A Selected Chronological Bibliography of Biology and Medicine — Part III

1885 — 11924

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

Dedicated to my loving family

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

Please forward any editorial comments to:

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


“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 (2476).

"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 (2094).

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 (2879).

Paul Ehrlich (DE) observed that certain vital dyes administered intravenously to small animals stained all of the organs except the brain. He interpreted this to mean that the brain had a lower affinity for the dye than the other tissues (955).

Max Lewandowsky (DE) coined the phrase blood-brain barrier (Bluthirnschranke) (1945).

Edwin Ellen Goldmann (DE) injected dye into the spinal fluid of the brain directly. He found that in this case the brain would become dyed, but the rest of the body would not. In light of Ehrlich’s finding this clearly demonstrated the existence of some sort of barrier between the two (1270, 1271). 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) (3004). 

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 with the exception of the elasmobranch fishes. In elasmobranchs glial cells form the blood-brain barrier (434, 435, 2602).

Michael W.B. Bradbury (GB) reported that the blood-brain-barrier is formed by a complex cellular system of endothelial cells, astroglia, pericytes, perivascular macrophages, and a basal lamina with lipid soluble substances easily penetrating the cerebral endothelial plasma membranes and readily attaining equilibrium between blood and brain tissue (396).

Robert Behrend (DE) and Adolf Pinner (DE) coined the words uracil and pyrimidine respectively (250, 2539).

Thomas Richard Fraser (GB) was the first to isolate strophanthinic acid, a cardioactive glycoside, from the strophanthus plant (1179).

Albert Fraenkel (DE) produced an injectable form of strophanthinic acid (1164).

Raphael Horace DuBois (FR) reported the first definitive experiments regarding the nature of the chemical components necessary for light production by organisms. He found that the luminous organs of a beetle would cease to emit light if immersed in hot water. He also noted, however, that a cold water extract, which ceased to luminesce, could be stimulated to emit light by adding the hot-water extract. He proposed that the hot water extract contained a substance stable to heat, luciferin, which was destroyed during its luminescent oxidation by a catalyst, luciferase, present in the cold-water extract (901).

E. Newton Harvey (US) found that certain fish possess light organs, which contain luminous bacteria as the source of their luminescence (1433).

William David McElroy (US), and Bernard L. Strehler (US) found that ATP could phosphorylate luciferin (2144). 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 (3175).

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 (2670). 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 (2470).

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 (2456-2458).

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 (219, 220, 2459).

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 (2147, 2148).

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 (941, 1121).

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 (390).

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” (2202).

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 (376, 383, 385, 388).

Sydney Ringer (GB) postulated the existence of an endogenousdigitalis” in mammals (2645).

Albert Imre Szent-Györgyi (HU-US) later revived Ringer’s idea (3062).

Vittorio Marchi (IT) and G. Aligeri (IT) discovered that the initial products of degeneration in myelinated nerve fibers could 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 (2088).

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 (1440).

Paul Clemens von Baumgarten (DE) clarified what is taking place at the tissue level during the tuberculous processes (3242).

David Douglas Cunningham (GB), in 1885, and Peter F. Borovsky (RU), in 1898, described Leishmania (368, 717, 1542). Borovsky is also referred to as Alfred Borovsky.

James Homer Wright (US) accurately described Leishmania tropica, the causative agent of oriental sore, also known as Delhi boil, or tropical ulcer (3581).

William Boog Leishman (GB) and Charles Donovan (IE) discovered the protozoan that causes kala-azar (Hindu for black fever), also known as dum-dum fever, tropical splenomegaly, and leishmaniasis, in the spleens of patients who died of the disease (872, 1928). The causative agent was later named Leishmania donovani in their honor.

Frederick George Novy (US) and Rudolph E. Knapp (US) discovered, identified, and cultured the spirochete of American relapsing fever, Spirochaeta novyi (2381).

Frederick George Novy (US) produced the first case of experimental infection with Leishmania (2380).

Antonio Carini (IT), Ulysses Paranhos (BR), and Adolph Lindenberg (BR) described Leishmania in the New World (520, 1972).

Gaspar de Oliveira Vianna (BR) found that the parasites of New World, cutaneous and mucocutaneous leishmaniasis in South America differed from those in Africa and India and created a new species, Leishmania braziliensis (3220).

Gaspar de Oliveira Vianna (BR) introduced the use of the tartar emetic (potassium antimony tartrate) for the treatment of parasitic Leishmaniasis by intravenous injection (3221). Antimonal compounds are still the main drugs for therapy in human and canine leishmaniasis.

Edmond Sergent (FR), Etienne Sergent (FR), Louis Parrott (FR), André Donatien (FR), Maurice Beguet (FR), Robert Knowles (GB), Lionel Everard Napier (GB), R.O.A. Smith (GB), Samuel Rickard Christophers (GB), Henry Edward Shortt (GB), and Philip James Barraud (GB) proved that the sandfly, Phlebotomus, is the vector of kala-azar (585, 1781, 2878).

Henrique de Beaurepaire Aragão (BR) discovered that the genus involved in transmission of New World leishmaniasis is actually Lutzomyia, a genus of sandfly (80).

Saul P. Adler (RU-GB-IL) and M. Ber (IL) determined that the precise mode of infection of Leishmania donovani is through the bite of the sandfly (30).

Ralph Lainson (GB) elaborated the complex life pattern of species of the Leishmania parasite, its vector, reservoir host, and disease (1865).

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 (1173).

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 (1807).

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 (2208).

Frank R. Cheshire (GB) and W. Watson Cheyne (GB) reported Bacillus alvei (Paenibacillus alvei) as the etiological agent of European foulbrood (576).

Friederich August Johannes Löffler (DE) discovered the cause of swine erysipelas, Erysipelothrix rhusiopathiae (2000, 2001). 

Edmond Isidore Étienne Nocard (FR) recognized a weakly acid-fast bacillus that causes avian tuberculosis (2367). 

Daniel Elmer Salmon (US) and Theobald Smith (US) isolated and described a motile, gram-negative, easily cultivable bacillus from a number of cases of hog cholera. They applied Koch’s postulates to prove that it was the causative agent of hog cholera (2766).

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 (797).

In honor of Salmon, the bacterium is today called Salmonella cholera suis (1055, 3049).

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) (1961).

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 (2453). 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 (955). Robert Joseph Lefkowitz (US) says this is “perhaps the earliest progenitor of the modern concept of receptors (1923).”

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 (430).

Hermann Senator (DE) had originated this idea of self-intoxication (2873).

Hermann Sahli (CH) developed a mixture of borax and methylene blue to stain bacteria of central nervous system infections (2764).

Augusta Marie Dejerine-Klumpke (US-FR) studied medicine in Paris and become the first woman to be named interne des hopitaux. She is known as a clinician and a neuropathologist. In 1885 she described the symptomatology of lower brachial plexus lesions (809).

Carl Garré (CH) inoculated himself by rubbing a axenic culture of Staphylococcus upon the uninjured skin of his forearm, with the result that a series of carbuncles was produced, seventeen scars remaining to testify to the success of the experiment (1219).

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 (1037, 1038).

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 (2476).

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 (470).

William Osler (CA) wrote the first comprehensive description of subacute bacterial endocarditis (2415).

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 (2073, 2074).

J. Leonard Corning (US) thought he had performed the first spinal block for anesthesia. He injected cocaine between the spinous processes of the lower dorsal vertebrae, first in a young dog and then in a generally healthy man (659). 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 (308). This represents the first successful intradural spinal block to induce anesthesia.

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

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) was the first to successfully suture a perforated gastric ulcer (3307).

Maximilian (Max) Ruppert Franz von Frey (AT-DE) and Max 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 (3277). 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 (78).

Louis Xavier Édouard Léopold Ollier (FR) used an especially designed elevator to perform subperiosteal bone resections and subcapsulo-subperiosteal joint excisions in humans (2394).

Ludwig Edinger (DE) identified the accessory nucleus of the 3rd oculomotor nerve (Edinger-Westphal nucleus) in the fetus (939, 940, 944).

Karl Friedrich Otto Westphal (DE) did the same in the adult brain (3440). This nucleus supplies pre-ganglionic parasympathetics to the eye, which constrict the pupil and accommodate the lens.

Hermann Ebbinghaus (DE) was the first to experimentally measure acquisition, recall, and recognition, i.e., memory (935).

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?” (1983).

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.


…curious to a vice, investigators to the point of cruelty, with uninhibited fingers for the unfathomable, with teeth and stomachs for the most indigestible, … arrangers and collectors from morning till late, misers of our riches and our crammed drawers, economical in learning and forgetting, inventive in schemes, occasionally proud of tables of categories, occasionally pedants, occasionally night owls of work even in broad daylight.” Friedrich Wilhelm Nietzsche (2358, 2359).

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 (1208).

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 his apochromatic oil-immersion objective microscope lenses by using oils, which match the refractive index of the lens (745).

Ernst August Schulze (CH) and E. Steiger (DE) isolated and named arginine in a precipitate resulting from mixing phosphotungstic acid with extract of germinating lupine seeds (Lupinus luteus) (2851, 2852).

Sven G. Hedin (SE) isolated arginine from horn (1452, 1453).

Friedrich Koch (DE) discovered xylose when he treated wood gum by acid hydrolysis (1787). 

Karl Peters (DE) was the first to describe the diene structure of linoleic acid (2507).

Paul Ehrlich (DE) introduced the acid haematoxylin stain, stabilizing the stain and the mordant (alum) with acid (956).

The first notice was made of a tobacco-soapsuds mixture advocated for aphid control. Lime-sulphur-salt spray was first noted as useful against scale insects. Hydrocyanic acid gas (HCN), one of most 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 (2879).

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 (1461-1464).

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 (1535).” He went on to describe the outgrowth of the axon from the neuroblast in various vertebrates. This was essential to the development of the neuron theory, which states that the neuron, or nerve cell, is the basic unit of the nervous system.

Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) wrote a highly influential review in which he stated that nerve cells terminate freely with end arborizations and that the neuron is the anatomical and physiological unit of the nervous system. This is the coining of the term neuron (3331). 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 (431).

Silas Weir Mitchell (US) and Edward Tyson Reichert (US) established that snake venom is protein in nature, and demonstrated the presence of toxic albumins (2218).

Leonard Charles Wooldridge (GB) proposed for the first time that the prothrombin activator is a protein/phospholipid complex derived from damaged tissue (3573).

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 (2054, 2055).

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” (3362-3364).

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 (1727, 1728). 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 (3366).

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 (3369, 3370). 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) (847), he used the term cytochrome oxidase to denote this enzyme, which he viewed as being equivalent to Warburg’s atmungsferment (1729).

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 (1730).

Eijiro Yakushiji (JP) and Kazuo Okunuki (JP) discovered cytochrome c1 (3592). 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 (1568).

Frederick L. Crane (US), Youssef Hatefi (IR-US), Robert L. Lester (US), and Christine Widmer (CH) discovered ubiquinone (coenzyme Q) as a new hydrogen carrier between the dehydrogenases and the electron transfer chain in beef heart mitochondria (691).

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 (2266-2268).

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 (3562). 

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 (319, 690). 

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 (264).

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 (3193).

St. Szez Zaleski (DE) and Gustav von Bunge (DE) discovered that the fetal liver in animals is used as a storage organ for iron (3249, 3612).

Carl Benda (DE) introduced the use of the iron-hematoxylin dye to histology (274).

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 (1151, 1275, 2306).

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" (1275, 1278).

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 (2583-2588, 2591).

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 (306). 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) (3212). 

Nathan Zuntz (DE) and August Julius Geppert (DE) created the Zuntz-Geppert respiratory apparatus for indirect calorimetry (3624).

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 (110, 111, 278).

William Holbrook Gaskell (GB), in studies of the autonomic nervous system, concluded that the “involuntary system” is composed of two antagonistic subsystems (1226).

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 (2959). 

Adolf Eduard Mayer (DE) demonstrated an infectious agent (virus) to be the most likely cause of tobacco mosaic disease in plants (2122, 2123).

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 (469, 1289). Note that this was six years before viruses were discovered.

Adolf Weil (DE) was the first to describe infectious jaundice or what was later called Weil’s disease (3406). 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 (2767, 2768). Although Smith made the discovery on his own, his supervisor, Daniel Elmer Salmon, usurped credit.

Josef von Fodor (HU) and Vladimir Wyssokowitch (DE) emphasized that the anti-putrefactive quality of circulating blood is part of the body’s defense mechanism. They demonstrated that bacteria introduced into the blood-stream rapidly disappear and apparently do not leave the body by any of the channels of secretion or excretion (3274-3276, 3589).

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 (3276).

George Henry Falkiner Nuttall (US-GB) confirmed observations by von Fodor and Wyssokowitch then discovered that the bacterial killing power of the blood was lost on aging, and destroyed by heating to 52°C for 10 to 30 minutes (2384, 2385). This represents the discovery of the complement system.

Jean Alfred Fournier (FR) described congenital syphilis and emphasized that syphilis could cause degenerative diseases (1162).

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) (3217).

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 (535).

Ernest Ordiozola (PE) introduced the term Carrión’s disease (2406).

Alberto Leopoldo Barton (PE) discovered that Carrión’s disease is caused by the rickettsium Bartonella bacilliformis (193). 

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) (3138).

Charles H.T. Townsend (US) provided evidence that lizards act as a reservoir for Bartonella bacilliformis (3139).

Richard Pearson Strong (US), Ernest E. Tyzzer (US), Charles Thomas Brues (US), Andrew Watson Sellards (US), and J.C. Gastiaburu (US) named the rickettsial microorganism in honor of Barton (3038). 

Hideyo Noguchi (JP-US) also demonstrated that Oroya fever and verruga peruana are both caused by the parasite Bartonella bacilliformis and are actually two different stages of the same infection called Carrion's disease, or bartonellosis (2373).

Marshall Hertig (US) definitely established the role of the sandfly (1496). 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 (466).

Felix Fränkel (DE) reported the first case of a tumor of the adrenal medulla (1177), 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 (2097, 2100).

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 (571, 1547, 3135). 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 (2660).

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 (286).

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 (1904).

Victor Alexander Haden Horsley (GB), using dogs, performed the first successful experimental hypophysectomy. Two dogs survived five and six months respectively after this operation (1572).

Victor Alexander Haden Horsley (GB) successfully operated on several cases of pituitary tumors in man (1573, 1574). 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 (2830).

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 (3260, 3262).

Julius von Hochenegg (AT) and I. Head (AT), in 1908, used the same superior transnasal approach to successfully treat a case of acromegaly (3296).

William MacCormac (GB) introduced an operation for the treatment of intraperitoneal rupture of the bladder (2042).

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 (3308).

Hermann Kümmell (DE), in 1886, attempted the first choledochotomy (surgical incision into the common bile duct) (1850).

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 (2210, 2328, 2329, 2820-2822, 3245, 3246).

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


“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 (1325).

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 (2201). 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 (3213).

Ernst August Schulze (CH) and E. Steiger (DE) developed a solution of zinc chloride-iodine-potassium iodide in water useful for testing for cellulose, which it colors blue (2853). Verify ref

Friedrich W. Semmler (DE) prepared divinyl ether (2871). 

Chauncey Depew Leake (US) and Mei-Yü Chen (US) first observed the anesthetic properties of divinyl ether (1915).

Chauncey Depew Leake (US), Peter K. Knoefel (US), and Arthur E. Guedel (US) introduced divinyl oxide as an anesthetic (1916). 

Julius Richard Petri (DE), one of Heinrich Hermann Robert Koch’s assistants, invented a dish now routinely used in microbiology, the petri dish (2513).

André Victor Cornil (FR), Victor Babès (FR), William Nicati (FR), and Maximillien Rietsch (FR) described very similar dishes a couple of years earlier (658, 2350).

Ernst Salkowski (DE) discovered phytosterol (phytosterin), the nucleus of vegetable fats (2765). 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 (1379).

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 (1622).

Klaus Weber (PL-DE-US) and Ute Groeschel-Stewart (DE) specifically visualized myosin containing filaments in non-muscle cells (3399).

Elias Lazarides (US) identified tropomyosin in non-muscle cells (1911).

Elias Lazarides (US) and Keith Burridge (GB-US) identified alpha-actin as a normal component of non-muscle cells (1912).

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 (2451, 2452).

Nina Strömgren Allen (US) discovered that endoplasmic filaments generate the motive force for rotational streaming in the green alga Nitella (52).

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 (3545, 3547).

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…” (3549).

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 (1480).

Emile Maupas (FR) and Richard Karl Wilhelm Theodor von Hertwig (DE) independently demonstrated exchange of micronuclei during conjugation by Paramecium (2119, 3295).

Jules Héricourt (FR) and Charles Robert Richet (FR) were the first to conceive the notion of producing an immune serum; that is, of injecting into an animal a particular substance to which it could then produce an antidote. (The injected material is an antigen; the countermaterial produced is an antibody). If the antigen is a bacterium or a bacterial toxin, then an antibody will exist that will prevent future infections. If serum containing this antibody is then injected into a human being, it may lend him immunity to a particular disease (1483). Richet tried to produce such an immune serum for tuberculosis but failed (2630). 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 (1722, 2881).

Enrique Paschen (DE) rediscovered these elementary bodies (2475). 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 (377).

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 (2306).

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 (2710, 2712).

Luigi Salvatore Savastano (IT) determined the bacterial cause of galling on olives (Olea europaea ) to be Pseudomonas savastanoi (2779). 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 (1096, 2523).

Thomas Peck Sprunt (US) and Frank Alexander Evans (US) are responsible for coining the phrase infectious mononucleosis (2971).

Howard A. Kelly (US) performed a hysterorrhaphy (suturing of a lacerated uterus) (1734).

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 (1357). 

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 (1426, 2763, 3374, 3375).

Henry Seebohm (GB) was the first ornithologist to recognize the importance of isolation in species formation (2868).

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 (89). This is an acute disease affecting cattle. The bacterium was named in honor of Auguste Chauveau (FR).

Paralytic polio was described as epidemic in Sweden (1803).

Heinrich Hermann Robert Koch (DE) observed a small bacillus, later identified as Haemophilus aegyptius, while examining a series of eye inflammations in Egypt (1788). 

John Elmer Weeks (US) was the first to cultivate Haemophilus aegypticus (3402). 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.

Margaret Pittman (US) and Dorland J. Davis (US) were the first to identify this organism as Haemophilus aegypticus (2542).

Anton Weichselbaum (AT) isolated the causative agent of septic meningitis, Neisseria meningitidis, and associated it with six cases of acute cerebrospinal meningitis (3403).

Johann Otto Leonhard Heubner (DE) was the first to isolate meningococci from the cerebrospinal fluid of living beings (1508).

Guido Banti (IT) pointed out that typhoid fever is caused by a bacterium (159).

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 (1057, 1314).

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 (74-76).

Paul Gerson Unna (DE) described seborrheic dermatitis and distinguished it from chronic eczema and psoriasis (3180).

Joseph Jules Déjérine (CH-FR) described Déjérine’s neuro-tabes (multiple peripheral neuritis with symptoms like those of locomotor ataxia) (806).

Oscar Minkowski; Oskar Minkowsky (DE) associated acromegaly with a hyperfunctional pituitary gland (2214).

Julius Wagner-Jauregg (AT) induced fevers in the mentally ill, using at turns tuberculin, typhus vaccine, and tertian malaria. In 1917, nine patients with general paresis (neurosyphilis) were treated by injecting blood from patients experiencing active malaria; three recovered, three showed temporary relief, and three showed no improvement (3342-3344). 

George Washington Crile (US) was the first to perform major operations with intraneural injections of cocaine. His first such operation was in 1887 (696, 698).

