takes place through the stomata(2524).

J.A. Notkin (DE) showed that the physiologically active principle of the thyroid gland resided in a protein substance which he called thyreoproteid(2525).

Adolf Magnus-Levy (DE) was the first to apply respiratory quotient studies to people with disease. He discovered that people with a hyperthyroid condition exhibited an elevation in metabolic rate, whereas those with myxedema and underfunctioning thyroids exhibited a lowered metabolic rate. This represents the origin of the use of metabolic rates in medical diagnosis(2526). This work helped bring about the realization that the thyroid and its secretion has an active function unrelated to detoxifying the blood but indispensable to health. See George Murray, 1891

Waldemar Mordecai Wolff Haffkine (RU-CH-FR) developed a vaccine for cholera by giving a subcutaneous injection of culture—attenuated by growth at an elevated temperature—followed five days later by a subcutaneous injection of virulent culture(2527).

Hans Klebahn (DE) proposed that Cyanobacteria (blue-green algae) contain granules (vacuoles) filled with gas. He suggested that the gas is directly concerned with their flotation(2528).

Erwin Frink Smith (US) described wilt in cucurbits, defined the disease, listed host plants, described geographical distribution and signs of the disease, and proved the etiological role of a specific bacterium. An abridgement of one of his experiments follows:

Inoculations of July 16, 1896

The plants were in a hothouse and the bacteria used were from…an eight day old culture…. Well-developed, young, healthy, and rapidly growing cucumber plants (Cucumis sativus variety White Wonder), were inoculated…. Many delicate pricks (40 to 70) were made in the apical part of one leaf-blade of each plant, covering an area of not more than one sq. cm. The pricks themselves did the plant no injury. The platinum loop and the steel needle used in the operation were flamed and cooled each time before using. A big loop of the fluid, containing many thousand of the bacteria (some of which were motile, as determined by examination under the microscope) was put on the clean surface of the leaf, spread a little, and then rapidly pricked in, taking special care to make the needle holes as small as possible…. The plants were examined every day for the first 8 days and frequently after that. Twenty-four plants were inoculated.

(Plant 355) This plant was 18 inches and very thrifty. The inoculation was made on the sixth leaf 9 inches away from the stem. The pricked leaf-blade was 5 inches broad. Up to the morning of July 21, there was no trace of disease but at 3 PM of the same day about 0.5 sq. cm. on one side of the pricks was wilted…. By noon of the seventh day, the wilt covered about 10 sq. cm., and reached half-way down the blade. The leaf was now cut off close to the stem with a hot knife. Four days later the vine was normal, apparently except for a droop of the first two blades below and a fainter one of the first two above the node which had borne the pricked leaf. I filled the pot several times with water, but an hour later the absorption of the water had not relieved the droop of the foliage. The next day in the afternoon, the first two leaves below were cut away. They had not recovered their turgor. Three days later…the blades of the next four showed a wilt. The eighteenth day the blades of the second and fourth leaves up were shriveled but the petioles were turgid. The fourth leaf was on the same side as the second. The blade of the third leaf which was on the opposite side was flabby but had not yet shriveled. The blades of the fifth, sixth, seventh and eighth leaves were drooping. The others were turgid. The twenty-third day after inoculation all the leaves were shriveled….

Similar results were obtained with the twenty-four other plants inoculated, and Smith continued:

Every one of the twenty-four plants contracted the disease, and in each case it appeared in the pricked area. Nineteen of the plants subsequently developed constitutional signs and died of the disease. No general signs appeared in the other five plants, i.e., the disease was stopped by the removal of the affected leaf…. In eighteen cases the amputation of the affected leaf did not check the spread of the disease.…The bacteria…pass down through the vessels of the leaf at the rate of about 0.75 inch to 2 inches (2 to 5 cm.) a day….

Between August 5 and 8 numerous freshly wilting leaves were cut from these plants and fixed in strong alcohol to determine whether the bacteria are actually in the vessels of the leaf at the time the secondary wilt appears or whether this wilt is due simply to the plugging of the vessels of the stem…. Thin microtome sections were made from the basal part of the petiole of 66 leaves…staining in carbol fuchsin. Bacteria can not be demonstrated in every one, but they occur in 61 of them; no fungi are present, neither are there any insect-injuries. In most cases the bacteria are confined strictly to the spiral vessels of the petioles, and they do not occur in all of these, nor in all of the bundles. They are not present in the phloem, the cortical parenchyma or the tissues between the bundles. Summarized, the amount of bacterial infection in the basal part of the petioles is as follows: (1) In a few petioles nearly every bundle is occupied and bacteria occur in many vessels…(2) in 5 no bacteria detected; (3) in by far the greatest number the bacteria are confined to a few vessels of a few bundles….

After a description of the Morbid Anatomy, Smith proceeded to The Parasite, Bacillus tracheiphilus. His summary reveals the thorough nature of his investigation:

Résumé of Salient Characters

Positive

A bacillus in the vascular bundles of cucurbits causing a wilt-disease; short rods (single, paired, in fours end to end, or in small clumps); motile, peritrichate; capsules; pseudozoogloeae; involution-forms; stains readily; smooth; white; viscid; glistening; slow grower on media; surface colonies small, round discrete; no growth at 37°C. or at 6°C. (16 days); aerobic; facultative anaerobic (with grape-sugar or fruit-sugar); from these sugars a non-volatile acid, soluble in ether; grows only in open end of F-tube with dextrine or glycerine, acid from glycerine; slime on steamed potato (Solanum tuberosum) is same color as the normal substratum; usually it grays potato after a time; clouds peptone-bouillon and Dunham’s solution thinly; growth retarded in acid juice of cucumber fruits; also retarded or inhibited by juice of many other vegetables, e.g., table beet, sugar-beet, turnip. etc.; grows on many media at 25°C., carrot (Daucus carotus), coconut (Cocos nucifera), Fermi, Uschinsky, etc.; asparagin as carbon food (?); thermal death point 53°C.; optimum for growth 25°C. to 30°C.; maximum, 34°C. to 35°C. (?); minimum (?) 8°C.or below; easily killed by dry air, sunlight, or freezing (50 per cent or more); ammonia production (moderate; feeble production of hydrogen sulfide; in litmus-milk persistent growth without reduction or distinct change in color of litmus; short-lived on many media; killed readily by acids, but lives long in cane-sugar-bouillon with carbonate of lime; grows on some media in hydrogen and carbon dioxide; dissolves middle lamella (cucumber-parenchyma); distributed by insects, especially by Diabrotica vittata.

Mealy or dendritic surface growths; negative grams stain; endospores; chains; filaments; growth not yellowish, piled up or wrinkled; pellicle on bouillon; liquefaction (gelatin, blood serum, egg-albumin, etc.); lactose and pure maltose in closed end fermentation-tube lab ferment; acid (in milk); gas (all media); pigment (except gray stain on potato); indol (?); nitrite from nitrates; starch-splitting; cellulose-dissolving (except possibly in host); asparagin as nitrogen food; ammonium salts as nitrogen food; steamed turnip, and cauliflower; Cohn’s solution; acid bouillon (+33); acid gelatin; nearly odorless; not a soft rot; not infectious to tomato, potato (Solanum tuberosum), etc. On steamed potato liable to be confounded with a non-infectious coccus (follower) which reddens litmus milk.

Any organism which reddens or blues litmus-milk decidedly, reduces the litmus, throws down the casein, or clears litmus-free milk without precipitation may be set down at once as something else.

It was during his study of the wilt of cucurbits that Smith established the methods for the critical and faultless study of bacterial plant diseases. He investigated a number of other diseases of this type, such as the brown rot of Solanaceae, the black rot of cucifers, the yellow disease of hyacinths, bean blight, mulberry blight, the black spot and canker of peach and plum, the angular leaf spot of cotton, the angular leaf spot of cucumber, the bacterial canker of tomato, the olive tubercle, and others(2529). 

Louis Hermann Pammel (US) discovered and described the microorganism causing black rot of cabbage. He named it Bacillus campestris, later changed to Xanthomonas campestris(2530).

K. Takata (JP) presented evidence that insects can be vectors of plant virus disease—dwarf disease of rice (Oryza sativa)(2531).

Hatsuzo Hashimoto (JP), a rice grower, was the first to prove experimentally the role of insect as plant disease vector. He observed and discussed but did not publish his findings on the leafhopper as vector for rice stunt virus(2532).

Alexander Marmorek (AT-FR) discovered that fluid cultures of streptococci lyse erythrocytes (2533).

J. Jackson Lister (GB) established the alternation of asexual and sexual generations in a recognized species of protozoa, Polystomella crispa a foraminiferan(2534).

Sir David Bruce (GB) and Lady Mary Elizabeth Steele Bruce (GB) while investigating an outbreak of nagana, a disease similar to surra, in cattle in Zululand, were looking for a bacterial cause and found trypanosomes in the blood of diseased cattle; they demonstrated experimentally that these caused nagana in cattle and horses and also infected dogs. They also observed that infected cattle had spent some time in the fly-infested "tsetse belt" and that the disease was similar to that in humans called negro lethargy and fly disease of hunters(2535-2538). The causative agent was later named Trypanosoma brucei in their honor. The Bruces were the first to prove that an insect can carry a protozoan of a pathological kind.

Gustave Nepveu (FR), in 1891, was the first to observe trypanosomes in human blood(2539).

Joseph Everett Dutton (GB) and Robert Michael Forde (GB) identified the trypanosome that causes Gambian or chronic sleeping sickness in humans as Trypanosoma brucei gambiense(2540-2542).

Aldo Castellani (Count of Chisiamaio) (IT) discovered Trypanosoma brucei gambiense in the cerebrospinal fluid of patients suffering from sleeping sickness (trypanosomiasis). He suggested that these trypanosomes cause the disease(2543).

Frederick George Novy (US) and Ward J. MacNeal (US) successfully established in vitro cultures of Trypanosoma brucei(2544).

Friedrich K. Kleine (DE) demonstrated the essential role of the tsetse fly (Glossina palpalis) in the life cycle of trypanosomes(2545).

John William Watson Stephens (GB) and Harold Benjamin Fantham (GB) described Trypanosoma brucei rhodesiense, the cause of Rhodesian or acute sleeping sickness(2546).

Sir Ronald Ross (GB) and David Thompson (GB) described the persistence of trypanosomes in the blood and the existence of successive waves of parasitemia in patients with African sleeping sickness(2547).

Walter Abraham Jacobs (US), Michael Heidelberger (US), Wade H. Brown (US), and Louise Pearce (US) synthesized the first drug found to be effective in the treatment of African sleeping sickness (the sodium salt of N-phenyl-glycineamide-p-arsonic acid)(2548, 2549). 

Matthew P. Cunningham (GB), Keith Vickerman (GB) and Antony G. Luckins (GB) determined how the parasite, Trypanosoma brucei, evades the immune response by what is called antigenic variation(2550-2552).

Jules Jean Baptiste Vincent Bordet (BE) showed anti-cholera serum heated to 55°C could be mixed with unheated normal serum and produce bacteriolysis of Vibrio cholera, however, if the normal serum was also heated the bacteriolysis failed to occur. He concluded that two substances or factors must be concerned in the lytic action. One of these substances is present both in normal and fresh immune serum and is thermolabile, the other is peculiar to the immune serum and is thermostable(2553-2555).

Wilhelm His (CH) was the first to accurately describe the hypothalamus; which he named(2556).

Jean-Martin Charcot (FR) and Jean Albert Pitres (FR) conclusively proved the existence of cortical motor centers in man(2557).

Harvey Williams Cushing (US) and Ernest Amory Codman (US) made a wager to see who could develop better control over the administration of surgical anesthesia and thereby limit the distress—and even accidental death—of patients during operations. The result was the ether chart, on which was recorded continuously the surgery patient’s pulse, respiration, temperature, and later blood pressure, when a pneumatic device for registering it became available. This innovation led to a considerable reduction in mortality rate from anesthesia and is one of the major contributions of American medicine to surgery. These charts are the earliest examples of meticulous documentation of a patient’s vital signs(2558).

Harvey Williams Cushing (US) demonstrated the value of observing blood pressure during surgery and predicted that the taking of a patient’s blood pressure would become routine medical practice(2559).

Jules Emile Péan (FR) is believed to have performed the first surgery to correct diverticula of the bladder(2496). 

Josef Breuer (DE) and Sigmund Freud (CZ-AT) discovered the subconscious mind and introduced psychoanalysis using hypnosis and free-association(2560, 2561). 

Josef Breuer (AT), in 1881, discovered what was called the "talking cure" (Kaminfagen). A particular female patient obtained some relief from psychotic symptoms if he could persuade her to talk about her hallucinations during her auto-hypnoses. He found that if he could persuade her to recall in reverse chronological order each past occurrence of a specific symptom, until she reached the very first occasion, most of them disappeared in the same way(2562).

Johannes Eugenius Bülow Warming (DK) wrote Plantesamfund [Oecology of Plants] , one of the first books dealing with plant ecology. In it we find,"Oecological plant geography seeks: (1) to find out which species are commonly associated together in similar habitats; (2) to sketch the physiognomy of the vegetation and the landscape; (3) to answer the questions: why do species congregate to form definite communities, and why do these have a characteristic physiognomy; and (4) to consider the economy of plants and their growth-form"(2563).

Ismar Isidor Boas (DE) founded Archiv für Verdauungs-Krankheiten, the first journal devoted to the subject of gastro-enterology.

1896

“Heredity provides for the modification of its own machinery” was James Mark Baldwin’s (US) way of saying that the capacity to respond to environmental conditions is itself hereditary, i.e., the evolutionary effect(707).

“Chemistry has taken possession of medicine, and will not let go." Pierre Émile Duclaux(2564).

Antoine Henri Becquerel (FR) discovered radioactivity. He planned to place a silver coin between uranium salts and a photographic plate wrapped in thick black paper, exposing the entire package to the sun. To his amazement, he discovered the coin’s shadow on the plate despite the fact that it had not been exposed to light. He concluded that this new radiation was an atomic property of uranium(2565-2567). During his studies of uranium salts found in pitchblende he concluded that it was more radioactive than could be accounted for by its uranium content and therefore might contain another more powerfully radioactive substance. He encouraged Pierre and Marie Curie to look into the matter.

Wilhelm Friedrich Ostwald (DE) made the first electrometric measurement of hydrogen ion concentration by the potential on a platinum electrode in solutions saturated with hydrogen gas(2568). He discovered that this potential is a logarithmic function of the strength of the acid.

Max Cremer (DE) discovered an electrical potential proportional to the acid concentration difference across thin glass membranes(2569).

Fritz Habër (DE) and Zygamunt Klemensiewicz (PO-GB-PO), in 1909, constructed and studied glass H+ electrodes(2570).

Karl Albert Hasselbalch (DK) and Christen Lundsgaard (DK) produced a modified Ostwald platinum electrode with which they measured blood pH at body temperature(2571).

Heinrich Dannneel () discovered the reaction of oxygen with a negatively charged metal (cathode), the basis of oxygen polarography, later developed by Jaroslav Heyrovsky (CZ)(2572).

Phyllis Tookey Kerridge (GB) constructed the first blood glass pH electrode(2573).

Poul Bjørndahl Astrup (DK) designed an apparatus with which it was possible to determine the acid-base imbalance in a patient(2574).

Richard W. Stow (US), Richard F. Baer (US), and Barbara F. Randall (US) conceived of an electrode for measuring PCO2(2575).

Leland C. Clark, Jr. (US) developed and perfected a PO2 electrode(2576).

Sodium fluoride was first used as an insecticide. Crude petroleum emulsions were tested as insecticides. The value of early-season control of boll-weevil was discovered; arsenicals were recommended for this purpose(138).

Sir Charles James Martin (GB) designed and constructed a high-pressure gelatin membrane ultrafilter for fractionation of snake venom. This represents the first application of ultrafiltration(2577).

Scipione Riva-Rocci (IT) introduced the mercury sphygmomanometer in its modern form (for determining arterial blood pressure)(2578-2581).

Marceli Nencki; Marcellus von Nencki (PL) established that porphyrins are made up of pyrrole nuclei. He proposed that the similar chemical properties of hemin and chlorophyll denotes a common origin of plant and animal life and that comparison of similar compounds of flora and fauna provides insight into chemical and organismal evolution(2582).

Edmund Beecher Wilson (US) established a synthesis of cytology, ontogenetics, and genetics(889).

Sakugaro Hirase (JP) and Seiichiro Ikeno (JP) were the first to prove the existence of motile spermatozoids in gymnosperms(2583-2586).

Herbert John Webber (US) reported that one of the higher plants, Zamia, produces swimming sperm(2587-2592). 

Richard Karl Wilhelm Theodor von Hertwig (DE) was the first to describe the artificially stimulated development of sea urchin eggs (parthenogenesis). He stimulated the eggs with chloroform or strychnine(2593).

Ernest Henry Starling (GB) was the first to point out that capillary blood pressure tends to force materials from the circulating blood into surrounding tissues (transudation) and serum proteins exert an osmotic pressure which tends to force the absorption of materials from the surrounding tissues; the interplay of these forces leads to transudation at times and absorption at others. They show that the pre- and post-capillary resistances can be estimated in isolated perfused hindlimbs(2594). Starling’s findings were confirmed by John Richard Pappenheimer (US) and Armando Soto-Rivera (VE)(2595).

John Richard Pappenheimer (US), Eugene M. Renkin (US), and Luis M. Borrero (CO) were the first to successfully attempt to relate physiological measurements of permeability to the structure of microvascular walls. The first to offer a comprehensive theoretical analysis of diffusion and convection of solutes through channels of molecular dimensions and the first to provide quantitative evidence supporting the hypothesis that permeability to hydrophilic solutes is restricted to the intercellular regions(2596). 

Theobald Smith (US) published papers on differences in virulence in tubercle bacilli from several sources. The tubercle bacilli which he isolated from the udder or other affected organs of tuberculous cattle and cultivated on artificial media were definitely more pathogenic for rabbits, as well as for cattle, than were organisms isolated from human sputum or affected human lungs at postmortem. Later, the designation human and bovine as applied to different strains of the tuberculosis bacillus became widely accepted(2597, 2598).

Johann Petruschky (DE) appears to be one of the first to have isolated Alcaligenes faecalis (Bacterium faecalis alcaligenes)(2599). He originated litmus milk as a bacterial culture medium. ref.

Emile M. P. van Ermengem (BE) isolated and named Clostridium botulinum, the etiological agent of botulism (L.botulus, sausage). He called it Bacillus botulinas. The source was pickled ham which had made a large number of people ill(2600, 2601).

P. Tessmer Snipe (US) and Hermann Sommer (US) purified botulinus toxin(2602). Note: See Carl Lamana, 1946.

Arnold Stanley Vincent Burgen (GB), Frank Dickens (GB), and Leonard J. Zatman (GB) discovered that botulinum toxin blocks neuromuscular transmission(2603).

Alan B. Scott (US) and Edward J. Schantz (US) were the first to work on a standardized botulinum toxin preparation for therapeutic purposes(2604, 2605).

Alan B. Scott (US) used botulinum toxin type A (BTX-A) in monkey experiments. In 1980, he officially used BTX-A for the first time in humans to treat strabismus (crossed eyes), a condition in which the eyes are not properly aligned with each other, and uncontrollable blinking (blepharospasm)(2606-2608).

Victor Morax (CH-FR) and Karl Theodor Paul Polykarpus Axenfeld (DE) independently described a small diplobacillus, (Moraxella lacunata) as responsible for chronic infections of the conjunctiva and cornea in man(2609, 2610). The organism is sometimes referred to as the Morax-Axenfeld bacillus.

Emile Charles Achard (FR) and Raoul Bensaude (FR) isolated a bacillus from the tissues of a patient recovering from a typhoid-like disease. The isolant resembled the typhoid bacillus but differed from it in important particulars. This probably represents the first isolation of a causative agent of paratyphoid fever(2611).

Benjamin Minge Duggar (US) described toxic septicemia of the squash bug, Anasa tristis DeG., and assigned the bacterium Bacillus entomotoxicon as the etiological agent(2612). It was later decided that the agent is Bacterium entomotoxicon.

Henry Koplik (US) found that red skin spots with a minute bluish-white center (Koplik spots) are absolutely diagnostic of measles (rubeola)(2613).

Robert Almer Harper (US) discovered the ascospore and sexual reproduction in the Ascomycetes(2614).

Thomas Casper Gilchrist (US) and W.R. Stokes (US) were the first to describe American blastomycosis (oidiomycosis), a well-defined skin disease which may evolve into a systemic infection. It has been called North American blastomycosis, Gilchrist’s disease, blastomycosis, and blastomycetic dermititis. The etiological agent is a dimorphic fungus(2615, 2616).

Gilchrist and Stokes cultured the fungus and named it Blastomyces dermatitidis(2617).

Adolfo Lutz (BR) was the first to describe a case of what later became known as South American blastomycosis(2618). This disease primarily attacks areas in and around the mouth and may invade lymphatics of the neck. It has also been called paracoccidioidal granuloma and Lutz-Splendore-Almeida’s disease because Alfonso Splendore (BR) and Floriano Paulo de Almeida (BR) also contributed to defining South American blastomycosis caused by Paracoccidioides brasiliensis(2619, 2620). It is also called Lutz-Splendore-de Almeida disease.

Jorge Lobo (BR) described lobomycosis or lacaziosis, a keloidal blastomycosis of the skin caused by Lacazia loboi (formerly named Loboa loboi) which is indigenous to South America(2621).

Rudolf Albert von Kölliker (CH) gave the name axon to the axis cylinder of the nerve cell(390). 

Abbott H. Thayer (US) proposed that camouflaged animals are concealed by the background not only because they blend into it but because of what he called countershading—a device that makes creatures look flat. In countershading, an animal’s colors are precisely graded to counteract the effects of sunlight and shadow. Countershaded animals are darkest on top, where most sunlight falls, and lightest on the bottom, e.g. penguins, orcas(2622). In 1903 he wrote, “Every possible form of advantageous adaptation must somewhere exist…. There must be unpalatability accompanied by warning coloration… and equally plain that there must be mimicry”(2623).

Josef Jadassohn (DE) introduced the concept of the patch test to dermatology and immunology(2624).

Emil Herman Grubbé (DE), in 1896, initiated irradiation treatment of a patient suffering from advanced recurrent cancer of the breast. The condition was relieved but she died shortly afterward of metastases. This represents the first attempt at medical treatment using irradiation. By 1902, Grubbé's practice reached the point where he was X-ray treating on an average over seventy cases daily. He found X-ray treatment curative in cases of lupus, epithelioma, nodular returns (post operative), primary breast cancer, tuberculous lung, tuberculous bone, cancers of soft internal organs, sarcomata, and osteo-sarcomata. Although he burned every one of these patients he considered this a necessary consequence. Grubbé remarked that in properly selected so-called incurable cases the X-ray brought about remarkable results(2625, 2626).

Thor Stenbeck (SE), in 1899, initiated the treatment of a 49-year-old woman's basal-cell carcinoma of the skin of the nose, delivering over 100 treatments in the course of 9 months. The patient was living and well 30 years later(2627). At the same time, Tage Anton Ultimus Sjörgen (SE) and Edvard Sederholm (SE) cured a squamous cell epithelioma with fifty treatments over 30 months(2628).

Francis Williams (US) presented to the Boston City Hospital staff several cases of carcinoma of the skin and of the lower lip healed by fractionated irradiation(2629).

Henri-Alexander Danlos (FR) and Paul Bloch (FR) investigated the use of radium in the treatment of skin diseases at the Saint Louis Hospital of Paris(2630).

Robert Abbe (US) used radium as a surgical adjuvant in treating cancer(2631).

Pierre Curie (FR), Charles Bouchard (FR), and Victor Balthazard (FR) studied the effect of radium on animals and discovered that it could destroy diseased cells. It cured tumors and certain kinds of cancer(2632). This type of therapy was to be called Curietherapy and finally radiation therapy.

Walter Koenig (DE) published radiographs of front teeth in the upper and lower jaw taken with x-rays. These were the first dental radiographs(2633).

Weston A. Price (US) showed that dental radiographies make it possible to obtain clear and precise images of the contour of the roots of the teeth(2634).

Vaughn Pendred (GB) was the first to draw attention to the association of goiter with deaf-mutism(2635).

Thomas Clifford Allbutt (GB) was the first to point out that in the middle and later stages of life men and women are liable to a rise of the mean arterial pressure (hypertension) to an abnormal and even high degree(2636).

Jean Hyacinthe Vincent (FR) described fusospirochetal disease or what was later called Vincent’s angina or trench mouth because he diagnosed it in the mouths of trench bound soldiers in World War I(2637-2639)

Henri-Jules-Marie Rendu (FR) gave a clinical description of hereditary hemorrhagic telangiectasia(2640).

Antoine Bernard-Jean Marfan (FR) described a five-year-old female patient, with long thin limbs, poor muscle development and an abnormally curved spine. Dr. Marfan’s name became synonymous with patients affected by a disorder of connective tissue affecting primarily the musculoskeletal system, the cardiovascular system and the eye. The patients have an asthenic build, with tall stature, long arms and legs and characteristic changes in the extremities, particularly long and spider-like fingers, an arm span greater than height, Marfan’s syndrome(2641).

William Pringle Morgan (GB) was the first to publish a report describing a congenital word-blind (dyslexia) patient(2642).

Fulgence Raymond (FR) did clinical and anatomical studies on chorea, hemi-anesthesia and tremor. His papers and books on these subjects are classics. This great clinician is also remembered for his investigation on brain stem syringomyelia, muscle disorders, tremors, infections, neuritis and especially tabes dorsalis(2643). 

Friedrich Ernst Krukenberg (DE) described a malignant tumor of the ovary he called fibrosarcoma ovarii mucocellulare carcinomatodes, now known to be most frequently secondary to malignancy of the gastrointestinal tract(2644).

Joseph Jules François Félix Babinski (PL-FR) discovered that while the normal reflex of the sole of the foot consists of a plantar reflex of the toes, an injury to the pyramidal tract will show up in an isolated dorsal flexion of the great toe - Babinski’s Sign(2645). Others had previously observed this reflex but Babinski was the first to realize its diagnostic significance.

Joseph Jules François Félix Babinski (PL-FR), Jean Nageotte (FR), Auguste Tournay (FR) published on cerebrospinal syphilis, cerebellar signs, and symptoms such as asynergia adiadochokinesia, on reflexes, on unilateral bulbar lesions and on dystrophia adiposogenitalia(2646-2649).

Sir George Thomas Beatson (GB) found that inoperable breast tumors regressed following surgical removal of the ovaries (oophorectomy) and ingestion of thyroid tablets(2650). This represents the first suggestion of a linkage between breast cancer and hormones (or hormone-secreting tissue).

Ludwig Wilhelm Carl Rehn (DE) was possibly the first surgeon to successfully suture the heart. This occurred following a knife stab wound in the right ventricle. Quoting Rehn, “I decided to suture the heart wound. I used a small intestinal needle and silk suture. The suture was tied in diastole. Bleeding diminished remarkably with the third suture, all bleeding was controlled. The pulse improved. The pleural cavity was irrigated. Pleura and pericardium were drained with iodoform gauze. The incision was approximated, heart rate and respiratory rate decreased and pulse improved post-operatively.” The patient made a complete recovery(2651-2653). Some consider this the origin of cardiac surgery.

Journal of Experimental Medicine was founded.

American Journal of Physiology was founded.

The Paul-Ehrlich-Institut was founded as Institut für Serumforschung und Serumprüfung (Institute for Serum Research and Serum Testing) at Steglitz near Berlin as a test and research institution.

1897

“This day designing God

Hath put into my hand

A wonderous thing. And God

Be praised. At his command

I have found thy secret deeds

Oh million-murdering Death.

I know that this little thing

A million men will save

Oh death where is thy sting?

Thy victory oh grave?” Sir Ronald Ross (GB) wrote in his notebook upon his discovery of the relationship between man, malaria and the Anopheles mosquito(2654).

Joseph John Thomson (GB) announced the existence of negatively charged particles smaller than an atom(2655, 2656). They were then called cathode rays but were later named electrons by George Johnstone Stoney (GB), in 1891(2657).

Karl Ferdinand Braun (DE) invented the oscilloscope(2658).

David T. Day (US) described the separation of petroleum fractions upon percolation through an adsorbent, a form of column chromatography(2659).

August Dupre (GB) suggested that the controlled oxidation by bacteria of decomposable substances might be made the basis of a process of sewage treatment. William Joseph Dibdin (GB), a chemist, carried out a series of experiments initiated by Dupre, which led in the early 1890s to the development of the contact filter, one of the first successful forms of biological sewage treatment(2660).

Eduard Buchner (DE) discovered that an extract of yeast, freed of intact cells by filtration, retains the ability to ferment glucose to ethanol. This observation demonstrated that the enzymes (enzyme = in yeast) of fermentation can function independently of cell structure, contrary to Pasteur’s earlier dictum that fermentations required living yeast cells. Buchner called the cell free extract zymase(2661, 2662). Note: the yeast extract was produced for use in animal experiments, but underwent change so rapidly that sugar was added as a preservative. The action of the extract upon this added sucrose drew Buchner’s attention to the fact that fermentation was proceeding in the absence of yeast cells.

This work is seminal: first, because it discounted long held and popular vitalistic theories that consider cellular processes as fundamentally different from other principles of chemistry; secondly, it introduced a methodology that would allow scientists to break down biochemical processes into their individual steps; and, finally, the discovery of cell-free fermentation opened the doors to one of the most important concepts in biochemistry- the enzymatic theory of metabolism.

In 1897, oil of citronella (plant genus Cymbopogon) was first used as an insect repellent(138). 

Herbert Spencer Jennings (US) and J.H. Crosby (US) began their pioneering studies on reactions to stimuli in unicellular organisms. This led to such concepts as the trial-and-error behavior and many important concepts concerning various forms of tropisms and taxes(2663-2669).

Filippo Bottazzi (IT) and Léon Frédéricq (BE) found that most marine invertebrates are isotonic with the ocean(2670-2672). 

John Jacob Abel (US) and Albert Cornelius Crawford (US) determined that the active ingredient of the blood-pressure-raising extract of the suprarenal capsule (of the adrenal gland) can be isolated as a monobenzoyl derivative. Epinephrin (epinephrine) was the name Abel assigned to it while the pharmaceutical firms insisted on calling it adrenaline. This was the first isolation of an endocrine secretion as a chemically pure substance(2673-2675).

Nikolai Kulchitsky (RU-GB) described a cell type in the epithelium of the small intestine. These are argentaffin cells found between the cells that line the glands of Lieberkühn of the intestine(2676). It is known as Kulchitsky’s cell.

B. Moore (GB), D.P. Rockwood (GB), Heinrich Otto Wieland (DE), and Hermann Sorge (DE) proposed that bile acids somehow form polymolecular complexes with fatty acids(2677, 2678).

Leon Lack (US) and Irwin M. Weiner (US) reported that the ileum actively transports conjugated bile acids, thus providing for the first time a mechanism for intestinal conservation of conjugated bile acids(2679). 

Bengt Borgström (SE), Göran Lundh (SE), and Alan F. Hofmann (US) performed perfusion studies which confirmed that the ileum is the major site of conjugated bile acid replacement in man(2680). 

Alan F. Hofmann (US) clarified the role of conjugated bile acids in enhancing lipid absorption by showing that conjugated bile acids form mixed micelles with fatty acids and monoglycerides in vitro(2681).

Alan F. Hofmann (US) and Bengt Borgström (SE)) isolated the micellar phase from small intestinal content during fat digestion(2682).

Suzie W. Huijghebaert (BE), Alan F. Hofmann (US), Ashok K. Batta (US), Gerald Salen (US), Sarah Shefer (US), Adrian Schmassmann (CH), M. Antonietta Angellotti (IT), Huong-Thu Ton-Nu (US), Claudio D. Schteingart (US), Carlo Clerici (IT), Steven S. Rossi (US), Marcus A. Rothschild (US), Bertram I. Cohen (US), Richard J. Stenger (US), Erwin H. Mosbach (US), Richard G. Quist (US), Jan Lillienau (SE), Kim E. Barrett (US), Sarah J. Longmire-Cook (US), Young S. Kim (US), Rudy G. Danzinger (CA), Oliver Esch (US), Hans Friedrich Fehr (CH), and Johannes Locher (CH) proved that cholylsarcosine has all of the desired properties of a conjugated bile acid replacement molecule making it potentially useful in the treatment of short bowel syndrome (SBS)(2683-2689). 

Ivan Petrovich Pavlov; Iwan Petrowitsch Pawlow (RU), using dogs, surgically produced a miniature stomach as a special pouch (Heidenhein-Pavlov pouch) attached to the main stomach, both retaining their nerve supply. The miniature stomach opened to the outside of the body and when food was received into the main stomach, the small pouch secreted gastric juice of the same quality as that secreted to deal with the food. By this means he succeeded for the first time in obtaining samples of gastric juice uncontaminated with food. In the animal with the gastric fistula Pavlov observed that after it saw or smelled food, an abundant flow of gastric juice occurred. In some dogs he brought the esophagus to the surface of the body, where it was sutured, and then cut so that food taken by mouth would pass out of the upper end and food introduced into the lower end passed into the stomach. Again the sight or smell of food caused copious secretion of both saliva and gastric juice, the volume of gastric juice increasing as the animal was fed even though the food never reached the stomach, but passed out the esophagus. This flow he termed psychic secretion and showed that it depended upon reactions integrated at the level of the cerebral cortex since removal of the cortex abolished the response. He also found that section of the vagus nerve abolished secretion of gastric juice indicating that it is the secretory nerve of the gastric glands(See, Brodie, 1814). Food introduced into the stomach of sleeping dogs through the esophageal opening stimulated gastric secretion. The volume, pepsin content, and acid content of the gastric secretion varied with the food type. Pavlov called this phenomenon chemical secretion(2690-2692).

Robert Mearns Yerkes (US) and Sergius Morgulis (US) report that Iwan Petrowitsch Pawlow or Ivan Petrovich Pavlov (RU) devised and introduced into research a valuable new method of investigating the physiology of the nervous system in its relations to the so-called psychic reactions of organisms. It is called the Pawlow salivary reflex method. They give a description of the method and a summary of important results it has yielded(2693).

Bernhard Krönig (DE) and Theodor Paul (DE) described for the first time many of the important methods needed to properly evaluate chemicals as antiseptics and disinfectants. They pointed out that disinfectants can only be accurately compared when certain conditions are fulfilled. The bacterial test organism must have the same resistance and the number of bacteria must be constant. After the application of the test agent for a specified length of time its action must be promptly and completely stopped. Following treatment the bacteria must be transferred to the most favorable medium and kept at optimum temperature. The result is determined by enumeration of survivors in plate cultures. They emphasized that bacterial cells are not all killed instantaneously, but that populations of cells die at a logarithmic rate with the rate of kill directly proportional to the concentration of disinfecting agent(2694).

George Neil Stewart (US) reported on the blood circulation time course and on the influences which affect it(2695).

Eugen Rehfisch (DE) established the paradigm that micturition is initiated and sustained by active primary relaxation of the sphincter(2696).

Walter Migula (DE) introduced the order Thiobacteria for those microbes which Winogradsky had called sulfur bacteria(2697).

W. Lembke (DE) found that a marked difference may be brought about in the character of the intestinal flora by the substitution of a bread for a meat diet(2698).

Helen Beatrix Potter (GB), of The Tale of Peter Rabbit fame, was an outstanding observer of nature. While working in the British Museum, she reached the conclusion that lichens represent a symbiotic relationship between fungi and algae. Because of her sex, she was not taken seriously. Her uncle, Sir Henry Roscoe, read her paper before the Linnean Society in London(2699, 2700). Note: while she was not the first to make this observation her work came shortly after that of Schwendener in 1869.

Michael Siedlecki (PL-DE) and Fritz Richard Schaudinn (DE) were the first to describe the life history of Coccidiae (scale insects)(2701).

Edwin Grant Conklin (US), using the annelid worm Nereis, and Edmund Beecher Wilson (US), using the limpet Crepidula, discovered that the early embryonic cleavage events are the same in these organisms from two different phyla. In both, the three quartets of micromeres came off in the typical pattern of spiral cleavage: the first quartet clockwise, the second counter-clockwise, and the third clockwise. But the truly startling discovery was that both formed a d4 cell from which all mesodermal structures are derived in later development(2340, 2702).

Adolf Wallenberg (DE), Cornelius Ubbo Ariëns-Kappers (NL), and Willem Frederik Theunissen (NL) related the olfactory system to recognition and taste for food(2703-2705).

Rudolf Kraus (AT) discovered that by injecting animals with the clear filtrates from liquid cultures of cholera, typhoid, or plague bacilli, he obtained sera which produce specific precipitates when mixed in vitro with samples of the filtrates which had been employed for the inoculation. Thus the serum of animals injected with cholera filtrates precipitated the latter but did not precipitate the filtrates of other cultures. Kraus’s discovery of precipitating sera (precipitin) was confirmed by many workers, and Jules Jean Baptiste Vincent Bordet (BE) showed that it also occurred with non-bacterial substances (2706, 2707).

Jacques Oudin (FR) modified this procedure by adding a small amount of agar to the anti-serum forming a gel in a tube. When this was over-layed with antigen a series of rings appeared in the gel corresponding to the number of specific antigens and antibodies in the materials(2708).

Örjan Ouchterlony (SE) adapted the analysis of precipitin reactions to gel plates. This greatly increased the precision of the analysis(2709-2711).

Masanori Ogata (JP) injected crushed fleas from rats dead of plague into two mice, one of which died after three days. On the basis of this meager evidence he correctly suggested that plague is transmitted by suctorial insects such as mosquitoes and fleas(2712).

Alexandre Émile Jean Yersin (CH) developed an antiserum to protect against the bubonic plague bacillus(2713).

Alessandro Lustig (IT) and Gino Galeotti (IT) were the first to isolate a toxin from Yersinia pestis(2714).

Paul-Louis Simond (FR) found organisms morphologically indistinguishable from plague bacilli in the stomach of fleas which had fed upon rats and mice dying of plague. He succeeded in infecting a mouse by injecting an extract of crushed fleas taken from a plague rat. Simond found that in the absence of fleas the plague was not transmitted from sick or dead rats to healthy rats in close proximity, but in at least two incidents he observed transmission when fleas were present. He concluded incorrectly that contaminated flea feces was being introduced at the site of flea bites(2715). This and Ogata’s work above represents the discovery that fleas vector the plague.

Heinrich Hermann Robert Koch (DE) demonstrated that the bubonic plague is transmitted by means of a body louse that infests rats. ref

Robert H. Pollitzer () concluded, “Pulex irritans plays the main role in the spread of human plague"(2716). 

Paul Ehrlich (DE) discovered that antibodies act by combining with the substances which incited their production and observed that the plant poison ricin caused mouse erythrocytes to agglutinate and that he could prevent this agglutination in vitro and in vivo with anti-ricin serum provided that the ratio of ricin to anti-ricin was proper. He discovered that if non-immune mice were given anti-ricin serum it could protect them from the effects of ricin. Finding that there is a direct union of ricin and anti-ricin in vitro, Ehrlich concluded that it was necessarily a chemical process. 

He discovered that the union of antitoxin and toxin is accelerated by mild heat and retarded by cold. He also demonstrated that the reaction took place more quickly in concentrated than in dilute solutions.

In trying to determine what proportions of antitoxin and toxin produced the optimum reaction Ehrlich discovered that toxins are unstable and have a tendency to deteriorate into less potent versions he called toxoids. Although these toxins slowly lose their toxicity he found that their ability to stimulate an immune response remained relatively constant over time. Based on these observations he theorized that a toxin consists of two portions, one of which, the haptophore, brings about the union with the antitoxin, whereas the other—the toxophore—is, as its name implies, the carrier of the toxic action. He studied a number of different samples of diphtheria toxin and from them laid down the principles for the accurate standardization of antitoxic sera.

Ehrlich improved Behring's diphteria antitoxin and established an international standard for this and other antitoxins. The first exposition of his side-chain theory of immunity also appeared in the 1897b paper(2717-2719).

Sir Almroth Edward Wright (GB) and Sir David Semple (GB) introduced a vaccine prepared from killed typhoid bacilli as a preventive of typhoid. Wright first inoculated himself to prove the safety of the vaccine before inoculating others. Preliminary trials in the Indian army produced excellent results, and typhoid vaccination was adopted for the use by British troops serving in the South African War(2720).

Sir Almroth Edward Wright (GB) and Frederick Smith (GB) devised an agglutination test for the diagnosis of undulant fever(2721).

Sir Ronald Ross (GB) while a medical officer in India uncovered the remarkable relationship existing between man, the Anopheles mosquito, and the malarial parasite. He then shifted his attention to bird malaria and was the first to demonstrate the mosquito cycle in bird malaria. Ross worked out the relationship between bird, malarial parasite, and mosquito (Culex). He proved transmission of Plasmodium by mosquitoes using Plasmodium relictum in sparrows(2722-2727). Note: In 1898 Sir Patrick Manson (GB) was convinced by Ronald Ross (GB) that mosquitoes could possibly transmit malaria. To test this theory Manson actually allowed Anopheles mosquitoes which had fed on a tertian malaria patient to bite his own son and his son came down with malaria! He then went with some friends to the Roman Compagna near Ostia, which was notorious for malaria, and lived in a mosquito-proof hut from July to October; he and his friends remained in perfect health. These experiments established clearly that mosquitoes carry malaria.

William George MacCallum (US) and Eugene Lindsay Opie (US) discovered that the plasmodium of malaria goes through a sexual cycle in the blood of its victim(2728-2730). Its asexual behavior was already known. 

Giovanni Battista Grassi (IT), Amico Bignami (IT), and Giuseppe Bastianelli (IT) were able to report their demonstration of the development of human plasmodium malarial parasites on the gut wall of Anopheles claviger(2731-2735).

Giovanni Battista Grassi (IT) and Amico Bignami (IT) showed that the plasmodium undergoes its sexual phase only in the Anopheles mosquito(2736). 

These works led to the preventative measure of protecting people from mosquitoes.

Alexandre Joseph Emilé Brumpt (FR) reported the existence of Plasmodium gallinaceum(2737). 

Étienne Sergent (FR) and Edmond Sergent (FR) used attenuated sporozoites of Plasmodium relictum to successfully immunize canaries against mosquito-borne malaria(2738).

Sydney P. James (GB) and Parr Tate (IE) discovered extra-erythrocytic stages of malaria with an avian plasmodium(2739).

Charles R. Anderson (US) achieved in vitro culture of the blood stages of avian Plasmodium(2740).

Alon Warburg (IL) and Louis H. Miller (US) achieved the first in vitro culture of the mosquito stage of any malaria parasite, using Plasmodium gallinaceum(2741).

Wilhelm Max Wundt (DE) added alkaline and metallic tastes to the four basic tastes: sour, sweet, bitter and salty. He is considered the father of modern psychology(2742).

Waldemar Mordecai Wolff Haffkine (RU-CH-FR) used killed plague microorganisms as a vaccine against the plague(2743).

Sir George Frederick Still (GB) identified the three categories of juvenile chronic arthritis. The systemic form is now often referred to as Still's Disease(2744).

Wilhelm Theodor Engelmann (DE) was the first to distinguish the four types of activity of the heart nerves: inotropic, bathmotropic, chronotropic, and dromotropic(2745).

Constantin von Monakow (RU-DE) wrote Gehirnpathologie with 3000 references, and articles on lead encephalopathy, aphasia and apraxia. His greatest work as a clinician was Die Localization in Grosshirn und der Abbau ler Funktion durch Korticale Herde. He introduced concepts which made present clinical neurology a truly biological science of organismal dynamics in human behavior(2746, 2747).

Leonard Erskine Hill (GB) and Harold Leslie Barnard (GB) described a simple and accurate form of sphygmometer or arterial pressure gauge contrived for clinical use(2748). 

Nikolai Sergeievich Korotkov (RU) discovered the auscultatory method of measuring arterial pressure, “The cuff of Riva-Rocci is placed on the middle third of the upper arm; the pressure within the cuff is quickly raised up to complete cessation of circulation below the cuff. Then, letting the mercury of the manometer fall one listens to the artery just below the cuff with a children's stethoscope. At first no sounds are heard. With the falling of the mercury in the manometer down to a certain height, the first short tones appear; their appearance indicates the passage of part of the pulse wave under the cuff. It follows that the manometric figure at which the first tone appears corresponds to the maximal pressure. With the further fall of the mercury in the manometer one hears the systolic compression murmurs, which pass again into tones (second). Finally, all sounds disappear. The time course of the cessation of sounds indicates the free passage of the pulse wave; in other words at the moment of the disappearance of the sounds the minimal blood pressure within the artery predominates over the pressure in the cuff. It follows that the manometric figures at this time correspond to the minimal blood pressure”(2749).

Max S. Löwenthal (GB) and Sir Victor Alexander Haden Horsley (GB) reported the inhibition of decerebrate (removal of the cerebrum) rigidity by localized stimulation of the cerebellar cortex(2750). 

Edward Flatau (PL) reported that the greater the length of the fibers in the spinal cord the closer they are situated to the periphery(2751).

John Benjamin Murphy (US) was the first to reunite a severed femoral artery (severed by a gunshot wound). He described this vascular surgery as follows: “A row of sutures was placed around the edge of the overlapping distal end [of the femoral artery], the sutures penetrating only the media of the proximal portion; the adventitia was then drawn over the line of union and sutured. The clamps were removed. Not a drop of blood escaped at the line of suture. Pulsation was immediately restored in the artery below the line of approximation…. A pulsation could be felt in the dorsalis pedis on October 11th, four days after the operation. There were no oedema of the leg and no pain”(2752). This is one of the earliest examples of vascular surgery.

