A Selected Chronological Bibliography of Biology and Medicine

 

Part 3A

 

1885—1902

 

 

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










 

1885

"The death of this child appearing to be inevitable, I decided, not without lively and sore anxiety, as may well be believed, to try upon Joseph Meister the method which I had found constantly successful with dogs…. I thus made thirteen inoculations, and prolonged the treatment to ten days…. On the last days, therefore, I had inoculated Joseph Meister with the most virulent virus of rabies… Three months and three weeks have elapsed since the accident, his state of health leaves nothing to be desired." Louis Pasteur (1267).

 

"Science meets with two obstacles, the deficiencies of our senses to discover facts and the insufficiency of our language to describe them. The object of the graphic methods is to get around these two obstacles; to grasp fine details which would be otherwise unobserved; and to transcribe them with a clarity superior to that of our words." Étienne-Jules Marey (FR) (1062).

 

Baits containing poisons (bran-arsenic) were developed for insect control purposes. The first insecticide (arsenic) was recommended for use in soil to control insects damaging plant roots (1478).

 

Paul Ehrlich (DE) observed that certain vital dyes administered intravenously to small animals stained all the organs except the brain. He interpreted this to mean that the brain had a lower affinity for the dye than the other tissues (507).

Max Lewandowsky (DE) coined the phrase blood-brain barrier (Bluthirnschranke) (984).

Edwin Ellen Goldmann (DE) injected dye into the spinal fluid of the brain directly. He found that in this case the brain would become dyed, but the rest of the body would not. Considering Ehrlich’s finding this clearly demonstrated the existence of some sort of barrier between the two (678; 679). Note: These experiments demonstrated that the central nervous system is separated from the blood by a barrier of some kind, i.e., the blood-brain barrier.

Lina Salomonovna Stern (LT-CH-RU) and Raymond Gautier (CH) proposed the existence of a blood-brain barrier (hemato-encephalic barrier) (1545).

Thomas S. Reese (US) and Morris John Karnovsky (US), Milton W. Brightman (US), Yngve Olsson (SE), and Igor Klatzo (RU-LT-PL-CA-US) identified the site of the blood-brain barrier as the vascular endothelial cells of the brain of all vertebrates except for the elasmobranch fishes. In elasmobranchs glial cells form the blood-brain barrier (240; 241; 1345).

Michael W.B. Bradbury (GB) reported that the blood-brain-barrier is formed by a complex cellular system of endothelial cells, astroglia, pericytes, perivascular macrophages, and a basal lamina where lipid soluble substances easily penetrate the cerebral endothelial plasma membranes and readily attain equilibrium between blood and brain tissue (228).

 

Robert Behrend (DE) and Adolf Pinner (DE) coined the words uracil and pyrimidine respectively (132; 1303).

 

Thomas Richard Fraser (GB) was the first to isolate strophanthinic acid, a cardioactive glycoside, from the strophanthus plant (617).

Albert Fraenkel (DE) produced an injectable form of strophanthinic acid (610).

 

Raphael Horace DuBois (FR) reported the first definitive experiments regarding the nature of the chemical components necessary for light production by organisms. He found that the luminous organs of a beetle would cease to emit light if immersed in hot water. He also noted, however, that a cold-water extract, which ceased to luminesce, could be stimulated to emit light by adding the hot-water extract. He proposed that the hot water extract contained a substance stable to heat, luciferine, which was destroyed during its luminescent oxidation by a catalyst, luciferase, present in the cold-water extract. DuBois coined both luciferine (luciferin) and luciferase (473).

E. Newton Harvey (US) found that certain fish possess light organs, which contain luminous bacteria as the source of their luminescence (749).

William David McElroy (US), and Bernard L. Strehler (US) found that ATP could phosphorylate luciferin (1091). In fireflies when luciferan-phosphate is split, light is emitted.

Shimon Ulitzur (IL) and J. Woodland Hastings (US) reported that the light-emitting reaction of luminous bacteria involves a luciferase-catalyzed oxidation of reduced flavin mononucleotide (FMNH2) by molecular oxygen, with the concomitant oxidation of a long-chain aliphatic aldehyde, probably tetradecanal (1634).

 

George John Romanes (GB) examined conduction in jellyfish as part of his exploration of the evolution of mental processes in animals. Through clever cutting experiments Romanes demonstrated that contractile waves are conducted diffusely across the subumbrella epithelium of the jellyfish Aurelia and will spread between any two blocks of subumbrellar tissue so long as a bridge of intact tissue larger than a millimeter or so in width joins these (1370). The diffuse conduction demonstrated physiologically by Romanes was consistent with the diffuse distribution of the nerve cells found in histological studies.

George Howard Parker (GB) used the cut and stimulate approach of Romanes and found that conduction in the column of anemones is also diffuse. Parker proposed (incorrectly) that conduction in the cells of the coelenterate nerve net is graded, and not all-or-nothing as in axons of higher animals (1264).

Carl Frederick Abel Pantin (GB) demonstrated a through-conducting nerve net, a locally conducting nerve net with interneural facilitation, and a group of muscles with differing requirements for neuromuscular facilitation (1253-1255).

Elizabeth Joan Batham (GB) and Carl Frederick Abel Pantin (GB) found that even under constant conditions anemones periodically expand, contract, sway, and even move about by gliding on the pedal disk (118; 119; 1256).

Ian D. McFarlane (GB) showed that there is not just one but rather several conducting systems in the column of anemones; a rapidly conducting system, probably the column nerve net, and at least two slow systems (1094; 1095).

 

Ludwig Edinger (DE) and Paul Emil Flechsig (DE) discovered that many dorsal root fibers, after ascending in the dorsal column, affect synapses in the bulbar nuclei with secondary neurons, which pass to the thalamus (495; 588).

 

Heinrich Lissauer (DE) provided a description of the dorso-lateral tract, a bundle of fibers between the apex of the posterior horn and the surface of the spinal cord marrow that was to become known as Lissauer's tract. They transmit surface sensibility, pain and temperature sensibility (997).

 

Henry Pickering Bowditch (US) demonstrated the indefatigability of nerves. This was accomplished by paralyzing the motor nerve-endings in the muscle with curare, the first experiment in producing a functional nerve block with a drug (224).

 

Eduard Aronsohn (DE) and Julius von Sachs (DE) discovered that the supraoptic region of the hypothalamus is the body’s thermoregulatory center. When stimulated this center caused an increase in body temperature (43).

Henry Gray Barbour (US) confirmed the finding of Aronsohn and Sachs (88).

Robert Georg Isenschmid (DE) and Albrecht Ludolph von Krehl (DE) discovered a second heat-control center in the brain posterior to first heat center. Stimulation of this center caused a decrease in body temperature and a loss of thermoregulation after transection (847).

Hans H. Meyer (AT) was the first to suggest that body temperature is regulated by a balance between two centers: one functioning to prevent heat gain (the anterior hypothalamus) and the other functioning to prevent heat loss (the posterior hypothalamus) (1112).

 

Johann Friedrich Miescher-Rüsch (CH), in a paper that is one of the masterpieces of physiology, summarized all the evidence available and reached the conclusion that it is the variations in the amount of carbon dioxide, which principally induce the immediate adjustments of respiration. In a classic phrase inspired by the insight of genius he wrote: "Over the oxygen supply of the body carbon dioxide spreads its protecting wings." (1118)

 

Theodor Boveri (DE) followed the embryonic development of enucleated eggs of one species of sea urchin, Sphaerechinus, when they were fertilized with the spermatozoa of other species of sea urchin, Psammechinus or Paracentrotus. The results indicated that before gastrulation the chromosomes exert only general effects; after gastrulation, the factors for species-specific characters come into play, in interaction between nucleus and cytoplasm. This was the first expression of the concept of phase-specific and time-bound action of genes during development. It attributed to the cytoplasm a more specialized significance than had heretofore been acknowledged. Boveri referred to the development of sperm fertilized enucleated ova as merogony (211; 218; 220; 222).

 

Sydney Ringer (GB) postulated the existence of an endogenousdigitalis” in mammals (1365).

Albert Imre Szent-Györgyi (HU-US) later revived Ringer’s idea (1565).

 

Vittorio Marchi (IT) and G. Aligeri (IT) discovered that the initial products of degeneration in myelinated nerve fibers can be stained selectively by osmic acid after preliminary mordanting with potassium bichromate. This method is still used to trace the origin, course, and destination of fiber connections in both experimental and clinicopathological material (1060).

 

Gustav Hauser (DE) was the first to describe the bacterial genus Proteus, named for the Greek sea god Proteus because it is pleomorphic and appears in many different sizes and shapes (752).

 

Paul Clemens von Baumgarten (DE) clarified what is taking place at the tissue level during the tuberculous processes (1666).

 

Albert B. Frank (DE) was the first to report that a symbiotic relationship can exist between tree roots and fungi. He introduced the term mycorrhiza (fungus root) to describe this phenomenon (613).

 

Julius Kollmann (CH) described and named the phenomenon of neoteny (the process of transformation whereby newts and similar creatures mature sexually while they are still in larval form, as observed in the axolotl form of Ambystoma tigrinum (922).

 

Pierre Marie Alexis Millardet (FR) observed that the Bordeaux mixture (also called Médoc Mixture) used to prevent pilferage of grapes along roadsides also protected them from infection by the downy mildew, Plasmopara viticola. This mixture became the primary fungicide on grapes for some sixty years. The formula for treatment consists of the following: In 100 liters of water one dissolves 8 kg of commercial copper sulfate. Separately, one prepares milk of lime by mixing 30 liters of water and 15 kg of lime. Both solutions are mixed together forming a blueish paste. The mixture is sprinkled on the leaves with a little broom, being careful not to touch the grapes. Although organic fungicides and antibiotics introduced during the 1940’s are today’s major fungicides, the old reliable Bordeaux mixture is still used (1124).

 

Frank R. Cheshire (GB) and W. Watson Cheyne (GB) reported Bacillus alvei (Paenibacillus alvei) as the etiological agent of European foulbrood (315).

 

Friederich August Johannes Löffler (DE) discovered the cause of swine erysipelas, Erysipelothrix rhusiopathiae (1014; 1015).

 

Edmond Isidore Étienne Nocard (FR) recognized a weakly acid-fast bacillus that causes avian tuberculosis (1198).

 

Daniel Elmer Salmon (US) and Theobald Smith (US) isolated and described a motile, gram-negative, easily cultivable bacillus from several cases of hog cholera. They applied Koch’s postulates to prove that it was the causative agent of hog cholera (1428). Note: Smith actually did the work.

Emil Alexander de Schweinitz (US) and Marion Dorset (US) found that a virus causes hog cholera, and that the bacillus is present as a secondary invader (411). Note: this was the first pestivirus

In honor of Salmon, the bacterium is today called Salmonella cholera suis (556; 1562).

Joseph Léon Marcel Ligniéres (FR) suggested that the entire group of bacteria to which the swine pest bacillus belongs, should be named Salmonella in honor of Daniel Elmer Salmon, an American pathologist (US) (989).

 

Arnold Paltauf (AT) reported a fatal fungal infection in a patient with involvement of the central nervous system; including dissemination to the brain. He thought the etiological agent was the fungus Mucor because of its appearance in the tissues (1251). These mucormycoses (phycomycoses) are caused by species from Mucor, Absidia, and Rhizopus. Compromised patients such as those with diabetes mellitus are at greatest risk.

 

Paul Ehrlich (DE) put forward a general theory of immunity, the side-chain or receptor theory (507). Robert Joseph Lefkowitz (US) says this is “perhaps the earliest progenitor of the modern concept of receptors (975).”

 

Ludwig Brieger (DE) found excess phenol, indigo, paraoxyphenylpropionic acid, paraoxyphenlacetic acid, and ethereal sulfates in the urine of many of his patients suffering from various disorders. He believed these represented by-products, in the colon, of microbial putrefactive action on proteins. Brieger named them ptomaines. He was also convinced that their absorption by the digestive tract was harmful (237).

Hermann Senator (DE) had originated this idea of self-intoxication (1474).

 

Hermann Sahli (CH) developed a mixture of borax and methylene blue to stain bacteria of central nervous system infections (1426).

 

Carl Garré (CH) inoculated himself by rubbing an axenic culture of Staphylococcus upon the uninjured skin of his forearm, with the result that a series of carbuncles was produced, seventeen scars remaining to testify to the success of the experiment (645).

 

Theodor Escherich (DE), a pediatrician and bacteriologist, isolated Bacterium coli commune from the excrement of a breast-fed infant. This organism was later to bear his name as Escherichia coli (551; 552).

 

Louis Pasteur (FR) described a way to protect (by vaccination) a dog from rabies even after it had received the virus from a bite of a rabid dog (1267).

On July 6, 1885 Louis Pasteur (FR) and his colleagues treated Joseph Meister, aged 9, who was suffering from bites on the hand, legs, and thighs from a dog certainly rabid. Sixty hours after the bites had been inflicted, Meister, the first human being treated by Pasteur’s method, was injected with attenuated rabbit marrow, fourteen days old. In a further twelve inoculations he received virus stronger and stronger until on 16 July he received an inoculation of virulent marrow only one day after it had left the body of a rabbit dead from rabies.

The virulence of the material used in the whole of Meister’s thirteen inoculations was controlled on rabbits, and it was shown that the boy in his last two inoculations had withstood a living virus, which in rabbits was shown to be of maximal virulence with a seven-day incubation period. The boy recovered completely (261).

 

William Osler (CA-GB) wrote the first comprehensive description of subacute bacterial endocarditis (1224).

 

Franklin Paine Mall (US) working with Karl Friedrich Wilhelm Ludwig (DE), in 1885, showed that the veins as well as the arteries of the portal system are under the control of nerves (1057; 1058).

 

Karl Friedrich Wilhelm Ludwig (DE) hired Ludwig Castagna (AT) from Vienna to make a pulse controller. This instrument was straped to the patient's wrist allowing their pulse rate to be tracked during surgery (1350).

 

James Leonard Corning (US) thought he had performed the first spinal block for anesthesia. He injected cocaine between the spinous processes of the lower dorsal vertebrae, first in a young dog and then in a generally healthy man (342). Later it was determined that Corning's injection was extradural, and that Bier deserves the laurels for introducing spinal anesthesia.

August Karl Gustav Bier (DE) and J. Friedrich A. von Esmarch (DE) reported the injection of cocaine by lumbar puncture into a 34-year-old patient for excision of a tuberculous capsule at the ankle joint. Bier and his assistant, a Dr. Hilderbrandt, also injected one another to personally experience and record the signs and symptoms (174). This represents the first successful intradural spinal block to induce anesthesia.

Heinrich Irenaeus Quincke (DE) and August Karl Gustav Bier (DE) popularized the technique mentioned above in Europe. Rudolph Matas (US) wrote extensively about his experience in the US.

Oskar Kreis (CH) helped pioneer the use of spinal anesthesia when he reported the administration of cocaine in the subarachnoid space of six pregnant women with complete cervical dilation (937). Cocaine had previously been shown to be effective for spinal anesthesia by August Bier in 1898. See, above

Richard von Steinbüchel (AT) pioneered in the use of opioids for labor analgesia. He described the technique called the "twilight sleep", which consisted of using systemic morphine and scopolamine (1711). Studies in subsequent years from two German doctors, Carl Gauss (DE) and Kronig Bernhardt (DE), popularized this technique. It does not promote a complete analgesia, but the scopolamine enhances the morphine and induces amnesia.

 

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) was the first to successfully suture a perforated gastric ulcer (1700).

 

Maximilian (Max) Ruppert Franz von Frey (AT-DE) and Max von Gruber (AT) described the artificial extrapulmonary oxygenation of blood. They used a blood pump in which gas exchange occurred as blood flowed onto a thin film over the inner surface of a slanted rotating cylinder (1682). Note: This is essentially an early prototype of a heart-lung machine.

 

Thomas Annandale (GB) performed the first deliberate and planned operation for the relief of internal derangement of the knee-joint caused by a displaced cartilage (32).

 

Louis Xavier Édouard Léopold Ollier (FR) used an especially designed elevator to perform subperiosteal bone resections and subcapsulo-subperiosteal joint excisions in humans (1217).

 

Joseph P. O’Dwyer (US), in 1885, introduced endotracheal intubation for treatment of obstructed larynx in patients with diphtheria. Not only did O’Dwyer describe the method for the procedure, but he developed instruments to perform it. Within a short time, intubation largely replaced tracheotomy in treatment of diphtheria with airway blockage (1210).

Franz Kuhn (DE) introduced orotracheal intubation (944).

Samuel James Meltzer (DE-US) and John Auer (US) perfected a method of intra-tracheal intubation to give “continuous respiration without respiratory movement” (535; 536; 1099). The clinical introduction of Kuhn’s, and Meltzer and Auer's methods mark the beginning of modern endotracheal anesthesia.

 

Ludwig Edinger (DE) identified the accessory nucleus of the 3rd oculomotor nerve (Edinger-Westphal nucleus) in the fetus (493; 494; 500).

Karl Friedrich Otto Westphal (DE) did the same in the adult brain (1772). This nucleus supplies pre-ganglionic parasympathetics to the eye, which constrict the pupil and accommodate the lens.

 

Augusta Marie Dejerine-Klumpke (US-FR) described a syndrome (Dejerine-Klumpke’s paralysis) displaying a lesion of the lower arm plexus associated with pain, paralysis, and atrophy of the small muscles of the hand and forearm; an area supplied by the ulnar nerve and the inner head of the median nerve. It is caused by injuries (including birth injuries, on breech delivery) of the lower primary trunk and affects particularly the nerves derived from the eight cervical and first thoracic roots. Paralysis of the cervical sympathetic nerves with Horner’s oculopupillary syndrome may be associated (419). Note: Augusta Déjerine-Klumpke was the first female neuroanatomist and the first female intern to work in a hospital in Paris (356).

 

Hermann Ebbinghaus (DE) was the first to experimentally measure acquisition, recall, and recognition, i.e., memory (490).

 

Richard Llewellyn Jones Llewellyn (GB) in writing of biorhythms said, "The tendency to rhythm is deep ingrained in protoplasm--write as plain in the systole and diastole of the heart, the inspiratory and expiratory phases of respiration as in the recurrence of the menstrual cycle. Do not our body cells, too, like the "laughing soil," respond to the call of the seasons, the biologic action of light, heat, and electrical stakes or disturbances?" (1003).

 

William Osler (CA) described an epidemic of smallpox in Montreal, Canada: “The disease smoulders here and there and when conditions are favorable becomes epidemic. This was well illustrated by the Montreal outbreak of 1885. For several years there had been no small-pox in the city, and a large unprotected population grew up among the French-Canadians, many of whom were opposed to vaccination. On February 28 a Pullman-car conductor, who had traveled from Chicago, was admitted into the Hôtel-Dieu, the civic small-pox hospital being closed at the time. Isolation was not carried out, and on the 1st of April a servant in the hospital died of small-pox. Following her disease, the authorities of the hospital dismissed all patients presenting no symptoms of contagion who could go home. The disease spread like fire in dry grass and, in nine months 3,164 persons died in the city of small-pox.” (1225)

 

Liberty Hyde Bailey, Jr. (US) established at Michigan State (Agricultural) College the department of horticulture and landscape gardening, the first of its kind in the United States.

 

1886

"… curious to a vice, investigators to the point of cruelty, with uninhibited fingers for the unfathomable, with teeth and stomachs for the most indigestible, ready for every feat that requires a sense of acuteness and acute senses, ready for every venture, thanks to an excess of "free will," with fore- and back-souls into whose ultimate intentions nobody can look so easily, with fore- and backgrounds which no foot is likely to explore to the end; concealed under cloaks of light, conquerors even if we look like heirs and prodigals, arrangers and collectors from morning till late, misers of our riches and our crammed drawers, economical in learning and forgetting, inventive in schemas, occasionally proud of tables of categories, occasionally pedants, occasionally night owls of work even in broad daylight; yes, when it is necessary even scarecrows - and today it is necessary; namely, insofar as we are born, sworn, jealous friends of solitude, of our own most profound, most midnightly, most middaily solitude: that is the type of man we are, we free spirits!" Friedrich Wilhelm Nietzsche (DE) characterizing the "new" philosophers (1193; 1194)

 

Francis Galton (GB) devised a new useful statistical tool, the correlation table. It is an excellent tool in applying statistical methods to many biological problems (638).

 

Ernst Karl Abbé (DE), working at Zeiss Optical Works, made a series of lenses that enabled microscopists to resolve structures at the theoretical limits of the light microscope. This included the apochromatic objective lens, which he invented. Apochromatic lenses eliminate both primary and secondary color distortions. He improved the resolution of his apochromatic oil-immersion objective microscope lenses by using oils, which match the refractive index of the lens (390).

 

Ernst August Schulze (CH) and Ernst Steiger (DE) isolated and named arginine in a precipitate resulting from mixing phosphotungstic acid with extract of germinating lupine seeds (Lupinus luteus) (1457; 1458).

Sven G. Hedin (SE) isolated arginine from horn (760; 761).

 

Friedrich Koch (DE) discovered xylose when he treated wood gum by acid hydrolysis (913).

 

Karl Peters (DE) was the first to describe the diene structure of linoleic acid (1284).

 

Paul Ehrlich (DE) introduced the acid hematoxylin stain, stabilizing the stain and the mordant (alum) with acid (508).

 

The first notice was made of a tobacco-soapsuds mixture advocated for aphid control. Lime-sulfur-salt spray was first noted as useful against scale insects. Hydrocyanic acid gas (HCN), one of most deadly gases known, was discovered as a fumigant for insect control purposes. Rosin fish-oil soap was first used as an insecticide for scale control in California (1478).

 

Friedrich Hermann Hellriegel (DE) and Hermann Wilfarth (DE) demonstrated the bacterial nature of the root nodules of leguminous plants and showed that without these nodules the plants were unable to fix nitrogen. A preliminary report came out in 1886 with the full article following in 1888 (765-768).

 

Wilhelm His (CH) proposed, "that every nerve-fiber arises as an offshoot from one single cell. This cell is its embryonic (genetisches), nutritive, and functional center, and other connexions of the fiber are either only indirect, or have originated secondarily." (798) He went on to describe the outgrowth of the axon from the neuroblast in various vertebrates. This was essential to the development of the neuron theory, which states that the neuron, or nerve cell, is the basic unit of the nervous system.

Heinrich Wilhelm Gottfried Waldeyer (DE) wrote a highly influential review in which he stated that nerve cells terminate freely with end arborizations and that the neuron is the anatomical and physiological unit of the nervous system. This is the coining of the term neuron (1723). This is one of the germinal ideas necessary to the neuron theory.

 

Ludwig Brieger (DE) discovered that some microbes produce and secrete poisonous substances called toxins (238).

 

Silas Weir Mitchell (US) and Edward Tyson Reichert (US) established that snake venom is protein in nature, and demonstrated the presence of toxic albumins (1134).

 

Leonard Charles Wooldridge (GB) proposed for the first time that the prothrombin activator is a protein/phospholipid complex derived from damaged tissue (1822).

 

Charles Alexander MacMunn (GB) observed myohematins and histohematins in representatives of almost all orders of the animal world. He proposed that these pigments are concerned with internal respiration of the tissues and organs (1046; 1047). Note: these pigments were later to be called cytochromes.

Otto Heinrich Warburg (DE) worked with charcoals of blood, and later of hemin and impure aniline dyes contaminated with iron salts in his attempt to understand intracellular respiration. He concluded, "… molecular oxygen reacts with divalent iron, whereby there results a higher oxidation state of iron. The higher oxidation state reacts with the organic substance with the regeneration of divalent iron …. Molecular oxygen never reacts directly with the organic substance." He defined the respiratory enzyme (atmungsferment) as "… the sum of all catalytically-active iron compounds present in the cell." Then went on to say, "The catalytically active substance in hemin-charcoal is therefore iron, but not iron in any form whatever, but iron bound to nitrogen." (1727-1729)

David Keilin (PL-GB) made spectral analysis of pigments he found in the muscles of horse bot flies (Gasterophilus intestinalis) and in yeast. He realized that they exhibited a four-banded absorption spectrum just like the myohematins and histohematins observed by Charles Alexander MacMunn (GB). Keilin concluded that the four-banded spectrum was associated with three separate hemochromogens which he named cytochromes a, b, and c and assigned them a significant role as oxidation catalysts in intracellular respiration (893; 894). The 1925 article by Keilin marked the beginning of studies of what Warburg later called the respiratory chain (atmungskette), many called the electron transfer chain, and David Green, the electron transport chain.

Otto Heinrich Warburg (DE) demonstrated that the oxygen uptake associated with respiration in yeast is inhibited by carbon monoxide and is a reversible reaction. He concluded, "… the Atmungsferment (equivalent to Keilin’s cytochrome) is an iron-pyrrole compound in which the iron is bound to nitrogen, as in hemoglobin." Warburg did not believe cytochrome and his atmungsferment to be equivalent (1731).

Otto Heinrich Warburg (DE) and Erwin Paul Negelein (DE) in a brilliant set of experiments used indirect determination of light absorption spectra to demonstrate that atmungsferment (Keilin’s cytochrome) is a porphyrin with a protein component (1732; 1733). This enzyme is now called cytochrome oxidase.

David Keilin (PL-GB) realizing that the cytochromes are not auto-oxidizable considered indophenol oxidase to be an enzyme capable of catalyzing the oxidation of cytochrome by oxygen. Later, at the suggestion of Malcolm Dixon (GB) (443), he used the term cytochrome oxidase to denote this enzyme, which he viewed as being equivalent to Warburg’s atmungsferment (895).

David Keilin (GB) and Edward Francis Hartree (GB) demonstrated the existence of the auto-oxidizable cytochrome a3, which Keilin had previously thought was indophenol oxidase. They noted that it combines with cyanide and carbon monoxide. Its spectroscopic properties agree with those of Warburg’s atmungsferment (896).

Eijiro Yakushiji (JP) and Kazuo Okunuki (JP) discovered cytochrome c1 (1838). In 1941, they placed c1 in the cytochrome chain in the order b-c1-c-a-a3.

Bernard Leonard Horecker (US) and Arthur J. Kornberg (US) found that cyanide reacts with cytochrome c (822).

Frederick L. Crane (US), Youssef Hatefi (IR-US), Robert L. Lester (US), and Christine Widmer (CH) discovered ubiquinone (coenzyme Q) as a new hydrogen carrier between the primary dehydrogenases and the electron transfer chain in beef heart mitochondria (354). Note: Without this discovery, progress on the electron transport chain would have been severely hampered.

Richard Alan Morton (GB), G.M. Wilson (GB), J.S. Lowe (GB), and W.M.F. Leat (GB) defined a compound obtained from vitamin A deficient rat liver to be the same as CoQ10. In their 1957 paper they named it ubiquinone; meaning the ubiquitous quinone (1161-1163).

Donald E. Wolf (US), Carl H. Hoffman (US), Nelson R. Trenner (US), Byron H. Arison (US), Clifford H. Shunk, (US) Bruce O. Linn (US), James F. McPherson (US), and Karl August Folkers (US) determined the precise chemical structure of CoQ10 to be 2,3 dimethoxy-5 methyl-6 decaprenyl benzoquinone, synthesized it, and were the first to produce it by fermentation (1817).

Frederick L. Crane (US), Clifford H. Shunk (US), Franklin M. Robinson (US), and Karl August Folkers (US) showed ubiquinone to be an isoprenoid compound closely related or identical to coenzyme Q (CoQ) (355).

Frederick L. Crane (US) reported the presence of two coenzyme Q type molecules and Norman I. Bishop (US) reported a quinone molecule, all of which are reactive in the light driven electron transport process of isolated chloroplasts. One of the coenzyme Q molecules and the quinone molecule would prove to be plastoquinone (179; 353).

Helmut Beinert (US) and Graham Palmer (US) used paramagnetic resonance (EPR) spectrometry to establish that copper, as well as, iron is involved in the oxidation of cytochrome c (144).

Humberto Fernández-Morán (VE-SE), Takuzo Oda (JP), Paul V. Blair (US), and David Ezra Green (US) chracterized a repeating particle associated with the cristae and the inner membrane of the external envelope in beef heart mitochondria by correlated electron microscopic and biochemical studies. Many thousands (c. 104 to 105) of these particles, disposed in regular arrays, are present in a single mitochondrion. The repeating particle, called the elementary particle (EP), consists of three parts: (1) a spherical or polyhedral head piece (80 to 100 A in diameter); (2) a cylindrical stalk (about 50 A long and 30 to 40 A wide); and (3) a base piece (40 x 110 A). The base pieces of the elementary particles form an integral part of the outer dense layers of the cristae. The elementary particles can be seen in electron micrographs of mitochondria in situ, of isolated mitochondria, and of submitochondrial particles with a complete electron transfer chain (571).

Bob F. van Gelder (NL) showed that cytochrome c oxidase takes up four electrons per molecule, one each into the hemes of cytochrome a and a3 and two into the copper atoms (1644).

 

St. Szez Zaleski (DE) and Gustav von Bunge (DE) discovered that the fetal liver in animals is used as a storage organ for iron (1671; 1850).

 

Carl Benda (DE) introduced the use of the iron-hematoxylin dye to histology (151).

 

Bartolomeo Camillo Emilio Golgi (IT), August H. Forel (CH) and Fridtjof Nansen (NO) concluded but could not prove that “transmission of a stimulus without direct continuity is possible” in the sensory organs. They favored contiguity, not continuity of nerve cells (605; 681; 1173).

Bartolomeo Camillo Emilio Golgi (IT) gave a precise description of the nerve cell. He distinguished between axons and dendrites and noted that nerve cells can have extensive protoplasmic branches. He described the "fine anatomy" of the convolutions located at front center and top of the occipital cortex (the structures to which contemporary research had attributed, respectively, motor and sensory function), the cerebellum, the foot d ' hippocampus, corpus callosum, and olfactory lobes. In addition, after a first chapter of a general nature on the nerve cell, there follows a chapter on neuroglia and one on methods of the "black reaction" (681; 685).

Santiago Ramón y Cajal (ES) improved Golgi’s silver-chromate stain for nerve tissue. Using his reduced silver nitrate technique he worked out the connections of the cells in the grey matter of the brain and spinal cord and the complexity of the system. His introduction of a gold chloride-mercury bichloride technique to demonstrate astrocytes was a monumental contribution as was his later work on degeneration and regeneration of the nervous system. Cajal also worked out the structure of the retina of the eye, describing in detail the major cell types in all three retinal layers and proclaiming that the nervous system consists entirely of neurons and their processes. He concluded: "(1) Nervous cells are independent units, they never anastomose either through their dendritic branches or through nerve fibers emanating from their axons. (2) Every axis cylinder terminates freely in varicose and flexuous arborizations…(3) These arborizations are applied either to the body or to the dendritic branches of other nervous cells establishing connexion by contiguity…, which is, just as efficacious in transmitting impulses as if there were real connexion of substance between the neurons. (4) The cell body of the dendritic branches is as much concerned with conduction of impulses as with neuronal nutrition. The dendrites carry impulses to the cell body, while axonal transmission is away from the cell body." He emphasized that the direction of conduction is from the receptors in the retina, through the horizontal, bipolar, and amacrine cells of the inner nuclear layer, ultimately to the ganglion cells, whose axons constitute the optic nerve (1330-1335; 1337).

Max Bielschowsky (DE) began his fundamental studies on the silver impregnation of nerve fibers. He truly replaced Santiago Ramon y Cajal’s method on which his was based (173). Bielschowsky is known as a superior neuropathologist with his contributions in the study of tuberous sclerosis, amaurotic family idiocy (late infantile type), Herpes zoster, paralysis agitans, Huntington’s chorea, and myotonia congenita.

 

Philippe Edouard Léon van Tieghem (FR) and Henri Douliot (FR) introduced the concept of the stele to the anatomy of the Pteridophyta (ferns, horsetails, and club-mosses) (1646; 1647).

 

Nathan Zuntz (DE) and August Julius Geppert (DE) created the Zuntz-Geppert respiratory apparatus for indirect calorimetry (1858).

Wilbur Olin Atwater (US) and Edward Bennett Rosa (US) constructed the Atwater-Rosa calorimeter with which they, along with Francis Gano Benedict (US) and Thorne Martin Carpenter (US), proved the law of conservation of energy in human beings and made it possible to calculate the caloric values of different foods (53; 54; 152). Note: Their measurements were so precise that their energy equivalents for protein, fat and carbohydrate are still used today. Atwater was first to adopt the word 'calorie' as an energy unit for food. (A calorie of food energy is actually equivalent to 1000 calories of thermal energy.)

 

William Holbrook Gaskell (GB), in studies of the autonomic nervous system, concluded that the “involuntary system” is composed of two antagonistic subsystems (653).

 

Franz Soxhlet (DE) reasoned that summer diarrhea in children might be caused by bacteria growing in the milk they consumed. When he sterilized the milk, a dramatic decrease in the frequency of summer diarrhea occurred (1525).

 

Adolf Eduard Mayer (DE-NL) demonstrated an infectious agent (virus) to be the most likely cause of tobacco mosaic disease in plants (1084; 1085).

 

James Brown Buist (GB) was probably the first to perform a laboratory-based diagnosis of a viral disease when he stained the lymph obtained from the skin lesions of patients with smallpox and saw elementary bodies, which he took to be the cause of the disease (260; 690). Note: this was six years before viruses were discovered.

 

Adolf Weil (DE) was the first to describe infectious jaundice or what was later called Weil’s disease (1755). The etiological agent is a spirochete. See Inada, 1916.

 

Daniel Elmer Salmon (US) and Theobald Smith (US) showed that dead swine plague bacilli could be used as a vaccine (1429; 1430). Although Smith made the discovery on his own, his supervisor, Daniel Elmer Salmon, usurped credit.

 

John Elmer Weeks (US) was the first to cultivate Haemophilus aegypticus (1750; 1751). It is now recognized as the cause of a highly contagious form of conjunctivitis known as pinkeye. This organism is sometimes referred to as the Koch-Weeks bacillus.

Heinrich Hermann Robert Koch (DE) observed a small bacillus, later identified as Haemophilus aegyptius, while examining a series of eye inflammations in Egypt (914).

Margaret Pittman (US) and Dorland J. Davis (US) were the first to identify this organism as Haemophilus aegypticus (1305).

 

Josef von Fodor (HU) and Vladimir Wyssokowitch (DE) emphasized that the anti-putrefactive quality of circulating blood is part of the body’s defense mechanism. They demonstrated that bacteria introduced into the blood-stream rapidly disappear and apparently do not leave the body by any of the channels of secretion or excretion (1679-1681; 1835).

Josef von Fodor (HU) found that blood mixed in vitro with anthrax bacilli at 38°C caused a rapid decrease in the number of cells capable of growing on gelatin plates (1681).

George Henry Falkiner Nuttall (US-GB) confirmed observations by von Fodor and Wyssokowitch then discovered that the bacterial killing power of the blood is lost on aging and destroyed by heating to 52°C for 10 to 30 minutes (1206; 1207). This represents the discovery of the complement system.

 

Jean Alfred Fournier (FR) described congenital syphilis and emphasized that syphilis could cause degenerative diseases (608).

 

Frantisek Vejdovsky (CZ), in 1886, separated the gordiaceans from the nematodes and hence his name, Nematomorpha for the gordiaceans. They are a class within the phylum Aschelminthes (Nemathelminthes) (1652).

 

Daniel Alcides Carrión (PE) inoculated himself (fatally) and proved that Oroya fever and verruga peruana are stages of a single disease now commonly known as Carrión’s disease (292).

Ernest Ordiozola (PE) introduced the term Carrión’s disease (1221).

Alberto Leopoldo Barton (PE) discovered that Carrión’s disease is caused by the rickettsium Bartonella bacilliformis (106).

Charles H. T. Townsend (US) found a species of Phlebotomus (sandfly) whose bite caused the outbreak of the disease. He named the sandfly Phlebotomus verrucarum (Lutzomyia verrucarum) (1613).

Charles H.T. Townsend (US) provided evidence that lizards act as a reservoir for Bartonella bacilliformis (1614).

Richard Pearson Strong (US), Ernest Edward Tyzzer (US), Charles Thomas Brues (US), Andrew Watson Sellards (US), and Julio C. Gastiaburu (PA) named the rickettsial microorganism in honor of Barton (1560).

Hideyo Noguchi (JP-US) also demonstrated that Oroya fever and verruga peruana are both caused by the parasite Bartonella bacilliformis and are two different stages of the same infection called Carrion's disease, or bartonellosis (1201).

Marshall Hertig (US) established the role of the sandfly (782). Note: Cosme Bueno (ES-PE), in 1764, wrote that Andean peoples of Peru attributed the diseases now known as leishmaniasis and bartonellosis to the bite of the uta or sand fly (259).

 

Felix Fränkel (DE) reported the first case of a tumor of the adrenal medulla (616), a type of tumor that has become known as pheochromocytoma. The patient in this case was an 18-year-old girl who had died suddenly of collapse. Her clinical history and autopsy findings pointed to a severe hypertensive crisis. This, combined with the discovery of an adrenal medullary tumor, presented what appears to be the first evidence, seer-, only in retrospect, of the relationship between the adrenal medulla and blood pressure.

 

Pierre Marie (FR) fully described and named the constellation of symptoms termed acromegaly: excessive growth of the viscera and the bones of the face, hands, and feet, and the thickening of soft tissues like the tongue, lips, and nose, which made the features of acromegalic patients gradually become strikingly coarse and elongated. Other signs and symptoms that Marie noted as characteristic of the chronic condition included severe headaches, intense thirst and appetite, cessation of menstruation, changes in the thyroid, and damaged vision. Then, in 1890 and 1891, Marie reported that enlarged pituitaries were always found in postmortern examinations of persons with acromegaly, and he hypothesized that the abnormal growth of the pituitary caused a glandular deficiency and hence toxemia. He was the first to correlate the clinical and pathological findings (1064; 1068).

 

William Rutherford (GB) suggested one of the “frequency theories” of hearing. He proposed that every sound stimulates every hair cell, and the larger the number of hair cells involved, the greater the sensitivity and accuracy of the transmission. He stressed that it was the brain’s job to interpret the vibratory patterns of stimulation and that this could be affected by practice (1408).

 

Jean-Martin Charcot (FR), Pierre Marie (FR), Howard Henry Tooth (GB), and Johann Hoffmann (DE) described what became known as Charcot-Marie-Tooth-Hoffmann syndrome. It is characterized by slowly progressive wasting and weakness of distal muscle of the arms and feet, caused by degeneration of the peripheral nerves, nerve roots, and even the spinal cord, with loss of reflexes, loss of cutaneous sensations and development of foot drop. Optic atrophy is sometimes present (309; 806; 1612). The disease had been described previously, but its neuropathic basis was not appreciated.

Benjamin B. Roa (US), Carlos A. Garcia (US), Ueli Suter (CH), Deanna A. Kulpa (US), Carol A. Wise (US), Jane Mueller (US), Andrew A. Welcher (US), G. Jackson Snipes (US), Eric M. Shooter (GB-US), Pragna I. Patel (IN-US), and James R. Lupski (US) determined that Charcot-Marie-Tooth disease type 1A (CMT1A), the most common form, is caused by a defect in the gene for myelin protein PMP22 (1367).

JoAnn Bergoffen (US), James A. Trofatter (US), Margaret A. Pericak-Vance (US), Jonathan L. Haines (US), Phillip F. Chance (US), and Kenneth H. Fischbeck (US) determined that the X-linked form of Charcot-Marie-Tooth disease (CMTX) is caused by mutations in the gap junction protein, connexin 32 (154).

Phileppe Latour (FR), Fransoise Blanquet (FR), Eva Nelis (BE), Christine Bonnebouche (FR), Frangoise Chapon (FR), Philippe Diraison (FR), Elizabeth Ollagnon (FR), Andre Dautigny (FR), Danielle Pham-Dinh (FR), Guy Chazot (FR), Michel Boucherat (FR), Christine Van Broeckhoven (FR), and Antoon Vandenberghe (FR) determined that Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by a defect in the gene for myelin protein Po (967).

 

Hilário de Gouvêa (BR) provided the first documented evidence that a susceptibility to cancer can be inherited from a parent to a child. He reported that two of seven children born to a father who was successfully treated for childhood retinoblastoma, a malignant tumor of the eye, also developed the disease (407; 408).

 

Victor Alexander Haden Horsley (GB), using dogs, performed the first successful experimental hypophysectomy. Two dogs survived five and six months respectively after this operation (826).

Victor Alexander Haden Horsley (GB) successfully operated on several cases of pituitary tumors in man (827; 828). The first of these operations was performed in 1889.

Hermann Schloffer (AT) reported the first successful resection of a pituitary tumor via a transphenoidal approach. Local anesthesia was provided by cocaine (1449).

Anton von Eiselsberg (AT) and Lothar von Frankl-Hochwart (AT) successfully drained a cystic tumor of the pituitary gland by way of a superior transnasal approach. The patient died 2 days later of purulent meningitis (1677; 1678).

Julius von Hochenegg (AT), in 1908, used the same superior transnasal approach to successfully treat a case of acromegaly (1692).

Jules Hardy (CA) popularized the transphenoidal approach and made contributions that advanced microscope pituitary surgery into the modern era.

 

 

William MacCormac (GB) introduced an operation for the treatment of intraperitoneal rupture of the bladder (1036).

 

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) was the first to make a plastic reconstruction of the esophagus after the resection of its cervical portion for carcinoma (1701).

 

Hermann Kümmell (DE), in 1886, attempted the first choledochotomy (surgical incision into the common bile duct) (946).

 

Gustav Adolf Neuber (DE) was one of the first to reject the use of antiseptic substances, particularly in wounds and dressings, and advocate a strict regime of anti-contamination instead. He called this strategy ‘asepsis’ to distance himself from Lister and his use of antiseptic chemicals. His system can be interpreted as a variety of the clean surgery concepts that existed in Britain along with Listerism. In retrospect Neuber himself pointed to that parallel.

Ernst Gustav Benjamin von Bergmann (DE) and Kurt Schimmelbusch (DE) helped to make the term ‘asepsis’ a widespread and powerful means of branding the new approach by encouraging the steam sterilization of surgical instruments and dressings. Because of this they are often counted among the inventors of aseptic surgery (1126; 1181; 1182; 1444-1446; 1668; 1669).

 

The world's first Ph.D. in psychology was awarded to Joseph Jastrow at Johns Hopkins University.

