A Selected Chronological Bibliography of Biology and Medicine

 

Part 2B

 

1858— 1884

 

 

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: James S. Steen, Ph.D., Professor Emeritus, jsteen08@bellsouth.net

 

1858

Stanislao Cannizzaro (IT) demonstrated the validity of Avogadro's number (265).

 

Friedrich August Kekulé (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 (951).

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 (337; 338).

Kekulé structures quickly became the most popular way of representing molecules. Kekulé along with Johann Friedrich Wilhelm Adolf 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." (1179)

 

Johann Peter Griess (DE) discovered the diazo compounds that are so important in the chemistry of dyestuffs (756).

 

Josef von Gerlach (DE) while experimenting with solutions of carmine and leaving a section of brain tissue in a dilute carmine solution overnight, reported good differential staining of the nucleus and nuclear granules compared with little or no staining of the cytoplasm and intercellular substance. He concluded that previous staining solutions had been too concentrated, and noted that the dye was absorbed by specific cellular elements and could not be washed out. He is regarded as the originator of controlled and standardized methods of staining in histology (1877; 1878).

 

Johann Florian Heller (AT) developed the caustic Potash Test for blood in the urine (818).

 

Otto Maschke (DE) succeeded in extracting the reserve protein of the Brazil nut and crystallizing it in his laboratory. Later this protein was called excelsin (1239; 1241).

 

Moritz Traube (PL) and Richard Gscheidlen (DE) proposed that catalytic power in tissues resides in proteins and that biological oxidations are based on the activation of molecular oxygen by intracellular enzymes (1809; 1811-1813).

 

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 (1448; 1449).

 

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 (1517-1523).

 

Robert Remak (PL-DE) concluded that cells with more than one nucleus arose by failure of the cell to complete its division (1554).

 

Karl Wilhelm 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 (1347).

 

Julius Gotthelf Kühn (DE) observed and described a fungus on diseased potato (Rhizoctonia solani) (1050).

 

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 (57).

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 mammals up to that time (56).

 

Louis Xavier Édouard Léopold Ollier (FR) described the inner layer of the periosteum, closest to the bone. The osteoblasts are in this layer (1406).

 

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 (1335).

Gustav Pommer (DE) carefully described the distinguishing histologic features of bone structure in rickets, osteomalacia, and osteoporosis (1516).

 

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 (1337; 1338).

 

Wilhelm Max Wundt (DE) described the isotonic curves produced by muscle under continuous and constant excitation (2015).

 

Rudolph Ludwig Karl 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 (1854; 1859). 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." (1209).

 

Maximilian Johann Sigismund Schultze (DE) described the sensory epithelium in the ear of fishes as composed of basal cells and cylinder cells, with numerous nuclei between them, surrounded by protoplasm and having prolongations upwards and downwards, the former passing between the cylinder cells, and the latter between the nuclei of the basal cells. These intermediate cells he called Fadenzellen (1673).

 

Rudolph Ludwig Karl 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 (1855).

 

Casimir Joseph Davaine (FR) and Giovanni Battista Grassi (IT) determined that humans become infected with Ascaris lumbricoides by ingesting the eggs (382; 742).

Casimir Joseph Davaine (FR) observed that living Ascaris larvae can be found in the small intestine of a rat 12 hours after feeding Ascaris eggs (384).

Francis Hugh Stewart (GB) was the first to observe that in host animals not all the hatched Ascaris larvae were promptly eliminated in the feces, but that some penetrated the wall of the alimentary canal, and wandered to other parts of the body, during which time they increased in size and underwent other morphologic changes (1754).

Francis Hugh Stewart (GB) observed further that the Ascaris larvae do not remain in the lungs, but migrate into the bronchi and up the trachea into the mouth of the rat or mouse (1755).

Francis Hugh Stewart (GB) noted that after the Ascaris larvae had passed into the bronchi and up the trachea they then were conveyed down the esophagus and into the intestine, and accumulated in the cecum and large intestine. After arrival in the large intestine, a large number of the larvae are voided in the feces without undergoing any marked change in size cr structure from the stage attained in the lungs (1756).

 

Ernst Leberecht Wagner (DE) presented the first important contribution to the knowledge of the gross pathology of uterine cancer (1932).

 

Robert Remak (PL-DE) having treated some 70 patients with galvanic current believed that it was superior to faradic current for electrotherapy (1555).

 

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 (752). Note: Gray died of smallpox (spotted death) at thirty-four years of age. Carter died of tuberculosis very near his sixty-sixth birthday. Note: "For the illustrations, he commissioned a medical student at St. George's named Henry Vandyke Carter for a payment of 150 pounds spread over fifteen months. Carter was painfully shy but highly gifted. All of his illustrations had to be drawn in reverse so that they would print the right way around on paper, which must have been an almost unimaginable challenge. Carter did not only all 363 drawings but also nearly all the preparatory dissection."

"As a collaborator, Gray was spectacularly petty. It is not clear whether he ever paid Carter in full or indeed at all. He certainly never shared royalties. He instructed the printers to reduce the size of Carter's name on the title page and to remove a reference to his medical qualifications, to make him look like a journeyman illustrator. Only Gray's name appeared on the spine, which is why it became known as Gray's Anatomy rather than Gray and Carter's, as it really should have."(242)

 

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 (1841; 1842).

 

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 (442; 445).

 

John Murray Carnochan (US) excised the superior maxillary nerve (including Meckel’s ganglion) for facial neuralgia (270).

 

Philip Lutley Sclater (GB) suggested six earthly zoological regions which he called the Palaearctic, Aethiopian, Indian, Australasian, Nearctic and Neotropical. They are still in use (1692).

 

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 (379). Darwin's monograph was published the following year (374).

 

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 (1692).

Philip and William Lutley Sclater (GB) later extended these studies to mammals, and it is still the basis for work in zoogeography (1693).

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 (1941; 1942).

 

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) (286; 1582; 1992).

 

Joseph Leidy (US) reported the findings by John Estaugh Hopkins (US), in 1838, and William Parker Foulke (US), in 1858, of the first relatively complete dinosaur skeleton. Leidy named this creature, found in New Jersey, Hadrosaurus foulkii (1114).

 

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 (373)

 

"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 (380)

 

"This depends not on a struggle for existence, but on a struggle between males for possession of the females; the result is not death to the unsuccessful competitor, but few or no offspring." Charles Robert Darwin (374). This is Darwin’s definition of sexual selection.

 

"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 (CH-US) (10)

 

John William Dawson (CA) discovered fossil plant remains (Psilophyton princeps) in Middle and Lower Devonian rocks from the Gaspé Peninsula in Eastern Canada (387; 388).

Thore Gustaf Halle (SE), Robert Kidston (GB), and William H. Lang (GB) later found similar confirming fossils and established the order Psilophytes (788; 964).

Harlan Parker Banks (US) subsequently split the Psilophytes into three divisions: Rhyniophytina (Rhyniophyta), Zosterophyllophyta, and Trimerophytina (Trimerophytophyta) (75).

 

Jean Baptiste Joseph Dieudonné Boussingault (FR) demonstrated a spontaneous increase of nitrates in plant-free soil (189).

 

Charles Hanson Greville Williams (GB) made the dye safranin (326).

 

Otto Maschke (DE) introduced the use of indigo to histology. He noted that the affinity of proteins for dyes might serve to differentiate between the different members of this group (1240).

 

Heinrich Müller (DE) developed a simple dichromate solution (Müllers fluid) with an indifferent salt (potassium sulfate) that was used as a primary tissue fixative. It has limited application as a preservative, but it may be used as a secondary fixative for post chroming (1336).

 

Wilhelm Friedrich Kühne (DE) used strong salt solutions to extract then characterize the protein he called myosin from muscle (1051; 1054; 1061).

 

Carl H.D. Boedeker (DE) established the biochemical basis for alcaptonuria by isolating the chemical cause for the darkening seen in the patient’s urine. The chemical is 2,5-dihydroxyphenylacetic acid or homogentisic acid; he named it alcapton then later alkapton (171; 172).

 

Friedrich Wilhelm Ernst Albrecht von Graefe (DE) first described central retinal artery occlusion (1879).

 

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 (1721).

 

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 (107).

 

Moritz Schiff (DE-FR-CH) proved that removal of the thyroid gland in dogs is fatal (1655). He later discovered that grafts or injections of thyroid extracts can prevent death (1657). 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.

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, later named myxoedema (myxedema) (770; 771).

William M. Ord (GB), who worked with Gull, is credited with coining the name myxedema for the non-pitting edema he observed in patients (1412).

Antonio-Maria Bettencourt-Rodrigues (PT) and Jose-Antonio 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 (132; 133).

George Redmayne Murray (GB) postulated that extracts of thyroid glands should be effective in hypothyroidism. In July 1891 he presented 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 (1342). Note: Her treatment was successful and she lived to be 74 years of age.

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 (603; 1198).

 

Thomas Henry Huxley (GB) compared the serous and mucous layers characterized by Christian Heinrich Pander with the ectoderm and endoderm of the Coelonterata (888). 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. Everything, 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." (374) See Anaximander, c.580 B.C.E. and Patrick Matthew, 1831.

David Lambert Lack (GB) wrote The Galapagos Finches (Geospizinae) a Study in Variation; Darwin’s Finches; The Life of the Robin; and Swifts in a Tower, all important contributions to ornithology and an introduction of competition theory into animal ecology, stressing the importance of ecological isolation in speciation, and providing a cogent model for adaptive radiation. Darwin's Finches, is a landmark work in which the differences in bill size of finches, which inhabit the Galapagos Islands, are interpreted as adaptations to specific food niches, an interpretation that has since been abundantly confirmed. Darwin's finches are a group of about 18 species of passerine birds(1074-1077). Note: "The person who more than anyone else deserves credit for reviving an interest in the ecological significance of species was David Lack... It is now quite clear that the process of speciation is not completed by the acquisition of isolating mechanisms but requires also the acquisition of adaptations that permit co-existence with potential competitors ."(1246)

 

Karl Gegenbaur (DE) emphasized that structural similarities among various animals provide clues to their evolutionary history. He noted that the most reliable clue to evolutionary history is homology, the comparison of anatomical parts which have a common evolutionary origin (675).

 

Albert Günther (GB) published his Catalogue of the Fishes of the British Museum. This large work contains descriptions of over 6,800 species and mentions another 1,700 (772).

 

Charles Robert Darwin (GB) performed the first experiment to strongly suggest dispersal of aquatic invasive species by movement of waterfowl (374). This phenomenon is known as epizoochory.

Jules de Guerne (FR) reported dispersal of algae by waterfowl (2024). This information came by way of a report by Zacharias.

Jules de Guerne (FR) reported dispersal of leeches by duck (401).

 

Florence Nightingale (GB) by training, example, will, and strength of character changed nursing forever; becoming the founder of modern nursing (1209; 1374; 1375). 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 despite 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 (1200).

 

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 (296).

 

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 (1708). This opened the way for studying the relationships between gases and the blood.

 

Samuel Wilks (GB) coined ulcerative colitis. The patient, a 42-year-old woman, had succumbed to an illness of diarrhea and fever, first mis-diagnosed as “arsenic poisoning.” Autopsy demonstrated a transmural inflammation of the entire colon and terminal ileum, initially labeled ulcerative colitis it was later re-classified as Crohn’s disease (547; 1982). See, Baillie 1793.

Antoni Lesniowski (PL) reported this condition (1121).

Thomas Kennedy Dalziel (GB) described what he called chronic interstitial enteritis (Crohn's disease) (365; 366).

Burrill Bernard Crohn (US), Leon Ginzburg (US), and Gordon D. Oppenheimer (US) described what they called regional ileitis, or cicatrizing enterocolitis (Crohn’s disease), a disease of the terminal ileum, affecting mainly young adults, characterized by a subcutate or chronic necrotizing and cicatrizing inflammation (349).

Hugh Evelyn Lockhart-Mummery (GB) and Basil C. Morson (GB) set out clearly the clinical and pathological features of Crohn’s disease of the large intestine as seen in a series of 75 patients. This combined clinical and pathological study makes it clear that Crohn’s disease is a different disease from ulcerative colitis and that the two do not occur together in the same patient (1158; 1159).

 

Auguste François Chomel (FR), in 1828, likely gave the first clinical description of a type of polyneuritis that would eventually be referred to as Guillain-Barré syndrome (300).

Jean-Baptiste Octave Landry (FR) described a case of what was later named Guillain-Barré syndrome (1085).

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 (764; 765).

H. Draganesco (FR) and J. Claudion (FR) named this condition Guillain-Barré syndrome (435).

Note: This condition is the most common form of acquired neuropathy, most frequently affecting young adults. A variant characterized by ophthalmoplegia, ataxia, and areflexia is called the Miller Fisher syndrome (577).

Note: 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. Campylobacter sp. infections are a common antecedent to the acute neurological disease, Guillain-Barré syndrome.

 

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 (1133).

 

Achille-Louis-Francois Foville (FR) described a syndrome (Foville’s syndrome) caused by the blockage of the perforating branches of the basilar artery in the region of the brainstem known as the pons. This produces ipsilateral horizontal gaze palsy and facial nerve palsy and contralateral hemiparesis, hemisensory loss, and internuclear ophthalmoplegia (601). Structures affected by the infarct are the paramedian pontine reticular formation, nuclei of cranial nerves VI and VII, corticospinal tract, medial lemniscus, and the medial longitudinal fasciculus.

 

Jean-Jacques Pouech (FR) was the first naturalist to discover dinosaur eggshells. The material was Late Cretaceous rock from the Pyrenees Mountains (1524).

 

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 (24; 1387).

 

Gustav Robert Kirchhoff (DE) and Robert Wilhelm Eberhard Bunsen (DE) introduced the technique of spectroscopy into chemical analyses (969).

 

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 (124). Bèchamp (FR) called this enzyme zymase.

Victor Paschutin (DE) and Claude Bernard (FR) independently discovered that the epithelial cells of the mucosa of the small intestine secrete invertase (112; 1447).

Horace T. Brown (BR) and John Heron (BR) discovered invertase in the leaves of higher plants (230).

 

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 (287).

 

Light trap development started for insect control; chiefly for cotton leaf worm (1707).

 

Thomas Henry Huxley (GB) debated Bishop Samuel Wilberforce (GB) and 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. Alas: The debate was not recorded.

 

Wilhelm Krause (DE) described specialized cutaneous nerve endings, which were later named Krause end bulbs (1044-1046).

 

Louis Pasteur (FR) wrote that he is a staunch upholder of the view that yeast is a living organism which, during its life, splits sugar not only into alcohol and carbon dioxide but also into other substances. Among these other substances he noted glycerol (1453; 1454).

He demonstrated that germs are not uniformly distributed in air by using several 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 several 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 (1,400-2,140 meters). In general, he found that the air in rural and elevated locations contained fewer germs than air from urban and low altitudes (1450-1452).

 

Robert Caspary (DE) discovered that light promotes the germination of certain seeds (276).

Adolph Cieslar (DE) found that some colors stimulate germination while others inhibit (302).

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 (585-588).

 

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 (1126).

 

John McCrady (US) and Fritz Müller (DE) were the first to identify the larvae of inarticulate brachiopods. The systematic position of these larvae was inferred correctly from the very beginning (1253; 1330).

Fritz Müller (DE) described the swimming behavior of these larvae, noting that they swim vertically because of the shell weight. He also observed that larvae clap their shells together and sink when disturbed and that they feed on diatoms (1331).

Felix Joseph Henri de Lacaze-Duthiers (FR) described larva of an articulate brachiopod at about the same time in France (Lacaze-Duthiers 1861).

 

Casimir Joseph Davaine (FR) wrote, Traité des Entozoaires et des Maladies Vermineuses de L'Homme et des Animaux Domestiques, a classic book in parasitology (383).

 

Theodor Ludwig Wilhelm 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 (144).

 

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 (543).

 

Rudolf Ludwig Carl Virchow (DE) was the first to describe the protozoan Isospora belli. He found it in the intestinal mucosa at autopsy (1857).

Charles Morley Wenyon (GB) officially named this parasite Isospora belli (1971). Isosporiasis is an uncommon diarrheal illness caused by Isospora belli. The genus Isospora is closely related to the genera Cryptosporidium, Cyclospora, and Toxoplasma. The parasite is now known as Cystoisospora belli and the infection as cystoisosporiasis.

H.M. Woodstock (GB) was the first to characterize a case of human infection (isosporiasis/ cystoisosporiasis) with Cystoisospora belli (2003).

 

Francois Jules Lemaire (FR), based on 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 (1119; 1120).

 

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) (527).

 

Rudolf Ludwig Karl Virchow (DE) noted the plasma origin of fibrin and named its precursor form fibrinogen (1856; 1858). See, Babington, 1830.

 

Pierre Bazin (FR) was the first person to coin the term psoriasis arthritique or arthritic psoriasis after the association between the two had been established by Jean-Louis Alibert (FR) in 1818 (89).

X. Villanova (), J. Pinol (), and Verna Wright (GB) declared psoriatic arthritis a nosologic entity, and not a coincidental occurrence of psoriasis with arthritides and Verna Wright (GB) psoriatic arthritis (1852; 2011).

John M.H. Moll (GB) and Verna Wright (GB) discribed the characteristics and uniqueness of psoriatic artheritis; clearly distinguishing it from rheumatoid artheritis (1310).

 

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 (1880).

 

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, and loss of emotional control with episodes of sudden laughing and crying (443). Duchenne’s syndrome is a synonym.

Adolph Wachsmuth (EE) suggested the name progressive bulbar paralysis (1931).

Jean Martin Charcot (FR) and Alexis Joffroy (FR) contributed the description of its characteristic pathology (293).

 

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 (1317).

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." (1040; 1041)

Paul Eugen Bleuler (CH) later introduced the term schizophrenia as synonymous with dementia praecox (161). "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." (162). See, Willis, 1664

 

Auguste Ambroise Tardieu (FR) first described battered-child syndrome (1776).

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 (263; 954). Note: 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 (1509).

David M. Raup (US) showed that global records of the Phanerozoic sedimentary rock record exhibit a pattern that is nearly the reverse of Britain by itself (1544).

 

Berliner Medicinische Gesellschaft was founded.

 

1861-1865

The U.S. Civil War brought epidemics of dysentery, typhoid fever, hepatitis, malaria, smallpox (spotted death), measles, and venereal diseases. More than three times as many soldiers died of infectious disease than died of battle wounds (1005).

 

“During the first year of war there were 21,676 reported cases of measles and 551 deaths in the Union Army alone. Deaths were primarily from respiratory and cerebral (brain) involvement. It was recorded, ‘This infection is always serious, often fatal either directly or through its sequelae. The Prognosis therefore should be guarded.

The American Civil War was the last large-scale military conflict fought before the germ theory of disease was developed… Two-thirds of soldiers who died in that war, 660,000 in all, were killed by uncontrolled infectious diseases. Of these, in the Union Army over 67,000 had measles and more than 4,000 died.” Michael B.A. Oldstone (1403).

 

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 (801).

 

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 Richard Owen (GB) (1434). 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” (528; 1702).

 

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." (982)

 

Ernst Wilhelm Brücke (DE) was the first to use adsorption methods for enzyme purification (236).

 

Friedrich Goppelsröder (CH) undoubtedly originated chromatography as an analytical laboratory tool. His work employed paper chromatography to separate individual dyes from complex mixtures (726; 727).

 

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 (736; 737).

Thomas Graham (GB) worked on understanding the colloidal state of matter and thus advanced the understanding of protoplasmic systems (738).

 

False hellebore (Veratrum californicum ) was first recommended as a bioicide for control of imported cabbageworm (1707). 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 (1682).

 

Gabriel Gustav Valentin (DE-CH) was the first to use polarized light in the study of plant and animal tissues (1831).

 

Maximilian 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 (1674).

 

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 could 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 Hermann Hoffmann (DE), removed all criticism on the question of air, as such, activating into life an organic infusion. If the bent neck of an open flask that had long remained sterile was cut off the infusion rapidly teemed with living things (856; 1456; 1460). See, Spallanzani, 1776.s

 

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 (1455; 1457; 1461).

 

Louis Pasteur (FR) showed that acidic infusions can be sterilized with temperatures around 100°C., but alkaline infusions require temperatures above 100°C (1456).

 

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 (1455; 1457).

 

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 (1455; 1458; 1466).

 

John Bennett Lawes (GB), Joseph Henry Gilbert (GB), and Evan Pugh (GB) firmly established that green plants alone are incapable of using atmospheric nitrogen (1111).

 

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." (1812)

 

Max Josef Pettenkofer (DE) designed a respiratory machine large enough to accommodate a man. He and Karl 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 (1155).

 

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 (1900).

 

Jean Louis René Antoine Édouard Claparéde (CH) discovered giant axons in annelid worms (303).

 

Thomas Henry Huxley (GB) wrote an essay, which was instrumental in humans being considered in zoological terms and their origin as a result of the evolutionary process (889). He also revised much of the information concerning fishes from the Devonian Epoch (890).

 

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 (297; 1228).

Frederick Henry Horatio Akbar Mahomed (GB),using a primitive sphygmograph, described high blood pressure (1206). He also linked left ventricular hypertrophy to hypertension due to nephritis and reported the presence of high blood pressure in patients without renal disease (1207; 1208).

 

Friedrich Wilhelm Felix von Bärensprung (DE) is credited with being the first to describe the involvement of the Gasserian ganglion of the trigeminal nerve with Herpes zoster on the face (1868).

 

Jeffrey Allen Marston (GB) provided the first modern clinical description of brucellosis, which he termed Mediterranean gastric remittent fever (1238).

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 (233-235).

Bernhard Laurits Frederik Bang (DK) and Valdemar Stribolt (DK) isolated Brucella abortus and determined the etiology of contagious abortion (Bang’s disease) in cattle (74).

M. Louis Hughes (GB) suggested the name undulant fever (882; 883).

Themistocles Zammit (MT) discovered that the Brucellae are transmitted to man chiefly through the consumption of raw goat or cow milk (2025-2027). 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 David Bruce (AU-GB) (542).

 

Hubert Luschka (DE) provided the first authentic description of polyposis of the colon (1184).

 

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) (1272-1274). Note: 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 (891).

 

Paul Louis Duroziez (FR) described the double intermittent murmur over the femoral arteries as a sign of aortic insufficiency (455).

 

Erastus Bradley Wolcott (US) performed the first nephrectomy. It was for renal tumor (2000).

 

Henri Dunant (CH) wrote, Un Souvenir de Solférino, which was inspired by his having witnessed the suffering at the Battle of Solférino in 1859 (452). Note: The impact of his book led directly to the founding of the Red Cross by the Geneva Convention of 1864.

 

1862

"Whoever, in the pursuit of science, seeks after immediate practical utility may rest assured that he seeks in vain." Hermann Ludwig Ferdinand von Helmholtz (1897)

 

William Thomson; Lord Kelvin (GB) computed the age of the Earth at between 25 million years and 400 million years (1796).

 

Max Josef Pettenkofer (DE) devised a quantitative test for free carbonic acid. The gaseous mixture is shaken up with baryta or limewater of known strength and the change in alkalinity ascertained by means of oxalic acid. He also devised a qualitative test for strophanthin (1501).

 

Friedrich Wilhelm Beneke (DE) introduced the use of the aniline dyes to histology. He employed acetic acid colored with what he called “lilac” anilin (98).

 

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 (367).

 

Ferdinand Gustav Julius 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 (1625; 1626; 1631).

Andreas Franz Wilhelm Schimper (DE) later named these green plastids chloroplasts (1658). 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 (1459).

 

Charles Robert Darwin (GB) wrote a book that propelled floral ecology into respectability (375).

 

George Bentham (GB) and 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 (103).

 

Pieter Bleeker (NL) published his Atlas Ichthyologique des Indes Orientales Néêrlandaises, a comprehensive account of his studies done in Indonesia, featuring over 1,500 illustrations. It was published in 36 volumes between 1862 and his death in 1878. Between 1977 and 1983, the Smithsonian republished the work in 10 volumes (160). Note: Bleeker published more than 500 papers on ichthyology, describing 511 new genera and 1,925 new species.