Cesar Roux (CH) attached the small intestine to the stapled off upper third of the stomach and joined it in a Y formation to the now quiescent exit from the lower two thirds of the stomach(2753). This is called a Roux-en-Y operation in his honor.

Carl B. Schlatter (CH), in 1897, performed the first successful complete gastrectomy(2754).

John Jacob Abel (US) was one of the most important individuals involved in the transfer of medical knowledge from Europe to America. After graduating from the University of Michigan in pharmacy in 1883 he spent one year at Johns Hopkins then studied medicine and chemistry in Europe under His, Braune, Schwalbe, Carl Ludwig, Oswald Schmiedeberg, Heinrich Ferdinand Edmund Drechsel, Hoppe-Seyler, Marcellus von Nencki, and Johannes Adolf Wislicenus. He earned the M.D. degree from the University of Strasbourg in 1888 then interned in Vienna. Upon returning to America he taught at the University of Michigan and Johns Hopkins University.

Louis-Antoine Ranvier (FR) and Édouard-Gérard Balbiani (FR) founded the Archives d'Anatomie Microscopique.

1898

Pierre Currie (FR), Marie Skodowska Curie (PL-FR), and Gustave Bémont (FR) presented the papers which announced the discovery of radium. They first proposed the name polonium, because Marie was from Poland, then changed it to radium(2755, 2756). Marie also presented this discovery in her doctoral thesis(2757).

Jacobus Hendricus van’t Hoff (NL) and Arthur Croft-Hill (GB) affirmed that enzymes, like inorganic catalysts, promote the rate of reversible reactions in both directions(2758, 2759).

Joseph H. Kastle (US) and Arthur S. Loevenhart (US) demonstrated the reversibility of enzymes using lipase(2760).

Arthur Croft-Hill (GB) announced the first enzymatic synthesis, that of isomaltose(2758). 

Frank George Edmed (GB) determined the structure of oleic acid(2761).

Carl Benda (DE) coined the name fädenkörner or mitochondrien (from the Greek meaning thread granule) to identify rod-like structures found in cytological preparations by Richard Altmann (DE). Altmann had called them bioblasts and regarded them as microorganisms; Benda recognized them as cell organs(2040, 2762). Today we call them mitochondria (sing. mitochondrium). Benda developed a staining technique using crystal violet and alizarin which was especially good at demonstrating mitochondria(2763).

Leonor Michaelis (DE-US) discovered that mitochondria can be stained selectively and supravitally with a dilute solution of Janus green; the method of choice until 1952(2764).

Margaret Reed Lewis (US) and Warren Harmon Lewis (US) described and pondered the location of mitochondria within cells(Lewis and Lewis 1915).

Frantisek Vejdovsky (CZ) and Alois Mrazek (CZ) are credited with the discovery of the centrosome in animal cells. They called it the periplast(2765).

Thomas Harrison Montgomery Jr. (US) performed comparative cytological studies, with especial regard to the morphology of the nucleolus(2766). 

Robert Adolf Armand Tigerstedt (FI) and Per Gustaf Bergman (FI) extracted rabbit kidney and showed that it contained a principle which raised blood pressure upon intravenous injection into other rabbits. They called the principle renin(2767). Renin would later be found to promote the release of angiotensin, a powerful pressor agent.

Edward Lee Thorndike (US) described his puzzle box and began work which led to his proposed psychological law of effect. In full it reads: "Of several responses made to the same situation those which are accompanied or closely followed by satisfaction to the animal will, other things being equal, be more firmly connected with the situation, so that, when it recurs, they will be more likely to recur; those which are accompanied or closely followed by discomfort to the animal will, other things being equal, have their connections to the situation weakened, so that, when it recurs, they will be less likely to occur. The greater the satisfaction or discomfort, the greater the strengthening or weakening of the bond." His works include Psychology of Learning and The Measurement of Intelligence(2768-2774).

Giuseppe Sanarelli (IT) discovered that myxomatosis is a virus disease of wild and domestic rabbits; benign in the South American rabbit but usually fatal in the European wild rabbit (Oryctolagus cuniculus). He first found it in a native South American rabbit, Sylvilagus braziliensis Linnaeus, in Brazil. This was the first time that a tumor disease in animals was shown to be caused by a filterable agent, i.e., virus(2775).

Shotaro Hori (JP) was the first to associate the plant disease bakanae (foolish seedlings) with infection by the fungus Gibberella fujikuroi, although he at first identified the fungus as Fusarium heterosporum(2776-2778).

Eiichi Kurosawa (CN) produced the symptoms of the bakanae disease in rice and maize seedlings solely by treating them with a culture medium in which Gibberella fujikuroi had been grown(2779).

Teijiro Yabuta (JP) and Yusuke Sumiki (JP) isolated the bakanae factor, crystallized it, and named it gibberellin(2780, 2781).

Edmond Isidore Étienne Nocard (FR), Pierre Paul Émile Roux (FR), Amédée Borrel (FR), Alexandre Salimbeni (FR), and Edouard Dujardin-Beaumetz (FR) grew the causative agent of cattle pleuropneumonia in vitro for the first time. It was grown on a serum-enriched medium and referred to as PPLO (pleuropneumonia-like organism)(2782). Today it is placed in either the genus Mycoplasma or Acholeplasma.

Louis Ladislaus Dienes (US) and Geoffrey Edsall (US) made the first isolation of mycoplasmas from man finding it as the apparent cause for suppuration of Bartholin’s gland(2783).

Monroe D. Eaton (US), Gordon Meikeljohn (US), and William Van Herick (US) isolated and cultivated the causative agent of atypical pneumonia in man(2784).

Maurice C. Shepard (US) discovered the so-called T strains (tiny colonies 15 to 20µ ) which appeared to produce nongonococcal urethritis in man(2785).

Robert Merritt Chanock (US), Leonard Hayflick (US), and Michael F. Barile (US) were the first to cultivate Mycoplasma pneumoniae on a artificial medium(2786).

Robert Merritt Chanock (US) named the agent Mycoplasma pneumoniae(2787). 

Kiyoshi Shiga (JP) and Shibasaburo Kitasato (JP), while studying an epidemic of dysentery in Japan, discovered the bacillus of dysentery, now named Shigella dysenteriae. They employed the methodology of Koch’s postulates and the agglutination of axenic cultures by serum from patients with dysentery(2788-2790).

Walther Kruse (DE) found the dysentery bacillus during an epidemic of dysentery in the Ruhr area(2791). This bacterium is often referred to as the (Shiga-Kruse bacillus).

Adrien Veillon (FR) and A. Zuber (?) found Bacteroides fragilis in 22 cases of appendicitis(2792). Since then it has been found in lung, pelvic and hepatic abscesses, in septicemias with metastatic abscesses, and in infections of the urinary tract. The bacterial genus Veillonella is named to honor Adrien Veillon.

Benjamin Robinson Schenck (US) isolated a fungus, Sporotrichum sp., from a patient with refractory subcutaneous abscesses on his arm(2793). He would later be commemorated when it was named Sporotrichum schenckii. The infection is called sporotrichosis.

Charles Lucien de Beurmann (FR) and Henri Gougerot (FR) carried out extensive and detailed studies of sporotrichosis(2794-2797).

Sporothrix schenckii was renamed Sporotrichum beurmanni.

Michael Siedlecki (PL-DE) published the first complete life cycle of a gregarine (Adelea ovata living in Lithobius forticatus)(2798).

Justin Jolly (FR) made a detailed in vitro study of the behavior of different kinds of leucocytes and ultimately succeeded in keeping the leucocytes of the newt (Triton) alive for one month(2799-2802).

Carl August Ljunggren (SE) demonstrated that human skin could still be successfully grafted after being stored for weeks in ascitic fluid(2803).

Jules Jean Baptiste Vincent Bordet (BE) discovered that immune hemolysis of erythrocytes can be the result of mixing the cells with heated anti-RBC serum and unheated normal serum. 

On adding to a suspension of rabbit’s blood corpuscles in salt solution a small quantity of guinea-pig immune serum, the blood corpuscles of the rabbit rapidly clumped together (agglutination), and the hemoglobin passed into the medium leaving behind the colorless stromata or shadows. Heated to 55°C. for half an hour the hemolytic property of the immune serum was found to have disappeared. If then to a mixture of rabbits’ corpuscles and inactive, i.e., to heated guinea-pig immune serum Bordet added a quantity of serum from a normal guinea-pig or a normal rabbit, the phenomenon of hemolysis soon took place. The guinea-pig immune serum was found to have no effect on the corpuscles of guinea-pigs or pigeons. In fact it had a specific effect only on the corpuscles of the animal (rabbit) with which the guinea-pig had been originally injected. Bordet also showed that a hemolytic destruction of corpuscles takes place in the peritoneal cavity of an immunized guinea-pig. If the immune serum is heated to 55°C. and is then mixed with the homologous red blood corpuscles, the latter are hemolyzed in the peritoneum of a normal animal.

In the nomenclature of Bordet the thermolabile factor in hemolysis was named alexine and the thermostable element the substance sensibilisatrice, whereas Paul Ehrlich (DE) and Julius Morgenroth (DE) spoke of them as complement and amboceptor respectively. The latter names have persisted(2804-2806).

Richard Friedrich Johannes Pfeiffer (DE) and Ernst Marx (DE) considered that anti-cholera antibodies are produced especially in the spleen, lymph nodes, and bone marrow, and this was supported by experiments of others(2807).

Walter Bradford Cannon (US) was the first to use Röntgen’s x-rays for physiological purposes. To do this, he devised a bismuth meal, a suspension of material of high atomic weight which was harmless and which was opaque to x-rays. After such a meal, the intestinal system would stand out as white against a black background, under x-rays. For the first time men could see the body’s soft internal organs on display while the outer skin remained intact. The diagnosis of gastric ulcer and malignancy of any part of the gastro-intestinal tract by means of a bismuth or barium meal followed by fluoroscopy or radiophotography became a common clinical method(2808).

Montoya (CO) and J.B. Flores (CO) were the first to definitely report tinea nigra as a disease state. They called it Caraté noir(2809). 

Alexandre Cerqueira (BR) produced a well documented description of tinea nigra in 1891 but it was not published until 1916 when his son Antonio G. Castro Cerqueira-Pinto (BR) described it as keratomycosis nigricans palmaris in his medical thesis(2810).

Paulo Parreiras Horta (BR) named the fungal agent Cladosporium wernickii(2811).

John McFadyean (GB) and Frederick Hobday (GB), in dogs, reported the first cell-free transmission of papillomas(2812).

Johann Petruschky (DE) suggested that convalescent cases of typhoid fever might be able to infect healthy individuals by means of typhoid bacilli in their urine(2813).

Paul Frosch (DE) confirmed the suggestion of Petruschky(2814, 2815).

Karl Wilhelm von Drigalski (DE) found that apparently healthy individuals may pass typhoid bacilli in their feces, i.e., healthy carriers(2816).

Henry Fairfield Osborn (US) enunciated the concept of adaptive radiation in evolution. Starting from an ancestral stock species, variations in the stock would allow a species to occupy niches previously unavailable(2817). 

Bernhard Naunyn (DE) published Der Diabetes Melitus in which he presented evidence to refute the prevailing opinion of the supposed benefit of a high-protein diet in the treatment of diabetes melitus(2818).

Sir Patrick Manson (GB) established tropical medicine as a specialty and founded a school of tropical medicine in London. He was among the first to suggest that mosquitoes might be the agents for spreading malaria(2819).

Guido Banti (IT) demonstrated that the spleen is the principal site for the destruction of erythrocytes, and that this normal function is exaggerated when the spleen becomes enlarged pathologically(2820-2822).

Francis Galton (GB) presented his ancestoral law of heredity(2823). Ronald Aylmer Fisher (GB) later found this law to be the natural consequence of Mendelian inheritance for polygenic traits. See, Fisher, 1918.

Charles Scott Sherrington (GB) described decerebrate (removal of the cerebrum) rigidity in the cat(2824).

Charles Scott Sherrington (GB) demonstrated axon branching and showed that the axonal pain pathways are proof of an organized sensory network. He worked on determining the region (dermatome) of skin supplied by each dorsal root(2825).

Sir Henry Head (GB) and Alfred Walter Campbell (GB) showed herpes zoster to be a hemorrhagic inflammation of the posterior nerve roots and the homologous spinal ganglia. They made a map of human dermatomes. Patients with herpes zoster provided valuable information to the development of this map(751, 752).

Otfrid Foerster (DE) made a thorough study of the human dermatomes, including overlap in nerve distributions. This overlapping is correct and conflicts with some of Head’s conclusions. Foerster suggested the concept of gate control. This theory asserts that large nerve fibers can inhibit small nerve fibers during a painful experience. He also introduced topographical localization of function, suggesting that pain fibers are in different locations from temperature and touch fibers(757).  

William Henry Howell (US) showed that the pituitary’s blood pressure lowering activity resides in the posterior lobe(2826).

John Newport Langley (GB) and William I. Dickinson (GB) coined the phrase autonomic nervous system, and the term parasympathetic(2827). 

Karel Frederik Wenckebach (NL-AT) described a sequence of cardiac cycles in the electrocardiogram. It is a form of incomplete atrioventricular heart block in which there is progressive lengthening of conduction time course in cardiac tissue with P-R interval increasing until there is not a ventricular response. This is followed by a conducted beat with a short P-R interval, and then the cycle repeats itself. This occurs frequently after an inferior myocardial infarction and tends to be self-limiting. Today it is referred to as a type 1 second-degree atrioventricular (AV) block or Wenckebach’s phenomenon(2828, 2829).

John Hay (GB) discovered the form of second-degree AV block currently known as type 2 block or Mobitz type 2 auriculoventricular block(2830).

Woldemar Mobitz (DE) provided electrocardiographic proof of Hay’s discovery(2831).

Georges Hayem (FR) gave the first adequate description of acquired hemolytic jaundice (Hayem-Widal’s disease)(2832).

John Benjamin Murphy (US) announced his technique of treating tubercular lungs by intentional pneumothorax(2833, 2834).

George H. Monks (US) developed a new method for restoration of a lower eyelid by plastic surgery. An apical patch was cut, pulled through the corner of the eye socket then attached below(2835).

Gustav Killian (DE) introduced bronchoscopy when he succeeded in the removal of a piece of bone from the right mainstem bronchus of a 63-year-old man(2836).

Leonardo Gigli (IT) developed a safe method for temporary cranial resection using a grooved probe and a wire saw(2837).

Gheorghe Marinescu (RO), between 1898 and 1901, made the first science films in the world:[1] The walking troubles of organic hemiplegy (1898), The walking troubles of organic paraplegies (1899), A case of hysteric hemiplegy healed through hypnosis (1899), The walking troubles of progressive locomotion ataxy (1900) and Illnesses of the muscles (1901)(2838).

Ernest Thompson Seton (GB-US) wrote Wild Animals I Have Known. This book had a profound positive impact on the public's perception of natural predators such as the wolf of North America(2839). 

The Russian Hydrographic Survey of the Biology of Lake Baikal was undertaken between 1876 and 1902. This survey, led by Fedor Kirillovich Drizhenko (RU), found several unique endemic freshwater animals that had become extinct in the rest of the world. The unique fauna in this lake exemplify the power of isolation in the evolutionary process(2840, 2841).

Paul Marchal (FR) founded the first agricultural entomology research unit. He was head of the Entomological Laboratory at INA, Paris, where basic and applied research on entomophagous insects took place.

1899

“The good physician treats the disease; The great physician treats the patient who has the disease.” Sir William Osler. ca. 1899-1905(2842).

The sixth cholera pandemic killed more than 800,000 in India before moving into the Middle East, northern Africa, Russia and parts of Europe. By 1923, cholera had receded from most of the world, although many cases were still present in India.

Carl Ernst Arthur Wichman (DE-NL) crystallized a protein from the albumin fraction of whey by addition of ammonium sulfate and acidification(2843).

Paul Gerson Unna (DE) and Artur Pappenheim (DE) developed the Unna-Pappenheim stain, the most common stain for blood smears. It was originally used for gonococci, but later used to demonstrate plasma cells during chronic inflammation. It detects RNA and DNA in tissue sections with the RNA staining red and the DNA staining green(2844, 2845)

Pierre Émile Duclaux (FR) observed that extracellular production of proteases and saccharase in Aspergillus occured in response to the addition of protein and sucrose to the medium in which the organism was grown. This is considered to be the origin of the analysis of the regulation of protein synthesis(2846). This phenomenon was later called enzymatic adaptation. Melvin Cohn (US),  Jacques Lucien Monod (FR), Martin Pollack (GB), Solomon Spiegelman (US), and Roger Yate Stanier (CA) named it enzyme induction(2847).

Frédéric Dienert (FR) showed that yeast grown on glucose breaks down glucose but not galactose, but yeast grown on galactose breaks down either galactose or glucose. If yeast is grown in the presence of glucose and galactose, then the glucose is broken down first. He obtained similar results with other sugars(2848).

Henning Karström (FI) was the first person to carefully investigate enzyme induction. He found that certain enzymes are always present, regardless of the medium type, whereas other enzymes are only formed when their substrates are present. He coined the term constitutive to describe those enzymes always present, and adaptive to describe those induced by substrate. His work is based on studies of carbohydrate metabolism in Gram negative enteric bacteria(2849).

Marjory Stephenson (GB) and John Yudkin (GB) demonstrated the adaptation of bacteria to different biochemical environments(2850-2852).

Jacques Lucien Monod (FR) observed that when Bacillus subtilis or Escherichia coli are grown on a mixture of two particular sugars, growth occurs in two distinct phases separated by a lag time. During the first phase only one of the two sugars is metabolized, and the second begins to be degraded only when the first sugar has totally disappeared. Glucose was found to be in the first category and lactose in the second(2853, 2854).

Jacques Lucien Monod (FR) christened this phenomenon diauxie, in bacteria. Diauxie is from a Greek root meaning double growth(2855, 2856).

Jacques Lucien Monod (FR) would relate enzymatic adaption to genetics and cellular differentiation(2857).

Rudolf Albert von Kölliker (CH) indicated in his memoirs that he had earlier identified and named osteoclasts, explaining that these multinucleated cells are active in osseous absorption and removal(2858).

Noël Bernard (FR) established that orchid seed germination requires a mycorrhizal relationship(2859, 2860).

Ludwig Edinger (DE) made many discoveries including his description of the ventral and dorsal spinocerebellar tract, clarifying polio-encephalon and neo-encephalitis, dividing the cerebellum on physiological as well as anatomical grounds into a paleo- and neocerebellum(1709, 2861, 2862).

Arthur Looss (DE), working in Egypt, was dropping cultures of hookworm larvae into the mouths of guinea pigs when he spilled some of the culture onto his hand. He noticed that it produced an itching and redness and wondered if infection would occur this way. He began examining his feces at intervals and, after a few weeks, found that he was passing hookworm eggs. The paper on this life cycle is considered a classic in the field(2863).

Theobald Smith (US) determined the thermal death time of Mycobacterium tuberculosis in milk to be 15 minutes at 60°C(2864).

Allan Macfayden (GB) and Sydney Rowland (GB) were the first to test the effect of extremely low temperatures on the viability of bacteria(2865).

Harvey Williams Cushing (US) reports that a vaginal gonococcus infection can ultimately lead to acute, diffuse peritonitis(2866). Hugh Hampton Young (US) performed nearly all of the bacteriological analyses leading to this discovery(2867).

Carl Franz Joseph Erich Correns (DE), unaware of Johann Gregor Mendel’s (Moravian-CZ) earlier work, independently discovered the laws of genetics while carrying out hybridization experiments with stock, maize, beans, peas, and lilies. Upon discovering that Mendel had preceded him he published his own work merely as confirmation(364, 2868, 2869).

Lucien Claude Jules Cuénot (FR) proved experimentally that sex is not influenced by exterior conditions and acknowledged that determination took place as early as the egg stage(2870). Note: obviously he did not choose organisms like some reptiles where the incubation temperature influences sex.

Lucien Claude Jules Cuénot (FR) proposed that armadillos from the same litter are true twins born of polyembryony(2870).

W. James Loughry (US), Paulo A. Prodöhl (US), Colleen M. McDonough (US) and John Charles Avise (US) confirmed this when they found that in the nine-banded armadillo (Dasypus novemcinctus) a litter of these animals always consists of four same-sex, genetically identical siblings. A single fertilized egg splits leads to four embryos each of which develops into a separate individual(2871).

Jules Jean Baptiste Vincent Bordet (BE) in his paper on the mechanism of agglutination, drew attention to the remarkable fact that agglutinins are absorbed from serum when the latter is saturated with the homologous organism. He showed that if immune horse serum is mixed with cholera vibrios and if after contact the vibrios are removed by centrifugation, the clear fluid of the supernatant fraction no longer retains its agglutinating property for cholera vibrios while its agglutinating power on typhoid bacilli persists. Conversely, by saturation first with typhoid bacilli the typhoid agglutinins are removed, whereas the supernatant fraction can still agglutinate cholera vibrios. This experiment pointed to a way of making a serum very specific by absorbing out unwanted agglutinins(2707).

Stabsarzt Slawyk (DE) isolated and cultured the influenza bacillus (Hemophilus influenzae) from the blood and spinal (lumbar puncture) fluid of a child with meningitis(2872).

Martha Wollstein (US) demonstrated the transmissibility of Hemophilus influenzae infection and the capacity of this organism to cause purulent meningitis(2873). She drew attention to the marked tendency for Hemophilus influenzae type b meningitis to occur in infants and young children.

LeRoy D. Fothergill (US) and Joyce Wright (US) noted the protective role of passively transmitted maternal antibodies, and the inadequacy of host immune response from infancy to age 3 years against Hemophilus influenzae type b meningitis(2874).

Jacques Loeb (DE-US) induced artificial parthenogenesis in annelida, frog, and sea urchin eggs by mechanically stimulating them(2875-2879).

Max Freudweiler (CH) made the connection that uric acid crystals cause gout(2880).

Wilhelm His, Jr. (CH) and Max Freudweiler (CH) clearly showed that urate crystals cause inflammation(2881, 2882).

Wilhelm Ebstein (DE) found that localized death of tissue (necrosis) is a primary event in gout(2883).

Caesar Peter Møller Boeck (NO) described a disease characterized by build-up of perivascular sarcomatoid tissue resulting from excessively rapid proliferation of epithelioid connective-tissue cells. He called it multiple benign sarcoid. Today it is called sarcoidosis(2884).

George Washington Crile (US) documented the results of his extensive experimental studies on shock and hypertension(2885, 2886).

George Washington Crile (US) developed a "shockless" method of anesthesia ("anoci-association") by which he attempted to isolate the operative site from the nervous system, where he believed surgical shock to originate. Anoci-association made use of generous premedication with morphine and atropine, regional (procaine) block, and anesthesia by inhalation of nitrous oxide and oxygen administered by trained anesthetists(2887).

Max Wilms (DE) described a case of nephroblastoma—Wilms tumor. He performed a successful nephrectomy but the cancer returned and the patient died(2888).

Jean-Louis Prévost (CH) and Frederic Batelli (CH) were the first to thoroughly study the effects of electrical discharge on the heart. They noted that if shock was applied within seconds of the onset of fibrillation, the result was defibrillation, which successfully restored sinus rhythm(2889).

Henry Chandler Cowles (US) studied plants on the Indiana sand dunes. This work yielded the first thorough working out of a complete plant successional series leading to a climax phenomenon(2890-2892).

Arthur George Tansley (GB) said, "It is to Henry Chandler Cowles that we owe, not indeed the first recognition or even the first study of succession, but certainly the first thorough working out of a strikingly complete and beautiful successional series"(2893). 

Hans Christian Cornelius Mortensen (DK) was the first person in the world to systematically ring birds. He started in 1899, ringing 165 young Starlings with numbered and addressed rings hoping that some of the birds would be found and the rings returned with information about finding place and date(2894, 2895). See, Audubon, 1810.

Robert Kirk (GB) produced sensitization to Primrose (Primula obconica) tissue by applying the plant repeatedly to irritated skin under occlusive dressings(2896).

Bruno Bloch (CH) and Aida Steiner-Wourlisch (CH) sensitized humans and guinea pigs to crystalline material from primrose leaves by applying it to the skin(2897, 2898).

N.S.Wedroff (RU) experimentally sensitized humans to 2:4 dinitrochlorobenzene (DNCB) through the skin(2899). 

Rudolf L. Mayer (DE) sensitized humans and guinea pigs to p-phenylenediamine using salve(2900).

Marin-Théodore Tuffier (FR) developed an extradural (epidural) anesthetic technique(2901).

Jean Athanse Sicard (FR) described injecting dilute solutions of cocaine through the sacral hiatus to treat patients suffering from severe intractable sciatic pain or lumbago(2902).

Fernand Cathlin (FR) gave sacral injections of cocaine(2903, 2904).

Fidel Pagés (ES) described a lumbar approach to epidural anesthesia(2905). 

Eugene Aburel (RO) injected chinocaine through a silk ureteral catheter to block the lumboaortic plexus of laboring women(2906).

Archile Mario Dogliotti (IT) performed abdominal surgery with single-shot lumbar epidural anesthesia(2907).

Alexandr Petrovich Karpinsky (RU) recorded his classic work on Paleozoic fossil sharks of the family Edestidae(2199, 2908).

Charles Doolittle Walcott (US) described an important clue in the search for Precambrian life when he discovered fossils in Precambrian carbon-rich shales on the slopes of a prominent butte deep within the Grand Canyon. The shales belonged to what is known as the Chuar Group of strata, so, Walcott named the fossils Chuaria. Chuaria is now known to be an unusually large, originally spheroidal, single-celled planktonic alga (technically, a "megasphaeromorph acritarch"). Walcott's specimens were indeed authentic fossils, the first true cellularly preserved Precambrian organisms ever recorded(2909).

Károly Gorjanović-Kramberger (HR), between 1899 and 1905, discovered Homo sapiens neanderthalensis (Homo neanderthalensis) fossil remains at a site near the Krapinica River at Krapina, Croatia. The find consisted of 13 men, women and children. The remains are dated to ca. 125,000 B.P(2910-2913).

The first meeting of the Society of American Bacteriologists (SAB) was held at Yale College, December 28, 1899 with 30 people in attendance. They declared their intention to promote “the science of bacteriology, the bringing together of American bacteriologists, and the demonstration of bacteriological methods.” It later became the American Society for Microbiology(2914, 2915).

The First International Congress of Genetics was held in London.   

ca. 1900

“Do not confuse biology and religion—one is a science to be proved or disproved, the other is a life to be lived,” Sir Quinton McGarel Hogg(2916).

The first known type-culture collection of microorganisms, the Kral Collection, was established in Prague, Czechoslovakia.

George Washington Carver (US) carried on a campaign, in the end successful, to plant peanuts (Arachis hypogaea) and sweet potatoes (Ipomea batatas) to return fertility to southern soils depleted by cotton (Gossypium spp.) and tobacco (Nicotiana tabacum). To use the surplus peanuts and potatoes he developed side-products. From peanuts alone, he developed some three hundred types of synthetic material, including everything from dyes and soap to milk and cheese substitutes.

Born a slave, his greatest contribution was the clear demonstration provided by his life story that it is tremendously worthwhile to educate individuals of any race.

1900

“That we are in the presence of a new principle of the highest importance is, I think, manifest. To what further conclusions it may lead us cannot be foretold.” William Bateson commenting on the work of Johann Gregor Mendel(2917).

“The general problems of embryology, heredity, and evolution are indissolubly bound up with those of cell structure.” Edmund Beecher Wilson(806).

Max Karl Ernst Ludwig Planck (DE) determined that energy is not infinitely subdivisible. Like matter it exists in particles. Planck called the energy particles quanta. He further determined that there is a constant relationship between the wavelength of a radiation and the size of its quantum (sing.). This constant is symbolized h (Planck’s constant) and is now recognized as one of the fundamental constants of the universe. This is the quantum theory(2918).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Friedrich Kutscher (DE) proposed that amino acids themselves and their spatial arrangement within the protein must become the chemical key to the understanding of proteins(2919).

Richard Martin Willstätter (DE) synthesized the amino acid proline by oxidizing hygrine and cuscohygrine, alkaloids from Peruvian cusco leaves. Hermann Emil Fischer (DE) was the first to isolate the amino acid proline from a protein hydrolysate of casein(2920, 2921).

Auguste Fernbach (FR) and Louis Hubert (FR) invented phosphate buffers for the purpose of controlling the acidity of a protease from malt and introduced the term tampon. Sørensen later called these solutions puffer; they became buffer in English(2922).

Erich Tschermak von Seysenegg (AT) unaware of Johann Gregor Mendel’s (Moravian-CZ) earlier work, independently discovered the laws of genetics(2923).

Hugo Marie de Vries (NL), unaware of Johann Gregor Mendel’s (Moravian-CZ) earlier work, independently discovered the laws of genetics using garden peas with some of the same characters used by Mendel. Upon discovering that Mendel had preceded him he published his own work merely as confirmation(2924).

Hugo Marie de Vries (NL), introduced the concept of segregation to genetics. He referred to it as spaltung (splitting)(2925).

Carl Franz Joseph Erich Correns (DE) associated the segregation of alleles with the reduction division in meiosis(2869).

Ernst Moro (DE) isolated Lactobacillus acidophilus from the feces of infants. It is a natural inhabitant of the infantile intestine and important in making certain sour milk products(2926). 

Henry Tissier (FR) isolated Bacillus bifidus communis (Lactobacillus bifidus) (Bifidobacterium) from the feces of breast-fed infants(2927).

Henry Tissier (FR) advocated intentional consumption of Bifidobacterium to improve one’s health(2928). 

Hugo Schottmüller (DE) used the specificity of bacterial agglutination reactions to separate the paratyphoid fevers (2929).

Simon Flexner (US) while working in the Philppines isolated a new and different species of dysentery bacillus now called Shigella flexnerii(2930).

Joseph Léon Marcel Ligniéres (FR) suggested that the entire group of bacteria to which the swine pest bacillus belongs, should be termed Salmonella in honor of Daniel Elmer Salmon (US)(2931).

Mary Mallon, a.k.a., Typhoid Mary (GB-US) was an American cook and immune carrier of typhoid fever who while moving from job to job infected more than 50 people with the disease between 1900 and 1907. After health officials found her, she was forced to live in relative seclusion for much of the rest of her life.

Clement Dukes (GB) distinguished the two disorders rubella (rose rash) and roseola infantum, and concluded that they were two similar, but etiologically and pathologically distinct, infections(2932).

Charles Franklin Craig (US) was probably the first to recognize a fourth type of human malaria; that caused by Plasmodium ovale. He described a malaria parasite which he found in the blood of American soldiers, returned from the Philippines, and noted especially its tertian fever pattern plus certain peculiar morphological characteristics not found in P. vivax(2933-2935).

Per Teodor Cleve (SE) wrote The Seasonal Distribution of Atlantic Plankton Organisms, a basic text in oceanography. He proposed that streams in the oceans can be characterized by the plankton they transport and conversely the existence of one type of plankton can determine the origin of a stream(2936). 

Sir Albert Charles Seward (GB) and Jane Gowan (GB) found fossil records indicating that the ginkgo or maidenhair tree, Ginkgo biloba, has existed on Earth since the Liassic (early Jurassic) period meaning that it has existed on earth longer than any other tree(2937-2941).

Randolph T. Major (US) found that resistance of Ginkgo biloba L. to pests accounts in part for the longevity of this species(2942).

A. Mayer (FR) found that serum osmolality is increased during thirst(2943).

Erich Leschke (DE) found that intravenous injections of hypertonic saline cause thirst in man(2944).

Avery Veryl Wolf (US) was the first to suggest that osmosensitive centers for thirst are located in the brain(2945).

Peter Arundel Jewell (GB) and Ernest Basil Verney (GB) localized the osmoreceptor to the anterior hypothalamus(2946).

Paul Ehrlich (DE) presented his general theory of immunity which, under the name of the side-chain or receptor theory, had for many years an enormous vogue. In this theory he visualized mammalian cells as possessing various specific receptors for all sorts of foreign chemical groups. When exposed to a foreign substance, the substance and its specific receptor would combine and thus stimulate the cell to produce more of these receptors some of which would spill into the blood. The combination of the receptor with the foreign substance would have a tendency to neutralize any harmful effect the foreign substance might have. In the absence of the foreign substance the blood level of receptors would slowly drop(2947).

Paul Ehrlich (DE) and Julius Morgenroth (DE) commented in 1900 that the organism "possesses certain contrivances, by means of which the immunity reaction, so easily produced by all kinds of cells, is prevented from acting against the organism's own elements and so giving rise to autotoxins [...] so that one might be justified in speaking of a horror autotoxicus”(2948). In other words, the body does not normally engage in autoimmune reactions.

Paul Ehrlich (DE) and Julius Morgenroth (DE) predicted that "when the internal regulating contrivances are no longer intact [...] great dangers arise. In the explanation of many disease-phenomena, it will in the future be necessary to consider the possible failure of the internal (i.e., immune) regulation"(2949).

Karl Landsteiner (AT-US) discovered that there are two types of erythrocyte agglutinins in human sera (alpha and beta) as well as two kinds of erythrocyte agglutinogens (A and B) on the cells. Cells were characterized as either A, B, or C. C was later changed to O(2950, 2951).

Alfred von Decastello (US) and Adriano Sturli (US) discovered that some erythrocytes possess both A and B agglutinogens; type AB(2952). The A,B,O blood types were the first known human polymorphism.

Georges Fernand Isidore Widal (FR), M. Paul Ravaut (FR) and Arthur Sicard (FR) introduced cytodiagnosis, the examination of the cellular elements suspended in the fluid of any serous cavity, as a tool to diagnose disease(2953, 2954). 

John M’Fadyean (GB) examined the etiological agent of African horse-sickness and found it to be filterable(2955).

Walter Reed (US), James Carroll (US), Aristides Agramonte y Simoni (US), and Jesse William Lazear (US) with the American Army Commission traced the transmission of the unknown virus of yellow fever to mosquitoes of the species now known as Aedes egypti. In the course of the rigorous and heroic tests to prove the theory Carroll acquired the disease in a mild form and Lazear lost his life. John R. Kissinger (US), John J. Moran (US), and Clara Louise Maass (US) volunteered to be bitten by mosquitoes to prove its role as a vector. Ms. Maass died of yellow fever. Yellow fever was the first human disease attributed to a virus(2956-2960).

Edwin Stephen Goodrich (GB) proposed that all invertebrate nephridia (except nephromixia) are homologous and the nephrostome is merely the opened proximal end of a protonephridium. There are genuine primary coelomic funnels which alone merit the name coelomostome and these connect to the exterior by genuine coelomic ducts or coelomoducts. Coelomostome plus coelomoduct constitute the genital duct of a coelomic invertebrate(2961).

Harvey Williams Cushing (US) and Louis E. Livingood (US) demonstrated that bacteria of the intestine in the fasting dog are reduced practically to zero except for a pocket in the cecum(2962).

Rudolph Matas (US) was the first to use positive pressure in thoracic surgery and introduced endotracheal anesthesia much as it is used today(2963).

Ernst Wertheim (AT), in 1898, performed his first radical abdominal operation for cervical cancer (hysterectomy). For his first twenty-nine operations he reported a mortality rate of 38 percent. By 1911 he had reduced the mortality rate to 10 percent and had treated 500 patients(2964-2966). See, Wilhelm Alexander Freund, 1878.

Henry Charlton Bastian (GB) believed a considerable amount of sensory information was provided by the muscles and that this information was used by the brain to coordinate motor acts(2967). He later introduced the phrase kinaesthetic sense to describe this relationship(2968). This gave way to Sherrington’s new term proprioception(2969).

Charles Scott Sherrington (GB) stated that the cerebellum is head ganglion of the proprioceptive system, holding that it functions as a whole because it deals with the musculature of the body as a whole rather than with individual muscles(2970). 

Graham Steell (GB) described the murmur of high-pressure in the pulmonary artery later called Graham Steell murmur(2971). The observation took place in 1888.

Sigmund Freud (CZ-AT) published Die Traumdeutung (The Intrerpretation of Dreams) which contains all the basic components of what became Freudian psychology—dreams are wish fulfillment, displacement, regression, the Oedipus complex, and the rest. The part of the dream remembered, is not as important as its latent content, or the symbolic meaning of the dream(2972, 2973). 

Vladimir Mikhailovich Bekhterev (RU) was the first to suggest that learning and memory are associated with the hippocampus portion of the limbic system in the brain(2974). He described two patients with a significant memory deficit who, on autopsy, were found to have softening of hippocampal and adjacent cortical tissue.

Brenda Milner (US) would present experimental evidence to support Bekhterev(2975).

Dukinfield Henry Scott (GB) wrote two significant books on paleobotany(2976, 2977).

Thomas Chrowder Chamberlain (US) was the first to suggest a continental freshwater origin of vertebrates during the Silurian and Devonian time(2978). Currently most scholars support a marine origin for vertebrates.

1901 

"To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all." William Osler(2979).

Philipp Lenard Wilhelm Konrad von Roentgen (Röntgen) (DE) was awarded the first Nobel Prize in Physics. It was for his discovery of a new form of penetrating radiation, which he named x-rays.

Jacobus Hendricus van’t Hoff (NL) was awarded the first Nobel Prize in Chemistry for formulating the osmotic pressure equation, and the theory of solutions that connected osmotic pressure, freezing-point depression, and the lowering of vapor pressure as thermodynamic properties.

Emil Adolf von Behring (DE) was awarded the first Nobel Prize in Physiology or Medicine "for his work on serum therapy, especially its application against diphtheria, by which he has opened a new road in the domain of medical science and thereby placed in the hands of the physician a victorious weapon against illness and deaths."

Hermann Emil Fischer (DE) and Ernest Francois Auguste Fourneau (FR) used amino acid monomers to synthesize polypeptides (a word Fischer coined) containing up to eighteen amino acid residues and demonstrated that digestive enzymes attacked these synthetic bonds just as they did those in natural polypeptides. Glycylglycine was the first peptide they synthesized(2921, 2980-2982).

Jokichi Takamine (JP-US) and Thomas Bell Aldrich (US) independently, were the first to crystallize the hormone epinephrine (adrenaline), an important step on the way to chemical identification. Takamine coined the name adrenalin (adrenaline)(2983-2985). This was the first hormone to be isolated in purified form. 

A thousand years earlier the Chinese were using mahuang (rich in ephedrine) with properties similar to adrenaline(2986). The drug is derived from plants of the genus Ephedra and is most commonly used to prevent mild or moderate attacks of bronchial asthma. Unlike epinephrine, ephedrine is slow to take effect and of mild potency and long duration. It is a bronchodilator and decongestant.

Takamine also isolated a starch-hydrolyzing diastase from rice (Oryza sativa).

Friedrich Wolfgang Martin Henze (DE) was the first to crystallize hemocyanin. He obtained it from octopus blood(2987).

Marceli Nencki; Marcellus von Nencki (PL) and Jan Zaleski (PL) found that when phylloporphyrin and hematoporphyrin are reduced the same pyrrol derivative, which they called hemopyrrol, was released(2988). The derivative was identified as methylpropylpyrrol.

Leonor Michaelis (DE-US) established the chemical principles of staining fat with various oil-soluble dyes(2989).

Count Karl Axel Hampus Mörner (SE) introduced the nitroprusside test, a rather specific test for sulfhydryl groups(2990).

Oscar Loew (US) discovered an enzyme which catalyzes the conversion of hydrogen peroxide to water and oxygen. Catalase was the name he gave it. The wide distribution of this enzyme in both plant and animal tissues explained why hydrogen peroxide, known to be toxic, failed to accumulate in tissues(2991).

Otto Cohnheim; Otto Kestner (DE) showed that the intestinal mucosa elaborates an enzyme which cleaves peptones to amino acids; he named it erepsin (peptidase). This suggested that dietary proteins are cleaved to amino acids in the gastrointestinal tract(2992-2995).

E. Wildiers (BE) discovered that yeast require trace amounts of a growth factor before they will produce alcohol from inorganic salts and glucose. The growth factor was later found to be a B vitamin(2996).

Sir William Boog Leishman (GB) developed Leishman's stain. It is a compound of methylene blue and eosin that soon became the standard stain for the detection of such protozoan parasites as Plasmodium (malaria parasite) in the blood(2997, 2998).

Paul Theodor Uhlenhuth (DE) built on the earlier work of Jules Bordet (BE) and developed the preciptin test which can show whether a blood stain is human or animal in origin(2999-3001). The first forensic application of his new technique was in the case of two murdered and dismembered children in the town of Göhren on the Baltic island of Rügen. The suspect in the case, Ludwig Tessnow claimed that the stains on his clothing were either cattle's blood or wood stain from a carpentry project. They were able to prove otherwise.

Hans Horst Meyer (DE) and Charles Ernest Overton (GB) reported the striking correlation between the solubility of general anesthetics in olive oil and their ability to anesthetize/immobilize tadpoles. As a result of these observations, it was proposed that anesthetic agents interfered with the structural and dynamic properties of the nerve cell membrane and, in so doing, altered the function of the neuron(3002, 3003).

Jean Friedel (FR) brought together the glycerol extract from fresh leaves with finely powdered leaves which had been rapidly and carefully dried, and found oxygen was evolved by the action of light, and carbonic acid taken up(3004).

Florence Rena Sabin (US) demonstrated that the lymphatics arise from veins by sprouts of endothelium, and that these sprouts or buds connect with each other as they grow outwards from the veins toward the periphery, so that the entire system is derived from already existing vessels. Further, she showed that the peripheral ends of the lymphatics are closed and that they neither open into the tissue spaces nor are derived from them(3005-3011).

Thomas Hunt Morgan (US) and Eugene Korschelt (DE) pioneered studies on regeneration and transplantation in salamanders(3012, 3013).

Clarence Erwin McClung (US) theorized that certain chromosomes whose synaptic mates were different in appearance or entirely absent were responsible for sex determination, e.g., Hermann Henking's accessory chromosomes. McClung discovered an accessory unpaired chromosome in a grasshopper which he assumed to be sex-determining although he at first supposed (wrongly) that sperms with the accessory were male determining. This was the first time that a trait (sex) was assigned to a chromosome. He suggested that this phenomenon might also be at work in other species(3014, 3015). See, Henking, 1891.

Hugo Marie de Vries (NL) proposed that different alleles of the same gene arise by a sudden, discontinuous change of that gene—a process to which he gave the name mutation (L. to change). This concept arose out of his observations of Oenothera lamarckiana (the evening primrose)(3016, 3017).

Alexander Ivanovitch Petrunkevitch (RU-US) gave the first statistically adequate cytological demonstration of the truth of Dzierzon’s hypothesis that worker and queen bees are developed from fertilized eggs, while drones are developed from unfertilized eggs by parthenogenesis. He found mosaic polyploidy in the honey-bee. There are only sixteen chromosomes in the first division of the nucleus of the drone-egg, but 64 in cells of the blastoderm of the later embryo(3018).

Friedrich Meves (DE) showed that while the diploid number (counted in the oogonia of the honey bee queen) is 32 and the haploid 16, more than 60 chromosomes are present in the follicle-cells of the testis(3019).

Jules Jean Baptiste Vincent Bordet (BE) and Octave Gengou (FR) developed the complement fixation test as follows. If to a quantity of unheated normal guinea-pig serum is added a quantity of sensitized erythrocytes (i.e., erythrocytes charged with specific antibody) hemolysis occurs. They made, however, the observation that if cholera vibrios are added to such a mixture they remain intact instead of undergoing spherulation and lysis, as might perhaps have been expected. The same occurs if the cholera vibrios and erythrocytes are introduced in the reverse order. On testing heated plague-serum mixed with plague bacilli and normal serum, Bordet and Gengou found that the subsequent addition of sensitized erythrocytes did not result in hemolysis. The explanation they gave was that the sensitizing substance in the plague-serum fixes the complement in the presence of plague bacilli so that it is prevented from acting on the sensitized erythrocytes. Other experiments indicated that the phenomenon was widespread and had applicability as a diagnostic test. They believed that it was possible to diagnose the existence of a sensitizer in the serum by the presence or absence of hemolysis of sensitized erythrocytes. Gengou showed further that sensitizers (antibodies) are developed in the blood of animals which have been injected with milk, and that such sensitizers are also capable of fixing complement. The same reaction also occurred in the sera of animals injected with egg albumin, fibrinogen, or other substances(3020).

Franz Hofmeister (CZ-DE) made one of the earliest proposals suggesting that intracellular metabolic reactions follow molecular pathways. “In the protoplasm synthesis and breakdown occurs by way of a series of intermediate steps, whereby it is not always the same kind of chemical reaction that is involved, but rather a series of reactions of different kinds …. A regular reaction sequence of the chemical reactions in the cell presupposes, however, the separate activity of the individual chemical agents and a definite direction of movement of the products that are formed, in short, a chemical organization … that helps to explain the speed and certainty with which it functions”(3021).

Martinus Willem Beijerinck (NL) announced that the blue-green algae (cyanobacteria), the free-living aerobic bacterium Azotobacter, and other microorganisms are capable of using atmospheric nitrogen as their sole source of nitrogen. He was the discoverer of Azotobacter.