 

1887

"It was from these dissections, from an elaborate course of reading, and from numerous visits to the pork and slaughter houses of Cincinnati, that I derived the knowledge upon which I founded my work on Pathological Anatomy." Samuel David Gross (707)

 

Albert Abraham Michelson (PL-US) and Edward Williams Morley (US) determined that the speed of light is constant regardless of whether it is emitted from a moving or a stationary object (1117). Michelson, in 1907, was the first American to receive a Nobel Prize in the sciences (physics).

 

 

Jacobus Hendricus van’t Hoff (NL) realized that the osmotic pressure generated by molecules (or later, ions) in solution was exactly the same as they would exert at the same concentration in a gas, thus linking solution theory to the long-established laws describing the behavior of gases. Subsequently, he formulated the osmotic pressure equation, and the theory of solutions that connected osmotic pressure, freezing-point depression, and the lowering of vapor pressure as thermodynamic properties (1648).

 

Friedrich W. Semmler (DE) prepared divinyl ether (1473).

Chauncey Depew Leake (US) and Mei-Yü Chen (US) first observed the anesthetic properties of divinyl ether (973).

Chauncey Depew Leake (US), Peter K. Knoefel (US), and Arthur E. Guedel (US) introduced divinyl oxide as an anesthetic (974).

 

Julius Richard Petri (DE), one of Heinrich Hermann Robert Koch’s assistants, invented a dish now routinely used in microbiology, the petri dish (1285).

André Victor Cornil (FR), Victor Babès (FR), William Nicati (FR), and Maximillien Rietsch (FR) described very similar dishes a couple of years earlier (341; 1188).

 

Ernst Salkowski (DE) discovered phytosterol (phytosterin), the nucleus of vegetable fats (1427). Phytosterols act as a structural component in the cell membrane of plants, analogous to the cholesterol in the cell of animals.

 

William Dobinson Halliburton (GB) gave the first credible experimental descriptions of actin's properties (731).

Harunori Ishikawa (JP), Richard Bischoff (US), and Howard Holtzer (US) detected actin filaments not just in muscle cells, but also in a wide variety of mammalian cell types (848).

Klaus Weber (PL-DE-US) and Ute Groeschel-Stewart (DE) specifically visualized myosin containing filaments in non-muscle cells (1748).

Elias Lazarides (US) identified tropomyosin in non-muscle cells (970).

Elias Lazarides (US) and Keith Burridge (GB-US) identified alpha-actin as a normal component of non-muscle cells (971).

Barry A. Palevitz (US), John F. Ash (US), and Peter K. Hepler (US) found actin present in Nitella (an alga) and suggested that myosin molecules attached to chloroplasts, which walk by forming crossbridging cycles generate active streaming in Nitella (1249; 1250).

Nina Strömgren Allen (US) discovered that endoplasmic filaments generate the motive force for rotational streaming in the green alga Nitella (21).

 

Sergei Nikolaevich Winogradsky (RU) discovered chemoautotrophic bacteria that oxidize hydrogen sulfide to sulfur and others which oxidize sulfur to sulfuric acid while using carbon dioxide as a carbon source. These studies of sulfur bacteria eventually led to the concept of the sulfur cycle (1811; 1813).

Sergei Nikolaevich Winogradsky (RU) discovered Beggiatoa minima, Clostridium pasteurianum, Cytophaga hutchinsonii, Nitrosococcus nitrosus, Nitrosocystis javaensis, N. coccoides, Nitrosomonas europaea, Nitrosospira briensis, N. antarctica, and Nitrobacter.

In his book Soil Microbiology, published in 1949, he wrote: "I started my work in 1885… impressed by the incomparable glitter of Pasteur’s discoveries, as a young student I entered this field of investigation and have remained faithful to it to the end… My first investigations dealt with filamentous bacteria found in sulfur and iron-containing springs; these were the first known autotrophs…" (1815)

 

Viktor Hensen (DE) introduced the term plankton to mean all particles and material which floats in a water column, regardless of whether it occurs in the upper or lower layers of the water column, or whether it is alive or dead. It is derived from the Greek planktos, to wander or drift. Hensen credits his colleague Professor Foerster with suggesting this term (772).

 

Emile Maupas (FR) and Richard Karl Wilhelm Theodor von Hertwig (DE) independently demonstrated exchange of micronuclei during conjugation by Paramecium (1079; 1691).

 

Jules Héricourt (FR) and Charles Robert Richet (FR) were the first to conceive the notion of producing an immune serum; that is, of injecting into an animal a substance to which it could then produce an antidote. (The injected material is an antigen; the counter material produced is an antibody). If the antigen is a bacterium or a bacterial toxin, then an antibody will exist that will prevent future infections. If serum containing this antibody is then injected into a human being, it may lend him immunity to a particular disease (775). Richet tried to produce such an immune serum for tuberculosis but failed (1359). Later, Emil Adolf Behring working along similar lines, succeeded with tetanus and diphtheria. Note: Richet was the first to injection serum into a human in 1890.

 

Maurice Kaufmann (FR) used European viper (Vipera berus) venom and guinea pigs while Henry Sewall (US) used rattlesnake venom and pigeons to independently discover that anti-venoms are produced in the blood of animals inoculated with small doses of venom, and that the degree of immunity can be built up by slowly increasing the dosage of venom in successive inoculations (888; 1480).

 

Enrique Paschen (DE) rediscovered these elementary bodies (1266). They were later named Paschen bodies in his honor. These elementary bodies or Paschen bodies are now recognized as collections of the virus.

 

Theodor Boveri (DE), while studying Ascaris megalocephala, was the first to recognize naturally occurring polyploidy (212).

 

Fridtjof Nansen (NO) was the first to point out that the posterior root nerve fibers divide on entering the spinal cord into ascending and descending branches (1173).

 

Wilhelm Roux (DE) demonstrated that shortly after fertilization of an amphibian egg a broad crescent develops in the lower hemisphere—opposite the point of sperm entry—loses some of its dark pigment and becomes the gray crescent. The gray crescent persists at most for a few cleavages. He found that the dorsal lip of the blastopore appears where the gray crescent had been, and he deduced that the plane of the first cleavage (median plane) bisects the blastopore dividing the embryo into a right and left half. The three axes of the future embryo are thus fixed before segregation of the egg begins (1390; 1392).

 

Luigi Salvatore Savastano (IT) determined the bacterial cause of galling on olives (Olea europaea ) to be Pseudomonas savastanoi (1436). This disease, called olive knot, was discovered in France.

 

Nil Feodorovich Filatov (RU) and Emil Pfeiffer (DE) independently gave early clinical descriptions of infectious mononucleosis (576; 1290).

Thomas Peck Sprunt (US) and Frank Alexander Evans (US) are responsible for coining the phrase infectious mononucleosis (1529). See, John R. Paul, 1932

 

Howard Atwood Kelly (US), in 1887, performed a hysterorrhaphy (suturing of a lacerated uterus) (898).

 

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) elaborated the concept of organic form and symmetry after studying the radiolaria brought back by the Challenger expedition; symmetry referring to the spatial relations and arrangements of parts in such a way as to form geometrical designs (724).

 

Harry Marshall Ward (GB) wrote the first English translation of Ferdinand Gustav Julius von Sach’s Lectures on the Physiology of Plants; The Oak; A Popular Introduction to Forest-Botany; Text-book of the Diseases of Trees, with Robert Hartig; and Grasses; A Handbook for the Use in the Field and Laboratory (747; 1423; 1734; 1735).

 

Henry Seebohm (GB) was the first ornithologist to recognize the importance of isolation in species formation (1471).

 

Saturnin Arloing (FR), Charles Cornevin (FR), and Onésine Thomas (FR) cultured Clostridium chauvoei and established its etiological relationship to blackleg, also known as quarter evil, and symptomatic anthrax (not to be confused with anthrax) and developed a method of prophylactic inoculation called the Lyon vaccine (41). This is an acute disease that affects cattle. The bacterium was named in honor of Auguste Chauveau (FR).

 

Paralytic polio was described as epidemic in Sweden (921).

 

William Thomas Councilman (US) described the characteristic apoptotic bodies seen in the livers of patients with yellow fever (347).

 

Anton Weichselbaum (AT) isolated the causative agent of septic meningitis, Neisseria meningitidis, and associated it with six cases of acute cerebrospinal meningitis (1752).

Johann Otto Leonhard Heubner (DE) was the first to isolate meningococci from the cerebrospinal fluid of living beings (790).

 

Guido Banti (IT) pointed out that typhoid fever is caused by a bacterium (82).

 

Johan Frederik Eykman (NL) and Maurits Greshoff (NL) independently described how the natives of India used snakeroot (Rauwolfia serpentina) to treat snakebites and the mentally ill. The Indian word for mental is chandrá meaning moon, e.g., moon disease or lunacy (559; 703).

 

Edward Hartley Angle (US) developed the Angle system of regulation and retention of the teeth, and treatment of fractures of the maxillae. This rapidly became the most popular orthodontic method in the world (29-31).

 

Jakob Stilling (DE), Siegmund Türk (DE-CH), and Alexander Duane (US) described a congenital syndrome of ocular and systemic abnormalities with fibrosis of the external rectus. This condition prevents outward movement of the eye (toward the ear), and in some cases may also limit inward eye movement (toward the nose). As the eye moves inward, the eyelids partially close and the eyeball pulls back (retracts) into its socket (Stilling-Türk-Duane syndrome) (469; 1552; 1629).

 

Paul Gerson Unna (DE) described seborrheic dermatitis and distinguished it from chronic eczema and psoriasis (1635).

 

Joseph Jules Déjérine (CH-FR) described Déjérine’s neuro-tabes (multiple peripheral neuritis with symptoms like those of locomotor ataxia) (417).

 

Oscar Minkowski; Oskar Minkowsky (RU-DE) associated acromegaly with a hyperfunctional pituitary gland (1130).

 

Julius Wagner-Jauregg (AT), to treat the mentally ill, induced fevers using at turns tuberculin, typhus vaccine, and tertian malaria. In 1917, nine patients with general paresis (neurosyphilis) were treated by injecting blood from patients experiencing active malaria; three recovered, three showed temporary relief, and three showed no improvement (1717-1719).

 

George Washington Crile (US) was the first to perform major operations with intraneural injections of cocaine. His first such operation was in 1887 (359; 361).

 

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) developed an operation for the treatment of disease of the accessory nasal sinuses (1704).

 

Adolf Gaston Eugen Fick (DE), in 1887, constructed and fitted what was to be considered the first successful model of a contact lens: an afocal sclaral contact shell made from heavy brown glass, which he tested first on rabbits, then on himself, and lastly on a small group of volunteers (575).

 

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) introduced the folded gauze pad for packing off the viscera in abdominal operations and used as sponge in general (1702).

 

Walter Hermann Heineke (DE) and Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) independently and almost simultaneously performed the first pyloroplasty. This was done to eliminate pyloric stenosis. A short longitudinal incision is made through all layers of the pylorus and closed transversely. Used after truncal vagotomy. F. Fronmüller described Heineke’s operation (630; 1703).

 

Henry L. Coit (US) began as early as 1887 to work to ensure a safe milk supply for infants, by educating the public, lawmakers, and the medical community. He coined the term "Certified Milk" and established the first Medical Milk Commission in New Jersey (334).

Abraham Jacobi (US) collaborated with the philanthropist Nathan Straus (US) to establish pasteurization plants and milk stations for poor infants in New York beginning in 1893. A 65% reduction in infant mortality was observed in just one year in the foundling hospital on Randall’s Island after Straus established a pasteurization plant there (333; 334).

In 1908, Chicago became the first city in the world to require pasteurization of milk (334).

 

Ludwig Lichtheim (DE) recognized a pathology of subacute spinal cord disease associated with pernicious anemia and different from tabes dorsalis (Lichtheim’s disease) (987; 988).

James Jackson Putnam (US) and Charles Loomis Dana (US) independently described a neurological disease with great variability of symptoms, characterized by degenerative changes in the white matter of the spinal cord associated with pernicious anemia. Onset was usually insidious with weakness, fatigue, and dyspnea on exertion. Other symptoms may include paralysis of the legs and arms, with tremor present when there is increase in muscle tone (static tremor), and in movement (kinetic or intentional); myalgia, edema of the feet and ankles, numbness and tingling in the distal portions of the extremities, glossitis, headache, malaise, and peculiar gait (Putnam-Dana syndrome) (395; 1324).

James Samuel Risien Russell (GB), Frederick Eustace Batten (GB), and James Collier (GB) gave the most complete account of this syndrome (1404). Note: malabsorption of vitamin B12, vitamin E and copper are etiological factors.

 

John Langdon Down (GB) coined the term idiot savant to apply to children who, while feeble-minded, exhibit special faculties, which are capable of being cultivated to a very great extent (453).

 

The Canadian Geological Survey found rich fossil beds containing Upper Cretaceous dinosaur fauna along the Red Deer River in Alberta (281).

 

The National Institutes of Health was established in the United States of America.

 

Annales de l’Institut Pasteur was founded.s

 

Annals of Botany was founded.

 

Zeitschrift fur Physikalische Chemie was founded.

 

1888

"Never advance anything which cannot be proved in a simple and decisive fashion. Worship the spirit of criticism. If reduced to itself, it is not an awakener of ideas or a stimulant to great things, but, without it, everything is fallible, it always has the last word."

"It is indeed a hard task, when you believe you have found an important scientific fact and are feverishly anxious to publish it, to constrain yourself for days, weeks, years sometimes, to fight with yourself, to try and ruin your own experiments and only to proclaim your discovery after having exhausted all contrary hypotheses."

"But when, after so many efforts, you have at last arrived at a certainty, your joy is one of the greatest which can be felt by a human soul, and the thought that you will have contributed to the honour of your country renders that joy still deeper."

"If science has no country, the scientist should have one, and ascribe to it the influence which his works may have in this world." Louis Pasteur (FR) (1639)page 443. Note: Remarks made at the dedication of the Pasteur Institute of Paris, 14 November, 1888 . The Pasteur Institute was erected in Paris and partially paid for with public donations from all over the world.

 

"The real enemy in most fevers is the noxious substance which invades the body, and there is nothing to prevent us from believing that fever is a weapon employed by Nature to combat assaults of this enemy. According to this view, the fever-producing agents light the fire, which consumes them. It is not incompatible with this conception of fever to suppose that the fire may prove injurious also to the patients and may require the controlling hand of the physician." William H. Welch (US) (1756)

 

Johann August Ludwig Friedrich Kehrmann (CH), Viktor Meyer; Victor Meyer (DE) and John Joseph Sudborough (GB) found that while atom groupings ordinarily can rotate freely about a single bond attaching them to the rest of the molecule, the bulk of nearby groups of atoms sometimes prevents this rotation. This they called steric hindrance (890; 1113; 1114).

 

Eugen Baumann (DE) and Alfred Kast (DE) discovered the hypnotic nature of sulphonal (883).

 

Erwin Frink Smith (US) postulated some sort of a virus as the cause of peach yellows (1510).

 

Auguste Fernbach (FR) tested for the presence of bacteria in 555 samples taken from the interiors of various plant tissues. Bacteria were found in only 6.3% of the samples. Fernbach considered that these growths were the result of accidental contaminations (572).

 

Martinus Willum Beijerinck (NL), in 1888, using Koch's postulates, isolated Bacillus radicicola, a root-nodule bacterium later referred to as genus Rhizobium. He was able to infect a legume to produce nitrogen- fixing root-nodules. Beijerinck's research was first to prove the known symbiotic relationship (partnership) between legume plants and some soil bacteria (135).

 

Sergei Nikolaevich Winogradsky (RU) described photosynthetic purple sulfur bacteria, including Chromatium (1812).

 

Nikolai Fedorovich Gamaléia (RU) discovered Vibrio metchnikovii in the intestinal tract and blood of fowls suffering from an epidemic disease resembling fowl cholera (643).

 

André Chantemesse (FR) and Georges Fernand Isidore Widal (FR) made the first observations of immunity conferred on experimental animals following injection with heat killed typhoid bacilli (307; 308).

Richard Friedrich Johannes Pfeiffer (DE), Wilhelm Kolle (DE), Almoth Edward Wright (GB), and David Semple (GB) prepared and recommended a heat inactivated vaccine for typhoid fever, which could be prepared from killed typhoid bacilli (1296; 1825-1827).

Almroth Edward Wright (GB) and David Semple (GB) introduced a vaccine prepared from killed typhoid bacilli as a preventive of typhoid. Wright first inoculated himself to prove the safety of the vaccine before inoculating others. Preliminary trials in the Indian army produced excellent results, and typhoid vaccination was adopted for the use by British troops serving in the South African War (1827).

 

Pierre Paul Émile Roux (FR) and Alexandre Émile Jean Yersin (CH) proved that Corynebacterium diphtheriae produces a soluble toxin responsible for the characteristic symptoms and lesions of diphtheria and thus demonstrated its etiological relationship to the disease (1387-1389).

 

Victor Babès (RO) and Paul Ernst (DE) discovered and described the metachromatic granules seen in the protoplasm of various gram-positive bacteria, algae, and protozoa. These granules stain deeply with aniline dyes and are now known as Babes-Ernst granules or bodies (62; 549; 550).

 

Victor Babès (RO) discovered a group of small protozoan parasites that invade the blood of various animals and are now placed in the genus Babesia, named to honor him (60; 61). Babesia microti is transmitted by the bite of infected Ixodes scapularis ticks—typically, by the nymph stage of the tick, which is about the size of a poppy seed.

 

Klaus Peter Hunfeld (DE), Anke Hildebrandt (DE), and Jeremy S. Gray (IE) report that in cattle, a major host, the disease is known as Texas cattle fever, redwater, or piroplasmosis. Human babesiosis is uncommon but reported cases have risen recently because of expanded medical awareness (837).

 

Auguste Trillat (FR), in 1888, discovered the germicidal value of formalin (40% formaldehyde in water) (1618; 1619). In 1891, Trillat patented the solution as Formolin.

Theodor Geuther (DE) discovered that formalin (Formolin) destroys the germinating power of smut spores (663).

 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) extended his theory of cellular immunity by showing that anthrax bacteria are actively phagocytized and destroyed by phagocytes from animals previous exposed to the bacterium (1104).

 

Wilhelm Roux (DE) experimentally produced a half-embryo by killing one blastomere of the two-celled frog embryo (1391).

 

N. Kastschenko (UA) observed that in elasmobranchs, ectoderm of the neural crest contributed to mesenchyme production in the nose, mouth, and branchial clefts (885).

Julia Barlow Platt (US) demonstrated that cartilage and the skeletal tissue that forms teeth in the head of a mudpuppy (Necturus maculosus) embryo develop from the ectoderm (1308). Note: Platt thus questioned the germ layer theory, which stated that ectoderm only produced skin and brain structures, while all vascular, bone, muscle, and connective tissues like cartilage were expected to develop from mesoderm.

Felix Anton Dohrn (DE), director and founder of the Stazione Zoologica in Naples, Italy, agreed with and defended Platt's results after examining his own data on shark embryos (447).

 

William Johnson Sollas (GB), geologist, paleontologist, and spongiologist wrote Report on the Tetractinellida Collected by H.M.S. Challenger During the Years 1873-1876; still considered a benchmark publication. In this monograph all tetractinellids known at that time are treated, including the many dredged by H.M.S. Challenger. Many of the genera and families erected by Sollas are still recognized as valid (1523). He is commemorated by Amphius sollasi Burton & Rao, 1932; Callipelta sollasi Lévi&Lévi, 1989; Erylus sollasi Von Lendenfeld, 1910; Isops sollasi Lendenfeld, 1910; Pachastrella sollasi Topsent, 1890; Penares sollasi Thiele, 1900; Proteleia sollasi Dendy & Ridley , 1886; Sollasella Lendenfeld, 1888; Sollasellidae Lendenfeld, 1888; Tethya sollasi Bergquist & Kelly-Borges, 1991, and Alcyonium sollasi.

 

Samuel Wendell Williston (US), in 1888, wrote the 1st edition of a very important and influential book on the North American diptera (1794).

 

Thomas Belt (GB) discovered that small stinging ants, Pseudomyrma bicolor, live in hollow thorns on the bull’s horn acacias where, in exchange for safe places to nest and feed, they protect acacias from depredations of other vegetarian animals. In his account of foraging or army ants Eciton predator, he mentioned that birds follow these ants and snap up any insects that take flight to escape the ants. Belt also discovered that leaf-cutting ants, Oecodoma, use the leaf parts to grow fungi, which they ate, in underground rooms (150).

 

Ambrosius Arnold Willem Hubrecht (NL) coined the word trophoblast for cells that form the outer layer of a blastocyst. They are present four days post-fertilization in humans. They provide nutrients to the embryo and develop into a large part of the placenta. They form during the first stage of pregnancy and are the first cells to differentiate from the fertilized egg to become extraembryonic structures and do not directly contribute to the embryo.

"The name Trophoblast was used for the first time by me in the meeting of the Anatomical Congress at Wiirzburg in 1888, and its earliest definition is found in the report of that meeting in Nos. 17 and 18 of the Anatomischer Anzeiger, Bd. III. "We there read, concerning a very early stage of the hedgehog (p. 510) : Die aussere Wand der Keimblase ist verdickt (drei bis vierschichtig) und besitzt wabige Lacunen. Fur diese aussere (epiblastische) Schicht sei der. Name Trophoblast gewahlt." (834)

 

Maximilian Fürbringer (DE) authored Untersuchungen zur Morphologie und Systematik der Vogel, one of the great classics in bird anatomy (635).

 

Edmond Isidore Étienne Nocard (FR) first described an infection in cattle called farcy, which is caused by an aerobic, partially acid-fast, branching type of actinomycete, Streptothrix farcinica (1199). Vittore Benedetto Trevisan (IT) erected the genus Nocardia in honor of Nocard (1617); the etiological agent became Nocardia farcinica.

 

Ivan Petrovich Pavlov (RU) and W.W. Kudrewezki (RU) discovered secretory fibers in the vagus, which diminish or abolish secretion by the pancreas. Pavlov showed that atropine paralyzes these secretory fibers (943; 1268).

 

 Victor Alexander Haden Horsley (GB) and Edward Albert Schäfer (GB) published a somatotopic map of the monkey motor cortex (829).

Charles Scott Sherrington (GB) described motor cortex of the brain. While studying the brain, he developed the concept of the synapse, coining the term synapse in the process (1492).

Albert Sidney Frankau Leyton (GB) and Charles Scott Sherrington (GB) provided the first detailed proof that there is indeed localization of function within the cerebral cortex. They were the first to establish precisely the true extent of the motor area, and to provide the first detailed ‘motor map' of the primate motor cortex. In addition, they showed that surgical extirpation of the cortical tissue that, when stimulated, gave rise to movement of a particular body part, resulted in a widespread weakness and loss of use of that same body part. There was, however, substantial recovery in the weeks that followed, recovery that was not lost on lesioning either the adjacent tissue in the same hemisphere or the equivalent cortical area of the opposite hemisphere. Finally, they were able to trace the course of the degenerating corticofugal and corticospinal fibers. They observed widespread degeneration in the cervical cord after a lesion of the hand and arm cortical area and noted that after such a lesion in the chimpanzee, ‘the whole of the cross-area of ventral horn has scattered through its many degenerating fibers…', which may be the first report of the direct cortico-motoneuronal projection (985).

Carl G. Bernhard (SE), E. Bohm (SE), I. Petersen (SE) and D. Taverner (GB) confirmed the existence of this projection physiologically (157-159).

Wilder Graves Penfield (US-CA) and Andrew Theodore Rasmussen (US) developed a map of the brain, often portrayed as a cartoon called the motor homunculus (miniature human being). This cartoon character has features drawn according to how much brain space they take up. Therefore, lips and fingers with their high number of nerve endings are larger than arms and legs (1282).

 

Hugo Schulz (DE) noted that many chemicals can stimulate growth and respiration of yeast at low doses but are inhibitory at higher levels (1455). This concept of a generalized low-dose stimulation-high-dose inhibition was gradually supported by similar observations with other chemicals and eventually became known as the Arndt-Schulz law—Rudolf Arndt (DE). Although Schulz ushered in the so-called modern concept of hormesis, i.e., to set in motion, Paracelsus writing in the 16th century, likewise noted that various toxic substances might be beneficial in small quantities. See, Paracelsus, c.1526.

The two phases (biphasic) of a drug's action are dose-dependent. For instance, it is widely recognized that normal medical doses of atropine block the parasympathetic nerves, causing mucous membranes to dry up, while exceedingly small doses of atropine cause increased secretions of mucous membranes.

 

Arnaldo Cantani (CZ-IT) proposed the concept of the neural spread of rabies: in laboratory animals the transection of limb nerves following peripheral inoculation prevented the evolution of the disease (284).

Alfonso Di Vestea (IT) and Giuseppe Zagari (IT) used laboratory animals to provide convincing evidence to support Cantani’s proposal (428).

Karl Schaffer (HU) produced evidence for the neural spread of rabies in humans (1438).

 

Byrom Bramwell (GB) recognized a connection between pituitary tumors and body fat and polyuria (229).

 

Ètienne-Louis-Arthur Fallot (FR) described a congenital form of heart disease which would later bear his name (tetralogy of Fallot) as follows: "Cyanosis, especially in the adult, is the result of a small number of cardiac malformations well determined…. One…is much more frequent than the others…. This malformation consists of a true anatomopathologic type represented by the following tetralogy: (1) Stenosis of the pulmonary artery; (2) Interventricular communication; (3) Deviation of the origin of the aorta to the right; and (4) Hypertrophy, almost always concentric in type, of the right ventricle. Failure of obliteration of the foramen ovale may occasionally be added in a wholly accessory manner." (565)

Niels Stensen (DK) had described this condition in 1671 (1539).

Thomas Bevill Peacock (GB) had described this disease in 1846 (1273).

 

Harald Hirschsprung (DK) described megacolon, a disease in which nerve ganglia are absent in the myenteric plexus of the rectosigmoid area of the large intestine, leading to improper development. The colon above the inactive area of the sigmoid dilates and there is chronic constipation, abdominal distension, and fecal impaction. The condition would later be named Hirschsprung’s disease (797).

Caleb Hillier Parry (GB) had been the first to report this disease (1265).

 

Samuel Jones Gee (GB), Christian Archibald Herter (US), Johann Otto Leonhard Heubner (DE), and Thorvald Einar Hess Thaysen (DK) described and defined a gastrointestinal disease resulting from defective fat and calcium absorption, with deficient capacity for metabolizing the gluten fraction gliadin. Gee stated, "to regulate the food is the main part of treatment. The allowance of farinaceous foods must be small, but if the patient can be cured at all, it must be by means of diet." (660; 781; 791; 1587)

Jan H. van de Kamer (NL), H. Ten Bookkel Huinink (NL), and Helmut A. Weyers (NL) developed the first accurate method of quantitating stool fat. They thereby proved that diets containing wheat, barley, and rye worsened fecal fat excretion and clinical symptoms in celiac patients (1640).

Willem-Karel Dicke (NL), in the food scarce days of WWII, noticed his hospitalized I toddlers, who existed on “gruel” (porridge) improved when rice or potato flour replaced wheat flour. When Swedish planes dropped bread in The Netherlands, his patients, who had improved on wheat-free diets, all relapsed (430).

Willem-Karel Dicke (NL), Hans A. Weijers (NL), and J. Hijmans van de Kamer (NL) discovered that celiac disease is cured when wheat is banished from the diet, and rice flour, maize starch, and peeled, boiled potatoes are given instead (431).

Cyrus E. Rubin (US), Lloyd L. Brandborg (US), Arnold L. Flick (US), Cherill M. Parmentier (US), and Sally Van Niel (US) observed acute small intestine changes brought about by wheat, barley, and rye in celiac disease (1395). Rubin refined the intestinal biopsy leading directly to the accurate diagnosis of celiac disease. Use of the Rubin Tube demonstrated that celiac sprue in children and in adults were identical disorders.

Walburga Dieterich (DE), Eberhardt Laag (DE), Heike Schöpper (DE),

Umberto Volta (IT), Anne Ferguson (GB), Helen Gillett (GB), Ernst Otto Riecken (DE), and Detlef Schuppen (DE) identified tissue transglutaminase (tTG) as the major if not sole endomysial autoantigen in celiac sprue. IgA anti-tTG and IgA endomysium (EMA) show an excellent correlation, further confirming the enzyme as the celiac disease autoantigen (437).

Lu Shan (US), Øyvind Molberg (NO), Isabelle Parrot (US), Felix Hausch (US), Ferda Filiz (US), Gary M. Gray (US), Ludvig M. Sollid (NO), and Chaltan Khosla (US) identified a 33-mer peptide that has several characteristics suggesting it is the primary initiator of the inflammatory response to gluten in celiac sprue patients. This peptide is resistant to attack by all gastric, pancreatic, and intestinal brush-border membrane proteases in these genetically predisposed patients. The peptide reacted with tissue transglutaminase (tTG), the major autoantigen in celiac sprue, with substantially greater selectivity than known natural substrates of this extracellular enzyme. It was a potent inducer of gut-derived human T cell lines from 14 of 14 celiac sprue patients. Homologs of this peptide were found in all food grains that are toxic to celiac sprue patients but are absent from all nontoxic food grains. The peptide could be detoxified in in vitro and in vivo assays by exposure to a bacterial prolyl endopeptidase, suggesting a strategy for oral peptidase supplement therapy for celiac sprue (1483).

Note: Terminology has changed as research confirmed that celiac disease diagnosed in children was the same disease as non-tropical sprue diagnosed in adults. The term "celiac disease" is now most commonly used. Another term for the same condition includes "gluten sensitive enteropathy." Dermatitis herpetiformis also known as Duhring's disease and gluten ataxia are generally considered specific manifestations of celiac disease. Non-celiac gluten sensitivity symptoms and treatment are just like celiac disease without HLA similarity. Only recently gluten sensitivity has been separated from the celiac disease umbrella.

             

Paul Ehrlich (DE) was the first to distinguish aplastic anemia (509).

 

Paul W. Furbringer (DE), in 1888, introduced his three-minute method of hand disinfection, in which he placed the use of alcohol between the mechanical soap-and-water, and the chemical disinfectant.

After shortening and cleaning the nails, he brushed the hands thoroughly for one minute each, in soap and hot water, in 80 percent alcohol, and in 1:500 sublimate solution (probably mercuric chloride) or Lysol. He saw two points of value in alcohol, its fat-dissolving power, and its miscibility with water, which enabled the alcohol to prepare the way for the watery sublimate solution to adhere to and act upon the bacteria in the skin. His work first introduced alcohol, and he defended his position with bacteriological examination of hands so cleansed (636). See, Semmelweis 1850, 1861

Egbert Braatz (DE), in 1893, noted the importance of using strictly sterile instruments, as well as water and alcohol in bottles with foot-power faucets, and sterile basins and brushes (226).

 

William Williams Keen, Jr. (US) was the first American to remove an intracranial meningioma (177).

 

William Richard Gowers (GB) and Victor Alexander Haden Horsley (GB) reported the first successful operation for the removal of an extramedullary tumor of the spinal cord (697). Note: Charles Alfred Ballance (GB) assisted Horsley in this operation, playing a critical role in its success.

Joseph Jules Francoise Felix Babinski (PL-FR), Paul Lècene (FR), F. Bourlot (FR), Thierry de Martel (FR), and Joseph Jumentié (FR) successfully removed spinal meningiomas (68; 69).

 

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) developed an operation to repair complete prolapse of the rectum (1705).

 

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) removed a bladder stone by a transperitoneal incision (sectio Alta interperitonealis). He closed the bladder using furrier’s suture and catheterized it for a time. In a case of carcinoma of the bladder, he deliberately opened the peritoneum and performed a combined intravesical and intra-abdominal operation (1410).

 

Rudolph Matas (US), in 1888, was the first to use intravenous fluids in a surgical patient. He amputated the leg of a young man and while the blood loss of the patient was “comparatively slight” according to Dr. Matas, the patient was in a state of shock with a “small, shallow, and rapid” pulse. Dr. Matas injected two pints of a warm saline solution into the patient, resulting in a strengthening and slowing of the pulse (841; 1075).

Rudolph Matas (US) reported the first known endoaneurysmorrhaphy. After ligation of the proximal and distal regions of a large traumatic brachial artery aneurysm of the left arm, an incision was made into the aneurysm, and the clot was removed. The orifices of the blood vessels that entered the sac then were sutured from within, which preserved the collateral blood supply to the extremity (1074; 1077). Note: This operation markedly reduced the incidence of gangrene and amputation that followed the procedure in a high percentage of patients who underwent the Hunterian ligation for popliteal aneurysm. This principle is still used.

Rudolph Matas (US) expanded the scope of intravenous fluid replacement to the surgical patient in July 1888. He had just performed an amputation at the thigh on a 26-yr.-old patient with a cavernous sarcoma of the leg. Six hours postoperatively, he found the patient to be "in a condition of profound shock when he was placed in bed, the pulse being very small, shallow, and rapid." Two pints of a salt solution were warmed and infused through the basilic vein at Dr. Matas' direction. After this infusion, Dr. Matas stated that the patient "felt as if a delightful cool wave were gently spreading over his body and was giving him new strength and life and wonderfully appeasing his thirst." (1078)

 

Ian Greaves (US) and Norbert Hirschhorn (US) proposed that Louisa May Alcott (US), famous American author, whose immediate cause of death in 1888 was a stroke, suffered a multi-system disease, possibly originating from effects of mercury on the immune system. A portrait of Alcott at the Alcott museum, Orchard House, in Concord, Mass exhibiting a distinctive "butterfly-rash," a pinkish hue across Alcott's cheeks and nose, that often accompanies lupus raises the possibility that she had systemic lupus erythematosus (SLE) (702).

 

William Osler (CA-GB) was the primary force behind bringing the best teaching methods from Europe to Johns Hopkins Medical School and making it the leading medical center in America. He wrote Principles and Practice of Medicine, the greatest textbook of medicine in its time (1225).

 

Harry Govier Seeley (GB) determined that dinosaurs consist of lizard-hipped (saurischian) and bird-hipped (ornithischian) branches (1472). He named Agrosaurus (1891), Anoplosaurus (1878), Aristosuchus (1887), Craterosaurus (1874), Macrurosaurus (1876), Orthomerus (1883), Priodontognathus (1875), Rhadionsaurus (1881), and Thecospondylus (1882).

 

The Marine Biological Station at Woods Hole, MA in the United States was established.

 

1889

Svante August Arrhenius (SE) presented his equation for temperature dependence of the rate of a chemical reaction and suggested the existence of 'energy of activation', an amount of energy that must be supplied to molecules before they will react (45).

 

Walther Hermann Nernst (DE) discovered the energetic equivalence of Faraday's constant F to PV/n of the gas laws, thereby mathematically linking electrometric ion activity to the behavior of gases (1178).

 

Martinus Willum Beijerinck (NL), in 1889, is generally credited with the first thin-layer chromatography (TLC). He diffused a drop of hydrochloric and sulfuric acid mix through a gelatin thin-layer and found that the hydrochloric acid traveled faster than the sulfuric acid, separating into concentric rings. He also pioneered the use of visualization reagents. The hydrochloric acid was visualized with silver nitrate, and the sulfuric acid with barium chloride (136).

Martinus Willum Beijerinck (NL) applied high-performance thin layer chromatography (HPTLC) in combination with bioluminescence detection using Aliivibrio fischeri bacteria (137).

 

Hendrik Paulus Wijsman, Jr. (NL) used Beijerinck's (TLC) technique to identify the active enzyme in malt diastase, which splits off maltose from soluble starch. He invented the first fluorescent indicator for (TLC) visualization by preparing a gelatin layer containing starch and a marine fluorescent bacterium; he diffused the amylase mixture through the gelatin, obtaining a fluorescent band only where the beta-amylase reacted with the starch (1783).

Nikolai A. Izmailov (RU) and Maria S. Shraiber (RU) developed the "drop-chromatographic method" which later became known as thin-layer chromatography. To separate a mixture of organic plant extracts they used microscope slides coated with a suspension of various adsorbents (calcium, magnesium, aluminum oxide), then deposited one drop of the mixture on this layer, followed by one drop of the same solvent which would be used in a column separation. The separated components appeared as concentric rings that fluoresced in various colors under a UV lamp (854).

James E. Meinhard (US) and Norris F. Hall (US) used thin-layer chromatography (TLC) to separate terpenes found in essential oils (1097).

Justus G. Kirchner (US), John M. Miller (US), George J. Keller (US), Randall G. Rice (US), Leslie S. Ettre (US), and Albert Zlatkis (US) at the US Department of Agriculture's Fruit and Vegetable Laboratory in California perfected thin-layer chromatography (TLC) by modifying the Meinhard & Hall technique, substituting silica gel as the adsorbent after investigation of over a dozen candidates and settling on gypsum as the least reactive binder (902-904; 1125).

 

Heinrich Ferdinand Edmund Drechsel (DE) isolated the amino acid lysine from hydrolyzed casein. He called it lysatine from the Greek meaning loosing (456).

 

Charles Tanret (FR) isolated ergosterol from plant tissue (rye) (1575; 1576).

 

Gerhard Lange (DE) isolated lignic acid from wood (958; 959).

 

Gerhard Lange (DE) determined the quantitative cellulose content within woods (960).

 

Franz Hofmeister (CZ-DE) crystallized ovalbumin from a half-saturated solution of ammonium sulfate. This was one of the first proteins to be isolated in pure form (812; 813).

 

Jean-Paul Vuillemin (FR) coined the term antibiosis (1714).

Selman Abraham Waksman (RU-US), in 1942, coined the term as antibiotic in its modern incarnation to mean chemical substances, including compounds and preparations that are produced by microbes and have antimicrobial properties (1721).

 

Rudolf Emmerich (DE) and Oscar Löw (DE) introduced an antibacterial agent from aged cultures of Pseudomonas. They named their material pyocyanase, thinking it was an enzyme. Although a potent antibiotic it proved to be so toxic that it was not clinically usable (537).

 

Albert Charrin (FR) and Marc Armand Ruffer (FR-GB) discovered that a filtered culture of pyocyanic bacillus can induce fever in rabbits in the absence of live or dead bacteria (312).

Richard Friedrich Johannes Pfeiffer (DE) and August Paul Wassermann (DE) concluded from their studies that wall material from young cultures of Vibrio cholerae contains a potent heat-stable toxic substance, which they named endotoxin (1292; 1298).

Eugenio Centanni (IT) recognized the intimate relationship between the pyrogenic and toxic properties of the bacterial poison, which he found to be chemically inseparable. This led him to name his material "pyrotoxina." (299)

Nous avons eu la joie de constater que ... en effet le sérum obtenu neutralisait des doses multiples d’endotoxine pesteuse... [It was a pleasure for us to state that ... the obtained serum indeed neutralized multiple doses of plague endotoxin... ] Alexandre Besredka (RU-FR)(165).

Ivan L. Bennett Jr. (US), Paul Beeson (US), and Elizabeth Roberts (US) were the first to extract a fever- producing substance from rabbit polymorphonuclear leukocytes (153).

Elisha Atkins (US) and W. Barry Wood Jr. (US) isolated a circulating endogenous pyrogen in the blood after the injection of typhoid vaccine (52).

Philip E. Auron (US), Andrew C. Webb (US), Lanny J. Rosenwasser (US), Steven F. Mucci (US), Alexander R. Rich (US), Sheldon M. Wolff (US), and Charles Dinarello (US) cloned the human interleukin-1β, known to be the endogenous pyrogen among many other activities (57).

Theresa T. Pizarro (US) and Fabio Cominelli (US) by cloning interleukin 1 (IL-1) ushered in the birth of a new era in cytokine biology (1306).

 

Albert Charrin (FR) and Marc Armand Ruffer (FR-GB) reported that a section of sciatic nerve favors the infectious process. They made a similar observation regarding a portion of the pneumogastric nerve (vagus nerve) after tracheal infection. This is likely one of the very first reports in neuroimmunology (313).

Lyudmila V. Borovikova (US), Svetlana Ivanova (US), Minghuang Zhang (US), Huan Yang (US), Galina I. Botchkina (US), Linda R. Watkins (US), Haichao Wang (US), Naji Abumrad (US), John W. Eaton (US), and Kevin J. Tracey (US) found that vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin (206).

 

Martinus Willem Beijerinck (NL) invented the technique of auxanography. Its application underlies the disk diffusion antibiotic assay and vitamin assays based on diffusion of the vitamin within a gel (136).

 

Theodor Boveri (DE) demonstrated the role of the nucleus in heredity by fertilizing nonnucleated fragments of uncleaved sea urchin eggs and found that in some cases, at least, normal larvae developed, as they did also on occasion from unfertilized egg fragments containing only the egg nucleus. This was a clear demonstration of the equivalence, for development, of the maternal and paternal nuclei (213).

 

August Julius Geppert (DE) demonstrated that while mercuric dichloride appears to be a potent antibacterial agent, its effect must be qualified. He found that on adding ammonium sulfide to precipitate all the mercury at the end of an experiment many of the cells, which appeared to be dead by Koch’s technique, were in fact still alive. They had been unable to develop because of the traces of mercuric chloride surrounding them. Without ammonium sulfide treatment, mercuric dichloride in a concentration of 1:1000 apparently killed all the anthrax spores in from 3 to 7 minutes, but if the mercury was precipitated as sulfide many of the spores were shown to have survived. Even after exposure to a concentration of 1:100 mercuric dichloride, anthrax spores were not destroyed with certainty when treated for 6 to 12 minutes (661).

 

Hans Ernst August Buchner (DE) confirmed the work of Josef von Fodor (HU) and George Henry Falkiner Nuttall (US-GB) by showing that antibacterial substances occur in the serum. He went on to show that this bactericidal quality of blood could be demonstrated in vivo. The carotid artery of a dog was exposed and connected with a cannula. The animal was then injected with a culture of typhoid bacilli, and 50 c.c. of blood allowed to flow from the cannula to ensure that the artery was filled with blood. A small quantity of blood was again run out and tested for the presence of typhoid bacilli. The artery above was then ligated in two places and the contents of the isolated segment was examined five hours later, when it was found that a profound reduction in the number of bacilli had ensued. During his prolonged researches Hans Buchner gradually elaborated the view of the existence of substances in the serum inimical to bacteria. He named the substances alexines (I defend) for their protective and defensive properties (256-258). This work is part of the discovery of the complement system. See, von Fodor 1887.

 

Otto Bütschli (DE) and Conrad Schwager (DE) wrote one of the first and most important monographs on the protozoa. The scale and range of this three-volume work is remarkable (267).

 

During 1889 and in 1892, there occurred among the caterpillars of the nun moth (Lymantria monacha Linn.), which was destroying large spruce forests in Europe, a peculiar disease that killed off enormous numbers of the insect. The disease, later found to be a virus-induced polyhedrosis called Wipfelkrankheit, is one of the first known examples of natural insect pest control (1537).