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) developed an operation for the treatment of disease of the accessory nasal sinuses (3311).

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 (1092).

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 (3309).

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 (1195, 3310).

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 (642).

Abraham Jacobi (US) collaborated with the philanthropist Nathan Straus (US) to establish pasteurization plants and milk stations for poor infants in New York beginning in 1893. A reduction in infant mortality of 65% was observed in just one year in the foundling hospital on Randall’s Island after Straus established a pasteurization plant there (637, 642).

In1908, Chicago became the first city in the world to require pasteurization of milk (642).

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 (879).

The Canadian Geological Survey found rich fossil beds containing Upper Cretaceous dinosaur fauna along the Red Deer River in Alberta (505).

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

Annales de l’Institut Pasteur was founded.

Annals of Botany was founded.

Zeitschrift fur Physikalische Chemie was founded.


“Put forward nothing that cannot be proved simply and conclusively. Venerate the critical spirit…. Without it all else is nothing. It always has the last word.” Louis Pasteur. Remarks made at the dedication of the Pasteur Institute of Paris 14 November (277).

The Pasteur Institute was erected in Paris and dedicated on November 14. It was paid for by public donations from all over the world (470).

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 (1724, 2188, 2189).

Erwin Frink Smith (US) postulated some sort of a virus as the cause of peach yellows (2929).

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 (1081).

Sergei Nikolaevich Winogradsky (RU) described photosynthetic purple sulfur bacteria; including Chromatium (3546).

Nikolai Fedorovich Gamaléia (RU) discovered Vibrio metchnikovii in the intestinal tract and blood of fowls suffering from an epidemic disease resembling fowl cholera (1213).

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 (569, 570).

Almoth Edward Wright (GB), Richard Friedrich Johannes Pfeiffer (DE) and Wilhelm Kolle (DE) prepared and recommended a heat inactivated vaccine for typhoid fever, which could be prepared from killed typhoid bacilli (2529, 3574, 3575).

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 (2707-2709).

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 (122, 1033, 1034).

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 (120, 121). 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.

K.P. Hunfeld (DE), A. Hildebrandt (DE), and J.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 (1595).

Auguste Trillat (FR), in 1888, discovered the germicidal value of formalin (40% formaldehyde in water) (3147, 3148). In 1891, Trillat patented the solution as Formolin.

Theodor Geuther (DE) discovered that formalin (Formolin) destroys the germinating power of smut spores (1242). 

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 (2174).

Wilhelm Roux (DE) experimentally produced a half-embryo by killing one blastomere of the two-celled frog embryo (2711).

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 (2952). 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 (3496).

Maximilian Fürbringer (DE) authored Untersuchungen zur Morphologie und Systematik der Vogel, one of the great classics in bird anatomy (1204).

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 (2368). Vittore Benedetto Trevisan (IT) erected the genus Nocardia in honor of Nocard (3146); the etiological agent became Nocardia farcinica.

Victor Alexander Haden Horsley (GB) and Edward Albert Schäfer (GB) published a somatotopic map of the monkey motor cortex (1576).

Charles Scott Sherrington (GB) described the synapse and motor cortex (2896).

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 it many degenerating fibers…', which may be the first report of the direct cortico-motoneuronal projection (1958).

C.G. Bernhard (SE), E. Bohm (SE), and D. Taverner (GB) confirmed the existence of this projection physiologically (294).

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 (2501).

Hugo Schulz (DE) noted that many chemicals are able to stimulate growth and respiration of yeast at low doses but are inhibitory at higher levels (2849). 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.

William Williams Keen, Jr. (US) was the first American to remove an intracranial meningioma (316).

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 (516).

Alfonso Di Vestea (IT) and Giuseppe Zagari (IT) used laboratory animals to provide convincing evidence to support Cantani’s proposal (821).

Karl Schaffer (HU) produced evidence for the neural spread of rabies in humans (2784).

Byrom Bramwell (GB) recognized a connection between pituitary tumors and body fat and polyuria (402).

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” (1064). 

Niels Stensen (DK) had described this condition in 1671 (2994).

Thomas Bevill Peacock (GB) had described this disease in 1846 (2488).

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 (1533).

Caleb Hillier Parry (GB) had been the first to report this disease (2474).

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 (1237, 1494, 1509, 3095).

J.H. van de Kamer (NL), H. Ten Bookkel Huinink (NL), and H.A. Weijers (NL) developed the first accurate method of quantitating stool fat. They thereby proved that diets containing wheat, barley, and rye worsened fecal fat excretion and clinical symptoms in celiac patients (3186).

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 (830).

Willem-Karel Dicke (NL), H.A. Weijers (NL), and J.H. van de Kamer (NL) discovered that celiac disease is cured when wheat is banished from the diet, and rice flour, maize starch, and peeled, boiled potatoes are given instead (831).

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 (2716).

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 (837).

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 (2884).  

Paul Ehrlich (DE) was the first to distinguish the aplastic type of anemia (957).

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 (1297).

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 (127, 128).

Rudolph Matas (US) reported the first known endoaneurysmorrhaphy, which he performed by opening the aneurysmal sac and narrowing the internal lumen by suture (2112, 2115).

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 (1607, 2113).

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) developed an operation to repair complete prolapse of the rectum (3312).

Ian Greaves (US) and Norbert Hirschhorn (US) proposed that Louisa May Alcott (US), famous Ameican author, whose immediate cause of death in 1888 was a stroke, suffered a multi-system disease, possibly originating from effects of mercury on the immune system. A portrait of Alcott at the Alcott museum, Orchard House, in Concord, Mass exhibiting a distinctive "butterfly-rash," a pinkish hue across Alcott's cheeks and nose, that often accompanies lupus raises the possibility that she had systemic lupus erythematosus (SLE) (1309).

William Osler (CA) was the primary force behind bringing the best teaching methods from Europe to Johns Hopkins Medical School and making it the leading medical center in America. He wrote Principles and Practice of Medicine, the greatest textbook of medicine in its time (2416).

Harry Govier Seeley (GB) determined that dinosaurs consist of lizard-hipped (saurischian) and bird-hipped (ornithischian) branches (2869). 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.


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 (91).

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 (2322).

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

Hendrik Paulus Wijsman, Jr. (NL) used Beijerinck's (TLC) technique to identify the active enzyme in malt diastase, which splits off maltose from soluble starch. He invented the first fluorescent indicator for (TLC) visualization by preparing a gelatin layer containing starch and a marine fluorescent bacterium; he diffused the amylase mixture through the gelatin, obtaining a fluorescent band only where the beta-amylase reacted with the starch (3480).

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 (1630).

James E. Meinhard (US) and Norris F. Hall (US) used thin-layer chromatography (TLC) to separate terpenes found in essential oils (2156).

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 (1754-1756, 2209).

Heinrich Ferdinand Edmund Drechsel (DE) isolated the amino acid lysine from hydrolyzed casein. He called it lysatine from the Greek meaning loosing (886).

Charles Tanret (FR) isolated ergosterol from plant tissue (rye) (3075, 3076).

Gerhard Lange (DE) isolated lignic acid from wood (1892, 1893).

Gerhard Lange (DE) determined the quantitative cellulose content within woods (1894).

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 (1550, 1551). 

Jean-Paul Vuillemin (FR) coined the term antibiosis (3337).

Selman Abraham Waksman (RU-US), in 1942, recoined the term as antibiotic in its modern incarnation to mean chemical substances, including compounds and preparations that are produced by microbes and have antimicrobial properties (3346).

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 (1016).

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 (253).

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 (378).

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 (1239).

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. In the course of his prolonged researches Hans Buchner gradually elaborated the view of the existence of substances in the serum inimical to bacteria. He named the substances alexines (I defend) for their protective and defensive properties (463-465). 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 (483). 

During 1889 and in 1892, there occurred among the caterpillars of the nun moth, Lymantria monacha Linn. that 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 (2991).

Edward Klein (DE) reported that Bacillus gallinarum was the cause of an outbreak of fowl cholera and reported it as an infectious enteritis (1770).

Veranus A. Moore (US) described the disease as infectious leukemia and named the organism Bacillus sanguinarum (2240, 2241).

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 (2618).

Leo F. Rettger (US) designated the disease as white diarrhoea (2619).

Frederick Cooper Curtice (1902) studied the disease in Rhode Island and named it fowl typhoid (728).

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 (2620).

Theobald Smith (US) and Carl TenBroeck (US) recorded that Salmonella gallinarum and Salmonella pullorum are serologically identical (2942).

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 (573).

Max Gruber (AT) and Herbert Edward Durham (GB) extended this observation by showing that the agglutination of bacteria by serum is specific (923, 1327-1330). This was quickly seized upon as a new diagnostic tool.

Georges Fernand Isidore Widal (FR), Arthur Sicard (FR) and Albert Sidney Frankau Grünbaum (GB)— Grünbaum later changed his name to Albert Sidney Frankau Leyton— showed that the agglutination of enteric bacteria can be used as an aid to identifying the infectious agent. This reaction is brought about by the addition of a patient’s serum to a uniform suspension of a known bacterium. The Widal Test is used for diagnosis of typhoid fever by mixing the patients serum with a 24-hour Salmonella typhi culture on a glass slide or other appropriate surface. Clumping of the cells after a 30 to 60 minute incubation is a positive reaction (1331, 3455, 3458, 3459).

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

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

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

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

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

(5) Texas fever in nature is transmitted from cattle 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" (2933, 2938).

Heinrich Hermann Robert Koch (DE) described the stages of Babesia bigemina developing in the tick's gut within the first 20 hours after repletion (1791).

Henri Parinaud (BE) discovered cat-scratch-fever (2466).

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) (2522).

Robert Anselme Debré (FR), Maurice Larny (FR), and Marie-Louise Jammet (FR) discovered that the cat is the natural reservoir of cat-scratch-fever (804).

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 (1026). Bartonella henselae or Bartonella clarridgeiae are known to cause this disease.