 

 The Congress of the United States created the Department of Agriculture and included within it a Division of Chemistry (327-329).

 

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 (80). This phenomenon is called Batesian mimicry in his honor.

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 (1332-1334).

 

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 (613).

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 (27).

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 (28).

Thomas Richard Fraser (GB) was able to counteract the effect of Calabar extract by use of atropine (613).

Adolf Weber (DE) reported the positive therapeutic value of Calabar bean extracts in treating glaucoma (1953).

 

Rudolf Albert von Kölliker (DE) and Wilhelm Friedrich Kühne (DE) discovered and described vertebrate muscle spindles (1052; 1901).

Bryan H.C. Matthews (GB) discovered that muscle spindles function as proprioceptive units (1243).

Ake B. Valbo (SE) and Karl-Erik Hagbarth (SE) made recordings from muscle spindle afferents in their own arm nerves to demonstrate the structures' natural function as tension receptors (1830).

John William Sutton Pringle (GB) discovered that the campaniform sensilla on the palps of the cockroach respond to strain and are mechanosensory proprioceptors. This paper was the first to completely describe the function of single campaniform sensilla (1528).

 

Herman Snellen (NL) invented the eye chart with black block shaped letters to test vision (1725).

 

Ernst Kohlschütter (DE) performed the first experiments to determine the depth of sleep throughout the night (1004).

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 (677).

George Thomas White Patrick (US) and J. Allen Gilbert (US) performed the first “controlled” sleep-deprivation study on human subjects (1489).

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 (403; 404).

Ludwig Mauthner (HU-AT) deduced that normal sleep could be due to “fatigue” of the cells in the gray matter 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 (1244).

Walter Rudolf 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 (832; 833).

 

Maurice Raynaud (FR) described local asphyxia and symmetrical gangrene of the extremities, i.e., Raynaud phenomenon (1546).

Alfred Washington Adson (US) undertook innovative neurosurgery for the treatment of glossopharyngeal neuralgia to relieve Raynaud’s Disease. Permanent relief lies in division of the glossopharyngeal nerve proximal to the superior ganglion, through an intracranial approach (9).

 

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." (108; 871)

 

Claude Bernard (FR) discovered that if he severed the cervical sympathetic nerve there was an accompanying rise in local skin temperature (108).

 

Friedrich Albert Zenker (DE) was the first to describe pulmonary fat embolism in man (2029).

Aldred Scott Warthin (US) provided a classic description of fat embolism (1952).

 

Richard Owen (GB) discovered the parathyroid glands while performing necropsy on a rhinoceros, which had died at the London Zoo (1433). The necropsy took place in 1850.

Ivor Sandström (SE) described human parathyroid glands (1638).

 

Austin Flint (US) described a type of heart murmur that 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 (584).

 

William Withey Gull (GB) described the clinical signs of syringomyelia (abnormal liquid filled cavities within the spinal cord) (769).

Hans Chiari (AT) coined the term syringomyelia (298).

 

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 Mec 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 (185; 262; 1005; 1370).

 

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 (1461)

 

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 is English Patent #3307 of 1863.

 

Heinrich Wilhelm Gottfried Waldeyer; Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) introduced the use of logwood extract (hematoxylin) to histology (1935).

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 (173). 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 tree Hematoxylon campechianum, in 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.

Hermann Emil Fischer (DE) published a paper on Eosin Y which is the commonly used eosin dye in histology. The ‘Y’ stands for ‘yellowish! Eosin Y is an anionic acidic dye which binds to positively charged components of the cytoplasm such as amino groups (558).

A. Wissowzky () introduced the combination of the hematoxylin and eosin (H&E) dyes to stain tissues (1997). Hematoxylin, or more correctly its oxidized form hematin binds with a mordant (typically Aluminum 3+) to stain DNA in cellular matter. It is thought to bind with the negatively charged phosphate groups that comprise the DNA backbone and then undergo complex coordination or conjugation to become a permanent stain of the nucleus. Together with its Aluminum 3+ mordant, the dye produces a blue color in neutral to basic conditions. Conversely, the anionic Eosin Y will bind to positively charged groups on proteins, such as amino groups. Lysine residues, for example have and ε-amino group with pKa’s in the range of 10, such that they will remain as positive ions throughout the staining process.

 

Rudolf Albert von Kölliker (CH) coined the term cytoplasm (1902).

 

Pierre Alain Bitot (FR) concluded that night blindness and xerophthalmia are manifestations of the same condition (145).

Masamichi Mori (JP) discovered that both night blindness and xerophthalmia could be cured by cod-liver oil (1319).

Hippocrates, c. 400 B.C.E., recommended eating raw liver as a treatment of night blindness (1153).

Elmer Verner McCollum (US), Marguerite Davis (US), Thomas Burr Osborne (US), Lafayette Benedict Mendel (US), Edna L. Ferry (US), and Alfred J. Wakeman (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) (1249-1251; 1421; 1422; 1424).

E. Freise (DE), Max Goldschmidt (DE-US), 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 (617; 693).

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 (166; 167).

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 (1252; 1260-1264). Later it was found that fat-soluble A is complex, containing among other things vitamin A (retinol) and vitamin D. Vitamin D proved to promote calcium deposition therefore, it was the antirachitic factor (1252).

 

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 (861).

 

Maximilian 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." (1675)

 

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 (468).

 

Carl Joseph Eberth (DE) observed ciliated epithelium within the air-passages and later in liver cysts (459; 460).

 

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 (1053).

 

Carl Remigius Fresenius (DE), in 1863, was among the first to use a solid culture medium (slices of potato) for culture of microorganisms (619). 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 that live with or without free oxygen (1461).

 

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 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 investigator to look into the role of microorganisms in putrefaction, putrid intoxication, wound infections, pyemia, and septicemia (1461).

 

John William Draper (GB-US) showed that plants grown in solutions of sodium bicarbonate could liberate oxygen in the light (436).

 

Carl Claus (DE) wrote a monograph on the marine free-living copepods. It represents a major starting point of our knowledge of these organisms (306).

 

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 (1127; 1128; 1132). Rudolf Ludwig Karl Virchow (DE) recorded the first instance of coccidiosis in the small intestine of man (1857).

 

Henry Walter Bates (GB) wrote The Naturalist on the River Amazons, perhaps the best natural history written during the nineteenth century (81).

 

Hermann Ludwig Ferdinand von Helmholtz (DE) proposed the resonance theory of hearing. He reasoned that there are tiny, independently tuned elements in the cochlea, like the discrete strings of a piano, that are set into sympathetic vibration by incoming sound (1893; 1894; 1896).

 

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 (41).

 

Rudolph Ludwig Karl Virchow (DE) wrote, Die Krankhaften Geschwülste, a book on tumors in which many tumor types were named and described for the first time (1860).

Rudolph Ludwig Karl Virchow (DE) was probably aware of the neural origin of the tumor that Wright in 1910 would name neurocytoma or neuroblastoma (1860).

William Pepper (US) published on a series of infant patients with massive hepatic infiltration associated with adrenal tumors without spread to bone (1493).

Robert Grieve Hutchison (GB) reported his experience with a similar pathologic process in older infants and children who had orbital and skull metastases (887).

James Homer Wright (US) described the "Homer Wright" pseudorosettes of neuroblastoma. He proposed that they represent tumors of undifferentiated neurocytes or neuroblasts rather than "sarcomatous" tumors (2005).

 

Alfred Baring Garrod (GB) determined that gout results from the failure to excrete excess uric acid (657).

 

John Hilton (GB) recognized how to detect a blockage in the flow of cerebrospinal fluid (838).

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 (1532).

 

Nikolaus Friedreich (DE) performed outstanding work on hereditary spinal ataxia (Friedreich's ataxia). It is characterized by speech impairment, lateral curvature of the spine, and swaying of the body with irregular movements (631-633; 635; 636). Note: Freidreich’s ataxia is a genetic mitochondrial disease that results from malfunction of the protein frataxin.

 

Albert von Bezold (DE) described a nerve ganglion (Bezold’s ganglion), located in the interauricular septum of the heart, that contains accelerator fibers (1872).

 

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 (416).

Otto Edward Henry Wucherer (DE-PT) found the microfilaria in urine (2012).

Timothy Richards Lewis (GB) was the first to find the microfilaria of Wuchereria bancrofti in human blood; he named it Filaria sanguini (11; 1136).

Joseph Bancroft (GB-AU), in 1876, discovered a microfilarial worm in blood and tissues of a patient with elephantiasis and described the adult worm in various patients (70-72).

Thomas Spencer Cobbold (GB) named these nematodes Filaria bancrofti in honor of Joseph Bancroft (311).

Patrick Manson (GB) discovered that the Culex pipiens quinquefasciatus mosquito is the intermediate host of Filaria bancrofti (1212).

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 (1213). 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 (73).

Patrick Manson (GB) discovered the nocturnal periodicity of microfilariaemia. By counting the number of microfilariae in the blood of infected patients, he found that their number peaked at around midnight (1219).

 

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 (139).

 

Thomas Henry Huxley (GB) wrote Evidence as to Man’s Place in Nature, which was the first attempt to apply evolution explicitly to humans (892).

 

Archiv fur Mikroskopische Anatomie was founded.

 

Berliner Klinische Wochenschrift was founded.

 

Hours after delivering the Gettysburg Address, President Abraham Lincoln suffered weakness, fever, and headache on the train back to Washington. Within a few days he developed widespread pustular lesions. Medical historians assert that Lincoln had smallpox (spotted death), which sickened him for almost four weeks. Lincoln, however, recovered, though his valet caught the disease and died (1265).

 

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

 

1864

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), i.e., the Law of Mass Action (1930).

 

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 (1653; 1654). This test is used to detect polysaccharides, DNA and proteins. It is variously called the aldehyde reaction and the nucleal reaction.

 

Maximilian Johann Sigismund Schultze (DE) stained the luminous organs of the male of the European glow-worm (Lampyris splendidula) using osmic acid (1676).

 

George Gabriel Stokes (GB) observed that green leaves contain both chlorophyll a and chlorophyll b; the pigments were separated using partition methods (1762).

 

Louis Pasteur (FR) published papers detailing his studies of the acetic acid fermentation (1462).

 

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 (393).

 

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 (190).

 

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 (1277).

 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) discovered alternation of generations in the nematodes (1278).

 

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 (400).

 

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 (464; 465).

 

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 (775-777).

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 (1963). 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 venous return (724).

 

Karl Friedrich Wilhelm Ludwig (DE) and Ludwig Thiry (AT) demonstrated that some nerves from the cervical medulla serve to maintain blood vessel tonus and thus blood pressure (1181).

 

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 (809).

 

James Augustus Grant (GB), in his book A Walk Across Africa (1864), describes how his leg became grossly swollen and stiff with later a copious discharge. This was almost certainly the severe edematous form of Buruli ulcer and is the first known description of the infection (741).

Albert Cook (GB), a British physician, at Mengo Hospital in Kampala, Uganda identified Buruli ulcer disease (330).

Peter MacCallum (AU), Jean C. Tolhurst (AU), Glen Buckle (AU), and Hubert Armand Sissons (AU) wrote a detailed description of Buruli ulcer while treating patients from the Bairnsdale district, near Melbourne, Australia. They were the first to identify Mycobacterium ulceans as the pathogen causing it. The disease was so named after Buruli County in Uganda (now called Nakasongola district, because of the many cases that occurred there in the 1960s (1188).

 

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 (1305). 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 (1303; 1304). William Williams Keen, Jr. was the first brain surgeon in the United States.

 

James Young Simpson (GB) introduced acupressure; a new method of arresting surgical hemorrhage and of accelerating the healing of wounds (1717).

 

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 (1724).

 

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 (1733-1736).

 

George Perkins Marsh (US) wrote a book that was an important influence on the conservation movement in America (1231).

 

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 (1632).

 

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.

 

c. 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 (1167)

 

"My philosophy is of the heart and not of the mind, and I give myself up, for instance, to those feelings about eternity which come naturally at the bedside of a cherished child drawing its last breath. At those supreme moments, there is something in the depths of our souls which tells us that the world may be more than a mere combination of phenomena proper to a mechanical equilibrium brought out of the chaos of the elements simply through the gradual action of the forces of matter." Louis Pasteur page 125 (1832).

 

1865

"The application of mathematics to natural phenomena is the aim of all science." Claude Bernard (109)

 

"The science of life is a superb and dazzlingly lighted hall, which may be reached only by passing through a long and ghastly kitchen." Claude Bernard (109)

 

"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 (109)

 

"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 (Moravian-CZ) (1266)

 

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 (1749)

 

"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 von Liebig (DE) (1599).

 

"To Conserve Health and to Cure Disease: Medicine is still pursuing a scientific solution of this problem, which has confronted it from the first. The present state of medical practice suggests that a solution is still far to seek. During its advance through the centuries, however, medicine has always been driven into action and from numberless ventures in the realm of empiricism has gained useful information. Though furrowed and overturned by all manner of systems so evanescent that, one by one, they have disappeared, it has none the less carried on research, acquired ideas and piled up precious materials which in due time will find their place and meaning in scientific medicine. To-day, thanks to the great development and powerful support of the physico-chemical sciences, study of the phenomena of life, both normal and pathological, has made progress which continues with surprising rapidity.

It is therefore clear to all unprejudiced minds that medicine is turning toward its permanent scientific path. By the very nature of its evolutionary advance, it is little by little abandoning the region of systems, to assume a more and more analytic form, and thus gradually to join in the method of investigation common to the experimental sciences.

In order to embrace the medical problem as a whole, experimental medicine must include three basic parts: physiology, pathology and therapeutics. Knowledge of causes of the phenomena of life in the normal state, i.e., physiology, will teach us to maintain normal conditions of life and to conserve health. Knowledge of diseases and of their determining causes, i.e., pathology, will lead us, on the one hand, to prevent the development of morbid conditions, and, on the other, to fight their results with medical agents, i.e., to cure the diseases.

In the empirical period of medicine, which must doubtless still be greatly prolonged, physiology and therapeutics could advance separately; for as neither of them was well established, they were not called upon mutually to support each other in medical practice. But this cannot be so when medicine becomes scientific: it must then be founded on physiology. Since science can be established only by the comparative method, knowledge of pathological or abnormal conditions cannot be gained without previous knowledge of normal states, just as the therapeutic action of abnormal agents, or medicines, on the organism cannot be scientifically understood without first studying the physiological action of the normal agents which maintain the phenomena of life.

But scientific medicine, like the other sciences, can be established only by experimental means, i.e., by direct and rigorous application of reasoning to the facts furnished us by observation and experiment. Considered in itself, the experimental method is nothing but reasoning by whose help we methodically submit our ideas to experience, — the experience of facts.

Reasoning is always the same, whether in the sciences that study living beings or in those concerned with inorganic bodies. But each kind of science presents different phenomena and complexities and difficulties of investigation peculiarly its own. As we shall later see, this makes the principles of experimentation incomparably harder to apply to medicine and the phenomena of living bodies than to physics and the phenomena of inorganic bodies.

Reasoning will always be correct when applied to accurate notions and precise facts; but it can lead only to error when the notions or facts on which it rests were originally tainted with error or inaccuracy. That is why experimentation, or the art of securing rigorous and well-defined experiments, is the practical basis and, in a way, the executive branch of the experimental method as applied to medicine. If we mean to build up the biological sciences, and to study fruitfully the complex phenomena which occur in living beings, whether in the physiological or the pathological state, we must first of all lay down principles of experimentation, and then apply them to physiology, pathology and therapeutics. Experimentation is undeniably harder in medicine than in any other science; but for that very reason, it was never so necessary, and indeed so indispensable. The more complex the science, the more essential is it, in fact, to establish a good experimental standard, so as to secure comparable facts, free from sources of error. Nothing, I believe, is to-day so important to the progress of medicine.

To be worthy of the name, an experimenter must be at once theorist and practitioner. While he must completely master the art of establishing experimental facts, which are the materials of science, he must also clearly understand the scientific principles which guide his reasoning through the varied experimental study of natural phenomena. We cannot separate these two things: head and hand. An able hand, without a head to direct it, is a blind tool; the head is powerless without its executive hand.

The principles of experimental medicine will be explained in this work from the triple point of view of physiology, pathology and medicine. But before going into general considerations and special descriptions of the operative procedure proper to each of these divisions, I deem it useful to give a few explanations in this introduction in relation to the theoretic and philosophic side of the method which this book, after all, treats merely on its practical side.

The ideas which we shall here set forth are certainly by no means new; the experimental method and experimentation were long ago introduced into the physico-chemical sciences, which owe them all their brilliancy. At different periods, eminent men have treated questions of method in the sciences; and in our own day Monsieur Chevreul, in all his works, is explaining very important ideas on the philosophy of experimental science. We shall therefore make no claim to philosophy. Our single aim is, and has always been, to help make the well-known principles of the experimental method pervade medical science. That is why we shall here recapitulate these principles, specially pointing out the precautions to be taken in their application, because of the very special complexity of the phenomena of life. We shall consider these difficulties, first in the use of experimental reasoning, and then in the practice of experimentation." Claude Bernard (FR) (115).

 

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 (862; 863).

 

Friedrich August Kekulé (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 (952).

 

Alexander Crum Brown (GB) and Thomas R. Fraser (GB) were the first to propose that there is a relationship between the chemical structure of a molecule and its biological activity (229).

 

Carl Wilhelm Kupffer (DE) described macrophages lining the walls of the hepatic sinusoids (1064; 1065). To honor him these are called Kupffer cells. Note: He initially suggested that this type of cell belonged to a group of perivascular cells of the connective tissues or to the adventitial cells (pericytes). Two decades later (1898), he revised his earlier analysis, stating that the cells form an essential component of the vascular walls and correlate to the specific cells of endothelium, capable of phagocytising foreign materials. Shortly afterwards, pathologist Tadeusz Browicz (PL) correctly identified them as macrophages.

 

Emil Cramer (DE) isolated the amino acid hydroxylalanine from hydrolyzed silk thinking it was serikos (serine) (344).

 

Franz Schweigger-Seidel (DE) and Adolf Johann Hubert von La Valette-St. George (DE) proved that a spermatozoon is a cell possessing a nucleus and cytoplasm (1687; 1907).

 

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 can 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 (109; 111; 114). Bernard wrote, "…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 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." (114) See, isonomy of Alcmaèon (GR), 520 B.C.E. and homeostasis of Walter Bradford Cannon (US), 1926.

 

Karl Friedrich Wilhelm Ludwig (DE) developed perfusion techniques for keeping animal organs alive while they were separated from the general circulation. He did this to study the metabolism of an isolated organ while keeping it alive by artificially circulating defibrinated blood through it (1180). Dr. Sczelkow (UA) was a helper during these studies.

 

Louis Pasteur (FR), in 1865, 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. During these studies of pébrine, the first disease of animals shown to be caused by a microorganism, transovarial transmission of an infectious agent was demonstrated for the first time (1464). Note: Nosema bombysis, the causative agent of pébrine is a microsporozoan. See, Balbiani, 1882a

 

Christian Herman Ludwig Stieda (DE) described sporogony of the coccidia in the rabbit (1757).

 

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 that 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 (85; 1266-1268). 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 (137).

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 (1123).

 

Ferdinand Gustav Julius Sachs (DE) observed that plant leaves grown in the light could induce flowering in dark-grown shoots (1627).

James E. Knott (US) and Mikhail Khristoforovich Chailakhyan (RU) independently discovered that the flowering process is prompted not by a substance(s) in the bud but rather by a substance(s) produced in the leaves. Knott said, "Though the response of the plant may be localized in the bud, the leaves appear to function in some way to hasten the reproductive response to the appropriate photoperiod….Accordingly, the part played by the foliage of spinach in hastening the response to a photoperiod favorable to reproductive growth may be in the production of some substance, or stimulus, that is transported to the growing point." Chailakhyan studied Saratov millet, Perilla nankinesis, Helianthus annuus and Helianthus tuberosus (sunflower) concluding, "the processes induced by the changes in the length of daylight and leading to the reproductive development of plants (flowering and fruiting) occur within the leaf tissues. The formative process occurring in the zones of growth (growing points) are secondary changes dependent upon the functional activity of the leaf." Chailakhyan further demonstrated that the chemical promoter of flowering is not specific to a species but can stimulate a number of species. He named this hormone florigen, flower former (281-283; 984).

 

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 (841).

 

Claude Bernard (FR) found that herbivores, which normally void turbid alkaline urine, if fasted would void clear acidic urine. He interpreted this to mean that a fasting herbivore was consuming its own flesh and metabolizing like a carnivore (109).

 

Otto Friedrich Karl Deiters (DE) differentiated dendrites from axons and described the lateral vestibular nucleus (Deiter’s nucleus) of the 8^th cranial nerve (413). The names axon and dendrite would be coined later, dendrite by Wilhelm His (CH) (845); neuron by Heinrich Wilhelm Gottfried Waldeyer; Heinrich Wilhelm Gottfried von Waldeyer-Hartz (1940), and axon by Rudolf Albert von Kölliker (1904).

Otto Friedrich Karl Deiters (DE) and Max Johann Sigismund Schultze probably provided the first image of an astrocyte from the brain (413).

Vladimir Mikhailovich Bekhterev (RU) distinguished between the anterior and posterior roots of the eighth cranial nerve (93; 94).

 

Enriei 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 (1706).

 

Max Josef Pettenkofer (DE) was the first professor of hygiene at any university (1248).

 

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 (1564).

 

Karl Thiersch (DE) demonstrated the epithelial origin of cancer and reported that there is a relationship between skin carcinomas and exposure to sunlight (1784).

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 (1829).

William Dubreuilh (FR), G. Marshall Findlay (GB), and Angel H. Roffo (AR) presented early epidemiologic studies of a connection between sunlight and skin cancer (441; 548; 1580).

Bruce S. Mackie (AU) and Vincent J. McGovern (AU) divided complexion and predisposition to solar carcinoma and sunburn into 3 types, depending on the degree of pigment in the skin (1199).

 

Jules Bernard Luys (FR), Johann Bernhard Aloys 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 (1187; 1886; 1913).

 

George Harley (GB) described paroxysmal hematuria (800).

 

Armand Trousseau (FR) gave the first description of hemochromatosis, in 1865, when he gave a lecture on glycosuria and a new syndrome presenting with diabetes, liver cirrhosis with yellow-grey granules and brown skin pigmentation in a 36-year-old male (1818).

Friedrich Daniel von Recklinghausen (DE) coined the term hemochromatosis after demonstrating that the yellowish brown pigment was caused by massive iron deposition (1916). See, Vilém Laufberger, 1937.

Note: The discovery of the iron-binding proteins ferritin and transferrin were milestones in the development of modern diagnostics and the treatment of haemochromatosis and other diseases of iron metabolism.

 

William Howship Dickinson (GB) described paroxysmal hemoglobinuria (420).

 

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 (1881; 1882; 1884).

 

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 (1575). Glutamic acid is also called aminoglutaric acid.

 

Friedrich August Kekulé (DE), in 1866, changed the name of glucose to dextrose because it rotates plane polarized light to the right and fructose to laevulose because it rotates plane polarized light to the left (953; 1134).

 

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 repeatedly 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 (313).

 

John Bennet Lawes (GB) and Joseph Henry Gilbert (GB) demonstrated that animals could 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 (1110).

Emerich Meissl (DE) and Fritz Strohmer (DE) provided definite proof that carbohydrates can be converted into fat within the animal body (1257).

 

Adolf Eugen Fick (DE), Johannes Adolf Wislicenus (DE), and Edward Frankland (GB) independently concluded that muscular energy comes principally from the oxidation of non-nitrogenous materials (546; 611).

 

Edward Frankland (GB) was the first to use a combustion calorimeter to study foods for the quantitative energy values, which they yielded on combustion (611).

 

Max Josef Pettenkofer (DE), Carl 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 (1174; 1502; 1920).

 

Julius Friedrich Cohnheim (DE) stained peripheral nerve endings with gold salts and thus introduced their use in histology (318).

 

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 (399).

 

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 (1463).

 

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 (394).

 

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 (758).

 

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 (1279).

 

Aleksandr Onufriyevich Kovalevsky; Alexander Onufriyevich Kowalewski; Alexander Kovalevski; Alexander Onufriyevich 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. He proposed that all animals go through a gastrulation phase (1031-1035).