“I shall call oligonitrophilic microbes those which in free competition with other microbes grow in nutrient solution where one has not willingly introduced nitrogen-containing substances but from which one has not removed the last traces of these compounds. They have the property of fixing free atmospheric nitrogen either alone or in symbiosis with other microbes”(2523).

Newton Barris Pierce (US) described Xanthomonas juglandis as the cause of blight of walnuts(3022).

Martinus Willem Beijerinck (NL) was a master practitioner of what is referred to as the enrichment culture technique. One of his early papers uses this methodology to isolate a bacterium capable of utilizing urea(3023).

Charles Louis Alphonse Laveran (FR) received a number of blood-smears—made by Arnold Theiler (CH-ZA)—from horses suffering with biliary fever (piroplasmosis). Laveran recognized intra-corpuscular parasites which he named Piroplasma equi (Babesia equi) (Theilera equi)(3024).

Sir Arnold Theiler (CH-ZA) showed that the horse sickness called biliary fever (piroplasmosis) and caused by Piroplasma equi (Babesia equi) (Theilera equi) is carried by the red-legged tick Rhipicephalus evertsi(3025, 3026).

Hugo Marie de Vries (NL) wrote Die Mutationstheorie and thereby advanced the thesis that species are not continuously connected but arise through sudden large changes(3017).

Lucien Claude Jules Cuénot (FR) defined the sexual cycle of the Gregarina(3027).

Theodor Boveri (DE) found that polarity in sea urchin eggs is associated with particular qualities of the cytoplasm. When he compared the development of isolated upper and lower portions of ova, he observed that the isolated upper portion could not gastrulate, while the lower could do so and could also differentiate primary mesenchyme. Boveri thought of the lower portion as a privileged region: “here differentiation began, and from here all other regions are influenced in their differentiation”(3028, 3029).

Albert Schütze (DE) working with iso-immunization of rabbits, produced the first evidence of homospecific antigens in the serum of mammals(3030, 3031).

Russell W. Cumley (US) and M.R. Irwin (US) demonstrated the existence of intraspecies genetically determined differences in certain serum proteins (heterogeneity), comparable to genetic variations in blood type, eye color, and other hereditary traits(3032, 3033).

Sarane Thompson (US), Joseph F. Foster (US), John W. Gowen (US), and Oscar E. Tauber (US) confirmed the work of Cumley and Irwin(3034).

Jacques Oudin (FR) discovered three rabbit antibody allotypes, a1, a2, and a3. These were later shown to be associated with the VH region of the antibody molecule(3035, 3036). 

Sarturnin Arloing (FR) and Paul Courmont (FR) developed a test for agglutinating antibodies in cases of tuberculosis(3037).

William Henry Howell (US) demonstrated the importance of inorganic salts in regulating heart rate(3038).

Gaston Milian (FR) was the first to study bleeding time course(3039-3041).

William Waddell Duke (US), in 1910, found that bleeding time (and the amount of blood shed) was increased in thrombocytopenia (thereby proving the primary function of blood platelets), he showed that a whole blood transfusion raised the platelet count, led to a cessation of clinical bleeding, and shortened the bleeding time to normal(3042).

V.O. Sivèn (SE), who weighed 143 pounds, found that he could keep his body in nitrogen equilibrium by consuming 25 to 31 grams of protein daily. He ate a liberal amount of carbohydrate, and his diet supplied 2,717 calories daily(3043).

Russell Henry Chittenden (US) concluded that for man the minimum "proteid" requirement was 93-103 mg N/kg body wt. (about 0.6-0.64 g protein·kg1·d), which anticipates, by 80 years, the mean requirement figure of 0.6 g protein·kg1·d1 proposed by FAO/WHO/UNU(3044-3046).

Eugene Lindsay Opie (US) stated, “It has been suggested by several observers that the islands of Langerhans may furnish an internal secretion to the blood…. Where diabetes is the result of pancreatic disease, do the islands exhibit lesions? I have examined microscopically the pancreas from eleven cases of diabetes, and in four instances such marked change was found [in the islands] that one could not doubt the relationship of the general disease to the lesion of the organ”(3047).

Alfred Fröhlich (AT) is remembered for his classic description of dystrophia adiposogenitalis or Fröhlich syndrome(3048).

Leo Loeb (US) described the transplantation of tumors(3049).

Mathieu Jaboulay (FR), in 1901, performed the first vagotomy on a human(3050, 3051).

André Latarjet (FR) and Pierre Wertheimer (FR) were the first to perform a local vagotomy for therapeutic reasons in the region of the stomach in man. The surgery was to treat an active peptic ulcer. They suggested, based on these studies, that the vagal nerves play a significant role in developing peptic ulcer(3052).

Lester Reynold Dragstedt (US) and Frederick W. Owens, Jr. (US) recommended vagotomy with pyloroplasty, for treatment of duodenal ulcer. This soon became the standard treatment(3053).

Max Wilms (DE) was the first to carry out full excision of burnt tissue, and sometimes grafted excised areas(3054).

Franz Kuhn (DE) introduced orotracheal intubation(3055).

Samuel James Meltzer (DE-US) and John Auer (US) perfected a method of intra-tracheal intubation to give “continuous respiration without respiratory movement”(3056-3058). The clinical introduction of Kuhn’s, and Meltzer and Auer's methods mark the beginning of modern endotracheal anesthesia.

James H. Sequeira (GB) saw in epithelial cells of a cancer treated by irradiation a “lysis” of both nucleus and protoplasm and a fatty degeneration(3059-3061).

Georg Clemens von Perthes (DE) was the originator of deep Röntgen-therapy and a prime mover of the treatment of cancer by irradiation(3062).

The Rockefeller Institute for Medical Research was founded with Simon Flexner (US) as its first director(1459).

Smallpox had its last major outbreak in the urban Northeast U.S., beginning in New York and spreading through other major cities(176).

Sir Grafton Elliott Smith (AU-GB), in 1901, discovered the oldest urological object on record, a bladder calculus, in a prehistoric Egyptian tomb, in the pelvis of a mummy. The calculus has a uric acid nucleus with concentric laminations of calcium oxalate and ammonium magnesium phosphate(3063).

The Journal of Hygiene was founded.

Biometrika was founded.

1902

"The sciences are not a series of abstract concepts, but rather the results of human endeavour; in their development, they are closely associated with the individual characters and fates of those who dedicate themselves to it." Hermann Emil Fischer.

"The type of condensation described here through formation of —CO—NH—CH= groups may thus explain both the building up of protein substances in the organism, as well as their breakdown in the intestinal tract and in the tissues. On the basis of these given facts one may therefore consider the proteins as for the most part arising by condensation of alpha-amino acids, whereby the linkage through the group —CO—NH—CH= has to be regarded as the regularly recurring one." Franz Hofmeister(3064).

Hermann Emil Fischer (DE) was awarded the Nobel Prize in Chemistry for his discoveries related to sugars and purine syntheses.

Sir Ronald Ross (GB) was the recipient of the Nobel Prize in Physiology or Medicine "for his work on malaria, by which he had shown how it enters the organism and thereby laid the foundation for successful research on this disease and methods of combating it."

Sir Ernest Rutherford (NZ-GB) and Frederick Soddy (GB) proposed that radioactive elements are transformed into each other by a process of exponential radioactive decay with the emission of material particles(3065, 3066).

Sir Ernest Rutherford (NZ-GB) was, along with Pierre Currie (FR) and Marie Skodowska Curie (PL-FR), the first to decide that rays given off by radioactive material were of several different kinds. Rutherford named the positively-charged ones alpha rays and the negatively-charged ones beta rays. He was able to demonstrate that the radiations discovered in 1900, and found not to be sensitive to a magnetic field, consisted of electromagnetic waves. He named these gamma rays(3067).

Sir William Thomson (Lord Kelvin) (GB) introduced the concept of the electron(3068).

Richard Adolf Zsigmondy (AT-DE) and Heinrich Friedrich Wilhelm Siedentopf (DE) developed the slit ultramicroscope, a dark field microscope which can detect particles with diameters below the wavelength of visible light. This was possible because of the Tyndall effect(3069, 3070).

Eugen Baumann (DE) discovered cysteine as a product of the reduction of cystine(3071).

Carl Alexander Neuberg (DE-US) discovered cysteine(3072). 

The United States Congress authorized the extermination and removal of water hyacinths by any mechanical, chemical, or other means. Various materials were tested including muriatic acid, sulfuric acid, carbolic acid, kerosene, steam, sodium arsenite, mercury bichloride, whale oil soap, formaldehyde, copper sulfate, potassium bichromate, and many others. Although there were no laws to regulate the use of pesticides, it was quickly learned that most of the chemicals which were effective against water hyacinth were also toxic to cattle and humans.

During 1944 to 1946, evaluations of a newly discovered herbicide, 2,4-D, as a control agent for water hyacinth were initiated by the U. S. Department of Agriculture, Jacksonville District Corps of Engineers, and the Everglades Experiment Station of the University of Florida. The herbicide 2,4-D proved extremely effective and economical, and above all was not toxic to fish, cattle, or humans.

Warren Thompson Clarke (US) perfected the lime-sulfur spray for the control of the peach twig-borer(3073).

Hermann Emil Fischer (DE) isolated the amino acid hydroxyproline from gelatin hydrolysate(3074). He called it oxyproline.

Hermann Emil Fischer (DE) and Franz Hofmeister (CZ-DE) independently described the peptide bond by which amino acids join to form polypeptides(3064, 3075). Fischer outlined a procedure for recovery of the amino acids following hydrolysis. The phrase, peptide bond, coined by Fischer, is derived from pepsin which is derived from the Greek root pepsis meaning cooked/digestion.

Max Rubner (DE) published what is called the isodynamic law of Rubner. It states that 100 calories in fat are the nutritive equivalent of the same number in carbohydrate. He further compared the caloric content of foods of different classes when given to an animal in moderate quantities. He found that the caloric content of 100 grams of fat is equivalent to 211 grams of protein, or 232 grams of starch, or 234 grams of cane sugar, or 256 grams of glucose. He found that when a dog was fed 100 calories in the form of meat his caloric output increased by 30 calories over that of a dog at rest and without food. When 100 calories were given as cane sugar the increase in caloric output was only 5.8 calories and when 100 calories as fat were given the increase was 4 calories. Any increase in the ingestion of protein led to a commensurate increase in caloric output by the dog. Rubner named this phenomenon specific dynamic action(1474).

Adolf Magnus-Levy (DE) was one of the first to suggest that acetylaldehyde is an intermediate product in various fermentations of sugar(3076). 

Adrian J. Brown (GB) and Victor Henri (FR) separately discovered that the rate of hydrolysis of cane sugar by saccharase was independent of the sugar concentration over a wide range, although it depended on the enzyme concentration. Brown for the first time deduced the formation of the enzyme-substrate complex from careful rate measurements that indicated the initial rate of cane-sugar hydrolysis, except for very dilute solutions, to be independent of the concentration of the cane sugar used. He concluded that mass action is concealed in the case of this substrate-independent rate by a time course factor associated with molecular combination. Henri derived a hyperbolic rate equation for a single-substrate enzymatic reaction and showed that his rate equation predicted the catalytic rate to be proportional to the substrate concentration at low, and independent of it at high substrate concentrations(3077-3079).

Leonor Michaelis (DE-US) and Maud Leonora Menten (CA) would later revive and extend this as the Henri-Michaelis-Menten theory. See Michaelis and Menten, 1913.

Charles Ernest Overton (GB) found that extracellular sodium ions are required for nerve excitability, and suggested that a sodium-potassium exchange is involved in signal conductance(3080). 

Ernest Henry Starling (GB) and Rudolf Magnus (NL) reported that pituitary extracts cause expansion of the kidney and a marked and often prolonged diuresis. This was the first indication that the hypophysis plays a part in the regulation of urine secretion(3081).

Gottlieb Friedrich Johann Haberlandt (AT) expressed the concept of the vegetable cellular totipotency and was probably the first to grow plant cells in tissue culture. He succeeded in getting a small cellular mass to survive in vitro some months, but without reproduction(3082).

"There has been, so far as I know, up to present, no planned attempt to cultivate the vegetative cells of higher plants in suitable nutrients. Yet the results of such attempts should cast many interesting sidelights on the peculiarities and capacities which the cell, as an elementary organism, possesses: they should make possible conclusions as to the interrelations and reciprocal influences to which the cell is subjected within the multicellular organism. Without permitting myself to pose further questions, I believe, in conclusion, that I am not making to bold a prediction if I point to the possibility that, in this way, one could successfully cultivate artificial embryos from vegetative cells"(3082).

Hans Lohmann (DE) discovered nanoplankton while studying tunicate stomachs(3083).

Robert Chodat (CH)  discovered the cause of the vine disease known as court noué and showed that it is caused by an acarid (mite); from then on it was called acariasis(3084).

Fred Neufeld (DE) described the Quellung phenomenon which consists of apparent capsular swelling when pneumococci are mixed with undiluted antiserum to the capsular polysaccharide(3085).

Fred Neufeld (DE) and Georg Willi Rimpau (DE) reported that the blood of animals immunized with pneumococci contained substances that greatly accelerated phagocytosis of the immunizing strain(3086).

Fred Neufeld (DE) and R. Etinger-Tulczynska (IL) applied the Quellung reaction to practical diagnosis(3087). 

Karl Wilhelm von Drigalski (DE) and Heinrich Conradi (DE) found that some bacteria such as Salmonella typhosa exhibit resistance to certain aniline dyes. They recommended the use of crystal violet for the isolation of organisms from feces and other contaminated material(3088).

José Lignières (AR) and Georges Spitz (AR) isolated a non-motile, non-branching, non-acid-fast gram-negative bacillus from the lesions of a disease of cattle resembling actinomycosis, with which it is frequently confused. The causative organism was named Actinobacillus lignieresii and the disease actinobacillosis(3089).

Paul Ravaut (FR) and Pierre-Ernest Pinoy (FR) reported the first incidence of actinobacillosis in man(3090).

Richard May (DE) and Ludwig Grünwald (DE) developed a stain for peripheral blood film and bone marrow(3091). Now popularly called the May-Grünwald stain.

Gustav Giemsa (DE) and James Homer Wright (US) introduced their respective stains formulated to demonstrate human blood elements and the malarial parasite(3092-3094).

Andre Huot (FR) discovered that some fish (lophobranchs) have aglomerular kidneys, proving that renal tubules can secrete and resorb substances(3095). 

Sir William Maddock Bayliss (GB) reported on the local reactions of the arterial wall to changes of internal pressure(3096).

Sir William Maddock Bayliss (GB) and Ernest Henry Starling (GB) discovered that the lining of the upper small-intestine, upon exposure to acidic food, stimulates the flow of bile from the gall bladder and the release of digestive enzymes and bicarbonate from the pancreas even when all the nerves between the small intestine and the pancreas are severed. They promptly made a crude extract from a piece of duodenum, injected it into the jugular vein of the dog, and within a few moments had the pleasure of seeing the pancreas respond with a heavy secretion. They postulated the existence of secretin, a blood-borne messenger, or hormone, that is released into the circulation by the lining of the duodenum(3097, 3098).

William Bate Hardy (GB) is credited with coining the word hormone (Gk. hormao, to excite or arouse to action) while visiting in the laboratory of Bayliss and Starling(3099).

Otto Loewi (DE-US) demonstrated that protein digested outside the body to the point that it would not give a positive biuret test could be fed to an animal and substitute for all of its food protein. This suggested that dietary proteins are cleaved to amino acids in the gastrointestinal tract, taken into the blood, and later oxidized or used to synthesize new proteins(3100).

Theodor Boveri (DE) proved the hypothesis that the physical basis of inheritance resides in the chromosomes by creating sea urchin embryos with abnormal chromosome sets. He also determined that every cell in the sea urchin embryo must have the normal set of 36 chromosomes if development is to be normal. In the 1902 article he gave his views on the importance of interaction between nucleus and cytoplasm as, “It appears to me that the quite peculiar interaction of the cytoplasm with its simple structure and differential division and the nucleus with its complex structure and manifold total multiplication may still achieve what Weismann and Roux attempted to explain with the help of differential nuclear division. When the primitive differences of the cytoplasm, as expressed in the existence of layers, are transferred to the cleaved egg without any change in the relationships of the layers, they affect the originally equal nuclei unequally by unfolding (activating) or suppressing certain nuclear qualities, as may be visualized directly in the cleavage of Ascaris. The inequalities of the nuclei, in some cases perhaps of temporary nature only, lend different potencies to the cytoplasm, that to begin with was differentiated only by degrees. Thus new cytoplasmic conditions are created which again release in certain nuclei the activation or suppression of certain qualities thus imprinting on these cells in turn a specific character and so on, and so on. In short: a continually increasing specification of the originally totipotent complex nuclear structure, and consequently, indirectly, of the cytoplasm of the individual cells, appears conceivable on the basis of physico-chemical events once the machine has been set in motion by the simple cytoplasmic differentiation of the egg. In this same article he speculated that multipolar mitosis might cause tumors and that mitotic aberrations might be caused by physical and chemical agents.” The 1904a paper states that chromatin is the substance that transforms into chromosomes during mitosis(892, 894, 3101, 3102).

William Bateson (GB) showed the validity of Johann Gregor Mendel’s (Moravian-CZ) principle of segregation in animals (poultry)(3103, 3104).

Archibald Edward Garrod (GB) provided the first evidence of the applicability of Mendelian genetics to man and perceived the relationship of hereditary factors to enzymes. He noted that several human hereditary traits (alkaptonuria, albinism, pentosuria, and cystinuria) were metabolic diseases characterized by failure of known chemical reactions to take place and hypothesized that such metabolic diseases, which he called inborn errors of metabolism, were due to the absence of specific enzymes that were synthesized under the direction of the wild-type genes. “Inborn errors of metabolism are due to the failure of a step in the metabolic sequence due to loss or malfunction of an enzyme.” Garrod’s deduction is one of the most outstanding in the history of biology—he discovered the function of genes(3105-3108). Garrod consulted Bateson, who in 1902 suggested that for alkaptonuria the available data could be understood if one assumed that alkaptonuria is caused by a recessive gene. This was the first Mendelian recessive discovered in man.

William Bateson (GB) and Edith Rebecca Saunders (GB) provided us with some of the basic terminology for Mendelian genetics: unit characters which exist in antagonistic pairs they called allelomorphs (later shortened to alleles), the zygote formed by the union of a pair of opposite allelomorphic gametes they called heterozygote, and the zygote formed by the union of a pair of gametes having similar allelomorphs they called homozygote. They introduced the use of F1, F2, and so on to designate filial generations(3103, 3109).

William Bateson (GB) introduced the term epistasis (the masking effect of one mutant gene pair over another mutant gene pair) into genetics(3110).

Lucien Claude Jules Cuénot (FR), William Ernest Castle (US) and Clarence Cook Little (US) showed that coat color in mice follows Mendelian segregation and behaves as though it has at least three alleles (multi-allelic)(3111-3118). These experiments along with Bateson’s on poultry represent the first extension of Mendel’s laws to animals. See Bateson, 1901. 

Carl Franz Joseph Erich Correns (DE), discovered the first exception to the random union of gametes assumed by Mendel. It was explained as the effects of a gene on the functioning of pollen grains in maize(3119).

Paul Portier (FR), Charles Robert Richet (FR), and Georges Richard (FR) discovered the remarkable fact that certain poisons of animal origin evoke a condition of hypersusceptibility instead of immunity, and that as a result of this hypersusceptibility death may ensue from a dose of the poison which is otherwise ineffective. By maceration of the tentacles of certain sea anemones (Actinia eqnina, Anemone sulcata) they obtained a poisonous fluid which, injected intravenously into dogs in a dose of 0.2 gm. per kilo, produced hypothermia, diarrhea, and death in two or three days. Doses smaller than 0.2 gm. produced only transient symptoms. If, however, several weeks after the injection of such a dose a second sub-lethal dose was administered, violent symptoms of poisoning set in and were sometimes followed by death of the animal in an hour but mostly in 12 to 24 hours. Richet coined the word anaphylaxis (Greek, removal of protection) to describe this reaction. It was intended to convey the idea of the opposite of prophylaxis (Greek, favoring protection)(3120-3123).

Milton Joseph Rosenau (US) and John F. Anderson (US) noted that animals receiving an injection of a foreign protein became sensitive to a second dose of the same protein(3124).

James MacKenzie (GB) began a systematic study of cardiac patients in 1883, devised a polygraph to study irregularities of the pulse, and wrote, The Study of the Pulse, followed by Diseases of the Heart. He classified irregularities of the pulse as the youthful type (sinus irregularity), the adult type (extra-systole), and the dangerous type (auricullar fibrillation)(3125, 3126).

J. Strasburger (DE) estimated the daily output of fecal microorganisms by humans to be eight grams(3127).

George Frederic Still (GB), England’s first professor of childhood medicine, described attention-deficit disorder (ADD)(3128).

Charles E. Gray (ZW) and William Robertson (ZW) recorded East Coast Fever in Africa(3129). East Coast fever (ECF) is the most important tick-borne disease in Eastern, Central and Southern Africa.

Sir Arnold Theiler (CH-ZA) proved that East African Coast Fever is caused by Piroplasma parva (Theileria parva)(3130).

Richard Gonder (ZA) identified the apicomplexan parasite Theileria parva as the cause of East Coast fever in South Africa(3131).

Emil von Dungern (DE) was the first to give evidence for local antibody production in the antigenically stimulated eye(3132).

Max Bielschowsky (DE) developed several stains which are still commonly used in diagnosing Alzheimer’s disease(3133, 3134).

Harvey Williams Cushing (US), Karl Hugo Kronecker (CH), and Emil Theodor Kocher (CH) demonstrated that as the spinal fluid pressure of a dog is increased, there is initially a vagal effect with bradycardia followed by a high rise in arterial blood pressure(3135, 3136).

John William Ballantyne (GB) wrote Manual of Antenatal Pathology and Hygiene, the most complete history of teratology in English(3137).

Gregorij Ivanovitsch Rossolimo (RU) described percussion of the plantar surface of the 2nd to 5th toes causing a flexion which is exaggerated greatly in pyramidal tract lesions(3138).

Sir William Richard Gowers (GB) was the first to describe a muscular disorder later called distal myopathy of Gowers(3139).

Alexis Carrel (FR-US) and Charles Claude Guthrie (US) using fine silk suture and meticulous technique successfully created a variety of vascular anastomoses and reconstructions, including the first-ever vein grafts, termed “biterminal venous transplantation.” Their perfected triangulation technique whereby blood vessels could be delicately sutured; that is, sewn together end to end with as few as three stitches enabled them to transplant limbs and organs, including the kidney, thyroid, adrenal, ovary, spleen, intestine, pancreas, and heart from one animal to another(3140-3146). Note: Themistocles Gluck (DE), in the 1880s, carried out not only the suture of vessels, but also venous grafts, long before the work of Alexis Carrel.

Hugh Hampton Young (US) devised and performed the first perineal prostatectomy, in 1902(3147). He performed the first radical perineal prostatectomy for cancer of the prostate in 1904, with assistance from his chief, William Stewart Halsted(3148, 3149). Through this technique, obstruction to the outlet of the urinary bladder caused by cancer of the prostate gland is relieved without interfering with the normal function of the bladder. Young invented numerous operating instruments such as the Young punch, an instrument used to excise the prostate(3150).

Jean Nageotte (FR) worked with tabes, and made special studies of the radial nerves in tabetus. Together with Joseph Jules Francoise Felix Babinski (PL-FR) he described the Babinski-Nageotte syndrome(3151) and wrote a book on cerebrospinal fluid. He made intensive study on nerve fibers, anatomic and degenerative in nature. He did considerable clinical and chemical research on the myelin sheath. He also did considerable work on connective tissue.

Harris Hawthorne Wilder (US) pioneered comprehensive studies of the methodology, inheritance, and racial variation of palmer and planter papillary ridge patterns as well as fingerprints. These represented the first serious study of palmer and plantar dermatoglyphics(3152, 3153).

Petr Alekseevich Kropotkin (RU) published Mutual Aid a Factor of Evolution, an important landmark in the future trend of population studies (leading to the widely spread anthropomorphic concept of "altruism")(3154).

1903

"The supreme qualities of all science are honesty, reliability, and sober, healthy criticism." Niels Ryberg Finsen(3155).

Antoine Henri Becquerel (FR) in recognition of the extraordinary services he had rendered by his discovery of spontaneous radioactivity and Pierre Curie (FR) and Marie Sklodowska Curie (PL-FR) in recognition of the extraordinary services they have rendered by their joint researches on the radiation phenomena discovered by Professor Henri Becquerel were awarded the Nobel Prize in Physics.

Svante August Arrhenius (SE) was awarded the Nobel Prize in Chemistry for his doctoral dissertation work in which he hypothesized ionic dissociation.

Niels Ryberg Finsen (DK) was awarded the Nobel Prize in Physiology or Medicine "in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science."

Carl Alexander Neuberg (DE-US) introduced the term biochemistry. Ref 1903

Carl Alexander Neuberg (DE-US) introduced the term phosphorylation in 1910. ref

Thomas Purdie (GB) and Sir James Colquhoun Irvine (GB) introduced an important methodology for the analysis of carbohydrate structure. Free hydroxyl groups were methylated followed by acid hydrolysis. The nature of the resulting monosaccharides could then be determined(3156).

Henry Lord Wheeler (US) and Treat Baldwin Johnson (US) synthesized cytosine(3157).

Felix Ehrlich (DE) isolated the amino acid isoleucine from nitrogenous substances in beet-sugar molasses(3158). 

Hermann Emil Fischer (DE) and Joseph von Mering (DE) were the first to synthesize a therapeutically active "barbiturate" by substituting two ethyl groups for two hydrogens attached to carbon in barbituric acid, the result was diethyl barbituric acid or diethylmalonylurea. It is frequently called (barbital or veronal). When they administered this new barbiturate to human subjects, the compound was found to induce sleep(3159, 3160). The term for a drug that causes sleep induction is a somnolent or a hypnotic.

Johann Friedrich Wilhelm Adolf von Baeyer (DE), in 1864, had synthesized barbiturhaltige säure (malonylurea) from a reaction of urea with malonic acid, a chemical found in apples. Malonylurea became known as barbituric acid, parent compound of well-known sleeping pills of today (3161). Later it was he who synthesized the dye indigo. 

In 1911-1912, two independent teams of German chemists synthesized what became known as Luminal, or phenobarbital with excellent hypnotic action and anticonvulsant activity. Ref

Alfred Hauptmann (DE) reported on the use of Luminal as a treatment for epilepsy(3162).

Manipulations of the side chain at position 5 have resulted in amobarbital (Amytal ) in 1923, pentobarbital (Nembutal ) in1930, and secobarbital (Seconal ) in 1930. These drugs have become widely known as drugs of abuse. Changes in position 2 have resulted in the short-acting barbiturates: hexobarbital (Evipal ), thiopental (Pentothal ) and methohexital (Brevital). Valium and Halcion are also barbiturates. Refs

James Carroll (GB-CA-US), on the suggestion of his mentor William Henry Welch (US), embarked on research which demonstrated that the agent of yellow fever passed through a Berkefeld infusorial bacteriological filter. This went a long way toward proving that the causative agent was a virus(3163).

Samuel Rideal (GB) and J.T. Ainslie Walker (GB) developed the original method for determining the phenol coefficient(Rideal and Walker 1903).

The Hygienic Laboratory Method (1921) is a modification of the Rideal-Walker Method(1921).

The Food and Drug Administration test (1931) is a combination of the best features of both of the above(1931).

Theobald Smith (US), in 1903, noted that guinea pigs used for the purpose of diphtheria anti-toxin testings frequently succumbed rapidly to a second injection of diphtheria, i.e., anaphylaxis. This phenomenon was not reported by Smith but communicated by him to Paul Ehrlich(3164).

Nicolas Maurice Arthus (FR) described a type of allergic reaction brought on by repeated injection of horse serum into rabbits. The reaction was characterized by a localized, acute necrotizing vasculitis. Later it became known as the Arthus reaction(3165).

Charles G. Cochrane (US), William O. Weigle (US), and Frank James Dixon (US) showed that this reaction is caused by the formation of relatively large amounts of antigen-antibody precipitates in the vessel walls. They found that polymorphonuclear leucocytes (PMNs) phagocytize and rapidly degrade antigen-antibody complexes but are themselves largely responsible for the inflammation and necrosis(3166).

Carl Oluf Jensen (DK) was the first to do experiments in transplantation immunity. He found that tumors which arose spontaneously in mice could sometimes be propagated by grafting them from one mouse to another. He passed one tumor through nineteen generations of grafting. Jensen recognized that mice of different races were not all equally susceptible to the growth of the tumors and spoke of an active immunity. This report discredited the theory of the infectivity of cancer(3167).

Georg Schöne (DE) coined the phrase transplantation immunity to distinguish it from reactions resulting from injections of foreign materials(3168, 3169).

Nicholas Senn (CH-US) was the first to use roentgen rays to treat leukaemia(3170).

Theobald Smith (US) and Arthur L. Reagh (US) noted that there are two types of antigens present in the Salmonella group, one associated with the cell substance and the other with the flagella(3171).

Edmund Weil (AT) and Arthur Felix (PL-GB) would designate these as the O and H antigens respectively(3172, 3173).

Louis Lapicque (FR) introduced a number of terms to describe excitability of nerve and muscle. Rheobase (lowest point of current) was defined as, “the intensity of a constant current of abrupt onset and prolonged duration which gives the threshold of excitability.” Chronaxie (value of time) was defined as, “the duration of constant current of abrupt onset which attains the threshold of stimulation with an intensity equal to double that of the rheobase, i.e., with a voltage of double that of the rheobase”(3174). This work was begun in 1903.

Ross Granville Harrison (US) discovered the mode of embryonic origin of the lateral line sense organs of aquatic vertebrates. He demonstrated that the growth cones of sensory neurites accompany the primordium, thereby, establishing a physical link between the cranial ganglion and the body neuromasts(3175).

Sir Almroth Edward Wright (GB) and Stewart R. Douglas (GB) showed that substances exist in immune serum which by their action render the microbe more susceptible to phagocytosis. They called these substances opsonins (Greek, I prepare)(3176, 3177). Today we know that opsonins are antibodies.

Dmitrii Iosifovich Ivanowski; Dmitrii Iosifovich Iwanowsky; Dmitrii Iosifovich Ivanovski (RU) described inclusion bodies caused by tobacco mosaic virus in tobacco plants(3178).

Adelchi Negri (IT) described the characteristic inclusion bodies found in the brain cells of animals infected with rabies. They are found most frequently in the pyramidal cells of Ammon's horn, and the Purkinje cells of the cerebellum(3179-3182).

Amédée Borrel (FR) proposed the virus theory of cancer(3183). 

Vilhelm Ellermann (DK) and Oluf Bang (DK) showed that leukemia in chickens can be transmitted by injecting bacteria-free filtrates from infected chickens into healthy chickens. This implied a viral origin of the leukaemia, i.e., oncogenic viruses(3184-3186).

Hugo Schottmüller (DE) was the first to use blood agar for determining hemolytic properties of bacteria. He proposed that different varieties of streptococci be classified based on their capacities to hemolyze erythrocytes(3187).

W.K. Stefansky (RU) and George A. Dean (GB) discovered Mycobacterium lepraemurium the etiological agent of rat leprosy(3188, 3189).

John Fleetezelle Anderson (US) described Rocky Mountain spotted fever as a new disease and suggested the wood tick as a possible carrier(3190).

Howard Taylor Ricketts (US) demonstrated tick transmission of Rocky Mountain spotted fever to guinea pigs. He found that the etiologic agent was present in blood from infected humans, and demonstrated that it could be removed via filtration(3191, 3192).

Howard Taylor Ricketts (US) demonstrated that a bipolar-staining bacillus of minute size and transmitted by the bite of the wood-tick (Dermacentor occidentalis) is the causative agent of Rocky Mountain spotted fever(3193). This bacterium would later be called Rickettsia rickettsia in his honor and Simeon Burt Wolbach (US) would offer final proof that Rickettsia rickettsia is the etiological agent(3194).

Frederick George Novy (US) and Ward J. McNeal (US) took blood from rats and succeeded in cultivating the trypanosome of rats, Trypanosoma lewisi, on blood agar(3195).

William Ernest Castle (US) wrote the first paper on Mendelism in America(3196).

William Ernest Castle (US) recognized the relationship between allele and genotype frequencies for the first time(3197).

Felix Mendel (DE) described his method for intracutaneous testing for tuberculin sensitivity. Within 24 to 72 hours the injected area becomes hard (indurated) and red in a person who is infected with tuberculosis or has been immunized with BCG vaccine(3198, 3199).

Clemens Peter Pirquet von Cesenatico; Clemens Peter Freiherr von Pirquet (AT) used tuberculin in a diagnostic skin scratch test and Charles Montoux (FR) used it to perform an intradermal test(3200-3203).

Charles Mantoux (FR) popularized Mendel’s test, thus the Mendel-Mantoux tuberculin test(3200).

Nicholas Senn (US) was the first to use roentgen rays to treat leukaemia(3204).

Alfred Walter Campbell (AU-GB) successfully studied the cytoarchitecture of the anthropoid cerebral cortex with the aim of establishing a correlation between physiologic function and histologic structure(3205).

Wilhelm Ludwig Johannsen (DK) demonstrated in plants that natural selection can only influence evolutionary change if there is a source containing multiple genotypes. Therefore, genetically pure lines (homozygous) would not lend themselves to natural selection. He introduced and defined the concepts of phenotype, genotype, and selection(3206-3208).

Richard Woltereck (DE) would confirm this restriction on natural selection as it applys to animals using parthenogenic freshwater crustaceans of the genus Daphnia(3209).

Ludwig Edinger (DE), Adolf Wallenberg (DE), Sir Gordon Morgan Holmes (GB), Sir Grafton Elliot-Smith (AU-GB), John B. Johnston (US), Cornelius Ubbo Ariëns-Kappers (NL), Gotthelf Carl Huber (US), and Elizabeth Caroline Crosby (US) established the anatomy of the avian brain. They suggested that the major subdivisions of the avian telencephalon correspond to different components of the mammalian basal ganglia with the avian spinal cord, midbrain, and thalamus being homologous to those of mammals, but that nearly all of the avian telencephalon corresponds to mammalian basal ganglia(2704, 2861, 2862, 3210-3212). 

Pietro Grocco (IT) and Karl Andreyevich Rauchfuss (RU) described the triangular area of dullness (Grocco’s triangle or Grocco-Rauchfuss triangle) on the patient’s back, on the side opposite to that on which a pleural effusion had occurred. Most commonly seen in children and adolescents(3213, 3214).

Adam Rydel (PL-DE) and Friedrich Wilhelm Seiffer (DE) found that vibratory sense and proprioceptive sense are closely related and that both senses are carried in the posterior columns of the spinal cord(3215).

Pierre Marie Félix Janet (FR) and Fulgence Raymond (FR) described psychasthenia for the first time (a neurosis marked by stages of pathologic fear or anxiety, obsessions, fixed ideas, tics, feelings of inadequacy, and self-accusation), i.e., obsessive compulsive disorder. Here bulimia is described in medical terms for the first time(3216).

Alfred Wolff-Eisner (DE) trephined the tibia and femur of experimental animals and suggested biopsy of bone marrow as a clinical procedure(3217).

Oscar Thorvald Bloch (DE) and Jan Mikulicz-Radecki; Johannes Freiherr von Mikulicz-Radecki (PL-AT) developed a two-stage operation for resection of tumors of the rectum. This operation is known as Bloch-Mikulicz operation(3218).

Maximilian Carl-Friedrich Nitze (DE) became one of the first to originate the idea of examining the anterior wall of the bladder and the bladder neck in 1903, a feat accomplished using his invention of the new retrograde view cystoscopes. Nitze’s last invention was in 1905: a ureteral occlusion balloon catheter with accompanying occlusive ureterocystoscope. refs

Otto Ringleb (DE) improved the cystoscope with his “orienting cystoscope,” a breakthrough in 1908(3219, 3220). Suprapubic prostatectomy had a mortality rate of 50% prior to the introduction of Ringleb’s new method, after which the rate went down to 10%.

Edwin Beer (US) devised a new method for surgical treatment of bladder tumors employing high frequency (Oudin) currents through a catheterizing cystoscope(3221).

Leo Buerger (US) constructed a universal urethroscope with two optical systems, direct or indirect viewing, and use for catheterizing and operating respectively. It was both a cystoscope and urethroscope(3222).

Maximilian Stern (DE-US), with Reinhold Wappler’s assistance, created the first instrument that used an electric loop to cut prostatic tissue(3223).

Ivan Petrovich Pavlov; Ivan Petrovic Pavlov (RU) reported in 1901 how he used salivary gland fistulas in dogs to demonstrate two types of reflexes—one inherited, the other developed from specific or psychic stimuli by training and association. The discovery of the second type, the conditioned reflex had a dramatic effect on the fields of physiology and psychology(3224-3227).

Ivan Mikhailovich Sechenov (RU) wrote Reflexes of the Brain, which Pavlov acknowledged as the single most important theoretical inspiration for his work on conditioning(436-438, 3228).

Ivan Petrovich Pavlov; Ivan Petrovic Pavlov (RU) and Vladimir Mikhailovich Bekhterev; Vladimir Mikhailovich Bechterev (RU) independently developed a theory of conditioned reflexes which describe automatic responses to the environment. What was called association reflex by Bekhterev is called the conditioned reflex by Pavlov, although the two theories are essentially the same. Because John Watson first discovered the salivation research completed by Pavlov, this research was incorporated into Watson’s famous theory of behaviorism, making Pavlov a house-hold name. While Watson used Pavlov’s research to support his behaviorist claims, closer inspection shows that in fact, Watson’s teachings are better supported by Bekhterev’s research(3229).

Sir William Osler (CA) was the first to recognize as a definite clinical entity, new to medicine, the disorder that today is known as polycythemia vera(3230).

August Karl Gustav Bier (DE) introduced artificial active and passive hyperemia as an adjuvant to surgical therapy(3231).

Die Neue Generation was founded.

1904

Ivan Petrovich Pavlov; Ivan Petrovic Pavlov (RU) received the Nobel Prize in Physiology or Medicine "in recognition of his work on the physiology of digestion, through which knowledge on vital aspects of the subject has been transformed and enlarged."

Thomas Chrowder Chamberlin (US) and Forest Ray Moulton (US) developed the planetesimal hypothesis for the origin of the Earth and other planetary bodies, i.e., the planets formed from the coalescing of rocky fragments ranging in size from boulders to asteroids called planetesimals(91, 3232).

Hantaro Nagaoka (JP), in 1904, proposed an atomic model with electrons rotating in rings about a central nucleus. “The system, which I am going to discuss, consists of a large number of particles of equal mass arranged in a circle at equal angular intervals and repelling each other with forces inversely, proportional to the square of distance. At the center of the circle, place a particle of large mass attracting the other particles according to the same law of force. If these repelling particles be revolving with nearly the same velocity about the attracting center, the system will generally remain stable, for small disturbances provided the attracting force be sufficiently great”(3233).

Sir Ernest Rutherford (New Zealand-GB) proposed the theory of the nuclear atom. He maintained that the atom contains a very tiny nucleus at its center which is positively charged and which contains all the protons of the atom and therefore virtually all of its mass. In the outer reaches of the atom are the negatively-charged electrons which are very light and which interpose no detectable barrier to the passage of alpha particles. This theory was deduced from experiments where gold foil was bombarded with alpha particles and their behavior observed(3234).

August Karl Johann Valentin Köhler (DE) and Moritz von Rohr (PL-DE) developed quartz monochromatic microscope objectives (quartz-fluorite) for working in the ultraviolet at 275 and 280 nm and designed the first ultraviolet microscope(3235, 3236). They found that cell nuclei absorb ultraviolet light strongly.

Friedrich Stolz (DE) and Henry Drysdale Dakin (US) determined the chemical formula for both epinephrine (adrenaline) and norepinephrine (noradrenaline) and achieved a total chemical synthesis of both substances(3237, 3238).

Albert Einhorn (DE) synthesized and patented procaine hydrochloride (Novocaine) in 1904. Heinrich Braun (DE) was the first to report its existence as Novocaine(3239). It supplanted cocaine as the local anesthetic of choice. Procaine is made artificially by combining two B vitamins—PABA (para amino benzoic acid) and DEAE (diethyl amino ethanol).

Richard Anton Burian (CS) discovered xanthine oxidase which catalyzes the conversion of xanthine to uric acid and hypoxanthine to xanthine(3240).

Potassium cyanide powder was advocated for the control of ants(138). 

Cornelis A. Pekelharing (NL) found that very minute quantities of a substance in the whey of milk are as capable as whole milk of promoting health in mice receiving adequate protein from some other source(3241, 3242).

Valdemar Henriques (NL) and C. Hansen (NL) demonstrated that autolyzed (self-digested) pancreas or mucosa not only supplied rats with amino acids for their protein synthesis but also supplied them with something of necessity in their diet other than amino acids, carbohydrates, fats, and salts(3243).

Marshall A. Barber (US) invented the technique for making glass capillary micropipettes and manipulating them in the field of a compound microscope(3244, 3245). He developed this method initially to clone bacteria and to confirm the germ theory of Koch and Pasteur. Later on, he refined his approach and was able to manipulate nuclei in protozoa and to implant bacteria into plant cells. Continuous improvement and adaptation of this method to new applications dramatically changed experimental embryology and cytology and led to the formation of several new scientific disciplines including animal cloning as one of its latest applications.

Joseph Everett Dutton (GB) and John Lancelot Todd (CA) working in the Congo and independently Philip Hedorland Ross (GB) and Arthur Dawson Milne (GB) working in Uganda discovered that human tick disease is caused by a spirochete (Borrelia duttonii) transmitted by the African soft-shelled or argasid tick, Orhithodoros moubata(3246-3249).

Heinrich Hermann Robert Koch (DE), in 1904, confirmed the role of Orhithodoros moubata and was the first to demonstrate that spirochetes are transmitted via eggs (transovarial transmission) to the progeny of the infected female ticks(3250, 3251).

Thomas Renton Elliott (GB) was the first to express the idea of chemical neurotransmission, but he did not support it experimentally. “Adrenalin (epinephrine) might then be the chemical stimulant liberated on each occasion when the impulse arrives at the periphery”(1018, 3252).This was one of the earliest statements of the neurotransmitter hypothesis. More years later von Euler showed that noradrenaline is the principal neurotransmitter in the post-ganglionic sympathetic nerves. See, von Euler 1933a, 1946, and 1948.

Henry Edward Crampton (US), a graduate student in Edmund Beecher Wilson’s laboratory, performed an experiment which suggested that there is an association between a region of egg cytoplasm and a particular type of development. He removed the polar lobe from cleaving eggs of the mollusk Dentalium and found that larvae showed a deficiency for the post-trochal and other regions. This effect was not seen when other regions of equivalent size were removed(1068, 3253).

Thomas Hunt Morgan (US) was the first to formulate the concept of cytoplasmic determination(3254).

Karl Illmensee (US) and Anthony P. Mahowald (US) clearly established this relationship when they were able to transform animal pole cells of a Drosophila embryo into gametes by transferring polar cytoplasm from the posterior to the anterior end of an egg(3255). 

Lorenz Hiltner (DE) introduced the concept of the rhizosphere(3256).

Cornelius Johan Koning (NL) suggested that fungi play an important role in the decomposition of organic matter and the formation of humus(3257).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Henry Drysdale Dakin (US) discovered the enzyme arginase which splits arginine into ornithine and urea(1138, 1139).

Antonino Clementi (IT) found that arginase is absent from the livers of animals which do not excrete urea (e.g., birds and reptiles)(3258).

George Henry Falkiner Nuttall (US-GB) investigated the serological relationships of animals by the precipitin reaction(1786).

Franz Schardinger (AT) isolated aerobic bacteria capable of producing industrial chemicals such as acetone, ethanol, and acetic acid(3259).

Karl Pearson (GB) correctly generalized the principle of segregation showing that the F2 ratio 1/4 AA : 1/2Aa : 1/4aa should maintain itself indefinitely in a large, random-breeding population. This was an explicit statement of the equilibrium principle for a single locus, and its application to multiple loci could have been inferred from this(3260). Note: this work precedes that of Hardy and Weinberg in 1908.

Theodor Boveri (DE) predicted what later became known as genetic linkage: “When in continued breeding experiments two characters either always appear together, or disappear together, the conclusion may be drawn with the greatest probability that the factors for the two characters are located on the same chromosome.” He also predicted that if in continued breeding experiments combinations in which traits actually appear is larger than the number of possible combinations, this might be the result “of an exchange of parts between homologous chromosomes”(894). See, Sutton, 1903.

Martinus Willem Beijerinck (NL) was the first to obtain the sulfur-oxidizing bacterium, Thiobacillus denitrificans in axenic culture(3261). Under anaerobic conditions it uses carbon dioxide as a source of carbon.

Albert Francis Blakeslee (US) analyzed mating type determination in the fungus Mucor and found that mating (conjugation) occurs between mycelia of opposite mating types, designated plus (+) and minus (-). The resulting sporangia produce either + or - spores, never both(3262).

Hans Burgeff (DE) demonstrated that dissimilar nuclei could be associated in the vegetative hyphae of Phycomyces nitens, a condition he called heterokaryosis(3263, 3264).

William B. Brierley (GB), H.N. Hansen (?), and R.E. Smith (?) discovered and elaborated on heterokaryosis in the Ascomycetes(3265-3267).