Georg Marius Reinald Levinsen (NL) was the first to describe a human case of infestation by gnathostoma when he found gnathostoma (a nematode) larva in an infested Thai woman (1944, 2222).

H.T. Chen (CN) reported a human ocular infection by Gnathostoma in China (575).

Ira van Gieson (US) introduced the first triple staining technique to histology. He used hematoxylin, acid fuchsin, and picric acid to stain nerve tissue (3194).

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 (1132).

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 (1536).

Carlo Giovanni Martinotti (IT) described a cortical neuron with an ascending axon (this neuron now bears his name, Martinotti cells) (2109).

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) (2285).

Francis Galton (GB) formulated the law of ancestral inheritance, a statistical description of the relative contributions to heredity made by one's ancestors (1209). This book is considered the beginning of modern biometry.

Henry Head (GB) demonstrated the action of the vagus nerve in respiration (1445).

Ludwig Edinger (DE), in 1889, discovered the direct connection of the spinal cord and thalamus in fish, frogs and cat embryos. He found that cells in the dorsal horn give rise to axons which pass through the ventral commissure, ascend in the opposite anterolateral funiculus and seemingly end in the thalamus. Ref

Leopold Auerbach (DE) confirmed this (113).

Eliza Dalgleish Ewart (GB) gave the first comprehensive description of the anatomy of the human lung (1053).

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 (449, 450).

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 (1437).

Ernst Fuchs (DE) described an outbreak of epidemic keratoconjunctivitis (EKC) (1199).

Ernest Jawetz (US), Samuel J. Kimura (US), Lavelle Hanna (US), Virginia R. Coleman (US), Phillips Thygeson (US), and A.N. Nicholas (US) discovered that this clinical picture of epidemic keratoconjunctivitis (EKC) is associated with adenovirus type 8 (1659, 1660).

August Pfeiffer (DE) described Yersinia pseudotuberculosis (2523). 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 (3621).

M. Bourdin (FR) reported that many species, most of them rodents or birds, could serve as healthy carriers of Y. pseudotuberculosis (374).

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 (3065).

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 (2446).

Ian Hart (GB) and Isaiah Fidler (US) performed experiments in mice, which verified Paget’s hypothesis (1425).

Joseph von Mering (DE) and Oskar Minkowski (DE) discovered the role of the pancreas in glucoregulation when they surgically removed the pancreas of dogs and found that their blood sugar and urine sugar would rise causing hyperglycemia and glycosuria (diabetes mellitus) (2215, 3305, 3306). 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 anaemic disease occurring in children under 3 years of age. A symptom complex characterised by acute haemolytic anaemia, hepatosplenomegaly, and infections associated with several chronic diseases, like tuberculosis, congenital syphilis, gastrointestinal disorders, and malnutrition. The patient presents with listlessness, weakness, gastrointestinal troubles and irregular fever (1442, 3297). 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 (3023).

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 (1389). He eventually achieved an unprecedented 72 percent five-year cure rate for patients whose disease had not spread to adjoining glands. Halsted first performed this operation in 1889.

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) performed the first enterocystoplasty (3313).

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 (195, 448, 1387). This is called herniorrhaphy.

Wilhelm Wagner (DE) used a scalpel, hammer, and chisel to resect a flap of scalp and skull hinged upon muscle so that it could be replaced. With such a large osteoplastic flap, the surgeon could cut the dura mater about an attached tumor or reflect the dura mater to explore much of the lateral cortex. This method could expose a much larger area of the brain’s surface than a trephine (3341).

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) (3244, 3247).

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 (2017).

Pierre Marie Félix Janet (FR) argued that "hysterical symptoms are due to subconscious fixed ideas that have been isolated and usually forgotten. Split off from consciousness – 'dissociated' – they embody painful experiences, but become autonomous by virtue of their segregation from the main stream of consciousness (1653). 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 (1603).

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 (1803).


“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 (880).

"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 (252).

Jakob Stilling (DE) reported the bacteriostatic action of the triphenylmethane dyes. Methyl violet and auramine were recommended as useful antiseptics (3014, 3015). 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 (589).

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 (2002).

Richard Altmann (DE) introduced the technique of freeze-drying to preserve tissue (53).

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 (2883).

Pierre Miquel (FR) obtained urease from bacteria (2217).

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 (379, 1338).

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" (1498).

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 (432, 1058, 1059).

Willoughby Dayton Miller (US) elucidated the bacteriology of dental caries (2211).

Christiaan Eijkman (NL), Gerrit Grijns (NL), Adolphe Guillaume Vorderman (NL), Henry Fraser (GB), and Ambroise Thomas Stanton (GB) discovered that a constituent of rice (Oryza sativa) husks (thiamine, vitamin B1) cured a neurological disease of birds (polyneuritis gallinarum) that resembles the human disease known as beriberi. They knew it was a dietary-deficiency-disease, although they did not know what was missing from a diet to cause it. They discovered that beriberi could be cured by adding rice shavings (outer layer) to the diet (981-983, 1178, 1316, 3332-3334).

Christiaan Eijkman (NL) and Gerrit Grijns (NL) described the properties of their antineuritic dietary factor (thiamine, vitamin B1) as soluble in water or dilute alcohol, and diffusable through a semi-permeable membrane (984).

Umetaro Suzuki (JP), Torai Shimamura (JP), and Seizaburo Okada (JP) isolated the antineuritic, anti-beriberi factor (thiamine, vitamin B1) as a crystalline picrate (3055).

Juan Antonio Collazo (UY) and Casimir Funk (PL-GB-FR-US) noted that pigeons placed on a diet deficient in the antineuritic, anti-beriberi factor (thiamine, vitamin B1) then fed a diet high in carbohydrates exhibited a toxic (beriberi) effect. He concluded that in this vitamin deficiency, normal carbohydrate metabolism couldn’t function properly (635).

Barend Coenraad Petrus Jansen (NL) and Willem Frederik Donath (NL) crystallized thiamine (vitamin B1) (1658).

Louis Sigurd Fridericia (DK), P. Freudenthal (DK), Skúli V. Gudjónnson (DK), G. Johansen (DK), and N. Schoubye (DK) demonstrated that rats are capable of adjusting their digestion to accommodate a diet deficient in thiamine (vitamin B1). They called this phenomenon refection. The microbiota of the cecum of refected rats differs significantly from that of rats on a diet containing thiamine (1189).

Carl Arthur Scheunert (DE), Martin Schieblich (DE), and Johannes Rodenkirchen (DE) associated this synthesis of thiamine (vitamin B1) in refected rats with the presence of intestinal vibrios (2814).

R. Inawashiro (JP), E. Hayasaka (JP), Henry Wulff Kinnersley (GB), Nicolai Gavrilescu (HU), and Rudolph Albert Peters (GB) demonstrated that vitamin B1 (thiamine) and pyrophosphate are associated with the breakdown and removal of pyruvic acid from animal tissue, since lactic acid disappeared more slowly from the blood of beriberi patients after exercise and lactic acid accumulated in the brain tissue of B1-deficient pigeons, and the addition of vitamin B1 and pyrophosphate to the minced tissue caused the rapid disappearance of pyruvic acid without the accumulation of lactic acid. They determined that the head retraction and opisthotonus of pigeons fed on polished rice (Oryza sativa) were of central and not peripheral nerve origin, and that vitamin B1 (thiamine) played a special part in tissue oxidations (1235, 1617, 1752, 1753, 2508-2510).

Adolf Otto Rheinhold Windaus (DE), Rudolf Tschesche (DE), Hans Ruhkopf (DE), Fritz Laquer (DE), and Fritz Schultz (DE) isolated the pure vitamin B1 from yeast and established its empirical formula (3534).

Adolf Otto Rheinhold Windaus (DE), Rudolf Tschesche (DE), and Hans Ruhkopf (DE) discovered that vitamin B1 (thiamine) contains sulfur (3533).

Ernst Auhagen (DE) discovered that yeast carboxylase, the enzyme which decarboxylates pyruvic acid to acetylaldehyde requires a heat-stable dialyzable coenzyme (114). It was first called co-carboxylase, and then later named thiamine (vitamin B1).

Robert Rampathnam Williams (US), Robert E. Waterman (US), and John C. Keresztesy (US) isolated the antineuritic, anti-beriberi factor (thiamine, vitamin B1) in highly purified form on a large scale (3488).

Robert Rampathnam Williams (US), Joseph K. Cline (US), Jacob Finkelstein (US), Alexander Robertus Todd (GB), Franz Bergel (GB), Hans Andersag (DE), Kurt Westphal (DE), Kurt Guenter Stern (GB-US), and Jesse W. Hofer (US) synthesized and determined the structure of the co-carboxylase (a pyrophosphoric ester of vitamin B1) discovered by Ernst Auhagen (DE). They characterized it as a pyrimidine ring linked by a methyl group to a thiazole ring and named it thiamine (vitamin B1) (64, 619, 3001, 3002, 3133, 3487).

Karl Lohmann (DE) and Philipp Schuster (DE) determined that thiamine pyrophosphate chloride (vitamin B1) functions as a coenzyme (co-carboxylase) which is necessary for the enzyme carboxylase active in the decarboxylation of many alpha-keto acids (2007).

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") (2422).

Julius Bernstein (DE), in 1902, stated his membrane theory as follows, “The electrical currents observed in many living organs of animals and plants have been the objects of much research. We detect such currents in muscles, nerves, secretory glands, and electric organs of fish as well as in plant tissue. It seems likely that all these currents have a similar, if not the same basis, and that their strength and potency depends on the structural conditions and chemical composition of the cells making up each organ.” He postulated that the membrane of the nerve cell is able to selectively pass certain kinds of ions. Bernstein made the suggestion that nerves are normally polarized with positive ions on the outside and negative ions inside and that the current he measured was the change in this polarization. Obviously when equilibrium is reached an electrical potential exists across the membrane - the transmembrane potential. The nerve impulse is simply a localized region of depolarization, or loss of this transmembrane potential, that travels down the nerve fiber with the membrane potential being immediately restored behind it (296, 297). 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 (1968).