 

Cornelis Adrianus Pekelharing (NL) was the first to report in vivo chemotaxis . He put cotton wool soaked with anthrax bacilli in the peritoneal cavity of a frog. Retrieving this cotton wool some time later, he showed that it contained significantly more leukocytes than those that had been soaked with neutral liquid. He came to the conclusion that bacteria produce chemoattractant factors (1279).

Jean Massart (FR) and Charles Bordet (FR) were the first to demonstrate that the host can make chemoattractant factors. They injected bovine bile subcutaneously in a frog. Then, they sampled the transudation liquid and transferred it in a capillary tube into the abdominal cavity of another frog. Twenty hours later, the capillary tube was full of leukocytes, whereas this was not observed with a capillary tube filled with normal lymph (1072).

Jean Massart (FR) and Charles Bordet (FR) injected s.c. bacteria (Micrococcus prodigiosus, nowadays known as Serratia marcescens) into a rabbit. Thirty-five minutes later, they sampled the blood, prepared the serum, placed it in a capillary tube and finally transferred it into the peritoneal cavity of another rabbit. Eight hours later, the capillary tube was full of leukocytes, whereas this was not the case when the tubes were filled with normal serum. For the first time, they had demonstrated that chemoattractant factors were produced in response to infection (1073).

Richard D. Granstein (US), Randall Margolis (US), Steven B. Mizel (US), and Daniel N. Sauder (CA) focused on investigations of interleukin 1 (IL-1) and established that it was produced by many cell types and had multiple biological activities by also stimulating a great variety of cell types. Subcutaneous injections of IL-1 had been shown to induce acute inflammatory responses with rapid margination of neutrophils followed by their extravascular infiltration (698). See, Auron, 1984.

Albert Zlotnik (US) and Osamu Yoshie (US) note that the discovery of well-identified chemoattractant factors, later called chemokines (the word was coined in 1992), was made in 1987 and 1988 with the description of interleukin-8 and macrophage inflammatory protein (MIP), renamed CXCL8 and CCL3 according to the revised nomenclature of chemokines (1856).

 

Edward Klein (DE) reported that Bacillus gallinarum was the cause of an outbreak of fowl cholera and reported it as infectious enteritis (911).

Veranus A. Moore (US) described the disease as infectious leukemia and named the organism Bacillus sanguinarum (1149; 1150).

Leo F. Rettger (US) (1899) was the first to isolate Salmonella pullorum and describe it as the cause of a fatal septicemia of young chicks (1353).

Leo F. Rettger (US) designated the disease as white diarrhea (1354).

Frederick Cooper Curtice (1902) studied the disease in Rhode Island and named it fowl typhoid (383).

Leo F. Rettger (US) and Frederick H. Stoneburn (US) expanded the term to bacillary white diarrhea to distinguish it from other diseases that might be classified under a common term of white diarrhea (1355).

Theobald Smith (US) and Carl TenBroeck (US) recorded that Salmonella gallinarum and Salmonella pullorum are serologically identical (1519).

 

Albert Charrin (FR) and Henri Louis Roger (FR) found that when Bacillus pyocyaneus is grown in the serum of an animal previously injected with B. pyocyaneus it does not grow diffusely through the medium, as it does in broth or normal serum, but in small masses which sink to the bottom of the tubes and the bacilli are found stuck together. The clumping of particulate matter, e.g., bacteria, due to immune serum is now called agglutination (311).

Max von Gruber (AT) and Herbert Edward Durham (GB) extended this observation by showing that the agglutination of bacteria by serum is specific (484; 1683-1686). This was quickly seized upon as a new diagnostic tool.

Georges Fernand Isidore Widal (FR), Jean-Marie-Athanase Sicard (FR) and Albert Sidney Frankau Grünbaum (GB) showed that the agglutination of enteric bacteria can be used as an aid to identify the infectious agent. This reaction is brought about by the addition of a patient’s serum to a uniform suspension of a known bacterium. The Widal test is used for diagnosis of typhoid fever by mixing the patients serum with a 24-hour Salmonella typhi culture on a glass slide or other appropriate surface. Clumping of the cells after a 30 to 60-minute incubation is a positive reaction (710; 1777; 1779; 1780). Note: Grünbaum later changed his name to Albert Sidney Frankau Leyton.

 

Theobald Smith (US) and Frederick Lucius Kilbourne (US), assisted by Frederick Cooper Curtice (US), discovered that the infectious agent of Texas cattle fever (tick fever, or bovine fever) is Pirosoma bigeminum (Babesia bigemina) (a protozoan) and that it is transmitted by the cattle tick, Boophilus bovis (Boophilus annulatus). Their 1893 paper is a masterpiece of orderly reasoning, experiments to answer specific questions, and complete details of each animal used; it is a recognized classic in medical literature. Quoting from a summary in the 1893 monograph,

“(1) Texas cattle fever is a disease of the blood, characterized by the destruction of red corpuscles. The symptoms are partly due to the anemia produced; partly to the large amount of debris in the blood, which is excreted with difficulty, and which causes derangement of the organs occupied with its removal.

(2) The destruction of the red corpuscles is due to a microorganism or micro-parasite, which lives within them. It belongs to the protozoa and passes through several distinct phases in the blood.

(3) Cattle from the permanently infected territory, though otherwise healthy, carry the micro-parasite of Texas fever in their blood.

(4) Texas fever may be produced in susceptible cattle as a direct inoculation of blood containing the micro-parasite.

(5) Texas fever in nature is transmitted from cattle that come from the permanently infected territory to cattle outside of this territory by the cattle tick (Boophilus bovis).

(6) The infection is carried by the transovarian passage through the progeny of the ticks that matured on infected cattle, and the organisms inoculated by them directly into the blood of susceptible cattle.

(7) Sick natives may be a source of infection (when ticks are present).

(8) Texas fever is more fatal to adult than to young cattle.

(9) Two mild attacks or one severe attack will probably prevent a subsequent fatal attack in every case.

(10) Sheep, rabbits, guinea pigs, and pigeons are susceptible to direct inoculation. (Other animals have not been tested.)

(11) In the diagnosis of Texas fever in the living animal the blood should always be examined microscopically if possible." (1513; 1518)

Heinrich Hermann Robert Koch (DE) described the stages of Babesia bigemina developing in the tick's gut within the first 20 hours after repletion (916).

Note: "The cause of Texas fever in cattle, which is characterised by lysis of erythrocytes leading to anaemia, icterus, haemoglobinuria, and death, remained unsolved for many decades and assorted theories were proposed as an explanation for a disease being transmitted by apparently healthy animals. From 1889 to 1893, Theobald Smith and Frederick L. Kilbourne could demonstrate in elegantly conducted experiments how the disease was spread from cattle to cattle by ticks serving as the vector of transmission. Furthermore, they were able to identify the pathogen of Texas fever, an intra-erythrocytic protozoan which Smith named Pyrosoma bigeminum. Today it is recognised that either of two species of the now renamed genus Babesia, Babesia bigemina and Babesia bovis, may be involved in Texas fever and that babesiosis is generally transmitted by ticks. In animals, genera like Boophilus spp., Dermacentor spp. and Rhipicephalus spp. are possible vectors. The first case of tick-transmitted babesiosis in a human was reported by Skrabalo and Deanovic in 1957 and occurred near Ljubliana in the small town of Strmec, Croatia. In humans, the vectors of most reported cases are ticks of the genus Ixodes, which are among the most predominant ticks in Austria. However, cases of human babesiosis in Austria remain to be studied. Smith and Kilbourne's work was the first demonstration that ticks transmit disease of any kind. Furthermore, by proving that ticks carry Babesia microti—which causes babesiosis in animals and humans—this is the first account of a zoonotic disease and the foundation of all later work on the animal host and the arthropod vector." (50)

 

Henri Parinaud (BE) discovered cat-scratch-fever (1260).

M. Petzetakis (GR) described cat-scratch- fever, an acute infectious disease, occurring most commonly in children and young adults. Patients had typically been scratched or bitten by cats or exposed to a penetrating wound (thorn, splinters, hooks) (1288).

Robert Anselme Debré (FR), Maurice Larny (FR), and Marie-Louise Jammet (FR) discovered that the cat is the natural reservoir of cat-scratch-fever (416).

Charles K. English (US), Douglas J. Wear (US), Andrew M. Margileth (US), Christopher R. Lissner (US), and Gerald P. Walsh (US), isolated the etiological agent of cat-scratch-fever (545). Bartonella henselae or Bartonella clarridgeiae, which is found in the saliva and claws of cats and kittens, are known to cause this disease.

 

Georg Marius Reinald Levinson (DK) was the first to describe a human case of infestation by gnathostoma when he found gnathostoma (a nematode) larva in an infested Thai woman (982; 983; 1135).

H.T. Chen (CN) reported a human ocular infection by Gnathostoma in China (314).

 

Ira van Gieson (US) introduced the first triple staining technique to histology. He used hematoxylin, acid fuchsin, and picric acid to stain nerve tissue (1645).

Walther Flemming (DE) introduced his triple stain to histology. It consisted of safranin, followed by gentian violet, and decolorization in orange G. It is a favorite with botanical cytologists and is valued for staining cells in mitosis (598).

 

Wilhelm His (CH) proved that the origins of neural parts of the nervous system are ectodermal and the vascular parts mesodermal. He further suggested that embryonal neuroglial fibers might guide the migration of early neuronal cells (799).

 

Carlo Giovanni Martinotti (IT) described a cortical neuron with an ascending axon (this neuron now bears his name, Martinotti cells) (1071).

Franz C. Müller-Lyer (DE) discovered the Müller-Lyer illusion (an optical illusion in which the orientation of arrowheads makes one line segment look longer than another) (1165).

 

Francis Galton (GB) formulated the law of ancestral inheritance, a statistical description of the relative contributions to heredity made by one's ancestors (639). This book is considered the beginning of modern biometry.

 

Henry Head (GB) demonstrated the action of the vagus nerve in respiration (756).

 

Ludwig Edinger (DE) discovered the direct connection of the spinal cord and thalamus in fish, frogs and cat embryos. He found that cells in the dorsal horn give rise to axons which pass through the ventral commissure, ascend in the opposite anterolateral funiculus and seemingly end in the thalamus (496; 497).

Leopold Auerbach (DE) confirmed this (55).

 

Eliza Dalgleish Ewart (GB) gave the first comprehensive description of the anatomy of the human lung (555).

 

Charles-Édouard Brown-Séquard (FR) reported that he had “rejuvenated” himself with subcutaneous injections of a testicular extract from freshly killed guinea pigs and dogs (246; 247).

 

Berthold Hatschek (CZ-AT) removed the ctenophores as a separate group recognizing that the coelonterata should be subdivided into Spongiara, Cnidaria, and Ctenophora. He gave a distinct name to the group as Phylum Ctenophora (751).

 

Ernst Fuchs (DE) described an outbreak of epidemic keratoconjunctivitis (EKC) (633).

Ernest Jawetz (US), Samuel J. Kimura (US), A.N. Nicholas (US), Phillips Thygeson (US), Lavelle Hanna (US) discovered that this clinical picture of epidemic keratoconjunctivitis (EKC) is associated with adenovirus type 8 (861; 862).

 

Joseph Hammond Bryan (US) presented a classic paper on diagnosis and treatment of sinusitis involving the antrum (252).

 

August Pfeiffer (DE) described Yersinia pseudotuberculosis (1290). It has also been called Pasteurella pseudotuberculosis, Shigella pseudotuberculosis, and Bacillus pseudotuberculosis.

V.A. Znamenskiy (RU) and A.K. Wishnyakov (RU), through self-inoculation, demonstrated that Y. pseudotuberculosis is, in fact, a causative agent of gastroenteritis in humans and the etiological agent of Far East scarlet-like fever (1857).

M. Bourdin (FR) reported that many species, most of them rodents or birds, could serve as healthy carriers of Y. pseudotuberculosis (210).

Masahiro Tahara (JP), Kiyoshi Baba (JP), Kenji Waki (JP), and Yoshio Arakaki (JP) presented data suggesting that Yersinia pseudotuberculosis infection might play a role in the developing mechanism of poor response to therapy and the tendency to develop coronary artery lesions in Kawasaki disease patients (1567).

 

Stephen Paget (GB) analyzed 735 case histories of fatal breast cancer where he found that metastases formed in the liver far more often than in any other organ — even those such as the spleen that could be considered to have the same exposure to the cancer cells because of similar blood flows. Paget reasoned that sites of secondary growths are not a matter of chance, and that some organs provide a more fertile environment than others for the growth of certain metastases. "The best work in the pathology of cancer is now done by those who... are studying the nature of the seed," he noted. "They are like scientific botanists; and he who turns over the records of cases of cancer is only a ploughman, but his observation of the properties of the soil may also be useful." This is referred to as the seed and soil hypothesis of cancer (1247).

Ian Hart (GB) and Isaiah Fidler (US) performed experiments in mice, which verified Paget’s hypothesis (746).

 

Joseph von Mering (DE) and Oskar Minkowski (RU-DE) discovered the role of the pancreas in glucoregulation when they surgically removed the pancreas of dogs and found that their blood sugar and urine sugar would rise causing hyperglycemia and glycosuria (diabetes mellitus) (1131; 1698; 1699). See Thomas Cawley, 1788.

 

Rudolf von Jaksch; Rudolf Jaksch von Wartenhorst (AT) and Georges Hayem (FR) described what Jaksch named anaemia leucaemica infantum, a chronic anemic disease occurring in children under 3 years of age. It was a symptom complex characterized by acute hemolytic anemia, hepatosplenomegaly, and infections associated with several chronic diseases, such as, tuberculosis, congenital syphilis, gastrointestinal disorders, and malnutrition. The patient presents with listlessness, weakness, gastrointestinal troubles and irregular fever (754; 1693). Note: It is also called also called Jaksch-Hayem-syndrome.

 

Barend Joseph Stokvis (NL) published the first case and clinical description of acute hepatic porphyria. This case of acute illness was provoked by the newly introduced hypnotic drugs sulfonmethane, also known as sulfonal. Stokvis observed the unusual dark red urine, discovered that it contained porphyrins, and coined the name "porphyria" for the condition. The patient's underlying condition was probably acute intermittent porphyria, which can be provoked by medicines (1556).

 

Augusta Marie Dejerine-Klumpke (US-FR) devotes a considerable part of her thesis on neuritis to lead poisoning. She recognizes general and localized forms. The generalized forms may be of slow or rapid progress or may be attended with fever. The localized forms may be of (1) the anti-brachial, or extensor type; (2) the upper brachial type, as in Erb’s shoulder-upper-arm paralysis; (3) the Aran-Duchenne, or thenar type; (4) the reronal type; (5) laryngeal paralysis (420).

 

William Stewart Halsted (US) pioneered the radical mastectomy operation that entailed removal of the breast and underlying muscles, and lymph nodes under the arm. This was in response to the high rate of cancer recurrence experienced at the time (741). He eventually achieved an unprecedented 72 percent five-year cure rate for patients whose disease had not spread to adjoining glands. Halsted first performed this operation in 1889. See, Patey, 1948

 

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT), in 1889, performed the first enterocystoplasty (1706).

 

Jean-Francis-Auguste Le Dentu (FR), in 1889, made the first attempt at a unilateral cuteneous ureterostomy to restore renal function in obstructive anuria caused by pelvic malignancy (972).

Ludwik Rydygier; Ludwig Anton Rydygier von Ruediger (PL-DE), in 1892, performed the first bilateral cuteneous ureterostomy. Ref

 

Edoardo Bassini (IT) and William Stewart Halsted (US) independently developed a surgical procedure for the radical repair of inguinal hernia (Bassini's operation) (Halsted’s operation 1). Bassini used cocaine as a local anesthetic in these operations (107; 245; 739). This is called herniorrhaphy.

Irving L. Lichtenstein (US), Alex G. Shulman (US), Parviz K. Amid (US), and Michele M. Montllor (US) pioneered the use of modern mesh prosthetics to repair all hernias without distortion of the normal anatomy and with no suture line tension. The technique is simple, rapid, less painful, and effective, allowing prompt resumption of unrestricted physical activity (986).

Nicholas C. Gallegos (GB), Jonathan Dawson (GB), M. Jarvis (GB), and Michael Hobsley (GB) found that although the elective repair of groin hernias is advised to prevent strangulation, the likelihood of this complication occurring is unknown. To quantify this risk, the cumulative probability of strangulation in relation to the length of history has been calculated for inguinal and femoral hernias presenting to their hospital between 1987 and 1989. The rate at which the cumulative probability of strangulation increased was in both cases greatest in the first 3 months, suggesting that patients with a short history of herniation should be referred urgently to hospital and given priority on the waiting list (637).

Johann Cunningham (CA), Walley Temple (CA), Philip Mitchell (CA), James Nixon (CA), Roy Preshaw (CA), and Neil Hagen (CA), concluded that pain or numbness are common late sequelae of traditional external surgical hernia repairs. They stressed that strategies need to be developed to reduce the risk of these complications (375).

The MRC Laparoscopic Groin Hernia Trial Group concluded that although laparoscopic hernia repair has advantages for patients, concerns about safety indicate that open repair is the more appropriate option for the general surgeon. Their findings lend support to the move towards laparoscopic hernia surgery becoming part of the domain of specialist surgeons (708).

Miguel Angel Carbajo (ES), Juan Carlos Martin del Olmo (ES), Jose Ignacio Blanco (ES), Carmen de la Cuesta (ES), Miguel Toledano Trincado (ES), Fernando Martin (ES), Carlos Vaquero (ES), and Luis Inglada (ES) Kamal M.F.Itani (US), Kwan Hur (US), Lawrence T. Kim (US), Thomas Anthony (US), David Berger (US), Domenic Reda(US), Leigh Neumayer (US), and Veterans Affairs Ventral Incisional Hernia Investigators (US) advocated the laproscopic approach because of reduced complications, operating time, shorter length of hospital stay, and faster return to normal activities (285; 850).

Leigh Neumayer (US), Anita Giobbie-Hurder (US), Olga Jonasson (US), Robert Fitzgibbons, Jr. (US), Dorothy Dunlop (US), James Gibbs (US), Domenic Reda (US), William Henderson (US), and the Veterans Affairs Cooperative Studies Program 456 Investigators (US) concluded that the open technique is superior to the laparoscopic technique for mesh repair of primary hernias (1187).

Dag Arvidsson (SE), Fritz H. Bernden (IS), Lars-Göran Larsson (SE), Carl-Eric Leijonmarck (SE), Gunnar Rimbeck (SE), Claes Rudberg (SE), Sam Smedberg (SE), Leif Spangen (SE), and Agneta K. Montgomery (SE) showed that the laparoscopic transabdominal preperitoneal patch operation represents an excellent alternative for primary inguinal hernia repair (47).

Robert J Fitzgibbons, Jr. (US), Anita Giobbie-Hurder (US), James O. Gibbs (US), Dorothy D. Dunlop (US), Domenic J. Reda (US), Martin McCarthy, Jr. (US), Leigh A. Neumayer (US), Jeffrey S. T. Barkun (US), James L. Hoehn (US), Joseph T. Murphy (US), George A. Sarosi, Jr. (US), William C. Syme (US), Jon S. Thompson (US), Jia Wang (US), and Olga Jonasson (US) determined that watchful waiting is an acceptable option for men with minimally symptomatic inguinal hernias. Delaying surgical repair until symptoms increase is safe because acute hernia incarcerations occur rarely. ClinicalTrials.gov Identifier: NCT00263250 (586).

Alvaro Sanabria (CO), Luis Carlos Domínguez (CO), Eduardo Valdivieso (CO), and Gabriel Gómez (CO) found that antibiotic prophylaxis use in patients submitted to mesh inguinal hernioplasty decreased the rate of surgical site infection by almost 50% (1431).

Lucia Chung (GB), John Norrie (GB), and Patrick J. O’Dwyer (GB) showed that most patients with a painless inguinal hernia develop symptoms over time. Surgical repair is recommended for medically fit patients with a painless inguinal hernia (320).

 

Wilhelm Wagner (DE) used a scalpel, hammer, and chisel to resect a flap of scalp and skull hinged upon muscle so that it could be replaced. With such a large osteoplastic flap, the surgeon could cut the dura mater about an attached tumor or reflect the dura mater to explore much of the lateral cortex. This method could expose a much larger area of the brain’s surface than a trephine (1716).

 

Ernst Gustav Benjamin von Bergmann (LV-DE) wrote a classic textbook on cranial surgery, which was later, incorporated into the five-volume work on surgery by von Bergmann and Paul von Bruns (DE) (1667; 1670).

 

Gottlieb Burckhardt (CH) was, in 1888, the first physician to perform modern psychotherapy (lobotomy) when he excised various brain regions from six psychiatric patients under his care. Aimed at relieving symptoms rather than effecting a cure, the theoretical basis of the procedure rested on his belief that psychiatric illnesses were the result of specific brain lesions. He reported the results at a Berlin medical conference in 1889 (262).

António Caetano Abreau Freire De Egas Moniz (PT) developed frontal lobootomy for treatment of certain clinical psychoses (1137; 1138).

Walter Jackson Freeman (US), with no qualifications for surgery, and James Winston Watts (US), in 1936, introduced a surgical technique for frontal lobe lobotomy into the U.S.A. The early 'technique' involved drilling burr-holes; later Freeman developed his famous/infamous transorbital approach, literally pushing an ice pick into the brain via the eye sockets (619; 620).

 

Paul Loye (FR) concluded that the loss of complete consciousness and brain death occurred immediately after decapitation, but various parts of the body, such as the heart, continued to work for several minutes as a reflex action (1029).

 

Pierre Marie Félix Janet (FR) argued that, "hysterical symptoms are due to subconscious fixed ideas that have been isolated and usually forgotten. Split off from consciousness – 'dissociated' – they embody painful experiences but become autonomous by their segregation from the main stream of consciousness." (860) This predated Freud's announcement of virtually, an identical discovery, by four years.

 

Jonathan Hutchinson (GB) originated the naming of clinical disorders after patients—Hilliard’s lupus—as opposed to naming them for the describing physician (840).

 

A worldwide epidemic of influenza, the most devastating to that time, began in central Asia in the summer of 1889, spread north into Russia, east to China and west to Europe. By December it had struck the major U.S. cities, and continued to spread through North America the following year. Parts of Africa and the Middle East were infected early in 1890; and India, Southeast Asia, Australia and New Zealand were reached between February and May. Completing the circle, Eastern China had the last major outbreak of this pandemic, in September and October of 1890 (921).

 

1890

"The broad fact that the invasion of the organism by microbes most often induces, on the one hand, an inflammatory reaction with its associated emigration of leukocytes, and that, on the other hand, the phagocytes are capable of including and destroying the invaders, leads us to admit that the afflux of phagocytes to the invaded region and their bactericidal properties are mechanisms which serve to ward off bacterial attack and to maintain the integrity of the organism." Elie Metchnikoff's address at the Institute Pasteur on December 29, 1890.

 

"When you have eliminated the impossible, whatever remains, however improbable, must be the truth." Sherlock Holmes from the Sign of the Four by Arthur Conan Doyle (454).

 

"The immunity of rabbits and mice which have been immunized against tetanus rests on the capability of cell-free blood serum to render harmless the toxic substances which the tetanus bacilli produce." Emil Adolf Behring, Shibasaburo Kitasato (134)

 

Jakob Stilling (DE) reported the bacteriostatic action of the triphenylmethane dyes. Methyl violet and auramine were recommended as useful antiseptics (1553; 1554). The bacteriostatic property of malachite green was reported later.

John W. Churchman (US) showed that derivatives of triphenylmethane such as gentian violet and brilliant green dyes are inhibitory to bacteria, particularly Gram positives; and crystal violet causes some inhibition of fungi (321).

 

Friederich August Johannes Löffler (DE) made a thorough investigation of and perfected the technique of staining bacterial flagella. He discovered that quite often the method had to be varied slightly with each different species of bacterium being stained. He discovered that the reaction in its relation to H-ion concentration is critical and that no one H-ion concentration is best for all bacteria (1016).

 

Richard Altmann (DE) introduced the technique of freeze-drying to preserve tissue (22).

Leon F. Shackell (US) reported on the principle of vacuum desiccation from the frozen state, a process essential to the production of a highly soluble product, which would retain its original biological properties (1482).

 

Pierre Miquel (FR) obtained urease from bacteria (1133).

 

Theodor Boveri (DE) and Jean-Louis-Léon Guignard (FR) established that the nuclei of egg and spermatozoon furnish to the zygote equivalent complements of chromosomes (214; 712).

Wilhelm August Oskar Hertwig (DE) reached the same conclusion as Boveri and Guignard above and concluded that, the polar body does not represent a part of the germ plasm removed from the egg but has, in fact, ''the morphological value of rudimentary egg cells" (783).

 

Knud Helge Faber (DK), Ludwig Brieger (DE), and Carl Fraenkel (DE) showed that the symptoms of tetanus (lockjaw) are due to a toxin produced by the bacterium Clostridium tetani (239; 560; 561).

 

Willoughby Dayton Miller (US) elucidated the bacteriology of dental caries (1127).

 

Wilhelm Friedrich Ostwald (LV-DE) laid the theoretical groundwork for the membrane theory of nerve conduction. He suggested that the electrical potential at artificial semipermeable membranes was due to their selective permeability to ions ("ion sieve") (1229).

Julius Bernstein (DE), in 1902, stated his membrane theory as follows, "The electrical currents observed in many living organs of animals and plants have been the objects of much research. We detect such currents in muscles, nerves, secretory glands, and electric organs of fish as well as in plant tissue. It seems likely that all these currents have a similar, if not the same basis, and that their strength and potency depends on the structural conditions and chemical composition of the cells making up each organ." He postulated that the membrane of the nerve cell can selectively pass certain kinds of ions. Bernstein suggested that nerves are normally polarized with positive ions on the outside and negative ions inside and that the current he measured was the change in this polarization. Obviously when equilibrium is reached an electrical potential exists across the membrane - the transmembrane potential. The nerve impulse is simply a localized region of depolarization, or loss of this transmembrane potential, that travels down the nerve fiber with the membrane potential being immediately restored behind it (160; 161). This is remarkably close to what is currently accepted as how a nerve impulse is generated.

Ralph Stayner Lillie (US) started experiments in 1909, which supported the membrane theory of nerve conduction (993).

Alan Lloyd Hodgkin (GB) supported this theory with experiment (804; 805).

 

Theodore T. Groom (GB) and Jacques Loeb (US) using barnacle nauplii, made the first detailed study of marine larval swimming behavior. In these papers, it was demonstrated that the sign of naupliar phototaxis could be reversed by modifying light intensity and that light in the ultraviolet region of the spectrum is especially effective in causing photopositive nauplii to become photonegative (705; 706).

Wolfgang F. Ewald (US) demonstrated that ultraviolet irradiation causes mortality among barnacle nauplii, thus providing an adaptive explanation for the negative phototaxis observed by Groom and Loeb (554).

 

Francois-Gilbert Viault (FR) found that following 23 days at 4392 meters of altitude his red cell count rose from 5 to 8 million per cubic millimeter (1654). He later confirmed that hemoglobin concentrations rise on ascent to higher altitudes.

 

Nicolas Maurice Arthus (FR), Calixte Pages (FR) and L. Sabbatini (FR) observed that precipitation of calcium inhibits coagulation, and that this effect is reversed when sufficient calcium is re-added. Calcium is not required for the reaction of thrombin with fibrinogen but is required for the conversion of the hypothetical prothrombin to thrombin (46; 1325; 1412).

Almroth Edward Wright (GB) showed that citrate keeps blood in a liquid state by decalcifying it and that citrate appears to more suitable for purposes of blood transfusion than is oxalate (1823; 1824).

H. Griesbach (DE) found that ammonium citrate inhibits blood clotting (704).

Cornelis Adrianus Pekelharing (NL) found that blood mixed with citrate remained fluid, realizing that the effect was due to the affinity of calcium for citric acid (1280).

Paul Morawitz (DE) synthesized various observations into one of the first formulations of the biochemistry of blood coagulation: prothrombin, he hypothesized, was converted into the enzyme thrombin by “thrombokinase” (tissue factor) in the presence of calcium; thrombin, in turn, converted fibrinogen to fibrin (1151).

Joseph Lister (GB) maintained that the blood has no spontaneous tendency to clot but that it only clots when brought into contact with a foreign body (998).

Paul Morawitz (DE) called these “zymoplastic substances” thrombokinase, and William Henry Howell (US) later denominated them "tissue thromboplastins" (factor III) (833; 1151).

John Mellanby (GB) described the inhibition of blood coagulation by oxalate and citrate (1098).

Arthur Edwin Boycott (GB) and Claude Gordon Douglas (GB) transfused rabbits with allogeneic blood using the citrate method. A total of 0.4-0.5 g of sodium citrate was found to be enough to keep any quantity up to about 100cc of rabbit blood liquid at 37° C for many hours, provided that blood was obtained from the first main gush which issues from the divided carotid (225).

James Bryan Herrick (US) proposed the association of blood clots with acute arterial occlusion (780).

Albert Hustin (BE) performed the first transfusion of citrated blood given to a human (839).

Francis Peyton Rous (US) and Jerrold R. Turner (US) found that glucose and sucrose had a marked effect in inhibiting lysis of red blood cells during storage (1381). Later studies showed glucose to be the superior of the two. A combination of glucose and citrate became the storage solution of choice for red blood cells.

Oswald Hope Robertson (GB-US), in 1917, built an ice chest from two ammunition cases, took 22 units of blood to a casualty-clearing station and used them to resuscitate Canadian soldiers judged too deep in shock for surgery. Eleven of the 20 recipients lived. This was the first use of cold blood storage or "banked blood". Robertson soon built a donor and transfusion service that would be recognized today. He found that if the blood of donors is taken under sterile conditions and mixed with a sterile sodium citrate solution it could be preserved in the cold for a month. This discovery also directly led to the establishment of the first blood 'depot' by the British during World War I. Robertson is credited as the creator of blood depots (blood banks) (789; 1368; 1369). Note: The 1918b article describes the "Robertson's bottle" for transfusing blood. It was widely used after the war. See Luis Agote, 1914 and Sergei Sergeivitch, 1931.

Percy Oliver (GB), as the secretary of the British Red Cross, established the world's first blood donor service in 1921. Volunteers were subjected to a series of physical tests to establish their blood group.

In 1929, New York's leading hospitals, surgeons, and blood researchers founded the Blood Transfusion Betterment Association (BTBA) to provide the local medical community with reliable, thoroughly tested donors on demand, and to provide financial support to blood researchers.

Sergei Yudin (RU), in 1930, organized one of the world's first blood banks. It was at the Nikolay Sklifosovskiy Institute, which set an example for the establishment of further blood banks in different regions of the Soviet Union and in other countries. By the mid-1930s the Soviet Union had set up a system of at least 65 large blood centers and more than 500 subsidiary ones, all storing "canned" blood and shipping it to all corners of the country (17).

Sergei Sergeevich Sergeivitch (RU), in 1931, introduced the blood bank into the practice of medicine in a Leningrad hospital. Ref

John H. Ferguson (US) discovered the presence of intrinsic thromboplastin under the name of tryptase (570).

Bernard Fantus (US), in 1937, started a hospital blood bank at Cook County Hospital in Chicago, IL. Blood was collected into a 2% solution of sodium citrate and refrigerated (566). Note: Fantus is credited with coining the phrase “blood bank”.

Charles Richard Drew (US), a medical supervisor of the "Blood for Britain Project," reported to the National Blood Transfusion Committee noting that for cases of shock, burns, and open wounds, plasma often worked better than whole blood. Plasma could also be stored and transported without refrigeration. Drew was able to transform small scale methods into the first successful mass production methodology for preparing and shipping large quantities of dried blood plasma (458).

John Freeman Loutit (GB) and Patrick L. Mollison (GB) perfected the acid-citrate-dextrose (ACD) solution, which reduced the volume of anticoagulant, thus permitting transfusions of greater volumes of blood and allowing longer-term storage (1026).

Marcus A. DeWood (US), Julie Spores (US), Robert Notske (US), Lowell T. Mouser (US), Robert Burroughs (US), Michael S. Golden (US), Henry T. Lang (US), L. David Hillis (US), Jeffrey Borer (US), Eugene Braunwald (US), James H. Chesebro (US), Lawrene S. Cohen (US), James Dalen (US), Harold T. Dodge (US), Charles K. Francis (US), Genell Knatterud (US), Philip Ludbrook (US), John E. Markis (US), Hiltrud Mueller (US), Patrice Desvigne-Nickens (US), Eugene R. Passamani (US), Eric R. Powers (US), A. Koneti Rao (US), Robert Roberts (US), William C. Roberts (US), Allan Ross (US), Thomas J. Ryan (US), Burton E. Sobel (US), David O. Williams (US), Barry L. Zaret (US), Michael J. Davies (GB), and Anthony C. Thomas (GB) resolved the significance of blood clotting in acute arterial events (401; 427; 794). See, Malpighi1669 through Zhang 2003 in Section 1b for details on coagulation.

 

Carl Fraenkel (DE) found that he could immunize guinea pigs against living Corynebacterium diphtheriae by giving an injection of a three-week-old heat killed (60-70°C for one hour) culture of the same species (611).

 

Emil Adolf Behring (DE) and Shibasaburo Kitasato (JP) discovered antitoxin while working on immunity to tetanus and diphtheria. They reported that when rabbits and mice were immunized to tetanus a protective element was present in the cell-free serum, which neutralized the effect of the toxin. This capacity was so durable that it still exhibited its activity when the immune serum was transferred to the bodies of other animals. They referred to the serum as possessing an antitoxic quality (133; 134).

 

Augosto Ducrey (IT) described the infection and isolated the bacterium, which now bears his name, Haemophilus ducreyi, from a lesion of the venereal disease called soft chancre or chancroid (476-479).

F. Bezancon (FR), V. Griffon (FR), and L.C. Le Sourd (FR) inoculated the forearms of human volunteers with culture-purified organisms and produced characteristic soft chancres from which the same organism was re-isolated (167).

F. Bezancon (FR), V. Griffon (FR), and L.C. Le Sourd (FR) obtained the organism in axenic culture (168).

 

Hans Eppinger (DE) was the first to describe an infection in humans caused by Nocardia spp. He called it Cladothrix, which was changed to Nocardia in 1895 by Blanchard. The fungus-like organism (a branching type of actinomycete) caused lesions in pulmonary and central nervous system tissues (nocardiosis) (546).

 

Johann Gottfried Hallier; Hans Gottfried Hallier (DE) insisted that only the broadest possible basis was sufficient for establishing the taxonomy of plants. He included not only the morphology of reproductive structures, but added comparative morphology of the vegetative organs; comparative anatomy, ontogeny and embryology; phytochemistry, physiology and ecology; structure of pollen and seed coat; relation to climate, seasons and the surrounding organic world, plant geography, paleophytology, etc (732-738). See, page 154 of the 1905 reference for articles going back to 1890.

 

Douglas Houghton Campbell (US) discovered the precise manner of formation of the archegonia and antheridia in the eusporangiate ferns. He also linked the ferns with the liverworts by way of Anthoceros (271-280).

 

Jacques Loeb (DE-US) introduced the concepts of forced movements, tropisms and animal conduct. He vehemently opposed any anthropomorphic or teleological interpretations of animal behavior (1007; 1008).

 

Giovanni Batista Grassi (IT) and Raimondo Feletti (IT) discovered and described avian malaria (699; 700).

 

Thomas Henry Huxley (GB) and Theodor Wilhelm Engelmann (DE) suggested that muscle fibrils are the likely location for the contractile mechanism (543; 842).

 

Vittorio Mibelli (IT) described and named angiokeratoma as, "The presence of small red spots could be seen, which resembled telangiectases and were covered already by a slightly elevated and horny epidermis…. The external appearance of the small tumors suggested the diagnosis of keratome." (1115)

 

David Paul von Hansemann (DE) proposed the concept of anaplasia of cancer cells. This theory postulates that the increased growth potential of the cancer cell was accompanied by a loss of differentiation and that asymmetrical mitoses were a characteristic of cancer (1688). He described changes in the chromosomes of cancer cells (1689).

 

Franz König (DE) gave a detailed description of joint involvement in hemophilia (925).

 

Allvar Gullstrand (SE) presented his theory of astigmatism and elucidated how the eye accomplishes intracapsular accommodation (714-718).

 

Pierre Marie (FR) described hypertrophic osteoarthropathy (digital Hippocratism) as follows: “The volume of all the phalanges of the fingers are increased, but above all in the case of the phalangette. The nail is enlarged; it has the Hippocratic appearance of a parrot's beak” (1065).

 

Odilon Marc Lannelongue (FR) performed the first thyroid transplantation, for treatment of cretinism (964).

 

William Rose (GB) performed a Gasserian ganglionectomy for trigeminal neuralgia; the patient lived for at least two years (1375).

 

Ludwig Courvoisier (CH) did important work concerned surgery to the biliary tract. It was he who developed the operation of cholecystectomy and he was one of the first surgeons to remove a stone from the common bile duct. The well-known Courvoisier's law is named after him stating that 'if in the presence of jaundice, the gallbladder is palpable, then the jaundice is unlikely to be due a stone.' He in his book The Pathology and Surgery of the Gallbladder first proposed this (349).

 

Charles Alfred Ballance (GB) popularized the operation of radical mastoidectomy for advanced middle ear infection in 1890 (79). Ballance also demonstrated cranial base approaches to treat infectious thrombophlebitis of the petrosal, lateral, and cavernous sinus.

 

Themistocles Gluck (DE), during the 1880s, performed 14 total joint replacements; five of them were still in function in 1891: three total knee replacements, one elbow, and one wrist total replacement. All total joints were made from ivory. For their fixation inside the marrow cavity Gluck often used a special form of very hot "bone cement" that hardened within one minute (670; 671).

 

Robert Lawson Tait (GB) developed an operation for placenta praevia (placenta partially or wholly blocks the neck of the uterus at birth) (1568). Note: Edoardo Pòrro (IT) developed this operation contemporaneously.

 

J. Knowsly Thornton (GB) is credited with the first known successful operation to remove an adrenal cancer (adrenalectomy). His patient was a 36-year-old, very hirsute female who was found at operation to have a 20-pound left adrenal tumor (1604). Note: Adrenocortical carcinoma, also adrenal cortical carcinoma (ACC) and adrenal cortex cancer, is an aggressive cancer originating in the cortex (steroid hormone-producing tissue) of the adrenal gland.

 

Friedrich Trendelenburg (DE) described the Trendelenburg position for surgery as, “If one places the body of a patient on the operating table in such a way that the symphysis pubis forms the highest point of the trunk and the long axis of the trunk forms an angle of at least 45 degrees with the horizontal” (1616).

 

Sergei Sergeievich Korsakoff (RU) described a special form of psychic disorder, which occurs in conjunction with multiple neuritis. This disorder is now known as Korsakoff's psychosis (929; 1657).

 

Heinrich Sebastian Frenkel (CH) was an early practitioner of neuro-rehabilitation, advocating a regimen of special exercises for patients with neurological disorders. Beginning in 1885, he achieved great success with therapeutic exercises for cerebellar ataxia and tabetic ataxia (621).

 

The Brooklyn Institute of Arts and Science in New York established the Biological Laboratory at the southwest corner of Cold Spring Harbor, Long Island, NY. Charles B. Davenport (US) became its first director. In 1904, he persuaded Andrew Carnegie to found for him the Station for Experimental Evolution on the same site as the Biological Laboratory. Davenport became the director of both. The two were formally joined in 1962 as the Cold Spring Harbor Laboratory.

 

In the United States, the first sewage treatment plant using chemical precipitation was built in Worcester, Massachusetts (1103).

 

 

The journal Zentralblatt für Allgemeine Pathologie und Pathologische Anatomie was founded.

 

1891

Johannes Diderik van der Waals (NL) presented his equation of state for gases and liquids, which explains molecular behavior when a substance is composed of two species (1641).

 

Hermann Nordtmeyer (DE) introduced a new filtering medium made of the compressed infusorial (diatomaceous) earth known as Kieselguhr (1202).

 

Alfred Werner (DE) formulated a new approach to inorganic chemistry that allowed the formulation of atomic groups about a metal ion. As applied to heme, the theory led to the recognition that the ferrous iron is hexacoordinate, with four valencies satisfied by the nitrogens of the pyrroles of the porphyrin ring and the other two available for other interactions (e.g., with O2, CO, imidazole, pyridine) (887).

 

Lead arsenate insecticide was first used as an insecticide for control of the gypsy moth. Carbon bisulfide was first tested for control of wireworms. Creosote oil was discovered as an ovicide for gypsy moth (1478).

 

Ernst August Schulze (CH) discovered that the woody substances of plants contain polysaccharides (hemicelluloses and pentosans) which are much more readily hydrolyzed to sugars by very dilute mineral acids than is cellulose. Among the sugars formed in this way he detected galactose, mannose, and the pentose sugars, arabinose and xylose. He coined the term hemicellulose (1456).

 

Isidor Traube (DE) discovered that many organic solutes are adsorbed at a water/air interface, with the polar ends of molecules in the water and non-polar parts sticking out into the air (1615).

 

Karl Voit (DE) showed that fasting hens stored glycogen in their livers not only when they were supplied with glucose but also when sucrose, fructose, or maltose were in their diet in place of glucose (1664).

 

Hermann Henking (DE) observed an unpaired chromatin-element in spermatogenesis of Pyrrhocoris apterus (Hemiptera) so that sperms of two different types were produced, half with and half without this element. Henking did not realize that the element was a chromosome, nor did he associate it with sex. He called it x. He also demonstrated that reductive division begins with conjugation of chromosomes, two by two (769). This is the first indication for a connection between chromosomes and sex.

Johannes Rückert (DE) suggested that the conjugants had come one from each parent, and that they could exchange material (1398).

William Austin Cannon (US) based on his studies of cotton helped provide a cytological basis for the Mendelian laws (282).

 

Ernst Malachowski (PL) stained malarial parasites using borax methylene blue, which had polychromed because of its age (2-3 years). The plasmodial chromatin took on a red-purple color (1056).

Dimitri Leonidovich Romanowsky; Dimitri Leonidovich Romanovsk (RU) developed a stain which allowed for differential identification of blood parasites, including malaria (1371).

 

Paul Ehrlich (DE) selectively stained mast cells using a dye called dahlia (510).

 

Liberty Hyde Bailey, Jr. (US) published the first detailed study of the growth of plants under artificial light (76; 77).

 

Sigmund Exner (AT) explained how the compound eye functions, describing the compound eye physiology of insects and crustaceans (557).