The groundwork for understanding the heterokaryotic nature of the dikaryon in the Basidiomycetes was laid by:

Karl Johannes Kniep; Hans Kniep (DE) developed a technique called tetrad analysis. It is commonly used in fungal genetics(3268).

Mathilde Bensaude (FR) discovered that the clamp connection structure in the basidiomycetes is used to ensure the production of cells, each of which contains two complementary nuclei(3269, 3270).

John Hubert Craigie (GB) discovered that the rusts are heterothallic, and confirmed Heinrich Anton de Bary’s findings that the pustules on Barberry and the rust on wheat (Triticum spp.) are both caused by the same organism and that the pycnospores are sperm(3271, 3272).

Leonard Doncaster (GB) explained the inheritance of tortoiseshell (sex-linked) and related colors in cats(3273). 

Friedrich Meves (DE) discovered mitochondria in plants (the tapetal cells of Nymphae anthers)(3274).

Anton Julius Carlson (SE-US) proved that the heart beat in the Limulus crab is neurogenic by section of the cardiac nerve(3275). This was soon shown to be inapplicable to the hearts of amphibia and mammals.

William Philipps Dunbar (US) proposed that hay-fever is a disease caused by vegetable poisons contained in the pollen of certain plants. These substances were connected with the proteid of the pollen grain and of a highly specific character. He developed methodologies for testing patients' sensitivity to certain pollens by minuscule exposure to pollen via their eyes or nasal passages. Dunbar determined that it was the dried cat saliva on cat hair that caused the allergic reaction. With regard to grass pollen, Dunbar identified the albumin fraction as the active toxin, discovered changes in the blood that accompanied exposure to the pollen, and was able to grade individuals' relative susceptibility to each type of pollen(3276, 3277).

Charles Scott Sherrington (GB) and Edward George Tandy Liddell (GB) investigated spinal reflexes such as the knee-jerk. They discovered reciprocal innervation of motor areas, i.e., when one set of muscles is stimulated, muscles working against the activity of the first will be inhibited (Sherrington’s law). The proprioceptive system, i.e., the brain is able to judge the tensions upon the muscles and joints and thereby possess a sense of position and equilibrium. They formulated the concepts of the final common pathway, i.e., “The reflex arcs (of the synaptic system) converge in their course so as to impinge upon links possessed by whole varied groups in common paths. This arrangement culminates in the convergence of many separately arising arcs upon the efferent-root neuron. This neuron thus forms a final common path for many different reflex arcs and acts. It is responsive in various rhythm and intensity, and is relatively unfatigable,” and the integrative action of the nervous system. Also they will be remembered for their contributions to the physiology of perception, reaction and behavior. They also discovered the stretch reflex(2969, 3278-3280).

Franz Knoop (DE) fed dogs the sodium salts of various straight-chain fatty acids in which the carbon atom farthest from the carboxyl group was linked to a phenyl group. Based on the urinary products he deduced that oxidative degradation of fatty acids occurs by oxidation at the beta-carbon thereby releasing two carbons at a time from the fatty acid. This became known as the beta oxidation theory(3281-3284). This represents one of the first experiments in which a metabolite was labeled in such a way that end products could provide evidence of how physiological conversions had occurred.

Gustav Georg Embden (DE) showed that pancreatectomized dogs convert lactic acid to glucose. This suggested that the glycolytic reactions are reversible. ref

Gershom Franklin White (US) reported the isolation of Bacillus X in honeybee (Apis mellifera Linn.) larvae suffering from American foulbrood(3285). White then renamed the organism Bacillus larvae(3286, 3287).


William Bateson (GB), Edith Rebecca Saunders (GB), and Charles C. Hurst (GB) discovered intermediate (blended) inheritance in the mint genus Salvia. In this same article they reported, for the first time, that one character or trait (comb shape in chickens) can be controlled by more than one gene. Further research by various geneticists was to show that this is the general rule rather than the exception. Most characters are controlled by more than one gene(3104, 3288).

Ross Granville Harrison (US) contributed to our knowledge of the relation of the nervous system to muscle differentiation in the embryo, and the development and regeneration of peripheral nerves(3289, 3290).

William Thomas Councilman (US), George B. Magrath (US), and Walter R. Brinckerhoff (US) observed round or oval acidophilic intranuclear inclusion bodies in variola infected cells of man(3291).

Léon Ambard (FR), Eugene Beaujard (FR) and André-Simon Weill (FR) discovered the link between salt and high blood pressure in hypertensive patients studied weeks under different schemes providing very different amounts of sodium chloride(3292-3294). 

Paul Emil Flechsig (DE) evolved a map of cortical function that appeared in a report of 1904 to the Central Committee for Brain Research(2352).

Karl Albert Ludwig Aschoff (DE) discovered granuloma in the myocardium specific for rheumatic fever(3295).

Ernst Ferdinand Sauerbruch (CH-DE) introduced a low pressure surgical cabinet for preventing lung collapse during thoracic surgery and is credited with the first operation on the open chest(3296).

Ludolph Brauer (DE) invented the airtight mask, that could be fitted over the face and connected with an oxygen container under the desired hyperpressure. The oxygen also passed through a bottle of ether, so that both the anesthetic and oxygen could be given under higher than atmospheric pressure. This method replaced the cabinet(3297).

Felix Jacob Marchand (DE) coined the term atherosclerosis because arteriosclerosis is not sufficient to include the entire disease processes of the primary fatty and atheromatous degeneration intimately involved in the sclerosing processes within the blood vessels. He suggested that atherosclerosis is responsible for nearly all obstructive processes in the arteries. The Greek athero refers to gruel(3298).

Julius Donath (AT) and Karl Landsteiner (AT-US) were the first to describe an autoimmune disease, paroxysmal hemoglobinuria. This disease is characterized by the discharge of massive amounts of hemoglobin, not intact erythrocytes, into the urine. It results from an antibody of the IgG class directed against the P blood group antigen and is associated with syphilis and viral infections and is responsible for paroxysmal cold hemoglobinuria(3299). 

Sir William Osler (CA) was the first to associate a renal affection or one affecting the central nervous system with cases of lupus erythematosus(3300, 3301).

Eduard Hitzig (DE) noted that electrical stimulation of a region in front of the pre-central gyrus in the dog caused combined movements of the head and eyes(3302).

T. Grainger Stewart (GB) and Gordon Holmes (IE) wrote a paper about precise localization of destructive lesions in the cerebellum. This paper contains the first description of the rebound phenomenon(3303). 

Sir Edward Albert Schäfer (GB) described a method for administering artificial respiration. It was especially effective with a person in danger of drowning(3304).

Kristian Igelsrud (NO) was the first to perform open-chest cardiac massage in 1901, but this was not reported until a few years later by William Williams Keen, Jr. (US)(3305). 

Harvey Williams Cushing (US) gave the first report of using a tourniquet with pneumatic pressure of a measurable degree. This inflatable cuff was the forerunner of the modern technique used generally in surgery(3306).

Joseph Grinnell (US) wrote, “two species of approximately the same food habits are not likely to remain long evenly balanced in numbers in the same region”(3307). Grinnell connected the idea of competitive exclusion to the term niche when he asserted that “no two species regularly established in a single fauna have precisely the same niche relationships”(3308, 3309). He was the first to use the word niche to refer to an animal’s ecological position in the world by defining the ecological or environmental niche as the ultimate distributional unit of one species or subspecies(3310). Grinnell more fully developed the idea when he wrote “…the concept of the ultimate distributional unit, within which each species is held by its structural and instinctive limitations, these being subject only to exceedingly slow modification down through time”(3311).

Georgi Frantsevitch Gause (RU) proposed what has come to be one of the laws of ecology when he wrote, “It is admitted that as a result of competition two similar species scarcely ever occupy similar niches, but displace each other in such a manner that each takes possession of certain peculiar kinds of food and modes of life in which it has an advantage over its competitor”(3312-3315). It is known as the competitive exclusion principle.

Francis Wall Oliver (AU) and Dunkinfield Henry Scott (GB) discovered evidence for the seed of Lyginodendron which led to the removal of the Cycadofilices from the Pteridophyta (ferns, horsetails, and club-mosses) and their inclusion with the gymnosperms(3316). “We now know that the true ferns were only present in the coal measures in small and archaic forms (Coenopteridales) very unlike living ferns and that probably all the conspicuous fernlike leaves of that era belonged to seed plants”(3317).

Charles H. Sternberg (US) discovered the fossil remains of a creature showing both amphibian and reptilian characteristics. Ferdinand Broili (DE) would name it Seymouria baylorensis for Seymour, Texas in Baylor county(3318).

The Journal of Experimental Zoology was founded.

1905

“Ludwig was absolutely unselfish. He loved his science and rejoiced in the scientific achievements of his students. He freely gave to every earnest worker from the vast store of his physiological knowledge, and his experience in experimental methods. He became at once the friend of each of his pupils, making him feel that he had a personal interest in him and in his work. This feeling spread throughout the laboratory, where good-fellowship reigned, each man becoming interested not only in his own problem, but glad to lend a helpful hand to every other, rejoicing when a research was successful and sorry when the problem baffled. I can recall Ludwig’s enthusiastic, joyous shout, as he called all who could leave their work to come and witness some physiological process revealing itself in its true light for the first time, or some unusually suggestive histological or anatomical preparation. Hearty congratulations followed, all rejoicing in the new discovery. And then came one of those delightful talks, leading us forward to the borderland of science, and giving us glimpses into that fascinating, mysterious land—the unknown.” Warren P. Lombard (US) speaking of Karl Friedrich Wilhelm Ludwig (DE) the great physiologist and his former teacher(3319). More than two hundred and fifty men from a dozen countries came to study under this great master.

“Science is built up of facts, just as a house is built up of stones; but an accumulation of facts is no more a science than a heap of stones is a house.” Henri Poincaré(3320).

“Nothing is constant but change! All existence is a perpetual flux of ‘being and becoming’! That is the broad lesson of the evolution of the world.” Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel(3321).

Johann Friedrich Wilhelm Adolf von Baeyer (DE) was awarded the Nobel Prize in Chemistry for his advancement of organic chemistry and the chemical industry, through his work on organic dyes and hydroaromatic compounds.

Heinrich Hermann Robert Koch (DE) was awarded the Nobel Prize in Physiology or Medicine "for his investigations and discoveries in relation to tuberculosis."

William Weber Coblentz (US), between 1903-1905, pioneered infrared spectrophotometry as a method for determining the presence of specific atomic groupings. He was the first to show that different atomic and molecular groupings absorbed specific and characteristic wavelengths in the infrared region(3322, 3323).

Richard Adolf Zsigmondy (AT-DE) applied the centrifuge to the study of colloids, making a more detailed understanding of protoplasmic constituents possible(3324).

W.I. Gulewitsch (RU) and R. Krimberg (RU) isolated a new compound from meat extracts. They named it carnitine from carnos (meat)(3325). 

Masaji Tomita (JP) and Yuzo Sendju (JP) determined the chemical structure of carnitine to be 3-hydroxy-4-trimethylamino butyric acid(3326).

Sir Arthur Harden (GB) and William John Young (GB) showed that the enzymes were not consumed during the breakdown of sugar by yeast, however the reaction slowed down even when there was ample sugar and enzyme present. If they added inorganic phosphate the reaction speeded up again. This was initially a puzzling finding because phosphorus is neither present in sugar, nor alcohol, nor carbon dioxide, nor enzyme. Their search for the fate of the added phosphate led them to discover that phosphorylated sugars are being manufactured. They isolated a hexose diphosphate (fructose 1,6-diphosphate) from the fermentation mix which became known as the Harden-Young ester(3327-3332). The structure of this ester would later be characterized by Phoebus Aaron Theodor Levene (RU-US) and Albert L. Raymond (US) as fructose-1,6-diphosphate(3333).

Leonid Aleksandrovich Ivanov (RU) had independently discovered that organic phosphates are produced during alcoholic fermentation(3334).

Sir Arthur Harden (GB) made another important set of observations revealing that in the presence of the inhibitor fluoride, fermenting yeast extracts showed an accumulation of two phosphate esters, 3-phosphoglycerate and 2-phosphoglycerate. On the other hand, the inhibitor iodoacetate caused an accumulation of fructose-1,6-diphosphate. Once these intermediates were identified, it became possible to study the enzymatic reactions by which they were formed and utilized. Harden’s work marks the beginning of the study of intermediary metabolism. ref

The first version of International Rules (Code) of Botanical Nomenclature (ICBN) was approved in Vienna, Austria.

Frederick Frost Blackman (GB) and Gabrielle Louise Caroline Matthaei (GB) proposed that photosynthsis consists of a light-dependent reaction (the 'light' reaction) and a temperature-dependent reaction (the 'dark' reaction). Both these reactions are going on simultaneously. The 'light' reaction feeds something to the 'dark' reaction. As the intensity of illumination is increased, the rate of photosynthesis (as measured, for example, by the volume of oxygen produced each minute) does not increase indefinitely but approaches a saturation state in which a further increase of light intensity has no effect. This suggests a two-stage process in which only one stage can be accelerated by light(3335, 3336).

Otto Heinrich Warburg (DE) later called the process of limiting the rate of carbon assimilation at high intensities of illumination the Blackman reaction(3337).

John Sidney Edkins (GB) showed that extracts of the gastric antral mucosa stimulate secretion of acid by the oxyntic mucosa, and postulated that his extracts contained a hormone which he called gastrin(3338, 3339).

H. Gregory (GB), Roderic Alfred Gregory (GB), Paul Martin Hardy (GB), D.S. Jones (GB), George Wallace Kenner (GB), Robert Charles Sheppard (GB) and Hilda J. Tracy (GB) determined the structure of gastrin(3340, 3341).

J.C. Anderson (GB), Moira A. Barton (GB), Roderic Alfred Gregory (GB), Paul Martin Hardy (GB), George Wallace Kenner (GB), John Keith MacLeod (GB), J. Preston (GB), Robert Charles Sheppard (GB) and John Selwyn Morley (GB) described the synthesis of gastrin(3342).

William Henry Howell (US) discovered the remarkable hypotensive effect of acetylcholine(3343).

John Newport Langley (GB) introduced the concept of receptor substance or synaptic substance, “probably not in the nerves, but in the cells in which they end”(1020).

Nettie Maria Stevens (US) and Edmund Beecher Wilson (US) independently discovered the existence of the so-called sex chromosomes. Stevens worked with the beetle Tenebrio while Wilson worked with several genera of hemipteran insects, including Anasa tristis(3344-3348). This was not the first time that sex determination was associated with a chromosome but it was the first proof. See, Henking, 1891 and McClung, 1901. Wilson is credited with coining the phrase X-chromosome.

Sir Roland H. Biffen (GB) reported the first proof that disease resistance in plants may be inherited in a Mendelian manner when he found that resistance to yellow rust in wheat is inherited as a simple Mendelian recessive to susceptibility(3349).

Carl Franz Joseph Erich Correns (DE) had previously found that in the four o’clock plant, Mirabilis jalapa, a gene determined a localized disease in the palisade cells called Sordago(2869, 3350).

William Bateson (GB), Edith Rebecca Saunders (GB), Reginald Crundall Punnett (GB), and Charles Chamberlain Hurst (GB) discovered linkage and genetic interaction(3351, 3352). Punnett has two species of marine worms named for him, Cerbratulus punnetti, Punnettia splendia.

William Bateson (GB), Edith Rebecca Saunders (GB), and Reginald Crundall Punnett (GB) discovered that flower color in Lathyrus (sweet peas) and Matthiola (stocks) is controlled by two genes behaving in a recessive epistatic mode(3104, 3353).

William Curtis Farabee (US) determined that brachydactyly in humans can be explained by Mendelian principles(3354).

The first human pedigree was published. It showed the inheritance of shortened hands and fingers in a Norwegian village(3355).

William Bateson (GB) and Reginald Crundall Punnett (GB) made several reports to the Evolution Committee of the Royal Society of London from 1905 to 1908 in which they related the discovery of two new genetic principles: gametic coupling and gene interaction. They studied poultry comb form, demonstrating significant departure from Mendelian ratios for some gene pairs(3104, 3356-3358).

Thomas Hunt Morgan (US) proposed that the frequency with which recombinants took place was related to the physical distance separating the genes on the chromosome and further proposed that this could be used for mapping the positions of genes relative to each other. This phenomenon was clarified and called gene linkage(3359).

Alfred Henry Sturtevant (US), based on his work with Morgan, created the first genetic map(3360). See Sutton, 1903.

Lucien Claude Jules Cuénot (FR) discovered a lethal allele: the yellow coat color allele in mice even though he did not interpret it correctly(3116).

William Ernest Castle (US) and Clarence Cook Little (US) proved that the yellow allele has two expressions: a dominant one on coat color, and a recessive one on viability, since yellow homozygotes died early in the embryonic state(3117). 

William B. Kirkham (US) later discovered that the homozygous yellow embryos died in utero(3361).

Konstantin Sergejewitsch (RU) proposed the theory of the symbiotic origin of the eukaryotic cell and introduced the term symbiogenesis to signify the emergence of new species with identifiably new physiologies and structures as a consequence of stable integration of symbionts. It stated that the chloroplast and mitochondria of eukaryotic cells had their origins from endosymbiotic cyanobacteria and aerobic bacteria, respectively, whose ancestors were once captured and incorporated by a primitive, anaerobic, heterotrophic host. Many others would later refine this theory(3362-3367).

Robert K. Trench (US), Richard W. Greene (US), Barbara G. Bystrom (US), Merriley E. Trench (US), and Leonard Muscatine (US) found contemporary organisms which offer some striking examples of symbiotic relationships with a similar history(3368, 3369).

Stamen Grigoroff (BG) isolated Lactobacillus bulgaricus from Bulgarian fermented milk(3370).

Alfred T. MacConkey (GB) used bile salts to select for lactose fermenting bacteria in fecal samples(3371, 3372).

M. Casimir Wize (PL) found that a chytridiaceous fungus was parasitizing the larvae and pupae of Cleonus and Anisolplia (Coleoptera). He named the fungus Olpidiopsis ucrainica (3373). 

Fritz Richard Schaudinn (DE) and P. Erich Hoffman (DE) used a special staining technique to demonstrate the spirochaete causing syphilis in serum obtained from a genital lesion by Hoffmann. They named it Spirochaeta pallida(3374, 3375). The organism is now called Treponema pallidum.

Aldo Castellani; Count of Chisiamaio (IT) discovered, Treponema pertenue, the spirochete causing yaws(3376). 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) noted that mononuclear phagocytes from animals resistant to certain bacterial infections had increased competence for ingesting and killing these microbes. This phenomenon became known as macrophage activation(3377).

Sergei Nikolaevich Winogradsky (RU) and Martinus Willem Beijerinck (NL) observed that the reason microbiologists so often succeed in isolating specific microbes from a given sample of soil or water is due to a methodological principle called the ecological approach, often designated as the principle of elective or enrichment culture. Its application depends on a well-considered selection of the conditions in a primary culture medium, thus causing preferential growth of a certain kind of germ, ultimately leading to a predominance of the conditionally fittest. Typically these enrichment cultures offer the microbe a single simple carbon compound as the sole source of carbon(3378).

Ludvig Hektoen (US) demonstrated by subcutaneous injections of volunteers with blood taken from measles patients that the measles (rubeola) virus circulates in the blood during the initial thirty hours of the rash(3379). Hektoen was also the first to grow blood cultures from living patients(3380).

Martinus Willem Beijerinck (NL) published little concerning his original concepts and approaches, however, upon being awarded the Leeuwenhoek medal by the Koninklijke Akademie van Wetenschappen in Amsterdam he said, “I am happy to note the way in which I approach microbiology has the approval of the best judges. This approach can be concisely stated as the study of microbial ecology, i.e., of the relation between environmental conditions and the special forms of life corresponding to them. It is my conviction that, in our present state of understanding, this is the most necessary and fruitful direction to guide us in organizing our knowledge of that part of nature which deals with the lowest limits of the organic world, and which constantly keeps before our mind the profound problem of the origin of life itself. Therefore it is a great satisfaction to me that the Academy apparently wishes to honor the experimenter who exploits this field.

In an experimental sense the ecological approach to microbiology consists of two complementary phases which give rise to an endless number of experiments. On the one hand it leads to investigating the conditions for the development of organisms that have for some reason or other, perhaps fortuitously, come to our attention; on the other hand to the discovery of living organisms that appear under predetermined conditions, either because they alone can develop, or because they are the more fit and win out over their competitors. Especially, this latter method, in reality nothing but the broadest application of the elective culture method, is fruitful and truly scientific, and it is no exaggeration to claim that the rapid and surprising advances in general microbiology are due to this methodology. Nevertheless, and this in spite of the fact that Leeuwenhoek, more than two hundred years ago, already used this aspect of micro-ecology in some of his studies, and that Pasteur was enabled to make most of his great discoveries because he was guided by the same principle, the number of conscious exponents has so far remained very small. And I feel that I certainly may be reckoned among them because of the enthusiasm that is in me to contribute to the grand task can here be accomplished”(3381, 3382).

Beijerinck’s (NL) major contributions can be considered as the first direct experimental investigations of Darwin’s principle of natural selection. In the enrichment cultures the experimentally defined environmental conditions are the selecting agent, and the outcome of the cultures can provide an unambiguous answer to the question as to what organisms among the many types present in the inoculum are best fit to cope with the environment (3383).

Shigetane Ishiwata (JP) discovered that the Sotto-Kin disease of silkworms is caused by a new species of bacterium, which he named Sotto-Bacillen. This organism would later be named Bacillus thuringiensis(3384). 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) and Pierre Paul Émile Roux (FR) demonstrated that syphilis may be transmitted to anthropoid apes, such as the chimpanzee and gibbon, and, with less certainty to monkeys(3385).

Louis Joseph Alcide Raillet (FR) and A. Henry (FR) described six female immature Oesophagostomum brumpti (nematode) worms that Alexandre Joseph Emilé Brumpt (FR) found in tumors of the caecum and colon, in 1902, when he performed autopsy on a 30-year old African man, who had been living near the River Omo, East-Africa(3386-3388). 

William Bateson (GB) coined the term genetics to denote the science of heredity, but the word had actually been used earlier(3389, 3390).

Count Grafen Emmerich Festetics (HU), a prominent sheep breeder from Hungary, wrote Genetic Laws. It included the observation that progeny inherit traits from their parents, and that traits of grandparents can reappear in the offspring of their offspring(3391, 3392).

Hugo Marie de Vries (NL), while studying the genetics of the evening primrose, Oenothera lamarckiana, found an unusual variant among his plants. O. lamarckiana has a chromosome number of 2N = 14. The variant had a chromosome number of 2N = 28. He found that he was unable to breed this variant with O. lamarckiana. He named this new species O. gigas(3393).

Anne Mae Lutz (US) proved that the gigas mutation in the evening primrose contains twice the usual chromosome number. This led to the analysis and artificial production of polyploidy(3394).

Lettice Digby (GB) observed that primrose the species Primula verticillata and P. floribunda can cross to produce a sterile hybrid. This hybrid was called the Kew primrose (P. kewensis) and possessed 18 chromosomes. Digby observed that these sterile hybrids occasionally gave rise to fertile Kew primroses. Using microscopic analysis she proved that the fertile hybrid was a polyploid containing 36 chromosomes. This was the first documented case of a polyploid hybrid(3395).

Øjvind Winge (DK), unaware of Digby's results, speculated that speciation could occur by interspecific hybridization followed by chromosome doubling. Winge believed that hybrid sterility was caused by unbalanced chromosome sets. He reasoned that upon doubling, a proper pairing partner would be available to each chromosome resulting in fertility(3396).

Roy Elwood Clausen (DK-US) and Thomas Harper Goodspeed (US) used Nicotiana tabacum to experimentally demonstrate Øjvind Winge’s hypothesis of the origin of species by amphidiploidy.

George D. Karpchenko (RU) did the same using radish and cabbage(3397-3400). It was soon realized that allopolyploids—hybrid species that contain two or more diploid sets of parental genomes—are common in nature.

W.C. Frank Newton (GB) and Caroline Pellew (GB) noted that spontaneous hybrids of Primula verticillata and P. floribunda set tetraploid seed on at least three occasions. These happened in 1905, 1923 and 1926(3401).

Edwin G. Conklin (US), used the ascidian Cynthia (now Steyla), for his discovery. The mature oocytes of these animals have a large transparent germinal vesicle. The interior consists of a mass of gray yolk and the periphery contains a yellow pigment. When the germinal vesicle ruptures at the onset of meiosis, it liberates a quantity of clear material. At fertilization the sperm enters near the vegetal pole, and this starts a dramatic rearrangement of the cytoplasm.

Conklin discovered that at the close of the first cleavage these distinctively colored regions of the embryo have a precise relationship with the structures that would form subsequently. The fate of the yellow crescent is to form muscles and mesenchyme, the gray yolky cytoplasm forms endoderm, and the clear cytoplasm of the animal hemisphere forms ectodermal structures(3402).

Charles Zeleny (CZ-US) showed that removal of the eyestalk shortened the intermolt period in crustaceans(3403).

Max Kauffmann (DE) showed that the nutritional value of various proteins depends upon their constituent amino acids. Proteins such as gelatin lack some necessary amino acids(3404).

Paul Ehrlich (DE) and Hugo Apolant (DE) demonstrated change of experimental carcinoma transplants into sarcoma(3405).

John Scott Haldane (GB) and John Gillies Priestley (GB) determined by observations on normal men that breathing is quite unaffected either by inhalation of oxygen-rich air or by such a moderate decrease of oxygen as occurs on first going to an altitude. On the other hand the breathing changes its volume automatically in such close adjustment to the amount of carbon dioxide produced in the body that the alveolar air is kept nearly constant in this respect. They concluded that carbon dioxide is the chief immediate respiratory hormone and its tension in the blood is the major stimulus for the respiratory center. They demonstrated that as carbon dioxide concentration of alveolar air rises there is an increase in depth of breathing. There was no alteration in frequency of ventilation until the alveolar concentration had been increased to about five times normal(3406).

Alfred Binet (FR) and Théodore Simon (FR) developed an intelligence test used particularly on children aged 3 to 15 years(3407).

Clemens Peter Pirquet von Cesenatico; Clemens Peter Freiherr von Pirquet (AT) and Béla Schick (HU-AT-US) described the essence of serum sickness—antibody combines with the foreign serum antigen to form a toxic compound which causes the disease(3408-3410).

Hans Curschmann (DE), Hans Gustav Wilhelm Steinert (DE), Frederick Eustace Batten (GB), and H.P. Gibb (GB) provided a clinical description of myotonic dystrophy (Curschmann-Steinert-Batten disease), the most common form of muscular dystrophy(3411-3413). Myotonic dystrophy (MD) is a neuromuscular disorder with autosomal dominant inheritance, associated with muscle weakness and myotonia, dilated cardiomyopathy, cataracts, and mental and endocrine abnormalities.

Alfred Walter Campbell (AU) wrote Histological Studies on the Localization of Cerebral Function, a classic. Campbell’s map of the human brain can be seen in nearly every well known textbook on neuroanatomy(3414).

Harvey Williams Cushing (US) reported a successful operative intervention in intracranial hemorrhage of the new-born(3415).

Sir William Arbuthnot Lane (GB) performed repair of cleft lip and palate in neonates(3416).

J. Winter (AT) used chloroform to suspend circulation and respiration in animals. He then injected adrenaline into the left ventricle of the heart thus restoring heart action when all other methods failed. He suggested that this technique be tried in humans(3417).  incomplete ref

Reinhard von den Velden (DE) attempted intracardiac injection in humans to restore heart action after complete cessation of heart action(3418).

Carl Boden (US) reports that J. Winter (AT), in 1905 was the first to atempt an intracardiac injection of adrenalin in humans(3419).

Henry Fairfield Osborn (US) described the Tyrannosaurus rex which Barnum Brown (US) discovered in 1902 in Hell Creek, Montana(3420).

Frederic Edward Clements (US) wrote the first American textbook in ecology, Research Methods in Ecology(3421).

John Jacob Abel (US) and Christian Archibald Herter (US) founded the Journal of Biological Chemistry

The Journal of Experimental Medicine initiated publication.

1906 

“The true contrast between science and myth is more nearly touched when we say that science alone is capable of verification.” George Santayana(3422).

"The beauty and genius of a work of art may be reconceived, though its first material expression be destroyed; a vanished harmony may yet again inspire the composer; but when the last individual of a race of living beings breathes no more, another heaven and another earth must pass before such a one can be again." Charles William Beebe(3423).

"It is as if the Milky Way entered upon some cosmic dance. Swiftly the brain becomes an enchanted loom, where millions of flashing shuttles weave a dissolving pattern, always a meaningful pattern though never an abiding one; a shifting harmony of subpatterns."Charles Scott Sherrington(2969).

“For this general concept of the changed capacity for reaction, I propose the term allergy. Allo denotes the deviation from the original state, from the behavior of the normal, as in allorhythmia, allotropy.” Clemens Peter Pirquet von Cesenatico; Clemens Peter Freiherr von Pirquet(3424). Introduction of the word allergy to the medical lexicon.

“ We may have been more plastic and receptive, but I doubt it; even our generation … had a practical demonstration of the slowness of the acceptance of an obvious truth in the long fight for the aseptic treatment of wounds … [It was] a long grievous battle, as many of us well know who had to contend in hospitals with the opposition of men who could not — not who would not — see the truth ….

In making knowledge effective we have succeeded where our masters failed. But this last and final stage, always of slow and painful consummation, is evolved directly from truths which cannot be translated into terms intelligible to ordinary minds.” Sir William Osler, 1906 in his Harveian Oration(3425).

Bartolomeo Camillo Emilio Golgi (IT) and Santiago Ramón y Cajal (ES) were awarded the Nobel Prize in Physiology or Medicine "in recognition of their work on the structure of the nervous system."

Walther Hermann Nernst (DE) proposed what we refer to as the third law of thermodynamics: entropy change approaches zero at a temperature of absolute zero(3426-3428).

Sir Ernest Rutherford (NZ-GB) measured the uranium and helium (helium is an intermediate decay product of uranium) contents of uranium-bearing minerals to calculate an age of the minerals. This is the origin of using radioactive decay for dating objects(3429, 3430).

Bertram Borden Boltwood (US) developed the chemical uranium to lead method. He was among the first to suggest that from the quantity of lead in uranium ores and from the known rate of uranium disintegration, it might be possible to determine the age of the earth’s crust. These first geochronology studies yielded the first absolute ages from geologic material and indicated that parts of the Earth's crust are hundreds of millions of years old. He published a list of geologic ages based on radioactivity, which were incredibly accurate for his time(3431).

Mikhail Semenovich (Semyonovich) Tswett (RU) is usually given credit for having originated and named the technique called chromatography (Greek, written in color) when he reported, “If a petroleum ether solution of chlorophyll is filtered through a column of an adsorbent (I use mainly calcium carbonate which is stamped firmly into a narrow glass tube), then the pigments, according to their absorption sequence, are resolved from top to bottom into various colored zones, since the more strongly adsorbed pigments displace the more weakly adsorbed ones and force them further downwards. This separation becomes practically complete if, after the pigment solution has flowed through, one passes a stream of solvent through the adsorbent column. Like light rays in the spectrum, so the different components of a pigment mixture are resolved on the calcium carbonate column according to a law and can be estimated on it qualitatively and also quantitatively. Such a preparation I term a chromatogram and the corresponding method, the chromatographic method.

It is self-evident that the adsorption phenomena described are not restricted to the chlorophyll pigments, and one must assume that all kinds of colored and colorless chemical compounds are subject to the same laws.” Twsett separated blue chlorophyll (chlorophyll a), from yellow chlorophyll ( chlorophyll b), using column chromatography, and called them chlorophyll alpha and beta, which later became a and b(3432, 3433). See, Goppelsröder, 1861. This methodology was presented for the first time in 1903 to a meeting of scientists in Warsaw, Poland.

George Barger (GB), Francis Howard Carr (GB), and Sir Henry Hallett Dale (GB) announced the first isolation of an active ergot alkaloid, which they named ergotoxine(3434).

Sir Henry Hallett Dale (GB) demonstrated that ergotoxine (ergotamine) produces effects at the end plates of the motor nerves in skeletal muscle and some involuntary organs(3435). Some consider this to be the origin of the concept later called beta blockers

Ergotoxine was later shown to be a mixture of three alkaloids.

Arthur Stoll (CH), in 1918, isolated ergotamine tartrate from the various alkaloids present in extracts of the sclerotia of the fungus Claviceps purpurea (ergot), which grow on rye and, to a lesser extent, on other grasses; he named it Gynergen. This was the first chemically pure ergot alkaloid. It found widespread therapeutic use in obstetrics as an oxytocic, and internal medicine for relief of migraines(3436, 3437).

Arthur Stoll (CH), Ernst Burckhardt (CH), M. Edward Davis (US), Fred L. Adair (US), Gerald Rogers (US), Morris Selig Kharasch (RU-US), Romeo R. Legault (US), Harold Ward Dudley (GB), John Chassar Moir (GB), and Marvin R. Thompson (GB) discovered ergonovine, the specific oxytocic principle of ergot(3438-3441). 

Mitsumaru Tsujimoto (JP) discovered a hydrocarbon in oils from shark liver he named squalene(3442). He later assigned the correct empirical formula C30H50 to squalene(3443).

Carbon disulfide was introduced as a herbicide and soil fumigant. ref

Sir Arthur Harden (GB), Stanley G. Walpole (GB), and Dorothy Norris (GB) found that acetoin; 2,3-butylene glycol; and acetylmethylcarbinol are produced by many bacteria(3444-3446).

Albert Jan Kluyver (NL), Hendrik Jean Louis Donker (NL), and F. Visser't Hooft (NL) found that when yeast produce acetylaldehyde during the alcohol fermentation it may be converted to acetoin if a strong hydrogen acceptor like methylene blue or oxygen is present. The acetoin may then be reduced to 2,3-butylene glycol(3447).

David Paretsky (US) determined the mechanism for the conversion of 2,3-butylene glycol to acetylmethylcarbinol in bacterial fermentation(3448, 3449).

Sir Arthur Harden (GB) and William John Young (GB) recognized the existence of a heat-stable coenzyme participating in fermentation reactions catalyzed by yeast juice. One component of this coenzyme was recognized as adenosine triphosphate (ATP), but the structure of the other, known for many years as cozymase remained unknown(3328).

Otto Fritz Meyerhof (DE-US) perfected a technique of using muscle extract which was very low in carbohydrate content to study the role of chemicals suspected of being intermediates or cofactors in the conversion of glycogen to lactic acid. He confirmed earlier findings that phosphate promotes the process, and that hexose diphosphate (Harden-Young ester) is converted into lactic acid. He found that glucose is not utilized effectively unless there is added, Harden’s heat-stable coferment and a heat-labile factor from yeast juice which Meyerhof called hexokinase(3450).

Otto Fritz Meyerhof (DE-US) demonstrated that glycogen in muscle is split by enzymes into two molecules of lactic acid per molecule of hexose. He stressed the identity of the reactions of glycogen in muscle and glucose in yeast. These experiments laid the foundation for the development of the Embden-Meyerhof-Parnas theory of glycolysis(3450-3453).

Hans Karl August Simon von Euler-Chelpin (DE-SE) Hjalmar Ohlsén (SE), and Sixten Kullberg (SE) had earlier postulated that an enzyme they named phosphatase acts upon a mixture of phosphate and the intermediate products of alcoholic fermentation, causing the formation of a carbohydrate ester(3454, 3455). 

Hans Karl August Simon von Euler-Chelpin (DE-SE), Ragnar Vestin (SE), Henry Albers (SE), Fritz Schlenk (SE), Karl August Simon (SE), Erich Adler (SE), Otto Heinrich Warburg (DE), and Walter Christian (DE) determined that nicotinic acid is an essential part of the coenzymes NAD (also called DPN, diphosphopyridine nucleotide, cozymase I, and coenzyme I) and NADP (also called TPN, triphosphopyridine nucleotide, codehydrogenase II, and coenzyme II)(3456-3463). This was the first evidence that nicotinic acid, in the form of its amide, formed a part of the structure of a coenzyme. Absence of nicotinic acid leads to failure of certain enzymes to function normally. The particular enzymes that fail are those that make use of coenzymes with a nicotinic acid moiety.

Otto Heinrich Warburg (DE) and Walter Christian (DE) proposed the names diphosphopyridine nucleotide (DPN) and triphosphopyridine nucleotide (TPN)(3463).

Nicolaas Louis Söhngen (NL) discovered that some bacteria produce methane and others can use it as both a carbon and energy source(3464).

Sir Frederick Gowland Hopkins (GB) concluded that the necessary precursor of epinephrine (adrenaline), a hormone which must be continuously formed, must be derived from the diet. He did not mention tyrosine, but apparently had this amino acid in mind as a precursor of some synthetic product important in metabolism. Hopkins introduced the idea that hormones are derived from digestion products of proteins(3465).

Ernst Joseph Friedmann (DE) was the first to characterize a hormone by revealing its chemical formula (epinephrine; adrenaline)(3466).

Hans Winterstein (DE) determined the capacity of the central nervous system to consume oxygen(3467).

Robert Heath Lock (GB) and Alfred Henry Sturtevant (US) were the first to clearly express the relationship between linkage and exchange of parts between homologous chromosomes(3468, 3469).

Leonard Doncaster (GB) and Gilbert H. Raynor (GB) were the first to discover a sex-linked character. They described a trait called lacticolor segregating among wild female currant moths (Abraxas grossulariate) but not among males(3470). 

William Bateson (GB), Reginald Crundall Punnett (GB), and Leonard Doncaster (GB) found that the female moth is heterogametic and the male, homogametic(3471, 3472).

The sex-linked, recessive inheritance of lacticolor was not understood until it was recognized that, in Abraxus and other Lepidoptera, the female is the heterogametic sex, not the male. See, Bridges, 1916.

Craig W. Woodworth (US) was the first to breed Drosophila in quantity, and it was he who suggested that William Ernest Castle (US) use Drosophila as experimental material for genetic studies. 

Edward Ernest Tyzzer (US) observed intranuclear inclusions in cells infected by varicella virus(3473). 

Erwin Bauer (DE) demonstrated graft transmission of abutilon mosaic and several other viruses which cause variegation, or infectious chlorosis in woody plants(3474, 3475).

Eduard von Frendenreich (DK) and Sigurd Orla-Jensen (DK) isolated and characterized propionic acid bacteria(3476).

Jules Jean Baptiste Vincent Bordet (BE) and Octave Gengou (FR) isolated the causative agent of whooping cough, Hemophilus pertussis (now Bordetella pertussis) and devised a method to immunize against it(3477, 3478).

Thorvald Johannes Marius Madsen (DK) and Bjorn Kristensen (DK) proved that Bordetella pertussis is the etiological agent of whooping cough(3479-3482).

Pearl Louella Kendrick (US) and Grace Eldering (US) cultured Bordetella pertussis in BG medium containing sheep’s blood then developed a vaccine for whooping cough(3483).

Pearl Louella Kendrick (US) and Gordon C. Brown (US) combined vaccines for diphtheria, whooping cough, and tetanus into the single DPT shot used today(3484, 3485). 

Thomas Lane Bancroft (GB-AU) showed that the mosquito Stegomyia fasciata (Aedes aegypti ) is the carrier for the dengue-fever pathogen(3486).

John Ashburton Thompson (AU) arrived at a theory of plague that involved or necessitated transmission by fleas(3487).

The Advisory Committee of the India Plague Commission (GB) concluded that the plague is carried from one rat to another and from (3488) rat to man by Xenopsylla cheopis (Rothschild), the rat flea(3489). They also determined that the plague bacilli multiply in the stomach of the flea(3490). Early members of the Commission were Charles Martin (GB), George Lamb (GB), William Glen Liston (GB), George Ford Petrie (GB), Sydnet Rowland (GB), Thomas Henry Gloster (GB), M. Kasava Pai (GB), V.L. Manker (GB), P.S. Ramachandrier (GB), and C.R. Arvi (GB).

Aldo Castellani; Count of Chisiamaio (IT) discovered the spirochete of spirochetal bronchitis (Castellani’s disease)(3491).

Samuel Taylor A. Darling (US) was the first to clinically describe the fungal disease histoplasmosis. He thought the etiological agent was protozoal and named it Histoplasma capsalata(3492-3495).

Henrique da Rocha-Lima (BR) concluded from histological studies that Darling’s agent was fungal(3496). Its identify would become Histoplasma capsulatum.

Katharine Dodd (US) and Edna H. Tompkins (US) reported the first intra vitam diagnosis. The diagnosis was made from the blood during life by finding the characteristic parasite in the large mononuclear cells(3497).

William DeMonbreum (US) described the dimorphic nature of Histoplasma capsulatum after being surprised by the growth of a mold from patient tissues displaying yeasts(3498).

Amos Christie (US) and J. Cyril Peterson (US) found that histoplasmosis is endemic to the Ohio River Valley(3499).

Chester W. Emmons (US) demonstrated that it is a soil saprophyte(3500).

Chester W. Emmons (US) and Libero W. Ajello (US) discovered its relationship to bats and avian habitats respectively(3501, 3502).

Maurice Nicolle (FR) and Felix Mesnil (FR) introduced the use of trypan-blue to treat trypanosomiasis(3503).

Georgii Norbertovich Gabritschewsky; Georgii Norbertovich Gabrichevskii (RU) used preparations of killed streptococci to vaccinate patients against scarlet fever(3504).

Friedrich Voelcker (DE) and Alexander von Lichtenberg (DE) devised retrograde pyelography (introduction of radiopaque medium into the kidney pelvis by way of the ureter) for the study of the urinary tract(3505).

August Paul von Wasserman (DE), Albert Ludwig Siegmund Neisser (DE), Carl Bruck (DE), Arthur J. Schucht (DE) and Felix Plaut (DE) discovered the presence of antibodies to syphilis antigen in the serum of syphilitic monkeys; then working with A. Schucht (DE) they demonstrated similar antibodies in the blood of human syphilitics. This became the basis of a complement fixation test for anti-syphilitic antibodies called the Wasserman test(3506-3509). This work is considered to include the first isolation of what Pangborn would call cardiolipin.

Karl Landsteiner (AT-US), Rudolf Müller (AT), and Otto Pötzl (AT) discovered the working principle of the Wassermann reaction(3510).

Mary C. Pangborn (US) coined the term cardiolipin to denote a lipid isolated from beef heart, and possessing antigenic properties in the complement-fixation test(3511).

Rudolf Müller (AT) and Moriz Oppenheim (AT) developed a complement fixation test for serodiagnosis of gonorrhea(3512).

Alfred Wolff-Eisner (DE) coined the terms pollen disease and pollen sensitivity. He suggested that hay-fever might be a form of hypersensitivity or anaphylaxis in the nose(3513).

The following is taken from Paul Ehrlich’s speech at the dedication of the Georg Speyer-Haus in Frankfurt Germany. It was a privately endowed institute dedicated entirely to the study of chemotherapy. Ehrlich was its first director (he was simultaneously the director of the Institute for the Investigation and Control of Sera). A portion of the address is repeated here so the reader can sense the working of the greatest medical mind of the nineteenth century. 

“Since throughout my whole life, my thoughts have been most intimately interwoven with the same fundamental ideas as are now due to give a lead to the enterprises of the Speyer-Haus, I ask for your indulgence, and hope that you will not impute it to me as lack of modesty, if now, somewhat unconventionally, I retrace some of my personal memories and unfold to you the story of the origin of my own ideas. I would not have done this, had I not thought that such a developmental presentation would be the simplest way of making clear to you the nature of the problems which give to this institute its special character.

It was some 33 years ago—I was then still quite a young student—when I came across a publication on lead poisoning, by Heubel. In order to elucidate the nature of this poisoning, the author had estimated quantitatively the lead content of the liver, the kidney, and the heart, and had discovered that there were remarkable differences in the amount of lead to be found in the various organs. When he immersed organs of normal animals in dilute lead-solutions and subsequently subjected the organs to chemical analysis, he believed that he obtained exactly the same differences. This experiment seemed to me, at that time, a revelation. The possibility emerged that this technique might be used also to ascertain the sites of action of poisons. That lead was found to be present in certain organs, e.g. the brain, provided merely the starting point for the investigation. The brain is a large structure and is made up of many constituents—cells, fibers, etc. The real problem was to determine in which of these cells the poison was stored. The immediate effect of this idea became almost a disaster for me, since it disrupted, more than a little, the normal course of my studies, without bringing me any nearer to the desired goal. I had nothing but failure from any of my attempts to detect, with the aid of the microscope, the presence of metals applied in high dilutions, and I was not a step further forward.

It became necessary, therefore, to approach the task from a more general standpoint and, first of all, to obtain some insight into the manner and the method of the distribution of substances within the body and its cells. When we see that certain poisons, e.g. strychnine, produce spasms which originate from the nerve cells of the spinal cord, and when we see that the American arrow-poison, curare, causes a paralysis of the extreme nerve-endings, which extend to the muscle, the possibility becomes clear that these effects can be caused only through strychnine making a direct connection with the cells of the spinal cord and curare with the ultimate finest nerve-endings. Conclusions such as these seem at once to be self-evident—to be, as I might express it, part of a man’s inborn inheritance. They can be traced back into antiquity and have assumed importance in several of the by-paths of medicine. They appear quite clearly, for example, in a statement of a mediaeval physician, who thought that drugs must possess spicules, by the aid of which they are able to anchor themselves in the various organs. But these ideas, like so many axioms, were as easy to express as they were difficult to prove; and this may well be the reason why they were completely ignored in the practical study of drugs and, despite their fundamental importance, have played no role in the development of pharmacology. If one had wished to put the storage-axiom to the test, one would have had to demonstrate, by the use of the microscope, that the poison under consideration was, in fact, present at these minute sites. This, however, was found to be impracticable.