Alan Lloyd Hodgkin (GB) supported this theory with experiment (1544, 1545).

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 (3222). He later confirmed that hemoglobin concentrations rise on ascent to higher altitudes.

Carl Fraenkel (DE) found that he could immunize guinea pigs against living Corynebacterium diphtheriae by giving an injection of a three week old heat killed (60-70°C for one hour) culture of the same species (1165).

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 (251, 252).

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 (905-908).

F. Bezancon (FR), V. Griffon (FR), and L.C. Le Sourd (FR) obtained the organism in axenic culture (301).

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 (302).

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) (1027).

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 (1380-1386). 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 (495-504).

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 (1988, 1990).

Thomas Henry Huxley (GB) and Theodor Wilhelm Engelmann (DE) suggested that muscle fibrils are the likely location for the contractile mechanism (1024, 1609).

Charles Smart Roy (GB) and Charles Scott Sherrington (GB) concluded that, “The chemical products of cerebral metabolism contained in the lymph which bathes the walls of the arterioles of the brain can cause variations of the caliber of the cerebral vessels; … in this reaction the brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with local variations of functional activity” (2715).

Henry S. Forbes (US) and Stanley Cobb (US) supported them and concluded that carbon dioxide is a major regulator of vasomotor activity in the brain (1149).

Vittorio Mibelli (IT) described and named angiokeratoma as, “The presence of small red spots could be seen, which resembled telangiectases and were covered already by a slightly elevated and horny epidermis…. The external appearance of the small tumors suggested the diagnosis of keratoma” (2197).

Franz König (DE) gave a detailed description of joint involvement in hemophilia (1810).

Allvar Gullstrand (SE) presented his theory of astigmatism and elucidated how the eye accomplishes intracapsular accommodation (1342-1346).

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” (2098).

Odilon Marc Lannelongue (FR) performed the first thyroid transplantation, for treatment of cretinism (1898).

William Rose (GB) performed a Gasserian ganglionectomy for trigeminal neuralgia; the patient lived for at least two years (2677).

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 (678).

Charles Alfred Ballance (GB) popularized the operation of radical mastoidectomy for advanced middle ear infection in 1890 (151). 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 (1254, 1255).

J. Knowsly Thornton (GB) is credited with the first known successful operation to remove an adrenal cancer. His patient was a 36-year-old, very hirsute female who was found at operation to have a 20-pound left adrenal tumor (3117). 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” (3145).

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 (1820, 1821).

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

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


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 (3190).

Hermann Nordtmeyer (DE) introduced a new filtering medium made of the compressed infusorial (diatomaceous) earth known as Kieselguhr (2377).

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) (1719).

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 (2879).

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 (2850).

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 (3140).

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 (3238).

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 (1475). 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 (2720).

William Austin Cannon (US) based on his studies of cotton helped provide a cytological basis for the Mendelian laws (506).

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 (2072).

Dimitri Leonidovich Romanowsky; Dimitri Leonidovich Romanovsk (RU) developed a stain which allowed for differential identification of blood parasites, including malaria (2671).

Paul Ehrlich (DE) selectively stained mast cells using a dye called dahlia (958).

Liberty Hyde Bailey, Jr. (US) published the first detailed study of the growth of plants under artificial light (144, 145).

Joseph F. Payne (GB) remarked on the infectious nature of warts (2487).

Merton B. Waite (US) discovered that bees and wasps are vectors of fire blight, a bacterial disease of pears and other orchard fruits (3345).

Pierre-Jean Achalme (FR) was the first to cultivate Clostridium perfringens. He incorrectly supposed it to cause articular rheumatism (14).

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 (3419).

Adolf Schenkl (CZ), R.R. von Limbeck (CZ), Emanuel Zaufal (CZ), et al. used animal studies to verify that a gram-positive spore-forming rod shaped microorganism that grew only under anaerobic conditions, was the etiologic agent of gas gangrene (2812). Note: this clinical entity is also called clostridial myonecrosis.

Eugen Fraenkel (DE) isolated this organism and designated it Bacillus phlegmonis emphysematosae (1166). 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 (1252).

Douglas McClean (GB) discovered and isolated hyaluronidase (spreading factor) from Clostridium perfringens (2126).

Leland S. McClung (US) found the Clostridium perfringens is capable of causing food poisoning (2137).

Marjorie Griffen Macfarlane (GB) and John D. MacLennan (GB) isolated a collagenase (kappa toxin) from Clostridium perfringens (2046).

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 (2386, 2387).

Ethel Bidwell (GB) and William E. van Heyningen (GB) determined that the kappa exotoxin of Clostridium perfringens is a collagenase (303).

Marjorie Griffen Macfarlane (GB) identified the alpha toxin of Clostridium perfringens as the enzyme lecithinase C (2045).

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 (2692).

Clostridium perfringens is the common leavening agent in salt rising bread (1701).

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 (959).

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 (960).

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 (1789).

Emil Adolf Behring (DE) and Shibasaburo Kitasato (JP) used their anti-diphtheria toxin to treat humans for the first time on Christmas night, 1891 (3432). The results were disappointing.

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

Hans Driesch (DE) separated a developing sea urchin embryo at the two-cell stage and found that each of the cells would form a complete, though small larva. He realized that if each half-egg forms a whole rather than a half-embryo, then an interaction must occur between the two cells to restrict their potentials in normal development. Dreisch's theory of totipotency contradicted Wilhelm Roux's mosaic theory (888). Driesch went on to show that up to the four-cell stage separated blastomeres would develop into perfect embryos, each of reduced size (890).

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) (1450).

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 (2538).

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 (565).

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 (949-952, 2997, 2998).

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

Louise Joy Brown (GB) the world’s first test tube baby (in vitro fertilization) was born in Oldham, Northern England, on July 25, 1978. Patrick Christopher Steptoe (GB) and Robert G. Edwards (GB) performed the operation (2997). 

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 (629).

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 (3051).

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 (1910).

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 (2450). 

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 (81-84, 3617).

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) (239).

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 (1349).

Luigi Luciani (IT) distinguished three stages of starvation in man - hunger, physiological inanition (exhaustion), and pathological inanition (2021).

John Benjamin Murphy (US) invented Murphy’s button, used to rapidly join the ends of a divided intestine. This devise revolutionized abdominal surgery (2286).

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 (2020).

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 (2034).

William Bennett Kouwenhoven (US), William R. Milnor (US), G. Guy Knickerbocker (US), and W.R. Chesnut (US) performed extensive closed chest defibrillation experiments in dogs (1828).

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 (137).

Otto Bollinger (DE) described a delayed traumatic apoplexy he called traumatische Spät-Apoplexie. Today this condition is called delayed traumatic intracerebral hematoma or (DTICH) (350).

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 (2575, 2577).

Walter Essex Wynter (GB) performed lumbar puncture to relieve spinal fluid pressure in four cases of tubercular meningitis (3588).

Berthold Earnest Hadra (US) introduced spine wiring to treat instability (1356).

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 (3156). Tuffier was ahead of his time.

Ivan Magill (GB) and E. Stanley Rowbotham (GB), working at Gillies' plastic-surgery unit, found their way back to the simplicity of the endotracheal tube and positive pressure (2061, 2713).

Ralph M. Waters (US), in 1931, showed that respiration can be controlled either by squeezing the anesthetic bag by hand or by using a small motor. Refs

Alexandr Petrovich Karpinsky (RU) was trained as a geologist and became an expert paleontologist. From fossil remains of ammonids he was able to relate ontogenesis and phylogenesis of these animals to their historical development. He constructed a genealogical tree of the ammonids and thus determined their phylogenetic relationships (1712, 1715).

Deutsche Zeitschrift für Nervenheilkunde was founded.

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


“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 (1760).

K. Bratuscheck () was the first to study phase relations within the microscope (404).

Julius Rheinberg (GB) and A.E. Conrady (GB) obtained photographs of a fine grating with a phase-contrast microscope (647, 2621, 2622).

Fritz Zernicke (NL) explained the physical principles of phase-contrast microscopy (3614-3616). 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 (2879).

Harold Picton (GB) and S. Ernest Linder (GB) were the first to demonstrate electric charge directly when they measured the movement of collloidal particles, including hemoglobin molecules in solution, under the influence of an electric field. This was the origin of moving boundary electrophoresis (2535, 2536).

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 (1411). A year later he discovered that proteins have an isoelectric point, a pH at which they have no net charge and therefore will not migrate. He therefore appreciated that pH could have a profound effect on the net charge of a protein further noting that at the isoelectric point a protein tends to coagulate or precipitate (1412).

Arne Vilhelm Kaurin Tiselius (SE), Stig Claesson (SE) and Paul König (AT) developed apparatus, which can effectively separate mixtures of proteins based on their electrophoretic mobility. Tiselius used a special tube arranged like a rectangular U within which the proteins could move and separate. Lenses were designed to detect changes in the index of refraction as protein concentration changed in the developing bands. It was by this method that blood proteins were first separated into albumin and globulin fractions. This technique is referred to as moving-boundry electrophoresis. König used filter paper as a stabilizing matrix for electrophoresis (1811, 3127, 3129). See, Hardy, 1899.

Arne Vilhelm Kaurin Tiselius (SE) and Elvin Abraham Kabat (US) used electrophoresis to show that antibodies make up part of the gamma globulin fraction of serum. They also found that antibodies are not uniform in electrical charge or sedimentation characteristics. This was the first clue that antibodies are physically heterogeneous. The alpha, beta, and gamma notation was coined by Tiselius and first used in the 1937b article (3128, 3130).

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” (342).

Leo Lilienfeld (AT) coined the word nucleohistone to apply to material extractable with distilled water from leucocytes or minced thymus and precipitatable from the aqueous extracts with acetic acid (1963, 1964).