William Bateson (GB) showed 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 (84). Later the hemichordates were placed in their own phylum (905).

 

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 (776). 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 (1867).

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. (776; 778; 783; 784)

 

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 (1718).

 

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 (1695-1697). This work had 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 (910-912; 915-927).

 

John Zachariah Laurence (GB) and Robert Charles Moon (GB-US) described a rare disorder associated with retinitis pigmentosa, polydactyly, spastic paraplegia, hypogonadism, and mental retardation (1105). This presentation was later named the Laurence-Moon syndrome and inherited as an autosomal recessive.

 

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 (1146).

 

"Certainly different in our views of life, in our actions and activities, but also presumably in our scientific convictions - but at least in the pursuit of truth, in the culture of knowledge, in love for our field, we are together anew, to state the progress of science in order to draw from the rich source of communal work and experiences in order to broaden our own horizon, to the extent of which the most unconscious but more dangerous barrier of individuality presses, together with old friends to liven up the picture of past beautiful days, to bring fresh strength, to bring freer minds with them, into the often oppressive atmosphere of recurring misgivings, troubles, worries which, despite all success, surround the faithful service of Asclepius" (1883).

 

Henry Clifton Sorby (GB) invented the microspectroscope (1728).

 

Moritz Traube (PL) developed artificial semipermeable membranes by precipitating ferrocyanide in a thin-layer over porous porcelain (1810).

 

Charles Lauth (FR) made the dye methyl violet (1106). 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 decemlineata (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 (91; 1707).

By 1872, Paris green was recommended for the control of cankerworms and cotton leaf worm. Petroleum was first recommended in U. S. for insect bites and stings (1707).

In 1878, Paris green was discovered to be effective for control of codling moth (1707).

 

Carl Huber (DE) crystallized salts of an organic acid he named nicotinic acid (niacin; vitamin B3). He also determined its elemental composition (880).

 

Friedrich Wilhelm Adolf Baeyer (DE) synthesized acetylcholine (51).

 

Eduard Schwarz (AT) introduced differentiation to histology by using the double stain technique. He stained with ammonium carminate followed by picric acid (1686).

Louis-Antoine Ranvier (FR) simplified the double stain technique by combining the two stains in one solution (1539).

 

Rudolf Albert von Kölliker (CH) described yellowish-pigmented granules inside neurons located beside the nucleus (1903).

H. Rosin (DE), in 1896, suggested that they contain fatty substance and called them lipofuscin (1589; 1590).

Ernst Theodor Sehrt (DE), in 1906, proved that lipofuscin is of a fatty nature because of the way it reacts when stained with Sudan III (837).

 

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 (859).

 

Federigo Delpino (IT) was a botanist who made early studies on pollination (415). He is commemorated by the genus Delphinium.

 

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 (1688-1691). 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.

Andrey S. Famintsyn (RU), and Josif O. V. (or W.) Baranetsky (UA) studied a cross-section of a lichen thallus and observed green cells (then called gonidia, now, phycobionts) fall out, and they cultured them separately and concluded that they completely resemble the alga Cystococcus (522; 523).

Bruce Fink (US) wrote a paper that was the earliest attempt to assess the influence of environmental factors on lichen colonization, therefore this was the first paper to consider lichen ecology (separate from considering symbiosis between fungus and alga) (550).

 

Alexander Onufrievich Kowalevsky (RU) determined on the basis of larval structure that ascidians were chordates (1030). Note: Ascidiacea, commonly known as the ascidians, tunicates, and sea squirts

 

Auguste Henri André Duméril (FR) demonstrated that the Axolotl was in fact the sexually mature larval form of the salamander then called Amblystoma, now known as Ambystoma (450).

Julius Konstantin Ernst Kollmann (DE-CH) later coined the term neoteny to describe the process of transformation whereby newts and similar animals mature sexually while still in the larval form (1008).

 

Thomas Henry Huxley (GB) wrote what is probably the first comprehensive, comparative study of a single avian organ system (skeleton) (893).

 

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 (773).

 

Paul Bert (FR) observed that the blood of cuttlefish turned from colorless to blue when exposed to air (120).

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 (615).

 

Ludimar Hermann (CH), in 1867, proposed that digestion consists of a series of hydrolytic breakdowns that 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 to make new ones’ (821).

 

Albert von Bezold (DE) and Ludwig Hirt (DE) injected rabbits with veratrine causing bradycardia, hypotension, and apnea (1873). 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 heartbeat (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 (935).

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 (836).

Domingo M. Aviado, Jr. (US) reported that nicotine has the same effect on the Bezold-Jarisch reflex as veratine (44).

 

Thomas Lauder Brunton (GB) discovered that amyl nitrite is useful in the relief of angina pectoris (241).

Norman Brachfeld (US), John Bozer (US), Richard Gorlin (US), Morris H. Smith (US), and Elin Alexanderson (US) presented evidence that although treatment with nitroglycerin produces coronary vasodilatation; it appears to be secondary to an increase in myocardial oxygen consumption. Hemodynamic observations revealed a general decrease in pressures in both peripheral and pulmonary circuits; caution is urged concerning the occasional severe hypotensive effects of nitroglycerin (206).

 

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 (1144-1148). 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 William Thomson (Lord Kelvin) as president of the Royal Society.

 

Richard Payne Cotton (GB) published on observations of unusually rapid action of the heart (335).

Léon Bouveret (FR) observed patients with paroxysmal supraventricular tachycardias (paroxysmal tachycardia), naming the condition tachycardie essentielle paroxystique (191).

August Hoffmann (DE) described observations of paroxysmal tachycardia over a period of many years (854).

Louis-Benedict Gallavardin (FR) differentiated the following: Paroxysmal tachycardia (maladie de Bouveret); tachycardie paroxystique a center excitable; extrasystoles a paroxysmes tachycardiques; and terminal tachycardia (643-645).

 

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 (1407).

Georg Axhausen (DE) showed that the survival and osteogenic property of the periosteum varied between different types of grafts: they were highest in autografts; significantly less so in allografts and null in xenografts (45-48).

Dallas Burton Phemister (US) performed a series of experiments in dogs to further investigate osteogenesis. His findings showed that other than the periosteum, the endosteum, and the contents of the Haversian canals also had the capacity for osteogenesis (1508). Note: Phemister proved that Axhausen’s claim that osteogenesis did not occur from transplanted bone devoid of periosteum and endosteum was incorrect.

 

John Eric Erichsen (GB) defined postconcussion syndrome or railway spine (shell-shocked) (513; 514).

Wilfred Batten Lewis Trotter (GB) studied post-head injury status remarking, "seriously disabling headache is a common sequel to head injuries of an apparently minor kind, in which evidence of any direct local injury of the brain has been altogether lacking." (1817) Note: The historical notion of functional impairment in the absence of structural change as a sine qua non for concussion no longer rang true.

Dorothy Gronwall (NZ) stated, "Cerebral concussion is a closed head injury that represents a usually transient alteration in normal consciousness and brain processes as a result of traumatic insult to the brain. The alterations may include loss of consciousness, amnesia, impairment of reflex activity, and confusion regarding orientation. Although most symptoms resolve within a few days in the majority of cases, some physical symptoms such as headache, and cognitive symptoms such as memory dysfunction, may persist for an undetermined time." (760)

Thomas A. Gennarelli (US), Nancy C. Kupina (US), Megan R. Detloff (US), Walter F. Bobrowski (US), Bradley J. Snyder (US), and Edward D. Hall (US) using studies in animals of experimentally induced concussion have uncovered a variety of histological changes—some reversible, some not (678; 1066).

 

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 (314).

 

The Canadian Medical Association was organized.

 

1868-1875

Smallpox (spotted death) 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 (1005).

 

c. 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 (688).

 

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 (839; 1285).

 

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 (1799-1802).

Theodor Wilhelm Engelmann (DE), at roughly this same time, also discovered that red light is absorbed by plants and promotes photosynthesis (499; 500; 503; 506).

 

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 (1647; 1648).

Heinrich Kiliani (DE) proved arabinose to be a pentose (965).

 

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 (894; 895; 897).

John Harold Ostrom (US) proposed that birds descended from theropods (dinosaurs) (1429).

Robert T. Bakker (US) proclaims that birds are descendants of the dinosaurs (58).

 

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 (385).

 

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 (1641; 1642).

 

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 (1094-1098).

 

Thomas Henry Huxley (GB) incorporated geographical distribution into his taxonomy while considering the gallinaceous birds (grouse, quail, and turkey) (896).

 

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 (19).

H. Eliot Howard (GB) rediscovered this concept in 1920 (878).

 

Franz Ernest Christian Neumann (DE) described the presence of nucleated erythrocytes in the bone marrow of humans and rabbits. Based on this observation, he was the first to conclude that during postembryonic life, erythropoiesis and leukopoiesis is taking place in the bone marrow. In the 1868a article he says, " In the so-called red bone marrow of man as well as the rabbit, one can regularly find, in addition to the well-known marrow cell, certain other elements which have not been mentioned until now; namely nucleated red blood cells, in every respect corresponding to embryonic stages of the red blood cells. … It is possible to trace the origin of these elements to the marrow cells. The high content of colorless elements in the blood of the marrow makes it likely that there is a migration of contractile marrow cells into the vessels." He coined the term "myeloid" in 1869, as he was the first to recognize white blood cells were made in the bone marrow (Greek: myelos = (bone) marrow) as opposed to the spleen (1362-1364).

Giulio Cesare Bizzozero (IT) confirmed that nucleated red blood cells in the marrow evolved into nonnucleated red cells and extended these observations to include the formation of white blood cells (146-148).

Franz Ernest Christian Neumann (DE) later says, "The present work intends to demonstrate the physiologic importance of the bone marrow and that it is an important organ for blood formation which has not been recognized. It operates continually in the de novo formation of red blood cells." (1365)

Karl Friedrich Mosler (DE) introduced the technique of bone marrow examination to diagnose leukemia (1321).

William Osler (CA) Osler gave a series of three Cartwright Lectures in New York, reviewing his own work and that of others on blood platelets, coagulation, and thrombosis. The first lecture was titled “The Blood Plaque or Third Corpuscle,” in which he focused on platelet morphology and number and speculated concerning their origin. He also discussed the role of these “plaques” in disease and referred to his own observations. He stated that these plaques were increased in chronic wasting diseases, possibly the initial description of reactive thrombocytosis. He also noted that they might be elevated in some cases of leukemia and Hodgkin's disease. In the third lecture, “The Relation of the Corpuscles to Coagulation and Thrombosis,” Osler reviewed his work and that of Bizzozero and others, indicating that platelets, not leukocytes, are the initial cellular element of thrombosis. He further noted that the red corpuscles in health are constantly degenerating and constantly being reproduced. He commented that there could be no doubt that nucleated red cells originate in the bone marrow, crediting both Neumann and Bizzozero. He speculated on the process used by these cells to convert into the ordinary red disk, as he noted the “transformation of the nucleated red into the ordinary forms … by the gradual disappearance of the nucleus.” He also commented on the controversy about other possible origins of red cells, noting that the “colorless corpuscles (white blood cells) constitute separate elements with important functions quite apart from the regeneration of red cells” (1427).

William Osler (CA) noted that marrow hemorrhages in smallpox (spotted death). In leukemia, “instead of fatty marrow, the medulla of the long bones may resemble the consistency of matter which forms the core of an abscess.” In pernicious anemia, the marrow resembles that of a child, predominantly red marrow secondary to cellular hyperplasia (1428).

Otto Naegeli (CH) first characterized the myeloblast, which is the malignant cell in acute myeloid leukemia (AML). He divided the leukemias into myeloid and lymphocytic (1346).

 

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 (1533).

 

Wilhem His (DE) was the first to distinguish and describe the neural crest in the chick embryo. He noticed a band of particular material lying on top of the neural tube, underneath the superficial ectoderm(Hornblatt), which he called “zwischenstrang”. The ectoderm was thus divided into three different territories: the neural plate, the two strips -that later join- of the zwischenstrang, and the Hornblatt. He also found that the neural crest cells migrating away from their source accumulated laterally to the neural tube, at the site where the spinal ganglia develop. For this reason, the name of “ganglionic crest” was coined to designate this transitory structure (842).

Ross Granville Harrison (US) produced the indisputable proof that Wilhelm His (DE) was correct in identifying the neural crest as the source of the cells forming the dorsal root ganglia (802).

Sven Otto Hörstadius wrote: ”It seems clearly established today that the neural crest forms a special rudiment already present in the open neural plate stage” (876). Note: M. Angela Nieto (ES), Michael G. Sargent (GB), David G. Wilkinson (GB), and Jonathan Cooke (GB) fully confirmed in modern times the pattern of gene expression in the dorsal ectoderm at early developmental stages (1373).

 

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 (2013; 2014).

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] (1201).

 

Paul Langerhans, Jr. (DE) described the dendritic cells in the skin, which now bear his name. Because of their morphology he believed them to be nerve cells (1088).

John G. Frelinger (US), Leroy E. Hood (US), Sharon Hill (US), Jeffrey A. Frelinger (US), Stephen I. Katz (US), Kunihiko Tamaki (US), and David H. Sachs (US) unequivocally established the hematopoietic nature of Langerhans cells (618; 948).

Florent Ginoux (SG) and Miriam Merad (SG) noted that Langerhans cells are strategically located at one of the body's largest interfaces with the external environment where they form the first line of defense against pathogens that breach the skin. Langerhans cells migrate from the epidermis to the skin draining lymph nodes through the lymphatic vessels, and present processed antigens to T lymphocytes (686).

 

Gustave Albert Schwalbe (DE) and Otto Christian Lovén (SE) independently discovered taste buds in rabbits, hares, man, horse, dog, pig, squirrel, and guinea pig (1175; 1684).

 

Guillaume Benjamin Amand Duchenne (FR) described the Duchenne-Erb palsy caused by upper brachial plexus injury during childbirth (444).

 

Karl Ewald Konstantin 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 (218; 820).

 

George I. Johnson (GB) reported studies on nephritis. He suggested that hyaline-fibroid alterations in the renal vessels were due to an impure condition of the blood, which was also responsible for left ventricular hypertrophy (938). Note: This work supported Richard Bright's conclusions in 1836.

 

Armand Trousseau (FR) described a type of hand contraction, which became known as Trousseau sign (1819). 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 (1288).

 

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 (288).

 

Jean-Martin Charcot (FR) and Paul Marie Louis Pierre Richer (FR) were perhaps the first to describe multiple sclerosis: shaking, diplopia, amblyopia, nystagmus, vertigo, paretic state with rigidity, early onset in young adults, and irregular progression with periods of remission. Young women were more often affected than men (289; 295). Note: multiple sclerosis is an autoimmune disease that attacks the myelin sheath on nerve cells leaving a sclerotic product in its place.

 

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 organism under the prodding of the virus makes the latter. The variolar virus is contained in the pus of the pustule but the pus is not the virus." Villemin was thus 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 (1853).

 

Johann Dogiel (LT) and Karl Friedrich Wilhelm Ludwig (DE) concluded that the first cardiac sound is chiefly due to contraction of the muscular fibers of the ventricles assisted by closure of the auriculoventricular valves (427).

 

Frans 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 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) (429; 430).

 

Jules Emile Péan (FR) and Eugène Koeberlé (FR) both claimed to have invented the operative hemostat (549; 1492).

 

John Stough Bobbs (US) was the first to perform cholecystotomy for gallstones (169; 170).

 

Louis Lartet (FR), in 1868, was the first to find fossil remains of Homo sapiens sapiens (Cro-Magnon man). These were in a rock shelter site near the village of Les Eyzies in Southwestern France (221). The remains were dated to c. 28 K 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 (1316).

 

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 (983; 1269; 1270).

 

Johannes Adolf Wislicenus (DE-CH) 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. Otto Meister (CH) 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." (1258; 1996)

 

Jakob Ernst Arthur Böttcher (DE) introduced the method of regressive staining—over-staining followed by de-staining, or differentiation, with alcohol (177).

 

Jules Raulin (FR) identified zinc as an essential trace metal in plants and animals (1543).

Gabriel Émile Bertrand (FR) and Boje Benzon (FR) were the first to determine that zinc is essential to animal nutrition (127; 128).

 

Giulio Cesare Bizzozero (IT), in 1869, was the first to describe giant cells of the bone marrow (149).

William Henry Howell (US) named Bizzozero’s giant bone marrow cells megakaryocytes (879). 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 (1577).

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 (175). These would later be named Bollinger bodies in honor of Otto 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 (858).

 

Léon Coze (DE) and Victor-Timothée 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 (340). Davaine was to later call this ‘passing’ through the animal (‘en passant si je puis ains dire dans l’économie d’un animal vivant’) (386).

Heinrich Hermann Robert Koch (DE), in 1876, used this "passing" technique to purify anthrax material (990).

 

Theodor Albrecht Edwin Klebs (DE) introduced paraffin imbedding to microtechnology (974).

 

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 amino acids possess only one nitrogen each they concluded that some type of biosynthesis must have been occurring (1677).

 

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, a word coined by Galton (647).

Francis Galton (GB) argued that ‘inferiority’ and ‘superiority’ could be objectively measured (650). Note: Doubtless man has been practicing selective breeding of animals (including humans) and plants, with the goal of "improvement," since before recorded history.

 

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 (1633).

 

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 (857; 858).

 

Adolf Eduard Mayer (DE) improved the Pasteur fluid for growing bacteria by using chemically pure solutions of the salts found in ash of yeast (1245).

 

Hinrich Nitsche (DE) proposed to divide the Bryozoa into two groups, Entoprocta, and Ectoprocta with Entoprocta used as a phylum name (1377; 1378).

 

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 (92).

Pedro Severiano de Magalhaes (BR) discovered a very similar fungal disease called black piedra (402). It is caused by Piedraia 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 (877). 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 (1089; 1090). These would later be named the Islets of Langerhans in his honor. See, Laguesse, 1894.

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 (290; 292; 294). 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 (1036).

Teepu Siddique (US) identified mutations in the superoxide dismutase gene SOD1 as a cause of familial amyotrophic lateral sclerosis (1715).

 

Carl Philipp Adolf Konrad 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." (1069) 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.

 

Johann Friedrich Horner (CH) is recognized as the first to provide a detailed and scientifically supported description of unilateral ptosis (a weak droopy eyelid), miosis (construction of the pupil), and anhydrosis (decreased sweating), commonly referred to as Horner syndrome or oculosympathetic paresis. Horner described manifestations of this syndrome in humans and accurately interpreted the signs of sympathetic nerve damage (870). Note: Horner's syndrome was commonly associated with syphilis.

 

Jacques-Louis Reverdin (CH), in1869, performed the first "fresh skin" allograft. The procedure consisted of removing tiny pieces of skin from a healthy area of the body and seeding them in a location that needs to be covered (1496; 1558).

 

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 (90; 1844).

 

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 (1115).

 

Marcelino de Santuola (ES), in 1869, discovered the Altamira Caves near Santillana del Mar, Spain. These caves contain important Paleolithic art 14-16 K years old (40).

 

American Journal of Obstetrics was founded.

 

1870

"The tragedy of science—the slaying of a beautiful hypothesis by an ugly fact." Thomas Henry Huxley (898)

 

Paul Bert (FR) was the first to clearly view the organism as a gas exchange system (121).

 

Johann Friedrich Wilhelm Adolf 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 (52).

 

Johann Friedrich Wilhelm Adolf Baeyer (DE) and Rudolf Fittig (DE) determined the molecular formula for glucose (52; 578).

 

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 (1707).

 

Johannes Ludwig Emil Robert von Hanstein (DE) was the first to describe the sequence of cell divisions in the development of the plant embryo (1887).

 

Bartolomeo Camillo Emilio Golgi (IT) demonstrated that the glial interstitial tissue in not amorphous but contains cells rounded or lenticular or stellar and distinct from elements of the nerve tissue (696; 719).

 

Heinrich Wilhelm Gottfried Waldeyer; Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) discovered the germinal epithelium (the ovarian surface epithelium). He demonstrated that the sexual organs in vertebrates are originally bisexual and proposed that female mammals cease production of oocytes at or shortly after birth (1936).

Solomon Zuckerman (GB) wrote a treatise in which he supported Waldeyer's proposal of the absence of postnatal oogenesis in mammals (2034). Note: As of 2020, the validity of the dogma that oogenesis and folliculogenesis do not persist in the ovaries of adult mammalian females is controversial.

 

Timothy Richards Lewis (GB) was the first to describe amoebas in the stools of humans although his descriptions do not allow identification (11; 1135).

 

Gustav Heinrich Theodor Eimer (DE) established the pathogenicity of trophozoites from his work on Cyclospora in the intestine of the mole (482).

 

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 (13).

 

Theodor Albrecht Edwin Klebs (DE) coined the name glomerulonephritis (975). He later described the hypercellularity in the patients dying in the acute nephritic phase of glomerulonephritis in 1875.

Theodor Langhans (DE) confirmed that glomerular hypercellularity attends glomerulonephritis (1091).

Theodor Langhans (DE), in 1885, described the leukocyte infiltrative component of nephritis.

 

Adolf Eugen Fick (DE), in 1870, was the first to measure cardiac output, using what is now called the Fick principle (inverse Fick equation). Its underlying principle is that the blood flow to an organ can be calculated using an indicator material if certain perimeters are known (544).

 

Moritz Schiff (DE-FR-CH) postulated the enterohepatic circulation of the bile (1656).

Ernst Stadelmann (EE) supported the experiments and claims of Schiff in regard to the enterohepatic circulation of the bile acids (1742-1744).

 

Franz Ernest Christian Neumann (DE) was the first to note changes in the bone marrow in leukemia, and he proposed the term myelogenous leukemia (1366).

 

Gustav Simon (DE) reported the first successful planned nephrectomy (kidney removal). It was prompted by a urinary tract fistula (1716). Note: This successful operation prompted the realization that humans can survive with just one kidney.

 

Theodore Gaillard Thomas (US) was the first to perform vaginal ovariotomy (1792).

 

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 (376)

 

"But we are not here concerned with hopes or fears, only with the truth as far as our reason permits us to discover it; and I have given the evidence to the best of my ability. We must, however, acknowledge, as it seems to me, that man with all his noble qualities, with sympathy which feels for the most debased, with benevolence which extends not only to other men but to the humblest living creature, with his godlike intellect which has penetrated into the movements and constitution of the solar system —with all these exalted powers — Man still bears in his bodily frame [behavioural repertoire] the indelible stamp of his lowly origin."Charles Robert Darwin (376).

In agreement, Peter B. Medawar (GB) says, "The existence of behavioural homologies makes it easy to understand that such human activities as play, showing off and sexual rivalry are not innovations of mankind but have deep evolutionary roots." (1255)

 

"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 (1290)

 

"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.” (1465)

 

Dimitri Ivanovich Mendeléev; Dimitri Ivanovich Mendeléeff (RU) predicted that the gaps in his periodic table represented elements undiscovered (1271).

 

Johann Friedrich Wilhelm Adolf Baeyer (DE) synthesized fluorescein by the condensation of phthalic anhydride with resorcin (53; 54).

 

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), during protein breakdown (850; 851).

 

Ernst Felix Immanuel Hoppe-Seyler (DE) discovered that yeast extract contains invertase, an enzyme that catalyzes the conversion of sucrose to glucose and fructose (1286).

 

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 (1289-1293). Note: Miescher completed this work in written form and presented it to his laboratory director, Ernst Felix Immanuel Hoppe-Seyler (DE), in 1869. Hoppe-Seyler delayed publication until 1871 during which time he personally repeated and verified Miescher's work.

Richard Altmann (DE), a biochemist and a student of Johann Friedrich Miescher, Jr. developed a method for producing nuclein preparations, which he considered to be free of protein; he named such protein-free nucleins nucleic acids (18).

 

Carl Weigert (DE) was the first to stain bacteria. While studying smallpox (spotted death) pustules he showed that the nuclear dye carmine would stain cocci (1958).

 

Ernst Tiegel (DE) used a porous unburned clay filter to separate anthrax from fluids containing it. This was the first successful filtration of bacteria from a liquid medium (1798).