It was, therefore, necessary to begin the investigation by 

an entirely different line of approach, and to utilize substances which, like dyes, are easily detected, even by the naked eye; it would suffice to remove and examine a small piece of an organ of an animal after it had been killed. A glance through the microscope would then give evidence immediately, and in the finest detail, concerning the distribution of the substance.

The fact that a large number of dyes exists which differ widely in their constitution, and the fact, too, that some of these dyes exhibit a high degree of toxicity, made such endeavors all the more feasible, and thus the method originated which , nowadays, is known briefly as vital staining. I do not intend to dwell on the wealth of results which this technique has yielded, especially in microscopic anatomy, but will just refer to the fact that the various dyes show quite characteristic differences in their distribution and localization. Thus, for example, methylene blue causes a really wonderful staining of the peripheral nervous system.

If a small quantity of methylene blue is injected into a frog, and a small piece of the tongue is excised and examined, one sees the finest twigs of the nerves beautifully stained, a magnificent dark blue, against a colorless background.

With many vital stains it is therefore extremely easy, almost at a glance, to ascertain their distribution in the different parts of the body—which parts they favor, which organs they avoid.

Of course, staining of the dead organs and tissues has for a long time been one of the most important tools of histological research. But staining of this kind can only give information concerning purely the anatomical structure of the tissues. If, however, one wishes to acquire an understanding of the properties and functions of the living cell, then the staining reaction must be made to take place in the body itself, i.e., one must stain the living substance. In this way one can gain an insight into the relationship between the individual tissues and certain dye-stuffs. I have denominated this affinity of the stains and other foreign substances by adjectives with the ending tropic, and, for example, describe a dye which stains only a single specific tissue as monotropic, and speak thus of neurotropic and myotropic substances, etc., while substances which have the capacity to stain several tissues should be called polytropic. In 1866, in my early study “ On the methylene-blue reaction of the living nerve-tissue,” I had already indicated the lines along which a further analysis of the process should proceed. Two questions had first of all to be answered:

1. Why does methylene-blue stain nerve cells ?

2. Why are nerves stained by methylene blue ?

As to the first question, the answer, by virtue of the nature of the problem, had, of necessity, to be in terms of pure chemistry; and I was able to prove that the nerve-staining property of methylene blue is conditioned by the presence of sulfur in the methylene-blue molecule. Synthetic chemistry has, in fact, given us a dye which, apart from the absence of sulfur, corresponds exactly in its chemical constitution to methylene blue. This is Bindschedler’s green. With the absence of sulfur, there is associated the inability to stain living nerves. The interest of the second question was heightened by the circumstance that, in higher animals, not all the nerve endings are stained by methylene blue. I have shown it to be probable that these differences between the individual nerve endings are not due to different degrees of avidity for methylene blue, but rather to certain associated environmental conditions; for bluing of the nerves is intimately associated with the degree of oxygen saturation, inasmuch as it is precisely at those places which are best supplied with oxygen that staining of the nerve endings by methylene blue also occurs. Further, one can easily ascertain that the nerve fibers that stain have also an alkaline reaction; and thus oxygen saturation and alkaline reaction provide the conditions which make possible the staining of nerve endings by methylene blue. Just as methylene blue accumulates only in alkaline fibers, so one must suppose, in the light of the investigations of Lieberkühn and Edinger, that certain other stains, such as alizarin blue, would stain the acid regions. One is, therefore, compelled to differentiate between alkaline, acid and also neutral fibers, and it is evidently to such differences, in conjunction with the degree of oxygen saturation, that the determinant role must be ascribed, in regulating the distribution and action of injected substances among the particular regions of the nervous system. It seemed, moreover, according to my earlier investigations on the methylene-blue staining of the nerve fibers, that an irreversible combination very soon takes place between dye and certain constituents of the nerve substance, since one can see that intensely blue granules appear in the axis cylinder, a phenomenon which may well be intimately associated with the fibrillic acid recently described by Bethe.

Very special conditions govern the uptake of dyes by the brain. The early anatomists, themselves, noticed that, even in the most severe jaundice, the brain remains snow-white, while all the other tissues are of a deep orange tint. I obtained this same effect on introducing into animals a large number of synthetic dyes, all of which, however, were alike in containing an acid group, such as the sulphonic acid radicle. In contrast to this, a large number of basic dyes which, like the alkaloids, form salts from acids, stain the brain very effectively. I have assumed that the reason for this behavior is that the alkalinity of the blood plays a decisive role. On this basis, it is now possible to look at all these phenomena from a common point of view. The difference in the behavior of acid and alkaline dyes may accordingly be ascribed to the fact that the former are chiefly bound in the blood in the form of salts, whereas the latter remain free. Thus, the brain plays the same role as does the ether in the method of recognizing poisons devised by Stas-Otto; this method, as is well known, depends on the fact that basic substances, such as alkaloids, are bound in acid solution and are, on that account, difficult to extract, whereas they can easily be shaken out with ether from an alkaline solution. I was, in fact, able to confirm this idea experimentally; for if one introduces acid groups, e.g. the sulphonic acid radicle, into neurotropic stains, then the neurotropic property of the resulting derivatives is immediately abolished. We can similarly explain the fact that toxic substances are so often weakened in their toxic properties by the introduction of a sulphonic acid radicle into the molecule. The accumulation of the toxic agent in the central nervous system is made impossible, merely by the introduction of this sulphonic acid radicle.

The analogy between the roles played, respectively, by the brain and by ether, in the storage of dyes in the one case and in the method of identifying poisons in the ether, is further emphasized by the fact, discovered by me, that neurotropic and lipotropic properties, as a rule, go together, i.e., that those dyes which are taken up by the brain are also deposited in adipose tissue. This similarity in the behavior of the adipose and nervous tissues finds a simple explanation in the fact that the brain contains an abundance of fat-like substances—myelin and lecithin. Fat and brain, therefore, behave in the body exactly as ether does in the extraction of alkaloids. This theory, moreover, many years after the publications dealing with my work on it, was taken up again by Hans Horst Meyer and Overton, as the lipid-theory, it plays today an important role in medicine.

These observations, based on my work with dyes, I developed also, during the years 1886 and 1887, in relation to a series of remedies. I demonstrated that thallin, like a large of dyestuff, is lipotropic. In order to detect thallin in the tissues, I made use of the property that, even in very dilute solutions, it is transformed by oxidizing agents (ferric chloride) into a dark green dyestuff. If this is immediately fixed, in statu nascendi, in an insoluble form, it is then easy to obtain an insight into the distribution of the thallin. The pronounced affinity of thallin for adipose tissue causes the thallin to be held for a long time in the body; and this long retention of so readily oxidizable a substance is explained by my discovery that there is no free oxygen in adipose tissue, but that this, on the contrary, has a maximal reducing power. All these observations led me to the view that the hitherto dualistic approach to the problem of the connection between chemical constitution and pharmacological action has been much too narrowly conceived, and that there exists another and, indeed, decisive element which must be considered—the distribution in the body. My investigations have shown that the distribution, i.e., the selective affinity for certain organs and systems, is a function of the chemical constitution.

But the establishment of the existence of this relationship between constitution, distribution and action fulfilled only one part of the program which I had planned for myself. For an action to produced on an organ, the first requirement is the fixation of chemical substances; but the simple storage of substances of any kind is not of itself enough to cause specific toxic effects. This requires a second determinant factor to be present in the chemical substance. With the alkaloids, which we will consider first, the conditions are very similar to those which had already been observed with the simpler dyestuffs. In these there are two different chemical constituents which are responsible for the dying property, a so-called chromophore group and , further, the auxochrome groups. In exactly the same way, one must postulate, when considering the alkaloids, that in the constitution of these powerfully acting substances two different factors must be distinguished: (1) a selective group which governs distribution, and (2) a pharmacophore group which evokes the specific activity. You will allow me, perhaps, to clarify this with an example. As is well known to you, cocaine, which, in medicine, plays so important a role as a local anesthetic, is the benzoyl derivative of an ecgoine ester. A large number of chemical homologues of cocaine can be synthesized by replacing the benzoyl radicle by those of other acids, e.g. of acetic acid or formic acid. All the substances obtained in this way are, by virtue of their chemical nature, homologues of cocaine, and all these different cocaines follow the same pattern of distribution in the body, because they belong, chemically, to the same class. But of all these substances, only one, the benzoyl-cocaine obtained from the coca plant, acts as a local anesthetic; and from this it is immediately obvious that the benzoic acid residue is the source of the specific action, and thus, that the benzoyl radicle functions here as the anaesthesiophore group.

The science of immunology provides the most striking examples of the relation between distribution and action. It has been found in this connection that the group which is responsible for the distribution of bacterial poisons, which I have called the haptophore group, is a quite separate complex, and that the toxic action is attributable to the presence of a second group, the usually very unstable toxophore group. A still further differentiation between the factors of distribution and of activity is to be found if we take into consideration such cell poisons (hemolysins and bacteriolysins) as are present even in a normal blood-serum, or are produced by immunization. For, in the case of these, each of the two properties is connected with a special molecule, one of which, called the amboceptor, is the carrier of the haptophore group, and the other, called the complement, that of the toxophore group. The hemolytic action of snake venom follows the same pattern. The factor contained in the snake venom represents solely the distributive component, whilst the appropriate pharmacophore group is present in lecithin. Neither snake venom nor lecithin is able, of its own accord, to destroy the blood cells. On the other hand, the product formed from them, the snake lecithide, corresponds, as was shown by Kyes, to a toxin, the haptophore group of which comes from snake venom and toxophore complex from the lecithin.

The concepts which have thus been developed indicate the direction which must be followed in the construction of new organotropic medicaments. It will, therefore, be on of the main tasks of the new institute to persevere along this path; and this entails, in the first instance, the discovery of substances and chemical groups which have an affinity for particular organs. The organotropic substances must then be furnished with pharmacophore groups which will bring about a therapeutic and pharmacological activity. We intend, as it were, to use certain chemical complexes as vehicles to carry appropriate pharmacophore groups to the desired types of cell. To begin with, however, the main emphasis will be put on the haptophore group, the distributive factor. For this represents the conditio sine qua non for any therapeutic action.

But the theoretical problem represents only one aspect of our objective; on the other hand, our main effort will be directed to the discovery of new, rational, curative remedies. As you are aware, the study of medicaments, or pharmacology, is a long-established field of research, which has been cultivated and developed in numerous institutes. But most pharmacological research is directed merely to determining the effects, on animals in good health, of the substances which are used as remedies, and to fix the limits of their safe administration in the clinic, by observations on their side-effects and their toxicity. Prior attentions, therefore, given to those substances (especially alkaloids) which produce interesting and important toxic effects. These highly toxic substances, however (if one excludes a few alkaloids such as morphine, cocaine, atropine, etc.), are frequently quite useless in clinical practice, and thus a large part of the research work is carried out in realms which are remote from any practical application in medicine. Admittedly, one obtains information about the risks which excessive dosage and otherwise unsuitable methods of administering particular substances involve, and this, of course, is of the greatest importance. Application of drugs in practice must be based on toxicological examination, and it need not be emphasized that toxicology, as such, represents a thoroughly justified and necessary type of science, which may even be of the greatest importance in biology and physiology—the very foundation of our medical knowledge. But it seems to me that, with the line of approach so predominantly in this one direction, some of the most important tasks of pharmacology are pushed all too readily aside, and practical medicine does not receive sufficient benefit. We must certainly be grateful to those who have safeguarded our departure [on the voyage of discovery] with beacons against toxic action—but they have not charted our course into the open sea of curative medicine”(3514).

Charles Scott Sherrington (GB) described the synapse and motor cortex(2969).

Karel Frederik Wenckebach (NL-AT) discovered the cardiac anatomical structure named for him: the Wenckebach bundle. It is the median bundle of the conductive system of the heart leading to the atrioventricular node(3515, 3516).

Charles Scott Sherrington (GB) coined the term proprioceptive as it refers to a sense of position and equilibrium(2969, 3279).

Sir Henry Hallett Dale (GB) discovered the oxytocic or uterine-contracting effect of the posterior pituitary extract(3435, 3517).

Paul Carnot (FR) and Catherine DeFlandre (FR) proposed the idea that erythropoiesis is regulated by hormones. After conducting experiments on rabbits subject to bloodletting, they attributed an increase in erythrocytes in rabbit subjects to a hemotopic factor they named hématopoïetine (haemopoietin)(3518).

Eva Bonsdorff (FI) and Eeva Jalavisto (FI) suggested that hématopoïetine be changed to erythropoietin because they found that it affects only the erythroid series(3519).

Allan Jacob Erslev (DK-US) concluded that plasma from rabbits rendered anemic by bleeding contains a factor (erythropoietin) capable of stimulating red cell production(3520).

Leon Orris Jacobson (US), Eugene Goldwasser (US), Walter Fried (US), and Louis F. Pizak (US) detected the production of erythropoietin by the kidney(3521).

Takaji Miyake (JP), Charles K. Kung (US) and Eugene Wasserman (US) were the first to isolate erythropoietin, their source was human urine(3522).

Fu-Kuen Lin (CN-US) identified the erythropoietin (EPO) gene(3523, 3524).

Sylvia Lee-Huang (US) cloned and obtained expression of recombinant human EPO gene(3525).

Alfred Vogt (CH) described a form of uveomeningoencephalitis endemic in the Far East. A disease, usually occurring in adult life, in which severe bilateral inflammation of the iris (iridocyclitis), ciliary body and choroid of the eye is associated with relapsing meningoencephalitis, deafness, alopecia, depigmentation of the skin and eye, symmetrical vitilligo and poliosis (whitening of the ends of the hairs)(3526). It is called Vogt-Koyanagi-Harada syndrome.

Robert Bárány (AT-SE) devised the caloric test for labyrinthine function. If the normal ear is irrigated with hot water at 110° to 120° F, a rotary nystagmus is developed away from the irrigated side. There is no nystagmus if the labyrinth is diseased(3527).

Robert Bárány (AT-SE) also developed a clinical pointing test for demonstrating the existence of disturbances of the vestibular apparatus and its paths in the brain. The patient is asked to point at a fixed object with a finger or a toe with the eyes alternatively open and closed. With eyes open the patient holds his arm upwards and then lowers it to a horizontal position, so that it points at the investigator's index finger. In damages of vestibularis there are disturbances of coordination and the patient points past(3528-3530).

Lodewijk (Louis) Bolk (NL) investigated the comparative anatomy of the cerebellum and its nerves. He determined that muscle coordination is localized to this portion of the brain(3531-3533).

Jules Joseph Déjérine (CH-FR) and Gustave Roussy (FR) described the Déjérine-Roussy or thalamic syndrome (superficial persistent hemianesthesia, mild hemiplegia, mild hemiataxia, complete astereognosis, severe pains in the hemiplegic side, and choreo-athetoid movements in the members of the paralyzed side)(3534).

Alois Alzheimer (DE) , in 1907, wrote, “A woman, 51 years old, showed jealousy toward her husband as the first noticeable sign…. Soon a rapidly increasing loss of memory could be noticed. She could not find her way around in her own apartment…. Her entire behavior bore the stamp of utter perplexity. She was totally disoriented to time and place…. The generalized dementia progressed…. After 4 1/2 years…death occurred…. The autopsy revealed a generally atrophic brain without macroscopic lesions…. Scattered through the…cortex…one found miliary foci that were caused by the deposition of a peculiar substance.” This is from his monumental work on Alzheimer’s Disease for which he will always be remembered(3535, 3536).

Emil Wilhelm Magnus Georg Kraepelin (DE) named Alzheimer's disease in 1910(3537).

George Washington Crile (US) was the first to describe radical neck dissection that encompasses the surgical removal of neck metastases contained between superficial and deep fascial layers of the neck(3538).

George Washington Crile (US) and David H. Dolley (US) pioneered the use of high-dose epinephrine (adrenaline) in the resuscitation of an animal near death from anesthetics and asphyxia(3539).

Christian J. Gauss (DE) and Bernard Krönig (DE) reported their successes with scopolamine-morphine anesthesia in obstetrics (twilight sleep)(3540-3542).

George Washington Crile (US), in August 1906, at St. Alexis Hospital in Cleveland, Ohio, performed the first successful transfusion of blood from one human to another in the United States. This was the first human to human blood transfusion in which Landsteiner’s discovery of blood types was used to match the donor and recipient(3543).

Edward Konrad Zirm (AT) performed the first successful cornea transplant in humans. The patient had sustained alkali burns. The donor was an 11 year old boy whose eye was enucleated because of penetrating scleral injury(3544).

Vladimir Petrovich Filatov (RU) and M.A. Bajenova (RU), in 1912, greatly improved the success rate in corneal transplants when he showed that material from a fresh cadaver is just as satisfactory as that from a living person and that eyes can be banked in a refrigerated, sterile receptacle. He used an egg membrane to adhere the graft(3545, 3546).

Mathieu Jaboulay (FR) carried out the first attempts at human kidney transplantation. On January 22, he transplanted a porcine kidney to the brachial vessels of a woman suffering from nephrotic syndrome. Three months later he repeated the experiment with a goat kidney(3547). Neither kidney xenograft lasted more than several hours.

Alexis Carrel (FR-US) performed a double nephrectomy followed by transplantation of both kidneys from another animal. He noted that the recipient animal could secrete almost normal urine and live in good health for at least a few weeks(3548).

Harold Neuhof (US) performed a xenotransplant of lamb kidney into a human in acute renal failure. The patient survived for nine days(3549).

Yu Yu Voronoy (UA) transplanted human kidneys(3550). 

Charles A. Hufnagel (US), Ernest Landsteiner (US), and David M. Hume (US), in 1947, performed a human renal transplant. The first patient was a young woman in renal failure following obstetrical complications. The purpose of the transplant was to provide temporary renal function until her own kidneys recovered from acute tubular necrosis. The donor kidney was anastomosed in the antecubital space under local anesthesia using a cutaneous ureterostomy. The patient died a few months later of fulminating hepatitis secondary to pooled plasma infusions which she had received in the course of her treatment. The temporary kidney transplant had been previously removed(3551).

David M. Hume (US), John Putnam Merrill (US), Benjamin F. Miller (US), and George Widmer Miller (US) performed nine cadaveric or free kidney transplantations in humans, eight to thigh and one to an orthotopic location. One thigh kidney transplant functioned for five months. No immunosuppression was used(3552).

J. Hartwell Harrison (US), John Putnam Merrill (US), Joseph Edward Murray (US), and Warren R. Guild (US), on 23 December, 1954, transplanted a kidney from a healthy twenty-four-year-old individual to his twin brother suffering from severe renal disease (cross skin grafting established genetic identity). This was the first time in medical history that a normal healthy person was to be subjected to a major surgical operation not for his own benefit. Post-operatively the transplanted kidney functioned immediately with a dramatic improvement in the patient's renal and cardiopulmonary status. This spectacular success was a clear demonstration that organ transplantation could be life saving(3553, 3554). Some consider this to be the first truly successful kidney transplantation.

Joseph Edward Murray (US), Stanley Lang (US), Benkamin J. Miller (US), and Gustave J. Dammin (US) developed a reproducible renal transplant operation in dogs using intra-abdominal vascular anastomoses and a uretero-cystostomy for urinary drainage, placing the kidney in the lower abdomen. This has become the universal renal transplant procedure since that time. Complete functional studies of some of these autografted kidneys two years after transplantation proved them to be completely normal(3555).

Joseph Edward Murray (US), John Putnam Merrill (US), Gustave J. Dammin (US), James B. Dealy, Jr. (US), Carl W. Walter (US), Marcus S. Brooke (US), Richard E. Wilson (US), J. Hartwell Harrison (US), and Eli A. Friedman (US) performed a renal allograft from a human fraternal twin to a recipient preconditioned with a sublethal total body irradiation. This was the first long survival of an organ allograft, an objective not previously achieved in an animal model(3556, 3557). The patient subsequently led a full active normal life until he died of cardiac problems 25 years later.

Joseph Edward Murray (US), John Putnam Merrill (US), Gustave J. Dammin (US), James B. Dealy, Jr. (US), Guy W. Alexandre (US), J. Hartwell Harrison (US), Richard E. Wilson (US), Frank J. Takacs (US), and Edward B. Hager (US) carried out clinical trials on the efficacy of 6-mercaptopurine and azathioprine as immunosuppressive agents to prolong the survival rates of allograft kidney transplants. One patient, transplanted in April 1962, was treated with azathioprine following a cadaveric renal allograft. He survived over one year and was the world's first successful unrelated renal allograft(3558-3560).

Jean Alban Bergonié (FR) and Louis Mathieu Frédéric Adrien Tribondeau (FR) presented the rationale for radiotherapy as follows: “The effect of radiations on living cells is the more intense: (1) the greater their reproductive activity, (2) the longer their mitotic phase lasts, and (3) the less their morphology and function are differentiated”(3561).

The Congress of the United States enacted the Food and Drugs Act, the first federal statute prohibiting the misbranding or adulteration of food(3562).

Alexandr Petrovich Karpinsky (RU) reported research on Devonian algae, the so called charophytes. His study of the contemporary charophytes showed their closeness to extinct Devonian forms and indicated that they likely had a common ancestor(2199, 3563). 

George Reber Wieland (US) researched plant material derived from the Upper Jurassic and Lower Cretaceous beds of Maryland, Dakota, and Wyoming where he discovered the hermaphrodite nature of the bennettitean flower and recognized an affinity between the mesozoic cycadophyta and the angiosperms. The angiosperm with which he specially compared the fossil type was the Tulip tree (Liriodendron) and certainly there is a remarkable analogy with the magnoliaceous flowers, and with those of related orders such as Ranunculaceae and the water-lilies(3564).

Charles William Andrews (GB), in 1900, discovered numerous early higher primate fossils in the Fayum Depression region east of Cairo, Egypt. These Eocene and Oligocene fossils include protomonkeys believed to be ancestral to Old World monkeys and thus in the lineage to hominids(3565).

The Biochemical Journal was founded.

The Biochemische Zeitschrift was founded.

1907-1916

Polio turned into a major problem in the U.S., with about a thousand cases in New York in 1907, and another outbreak in 1911. The disease was recognized as contagious, but there was no understanding yet of exactly how it was spread. The first widespread outbreak, seriously affecting 26 states, occurred in 1916. About 7,000 deaths were recorded(176).

1907

Eduard Buchner (DE) was awarded the Nobel Prize in Chemistry for his discovery that fermentation can function independently of cell structure.

Charles Louis Alphonse Laveran (FR) was awarded the Nobel Prize in Physiology or Medicine "in recognition of his work on the role played by protozoa in causing diseases."

Paul Ehrlich (DE) had a fascination with dye affinity for specific cells going back to his days as a medical student at Strassburg. While there he devised a fuchsin stain which could demonstrate lead in the tissues. Later this concept would reemerge in his interest in affinity of antitoxins for toxins and drugs for target microbes, which led to his discovery of arsphenamine (Salvarsan), a cure for syphilis.

Ehrlich and his colleagues had discovered that the dye trypan red killed the trypanosome which causes sleeping sickness. Ehrlich kept looking for something better. He decided that the action of trypan red is caused by the nitrogen atom combinations it contains. Arsenic atoms resemble nitrogen atoms in chemical properties and, in general, introduce a more poisonous quality into compounds. By 1907 he and Sahachiro Hata (JP-DE) had synthesized 606 different compounds. Number 606, dihydroxydiamino-arsenobenzene hydrochloride, did not work very well against trypanosomes but later an assistant (H. Sachs) tested it against syphilis and found it to be deadly. It was called arsphenamine or Salvarsan; the latter being the name under which it was marketed. Today it is called arsphenamine. Ehrlich knew that dyes often exhibit exquisite specificity and reasoned that it might be possible to create a chemical which was very specific and toxic for a parasite and yet harmless to its host. He often referred to these chemicals as magic bullets. Ehrlich’s success represents the beginning of chemotherapy (a word he coined) as a laboratory science(3566-3574). 

Percival Hartley (GB), using liver tissue, was the first to isolate arachidonic acid(3575). 

Adolf Otto Reinhold Windaus (DE) and W. Vogt (DE) prepared histamine synthetically by the decarboxylation of histidine(3576). 

Friedrich Alfred Bauer (DE), Carl Alexander Neuberg (DE-US) and Benno Brahn (DE) discovered that inosinic acid contains a pentose(3577-3579).

A.V. Braun (DE) and Joseph Tcherniac (DE) prepared the phthalocyanine nucleus of a new class of dyes called the phthalocyanins from phthalimide and acetic andydride(3580). These did not find use as biological stains until 1950 when alcian blue was used to stain acid mucins(3581).

Walter Morley Fletcher (GB) and Sir Frederick Gowland Hopkins (GB) showed that, after being formed in muscular contraction, some lactic acid is oxidized to furnish energy for resynthesis of glycogen from the remaining lactic acid. They demonstrated rigorously that muscle contraction is accompanied by the anaerobic formation of lactic acid, which is removed aerobically, at a rate depending on the level of exposure to oxygen(3582).

Carl Franz Joseph Erich Correns (DE), gave the first experimental evidence that sex-difference behaved as a Mendelian character. The work was carried out using the dioecious plant, Bryonia where he found that the pollen was of two types, half male-determining, half female-determining, while the eggs, in respect to sex, were alike. The male was heterogametic, while the female was homogametic(3583).

Erwin Baur (DE) was the first to clearly demonstrate a lethal allele in Antirrhinum (snapdragon)(3584). 

Svante August Arrhenius (SE) enriched immunology by observing that antigen-antibody reactions obey the law of mass action, emphasizing quantification, encouraging mathematical and graphic evaluation, applying physics and coining the term immunochemistry(3585).

Eduard Pfuhl (DE) described how he had made use of the catalytic properties of spongy platinum to obtain anaerobic conditions for the culture of organisms(3586).

Sir Patrick Playfair Laidlaw (GB) suggested the use of platinized charcoal and colloidal platinum for the same purpose(3587).

James McIntosh (GB), Paul Gordon Fildes (GB), and William Bulloch (GB) developed the highly successful 'McIntosh-Fildes Jar'; an anaerobic jar(3588).

John Hanna Brewer (US) and J. Howard Brown (US) devised a safe method of accomplishing anaerobiosis for culturing microorganisms. It used an electrically heated platinized catalyst in a closed system with illuminating gas or hydrogen(3589).

John Hanna Brewer (US) devised a bacterial culture medium to which thioglycollate was added to maintain a reducing environment(3590).

The modern anaerobic jar is based on that originally described by J. Howard Brown (US) and later modified by John Hanna Brewer (US), Anita A. Heer (US), C. Baxter McLaughlin (US) and Daniel L. Aligeier (US) in which palladium is used to catalyze the reduction of oxygen with hydrogen generated from sodium borohydride and water(3591-3593).

Hans Molisch (CZ) pioneered in isolating and describing a number of species of non-sulfur purple photosynthetic bacteria in pure culture. He demonstrated conclusively that oxygen is not produced by such organisms and discovered the photoheterotrophic growth mode(3594).

Adolfo Ferrata (IT), Hans Ritz (DE), Arthur F. Coca (US), John Gordon (GB), Hugh Robinson Whitehead (GB), Arthur Wormall (GB), Herbert Joseph Rapp (US), A.B. Taylor (US), Myron A. Leon (US), Kusuya Nishioka (JP), William D. Linscott (US), Kozo Inoue (US), Robert A. Nelson, Jr. (US), Joerg Jensen (US), Irma Gigli (AR-US), Noboru Tamura (JP), Hans Joachim Müller-Eberhard (DE-US), Irwin H. Lepow (US), George B. Naff (US), Earl W. Todd (US), Jack Pensky (US), Carl F. Hinz, Jr. (US), and Anne L. Haines (US) made discoveries which revealed the numerous factors of the complement system in the blood(3595-3611).

Stanislas Josef Matthias von Provazek (AT) demonstrated that material from silkworms (Bombyx mori) suffering from the polyhedral disease which the breeders called jaundice was infectious after the polyhedra were removed by filtration through many layers of filter paper. This pointed the way to the eventual realization that some insect diseases are caused by viruses. In this same paper he suggested that viruses may someday be useful in controlling insect pests(3612). These are now considered Baculovirus.

Giuseppe Ciuffo (IT) realized the viral nature of genital warts when he induced warts after autoinoculation of cell-free wart extracts(3613).

Karl Bernhard Lehmann (DE) and Rudolf Otto Neumann (DE) started a formal manual for classification of bacteria in which for the first time staining reactions and the formation of the highly heat resistant endospores were considered formal diagnostic features(3614).

Raymond Jacques Adrien Sabouraud (FR) discovered that Epidermophyton inguinale can cause human dermatomycosis(3615).

Anatole Chauffard (FR) made original contributions to the understanding of the pathophysiology of the red cell abnormalities present in hereditary spherocytosis(3616). This work led him to develop the osmotic fragility of erythrocytes test which finally enabled physicians to distinguish hepatic and hemolytic jaundice. RBCs from hepatic jaundice are much more resistant to lysis than those from hemolytic jaundice patients.

Clarence Cook Little (US) produced the first inbred strain of mice by carrying out brother sister matings for over 20 generations. The animals chosen carried recessive genes for dilution, brown, and nonagouti. Today this strain is called DBA(3617). He also established the black C57BL inbred strain of mice.

It was Clarence Cook Little who, with funds from the Jackson and Ford families, established the Jackson Laboratory at Bar Harbor, Maine during the late 1920’s. This laboratory is one of the world’s most important sources of inbred animals for research.

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) proposed that human life could be prolonged by introducing bacteria into the diet which would compete with the proteolytic types present in the colon. He recommended that Bacillus bulgaricus, an organism he isolated from sour milk in Bulgaria, be used for this purpose. He found that if this organism was introduced in sufficient numbers it would replace the putrefactive bacteria normally present in the colon. He also determined that its growth was promoted by lactose(3618).

Ludwig Halberstäedter (DE-IL) and Stanislas Josef Matthias von Prowazek (AT) were the first to describe the inclusions (Halberstäedter –Prowazek bodies) found in cells of a trachoma infection. They thought the organism was closely related to the smallpox virus(3619, 3620).

Hideyo Noguchi (JP-US) established the etiology of trachoma when he isolated Bacterium granulosis from cases of trachoma then inoculated it into monkeys and obtained granulomatous lesions of the conjunctiva(3621).

Tang Feifan (), Yung T. Huang (), H.L. Chang (), K.C. Wong () were the first to isolate Chlamydia trachomatis as an etiological agent of trachoma(3622).

Erwin Frink Smith (US) and Charles O. Townsend (US) in describing Agrobacterium tumefaciens as the causative agent of crown gall in plants wrote the following: 

“For two years the writers have been studying a tumor or gall which occurs naturally on the cultivated marguerite, or Paris daisy. It has been difficult to isolate the organism and to demonstrate it unmistakably in stained sections. Recently the bacteria (seen in small numbers in the unstained tissues on the start) have been plated out successfully. With subcultures from poured plate colonies, thus obtained, the galls have been reproduced abundantly and repeatedly during the last few months, the inoculations having been made by needle-pricks. From galls thus produced the organism has been reisolated in axenic culture and the disease reproduced, using subcultures from some of the colonies thus obtained and puncturing with the needle as before. More than 300 galls have been produced by puncture inoculations. Under the most favorable conditions (young tissues) the swellings begin to be visible in as short a time as four or five days, and are well developed in a month, but continue to grow for several months, and become an inch or two in diameter.

In some of our experiments one hundred percent of the inoculations have given positive results (40 punctures out of 40 in one series; 62 punctures out of 62 in another), while the check plants have remained free from tumors, and also, in nearly every case, the check punctures on the same plant. In the two series just mentioned there were 110 check punctures on the same plants, all of which healed normally and remained free from galls. Old tissues are not very susceptible. The tumors grow rapidly only in young fleshy organs. The organism attacks both roots and shoots. It frequently induces abnormal growths on the wounded parts of young cuttings. Its power to produce hyperplasia is not confined to the marguerite. Well-developed small tumors have been produced in a few weeks on the stems of tobacco (Nicotiana tabacum), tomato and potato (Solanum tuberosum) plants and on the roots of sugar beets (Beta vulgaris). More interesting economically is the fact that galls closely resembling the young stages of crown-gall have been produced on the roots of peach trees by needle-pricks, introducing this organism. In eighteen days these growths have reached the size of small peas, the checks remaining unaffected. It is too early, perhaps, to say positively that the cause of the widespread and destructive crown-gall of the peach has been determined by these inoculations, but it looks that way. Of course, the most that can be affirmed absolutely at this writing is that we found an organism which when inoculated into the peach produces with great regularity galls which in early stages of their growth can not be distinguished from crown-gall. The matured daisy galls look astonishingly like the peach gall. Numerous experiments which ought to settle the matter definitely in the course of the next three months are now under way. In the best series of experiments on peach roots (that inoculated from a standard nutrient agar culture five days old) 14 groups of needle-punctures (5 in each group) were made on nine trees, 13 tumors resulting. The fourteenth group was on a weak tree which did not leaf out, and might therefore be left out of the count. In that case we have 100 per cent of infections. On the roots of nine young trees from the same lot, held as checks, 75 punctures were made, using a sterile needle, but no galls resulted. In another series of nine peach trees inoculated at the same time as the preceding and examined on the twenty-third day, 75 per cent of the punctures had yielded galls (9 tumors on 7 plants). These roots were inoculated by needle-pricks from a culture believed to be rather too old (glycerin agar streak 6 days), but the plants were set out again, and it is not unlikely that galls will finally develop on the roots of the other two plants. The plants, inoculated and uninoculated, were set, immediately after making the needle-punctures, in good greenhouse soil, in new ten-inch pots, and have been subject to the same conditions as to light, heat and water”(3623).

Rudolf Massini (DE) isolated a mutant strain of Escherichia coli that he called mutabile and that, in contrast to ordinary Escherichia coli strains, was unable to ferment lactose. The metabolic defect of this lactose-negative strain could be readily observed by plating the strain on a special sugar-utilization indicator medium called EMB agar. This agar contains a nutrient broth medium containing the dyes eosin yellow and methylene blue and the sugar whose fermentation is to be tested. On EMB agar, a bacterium able to ferment the sugar produces a dark red colony, whereas a nonfermenting bacterium produces a white colony. (The red and white colors reflect alternative states of the indicator dyes, which in turn signal the respective chemical changes produced in the agar during bacterial growth with or without fermentation of the test sugar.) Thus when the lactose-negative Escherichia coli mutabile is plated on EMB-lactose agar, its colonies are white. Upon prolonged incubation of these plates, however, isolated dark red spots or papillae, appear on the colonies. Upon picking and replating the bacteria present in the red papillae on EMB-lactose agar, Massini found that these bacteria had regained the capacity to ferment lactose—that is, they had become lactose-positive Thus during the growth of the colony initiated by a lactose-negative bacterium, mutations of the type lactose-negative tolactose-positive had taken place, and these gave rise to subclones of bacteria to which the capacity for lactose fermentation, characteristic of ordinary Escherichia coli had been restored(3624). In Massini’s day it did not seem possible to prove conclusively the genetic nature of these changes.

Edward Ernest Tyzzer (US) discovered Cryptosporidium, a coccidian protozoan parasite, in the gastric mucosa of mice(3625-3628).

F.A. Nime (), J. D. Burek (), David L. Page (US), Myron A. Holscher (US), John Howard Yardley (US), John Lawrence Meisel (US), David Rhodes Perera (US), Criss Meligro (US), and Cyrus E. Rubin (US) reported cases of Cryptosporidium parvum infections in humans(3629, 3630). From 1981 onward, numerous new cases began to be recognized in AIDS patients.

Ross Granville Harrison (US), Milton J. Greenman (US), Franklin P. Mall (US), and Clarence M. Jackson (US) cultivated amphibian spinal cord in a lymph clot, thereby demonstrating that axons are produced as extensions of single nerve cells(3631-3633) Some people consider this work as the origin of modern tissue culture (See Justin Jolly, 1898). 

Henry V. Wilson (US) demonstrated that if cells from two different species of sponges are teased apart then mixed together the cells recognize their own species, congregate together, and ignore the cells of the other species(3634).

Edward Babák (CZ) reported that the size of the external gills of the frog are increased by prolonged hypoxia and lessened by prolonged hyperoxia of ambient water(3635).

Alfred Wolff-Eisner (DE), in an attempt to explain the origin of contact-type immune reactions, proposed that dermatological problems result from the complexing of medications with the patient’s tissues (self)(3636). Later experiments would prove him correct.

Béla Schick (HU-AT-US) accurately postulated the immunological origin of the delayed sequelae to streptococcal infections, which include rheumatic fever and glomerulonephritis. Like serum sickness, they are part of a systemic Arthus-type reaction, and hence are diseases caused by circulating immune complexes(3637, 3638).

Ludvig Hektoen (US) described what would become the major and minor crossmatches for blood(3639). He later suggested that the safety of blood transfusions might be improved by crossmatching blood between donors and patients to exclude incompatible mixtures.

Reuben Ottenberg (US) performed the first human-to-human blood transfusion using blood typing and crossmatching. Over the next several years he successfully used the procedure in 128 cases, virtually eliminating transfusion reactions(3640).

Reuben Ottenberg (US) observed the Mendelian inheritance of blood groups and recognized the universal utility of group O donors(3641).

Ivar Wickman (DE) was the first to produce evidence confirming the infectious nature of poliomyleitis(3642).

Wilhelm Türk (AT) provided the first case description of complete agranulocytosis(3643).

Joseph Marek (HU) described a disease in adult cockerels which were affected by paralysis of the legs and wings. He called it neuritis interstitialis or polyneuritis(3644). There is little doubt that this is the first clinical description of what became known as Marek’s disease (MD). Poultrymen call it range paralysis.

Anthony E. Churchill (GB) and Peter Martin Biggs (GB) isolated a herpes virus associated with the disease and proved it to be the etiological agent(3645, 3646).

Maurice Ralph Hilleman (US) developed a vaccine to Marek’s disease. It became the first practical vaccine against a tumor disease of any type in any species(3647).

Simon Flexner (US) and James Wesley Jobling (US) produced a serum that remained the best treatment for cerebral spinal meningitis until the sulfa drugs were introduced(3648-3650).

George Hoyt Whipple (US) described a disease characterized by an accumulation of granular material in the walls of the small intestine and lymph nodes. He called it lipodystrophia intestinalis. Others would later name it Whipple’s disease(3651).

Chevalier Jackson (US) introduced the bronchoscope into the practice of medicine(3652). The introduction probably took place ca. 1899.

Arthur Robertson Cushny (GB) and Charles Wallis Edmunds (US) published the first case report of atrial fibrillation. The patient was 3 days post-operative following surgery on an "ovarian fibroid" when she developed a "very irregular" pulse at a rate of 120 - 160 bpm(3653).

Friedrich Jamin (DE) and Hermann Merkel (DE), published the first roentgenographic atlas of the human coronary arteries. It contained a study of 29 hearts in which the coronary arteries were injected with a suspension of red lead in gelatin(3654).

Thomas Peel Dunhill (AU) performed his first thyroid lobectomy under local anesthesia for toxic goiter. He advocated a bilateral attack on the thyroid and thyroidectomy in the thyrocardiac patient(3655).

Anton Freiherr von Eiselsberg (AT) performed  the first operation on a patient with adiposogenital syndrome(3656).

Sir William Arbuthnot Lane (GB) introduced the ‘no-touch technique’ in open reduction and plating of long bone fractures by “Lane's steel plates”(3657).

Anton Freiherr von Eiselsberg (AT) and Otto Marburg (AT) performed the first successful resection of an intramedullary spinal cord tumor in 1907(3658).

Alexander G. Ruthven (US) wrote a pioneering paper in ecology based on field studies in the American Southwest(3659).

Charles Henry Turner (US) was the first to prove that insects can hear and distinguish pitch and that cockroaches learn by trial and error(3660-3665).

Alfred Adler (AT) introduced the concept of inferiority complex and the method of compensation needed to overcome it(3666).

Lightner Witmer (US) coined the phrase clinical psychology(3667).

USDA's Pure Food and Drug Act became effective. The Pure Food and Drug Act of June 30, 1906, is a United States federal law that provided federal inspection of meat products and forbade the manufacture, sale, or transportation of adulterated food products and poisonous patent medicines(3668).

Archiv fur Geschichte der Medizin was founded.

1908

“Treasure  your exceptions! When there are none the work gets so dull that no one cares to carry it further. Keep them always uncovered and in sight. Exceptions are like the rough rock work of a growing building which tells that there is more to come and shows where the next construction is to be.” - William Bateson(3669).

Sir Ernest Rutherford (NZ-England) was awarded the Nobel Prize in Chemistry for his investigations into the disintegration of the elements, and the chemistry of radioactive substances.

Ilya Ilyich Mechnikov (RU-FR) and Paul Ehrlich (DE) were awarded the Nobel Prize in Physiology or Medicine "in recognition of their work on immunity."

William Sealy Gosset (GB) derived the statistical method that came to be known as Student’s t test. The test consists of rejecting a hypothesis if, and only if, the probability (derived from t) of erroneous rejection is small. Gosset published all his papers under the pseudonym Student(3670, 3671).

Sir Ernest Rutherford (NZ-GB), Johannes (Hans) Wilhelm Geiger (DE), and Thomas Royds (GB) proved that alpha particles are the equivalent of helium nuclei. They used a scintillation counter to determine that one gram of radium emits 37 million alpha particles per second. This quantity of alpha particles per second is now referred to as a curie(3672-3674). One million emissions per second is a rutherford.

Lawrence Joseph Henderson (US) formulated the theory of acid-base equilibrium in animal tissues(3675). Henderson later explained the respiratory function of the blood and demonstrated the quantitative relationships of eight blood variables(3676). 

Svante August Arrhenius (SE) pointed out that carbon dioxide in the atmosphere serves as a heat-trap, for it allows the high frequency sunlight to penetrate freely to the earth’s surface but is opaque to the low frequency infrared radiation which the earth reradiates at night. He also theorized that life began on earth when living spores had reached it across the emptiness of space (panspermia)(3677).

Richard Martin Willstätter (DE) and Arthur Stoll (CH) worked out the way in which the magnesium atom is placed in the chlorophyll molecule and showed that the iron atom is held in similar fashion in heme, the colored portion of the hemoglobin molecule. They determined the chemical composition of blue-greenish chlorophyll a as 137 atoms (C55H72N4O5Mg), and yellowish-green chlorophyll b as 136 atoms (C55H70N4O6Mg)(3678, 3679).

Richard Martin Willstätter (DE) and Ernst Hug (DE) were the first to separate chlorophyll –a, chlorophyll-b, carotin (carotene), and xanthophyll(3680).

Richard Martin Willstätter (DE) and Arthur Stoll (CH) discovered and named phytol (the major esterifying alcohol of chlorophyll at position 7 of the macrocycle), pheophorbide (chlorophyllide without the central Mg-atom), chlorophyllase (the enzyme that de-esterifies chlorophyll) and allomerization(3681).

Hans Fischer (DE) and Adolf Stern (DE) proposed a correct structure of chlorophyll, except for the position of the two extra hydrogens which are now recognized to be located on ring IV at positions 7 and 8 of the macrocycle(3682, 3683).

Hans Fischer (DE) and Hermann Wenderoth (DE) correctly assigned the two extra hydrogens of chlorophyll to positions 7 and 8 on ring IV(3684).

K. Noack (DE) and E. Schneider (DE) started the study of bacteriochlorophyll(3685).

Hans Fischer (DE), Robert Lambrecht (DE), and Hellmuth Miittenzwei (DE) established the chemical relationship of bacteriochlorophyll to chlorophyll by the preparation of common derivatives(3686, 3687). 

Phoebus Aaron Theodor Levene (RU-US) and Walter Abraham Jacobs (US) showed that the five-carbon sugar D-ribose is to be found in inosinic acid, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid. They established unequivocally that the arrangement of the three components of inosinic acid, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid is nitrogenous base-ribose-phosphate with the purine or pyrimidine connected to the sugar by a glycosidic linkage and the phosphate attached to the carbon 5 of the ribose by an ester linkage. They also discovered that mild hydrolysis of adenylic acid, cytidylic acid, uridylic acid, and guanylic acid yielded adenosine, cytosine, uridine, and guanosine. They named compounds such as inosinic acid, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid nucleotides, and compounds such as hypoxanthine, adenosine, cytosine, uridine, and guanosine, nucleosides They concluded (incorrectly) that intact nucleic acid is composed of the four nucleotides, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid in equivalent proportions to form a tetranucleotide(3688-3691).

Helen Dean King (US) saw the accumulation of amplified ribosomal RNA during pachytene in the American toad Bufo lentiginosus (= B. americanus) and its subsequent migration to the nuclear periphery as nucleoli(3692). Helen Dean King (US) led the development and production of the first line of standardized laboratory rats, known as Wistar Rats, produced between 1906 and 1940.

San Jose scale insect resistance to lime-sulfur was reported from orchards in the Pacific northwest. ref

Daniel Trembly MacDougal (US) wrote Botanical Features of North American Deserts which  contains geology, geography, physiology, ecology, the dominant flora, adaptive mechanisms of desert plants, and superb illustrations(3693). 