 

Joseph F. Payne (GB) remarked on the infectious nature of warts (1272).

 

Merton B. Waite (US) discovered that bees and wasps are vectors of fire blight, a bacterial disease of pears and other orchard fruits (1720).

 

Pierre-Jean Achalme (FR) was the first to cultivate Clostridium perfringens. He incorrectly supposed it to cause articular rheumatism (9).

William Henry Welch (US) and George Henry Falkiner Nuttall (US-GB) isolated and characterized the same organism from the foamy organs of a cadaver, naming it Bacillus aerogenes capsalatus (1209).

Adolf Schenkl (CZ), Rudolf Ritter von Limbeck (CZ), Emanuel Zaufal (CZ), et al. used animal studies to verify that a gram-positive spore-forming rod-shaped microorganism that grew only under anaerobic conditions, was the etiologic agent of gas gangrene (1442). Note: this clinical entity is also called clostridial myonecrosis.

Eugen Fraenkel (DE) isolated this organism and designated it Bacillus phlegmonis emphysematosae (612). It has been called by various names including: Clostridium welchii, Clostridium perfringens (L. perfringens, breakthrough), and Fraenkel’s bacillus.

Alexander Thomas Glenny (IE), Mollie Barr (GB), Mona Llewellyn-Jones (GB), Thomas Dalling (GB), and Helen E. Ross (GB) discovered that the alpha toxin of Clostridium perfringens type A contains lethal, hemolytic, and necrotic activities (669).

Douglas K. McClean (GB) discovered and isolated hyaluronidase (spreading factor) from Clostridium perfringens (1087).

Leland S. McClung (US) found the Clostridium perfringens can cause food poisoning (1090).

Marjorie Griffen Macfarlane (GB) and John D. MacLennan (GB) isolated a collagenase (kappa toxin) from Clostridium perfringens (1040).

Cyril Leslie Oakley (GB), G. Harriet Warrack (GB), William E. van Heyningen (GB), and Marion E. Warren (GB) discovered that Clostridium welchii produces a collagenase, which they named the kappa toxin (1211; 1212).

Ethel Bidwell (GB) and William E. van Heyningen (GB) determined that the kappa exotoxin of Clostridium perfringens is a collagenase (169).

Marjorie Griffen Macfarlane (GB) identified the alpha toxin of Clostridium perfringens as the enzyme lecithinase C (1039).

Florence B. Roth (US) and Louis Pillemer (US) determined that of all the exotoxins produced by Clostridium perfringens the alpha exotoxin is the most damaging to humans (1380).

Gregory Juckett (US), Genevieve Bardwell (US), Bruce McClane (US), and Susan Brown (US) found that Clostridium perfringens is the common leavening agent in salt rising bread (877).

 

Paul Ehrlich (DE) during his studies of ricin from the castor bean and abrin from the Indian licorice seed showed that each of these vegetable poisons induces the production of an antitoxin, which is specific. He also discovered that there is always a delay (latent period) in the production of antitoxin following the administration of toxin. In mice this production did not begin to appear until the fifth day post-inoculation. It was in this article that Ehrlich coined the term antibody (511).

Paul Ehrlich (DE) pointed out that there is a difference between active and passive immunization. He injected mice with abrin, ricin, robin (a phytotoxin from locust tree bark), or tetanus poisons and showed that males highly immunized with abrin are incapable, when paired with normal females, of transmitting their immunity to their offspring, in other words the immunizing principle is not carried in the genes of the sperma. Female mice immunized before conception bore immune young, but the immunity was of a passive type in that it disappeared in a relatively short space of time. Further, the immunity was not transmitted in the next generation and was not truly hereditary. Investigating the matter still further, Ehrlich observed that immunity in the offspring of mice actively immunized against ricin lasted longer than the immunity of adult mice passively immunized with antitoxin. To test this further he took the young of the non-immunized mother and put them to the breast of an immunized mother and the young of the immunized mother and put them to the breast of a non-immunized mother. The result was conclusive. The young of the immunized mother lost their immunity while sucking the normal mother, whereas the young of the non-immune mother put to the breast of an immunized mouse rapidly developed an immunity, which must have been lactogenic (512; 513).

Rudolf Fischl (DE) and Gustav von Wunscheim (AT) found diphtheria antitoxin in fetal blood (585).

 

Heinrich Hermann Robert Koch (DE) made his much-awaited announcement of the composition of his remedy for tuberculosis. It was a simple culture extract, which was soon referred to as Koch’s Lymph and later became known as tuberculin (915).

 

Emil Adolf Behring (DE) and Shibasaburo Kitasato (JP) used their anti-diphtheria toxin to treat humans for the first time on Christmas night, 1891 (1763). The results were disappointing.

Alexander T. Glenny (GB), Barbara Hopkins (GB) and Gaston Ramon (FR) produced an effective toxoid vaccine to diphtheria. With subsequent improvements this became one of the most effective vaccines available in medicine. See, Glenny, Hopkins, and Ramon, 1923.

 

Sydney Arthur Monkton Copeman (GB) showed that glycerin acts as a germicide when added to the lymph used in vaccination. He demonstrated this at the London International Hygeine Congress of 1891 (340). Note: As glycerin came to be widely used, it reduced transmission of harmful microbes via the lymph. Vaccine lymph is the fluid and some particulate matter collected from the vesicles of vaccinia infection, and used for active immunization against smallpox.

 

Hans Adolf Eduard Driesch (DE) separated developing sea urchin embryos at the two-cell stage and found that each of the cells would form a complete, though small larva. He realized that if each half-egg forms a whole rather than a half-embryo, then an interaction must occur between the two cells to restrict their potentials in normal development. Driesch's theory of totipotency contradicted Wilhelm Roux's mosaic theory (459). Driesch went on to show that up to the four-cell stage separated blastomeres would develop into perfect embryos, each of reduced size (461).

 

Walter Heape (GB) was the first to achieve normal embryonic development and birth following the transfer of a fertilized ovum (zygote) from one female to the uterus of another variety of the same animal (rabbits) (759).

Gregory Goodwin Pincus (US) and Ernst Vincenz Enzmann (US) isolated a rabbit ovum, fertilized it in a watch glass then reimplanted it in a rabbit doe other than the one, which furnished the oocyte. A successful pregnancy was thus inaugurated in the unmated recipient (1302).

Min Chueh Chang (CN-US) demonstrated that ova from a black rabbit fertilized in vitro by capacitated sperm from a black male and transferred to a white female resulted in the birth of a litter of black young. This represents the first verified in vitro fertilization in which the resulting zygotes were brought to term (304).

Robert G. Edwards (GB), Barry D. Bavister (GB), Patrick Christopher Steptoe (GB), and Jean M. Purdy (GB) achieved in vitro fertilization of a human ovum, a technological advance that has revolutionized the treatment of human infertility (503-506; 1542; 1543).

Yves Menezo (FR) developed the world's first B2 culture medium; known as "the French medium" it reflected the follicular, tubal, and uterine environments of sheep, rabbits and humans (1100).

Louise Joy Brown (GB) the world’s first test tube baby (in vitro fertilization) was born in Oldham, Northern England, on July 25, 1978. Patrick Christopher Steptoe (GB) and Robert G. Edwards (GB) performed the operation (1542).

Mark E. Cohen (US) discussed some of the legal aspects attendant to the first successful human in vitro fertilization (IVF) and subsequent live birth of Louise Joy Brown (325).

Elizabeth Jordan Carr (US) was born December 1981, the first baby in the United States to be conceived using in vitro fertilization (IVF) and the 15th in the world. Howard Jones (US) and Georgeanna Seegar Jones (US) directed the process. Mason Andrews (US) delivered her (1563).

Andrea Laws-King (AU), Alan Trounson (AU), A. Henry Sathananthan (AU), and Ismail Kola (ZA) reported a technique that would revolutionize assisted reproductive technology and offer hope to couples where other infertility treatments had failed. The technique — referred to as SUZI (sub-zonal insertion)— involved the microinjection of sperm under the zona pellucida of human oocytes. Using preovulatory oocytes and spermatozoa that had undergone capacitation through chemical exposure, a single spermatozoon was microinjected into the perivitelline space. Of five out of seven oocytes fertilized, three went on to cleave and one reached the six-cell stage of cleavage (969).

The SUZI technique had profound implications for the treatment of severe male infertility, and offered hope to men with completely immotile, immature or abnormal spermatozoa. However, there were drawbacks. When the technique was used for treating infertility, multiple sperm were injected under the zona pellucida to increase the chance of fertilization. This increased the risk of polyspermy, a lethal condition when more than one sperm enters the oocyte.

Gianpiero Palermo (BE), Hubert Joris (BE), Paul Devroey (BE), and André C. Van Steirteghem (BE) obtained successful human pregnancies in three out of four couples that had previously been unsuccessful with SUZI and other in vitro techniques. Successful fertilization using the ICSI (intracytoplasmic sperm injection) method required the microinjection of just a single spermatozoon into the ooplasm of an oocyte, thereby bypassing spermatozoa binding and penetration into the zona pellucida and the fusion of sperm by the acrosome reaction (1248).

 

Trasaburo Araki (JP) and Hermann Zillessen (DE) found that if they interrupted oxygen supply to muscles in mammals and birds, lactic acid was formed and increased. This was the first demonstration of the relationship between tissue hypoxia and the formation of lactate (35-38; 1855).

 

William Maddock Bayliss (GB) and Ernest Henry Starling (GB) demonstrated a delay of about 0.13 seconds between atrial stimulation and ventricular depolarization (later called the PR interval) (124).

 

Paul Guttmann (DE) and Paul Ehrlich (DE) were the first to report the antimalarial properties of a synthetic, rather than a natural, material when they described the clinical cure of two patients after oral administration of a thiazine dye, methylene blue (720).

 

Luigi Luciani (IT) distinguished three stages of starvation in hunger of man, physiological inanition (exhaustion), and pathological inanition (1031).

 

George Redmayne Murray (GB) treated myxedema (hypothyroidism) successfully with typhoid extreact (1170).

 

John Benjamin Murphy (US) invented Murphy’s button, used to rapidly join the ends of a divided intestine. This devise revolutionized abdominal surgery (1166).

 

Luigi Luciani (IT-DE) proposed that the cerebellar region of the brain functions as a regulator of tonic and static motor activity. From his experimental results he assigned a generalized (unitary) refining role to the cerebellum such that it acts on voluntary movements initiated by higher centers (1030).

 

Friedrich Maass (DE) was the first to clinically describe closed-chest cardiopulmonary resuscitation (CPR). He resuscitated a teenager for 60 minutes with closed-chest cardiac massage in 1891 (with return of mental function) and described that the optimal technique was to apply forceful pressure and to do so at a rapid rate (1035).

William Bennett Kouwenhoven (US), William R. Milnor (US), G. Guy Knickerbocker (US), and William R. Chesnut (US) performed extensive closed chest defibrillation experiments in dogs (933).

Henry T. Bahnson (US), in 1958, resuscitated a two-year-old child whose heart was in ventricular fibrillation with the combined method of external cardiac compression and closed chest defibrillation (74).

 

Otto Bollinger (DE) described a delayed traumatic apoplexy he called traumatische Spät-Apoplexie. Today this condition is called delayed traumatic intracerebral hematoma or (DTICH) (194).

 

Heinrich Irenaeus Quincke (DE) introduced the lumbar puncture as a diagnostic and therapeutic technique; using it to accurately measure pressure at the beginning and the end of the procedure, measure protein and sugar values, and describe the low sugar occurring in the cerebrospinal fluid (CSF) in purulent meningitis. He diagnosed tuberculous meningitis by demonstrating tubercle bacilli in the CSF and was the first person to puncture the lateral ventricle to obtain CSF in infants with hydrocephalus (1326; 1328).

Walter Essex Wynter (GB) performed lumbar puncture to relieve spinal fluid pressure in four cases of tubercular meningitis (1834).

 

Ludwik Rydygier; Ludwig Anton Rydygier von Ruediger (PL-DE), in 1891, presented another new concept in urinary tract surgery, namely grafting the ends of a ureter damaged over a fairly long distance into the abdominal integuments and, in a second stage of the operation, making up the loss with a duct formed by a flap of skin. Ref

 

Berthold Earnest Hadra (US) introduced spine wiring to treat instability (723).

 

Marin-Théodore Tuffier (FR) used inhalational anesthesia administered under pressure to successfully remove the apex of a tuberculous lung; he even added an inflatable cuff around the tube inserted in the trachea to ensure a gas-tight fit (1621; 1622). Tuffier was ahead of his time.

Ivan Magill (GB) and Edgar Stanley Rowbotham (GB), working at Gillies' plastic-surgery unit, found their way back to the simplicity of the endotracheal tube and positive pressure (1050; 1393).

Ralph Milton Waters (US) perfected an apparatus for administering anesthetics. At one end is a mask which fits over the face of the patient, at the other is a rubber bag. Respiration can be controlled either by squeezing the anesthetic bag by hand or by using a small motor (1738; 1739).

 

Georg Avellis (DE) described Alvellis’ paralysis syndrome, a condition characterized by paralysis of the soft palate and vocal cords on one side and loss of pain sensation and temperature sense on the other side, including the extremities, trunk, and neck. It usually results from occlusion of the vertebral artery in lesions of the nucleus ambiguous and pyramidal tract. In the original description, the vagus and glossopharyngeal nerves were involved; concomitant involvement of the neighboring cranial nerves was observed later (58).

 

Guido Werdnig (AT) and Johann Hoffmann (DE) described an infantile familial form of progressive spinal muscular atrophy resulting from degeneration of the anterior horn cells of the spinal cord (Werdnig-Hoffmann syndrome) (807-809; 1761; 1762).

 

Alexandr Petrovich Karpinsky (RU) was trained as a geologist and became an expert paleontologist. From fossil remains of ammonids he was able to relate ontogenesis and phylogenesis of these animals to their historical development. He constructed a genealogical tree of the ammonids and thus determined their phylogenetic relationships (879; 881).

 

Deutsche Zeitschrift für Nervenheilkunde was founded.

 

Skandinavische Archiv fur Physiologie was founded. It became Acta Physiologica Scandinavica in 1939.

 

1892

"Even if I erred and the experiment threatened my life, I would look Death calmly in the eye, for it would not have been a frivolous suicide; I would die in the service of science like a soldier on the field of honor. Health and life are indeed very high earthly goods, but not after all the highest for human goods. Man, who wants to stand in a higher position than the animal, must be willing to sacrifice even life and health for higher, ideal goods." Max Josef von Pettenkofer (DE) referring to a famous experiment in which he drank a diluted culture of the cholera vibrio (906).

 

K. Bratuscheck (DE) was the first to study phase relations within the microscope (230).

Julius Rheinberg (GB) and Alexander Eugen Conrady (GB) obtained photographs of a fine grating with a phase-contrast microscope (337; 1356; 1357).

Fritz Zernicke (NL) explained the physical principles of phase-contrast microscopy (1851-1853). The 1934 article announced Fritz Zernicke's discovery of the phase contrast principle.

 

Lead arsenate was first proposed as an insecticidal spray for codling moth control. The first published results of the use of kerosene as means of mosquito control was made. This was the result of the accidental discovery made in 1867 following spilling of kerosene into a mosquito-infested watering trough while filling a lantern. The first record of dinitrophenols as insecticides was made in Germany (1478).

 

Harold Picton (GB) and S. Ernest Linder (GB) were the first to demonstrate electric charge directly when they measured the movement of colloidal particles, including hemoglobin molecules in solution, under the influence of an electric field. This was the origin of moving boundary electrophoresis (996; 1300).

William Bate Hardy (GB) studied the migration of egg white in an electrical field and found that under the influence of a constant current the albumin moves with the negative stream if the reaction of the fluid is alkaline, with the positive stream if the reaction is acid (743). A year later he discovered that proteins have an isoelectric point, a pH at which they lack a net charge and therefore will not migrate. He therefore appreciated that pH could have a profound effect on the net charge of a protein further noting that at the isoelectric point a protein tends to coagulate or precipitate (744).

Arne Vilhelm Kaurin Tiselius (SE), Stig Claesson (SE) and Paul König (AT) developed apparatus, which can effectively separate mixtures of proteins based on their electrophoretic mobility. Tiselius used a special tube arranged like a rectangular U within which the proteins could move and separate. Lenses were designed to detect changes in the index of refraction as protein concentration changed in the developing bands. It was by this method that blood proteins were first separated into albumin and globulin fractions. This technique is referred to as moving-boundary electrophoresis. König used filter paper as a stabilizing matrix for electrophoresis (926; 1606; 1608). See, Hardy, 1899.

Arne Vilhelm Kaurin Tiselius (SE) and Elvin Abraham Kabat (US) used electrophoresis to show that antibodies make up part of the gamma globulin fraction of serum. They also found that antibodies are not uniform in electrical charge or sedimentation characteristics. This was the first clue that antibodies are physically heterogeneous. The alpha, beta, and gamma notations were coined by Tiselius and first used in the 1937b article (1607; 1609).

 

Johann Friedrich Miescher, Jr. (CH), with remarkable insight, wrote his uncle and expressed his thoughts that nuclein might convey the hereditary message, "just as the words and concepts of all languages can find expression in 24-30 letters of the alphabet" (192).

 

Leo Lilienfeld (AT) coined the word nucleohistone to apply to material extractable with distilled water from leukocytes or minced thymus and precipitatable from the aqueous extracts with acetic acid (991; 992).

 

Martinus Willem Beijerinck (NL) published his work on tobacco mosaic disease, showing that the causal agent had many of the qualities associated with a living organism. He hypothesized that the agent must be incorporated into host cells before it could reproduce and that its reproduction was linked to the reproduction of the host cell. These papers along with those of Adolf Eduard Mayer (DE-NL), in 1886, and Dimitrii Iosifovich Ivanowsky; Dimitrii Iwanowski; Dimitrii Ivanovski; Dmitry Ivanovsky (RU), in 1892, and Erwin Baur (DE), in 1904, are considered to show the co-discoveries of plant diseases caused by filterable agents (viruses) (122; 139; 140; 143; 851-853; 1084; 1085). Note: Beijerinck is credited with being the first to call these infectious agents virus from the latin word for "toxin." He had first called them contagium vivum fluidum. Adolf Eduard Mayer (DE-NL) coined the name, tobacco mosiac disease (1083).

Friederich August Johannes Löffler (DE) and Paul Frosch (DE) demonstrated that the causative agent of foot-and-mouth disease of cattle could pass through a bacteriological filter. This paper represents the first evidence for the presence of animal pathogens, which we now call filterable viruses. They concluded "that the activity of the filtrate is not due to the presence in it of a soluble substance, but due to the presence of a causal agent capable of reproducing. This agent must then be obviously so small that the pores of a filter which will hold back the smallest bacterium will still allow it to pass… If it is confirmed by further studies … that the action of the filtrate … is actually due to the presence of such a minute living being, this brings up the thought that the causal agents of a large number of other infectious diseases … which up to now have been sought in vain, may also belong to this smallest group of organisms." (1017; 1018) Note: the first virus, the first vertebrate virus, the first picornavirus

Eugenio Centanni (IT), Ezio Savonuzzi (IT), Arnaldo Maggiora (IT), Gian Luoa Valenti (IT), Alois Lode (AT), and J. Gruber (AT) demonstrated the filterability (viral nature) of the etiological agent of fowl plague (300; 301; 1006; 1048). Note: the first orthomyxovirus

Arnaldo Maggiora (IT) and Gian Luoa Valenti (IT) concluded that the etiological agent of fowl plague behaved as a true virus (1049).

Émile Marchoux (FR) reported successful in vitro culture of the fowl plague virus (1061).

Vilhelm Ellermann (DK) and Oluf Bang (DK) showed that chicken leukosis, a form of leukemia and of lymphoma, was caused by a virus (533; 534). Note: The agents discovered by Ellermann and Bang are now known under the collective term avian leukosis virus or ALV. This is the first known example of a virus inducing cancer.

Werner Schafer (DE) determined that fowl plague (FP) virus is one of the influenza A viruses (1437).

 

Frederick Cooper Curtice (US) was widely scorned by his peers when he proposed the vector theory: that ticks could transmit a disease-causing agent to animals, including humans (381; 382; 1019).

Bulletin No. 1 of the Bureau of Animal Industry, issued in 1893, announced the momentous discovery that infection can be carried from one animal to another through the agency of an intermediate host the tick. The disease was Texas cattle fever also known as tick fever and southern cattle fever. Note: this was the first demonstration of arthropod transmission of disease. See, Theobald Smith, 1893.

 

Joseph Barcroft (GB) and John Scott Haldane (GB) designed a blood-gas manometric apparatus, which was modified by Thomas Gregor Brodie in 1910 and became known as the Warburg apparatus in honor of Otto Heinrich Warburg (DE). Warburg had devised a method for preparing thin slices of still-respiring tissue and measuring the uptake of oxygen by the decrease in pressure in a small flask, this decrease being determined by the change in level of a fluid in a thin U-shaped tube attached to the flask. Carbon dioxide was absorbed by a small well of alkaline solution within the flask. Such a Warburg manometer to which Warburg flasks were attached proved a powerful tool for studying respiration (100; 728-730; 1730).

Joseph Barcroft (GB) demonstrated that in the submaxillary gland oxygen consumption increased significantly during stimulation and continued even after the flow of saliva stopped (89-91).

Joseph Barcroft (GB), Thomas Gregor Brodie (GB), Ernest H. Starling (GB), Lewis E. Shore (GB), Francis Gotch (GB), and Walter E. Dixon (GB) also quantified tissue oxygen consumption in the kidney (95-97), pancreas (104), liver (103; 695) and heart (99). Note: These studies demonstrated for the first time several quantitative aspects of organ metabolism under various circumstances, and led to the concept of oxygen ‘debt’ in muscle and other tissues.

Joseph Barcroft (GB), John Scott Haldane (GB), Mario Camis (IT), M. Nagahashi (JP), F.F. Roberts (GB), Carl A. Binger (GB), Arlie V. Bock (GB), James Hamilton Doggart (GB), Henry S. Forbes (GB), Henry S. Harrop (GB), Jonathan C. Meakins (GB), Alfred C. Redfield (GB), Harold Whitridge Davies (GB), James Matthews Duncan Scott (GB), W.J. Duncan Fetter (GB), Cecil D. Murray (GB), and Arthur Keith (GB) characterized the properties of haemoglobin, exploring its affinity and reversible equilibrium with oxygen, thus defining the oxyhaemoglobin saturation [HbO2] curve, and its shift in response to changes in temperature, electrolytes, carbon dioxide and other factors (92-94; 98; 100-102).

 

Curt Herbst (DE) observed that the blastomeres of the cleaving sea urchin egg spontaneously separate from each other after a brief exposure to calcium-free seawater. This produced an elegant method for isolating undamaged blastomeres and for following their development independently (774).

 

Ludwig Edinger (DE) introduced the concept of centrally arising pains (498).

 

Lewis Erle Shore (GB) found that the tip of the human tongue is more sensitive to sweet, whereas the edges are more sensitive to sour, and the base of the tongue is most sensitive to bitter. The mid-dorsum was found to be insensitive to all tastes. All but the mid-dorsum are sensitive to salty (1498).

 

George Miller Sternberg (US) found that calves infected with vaccinia virus produced specific antibody, which could neutralization the virus (1546).

 

Dmitrii Iosifovich Ivanowski; Dmitrii Iosifovich Iwanowsky; Dmitrii Iosifovich Ivanovski (RU) demonstrated that the mosaic disease of tobacco (Nicotiana tabacum) could be transmitted by the juice from infected plants which had been passed through a filter that would stop bacteria (835; 851-853; 1085). Note: He is one of the co-discoverors of viruses.

 

Guiseppe Guarnieri (IT) observed homogenous acidophilic inclusion bodies, 2 to 10 millimicrons in size, in the cytoplasm of epithelial cells from patients with Variola (smallpox) (711). These structures are frequently referred to in the literature as Guarnieri bodies.

 

Richard Friedrich Johannes Pfeiffer (DE) isolated Haemophilus influenzae during the influenza pandemic of 1889 and erroneously thought that it was the causative agent of influenza, hence its name. This organism may have behaved synergistically with the virus to produce a more severe disease. It is sometimes called Pfeiffer’s bacillus (1291; 1293).

 

William Thompson Sedgwick (US) and John L. Batchelder (US) demonstrated the relationship of the bacterial count of milk to its sanitary quality (1468; 1469).

 

Roland Thaxter (US) first described the Myxobacteria (1582-1584).

 

Konstantin Wingradoff (RU) was the first to describe infections of Opisthorchis in humans (1810).

Hans Vogel (DE) discovered the snail and fish hosts and their roles in the life cycle of Opisthorchi (1663).

 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) presented his theory of cellular immunity. He noted that phagocytic cells protected invertebrates from some fungus infections and not from others. He predicted that abnormalities of the phagocytic cells would compromise host defenses. Metchnikoff indicates that phagocytes should be considered as an active participant of inflammation, and inflammation should not be seen only as being deleterious (1105; 1106).

 

Joseph Marcos Malbran (AR), in Argentina during 1892, discovered the first case of rhinosporidiosis when he examined a polyp from the nose. He regarded the infectious agent as a sporozoon (410).

Guillermo Seeber (AR) thought it was a protozoon when he described it (1470).

Roberto Johann Wernicke (AR) named it Coccidium seeberia after the protozoal subdivision Coccidia and his pupil, Guillermo Seeber (AR) (149).

Guillermo Seeber (AR) then renamed it Rhinosporidium seeberi (1470).

Roger A. Herr (US), Libero Ajello (US), John W. Taylor (US), Sarath N. Arseculeratne (LK) and Leonel Mendoza (CR-US) performed nucleic acid analysis on R. seeberi and found it to be the only microorganism that is classified in the class Mesomycetozoea and is pathogenic to mammals and birds (779). The class Mesomycetozoea includes a heterogeneous group of microorganisms that are at the animal-fungal boundary and consists of two orders, Dermocystida and Ichthyophonida.

 

Alejandro Posadas (AR) and Roberto Johann Wernicke (AR) found the tissue form of coccidioidomycosis in a patient in Argentina (1315; 1764; 1765).

William Ophüls (US) and Herbert C. Moffitt (US) demonstrated the mycotic nature of the infection (1218; 1219). The etiological agent was named Coccidioides immitis under the mistaken impression that it was a protozoan. The disease is usually an acute, benign, self-limiting, respiratory infection, which may occasionally become systemic and life threatening.

Robert A. Stewart (US), Karl Friedrich Meyer (CH-US), and Chester W. Emmons (US) demonstrated that the soil is a reservoir for Coccidioides immitis (538; 539; 1549).

Ernest Charles Dickson (US) offered proof that the inhalation of the fungal chlamydospores of Coccidioides immitis can lead to the disease variously called coccidioidomycosis, coccoidioidal granuloma, valley fever, or desert fever (432; 433).

Charles E. Smith (US) developed a skin test for detecting prior exposure to Coccidioides immitis. This permitted the determination of the endemic area for the fungus (1509).

 

Francis Galton (GB), a cousin to Charles Robert Darwin, was the first to suggest that fingerprints would be useful in tracing criminals (640; 641). Note: In ancient Babylon c. 1.9 k BCE, fingerprints were used on clay tablets for business transactions. Clay seals bearing friction ridge impressions were used during both the Qin and Han Dynasties (221 BC - 220 AD).

 

Julius Wolff (DE) stated, “the external form and internal architecture of a bone are related to the forces which act upon it.” This is known as Wolff’s Law (1819).

 

Johann von Mikulicz-Radecki (PL-AT) is generally credited with the first description of Sjögren’s syndrome. In 1892, he described a 42-year-old man with enlargement of the parotid and lacrimal glands associated with a round-cell infiltrate and acinar atrophy (1707).

 

Carl Ludwig Schleich (DE) was the first to demonstrate infiltration anesthesia (local anesthesia) on humans. He used dilute cocaine (1448).

 

Arnold Pick (CZ) did work on lobar cortical atrophy, which made him famous (Pick’s disease) (1299). This is a rare and fatal degenerative disease of the nervous system. Clinically there are major overlaps with Alzheimer's presenile dementia.

 

Sape Talma (NL) described acquired myotonia, a condition marked by prolonged contraction and spasm of muscles. Talma's disease usually develops in adult life after trauma, acute infection, or intoxication (1574).

 

Josef Albert Amann (DE) and Gotthard Schubert (DE) independently developed an operation used in cases of congenital absence of vagina, making an artificial vagina from the ampulla recti. Schubert created an artificial vagina using transplants from the anus and rectum (23; 1454).

 

William Stewart Halsted (US) performed the first successful ligation of the left subclavian artery (740).

 

William Arbuthnot Lane (GB) introduced mastoid drainage in purulent otitis media with specially designed chisels and gouges (956).

 

Clinton Hart Merriam (US) hypothesized that animals and plants are restricted in their northward distribution by the total quantity of heat during the season of growth and reproduction, and the mean temperature restricts their southward distribution during the hottest part of the year. This established life zones (1101; 1102).

 

Marie Eugène François Thomas Dubois (NL) found a fossil skullcap, teeth, and femur in the Javan town of Trinil. He insisted that these fossils belonged to the same type individual, a missing link between humans and apes. These finds were reported in the quarterly and annual reports to the Dutch East Indies government but not to the scientific community at large until 1920 (470-472). Opposition to his claim remained widespread and many doubted that the bones all belonged to the same individual. He adopted the name Anthropithecus erectus then changed it to Pithecanthropus, which had been coined earlier by the German zoologist Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel, calling his discoveries Pithecanthropus erectus (upright ape-man) (1591). This specimen of Homo erectus is commonly called Java man. Note: Estimated to be between 700 K and 1M years old, it was, at the time of its discovery, the oldest hominid fossils ever found, and it remains the type specimen for Homo erectus.

Davidson Black (CA) coined the name Sinanthropus pekinensis, for what was popularly called Peking man (182; 183). Note: Peking Man is a group of fossil specimens of Homo erectus, dated from roughly 750 K years ago.

Franz Weidenreich (DE-US) and Lucile Swan (DE) prepared the original reconstruction from the fossil remains of several different individuals found in the caves at Zhoukoudian, China (1753; 1754).

Pierre Teilhard de Chardin (FR), a Jesuit priest, also did early work on Peking man, a Homo erectus, also known as Pithecanthropus pekinenses and Sinanthropus pekinensis (1580; 1581).

Towikromo (ID) discovered another Homo erectus, Sangiran 17, in 1969 in Java, Indonesia. Sastrohamidjojo Sartono (ID) first described it as Pithecanthropus erectus in 1971 (1435). Modern paleontologists consider this Java man to be Homo erectus.

 

Andrew Taylor Still (US) founded the first school of osteopathy – the American School of Osteopathy (now A.T. Still University of the Health Sciences) in Kirksville, Missouri in 1892 (1620).

 

The American Psychological Association was formed.

 

1893

"The mother has supplied a hundred or thousand-fold more protoplasm to the fertilized egg-cell, competent for development, yet no greater portion of the hereditary properties than the father." Joseph Gottlieb Kölreuter (923)

 

August Karl Johann Valentin Köhler (DE) discovered the manipulation of light technique, which became known as "Köhler illumination" (920).

 

Adolf Pinner (DE) determined the structure of nicotine as known today (1304).

 

Nikolay A. Monteverde; Nikolai A. Monteverde (RU) isolated chlorophyll crystals and determined their spectroscopic properties (1145).

 

Karl Wilhelm von Nägeli (CH) coined the phrase oligodynamic action to describe the antimicrobial activity of microgram quantities of silver ions (1710).

 

Ferdinand Blum (DE) originated tissue fixation with formaldehyde (188).

 

Wilhelm August Oskar Hertwig (DE) centrifuged frog eggs and demonstrated the effect of yolk distribution on cleavage (786).

 

Francisco Sanfelice (IT) found that nontoxic “pseudotetanus” clostridia when inoculated into filtrates of the anaerobic spore forming Clostridium tetani became toxicogenic, the acquired toxicity persisting for several transfers (1433). This change could possibly be attributed to the transforming factor (DNA) or the presence of lysogenic phage.

 

Bartolomeo Camillo Emilio Golgi (IT) described the anatomy of an area of the midbrain considered to be the nucleus of the trigeminal nerve and the trochlear (682; 686).

 

Bartolomeo Camillo Emilio Golgi (IT) described the histology of the peptic glands, including the discovery of a system of canaliculi in the parietal cells of the glands (683; 687).

 

Bartolomeo Camillo Emilio Golgi (IT) described perineuronal nets (PNN) enwrapping the cell bodies and proximal dendrites of certain neurons in the adult mammalian central nervous system and suggested that they represent a supportive and protective scaffolding (682; 684).

Antonio Bertolotto (IT), Gabriella Rocca (IT), Davide Schiffer (IT), Amico Bignami (US), George Perides (US), Firoz Rahemtulla (US), Marco R. Celio (CH), Ruth Chiquet-Ehrismann (CH), and Shinobu C. Fujita (JP) showed that perineuronal nets consist of an accumulation of at least three classes of substances: hyaluronan, glycoproteins and proteoglycans (162; 176; 298; 634).

Kimberly E. Dow (CA), S. E. Mirski (CA), John C. Roder (CA), Richard J. Riopelle (CA), Richard Asher (US) and Amico Bignami (US) reported that hyaluronan, glycoproteins and proteoglycans are produced by glial cells (48; 452).

Aurea Guimaraes (US), Sam Zaremba (US), Susan Hockfield (US), Robert G. Kalb (US), and Hugh J.L. Fryer (US) found that the formation of PNNs occurs during early postnatal development and coincides with the maturation of synapses and closure of critical periods (713; 802).

Kate E. Rhodes (GB), James W. Fawcett (GB) reported that closure of the critical period in both visual and somatosensory systems is dependent upon normal sensory stimulation during a discrete developmental timeline. The absence of an appropriate experience required to form appropriate neuronal synapses during this developmental window may lead to the formation of incorrect neural connections (1358).

Marine Beurdeley (FR), Julien Spatazza (FR), Henry H. C. Lee (US), Sayaka Sugiyama (US), Clémence Bernard (FR), Ariel A. Di Nardo (FR), Takao K. Hensch (FR), and Alain Prochiantzrecent (FR) noted that changes in the composition of chondroitin sulfate proteoglycans (CSPGs) seem to regulate the maturation of synapses (166).

Ciro De Luca (IT), Michele Papa (IT), Barbara A. Sorg (US), Sabina Berretta (US), Jordan M. Blacktop (US), James W. Fawcett (GB), Hiroshi Kitagawa (JP), Jessica C.F. Kwok (GB), Marta Miquel (ES), Wolfgang Härtig (DE), Simon Appel (DE), Anne Suttkus (DE), Jens Grosche (DE), and Dominik Michalski (DE) provided evidence suggesting that perineuronal nets are altered in various neurodevelopmental and neurodegenerative disorders associated with changes in brain activity (409; 748; 1524).

Jon R. Backstrom (US),Giselle P. Lim (US),Michael J. Cullen (US),and Zoltán A. Tökés (US), Stefan Lorenzl (US), David S. Albers (US), Norman Relkin (US), Terry Ngyuen (US), Sarah L. Hilgenberg (US), Jason Chirichigno (US), Merit E. Cudkowicz (US), M. Flint Beala (US), Janusz K. Rybakowski (PL), Maria Skibinska (PL), Pawel Kapelski (PL), Leszek Kaczmarek (PL), Joanna Hauser (PL), Gyung W. Kim (KR), Hyun-Jeong Kim (KR), Kyoung-Joo Cho (KR), Hyun-Woo Kim (KR), Yang-Je Cho (KR), Byung I. Lee (KR), Haoqian Zhang (US), Mayland Chang (US), Christopher N. Hansen (US), D. Michele Basso (US), Linda J. Noble-Haeusslein (US), Hidenaga Yamamori (JP), Ryota Hashimoto (JP), Tamaki Ishima (JP), Fukuko Kishi (JP), Yuka Yasuda (JP), Kazutaka Ohi (JP), Michiko Fujimoto (JP), Satomi Umeda-Yano (JP), Akira Ito (JP), Kenji Hashimoto (JP), Masatoshi Takeda (JP), Jialing Liu (US), Yongting Wang (CN), Yosuke Akamatsu (JP-US), Chih Cheng Lee (US), R. Anne Stetler (US), Michael T. Lawton (US), Guo-Yuan Yang (CN), Elyse K. Rankin-Gee (US), Paulette A. McRae (US), Esther Baranov (US), Stephanie Rogers (US), Luke Wandrey (US), Brenda E. Porter (US), Katarzyna Lepeta (PL), Katarzyna J. Purzycka (PL), Katarzyna Pachulska-Wieczorek (PL), Marina Mitjans (DE), Martin Begemann (DE), Behnam Vafadari (PL), Krystian Bijata (PL), Ryszard W. Adamiak (PL), Hannelore Ehrenreich (DE), Magdalena Dziembowska (PL), and Leszek Kaczmarek (PL) found that a number of central nervous system diseases exhibit dysregulated expression of enzymes necessary for perineuronal net cleavage and reorganization (73; 901; 980; 1001; 1024; 1339; 1409; 1839; 1854). Note: Like the perineuronal net (PNN), the perinodal extracellular matrix (ECM) surrounds the axonal nodes of Ranvier and appears as myelination is completed, acting as an ion-diffusion barrier that affects axonal conduction speed.

 

Ralph Stockman (GB) refuted the idea that only organic iron is useful in treating anemia. He demonstrated that inorganic iron has great value as a nutrient (1555).

 

Jean Baptiste Emile Vidal (FR) was likely the first to successfully transmit Herpes fibrilis from one human to another (1658).

Jean Baptiste Emile Vidal (FR) reported human-to-human transmission of Herpes simplex virus infections, identifying the necessity of intimate human contact for spread of infection (1659; 1788).

A. Lowenstein (DE) performed experimental transmission of Herpes simplex virus type 1 (HSV-1) from human lesions to rabbit corneas (1027). This work supported the proposal put forth in 1893 by Jean Baptiste Emile Vidal (FR) that person-to-person transmission could result in the spread of cold sores caused by HSV.

 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR), Pierre Paul Emile Roux (FR), Alexandre Taurelli-Salimbeni (IT), and Brau et Denier (FR) concluded from their experiments that the cholera vibrio produces a soluble exotoxin which, by injection, can be used to produce an antitoxin (553; 1107-1110).

 

Friedrich August Ferdinand Christian Went (NL) was the first to describe the fungal infection of sugar cane, which became known as Red Rot of the Stem (1760). He was also the first to describe the fungus that produced the disease, Colletotrichum falcatum.

 

August Paul Wassermann (DE) was able to vaccinate guinea pigs against the intraperitoneal infection with living cholera bacilli. To achieve this, he found that cholera vibrios or their body substance must be injected in such doses that a mild specific illness, a general reaction, follows (1737).

 

Pierre Paul Émile Roux (FR) and Louis Vaillard (FR) demonstrated that antitoxin is something created or newly produced in the body because of the injection of toxin. The antitoxin (antibody) was found not to appear immediately after the injection of the toxin (antigen) (1386).

 

Wilhelm August Oskar Hertwig (DE) obtained twin embryos in the newt by constricting the egg by means of fine ligatures (784).

Hermann Endres (DE), Amedeo Herlitzka (IT) and Hans Spemann (DE) confirmed and extended his results with very similar experiments (540; 541; 776-778; 1526-1528).

 

Wilhelm August Oskar Hertwig (DE) proposed that all cells in an animal embryo receive the same number of chromosomes (785).

 

Wilhelm August Oskar Hertwig (DE) wrote Die Zelle und die Gewebe in which he clearly distinguished histology as the science of tissues from cytology as the science of cell structure and function. Cytology as a field of study dates from this work (787).

 

Charles Reid Barnes (US) proposed that the biological process for synthesis of complex carbon compounds out of carbonic acid, in the presence of chlorophyll, under the influence of light should be designated as either photosyntax or photosynthesis. He preferred the word photosyntax, but photosynthesis came into common usage as the term of choice (105).

 

Edmund Beecher Wilson (US) and Albert Prescott Mathews (US) were able to show that triploblastic animals (those having three germ layers) fall into two large groups in terms of the mode of mesodermal formation. One group, including annelids, arthropods, and molluscs, shows the spiral or mosaic pattern he had observed in the earthworm. See Edmund Beecher Wilson, 1880. The other group, including the echinoderms, primitive chordates, and invertebrates, shows a pattern called radial in which the mesoderm originates from pouches in the endoderm of the gastrula (1799; 1800; 1802; 1804).

 

Alexander Stanislavovic Dogiel (RU) described bulb-type nerve endings (444; 445).

 

Gustave-Édouard Laguesse (FR) named the small cellular clusters of the pancreas the "Islets of Langerhans", in honor of their discoverer Paul Langerhans, Jr. (DE) and postulated that the Islets of Langerhans produced secretions that played a regulatory role in digestion. In the 1893 paper he coined the term "endocrine" for the first time; to distinguish their function from that of the exocrine acinar cells (950-952).

 

Edouard Brissaud (FR) produced an atlas of the human brain drawn completely by hand (242).

 

Joseph Jules Déjérine (CH-FR) and Jules Sottas (FR) described Déjérine-Sottas disease (hypertrophic progressive interstitial neuritis) (418). It is believed to be an autosomal dominant trait.

 

Luigi Luciani (IT) succeeded in keeping dogs alive after total extirpation of the cerebellum and initiated the modern study of cerebellar function (1032).

 

Pierre Marie (FR) described hereditary cerebellar ataxia (1066).

 

Heinrich Irenaeus Quincke (DE) recognized the syndrome of meningitis serosa (1327).

 

Paul Emil Flechsig (DE), in 1893, embarked on the study of myelogenesis in the brain hemispheres and supplemented his myelogenetic findings with clinical observations and data from degeneration experiments. He very precisely traced neuronal projections to the visual cortex from areas such as the lateral geniculate nucleus, then reported that the fibers from the medial geniculate body to the temporal lobe are concerned with hearing (589-591; 593-597).

Paul Emil Flechsig (DE) outlined the auditory radiation (592) and could list twelve cortical areas that are myelinated – and therefore functional before birth – as well as twenty-four in which myelinization occurs after birth; these he arranged chronologically according to the time course of myelinization.

 

William Alvin Macewen (GB) recorded 25 cases of brain abscess. Nineteen of these patients came to his attention in time to undergo surgery, resulting in 18 recoveries. All five of his patients with extradural abscess recovered; at that time most, other surgeons had 100 percent mortality rates for this condition (1037). Note: His achievement remained unequaled until the discovery of penicillin.