 

David Douglas Cunningham (GB) described what was probably Endamoeba coli in the stools of humans (353).

 

Henry Pickering Bowditch (US), using the isolated frog heart preparation, discovered the staircase, Treppe, phenomenon that 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 in the atrium and the atrioventricular area (202; 640).

Francis Gotch (GB) determined that the nerve action potential is an all-or none phenomenon (730).

Frederick Haven Pratt (US) would later demonstrate that skeletal muscles also follow the all-or-none principle of contraction (1526).

 

Wilhelm Max Wundt (DE) described reaction time course and reflex time course through the spinal cord and ganglia, and muscle sense (2016).

 

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 (2035).

 

Johann Ernst Oswald Schmiedeberg (RU-DE) and Karl Friedrich Wilhelm Ludwig (DE) traced the accelerator fibers of the vagus nerve in the dog (1664).

 

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 must be left intact for normal vasomotor tone and reflexes (422; 423; 1435). 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 (448).

 

Franz Ernst Christian Neumann (DE) described a benign muscle tumor of the newborn, which he named congenital epulis (CE) (1367).

 

C. Hilton Fagge (GB) concluded that degeneration, atrophy, or loss of the thyroid gland resulted in cretinism (521).

 

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 (1816).

Friedrich Daniel von Recklinghausen (DE) named the condition hemochromatosis (1916). 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 (1309).

 

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 (886).

 

Karl Friedrich Otto Westphal (DE) first described agoraphobia (fear of open places) (1977).

Pieter Forest; Petrus Forestus; Pieter van Foreest (NL) described agoraphobia in 1592 (1530).

 

Silas Weir Mitchell (US) provided a detailed account of phantom limb syndrome (1301; 1302).

 

George D. Pollock (GB) introduced the treating of burn patients with epidermal grafts (1515).

 

Theodor Albrecht Edwin Klebs (DE), over a two-month period, autopsied 115 men who died of gunshot 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 various forms in nearly every case (976; 977).

 

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 (792).

Hugo Mella (US) offered experimental confirmation of the importance of the striatum in athetosis (1259).

 

Campbell de Morgan (GB) argued, rationally and logically, that cancer arises locally and then spreads, first to the lymph nodes and then further afield (405-407).

De Morgan presented his thesis in an address to the Pathological Society of London on 3 March 1874. He fully accepted that the local development of a tumor is influenced by host susceptibility factors, that cancers occasionally undergo spontaneous regression, and that, in some cases, spontaneous regression of cancer is associated with infections and, particularly, with the onset of tuberculosis. He noted that cancer is uncommon in, and rarely coexists in, families affected by tuberculosis (408).

Paul Bruns (DE) confirmed De Morgan's observation that regressions and even complete resolutions of cancer were occasionally associated with severe infections, notably erysipelas (240).

William B. Coley (US), using a virulent strain of Streptococcus pyogenes, successfully induced erysipelas in a patient with advanced sarcoma of the neck and the tumor disappeared completely (321). Coley later found that Bacillus prodigiosus worked just as well (322).

William B. Coley (US) experimented with bacteria-free extracts and eventually found that a mixture of extracts of Streptococcus pyogenes and Serratia marcescens (‘Bacillus prodigiosus’) was as effective as living streptococci (323).

Steven A. Rosenberg (US), Paul Spiess (US), and Rene Lafreniere (CA) issued the first report of successful immunotherapy with autologous cytotoxic lymphocytes specific for the patient's tumor antigens (1587).

Chen Dong (US) and Richard A. Flavell (US) discovered that T helper cells mature along (at least) two distinct pathways, yielding Th1 and Th2 cells (431). These T cell types produce or induce different cytokines and thereby affect a range of quite different immune reactions. Accordingly, it is now possible to analyze immune responses in detail and to design therapeutic strategies to induce protective responses and to down-regulate inappropriate ones.

Mario Clerici (IT), Enrico Clerici (IT), Gene M. Shearer (US), Takashi Nishimura (JP), Minoru Nakui (JP), Marimo Sato (JP), Kenji Iwakabe (JP), Midemitsu Kitamura (JP), Akio Ohta (JP), Toshiaki Koda (JP), Shinichiro Nishimura (JP), Michele Orditura (IT), Ciro Romano (IT), Ferdinando De Vita (IT), Gennaro Galizia (IT), Eva Lieto (IT), Stefania Infusino (IT), Giuseppe De Cataldis (IT), and Giuseppe Catalano (IT) presented evidence that Th1 reactivity mediates protection against tumors and that many common cancers are associated, as either cause or effect, with immune dysregulation leading to a drift towards Th2 reactivity (309; 1376; 1413).

 

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 (376).

 

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) (651).

 

In London, England the annual smallpox (spotted death) mortality was greatest in 1871; the annual sum for that year was 7,982, and Creighton’s table indicated 7,912. In all other years in which records were kept, there were fewer than 4,000 smallpox deaths (866).

 

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) (1302)

 

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 several proteins in terms of the ratio of ammonia nitrogen to the total nitrogen (1355-1357).

 

Charles Lauth (FR) and H. Baubigny (FR), in 1872, made the dye methyl green (326). 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 (1067; 1068).

 

Louis Jullien (FR) was the first to develop a stain for connective tissue. It consisted of saturated aqueous indigo carmine acidified with oxalic acid then added to saturated picric acid (943).

 

Gustav Albert Schwalbe (DE) discovered Paneth cells of the duodenum (1685).

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 (1443). They are functionally like neutrophils. When exposed to bacteria or bacterial antigens, Paneth cells secrete several 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 containing sturgeon’s glue, one of the first uses of a solid medium in bacteriology (275). 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 supported 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) (77; 1467; 1468).

 

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 could. 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 might differ from each other in their physiological characteristics, and in their products. In this paper he coined the genus name Bacillus (315).

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 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 close group of organisms which show no relation to yeasts or molds but have close affinities with certain blue-green algae, i.e., cyanobacteria (315-317).

 

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” (777; 780).

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) like 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 (780).

 

Casimir Joseph Davaine (FR) found that the blood of animals suffering or dead from putrid injections can induce 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. Within a species, young were more susceptible than older animals (386).

 

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 (1670).

 

Carl 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 could produce anthrax in a healthy animal (461).

 

Julius Oscar Brefeld (DE) laid down the principles that 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 (216).

 

August Heinrich Rudolf Grisebach (DE) wrote one of the first comprehensive reviews of knowledge of the Earth’s vegetation (759).

 

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 (766-768).

Sewall Green Wright (US) would later popularize Gulick’s discovery as random genetic drift (the Sewall-Wright effect) (2006-2010).

 

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 (336).

 

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 Charles Wyville Thomson (GB). They included the 'naturalists' 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, during 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. Thomas 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 laid the cornerstone of scientific oceanography and begun its introduction to the wider scientific and lay community. John Murray correctly described the findings of the cruise in 1895 as "the greatest advance in the knowledge of our planet since the celebrated discoveries of the fifteenth and sixteenth centuries" (220).

 

Morrill Wyman (US) stressed family predispositions to hay cold due to pollens (2018).

 

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 (1042). 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 (808).

Rudolf Ludwig Karl Virchow (DE) detected microbes in endocarditis vegetations (1861).

Anton Weichselbaum (AT), in 1883, cultivated both streptococci and staphylococci from endocardial vegetations (1956).

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 (1418; 1561; 2019).

Hugo Schottmüller (DE) presented proof of the bacterial nature of malignant endocarditis (acute and subacute endocarditis) (1669).

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 rheumatic heart disease (312; 331; 1525).

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 (458).

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 (458).

The normal biofilm of microorganisms on human tissues often excludes would be pathogens from gaining a foothold (458).

Adherent microorganisms in a thick glycocalyx are significantly more resistant to chemical biocides than are their otherwise equivalent planktonic counterparts (458).

Adhesion of bacteria to phagocytes is essential to the successful function of the phagocytic defense system (458).

 

Ferdinand Karl Franz 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) (213; 946; 1891; 1892).

 

Ferdinand Karl Franz von Hebra (AT) was the first to describe impetigo herpetiformis (1890).

Moriz Kohn Kaposi (HU) completed and refined the description of impetigo herpetiformis (947).

 

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." (1808).

 

Emil Jacob Noeggerath (US) described the effects of latent gonorrhea in women (1383; 1384).

 

Christian Albert Theodor Billroth (DE-AT) performed the first resection of the esophagus in laboratory animals (140).

Vincenz Czerny (CZ-DE) performed the first successful resection of the thoracic region of the esophagus in humans (esophagectomy) (360; 1588).

Franz Torek (DE-US) performed the first successful transthoracic resection of the esophagus for carcinoma (1804).

Marc B. Orringer (US) and Herbert Sloan (US) presented their surgical technique of esophagectomy without thoracotomy (1417). This was a revival of an incidental technique carried out by George Grey-Turner (GB) in 1933 (754).

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 (653-655).

 

Robert Battey (US) was the first to perform oöphorectomy (ovariectomy). Often this operation is to remove normal ovary or ovaries for such non-ovarian conditions as painful menstruation and neuroses (86).

Robert Lawson Tait (GB), in 1879, reported the removal of normal ovaries in 1871, 16 days prior to Battey’s operation (1772).

William Williams Keen, Jr. (US) reported three cases of removal of the ovaries and fallopian tubes (949).

 

Frank Eastman Bundy (US) and William Ingalls (US), on 8 October 1872, carried out the first nephrolithotomy, a surgical procedure in which the kidney is cut to remove a stone (244).

 

Louis Xavier Édouard Léopold Ollier (FR) introduced split-skin grafting (1408).

Karl Thiersch (DE) improved Ollier's split-skin grafting technique in 1874 (1785).

 

Johann Otto Leonhard Heubner (DE) described the vascularization of the anterior part of the caudate nucleus within the brain (834).

Henri Duret (FR) using injections of colored gelatin, was the first to describe the distribution of supply arteries in the brainstem and then in the cortex. His descriptions correlated irrigated territories, infarcted zones and secondary neurological deficits (454).

 

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 (61; 62; 1318; 1419; 1420; 1731; 1732). Note: This became known as the Baldwin effect.

Douglas Alexander Spalding (GB) discovered stamping-in (imprinting) (1732).

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 (1170-1173). 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 rediscovered 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 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) (812; 813).

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 an example (1981). See, Schrader 1921, Solter in 1984 and Jablonka in 2009 for a different types.imprinting.

 

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.

 

1873-1890

Christian Karl Hoffmann (NL) compiled the first general compendium of data on the morphology of amphibians and reptiles in Heinrich Georg Bronn's (DE) publication Klassen und Ordnungen des Thierreichs (225; 855).

 

1873

Johannes Diderik van der Waals (NL) described the weakest of the electrostatic attractions between atoms of opposite charge (1843). 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 (1).

 

Casimir Joseph Davaine (FR) discovered the antimicrobial properties of iodine (411).

 

Emil Godlewski, Sr. (PL) discovered that starch formation in illuminated leaves was correlated with the presence of carbon dioxide within the atmosphere (689).

 

Kerosene, applied by paintbrush to tree limbs, was advocated for the control of woolly apple aphid. By 1875 a kerosene emulsion spray had been developed (1707).

 

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 (852; 853).

 

Bartolomeo Camillo Emilio Golgi (IT) and Nicolò 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" or "response cromoargentica." 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 (a term coined by R.A. von Kölliker in 1896) are invested with co-lateral branches (695; 702; 711; 721; 723).

 

Alfred Wilhelm Volkmann (DE) described the canals in bone carrying blood vessels from the periosteum (Volkmann's canals) (1863).

 

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 (1047; 1182; 1959).

 

Theodor Wilhelm Engelmann (DE) discovered that I (isotropic) bands shorten during contraction of striated muscle (492; 493).

 

John Hughlings Jackson (GB) was the first to state clearly that the brain, the organ of mind, possesses motor functions (913; 914).

 

Sebastiano Rivolta (IT) determined that epizootic lymphangitis (African glanders) is caused by the yeast Cryptococcus farciminosus (1576). In 1934 it would be renamed Histoplasma farciminosum.

 

Giulio Cesare Bizzozero (IT) was also the first—10 years before Metchnikoff—to propose that the process of phagocytosis could be protective against infection: "…this fact [ingestion of infective particles by reticular cells] is, perhaps, the cause of the stoppage of some infections to the lymphatic glands which are connected to the part covered by the infection through the lymphatic vessels." (150; 1247)

William Osler (CA) reported in 1875-1876 the presence of carbon particles within cells harvested from the lungs of coal miners (1426).

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 Metchnikoff, and the process phagocytosis. He first observed this phagocytic activity 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 bicuspidate. In frogs, lizards, turtles, guinea pigs, and rabbits he introduced a solution of anthrax under the skin or by injection into both immunized and nonimmunized animals, concluding (incorrectly) that phagocytosis was responsible for all protection (1280-1283). Note: It is in Metchnikoff's 1883b article that the word phagocyte appears for the first time in scientific literature. He Austrian friend Carl Friedrich Wilhelm Claus (DE) suggested it as the Greek equivalent to fresszellen (devouring cells), phagocyte (phagein [to eat] and kytos [cell]) (1777).

 

Otto Hugo Franz Obermeier (DE) while examining the blood of patients with European relapsing fever discovered Borrelia recurrentis, the bacterial cause of relapsing fever (1393). This organism has been called Obermeier’s spirillum.

Gregor Münch (DE), in 1878, suggested that relapsing fever might be transmitted by the bite of blood-sucking arthropods such as lice, fleas, and bugs (1527).

Joseph Everett Dutton (GB), John L. Todd (GB), and Robert Newstead (GB) discovered that B. duttoni is an alternative vector to the soft tick Ornithodoros moubata in human tick-fever(457). Note: Dutton relapsing fever

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 during an important epidemic occurring at the Algerian-Moroccan border between 1907-1910 (592).

 

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 several 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 (978).

 

Theodor Albrecht Edwin Klebs (DE) produced tuberculosis in cattle by feeding them infected milk (979).

 

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 (1540).

 

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 (1392).

 

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 (158).

 

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 (1414-1416).

 

James Paget (GB) described eczema of the nipple with subsequent mammary carcinoma, i.e., Paget’s disease of the nipple (1436).

 

Christian Albert Theodor Billroth (DE-AT) and Carl Gussenbauer (DE), in 1873, performed the first total laryngectomy (143; 774; 1588).

 

Nikolaus Friedreich (DE) wrote a monograph on progressive muscular atrophy (634).

 

Jean Joseph Emile Letievant (FR) was the first to describe cranial and peripheral neurectomy to alleviate pain (1124).

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 (2).

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 (101).

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 (875). 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 (803).

Fedor Krause (DE) performed an intracranial neurectomy in the fifth nerve (1043).

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 (806; 807).

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 (357).

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 (1739).

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 (1740).

Charles Harrison Frazier (US) perfected the operation for the radical cure of trigeminal neuralgia (614).

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 (591).

Egas Moniz (FR) reported successful control of intractable pain after frontal lobotomy (1311).

 

David Ferrier (GB) and William Aldren Turner (GB) began reporting their neurological studies, which according to 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 especially 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." (532-541; 1709; 1726)

 

Pierre-Joseph van Bénéden (BE) introduced the terms commensalism and mutualism (1837). He defined a commensal individual as requiring "a simple place on his vessel, and does not partake of his provisions...animals which live on each other, without being either parasites or messmates; many of them are towed along by others; some render each other mutual services, others again take advantage of some assistance which their companions can give them; some afford each other an asylum...” (1839).

 

Archives for Experimental Pathology and Pharmacology was founded.

1874

Josiah Willard Gibbs (US) published, between 1874 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 (682).

 

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 (1112; 1846-1848).

 

Heinrich Caro (DE) synthesized the dye eosin in 1874. It is a phthalein product consisting of brominated fluorescein (119). Eosin would later prove useful for selectively staining cytoplasmic proteins.

 

Max Jaffé (DE) isolated and named urocanic acid (Gk. ouro, urine + L. canis, dog) from dog’s urine (929; 930).

Andrew Hunter (US) determined that urocanic acid is an imidazole derivative, and a product of the deamination of the amino acid histidine (885).

 

Jules Piccard (CH) discovered that the hydrolysis of nucleoproteins yields the purines, guanine, and xanthine (1510).

 

Walther Flemming (DE) used carmine to stain the eggs of Anodonta (freshwater muscle) (581).

 

Frédéric Alphonse Musculus (FR) obtained an enzyme (urease) from putrid urine, which he found capable of decomposing urea in aqueous solutions (1344; 1345).

 

Albert Wojciech Adamkiewicz (PL) presented his reagent, which gives a color reaction with proteins. It was later found to give a positive reaction with tryptophan (4; 5; 867).

Richard Neumeister (DE) coined the name tryptophan for that substance which gives a color reaction with chlorine water following extensive degradation of a protein (the Adamkiewicz Test) (1369).

Frederick Gowland Hopkins (GB) and Sydney William Cole (GB) isolated tryptophan from a trypsin digest of casein and showed that some proteins did not contain it, e.g. gelatin (868).

Alexander Ellinger (DE) and Max Geutzen (DE) found that tryptophan could act as a precursor to indole production in the intestine (486; 487).

Edith G. Willcock (GB) and 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 (tryptophan) in nutrition. Willcock and Hopkins thus originated(1983). 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 couldn’t survive on zein of corn as their sole dietary protein unless tryptophan and lysine are added. This was also an early indicator that animals might require individual amino acids (1423).

Otto Folin (SE-US) and Vintila Ciocalteu (US) developed a method of determining the tyrosine and tryptophan in proteins (593).

 

Henry D. Schmidt (US) described intersegmental clefts in the myelin sheath of peripheral nerves (1663). To honor him these are called Schmidt's Clefts.

 

William Roberts (GB) found that when infusions of hay are carefully neutralized they could 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 (1578).

 

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) (395; 524).

 

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 alga—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 (141).

 

Jean Baptiste André Dumas (FR) reported that sulfite can inhibit alcoholic fermentation (449).

 

Tadeusz Browicz (PL) was the first to describe the bacillus that causes typhoid fever, later to be known as Salmonella typhi (227).

 

Charles-Marie Benjamin Rouget (FR) was the first to describe a contractile, motile cell surrounding capillaries in a tunic-like fashion. In the brain these pericytes, originally called Rouget cells, are in precapillary arterioles, capillaries and postcapillary venules where they are part of the blood-brain barrier. Pericytes are local regulatory cells that are important for the maintenance of homeostasis and hemostasis and are a source of adult pluripotent stem cells (1600).

 

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 during normal embryonic development identifiable regions of the early embryo develop into specific structures of the older embryo (843; 1990).

 

Pierre-Joseph van Bénéden (BE) was able to show through his studies of the digestive tracts of many fishes that cysticerci are larvae of intestinal worms called taeniae (adult tapeworms). His work covered a wide range of parasites in diverse animals (1838). About 1859 he began a study of fossil and recent whales, which resulted in a major work, written in collaboration with Paul Gervais (BE) (1840). 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 (264; 512).

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 (1560).

 

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 (797-799). This was the first bacterium to be implicated as the probable cause of an infectious disease in humans.

Albert Ludwig Siegmund Neisser (DE) used aniline dyes to convincingly demonstrate that Mycobacterium leprae is the etiological agent of leprosy (1360).

 

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 (176; 1125).

Walery Jaworski (PL) isolated a spiral bacterium characteristically present in stomach cancer and ulcer. He called the bacterium Vibrio rugula (936).

Giulio Cesare Bizzozero (IT) noted spirochetes in the gastric mucosa infiltrating gastric glands and found them within the cytoplasm and vacuoles of parietal cells of dogs (151). These organisms were named Helicobacter bizzozeronii in 1996.

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." (1329)

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 (1237; 1951).

Charles Stewart Goodwin (AU), John A. Armstrong (AU), Terry Chilvers (AU), Michelle Peters (AU), M. David Collins (GB), Lindsay I. Sly (AU), William McConnell (AU), and William E.S. Harper (AU) presented compelling evidence that this organism should be placed in a new genus as Helicobacter pylori (725).

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 James 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 (735; 906; 1235; 1446; 1500).

Barry J. Marshall (AU), David B. McGechie (AU), Peter A. Rogers (AU), and Ross James Glancy (AU) associated pyloric Campylobacter infection with gastroduodenal disease (1236).

Thomas J. Borody (AU), Peggy Cole (AU), Suzanne Noonan (AU), Anne Morgan (AU), Jennifer Lenne, Lorraine Hyland (AU), Susan Brandl (AU), Edith G. Borody (AU), and Laura L. George (AU) reported the recurrence of duodenal ulcer and Campylobacter pylori infection after eradication (174).

Laura L. George (AU), Thomas J. Borody (AU), Peter Andrews (AU), Michele Devine (AU), Deborah Moore-Jones (AU), Mary Walton (AU), and Susan Brandl (AU) described a cure of duodenal ulcer after eradication of Helicobacter pylori (679).

 

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 anemia in adults, and its cure can normalize the hematologic picture (1230).

 

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 (439).

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 (600). Absolute proof of the existence of the synapse came in 1959 with the electron micrographs of Edward George Gray (GB) (751).

 

Rudolf Peter Heinrich Heidenhain (DE) and Albert Ludwig Siegmund Neisser (DE), based on carefully controlled dye injection studies, provided experimental proof for the existence of proximal tubular secretion as a principal transport process involved in urine formation (811).

 

William Osler (CA) was doubtless describing platelets (thrombocytes) when he reported, "Careful investigation of the blood proves that, in addition to the usual elements, there exist 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." (1425)

 

Vladimir Alekseyevich Betz; Vladimir Aleksandrovich Betz (UA) 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 (134).

W. Bevan Lewis (GB) and Henry Clarke (GB) published work on the giant pyramidal cells of human pre-central gyrus (1139; 1140).

 

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 also all eggs and sperm, even the giant eggs of birds and reptiles, are single cells. Gegenbaur applied the term syncytium to striated muscle (676).

 

Johann H. Schultz (DE) and F. Baumstark (DE) made the first clinical presentations of porphyria. Baumstark named two pigments derived from the urine of his patient—urorubrohaematin and urofuscohaematin. He interpreted the source of the porphyrin pigments as an error in biosynthesis. This was the first association of this class of pigments in urine with a disease in humans (87; 1672).

 

Francis Galton (GB) used the phrase nature and nuture to explain heredity and environment (648).

 

Hugo Kronecker (DE) and William Stirling (GB) showed that the heart muscle cannot be tetanized (1048).

 

Roberts Bartholow (US) was the first to electrically stimulate the human cortical tissue (76).

 

Karl Ludwig Kahlbaum (DE) coined the term catatonia to denote an organic illness with somatic and mental symptoms (945). Note: It came to mean abnormality of movement and behavior arising from a disturbed mental state (typically schizophrenia). Informally it means a state of immobility and stupor.

 

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 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 (466; 1972). See Broca, 1856. Sensory aphasia is due to cortical lesions in the posterior portion of the left first temporal convolution.

 

Carl Philipp Adolf Konrad Kussmaul (DE) and Anton Frey (DE), his assistant, suggested the name poliomyelitis anterior acuta for acute myelitis of the anterior cornua. This affliction is more common in children. The word polio means grey in Greek and refers to the inflammed grey matter in the spinal cord. It was frequently called infantile paralysis (622-624).

 

Carl Philipp Adolf Konrad Kussmaul (DE) described a deep and labored hyperventilation, which is found in patients dying with severe diabetic ketoacidosis. It is called 'Kussmaul respirations' (or breathing) (1070).

 

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 (1785).

 

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 catgut 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 (762).

 

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 (65M B.C.E.-54.9M B.C.E.) of the Cenozoic Era based on a study of floral samples from the Paris Basin (1659).

 

The Botanischer Jahresbericht was founded.

 

c. 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 (1583).

 

Edward Frankland (GB) conducted experiments at the sewage farm in Croydon, England, and was able to demonstrate that filtration of sewerage through porous gravel produced a nitrified effluent (the ammonia was converted into nitrate) and that the filter remained unclogged over long periods of time (1610).