Charles Edward Spearman (GB) and G. Kärber (DE) developed a nonparametric procedure for computing an ED50 estimate (and fiducial limits) during drug research(3694, 3695). This became known as the "Spearman-Karber estimator", which is frequently used in drug screening.

 Julius Wohlgemuth (DE) described a method for measuring the concentration of amylase (diastase) in the serum, thereby introducing the potential for diagnosing acute pancreatitis prior to laparotomy or autopsy(3696).

Karl Landsteiner (AT-US) and Erwin Popper (DE) demonstrated that a filterable agent (virus) from a human case of poliomyelitis would cause paralysis if injected intraperitoneally into monkeys(3697, 3698). This was considered proof that poliovirus is the etiological agent of poliomyelitis.

Constantin Levaditi (RO-FR) and Karl Landsteiner (AT-US) were the first to isolate the poliomyelitis virus and were among the first to use monkeys in polio research(3699).

Robert Doerr (DE) reported that the virus of pappataci fever, also called sand-fly fever, phlebotomus fever, or three-day fever is transmitted by sand flies that have fed on the blood of patients with the fever(3700).

Clemens Peter Pirquet von Cesenatico; Clemens Peter Freiherr von Pirquet (AT) noted that the tuberculin skin test response of immune individuals is transiently depressed during the course of acute measles (rubeola) virus infection, from just prior to the rash until 7-20 or more days following its appearance(3701). This phenomenon is called virus-induced immunosuppression.

Martinus Willem Beijerinck (NL) demonstrated that Azotobacter is capable of fixing atmospheric nitrogen when it is grown in axenic culture(3702).

Jules Brunel (CA) related the antibacterial properties of the Penicillia through an anecdote told by Doctor A.E. Cliffe, a biochemist from Montreal. …”It was during a visit through Central Europe in 1908 that I came across the fact that almost every farmhouse followed the practice of keeping a moldy loaf on one of the beams in the kitchen. When asked the reason for this I was told that this was an old custom and that when any member of the family received an injury such as a cut or bruise, a thin slice from the outside of the loaf was cut off, mixed into a paste with water and applied to the wound with a bandage. I was assured that no infection would then result from such a cut”(3703). 

George Harrison Shull (US) used a Mendelian interpretation to explain the phenomenon of hybrid vigor and its association with plant productivity in corn (Zez mays). This represents the introduction of the concept of heterosis (superiority of heterozygotes) although the word was not used until 1914. George Harrison Shull (US) showed that self-pollination in corn, a naturally cross-pollinating plant, results in the isolation of inbred strains that are uniform and true breeding. Following Johanssen he called these pure lines. They are much less vigorous than the open-pollinated varieties from which they are derived. However, when two such lines are crossed, the F1 hybrids are uniform, like their inbred parents, but much more vigorous and in some cases more productive than the original open-pollinated varieties,. There is only one shortcoming: The hybrid seed is borne on the weak, unproductive plants of the inbred strains used as the female(3704-3706).

Donald Forsha Jones (US) solved this problem in 1917 when he invented the double-cross method of hybrid seed production. He crossed the single cross of two strains of Chester’s Leaming with a single cross of two strains of Burr White. Grown in 1918, this double cross yielded more than the best open-pollinated varieties(3707-3711) 

Donald Forsha Jones (US) made a significant contribution to hybrid corn production when he employed fertility-restoring genes to overcome cytoplasmic male sterility. This method employs hereditary factors in the cytoplasm to make male corn flowers sterile when sterility is an asset and uses heredity factors on the chromosomes to make it fertile when fertility is essential(3712-3714). A patent on using genetic restorers in hybrid-seed corn production was issued to Jones in 1956. It was the first patent on a genetic technique to be granted in the United States. ref

Marcus Morton Rhoades (US) was the first to describe cytoplasmic male sterility in corn. This represented the first instance in plants where a phenotype other than chlorophyll variegation was shown to be determined by cytoplasmic factors(3715).

Godfrey Harold Hardy (GB), and Wilhelm Weinberg (DE), independently formulated the theorem that in the absence of mutation and selection, the frequency of a gene in any large, randomly mating population will reach an equilibrium in one generation and remain in equilibrium thereafter regardless of whether the gene is dominant or recessive. Also, the genotypic frequencies of a population in equilibrium with two alleles with frequencies p and q are given by the formula p2 + 2pq + q2. This theorem forms the mathematical basis for population genetics(3208, 3716-3719). See, Karl Pearson, 1904.

Paul Jaccard (FR) devised the Jaccard index (Jaccard similarity index; Jaccard coefficient; coefficients of association) which provides numerical expression of taxonomic similarity based on presence-absence of species. It directly expresses the percentage of taxa shared between two collections(3720).

Carlo Moreschi (IT) observed that incubation of typhoid bacteria with a diluted (goat) anti-thyphoid serum did not lead to agglutination. However, bacterial agglutination could be induced by the addition of anti-goat serum, thus documenting the antiglobulin reaction which would later be explained by Coombs, et al(3721, 3722). See, Coombs, 1945. Although Moreschi did not realize it he had discovered weak or incomplete antibodies.

Vladimir Mikhailovich Bekhterev (Bechterev) (RU) described the superior nucleus of the vestibular nerve (Bekhterev's nucleus). ref

Note: In 1927 Bekhterev diagnosed Joseph Stalin with “grave paranoia.” Later that day Bekhterev suddenly died, causing speculation that he was killed by Stalin as revenge for the diagnosis. Moreover, after Bekhterev’s death, Stalin had Bekhterev’s name and all of his works removed from textbooks.

Korbinian Brodmann (DE) described 52 discrete cortical areas. He is responsible for establishing the basis upon which the present day science of comparative cytoarchitectonics of the mammalian cortex rests. All confusion of brain area nomenclature disappeared with Brodmann’s contribution(3723).

Konstantin von Economo; Konstantin Baron Economo von San Serff (AT) and Georg N. Koskinas (AT) revised Brodmann's cortical nomenclature of the cerebral cortex(3724).

Leon Abgarovich Orbeli (RU) showed that a change in the intensity of light could serve as a conditioned stimulus for a dog, even though the dog could not distinguish the color(3725).

John Mellanby (GB) described the inhibition of blood coagulation by oxalate and citrate(3726). This finding would prove to be immensely valuable for subsequent studies. Citrate is used for preservation of blood for transfusion.

Yandell Henderson (US) suggested that acapnia, or deficiency of carbon dioxide in the blood and tissues, is an important factor contributing to the depression of respiratory and circulatory activity which accompanies operation and anesthesia(3727).

Yandell Henderson (US), Felix Percy Chillingworth (US), and James Ryle Coffey (US) showed that acapnia (diminished carbon dioxide in the blood) may induce acute disturbance of the heart and failure of the peripheral circulation. These conditions resemble the functional depression of shock in patients after prolonged anesthesia and major operations. On the other hand it was found that if the carbon dioxide content of the body is conserved by partial rebreathing, the vitality of an animal, even under prolonged and extensive operation and trauma, is but little depressed(3728, 3729).

Yandell Henderson (US), Howard W. Haggard (US) and Raymond C. Coburn (US) carried their observations to the clinic and found that when inhalations of carbon dioxide (8%) in air were administered to patients after major surgical operations under open ether anesthesia, the effects were strikingly beneficial. With the return of deep breathing, the cyanosis then common after anesthesia disappeared. The cutaneous circulation improved. The skin changed in color and temperature, from blue-gray and cold to pink and warm. The volume of the pulse, previously thready, rapidly became full; and arterial pressure was restored to normal. Owing to the increased volume of breathing, the anesthetic (ether) was rapidly ventilated out of the blood and consciousness returned within a few minutes, even after profound anesthesia. Nausea and vomiting were either greatly reduced or entirely absent and after the inhalation the patient dropped off to sleep. In continuation of these observations, White found that when slow hemorrhage occurs after operations upon the brain, the rate of breathing gradually decreases until death is imminent. In several such cases life was saved by stimulation of respiration with inhalation of carbon dioxide(3730, 3731).

Yandell Henderson (US) pointed out the importance of acapnia, showed that fatal apnea could result from excessive forced breathing, and recommended the administration of carbon dioxide in conditions of shock, particularly in collapse due to anesthesia. He also pointed out that high altitude flying could produce decompression sickness or caisson disease(3732). Atelectasis of a lobe, or even a massive collapse of an entire lung, may develop.

Pol N. Coryllos (US) and George L. Birnbaum (US), on the basis of bronchoscopic investigations on dogs, considered lobar pneumonia to be a “pneumococcal atelectasis,” caused by an obstruction of a bronchus by the production of an excessive and sticky secretion. They demonstrated experimentally that pneumonia may develop if pathogenic organisms happen to be present because they find in an atelectatic lung conditions favorable to their growth(3733-3735).

Percy Theodore Herring (GB) thoroughly described hyaline or colloid masses (Herring bodies) scattered throughout the posterior lobe of the pituitary gland in both mammals and nonmammals. These nerve-end organs had first been reported by Harry J. Berkley (US)(3736, 3737).

Leo Buerger (US) described thromboangiitis obliterans (Buerger disease), a recurring inflammation and thrombosis (clotting) of small and medium arteries and veins of the hands and feet (3738).

George Coats (GB) described an exudative vasculopathy which became known as Coat’s Disease. It is neither inherited nor associated with systemic vascular abnormalities, but ocular disorders, such as retinitis pigmentosa, may be seen with retinal telangiectasia(3739).

Franklin Paine Mall (US) wrote A Study of the Causes Underlying the Origin of Monsters. Third Contribution to the Study of the Pathology of Human Embryos in which he concluded that every human egg has the possibility of becoming an abnormal embryo if the environment is unfavorable at critical times in its development. By monsters he simply meant embryos that had failed to develop in a normal way(3740, 3741).

Noël Fiessinger (FR) elucidated the histogenesis of cirrhosis. Showing that the course of the destruction is the same whatever the conditions, pathological or otherwise, which determine it(3742).

William Halse Rivers Rivers (GB) and Sir Henry Head (GB) set up experiments based on Head’s submitting to the division of his own left radial and external cutaneous nerves. Their findings of the loss and restoration thus brought about, led to a reclassification of the sensory pathways(3743).

Sir William Ernest Miles (GB) carried out the first abdominoperineal resection for cancer of the rectum; that is, the cancer was attacked both from the abdomen and from below through the perineum (the area between the anus and the genitals)(3744).

Friedrich Trendelenburg (DE) described his first unsuccessful pulmonary embolectomy in a human(3745). This operation became famous and is known as the Trendelenburg operation.

Martin Kirschner (DE), Trendelenburg’s student, surgically treated pulmonary embolism with more success(3746).

Sir Victor Alexander Haden Horsley (GB) and Robert H. Clarke (GB) developed the Horsley-Clarke system and apparatus for performing the so-called stereotactic surgery of the brain, whereby a set of precise numerical coordinates are used to locate each brain structure(3747).

Lars Leksell (SE) improved this apparatus considerably when he introduced his stereotactic instrument for human functional neurosurgery(3748).

Harvey Williams Cushing (US) developed surgical temporal decompression to relieve cerebral contusion and edema(3749).

Robert Mearns Yerkes (US) and John D. Dodson (US) found in their studies of the mouse that: 1) the rapidity of learning increases as the amount of difference in the brightness of the electric boxes between which the mouse is required to discriminate is increased, 2) the relation of the strength of electrical stimulus to rapidity of learning or habit-formation depends upon the difficultness of the habit, 3) the rapidity of learning increases as the strength of the electrical stimulus is increased from the threshold of stimulation to the point of harmful intensity, 3) when task discrimination is extremely difficult the rapidity of learning at first rapidly increases as the strength of the stimulus is increased from the threshold, but, beyond an intensity of stimulation which is soon reached, it begins to decrease, 5) as the difficultness of task discrimination is increased the strength of that stimulus which is most favorable to habit formation approaches the threshold(3750). 

Karl Grobben (AT) proposed a division of the animal kingdom into two great stems determined by the fate of the blastopore in the earliest stages of development. These two stems were Protostomia (annelids, arthropods, and molluscs) and the Deuterostomia (chordates, hemichordates, and echinoderms). He proposed the name Aschelminthes (Gk. ascos, cavity, helminth, worm) to replace Nemathelminthes(3751).

Amédée Bouyssonie (FR), Jean Bouyssonie (FR)  and Louis Bardon (FR) found skeletal remains of Homo sapiens neanderthalensis; Homo neanderthalensis near the village of La Chapelle-aux-Saints in France(3752). The remains are dated at ca. 60K B.P.

Otto Schoetensack (DE) described and named archaic forms of Homo sapiens uncovered by gravel pit workers in 1907 near Heidelberg in Germany. Estimated age is between 400,000 and 700,000 B.P. This find consisted of a lower jaw with a receding chin and all its teeth. The jaw is extremely large and robust, like that of Homo erectus, but the teeth are at the small end of the erectus range. They were named Homo heidelbergensis(3753). 

Arthur Smith Woodward (GB) described a more complete skull from the Broken Hill Mine, Kabwe, Zambia and named it Homo rhodesiensis: Homo sapiens rhodesiensis(3754). It is dated at late Middle Pleistocene; ca. 300,000 B.P.

George Henry Falkiner Nuttall (US-GB) founded and edited the journal Parasitology.

1909 

“There is no alleviation for the sufferings of mankind except veracity of thought and action, and the resolute facing of the world as it is, when the garment of make-believe, by which pious hands have hidden its uglier features, is stripped off.” Thomas Henry Huxley(3755).

Emil Theodor Kocher (CH) was awarded the Nobel Prize in Physiology or Medicine for his investigations on physiology, pathology, and surgery of the thyroid gland. He was one of the first surgeons to resect and unite the intestines.

Søren Peder Lauritz Sørensen (DK) suggested that chemists express hydrogen ion concentration as the negative logarithm (pH) of the molar concentration of the ion. A chemist, instead of speaking of a hydrogen ion concentration of 10-7 moles per liter, would speak of a pH of 7. This represents the introduction of the quantitative formulation of the concept of pH(3756).

Søren Peder Lauritz Sørensen (DK)  pointed out the effect of pH on enzyme activity(3757).

Lawrence Joseph Henderson (US) was the first to understand and express quantitatively the buffering effect of carbon dioxide and bicarbonate interacting with hydrogen ions in blood. Later Karl Albert Hasselbalch (DK) converted Henderson’s dissociation equations to the logarithmic form using the pH concept of Sørenson(3758, 3759). Lawrence Joseph Henderson (US) rewrote the laws of mass action for weak acids and their salts(3676).

Otto Wallach (DE) proposed the isoprene rule which states that chemicals can be considered terpenes if their molecular formulas have a carbon to hydrogen ratio of 5:8(3760, 3761).

Leopold Stefan Ruzicka (HR-CH), Jules Meyer (CH), Max Stoll (CH) and M. Mingazzini () demonstrated that isoprene is a structural unit of the terpenes. This was a reintroduction of the isoprene rule and helped in the understanding of the structure of turpentine oil, sesquiterpenes, diterpenes, triterpenes, squalene, cholesterol, and the bile acids(3762-3764).

Leopold Stefan Ruzicka (HR-CH), Albert Eschenmoser (CH), Oskar Jeger (CH), and Duilio Arigoni (CH) further refined the concept of the isoprene rule(3765, 3766).

Federico Battelli (IT) and Lina Salomonovna Stern (LT-CH-RU) reported their discovery that animal liver material can oxidize ethanol to acetaldehyde and acetic acid (and possibly other volatile acids). This represents the discovery of alcohol dehydrogenase(3767-3769).

Elmer Verner McCollum (US), in work with laying hens, found that all organic forms of phosphorus of biological importance could be synthesized in the animal body from orthophosphates in the food(3770). 

Archibald Vivian Hill (GB) and William Hartree (GB), using delicate thermocouples, discovered that contracting frog leg muscle fibers produce heat in two phases. Heat is first produced quickly as the muscle contracts. Then, after the initial contraction, further heat is evolved more slowly but often in greater amounts. Hill also showed that molecular oxygen is consumed after the work of the muscles is over but not during muscular contraction. Hill and C.L. Evans (GB) deduced that the heat liberated in the presence of contraction and recovery are not sufficient for the complete combustion of the lactic acid formed(3771-3775).

Wallace Osgood Fenn (US) studied the production of heat by muscle. In particular he showed that there is a fairly good quantitative relation between the heat production of muscles and the work which they perform, and that a muscle which does work liberates, ipso facto, an extra supply of energy which does not appear in any isometric contraction. (Archibald Vivian Hill (GB) referred to this as the Fenn effect.) Fenn’s heat data showed first of all that if a muscle shortens, no matter how little and no matter how lightly loaded, it produces more heat than during an isometric contraction over the same period. He then showed that this extra heat production is proportional to the external work done by the muscle. It was clearly not determined by load alone, nor by the change in length. This was the first evidence, and remains today the best evidence, that shortening is an active process and that muscle is not simply a prestretched spring shortening passively(3776, 3777).

Stanley Rossiter Benedict (US) developed Benedict’s reagent to test for reducing sugars(3778).

Otto Neubauer (DE) showed that in normal animal tissues amino acids are deaminated to their corresponding keto acids (e.g., alanine to pyruvic acid)(3779).

A.I. Ignatowski (RU) observed a possible relation between cholesterol-rich foods and experimental atherosclerosis(3780). See, Felix Jacob Marchand, 1904.

Adolf Otto Rheinhold Windaus (DE) showed that atheromatous lesions contain 6 times as much free cholesterol as a normal arterial wall and 20 times more esterified cholesterol(3781).

Nikolai Nikolaevich Anichkov; Nikolai Nikolajewitsch Anitschkow (RU-DE-RU) and Semen Sergejewitsch Chalatov (RU), using cholesterol-fed rabbits to produce experimental atherosclerosis, demonstrated that it was cholesterol alone that caused atherosclerotic changes in the rabbit intima(3782). English translation found in: Arteriosclerosis, 1983, 3: 178-182.

Jean De Meyer (BE) suspected, but did not prove, that a hormone was produced by the pancreatic islets of Langerhans. He suggested naming it insuline from the Latin word for island(3783).

Sir Edward Albert Schäfer (GB) predicted that the islands of Langerhans must secrete a substance which controls carbohydrate metabolism(3784).

Franciscus Alphonsius Janssens (BE) suggested that the chiasmata observed between synaptic chromosomes could be taken as observational evidence for the phenomenon of crossing over among linked genes, although he could not prove it(3785).

Klaus Peter (DE) reported that the loops of Henle are present in the kidney of mammals only, and that they are proportionally more developed in species living in a dry habitat and producing a concentrated urine(3786).

Keith Lucas (GB) and Lord Edgar Douglas Adrian (GB) published work on the all-or-none principle in nerve stimulation(3787-3789).

Carl Franz Joseph Erich Correns (DE) and Erwin Baur (DE) independently and in the same year proposed that inheritance of leaf color in Pelargonium zonale (geranium) and Mirabilis jalapa (the four-o’clock) respectively is due to genes carried in the maternal cytoplasm (non-Mendelian), perhaps in the chloroplasts. This was the first indication that mitochondria and chloroplasts may have their own genetic systems. Baur favored the idea that the plastids were the genetic determinants—the Plastom theory— while Correns favored the idea that the inheritance was carried by nonparticulate cytoplasmic material—non-Plastom theory(3790-3792).

Wilhelm Ludwig Johannsen (DK) suggested that Johann Gregor Mendel’s factors of inheritance be called genes from a Greek word meaning to give birth to by dropping the first syllable of the pangene of Darwin and de Vries and suggested that the genes “…may be tentatively considered to be chemical factors of various kinds….” Johannsen also introduced other terms such as phenotype and genotype(3793, 3794).

William Ernest Castle (US) and John C. Phillips (US) performed an experiment which was important to the demise of the concept of acquired characteristics and the notion that the genotype of body cells might in some way influence the genotype of germ cells. They transplanted the ovary from a pure line of black (recessive) guinea pigs into an albino recipient. The albino foster mother when mated to an albino male bore three litters consisting entirely of fully black offspring. No influence of the albino foster mother, in whose body the eggs had been produced, could be seen(3795). 

Muriel Wheldale(GB) was the first to attempt to understand the events relating gene to phenotypic expression. She investigated flower color mutants and the pigments produced in several species(3796).

Hubert Dana Goodale (US) demonstrated that the barred plumage pattern of Plymouth Rock fowls is inherited in a sex-linked mode(3797).

Nils Herman Nilsson-Ehle (SE) analyzed the inheritance of color in wheat and found that three different gene pairs R1r1, R2r2, and R3r3 were segregating, each pair acting in the same way on the same quality, seed-coat color. The effects of the different pairs were additive R1R1R2R2r3r3 being redder than R1R1r2r2r3r3(3798).

This work along with that of Edward M. East (US) showed that continuous hereditary variation could be explained by discontinuous genetical variations (i.e., genes altered by mutation)(3799).

Richard Woltereck (DE) performed experiments which probed the interaction of genotype and environment. He studied quantitatively varying and readily measurable characters, chiefly head form within and between pure lines of the micro-crustacean, Daphnia (3209). 

Albert A. Epstein (US) and Reuben Ottenberg (US) pointed out that the human blood groups (A, B, O) are inherited in accord with Mendelian principles(3800).

Emil von Dungern (DE) and Ludwik Hirszfeld (PL) proposed that the heredity of the ABO blood group system depends on two independently segregating loci with allele pairs A, a and B, b respectively(3801).

Lewis Ralph Jones (US) demonstrated bacterial pectolytic exoenzymes for the first time(3802). This led to an understanding of bacterial soft rot.

Paul Ehrlich (DE) was the first to propose that immune mechanisms are involved in protection against aberrant cells from within the organism itself when he said, “I am convinced that during development and growth malignant cells arise extensively and frequently but that in the majority of people they remain latent due to the protective action of the host. I am also convinced that this natural immunity is not due to the presence of antimicrobial bodies but is determined purely by cellular factors. These may be weakened in the older age groups in which cancer is more prevalent”(3803, 3804). This can be considered the origin of immune surveillance. See Lewis Thomas, 1959.

Richmond T. Prehn (US) and Joan M. Main (US) showed that tumors induced by chemical carcinogens in mice can stimulate tumor-specific responses that are able to reject those same tumors on challenge. They concluded that tumor immunity was induced by antigens unique to the chemically-induced tumor, but found that spontaneously arising tumors were not rejected when tested in the same experimental manner(3805).

Ludwik Gross (US), Edgar J. Foley (US), Richmond T. Prehn (US) and Joan M. Main (US) demonstrated that mice can be rendered resistant to tumor transplantation by preimmunization with the same tumor(3805-3807).

Aline van Pel (BE) and Thierry Boon (BE) reported that specific immunity to spontaneous tumors can be induced by vaccinating mice with mutagenized tumor cells. Their study showed that spontaneous tumors are not inherently deficient in tumor antigens, but instead failed to stimulate an effective immune response(3808).

Pierre van der Bruggen (BE), Catia Traversari (IT), Patrick Chomez (BE), Christophe Lurquin (BE), Etienne De Plaen (BE), Benoit Van den Eynde (BE), Alex Knuth (DE), and Thierry Boon (BE) reported the first identification of a tumor-specific antigen recognized by cytolytic T cells in humans, reinforcing the idea that tumor antigens can elicit a detectable tumor-specific response(3809).

Ward J. McNeal (US), Lenore L. Latzer (US), and Josephine E. Kerr (US) investigated the bacteriacidal effects of gastric juice and found that it killed nearly all bacteria which pass through the stomach(3810).

Max Einhorn (PL-US) invented the duodenal tube for aspirating contents of the intestine below the pylorus(3811, 3812).

Janus von Bókay (AT) proposed that there is a relationship between varicella (chickenpox) and herpes zoster (shingles)(3813).

Karl Kundratitz (DE) demonstrated that varicella (chickenpox) and herpes zoster are caused by the same infectious agent(3814).

Joseph Garland (US) hypothesized that herpes zoster might become manifest as immunity to the varicella-zoster-virus (VZV) waned(3815).

Thomas Huckle Weller (US) and Marguerite B. Stoddard (US) isolated viruses from chickenpox and herpes zoster to confirm this relationship(3816).

R. Edgar Hope-Simpson (GB), after studying numerous cases of varicella and zoster, supported Garland’s hypothesis(3817). 

Sigurd Orla-Jensen (DK) emphasized the importance of physiological characteristics in a logical classification of bacteria. Organisms were assigned to genera using a combination of morphological and physiological characters(3818). 

Charles Jules Henri Nicolle (FR), Charles Compte (FR) and Ernest Conseil (FR) discovered that typhus fever is transmitted from person to person by the body louse, Pediculus vestimenti(3819, 3820).

John McFadyean (GB) and Stewart Stockman (GB) discovered that the microaerophilic campylobacters (formerly Vibrio fetus) can cause abortion in cattle and sheep(3821).

Charles Jules Henri Nicolle (FR) and Louis Herbert Manceaux (FR) discovered and described Toxoplasma gondii as the causative agent of a disease in the gondi (Ctenodactylus gondi), a small North African rodent. They named it toxoplasmosis. Toxaplasma is from the Greek toxón, a bow or arc, and gondii from the name of the rodent(3822).

Alfonso Splendore (BR) described the same disease the same year in laboratory rabbits(3823). 

Josef Janku (CZ) was the first to definitively recognize the parasite, Toxoplasma gondii, in humans(3824, 3825).

Arne Wolf (US) and David Cowen (US) established that an association exists between Toxoplasma gondii and human congenital disease(3826). This association was followed by the realization that T. gondii rarely causes disease even though it is a very common parasite of adults but that in pregnant women the parasite can cross the placenta and can damage the fetus.

William McPhee Hutchison (GB), J. Findlay Dunachie (GB), J. Chr Siim (DK), and Kresten Work (DK) worked out the life cycle of Toxoplasma gondii and the role of the domestic cat in transmission of toxoplasmosis(3827-3829).

Theobald Smith (US) discovered that immunity to diphtheria can be generated in guinea pigs by giving them a mixture of diphtheria toxin and antitoxin (antibodies to the toxin). The toxin alone is so potent that only trace amounts are harmful to the animals (3830).

Karl Bogislaus Reichert (DE) determined optimum conditions for visualizing moving flagella and described them in great detail(3831).

Benjamin Minge Duggar (US) wrote Fungous Diseases of Plants, with Chapters on Physiology, Culture Methods and Technique which was the first plant pathology text published in America(3832).

Ernst Lowenstein (AT) discovered that formaldehyde treatment could be used to convert toxins into relatively inert but still antigenic toxoids(3833).

Richard Richter (DE) was the first to publish concerning a intrauterine device (IUD). The device he inserted was a ring made of silkworm gut, with 2 ends which protruded from the cervical os enabling him both to check the device and remove it(3834).

Herbert McLean Evans (US) determined that during embryonic development in vertebrates the aorta, cardinal and umbilical veins, and other large blood vessels begin as a network of capillaries(3835).

Simeon Burt Wolbach (US) and Tadasu Saiki (JP) have shown that anaerobic bacteria are almost always present in aseptically-removed dog livers. They mention that the presence of these bacteria may account for many of the changes occurring in so-called autolysis of aseptically-removed liver. These pathogenic anaerobic bacteria are typically of the Bacillus welchii (Clostridium welchii) type(3836).

Frank Charles Mann (US) noted, in 1923, that if these fragments were allowed into the peritoneal cavity during surgery that a serious peritonitis was likely to follow. ref

Lester Reynold Dragstedt (US) and James C. Ellis (US) proved that Mann was correct(3837, 3838).

Lester Reynold Dragstedt (US), H.E. Haymond (US), and James C. Ellis (US) demonstrated that the pancreas contains the pathogenic anaerobic Clostridium welchii(3839).

Léon Charles Albert Calmette (FR), Jean-Marie Camille Guérin (FR), Benjamin Weill-Hallé (FR), Alfred Bouquet (FR), Leopold Nègre (FR), Wilbert (FR), Marcel Léger (FR), and Raymond Turpin (FR) developed a bovine strain of tubercle bacillus which was rendered completely avirulent by 230 transfers over 18 years (1906-1924) on bile-glucose-potato medium. This strain is designated as BCG (Bacille-Calmette-Guérin) and is widely used outside the U.S.A. as a vaccine for tuberculosis in cattle and man(3840-3844).

Carlos Ribeiro Justiniano Chagas (BR) gathered preliminary evidence that South American trypanosomiasis or Chagas’ disease is caused by Schizotrypanosome (Trypanosoma) cruzi and transmitted by the Reduviid bug of the genus Triatoma. He proved it in 1916(3845-3847).

Alexandre Joseph Emilé Brumpt (FR) demonstrated transmission of South American trypanosomiasis or Chagas’ disease via the fecal route of the Reduviid bug(3848).

Fritz Köberle (AT-BR) established the links between infection with Trypanosoma cruzi and the various signs of Chagas' disease, such as distended colon and esophagus and cardiac failure(3849).

Carlos Ribeiro Justiniano Chagas (BR) and Antonio Carini (IT-BR) described Pneumocystis from humans but mistook it as a stage in the life cycle of a trypanosome. Chagas placed it in a new genus, Schizotrypanum(3850, 3851).

Antonio Carini (IT-BR) observed cysts in rats with experimental trypanosomiasis, but suspected the cysts were from an unknown organism. He sent samples to his colleague, Charles Louis Alphonse Laveran (FR), for further examination. In 1912, Laveran's students, Pierre Delanoe (FR) and Maria Delanoe (FR), found similar cysts restricted to the lungs of trypanosoma-free sewer rats, and named the new organism Pneumocystis carinii(3852).

J. Wätjen (DE) was the first to render a clinical description of the pulmonary pneumocystosis associated with Pneumocystis carinii(3853).

Otto Ammich (DE) and Everett Smith Beneke (US) established pulmonary pneumocystosis as a definite clinicopathologic entity(3854, 3855).

M.G. van der Meer (NL) and S. Li Brug (NL) described Pneumocystis carinii as the infecting organism in a 3-month-old infant with congenital heart disease and in 2 of 104 autopsy cases (a 4-month-old infant and a 21-year-old adult). This paper contains the first light microscopy photographs of Pneumocystis trophic and cystic forms in human beings(3856).

Christian Georg Schmorl (DE) showed that the first sign of healing in rachitic children is the reformation of the provisional zone of calcification on the epiphyseal side of the metaphysis(3857).

Karl Bruno Stargardt (DE) described familial juvenile macular degeneration (Stargardt macular dystrophy) which is the most frequently encountered juvenile onset macular degeneration(3858).

Thomas Lewis (GB) described atrial fibrillation in considerable detail. He also discussed pulsus alternans, the alternating pulse, which usually meant death was close at hand(3859-3862).

Charles Rupert Stockard (US) studied the effects of chemicals on embryologic development and produced cyclopia and other monstrosities by the use of lithium and other agents(3863, 3864).

Harvey Williams Cushing (US) was the greatest neurosurgeon of the twentieth century and the first to devote himself entirely to surgery of the brain. He authored The Pituitary Body and its Disorders. His contributions to neurosurgery were numerous, among which was his analysis of the function of the human brain by stimulating motor and sensory areas while patients were under local anesthesia. These studies provided for the first time direct evidence that irritation of the post-central gyrus gives rise to sensations like those which precede epileptic attacks. He distinguished between excess function of the anterior lobe of the pituitary (as in gigantism and acromegaly) and deficiency of its function (as in dwarfism and Frohlich's asexual adiposity)(3865-3867).

Philip Edward Smith (US), Herbert McLean Evans (US), Miriam E. Simpson (US), Karl Meyer (US), Frederick L. Reichert (US), Alexander J. Szarka (US), Richard I. Pencharz (US), Robert E. Cornish (US), and Paul R. Austin (US), working with rats and dogs, found that the anterior pituitary gland produces a substance or substances which stimulate sleletal growth with weight increase, increase the size of the viscera(somatotropin or growth hormone/GH), and promote activity of the adrenal cortex (adrenocorticotropic hormone/ACTH), thyroid gland (thyrotropic stimulating hormone/TSH), and gonads (luteinizing hormone/LH or interstitial cell-stimulating hormone/ICSH and follicle stimulating hormone/FSH)(3868-3871).

Carl Richard Moore (US) and Dorothy Price (US) discovered that a substance from the anterior pituitary lobe stimulates the gonads (luteinizing hormone/LH or interstitial cell-stimulating hormone/ICSH and follicle stimulating hormone/FSH) and in turn the gonads produce a substance which depresses the production of the pituitary substance(3872). This is historically one of the earliest known examples of a biologic feedback mechanism.

James Bertram Collip (CA), Evelyn Mary Anderson (CA), and David Landsborough Thomson (GB-CA) had by 1933 found that separate substances from the anterior pituitary regulate the adrenal cortex (adrenocorticotropic hormone/ACTH) and the thyroid gland (thyroidstimulating hormone/TSH). See Collip, 1933.

Fuller Albright (US), William Parson (US), and Esther Bloomberg (US) unraveled the pathogenesis of Cushing’s syndrome(3873, 3874).

Wilder Graves Penfield (US-CA), Lyle Gage (CA) and Edwin Boldrey (CA) confirmed Cushing’s studies on electrical stimulation of the brains of epileptics(3875, 3876).

Hermann Oppenheim (DE), and Fedor Krause (DE),  in1908, were the first to successfully remove an intervertebral disc from a human(3877).

John Jacob Abel (US) founded the Journal of Pharmacology and Experimental Therapeutics.

Albert J. Cook (US) founded the Journal of Entomology which became the Journal of Entomology and Zoology in 1913.

1910

"Enough has been advanced here to make it extremely probable that the inorganic composition of the blood plasma of vertebrates is an heirloom of life in the primeval ocean." Archibald Byron Macallum(3878).

Johannes Diderik van der Waals (NL) was awarded the Nobel Prize in Physics for his work on the equation of state for gases and liquids.

Albrecht Karl Ludwig Martin Leonard Kossel (DE) was awarded the Nobel Prize in Physiology or Medicine in recognition of the contributions to our knowledge of cell chemistry made through his work on proteins, including the nucleic substances.

H. Lehmann (DE) developed a filter which when placed in front of an iron arc lamp produced a beam rich in ultraviolet light. Lehmann knew of the more primitive nitrosodimethylaniline dye UV filter made by Robert Wood (US) in 1903(3879).

Siegfried Ruhemann (GB) produced triketohydrindene hydrate (ninhydrin) then discovered its reaction with amines to form the colored reaction product known as Ruhemann's purple(3880). The reaction of amines, amino acids, peptides and related compounds with ninhydrin has found extensive use in the qualitative and quantitative analysis of such compounds in chemistry and biochemistry.

George Barger (GB) and Sir Henry Hallett Dale (GB) derived and isolated histamine from ergot by the chemical decarboxylation of the amino acid histidine. They found that beta-phenylethanolamine derivatives simulated the effects of sympathetic nerve stimulation with varying degrees of intensity and precision, and they coined the term sympathomimetic amines(3881). Amphetamine, methamphetamine, and mescaline are well known sympathomimetic amines.

Sir Henry Hallet Dale (GB) and Sir Patrick Playfair Laidlaw (GB) in their studies on the effects of histamine on the circulation observed the similarity between the physiological effects of histamine and the symptoms of anaphylaxis(3882).

Sir Henry Hallet Dale (GB) and Alfred Newton Richards (US) found that histamine effects blood pressure by causing dilatation of peripheral capillaries and small arterioles(3883).

Jakub (Jacob) Karol Parnas (PL) reported that an aldehyde mutase present in animal tissues can catalyze the conversion of an aldehyde into the corresponding alcohol and acid, indicating that this dismutation involves a process in which one molecule of the aldehyde is acting as the hydrogen acceptor (to form the alcohol) and the other as the hydrogen donor (to form the acid). This concept was rapidly accepted as an explanation for some of the molecular behavior in alcoholic fermentation(3884).

Gustav Georg Embden (DE) discovered that if a dog’s liver is perfused with alpha-keto acids and ammonia it converts them to the corresponding amino acids. This provided evidence of a metabolic linkage between proteins, carbohydrates, and fats. ref

Graham Lusk (US) showed that the animal body can convert glycine, alanine, glutamic acid, and aspartic acid into glucose(3885).

Francis Gotch (GB) described a refractory phase between nerve impulses(3886). 

Schack August Steenberg Krogh (DK) proved that the mechanism of gas exchange in the lungs is uniquely explained by the physical forces of diffusion(3887).

Jean Eugene Bataillon (FR) discovered that it is possible to trigger the frog's egg development by pricking it with a needle dipped in serum(3888).

Archibald Byron Macallum (CA) found a close resemblance between the ionic composition of blood sera and that of sea water and suggested that tissue cells can only live within a relatively narrow range of physiochemical conditions—conditions which represent those of the ancient ocean in which cells of ancestral organisms arose(3878, 3889). 

Gustav Georg Embden (DE) and Hermann Tachau (DE) discovered the presence of free amino-acids in human sweat when they isolated serine from this secretion(3890).

Léon Ambard (FR) defined his law of urea output. With the urinary urea concentration constant, the output of urea varies directly as the square of the concentration of the blood urea. With the blood urea concentration constant, the output of urea varies inversely as the square root of the urinary concentration(3891).

Samuel James Crowe (US), Harvey Williams Cushing (US), and John Homans (US) provided the first experimental evidence of the relationship between the pituitary gland and the reproductive system(3892).

Kurt Goldstein (DE-US) charted the course of the lateral spinothalamic tract to its termination and demonstrated the phylogenetic development of the diencephalon(3893). ref on diencephalon

Harry B. Shaw (US) found that the beet leafhopper (Euttetix tenellus) is an insect vector for sugar beet (Beta vulgaris) curly-top virus(3894). First known example of insect transmission of a plant virus.

Howard Taylor Ricketts (US) and Russell M. Wilder (US) described a bacterium, later named Rickettsia prowazekii, found in the gut of lice feeding on typhus patients(3895, 3896). 

Nathan Edwin Brill (US) described 221 cases of what was probably recrudescent epidemic typhus in the New York area(3897). This has been called Brill’s disease, as though it were a new entity, but Hans Zinsser (US) demonstrated that it is identical to Old World typhus caused by Rickettsia prowazeki da Rocha Lima(3898-3901). The disease was renamed Brill-Zinsser’s disease.

William D. Frost (US) presented arguments in favor of the use of dehydrated media to culture microorganisms. This is the earliest reference, in America, to the preparation and use of dehydrated media(3902).

Dankwart Ackermann (DE), using defined media, showed that bacteria can produce putrescine from ornithine and cadaverine from lysine(3903-3906).

Sir Ronald Ross (GB) and David Thomson (GB) demonstrated antigenic variation in African trypanosomes(3907).

John E. Donelson (US) and Mervyn J. Turner (GB) determined how antigenic variation is accomplished by the trypanosomes(3908).

Aldo Castellani; Count of Chisiamaio (IT) discovered that Endodermophyton concentricum can cause human dermatomycosis(3909).

Helmut Bruchmann (DE) was the first to obtain spore germination leading to mature prothalli in a species of Lycopodium(3910).

Ernst Küster (DE) demonstrated the ability of onion epidermal protoplasts to fuse upon de-plasmolysis(3911).

Theodor Boveri (DE) demonstrated the direct influence of the cytoplasm on the nucleus in Ascaris. Either by dispermy or by centrifugation of eggs and shifting the plane of the spindle through 90 degrees, he brought two nuclei, instead of only one, into the proximity of a particular part of the cytoplasm. The result was that the chromosomes exhibited a peculiar visible behavior at one pole and not at the other(3912). 

Ludwig Plate (DE) is credited with coining the term pleiotropy, i.e., a single gene or allele which may produce two or more characters (traits) which are not obviously related(3913, 3914). This was the 4th edition.

Thomas Hunt Morgan (US) initiated the use of the fruit fly, Drosophila melanogaster (black-bellied honey lover) for genetic research and described the important discovery of a sex linked character in these animals as follows: “In a pedigree culture of Drosophila which had been running for nearly a year through a considerable number of generations, a male appeared with white eyes. The normal flies have brilliant red eyes. 

The white-eyed male, bred to his red-eyed sisters, produced 1,238 red-eyed offspring, (F1), and three white-eyed males. The occurrence of these three white-eyed males (F1) (due evidently to further sporting) will, in the present communication be ignored.

The F1 hybrids, inbred, produced: 2,459 red-eyed females, 1,011 red-eyed males, 782 white-eyed males. No white-eyed females appeared. The new character showed itself therefore to be sex limited in the sense that it was transmitted only to the grandsons.” It was in his 1910 review that Morgan articulated the view that chromosomes consisted of linear arrangements of genes in an order that could be mapped by experimental breeding methods(3915, 3916).

Calvin Blackman Bridges (US) is given credit for discovering the white-eyed Drosophila mutant in Morgan’s laboratory(541).

Erwin Baur (DE) described the first sex-linked plant gene. It was a mutant of Silene alba (Melandrium album) with narrow leaves. He could prove that this feature is sex-linked(3917).

Montrose Thomas Burrows (US) was the first to grow chick embryo tissue in cell culture by placing explants in hen plasma clot hanging drops where connective tissue, muscle cells, and nerve cells were observed to proliferate(3918).

Alexis Carrel (FR-US) and Montrose Thomas Burrows (US) grew a variety of adult tissues taken from a variety of species in cell culture. They observed that initially the new cells were differentiated and represented the tissue types of origin, however, as the tissues aged they eventually contained dividing cells of only two types, one resembling connective tissue cells, and the other epithelial cells(3919).

Alexis Carrel (FR-US) and Montrose Thomas Burrows (US) were the first to grow tumor tissue in vitro. The tissue was Rous sarcoma(3920).

Francis Peyton Rous (US) demonstrated that a spindle-cell sarcoma in Plymouth Rock chickens was caused by an agent which passed through filters stopping bacteria. Rous was reluctant to pronounce it a virus. Today this virus is called the Rous sarcoma virus and was the first of the tumor viruses to be demonstrated(3921-3924). See Ellermann and Bang, 1908.

Francisco Duran-Reynals (ES-US) proved that the Rous sarcoma - the cell-destroying virus of chicken cancer - was not confined to chickens but could leap the so-called species barrier and incite cancers in ducks and turkeys. Indeed, the virus sometimes gained virulence as it passed from one species to another. He showed how a virus could lie dormant for many years before inciting cancer(3925, 3926).

John Zahorsky (US) was the first to recognize exanthem subitum (roseola infantum, roseola subitum) as a separate clinical entity which occurs almost exclusively in infants and young children(3927).

Arvid Afzelius (SE) reported on a severe bulls-eye shaped skin rash that followed bites of the tick Ixodes ricinus(3928, 3929). There is little doubt that the condition he named erythema chronicum migrans is synonymous with Lyme disease. It has also been called Afzelius’s disease. Borrelia afzelii, one of the borrelia species that is an agent of Lyme disease, is named in his honor

James Bryan Herrick (US) gave the first description of sickle cell anemia when he found "peculiar, elongated and sickle-shaped red blood corpuscles" in the blood of a 20 year old black patient with symptoms of severe anemia. He did not use the phrase sickle cell anemia(3930).

Isaac Ott (US) and John C. Scott (US) discovered that an extract from the posterior pituitary gland can behave as a galactogogue (an agent that promotes the flow of milk or lacteal secretion)(3931).

Isaac Ott (US) and John C. Scott (US) were the first investigators to demonstrate that the corpus luteum is a rich source of oxytocin. These researchers reported that an aqueous extract of the corpus luteum when injected into a goat, stimulated immediate milk flow(3932).

Alfred Fröhlich (AT) and Lothar von Frankl-Hochwart (AT) concluded that obstetricians and urologists could consider pituitrin (a proprietary preparation of the posterior lobe of the pituitary gland) as essentially non-toxic and safe to use in therapeutically stimulating the contraction of the uterus(3933).

Walter Lee Gaines (US) discovered that pituitrin causes contraction of smooth muscle of the milk passages in the mammary gland(3934).

Noël Fiessinger (FR) and Pierre-Louis Marie (FR) demonstrated the existence of enzymes in the white cells of the blood, and showed that these cells, according to their type, contain either protease or lipase. The presence of protease accounts for the dissolution of internal blood clots or purulent collections, while lipase weakens the lipidic membrane of the Koch bacilli, thus permitting their attack by the protease-carrying white cells(3935, 3936).

John Auer (US) and Paul Adin Lewis (US) gave the first adequate account of the physiological reactions leading to fatal anaphylactic shock(3937).

Corrado Donato Da Fano (GB) and James B. Murphy (US) gave experimental evidence that the destruction of a graft of foreign tissue is carried out by the hostile activities of the recipient’s lymphoid cells(3938-3942).

Samuel James Meltzer (DE-US) concluded that bronchial asthma is due to anaphylaxis, although he did not appreciate that all cases of asthma are so caused(3943).

Sir Berkeley George Andrew Moynihan (GB) offered a methodology to distinguish duodenal from gastric ulcer, “In the differentiation from gastric ulcer there is, as a rule, no great difficulty. If pain after food does not appear for two hours or more, it may be said with reasonable confidence that the ulcer is in the duodenum…. If pain appears early, within an hour or so, the ulcer is certainly in the stomach, probably on the lesser curvature…. The period of relief from pain conferred by the taking of a meal is then the first and a chief point to be considered in the differential diagnosis”(3944).

Samuel J. Mixter (US) and Robert Bayley Osgood (US) performed the first successful surgical stabilization of atlanto-axial (C1-C2) instability(3945).