Martinus Willem Beijerinck (NL) published his work on tobacco mosaic disease, showing that the causal agent had many of the qualities associated with a living organism. He hypothesized that the agent must be incorporated into host cells before it could reproduce and that its reproduction was linked to the reproduction of the host cell. These papers along with those of Adolf Eduard Mayer (DE) in 1886 and Dimitri Ivanowsky; Dimitri Iwanowski; Dimitri Ivanovski (RU) in 1892 and Erwin Baur (DE), in 1904, are considered the co-discoveries of plant diseases caused by filterable agents (viruses) (233, 255, 256, 1626-1628, 2122, 2123).

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” (2003, 2004).

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 (553, 554, 1987, 2059).

Arnaldo Maggiora (IT) and Gian Luoa Valenti (IT) concluded that the etiological agent of fowl plague behaved as a true virus (2060).

Émile Marchoux (FR) reported successful in vitro culture of the fowl plague virus (2089).

Werner Schafer (DE) determined that fowl plague (FP) virus is actually one of the influenza A viruses (2783).

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 (726, 727, 2005).

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 (177, 1374, 1375, 1377, 3365).

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 (1482).

Ludwig Edinger (DE) introduced the concept of centrally arising pains (942).

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 (2906).

George Miller Sternberg (US) found that calves infected with vaccinia virus produced specific antibody, which could neutralization the virus (3006). 

Dmitrii Iosifovich Ivanowski; Dmitrii Iosifovich Iwanowsky; Dmitrii Iosifovich Ivanovski (RU) demonstrated that the mosaic disease of tobacco (Nicotiana tabacum) could be transmitted by the juice of infected plants which had been passed through a filter that would stop bacteria (1591, 1626-1628, 2123). This is considered to be one of the co-discoveries of viruses.

Guiseppe Guarnieri (IT) observed homogenous acidophilic inclusion bodies, 2 to 10 millimicrons in size, in the cytoplasm of epithelial cells from patients with variola (smallpox) (1335). 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 (2524, 2526).

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 (2525, 2531).

William Thompson Sedgwick (US) and John L. Batchelder (US) demonstrated the relationship of the bacterial count of milk to its sanitary quality (2865, 2866).

Roland Thaxter (US) first described the Myxobacteria (3090-3092).

Konstantin Wingradoff (RU) was the first to describe infections of Opisthorchis in humans (3544).

Hans Vogel (DE) discovered the snail and fish hosts and their roles in the life cycle of Opisthorchi (3235).

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 (2175, 2176).

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 (794).

Guillermo Seeber (AR) thought it was a protozoon when he described it (2867).

Roberto Johann Wernicke (AR) named it Coccidium seeberia after the protozoal subdivision Coccidia and his pupil, Guillermo Seeber (AR) (273).

Guillermo Seeber (AR) then renamed it Rhinosporidium seeberi (2867).

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 (1490). 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 (2557, 3433, 3434).

William Ophüls (US) and Herbert C. Moffitt (US) demonstrated the mycotic nature of the infection (2397, 2398). 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 (US), and Chester W. Emmons (US) demonstrated that the soil is a reservoir for Coccidioides immitis (1017, 1018, 3010).

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 (832, 833).

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 (2928).

Francis Galton (GB), a cousin to Charles Robert Darwin, was the first to suggest that fingerprints would be useful in tracing criminals (1210, 1211).

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 (3564).

Gheorghe Marinescu (RO) and Paul Oscar Blocq (FR) were the first to describe plaques in brain tissue of senile patients (2102).

Carl Ludwig Schleich (DE) was the first to demonstrate infiltration anesthesia (local anesthesia) on humans. He used dilute cocaine (2828).

Arnold Pick (CZ) did work on lobar cortical atrophy, which made him famous (Pick’s disease) (2534). This is a rare and fatal degenerative disease of the nervous system. Clinically there are major overlaps with Alzheimer's presenile dementia.

Josef Albert Amann (DE) and Gotthard Schubert (DE) independently developed an operation used in cases of congenital absence of vagina. Amann making an artificial vagina from the ampulla recti. Schubert creating an artificial vagina using transplants from anus and rectum (58, 2848).

William Stewart Halsted (US) performed the first successful ligation of the left subclavian artery (1388).

William Arbuthnot Lane (GB) introduced mastoid drainage in purulent otitis media with specially designed chisels and gouges (1886).

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 (2169, 2170).

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 (898-900). 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) (3100). This specimen of Homo erectus is commonly called Java man.

Davidson Black (CA) coined the name Sinanthropus pekinensis, for what was popularly called Peking man (322, 323).

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 (3404, 3405).

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 (3082, 3083). 

Towikromo (ID) discovered another Homo erectus, Sangiran 17, in 1969 in Java, Indonesia. Sastrohamidjojo Sartono (ID) first described it as Pithecanthropus erectus in 1971 (2774). 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 (3150).

The American Psychological Association was formed.


“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 (1808).

August Karl Johann Valentin Köhler (DE) discovered the technique, which became known as "Köhler illumination" (1800).

Adolf Pinner (DE) determined the structure of nicotine as known today (2540).

N.A. Monteverde (RU) isolated chlorophyll crystals and determined their spectroscopic properties. Ref

Karl Wilhelm von Nägeli (CH) coined the phrase oligodynamic action to describe the antimicrobial activity of microgram quantities of silver ions (3317).

Ferdinand Blum (DE) originated tissue fixation with formaldehyde (339). 

Wilhelm August Oskar Hertwig (DE) centrifuged frog eggs and demonstrated the effect of yolk distribution on cleavage (1501). 

Francisco Sanfelice (IT) found that nontoxic “pseudotetanus” clostridia when inoculated into filtrates of the anaerobic sporeforming Clostridium tetani became toxicogenic, the acquired toxicity persisting for several transfers (2770). 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 (1276, 1279).

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 (1277, 1280).

Wilhelm His, Jr. (CH-DE) researched the development of the embryonic heart during which he discovered the auriculo-ventricular bundle (bundle of His), also called the fasciculus atrioventricularis. He demonstrated that there is a muscular AV connection, and was the first to describe the function of this AV conduction system (1538).

Albert Frank Stanley Kent (GB) discovered a similar bundle, which runs from the posterior wall of the right atrium to the ventricular septum, permitting premature excitation of the ventricles by the sinus node (1740).

Wilhelm His, Jr. (CH-DE) showed that following section of the A-V bundle, the auricular and ventricular beats became dissociated (1539). It would later be realized that this observation explained the Adams-Stokes syndrome (slow pulse, vertigo, and epileptoid seizures).

Sunao Tawara (JP) and Karl Albert Ludwig Aschoff (DE) discovered the auriculoventricular (AV) node of the heart, a small node of modified cardiac muscle that transmits the impulses originating in the sinus node down to the ventricles. It is the beginning of the auricular-ventricular bundle of His (3079). Today it is called the Aschoff-Tawara node or the AV node.

Arthur Berridale Keith (GB), and Martin William Flack (GB) discovered the sinoauricular node (SA) of the heart, often called the pacemaker of the heart and noted that the auriculo-ventricular system discovered by His and Kent is but part of a system of fibers which extend to the whole heart and determine its rhythm (1731). It is also called the Keith-Flack node or sinus node.

Jean George Bachmann (FR-US) described the interatrial bundle (Bachmann’s bundle) as an interatrial link allowing conduction from the right to the left atrium (132).

Thomas Naum James (US) identified bypass fibers of an internodal connection. This represents a circumvention of the AV node, originating in the atrial conduction system and running below the AV node and extending to the bundle of His and to the fascicles (1651).

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 (3020).

Jean Baptiste Emile Vidal (FR) was likely the first to successfully transmit herpes fibrilis from one human to another (3225).

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 (3226, 3485).

A. Lowenstein (DE) performed experimental transmission of herpes simplex virus type 1 (HSV-1) from human lesions to rabbit corneas (2013). 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 (1039, 1040, 2180-2183).

Hans Lohmann (DE) wrote a report about plankton from the German Plankton Expedition. He discovered the existence of nanoplankton (751). He is commemorated by the genus Lohmannella, Trouessart, 1901.

Friedrich August Ferdinand Christian Went (NL) was the first to describe the fungal infection of sugar cane which became known as Red Rot of the Stem (3429). 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. In order to achieve this, he found that cholera vibrios or their body substance must be injected in such doses that a mild specific illness, a general reaction, follows (3379).

Pierre Paul Émile Roux (FR) and Louis Vaillard (FR) demonstrated that antitoxin is something created or newly produced in the body as a result of the injection of toxin. The antitoxin (antibody) was found not to appear immediately after the injection of the toxin (antigen) (2706).

Wilhelm August Oskar Hertwig (DE) obtained twin embryos in the newt by constricting the egg by means of fine ligatures (1499).

Hermann Endres (DE), Amedeo Herlitzka (IT) and Hans Spemann (DE) confirmed and extended his results with very similar experiments (1021, 1022, 1487-1489, 2962-2964).

Wilhelm August Oskar Hertwig (DE) proposed that all cells in an animal embryo receive the same number of chromosomes (1500).

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 (1502). 

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 (182).

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 (3509, 3510, 3512, 3522).

Edouard Brissaud (FR) produced an atlas of the human brain drawn completely by hand (437).

John Newport Langley (GB) introduced the terms pre-ganglionic and post-ganglionic in 1893 and gave the autonomic nervous system its name in 1898. He named the cranial and sacral divisions of the autonomic nervous system, which seemed to be involved with the restoration and conservation of bodily resources, parasympathetic (3536).

Joseph Jules Déjérine (CH-FR) and Jules Sottas (FR) described Déjérine-Sottas disease (hypertrophic progressive interstitial neuritis) (808). 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 (2022).

Pierre Marie (FR) described hereditary cerebellar ataxia (2099).

Heinrich Irenaeus Quincke (DE) recognized the syndrome of meningitis serosa (2576).

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 (1122-1124, 1126-1130).

Paul Emil Flechsig (DE) outlined the auditory radiation (1125) 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 the condition (2044).

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’ (651, 987-992, 994, 2945). See, Waller, 1887.