Edward Ardern (GB) and William T. Lockett (GB) discovered the activated sludge process. They aerated the waste-water continuously for about a month and were able to achieve a complete nitrification of the sample material. Believing that the sludge had been activated (in a similar manner to activated carbon) the process was named activated sludge. Not until much later was it realized that what had actually occurred was a means to concentrate biological organisms, decoupling the liquid retention time (ideally, low, for a compact treatment system) from the solids retention time (ideally, fairly high, for an effluent low in biological oxygen demand and ammonia (25; 26). Note: During the half-century around 1900, public health interventions such as sewage treatment succeeded in drastically reducing the incidence of water-borne diseases among the urban population, and were an important cause in the increases of life expectancy experienced at the time (359).

 

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. Atwater was the first director of the Office of Experiment Stations (1888).

 

Hermann Emil Fischer (DE) discovered phenylhydrazine in 1875, and 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 (557; 559; 561-563; 566; 568; 570-576).

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." (564; 565; 570) During 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 and L forms of mannoic acid were the first pair of enantiomorphs to be discovered in this group of sugars (561; 570).

Hermann Emil Fischer (DE) related the optical activity of sugars to that of tartaric acid (567).

 

Wilhelm Friedrich Kühne (DE) showed that indole appears after proteinaceous material putrifies. The protein will give a violet color when nitric acid is added (1055).

 

Whale oil, soap, and kerosene were advocated as insecticidal spray for numerous insect pests (1707).

 

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 (333).

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 (470).

 

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 (29). 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 (316).

 

Jules Emile Planchon (FR) discovered the fungus Phylloxera that causes a severe disease of grapevines (1512).

 

Edouard Joseph Louis Marie van Bénéden (BE) coined the term nucleoplasm (1833).

Walther Flemming (DE) coined the term karyoplasm (582).

 

Heinrich Wilhelm Gottfried Waldeyer; Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) was the first to name a cell type as plasma cell, nevertheless, there is a possibility that what he described was mast cells (1937).

 

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 demonstrated 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 (259-261).

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 (824).

Giulio Cesare Bizzozero (IT) and Alessandro Augusto Torre (IT) produced images of mitosis as it occurs in the spleen of the triton (152).

Édouard Joseph Louis Marie van Bénéden (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 (1835). Note: Édouard Joseph Louis Marie van Bénéden (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 (835).

August Friedrich Leopold Weismann (DE) wrote an article, which emphasized meiosis as an exact mechanism of chromosome distribution (1965).

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 (583).

Theodor Boveri (DE), working with Ascaris megalocephala (now Parascaris equorum) 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 (195; 196; 201).

August Friedrich Leopold Weismann (DE) elaborated an all-encompassing theory of chromosome behavior during cell division and fertilization and predicted the occurrence of meiosis (1966).

Édouard Joseph Louis Marie van Bénéden (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 as independent and permanent cell organelles that, by self-replication, were passed on from the mother cell to the daughter cells and appeared to act as organizing centers of cell division. Boveri named it centromere in 1887; van Bénéden and Neyt called it corpuscule central in 1887. Boveri wrote in 1887 that "the centrosome represents the dynamic center of the cell; its division creates the centers of the forming daughter cells, around which all other cellular components arrange themselves symmetrically. … The centrosome is the true division organ of the cell, it mediates the nuclear and cellular division." (192-196; 1836)

One year later Boveri recognized a minute, denser granule in the centre of the centrosome (196). Twelve years later, he described the cyclical behaviour of this granule in detail and named it centriole (197).

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 (1967).

August Brauer (DE) described meiosis (spermatogenesis) in Ascaris megalocephala males. The diploid chromosome number in Ascaris is four. The cells of the testis that will later form the sperm are diploid. The four chromosomes undergo synapsis then 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 two pairs of synapsed chromosomes forms a tetrad. At the first meiotic division the two 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 two cells are formed. Each of these contains two dyads. In the second meiotic division the dyads of the two cells are pulled apart. At the end of this division there are four cells. Each of these contains two chromosomes, the haploid number. There is no further division of these four cells and they develop directly into sperm (212).

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 (1764).

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 (266; 1989).

Hans von Winiwarter (FR) and G. Saintmont (FR) analyzed the development of the ovary in mammals (rabbit, human, cat). They were able to follow early changes occurring in the nuclei of the oocytes and to determine their sequence. Its intricacy could be resolved into the following steps: resting stage → leptotene (or thin threads) → synapsis (or lateral association of two thin threads; the term was replaced later on by zygotene) → pachytene (shortening and thickening of the threads) → diplotene (decondensation into double thin filaments) → new resting stage (before maturation) (1923; 1924).

 

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 (1312-1314).

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 (198-200; 334; 1767-1770). Note: In his 1902 paper, Sutton reports cytological studies of grasshopper chromosomes that lead him to conclude that (a) chromosomes have individuality, (b) that they occur in pairs, with one member of each pair contributed by each parent, and (c) that the paired chromosomes separate from each other during meiosis.

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 tend 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 despite 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 (1769). 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 (1765).

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) (525). Strasburger had described meiosis in pollen mother cells and the embryo sac (1763).

Charles E. Allen (US) was the first to observe meiosis in the algae; his material was Coleochaete (14).

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 (934).

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 because of the location of Mendelian factors in chromosomes. The evidence became overwhelming that chromosome pairs behave in meiosis like pairs of alleles (271).

 

August Wilhelm Eichler (DE) produced Bluthendiagramme, a book containing analytical drawings of the flower and inflorescence structure of all Angiosperm families then known (477).

 

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 (690).

 

Louis-Antoine Ranvier (FR) observed that a frog’s leukocytes can engulf (phagocytize) particles of carmine which remain visible within the leukocytes as they pass through the walls of the capillaries (1541).

 

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 (55).

 

Leon Semenowitj Cienkowski (PL-RU) was the first to observe the formation of multinucleated cells from single cells in invertebrates (301).

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 (1086).

 

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 (1960).

 

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) (1960).

 

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 (1813).

 

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 (899-901; 903).

 

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 (1389).

Alexandre Joseph Émile Brumpt (FR), in 1890, recognized that the infection occurs most commonly along riverbanks, and that the microfilariae in the skin come from deeper cutaneous nodules where adult filariae reside (238).

Patrick Manson (GB) described adult Onchocerca from material given him by Karl Georg Friedrich Rudolf Leuckart (1215).

Karl Georg Friedrich Rudolf Leuckart (DE), in 1893, developed a method of evaluating microfilaria densities of Onchocerca volvulus (1511).

Louis Joseph Alcide Railliet (FR) and Albert Henry (FR) named it Onchocerca volvulus (1537).

Rodolfo Robles (GT), in 1915, proved that onchocerciasis is caused by a species of filaria, Onchocerca caecutiens (1579).

Jean Montpellier (FR) and Adrien Lacroix (FR) established the role of the microfilaria in causing the skin lesions (1315).

Donald Breadalbane Blacklock (GB), working in Sierra Leone, determined that Onchocerca volvulus is transmitted by black flies (Simulium damnosum) (159).

Jean Hissette (BE) discovered the part played by microfilaria in blindness (848).

 

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 (1081).

 

Richard Volkmann (DE) gave the first description of industrial tar and paraffin cancer (1864).

 

Carl von Rokitansky (CZ-AT) wrote his great memoir on defects in the septum of the heart (1917).

 

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 (179).

 

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 (110).

 

Johannes Adolf von Kries (DE) was the first to measure capillary pressure (1905).

 

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 (217; 352; 1197).

 

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 (510; 1978).

 

William Howship Dickinson (GB) reported familial albuminuria (421).

 

Hugh Owen Thomas (GB) developed a way to immobilize a fractured thigh and hip (Thomas hip-splint) (1791).

 

A particularly bad epidemic of scarlet fever swept Australia, with high mortality rates (1005).

 

Moritz Litten (DE) reported that acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) leads to abdominal catastrophe and death (1151).

 

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 (1667; 1668).

 

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

 

Deutsche Medicinische Wochenschrift was founded.

 

1876-1922

David Starr Jordan (US) wrote 650 articles and books about ichthyology. Over 32 fishes have been named in his honor. The genera Jordania Starks, 1895, Davidijordania Popov, 1931, and Jordanella Goode & Bean, 1879 are named for him.

David Starr Jordan (US) and Barton Warren Evermann (US), from 1896-1900, authored The Fishes of North and Middle America (941).

 

1876

"…we have now recognized that the most significant occurrence in fertilization is the fusion of the two cell nuclei." (824)

 

"All nervous centres from the lowest to the very highest (the substrata of consciousness), are made up of nothing else than nervous arrangements, representing impressions and movements... I do not see of what other materials the brain can be made." John Hughlings Jackson (919)

 

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 (1998).

Otto Nikolaus Witt (CH-DE), in 1876, was the first to prepare the dyestuff chrysoidine (diamino-azo-benzene) (1999).

 

Heinrich Caro (DE) made the dye methylene blue (326).

 

Charles Lauth (FR) made the dye thionin (Lauth’s violet) (3,7-diamino-5-phenothiazinium chloride) (326).

 

Johann Friedrich Miescher, Jr. (CH) was probably the first protein chemist to recognize the amphoteric properties of proteins (1293).

 

Louis Pasteur (FR) published his book Études sur la Bière in which he stated that fermentations are essentially the result of life without oxygen (1469).

 

Louis Pasteur (FR) described methods to demonstrate fermentation under anaerobic conditions (1469).

 

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 airtight 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 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 (1821-1824; 1826; 1827).

 

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 (1636; 1637).

 

Philippe Édouard Léon van Tieghem (FR), in 1876, was the first to describe blastomycosis. Ref

Thomas Casper Gilchrist (GB-US) and William Royal Stokes (US) were the first to describe American blastomycosis (oidiomycosis), a well-defined skin disease that 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 (683; 684).

Gilchrist and Stokes cultured the fungus and named it Blastomyces dermatitidis (685).

Adolfo Lutz (BR) was the first to describe a case of what later became known as South American blastomycosis (1186). 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 (389; 1741).

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 (1154).

 

Édouard Joseph Louis Marie van Bénéden (BE) coined the term Mesozoa to include animals intermediate in structure between Protozoa and Metazoa (1834).

 

Alfred Russel Wallace (GB) speculated with considerable insight that: "The univalve and bivalve mollusca, of which the whelk and the cockle may be taken as types, move so slowly in their adult state, that we should expect them to have an exceedingly limited distribution; but the young of all these are free-swimming embryos, and they thus have a powerful means of dispersal, and are carried by tides and currents so as ultimately to spread over every shore and shoal that offers conditions favourable for their development." (1942)

Rudolf Scheltema (US), at Woods Hole Laboratory, demonstrated convincingly the role of such larvae in transatlantic dispersal (1649-1651).

 

Karl Wilhelm von Kupffer (DE) discovered stellate liver cells, which bear his name. However, he incorrectly believed that these cells were an integral part of the liver blood vessel's endothelium (1906).

Tadeusz Browicz (PL) correctly identified them as macrophages (228).

 

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 (940).

 

Joel Asaph Allen (US) wrote important monographs on Bison and the pinnipeds of North America (15; 17).

 

Joseph Marie Jules Parrot (FR) was the first to describe the primary lesion in pulmonary tuberculosis in children (Gohn’s primary focus) (1444).

 

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 (761; 1386).

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 (88).

Karl Georg Friedrich Rudolf Leuckart (DE) discovered the alternation of generations involving parasitic and free-living phases of Strongyloides (1131).

Max Askanazy (DE-CH) demonstrated that the Strongyloides worms may actually penetrate into the intestinal submucosa (38).

Paul van Durme (BE) discovered that infection by Strongyloides occurs through the skin (1845).

Arthur Looss (DE) purposely infected himself by putting larvae of Strongyloide stercoralis on his skin and finding larvae in his feces 64 days later (1169).

Friedrich Fülleborn (DE), working with dogs, described the phenomenon of autoinfection and discovered how Strongyloides stercoralis (and Ancylostoma spp.) migrates around the body before ending up in the intestine (638).

 

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 (580).

 

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 (1229). In 1896, he described the unexcitable phase of the cardiac cycle as the 'refractory period'. See, Fontana, 1780.

 

Giovanni Paladino (IT) reported atrial fibers descending over the auriculo-ventricular valves and ventricular fibers ascending into the same areas and making connections with the atria. He speculated about the function of these fibers in AV valve closure and heart block. (1442).

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. He concluded, "The muscular connections between the auricle and ventricle in the heart of man is not single and confined to the AV bundle but is multiple." (955-957) The work of Paladino and Kent is the discovery of the cardiac "bundle of Kent."

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 (846).

Wilhelm His, Jr. (CH-DE) showed that following section of the A-V bundle, the auricular and ventricular beats became dissociated (847). It would later be realized that this observation explained the Adams-Stokes syndrome (slow pulse, vertigo, and epileptoid seizures).

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 (1969; 1970).

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 (36; 1778). Today it is called the Aschoff-Tawara node or the AV node.

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, Paladino, and Kent is but part of a system of fibers which extend to the whole heart and determine its rhythm (950). 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 (50).

John C. Cardwell (US) and David I. Abramson (US) showed that the Purkinje fibers of the auriculoventricular bundle penetrated deeply into the ventricular myocardium, forming a three-dimensional meshwork, rather than a subendocardial network (267).

 

Ivan Mahaim (BE) and Alfred Benatt (BE), in a series of comprehensive serial-section studies, showed that in man, dog, sheep, calf, rabbit and cat, small connections are frequently present between the bundle of His and the origin of the left branch and the septum and, occasionally, between the A-V node and the septum. In the rabbit and cat, such connections are commonly found between the beginning of the right branch and septum, but this is never found in man (1204; 1205). Note: The term “Mahaim fibers” refers to atriofascicular bypass tracts that connect the right atrium to the distal right bundle.

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 (932).

 

Thomas John MacLagan (GB) was the first European physician to treat acute rheumatism with salicin (salicylates) (1202).

 

Ernst Viktor von Leyden (DE) gave the first description of myotonia congenita (delayed muscle relaxation and muscle stiffness) (1908).

Asmus Julius Thomas Thomsen (DK) gave a comprehensive description of myotonia cogenita as found in his family. He discussed 20 cases and tracked the trait through six generations of his family (1793-1795). Today it is called Thomsen’s disease.

 

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 (1210).

 

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 (1925; 1926).

 

Wilhelm His, Jr. (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

"Um Missverständnissen vorzubeugen und lästige Umschreibungen zu vermeiden schlägt Vortragender vor, die ungeformten oder nicht organisirten Fermente, deren Wirkung ohne Anwesenheit von Organismen und ausserhalb derselben erfolgen kann, als Enzyme zu bezeichnen." [In order to avoid misunderstandings and cumbersome circumlocutions, the presenter proposes to designate as "enzymes" the unformed or not organized ferments, whose action can occur without the presence of organisms and outside of the same.] Wilhelm Friedrich Kühne (1056) Note: Kühne is credited with coining "enzyme."

 

"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 (1895)

 

"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 or 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) (1895)

 

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. Ehrlich was the first to identify mast cells and showed that eosinophil leukocytes were produced by the bone marrow(467). He realized that the nuclear region of cells had an affinity for basic dyes therefore he referred to them as basophilic.

Ralph O. Smith (US) and W. Barry Wood, Jr. (US) explained the important role of mast cells in an anti-infectious response (1723).

Earl P. Benditt (US), Joel S. Bader (US), and Phillip K.N. Lam (US) discovered the association between mast cells and histamine (97).

Ivan Mota (US) discovered the link between mast cells and inflammation thus laying the foundations for modern research into allergy and anaphylaxis (1328).

 

Wilhelm Friedrich Kühne (DE) discovered the protein-digesting enzyme trypsin (1057).

 

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 (446).

 

Carbon disulfide was first recommended in the U. S. as a fumigant for insect control (1707).

 

Max Jaffé (DE) discovered that when he fed benzoic acid to birds 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 (928).

 

Nathanael Pringsheim (DE) discovered asexual reproduction and alternation of generation in the bryophytes (liverworts and mosses) (1529).

 

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 (434).

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 (553).

Niels Ryberg Finsen (DK) used light to successfully treat certain skin diseases such as lupus vulgaris (cutaneous tuberculosis) (554-556).

Frederick L. Gates (US) related the effective wavelengths of ultraviolet radiation for killing bacteria to its observed absorption by nucleic acids (666-668).

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 (860).

 

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 (304).

 

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 (1825).

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 (243).

 

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 (991).

 

Albert B. Frank (DE) coined the term “symbiotismus” (symbiosis). " ...where two different species live on or in one another under a comprehensive concept which does not consider the role which the two individuals play but is based on the mere coexistence and for which symbiosis is to be recommended."(610; 1640)

Heinrich Anton de Bary (DE) adopted the term "symbiose," defining it as "the living together of unlike named organisms." (396; 1640).

 

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 (277).

Francis Gotch (GB) and 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 (731).

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 (105; 106). 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.

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 (8).

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 (1946; 1947).

William Grey Walter (GB) and Vivian J. Dovey (GB) discovered theta brain waves in 1943. Theta waves occur mainly in children ages 2–5 years old (1948).

 

Louis Pasteur (FR) and Jules Francois Joubert (FR) were the first to identify a pathogenic species of Clostridium, Clostridium septicum or Vibrion septique (1485).

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) (1486). 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 (1660).

 

Theodor Wilhelm Engelmann (DE) proposed intercellular current flow (494; 495).

Howard J. Curtis (US) and David M. Travis (US) gave the first direct evidence for intercellular current flow (356).

 

Gualtherus Carel Jacob Vosmaer (NL), in 1877, separated the sponges from the coelenterates (904). Several sea creatures were given genus and species names in his honor.

Berthold Hatschek (AT) split Frey and Leuckart's Coelenterata into three phyla: Spongiaria, Cnidaria and Ctenophora (805).

 

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 (491).

 

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 (112).

 

Claude Bernard (FR) found evidence for a diastase (amylase) in the liver (113). 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 (114).

 

Gabriel Madeleine Camille Dareste (FR) described the successful production of developmental monstrosities by experimental means (372).

 

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 (440; 488; 489; 1093).

John Newport Langley (GB) was the first to suggest the presence of receptive substances on cells (1092).

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 (305; 822; 1380-1382; 1490). 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 (496; 1222).

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” (1944; 1945).

Gabriel Jonas Lippmann (FR-LU) invented the capillary electrometer used by Waller in his studies (1143).

 

J.W. Gordon (GB) introduced the concept of ballistocardiography (728). A ballistocardiograph is an instrument that records the motions of the body imparted to it by the heartbeat.

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” (819).

Isaac Starr (US), Arthur Joy Rawson (US), Henry A. Schroeder (US), and Norman Ross Joseph (US) coined the term ballistocardiogram (1746).

Issac Starr (US) discussed the prognostic value of ballistocardiograms (1745).

 

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 (320).

 

Julius Friedrich Cohnheim (DE) described a case of paradoxical embolism, "I recently had a case of a deadly embolus in the frontal lobe of a 35-year old woman with apoplexy. In the lower extremity a long thrombus was found and ... what I found next I never thought of, to put these two together, until I had a close look at the heart. I found a very large foramen ovale through which I could pass three fingers with ease. Now I could no longer ignore the fact that a torn-off piece of thrombus arising from the lower extremity, while traveling through the heart, passed out of the RA into the LA and to the frontal lobe." (319)

 

Friedrich Bezold (DE) provided the first clear description of mastoiditis (135; 136).

 

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 (291).

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 (418).

 

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 (63).

Francis Maitland Balfour (GB) wrote his monograph on the development of elasmobranch fishes (64). This was the most important addition to vertebrate embryology since Johannes Muller.

 

James Paget (GB) described Paget’s disease of the bone (osteitis deformans) (1437).

 

Karl Friedrich Otto Westphal (DE) was the first physician to provide a clinical description of narcolepsy and cataplexy (1979).

Jean Baptiste Edouard Gélineau (FR) coined the term narcolepsy {Gélineau, 1880 #12954.

Richard Henneberg (DE) coined the term cataplexy for emotionally induced muscle weakness, a prominent symptom of narcolepsy {Henneberg, 1916 #22816}.

 

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 (1730). These tubes are helpful in treating congestive heart failure.

 

Carl Philipp Adolf Konrad 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” (1071).

 

Carl Nicoladoni (AT) performed the first operation for an esophagus diverticulum (1371). 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 (2001; 2002).

 

Vincent Czerny (CZ-DE) performed the first open partial nephrectomy for renal carcinoma (361).

 

Ernest-Charles Lasègue (FR) and Jean-Pierre Falret (FR) diagnosed a communal psychotic disorder sometimes referred to as "Lasègue-Falret syndrome" (folie à deux). The syndrome is characterized by the coincidental appearance of psychotic symptoms in family members while living together, as well as retention of the symptoms when the individuals are separated. This syndrome can also involve a situation where a diseased family member transmits psychotic symptoms to healthy members of the family (1100).

 

Joel Asaph Allen (US) proposed that animals adapted to cold climates have shorter limbs and bodily appendages than animals adapted to warm climates. More specifically, it states that the body surface-area-to-volume ratio for homeothermic animals varies with the average temperature of the habitat to which they are adapted (i.e. the ratio is low in cold climates and high in hot climates). This is known as Allen's rule (16).

 

Ernst Felix Immanuel Hoppe-Seyler (DE) founded the journal Zeitschrift für Physiologische Chemie. He used the term biochemie (biochemistry) in the foreword to the first issue of Zeitschrift für Physiologische Chemie in 1877.

 

 

Othniel Charles Marsh (US) introduced and briefly described Apatosaurus ajax, (now known to be synonymous with Brontosaurus) (1232; 1233). Two years later he described and introduced Brontosaurus, thinking they were different animals (1234). Note: Apatosaurus means “deceptive lizard”; Brontosaurus means “thunder lizard”

 

1878

"If the conquests useful for humanity touch your heart, if you are overwhelmed before the astonishing results of electric telegraphy, of the deguerrotype, of anesthesia, and of other wonderful discoveries, if you are jealous of the part your country may claim in the spreading of these marvelous things, take an interest, I beg of you, in those sacred places to which we give the expressive name of laboratories. Demand that they be multiplied and ornamented, for these are the temples of the future, of wealth, and of well-being. It is in them that humanity grows, fortifies itself, and becomes better. There it may learn to read in the works of nature the story of progress and of universal harmony, even while its own creations are too often those of barbarism, fanaticism, and destruction." Louis Pasteur (355; 2028)

 

"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 (1167)

 

"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 (114) 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 (224; 992)

 

"If he were a surgeon, the laboratory scientist Louis Pasteur wrote in 1878, he would not only clean his instruments thoroughly, ‘but after having cleaned my hands with the greatest of care, I would subject them to rapid flaming’. Pasteur did this in his laboratory with all objects that came into contact with his microbial cultures, in order to avoid contamination. Furthermore, he ‘would use only lint, bandages and sponges previously exposed to air temperatures of 130–and use water that had been heated to temperatures of 110–’. These were the kinds of technologies that had enabled Pasteur to subject microorganisms to control by his eyes and hands and allowed him to make far-reaching claims about the cause of infectious diseases and ways to prevent them. In the passage above, he recommends adopting the same strategy in the surgical work environment. The power of controlling microorganisms in the laboratory was to be transferred to a specific part of the outside world—the operating room." Karl B. Absolon, Mary J. Absolon, Ralph Zientek, Louis Pasteur, Jules Francois Joubert, and Charles Édouard Chamberland (3; 1487)

 

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

 

Heinrich Baum (DE) synthesized the dye C.I. acid orange G (acid orange 10) (204). Note: 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 DNA molecule, and polyacrylamide gel electrophoresis.

 

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" (1072).

Bartolomeo Camillo Emilio Golgi (IT) discovered the cell organelle, which bears his name, Golgi apparatus or Golgi body, while studying cells of the spinal dorsal root ganglia where he observed a characteristic filamentous structure within the cell bodies. He also found this apparatus within Purkinje cells from the cerebellum of a barn owl. Golgi and his students would eventually induce the existence of this internal reticular apparatus in all eukaryotic cells. They called it apparato reticulare interno (695; 711; 720; 1405).

Gustaf Platner (DE) also gave an early description of the "nebenkern" (Golgi apparatus) in snail spermatocytes (1513).