Alexis Carrel (FR-US) reported a series of experiments that constitute the earliest forms of direct coronary artery bypass, by anatomizing the innominate artery of one dog into distal coronary of another and also by using a free carotid autograft between descending thoracic aorta and distal coronary artery. This was presented before the American Surgical Association in 1910 where he stated, unfortunately the operation was too slow. 3 minutes after the interruption of the circulation, fibrillary contraction appeared, but the anastomoses took 5 minutes. By massage the dog was kept alive, but he died 2 hours later. His experiments with animals were the precursor to the bypass operations of modern human surgery, including the Blalock-Taussig shunt(3946).

Hans Christian Jacobaeus (SE) described his endoscopic investigations of the abdominal cavity of man(3947-3949).

Sir Marc Armand Ruffer (GB) found Schistosoma haematobium eggs in two Egyptian mummies dating from the 20th dynasty, 1250 to 1000 B.C.E.(3950). This finding is generally regarded as the beginning of paleoparasitology.

Max Schlosser (DE) conducted further excavations of Oligocene primate remains from the Fayum of Egypt(3951). 

The Rockefeller Institute Hospital opened its doors, becoming the first clinical research hospital in the United States.

The regulation of pesticides by the United States federal government began in 1910 with the passage of the Federal Insecticide Act by Congress. This act was passed in response to concerns from the United States Department of Agriculture (USDA) and farm groups about the sale of fraudulent or substandard pesticide products. Congress subsequently enacted the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) of 1947 that, broadened the federal government's control of pesticides. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) of 1972 was later enacted.

The Journal of Genetics was founded.

1911

Marie Sklodowska Curie (PL-FR) was awarded the Nobel Prize in Chemistry in recognition of her services to the advancement of chemistry by the discovery of the elements radium and polonium, by the isolation of radium and the study of the nature and compounds of this remarkable element.

Allvar Gullstrand (SE) was awarded the Nobel Prize in Physiology or Medicine for his work on the dioptrics of the eye. He elucidated how the eye accomplishes intracapsular accommodation.

Frederick Soddy (GB) introduced the term isotope and the concept that it represents a variation on the common atom of an element. The isotope possessing a number of neutrons different from that found in the atom most common to the element(3952, 3953). Radioactive isotopes have proved to be of great importance in biological research because they make it possible to trace the course of various elements in living organisms. 

Fritz Pregl (Slovenian-AT) developed techniques and equipment which laid the foundation of microchemistry(3954).

Carl Alexander Neuberg (DE-US) and Ladislaus Karczag (DE), in 1910, discovered that pyruvic acid is broken down into carbon dioxide and acetaldehyde by all yeasts that ferment hexoses as well as by the enzyme preparations (carboxylase) prepared from the former(3955). Note: This is the first success in the search for intermediary products.

Otto Neubauer (DE) and Konrad Fromherz (DE), from their studies on yeast, postulated that the deamination of alanine would yield pyruvic acid, whose decarboxylation would yield acetylaldehyde, which might be reduced to ethanol. They proposed that pyruvic acid might be intermediate in the alcoholic fermentation(3956).

Carl Alexander Neuberg (DE-US), Arnold Hildesheimer (DE), and L. Tir (DE) isolated the enzyme pyruvate carboxylase which catalyzes the decarboxylation of pyruvic acid to acetylaldehyde and carbon dioxide(3957, 3958).

Auguste Fernbach (FR) and Moise Schoen (FR) were the first to demonstrate that pyruvic acid is present during the fermentation process(3959-3961).

Sir Arthur Harden (GB) and William John Young (GB) found that two fractions of yeast extracts are required for alcoholic fermentation to take place, a heat-labile fraction, called zymase, presumably containing the enzymes required for the process, and a heat-stable fraction (cozymase) required for the activity of zymase(3330).The heat-stable fraction was later shown to contain two essential components, the oxidation-reduction coenzyme nicotinamide adenine dinucleotide, or NAD, and a mixture of the adenine nucleotides ADP and ATP(3962).

Federico Battelli (IT) and Lina Salomonovna Stern (LT-CH-RU), and Torsten Ludvig Thunberg (SE) discovered malate dehydrogenase(3963, 3964).

Carbon tetrachloride was recommended as a substitute for carbon disulfide in fumigation of grain. From this first use of carbon tetrachloride as an insecticide came its later use as a control of hookworm; the latter discovery was acclaimed one of world's most outstanding accomplishments(138).

Hubert Dana Goodale (US) introduced vital staining of the amphibian embryo as a method of tracing the fate of embryonic parts(3965, 3966).

Edwin B. Hart (US), Elmer Verner McCollum (US), Harry Steenbock (US), and George C. Humphrey (US) performed a long experiment with cattle, the results of which, provided the first clear evidence that the nutritive value of a diet depends on factors other than its content of protein, a few minerals, and energy sources(3967).

Otto Heinrich Warburg (DE) came to the conclusion that in cells “…the oxidative processes stand in closest connection with the physical state of the lipids”(3968).

Horace Middleton Vernon (GB) showed that oxidation of indophenol blue in cerebral tissue is due to the enzyme indophenol oxidase (cytochrome oxidase) which is especially abundant in grey matter and other respiring tissues(3969).

Gheorghe Marinescu (RO) demonstrated that grey matter can easily be distinguished from white matter when treated in vitro with Ehrlich’s indophenol reagent. The sharp delineation being due to the presence of indophenol oxidase in the cell bodies and dendrites (plentiful in grey matter) and absent from axons (plentiful in white matter). This paper also indicated that the cerebral area is very rich in dendrites(3970).

Gheorghe Marinescu (RO) was also the first to suggest that indophenol oxidase is located in the mitochondria(3971).

Arend Lourens Hagedoorn (NL) expressed the concept that the gene is autocatalytic(3972).

Edmund Beecher Wilson (US) surmised that the heredity factor causing color-blindness in humans is linked to the X chromosome(3973). This was the first gene assigned to a human chromosome.

Thomas Hunt Morgan (US) proposed that the genes for white eyes, yellow body, and miniature wings in Drosophila are linked together on the X chromosome(3974).

Thomas Hunt Morgan (US) provided incontrovertible evidence of recombination between sex-linked genes in Drosophila thus supporting Franciscus Alphonsius Janssens’ (BE) cytological evidence of crossing over(3359).

Walter Stanborough Sutton (US) had already predicted linkage in 1903. Interestingly enough these two men both worked at Columbia University just down the hall from one another in 1903. See, Sutton, 1903.

Schack August Steenberg Krogh (DK) studied the hydrostatics of the air bladder of Corethra larvae during 1896. He demonstrated that these organs function like diving tanks of a submarine(3975). This is a type of gnat whose larvae are often fed upon by fish.

Henry Bryant Bigelow (US) wrote a paper on the Siphonophorae which was at that time one of the most important reports ever written on this group(3976). These are in the phylum Cnidaria.

Thomas Burr Osborne (US) and Lafayette Benedict Mendel (US) reported that the coprophagy exhibited by rats benefits their health and growth(3977).

Margaret Reed Lewis (US) and Warren Harmon Lewis (US) were the first to culture eukaryotic cells on cover slips in vitro. They were also the first to attempt in vitro cultivation of eukaryotic cells using simple salt solutions(3861, 3978).

Marshall Albert Barber (US) proposed a new technique—the microinjection technique. He developed this method initially to clone bacteria and to confirm the germ theory of Koch and Pasteur(3979). Later on, he refined his approach and was able to manipulate nuclei in protozoa and to implant bacteria into plant cells.

George Lester Kite (US) used microsurgical techniques to study the fine structure of cells. He found that protoplasm exists in the form of sols and gels of varying consistency with that of plants generally of a lower viscosity. That the nucleus contains a gel of high viscosity and that the membrane of the nucleus is a definite morphological structure belonging to the nucleus(3980-3982).

Alexis Carrel (FR-US) and Montrose Thomas Burrows (US) successfully explanted malignant cells from Rous sarcoma, Ehrlich and Jensen rat sarcomas, a canine breast carcinoma, a primary human breast carcinoma, and a human sarcoma of the tibula into in vitro cell culture(3983).

Frederick P. Gay (US) coined the word immunology(3984).

Walter Bradford Cannon (US) and Daniel de la Paz (PH) argued that strong emotions stimulated the sympathetic nerves and thence the secretion of epinephrine (adrenaline); all the varied effects of the hormone on the body could be seen as quick preparations for "fight or flight"(3985-3988). “Fight or flight” was coined in the 1915 reference.

Sir Henry Head (GB) and Gordon Morgan Holmes (GB) gave the first systematic account of the functions of the thalamus and its relationship to the cerebral cortex(3989).

Francis Peyton Rous (US) and James B. Murphy (US) were the first to use embryonated eggs to grow a virus(3990).

Joseph Goldberger (SK-US) and John Fleetezelle Anderson (US) established the viral etiology of measles (rubeola) when filtered respiratory tract secretions of measles patients were inoculated into macaque monkeys resulting in measles-like symptoms in these animals(3991, 3992).

Hideyo Noguchi (JP-US) used an in vitro mixture of serum water containing fresh rabbit kidney or testicle to grow Treponema pallidum under anaerobic conditions(3993).

Hideyo Noguchi (JP-US) developed a serum diagnosis for syphilis and established the presence of Treponema pallidium in the lesions of syphilis in the central nervous system(3994).

George W. McCoy (US) and Charles W. Chapin (US) reported that they had recovered the organism responsible for tularemia from fleas (Diamanus montanus Baker = Ceratophyllus acutus Baker) taken from sick or dead ground squirrels and tested in guinea pigs(3995). This is the first scientific paper on tularemia, which gets its name from Tulare County, California where it was first known as plague-like disease of rodents(3996).

Edward Francis (US) proved that the disease known in Utah as deer fly fever is tularemia and is transmitted from infected rabbits to man by the bite of the fly Chrysops discalis. He would later show that Pasteurella tularensis (now Francisella tularensis) was present in rabbits at the market place and that rabbit fever was not infrequent among humans in contact with rabbits(3997-4000).

Hachiro Ohara (JP) discovered the Japanese form of tularemia, Ohara's disease. It is also called yato-byo, meaning rabbit fever(4001).

Alberto Ascoli (IT) presented his thermo precipitation test for the diagnosis of anthrax using a tissue extract and anthrax antiserum. This test is used for detection of anthrax bacilli in animal hides and meat(4002).

Charles Manning Child (US) formulated his axial gradient theory of embryonic development, proposing that certain regions of the developing embryo dominate others and mold them into subsidiary forms. He showed that these gradients are physiological in various ways by demonstrating that regions with different rates of growth differ in their susceptibility to poisons and narcotics that interfere with respiration and other functions of living cells(4003-4005). Though present knowledge views his theory as incorrect, in its time, it represented an early approach to understanding functional organization within organisms

Leland Ossian Howard (US) and William F. Fiske (US) were entomologists who recognized clearly that, of the numerous factors which influence the morphology and natality of insects, only those which act with increasing severity as populations become larger are capable of adjusting populations to their environments(4006). Other biologists would later refer to these factors which operate with increasing intensity as a population grows as density-dependent factors, and those which do not do so as density-independent factors.

Leonard Noon (GB) and John Freeman (GB) helped establish the basis for immunotherapy or allergy shots, i.e., allergen-specific immunotherapy (SIT)(4007, 4008). Immunotherapy involves injecting the allergy sufferer with small, gradually increasing amounts of the substance that is causing the reaction. The idea is that over a time course, the body's immune system will become less sensitive to the substance and the allergy symptoms will be reduced or eliminated.

Hans Günther (DE) described acute porphyria (porphyrinuria) and noted that the signs and symptoms include red porphyrins in the urine, periodic attacks of abdominal pain, and mental disorder similar to schizophrenia or paranoia(4009).

Thomas Chalmer Addis (GB) made his claim that the fault in hemophilic blood is due to an inherited qualitative defect in the prothrombin(4010).

Ethel Browne Harvey (US) described the changes which take place in the cortical region of an egg during fertilization. For example, the granules near the surface disappear in a wavelike manner around the egg(4011). These granules release material during their breakdown that promotes formation of the fertilization membrane.

Gordon R. Ward (GB) diagnosed human fascioliasis by finding eggs in feces(4012).

Erich Lexer (DE) stated that homografts (allografts) are invariably unsuccessful, even when transplanted from parent to child and vice versa(4013, 4014).

Hans Winterstein (DE) suggested that CO2 stimulated breathing by acidifying extracellular fluid near the "respiratory centers”(4015).

Rudolph Matas (US) wrote a landmark article in which he described a challenge test to assess the degree and efficacy of the collateral circulation in patients under consideration for permanent occlusion of a major vessel. Matas studied the feasibility of such a test by temporarily occluding the carotid and femoral arteries in dogs for variable periods of time. In the introduction to his seminal article on the subject, he stated that "the chief object of this inquiry has been to determine whether the large arteries can be occluded long enough to make it possible to observe the effect of the arrested circulation in the territory supplied by the occluded vessel, without irreparably damaging the artery during the period of observation"(4016). See, Celsus, 30 B.C.E. and John Hunter, 1793b.

Sir William Arbuthnot Lane (GB) performed resection of the cervical esophagus for cancer and reconstruction by skin graft(4017).


Harvey Williams Cushing (US) developed techniques to control bleeding in operations for brain tumors where ligature was not possible(4018). 

Charles Doolittle Walcott (US) discovered a rich assemblage of algae and invertebrate fossils from the Middle Cambrian Period of the Paleozoic Era in the Burgess shale located in Yoho National Park in the Rocky Mountains, near Field, British Columbia, Canada(4019). The word Cambrian is taken from a Latin form of the Welsh name for Wales. Other fossil rich Cambrian sites include Chengjiang, China, the Wheeler Formation in Utah, and the Croixan Series in Minnesota-Wisconsin. (Shale is rock formed by condensation of layers of clay or mud, along with phytoplankton and other debris, sedimented at the bottoms of lakes or ocean basins.)

Samuel Wendell Williston (US) and Ermine Cowles Case (US) described Seymouria and other labyrinthodont amphibian and reptile fossils from the Permian beds of Texas and New Mexico(4020-4023).

Louis Capitan (FR) and Denis Peyrony (FR) found a fossil remains of Homo sapiens neanderthalensis; Homo neanderthalensis dated at ca. 38,000 years old. The site was near La Ferrassie, France(4024).

1912

Alexis Carrel (FR-US) was awarded the Nobel Prize in Physiology or Medicine in recognition of his work on vascular suture and the transplantation of blood-vessels and organs. He was the first American to receive the prize in physiology and medicine.

Max Theodor Felix von Laue (DE) theorized that it might be possible to determine the wavelength of x-rays —known to be extremely short—by using crystalline lattices as diffraction gratings(4025-4028).

Walther Friedrich (DE), Paul Knipping (DE), and Max Theodor Felix von Laue (DE) were the first to obtain x-ray diffraction patterns. They passed x-rays through a crystal of zinc sulfide. Laue had theorized that it might be possible to determine the wavelength of x-rays —known to be extremely short—by using crystalline lattices as diffraction gratings. However, because the crystal had lines of atoms in various directions, the results would be complicated. There would be beams located at varying distances and angles from the center, those distances and angles depending on the structure of the crystal. By beginning with a crystal of known structure, and measuring the amount of diffraction, the wavelength of the x-rays could be calculated. See, Braggs, 1915. Second, by using x-rays of known wavelength it was possible to deduce the structure of a crystal from the patterns produced on x-ray film. This was the beginning of x-ray crystallography(4029).

William C. Piper (US) developed calcium arsenate as a replacement for Paris Green and lead arsenate. It soon became important for controlling the boll weevil on cotton in the United States. ref

William Küster (DE) proposed a correct formula for the ring system of porphyrins in which four pyrrole rings are linked together into a macrocycle by 4 methine bridges(4030). Porphyrin comes from the Greek meaning purple.

Sir Henry Hallett Dale (GB) and Sir Patrick Playfair Laidlaw (GB) prepared very active solutions of the hormone secretin(4031).

Gunnar Agren (SE), Einar Hammarsten (SE), and Olof Wilander (SE), crystallized secretin(4032).

Paul Mayer (DE) was the first to demonstrate that pyruvic acid is often reduced to lactic acid in various tissues. He also showed that pyruvic acid can be converted to glucose in fasting rabbits(4033). 

Gustav Georg Embden (DE) and Max Oppenheimer (DE) confirmed Mayer’s findings(4034). 

Gustav Georg Embden (DE), Karl Baldes (DE), and Ernst Schmitz (DE) noted that yeast juice and working muscle produced the same intermediate, which they believed to be glyceraldehyde(4035).

Donald Dexter Van Slyke (US) described a procedure for the direct determination of amino acid (alpha-amino) nitrogen in protein hydrolysates and in extracts of animal tissues, in the presence of various other organic nitrogenous compounds which occur in animal tissues(4036).

Donald Dexter Van Slyke (US) and Gustav M. Meyer (US) were the first to determine that amino acids, liberated during digestion in the intestine, are absorbed into the bloodstream, that they are removed from the blood by the other tissues, and that the liver alone possesses the ability to convert the amino acid nitrogen to urea(4037-4041).

Otto Folin (SE-US) and Willey Glover Denis (US), by direct chemical analysis, proved that it is amino acids rather than more complex intermediary products of protein digestion which are absorbed by the intestine and enter the blood. They determined that ammonia is present in excessive amounts only in blood which had just passed through the walls of parts of the colon in which putrefaction of fecal residues is in progress. They proved that ammonia is absorbed in fairly large quantities from such fecal putrefaction(4042-4046).

Casimir Funk (PL-GB-FR-US) suggested that the chemicals required in small quantities to prevent diseases such as beriberi, scurvy, pellagra, and rickets be called vitamines(4047). This name occurred to him when he was investigating Christiaan Eijkman’s anti-beriberi factor and found it to contain an amine group. He assumed that all of these factors required in small quantities contained an amine group(4047-4049). When it was discovered that this was incorrect Jack Cecil Drummond (GB) suggested dropping the final e producing vitamin. “The suggestion is now advanced that the final "-e" [of Funk's "vitamine"] be dropped, so that the resulting word Vitamin is acceptable under the standard scheme of nomenclature adopted by the Chemical Society…. It is recommended that the somewhat cumbrous nomenclature introduced by McCollum (Fat-soluble A, Water-soluble B), be dropped, and that the substances be spoken of as Vitamin A, B, C, etc”(4050). The anti-beriberi factor was called vitamine B1 (thiamine) because it was the first water soluble vitamin characterized. It is also called the antineuritic vitamin because the deficiency syndrome is predominantly neurological. Funk also isolated nicotinic acid from rice (Oryza sativa) polishings, but failed to discover its relationship to pellagra.

Agnes Robertson Arber (GB), Bruce Rogers (GB), and Pforzheimer Rogers (GB) authored The Herbals, Their Origin and Evolution which has remained the basic reference for the herbals(4051).

Julien Tournois (FR) discovered that in the Japanese hop, Humulus japonicus, a decrease in day-length during the normal growth period provokes some floral reproduction. After obtaining similar results with another species of hop and hemp, he concluded that young plants flower when exposed to short days from germination onward. And he deduced that night-length, rather than the brevity of the day, was the determining factor(4052, 4053). These papers represent the origin of the study of photoperiodism.

Georg Albrecht Klebs (DE), from his studies of the house leek (Sempervivum funkii), reached a similar conclusion in 1918(4054).

Wightman Wells Garner (US) and Harry Ardell Allard (US) performed extensive experiments with three strains of tobacco (Nicotiana tabacum), four varieties of soybean (Glycine max) beans from Peru and Bolivia, radish (Raphanus sativus), carrot (Daucus carotus), lettuce (Lactuca sativa), cabbage (Capitata), wild aster (Symphyotrichum), climbing hempweed (Mikania scandens), ragweed (Ambrosia artemisiifolia), hibiscus, wild violet (Viola papilionacea), and goldenrod (Solidago). They concluded that of the various factors of the environment which affect plant life the length of the day is unique in its action on sexual reproduction. Unlike temperature, rainfall, or light intensity, daylight is “the only consistently rhythmic feature of the external environment.” They coined and defined the terms short-day plants (SDP), long-day plants (LDP), intermediate plants, and indeterminante or day-neutral plants. Their terminology is descriptive of the length of the period of continuous illumination to which the plants are exposed during each 24-hour period. Garner also introduced the term photoperiodism for the response of organisms to relative length of night and day(4055, 4056).

Karl C. Hamner (US) and James Frederick Bonner (US) proved that Tournois was correct. The length of night is more important to short-day plants than length of day in floral initiation. They found that the cocklebur (Xanthium strumarium) must have about 8.5 hrs. of uninterrupted night for flowering. This was the discovery of the night-break phenomenon(4057). 

Alexei F. Kleshnin (RU) concluded “It is only the amount of energy absorbed by some acceptor of the leaf that is important…” “For every region of the spectrum there is a definite threshold of radiation intensity below which this region is perceived as darkness in the photoperiodical process; this threshold is different for different plants”(4058).

Lord Edgar Douglas Adrian (GB) published a study on the effects of the block of nerve conduction induced by application of alcohol vapors to small segments of nerves from which he derived the conclusion that nerve signals regenerate along the nerve fiber during the conduction process(4059).

Oil barriers were recommended for control of chinch bugs (genus Blissus). They are considered pests that feed on stems of turfgrass. Paradichlorobenzene was first used in the U. S. as an insecticide: used for clothes moth control. Eugenol derivatives were first noted as entomological attractants. Nicotine insecticides were developed for control of onion thrips. Hydrocyanic acid gas was adopted by U. S. Public Health Service as a standard fumigant(138).

Friedrich Baltzer (DE) reported the first valid case of environmental sex determination in nature. He observed in the marine Bonellia (Echiuridae) that if a larvae finds a suitable substrate, it will settle and most probably develop into a female. However, if it is picked up by the proboscis of an adult female, the larva will attach itself to the proboscis with the help of an "underwater glue" and develop into a male(4060).

Oscar M. Schloss (US) proposed cutaneous tests (skin test or scratch) in the diagnosis of the food allergy(Schloss 1912; Schloss 1915).

Fritz B. Talbot (US) used the scratch test, to associate asthma to a food "intoxication" by egg(4061).

Alfred Erich Frank (DE) showed that the posterior lobe of the pituitary gland produces an antidiuretic hormone (vasopressin) which controls diabetes insipidus(4062).

Jost Frederick Gudernatsch (DE) caused a female frog to ovulate in September, some seven months before the normal breeding period, by subcutaneously implanting six pituitary glands from adult female donors. The eggs were artificially inseminated. When the tadpoles developed hindlimb buds, minute amounts of thyroxin (bits of horse thyroid) were added to the water. In about three weeks, the treated tadpoles reabsorbed their swimming tails, grew hindlimbs and then forelimbs, lost their horny teeth (used for plant feeding), shortened their intestinal tracts in preparation for carnivorous feeding, modified their respiratory and integumentary systems for terrestrial environments, and emerged as normal but miniature air-breathing adult frogs.

Since thyroxin initiated the metamorphic changes long before they would normally occur, the resulting froglets are about one-third the size of those metamorphosing in nature. Thyroid-ectomized tadpoles never metamorphose, but grow to giant size(4063, 4064).

Wilbur Willis Swingle (US) reproduced Gudernatsch's results on metamorphosis in frogs by providing or withholding inorganic iodine(4065).

Martinus Willem Beijerinck (NL) was possibly the first person to recognize that bacterial variation might reflect the occurrence of gene mutation(4066).

Thomas Hunt Morgan (US) reported the first sex-linked recessive lethal gene in Drosophila(4067).

Thomas Hunt Morgan (US) and Clara J. Lynch (US) were the first to publish a case of autosomal linkage in Drosophila(4068).

Montrose Thomas Burrows (US) devised a perfusion chamber which, for the first time, allowed cells grown in vitro to be continuously supplied with fresh medium(4069).

Charles Louis Alphonse Laveran (FR) and Félix Mesnil (FR) discovered that trypanosomes could be maintained indefinitely in rats and mice by serial passages(4070).

Christian Champy (FR) noted that eukaryotic cells grown in vitro often lost some of the specific features that characterized them in their normal in vivo habitat. He denominated the process dedifferentiation(4071, 4072).

Robert A. Lambert (US) was the first to describe the formation of multinucleated cells in vitro(4073).

Charles C. Bass (US) and Foster M. Johns (US) succeeded in the in vitro culturing of the malarial protozoan(4074).

At about this time it became routine to record the four vital signs (temperature, respiration, pulse rate, blood pressure) on all patients’ charts. See, Cushing, 1895.

Isaac A. Adler (GB) was the first to link lung cancer to cigarettes(4075).

Franz H. Müller (DE) indicated that non-smokers were more common in healthy populations than among lung cancer patients(4076).

Ernest Ludwig Wynder (US) and Evarts Ambrose Graham (US) observed a relationship between lung cancer and smoking. Together they performed the most systematic and detailed survey to date showing links between smoking and cancer(4077).

William Richard Shaboe Doll (GB), Sir Austin Bradford Hill (GB), and Richard Peto (GB) almost simultaneously reached the same conclusions. They were also able to show that stopping smoking immediately reduces the risk of cancer(4078-4082).

E. Cuyler Hammond (US) and Daniel Horn (US) issued their report entitled: Smoking and death rates: report on forty-four months of follow-up of 187,783 men. They announced a link between cigarettes and both lung cancer and heart disease. Regular cigarette smokers were reported to be ten times more likely to die from lung cancer than non-smokers. They revealed that the chances of heart attack were seventy percent higher for smokers than for non-smokers(4083-4085)

The United States Surgeon General concluded that "Cigarette smoking is causally related to lung cancer in men; the magnitude of the effect of cigarette smoking far outweighs all other factors"(4086).

Mikhail F. Denissenko (US), Annie Pao (US), Moon-shong Tang (US), and Gerd P. Pfeifer (US) found the first direct biological link between cigarette smoking and lung cancer. DNA mutations caused by the cigarette smoke by-product benzo[a]pyrene in the tumor suppressor gene p53 were found to be the same as those found in lung cancer cells(4087). See, von Sömmerring, 1795.

Roger I. Lee (US) and Paul Dudley White (US) developed the Lee-White clotting time course test. Lee demonstrated that it is safe to give group O blood to patients of any blood group, and that blood from all groups can be given to group AB patients. The terms "universal donor" and "universal recipient" are coined(4088).

Hakaru Hashimoto (JP) described four patients with a chronic disorder of the thyroid, which he termed struma lymphomatosa (Hashimoto’s thyroiditis). The thyroid glands of these patients were characterized by diffuse lymphocytic infiltration, fibrosis, parenchymal atrophy, and an eosinophilic change in some of the acinar cells(4089). It is now appreciated that the progressive enlargement of the thyroid gland is due to autoimmunization against the patient’s own thyroglobulin circulating in the blood.

Wilhelm Weinberg (DE) made a detailed study of the dwarfism trait, achondroplasia, which he knew to be inherited as a Mendelian dominant. Specifically, he noted that an affected child born from normal parents tended to be among the last-born children in the sibship. From this he suggested that these were new mutations(4090).

Lionel Sharples Penrose (GB) relates achondroplasia to advanced paternal age and spontaneous mutation in the male gamete that has experienced many divisions(4091, 4092).

Samuel Alexander Kinnier Wilson (GB) reported on progressive lenticular degeneration (Wilson’s disease): A familial nervous disease associated with cirrhosis of the liver. Karl Friedrich Otto Westphal (DE) and Ernst Adolf Gustav Gottfried von Strümpell (DE) had previously described Westphal-Strümpell's pseudosclerosis but they failed to discuss the lenticular or hepatic aspects, thus they failed to recognize the two major signs of the disorder(4093-4096).

Gleb von Anrep (LB-GB) discovered a regulatory mechanism of the heart whereby cardiac performance improves as the afterload (aortic pressure) is increased. It is called homeometric autoregulation because it is independent of muscle length(4097).

Arthur Läwen (DE) used curare to relax the abdomen during surgery keeping the patient alive by artificial ventilation(4098).

Hürter (DE) made the first arterial punctures in humans. He was able to show that the arterial oxygen saturation in four normal subjects was between 93% and 100%(4099).

William Christopher Stadie (US) is believed to have been the first to introduce arterial puncture into clinical medicine where he used it to compare the oxygen content of air inhaled with that in arterial blood. He demonstrated that cynosis is due to arterial anoxemia(4100).

William Christopher Stadie (US) treated cases of cynosis in hyperbaric oxygen rooms he developed(4101).

Frizt Bleichroeder (DE), Ernst Unger (DE), and Walter Loeb (DE) were among the first to perform human vascular catheterization. They inserted catheters into the blood vessels without x-ray visualization. After numerous experiments on dogs without any accident, Bleichroeder successfully catheterized the heart of Joseph Portmann, laboratory technician at the hospital. Bleichroeder's approach to the heart was from the femoral vein. The procedure was done with a ureteral catheter(4102).

Ernst Unger (DE) inserted ureteric catheters transcubital into the axillary vein, through the femoral vein into the inferior vena cava, and through the femoral artery into the abdominal aorta, and, through the ulnar artery into the arch of the aorta(4102, 4103).

Werner Theodor Otto Forssmann (DE), a surgical trainee, was the first to document right heart catheterization in humans using radiographic techniques. In his own words, “After the experiments in the cadavers had been successful, I undertook the first experiments in living man by experimenting on myself…. I carried out under local anesthesia a venesection in my left elbow and introduced the catheter without resistance in its whole length of 65 cm…. I checked the position of the catheter in the roentgen picture and I observed the forward advance of the catheter in a mirror held in front of the fluoroscope screen by a nurse…. The method…has opened numerous prospects for metabolic studies and for studies of cardiac activity”(4104, 4105). In return, he was fired from his position at the hospital and won the Nobel Prize in 1956. See, Claude Bernard, 1844.

Otto Klein (DE) published 11 successful experiments on humans in which he catheterized and measured cardiac output(4106).

George P. Robb (US) and Israel Steinberg (US) successfully performed cardiac catheterization (introduction of a small tube into the heart by way of veins or arteries) on humans and were able to visualize the chambers of the heart on x-ray film(4107).

André Frédéric Cournand (FR-US) and Hilmert A. Ranges (US) inserted a catheter into the right atrium of a human and measured cardiac output. They found that the catheter could be left in place for considerable periods of time without harm(4108). See Forssmann, 1929.

André Frédéric Cournand (FR-US), Richard L. Riley (US), Stanley E. Bradley (US), Ernest S. Breed (US), Robert P. Noble (US), Henry D. Lauson (US), Magnus I. Gregersen (US), and Dickinson Woodruff Richards, Jr. (US) investigated traumatic shock in man and found: 1) that with a deficit of 40 to 50 percent in blood volume, there is a critical depression in cardiac output and in return of blood to the right heart worsening as shock continues unrelieved, 2) that peripheral resistance tends to be maintained in hemorrhage and skeletal trauma, and greatly increases in severe burns, 3) that peripheral blood flow is reduced particularly in the kidneys, and 4) that whole blood offers great advantages over plasma as sustaining therapy(4109, 4110).

André Frédéric Cournand (FR-US) demonstrated the feasibility of making accurate measurements of cardiac output in man under physiological conditions. He reached the conclusion that the quantity of oxygen absorbed by the body per minute must be equal to that taken up at the lungs, which would in turn be equal to the total pulmonary blood flow multiplied by the difference in oxygen concentration between the blood entering and leaving the lungs(4111).

Dickinson Woodrruff Richards (US) measured cardiac output by catheterization(4112). 

Richard A. Bloomfield (US), Henry D. Lauson (US), André Frédéric Cournand (FR-US), Ernest S. Breed (US), and Dickinson Woodruff Richards (US) used cardiac catheterization to record right heart pressures in normal subjects and in patients with chronic pulmonary disease and various types of cardiocirculatory disease(4113).

André Frédéric Cournand (FR-US), Janet S. Baldwin (US), and Aaron Himmelstein (US) were among the first to apply cardiac catheterization to the diagnosis of congenital heart lesion(4114, 4115).

André Frédéric Cournand (FR-US) and Dickinson Woodruff Richards (US) continued to develop venous catheterization(4116, 4117).

John A. Hartwell (US), Joseph P. Hoguet (US), and Fenwick Beekman (US) concluded from experiments on dogs that death following experimental intestinal obstruction is due, first, to a dehydration or loss of water from the tissues as a result of the excessive drain into the lumen of the intestine and vomiting, and, second, to the presence of a toxin in the circulating blood. They demonstrated that duodenojejunal obstruction in dogs responds well to liberal intravenous administration of saline(4118-4121).

Edward Flatau (PL) wrote a classic monograph on migraine(4122).

James Bryan Herrick (US) was the first observer to identify and describe the clinical features of sudden obstruction of the coronary arteries, i.e, coronary thrombosis(4123).

Henri-Charles-Jules Claude (FR) and Marie Loyez (FR) described syndromes of lesions in the brain stem. The Claude syndrome of ipsilateral oculomotor nerve paralysis and asynergia on the other side together with dysarthria is a major contribution as is Claude’s Hyperkinesis where there is reflex movements of paretic muscles elicited by painful stimuli(4124). need hyperkinesis ref

Rudolf Magnus (NL) and Adriaan de Kleijn (NL) found that standing, walking, and bodily balance in general, are reflexes which are affected, partly by the position of the head in space and partly by its position in relation to the neck. Both groups, which can reinforce or weaken each other according to a definite pattern, have been combined under the name of attitudinal or standing reflexes since they enable the animal to stand up. They discovered a special group of ‘righting reflexes’ which are elicited, partly by the vestibular apparatus in the inner ear, and the neck, partly by the eyes, and, partly, by the trunk of the body. It is these complex reflexes which enable a cat always to land on its feet(4125-4127). 

Rudolf Magnus (NL) gives a clear definition of tonic reflexes. These reflexes are called tonic, because they last as long as the head keeps a certain position; and that not only for minutes and hours, but for days, months and even years. He was aware of two classes of tonic reflexes, those that originate in the labyrinthine and depend solely on head position in space. These can be contrasted to the neck tonic reflexes which depend only upon the position of the head on the neck and are independent of body position in space. Magnus also showed that there is a shift in excitation, so that a reflex evoked with the head straight can be much different than when the neck is flexed. The classic picture of the anencephalic infant with its head turned to the side, with the viewed limb extended, and the contralateral limb flexed, is the epitome of the neck reflexes that underlie normal posture. Magnus also showed that the neck reflexes cause the forelimbs to extend when the head is flexed back and the forelimbs to be flexed when the neck is flexed forward. Finally, he and his group demonstrated that processing for the neck reflexes is in the upper cervical segments, whereas the vestibulospinal reflexes are processed in the medulla(4128-4130). 

Marin-Théodore Tuffier (FR), in 1912, performed the first operation to open a stenotic (narrowed) heart valve. Using his finger he attempted to push the wall of the aorta near the heart through the stenotic aortic valve and dilate the valve(4131). The patient recovered and improved. Tuffier was also the first to transport a wounded soldier by airplane.

Elliott Cutler (US) and Samuel A. Levine (US) used a tenotome (a tendon-cutting instrument) to successfully relieve a patient’s mitral stenosis (a narrowing of the mitral valve between the upper and lower chambers of the left side of the heart). The patient was a 12 year old girl whose mitral valve had been narrowed by rheumatic fever(4132). This was a very dangerous operation which was soon abandoned because of its low rate of success.

Henry Sessions Souttar (GB) performed the first successful transauricular mitral valvotomy. It was on a 15-year-old girl. He approached the valve from the left auricular appendage and used a finger as the basic instrument to dilate the stenotic mitral valve. He passed his finger through the mitral valve orifice into the left ventricle and did not cut the valve cusps. The patient made an excellent recovery(4133).

Dwight Emary Harken (US), Laurence B. Ellis (US), Paul F. Ware (US), Leona R. Norman (US), Charles Philamore Bailey (US), Charles Baker (GB), Russell C. Brock (GB), and John Maurice Hardman Campbell (GB) reported on a daring procedure to correct mitral stenosis. Harken had first performed this on WWII shrapnel victims by cutting a small hole in the side of a beating heart then inserting a finger and very carefully widening the narrowed valve(4134-4137). Charles P. Bailey (US) was the first to perform this operation, June 10, 1948. Russel C. Brock (GB) performed the same operation just months later.

Janet Elizabeth Lane-Claydon (GB) published a ground-breaking study of two cohorts (groups) of babies, fed cow's milk and breast milk respectively. Lane-Claypon found that those babies fed breast milk gained more weight, and she used statistical methods to show that the difference was unlikely to occur by chance alone. She also investigated whether something other than the type of milk could account for the difference, an effect known as "confounding"(4138). This study may have been the first epidemiologic implementation of a retrospective (historical) cohort study, the first modern description of "confounding" with an accompanying analysis, and the first use of Student’s t test to assess the difference of means in small samples. Lane-Claydon credits Major Greenwood for his help in the statistical analysis of her data.

Just Marie Marcelin Lucas-Championnière (FR) described Neolithic human skulls from nearly all parts of the world with disks of bone removed. This process, called trephining, represents the first evidence of man’s intervention in an attempt to heal his fellow man. This surgical procedure was likely done to release confined demons associated with epilepsy, infantile convulsions, headache, and various cerebral diseases(4139).

Jacques Loeb (DE-US) wrote The Mechanistic Conception of Life: Biological Essays(4140).

Sir John Murray (GB) and Johan Hjört (NO) wrote, The Depths of the Ocean, a pioneering work in oceanography(4141).

Charles Dawson (GB), Arthur Smith Woodward (GB), and Elliot Smith (GB) reported to the Geographical Society of London announcing their discovery of the fossil remains of Piltdown man(4142). This became the most infamous hoax in the history of paleontology.

1913

“There is no harder scientific fact in the world than the fact that belief can be produced in practically unlimited quantity and intensity, without observation or reasoning, and even in defiance of both, by the simple desire to believe founded on a strong interest in believing.” George Bernard Shaw(4143).

Corpora non agunt nisi fixata” [a substance is not (biologically) active unless it is "fixed" (bound by a receptor)]. Paul Ehrlich(4144).

Charles Robert Richet (FR) was awarded the Nobel Prize in Physiology or Medicine for his work on anaphylaxis.

Niels Henrik David Bohr (DK) produced a theory of the energy status of the atom (in particular, the hydrogen atom) that showed its structure to be mathematical. He assumed that the electrons could revolve about the nucleus in definite orbital paths, and he then established a rigorous mathematical theory to account for all those possible states. While the electrons remained in their predicted paths they emitted no energy, but when one would jump spontaneously from an outer to an inner orbit, it would emit energy as a quantum of light(4145). 

Joseph John Thomson (GB), using equipment he calls a "positive-ray" apparatus, observed that neon atoms have two different atomic weights (20 and 22). The existence of isotopes is confirmed(4146).

Arthur Holmes (GB) concluded that the breakdown of radioactive isotopes in igneous rocks can be used to determine when the rocks solidified. The ability to determine the absolute ages of rocks enables scientists to better date fossils. Using his quantitative time scale and other factors, he made an estimate of Earth's age that was far older than anyone had suggested until then – at least 3 billion years. His initial estimates of Earth's eras have held up remarkably well over time: For example, he placed the beginning of the Cambrian period at around 600 million years ago; today 590 million years is the time frame largely accepted(4147).

Charles Marie Paul Auguste Fabry (FR) and Henri Buisson (FR) used spectrographic techniques to demonstrate that the principal atmospheric location of ozone is in the stratosphere. They noted that it is important for filtering out ultraviolet radiation(4148). 

E. Riehm (DE) discovered that organo-mercurial treatment of cereal seed will protect it from fungal attack. It was used to prevent a disease called bunt in wheat(4149).

Leonor Michaelis (DE-US) and Maud Leonora Menten (CA) used the rules of chemical kinetics to propose an equation which describes how the rate of an enzyme-catalyzed reaction varies with the concentration of the substrate. They postulated that a complex is formed between an enzyme and its substrate, which complex then decomposes to yield free enzyme and the reaction product. The rate at which this occurs determines the overall rate of substrate-product conversion. The velocity of such a reaction is greatest when all the sites at which catalytic activity can take place on the enzyme molecules (active sites) are filled with substrate; i.e., when the substrate concentration is very high. These relationships provide the basis for all kinetic studies of enzymes and also have been applied to investigations of the effects of carriers upon the transport of substances through cell membranes(4150). This work was influenced by the work of Victor Henri (FR)(3079).

Kurt G. Stern (US) spectroscopically demonstrated the existence of an intermediate enzyme-substrate complex for the enzyme catalase, thus confirming the Henri-Michaelis-Menten hypothesis(4151).

Torsten Ludvig Thunberg (SE) and Heinrich Otto Wieland (DE) maintained, as a result of their experiments over a number of years, that the crucial reaction in living tissue is dehydrogenation (removal of hydrogen atoms from foodstuffs, two at a time). It is this, they maintained, and not the addition of oxygen, that is enzymatically catalyzed(4152-4158). They were opposed by Otto Heinrich Warburg (DE) who, as a result of his own experiments, maintained that it is the addition of oxygen that is crucial and that this reaction is catalyzed by enzymes containing iron atoms. He wrote, “ … that the oxygen respiration in the egg [sea-urchin] is an iron catalysis; that the oxygen consumed in the respiratory process is taken up initially by dissolved or adsorbed ferrous ions”(4159).

As it turned out both were correct. Together they made a good start toward working out the respiratory chain in tissues, the route by which the body converts organic molecules to water and carbon dioxide, releasing energy in the process.

Santiago Ramón y Cajal (ES) developed gold chloride-mercury stain to show astrocytes(4160).

Georg Albrecht Klebs (DE), from a thorough study of the house leek, Sempervivum funkii, deduced that light operates perhaps not as a nutritive factor, but, on the contrary, more catalytically(4161).

Henry Drysdale Dakin (US) and Harold Ward Dudley (US) discovered the enzyme glyoxalase which is widely distributed in nature and catalyzes the interconversion of methyl glyoxal and lactic acid(4162).

Carl Alexander Neuberg (DE-US) and Johannes Kerb (DE) while researching alcoholic fermentation by yeast, proposed an interpretation of this process as the net result of a series of consecutive step reactions (pathway), each one chemically conceivable and simple in nature, i.e., glycolysis(4163). Glycolysis occurs (with some variations) in nearly all organisms, both aerobic and anaerobic.

Robert Chodat (CH) was one of the first to obtain axenic cultures of algae(4164).

Peter Boysen-Jensen (DK) working with coleoptiles of barley seedlings established the existence of phytohormones or auxins (Greek, to increase) which are responsible for the chemical transmission of growth responses of higher plants. He demonstrated that the phototropic influence is a chemical agent, since it can cross an incision, but cannot pass through a mica barrier(4165, 4166).

Frits Warmolt Went (NL-US) hypothesized, as had others, that a plant’s growing tip is a source of substances promoting the growth of cells lower down the organ. His creative innovation was to collect such growth hormones by allowing them to diffuse from the cut surface of the excised tip into gelatin blocks. When applied symmetrically to the subapical tissue, these gelatin blocks promoted elongation of the decapitated coleoptile, and when applied asymmetrically, they caused curvature in a dose-dependent manner. This experiment, which succeeded in the spring of 1926, was the first unequivocal demonstration of the existence of a growth-promoting hormone (later named auxin) in plant tissues(4167).

Fritz Kögl (NL), between 1931-1935, extracted minute quantities of  plant growth promoters from the urine of man and other animals. He named them auxins which were later identified as auxin a and auxin b. Kögl identified auxin b as 3-indoleacetic acid(4168).

Fritz Kögl (NL), Arie Jan Haagen-Smit (NL-US), and Hanni Erxleben (NL) isolated auxin a from human urine(4169).

Fritz Kögl (NL), Arie Jan Haagen-Smit (NL), Hanni Erxleben (NL), Désiré George Florent Rudolphe Kostermans (NL), Kenneth Vivian Thimann (GB-US), and Joseph B. Koepfli (US) identified the first known plant hormone, indoleacetic acid (IAA)(4170-4172).

Fritz Kögl (NL), Arie Jan Haagen-Smit (NL-US), and Hanni Erxleben (NL) isolated auxins and characterized them chemically(4173).

George Robert Sabine Snow (GB) found that indoleacetic acid (IAA) stimulates cambial activity(4174).

James Frederick Bonner (US) and Samuel G. Wildman (US) demonstrated that indolacetic acid is a principal native auxin of higher plants(4175).

Harry Federley (FI) proposed that mules are sterile due to a failure of normal sperm production by meiosis, the type of cell division that gives rise to germ cells. Specifically the failure occurs at the stage of synapsis, when the homologous chromosomes of maternal and paternal origin come together(4176).

Elbert Thomas Bartholomew (US) studied potato black heart where he elucidated the effects of abnormal environmental conditions on the metabolism of the host cells. This study showed how environment can bring on disease(4177, 4178).

Howard P. Barss (US) was the first to describe bacterial blight of hazelnuts (Corylus avellana)(4179).

Shiro Tashiro (JP-US) discovered that the production of the nerve impulse depends upon the metabolic activity of the nerve fiber (cell)(4180).

Antonio Berlese (IT) theorized that the insect larvae is a free-living, feeding embryo. He believed that the larval stage is equivalent to the pro-nymph stage of more primitive insects with incomplete metamorphosis, like grasshoppers(4181). 

Vilém Laufberger (CZ) demonstrated that desiccated cattle thyroid glands can induce the metamorphosis of the amphibian Amblyostoma mexicanum (Siredon mexicanum) from its neotenic form to the adult form which is not found in nature(4182, 4183).