 

Willem Einthoven (NL) initiated electrocardiology when he began to explore the use of the capillary electrometer to record minute electrical currents. In 1895, he was able to detect recognizable waves, which he labeled “P, Q, R, S, and T.” The limitations of capillary electrometers led Einthoven to develop the first-string galvanometer. This consisted of a delicate conducting string stretched across a magnetic field. A current flowing through the thread would cause it to deviate at right angles to the magnetic lines of force, the extent of deviation being proportional to the strength of the current. The sensitivity of this instrument meant that it could be used to detect and measure the varying electrical potentials of the heart, i.e., an electrocardiograph. It was subsequently applied to the taking of electroencephalograms (graphs). With his new technique, he standardized the tracings and formulated the concept of “Einthoven’s triangle” by mathematically relating the 3 leads (Lead III = Lead II – Lead I). He described bigeminy, complete heart block, “P mitrale,” right and left and ventricular hypertrophy, atrial fibrillation and flutter, the U wave, and examples of various heart diseases. It was Einthoven who introduced the term electrocardiogram and used the abbreviation ‘EKG’ (339; 523-528; 530; 1520). See, Waller, 1887.

Willem Einthoven (NL) documented his clinical use of the electrocardiogram (529).

Why PQRST and not ABCDE? The four deflections prior to the correction formula were labeled ABCD and the 5 derived deflections were labeled PQRST. The choice of P is a mathematical convention by using letters from the second half of the alphabet. N has other meanings in mathematics and O is used for the origin of the Cartesian coordinates. In fact, Einthoven used O ... X to mark the timeline on his diagrams. P is simply the next letter. A lot of work had been undertaken to reveal the true electrical waveform of the ECG by eliminating the damping effect of the moving parts in the amplifiers and using correction formulae. If you look at the diagram in Einthoven's 1895 paper, you will see how close it is to the string galvanometer recordings and the electrocardiograms we see today. The image of the PQRST diagram may have been striking enough to be adopted by the researchers as a true representation of the underlying form. It would have then been logical to continue the same naming convention when the more advanced string galvanometer started creating electrocardiograms a few years later.

Willem Einthoven (NL), George Fahr (NL), and Alfred de Waart (NL) described the Einthoven triangle as the basis for calculations of electrocardiograms (531; 532).

Max Cremer (DE) introduced esophageal electrocardiography when he passed an electrode down the throat of a professional sword swallower. This technique allows for analysis of atrial stress, ectopic impulse formation, and conduction abnormalities (357).

Charles C. Wolferth (US) and Francis Clark Wood (US) introduced the use of chest leads to electrocardiography (1818).

Frank N. Wilson (US), Franklin D. Johnston (US), A. Garrard MacLeod (US), and Paul S. Barker (US) introduced unipolar chest wall leads for the electrocardiogram (1805).

Fritz Makiri Schellong (DE), S. Heller (DE), and E. Schwingel (DE) introduced vector electrocardiography (1440).

H. Frank Macinnis (CA) and Norman Jefferis Holter (US) independently applied bioelectrical signal telemetry to continuous ECG recording (818; 819; 1043). Norman Jefferis Holter (US) and Joseph Anthony Gengerelli (US) had invented bioelectrical signal telemetry (820).

Emanuel Goldberger (US) introduced the unipolar extremity electrode system (673).

Ernest Frank (US) designed the corrected orthogonal lead system (615).

Paul Puech (FR), in 1957, was he first to demonstrate electrical potentials coming from the bundle of His. This occurred during a catheterization of a patient with tetralogy of Fallot (1322).

Gaston Giraud (FR), Paul Puech (FR), Hugues Latour (FR), and Jean Hertault (FR) developed intracardiac leads (668).

Dirk Durrer (NL), Leo Schoo (NL), Reinier M. Schuilenburg (NL), Hein Joan Joost Wellens (NL) and Jan P. Roos (NL) introduced electrical stimulation of the heart as a diagnostic tool in cardiology. Their epicardial mapping allowed intraoperative identification of accessory pathways in the human heart (485; 486; 662).

Benjamin J. Scherlag (US), Sun H. Lau (US), Richard H. Helfant (US), Walter D. Berkowitz (US), Emmanuel Stein (US), and Anthony N. Damato (US) developed a catheter technique for recording His bundle activity in man (1443).

Hein Joan Joost Wellens (NL), Reinier M. Schuilenburg (NL), and Dirk Durrer (NL) described the mechanism of reentry tachycardia. They founded the modern era of tachycardia management concerning atrial and ventricular arrhythmias (1757).

Guy Fontaine (FR), Robert Frank (FR), Gerard Guiraudon (FR), Jacques Vedel (FR), Yves Grosgogeat (FR), and Christian Cabrol (FR) devised a method of depicting ventricular late potentials in patients with ventricular tachycardia. It is believed that late potentials arise in the peripheral zones of old myocardial infarcts and can be demonstrated in patients with a tendency toward ventricular tachycardia originating in the area immediately surrounding the old infarct location (602).

 

Friedrich Müller (DE) demonstrated that exophthalmic goitre is accompanied by an increased metabolism (1164).

 

Aleksei Yakovlievich Kozhevnikov (RU) reported a mild continuous epilepsia characterized by almost continuous, rhythmic muscular contractions affecting a limited part of the body for a period of hours, days, or even years (934; 935). It is called Kozhevnikov’s syndrome I.

 

Adam Politzer (AT) was the first to describe otosclerosis as a specific disease fixating the stapes (1309; 1310).

 

George Ryerson Fowler (US) performed the first known thoracoplasty (609). Thoracoplasty is the surgical removal of ribs to gain access during surgery or to collapse the chest wall.

 

Charles Barrett Lockwood (GB) devised an operation for radical repair of femoral and inguinal hernia (1005).

 

César Roux (CH), in 1893, performed reconstruction of the esophagus with a part of the jejunum translocated to the anterior part of the thorax (1382).

Ludwik Rydygier; Ludwig Anton Rydygier von Ruediger (PL-DE) was the second man to perform this operation. Ref for Rydygier

 

In 1893, the first large recorded outbreak of polio in the U.S. began in Boston, and spread into New England, particularly Vermont. Of 132 cases documented in Vermont, there were 18 deaths and 30 victims left with permanent paralysis (921). Note: The contagious nature of polio would be established in 1905.

 

Vladimir Mikhailovich Bekhterev (RU), Adolf Strümpell (DE), and Pierre Marie (FR) were the first to give adequate descriptions which permitted an accurate diagnosis of ankylosing spondylitis (AS) prior to severe spinal deformity. AS is also known as Bekhterev Disease, Bechterew's Disease or Marie–Strümpell Disease (145; 146; 1067; 1561). Note: AS is believed to involve a combination of genetic and environmental factors. More than 90% of those affected have a specific human leukocyte antigen known as the HLA-B27 antigen.The underlying mechanism is believed to be autoimmune or autoinflammatory (1487; 1512).

 

Josef Breuer (DE) and Sigmund Freud (CZ-AT) discovered the subconscious mind and introduced psychoanalysis using hypnosis and free-association (235; 236).

Josef Breuer (AT), in 1881, discovered what was called the "talking cure" (Kaminfagen). A particular female patient obtained some relief from psychotic symptoms if he could persuade her to talk about her hallucinations during her autohypnoses. He found that if he could persuade her to recall in reverse chronological order each past occurrence of a specific symptom, until she reached the very first occasion, most of them disappeared in the same way (872).

 

 Louis Antoine Marie Joseph Dollo (FR-BE) proposed that evolution never repeats itself, i.e., it is irreversible. This became known as Dollo’s law. Darwin's natural selection does not necessarily prescribe progress or regression, does not imply a direction of evolution in time, it only states an environmental constraint. Indirectly, Dollo's law does: it prescribes a trend towards more and more complex, and more and more ordered, living structures. Dollo's law expresses the visible fact that reproduction, ontogeny and phylogeny are biological organizations whose behavior is irreversible: both during growth and during evolution, entropy of biological information constantly increases. We evolved from bacteria to humans; we grew from children to adults (448-451).

Rachel Collin (US), Roberto Cipriani (VE), Michael F. Whiting (US), Sven Bradler (DE), and Taylor Maxwell (US) presented evidence that there may be exceptions to Dollo’s law (331; 1775).

 

The Index Kewensis was founded. It is a publication that aims to register all botanical names for seed plants at the rank of species and genera. It later came to include names of taxonomic families and ranks below that of species. The Index is maintained by the Royal Botanic Gardens at Kew in London, England.

 

1894

"The restricted action of the enzymes on glucosides could be explained by the assumption that only in the case of similar geometrical structure can the molecules approach each other sufficiently closely to initiate a chemical action. To use a metaphor, I would like to say that enzyme and glucoside have to fit together like lock and key in order to exert a chemical effect on each other." Hermann Emil Fischer (577)

 

"The students of adaptation forget that even on the strictest application of the theory of selection it is unnecessary to suppose that every part of an animal has, and everything which it does, is useful and for its good. We, animals, live not only by virtue of, but in spite of what we are." William Bateson (110)

 

Arvid Gustaf Högbom (SE) suggested an internal source for our atmosphere because of gradual, episodic, or rapid volcanic outgassing and weathering (816).

Steffen L. Thomsen (DE), Claude J. Allègre (FR), Thomas Staudacher (FR), and Philippe Sarda (FR) determined that early catastrophic outgassing occurred on the young Earth (20; 1594). This would have released significant amounts of nitrogen, carbon dioxide, carbon monoxide, methane, water, hydrogen, sulfur dioxide, and hydrogen sulfide.

 

Georg Bredig (DE) described what he called an inner salt because it existed as a molecule containing both positive and negative charges (233).

Friedrich Wilhelm Küster (DE), while working with methyl orange, coined the name zwitterion for molecules carrying opposite charges (948). Bredig accepted this name and pointed out that amino acids also form zwitterions (234).

Karl Ludwig Winkelblech (DE) proposed that simple amino acids in their state of neutrality are dipolar ions (1808).

Elliot Quincy Adams (US) suggested that amino acids are zwitterions at their isoelectric pH (14).

Niels Janniksen Bjerrum (DK) used the strength constants of acids and bases to study the dissociation of other compounds. He also demonstrated that amino acids in their isoelectric state are not uncharged molecules but are zwitterionen (dipolar ions) (Bjerrum 1923) (181).

Hans Hermann Weber (DE) was the first to show by direct demonstration that isoelectric proteins are zwitterions truly bristling with charges (+ and – in equal number) (1746; 1747).

 

Wilhelm Friedrich Ostwald (LV-DE) postulated that enzymes acting as catalysts speed up both directions of reversible reactions. He pointed out that the theories of Josiah Willard Gibbs (US) made it necessary to assume that catalysts hasten a reaction without altering the energy relationships of the substances involved. To Ostwald catalysts could not alter the free energy relationships. It cannot make a reactin go, that would not go without it—though it can make a reaction go rapidly that in its absence would proceed with only imperceptible speed (1230). Ostwald is generally believed to be the first to understand the nature of catalytic reactions. See, Ostwald 1874

 

Hermann Emil Fischer (DE) and Paul Lindner (DE) found that cane sugar, alpha-methylglucoside, is hydrolyzed by invertin (alpha-glycosidase), extracted from dried yeast, but not by emulsin, whereas beta-methylglucoside is cleaved by emulsin but not invertin. He concluded, "…I will say that the enzyme and the glucoside have to adapt with each other like a key in a lock ('Schloss und Schlüssel') to carry out a chemical action one on the other…. The finding that the activity of enzymes is limited by molecular geometry to so marked a degree should be of some use for physiological research." This is Fischer’s famous lock-and-key hypothesis explaining enzyme specificity (577; 584).

 

Jokichi Takamine (JP-US) isolated a starch-hydrolyzing diastase from rice (Oryza sativa). In 1894, Takamine applied for, and was granted, a patent titled "Process of Making Diastatic Enzyme" the first patent on a microbial enzyme in the United States. Takamine developed his diastase from koji, a fungus used in the manufacture of soy sauce and miso. Its Latin name is Aspergillus oryzae (1570). Note: Takamine became a wealthy business man who funded the gift of the cherry trees from the Mayor of Tokyo to Washington, DC, where they still adorn the Tidal Basin.

 

Olaf Hammarsten (SE) isolated beta-nucleoprotein from ox pancreatic nucleoprotein (742).

Ivar Christian Bang (SE) prepared guanylic acid from Hammarsten’s beta-nucleoprotein, then elucidated its structure as a compound of guanine, pentose, and phosphoric acid in equimolar proportions (81).

 

August Gürber (DE) crystallized horse serum albumin (719).

 

Franz Nissl (DE) developed a staining procedure, which shows Nissl's substance (extranuclear RNA) in the nerve cells. These Nissl’s granules or Nissl’s bodies are found in the cell bodies and dendrites of neurons, but absent from axons. They are concerned with protein synthesis and metabolism; their condition varies with physiological and pathological conditions (1195; 1196).

 

Arsenite of copper was discovered to be an insecticide (1478).

 

Giulio Cesare Bizzozero (IT) noticed a link between mitosis and regenerative capacity. He divided mitotic cells into three categories: 1) labile cells which demonstrate mitosis throughout life, e.g., bone marrow, 2) stable cells in which spontaneous mitotic activity is uncommon following birth, e.g., connective tissue, and 3) permanent cells which are mitotic in adulthood but do not regenerate, e.g., striated muscle (180).

 

Martin Heidenhain (DE) coined the term telophase as it applies to cell division (763).

 

Hans Adolf Eduard Driesch (DE) theorized that all cell nuclei of an organism are equipotential but vary in their activity in accordance with the differentiation of tissues (460).

 

Emil Friedrich August Walter Migula (DE) described bacteria as belonging to two major divisions, the Eubacteria (true bacteria) and the Thiobacteria (sulfur bacteria). The first group contained bacteria that were nonnucleated and colorless; the second group contained nonnucleated cells that had granules of sulfur or a bacterial pigment (1119).

 

Martinus Willem Beijerinck (NL) was the first to isolate a bacterium capable of reducing sulfates, Spirillum desulfuricans (Desulfovibrio desulfuricans) (138).

 

Shibasaburo Kitasato (JP) and Alexandre Émile Jean Yersin (CH) independently discovered the plague bacillus, later named Yersinia pestis (907-909; 1841; 1842).

 

Joseph Denys (BE) and Jules Havet (BE) found that dogs’ serum is less bactericidal than dogs’ whole blood. Working with Bacillus coli, Bacillus subtilis, and Staphylococcus they found that the leukocytes play a fundamental part, for when they are removed the plasma is robbed of a considerable part of its bactericidal properties. Microscopic examination of the blood showed all stages of phagocytosis. This was the first demonstration that phagocytosis was enhanced by the presence of immune serum (423). Quoting Joseph Denys (BE) and Joseph Leclef (BE), "In vaccinated rabbit, leukocytes get from sera their power to engulf and destroy Streptococcus pyogenes." (424)

 

Angelo Ruffini (IT), using gold chloride as a stain, described encapsulated nerve endings that respond to warmth. These later became known as Ruffini corpuscles (1399-1401).

 

William Bateson (GB) emphasized the importance of discontinuous variations, foreshadowing the rediscovery of Mendel's work. In this work he conjectured that all organisms are made from an orderly series of parts or segments, and coined the term homeosis for it (110; 111).

 

Edmund Faustyn Biernacki (PL) noted the increased sedimentation rate of blood from ill individuals and realized that it was due to the presence of fibrinogen (175).

Robert Sanno Fåhraeus (SE) furthered Biernacki's work. His initial motivation to study the erythrocyte sedimentation rate (ESR) was as a pregnancy test but his interest expanded to the study of the ESR in disease states (562-564).

Alf Vilhelm Albertsson Westergren (SE) refined the technique of performing the erythrocyte sedimentation rate (ESR) and reported its usefulness in determining the prognosis of patients with tuberculosis (1771).

 

Frederick George Novy (US) isolated the bacterium he called Bacillus oedematis maligni during his study of malignant edema in guinea pigs (1204). It was named Bacillus novyi by Walter Migula in 1900. It now bears the name Clostridium novyi and is one of the important causes of gas gangrene.

 

William Hallock Park (US) and Alfred L. Beebe (US) demonstrated that there are well individuals who are carriers of diphtheria (1262; 1263).

 

Richard Friedrich Johannes Pfeiffer (DE) and Vasily Isayevich Isayev; Vassilii Issaevicj Issaev (last name also spelled Issaeff) (RU) began their classic researches which showed that the destruction of the cholera vibrio takes place by a kind of dissolution which they called bacteriolysis. Cholera vibrios were destroyed in vitro in the serum of animals immunized against cholera, and the same effect took place in the peritoneal cavity of the living animal. By an ingenious and simple technique, they showed that in the normal peritoneal cavity vibrios multiply rapidly, whereas in the immunized animal they disappear. They removed drops of peritoneal fluid by means of capillary pipettes and found in the case of the immune animal that cholera vibrios, which had been injected, were almost instantly rendered motionless and swollen. They then changed into micrococcus like bodies which became more and more difficult to see and ultimately, they disappeared altogether. This process of lysis occupied about 20 minutes and was apparently independent of any cellular intervention. They showed that the serum also acts in vitro but its activity is abolished by dilution or heat at 60°C. The solution or lysis of vibrios in the peritoneal cavity of an immunized animal is spoken of as Pfeiffer’s phenomenon, and is, as they showed, highly specific in that vibrios closely related to Vibrio cholerae are not destroyed by cholera serum. They also observed that cholera immunity could be passively transmitted, for when anti-cholera serum from an immunized guinea-pig was injected into the peritoneum of a normal guinea-pig cholera vibrios subsequently introduced into the latter underwent the characteristic bacteriolysis (849; 1294; 1295).

 

Jakob Eriksson (DE) was the first to describe physiological races of fungal rusts (548).

 

Pierre-Augustin Dangeard (FR) discovered sexual reproduction in the Basidiomycetes and Ascomycetes (396-399).

 

Henry Horatio Dixon (IE) and John Joly (IE) proposed the cohesion or tension-cohesion theory as an explanation for how water (sap) rises in a tree (438-442).

Eugen Askenasy (DE) made a very similar proposal only one year later (49). The most important common feature to both sets of papers was the identification of the cell walls of parenchyma cells, whether living or dead, as the sites where surface tensions develop due to the transpiration of water. Both papers emphasized that a moist cell wall is impermeable to air, so that even at negative pressures air cannot be sucked into conducting elements.

 

Raymond Jacques Adrien Sabouraud (FR) made mycological and clinical studies of fungi which attack the hair, in man and other animals—the so-called tineas, ringworms, favus, and so on (1420-1422).

 

Theodor Wilhelm Engelmann (DE) was able to prove that oxygen is generated by chloroplasts by varying the points of illumination and recording the distribution of bacteria near the chloroplasts (542).

 

Ramón y Cajal (ES) discovered a nerve-fiber bundle between the hypothalamus and the pituitary gland in the rat (1336).

 

George Oliver (GB) and Edward Albert Sharpey-Schäfer (GB) were the first to extract a hormone from an endocrine organ when they showed that a preparation from the adrenal medulla of sheep and calves increases blood pressure (presser effect), accelerates the heartbeat, and depresses kidney function (antidiuretic) (1214; 1215).

Ladislaus Szymonowicz (PL) and Napoleon Cybulski (PL) independently performed experiments quite similar to those of Oliver and Schäfer in 1894 (1566).

Note: This famous "fight or flight" hormone of the medulla was later named adrenaline then later epinephrine.

William Osler (CA-GB) prepared an extract of the adrenal medulla which relieved one patient with Addison's disease (1226).

 

Karl Pearson (GB) published the first in a long series of contributions to the mathematical theory of evolution. Here he introduces the method of moments and applies it to estimating a mixture of normal distributions (1276).

Karl Pearson (GB) developed normal correlation and regression and applied them to heredity (1277).

Karl Pearson (GB) introduced the chi-square goodness of fit test (1278).

 

Walter Garstang (DE) theorized that primitive chordates were sessile, filter-feeding marine organisms very similar to present day ascidians. The tadpole ascidian larvae, with its basic organization of a vertebrate, which had evolved within the group by progressive evolution and by neoteny became sexually mature, ceased to metamorphose into a sessile, mature ascidian, and became the ancestral vertebrate (651; 652).

 

Harris Hawthorne Wilder (US) discovered that certain salamanders do not possess lungs (1784).

 

Conwy Lloyd Morgan (GB) established the basic principles in the study of animal behavior including his famous canon that the actions of an animal should be interpreted in terms of the simplest mental processes (1153).

 

Arthur König (DE), Edward Nevill Willmer (GB), and W. David Wright (GB) provided psychophysical evidence that the center of the human fovea is tritanopic (blind to blue) for very small objects (924; 1795).

W. David Wright (GB) found that blue-blindness is very rare in man, not sex-linked, and affecting only about 1 in 2000 persons, about 40 percent are women (1831).

 

Léon Charles Albert Calmette (FR) prepared horse anti-cobra anti-venom, which he used to protect chickens (268-270). He later became the first to prepare commercial anti-venom for medical use.

 

Guido Banti (IT) described Banti’s syndrome (splenic anemia attended with cirrhosis of the liver, hypertrophy of the spleen, and ascites) (83; 84).

 

Pierre Paul Émile Roux (FR), Louis M. Martin (FR), and M. Auguste Chaillou (FR) treated diphtheritic children with antiserum they produced in horses (1384; 1385). No mention of serum sickness accompanies these reports.

Johannes Andreas Grib Fibiger (DK) investigated the effect of serum treatment on diphtheria. It was the first clinical trial in which random allocation was used and emphasized as a pivotal methodological principle. This pioneering improvement in methodology, combined with many patients and rigorous planning, conduct, and reporting, makes this trial a milestone in the history of clinical trials (574).

 

Gustav Mann (GB-US) discovered a relationship between Nissl Granules or Bodies and nervous activity when he demonstrated that these bodies disappear from the spinal anterior horn cells of dogs after excessive muscular exercise and likewise they are diminished within pyramidal cells in the occipital cortex after exposure of the eye to light. He concluded that the chromatic material within these bodies builds up during rest and diminishes during function (1059).

Hans Held (DE) determined that the intraneuronal Nissl Granules or Bodies are composed of nucleoalbumin (nucleoprotein). This represents the first-time nucleoprotein was located within the cytoplasm (764).

Jean Louis Brachet (FR) proved that Nissl bodies contain ribonucleic acid (227).

 

Otto Busse (DE) and Abraham Buschke (DE) first described this yeast as a human pathogen when they isolated a "Saccharomyces-like" organism from a bone infection in a young woman with chronic tibial subperiosteal inflammation, thought to be a “softened” sarcoma (264-266). Note: Called Busse-Buschke disease

Jean-Paul Vuillemin (FR) renamed the organism Cryptococcus neoformans because it did not produce ascospores, which is a defining characteristic of the genus Saccharomyces (1715). Note: Disease now called Cryptococcosis

Note: The genomes of C. neoformans and C. gattii diverged over 34 million years ago, yielding species with marked ecological and pathological differences.

David Paul von Hansemann (DE) was the first to describe a case of meningitis caused by the fungus Torula histolytica. Later it was realized that the etiological agent was the yeast Cryptococcus neoformans (1690).

 

Carl Ludwig Schleich (DE) suggested that neuroglia moderate neuronal activity through an inhibitory action (436).

 

Edward Treacher Collins (GB) was the first to report what later became known as von Hippel-Lindau disease (332).

Arvid Lindau (SE) described retinal hemangioblastoma and noted that very similar tumors occurred in other organs such as the brain and kidney (995). Note: along with retinal angiomas, hemangioblastomas also occur in endolymphatic sac tumors, renal cell carcinoma, pheochromocytomas, pancreatic cysts, and neuroendocrine tumors

Farida Latif (GB), Kalman Tory (GB), James Gnarra (GB), Mingnan Yao (GB), Fuh-Mei Duh (GB), Mary Lou Orcutt (GB), Thomas Stackhouse (GB), Igor Kuzmin (GB), William S. Modi (GB), Laura Geil (GB), and A.C. Chinault (GB) identified the von Hippel-Lindau disease tumor suppressor gene (966).

 

Gustav Born (DE) originated heteroplastic transplantation by joining together parts of embryos belonging to different species such as frog and toad, i.e., chimeras. He obtained individuals, which continued to develop (204; 205). Hans Winkler (DE) was the first to produce plant chimeras by grafting tomato and nightshade (1809).

 

Max Rubner (DE) painstakingly tested the energy consumption of dogs using large calorimeters. He measured the nitrogen content of urine and feces, and carefully estimated the quantity of the various foodstuffs in the diet he fed his subjects. He found that the heat produced by the animal equaled the heats of combustion of the fats, carbohydrates, and protein minus that of the urinary matter. He concluded, that no one foodstuff supplied all the energy. The body made use of fats, carbohydrates, and proteins with equal readiness. The nitrogen portion of the proteins was split away before it was used as a fuel, he maintained, and in this he was correct (1396).

 

Archibald Edward Garrod (GB) was apparently the first to document congenital heart disease as a component of Down syndrome (646).

 

Siegmund Exner (AT) first formulated the concept of a neural network, a concept later used in computer design (558).

 

Eugen Steinach (AT) conducted experiments in the transplantation of a male guinea pig's testes into a female and the castration of the male. The testes secretion, now known as testosterone, resulted in the female guinea pig developing male sexual behaviour such as mounting the partner. This led Steinach to theorize that the gland's secretions were responsible for sexuality (1533-1536).

 

Toma Ionescu; Thomas Jonnesco (HU) gave the original description of rectal fascia (rectum sheath) (845).

 

Simplacio Del Vecchio (IT), in 1894, exhibited a dog with a sutured cardiac wound before the 11th International Medical Congress in Rome. Del Vecchio described to the Congress how the suturing is possible and proved that the heart is more resilient than previously believed (421).

 

Edmond Delorme (FR) performed the first decortication (removal of pleura) of the lung for treatment of chronic empyema (422).

 

Jules Emile Péan (FR) is widely credited with having performed the first total shoulder replacement on March 11, 1893 (1274).

 

Mathieu Jaboulay (FR) is credited with the first interilio-abdominal amputation (amputation of a lower limb through the sacroiliac joint). It is also called a hemipelvectomy (855).

 

Otto Ludwig Binswanger (CH) described a new clinical and neuropathological picture that he termed "encephalitis subcorticalis chronica progressiva" (178). It is this disease that is named after him, Binswanger’s disease. It is also known as ischemic periventricular leukoencephalopathy and subcortical dementia. This dementia is characterized by damage to small penetrating blood vessels in the subcortical regions of the brain. These cerebrovascular lesions are deep in the white matter of the brain.

 

Eugéne Devic (FR) and Fernand Gault (FR) described a rare nervous condition that affected the spinal cord and optic nerves that resembled multiple sclerosis. Today this disorder is referred to as Devic's disease or neuromyelitis optica (426; 654).

 

Jules Emile Péan (FR) is believed to have performed the first surgery to correct diverticula of the bladder (1274).

 

In 1894, five men and two women with Hansen's disease, then called leprosy, were brought by barge to an abandoned sugar plantation, known only as Indian Camp, on a bend of the Mississippi River between Baton Rouge and New Orleans. Named the Gillis W. Long Hansen's Disease Center, it is now known as the National Hansen's Disease Programs.

 

William Crawford Williamson (GB) and Dunkinfield Henry Scott (GB) sent three memoirs to the Royal Society of London, which included a description of the evolutionary links between ferns and cycads. This led to the development of phylogenetic theories of plants (1790-1792).

 

The journal Wilhelm Roux' Archiv fur Entwicklungsmechanik der Organismen was founded. This was the first journal of experimental embryology.

 

c. 1895

Josef Albert Amann (DE) introduced his original abdominal seam, the transperitoneal method of extirpation of carcinoma of the uterus. He also had suggestions for limiting the risk of infections, during surgery of the uterus. Ref

 

1895

"Every great operation in surgery has a period of evolution of varying duration. Each marked advance in medicine and surgery is preceded by attempts which led to the elucidation of old ideas or the conception of new ones. All great discoveries are overshadowed by the labors of a host of earnest and progressive workers which ultimately crown the efforts of a favored few. Nearly all of the improvements in medicine and surgery which have characterized the present progressive age are only a repetition of the work of our professional ancestors. Many a so-called modern operation is only a recent and not always an improved edition of the operative technique as devised and described by one of the old masters." N. Senn (US) (1475).

 

Philipp Lenard Wilhelm Conrad Röntgen; Philipp Lenard Wilhelm Conrad Roentgen (DE) observed that a new form of penetrating radiation, which he named x-rays, was produced when cathode rays (electrons) hit a metal target (1372-1374; 1564). Note: This initial article summarizing this discovery of X-rays was submitted to the Wurzburg Physico-Medical Society on December 28, 1895, and the fields of radiology and radiation oncology were born.

 

John William Strutt (GB) and William Ramsay (GB) collaborated to discover argon, the first of the “inert” or Noble gases (1342). Ramsay went on to discover helium, neon, krypton, and xenon.

 

Sven G. Hedin (SE) and Albrecht Karl Ludwig Martin Leonard Kossel (DE), working independently, isolated the amino acid histidine. Kossel isolated it from sturgeon sperm and called it histidin from the Greek word meaning tissue. Hedin isolated it from animal horn (762; 931).

 

Charles Frederick Cross (GB), Edward John Bevan (GB), and Clayton Beadle (GB) were the first to purify cellulose from wood (365).

 

Henry Edward Schunck (DE) and Leon Paul Theodor Marchlewski (DE) prepared pure phylloporphyrin from chlorophyll and later discovered how similar its absorption spectrum is to that of hematoporphyrin (1459; 1460).

 

Gabriel Émile Bertrand (FR) isolated the enzyme laccase from latex (163). Note: This was the first isolated enzyme of the oxidation-reduction type. Up to this point all isolated enzymes had been of the hydrolytic type.

Gabriel Émile Bertrand (FR) coined the term oxidases to describe several plant enzymes, which catalyzed oxidation reactions. He also discovered that some oxidases are likely to require metals, which he named coferments or coenzymes, and were therefore catalytic metalloproteins (164).

 

Charles Ernest Overton (GB) analyzed how substances pass into cells from outside through the boundary layer. He discovered that non-polar solutes pass though more easily than polar solutes and concluded that the boundary layer has the dissolving qualities of fatty oil. He guessed that it must contain lipids calling the layers surrounding cells “lipoids” made from lipids and cholesterol. He reported active transport of solutes across a cell membrane against a concentration gradient (1240-1242).

 

Tamás Marschalkó; Thomas von Marschalko (HU) was the first to describe the characteristics of plasma cells, including blocked chromatin, eccentric position of the nucleus, aperinuclear pale area (hof) and a spherical or irregular cytoplasm (1697).

Paul Gerson Unna (DE) used the term plasma cell but it is not known precisely what type of cell he was viewing (1636).

Paul Gerson Unna (DE) defined the plasma cell as a protoplasm poor cell, which is frequently an important component of the infiltration of the skin in several diseases (1638).

 

Frank Spiller Locke (GB) recognized that calcium ions are necessary for effective neuromuscular transmission (1004).

 

Sergei Nikolaevich Winogradsky (RU) discovered chemoautotrophic bacteria that oxidize ammonia to nitrite (Nitrosococcus), and other chemoautotrophs, which oxidize nitrite to nitrate (Nitrobacter). These organisms contain no chlorophyll, yet they could assimilate carbon dioxide and make organic material in the dark. This work provided a firm foundation for his concept of the chemoautotrophic life style (1814).

 

Sergei Nikolaevich Winogradsky (RU) isolated a free-living anaerobic nitrogen fixing bacterium and named it Clostridium pasteurianum (1814). Martinus Willum Beijerinck (NL) later isolated and identified it as Azotobacter chroococcum (142).

 

Frederick Frost Blackman (GB) proved that most of the gaseous exchange between the leaves of a plant and the surrounding atmosphere takes place through the stomata (184).

 

I[gnatij] A[dolfovié] Notkin (DE) showed that the physiologically active principle of the thyroid gland resided in a protein substance, which he called thyreoproteid (1203).

 

Adolf Magnus-Levy (DE-US) was the first to apply respiratory quotient studies to people with disease. He discovered that people with a hyperthyroid condition exhibit an elevation in metabolic rate, whereas those with myxedema and underfunctioning thyroids exhibited a lowered metabolic rate. This represents the origin of the use of metabolic rates in medical diagnosis (1053). This work helped bring about the realization that the thyroid and its secretion have an active function unrelated to detoxifying the blood but indispensable to health. See, George Redmayne Murray, 1891.

 

George Henry Falconer Nuttall (US-GB) and Hans Thierfelder (DE) demonstrated the importance of intestinal bacteria in digestion (1208).

 

Waldemar Mordecai Wolff Haffkine (RU-CH-FR) developed a vaccine for cholera by giving a subcutaneous injection of culture—attenuated by growth at an elevated temperature—followed five days later by a subcutaneous injection of virulent culture (726).

 

Hans Klebahn (DE) proposed that Cyanobacteria (blue-green algae) contain granules (vacuoles) filled with gas. He suggested that the gas is directly concerned with their flotation (910).

 

William Ernest Castle (US) proved that in Ciona intestinalis, a hermaphrodite ascidian, self-fertilization is prevented not, as had been supposed, by ripening of eggs and sperm at different times but by a different means which Castle revealed for the first time in an animal. This was that, in general, sperm and eggs produced by the same individual are unable to unite in fertilization. The failure of sperm, in Ciona, to penetrate eggs of the same individual was comparable, in Castle's view, to the self-sterility (later called incompatibility), which had been found in certain flowering plants (294).

 

Wilhelm August Oskar Hertwig (DE) centrifuged frog eggs and demonstrated the effect of yolk distribution on cleavage (788).

 

Erwin Frink Smith (US) described wilt in cucurbits, defined the disease, listed host plants, described geographical distribution and signs of the disease, and proved the etiological role of a specific bacterium. An abridgement of one of his experiments follows:

Inoculations of July 16, 1896

The plants were in a hothouse and the bacteria used were from…an eight-day old culture…. Well-developed, young, healthy, and rapidly growing cucumber plants (Cucumis sativus variety White Wonder), were inoculated…. Many delicate pricks (40 to 70) were made in the apical part of one leaf-blade of each plant, covering an area of not more than one sq. cm. The pricks themselves did the plant no injury. The platinum loop and the steel needle used in the operation were flamed and cooled each time before using. A big loop of the fluid, containing many thousands of the bacteria (some of which were motile, as determined by examination under the microscope) was put on the clean surface of the leaf, spread a little, and then rapidly pricked in, taking special care to make the needle holes as small as possible…. The plants were examined every day for the first 8 days and frequently after that. Twenty-four plants were inoculated.

(Plant 355) This plant was 18 inches and very thrifty. The inoculation was made on the sixth leaf 9 inches away from the stem. The pricked leaf-blade was 5 inches broad. Up to the morning of July 21, there was no trace of disease but at 3 PM of the same day about 0.5 sq. cm. on one side of the pricks was wilted…. By noon of the seventh day, the wilt covered about 10 sq. cm., and reached halfway down the blade. The leaf was now cut off close to the stem with a hot knife. Four days later the vine was normal, apparently except for a droop of the first two blades below and a fainter one of the first two above the node, which had borne the pricked leaf. I filled the pot several times with water, but an hour later the absorption of the water had not relieved the droop of the foliage. The next day in the afternoon, the first two leaves below were cut away. They had not recovered their turgor. Three days later…the blades of the next four showed a wilt. The eighteenth day the blades of the second and fourth leaves up were shriveled but the petioles were turgid. The fourth leaf was on the same side as the second. The blade of the third leaf, which was on the opposite side, was flabby but had not yet shriveled. The blades of the fifth, sixth, seventh and eighth leaves were drooping. The others were turgid. The twenty-third day after inoculation all the leaves were shriveled….

Similar results were obtained with the twenty-four other plants inoculated, and Smith continued:

Every one of the twenty-four plants contracted the disease, and in each case, it appeared in the pricked area. Nineteen of the plants subsequently developed constitutional signs and died of the disease. No general signs appeared in the other five plants, i.e., the disease was stopped by the removal of the affected leaf…. In eighteen cases the amputation of the affected leaf did not check the spread of the disease.…The bacteria…pass down through the vessels of the leaf at the rate of about 0.75 inch to 2 inches (2 to 5 cm.) a day….

Between August 5 and 8 numerous freshly wilting leaves were cut from these plants and fixed in strong alcohol to determine whether the bacteria are actually in the vessels of the leaf at the time the secondary wilt appears or whether this wilt is due simply to the plugging of the vessels of the stem…. Thin microtome sections were made from the basal part of the petiole of 66 leaves…staining in carbol fuchsin. Bacteria cannot be demonstrated in everyone, but they occur in 61 of them; no fungi are present, neither are there any insect-injuries. In most cases the bacteria are confined strictly to the spiral vessels of the petioles, and they do not occur in all of these, nor in all of the bundles. They are not present in the phloem, the cortical parenchyma or the tissues between the bundles. Summarized, the amount of bacterial infection in the basal part of the petioles is as follows: (1) In a few petioles nearly every bundle is occupied, and bacteria occur in many vessels…(2) in 5 no bacteria detected; (3) in by far the greatest number the bacteria are confined to a few vessels of a few bundles….

After a description of the Morbid Anatomy, Smith proceeded to The Parasite, Bacillus tracheiphilus. His summary reveals the thorough nature of his investigation:

Résumé of Salient Characters

Positive

A bacillus in the vascular bundles of cucurbits causing a wilt-disease; short rods (single, paired, in fours end to end, or in small clumps); motile, peritrichate; capsules; pseudozoogloeae; involution-forms; stains readily; smooth; white; viscid; glistening; slow grower on media; surface colonies small, round discrete; no growth at 37°C. or at 6°C. (16 days); aerobic; facultative anaerobic (with grape-sugar or fruit-sugar); from these sugars a non-volatile acid, soluble in ether; grows only in open end of F-tube with dextrine or glycerine, acid from glycerine; slime on steamed potato (Solanum tuberosum) is same color as the normal substratum; usually it grays potato after a time; clouds peptone-bouillon and Dunham’s solution thinly; growth retarded in acid juice of cucumber fruits; also retarded or inhibited by juice of many other vegetables, e.g., table beet, sugar-beet, turni, etc.; grows on many media at 25°C., carrot (Daucus carotus), coconut (Cocos nucifera), Fermi, Uschinsky, etc.; asparagin as carbon food (?); thermal death point 53°C.; optimum for growth 25°C. to 30°C.; maximum, 34°C. to 35°C. (?); minimum (?) 8°C.or below; easily killed by dry air, sunlight, or freezing (50 per cent or more); ammonia production (moderate; feeble production of hydrogen sulfide; in litmus-milk persistent growth without reduction or distinct change in color of litmus; short-lived on many media; killed readily by acids, but lives long in cane-sugar-bouillon with carbonate of lime; grows on some media in hydrogen and carbon dioxide; dissolves middle lamella (cucumber-parenchyma); distributed by insects, especially by Diabrotica vittata.

Mealy or dendritic surface growths; negative grams stain; endospores; chains; filaments; growth not yellowish, piled up or wrinkled; pellicle on bouillon; liquefaction (gelatin, blood serum, egg-albumin, etc.); lactose and pure maltose in closed end fermentation-tube lab ferment; acid (in milk); gas (all media); pigment (except gray stain on potato); indol (?); nitrite from nitrates; starch-splitting; cellulose-dissolving (except possibly in host); asparagin as nitrogen food; ammonium salts as nitrogen food; steamed turnip, and cauliflower; Cohn’s solution; acid bouillon (+33); acid gelatin; nearly odorless; not a soft rot; not infectious to tomato, potato (Solanum tuberosum), etc. On steamed potato liable to be confounded with a non-infectious coccus (follower) which reddens litmus milk.

Any organism which reddens or blues litmus-milk decidedly, reduces the litmus, throws down the casein, or clears litmus-free milk without precipitation may be set down at once as something else.

It was during his study of the wilt of cucurbits that Smith established the methods for the critical and faultless study of bacterial plant diseases. He investigated a number of other diseases of this type, such as the brown rot of Solanaceae, the black rot of cucifers, the yellow disease of hyacinths, bean blight, mulberry blight, the black spot and canker of peach and plum, the angular leaf spot of cotton, the angular leaf spot of cucumber, the bacterial canker of tomato, the olive tubercle, and others (1511).

 

Louis Hermann Pammel (US) discovered and described the microorganism causing black rot of cabbage. He named it Bacillus campestris, later changed to Xanthomonas campestris (1252).

 

K. Takata (JP) presented evidence that insects can be vectors of plant virus disease—dwarf disease of rice (Oryza sativa) (1573).

Hatsuzo Hashimoto (JP), a rice grower, was the first to prove experimentally the role of insect as plant disease vector. He observed and discussed but did not publish his findings on the leafhopper as vector for rice stunt virus (15).

 

Alexander Marmorek (AT-FR) discovered that fluid cultures of streptococci lyse erythrocytes (1069).

 

J. Jackson Lister (GB) established the alternation of asexual and sexual generations in a recognized species of protozoa, Polystomella crispa a foraminiferan (999).

 

David Bruce (GB) and Mary Elizabeth Steele Bruce (GB) while investigating an outbreak of nagana, a disease like surra, in cattle in Zululand, were looking for a bacterial cause and found trypanosomes in the blood of diseased cattle; they demonstrated experimentally that these caused nagana in cattle and horses and infected dogs. They also observed that infected cattle had spent some time in the fly-infested "tsetse belt" and that the disease was like that in humans called negro lethargy and fly disease of hunters (248-251). The causative agent was later named Trypanosoma brucei in their honor. The Bruces were the first to prove that an insect can carry a protozoan of a pathological kind.

Gustave Nepveu (FR), in 1891, was the first to observe trypanosomes in human blood (1177).

Joseph Everett Dutton (GB) and Robert Michael Forde (GB) identified the trypanosome that causes Gambian or chronic sleeping sickness in humans as Trypanosoma brucei gambiense (487; 488; 603; 604).

Aldo Castellani (Count of Chisiamaio) (IT) discovered Trypanosoma brucei gambiense in the cerebrospinal fluid of patients suffering from sleeping sickness (trypanosomiasis). He suggested that these trypanosomes cause the disease (293).

Frederick George Novy (US) and Ward J. MacNeal (US) successfully established in vitro cultures of Trypanosoma brucei (1205).

Friedrich K. Kleine (DE) demonstrated the essential role of the tsetse fly (Glossina palpalis) in the life cycle of trypanosomes (912).

John William Watson Stephens (GB) and Harold Benjamin Fantham (GB) described Trypanosoma brucei rhodesiense, the cause of Rhodesian or acute sleeping sickness (1540).