Willem Einthoven (NL) documented his clinical use of the electrocardiogram (993).

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 (995, 996).

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 (692).

Charles C. Wolferth (US) and Francis Clark Wood (US) introduced the use of chest leads to electrocardiography (3563).

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 (3523).

Fritz Schellong (DE), S. Heller (DE), and E. Schwingel (DE) introduced vector electrocardiography (2810).

H. Frank Macinnis (CA) and Norman Jefferis Holter (US) independently applied bioelectrical signal telemetry to continuous ECG recording (1558, 1559, 2048). Norman Jefferis Holter (US) and Joseph Anthony Gengerelli (US) had invented bioelectrical signal telemetry (1560).

Emanuel Goldberger (US) introduced the unipolar extremity electrode system (1256).

Ernest Frank (US) designed the corrected orthogonal lead system (1175).

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 (2567).

Gaston Giraud (FR), Paul Puech (FR), Hugues Latour (FR), and Jean Hertault (FR) developed intracardiac leads (1247).

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 (924, 925, 1241).

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 (2813).

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 (3420).

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 (1147).  

Friedrich Müller (DE) demonstrated that exophthalmic goitre is accompanied by an increased metabolism (2278).

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 (1829, 1830). It is called Kozhevnikov’s syndrome I.

Adam Politzer (AT) was the first to describe otosclerosis as a specific disease fixating the stapes (2550, 2551).

George Ryerson Fowler (US) performed the first known thoracoplasty (1163). 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 (1986).

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 (1803).

Louis Antoine Marie Joseph Dollo (FR-BE) proposed that evolution never repeats itself, i.e., is irreversible. This became known as Dollo’s law. Darwin's natural selection does not necessarily prescribe progress or regression, does not imply a direction of evolution in time, it only states an environmental constraint. Indirectly, Dollo's law does: it prescribes a trend towards more and more complex, and more and more ordered, living structures. Dollo's law expresses the visible fact that reproduction, ontogeny and phylogeny are biological organizations whose behavior is irreversible: both during growth and during evolution, entropy of biological information constantly increases. We evolved from bacteria to humans; we grew from children to adults (862-865).

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 (636, 3451).

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.


“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 (1105).

“The students of adaptation forget that even on the strictest application of the theory of selection it is unnecessary to suppose that every part of an animal has, and every thing which it does, is useful and for its good. We, animals, live not only by virtue of, but in spite of what we are.” William Bateson (200).

Arvid Gustaf Högbom (SE) suggested an internal source for our atmosphere as a result of gradual, episodic, or rapid volcanic outgassing and weathering (1554).

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 (48, 3106). 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 (410).

Friedrich Wilhelm Küster (DE), while working with methyl orange, coined the name zwitterion for molecules carrying opposite charges (1855). Bredig accepted this name and pointed out that amino acids also form zwitterions (411).

Karl Ludwig Winkelblech (DE) proposed that simple amino acids in their state of neutrality are dipolar ions (3541).

Elliot Quincy Adams (US) suggested that amino acids are zwitterions at their isoelectric pH (24).

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) (321).

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) (3397, 3398). 

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 (2423). Ostwald is generally believed to be the first to understand the nature of catalytic reactions.

Hermann Emil Fischer (DE) and Paul Lindner (DE) found that cane sugar, alpha-methylglucoside, is hydrolyzed by invertin (alpha-glycosidase), extracted from dried yeast, but not by emulsin, whereas beta-methylglucoside is cleaved by emulsin but not invertin. He concluded, “…I will say that the enzyme and the glucoside have to adapt with each other like a key in a lock ('Schloss und Schlüssel') to carry out a chemical action one on the other…. The finding that the activity of enzymes is limited by molecular geometry to so marked a degree should be of some use for physiological research.” This is Fischer’s famous lock-and-key hypothesis explaining enzyme specificity (1105, 1113).

Olaf Hammarsten (SE) isolated beta-nucleoprotein from ox pancreatic nucleoprotein (1393).

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 (155).  

August Gürber (DE) crystallized horse serum albumin (1348).

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 (2363, 2364).

Arsenite of copper was discovered to be an insecticide (2879).

Giulio Cesare Bizzozero (IT) noticed a link between mitosis and regenerative capacity. He divided mitotic cells into three catagories: 1) labile cells which demonstrate mitosis throughout life, e.g., bone marrow, 2) stable cells in which spontaneous mitotic activity is uncommon following birth, e.g., connective tissue, and 3) permanent cells which are mitotic in adulthood but do not regenerate, e.g., striated muscle (320).

Carl Ludwig Schleich (DE) suggested that neuroglia moderate neuronal activity through an inhibitory action (836).

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 (366, 367). Hans Winkler (DE) was the first to produce plant chimeras by grafting tomato and nightshade (3542).

Max Rubner (DE) painstakingly tested the energy consumption of dogs using large calorimeters. He measured the nitrogen content of urine and feces, and carefully estimated the quantity of the various foodstuffs in the diet he fed his subjects. He found that the heat produced by the animal equaled the heats of combustion of the fats, carbohydrates, and protein minus that of the urinary matter. He concluded, that no one particular type of foodstuff supplied all the energy. The body made use of fats, carbohydrates, and proteins with equal readiness. The nitrogen portion of the proteins was split away before it was used as a fuel, he maintained, and in this he was correct (2718).

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 (200, 201).

Martin Heidenhain (DE) coined the term telophase as it applies to cell division (1455).

Hans Driesch (DE) theorized that all cell nuclei of an organism are equipotential but vary in their activity in accordance with the differentiation of tissues (889). 

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 (2203).

Martinus Willem Beijerinck (NL) was the first to isolate a bacterium capable of reducing sulfates, Spirillum desulfuricans (Desulfovibrio desulfuricans) (254).

Shibasaburo Kitasato (JP) and Alexandre Émile Jean Yersin (CH) independently discovered the plague bacillus, later named Yersinia pestis (1761-1763, 3596, 3597).

Joseph Denys (BE) and Jules Havet (BE) found that dogs’ serum is less bactericidal than dogs’ whole blood. Working with Bacillus coli, Bacillus subtilis, and Staphylococcus they found that the leucocytes play a fundamental part, for when they are removed the plasma is 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 (819).

Angelo Ruffini (IT), using gold chloride as a stain, described encapsulated nerve endings that respond to warmth. These later became known as Ruffini corpuscles (2723-2725)

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 (309).

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 (1061-1063).

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 (3438).

Frederick George Novy (US) isolated the bacterium he called Bacillus oedematis maligni during his study of malignant edema in guinea pigs (2379). 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 (2467, 2468). 

Richard Friedrich Johannes Pfeiffer (DE) and Vasily Isayevich Isayev; Vassilii Issaevicj Issaev (last name also spelled Issaeff) (RU) began their classic researches which showed that the destruction of the cholera vibrio takes place by a kind of dissolution which they called bacteriolysis. Cholera vibrios were destroyed in vitro in the serum of animals immunized against cholera, and the same effect took place in the peritoneal cavity of the living animal. By an ingenious and simple technique they showed that in the normal peritoneal cavity vibrios multiply rapidly, whereas in the immunized animal they disappear. They removed drops of peritoneal fluid by means of capillary pipettes and found in the case of the immune animal that cholera vibrios, which had been injected, were almost instantly rendered motionless and swollen. They then changed into micrococcus like bodies which became more and more difficult to see and ultimately they disappeared from view altogether. This process of lysis occupied about 20 minutes and was apparently independent of any cellular intervention. They showed that the serum also acts in vitro but its activity is abolished by dilution or heat at 60°C. The solution or lysis of vibrios in the peritoneal cavity of an immunized animal is spoken of as Pfeiffer’s phenomenon, and is, as they showed, highly specific in that vibrios closely related to Vibrio cholerae are not destroyed by cholera serum. They also observed that cholera immunity could be passively transmitted, for when anti-cholera serum from an immunized guinea-pig was injected into the peritoneum of a normal guinea-pig cholera vibrios subsequently introduced into the latter underwent the characteristic bacteriolysis (1624, 2527, 2528).

Otto Busse (DE) and Abraham Buschke (DE) described a generalized fatal infection apparently caused by yeast. This was most likely what is today called cryptococcosis, caused by Cryptococcus neoformans (480-482).

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 (3294).

Jakob Eriksson (DE) was the first to describe physiological races of fungal rusts (1031).

Pierre-Augustin Dangeard (FR) discovered sexual reproduction in the Basidiomycetes and Ascomycetes (768-771).

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 (842-846).

Eugen Askenasy (DE) made a very similar proposal only one year later (102). The most important common feature to both sets of papers was the identification of the cell walls of parenchyma cells, whether living or dead, as the sites where surface tensions develop due to the transpiration of water. Both papers emphasized that a moist cell wall is impermeable to air, so that even at negative pressures air cannot be sucked into conducting elements.

Raymond Jacques Adrien Sabouraud (FR) made thorough mycological and clinical studies of fungi which attack the hair, in man and other animals—the so-called tineas, ringworms, favus, and so on (2759, 2760, 2762).

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 (1023).

Ramón y Cajal (ES) discovered a nerve-fiber bundle between the hypothalamus and the pituitary gland in the rat (2589).

George Oliver (GB) and Edward Albert Schäfer (GB) were the first to extract a hormone from an endocrine organ when they showed that a preparation from the adrenal medulla of sheep and calves increases blood pressure, accelerates the heart beat, and depresses kidney function. They also demonstrated that an extract of the pituitary gland raises blood pressure (2392, 2393). The words "endocrine" and "endocrinology," (from the Greek, I separate within)

Ladislaus Szymonowicz (PL) and Napoleon Cybulski (PL) independently performed experiments quite similar to those of Oliver and Schäfer in 1894 (3064).

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 (2492).

Karl Pearson (GB) developed normal correlation and regression and applied them to heredity (2493).

Karl Pearson (GB) introduced the chi-square goodness of fit test (2494).

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 (1224, 1225).