Julian Sorell Huxley (GB), unaware of Laufbergers work, performed the same experiment on the axolotl(4184). 

William Bateson (GB) discovered that dominance, in a genetic context, is not always absolute(4185). As a result, terminology such as partial dominance, incomplete dominance, codominance, lack or absence of dominance, intermediate dominance, imperfect dominance, egalitarian dominance, and transdominance came into use. 

Alfred Henry Sturtevant (US) and Thomas Hunt Morgan (US) discovered that despite their physical linkage some recombination does take place between genes on the same chromosome. They reasoned that the mechanism responsible is crossing over between homologous chromosomes. By measuring the frequency with which linked genes segregate Morgan and Sturtevant were able to construct a genetic map of the four chromosomes of Drosophilia; a map which turned out to be linear(3360, 4186).

Alfred Henry Sturtevant (US) and George Wells Beadle (US) postulated that the genes are arranged in a manner similar to beads strung on a loose string(4187). 

Rollins Adams Emerson (US) and Edward Murray East (US) discovered multiple allelomorphism in maize and also in beans(4188, 4189).

Gershom Franklin White (US) showed the cause of sacbrood in honeybees, Apis mellifera Linn., to be a filterable agent, i.e., virus(4190).

Alexander Ivanovitch Petrunkevitch (RU-US) began what became an important group of monographs on fossil arachnids(4191-4195).

Sir John Murray (GB) and Johan Hjört (NO) led the Michael Sars deep-sea expedition. This expedition greatly expanded knowledge about deep-sea animals, including ecological patterns(4196). Michael Sars was a Norwegian zoologist (1805-1869). 

Alfred Whitmore (GB) described melioidosis, a glanders-like disease of rodents, transmissible to man, occurring in India, the Malay states, and Indo-China, caused by Burkholderia pseudomallei (Malleomyces pseudomallei)(4197).

Nicolaas Louis Söhngen (NL) reported that the presence of a solid phase can influence a diversity of bacterial processes, such as nitrogen fixation, alcohol oxidation, nitrification, and denitrification (4198). 

Chlorophenol was introduced as a fungicide. ref

Albert Francis Blakeslee (US) discovered that copulation between two fungal thalli of opposite mating types precedes the formation of zygospores in Rhizopus(4199).

Rollins Adams Emerson (US) discovered and analyzed variegated pericarp, a highly mutable gene in maize and an example of multiple allelomorphism. With this work he provided evidence that mutations can arise in somatic cells contrary to the prevailing opinion that they occurred only in germinal tissue(4200).

Victor Ernest Shelford (US) studied succession in dune environments; this included his famous relating of variations in tiger beetle coloration to their presence in different successional stages, and in turn to a law of tolerance that related presence/absence to limiting factors in the environment(4201).

Charles C. Adams (US) and Victor Ernest Shelford (US) wrote two of the earliest books dealing with animal ecology(4201, 4202).

Carl A. Kling (DE) worked out the viral etiology of varicella (chickenpox)(4203).

Emil Adolf von Behring (DE) reported the successful use of toxin-antitoxin mixtures in the immunization of children against diphtheria. The vaccine proved unreliable and only gave consistent results after it was standardized by Paul Ehrlich(4204).

Béla Schick (HU-AT-US) developed the Schick Test, a practical method for distinguishing non-immune individuals from those already immune to diphtheria. It consists of injecting into the skin a very low dose of diphtheria toxin and observing the local reaction. In those whose blood serum contains no antitoxin, a characteristic reddish swelling develops at the site of injection, i.e., the Römer reaction. In those who are immune, the antitoxin already present in the circulation neutralizes the injected toxin and prevents the reaction from occurring(4205).

James Cecil Mottram (GB) showed that in both plant and animal tissues (the tips of bean shoots and ova of Ascaris megalocephala) cells are more vulnerable to damage by beta and gamma radiation when they are in process of division than in the resting stage, and that the metaphase is the most vulnerable stage. This damage results in profound nuclear changes affecting chromatin(4206).

 Claude Gordon Douglas (GB), John Scott Haldane (GB), Yandell Henderson (US), Edward C. Schneider (US), Gerald B. Webb (GB), and J. Richards (GB) demonstrated that at a given carbon dioxide pressure, oxygenated blood takes up less carbon dioxide than deoxygenated blood(4207).

Reinhard von den Velden (DE), A. Farini (IT), and B. Ceccaroni (IT) discovered the antidiuretic effect of posterior lobe pituitary gland extract (vasopressin). Each had patients with disease or damage to the pituitary accompanied by polyuria and, interpreting this to be due to the gland’s impaired function, they easily controlled the excessive water loss by administration of extracts of the posterior lobe(4208, 4209). See Frank, 1912

Eli Kennerly Marshall, Jr. (US) developed a rapid (urease) method for the quantitative determination of urea in urine and blood(4210-4212).

Roger I. Lee (US) and Paul Dudley White (US) reported on a clinical study of the coagulation time course of blood(4088).

Frank Rattray Lillie (US) hypothesized the existence of a substance in the jelly coat of eggs which causes sperm cells to clump together. He coined the name fertilizin for this substance(4213).

Lillie elaborated on this thoughts in a follow-up paper(4214).

Jules Jean Baptiste Vincent Bordet (BE) and Léon Delange (BE) described a lecithin rich activator (cytozyme) in an alcohol extract of blood platelets(4215).

William Henry Howell (US) discovered that Bordet’s cytozyme (thromboplastic substance, or tissue fibrinogen) is a cephalin (phosphatidylethanolamine) rather than a lecithin(4216, 4217).

George Hoyt Whipple (US) reported the absence of prothrombin in a case of melena neonatorum in a 3-day-old infant who developed melena and other hemorrhagic symptoms(4218). He also described abnormal hemorrhage associated with prothrombin deficiency in a patient with obstructive jaundice. In this paper Whipple describes the first known method for determining prothrombin-time(4219).

Aldred Scott Warthin (US) discovered a relationship between heredity and carcinoma as shown by the study of the cases examined in the pathological laboratory of the University of Michigan, 1895-1913(4220).

Aldred Scott Warthin (US) gave the classic description of pulmonary fat embolism(269).

John Jacob Abel (US), Leonard George Rowntree (CA-US), and Benjamin Bernard Turner (US) invented the artificial kidney when they developed a device for vivi-diffusion of blood of small animals. This was similar to a shell-and-tube heat exchanger. A series of handmade nitrocellulose tubes of 8 mm inside diameter was connected by glass manifolds and enclosed in a glass shell. Blood flowed through the collodion tubes, while isotonic saline solution flowed around the tubes. To prevent clotting of the blood in the extracorporal circuit, hirudin, obtained by crushing the heads of leeches, was used as an anticoagulant. 

The authors noted the potential of this invention when they stated, “There are numerous toxic states in which the eliminating organs of the body, more especially the kidneys, are incapable of removing at an adequate rate the natural or unnatural substances whose accumulation is detrimental to life. In hope of providing a substitute … a method has been devised by which the blood of a living animal may be submitted to dialysis outside the body”(4221, 4222).

William Thalhimer (US), Donald Y. Solandt (US), and Charles Herbert Best (US-CA) contributed to the evolution of hemodialysis with the demonstration that commercially available cellophane tubing could be used for in vivo dialysis(4223-4225).

Willem Johan Kolff (NL-US), Henrick T. J. Berk (NL), Maria ter Weele (NL), A.J.W. van der Ley (NL), E.C. van Dijk (NL), and Jacob van Noordwijk (NL) invented the artificial kidney for use with humans. It was a rotating drum artificial kidney, made by winding 100 feet of cellophane in a spiral pattern around a large horizontal drum, which revolved in an enamel tube containing a rinsing fluid. Gravity drew blood in the cellophane to the lowest point, and as the drum turned, the blood worked its way from one end of the cellophane tube to the other, releasing its impurities into the surrounding fluid as it traveled(4226).

Willem Johan Kolff (NL-US) demonstrated that in vivo dialysis can replace all known excretory functions of the kidney and regulate the electrolyte pattern of the blood plasma water in patients(4227).

Abraham Albert Hijmans van den Bergh (NL) and Isidore Snapper (NL-US) reported, relative to jaundice, that it was suspected that bilirubin passes into the urine once its blood level passes a threshold value. The threshold value was not known. They devised a test to detect the presence of bilirubin in blood serum or plasma(4228).

Guido Banti (IT) concluded that the leukaemias are systematic diseases arising from hemopoietic structures, lymph glands, and bone marrow, and that they are the consequence of limitless proliferative power of staminal blood cells(4229). This is still the basic definition of leukaemia.

Edmond Barthe de Sandfort (FR) developed keritherapy, the treatment of burns by using the paraffin-resin solution ambrine(4230).

Edmond Barthe de Sandfort (FR) advocated keritherapy in the treatment for rheumatism by plunging of the whole body or the parts affected into heated paraffin(4231).

Hugh Morriston Davies (GB) performed a hilar dissection and ligation of individual pulmonary arteries and veins and sutured the bronchial stump closed in a patient with lung cancer(4232). 

Evarts Ambrose Graham (US) and Jacob Jesse Singer (US) removed a whole lung for cancer, performing a simultaneous thoracoplasty to avert the high risk of empyema(4233). The patient, a doctor, was still alive at the time of Graham's death in 1957(4234).

Paul Ferdinand Schilder (AT-US), Charles Foix (FR), and Julien Marie (FR) described intracerebral centrolobular sclerosis(4235, 4236).

Ludwig Wilhelm Carl Rehn (DE) and Ernst Ferdinand Sauerbruch (CH-DE) independently performed the first pericardial resection in which an inflammed pericardium was partially excised because it constricted the movement of the heart. A left anterolateral thoracotomy approach was used(4237, 4238).

Edward Delos Churchill (US) was the first in the U.S.A. to perform decortication of the heart to relieve adhesive pericarditis(4239).

Edmond Delorme (FR) had been the first to suggest that an operation to relieve adherent pericardium, i.e. restrictive pericarditis, had a likelihood of success(4240).

Hermann Oppenheim (DE) and Fedor Krause (DE) performed the first successful removal of a pineal gland tumor(4241).

John Broadus Watson (US) founded the behaviorist school of psychology, which emphasized the study of observable behavior rather than conscious and unconscious mental processes(4242, 4243).

Albert Schweitzer (DE) opened a hospital for the leprous in Lambaréné, located in West Africa.

1914

“All the evidence points to the nuclear germ-plasm as the essential carrier of hereditary characters. We are thus compelled, on the mechanistic hypothesis, to attribute to the germ-plasm, or germinal nuclear substance, a structure so arranged that in presence of suitable pabulum and stimuli it produces the whole of the vast and definitely ordered assemblage of mechanisms existing in the adult organism.” John Scott Haldane(4244).

Max Theodor Felix von Laue (DE) was awarded the Nobel Prize in Physics for obtaining the first x-ray diffraction patterns by passing x-rays through a crystal of zinc sulfide. 

Robert Bárány (AT-SE) was awarded the Nobel Prize in Physiology or Medicine for his work on the physiology and pathology of the vestibular apparatus.

Hermann Emil Fischer (DE), Burckhardt Helferich (DE), and Kálmán V. Fodor (HU) became the first to synthesize a nucleotide(4245).

Yotako Koga (JP) and Ryo Ohtake (JP) isolated citrulline from watermelon (Citrullus vulgaris) juice(4246).

Mitsunori Wada (JP) coined the term citrulline from watermelon (Citrullus vulgaris) then proved through chemical synthesis that it is synonymous with delta-ureido-ornithine or alpha-amino-delta carbamido-n-valeric acid(4247).

Phoebus Aaron Theodor Levene (RU-US) and Frederick B. LaForge (US) correctly identified the structure of hexosamine, which they called chondrosamine (now called galactosamine)(4248, 4249).

Phoebus Aaron Theodor Levene (RU-US) was the first to obtain sphingomyelin in pure form and determine its structure(4250).

John Charles Grant Ledingham (GB) and William James Penfold (GB) discussed the mathematics of the lag phase and log phase of bacterial growth(4251).

Donald Dexter Van Slyke (US) and Glenn E. Cullen (US) developed a gasometric method of quantitatively determining urea concentration in blood and urine(4252). 

Herbert McLean Evans (US) and Werner Schulemann (DE) introduced the use of the acid dis-azo dyes for use in vital staining. Among the best known of these vital dyes are trypan red, trypan blue, vital red, and Evans blue(4253, 4254).

Sir Henry Hallett Dale (GB) showed the obvious relation of acetylcholine’s action on the parasympathetic system to that of epinephrine (adrenaline) on the true sympathetic system. He found that of all the various choline esters (natural and synthetic) active on striated muscle, acetylcholine was the most potent one(4255). Dale coined the terms adrenergic and cholinergic systems.

Stanislav von Provazek (CZ) introduced the use of fluorescent dyes for the staining of cells and tissues(4256).

Robert Joachim Feulgen (DE) applied the aldehyde reaction of Hugo Schiff (fuchsin sulfurous acid) to thymic nucleic acid (apurinic acid) (DNA) and reported that a neutralized acid hydrolysate of thymic nucleic acid restores the color of a fuchsin solution previously decolorized by sulfur dioxide(4257).

Petroleum oils were introduced as herbicides for use along drainage ditches in the Western United States and as a selective herbicide in carrots (Daucus carotus). ref

Gustav Georg Embden (DE) and Fritz Oscar Laquer (DE) discovered a compound formed from glycogen (fructose-1,6-diphosphate) as a metabolic intermediate in muscle. They named it lactacidogen(4258, 4259).

Gustav Georg Embden (DE) and Fritz Oscar Laquer (DE) discovered that if the hexose diphosphate from a yeast alcoholic fermentation is added to press juice from muscle that lactic acid is produced. This strongly suggested that the pathways of carbohydrate breakdown in the alcoholic fermentation by yeast and the lactic acid glycolysis by muscle are very similar(4258, 4260).

Sir Arthur Harden (GB) and Robert Robison (GB) found hexose monophosphate in a carbohydrate fermentation mixture(4261). Robert Robison (GB) later determined that it was a mixture of isomeric hexose monophosphates, probably those of glucose and fructose(4262).

Gustav Georg Embden (DE) and Margarete Zimmerman (DE) isolated a hexose monophosphate, Embden ester, from muscle(4263). Embden ester turned out to be a mixture of hexose monophosphates that were subsequently identified: fructose-6–P (Neuberg ester), glucose-6–P (Robison ester), and eventually glucose-1–P (Cori ester)(4262, 4264, 4265).

Robert Robison (GB) and Earl Judson King (GB) isolated glucose monophosphate (Robison ester) from a carbohydrate fermentation mixture(4266, 4267). This Robison ester would prove to be glucose-6-phosphate.

Calvin Blackman Bridges (US) presented papers on nondisjunction offering the final and conclusive proof that genes are parts of chromosomes(4268, 4269).

Hiram Bentley Glass (US) presented data illustrating the nondisjunction of chromosomes(4270, 4271).

Karl von Frisch (AT), Herbert Heran (DE), and Martin Lindauer (DE) studied communication in the honeybee, Apis mellifera Linn. They performed pioneering and imaginative studies which led eventually to an understanding of some of the ways in which honey bees communicate with one another. Through a dance (usually performed on the comb) workers can communicate the direction and distance to food. They also discovered that bees have the ability to discriminate some colors (they cannot see red but can see ultraviolet) and orient themselves by direction of light polarization in the sky(4272-4287).

Edmund M. Walker (CA) discovered that rock crawlers/ice bugs (Grylloblattodea), are a new order of insects. They inhabit cold areas, often in mountains, under rocks and in litter in forests, and in caves. During summer the North American species feed at night on insects frozen on the surface of snow fields; they are somewhat omnivorous. Their range includes Western North America, Japan, Korea, China, Siberia(4288). (Gryll = cricket, blatta = cockroach)

Walther Kruse (DE) passed nasal washings from individuals with the common cold through Berkefeld filters, then used these to inoculate healthy individuals. Successful transmission of the common cold to these healthy human volunteers strongly suggested that the etiological agent was a virus(4289).

George B. Foster, Jr. (US) performed a very similar experiment during 1916-17(4290, 4291).

Jacob Traum (US) was the first to describe brucellosis in swine. It was in a swine herd in Indiana(4292).

Alice Catherine Evans (US) confirmed these results and those of earlier work on Malta fever and cattle abortion(4293).

Irwin F. Huddleson (US) identified and named as a separate species the Brucellae causing swine brucellosis (Brucella suis)(4294).

Marshall A. Barber (US) observed the relationship of Staphylococcus albus to acute gastrointestinal upsets associated with drinking milk from a cow with mastitis(4295).

Harry Plotz (US), Peter K. Olitsky (US), and Geoege Baehr (US) isolated and identified the etiological agent of typhus fever as Rickettsia prowazekii(4296, 4297).

Harry Plotz (US), Peter K. Olitsky (US), and Geoege Baehr (US) developed a vaccine which proved effective against typhus fever(4298). 

Arthur William Bacot (GB) and Sir Charles James Martin (GB) determined that humans are infected with the plague bacillus when a flea carrying the bacillus regurgitates during a blood meal(4299).

Albert Hustin (BE) showed that addition of citrate can prevent blood from clotting and that citrated blood can be safely transfused into the dog. He then used citrated blood to transfuse a human(4300, 4301).

Luis Agote (AR) discovered that sodium citrate, when added to freshly drawn blood, prevents clotting. This meant that donors could go home rather than being present during transfusion. He performed a successful blood transfusion in humans using sodium citrate as an anticoagulant(4302, 4303).

Richard Lewisohn (US) determined the maximum amount of citrate that can be transfused into dogs without toxicity and thus determined the optimum concentration that can be added to blood for the best anticoagulant effect(4304).

Henry M. Thomas (US) and Kenneth Daniel Blackfan (US) detailed a case of a boy who died of lead poisoning after ingesting white lead paint from the railings of his crib(4305).

Carl Voegtlin (US) provided the earliest study which proved that human pellagra is unquestionably caused by dietary deficiency(4306).

Joseph Goldberger (SK-US), George A. Wheeler (US), William F. Tanner (US), Ralph Dougall Lillie (US), and L. M. Rogers (US) discovered that pellagra is caused by a dietary deficiency of a vitamin belonging to the B-complex and is not infectious(4307-4312).

T.N. Spencer (US) was the first to call attention to the similarity between the symptoms of a spontaneous canine disease known to veterinarians as black-tongue and those of human pellagra(4313).

 Joseph Goldberger (SK-US) and William F. Tanner (US) learned which foods are rich in the P-P (pellagra-preventive) factor, as they called it, and thus they could prevent pellagra by diet modification(4314).

Sir William Boog Leishman (GB) developed a vaccine against typhoid fever. It was a whole vaccine killed by heat at 53 ° C. and preserved with 0.25 per cent tricresol(4315).

Malaria control by fluctuating water levels was first observed(138).

Erich Schmidt (DE) measured high serum cholesterol levels in patients with xanthomatosis making this the first time that an essential hypercholesterolemia was recognized(4316).

Franz Volhard (DE) and Karl Theodor Fahr (DE) gave the first full description of pure nephrosis, relating clinical features to morbid anatomy(4317).

Karel Frederik Wenckebach (NL-AT) published his classic book on cardiac arrhythmias. Here he described the effect of quinine on atrial fibrillation, when he was able to rid a patient of tachycardia with a dosage of one gram of quinine(4318).

Walter Frey (CH) proved that quinidine, an optical isomer of quinine, is the most effective of all quinine derivatives against atrial flutter(4319).

Richard Clarke Cabot (US), following an analysis of 600 cases of heart disease divided them all into four categories. He reported that 93% of the cases were of either rheumatic, atherosclerotic, syphilitic, or nephritic etiology(4320). 

Walter Edward Dandy (US) and Kenneth Daniel Blackfan (US) produced a classic account of the pathogenesis and management of hydrocephalus. They produced hydrocephalus experimentally and explained that various types of hydrocephalus are due to obstruction of the aqueduct of Silvius, obstruction of the foramina of Magendie and Luschka, and devised surgical operations for the relief of the different varieties(4321).

Joseph Jules François Félix Babinski (PL-FR) described and named anosognosia (Babinski-Anton syndrome). When the right hemisphere of the brain is damaged, there is usually complete paralysis of the left side of the body. Patients with anosognosia obstinately insist that their left arm is not paralyzed even though they are mentally lucid in other respects. They may even deny ownership of their left arm, asserting that it belongs to someone else(4322, 4323).

Lucien Claude Jules Cuénot (FR) proposed the theory of preadaptation: the empty space or ecological niche is populated with mutants already showing characteristics adapted to the conditions of the empty space(4324).

David Meredith Seares Watson (GB) provided the first evidence that mammals evolved from reptiles. This conclusion was based on the fossilized remains of primitive reptiles and mammals he collected on trips to South Africa and Australia during 1911-1914(4325).

Hans Reck (DE) discovered rich deposits of early mammalian fossils including Stone Age artifacts at Olduvai Gorge in East Africa. Among other fossils he unearthed a fully human skeleton on the northern slope of the gorge; naming it Olduvai Hominid 1 (OH 1)(4326, 4327).

ca. 1915

Konstantin von Economo; Konstantin Alexander Economo Freiherr von San Serff (RO-AT) started his monumental studies on encephalitis lethargica (lethargic encephalitis), an epidemic disease of the central nervous system marked mainly by pronounced somnolence (lethargy), myalgias, fever, stupor, ophthalmoplegia, and paresis(4328, 4329). The disease, sometimes called type A encephalitis is now considered extinct. The etiological agent was never identified.

1915

William Henry Bragg (GB) and his son Sir William Lawrence Bragg (GB) shared the Nobel Prize in Physics for their formulation of the mathematical equations needed to calculate wavelength of the x-rays from the scattering pattern. They also used the x-ray diffraction patterns to deduce molecular structure of crystals. William Lawrence Bragg, at age twenty-five, was the youngest Nobel laureate ever. This coincidentally gave striking confirmation of the tetrahedral nature of the carbon atom(4330-4334).

Richard Martin Willstätter (DE) was awarded the Nobel Prize in Chemistry for his researches on plant pigments, especially chlorophyll.

Chaim Weizmann (RU-GB-IL) discovered a way to produce acetone via bacterial fermentation. He modified the process slightly and got the bacteria to produce butyl alcohol(4335, 4336).

Alfred Franklin Burgess (US) was in charge of moth work in the United States through the Plant Quarantine and Control Administration. They used lead arsenate for control of the gypsy moth (Lymantria dispar) in Massachusetts, US(4337).

Edna Steinhardt (US) and Marie Grund (US) neutralized the growth of vaccinia on rabbits' skin using convalescent serum(4338).

Torsten Ludvig Thunberg (SE), Fédérico Battelli (IT), and Lina Salomonovna Stern (LT-CH-RU) demonstrated that anaerobic suspensions of minced animal tissues catalyze the transfer of hydrogen atoms from certain organic acids known to occur in cells—especially succinic, malic, and citric acids—to the reducible dye methylene blue, giving its colorless reduced form. Enzymes catalyzing such reactions were named dehydrogenases(4339-4341). In later years several investigators using manometric measurement of the oxygen-utilization rate of minced-tissue suspensions found that succinate, fumarate, malate, and citrate are rapidly oxidized to carbon dioxide by molecular oxygen(2242).

Sir Thomas Lewis (GB) and Marcus A. Rothschild (GB) described how the excitatory process in the dog's heart first reveals itself in the region of the sino-auricular node then spreads from this node in every direction, progressing to all the margins of the musculature(4342).

Alexander Forbes (US) and Alan Gregg (US) made a systematic analysis of nerve impulses originating from the central nervous system and compared them with those evoked by artificial stimulation of a peripheral nerve. Their conclusion was that nerve impulses are always of the same nature regardless of their origin(4343).

Francis Arthur Bainbridge (GB) demonstrated that an increase in pressure on the venous side of the heart results in an increase of heart rate due to the inhibition of vagal influences and the excitation of some accelerator mechanisms(4344).

Sir Arnold Theiler (CH-ZA), Henry H. Green (ZA), and Philip Rudolph Viljoen (ZA) were the first to assert that the nutritive requirements of the ruminants are quite different from the omnivores and carnivores. They stated, “We … think it is at least possible that the vitamin requirements of cattle are so low that they may even be covered indirectly by synthesis carried out by the extensive bacetrial flora of the intestines”(4345).

Otto Folin (SE-US) and Willey Glover Denis (US) developed excellent methodology for the determination of phenols and conjugated phenols. They concluded from their studies of blood and urine that by no means can all of the phenols formed in the colon and absorbed into the blood be conjugated and detoxified(4346).

Mac H. McCrady (US) developed the most probable number, multiple-tube fermentation technique as a quantitative approach for analyzing water samples for coliforms(4347).

Richard Benedikt Goldschmidt (DE-US) was the first to successfully grow insect cells in vitro(4348, 4349).

Paradichlorobenzene was first recommended in the U. S. for control of clothes moth and carpet beetles(138).

Constantine Janicki (PL) coined the term karyomastigont to refer to a conspicuous organellar system he observed in certain protists: the mastigont (“cell whip”, eukaryotic flagellum, or undulipodium, the [9 (2) +(2)] microtubular axoneme underlain by its [9 (3) + 0] kinetosome) attached by a nuclear connector or rhizoplast to a nucleus. He observed this structure in highly motile trichomonad symbionts in the intestines of termites where karyomastigonts dominate the cells(4350).

Joel B. Dacks (CA) and Rosemary J. Redfield (CA) reported that the karyomastigont is an ancestral feature of eukaryotes present in early branching protists(4351).

Thomas Hunt Morgan (US), Alfred Henry Sturtevant (US), Calvin Blackman Bridges (US), and Hermann Joseph Muller, Jr. (US) had their book, The Mechanism of Mendelian Heredity, published(3916).

Thomas Hunt Morgan (US) and his colleagues settled decisively the mechanism of sex determination in Drosophila and based on evidence concerning eye color control in Drosophila they hypothesized the possibility that genes could have multiple alleles(3916).

James Allen Nelson (US) made an extensive study of the embryology of the honeybee, Apis mellifera Linn(4352).

Frederick William Twort (GB) discovered a transmissible, and filterable agent that destroys bacteria producing a phenomenon on agar plates he called glassy transformation. He speculated that this agent might be virus or an enzyme(4353). At about this same time Félix Hubert d’Herelle (CA) observed this same filterable disease of bacteria while in Mexico studying diarrhea of locusts(4354). Two years later bacterial viruses were independently discovered by Félix Hubert d’Herelle (CA) and he named them bacteriophage (from the Gk. phagein, to devour)(4355).

Hideyo Noguchi (US) found that vaccinia virus freed from all associated bacteria by means of suitable disinfecting agents can be propagated in a pure state in the testicles of rabbits and bulls(4356).

Ernst Berliner (DE) described a sporeforming bacterium, which he named Bacillus thuringiensis, isolated from diseased larvae of the Mediterranean flour moth, Ephestia kühniella Zell(4357).

David Shepherd (US) was the first to use this bacterium as a natural control of an insect pest, the slender-horned flour beetle, Echocerus cornutus (4358). 

Major J. Graham (GB) described trench fever in the medical literature for the first time. He characterized it as relapsing febrile illness of unknown origin(4359).

George H. Hunt (GB) and Alan C. Rankin (CA) dubbed it trench fever less than two months later(4360). It has also been called five day fever, quintan fever, and urban trench fever.

Sir John William McNee (GB), Arnold Renshaw (GB), and E.H. Brent (GB) described human experimentation on enlisted volunteers and showed that trench fever is transmitted by whole blood, but not by serum, and is most likely carried "by one of the common flies or parasites found in the trenches”(4361).

J. William Vinson (US), Henry S. Fuller (US), Gerardo Varela (MX), and C. Molina-Pasquel (MX) demonstrated that trench fever is transmitted by the body louse and caused by the bacterium Rickettsia quintana(4362-4364).

Erich August Hübener (DE), Hans Conrad Julius Reiter (DE), Paul Theodor Uhlenhuth (DE), Walther Fromme (DE), Ryokichi Inada (JP), Yutaka Ido (JP), Rokuro Hoki (JP), Renjiro Kaneko (JP), and Hiroshi Ito (JP) discovered the spirochete Spirochaeta icterohaemorrhagiae to be the etiological agent of infectious jaundice, also called Weil’s disease. They found that it is usually transmitted to man from infected rats(4365-4367).

Ido Yutaka (JP), Rokuro Hoki (JP), Hayozo Ito (JP), and Hidetsune Wani (JP) found that rats are the carriers of Leptospira icterohaemorrhagiae (4368).

Harold Mellor Woodcock (GB) observed coccidian oocysts of Isospora belli in the feces of World War I soldiers overseas(4369). This coccidian is frequently found in asymptomatic immunocompetent individuals and is associated with diarrhea in AIDS patients. The clinical entity is referred to as isosporiasis.

.

The first director of the International Health Board of the Rockefeller Foundation, Wickliffe Rose (US) appointed William Crawford Gorgas (US) to head the Yellow Fever Commission. Gorgas would effectively eliminate malaria and yellow fever in the Panama Canal Zone by eradicating the Aëdes and Anopheles mosquitoes.

Francis Peyton Rous (US) and Joseph R. Turner (US) developed the simple finger-prick method of crossmatching which enables one to determine within a few minute whether or not the blood of a donor is suitable for transfusion(4370).

Richard Weil (US) demonstrated the feasibility of refrigerated storage of anticoagulated blood. He found that it could be stored for 2 days and still be effective when transfused into guinea-pigs and dogs which had lost blood(4371).

Francis Peyton Rous (US) and Joseph R. Turner (US) used rabbits to demonstrate that, with certain additives and proper treatment, citrated blood can be stored for 14 days and still be successfully transfused(4372).

Abbie E.C. Lathrop (US) and Leo Loeb (US) reported the influence of internal secretions from the corpus luteum (ovarian follicles) on the development of spontaneous tumors in mice. Their study showed that tumor incidence was delayed and reduced from 60–90% to 9% in female mice castrated before 6 months of age. As it was already known that the corpus luteum secreted an uncharacterized substance that induced growth of the breast during pregnancy, the authors speculated that this chemical might be involved in tumor formation(4373).

Edgar V. Allen (US) and Edward Adelbert Doisy (US) demonstrated in mice and rats that ovarian follicles influence the estrous cycle by releasing a hormone which they called oestrin (estrogen)(4374).

Edgar V. Allen (US) reported that “menstruation is a catabolic process due to the temporary absence of ovarian follicular hormone or its decrease below a subliminal amount after its anabolic influence has induced the growth of a certain amount of genital tissue”(4375).

Elwood Vernon Jensen (US) discovered the estrogen receptor (ER)(4376).

Elwood Vernon Jensen (US), George E. Block (US), Sylvia Smith (US), Kay Alvin Kyser (US), and Eugene R. DeSombre (US) studied the effect of adrenalectomy on human breast cancer. They found that breast tumors fall into two categories — ER-rich and ER-poor — and patients who had tumors with a high level of ER expression were more responsive to hormone-ablative therapy. This led Jensen to propose that the ER status of a tumor could predict the response to therapy(4377).

Virgil Craig Jordan (US) and T. Jaspan (US) showed that long-term tamoxifen treatment targeted to the estrogen receptor (ER) could successfully treat and prevent rat mammary cancer(4378).

Bernard Fisher (US), Joseph P. Costantino (US), D. Lawrence Wickerham (US), Carol K. Redmond (US), Maureen Kavanah (US), Walter M. Cronin (US), Victor Vogel (US), André Robidoux (US), Nikolay Dimitrov (US), James Atkins (US), Mary Daly (US), Samuel Wieand (US), Elizabeth Tan-Chiu (US), Leslie Ford (US), Norman Wolmark (US), and other National Surgical Adjuvant Breast and Bowel Project Investigators found that tamoxifen decreases the incidence of invasive and noninvasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease(4379).

Bertram Welton Sippy (US) developed a method for medical care of gastric and duodenal ulcers by accurately protecting the ulcer from gastric juice corrosion until healing of the ulcer takes place(4380).

Sir Thomas Clifford Allbutt (GB) proved that angina is caused by narrowing of the coronary artery(4381).

Booker Taliaferro Washington (US) died of systemic "hypertension so severe and so protracted that by the time of his final hospitalization, it had destroyed his kidneys, damaged his heart and brain and would shortly take his life." Born into slavery in 1856, he died as a famous, influential, and greatly admired American who had guided the creation and maturation of the Tuskegee Institute from 1881 until his death in 1915(126). He was cared for by some of America's best physicians who had the tools but lacked the knowledge to effectively manage hypertension. It was not until 1946 that pentaquine, the first drug shown to have anti-hypertensive activity was available.

Otto Binswanger (DE), during the conflict of WW I, made an effort to identify risk factors for the disorder we now know as post-traumatic-stress-disorder (PTSD)(4382).  

Charles S. Myers (GB) kept a diary during World War I which became the basis of the first systematic investigation of combat-related neurosis. It was Myers who coined the phrase "shell shock" to call attention to the importance of the physical effects of bursting shells in creating the disorder(4383).

The Proceedings of the National Academy of Sciences of the United States of America was first published.

1916

Karol Mayer (PL) described the principles and practical uses of tomography(Mayer 1916).

Andre-Edmund-Marie Bocage (FR) applied for a patent on a machine in which both x-ray source and film were moved reciprocally and proportionately, i.e., tomography. He had designed a linear device, pluri-directional device and a curvilinear device(4384). 

Allan MacLeod Cormack (ZA-US) developed mathematical theory and built machines to achieve two-dimensional x-ray image reconstruction, i.e., axial tomagraphy(4385, 4386).

Sir Godfrey Newbold Hounsfield (GB) introduced computerized axial tomography (CAT scan)(4387).

Gilbert Newton Lewis (US) was the first to suggest that a bond between two elements can be formed not only through the transfer of electrons, but through the sharing of electrons. Each bond in an organic compound represents the sharing of one pair of electrons, the final result being that all atoms achieve the stable electronic configuration of the inert gas atom(4388).

Alfred Stock (DE) and Karl Somieski (DE) were the first to use the term ligand (ligare L.). It was in relation to silicon chemistry(4389).

Heinrich Otto Wieland (DE), Bonifaz Flaschenträger (DE), Albert Rewolle (DE), Hermann Sorge (DE), Hedwig Stender (DE), Albert Kulenkampff (DE), Franz Adickes (DE), Werner Mothes (DE), Gustav Reverey (DE), and Richard Jacobi (DE) studied the three bile acids which had been isolated and showed how closely related they are in basic structure and the detailed manner in which they differ. The molecular skeleton they showed to be steroid—term not yet coined— in nature, related to the well-known molecule, cholesterol(2678, 4153, 4154, 4390-4400).

Heinrich Otto Wieland (DE) later suggested a structure for cholic acid(4401).

Leon Popielski (PL) discovered the role of histamine (beta-imidazolylethylamine) as an agent increasing the secretion of gastric hydrochloric acid(4402).

Harold Ackroyd (GB) and Frederick Gowland Hopkins (GB) concluded that a rat’s diet must contain either arginine or histidine(4403).

William Cumming Rose (US) and Gerald J. Cox (US) discovered that histidine is an essential amino acid in rats(4404).

Elliott Proctor Joslin (US) and Francis G. Benedict (US), in 1908, carried out extensive metabolic balance studies examining fasting and feeding in patients with varying severities of diabetes. They noted a 20 percent decrease in the mortality of patients after instituting a program of diet and exercise(4405).

William Beecroft Bottomly (GB) noted that incubation of peat with a mixed culture of aerobic soil bacteria resulted in stimulation of wheat seedling's growth in this peat(4406).

August J.P. Pacini (US) and Dorothy Wright Russell (US) demonstrated the formation of a bacterial substance capable of stimulating animal growth. They showed that a water extract of the typhoid bacillus produced a marked growth response in rats ingesting a "vitamin B"- deficient ration(4407). These two papers offer evidence that microorganisms produce factors beneficial to the nutrition of plants and animals.  

Walter Abraham Jacobs (US) was the first to observe the germicidal properties of quaternary ammonium compounds(4408).

Søren Peder Lauritz Sørensen; Søren Peer Lauritz Sørensen (DK), during 1916-17, published a series of papers in which he reported the molecular weights of various proteins based on measurements of osmotic pressure. Although he underestimated their size his work pointed the way to visualizing proteins as having molecular weights in the 10s of thousands(4409-4411).  

Jay McLean (US) found that certain phosphatides and fat-soluble extracts from fresh brain, heart, and liver tissues accelerated blood clotting, but after storage for some months they lost their coagulant activity, and indeed were now acting as anticoagulants. Many consider this to represent the discovery of heparin(4412).

William Henry Howell (US) and L. Emmett Holt, Jr. (US) coined the term heparin to denote the presence of a fat-soluble anticoagulant in the liver (hepar)(4413).

William Henry Howell (US) later claimed to isolate heparin in such a way that it could not be the same substance as those isolated in either 1916 or 1918(4414). Priority of discovery has yet to be settled, however, James A. Marcum in a very scholarly article credits Howell with the discovery(4415).

D.W. Gordon Murray (CA), Louis B. Jaques (CA), T.S. Perrett (CA), and Charles Herbert Best (CA), beginning in 1934, conducted a series of tests on heparin in dogs for both "the prevention of venous thromboembolism" and also "for its use in vascular surgery," thereby becoming the first to demonstrate that such procedures could be performed with the assistance of heparin. They used heparin prophylactically against deep-vein thrombosis following surgery in humans(4416, 4417).

Erik Jorpes (SE) and Clarence Crafoord (SE) conducted similar experiments in the Karolinska Institute in Stockholm(4418, 4419).

George Henry Alexander Clowes (US) suggested that watery and lipoidal phases might exist together in a cell membrane by the action of balanced ions, postulating phase-reversal such as one can obtain in oil-water emulsions by modifying the critical balance of sodium and calcium ions, or other monovalent and divalent cations(4420).

Henry Josef Quayle (US) reported resistance to cyanide fumigation in the California red scale, Aonidiella aurantii. This is the first known case of insect resistance to chemicals(4421-4423).

Charles C. Macklin (CA) showed that when two nuclei in a binucleate heterokaryon enter mitosis together, the two sets of chromosomes commonly join a single metaphase plate and are then systematically distributed to two mononucleate daughter cells each of which can subsequently be shown to contain within a single nucleus the chromosomes of both parents(4424).

Hermann Joseph Muller (US) reported his definitive work on crossing over among chromosomes(4425).

Frank Rattray Lillie (US) demonstrated that sex hormones are concerned in the embryonic differentiation of sex characters among vertebrates. He showed that when the fetal membranes of male and female calf embryos become united in the uterus so that the blood vessels of the two are continuous, the female embryo is modified in the male direction, forming the so-called freemartin(4426).

Henrique da Rocha-Lima (BR) showed that the bacterium which Ricketts and Wilder found in the gut of lice feeding on typhus patients is an intracellular parasite and very likely the cause of typhus. He named the organism Rickettsiae prowazekii in honor of Howard Taylor Ricketts (US), who had died in 1910 of typhus fever during an investigation of that disease, and Stanislas Josef Matthias von Prowazek (AT) who also died of typhus while studying it(4427).

Edmund Weil (AT) and Arthur Felix (PL-GB) reported that certain strains of the bacterium Proteus, originally isolated from the urine of a typhus fever victim, are agglutinated by the sera of patients suffering from typhus (the OX-2 and OX-19 strains of Proteus are commonly used). Serum from normal persons did not produce a similar result(3172, 4428, 4429). Later studies showed that Proteus spp. are not the cause of typhus fever and that antibodies against Proteus spp. normally occur quite commonly in humans. Today this procedure is called the Weil-Felix test.

William Fletcher (MY) and J.E. Lesslar (MY) found that the Proteus OX-K strain appears specifically to agglutinate with antibodies to Rickettsia tsutsugamushi(4430).

M. Ruiz Castañeda (MX) and Samuel J. Zia (MX) found that there is a common antigenic factor in Rickettsiae and Proteus X-19 which explains the Well-Felix reaction(4431).

Kenzo Futaki (JP), Ftsuma Takaki (JP), Tenji Tangiguchi (JP), and Shimpachi Osumi (JP) discovered that Spirillum minor is the etiological agent of rat-bite fever or sodoku(4432).

Hans Conrad Reiter (DE) described a disease he called spirochetosis arthritica. Currently it is called Reiter syndrome(4433).

Francis Peyton Rous (US) and Frederick S. Jones (US) were the first to liberate individual cells from plasma clot cell culture — using the enzyme, trypsin — with the objective of growing the individual cells in vitro(4434).

James B. Murphy (US) appears to have been the first to observe a graft-versus-host reaction. He was inoculating the chorioallantoic membranes of 7-day embryos with adult chicken spleen and bone marrow. He did not correctly interpret the phenomenon(4435). This has also been called runt disease.

William J. Dempster (GB), Morten Simonsen (DK), J. Buemann (DK), A. Gammeltoft (DK), F. Jensen (DK), and K. Jorgensen (DK) were the first to correctly interpret the graft-versus-host reaction as the graft mounting a response to the host(4436-4438).

David W.H. Barnes (GB), Michael J. Corp (GB), John Freeman Loutit (GB), and Frank E. Neal (GB) described graft-versus-host disease (GVHD) in mice(4439).

Morten Simonsen (DK), Rupert Everett Billingham (GB-US), and Leslie Brent (GB) independently demonstrated graft-versus-host disease (GVHD) in chick embryos (manifested as pancytopenia) and mice (runt disease) after intravenous injection of adult spleen cells(4440, 4441).

Alan G. Cock (GB) and Morten Simonsen (DK) introduced the phrase graft-versus-host reaction to describe the direction of the immunological damage caused by introduction of immunologically competent cells into an immunocompromised host(4442).

Rupert Everett Billingham (GB-US) proposed 3 conditions required for the development of GVHD, as follows: (1) the graft must contain immunologically competent cells, (2) the host must possess important transplant alloantigens that are lacking in the donor graft so that the host appears foreign to the graft, and (3) the host itself must be incapable of mounting an effective immunological reaction against the graft(4443).

Henry Edward Crampton (US) described geographical races of the snail Partula in Tahiti. Beginning around 1916, he studied this snail over a period of 50 years, concluding (1) that the variation in the color, banding, and chirality of the shells was Mendelian in nature, (2) that these characters are unaffected by selection, and (3) that active evolution was demonstrable in the short time between his successive samples. Although the second and third of these conclusions appear to be badly flawed, the Partula studies nevertheless exerted an important influence on the modern synthesis of evolutionary biology(4444). Note: The last member of the snail species Partula turgida died at the London Zoo in 1996. Also known as the Polenesian Tree Snail, it was wiped out in the wild in a bungled attempt to control a nuisance snail with an introduced species.

George Edward Nicholls (AU) discovered that the vertebral column is important in classifying Salientia (frogs, toads, and tree toads)(4445).

Frederic Edward Clements (US) stated his ecological theory, that when a geographical area is newly vacated it becomes occupied by a succession of species gradually leading to a climax community and the plant community can be treated as a complex organism undergoing a life cycle and evolutionary history analogous to the individual organism(4446, 4447). See, Cowles, 1899.

Delafield Du Bois (US) and Eugene F. Du Bois (US) introduced a formula to estimate the approximate surface area of the body if height and weight are known(4448).

Arthur Isaac Kendall (US) has shown that the total abstinence from food for thirty-one days did not eliminate the bacteria from the lower intestine of man(4449).

Francis Peyton Rous (US) and Joseph R. Turner (US) determined that rabbit blood cells could be useful in transfusion after storage for a long time in vitro. They suggested that kept human cells could be profitably employed in the same way(4450).

Richard Henneberg (DE) coined the term cataplexy for emotionally induced muscle weakness, a prominent symptom of narcolepsy. ref

Joannes Gregarius Dusser de Barenne (NL-US) did considerable work on posture and was a pioneer in demonstrating the major functional subdivisions of the sensory cortex. His contributions to the knowledge of the analysis of the interaction of various cortical and subcortical regions of the brain were considerable(Dusser de Barenne 1916; Dusser de Barenne 1924).

Georges Charles Guillain (FR), Jean-Alexandre Barré (FR), and André Strohl (FR) described two soldiers acutely ill with muscular weakening, paresthesias, and muscular pain with major pathology in the Achilles reflex and the quadriceps muscle(4451, 4452). This condition is the most common form of acquired neuropathy, most frequently affecting young adults.

H. Draganesco (FR) and J. Claudion (FR) named this condition Guillain-Barré syndrome(4453).

Auguste François Chomel (FR), in 1828, was the first to give a clinical description of this condition.

Today this syndrome is recognized as the most common form of acquired neuropathy affecting both sexes, most frequently affecting young adults and believed to be a form of autoimmune disease with a delayed hypersensitivity reaction.

J. Darier (FR) was the first to describe erythema anulare centrifugum. A skin lesion which consists of redness (erythema) in a ring form (anulare) that spreads from the center (centrifugum)(4454).

The first record of carbolineum being used for control of poultry parasites appears (a heavy oily substance distilled from an anthracene-oil or creosote-oil fraction of coal tar and used as a wood preservative, disinfectant, or insecticide). Calcium arsenate was  discovered effective for control of the boll weevil. Sodium fluoride was discovered to be effective for control of lice on poultry(138).

Lennart von Post (SE) initiated the modern discipline of palynology when he reported on almost perfectly preserved pollen grains fr