Ronald Ross (GB) and David Thompson (GB) described the persistence of trypanosomes in the blood and the existence of successive waves of parasitemia in patients with African sleeping sickness (1378).

Walter Abraham Jacobs (US), Michael Heidelberger (US), Wade H. Brown (US), and Louise Pearce (US) synthesized the first drug found to be effective in the treatment of African sleeping sickness (the sodium salt of N-phenyl-glycineamide-p-arsonic acid) (858; 1275).

Matthew P. Cunningham (GB), Keith Vickerman (GB) and Antony G. Luckins (GB) determined how the parasite, Trypanosoma brucei, evades the immune response by what is called antigenic variation (376; 1655; 1656).

James E. Taylor (GB) and Gloria Rudenko (GB) were astonished to find in the T. brucei genome sequence that <7% of the sequenced variant surface glycoproteins (VSGs) seem to have fully functional coding regions. This preponderance of pseudogenes in the VSG gene repertoire will necessitate a rethink of how antigenic variation in African trypanosomes operates (1579).

 

Jules Jean Baptiste Vincent Bordet (BE) showed anti-cholera serum heated to 55°C could be mixed with unheated normal serum and produce bacteriolysis of Vibrio cholera, however, if the normal serum was also heated the bacteriolysis failed to occur. He concluded that two substances or factors must be concerned in the lytic action. One of these substances is present both in normal and fresh immune serum and is thermolabile; the other is peculiar to the immune serum and is thermostable (197-199).

 

Wilhelm His (CH) was the first to accurately describe the hypothalamus, which he named (800).

 

George Oliver (GB) and Edward Albert Sharpey-Schäfer (GB) were the first to detect the neurohypophysial hormone arginine vasopressin (Avp). They demonstrated that extracts of the pituitary altered blood pressure (1216).

Rudolf Magnus (GB) and Edward Albert Sharpey-Schäfer (GB) demonstrated that the posterior pituitary extract had a pressor and antidiuretic activities (1051).

Henry Hallett Dale (GB) discovered the oxytocic or uterine-contracting effect of the posterior pituitary extract (392; 393). Note: The hormone responsible was named oxytocin.

Isaac Ott (US) and John C. Scott (US) were the first investigators to demonstrate that the corpus luteum is a rich source of oxytocin. These researchers reported that an aqueous extract of the corpus luteum when injected into a goat, stimulated immediate milk flow (1233).

Alfred Erich Frank (DE) showed that the posterior lobe of the pituitary gland produces vasopressin, an antidiuretic hormone, which controls diabetes insipidus (614).

Reinhard von den Velden (DE), A. Farini (IT), B. Ceccaroni (IT) Walter Frey (DE), K. Kumpiess (DE), Artur von Konschegg (DE), and Ernest Joseph Schuster (DE) discovered the antidiuretic effect of posterior lobe pituitary gland extract (vasopressin). Each had patients with disease or damage to the pituitary accompanied by polyuria and, interpreting this to be due to the gland’s impaired ; function, they easily controlled the excessive water loss by administration of extracts of the posterior lobe (568; 627; 1673; 1696).

Oliver Kamm (US), Thomas B. Aldrich (US), Irvine W. Grote (US), Louis W. Rowe (US), and Edwin P. Bugbee (US) reported obtaining posterior lobe pituitary preparations with high oxytocic activity and low pressor activity and, conversely, preparations with high pressor activity and low oxytocic activity (878). Note: These would later be associated with oxytocin and vasopressin.

Robert A. Turner (US), John G. Pierce (US), Vincent du Vigneaud (US), Charlotte Ressler (US), Stuart Trippett (US), John Melvin Swan (AU), Carleton W. Roberts (US), Panayotis G. Katsoyannis (GR), Samuel Gordon (US), and Hans Tuppy (AT) determined the primary structure of oxytocin (a polypeptide hormone from the posterior pituitary gland), synthesized it in vitro, and demonstrated that it is identical to the natural material. Oxytocin was the first protein hormone ever synthesized (466-468; 1628; 1630).

Vincent du Vigneaud (US), H. Claire Lawler (US), Edwin A. Popenoe (US), Duane T. Gish (US), Panayotis G. Katsoyannis (GR), Roger Acher (FR), and Jacqueline Chauvet (FR) determined the primary structure of vasopressin (antidiuretic polypeptide hormone from the posterior pituitary gland), synthesized it in vitro, and demonstrated that it is identical to the natural material (12; 13; 464; 465).

Miklos Bodanszky (HU-US) developed a new procedure for the coupling of amino acids to each other—the nitrophenyl ester method. He and Vincent du Vigneaud (US) synthesized oxytocin (189-191).

Howard Sachs (US), Yutaka Takabatake (JP-US), Peter Fawcett (US), and Ronald Portanova (US) demonstrated that arginine vasopressin initially appeared in the hypothalamus and was then transported to the posterior pituitary. Because the synthesis was inhibited by protein synthesis inhibitors, they proposed that oxytocin and arginine vasopressin were intially incorporated into protein precursors that would be cleaved into the bioactive components (1424; 1425; 1569).

Philip W. Gold (US), Frederick K. Goodwin (US), and Victor I. Reus (US) were the first to propose a role for vasopressin in mood disorders; studies since then have upheld this idea (672).

Roger Acher (US) found that the evolutionary progenitor of the human Avp, vasotocin, is found in birds and reptiles (11).

 

 Edward Albert Sharpey-Schäfer (GB) wrote that all tissues take up materials from the blood, metabolize them and return them to the circulating fluid. Certain glands (liver, pancreas, and kidney), provided with ducts, have important external and internal secretions. Other glands (thyroid, adrenals, pituitary) have internal secretions only (1485).

 

Hendrik Zwaardemaker (NL) originated the concept of odor conjugates. He discovered that certain odors can be prevented from detection by smell senses when mixed with various essential oils. These combinations of odors are referred to as Zwaardemaker Pairs, (or Z-pairs) (1859).

 

Jean-Martin Charcot (FR) and Jean Albert Pitres (FR) conclusively proved the existence of cortical motor centers in man (310).

 

Theobald Smith (US) reported that guinea pigs died of a peculiar hemorrhagic disease when fed on a cereal diet without succulent vegetables (1514). Note: It was later learned that this hemorrhagic condition is essentially scurvy.

 

Harvey Williams Cushing (US) and Ernest Amory Codman (US) made a wager to see who could develop better control over the administration of surgical anesthesia and thereby limit the distress—and even accidental death—of patients during operations. The result was the ether chart, on which were recorded continuously the surgery patient’s pulse, respiration, temperature, and later blood pressure, when a pneumatic device for registering it became available. This innovation led to a considerable reduction in mortality rate from anesthesia and is one of the major contributions of American medicine to surgery. These charts are the earliest examples of meticulous documentation of a patient’s vital signs (388).

Harvey Williams Cushing (US) demonstrated the value of observing blood pressure during surgery and predicted that the taking of a patient’s blood pressure would become routine medical practice (387).

 

William MacEwen (GB), in 1895, performed the first pneumonectomy for tuberculosis in a patient who survived (1038).

 

Vincenz Czerny (CZ-DE) performed the first autogenous breast reconstruction when he replaced breast tissue with a non-cancerous lumbar lipoma (391; 680).

 

Robert Tuttle Morris (US), who performed the first human ovarian grafting in 1895, published the same year a presentation of his idea of gland grafting, description of technique, and a report upon cases. In May 1906, in the New York Medical Record, he published a report of the birth of a living child after heteroplastic ovarian grafting (1159; 1160; 1504).

Josef von Halban (AT) used ovarian transplants in baboons to restore their periods. He concluded, correctly, that in internal secretion the production and presence of hormones is not sufficient; the target organ must also be able to react and respond to the stimulus.

Josef von Halban (AT) reported his experiments with ovarian transplants in castrate newborn guinea pigs, with the result that there was normal development of the uterus and the salpinges. He concluded that the host of the transplant developed a new blood supply that transported a substance or substances from the transplant to the uterus and the other genital organs and furthermore this substance is necessary to maintain the development of the sexual organs and the mammary glands (1687).

 

Johannes Eugenius Bülow Warming (DK) wrote Plantesamfund - Grundtræk af den økologiske Plantegeografi [Oecology of Plants: An Introduction to the Study of Plant Communities], one of the first books dealing with plant ecology. In it we find, "Oecological plant geography seeks: (1) to find out which species are commonly associated together in similar habitats; (2) to sketch the physiognomy of the vegetation and the landscape; (3) to answer the questions: why do species congregate to form definite communities, and why do these have a characteristic physiognomy; and (4) to consider the economy of plants and their growth-form." (1736)

 

Ismar Isidor Boas (DE) founded Archiv für Verdauungs-Krankheiten, the first journal devoted to the subject of gastroenterology.

 

1896

"Heredity provides for the modification of its own machinery" was James Mark Baldwin’s (US) way of saying that the capacity to respond to environmental conditions is itself hereditary, i.e., the evolutionary effect (78).

 

"Chemistry has taken possession of medicine and will not let go." Pierre Émile Duclaux (474)

 

Antoine Henri Becquerel (FR) "discovered radioactivity." He planned to place a silver coin between uranium salts and a photographic plate wrapped in thick black paper, exposing the entire package to the sun. To his amazement, he discovered the coin’s shadow on the plate even though it had not been exposed to light. He concluded that this new radiation was an atomic property of uranium (129-131). During his studies of uranium salts found in pitchblende he concluded that it was more radioactive than could be accounted for by its uranium content and therefore might contain another more powerfully radioactive substance. He encouraged Pierre and Marie Curie to research the matter. See, Claude-Félix-Abel Niepce de Saint-Victor, 1857.

Leopold Freund (AT) is accepted as having been the first to use X-rays logically and scientifically within the limits of the age. His patient, a 5-year-old girl with a hairy nevus 36 cm in length, started treatment on November 24, 1896—X-rays having been discovered only 12 months earlier, on November 6, 1895. After successful epilation, an X-ray ulcer persisted for about 6 years, but it was cured in 1902 when only a scar remained (626).

 

Wilhelm Friedrich Ostwald (DE) made the first electrometric measurement of hydrogen ion concentration by the potential on a platinum electrode in solutions saturated with hydrogen gas (1231). He discovered that this potential is a logarithmic function of the strength of the acid.

Max Cremer (DE) discovered an electrical potential proportional to the acid concentration difference across thin glass membranes (358).

Fritz Habër (DE) and Zygamunt Klemensiewicz (PO-GB-PO), in 1909, constructed and studied glass H+ electrodes (721).

Karl Albert Hasselbalch (DK) and Christen Lundsgaard (DK) produced a modified Ostwald platinum electrode with which they measured blood pH at body temperature (750).

Heinrich Dannneel () discovered the reaction of oxygen with a negatively charged metal (cathode), the basis of oxygen polarography, later developed by Jaroslav Heyrovsky (CZ) (792).

Phyllis Tookey Kerridge (GB) constructed the first blood glass pH electrode (899).

Poul Bjørndahl Astrup (DK) designed an apparatus with which it was possible to determine the acid-base imbalance in a patient (51).

Richard W. Stow (US), Richard F. Baer (US), and Barbara F. Randall (US) conceived of an electrode for measuring PCO2 (1558).

Leland C. Clark, Jr. (US) developed and perfected a PO2 electrode (322).

 

Svante Arrhenius (SE) in developing a theory to explain the ice ages was the first to use basic principles of physical chemistry to calculate estimates of the extent to which increases in atmospheric carbon dioxide (CO2) will increase Earth's surface temperature through the greenhouse effect (44).

 

Sodium fluoride was first used as an insecticide. Crude petroleum emulsions were tested as insecticides. The value of early-season control of boll weevil was discovered; arsenicals were recommended for this purpose (1478).

 

Charles James Martin (GB) designed and constructed a high-pressure gelatin membrane ultrafilter for fractionation of snake venom. This represents the first application of ultrafiltration (1070).

 

Scipione Riva-Rocci (IT) introduced the mercury sphygmomanometer in its modern form (for determining arterial blood pressure) (148; 1316; 1366; 1403).

 

Marceli Nencki; Marcellus von Nencki (PL) established that porphyrins are made up of pyrrole nuclei. He proposed that the similar chemical properties of hemin and chlorophyll denotes a common origin of plant and animal life and that comparison of similar compounds of flora and fauna provides insight into chemical and organismal evolution (1175).

 

Edmund Beecher Wilson (US) in his great book, The Cell in Development and Inheritance, established a synthesis of cytology, ontogenetics, and genetics. He presented compelling evidence that the cell nucleus contains the physical basis of inheritance; and that chromatin, its essential constituent, is the idioplasm postulated in Nägeli's theory. First, the persistent accuracy with which the chromosomes replicate and are distributed, in contrast with the often-random division of the cytoplasm by region, indicates the importance of ensuring that each daughter cell receives a full complement of chromosomes. Second, the work of Boveri in particular (1887) had suggested that chromosomes maintain their individuality and continuity from one generation to the next. Third, abundant cytological evidence showed that while sperm and egg had enormously different cytoplasmic components (the sperm has virtually no cytoplasm) they seemed, overall, to affect the heredity of the offspring equally. Thus, it would appear, Wilson pointed out, that the cytoplasm has relatively little hereditary function. Fourth, numerous experiments by others indicated that enucleated cells do not function normally. Whatever the exact function of the nucleus, it is necessary to the normal maintenance of cell activity. Wilson maintained that the nucleus is the seat of constructive (anabolic), and the cytoplasm of destructive (catabolic), processes (see Claude Bernard, 1878-1879) (1801).

 

Franz Julius Keibel (PL-DE) described the complex formation of the urogenital system. This was the first in-depth treatise of the formation of a body system (891). Keibel also edited a landmark series of 16 volumes on vertebrate embryos that defined for the first time standard divisions of human development by utilizing plates of normal embryos at multiple ages and included tables of their measurements. The volumes were a major rebuttal to Haeckel’s proposal that ontogeny recapitulated phylogeny (892).

 

Hans Lohmann (DE) was the first to promote the idea that natural waters contain more small life form than previously suspected. Working on the phytoplankton from the coast of Sicily, he was the first to use the technique of pumping sea water through filter paper and in this way, he was able to collect and identify many minute species for which he later suggested the name ‘ Nannoplankton’(nanoplankton) (1020-1022). He is commemorated by the genus Lohmannella, Trouessart, 1901.

Sallie W. Chisholm (US), Robert J. Olson (US), Erik R. Zettler (US), Ralf Goericke (US), John B. Waterbury (US), and Nicholas A. Welschmeyer (US) discovered that the bacteria-sized cyanobacterium, Prochlorococcus sp., is abundant in the open ocean, with counts of up to 20,000 cells per drop of seawater (316).

 

Sakugaro Hirase (JP) and Seiichiro Ikeno (JP) were the first to prove the existence of motile spermatozoids in gymnosperms (795; 796; 843; 844).

Herbert John Webber (US) reported that one of the higher plants, Zamia, produces swimming sperm (1740-1745).

 

Ernest Henry Starling (GB) was the first to point out that capillary blood pressure tends to force materials from the circulating blood into surrounding tissues (transudation) and serum proteins exert an osmotic pressure, which tends to force the absorption of materials from the surrounding tissues; the interplay of these forces leads to transudation at times and absorption at others. They show that the pre- and post-capillary resistances can be estimated in isolated perfused hindlimbs (1530).

Albert A. Epstein (US) applied Starling's concept to explain the edema of patients with the nephrotic syndrome. He found extremely low albumin- and almost normal globulin-levels in sera from patients with chronic parenchymatous nephritis. In contradistinction to the findings in patients with cardiac disease, almost no protein, and particularly no albumin, was detected in serous effusions and edema fluid of patients with nephrotic syndrome (547).

John Richard Pappenheimer (US) and Armando Soto-Rivera (VE) confirmed Starling’s findings (1259).

John Richard Pappenheimer (US), Eugene M. Renkin (US), and Luis M. Borrero (CO) were the first to successfully attempt to relate physiological measurements of permeability to the structure of microvascular walls. The first to offer a comprehensive theoretical analysis of diffusion and convection of solutes through channels of molecular dimensions and the first to provide quantitative evidence supporting the hypothesis that permeability to hydrophilic solutes is restricted to the intercellular regions (1258).

 

Theobald Smith (US) published papers on differences in virulence in tubercle bacilli from several sources. The tubercle bacilli which he isolated from the udder or other affected organs of tuberculous cattle and cultivated on artificial media were more pathogenic for rabbits, as well as for cattle, than were organisms isolated from human sputum or affected human lungs at postmortem. Later, the designation human and bovine as applied to different strains of the tuberculosis bacillus became widely accepted (1515; 1516).

 

Johann Petruschky (DE) appears to be one of the first to have isolated Alcaligenes faecalis (Bacterium faecalis alcaligenes) (1286). He originated litmus milk as a bacterial culture medium. Ref

 

Emile M. P. van Ermengem (BE) isolated and named Clostridium botulinum, the etiological agent of botulism (L. botulus, sausage). He called it Bacillus botulinas. The source was pickled ham, which had made many people ill (1642; 1643).

P. Tessmer Snipe (US) and Hermann Sommer (US) purified botulinus toxin (1521). Note: See Carl Lamana, 1946.

Arnold Stanley Vincent Burgen (GB), Frank Dickens (GB), and Leonard J. Zatman (GB) discovered that botulinum toxin blocks neuromuscular transmission (263).

Alan B. Scott (US) and Edward J. Schantz (US) were the first to work on a standardized botulinum toxin preparation for therapeutic purposes (457; 1484).

Alan B. Scott (US) used botulinum toxin type A (BTX-A) in monkey experiments. In 1980, he officially used BTX-A for the first time in humans to treat strabismus (crossed eyes), a condition in which the eyes are not properly aligned with each other, and uncontrollable blinking (blepharospasm) (1439; 1464; 1465).

 

Victor Morax (CH-FR) and Karl Theodor Paul Polykarpus Axenfeld (DE) independently described a small diplobacillus, (Moraxella lacunata) as responsible for chronic infections of the conjunctiva and cornea in man (59; 1152). The organism is sometimes referred to as the Morax-Axenfeld bacillus.

 

Emile Charles Achard (FR) and Raoul Bensaude (FR) isolated a bacillus from the tissues of a patient recovering from a typhoid-like disease. The isolant resembled the typhoid bacillus but differed from it in important particulars. This probably represents the first isolation of a causative agent of paratyphoid fever (10).

 

Benjamin Minge Duggar (US) described toxic septicemia of the squash bug, Anasa tristis DeG., and assigned the bacterium Bacillus entomotoxicon as the etiological agent (480). It was later decided that the agent is Bacterium entomotoxicon.

 

Henry Koplik (US) found that red skin spots with a minute bluish-white center (Koplik spots) are diagnostic of measles (rubeola) (927).

 

Robert Almer Harper (US) discovered the ascospore and sexual reproduction in the Ascomycetes (745).

 

Rudolf Albert von Kölliker (CH) gave the name axon to the axis cylinder of the nerve cell (1694).

 

Abbott H. Thayer (US) proposed that the background not only conceals camouflaged animals because they blend into it but because of what he called countershading—a device that makes creatures look flat. In countershading, an animal’s colors are precisely graded to counteract the effects of sunlight and shadow. Countershaded animals are darkest on top, where most sunlight falls, and lightest on the bottom, e.g. penguins, orcas (1585). In 1903 he wrote, "Every possible form of advantageous adaptation must somewhere exist…. There must be unpalatability accompanied by warning coloration… and equally plain that there must be mimicry." (1586)

 

Josef Jadassohn (DE) introduced the concept of the Patch Test to dermatology and immunology (859).

 

Emil Herman Grubbé (DE), in 1896, initiated irradiation treatment of a patient suffering from advanced recurrent cancer of the breast. The condition was relieved, but she died shortly afterward of metastases. This represents the first attempt at medical treatment using irradiation. By 1902, Grubbé's practice reached the point where he was X-ray treating on an average over seventy cases daily. He found X-ray treatment curative in cases of lupus, epithelioma, nodular returns (post-operative), primary breast cancer, tuberculous lung, tuberculous bone, cancers of soft internal organs, sarcomata, and osteo-sarcomata. Although he burned every one of these patients he considered this a necessary consequence. Grubbé remarked that in properly selected so-called incurable cases the X-ray brought about remarkable results (709; 803).

Thor Stenbeck (SE), in 1899, initiated the treatment of a 49-year-old woman's basal-cell carcinoma of the skin of the nose, delivering over 100 treatments during 9 months. The patient was living and well 30 years later (1538). At the same time, Tage Anton Ultimus Sjörgen (SE) and Edvard Sederholm (SE) cured a squamous cell epithelioma with fifty treatments over 30 months (1507).

Francis Williams (US) presented to the Boston City Hospital staff several cases of carcinoma of the skin and of the lower lip healed by fractionated irradiation (1789).

Henri-Alexander Danlos (FR) and Paul Bloch (FR) investigated the use of radium in the treatment of skin diseases at the Saint Louis Hospital of Paris (400).

Robert Waldo Abbe (US) used radium as a surgical adjuvant in treating cancer (5).

Pierre Curie (FR), Charles Bouchard (FR), and Victor Balthazard (FR) studied the effect of radium on animals and discovered that it can destroy diseased cells. It cured tumors and certain kinds of cancer (378). This type of therapy was to be called Curietherapy and finally radiation therapy.

 

Walter Koenig (DE) published radiographs of front teeth in the upper and lower jaw taken with x-rays. These were the first dental radiographs (917).

Weston A. Price (US) showed that dental radiographies make it possible to obtain clear and precise images of the contour of the roots of the teeth (1321).

 

Vaughn Pendred (GB) was the first to draw attention to the association of goiter with deaf-mutism (1281).

 

W. Lembke (DE) found that a marked difference might be brought about in the character of the intestinal flora by the substitution of bread for a meat diet (978; 979).

 

Thomas Clifford Allbutt (GB) was the first to point out that in the middle and later stages of life men and women are liable to a rise of the mean arterial pressure (hypertension) to an abnormal and even high degree (19).

 

Jean Hyacinthe Vincent (FR) described fusospirochetal disease or what was later called Vincent’s angina or trench mouth because he diagnosed it in the mouths of trench bound soldiers in World War I (1660-1662).

 

Henri-Jules-Marie Rendu (FR) gave a clinical description of hereditary hemorrhagic telangiectasia (1352).

William Osler (CA-GB) described a family form of recurring epistaxis, associated with multiple telangiectases of the skin and mucous membranes (1228).

 

Antoine Bernard-Jean Marfan (FR) described a five-year-old female patient, with long thin limbs, poor muscle development and an abnormally curved spine. Dr. Marfan’s name became synonymous with patients affected by a disorder of connective tissue affecting primarily the musculoskeletal system, the cardiovascular system and the eye. The patients have an asthenic build, with tall stature, long arms and legs and characteristic changes in the extremities, particularly long and spider-like fingers, an arm span greater than height, Marfan’s syndrome (1063).

 

William Pringle Morgan (GB) was the first to publish a report describing a congenital word-blind (dyslexia) patient (1156).

 

Fulgence Raymond (FR) did clinical and anatomical studies on chorea, hemi-anesthesia and tremor. His papers and books on these subjects are classics. This great clinician is also remembered for his investigation on brain stem syringomyelia, muscle disorders, tremors, infections, neuritis and especially tabes dorsalis (1343).

 

Friedrich Ernst Krukenberg (DE) described a malignant tumor of the ovary he called fibrosarcoma ovarii mucocellulare carcinomatodes, now known to be most frequently secondary to malignancy of the gastrointestinal tract (941).

 

Joseph Jules François Félix Babinski (PL-FR) discovered that while the normal reflex of the sole of the foot consists of a plantar reflex of the toes, an injury to the pyramidal tract would show up in an isolated dorsal flexion of the great toe - Babinski’s sign (63). Others had previously observed this reflex, but Babinski was the first to realize its diagnostic significance.

Joseph Jules François Félix Babinski (PL-FR), Jean Nageotte (FR), Auguste Tournay (FR) published on cerebrospinal syphilis, cerebellar signs, and symptoms such as asynergia adiadochokinesia, on reflexes, on unilateral bulbar lesions and on dystrophia adiposogenitalia (64; 65; 70; 72).

 

George Thomas Beatson (GB) found that inoperable breast tumors regressed following surgical removal of the ovaries (oöphorectomy) and ingestion of thyroid tablets (128). This represents the first suggestion of a linkage between breast cancer and hormones (or hormone-secreting tissue). Note: Beateson suggested that the ovary and the testicle sent out "subtle and mysterious influences" and that the ovaries influenced lactation, so he undertook oöphorectomy. See, Cooke, 1979

 

Marin-Théodore Tuffier (FR) and Louis Hallion (FR), in 1896, published their experiments on artificial respiration using intratracheal intubation with an inflatable cuff tube (1624-1626). Note: In 1910, he reported three successful uses of extrapleural pneumothorax.

Herbert Meyrick Nelson Milton (GB-EG) designed a vertical sternal-splitting approach for the excision of tuberculous mediastinal nodes and employed it successfully in a patient (1129). See, Marin-Théodore Tuffier 1892 and Andreas Wesele Vesalius 1543.

 

 John Benjamin Murphy (US) was the first to reunite a severed femoral artery (severed by a gunshot wound). He described this vascular surgery as follows: "A row of sutures was placed around the edge of the overlapping distal end [of the femoral artery], the sutures penetrating only the media of the proximal portion; the adventitia was then drawn over the line of union and sutured. The clamps were removed. Not a drop of blood escaped at the line of suture. Pulsation was immediately restored in the artery below the line of approximation…. A pulsation could be felt in the dorsalis pedis on October 11th, four days after the operation. There were no oedema of the leg and no pain" (1167). This is one of the earliest examples of vascular surgery.

 

Ludwig Wilhelm Carl Rehn (DE) was possibly the first surgeon to successfully suture the heart. This occurred following a knife stab wound in the right ventricle. Quoting Rehn, "I decided to suture the heart wound. I used a small intestinal needle and silk suture. The suture was tied in diastole. Bleeding diminished remarkably with the third suture; all bleeding was controlled. The pulse improved. The pleural cavity was irrigated. Pleura and pericardium were drained with iodoform gauze. The incision was approximated, heart rate and respiratory rate decreased, and pulse improved post-operatively." The patient made a complete recovery (871; 1347; 1348). Some consider this the origin of cardiac surgery.

Ludwig Wilhelm Carl Rehn (DE) eleven years later reported 124 operations to suture cardiac wounds with a survival rate of 40 %. Rehn's operations moved cardiac surgery from the realm of unethical adventure to possible success in saving lives (1349). confirm ref

 

Journal of Experimental Medicine was founded.

 

American Journal of Physiology was founded.

 

The Paul-Ehrlich-Institut was founded as Institut für Serumforschung und Serumprüfung (Institute for Serum Research and Serum Testing) at Steglitz near Berlin as a test and research institution.

 

1897

"This day designing God

Hath put into my hand

A wonderous thing. And God

Be praised. At his command

I have found thy secret deeds

Oh million-murdering Death.

I know that this little thing

A million men will save

Oh, death where is thy sting?

Thy victory oh grave?" Ronald Ross (GB) wrote in his notebook upon his discovery of the relationship between man, malaria and the Anopheles mosquito (606).

 

"Hypotheses come and go, but data remain." Santiago Ramón y Cajal (1338)

 

"Mastery of technique, [which is] so important that [...] it may be stated that great discoveries are in the hands of the finest and most knowledgeable experts on one or more of the analytical methods." (1338)

 

Joseph John Thomson (GB) announced the existence of negatively charged particles smaller than an atom (1595; 1596). They were then called cathode rays but were later named electrons by George Johnstone Stoney (GB), in 1891 (1557).

 

Karl Ferdinand Braun (DE) invented the oscilloscope (231).

 

David T. Day (US) described the separation of petroleum fractions upon percolation through an adsorbent, a form of column chromatography (402).

 

August Dupre (GB) suggested that the controlled oxidation by bacteria of decomposable substances might be made the basis of a process of sewage treatment. William Joseph Dibdin (GB), a chemist, carried out a series of experiments initiated by Dupre, which led in the early 1890s to the development of the contact filter, one of the first successful forms of biological sewage treatment (429).

 

Eduard Buchner (DE) discovered that an extract of yeast, freed of intact cells by filtration, retains the ability to ferment glucose to ethanol. This observation demonstrated that the enzymes (enzyme = in yeast) of fermentation could function independently of cell structure, contrary to Pasteur’s earlier dictum that fermentations required living yeast cells. Buchner called the cell free extract zymase (253-255). Note: the yeast extract was produced for use in animal experiments but underwent change so rapidly that sugar was added as a preservative. The action of the extract upon this added sucrose drew Buchner’s attention to the fact that fermentation was proceeding in the absence of yeast cells.

This work is seminal: first, because it discounted long held and popular vitalistic theories that consider cellular processes as fundamentally different from other principles of chemistry; secondly, it introduced a methodology that would allow scientists to break down biochemical processes into their individual steps; and, finally, the discovery of cell-free fermentation opened the doors to one of the most important concepts in biochemistry- the enzymatic theory of metabolism.

Augustyn Wróblewski (LV-RU-PL) showed that phosphate stimulates zymase activity (1832).

 

In 1897, oil of citronella (plant genus Cymbopogon) was first used as an insect repellent (1478).

 

Herbert Spencer Jennings (US) and John Hunt Crosby (US) began their pioneering studies on reactions to stimuli in unicellular organisms. This led to such concepts as the trial-and-error behavior and many important concepts concerning various forms of tropisms and taxes (863-869).

 

Filippo Bottazzi (IT) and Léon Frédéricq (BE) found that most marine invertebrates are isotonic with the ocean (208; 209; 618).

 

Arthur Ernst Eichengrün (DE) is known for developing the highly successful anti-gonorrhea drug silver proteinate (Protargol), the standard treatment for 50 years until the adoption of antibiotics. It was also used to treat adenoiditis, pharyngitis, Otis media, conjunctivitis, ophthalmia, and rhinitis (1650).

 

John Jacob Abel (US) and Albert Cornelius Crawford (US) determined that the active ingredient of the blood-pressure-raising extract of the suprarenal capsule (of the adrenal gland) could be isolated as a monobenzoyl derivative. Epinephrin (epinephrine) was the name Abel assigned to it while the pharmaceutical firms insisted on calling it adrenaline. This was the first isolation of an endocrine secretion as a chemically pure substance (6; 7).

 

Nikolai Kulchitsky (RU-GB) described a cell type in the epithelium of the small intestine. These are argentaffin cells found between the cells that line the glands of Lieberkühn of the intestine (945). It is known as Kulchitsky’s cell.

 

Benjamin Moore (GB), D.P. Rockwood (GB), Heinrich Otto Wieland (DE), and Hermann Sorge (DE) proposed that bile acids somehow form polymolecular complexes with fatty acids (1148; 1782).

Leon Lack (US) and Irwin M. Weiner (US) reported that the ileum actively transports conjugated bile acids, thus providing for the first time a mechanism for intestinal conservation of conjugated bile acids (949).

Bengt Borgström (SE), Göran Lundh (SE), and Alan F. Hofmann (US) performed perfusion studies, which confirmed that the ileum is the major site of conjugated bile acid replacement in man (203).

Alan F. Hofmann (US) clarified the role of conjugated bile acids in enhancing lipid absorption by showing that conjugated bile acids form mixed micelles with fatty acids and monoglycerides in vitro (810).

Alan F. Hofmann (US) and Bengt Borgström (SE)) isolated the micellar phase from small intestinal content during fat digestion (811).

Suzie W. Huijghebaert (BE), Alan F. Hofmann (US), Ashok K. Batta (US), Gerald Salen (US), Sarah Shefer (US), Adrian Schmassmann (CH), M. Antonietta Angellotti (IT), Huong-Thu Ton-Nu (US), Claudio D. Schteingart (US), Carlo Clerici (IT), Steven S. Rossi (US), Marcus A. Rothschild (US), Bertram I. Cohen (US), Richard J. Stenger (US), Erwin H. Mosbach (US), Richard G. Quist (US), Jan Lillienau (SE), Kim E. Barrett (US), Sarah J. Longmire-Cook (US), Young S. Kim (US), Rudy G. Danzinger (CA), Oliver Esch (US), Hans Friedrich Fehr (CH), and Johannes Locher (CH) proved that cholylsarcosine has all of the desired properties of a conjugated bile acid replacement molecule making it potentially useful in the treatment of short bowel syndrome (SBS) (120; 836; 994; 1023; 1329; 1450; 1451).

 

John Newport Langley (GB) introduced the terms pre-ganglionic and post-ganglionic in 1897 and gave the autonomic nervous system its name in 1903. He named the cranial and sacral divisions of the autonomic nervous system, which seemed to be involved with the restoration and conservation of bodily resources, parasympathetic (961; 962; 1807).

 

Ivan Petrovich Pavlov; Iwan Petrowitsch Pawlow (RU), using dogs, surgically produced a miniature stomach as a special pouch (Heidenhein-Pavlov pouch) attached to the main stomach, both retaining their nerve supply. The miniature stomach opened to the outside of the body and when food was received into the main stomach, the small pouch secreted gastric juice of the same quality as that secreted to deal with the food. By this means he succeeded for the first time in obtaining samples of gastric juice uncontaminated with food. In the animal with the gastric fistula Pavlov observed that after it saw or smelled food, an abundant flow of gastric juice occurred. In some dogs he brought the esophagus to the surface of the body, where it was sutured, and then cut so that food taken by mouth would pass out of the upper end and food introduced into the lower end passed into the stomach. Again, the sight or smell of food caused copious secretion of both saliva and gastric juice, the volume of gastric juice increasing as the animal was fed even though the food never reached the stomach, but passed out the esophagus. This flow he termed psychic secretion and showed that it depended upon reactions integrated at the level of the cerebral cortex since removal of the cortex abolished the response. He also found that section of the vagus nerve abolished secretion of gastric juice indicating that it is the secretory nerve of the gastric glands (See, Brodie, 1814). Food introduced into the stomach of sleeping dogs through the esophageal opening stimulated gastric secretion. The volume, pepsin content, and acid content of the gastric secretion varied with the food type. Pavlov called this phenomenon chemical secretion (1269-1271).

Robert Mearns Yerkes (US) and Sergius Morgulis (US) report that Iwan Petrowitsch Pawlow or Ivan Petrovich Pavlov (RU) devised and introduced into research a valuable new method of investigating the physiology of the nervous system in its relations to the so-called psychic reactions of organisms. It is called the Pawlow salivary reflex method. They give a description of the method and a summary of important results it has yielded (1840).

 

Ivan Petrovich Pavlov; Iwan Petrowitsch Pawlow (RU) discovered enterokinase, an enzyme in the duodenum that activates trypsin, described the neural control of the pancreas and pancreatic control as a response to different foods, demonstrated that chewing and swallowing alone would cause gastric secretion, concluded that the secretory nerve that controls the gastric glands is the vagus nerve, demonstrated that variance in types and amounts of secretions of the stomach is a response to different foods, and observed that the mere sight of food stimulates salivary and gastric secretion (1268-1271).

 

Bernhard Krönig (DE) and Theodor Paul (DE) described for the first time many of the important methods needed to properly evaluate chemicals as antiseptics and disinfectants. They pointed out that disinfectants could only be accurately compared when certain conditions are fulfilled. The bacterial test organism must have the same resistance and the number of bacteria must be constant. After the application of the test agent for a specified length of time its action must be promptly and completely stopped. Following treatment, the bacteria must be transferred to the most favorable medium and kept at optimum temperature. The result is determined by enumeration of survivors in plate cultures. They emphasized that bacterial cells are not all killed instantaneously, but that populations of cells die at a logarithmic rate with the rate of kill directly proportional to the concentration of disinfecting agent (938).

 

George Neil Stewart (US) reported on the blood circulation time course and on the influences, which affect it (1548).

 

Eugen Rehfisch (DE) established the paradigm that micturition is initiated and sustained by active primary relaxation of the sphincter (1346).

 

Walter Migula (DE) introduced the order Thiobacteria for those microbes, which Winogradsky had called sulfur bacteria (1120).

 

Helen Beatrix Potter (GB), of The Tale of Peter Rabbit fame, was an outstanding observer of nature. While working in the British Museum, she reached the conclusion that lichens represent a symbiotic relationship between fungi and algae. Because of her sex, she was not taken seriously. Her uncle, Henry Roscoe, read her paper before the Linnean Society in London (1317; 1318; 1434). Note: while she was not the first to make this observation, her work came shortly after that of Schwendener in 1869.

 

Michael Siedlecki (PL-DE) and Fritz Richard Schaudinn (DE) were the first to describe the life history of Coccidiae (scale insects) (1503).

 

Edwin Grant Conklin (US), using the annelid worm Nereis, and Edmund Beecher Wilson (US), using the limpet Crepidula, discovered that the early embryonic cleavage events are the same in these organisms from two different phyla. In both, the three quartets of micromeres came off in the typical pattern of spiral cleavage: the first quartet clockwise, the second counter-clockwise, and the third clockwise. But the truly startling discovery was that both formed a d4 cell from which all mesodermal structures are derived in later development (335; 1802).

 

Thomas Hunt Morgan (US) attempted to bring together the most important results of studies of the development of the frog's egg to give a continuous account of the development, as far as that was possible, from the time when the egg is forming to the moment when the young tadpole issues from the jelly-membranes (1154).

 

Adolf Wallenberg (DE), Cornelius Ubbo Ariëns-Kappers (NL), and Willem Frederik Theunissen (NL) related the olfactory system to recognition and taste for food (39; 40; 1726).

 

Rudolf Kraus (AT) discovered that by injecting animals with the clear filtrates from liquid cultures of cholera, typhoid, or plague bacilli, he obtained sera, which produce specific precipitates when mixed in vitro with samples of the filtrates, which had been employed for the inoculation. Thus, the serum of animals injected with cholera filtrates precipitated the latter but did not precipitate the filtrates of other cultures. Kraus’s discovery of precipitating sera (precipitin) was confirmed by many workers, and Jules Jean Baptiste Vincent Bordet (BE) showed that it also occurred with non-bacterial substances (201; 936).

Jacques Oudin (FR) modified this procedure by adding a small amount of agar to the anti-serum forming a gel in a tube. When this was overlaid with antigen a series of rings appeared in the gel corresponding to the number of specific antigens and antibodies in the materials (1237).

Örjan Ouchterlony (SE) adapted the analysis of precipitin reactions to gel plates. This greatly increased the precision of the analysis (1234-1236).

 

Masanori Ogata (JP) injected crushed fleas from rats dead of plague into two mice, one of which died after three days. Based on this meager evidence he correctly suggested that suctorial insects such as mosquitoes and fleas transmit plague (1213).

Alexandre Émile Jean Yersin (CH) developed an antiserum to protect against the bubonic plague bacillus (1843).

Alessandro Lustig (IT) and Gino Galeotti (IT) were the first to isolate a toxin from Yersinia pestis (1033).

Paul-Louis Simond (FR) found organisms morphologically indistinguishable from plague bacilli in the stomach of fleas, which had fed upon rats and mice dying of plague. He succeeded in infecting a mouse by injecting an extract of crushed fleas taken from a plague rat. Simond found that in the absence of fleas the plague was not transmitted from sick or dead rats to healthy rats in close proximity, but in at least two incidents he observed transmission when fleas were present. He incorrectly concluded that contaminated flea feces were being introduced at the site of fleabites (1505). This and Ogata’s work above represents the discovery that fleas vector the plague.

Robert H. Pollitzer (AT-US) concluded, "Pulex irritans plays the main role in the spread of human plague" (1311). Note: this is the human flea.

 

Paul Ehrlich (DE) discovered that antibodies act by combining with the substances, which incited their production and observed that the plant poison ricin causes mouse erythrocytes to agglutinate and that he could prevent this agglutination in vitro and in vivo with anti-ricin serum provided the ratio of ricin to anti-ricin was proper. He discovered that if non-immune mice are given anti-ricin serum it can protect them from the effects of ricin. Finding that there is a direct union of ricin and anti-ricin in vitro, Ehrlich concluded that it was necessarily a chemical process.

He discovered that the union of antitoxin and toxin is accelerated by mild heat and retarded by cold. He also demonstrated that the reaction took place more quickly in concentrated than in dilute solutions.

In trying to determine what proportions of antitoxin and toxin produced the optimum reaction Ehrlich discovered that toxins are unstable and tend to deteriorate into less potent versions he called toxoids. Although these toxins slowly lose their toxicity he found that their ability to stimulate an immune response remained relatively constant over time. Based on these observations he theorized that a toxin consists of two portions, one of which, the haptophore, brings about the union with the antitoxin, whereas the other—the toxophore—is, as its name implies, the carrier of the toxic action. He studied several different samples of diphtheria toxin and from them laid down the principles for the accurate standardization of antitoxic sera.

Ehrlich improved Behring's diphtheria antitoxin and established an international standard for this and other antitoxins. The first exposition of his side-chain theory of immunity also appeared in the 1897b paper (514-516).

 

Almroth Edward Wright (GB) and Frederick Smith (GB) devised an Agglutination Test for the diagnosis of undulant fever (1828).

 

Arnaldo Angelucci (IT) was the first to describe a nonbacterial conjunctivitis characteristically occurring in the spring. It is accompanied by tachyardia, vasomotor lability, lacrimation, photophobia, and sometimes hyperexcitability. Believed to be of allergic origin, affecting both sexes and all ages. A cutaneous or mucous itching with sudden onset and sudden termination are typical. Etiology unknown (28). This condition is known as Angelucci’s syndrome

 

Wilhelm Max Wundt (DE) added alkaline and metallic tastes to the four basic tastes: sour, sweet, bitter and salty. He is considered the father of modern psychology (1833).

 

Waldemar Mordecai Wolff Haffkine (RU-CH-FR) used killed plague microorganisms as a vaccine against the plague (727).

 

Josef Albert Amann (DE) published the first textbook of microscipical gynaecological diagnostics (24).

 

George Fredericc Still (GB) identified the three categories of juvenile chronic arthritis. The systemic form is now often referred to as Still's Disease (1550).

 

Wilhelm Theodor Engelmann (DE) was the first to distinguish the four types of activity of the heart nerves: inotropic, bathmotropic, chronotropic, and dromotropic (544).

 

Constantin von Monakow (RU-DE) wrote Gehirnpathologie with 3000 references, and articles on lead encephalopathy, aphasia and apraxia. His greatest work as a clinician was Die Localization in Grosshirn und der Abbau ler Funktion durch Korticale Herde. He introduced concepts, which made present clinical neurology a truly biological science of organismal dynamics in human behavior (1708; 1709).