Emil Algot Holmgren (SE) described this organelle as canaliculi and observed it in several cell types (864; 865).

Santiago Ramón y Cajal (ES) coined the name Golgi-Holmgren canals (1538).

 

London purple was introduced in 1878. It was used for control of the Colorado potato beetle (1707).

 

Wilhelm Friedrich Kühne (DE) and Carl Anton Ewald (DE) isolated rhodopsin from retinas (517; 1058; 1059; 1862).

 

Arthur Gamgee GB), c. 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 (652).

 

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 (23; 1256).

 

Charles Otis Whitman (US) was the first to use the term cytokinesis to denote the cytoplasmic changes occurring during cell division (1980; 1991).

 

Edoardo Perroncito (IT) described and isolated the bacterial agent of fowl cholera (Pasteurella multocida), a serious disease of chickens in Italy (1494; 1495).

Jean-Joseph-Henri Toussaint (FR) also isolated the bacterial agent of fowl cholera (1805; 1806). 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 affect 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) (122; 123).

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 most modern decompression theories. They developed practical dive tables based on research that included slower ascent rates as the diver approached the surface (205).

 

Karl Brandt (DE), Adolphe-Adrien Certes (FR) and Paul Ehrlich (DE) introduced true vital staining to biology. In 1878, Brandt 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 leukocytes, using cyanine and quinolene blue for the differential staining of frog's leukocytes and noticed that they retained their motility for a short time course while taking up the dye (210; 278-280; 475).

 

Louis-Antoine Ranvier (FR) discovered myelin and the short-specialized interruptions in the myelin sheath occurring along myelinated nerve fibers (1542). 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 (1078; 1701).

 

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 (1149). 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 (992; 997). 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 (1487).

Louis Pasteur (FR), Jules Francois Joubert (FR), and Charles Édouard Chamberland (FR), in 1878, credited Schwann as the real founder of the germ theory of fermentation (616).

 

Timothy Richards Lewis (GB) reported that microscopic organisms found in the blood of man and other animals could cause disease (1137).

 

Heinrich Hermann Robert Koch (DE) isolated Erysipelothrix muriseptica from mice, which had been injected with putrefying blood (992).

Anton Julius Friedrich Rosenbach (DE) isolated the same 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 (1585; 1586). 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 Lake Alexandrina in South Australia, which was heavily infested with blue-green algal (cyanobacterial) blooms (269; 609).

 

Michael Stephanovitch Woronin (DE) was the first to describe the fungus Olpidium brassicae (2004).

 

Patrick Geddes (FR) found that certain green planaria were in fact green because they contained symbiotic algae. He argued that the alga involved was not a parasite and the relationship was one of mutual benefit (672-674).

 

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 (804).

 

Giovanni Battista Grassi (IT), Corrado Parona (IT), and Ernesto Parona (IT) developed the first diagnostic method for examining hookworm ova (747).

 

Coenraad Kerbert (NL) described the lung fluke, Distoma westermanii, from the lungs of a tiger in the Amsterdam Zoo (958).

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 (761; 1339).

Maximillian Gustav Christian Carl Braun (DE) suggested the name Paragonimus westermani for the fluke (214). Note: Paragonimiasis is a parasitic infection caused by trematodes (or lung flukes) of the genus Paragonimus. The parasite has a complex life cycle including two intermediate hosts and a definitive mammalian host. Humans are accidental hosts who become infected by eating raw or improperly cooked crab or crawfish.

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 (68; 1214).

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 (985-988; 1306; 1307; 1348-1353; 2020; 2021).

 

Adam Politzer (AT) wrote Lehrbuch der Ohrenheilkunde, the most outstanding textbook on the ear in the 19th and 20th centuries (1514).

 

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 (810). 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.

 

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 (732).

 

Martin Max Bernhardt (DE) described meralgia paraesthetica (Bernhardt‐Roth syndrome) as a distinctive condition, more common in men than in women, characterized by paresthesia and often burning pain over the anterolateral aspect of the thigh (116). Note: Compression in the groin is the common cause.

Vladimir Karlovich Roth (RU) described the same condition, coining meralgia paraesthetica in the process (1598).

 

Richard Volkmann (DE) performed the first excision of carcinoma of the rectum (1865).

 

Wilhelm Alexander Freund (DE) undertook the first abdominal extirpation of a cancerous uterus. It was not reported until 1885 (621).

 

Pierre Paul Broca (FR) described and named the great limbic lobe of the brain (222). 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 killing more than 13,000 people in the lower Mississippi Valley. At the time, it was one of the worst medical disasters in U.S. history (1005).

 

The Yuma tribes along the Gila River in southern Arizona noted that measles killed many children from 1878-1879 (1265).

 

Journal of Physiology (London) was founded.

 

1879

"Every science begins by accumulating observations, and presently generalizes these empirically; but only when it reaches the stage at which its empirical generalizations are included in a rational generalization does it become developed science." Herbert Spencer (GB) (1737)

 

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 (351).

 

Pierre Eugène Marcellin Berthelot (FR) coined the terms endothermic and exothermic (125).

 

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 use the technique of staining blood films to classify the blood granulocytes into the three types we know today (469-471).

Paul Ehrlich (DE) discovered the eosinophil when he stained fixed blood smears with aniline dyes (840).

 

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 (437; 763).

 

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 (1011-1013; 1016; 1023; 1024; 1027).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) discovered that DNA contains guanine (1014; 1015).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Albert Neumann (DE) discovered that DNA contains adenine and thymine (1017-1022; 1025; 1026).

Alberto Ascoli (IT) described uracil (37).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Hermann Z. Steudel (DE) discovered that DNA contains cytosine (1028).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Hermann Z. Steudel (DE) discovered that DNA contains uracil (1029).

 

Bartolomeo Camillo Emilio Golgi (IT) and R. Rezzonico (IT) reported on the histological structure of myelin. They said that it appeared in the guise of a chain of conical funnels inserted into each other, through which passes the nerve fiber (722; 723).

LouisAntoine Ranvier (FR) confirmed this observation (1541).

 

Fredrick Schmitz (DE) reported syngamy, the fusion of the male and female gametes in plants (1665).

 

Julius Arnold (DE) made drawings of human chromosomes in cancer cells (sarcoma) (30).

 

Timothy Richards Lewis (GB) found parasitic trypanosomes in the blood of healthy rats (Trypanosoma lewisi) in India (1138).

George Evans (GB) found parasitic trypanosomes (Trypanosoma evansi) in horses and camels in India (516).

 

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…" (1359) 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 (1968).

Leo Leistikow (DE) isolated Neisseria gonorrhoeae (1117; 1118).

Ernst von Bumm (DE) grew axenic cultures of Neisser’s gonococcus, Neisseria gonorrhoeae, and proved by inoculations of humans that it causes gonorrhea (1875; 1876).

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 (1974).

Ernst Wertheim (AT) demonstrated the gonococcus in acute cystitis (1975).

Ernst Wertheim (AT) emphasized the importance of latent uterine gonorrhea (1976).

 

Theodor Albrecht Edwin Klebs (DE) successfully inoculated monkeys with syphilis (980).

 

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 (646).

 

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 (1470; 1477-1479).

 

Erwin Otto Eduard Bälz (DE) and S. Kawakami (JP) were the first to recognize the disease known as tsutsugamushi in certain isolated river valleys in Japan (69). 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 (507; 508). 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 (129-131). 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 (782).

 

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. In the 7th series on pages 363-4 he describes how he discovered that a female Great Peacock moth (Saturnia pyri), newly emerged from pupation, attracted over 40 males from every direction. He concluded that the female was releasing a powerful attractant (pheromone) into the air (520). See, Bethe, 1932; Karlson, 1959; Butenandt, 1961; Corpchot, 1985; Cutler, 1986.

 

Giovanni Battista Grassi (IT), Corrado Parona (IT), and Ernesto Parona (IT) described the life cycle of Strongyloides stercoralis (a parasitic nematode) (748). The organism was first described in 1876 in French soldiers returning from Cochin China (now Vietnam) who were suffering from intractable diarrhea.

 

Sigmund Exner (DE) stated that reaction time course (time between stimulus and response) is often devoid of free will (518).

 

Wilhelm August Oskar Hertwig (DE) and Richard Karl Wilhelm Theodor von Hertwig (DE) developed the germ theory proposed by Ernst Heinrich Philipp August Haeckel (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 (779; 781; 825-827; 829-831).

 

Ivar Victor Sandström (SE) discovered the parathyroid glands and named them glandulae parathyreoideae (1639). See, Owen, 1862.

Gerhard Engel (DE) and Friedrich Daniel Recklinghausen (DE) described osteitis cystica (primary hyperparathyroidism syndrome) (490; 1547).

Max Askanazy (DE) was the first to associate osteitis fibrosa cystica with tumors of the parathyroid gland (39).

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 (511).

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 calcium diabetes with loss of large amounts of calcium in the urine (1191; 1192).

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 (790; 791).

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 (325).

Gerald D. Aurbach (US) purified and isolated parathyroid hormone (43).

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 because of hypercalcemia. They suggested that it be named calcitonin (332).

Allen M. Spiegel (US), Michael Alan Levine (US), Gerald D. Aurbach (US), Robert W. Downs, Jr. (US) , Stephen J. Marx (US), Roz D. Lasker (US), Arnold M. Moses (US), and Neil A. Breslau (US) demonstrated that pseudohypoparathyroidism is a disorder of the parathyroid hormone receptor complex (1738).

 

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." (1581).

 

William Murrell (GB) introduced nitroglycerin to treat angina pectoris (1343).

 

Heinrich Obersteiner (AT) described concussion of the spinal cord and status epilepticus (1394). He wrote an important volume on general paresis and tabes dorsalis, also a neurology text on the anatomy of the nervous system (1395). 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 (1396).

 

William Allen Sturge (GB) and Frederick Parks Weber (GB) described a congenital disorder exhibiting a port-wine nevus on the scalp along the distribution of the trigeminal nerve, combined with glaucoma and intracranial vascular abnormalities. A right-sided hemiplegia, accompanied by left-side brain lesions is also typical (Sturge-Weber syndrome) (1766; 1954).

 

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 (223).

Angelo Mosso (IT) conceived the plethysmograph, a device that could measure cerebral blood flow variations by recording brain pulsations in patients with skull defects (1322; 1323).

Angelo Mosso (IT) developed the ‘human circulation balance’ to measure brain activity in normal patients. A delicately balanced table which could tip downwards either at the head or the foot if the weight of either end were increased. He stated that the increase in cerebral blood flow was thus proportional to the complexity of a cognitive task, and he further measured the cerebral response to emotional stimuli, both in isolation and in interaction with cognition. Mosso noticed that subjects did not react equally to the same stimulus (1324-1327).

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." (1605).

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 (594).

John F. Fulton (US) reported on a patient presenting with an arteriovenous malformation of the occipital cortex. Surgical removal of the malformation was attempted but was unsuccessful, leaving the patient with a bony defect over the primary visual cortex. Fulton elicited a history of a cranial sound audible to the patient whenever he engaged in a visual task. Based on this history Fulton pursued a detailed investigation of the behavior of the sound that he could auscultate and record over the occipital cortex. Remarkably consistent changes in the character of the sound could be appreciated depending upon the visual activities of the patient. Although opening the eyes produced only modest increases in the intensity of the sound, reading produced striking increases (639). Cortical blood flow is thus related to the complexity of the visual task and the attention of the subject to that task.

Paul R. Dumke (US), Carl Frederic Schmidt (US), and Harry H. Pennes (US) made the first quantitative measurements of the cerebral blood flow in lightly anesthetized macaque monkeys and determined cerebral oxygen consumption in the same state and under deeper anesthesia as well as convulsive activity (451; 1662).

Seymour Solomon Kety (US) and Carl Frederic Schmidt (US) described a quantitative method for measuring cerebral blood flow in humans using nitrous oxide (Kety-Schmidt technique) (960; 961; 1661). The method is based upon the uptake by the brain of the diffusible nitrous oxide supplied by way of the arterial blood. These works led directly or indirectly to the development of current methods for the measurement of regional blood flow, metabolism, and the visualization of functional activity throughout the human brain.

Fritz A. Freyhan (US), Rachel B. Woodford (US), Seymour Solomon Kety (US), Darab K. Dastur (US), Mark H. Lane (US), Douglas B. Hansen (US), Robert N. Butler (US), Seymour Perlin (US), and Louis Sokoloff (US) concluded that cerebral circulation and oxygen consumption are not diminished in the normal elderly individual, but show a significant reduction, highly correlated with the degree of mental impairment, in senile dementia (381; 627).

William M. Landau (US), Walter H. Freygang, Jr. (US), Lewis P. Rowland (US), Louis Sokoloff (US), and Seymour Solomon Kety (US) provided their results of quantitative changes in blood flow in the brain related directly to brain function (959; 1080).

Renward Mangold (US), Louis Sokoloff (US), Eugene Conner (US), Jerome Kleinerman (US), Per-Olof Therman (US), and Seymour Solomon Kety (US) found that during sleep there is no decrease in oxygen consumption by the brain (1211).

Niels A. Lassen (DK), Kai Hoedt-Rasmussen (DK), S.C. Sorensen (SE), Erik Skinhøj (SE), Sten Cronquist (SE), Bengt Bodforss (SE), David H. Ingvar (SE) and Jarl Risberg (SE) were the first to directly demonstrate in normal human subjects that cerebral blood flow changes regionally during changes in brain functional activity (908; 1103; 1104).

 

Vincenz Czerny (CZ-DE) performed his first vaginal hysterectomy to treat cervical cancer. The operation took two hours, and the patient later died on 19 January 1879, five months after the surgery, from a urinary tract infection(362).

 

Jules Émile Péan (FR) performed the first resection of the stomach for cancer. The patient died five days later (1491).

Ludwik Rydygier; Ludwig Anton Rydygier von Ruediger (PL-DE) was the second to perform partial stomach resection. He performed a pylorectomy on a patient suffering from cancer, reconstructing the continuity of the digestive tract. Unfortunately, the patient died from shock twelve hours after the operation (1612-1614). Note: This operation was often referred to as a Billroth I.

Anton Wölfler (AT) performed a gastroenterostomy, the surgical junction ( anastomosis ) between the stomach and the small intestine, on a patient suffering from an inoperable carcinoma of the pylorus (2001; 2002).

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 carbolized silk sutures. Using chloroform anesthesia, he took an hour and a half to remove the cancer (142; 1611).

Ludwik Rydygier; Ludwig Anton Rydygier von Ruediger (PL-DE) performed the first pylorectomy on a woman with pyloric stenosis due to gastric ulcer. She achieved complete recovery (1615; 1616).

Ludwik Rydygier; Ludwig Anton Rydygier von Ruediger (PL-DE) was the first to perform gastroenterostomy on a duodenal peptic ulcer with stenosis (1617).

 

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 (1780).

 

Charles Alfred Ballance (GB), Hamilton A. Ballance (GB) and James Purves Stewart (GB), in 1895, performed the first reported facial nerve to spinal accessory nerve anastomosis for treatment of facial palsy (66). Note: there is circumstantial evidence that Thomas Drobnik (PL), in 1879, performed the first anastomosis of the proximal branch of the spinal accessory nerve to the distal branch of the facial nerve.

Jean-Louis Faure (FR) and Francis Furet (FR), in 1898, performed a faciospinal-accessory anastomosis for traumatic division of the facial nerve (526).

 

William Alvin Macewen (GB), in 1879, was the first to perform a bone allograft in humans. Using the tibia of a child with rickets, he transplanted the allograft onto the humeral shaft of a young boy whose humerus was lost through osteomyelitis. This work was described in 1881 (939; 1196). The allograft was a success because Macewen operated under antiseptic conditions as introduced by Joseph Lister.

William Alvin Macewen (GB) originated neurosurgery when he performed exeresis of a meningioma (1193).

 

Henri Judet (FR) reported a whole-joint transplantation — femur, tibia and patella — in the knee joint of man. The procedure, as he described, could be carried out to treat the trauma of infective arthritis or tuberculosis (255; 942).

R. Geoffrey Burwell (GB), Gerald Gowland (GB) and Franklin Dexter (GB) showed that the bone marrow was responsible for the immune response to fresh allogenic bone and that frozen bones performed better compared to fresh allogenic bones. More significantly, their experiments shed light on the science of bone preservation and led to the development of the protocol for bone preservation we use today (249-254; 256-258).

Leif T. Ostrup (US) and John M. Frederickson (US) performed the first free vascularized bone graft (1430).

 

 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 (1099). The Ordovician Period of the Paleozoic Era (from the name of an ancient British tribe, the Ordovices) extended from 505 M until 438 M. 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 like 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 Cincinnatian 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 (1122).

 

Index Medicus was founded.

 

1880

"Life should be made into a dream and a dream into a reality." Pierre Curie, c. 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 (485). 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 (354).

 

Johann Friedrich Wilhelm Adolf 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 (1707).

 

Zdenko Hans Skraup (CZ) synthesized quinoline which can be used as an antimalarial (1720).

 

Ernst Felix Immanuel Hoppe-Seyler (DE) found that heme or iron-protoporphyrin and the magnesium containing chlorophyll are structurally related (869).

 

Bronislaus Radziszewski (PL) made pioneering studies of the chemiluminescence of various organic compounds and the establishment of the enzyme theory of biological oxidations (1536).

 

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 (2017).

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 (1390).

 

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 (1888).

 

Louis Pasteur (FR) was the first to show the presence of staphylococci in pus (1474).

 

Robert Bentley (GB) and Henry Trimen (GB) wrote a four volume work on medicinal plants containing over three hundred hand-colored plates by botanist David Blair (104).

 

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. He discovered Streptococcus pyogenes in the blood of a patient with puer­peral septicemia (1471).

 

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 (1807).

 

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 several 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, however, if the interval between two successive transfers is extended 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 (1472; 1473).

Louis Pasteur (FR) produced the first laboratory-developed vaccine: the vaccine for chicken cholera (Pasteurella multocida) (1265).

 

Carl Joseph Eberth (DE) was the first to describe the typhoid bacillus. First known as Eberthella typhosa, it was later named Salmonella typhi (462; 463).

Georg Theodor August Gaffky (DE) isolated the bacterial cause of typhoid, Salmonella typhosa, in axenic culture (642).

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 (658). This was possibly the first clear indication that microorganisms could cause food poisoning.

 

James Kingston Fowler (GB) drew attention to the association of throat infection with acute rheumatism (602).

 

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 (95).

 

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 (1203).

 

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 (1107-1109). Note: 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 (1223; 1224; 1226; 1227).

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 (703-709; 714-717).

Bartolomeo Camillo Emilio Golgi (IT) identified the parasite that causes malignant tertian fever (710; 718).

Cheslav Ivanovich Khentsinsky (RU) presented thorough descriptions and drawings of various forms and stages of malarial parasites in the blood, also the exflagellation of P. falciparum gametocytes and findings of P. falciparum in the liver (962; 963).

Nikolaj Alekseevic Sacharov; Sacharoff; Sacharow; Sakharoff (RU) injected himself with intestinal contents of a leech that 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 (1635).

Nikolaj Alekseevic Sacharov; Sacharoff; Sacharow; Sakharoff (RU) described the flagellate bodies as phases in the development of plasmodia outside the human body (1621; 1634).

Nikolaj Alekseevic Sacharov; Sacharoff; Sacharow; Sakharoff (RU) published comprehensive descriptions of Plasmodium falciparum, the pathogen of aestivo-autumnal malaria (1619; 1620).

Patrick Manson (GB) reported on the nature and significance of the crescentic and flagellated bodies in malarial blood (1216).

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 (1591-1597). Note: in 1898

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 (1189; 1190; 1409). Note: Its asexual behavior was already known.

Patrick Manson (GB) established tropical medicine as a specialty and founded a school of tropical medicine in London. He—based on the work of Patrick Ross (GB) — was among the first to suggest that mosquitoes might be the agents for spreading malaria (1217; 1218).

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 (79; 138; 743-745).

Giuseppe Bastianelli (IT) and Amico Bignami (IT) gave a detailed description of tertian and crescentic parasites, the publication being accompanied by the best coloured plates hitherto published, illustrating their development. They proved that a single infected Anopheles claviger can communicate malaria (tertian) to man (78).

Patrick Manson (GB) was convinced by Ronald Ross (GB) that mosquitoes could possibly transmit malaria. To test this theory Manson 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 (1220; 1221).

Giovanni Battista Grassi (IT) and Amico Bignami (IT) showed that the plasmodium undergoes its sexual phase only in the Anopheles mosquito (746). These works led to the preventative measure of protecting people from mosquitoes.

Hans R.P. Ziemann (DE) observed the development of the parasites of tropical malaria in two species of Anopheles, as also the development of tertian parasites in one species of Anopheles. He followed the development to the appearance of sporozoites in the salivary glands of the insects. He subsequently found that the parasites would not develop in Cimex lectularius nor in sandflies (2032; 2033).

Étienne Sergent (FR) and Edmond Sergent (FR) used attenuated sporozoites of Plasmodium relictum to successfully immunize canaries against mosquito-borne malaria (1705).

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 (341-343).

Alexandre Joseph Emilé Brumpt (FR) reported the existence of Plasmodium gallinaceum (237).

Sydney P. James (GB) and Parr Tate (IE) discovered extra-erythrocytic stages of malaria with an avian plasmodium (931).

Henry Edward Shortt (GB), Percy Cyril Claude Garnham (GB), Gordon Covell (GB), and Percy G. Shute (GB) discovered the primary tissue phase, the exoerythrocytic cycle, of the malarial parasite, Plasmodium vivax (1712-1714).

Henry Edward Shortt (GB), Neil Hamilton Fairley (AU), Gordon Covell (GB), Percy G. Shute (GB), and Percy Cyril Claude Garnham (GB) used liver biopsy material from a human volunteer to discover the primary tissue phase, the exoerythrocytic cycle, of the malarial parasite, Plasmodium falciparum (1710; 1711).

Charles R. Anderson (US) achieved in vitro culture of the blood stages of avian Plasmodium (21).

Percy Cyril Claude Garnham (GB), Robert Stow Bray (AU-GB), W. Cooper (GB), Ralph Lainson (GB-BR), F.I. Awad (), and John Williamson (GB) discovered the primary tissue phase, the exoerythrocytic cycle, of the malarial parasite, Plasmodium ovale (215; 656).

Wojciech A. Krotoski (US), William E. Collins (US), Robert S. Bray (AU-GB), Percy Cyril Claude Garnham (GB), Frank B. Cogswell (US), Robert W. Gwadz (BE), Robert Killick-Kendrick (US), Robert E. Wolf (US), Robert E. Sinden (GB), Louis C. Koontz (US), and Peggy S. Stanfill (US) proposed that some Plasmodium vivax sporozoites in the liver remain latent (hypnozoites) for several months, causing relapses later on (1049).

Elizabeth H. Nardin (US), Victor Nussenzweig (US), Ruth Sonntag Nussenzweig (US), William E. Collins (US), Khunying Tranakchit Harinasuta (TH), Pramuan Tapchaisri (TH), and Yaovamarn Chomcharn (TH) characterized the first defined malaria antigen, the circumsporozoite protein (1354). The circumsporozoite proteins of Plasmodium falciparum and Plasmodium vivax play a role in protection from the host's immune system.

Alon Warburg (IL) and Louis H. Miller (US), using Plasmodium gallinaceum, achieved the first in vitro culture of the mosquito stage of any malaria parasite (1949).

 

Friedrich Siegmund Merkel (DE) described one form of sensory "tactile" nerve ending (1275; 1276). The eponym Merkel’s corpuscles designate them.

 

Bartolomeo Camillo Emilio Golgi (IT) described the musculo-tendineous organs (later to be known 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 proprioceptive sensitivity (697; 723).

Bartolomeo Camillo Emilio Golgi (IT) reported on a disease condition in which there is fusion within the neuro-muscular junction (700; 723).

 

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 (1986-1988).

 

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 during their life be grouped in the phylum Chordata; that suggestion was accepted (65).

 

Thomas Henry Huxley (GB) subdivided the Mammalia into three groups. Prototheria (monotremes), Metatheria (marsupials), and Eutheria (placentals) (902).