 

Leonard Erskine Hill (GB) and Harold Leslie Barnard (GB) described a simple and accurate form of sphygmometer or arterial pressure gauge contrived for clinical use (793).

Nikolai Sergeievich Korotkov (RU) discovered the auscultatory method of measuring arterial pressure, "The cuff of Riva-Rocci is placed on the middle third of the upper arm; the pressure within the cuff is quickly raised up to complete cessation of circulation below the cuff. Then, letting the mercury of the manometer fall one listens to the artery just below the cuff with a children's stethoscope. At first no sounds are heard. With the falling of the mercury in the manometer down to a certain height, the first short tones appear; their appearance indicates the passage of part of the pulse wave under the cuff. It follows that the manometric figure at which the first tone appears corresponds to the maximal pressure. With the further fall of the mercury in the manometer one hears the systolic compression murmurs, which pass again into tones (second). Finally, all sounds disappear. The time course of the cessation of sounds indicates the free passage of the pulse wave; in other words, at the moment of the disappearance of the sounds the minimal blood pressure within the artery predominates over the pressure in the cuff. It follows that the manometric figures at this time correspond to the minimal blood pressure." (928).

 

Claudien Philippe (FR) Max S. Löwenthal (GB) and Victor Alexander Haden Horsley (GB) reported the inhibition of decerebrate (removal of the cerebrum) rigidity by localized stimulation of the cerebellar cortex (1028).

 

Edward Flatau (PL) reported that the greater the length of the fibers in the spinal cord the closer they are situated to the periphery (587).

 

George Frederic Still (GB) provided the landmark description of chronic arthritis in children when he described 22 children with chronic arthritis and commented that most had a disease that differed from chronic arthritis as described in adults (1550).

 

Cesar Roux (CH) attached the small intestine to the stapled off upper third of the stomach and joined it in a Y formation to the now quiescent exit from the lower two thirds of the stomach (1383). This is called a Roux-en-Y operation in his honor.

 

Carl B. Schlatter (CH), in 1897, performed the first successful complete gastrectomy (1447).

 

John Jacob Abel (US) was one of the most important individuals involved in the transfer of medical knowledge from Europe to America. After graduating from the University of Michigan in pharmacy in 1883 he spent one year at Johns Hopkins then studied medicine and chemistry in Europe under His, Braune, Schwalbe, Carl Ludwig, Oswald Schmiedeberg, Heinrich Ferdinand Edmund Drechsel, Hoppe-Seyler, Marcellus von Nencki, and Johannes Adolf Wislicenus. He earned the M.D. degree from the University of Strasbourg in 1888 then interned in Vienna. Upon returning to America he taught at the University of Michigan and Johns Hopkins University.

 

Louis-Antoine Ranvier (FR) and Édouard-Gérard Balbiani (FR) founded the Archives d'Anatomie Microscopique.

 

1898

"When reading Beijerinck's 1898 publication, one must conclude that he was the first to internationally voice the novel nature of the agent causing tobacco mosaic, completely different from microbial corpuscular organisms. When he claims that 'the infection is not caused by a microbe, but by a contagium vivum fluidum', thence in his paper called a virus, he specifies it to be a 'liquid or soluble agent' that "reproduces itsef in the living plant". Martinus Willum Beijerinck (139; 207).

 

Pierre Currie (FR), Marie Skodowska Curie (PL-FR), and Gustave Bémont (FR) presented the papers, which announced the discovery of radium. They first proposed the name polonium, because Marie was from Poland, then changed it to radium (379; 380). Marie also presented this discovery in her doctoral thesis (377).

 

Jacobus Hendricus van’t Hoff (NL) and Arthur Croft-Hill (GB) affirmed that enzymes, like inorganic catalysts, promote the rate of reversible reactions in both directions (364; 1649).

Joseph H. Kastle (US) and Arthur S. Loevenhart (US) demonstrated the reversibility of enzymes using lipase (884).

 

Arthur Croft-Hill (GB) announced the first enzymatic synthesis, that of isomaltose (364).

 

Frank George Edmed (GB) determined the structure of oleic acid (502).

 

Frantisek Vejdovsky (CZ) and Alois Mrazek (CZ) are credited with the discovery of the centrosome in animal cells. They called it the periplast (1653).

 

Thomas Harrison Montgomery Jr. (US) performed comparative cytological studies, with especial regard to the morphology of the nucleolus (1146).

 

ValentinHaecker (DE) while sorting material collected on the great German plankton expedition, first recognized that oceanic pelagosphaeras were in fact larval sipunculans (725). Note: Sipunculans are bilaterally symmetrical, unsegmented marine worms.

 

Karl von Sternberg (AT) and Dorothy Mendenhall née Reed (US) provided the first definitive microscopic descriptions of Hodgkin's disease. They described what are now called Reed–Sternberg cells (also known as lacunar histiocytes). These are giant cells usually derived from B lymphocytes, classically considered crippled germinal center B cells, meaning they have not undergone hypermutation to express their antibody (1344; 1712).

 

Robert Adolf Armand Tigerstedt (FI) and Per Gustaf Bergman (FI) extracted rabbit kidney and showed that it contained a principle, which raised blood pressure upon intravenous injection into other rabbits. They called the principle renin (1605). Renin would later be found to promote the release of angiotensin, a powerful pressor agent.

Franz Volhard (DE) suggested that pallid (renal) hypertension results from a pressor substance released from ischemic kidney(s) contributing—via a vicious cycle—to a further rise in blood pressure with subsequent renovascular injury and aggravation of hypetension (1665).

Adolf Hartwich (DE), one of Volhard's disciples, demonstrated in 1930 that ligation of the renal artery in dogs caused a transient rise in blood pressure (939).

John Loesch (AT-HU-US) induced essential hypertension in experimental animals using renal ischemia (1010; 1011).

Harry Goldblatt (US), James Lynch (US), Ramon F. Hanzal (US), and Ward W. Summerville (US) reported experiments in dogs in which they induced high blood pressure (hypertension) by constricting either one or both main renal arteries with an adjustable silver clamp they had devised (677). They produced severe renal ischemia with a resulting syndrome, which closely simulated the malignant phase of human essential hypertension (675-677).

Harry Goldblatt (US) proposed the existence of a humoral mechanism due to the release of a pressor substance by the kidney (674). Note: These experiments led to the elucidation of the renin-angiotensin system and its relationship to many other volume-pressure regulatory mechanisms such as aldosterone, prostaglandins, kinases, and lately nitric oxide (NO) among others.

Eduardo Braun-Mendendez (AR), Alberto C. Taquini (AR), Juan Carlos Fasciolo (AR), Bernardo Alberto Houssay (AR), and Irvine Heinly Page (US) demonstrated renal secretion of a pressor agent similar to renin (569; 1245; 1578). Their subsequent investigations showed that renin acted enzymatically on a plasma protein to produce a pressor substance. In Buenos Aires, it was called hypertensin. In the United States, it was called angiotonin. Angiotensin was born out of angiotonin and hypertensin (232). The substrate in the plasma acted on by renin was named angiotensinogen.

 

Edward Lee Thorndike (US), and Richard Sessions Woodworth (US) described his puzzle box and began work, which led to his proposed psychological law of effect. In full it reads: "Of several responses made to the same situation those which are accompanied or closely followed by satisfaction to the animal will, other things being equal, be more firmly connected with the situation, so that, when it recurs, they will be more likely to recur; those which are accompanied or closely followed by discomfort to the animal will, other things being equal, have their connections to the situation weakened, so that, when it recurs, they will be less likely to occur. The greater the satisfaction or discomfort, the greater the strengthening or weakening of the bond." His works include Psychology of Learning and The Measurement of Intelligence (1598-1603; 1821).

 

Giuseppe Sanarelli (IT) discovered that myxomatosis is a virus disease of wild and domestic rabbits, benign in the South American rabbit but usually fatal in the European wild rabbit (Oryctolagus cuniculus). He first found it in a native South American rabbit, Sylvilagus braziliensis Linnaeus, in Brazil. This was the first time that a tumor disease in animals was shown to be caused by a filterable agent, i.e., virus (1432). Note: the first poxvirus

 

Shotaro Hori (JP) was the first to associate the plant disease bakanae (foolish seedlings) with infection by the fungus Gibberella fujikuroi, although he at first identified the fungus as Fusarium heterosporum (823-825).

Eiichi Kurosawa (CN) produced the symptoms of the bakanae disease in rice and maize seedlings solely by treating them with a culture medium in which Gibberella fujikuroi had been grown (947).

Teijiro Yabuta (JP) and Yusuke Sumiki (JP) isolated the bakanae factor, crystallized it, and named it gibberellin (1836; 1837).

 

Edmond Isidore Étienne Nocard (FR), Pierre Paul Émile Roux (FR), Amédée Borrel (FR), Alexandre Salimbeni (FR), and Edouard Dujardin-Beaumetz (FR) grew the causative agent of cattle pleuropneumonia in vitro for the first time. It was grown on a serum-enriched medium and referred to as PPLO (pleuropneumonia-like organism) (1200). Today it is placed in either the genus Mycoplasma or Acholeplasma.

Louis Ladislaus Dienes (US) and Geoffrey Edsall (US) made the first isolation of mycoplasmas from man finding it as the apparent cause for suppuration of Bartholin’s gland (435).

Monroe D. Eaton (US), Gordon Meikeljohn (US), and William Van Herick (US) isolated and cultivated the causative agent of atypical pneumonia in man (489).

Maurice C. Shepard (US) discovered the so-called T strains (tiny colonies 15 to 20µ) which appeared to produce nongonococcal urethritis in man (1488).

Robert Merritt Chanock (US), Leonard Hayflick (US), and Michael F. Barile (US) were the first to cultivate Mycoplasma pneumoniae on an artificial medium (306).

Robert Merritt Chanock (US) named the agent Mycoplasma pneumoniae (305).

 

Kiyoshi Shiga (JP) and Shibasaburo Kitasato (JP), while studying an epidemic of dysentery in Japan, discovered the bacillus of dysentery, now named Shigella dysenteriae. They employed the methodology of Koch’s postulates and the agglutination of axenic cultures by serum from patients with dysentery (1493-1495).

Walther Kruse (DE) found the dysentery bacillus during an epidemic of dysentery in the Ruhr area (942). This bacterium is often referred to as the (Shiga-Kruse bacillus).

 

Adrien Veillon (FR) and Alfred Zuber (FR) found Bacteroides fragilis in 22 cases of appendicitis (1651). Since then it has been found in lung, pelvic and hepatic abscesses, in septicemias with metastatic abscesses, and in infections of the urinary tract. The bacterial genus Veillonella is named to honor Adrien Veillon.

 

Benjamin Robinson Schenck (US) isolated a fungus, Sporotrichum sp., from a patient with refractory subcutaneous abscesses on his arm (1441). He would later be commemorated when it was named Sporotrichum schenckii. The infection is called sporotrichosis.

Charles Lucien de Beurmann (FR) and Henri Gougerot (FR) carried out extensive and detailed studies of sporotrichosis (403-406).

Sporothrix schenckii was renamed Sporotrichum beurmanni.

 

Justin Jolly (FR) made a detailed in vitro study of the behavior of different kinds of leukocytes and ultimately succeeded in keeping the leukocytes of the newt (Triton) alive for one month (873-876).

 

Carl August Ljunggren (SE) demonstrated that human skin could still be successfully grafted after being stored for weeks in ascitic fluid (1002).

 

Jules Jean Baptiste Vincent Bordet (BE) discovered that immune hemolysis of erythrocytes can be the result of mixing the cells with heated anti-RBC serum and unheated normal serum.

On adding to a suspension of rabbit’s blood corpuscles in salt solution a small quantity of guinea-pig immune serum, the blood corpuscles of the rabbit rapidly clumped together (agglutination), and the hemoglobin passed into the medium leaving behind the colorless stromata or shadows. Heated to 55°C. for half an hour the hemolytic property of the immune serum was found to have disappeared. If then to a mixture of rabbits’ corpuscles and inactive, i.e., to heated guinea-pig immune serum Bordet added a quantity of serum from a normal guinea-pig or a normal rabbit, the phenomenon of hemolysis soon took place. The guinea pig immune serum was found to have no effect on the corpuscles of guinea pigs or pigeons. In fact, it had a specific effect only on the corpuscles of the animal (rabbit) with which the guinea pig had been originally injected. Bordet also showed that a hemolytic destruction of corpuscles takes place in the peritoneal cavity of an immunized guinea pig. If the immune serum is heated to 55°C. and is then mixed with the homologous red blood corpuscles, the latter are hemolyzed in the peritoneum of a normal animal.

In the nomenclature of Bordet, the thermolabile factor in hemolysis was named alexine and the thermostable element the substance sensibilisatrice, whereas Paul Ehrlich (DE) and Julius Morgenroth (DE) spoke of them as complement and amboceptor respectively. The latter names have persisted (200; 519; 520).

 

Richard Friedrich Johannes Pfeiffer (DE) and Ernst Marx (DE) considered that anti-cholera antibodies are produced especially in the spleen, lymph nodes, and bone marrow, and this was supported by experiments of others (1297).

 

Walter Bradford Cannon (US) was the first to use Röntgen’s x-rays for physiological purposes. To do this, he devised a bismuth meal, a suspension of material of high atomic weight which was harmless, and which was opaque to x-rays. After such a meal, the intestinal system would stand out as white against a black background, under x-rays. For the first time, men could see the body’s soft internal organs on display while the outer skin remained intact. The diagnosis of gastric ulcer and malignancy of any part of the gastro-intestinal tract by means of a bismuth or barium meal followed by fluoroscopy or radiophotography became a common clinical method (283).

 

William Thomas Councilman (US), Frank Burr Mallory (US), and James Homer Wright (US) provided a detailed study of cerebrospinal meningitis and its relation to other forms of meningitis (348).

 

Montoya (CO) and J.B. Flores (CO) were the first to report tinea nigra as a disease state. They called it Caraté noir (1147).

Alexandre Cerqueira (BR) produced a well-documented description of tinea nigra in 1891 but it was not published until 1916 when his son Antonio Gentil de Castro Cerqueira-Pinto (BR) described it as keratomycosis nigricans palmaris in his medical thesis (302).

Paulo Parreiras Horta (BR) named the fungal agent Cladosporium wernickii (830).

 

John McFadyean (GB) and Frederick Hobday (GB), in dogs, reported the first cell-free transmission of papillomas (1093).

 

Johann Petruschky (DE) suggested that convalescent cases of typhoid fever might be able to infect healthy individuals by means of typhoid bacilli in their urine (1287).

Paul Frosch (DE) confirmed the suggestion of Petruschky (631; 632).

Karl Wilhelm von Drigalski (DE) found that apparently healthy individuals might pass typhoid bacilli in their feces, i.e., healthy carriers (1674).

 

Henry Fairfield Osborn (US) enunciated the concept of adaptive radiation in evolution. Starting from an ancestral stock species, variations in the stock would allow a species to occupy niches previously unavailable (1222).

 

Bernhard Naunyn (DE) published Der Diabetes Melitus in which he presented evidence to refute the prevailing opinion of the supposed benefit of a high-protein diet in the treatment of diabetes melitus (1174).

 

Guido Banti (IT) demonstrated that the spleen is the principal site for the destruction of erythrocytes, and that this normal function is exaggerated when the spleen becomes enlarged pathologically (85-87).

 

Francis Galton (GB) presented his ancestoral law of heredity (642). Ronald Aylmer Fisher (GB) later found this law to be the natural consequence of Mendelian inheritance for polygenic traits. See, Fisher, 1918.

 

Walther Flemming (DE) postulated that the diploid chromosome number in man was 24 (599). See, Tjio 1956 for the correct cound.

 

Charles Scott Sherrington (GB) described decerebrate (removal of the cerebrum) rigidity in the cat (1490).

 

Charles Scott Sherrington (GB) demonstrated axon branching and showed that the axonal pain pathways are proof of an organized sensory network. He worked on determining the region (dermatome) of skin supplied by each dorsal root (1489).

Henry Head (GB) and Alfred Walter Campbell (AU-GB) reported that the cardinal pathologic features of Herpes zoster (shingles) are inflammation and hemorrhagic necrosis with associated neuritis, localized leptomeningitis, unilateral segmental poliomyelitis, and degeneration of related motor and sensory roots. They established the concept of the dermatome based on the correlation between the area of skin affected by the Herpes zoster rash and the consequent scarring and degeneration in the trigeminal and dorsal root ganglia found at autopsy.

They found that many herpetic areas representing the peripheral distribution of single roots or individual sections of the cord corresponded closely with areas of referred pain from diseases of different internal organs. This led Head to conclude that irradiation of abnormal afferent impulses produces a state of excessive irritability in the grey matter of the dorsal horn at the level where they enter it. Because of this, impulses from the skin that pass through it are exaggerated or disordered so that a stimulus that would not usually provoke a painful reaction does so (757; 758).

Otfrid Foerster (DE) made a thorough study of the human dermatomes, including overlap in nerve distributions. This overlapping is correct and conflicts with some of Head’s conclusions. Foerster suggested the concept of gate control. This theory asserts that large nerve fibers can inhibit small nerve fibers during a painful experience. He also introduced topographical localization of function, suggesting that pain fibers are in different locations from temperature and touch fibers (601).

 

William Henry Howell (US) showed that the pituitary’s blood pressure lowering activity resides in the posterior lobe (831).

 

John Newport Langley (GB) and William I. Dickinson (GB) coined the phrase autonomic nervous system, and the term parasympathetic (963).

 

Karel Frederik Wenckebach (NL-AT) described a sequence of cardiac cycles in the electrocardiogram. It is a form of incomplete atrioventricular heart block in which there is progressive lengthening of conduction time course in cardiac tissue with P-R interval increasing until there is not a ventricular response. This is followed by a conducted beat with a short P-R interval, and then the cycle repeats itself. This occurs frequently after an inferior myocardial infarction and tends to be self-limiting. Today it is referred to as a type 1 second-degree atrioventricular (AV) block or Wenckebach’s phenomenon (1758; 1759).

John Hay (GB) discovered the form of second-degree AV block currently known as type 2 block or Mobitz type 2 auriculoventricular block (753).

Woldemar Mobitz (DE) provided electrocardiographic proof of Hay’s discovery (1136).

 

Georges Hayem (FR) gave the first adequate description of acquired hemolytic jaundice (Hayem-Widal’s disease) (755).

 

John Benjamin Murphy (US) announced his technique of treating tubercular lungs by intentional pneumothorax (1168; 1169).

 

George H. Monks (US) developed a new method for restoration of a lower eyelid by plastic surgery. An apical patch was cut, pulled through the corner of the eye socket then attached below (1139).

 

Gustav Killian (DE) introduced bronchoscopy when he succeeded in the removal of a piece of bone from the right main stem bronchus of a 63-year-old man (900).

 

Marin-Théodore Tuffier (FR) and Louis Hallion (FR) incised a dying patient’s chest on the wards of La Pitie Hospital and carried out manual cardiac massage. This act, based on animal experimentation, led to the first published surgical exposure of the unwounded human heart. Although the patient recovered briefly, the recovery could not be sustained because of a clot in the pulmonary artery (1627).

 

Leonardo Gigli (IT) developed a safe method for temporary cranial resection using a grooved probe and a wire saw (667).

 

Ernst Wertheim (AT-HU), in 1898, performed the first radical abdominal hysterectomy for cervical cancer. This operation involved removal of the uterus, parametrium, tissues surrounding the upper vagina, and pelvic lymph nodes, but leaving the ovaries intact (1766; 1768).

 

Gheorghe Marinescu (RO), between 1898 and 1901, made the first science films in the world: [1] The walking troubles of organic hemiplegy (1898), The walking troubles of organic paraplegies (1899), A case of hysteric hemiplegy healed through hypnosis (1899), The walking troubles of progressive locomotion ataxy (1900) and Illnesses of the muscles (1901) (483).

 

Ernest Thompson Seton (GB-US) wrote Wild Animals I Have Known. This book had a profound positive impact on the public's perception of natural predators such as the wolf of North America (1479).

 

The Russian Hydrographic Survey of the Biology of Lake Baikal was undertaken between 1876 and 1902. This survey, led by Fedor Kirillovich Drizhenko (RU), found several unique endemic freshwater animals that had become extinct in the rest of the world. The unique fauna in this lake exemplify the power of isolation in the evolutionary process (462; 463).

 

Paul Marchal (FR) founded the first agricultural entomology research unit. He was head of the Entomological Laboratory at INA, Paris, where basic and applied research on entomophagous insects took place.

 

1899

"The good physician treats the disease; the great physician treats the patient who has the disease." William Osler (CA-GB), c. 1899-1905 (1313)

 

The sixth cholera pandemic killed more than 800,000 in India before moving into the Middle East, northern Africa, Russia and parts of Europe. By 1923, cholera had receded from most of the world, although many cases were still present in India.

 

Carl Ernst Arthur Wichman (DE-NL) crystallized a protein from the albumin fraction of whey by addition of ammonium sulfate and acidification (1776).

 

Paul Gerson Unna (DE) and Artur Pappenheim (DE) developed the Unna-Pappenheim stain, the most common stain for blood smears. It was originally used for gonococci, but later used to demonstrate plasma cells during chronic inflammation. It detects RNA and DNA in tissue sections with the RNA staining red and the DNA staining green (1257; 1637)

 

Pierre Émile Duclaux (FR) observed that extracellular production of proteases and saccharase in Aspergillus occurred in response to the addition of protein and sucrose to the medium in which the organism was grown. This is the origin of the analysis of the regulation of protein synthesis (475). This phenomenon was later called enzymatic adaptation. Melvin Cohn (US), Jacques Lucien Monod (FR), Martin Pollack (GB), Solomon Spiegelman (US), and Roger Yate Stanier (CA) named it enzyme induction (326).

Frédéric Dienert (FR) showed that yeast grown on glucose breaks down glucose but not galactose, but yeast grown on galactose breaks down either galactose or glucose. If yeast is grown in the presence of glucose and galactose, then the glucose is broken down first. He obtained similar results with other sugars (434).

Henning Karström (FI) was the first person to carefully investigate enzyme induction. He found that certain enzymes are always present, regardless of the medium type, whereas other enzymes are only formed when their substrates are present. He coined the term constitutive to describe those enzymes always present, and adaptive to describe those induced by substrate. His work is based on studies of carbohydrate metabolism in Gram-negative enteric bacteria (882).

Marjory Stephenson (GB) and John Yudkin (GB) demonstrated the adaptation of bacteria to different biochemical environments (1541; 1848; 1849).

Jacques Lucien Monod (FR) observed that when Bacillus subtilis or Escherichia coli are grown on a mixture of two sugars, growth occurs in two distinct phases separated by a lag time. During the first phase only one of the two sugars is metabolized, and the second begins to be degraded only when the first sugar has totally disappeared. Glucose was found to be in the first category and lactose in the second (1140; 1141).

Jacques Lucien Monod (FR) christened this phenomenon diauxie, in bacteria. Diauxie is from a Greek root meaning double growth (1142; 1143).

Jacques Lucien Monod (FR) would relate enzymatic adaption to genetics and cellular differentiation (1144).

 

Rudolf Albert von Kölliker (CH) indicated in his memoirs that he had earlier identified and named osteoclasts, explaining that these multinucleated cells are active in osseous absorption and removal (1695).

 

Noël Bernard (FR) established that orchid seed germination requires a mycorrhizal relationship (155; 156).

 

Ludwig Edinger (DE) made many discoveries including his description of the ventral and dorsal spinocerebellar tract, clarifying polio-encephalon and neo-encephalitis, dividing the cerebellum on physiological as well as anatomical grounds into a paleo- and neocerebellum (499-501).

 

Heinrich Wilhelm Gottfried Waldeyer (DE) wrote Das Becken, one of the most complete books which has ever been accomplished in the field of topographic anatomy; it is a real treasure trove of everything scientific, both for the specialist anatomists and for the practical physicians (1724).

 

Theobald Smith (US) determined the thermal death time of Mycobacterium tuberculosis in milk to be 15 minutes at 60°C (1517).

 

Maurice Nicolle (FR) and Mustafa Adil-Bey (TR) discovered that the etiological agent of rinderpest or cattle plague is a virus (1190-1192). Note: first morbillivirus

Richard Edwin Shope (US) developed a vaccine to rinderpest, which was grown and attenuated in hen’s eggs (1497).

The Rinderpest Virus Eradication Campaign, begun in 1945 by the United Nations Food and Agricultural Organization (FAO) was officially declared a success during June 2011 in Rome (1096). The announcement proclaimed, “…for only the second time in history, a disease has been wiped off the face of the earth”. This long but little-known campaign to conquer rinderpest is a tribute to the skill and bravery of “big animal” veterinarians, who fought the disease in remote and sometimes war-torn areas — across arid stretches of Africa larger than Europe, in the Arabian desert, and on the Mongolian steppes.

 

Allan Macfayden (GB) and Sidney Rowland (GB) were the first to test the effect of extremely low temperatures on the viability of bacteria (1042).

 

Harvey Williams Cushing (US) reports that a vaginal gonococcus infection can ultimately lead to acute diffuse peritonitis (384).

Hugh Hampton Young (US) performed most of the bacteriological analyses leading to this discovery (1).

 

Carl Franz Joseph Erich Correns (DE), unaware of Johann Gregor Mendel’s (Moravian-CZ) earlier work, independently discovered the laws of genetics while carrying out hybridization experiments with stock, maize, beans, peas, and lilies. Upon discovering that Mendel had preceded him he published his own work merely as confirmation (343; 344; 346; 1544).

 

Lucien Claude Jules Cuénot (FR) proved experimentally that sex is not influenced by exterior conditions and acknowledged that determination took place as early as the egg stage (366). Note: obviously he did not choose organisms like some reptiles where the incubation temperature influences sex.

 

Adolf Oswald (DE) demonstrated that the iodine of the thyroid is firmly bound to a globulin-like protein and introduced the term thyroglobulin (1232).

 

Lucien Claude Jules Cuénot (FR) proposed that armadillos from the same litter are true twins born of polyembryony (366).

W. James Loughry (US), Paulo A. Prodöhl (US), Colleen M. McDonough (US) and John Charles Avise (US) confirmed this when they found that in the nine-banded armadillo (Dasypus novemcinctus) a litter always consisted of four same-sex, genetically identical siblings. A single fertilized egg splits, leading to four embryos each of which develops into a separate individual (1025).

 

Jules Jean Baptiste Vincent Bordet (BE) in his paper on the mechanism of agglutination, drew attention to the remarkable fact that agglutinins are absorbed from serum when the latter is saturated with the homologous organism. He showed that if immune horse serum is mixed with cholera vibrios and if after contact the vibrios are removed by centrifugation, the clear fluid of the supernatant fraction no longer retains its agglutinating property for cholera vibrios while its agglutinating power on typhoid bacilli persists. Conversely, by saturation first with typhoid bacilli the typhoid agglutinins are removed, whereas the supernatant fraction can still agglutinate cholera vibrios. This experiment pointed to a way of making a serum very specific by absorbing out unwanted agglutinins (201).

 

Paul Ehrlich (DE) and Julius Morgenroth (DE) presented Ehrlich’s Theory of the Lysins. Normal serum is often strongly bacteriolytic for certain species of bacteria (typhoid, cholera, etc.). The bacteriolytic action is due to two distinct principles acting in concert, the intermediate body (Zwischenkörper) and the complement. The intermediate body has an affinity for the bacillus, or rather for certain of the albumin molecules that go to make up the protoplasm of the bacillus and enters chemical combination with such molecules. The complement then enters combination with the intermediate body and by its enzymatic nature can dissolve or destroy the albumin molecules of the bacillus to such an extent that the bacillus itself is destroyed (518).

 

Michael Siedlecki (PL-DE) published the first complete life cycle of a gregarine (Adelea ovata living in Lithobius forticatus) (1502).

 

Stabsarzt Slawyk (DE) isolated and cultured the influenza bacillus (Hemophilus influenzae) from the blood and spinal (lumbar puncture) fluid of a child with meningitis (1508).

Martha Wollstein (US) demonstrated the transmissibility of Hemophilus influenzae infection and the capacity of this organism to cause purulent meningitis (1820). She drew attention to the marked tendency for Hemophilus influenzae type b meningitis to occur in infants and young children.

LeRoy D. Fothergill (US) and Joyce Wright (US) noted the protective role of passively transmitted maternal antibodies, and the inadequacy of host immune response from infancy to age 3 years against Hemophilus influenzae type b meningitis (607).

 

Max Freudweiler (CH) made the connection that uric acid crystals cause gout (624).

Wilhelm His, Jr. (CH) and Max Freudweiler (CH) clearly showed that urate crystals cause inflammation (625; 801).

Wilhelm Ebstein (DE) found that localized death of tissue (necrosis) is a primary event in gout (491).

 

Caesar Peter Møller Boeck (NO) described a disease characterized by build-up of perivascular sarcomatoid tissue resulting from excessively rapid proliferation of epithelioid connective-tissue cells. He called it multiple benign sarcoid. Today it is called sarcoidosis (193).

 

George Washington Crile (US) documented the results of his extensive experimental studies on shock and hypertension (360; 362).

George Washington Crile (US) developed a "shockless" method of anesthesia ("anoci-association") by which he attempted to isolate the operative site from the nervous system, where he believed surgical shock to originate. Anoci-association made use of generous premedication with morphine and atropine, regional (procaine) block, and anesthesia by inhalation of nitrous oxide and oxygen administered by trained anesthetists (363).

 

Max Wilms (DE) described a case of nephroblastoma—Wilms tumor. He performed a successful nephrectomy, but the cancer returned and the patient died (1797).

 

Jean-Louis Prévost (CH) and Frederic Batelli (CH) were the first to thoroughly study the effects of electrical discharge on the heart. They noted that if shock was applied within seconds of the onset of fibrillation, the result was defibrillation, which successfully restored sinus rhythm (1320).

 

Henry Chandler Cowles (US) studied plants on the Indiana sand dunes. This work yielded the first thorough working out of a complete plant successional series leading to a climax phenomenon (350-352).

Arthur George Tansley (GB) said, "It is to Henry Chandler Cowles that we owe, not indeed the first recognition or even the first study of succession, but certainly the first thorough working out of a strikingly complete and beautiful successional series." (1577)

 

Hans Christian Cornelius Mortensen (DK) was the first person in the world to systematically ring birds. He started in 1899, ringing 165 young Starlings with numbered and addressed rings hoping that some of the birds would be found and the rings returned with information about finding place and date (4; 1499). See, Audubon, 1810.

 

Robert Kirk (GB) produced sensitization to Primrose (Primula obconica) tissue by applying the plant repeatedly to irritated skin under occlusive dressings (905).

Bruno Bloch (CH) and Aida Steiner-Wourlisch (CH) sensitized humans and guinea pigs to crystalline material from primrose leaves by applying it to the skin (186; 187).

N.S.Wedroff (RU) experimentally sensitized humans to 2:4 dinitrochlorobenzene (DNCB) through the skin (1749).

Rudolf L. Mayer (DE) sensitized humans and guinea pigs to p-phenylenediamine using salve (1086).

 

Gabriel Anton (AT) and Joseph Jules Francois Félix Babinski (FR) provided a detailed description and explanation of visual anosognosis and asomatoagnosia associated with Anton-Babinski syndrome. Asomatoagnosia is a rare phenomenon where a patient is in denial of a body part. Anosognosia is a deficit of self-awareness, a condition in which a person who suffers a certain disability seems unaware of the existence of his or her disability (33; 34; 66; 67). Anton–Babinski syndrome is mostly seen following a stroke but may also be seen after head injury.

 

Marin-Théodore Tuffier (FR) developed an extradural (epidural) anesthetic technique (1623).

Jean-Marie-Athanase Sicard (FR) described injecting dilute solutions of cocaine through the sacral hiatus to treat patients suffering from severe intractable sciatic pain or lumbago (1500).

Fernand Cathlin (FR) gave sacral injections of cocaine (296; 297).

Fidel Pagés (ES) described a lumbar approach to epidural anesthesia (1246).

Eugene Aburel (RO) injected chinocaine through a silk ureteral catheter to block the lumboaortic plexus of laboring women (8).

Archile Mario Dogliotti (IT) performed abdominal surgery with single-shot lumbar epidural anesthesia (446).

 

Alessandro Codivilla (IT), in 1898, performed the first pancreatoduodenectomy. This intervention involves removing the head of the pancreas, the duodenum, the gallbladder, and often but not always, part of the stomach (1452).

Walther Carl Eduard Kausch (DE), in 1909, performed the first resection for a periampullary cancer. He described it in 1912 (889).

 

 Alexandr Petrovich Karpinsky (RU) recorded his classic work on Paleozoic fossil sharks of the family Edestidae (880; 881).

 

Charles Doolittle Walcott (US) described an important clue in the search for Precambrian life when he discovered fossils in Precambrian carbon-rich shales on the slopes of a prominent butte deep within the Grand Canyon. The shales belonged to what is known as the Chuar Group of strata, so, Walcott named the fossils Chuaria. Chuaria is now known to be an unusually large, originally spheroidal, single-celled planktonic alga (technically, a "megasphaeromorph acritarch"). Walcott's specimens were indeed authentic fossils, the first true cellularly preserved Precambrian organisms ever recorded (1722).

 

Károly Gorjanović-Kramberger (HR), between 1899 and 1905, discovered Homo sapiens neanderthalensis (Homo neanderthalensis) fossil remains at a site near the Krapinica River at Krapina, Croatia. The find consisted of 13 men, women and children. The remains are dated to c. 125 K B.P (691-694).

 

The first meeting of the Society of American Bacteriologists (SAB) was held at Yale College, December 28, 1899 with 30 people in attendance. They declared their intention to promote "the science of bacteriology, the bringing together of American bacteriologists, and the demonstration of bacteriological methods." It later became the American Society for Microbiology (336; 955).

 

The First International Congress of Genetics was held in London.

 

c. 1900

"Do not confuse biology and religion—one is a science to be proved or disproved, the other is a life to be lived." Quintin Hogg (GB) (817)

 

The first known type-culture collection of microorganisms, the Kral Collection, was established in Prague, Czechoslovakia.

 

George Washington Carver (US) carried on a campaign, in the end successful, to plant peanuts (Arachis hypogaea) and sweet potatoes (Ipomea batatas) to return fertility to southern soils depleted by cotton (Gossypium spp.) and tobacco (Nicotiana tabacum). To use the surplus peanuts and potatoes he developed side-products. From peanuts alone, he developed some three hundred types of synthetic material, including everything from dyes and soap to milk and cheese substitutes.

Born a slave, his greatest contribution was the clear demonstration provided by his life story that it is tremendously worthwhile to educate individuals of any race.

 

1900

"That we are in the presence of a new principle of the highest importance is, I think, manifest. To what further conclusions it may lead us cannot be foretold." William Bateson (GB) commenting on the work of Johann Gregor Mendel (112).

 

"The general problems of embryology, heredity, and evolution are indissolubly bound up with those of cell structure." Edmund Beecher Wilson (GB) (1803)

 

Max Karl Ernst Ludwig Planck (DE) determined that energy is not infinitely subdivisible. Like matter it exists in particles. Planck called the energy particles quanta. He further determined that there is a constant relationship between the wavelength of a radiation and the size of its quantum (sing.). This constant is symbolized h (Planck’s constant) and is now recognized as one of the fundamental constants of the universe. This is the quantum theory (1307).

 

Friedrich Walkoff (DE) and Friedrich Giesel (DE) gave the first reports in the literature of self-exposure experiments showing radium causing skin burns (666; 1725).

 

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Friedrich Kutscher (DE) proposed that amino acids themselves and their spatial arrangement within the protein must become the chemical key to the understanding of proteins (932).

 

Richard Martin Willstätter (DE) synthesized the amino acid proline by oxidizing hygrine and cuscohygrine, alkaloids from Peruvian cusco leaves. Hermann Emil Fischer (DE) was the first to isolate the amino acid proline from a protein hydrolysate of casein (578; 1796).

 

Auguste Fernbach (FR) and Louis Hubert (FR) invented phosphate buffers for controlling the acidity of a protease from malt and introduced the term tampon. Sørensen later called these solutions puffer; they became buffer in English (573).

 

Allan Macfayden (GB), George Harris Morris (GB), and Sidney Rowland (GB) estimated the carbon dioxide evolved in fermentation by passing it through sodium hydroxide then titrating (1041).

 

Erich von Tschermak (AT), unaware of Johann Gregor Mendel’s (Moravian-CZ) earlier work, independently discovered the laws of genetics (1713).

Hugo Marie de Vries (NL), unaware of Johann Gregor Mendel’s (Moravian-CZ) earlier work, independently discovered the laws of genetics using garden peas with some of the same characters used by Mendel. Upon discovering that Mendel had preceded him he published his own work merely as confirmation (412).

Hugo Marie de Vries (NL) introduced the concept of segregation to genetics. He referred to it as spaltung (splitting) (413).

 

Carl Franz Joseph Erich Correns (DE) associated the segregation of alleles with the reduction division in meiosis (344).

 

Ernst Franz Moro (AT-DE) isolated Lactobacillus acidophilus from the feces of infants. It is a natural inhabitant of the infantile intestine and important in the manufacture of certain sour milk products (1158).

 

Henry Tissier (FR) isolated Bacillus bifidus communis (Lactobacillus bifidus) (Bifidobacterium) from the feces of breast-fed infants (1610).

Henry Tissier (FR) advocated intentional consumption of Bifidobacterium to improve one’s health (1611).

 

Hugo Schottmüller (DE) used the specificity of bacterial agglutination reactions to separate the paratyphoid fevers (1453).

 

Simon Flexner (US) while working in the Philppines isolated a new and different species of dysentery bacillus now called Shigella flexnerii (600).

 

Theodor Boveri (DE) based on microscopic observations of cleaving eggs of sea urchins and the roundworm parasite Ascaris arrived at a unified theory of centrosome function.

 

Mary Mallon, a.k.a., Typhoid Mary (GB-US) was an American cook and immune carrier of typhoid fever who while moving from job to job infected more than 50 people with the disease between 1900 and 1907. After health officials found her, she was forced to live in relative seclusion for much of the rest of her life.

 

Clement Dukes (GB) distinguished the two disorders rubella (rose rash) and roseola infantum, and concluded that they were two similar, but etiologically and pathologically distinct, infections (482).

 

Per Teodor Cleve (SE) wrote The Seasonal Distribution of Atlantic Plankton Organisms, a basic text in oceanography. He proposed that the plankton ocean streams transport can characterize them and conversely the existence of one type of plankton can determine the origin of a stream (324).

 

Andre Mayer (FR) found that serum osmolality is increased during thirst (1082).

Erich Leschke (DE) found that intravenous injections of hypertonic saline cause thirst in man (981).

Avery Veryl Wolf (US) was the first to suggest that osmosensitive centers for thirst are located in the brain (1816).

Peter Arundel Jewell (GB) and Ernest Basil Verney (GB) localized the osmoreceptor to the anterior hypothalamus (870).

 

Paul Ehrlich (DE) presented his general theory of immunity, which, under the name of the side-chain or receptor theory, had for many years an enormous vogue. In this theory he visualized mammalian cells as possessing various specific receptors for all sorts of foreign chemical groups. When exposed to a foreign substance, the substance and its specific receptor would combine and thus stimulate the cell to produce more of these receptors some of which would spill into the blood. The combination of the receptor with the foreign substance would tend to neutralize any harmful effect the foreign substance might have. In the absence of the foreign substance the blood level of receptors would slowly drop (517).

 

Paul Ehrlich (DE) and Julius Morgenroth (DE) commented in 1900 that the organism "possesses certain contrivances, by means of which the immunity reaction, so easily produced by all kinds of cells, is prevented from acting against the organism's own elements and so giving rise to autotoxins [...] so that one might be justified in speaking of a horror autotoxicus" (521) In other words, the body does not normally engage in autoimmune reactions.

Paul Ehrlich (DE) and Julius Morgenroth (DE) predicted, "When the internal regulating contrivances are no longer intact [...] great dangers arise. In the explanation of many disease-phenomena, it will in the future be necessary to consider the possible failure of the internal (i.e., immune) regulation." (522)

 

Karl Landsteiner (AT-US) discovered that there are two types of erythrocyte agglutinins (antibodies) in human sera (anti-alpha and anti-beta) as well as two kinds of erythrocyte agglutinogens (antigens), A and B, on the cells. Cells were characterized as either A, B, or C. C was later changed to 0 (954). Note: Although Landsteiner named the third agglutinogen 0 (zero); by common usage, it is now called O.

Landsteiner, the previous year, had noted the anti-fermentation, lytic, and agglutinating effects of blood serums and lymph (953).

Alfred von Decastello (US) and Adriano Sturli (US) discovered that some erythrocytes possess both A and B agglutinogens, type AB (1672). The A,B,O blood types were the first known human polymorphism.

 

Georges Fernand Isidore Widal (FR), Paul Ravaut (FR), and Jean-Marie-Athanase Sicard (FR) introduced cytodiagnosis, the examination of the cellular elements suspended in the fluid of any serous cavity, as a tool to diagnose disease (1778; 1781).

 

John McFadyean (GB) demonstrated the filterability of the infectious agent of Africian horse-sickness by successfully transmitting the disease using a bacteria-free blood filtrate from an infected horse. This finding was later confirmed by Arnold Theiler (CH-ZA) and Edmond Nocard (FR), who concluded that the disease was caused by a virus (770; 1092). Note: the first orbivirus. Hematophagous arthropods of the genus Culicoides (biting midges) vector this virus.

 

Edwin Stephen Goodrich (GB) proposed that all invertebrate nephridia (except nephromixia) are homologous and the nephrostome is merely the opened proximal end of a protonephridium. There are genuine primary coelomic funnels which alone merit the name coelomostome and these connect to the exterior by genuine coelomic ducts or coelomoducts. Coelomostome plus coelomoduct constitute the genital duct of a coelomic invertebrate (689).

 

Harvey Williams Cushing (US) and Louis E. Livingood (US) demonstrated that bacteria of the intestine in the fasting dog are reduced practically to zero except for a pocket in the cecum (389).

 

Rudolph Matas (US) was the first to use positive pressure in thoracic surgery and introduced endotracheal anesthesia much as it is used today (1076).

 

Ernst Wertheim (AT), in 1898, performed his first radical abdominal operation for cervical cancer (hysterectomy). For his first twenty-nine operations he reported a mortality rate of 38 percent. By 1911 he had reduced the mortality rate to 10 percent and had treated 500 patients (1767; 1769; 1770). See, Wilhelm Alexander Freund, 1878.