 

Etienne Lancereaux (FR) made the distinction between fat and thin diabetes: diabete gras and diabete maigre (1079). In the pre-insulin 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 and published a series of side views of human embryos age 15 days to 8½ weeks (844).

 

Maximilian von Vintschgau (AT) limited the qualities of taste to: sour, sweet, salty, and bitter (1919).

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 several different types of taste buds; the taste buds themselves were probably specific to the primaries (1401; 1402).

 

Désiré-Magloire Bourneville (FR) provided an early description of a multi-symptom disorder that was to become known as Bourneville's syndrome, now known as tuberous sclerosis. This genetic condition may lead to mental retardation, epilepsy, a disfiguring facial rash and benign tumors in the brain, heart, kidney and other organs (186-188).

 

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 (pyelolithotomy) (1320).

Vincenz Czerny (CZ-DE) 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 (364).

Jean-Francois-Auguste Le Dentu (FR) carried out a successful nephrolithotomy (removal of kidney stones). (1113).

 

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 (476).

 

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 (677).

 

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 (595).

 

The Zoologischer Jahresbericht was founded.

Zeitschrift für Klinische Medizin was founded.

 

New York journalist John Michaels founded Science 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 (1005).

 

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 (126). 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 (1707).

 

Emile Clément Jungfleisch (FR) and Edmond Lefranc (FR) were the first to crystallize levulose (fructose) (944).

 

Ernst August Schulze (CH) and Johann Barbieri (DE) identified the amino acid phenylalanine as a constituent of plant proteins from lupine (Lupinus luteus) (1679; 1680).

Friedrich Gustav Carl Emil Erlenmeyer (DE) and Andreas Lipp (DE) determined the constitution of phenylalanine, which they synthesized from phenylacetaldehyde, hydrogen cyanide, and ammonia (515).

It was later determined by others that phenylalanine is the source of the benzoic acid that 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 led to the conclusion that chromatin, chromosomes, and nuclein comprised one and the same substance (2023).

 

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 (59). 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 (817).

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 that became so closely identified with Drosophila genetics (1438-1441). 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 (Yugoslavian -US) and Margaret E. Hoover (US) pointed out the correspondence between giant salivary gland chromosome bands and gene maps (417).

Nikolai Konstantinovich Koltzoff (RU) and Calvin Blackman Bridges (US) independently suggested that the giant chromosomes of Diptera are polytenic (219; 1009).

Johann Heinrich Emil Heitz (DE) reported that the banding pattern of polytene chromosomes is consistent (814).

Gunther Hertwig (DE) noted that the gigantic dimensions of polytene chromosomes are achieved by real growth, i.e., by multiple doubling of the genome (823).

 

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 (1556; 1557).

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 (1388).

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 (1849; 1850).

Ebba Andersson-Cedergren (SE) described a part of the muscle cell reticulum having the form of transversely oriented tubules (T tubules) (22). 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 as branches of nerve fibers out of the medullary cords (698; 699; 702; 712).

 

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 (378).

 

Nicholas Ivanovich Lunin (RU) studied the effect of milk on the survival rate of mice feed artificial diets and concluded that milk contained some, yet unknown, substance necessary to sustain life. That substance was not protein, fat, sugar, salts or water (1183).

 

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 (1562).

 

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 (211).

 

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 (497).

Wilhelm Friedrich Philipp Pfeffer (DE) also discovered chemotaxis and determined that motile bacteria can exhibit a positive as well as a negative chemotaxis (1503-1505).

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 (6).

 

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 dichloride are bacteriostatic and bactericidal for endospores and vegetative cells of the most resistant microorganisms (993).

 

Heinrich Hermann Robert Koch (DE) introduced the use of heat as a method of fixing bacterial smears (993).

 

Paul Ehrlich (DE) introduced the use of methylene blue as a bacterial stain (472).

 

Heinrich Hermann Robert Koch (DE) and Gustav Wolffhügel (DE) determined the exact value of hot air as a sterilizing agent (999).

 

Albert Ludwig Siegmund Neisser (DE) while staining the leprosy microorganism noted what would later be appreciated as its acid-fast nature (1361).

 

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 (998).

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 several 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 that 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 chloride 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 (994).

 

Wilhelm Olbers Focke (DE) coined the term xenia to denote the immediate effect of pollen on the endosperm in the maize seed (590).

 

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 (831).

 

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 meetinghouse. 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." (1116)

 

Charles Robert Darwin (GB) was the first to report how important worms are to soil fertility (377).

 

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 (1483; 1484).

 

Joseph Marie Jules Parrot (FR) mentions a Pneumococcus associated with human infection (1445).

Louis Pasteur (FR), Charles Édouard Chamberland (FR), Pierre Paul Emile Roux, (FR), and Louis Thuillier (FR) isolated Streptococcus pneumoniae, from the saliva of a patient with rabies (1483).

George Miller Sternberg (US) almost simultaneously announced the discovery of the Pneumococcus (1752).

Albert Fraenkel (DE) and Anton Weichselbaum (AT) grew Pneumococcus (Streptococcus pneumoniae) in a pure state and established its relationship to lobar pneumonia (604-608; 1955; 1957).

 

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 (1161).

 

Carl Joseph Eberth (DE) isolated the typhoid bacillus from the mesenteric glands and the spleen of persons dying from typhoid fever (463).

 

Georg Theodor August Gaffky (DE) isolated Gaffkya tetragena from the pulmonary cavities of patients with phthisis (pulmonary tuberculosis) (641).

 

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 (spotted death) (1475; 1479-1481). Note: In May 1881, Pasteur performed a famous public experiment at Pouilly-le-Fort to demonstrate his concept of vaccination. He prepared two groups of 25 sheep, one goat and several cows. The animals of one group were twice injected, with an interval of 15 days, with an anthrax vaccine prepared by Pasteur; a control group was left unvaccinated. Thirty days after the first injection, both groups were injected with a culture of live anthrax bacteria. All the animals in the non-vaccinated group died, while all of the animals in the vaccinated group survived (412).

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 (519).

 

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. In addition to abscesses, Ogston examined lesions associated with gonorrhea, soft chancre, sycosis, sputa from phthisis (pulmonary tuberculosis), and 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 (1397-1400).

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 (529; 1584).

 

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) (1552; 1553). These are pseudocoelomate invertebrates that are widespread in mud or sand at all depths.

 

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 (551). 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." (729)

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 (274).

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 (552; 1753). 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), 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. During 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 (1548-1550).

William Crawford Gorgas (US) studied the effects of removing the Aedes aegypti mosquito population on yellow fever rates. He started his work in Havana in February: workers drained or covered open water containers and fumigated areas to kill adult mosquitoes. Yellow fever cases began to drop, and by October, none were reported. Reports of malaria dropped as well (729).

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 (273). Note: first human virus, the first arbovirus, and the first flavivirus

Adrian Stokes (GB), Johannes H. Bauer (US), N. Paul Hudson (US), Constant Mathis (FR), Andrew Watson Sellards (US), and Jean Laigret (FR), working in West Africa, proved that yellow fever is caused by a virus and transferable to monkeys (1242; 1760; 1761). Stokes died of a yellow fever infection.

Wilbur A. Sawyer (US), Stuart F. Kitchen (US), Martin M. Frobisher, Jr. (US), and Wray Lloyd (US) determined the relationship of yellow fever of the Western hemisphere to that of Africa and leptospiral jaundice (1643).

Max Theiler (ZA-US) and Hugh H. Smith (US) grew the yellow fever virus in rhesus monkeys (Macacus rhesus), and then passed it to mice. In mice, it developed as encephalitis. They passed it from mouse to mouse, and then eventually back to the monkeys, where it produced a full immunity to the most virulent form of the virus. This attenuated strain could also be used to vaccinate man (1781; 1782).

Wilbur A. Sawyer (US) and Wray Lloyd (US) developed a serum neutralization test for the presence of yellow fever (1645).

Wilber A. Sawyer (US), Stuart F. Kitchen (US), and Wray Lloyd (US) developed a vaccine to yellow fever using the attenuated virus. The vaccine had two parts: a ten-percent suspension of mouse-brain tissue with yellow fever virus in fresh sterile human serum, and human immune serum from people recently recovered from yellow fever (1644).

Fred L. Soper (US), Elmer R. Rickard (US), and Peter J. Crawford (US) perfected the postmortem diagnosis of yellow fever by viscerotomy (histological examination of the liver) (1727). This greatly aided in field surveys of yellow fever.

Max Theiler (ZA-US), Hugh Hollingsworth Smith (US), Henrique A. Penna (BR), and Adhemar Paoliello (BR) carried out successful field trials of their yellow fever vaccine (1722; 1783).

 

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 microorganisms. These organisms attack first the organic material, and feeding upon it create an acid, which removes the lime-salts (1294).

 

Carl Wernicke (PL-DE) first diagnosed Wernicke's encephalopathy. This first diagnosis noted symptoms including paralyzed eye movements, ataxia, and mental confusion. Also noticed were hemorrhages in the gray matter around the third and fourth ventricles and the cerebral aqueduct. Brain atrophy was only found upon post-mortem autopsy. Wernicke believed these hemorrhages were due to inflammation and thus the disease was named polioencephalitis haemorrhagica superior (1973).

That this disease state was the result of a deficiency in thiamine (vitamin B-1) would be discovered in the 1930s.

Note: The condition is part of a larger group of diseases related to thiamine insufficiency, including beriberi in all its forms, and Korsakoff syndrome.

Sergei Korsakoff (RU) was studying long-term alcoholic patients and noticed a decline in their memory function (1010).

 

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 (350).

 

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 (346; 347).

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 (1646).

 

Richard 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 (1866). These are now called Volkmann ischemic contractures.

 

Hermann Munk (DE) placed the cerebral center for hearing in the temporal lobes of the brain (1341; 1874).

 

Théodule Ribot (FR) cited several cases from the literature to illustrate the occasional separation of procedural (ways of doing things) from declarative (factual) memory (1563).

Sanger Brown (GB) and Edward Albert Schäfer (GB) reported that damage to the temporal lobes and the underlying hippocampus may affect memory (231).

William B. Scoville (US) and Brenda Milner (US) reported on a patient in whom 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 (1694).

 

Moritz Litten (DE) was the first physician to describe vitreous bleeding in correlation with subarachnoid hemorrhage (SAH) (1152).

 

William Alvin 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 (1150; 1194).

 

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 (661).

 

William Richard Gowers (GB) gave a classic description of epilepsy (733).

 

Waren Tay (GB) and Bernard Parney 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 (1622-1624; 1779). Note: Tay-Sachs disease occurs predominantly, but not exclusively, in Jewish children of eastern and central European (Ashkenazi) families. 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. J.J. Forst (FR), one of his pupils reported it years later (599).

 

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 (1287; 1814; 1815).

 

Vincenz Czerny (CZ-DE) introduced the operation of enucleation of subperitoneal uterine fibroids by the vaginal route (363).

 

Nikolaus Friedreich (DE) was the first to describe paramyoclonus multiplex (637).

 

Emil Wilhelm Magnus Georg Kraepelin (DE) wrote about the influence of infectious diseases on the onset of mental illness (1037; 1038).

 

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 (1912).

 

William Alvin Macewen (GB) reported the successful removal of a brain tumor of the left frontal dura mater, likely a meningioma, in a 14-year-old girl. This is the first successful surgical removal of a brain tumor (1195). The operation was performed in 1879.

Hermann Oppenheim (DE) and Rudolf Albrecht Koehler (DE) reported the successful removal of a brain tumor. Koehler was the surgeon (1410).

 

Francesco Durante (IT) successfully removed a cranial base meningioma. Durante performed a large left frontal craniotomy and removed an "apple-sized sarcoma." The patient recovered from the surgery without incident (453). 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 (99; 100).

 

Max Schüller (DE) performed the first successful operation for non-descending testicle (1671).

 

Richard Clement Lucas (GB), in 1879, removed a kidney with a most successful result, as the patient was shown more than twenty years afterwards (1178).

 

John Girdner (US) described the first allograft skin transplantation using skin from a human cadaver. Girdner procured skin from the inner thigh of a young German boy within 6 hours of his death and transplanted the skin onto the shoulder blade of a 10-year-old boy who had been struck by lightning (687; 1391).

 

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 (1704).

 

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 (753).

 

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 Freund (AT) discovered and described cyclopropane (trimethylene) (620).

George H. W. Lucas (CA) and Vilyien E. Henderson (CA) showed that cyclopropane has anesthetizing properties (1177).

John A. Stiles (US), William B. Neff (US), Emery A. Rovenstine (US), and Ralph M. Waters (US) began to use cyclopropane clinically (1758).

 

Ferdinand Gustav Julius Sachs (DE) suggested that nuclein carries 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 (1629; 1630).

 

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 (498; 502; 505).

 

White arsenic is first used to control codling moth. Napthalene is first used for insect control purposes. It is used in a cone form (1707).

 

Johannes Ludwig Emil Robert von Hanstein (DE) coined the name microsome for some small granules common in the cytoplasm (1889).

 

Ferdinand Gustav Julius Sachs (DE), in 1882, noted that plants synthesize organ-forming substances that are typically distributed to the cell's poles (1628).

 

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 (60).

 

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 (473).

Franz Ziehl (DE) described a method for staining the tubercle bacilli. His technique did not employ a counterstain (2031).

Friedrich Carl Neelsen (DE) introduced what we may call the classic procedure for staining acid-fast bacteria (1358). Today it is referred to as the Ziehl-Neelsen method. A. Johne (DE) first mentioned it in a paper (937).

 

Paul Ehrlich (DE) used the fluorescent dye uranin (a sodium salt of fluorescein) to determine the pathway of secretion of the aqueous humor in the eye of the rabbit (474). This represents the first use of a fluorescent dye in animal physiology.

 

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 (1565-1574). 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 (1156; 1157).

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 (1759).

 

Hermann 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 necessary if the ruminant was to lead a normal life (1774; 1775).

 

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 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 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 (348; 1060).

 

Bartolomeo Camillo Emilio Golgi (IT) used his "black reaction" staining technique to trace the olfactory nerves in man and other mammals (701; 702; 713).

 

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 (1918).

 

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 (1618). 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 (1914).

 

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 (995).

 

Thomas Jonathan Burrill (US) discovered and described the bacillus that 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 (245-248). See, Wakker in 1883.

 

Ludwig von Graff (AT) proposed the planuloid-acoeloid theory to explain how the bilateral animals evolved from radial animals (1885).

Libbie Henrietta Hyman (US) has vigorously promoted the planuloid-acoeloid theory (904).

 

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 Amphibian and Reptilian, and was to shape zoological thinking in Europe for many years (180-184).

 

Harry Marshall Ward (GB) stressed the relationship of environment to the epidemiology of coffee rust in Ceylon (1950).

 

Joseph Jules François Felix Babinski (FR) published a treatise on typhoid fever (49).

 

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 anemic culture, and finally (4) be found again in the lesions of this artificially produced disease (995).

He described how alkaline ethylene 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 (995). 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 (1869-1871).

 

Carl Friedlander (DE) discovered a bacterium, which causes pneumonia in humans and named it Bacillus pneumoniae (629; 630). 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 (1962).

 

Kenneth McLeod (GB) first described Donovanosis in Madras, India as a ‘serpiginous ulcer’ (1254).

Charles Donovan (IE) described the presence of intracellular microorganisms from an oral lesion in a case of Donovanosis (432).

Max A. Goldzeiher (HU-US) and Samuel Mortimer Peck (US) provided the classical description of the disease and recognized Donovan bodies in histological sections (694).

Edgar R. Pund (US) and Robert B. Greenblatt (US) described the pathognomonic cells of granuloma inguinale (Donovanosis) consisting of large mononuclear cells filled with intracytoplasmic cysts containing deeply staining bodies (1531).

Donovanosis (granuloma inguinale) is caused by the obligately intracellular gram-negative bacterium Klebsiella granulomatis, previously called Calymmatobacterium granulomatis, and Donovania granulomatis.

 

Carle Gessard (FR) discovered that the blue or blue-green stains that sometimes appeared on surgical dressings are caused by the presence of Pseudomonas pyocyanea (Pseudomonas aeruginosa) (680; 681).

 

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 (1399).

 

Rudolf von Jaksch; Rudolf Jaksch von Wartenhorst (AT) identified acetoacetic acid in the urine of diabetics. It would, with the loss of carbon dioxide, break down into acetone (1898; 1899).

 

Heinrich Irenaeus Quincke (DE) described angioneurotic edema (1535). 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 (1915).

 

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 who 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 (272; 909). 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 (669).

Hans Lieb (DE) and Emil Epstein (DE) isolated a fatty substance (the cerebroside, kerasin) from the spleens of patients with Gaucher disease (509; 1142).

Henriette Aghion (FR) identified this fatty substance as glucocerebroside (Aghion 1934).

William Bloom (US) described the histopathology of Gaucher’s and Niemann’s diseases (168).

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 (207-209).

 

Franz Ernst Christian Neumann (DE) postulated the law of dissemination concerning yellow and red bone marrow. In effect, he recognized a phenomenon that is sometimes referred to us as Neumann's law. It states that at birth all bones that contain marrow contain red marrow. With age, the blood producing activity contracts toward the center of the body, leaving the more peripheral bones with only fatty marrow (1368).

 

Ernst Ziegler (DE), in 1882, described a decrease in bone mass, which would later be called osteoporosis (2030).

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 (1506).

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 (1943).

 

Walter Holbrook Gaskell (GB) made many cardiac contributions including the following: 1) the recognition of certain inherent properties of cardiac muscle, which he termed “rhythmicity, excitability, contractility, conductivity and tonicity” (662; 663; 665); 2) the experimental proof that led to the acceptance of the myogenic theory, as opposed to the neurogenic theory of the origin of the heartbeat (663; 665); 3) the mapping of the anatomy of the sympathetic nervous system (664); 4) the understanding of the dual autonomic control of the heart (663-665); 5) the discovery of the vasodilating effect of sympathetic stimulation on blood flow through skeletal muscle arteries (659; 660); and 6) the introduction of the concept of heart block (663; 665).

 

Wilhelm August Balser (DE) and Reginald Heber Fitz (US) described acute hemorrhagic pancreatitis and some of its attendant problems (67; 579; 1604).

 

Heinrich Irenaeus Quincke (PL-DE) described angioneurotic edema (or angioedema), a form of localized swelling of the deeper layers of the skin and fatty tissues beneath the skin. Hereditary angioneurotic edema (or hereditary angioedema) is a genetic form of angioedema (1534). Persons with it are born lacking an inhibitor protein (called C1 esterase inhibitor) that normally prevents activation of a cascade of proteins leading to the swelling of angioedema.

 

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 (239).

 

Ernst Viktor von Leyden (DE) described fatty infiltration of the heart for the first time (1909).

 

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 (12).

 

Carl August Langenbuch (DE), in 1882, performed the first successful cholecystectomy (removal of the gall bladder) (1087).

 

Alexander von Winiwarter (AT-BE) was the first to successfully perform a cholecystoenterostomy in man (surgical anastomosis of the gallbladder and intestinal tract) (1921; 1922).

 

Adolf Eugen Fick (DE) introduced the concept and methodology of isotonic and isometric determination of the process of muscular contraction (545).

 

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

"There is something fascinating about science. One gets such wholesale returns of conjecture out of such a trifling investment of fact." Samuel Langhorne Clemens (Mark Twain) (308)

 

Johan Gustav Christoffer Thorsager Kjeldahl (DK) described his method for determination of nitrogen in organic materials (972; 973).

 

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 (1729).

 

Heinrich August Bernthsen (DE) made the dye azure B (117; 118).

 

Franz Hundeshagen (DE) synthesized lecithin (884).

 

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 (1606-1609).

 

Jacques-Louis Soret (CH) discovered a strong absorption band of hemoglobin in the violet and ultra-violet portion of the spectrum(1729).

 

Karl James Peter Graebe (DE) and Heinrich Caro (DE) discovered acridine orange (734).

L. Benda (DE) synthesized acridine orange and proflavine (96).

Carl Hamilton Browning (GB) and Walter Gilmour (GB) recognized the antimicrobial properties of acriflavine (232).

 

Ernst August Schulze (CH) and Emil Bosshard (CH) isolated the amino acid glutamine from beet juice (1681).

Ernst August Schulze (CH) established that asparagine and glutamine are important in plant metabolism (1678).

 

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 (1295; 1296).

 

Bronislaw Lachowicz (PL) and Marceli Nencki; Marcellus von Nencki (PL) reported putrefaction under conditions in which no free oxygen could be detected even by the most sensitive tests (1073).

 

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 (2022).

 

Sydney Ringer (GB) reported that calcium ions are required in the bathing medium to maintain the contraction of an isolated frog heart (1566).

 

Arthur Meyer (DE) described the chloroplast as consisting of a colorless, homogeneous matrix in which grana are embedded (1284).

S. Jenny Doutreligne (NL) and Johann Heinrich Emil Heitz (DE) described chloroplasts as consisting of a lighter-colored stroma impregnated with several darker grana (433; 815; 816).

Bert Hubert (NL) and Albert Frey-Wyssling (CH) postulated that grana contain alternate proteidic and lipoidic layers with chlorophyll molecules attached (625; 626; 881).

 

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 (501).

 

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 (996).

 

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, and then poured onto cold sterile glass plates. This method for obtaining axenic cultures soon became the method of choice (996).

 

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 (671).

 

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 (793-796).

 

Alphonse de Candolle (FR) wrote Origine des Plantes Cultivée that identified the geographic origin of most agronomic, horticultural, and fruit crop plants (398).

 

Moriz Loewit (AT) described the development of the erythrocyte from a non-hemoglobiniferous small round cell (1160).

 

Franz von Leydig (DE) described large vesicular cells that occur in the connective tissue and in the walls of blood vessels in crustaceans (1910). Note: Four different types of the latter have been determined.

 

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 (1933). 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 (981).

 

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 (529). 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 (1488).

 

Albert Freeman Africanus King (US) wrote a paper in which he gave 19 reasons why mosquitoes were likely to be the vector of malaria (966).

 

Paul Gerson Unna (DE) recognized human transmission of Herpes simplex virus infections between individuals (1828).

 

Victor Alexander Haden Horsley (GB) described the effects of nitrous oxide anesthesia (872).

 

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. This theory held that differentiation during ontogeny was caused by the qualitative nuclear division of the hereditary material during cleavage; as development progressed, cells gradually lost more and more hereditary potential in terms of the kinds of adult tissues they could form (1601; 1602).

Wilhelm Roux (DE) was the first to culture 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 pressure from the surrounding tissues (1603).

Wilhelm Roux (DE) founded what he called entwickelungsmechanik (developmental mechanics) which became experimental embryology then analytical embryology (1411).

 

Magnus Gustaf Blix (SE), Johannes Karl Eugen Alfred Goldscheider (DE), and Henry Herbert Donaldson (US) discovered that a person's thermal sensations are associated with stimulation of localized sensory spots on the skin. Further investigation revealed a distinction between hot spots and cold spots; i.e., specific places in the human skin that were selectively sensitive to warm or cold stimuli (163-165; 428; 692).

 

Emil Theodor Kocher (CH) showed the relationship of goiter to activity of the thyroid gland (1002). 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. Note: Kocher and others later discovered that the complete removal of the thyroid could lead to cretinism (termed cachexia strumipriva by Kocher) caused by a deficiency of thyroid hormones. The phenomena was reported to Kocher first in 1874 by the general practitioner August Fetscherin (CH).

His other significant contributions to surgery were descriptions of a maneuver to reduce a subluxed shoulder in1870, radical surgery for carcinoma of the tongue in1880, and an operation for inguinal hernias in 1892 (1000; 1001; 1003). Note: 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.

Felix Semon (DE-GB) proposed that cretinism, myxoedema and cachexia strumipriva were all associated with absence or degeneration of the thyroid gland (1703).

 

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 (1129; 1130; 1786-1790). 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 (1185).

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 biliary passages where they mature (1719).

 

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 (531). Note: Ferrán later treated over 50,000 people in Spain with his live attenuated vaccine for cholera.

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 (243; 785).