 

Henry Charlton Bastian (GB) believed the muscles provided a considerable amount of sensory information, which was used by the brain to coordinate motor acts (108). He later introduced the phrase kinaesthetic sense to describe this relationship (109). This gave way to Sherrington’s new term proprioception (1492).

Charles Scott Sherrington (GB) stated that the cerebellum is head ganglion of the proprioceptive system, holding that it functions because it deals with the musculature of the body rather than with individual muscles (1491).

 

Graham Steell (GB) described the murmur of high-pressure in the pulmonary artery later called Graham Steell murmur (1532). The observation took place in 1888.

 

Mathieu Jaboulay (FR), in 1900, performed the first vagotomy on a human. He also reports the first sympathetectomy for the relief of vascular disease (18; 856).

André Latarjet (FR) and Pierre Wertheimer (FR) were the first to perform a local vagotomy for therapeutic reasons in the region of the stomach in man. The surgery was to treat an active peptic ulcer. They suggested, based on these studies, that the vagal nerves play a significant role in developing peptic ulcer (965).

Lester Reynold Dragstedt (US) and Frederick Mitchum Owens, Jr. (US) recommended and performed vagotomy with pyloroplasty, for treatment of duodenal ulcer. This soon became the standard treatment (455).

 

Fritz Lange (DE) successfully sutured active muscle directly into the periosteum of a suitable bone. The active muscle therefore acquires a new attachment to a bone, with which it is not connected in the normal condition. This surgery, which did not use atrophied tendon, was to overcome a paralyzed muscle and restore motion (957).

 

Hermann Johannes Pfannenstiel (DE) perfected the “Pfannenstiel incision”, a type of abdominal surgical incision that allows access to the abdomen. It is used for gynecologic and orthopedics surgeries, and it is the most common method for performing Caesarian sections today. This incision is also used in Stoppa approach for orthopedics surgeries to treat pelvic fractures. He published his paper in 1900 when he described 51 cases (1289).

 

Sigmund Freud (CZ-AT) published Die Traumdeutung (The Intrerpretation of Dreams) which contains all the basic components of what became Freudian psychology—dreams are wish fulfillment, displacement, regression, the Oedipus complex, and the rest. The part of the dream remembered, is not as important as its latent content, or the symbolic meaning of the dream (622; 623).

 

Vladimir Mikhailovich Bekhterev (RU) was the first to suggest that learning and memory are associated with the hippocampus portion of the limbic system in the brain (147). He described two patients with a significant memory deficit who, on autopsy, were found to have softening of hippocampal and adjacent cortical tissue.

Brenda Milner (GB-CA) would present experimental evidence to support Bekhterev (1128).

 

Dukinfield Henry Scott (GB) wrote two significant books on paleobotany (1466; 1467).

 

Albert Charles Seward (GB) and Jane Gowan (GB) found fossil records indicating that the ginkgo or maidenhair tree, Ginkgo biloba, has existed on Earth since the Liassic (early Jurassic) period meaning that it has existed on earth longer than any other tree; 200-176 M (3; 75; 394; 1034; 1481).

Randolph T. Major (US) found that resistance of Ginkgo biloba L. to pests accounts in part for the longevity of this species (1055).

 

Thomas Chrowder Chamberlain (US) was the first to suggest a continental freshwater origin of vertebrates during the Silurian and Devonian time (303). Currently most scholars support a marine origin for vertebrates.

 

1901

"To study the phenomena of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all." William Osler (CA-GB) (1227)

 

Philipp Lenard Wilhelm Conrad Röntgen (DE) was awarded the first Nobel Prize in Physics. It was for his discovery of a new form of penetrating radiation, which he named x-rays.

 

Jacobus Hendricus van’t Hoff (NL) was awarded the first Nobel Prize in Chemistry for formulating the osmotic pressure equation, and the theory of solutions that connected osmotic pressure, freezing-point depression, and the lowering of vapor pressure as thermodynamic properties.

 

Emil Adolf von Behring (DE) was awarded the first Nobel Prize in Physiology or Medicine "for his work on serum therapy, especially its application against diphtheria, by which he has opened a new road in the domain of medical science and thereby placed in the hands of the physician a victorious weapon against illness and deaths."

 

Ernst Hermann Riesenfeld (DE) and Walther Hermann Nernst (DE) discussed the behavior of the potential difference across the phase boundary between two immiscible electrolyte solutions (1179; 1180; 1363; 1364). The determination of the free energies of ion transfer between aqueous and organic solutions is of great importance for biology, physiology, pharmacy, and for liquid-liquid extraction in chemistry.

 

Frederick Gowland Hopkins (GB) and Sydney William Cole (GB) were the first to isolate the amino acid tryptophan. It came from a tryptic digest of casein (821).

 

 Hermann Emil Fischer (DE) and Ernest Francois Auguste Fourneau (FR) used amino acid monomers to synthesize polypeptides (a word Fischer coined) containing up to eighteen amino acid residues and demonstrated that digestive enzymes attacked these synthetic bonds just as they did those in natural polypeptides. Glycylglycine was the first peptide they synthesized (578; 581-583).

 

Jokichi Takamine (JP-US) and Thomas Bell Aldrich (US) independently, were the first to crystallize the hormone epinephrine (adrenaline), an important step on the way to chemical identification. Takamine coined the name adrenalin (adrenaline) (16; 1571; 1572). This was the first hormone to be isolated in purified form.

A thousand years earlier the Chinese were using mahuang (rich in ephedrine) with properties similar to adrenaline (223). The drug is derived from plants of the genus Ephedra and is most commonly used to prevent mild or moderate attacks of bronchial asthma. Unlike epinephrine, ephedrine is slow to take effect and of mild potency and long duration. It is a bronchodilator and decongestant.

Harriet Isabel Edgeworth (US) described the beneficial effects of ephedrine in treating myasthenia gravis (492).

 

Friedrich Wolfgang Martin Henze (DE) was the first to crystallize hemocyanin. He obtained it from octopus blood (773).

 

Marceli Nencki; Marcellus von Nencki (PL) and Jan Zaleski (PL) found that when phylloporphyrin and hematoporphyrin are reduced the same pyrrol derivative, which they called hemopyrrol, was released (1176). The derivative was identified as methylpropylpyrrol.

 

Leonor Michaelis (DE-US) established the chemical principles of staining fat with various oil-soluble dyes (1116).

 

Count Karl Axel Hampus Mörner (SE) introduced the Nitroprusside Test, a rather specific test for sulfhydryl groups (1157).

 

Oscar Loew (US) discovered an enzyme that catalyzes the conversion of hydrogen peroxide to water and oxygen. Catalase was the name he gave it. The wide distribution of this enzyme in both plant and animal tissues explained why hydrogen peroxide, known to be toxic, failed to accumulate in tissues (1012).

 

Otto Cohnheim; Otto Kestner (DE) showed that the intestinal mucosa elaborates an enzyme which cleaves peptones to amino acids; he named it erepsin (peptidase). This suggested that dietary proteins are cleaved to amino acids in the gastrointestinal tract (327-330).

 

Eugene Wildiers (BE) discovered that yeast require trace amounts of a growth factor before they will produce alcohol from inorganic salts and glucose. The growth factor was later found to be a B vitamin (1787).

 

William Boog Leishman (GB) developed Leishman's stain. It is a compound of methylene blue and eosin that soon became the standard stain for the detection of such protozoan parasites as Plasmodium (malaria parasite) in the blood (976; 977).

 

Paul Theodor Uhlenhuth (DE) built on the earlier work of Jules Bordet (BE) and developed the precipitin test, which can show whether a bloodstain is human or animal in origin (1631-1633). The first forensic application of his new technique was in the case of two murdered and dismembered children in the town of Göhren on the Baltic island of Rügen. The suspect in the case, Ludwig Tessnow claimed that the stains on his clothing were either cattle's blood or wood stain from a carpentry project. They were able to prove otherwise.

 

Hans Horst Meyer (DE) and Charles Ernest Overton (GB) reported the striking correlation between the solubility of general anesthetics in olive oil and their ability to anesthetize/immobilize tadpoles. Because of these observations, it was proposed that anesthetic agents interfered with the structural and dynamic properties of the nerve cell membrane and, in so doing, altered the function of the neuron (1111; 1243).

 

Jean Friedel (FR) brought together the glycerol extract from fresh leaves with finely powdered leaves which had been rapidly and carefully dried, and found oxygen was evolved by the action of light, and carbonic acid taken up (628).

 

Florence Rena Sabin (US) demonstrated that the lymphatics arise from veins by sprouts of endothelium, and that these sprouts or buds connect with each other as they grow outwards from the veins toward the periphery, so that the entire system is derived from already existing vessels. Further, she showed that the peripheral ends of the lymphatics are closed and that they neither open into the tissue spaces nor are derived from them (1413-1419).

 

Thomas Hunt Morgan (US) and Eugene Korschelt (DE) pioneered studies on regeneration and transplantation in salamanders (930; 1155).

 

Clarence Erwin McClung (US) theorized that certain chromosomes whose synaptic mates were different in appearance or entirely absent were responsible for sex determination, e.g., Hermann Henking's accessory chromosomes. McClung discovered an accessory unpaired chromosome in a grasshopper, which he assumed to be sex determining although he at first supposed (wrongly) that sperms with the accessory were male determining. This was the first time that a trait (sex) was assigned to a chromosome. He suggested that this phenomenon might also be at work in other species (1088; 1089). See, Henking, 1891.

 

Hugo Marie de Vries (NL) proposed that different alleles of the same gene arise by a sudden, discontinuous change of that gene—a process to which he gave the name mutation (L. to change). This concept arose out of his observations of Oenothera lamarckiana (the evening primrose) (414; 415).

 

Jules Jean Baptiste Vincent Bordet (BE) and Octave Gengou (FR) developed the Complement Fixation Test as follows. If to a quantity of unheated normal guinea-pig serum is added a quantity of sensitized erythrocytes (i.e., erythrocytes charged with specific antibody) hemolysis occurs. They made, however, the observation that if cholera vibrios are added to such a mixture they remain intact instead of undergoing spherulation and lysis, as might perhaps have been expected. The same occurs if the cholera vibrios and erythrocytes are introduced in the reverse order. On testing heated plague-serum mixed with plague bacilli and normal serum, Bordet and Gengou found that the subsequent addition of sensitized erythrocytes did not result in hemolysis. The explanation they gave was that the sensitizing substance in the plague-serum fixes the complement in the presence of plague bacilli so that it is prevented from acting on the sensitized erythrocytes. Other experiments indicated that the phenomenon was widespread and had applicability as a diagnostic test. They believed that it was possible to diagnose the existence of a sensitizer in the serum by the presence or absence of hemolysis of sensitized erythrocytes. Gengou showed further that sensitizers (antibodies) are developed in the blood of animals that have been injected with milk, and that such sensitizers are also capable of fixing complement. The same reaction also occurred in the sera of animals injected with egg albumin, fibrinogen, or other substances (202).

 

Franz Hofmeister (CZ-DE) made one of the earliest proposals suggesting that intracellular metabolic reactions follow molecular pathways. "In the protoplasm synthesis and breakdown occurs by way of a series of intermediate steps, whereby it is not always the same kind of chemical reaction that is involved, but rather a series of reactions of different kinds… A regular reaction sequence of the chemical reactions in the cell presupposes, however, the separate activity of the individual chemical agents and a definite direction of movement of the products that are formed, in short, a chemical organization … that helps to explain the speed and certainty with which it functions." (814)

 

Martinus Willem Beijerinck (NL) announced that the blue-green algae (cyanobacteria), the free-living aerobic bacterium Azotobacter, and other microorganisms can use atmospheric nitrogen as their sole source of nitrogen. He was the discoverer of Azotobacter.

"I shall call oligonitrophilic microbes those which in free competition with other microbes grow in nutrient solution where one has not willingly introduced nitrogen-containing substances but from which one has not removed the last traces of these compounds. They have the property of fixing free atmospheric nitrogen either alone or in symbiosis with other microbes." (142)

 

Newton Barris Pierce (US) described Xanthomonas juglandis as the cause of blight of walnuts (1301).

 

Martinus Willem Beijerinck (NL) was a master practitioner of what is referred to as the enrichment culture technique. In one of his early papers he uses this methodology to isolate a bacterium capable of utilizing urea (141).

 

Charles Louis Alphonse Laveran (FR) received several blood-smears—made by Arnold Theiler (CH-ZA)—from horses suffering with biliary fever (piroplasmosis). Laveran recognized intra-corpuscular parasites, which he named Piroplasma equi (Babesia equi) (Theilera equi) (968).

Arnold Theiler (CH-ZA) showed that the horse sickness called biliary fever (piroplasmosis) and caused by Piroplasma equi (Babesia equi) (Theilera equi) is carried by the red-legged tick Rhipicephalus evertsi (1589; 1590).

 

Hugo Marie de Vries (NL) wrote Die Mutationstheorie and thereby advanced the thesis that species are not continuously connected but arise through sudden large changes (415).

 

Lucien Claude Jules Cuénot (FR) defined the sexual cycle of the Gregarina (367).

 

Theodor Boveri (DE) found that polarity in sea urchin eggs is associated with qualities of the cytoplasm. When he compared the development of isolated upper and lower portions of ova, he observed that the isolated upper portion could not gastrulate, while the lower could do so and could also differentiate primary mesenchyme. Boveri thought of the lower portion as a privileged region: "here differentiation began, and from here all other regions are influenced in their differentiation." (215; 216)

 

Albert Schütze (DE) working with iso-immunization of rabbits produced the first evidence of homospecific antigens in the serum of mammals (1462; 1463).

Russel W. Cumley (US) and Malcolm Robert Irwin (US) demonstrated the existence of intraspecies genetically determined differences in certain serum proteins (heterogeneity), comparable to genetic variations in blood type, eye color, and other hereditary traits (374; 846).

Sarane Thompson (US), Joseph F. Foster (US), John W. Gowen (US), and Oscar E. Tauber (US) confirmed the work of Cumley and Irwin (1593).

Jacques Oudin (FR) discovered three rabbit antibody allotypes, a1, a2, and a3. These were later shown to be associated with the VH region of the antibody molecule (1238; 1239).

 

Sarturnin Arloing (FR) and Paul Courmont (FR) developed a test for agglutinating antibodies in cases of tuberculosis (42).

 

William Hallock Park (US) championed procedures to reduce bacterial contamination in every stage of milk production and the introduction of refrigeration and pasteurization. New York soon had the safest milk supply in the world (1261). Note: This work led to a rapid reduction in cases of childhood diphtheria and tuberculosis in New York.

 

William Henry Howell (US) demonstrated the importance of inorganic salts, especially potassium, in regulating heart rate (832).

 

Charles Sedgwick (US) described marrow sinusoids (1132).

 

Gaston Milian (FR) was the first to study bleeding time course (1121-1123).

William Waddell Duke (US), in 1910, found that bleeding time (and the amount of blood shed) was increased in thrombocytopenia (thereby proving the primary function of blood platelets), he showed that a whole blood transfusion raised the platelet count, led to a cessation of clinical bleeding, and shortened the bleeding time to normal (481).

 

V.O. Sivèn (SE), who weighed 143 pounds, found that he could keep his body in nitrogen equilibrium by consuming 25 to 31 grams of protein daily. He ate a liberal amount of carbohydrate, and his diet supplied 2,717 calories daily (1506).

Russell Henry Chittenden (US) concluded that for man the minimum "proteid" requirement was 93-103 mg N/kg body wt. (about 0.6-0.64 g protein·kg1·d), which anticipates, by 80 years, the mean requirement figure of 0.6 g protein·kg1·d1 proposed by FAO/WHO/UNU (317; 318; 567).

 

Eugene Lindsay Opie (US) stated, “It has been suggested by several observers that the islands of Langerhans may furnish an internal secretion to the blood…. Where diabetes is the result of pancreatic disease, do the islands exhibit lesions? I have examined microscopically the pancreas from eleven cases of diabetes, and in four instances such marked change was found [in the islands] that one could not doubt the relationship of the general disease to the lesion of the organ” (1220). See, Laguesse, 1893.

 

Alfred Fröhlich (AT) is remembered for his classic description of dystrophia adiposogenitalis or Fröhlich syndrome (629).

 

Félix Dévé (FR) investigated echinococcus and presented his thesis on secondary echinococcus (425).

 

Leo Loeb (US) described the transplantation of tumors (1009).

 

Max Wilms (DE) was the first to carry out full excision of burnt tissue, and sometimes grafted excised areas (1798).

 

James Horner Wright (US) and Elliott Proctor Joslin (US) published one of the first articles describing the pathological loss of pancreatic islet cells in diabetes (1830).  

 

James H. Sequeira (GB) saw in epithelial cells of a cancer treated by irradiation a “lysis” of both nucleus and protoplasm and a fatty degeneration (2; 1476; 1477).

Georg Clemens Perthes (DE) was the originator of deep Röntgen-therapy and a prime mover of the treatment of cancer by irradiation (1283).

 

Georg Kelling (DE), in 1901, performed the first endoscope-guided laparoscopy (on a dog) (897). Note: This marks the birth of laparoscopy.

Hans Christian Jacobaeus (SE), in 1910, published an account of two cases in which he performed thoracoscopic explorations of the pleural cavities of humans (857). Note: These cases are the beginning of human laparoscopy.

 

The Rockefeller Institute for Medical Research was founded with Simon Flexner (US) as its first director (1394).

 

Smallpox had its last major outbreak in the urban Northeast U.S., beginning in New York and spreading through other major cities (921).

 

Grafton Elliott Smith (AU-GB), in 1901, discovered the oldest urological object on record, a bladder calculus, in a prehistoric Egyptian tomb, in the pelvis of a mummy. The calculus has a uric acid nucleus with concentric laminations of calcium oxalate and ammonium magnesium phosphate (1377; 1486).

 

The Journal of Hygiene was founded.

 

Biometrika was founded.

 

1902

"The sciences are not a series of abstract concepts, but rather the results of human endeavor; in their development, they are closely associated with the individual characters and fates of those who dedicate themselves to it." Hermann Emil Fischer (DE)

 

"The type of condensation described here through formation of —CO—NH—CH= groups may thus explain both the building up of protein substances in the organism, as well as their breakdown in the intestinal tract and in the tissues. Based on these given facts one may therefore consider the proteins as for the most part arising by condensation of alpha-amino acids, whereby the linkage through the group —CO—NH—CH= has to be regarded as the regularly recurring one." Franz Hofmeister (815).

 

Hermann Emil Fischer (DE) was awarded the Nobel Prize in Chemistry for his discoveries related to sugars and purine syntheses.

 

Ronald Ross (GB) was the recipient of the Nobel Prize in Physiology or Medicine "for his work on malaria, by which he had shown how it enters the organism and thereby laid the foundation for successful research on this disease and methods of combating it."

 

Ernest Rutherford (NZ-GB) and Frederick Soddy (GB) proposed that a process of exponential radioactive decay with the emission of material particles transforms radioactive elements into each other (1406; 1407).

Ernest Rutherford (NZ-GB) was, along with Pierre Currie (FR) and Marie Skodowska Curie (PL-FR), the first to decide that rays given off by radioactive material were of several different kinds. Rutherford named the positively charged ones alpha rays and the negatively charged ones beta rays. He was able to demonstrate that the radiations discovered in 1900 and found not to be sensitive to a magnetic field, consisted of electromagnetic waves. He named these gamma rays (1405).

 

William Thomson (Lord Kelvin) (GB) introduced the concept of the electron (1597).

 

Heinrich Friedrich Wilhelm Siedentopf (DE) and Richard Adolf Zsigmondy (AT-DE) developed the slit ultramicroscope, a dark field microscope that can detect particles with diameters below the wavelength of visible light. This was possible because of the Tyndall effect (1501).

 

Eugen Baumann (DE) discovered cysteine as a product of the reduction of cystine (121).

Carl Alexander Neuberg (DE-US) discovered cysteine (1183).

 

The United States Congress authorized the extermination and removal of water hyacinths by any mechanical, chemical, or other means. Various materials were tested including muriatic acid, sulfuric acid, carbolic acid, kerosene, steam, sodium arsenite, mercury bichloride, whale oil soap, formaldehyde, copper sulfate, potassium bichromate, and many others. Although there were no laws to regulate the use of pesticides, it was quickly learned that most of the chemicals, which were effective against water hyacinth, were also toxic to cattle and humans.

During 1944 to 1946, the U. S. Department of Agriculture, Jacksonville District Corps of Engineers, and the Everglades Experiment Station of the University of Florida initiated evaluations of a newly discovered herbicide, 2,4-D, as a control agent for water hyacinth. The herbicide 2,4-D proved extremely effective and economical, and above all was not toxic to fish, cattle, or humans.

 

Warren Thompson Clarke (US) perfected the lime-sulfur spray for the control of the peach twig borer (323).

 

Hermann Emil Fischer (DE) isolated the amino acid hydroxyproline from gelatin hydrolysate (579). He called it oxyproline.

 

Hermann Emil Fischer (DE) and Franz Hofmeister (CZ-DE) independently described the peptide bond by which amino acids join to form polypeptides (580; 815). Fischer outlined a procedure for recovery of the amino acids following hydrolysis. The phrase, peptide bond, coined by Fischer, is derived from pepsin, which is derived from the Greek root pepsis meaning cooked/digestion.

 

Max Rubner (DE) published what is called the isodynamic law of Rubner. It states that 100 calories in fat are the nutritive equivalent of the same number in carbohydrate. He further compared the caloric content of foods of different classes when given to an animal in moderate quantities. He found that the caloric content of 100 grams of fat is equivalent to 211 grams of protein, or 232 grams of starch, or 234 grams of cane sugar, or 256 grams of glucose. He found that when a dog was fed 100 calories in the form of meat his caloric output increased by 30 calories over that of a dog at rest and without food. When 100 calories were given as cane sugar the increase in caloric output was only 5.8 calories and when 100 calories as fat were given the increase was 4 calories. Any increase in the ingestion of protein led to a commensurate increase in caloric output by the dog. Rubner named this phenomenon specific dynamic action (1397).

 

Adolf Magnus-Levy (DE) was one of the first to suggest that acetylaldehyde is an intermediate product in various fermentations of sugar (1054).

 

Adrian J. Brown (GB) and Victor Henri (FR) separately discovered that the rate of hydrolysis of cane sugar by saccharase is independent of the sugar concentration over a wide range, although it depends on the enzyme concentration. Brown for the first time deduced the formation of the enzyme-substrate complex from careful rate measurements that indicated the initial rate of cane-sugar hydrolysis, except for very dilute solutions, to be independent of the concentration of the cane sugar used. He concluded that mass action is concealed in the case of this substrate-independent rate by a time course factor associated with molecular combination. Henri derived a hyperbolic rate equation for a single-substrate enzymatic reaction and showed that his rate equation predicted the catalytic rate to be proportional to the substrate concentration at low, and independent of it at high substrate concentrations (243; 244; 771).

Leonor Michaelis (DE-US) and Maud Leonora Menten (CA) would later revive and extend this as the Henri-Michaelis-Menten theory. See Michaelis and Menten, 1913.

 

George Potts (DE) was the first to postulate that cellular slime molds use chemotaxis (1319).

Ernest H. Runyon (US) found in Dictyostelium that separate cells aggregate to form a multicellular body (1402).

Kenneth Bryan Raper (US) observed a pseudoplasmodium formation and organization in Dictyostelium discoideum (1340).

John Tyler Bonner (US) and Leonard Jimmie Savage (US) presented evidence that the amoebae of cellular slime molds first undergo growth as separate cells and then aggregate to form cell masses that become differentiated multicellular organisms. This paper gave evidence that aggregation occurred by chemotaxis, and the chemical attractant was given the name acrasin (196).

 

Charles Ernest Overton (GB) found that extracellular sodium ions are required for nerve excitability and suggested that a sodium-potassium exchange is involved in signal conductance (1244).

 

Rudolf Magnus (NL) and E.A. Shäfer (NL) reported that pituitary extracts cause expansion of the kidney and a marked and often prolonged diuresis. This was the first indication that the hypophysis (pituitary gland) plays a part in the regulation of urine secretion (1052).

 

Alexander A. Maximow (RU-US) characterized macrophages of the connective tissues and named them clasmatocytes; a name no longer used (1080).

 

Gottlieb Friedrich Johann Haberlandt (AT) expressed the concept of the vegetable cellular totipotency and was probably the first to grow plant cells in tissue culture. He succeeded in getting a small cellular mass to survive in vitro some months, but without reproduction (722).

"There has been, so far as I know, up to present, no planned attempt to cultivate the vegetative cells of higher plants in suitable nutrients. Yet the results of such attempts should cast many interesting sidelights on the peculiarities and capacities, which the cell, as an elementary organism, possesses: they should make possible conclusions as to the interrelations and reciprocal influences to which the cell is subjected within the multicellular organism. Without permitting myself to pose further questions, I believe, in conclusion, that I am not making to bold a prediction if I point to the possibility that, in this way, one could successfully cultivate artificial embryos from vegetative cells" (722).

Roger-Jean Gautheret (FR) reported a 50 to 150-fold increase in initial length of 0.5 to 1.0 mm excised tips of corn roots cultured 3 months in a dilute Knop's solution containing, 2% glucose and cysteine hydrochloride (655).

Philip Rodney White (US) obtained potentially unlimited growth of excised tomato root tips in a liquid medium (1773).

Fritz Kögl (NL), Arie Jan Haagen-Smit (NL), Hanni Erxleben (NL), Désiré George Florent Rudolphe Kostermans (NL), Kenneth Vivian Thimann (GB-US), and Joseph B. Koepfli (US) identified the first known plant hormone—indoleacetic acid (IAA) (918; 919; 1592).

James Frederick Bonner (US) discovered that the most important growth constituent of the yeast extract is thiamine (vitamin B1) and subsequently White found that the effect of the yeast extract could be obtained by substituting the B-group—thiamine, pyridoxine and niacin—instead (195).

Roger-Jean Gautheret (FR) successfully cultured wound tissue or callus from the excised cambial tissue of Salix capraea and Populas alba. He used nutrient media solidified with agar but found that after 6 months the activity of the cultures ceased (656). By including indoleacetic acid (IAA) and the vitamins B in his media Gautheret extended the culture period of the Salix callus to 18 months and was able to subculture. However, after 18 months once again growth ceased.

George Robert Sabine Snow (GB) demonstrated that indoleacetic acid stimulates cell division within the cambium layer (1522).

Roger-Jean Gautheret (FR), Philip Rodney White (US), and Pierre Nobécourt (FR), had by 1939, independently established long-lived cultures of carrot root, carrot (Daucus carotus), and tobacco (Nicotiana tabacum) respectively (657; 658; 1197; 1774).

Roger-Jean Gautheret (FR) suggested that plant cells could perhaps grow like bacteria in suspension culture (659).

Louis G. Nickell (US) confirmed that idea with the continuous submerged cultivation of plant tissue as single cells (1189).

Frederick Campion Steward (GB-US), Marion O. Mapes (US), Jakob Reinert (DE), Kath Mears (US), and Lawrence M. Blakely (US) showed that in vitro plant culture can, starting with one carrot cell, produce a callus and from it a new carrot plant (Daucus carotus) (185; 1351; 1547).

Hiroyuki Kato (JP) and Masayuki Takeuchi (JP) obtained a complete carrot plant (Daucus carotus) from a single carrot root cell in tissue culture (886).

Toshiyuki Nagata (JP) and Itaru Takebe (JP) showed that protoplasts isolated enzymatically from tobacco (Nicotiana tabacum) leaves regenerated cell walls and divided to form cell clusters under suitable conditions. Plants were developed from the cell clusters (1171; 1172).

H.J. Gambow (), K.N. Kao (CA), Raymond A. Miller (CA), and Oluf L. Gamborg (DK-CA) developed whole carrot plants (Daucus carotus) from carrot protoplasts (644).

H.J. Wilson (US), Herbert W. Israel (US), and Frederick Campion Steward (GB-US) developed methods to grow whole carrots (Daucus carotus) from single carrot cells rather than from the seed (1806).

 

William Bateson (GB) although not considered to be one of the “official” rediscovers of Mendel’s work was the first English-speaking scientist to recognize the importance of Mendel’s work and he immediately set out to bring Mendel’s work to the attention of the scientific community. This 1928 publication contains his application, in 1902, to the Trustees of the Carnegie Institution in Washington seeking financial support (£600 a year) to support his use of Mendelian methods in investigating the mechanism of heredity (116). The proposal was declined.

 

Aladar Aujeszky (HU) first described and reproduced the disease now called pseudorabies or Aujeszky's disease that is found in a wide range of domestic stock and wild animals (56). Note: It is called pseudorabies because of some clinical resemblance to rabies. The the first herpesvirus and now named Herpes suis or porcine herpesvirus type 1.

Richard Edwin Shope (US) found that mad-itch is the same disease as pseudorabies (1496).

 

Robert Chodat (CH) discovered the cause of the vine disease known as court noué and showed that it is caused by an acarid (mite); from then on it was called acariasis (319).

 

Fred Neufeld (DE) described the Quellung phenomenon, which consists of apparent capsular swelling when pneumococci are mixed with undiluted antiserum to the capsular polysaccharide (1184).

Fred Neufeld (DE) and Georg Willi Rimpau (DE) reported that the blood of animals immunized with pneumococci contained substances that greatly accelerated phagocytosis of the immunizing strain (1186).

Fred Neufeld (DE) and R. Etinger-Tulczynska (IL) applied the Quellung reaction to practical diagnosis (1185).

 

Karl Wilhelm von Drigalski (DE) and Heinrich Conradi (DE) found that some bacteria such as Salmonella typhosa exhibit resistance to certain aniline dyes. They recommended the use of crystal violet for the isolation of organisms from feces and other contaminated material (1675).

 

José Léon Marcel Lignières (FR) and Georges Spitz (AR) isolated a non-motile, non-branching, non-acid-fast gram-negative bacillus from the lesions of a disease of cattle resembling actinomycosis, with which it is frequently confused. The causative organism was named Actinobacillus lignieresii and the disease actinobacillosis (990).

Paul Ravaut (FR) and Pierre-Ernest Pinoy (FR) reported the first incidence of actinobacillosis in man (1341).

 

Richard May (DE) and Ludwig Grünwald (DE) developed a stain for peripheral blood film and bone marrow (1081). Now popularly called the May-Grünwald stain.

 

Gustav Giemsa (DE) and James Homer Wright (US) introduced their respective stains formulated to demonstrate human blood elements and the malarial parasite (664; 665; 1829).

 

Andre Huot (FR) discovered that some fish (lophobranchs) have aglomerular kidneys, proving that renal tubules can secrete and resorb substances (838).

 

William Maddock Bayliss (GB) reported on the local reactions of the arterial wall to changes of internal pressure. He suggested that distension of the vessel by the blood pressure could act as a mechanical stimulus to the muscle cells, thereby contributing to their tone (123).

 

William Maddock Bayliss (GB) and Ernest Henry Starling (GB) discovered that the lining of the upper small intestine, upon exposure to acidic food, stimulates the flow of bile from the gall bladder and the release of digestive enzymes and bicarbonate from the pancreas even when all the nerves between the small intestine and the pancreas are severed. They promptly made a crude extract from a piece of duodenum, injected it into the jugular vein of the dog, and within a few moments had the pleasure of seeing the pancreas respond with a heavy secretion. They postulated the existence of secretin, a blood-borne messenger, or hormone that is released into the circulation by the lining of the duodenum (125; 126).

William Bate Hardy (GB) is credited with coining the word hormone (Gk. hormao, to excite or arouse to action) while visiting in the laboratory of Bayliss and Starling (1531).

 

Otto Loewi (DE-US) demonstrated that protein digested outside the body to the point that it would not give a positive Biuret Test could be fed to an animal and substitute for all its food protein. This suggested that dietary proteins are cleaved to amino acids in the gastrointestinal tract, taken into the blood, and later oxidized or used to synthesize new proteins (1013).

 

Theodor Boveri (DE) proved the hypothesis that the physical basis of inheritance resides in the chromosomes by creating sea urchin embryos with abnormal chromosome sets. He also determined that every cell in the sea urchin embryo must have the normal set of 36 chromosomes if development is to be normal. In the 1902 article he gave his views on the importance of interaction between nucleus and cytoplasm as, “It appears to me that the quite peculiar interaction of the cytoplasm with its simple structure and differential division and the nucleus with its complex structure and manifold total multiplication may still achieve what Weismann and Roux attempted to explain with the help of differential nuclear division. When the primitive differences of the cytoplasm, as expressed in the existence of layers, are transferred to the cleaved egg without any change in the relationships of the layers, they affect the originally equal nuclei unequally by unfolding (activating) or suppressing certain nuclear qualities, as may be visualized directly in the cleavage of Ascaris. The inequalities of the nuclei, in some cases perhaps of temporary nature only, lend different potencies to the cytoplasm that to begin with was differentiated only by degrees. Thus, new cytoplasmic conditions are created which again release in certain nuclei the activation or suppression of certain qualities thus imprinting on these cells in turn a specific character and so on, and so on. In short: a continually increasing specification of the originally totipotent complex nuclear structure, and consequently, indirectly, of the cytoplasm of the individual cells, appears conceivable based on physico-chemical events once the machine has been set in motion by the simple cytoplasmic differentiation of the egg. In this same article, he speculated that multipolar mitosis might cause tumors and that mitotic aberrations might be caused by physical and chemical agents.” The 1904a paper states that chromatin is the substance that transforms into chromosomes during mitosis (217; 219; 221; 1793).

 

William Bateson (GB) showed the validity of Johann Gregor Mendel’s (Moravian-CZ) principle of segregation in animals (poultry) (113; 1323).

 

Archibald Edward Garrod (GB) provided the first evidence of the applicability of Mendelian genetics to man and perceived the relationship of hereditary factors to enzymes. He noted that several human hereditary traits (alkaptonuria, albinism, pentosuria, and cystinuria) were metabolic diseases characterized by failure of known chemical reactions to take place and hypothesized that such metabolic diseases, which he called inborn errors of metabolism, were due to the absence of specific enzymes that were synthesized under the direction of the wild-type genes. “Inborn errors of metabolism are due to the failure of a step in the metabolic sequence due to loss or malfunction of an enzyme.” Garrod’s deduction is one of the most outstanding in the history of biology—he discovered the function of genes (647-650). Garrod consulted Bateson, who in 1902 suggested that for alkaptonuria the available data could be understood if one assumed that alkaptonuria is caused by a recessive gene. This was the first Mendelian recessive discovered in man.

 

William Bateson (GB) and Edith Rebecca Saunders (GB) provided us with some of the basic terminology for Mendelian genetics: unit characters which exist in antagonistic pairs they called allelomorphs (later shortened to alleles), the zygote formed by the union of a pair of opposite allelomorphic gametes they called heterozygote, and the zygote formed by the union of a pair of gametes having similar allelomorphs they called homozygote. They introduced the use of F1, F2, and so on to designate filial generations (113; 117).

William Bateson (GB) introduced the term epistasis (the masking effect of one mutant gene pair over another mutant gene pair) into genetics. Here he presented evidence that man exhibits Mendelian inheritance (114; 115).

 

Lucien Claude Jules Cuénot (FR), William Ernest Castle (US) and Clarence Cook Little (US) showed that coat color in mice follows Mendelian segregation and behaves as though it has at least three alleles (multi-allelic) (295; 368-373; 1000). These experiments along with Bateson’s on poultry represent the first extension of Mendel’s laws to animals. See Bateson, 1901.

 

Carl Franz Joseph Erich Correns (DE) discovered the first exception to the random union of gametes assumed by Mendel. It was explained as the effects of a gene on the functioning of pollen grains in maize (345).

 

Paul Portier (FR), Charles Robert Richet (FR), and Georges Richard (FR) discovered the remarkable fact that certain poisons of animal origin evoke a condition of hypersusceptibility instead of immunity, and that because of this hypersusceptibility death may ensue from a dose of the poison which is otherwise ineffective. By maceration of the tentacles of certain sea anemones (Actinia eqnina, Anemone sulcata) they obtained a poisonous fluid which, injected intravenously into dogs in a dose of 0.2 gm. per kilo, produced hypothermia, diarrhea, and death in two or three days, doses smaller than 0.2 gm. produced only transient symptoms. If, however, several weeks after the injection of such a dose a second sub-lethal dose was administered, violent symptoms of poisoning set in and were sometimes followed by death of the animal in an hour but mostly in 12 to 24 hours. Richet coined the word anaphylaxis (Greek, removal of protection) to describe this reaction. It was intended to convey the idea of the opposite of prophylaxis (Greek, favoring protection) (1314; 1360-1362).

Milton Joseph Rosenau (US) and John F. Anderson (US) noted that animals receiving an injection of a foreign protein became sensitive to a second dose of the same protein (1376).

 

James MacKenzie (GB) began a systematic study of cardiac patients in 1883, devised a polygraph to study irregularities of the pulse, and wrote, The Study of the Pulse, followed by Diseases of the Heart. He classified irregularities of the pulse as the youthful type (sinus irregularity), the adult type (extra-systole), and the dangerous type (auricular fibrillation) (1044; 1045).

 

Julius Strasburger (DE) estimated the daily output of fecal microorganisms by humans to be eight grams (1559).

 

George Frederic Still (GB), England’s first professor of childhood medicine, described attention-deficit disorder (ADD) (1551).

 

Charles E. Gray (ZW) and William Robertson (ZW) recorded East Coast Fever in Africa (701). East Coast fever (ECF) is the most important tick-borne disease in Eastern, Central and Southern Africa.

Arnold Theiler (CH-ZA) proved that East African Coast Fever is caused by Piroplasma parva (Theileria parva) (1588).

Richard Gonder (ZA) identified the apicomplexan parasite Theileria parva as the cause of East Coast fever in South Africa (688).

 

Emil von Dungern (DE) was the first to give evidence for local antibody production in the antigenically stimulated eye (1676).

 

Max Bielschowsky (DE) developed several stains that are still commonly used in diagnosing Alzheimer’s disease (171; 172).

 

Arthur Biedl (AT) and Josef Wiesel (AT) proved that the paraganglion aorticum in the cardiac plexus contained adrenaline (170).

 

Harvey Williams Cushing (US), Karl Hugo Kronecker (CH), and Emil Theodor Kocher (CH) demonstrated that as the spinal fluid pressure of a dog is increased, there is initially a vagal effect with bradycardia followed by a high rise in arterial blood pressure (385; 386).

 

John William Ballantyne (GB) wrote Manual of Antenatal Pathology and Hygiene, the most complete history of teratology in English (80).

 

Gregorij Ivanovitsch Rossolimo (RU) described percussion of the plantar surface of the 2nd to 5th toes causing a flexion, which is exaggerated greatly in pyramidal tract lesions (1379).

 

William Richard Gowers (GB) was the first to describe a muscular disorder later called distal myopathy of Gowers (696).

 

Paul Schuster (DE), based on 785 cerebral tumor cases, divided the psychical changes seen in these patients into categories. He wrote that the most frequent symptoms were general “mental paralyzation,” irritability, hypomania, and Witzelsucht (sarcastic joking). In agreement with other authors of the day, he acknowledged that unilateral pre-frontal cortex damage was not always associated with these mental and emotional symptoms. Yet he added that when symptoms were seen with unilateral tumors left frontal damage had more of an effect on intellect, whereas right frontal damage had more of an effect on emotion and temperament (1461).

 

Alexis Carrel (FR-US) and Charles Claude Guthrie (US) using fine silk suture and meticulous technique successfully created a variety of vascular anastomoses and reconstructions, including the first-ever vein grafts, termed “biterminal venous transplantation.” Their perfected triangulation technique whereby blood vessels could be delicately sutured; that is, sewn together end to end with as few as three stitches enabled them to transplant limbs and organs, including the kidney, thyroid, adrenal, ovary, spleen, intestine, pancreas, and heart from one animal to another (286-291; 338). Note: Themistocles Gluck (DE), in the 1880s, carried out not only the suture of vessels, but also venous grafts, long before the work of Alexis Carrel.

 

Attila E. Pólya (SK-DE) and Desider von Navratil (SK-DE) described lymphatic drainage of buccal mucosa, alveolus, fauces, and lips. In addition, they discussed patterns of local tumor spread and metastasis to lymph nodes, on the basis of which they gave a rational plan for surgical treatment of buccal carcinoma with the aim of both cure and conservation of uninvolved tissues (1312).

 

Ludwik Rydygier; Ludwig Anton Rydygier von Ruediger (PL-DE), in 1897, modified the procedure of prostatic adenoma removal. The method consisted of making a median incision, from the scrotum as far as the anus, and intracapsular removal of the adenoma while preserving two bands of gland tissue to ensure continuity of the urethra. He called this type of operation resectio prostatae intracapsularis (1411).

 

Hugh Hampton Young (US) devised and performed the first perineal prostatectomy, in 1902 (1844). He performed the first radical perineal prostatectomy for cancer of the prostate in 1904, with assistance from his chief, William Stewart Halsted (1845; 1847). Through this technique, obstruction to the outlet of the urinary bladder caused by cancer of the prostate gland is relieved without interfering with the normal function of the bladder. Young invented numerous operating instruments such as the Young punch, an instrument used to excise the prostate (1846).

 

Jean Nageotte (FR) worked with tabes and made special studies of the radial nerves in tabetus. Together with Joseph Jules Francoise Felix Babinski (PL-FR) he described the Babinski-Nageotte syndrome (71) and wrote a book on cerebrospinal fluid. He made intensive study on nerve fibers, anatomic and degenerative in nature. He did considerable clinical and chemical research on the myelin sheath and connective tissue.

 

Harris Hawthorne Wilder (US) pioneered comprehensive studies of the methodology, inheritance, and racial variation of palmer and planter papillary ridge patterns as well as fingerprints. These represented the first serious study of palmer and plantar dermatoglyphics (1785; 1786).

 

Henry Fairfield Osborn (US) enunciated the concept of adaptive radiation in evolution (1223).

 

Petr Alekseevich Kropotkin (RU) published Mutual Aid a Factor of Evolution, an important landmark in the future trend of population studies (leading to the widely spread anthropomorphic concept of "altruism") (940).

 

Charles William Andrews (GB) and Hugh John Llewellyn Beadnell (GB), in 1900, discovered numerous early higher primate fossils in the Fayum Depression region east of Cairo, Egypt. These Eocene and Oligocene fossils include protomonkeys believed to be ancestral to Old World monkeys and thus in the lineage to hominids. Aegyptopithecus is the best known of the propliopithecids from the Fayum, about the size of a cat. Aegyptopithecus is often placed at the base of the Catarrhine radiation (25-27; 127).

 

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; 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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