 

Francis Galton (GB) coined the term eugenic (wellborn) to refer to the breeding of members of a species in such a way as to concentrate desirable traits within offspring (649).

 

Kanehiro Takaki (JP), c. 1883, because of rampant cases of beriberi, made a petition to Emperor Meiji to fund an experiment with an improved diet for the naval seamen that included more meat, milk, bread and vegetables. He succeeded. This experiment convinced the Imperial Japanese Navy that poor diet was the prime factor in beriberi, and the disease was soon eliminated from the fleet. Takaki's success occurred ten years before Christiaan Eijkman (NL) working in Batavia, advanced his theory that beriberi was caused by a nutritional deficiency, with his later identification of vitamin B1 (1176).

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 can be cured by adding rice shavings (outer layer) to the diet (478-480; 612; 757; 1927-1929).

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 diffusible through a semi-permeable membrane (481).

Umetaro Suzuki (JP), Torai Shimamura (JP), and Seizaburo Okada (JP) isolated the antineuritic, anti-beriberi factor (thiamine, vitamin B1) as a crystalline picrate (1771).

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 couldn’t function properly (324).

Barend Coenraad Petrus Jansen (NL) and Willem Frederik Donath (NL) crystallized thiamine (vitamin B1) (933).

Louis Sigurd Fridericia (DK), P. Freudenthal (DK), Skúli V. Gudjónnsson (DK), G. Johansen (DK), and N. Schoubye (DK) demonstrated that rats can adjust 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 (628).

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 (1652).

Rokuro Inawashiro (JP), Enaji Hayasaka (JP), Henry Wulff Kinnersley (GB), Nicolai Gavrilescu (HU), and 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 (670; 907; 967; 968; 1497-1499).

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 (1994).

Adolf Otto Rheinhold Windaus (DE), Rudolf Tschesche (DE), and Hans Ruhkopf (DE) discovered that vitamin B1 (thiamine) contains sulfur (1993).

Ernst Auhagen (DE) discovered that yeast carboxylase, the enzyme which decarboxylates pyruvic acid to acetylaldehyde requires a heat-stable dialyzable coenzyme (42). It was first called co-carboxylase, and 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 (1985).

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) (20; 310; 1750; 1751; 1803; 1984).

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 (1166).

 

George Oliver (GB) described filter paper (or cloth) bedside tests for glucose and protein in urine (1404).

Fritz Feigl (AT-BR) and Vinzenz Anger (AT), c. 1920, based their method for bedside determination of protein in the urine on the interaction of proteins with hydrogen ions using the dye tetrabromophenol blue in designing a spot test (still used in dipsticks). Protein inhibited the effect of acid on the colour of the compound, so in an acid buffer its color changes from yellow to blue as protein concentration increases (530). See, Alfred H. Free, 1957

 

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 (749; 750).

 

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 (691).

 

H. Leyden (DE) performed the first percutaneous needle biopsy of the lung. It consisted of the examination 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 (1141).

Lloyd F. Craver (US) and J. Samuel Binkley (US) performed transthoracic needle biopsy of the lung at Memorial Hospital in New York City as early as 1927 (345).

 

Jacques-Louis Reverdin (CH) and Auguste Reverdin (CH) observed that myxedema occurred as a delayed complication when the thyroid gland was surgically removed (1559).

 

Robert Lawson Tait (GB) was the first to successfully surgically manage a ruptured tubal pregnancy when he performed a laparotomy and ligated the ruptured tube and the broad ligament (1773). A series of thirty-five cases with only two deaths speedily followed, and the operation took its place as a recognized method of treating a condition that had previously been looked upon as desperate.

 

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 (1039).

 

Oskar Kobylinski (ES) describes the first reported patient with what is now called Noonan syndrome (989).

Jacqueline A. Noonan (US) noticed that children with a rare type of heart defect, valvular pulmonary stenosis, often had a characteristic physical appearance, with short stature, webbed neck, wide spaced eyes, and low-set ears. Both boys and girls were affected. These characteristics were sometimes seen running in families but were not associated with gross chromosomal abnormalities (1385). This condition was later named Noonan syndrome.

 

John Cleland (GB) was the first to describe Chiari II or Arnold–Chiari malformation on his report of a child with spina bifida, hydrocephalus, and anatomical alterations of the cerebellum and brainstem (307).

Hans Chiari (AT) described the case of a 17-year-old woman with elongation of the tonsils into cone shaped projections, which accompany the medulla and are crammed into the spinal canal (298; 299).

Julius Arnold (DE) described the pathological findings in an infant dying shortly after delivery. The child had a large herniation of the spinal cord thoracolumbaly. He also described the brainstem as underdeveloped with a downward draw of some of the lower parts of the cerebellum and the 4th ventricle in the spinal canal (31).

Ernst Schwalbe (DE) and Martin Gredig (DE) described four cases of meningomyelocele and alterations in the brainstem and cerebellum, and gave the name Arnold-Chiari to these malformations (1683). Note: Arnold-Chiari malformation is a condition in which the inferior poles of the cerebellar hemispheres (cork-like protrusions) and the medulla oblongata protrude through the foramen magnum into the spinal canal, without displacing the lower brain stem.

 

William Keith Brooks (US) provided one of the clearest discussions of variability. Alluding to "one of the most remarkable and suggestive of the laws of variation," that parts exclusively male or of greater importance in males were "very much more variable" than parts confined to or more important in females. Brooks derived a general corollary, "that males are as a rule more variable than females." Brooks believed that he could offer a hereditary explanation for male variability in the differing functions of the sex cell. The male cell had developed "a peculiar power to gather and store up germs." Critical to this theory was the assumption that the transmission was sex-linked, so that variations accumulated exclusively in the male line. "According to this view, the male element is the originating and the female the perpetuating factor; the ovum is conservative, the male cell progressive." (226)

 

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 (589).

 

Karl August Möbius (DE) expressed the concept of community (he called it biocoenosis), however, his essay lacked the detail and impact of later papers (1308).

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 (596-598).

 

The Journal of the American Medical Association was founded (1209).

 

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) (1934). These pillar like structures called Cryptozoon (hidden life) are now called stromatolites.

 

Max Josef 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 (DE) (1964)

 

"For in disease the most voluntary or most special movements, faculties, etc., suffer first and most, that is in an order the exact opposite of evolution. Therefore I call this the principle of Dissolution." John Hughlings Jackson (GB) (922)

 

Svante August Arrhenius (SE), in 1884, proposed in his doctoral dissertation that some substances when dissolved in water would behave as electrolytes and thus carry a current because they exist as charged ions in solution. Substances, which cannot behave as electrolytes, are non-ionic. He defined acids as substances that release hydrogen ions when dissolved in water to become negatively charged ions highly capable of reacting with other compounds (33-35).

Wilhelm Friedrich Ostwald (LV-DE) proffered his dissolution law (1431). See, Sørensen 1909 for pH

 

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. Congo red is the essential histologic stain for demonstrating the presence of amyloidosis in fixed tissues (178).

H. Griesbach (DE), in 1886, was the first to report using Congo red to stain tissue (755).

Hermann Bennhold (DE), in1922, reported that Congo red was found to bind avidly to amyloid protein (102).

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 (424-426).

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 (1300; 1545). 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 (560; 569).

 

Carl Weigert (DE) introduced hematoxylin stain for myelin (1961).

 

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, which determined 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 that 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 (409; 410).

 

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 (1298). 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." (1797). Thudichum is 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." (827-829)

 

Heinrich Anton de Bary (DE) called for the blue-green algae (cyanobacteria) to be considered bacteria and not algae (397).

 

Charles T. Druery (GB) and Frederick Orpen Bower (GB) discovered apospory in the Pteridophyta (ferns, horsetails, and club-mosses) (203; 438).

 

Theodor Wilhelm Engelmann (DE) concluded that all plastid pigments, and not merely chlorophyll, could mediate photosynthetic oxygen evolution (504).

 

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 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 (739; 740).

 

Agar-agar replaced gelatin as the solidifying agent of choice in bacteriological media. Angelina Fannie Hesse, the wife of Walther Hesse, one of Heinrich Hermann Robert Koch’s early co-workers, introduced it. 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 (849).

 

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 (284).

 

Louis Théophile Joseph Landouzy (FR) was the first to suggest the infectious nature of Herpes (1082).

 

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 (284; 285).

 

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 (1507).

 

Ettore Marchiafava (IT), and Angelo Celli (IT) stained diplococci in meningeal exudates from patients with meningitis (1225).

 

Friederich August Johannes Löffler (DE) and Theodor Albrecht Edwin Klebs (DE) stained and described Corynebacterium diphtheriae, the bacterium that 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. Koch has overcome the inadequacies of the experimental methods.

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 encountered 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 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 diagnoses 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 (spotted death), 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 like 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 11^th 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 is 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 13^th 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 7^th 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 an 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 25^th 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 30^th 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 9^th 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 6^th 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." (1162; 1163)

 

Friederich August Johannes Löffler (DE) was the first to recognize Fusobacterium necrophorum as the cause of an infection, namely, calf diphtheria (1164).

Georg Schmorl (DE) was the first to describe a human infection by Streptothrix cuniculi, later named Fusobacterium necrophorum. It involved an animal strain (1666).

Jean Hallé (FR) gave the first description of the isolation from a human of what we now call F. necrophorum subsp. funduliforme as part of a Ph.D. thesis on the bacteriology of the female genital tract. He called the organism Bacillus funduliformis (787).

Paul Courmont (FR) and André Cade (FR) gave the first description of Lemierre's syndrome, i.e., a human postanginal septicemic infection with F. necrophorum (339).

John Wesley Long (US) first recognized a case of postanginal sepsis with internal jugular venous thrombophlebitis as caused by Fusobacterium necrophorum (1168).

 

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 (1476; 1482).

 

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 (1476).

 

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 (368-371).

 

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 (268). 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 (1372). 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 (970). He also proved the inability of the tetanus bacillus to invade the blood stream and showed the disease to be intoxication (971).

Edmond Isidore Étienne Nocard (FR) demonstrated the protective effect of passively transferred tetanus antitoxin in horses. The Pasteur Institute supplied the antitoxin (1379). Passive immunization in humans was used during World War I.

Pierre A. Descombey (CA) prepared tetanus toxoid (419). 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 (1698). 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 (1699; 1700).

 

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 (82; 83).

 

Issac Ott (US) discovered that the center for temperature regulation is in the corpora striata region of the brain (1432).

 

Heinrich Wilhelm Gottfried Waldeyer; Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) was the first to make detailed anatomical and histologic studies of a ringed arrangement of lymphoid organs in the pharynx. Waldeyer's ring surrounds the naso-and oropharynx, with some of its tonsillar tissue located above and some below the soft palate (and to the back of the mouth cavity) (1938; 1939).

 

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 (153-157).

 

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 (1101; 1102).

 

Karl Koller (CZ-US) was the first physician to explore the use a local anesthetic for surgery. He instilled a 2% solution of cocaine into his own eye and tested its effectiveness as a local anesthetic by pricking the eye with needles (1006; 1007). Anesthesia in the form of eye drops (cocaine) obviated the hazards of general anesthesia and its post-operative complications.

William Stewart Halsted (US), in 1884, performed the first brachial plexus block when he injected the brachial plexus in the supraclavicular region with cocaine under direct vision (789). This is sometimes called conduction anesthesia.

Richard John Hall (US), in 1884, described how using cocaine he blocked a cutaneous branch of the ulnar nerve in his own forearm (786).

William Stewart Halsted (US), by injecting Richard John Hall (US), discovered the technique for blocking the inferior alveolar nerve and the antero-superior dental nerve using cocaine as an anaesthetic (789). The anaesthetic technique, described perfectly by both surgeons in 1885, has been revolutionary in the practice of odontology since its introduction, offering dentists the possibility of performing invasive interventions to the maxillary without pain.

K. Mulley (DE) developed the interscalene approach to brachial plexus block to avoid pneumothorax (1340).

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 (1995).

Harvey Williams Cushing (US) applied cocaine to the brachial plexus prior to dividing it, during a forequarter amputation for sarcoma (358).

Diedrich Kulenkampff (DE) performed the first percutaneous supraclavicular block, using himself to test the block (1062).

Diedrich Kulenkampff (DE) and M.A.Persky (US) published their experiences with a thousand blocks without apparent major complications (1063).

Alfred Einhorn (DE) and Emil Uhlfelder (DE) produced an alkamin ester of para-aminobenzoic acid, which they named procaine (483; 484). 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 (1165). 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. Note: For spinal block see James Leonard Corning, 1885, Part 3A.

 

Ludwig Wilhelm Carl Rehn (DE) performed the first thyroidectomy for exophthalmic goiter. The operation reported was performed in 1880. He proposed that toxic goiter (enlarged thyroid gland) was due to thyroid excess (1551).

 

Charles Louis Xavier Arnozan (FR) and Louis Vaillard (FR) found that ligation of the pancreatic ducts led to atropy of the acinar tissue, while the islets remained intact no diabetes took place (32).

Joseph von Mering (DE) and Oskar Minkowski (DE) showed that removing the pancreas from a dog caused the animal to exhibit a disorder quite similar to human diabetes mellitus (elevated blood glucose and metabolic changes) (1911).

Oskar Minkowski (DE) confirmed that pancreatectomy caused diabetes in the dog, but importantly, showed pancreatic autograft under the skin could prevent the diabetes from appearing (1299).

 

Louis A. Duhring (US) provided a description of dermatitis herpetiformis, which has remained valid to this day (447). It is also called Duhring’s disease.

 

Louis Théophile Joseph Landouzy (FR) and Joseph Jules Dejerine (FR) described a form of childhood progressive muscle atrophy with a characteristic involvement of facial muscles and distinct from pseudohypertrophic (Duchenne’s MD) and spinal muscle atrophy in adults (1083).

Louis Théophile Joseph Landouzy (FR) and Joseph Jules Dejerine (FR) described progressive muscular atrophy of the scapulo-humeral type. They drew attention to the familial nature of the disorder and mentioned that four generations were affected in the kindred that they had investigated (1084).

Frank H. Tyler (US) and Fayette E. Stephens (US) studied 1249 individuals from a single kindred with facioscapulohumeral dystrophy traced to a single ancestor and described a typical autosomal dominant Mendelian inheritance pattern with complete penetrance and highly variable expression. The term facioscapulohumeral dystrophy is introduced (1820). Note: This condition is also called Landouzy-Dejerine dystrophy.

 

Moses Allen Starr (US) reported that lesions in the region of the Rolandic fissure could 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 deficiencies 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 judgment (1747; 1748).

Henri Verger (FR), Joseph Jules Déjérine (CH-FR), and Jean 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 (414; 1851).

Mieczyslaw Minkowski (CH), using monkeys, concluded that cutaneous discriminative ability is chiefly, but not exclusively, represented in the post-central gyrus of the brain (1297).

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 (390-392).

Edgar Douglas Adrian (GB) discovered a second somatosensory cortex, just above the Sylvian fissure in the brain of the cat (7).

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 (456).

 

Victor Alexander Haden Horsley (GB) induced both cretinism and myxedema in monkeys by experimentally removing the thyroid gland. He concluded that the cretinous symptoms following thyroidectomy are due to the arrest of a function of the thyroid gland (873; 874). Note: Some of the symptoms he described are now known to have been due to removal of the parathyroid glands.

 

English country names and code elements taken from the International Organization for Standardization:

DZ = Algerian; US = American; AR = Argentinian; AU = Australian; AT = Austrian; AT/HU = Austro/Hungarian; BA = Bosnian-Herzegovinian; BE = Belgian; BR = Brazilian; GB = British; BG = Bulgarian; CM = Cameroonian; CA = Canadian; TD = Chadian; CL = Chilean; CN = Chinese; CO = Colombian; CR = Costa Rican; HR = Croatian; CU = Cuban; CY = Cypriot; CZ = Czechoslovakian; DK = Danish; NL = Dutch; EC = Ecuadorian; EG = Egyptian; EE = Estonian; ET = Ethiopian; FI = Finnish; FR = French; DE = German; GR = Greek; GT = Guatemalan; GU = Guamanian; HU = Hungarian; IS = Icelander; IN = Indian; ID = Indonesian; IR = Iranian; IQ = Iraqi; IL = Israeli; IE = Irish; IT = Italian; JP = Japanese; KE = Kenyan; KR = South Korean; KW = Kuwaiti ; LV = Latvian; LB = Lebanese; LT = Lithuanian; LU = Luxembourgian; MK= Macedonian; MG = Malagasy; MT = Maltese; MY = Malaysian; MX = Mexican; NA = Namibian; NZ = New Zealander; NG = Nigerian; NO = Norwegian; PK = Pakistani; PA = Panamanian; PE = Peruvian; PH = Filipino; PL = Polish; PT = Portuguese; PR = Puerto Rican; RO = Romanian; RU = Russian; SA = Saudi Arabian; SN = Senegalese; CS = Serbian-Montenegrin; SG = Singaporean; SK = Slovakian; ZA = South African; ES = Spanish; LK = Sri Lankan; SE = Swedish; CH = Swiss; SY = Syrian; TW = Taiwanese; TH = Thai; TN = Tunisian; TR = Turkish; UG = Ugandan; UA = Ukrainian; UY = Uruguayan; VE = Venezuelan; ZW = Zimbabwean

 

 

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1846.   van't Hoff JH. 1874. Voorstel tot Uitbreiding der Tegenwoordige in de Scheikunde Gebruikte Structuurformules in de Ruimte, Benevens een Daarmee Samenhangende Opmerking Omtrent het Verband Tusschen Optisch Actief Vermogen en Chemische Constitutie van Organische Verbindingen [Proposal for the Extension of Current Chemical Structural Formulas into Space, Together with Related Observation on the Connection Between Optically Active Power and the Chemical Constitution of Organic Compounds]. Utrecht: J. Greven. 14 pp.

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1854.   Virchow RLK. 1858a. Die Cellularpathologie in Ihrer Begründung auf Physiologische und Pathologische Gewebelehre [Cellular Pathology as Based Upon Physiological and Pathological Histology]. Berlin: Verlag von August Hirschwald. 440 pp.

1855.   Virchow RLK. 1858b. Über die natur der constitutionell-syphilitischen affectionen [About the nature of the constitutionally-syphilitic affections]. Arch. Path. Anat. Physiol. Klin. Med. 15:217-336

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1863.   Volkmann AW. 1873. Über die naheren bestandtheile der menschlichen knochen [About the more detailed constituents of human bones]. Ber. Verh. Akad. Wiss. 25:275-

1864.   Volkmann R. 1875. Beiträge zur Chirurgie, Anschliessend an Einen Bericht über die Thätigkeit der Chirurgischen Universitäts-Klinik zu Halle im Jahre 1873 [Contributions to Surgery, Then a Report on the Activity of the Surgical University Hospital in Halle in 1873]. Leipzig: Breitkops & Härtel. 388 pp.

1865.   Volkmann R. 1878. Über den mastdarmkrebs und die exstirpatio recti [On rectal cancer and the exstirpatio recti]. Samml. Klin. Vort. Chir. 131:1113-28

1866.   Volkmann R. 1881. Ischämische muskellähmungen und -kontrakturen [Ischemic paralysis and contractures]. Zentralbl. Chir. 8:801-3

1867.   von Baer KE. 1828-1837. Uber Entwickelungsgeschichte der Thiere, Beobachtungen und Reflexionen  [On the Developmental History of Animals, Observation and Reflection ]. Konigsberg: Gebrüder Bornträger

1868.   von Bärensprung FWF. 1861. Die Gürtelkrankheit [The Belt Disease]. Berlin: A.W. Schade. 88 pp.

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1873.   von Bezold A, Hirt L. 1867. Über die physiologischen wirkungen des essigsauren veratrine [About the physiological effects of veratrine in vinegar]. Untersuch. Physiol. Lab. Wurzburg 1:73-123

1874.   von Bonin G. 1960. Some Papers on the Cerebral Cortex. Springfield, IL: Charles C Thomas. 396 pp.

1875.   von Bumm E. 1885a. Der mikro-organismus der gonorrhöischen schleimhaut-erkrankungen, gonococcus Neisser [The microorganism of gonorrhea mucosal disease , "Gonococcus Neisser"]. Dtsch. Med. Wochenschr. 11:508-9

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1877.   von Gerlach J. 1858a. Mikroskopische Studien aus dem Gebiete der Menschlichen Morphologie [Microscopic Studies From the Field of Human Morphology]. Erlangen: Enke. 72 pp.

1878.   von Gerlach J. 1858b. Ueber die einwirkung von farbstoff auf  lebende gewebe [Concerning the influence of dye on living tissue]. Wiss. Mitt. Phys. Med. Soc. Erlangen 1:5-12

1879.   von Graefe FWEA. 1859. Ueber embolie der arteria centralis retinae als ursache plotzlicher erblindung. Archiv. Ophthalm. 5:136-57

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1882.   von Graefe FWEA. 1866. Nachträgliche bemerkungen üeber modificirte linearextraction [Subsequent comments about modified linear extraction]. Arch. Ophthalmol. 12:150-223

1883.   von Graefe FWEA. 1868. Eröffnungsrede am 4. September anlässlich der eröffnung der tagung der Ophthalmologischen Gesellschaft (Opening speech on 4th September on the occasion of the opening of the meeting of the ophthalmological society). Klin. Monbl. Augenheilkd. 6:291-3

1884.   von Graefe FWEA. 1868. Weltere zusätze über das verfahren des peripheren linearschnittes [Furter remarks upon the peripheral linear section for cataract] Arch. Ophthalmol. 14:106-48

1885.   von Graff L. 1882. Monographie der Turbellarien I. Rhabdocoelida [Monograph of Turbellarians I. Rhabdocoela]. Leipzig: W. Engelmann. 441 pp.

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1887.   von Hanstein JLER. 1870. Die Entwicklung des Keimes der Monokotylen und Dikotylen [The Development of the Embryo of Monocots and Dicots]. Bonn: Adolph Marcus. 112 pp.

1888.   von Hanstein JLER. 1880. Das Protoplasma als Trager der Pflanzlichen und Thierischen Lebensverrichtungen [The Protoplasm as Carrier of Plant and Animal Life Chores]. In Sammlung von Vortragen fur das Deutsche Volk [Collection of Lectures for the German People], ed. W Frommel, AF Pfaff. Heidelberg: Winter. Number of.

1889.   von Hanstein JLER. 1882. Beiträge zur Allgemeinen Morphologie der Pflanzen [Contributions to the General Morphology of Plants] Bonn: Adolph Marcus. 244 pp.

1890.   von Hebra FKF. 1872. Über einzelne während der schwangerschaft, dem wochenbett, und bei uterina krankheiten der frauen zu beobachtende hautkrankheiten [About the individual during pregnancy, the postpartum period, uterine diseases in women, and observed skin diseases]. Wien. Med. Wochenschr. 48:1197-202

1891.   von Hebra FKF, Kaposi MK. 1874-1876a. Lehrbuch der Hautkrankheiten [Textbook on Diseases of the Skin]. Stuttgart: Enke

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1893.   von Helmholtz HLF. 1863. Die Lehre von dem Tonempfindungen als Physiologische Grundlage für die Theorie der Musik [On the Sensations of Tone as a Physiological Basis for the Theory of Music]. Braunschweig: F. Vieweg und Sohn. 600 pp.

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1898.   von Jaksch R. 1882. Über das vorkommen mit eisenchlorid sich roth färbender harne beim diabetes und bei akuten exanthemen [On the presence of ferric chloride Roth coloring urine in diabetes and in acute rashes]. Z. Heilk.

1899.   von Jaksch R. 1885. Über Acetonurie und Diaceturie [About Acetonuria and Diaceturie]. Berlin: Hirschwald. 156 pp.

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1902.   von Kölliker RA. 1863. Handbuch der Gewebelehre des Menschen für Aerzte und Studirende [Handbook of Human Tissue Theory for Doctors and Students]. Leipzig: Wilhelm Engelmann. 730 pp.

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1914.   von Nägeli KW. 1882. Untersuchungen Über Niedere Pilze aus dem Pflanzenphysiologischen Institut in Munchen [Studies on Lower Fungi: Plantphysiology Institute in Munich]. München: R. Oldenbourg. 75 pp.

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