Harris Hawthorne Wilder (US) discovered that certain salamanders do not possess lungs (3481).

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 (2245).

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 (1809, 3500).

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 (3583).

Léon Charles Albert Calmette (FR) prepared horse anti-cobra anti-venom, which he used to protect chickens (485-487). He later became the first to prepare a commercial anti-venom for medical use.

Paul Gerson Unna (DE) was convinced that UV and, possibly, the violet-blue rays of sunlight were responsible for increased skin thickness, pigmentation, and skin cancer in sailors (3184).

Guido Banti (IT) described Banti’s syndrome (splenic anemia attended with cirrhosis of the liver, hypertrophy of the spleen, and ascites) (160, 161).

Pierre Paul Émile Roux (FR), Louis M. Martin (FR), and M. Auguste Chaillou (FR) treated diphtheritic children with antiserum they produced in horses (2704, 2705). No mention of serum sickness accompanies these reports.

Johannes Andreas Grib Fibiger (DK) investigated the effect of serum treatment on diphtheria. It was the first clinical trial in which random allocation was used and emphasized as a pivotal methodological principle. This pioneering improvement in methodology, combined with a large number of patients and rigorous planning, conduct, and reporting, makes this trial a milestone in the history of clinical trials (1091).

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 (2080).

Hans Held (DE) determined that the intraneuronal Nissl Granules or Bodies are composed of nucleoalbumine (nucleoprotein). This represents the first time nucleoprotein was located within the cytoplasm (1460).

Jean Louis Brachet (FR) proved that Nissl bodies contain ribonucleic acid (395).

Siegmund Exner (AT) first formulated the concept of a neural network, a concept later used in computer design (1056).

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 (810).

Edmond Delorme (FR) performed the first decortication (removal of pleura) of the lung for treatment of chronic empyema (813).

Jules Emile Péan (FR) is widely credited with having performed the first total shoulder replacement on March 11, 1893 (2489).

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 (1631).

Otto Binswanger (CH) described a new clinical and neuropathological picture that he termed "encephalitis subcorticalis chronica progressiva" (317). It is this disease that is named after him, Binswanger’s disease. It is also known as ischemic periventricular leukoencephalopathy and subcortical dementia. This dementia is characterized by damage to small penetrating blood vessels in the subcortical regions of the brain. These cerebrovascular lesions are deep in the white matter of the brain.

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

William Crawford Williamson (GB) and Dunkinfield Henry Scott (GB) sent three memoirs to the Royal Society of London, which included a description of the evolutionary links between ferns and cycads. This led to the development of phylogenetic theories of plants (3490-3493).

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

ca. 1895

Josef Albert Amann (DE) introduced his original abdominal seem, the transperitoneal method of extirpation of carcinoma of the uterus, his suggestion for limiting the risk of infections, during surgery of the uterus. Ref 


Philipp Lenard Wilhelm Conrad Röntgen (DE) observed that a new form of penetrating radiation, which he named x-rays, was produced when cathode rays (electrons) hit a metal target (2672-2674, 3060).

John William Strutt (GB) and William Ramsay (GB) collaborated to discover argon, the first of the “inert” or Noble gases (2598). 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 (1454, 1823).

Charles Frederick Cross (GB), Edward John Bevan (GB), and Clayton Beadle (GB) were the first to purify cellulose from wood (705).

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 (2854, 2855).

Gabriel Émile Bertrand (FR) isolated the enzyme laccase from latex (298). Note: This was the first isolated enzyme of the oxidation-reduction type. Up to this point all isolated enzymes had been of the hydrolytic type.

Gabriel Émile Bertrand (FR) coined the term oxidases to describe a number of plant enzymes, which catalyzed oxidation reactions. He also discovered that some oxidases were likely to require metals, which he named coferments or coenzymes, and were therefore catalytic metalloproteins (299).

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 (2438-2440).

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 (3304).

Paul Gerson Unna (DE) used the term plasma cell but it is not known precisely what type of cell he was viewing (3181).

Paul Gerson Unna (DE) defined the plasma cell as a protoplasm poor cell, which is frequently an important component of the infiltration of the skin in a number of diseases (3183).

Frank Spiller Locke (GB) recognized that calcium ions are necessary for effective neuromuscular transmission (1985).

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 (3548).

Sergei Nikolaevich Winogradsky (RU) isolated a free-living anaerobic nitrogen fixing bacterium and named it Clostridium pasteurianum (3548). Martinus Willum Beijerinck (NL) later isolated and identified it as Azotobacter chroococcum (258).

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 (325).

J.A. Notkin (DE) showed that the physiologically active principle of the thyroid gland resided in a protein substance, which he called thyreoproteid (2378).

Adolf Magnus-Levy (DE) was the first to apply respiratory quotient studies to people with disease. He discovered that people with a hyperthyroid condition exhibited an elevation in metabolic rate, whereas those with myxedema and underfunctioning thyroids exhibited a lowered metabolic rate. This represents the origin of the use of metabolic rates in medical diagnosis (2069). 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 Murray, 1891

Waldemar Mordecai Wolff Haffkine (RU-CH-FR) developed a vaccine for cholera by giving a subcutaneous injection of culture—attenuated by growth at an elevated temperature—followed five days later by a subcutaneous injection of virulent culture (1359).

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 (1767).

William Ernest Castle (US) proved that in Ciona intestinalis, an 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 (541).

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

Inoculations of July 16, 1896

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

(Plant 355) This plant was 18 inches and very thrifty. The inoculation was made on the sixth leaf 9 inches away from the stem. The pricked leaf-blade was 5 inches broad. Up to the morning of July 21, there was no trace of disease but at 3 PM of the same day about 0.5 sq. cm. on one side of the pricks was wilted…. By noon of the seventh day, the wilt covered about 10 sq. cm., and reached 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 every one, but they occur in 61 of them; no fungi are present, neither are there any insect-injuries. In most cases the bacteria are confined strictly to the spiral vessels of the petioles, and they do not occur in all of these, nor in all of the bundles. They are not present in the phloem, the cortical parenchyma or the tissues between the bundles. Summarized, the amount of bacterial infection in the basal part of the petioles is as follows: (1) In a few petioles nearly every bundle is occupied and bacteria occur in many vessels…(2) in 5 no bacteria detected; (3) in by far the greatest number the bacteria are confined to a few vessels of a few bundles….

After a description of the Morbid Anatomy, Smith proceeded to The Parasite, Bacillus tracheiphilus. His summary reveals the thorough nature of his investigation:

Résumé of Salient Characters


A bacillus in the vascular bundles of cucurbits causing a wilt-disease; short rods (single, paired, in fours end to end, or in small clumps); motile, peritrichate; capsules; pseudozoogloeae; involution-forms; stains readily; smooth; white; viscid; glistening; slow grower on media; surface colonies small, round discrete; no growth at 37°C. or at 6°C. (16 days); aerobic; facultative anaerobic (with grape-sugar or fruit-sugar); from these sugars a non-volatile acid, soluble in ether; grows only in open end of F-tube with dextrine or glycerine, acid from glycerine; slime on steamed potato (Solanum tuberosum) is same color as the normal substratum; usually it grays potato after a time; clouds peptone-bouillon and Dunham’s solution thinly; growth retarded in acid juice of cucumber fruits; also retarded or inhibited by juice of many other vegetables, e.g., table beet, sugar-beet, turnip. etc.; grows on many media at 25°C., carrot (Daucus carotus), coconut (Cocos nucifera), Fermi, Uschinsky, etc.; asparagin as carbon food (?); thermal death point 53°C.; optimum for growth 25°C. to 30°C.; maximum, 34°C. to 35°C. (?); minimum (?) 8°C.or below; easily killed by dry air, sunlight, or freezing (50 per cent or more); ammonia production (moderate; feeble production of hydrogen sulfide; in litmus-milk persistent growth without reduction or distinct change in color of litmus; short-lived on many media; killed readily by acids, but lives long in cane-sugar-bouillon with carbonate of lime; grows on some media in hydrogen and carbon dioxide; dissolves middle lamella (cucumber-parenchyma); distributed by insects, especially by Diabrotica vittata.

Mealy or dendritic surface growths; negative grams stain; endospores; chains; filaments; growth not yellowish, piled up or wrinkled; pellicle on bouillon; liquefaction (gelatin, blood serum, egg-albumin, etc.); lactose and pure maltose in closed end fermentation-tube lab ferment; acid (in milk); gas (all media); pigment (except gray stain on potato); indol (?); nitrite from nitrates; starch-splitting; cellulose-dissolving (except possibly in host); asparagin as nitrogen food; ammonium salts as nitrogen food; steamed turnip, and cauliflower; Cohn’s solution; acid bouillon (+33); acid gelatin; nearly odorless; not a soft rot; not infectious to tomato, potato (Solanum tuberosum), etc. On steamed potato liable to be confounded with a non-infectious coccus (follower) which reddens litmus milk.

Any organism which reddens or blues litmus-milk decidedly, reduces the litmus, throws down the casein, or clears litmus-free milk without precipitation may be set down at once as something else.

It was during his study of the wilt of cucurbits that Smith established the methods for the critical and faultless study of bacterial plant diseases. He investigated a number of other diseases of this type, such as the brown rot of Solanaceae, the black rot of cucifers, the yellow disease of hyacinths, bean blight, mulberry blight, the black spot and canker of peach and plum, the angular leaf spot of cotton, the angular leaf spot of cucumber, the bacterial canker of tomato, the olive tubercle, and others (2930). 

Louis Hermann Pammel (US) discovered and described the microorganism causing black rot of cabbage. He named it Bacillus campestris, later changed to Xanthomonas campestris (2454).

K. Takata (JP) presented evidence that insects can be vectors of plant virus disease—dwarf disease of rice (Oryza sativa) (3068).

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 (41).

Alexander Marmorek (AT-FR) discovered that fluid cultures of streptococci lyse erythrocytes (2103).

J. Jackson Lister (GB) established the alternation of asexual and sexual generations in a recognized species of protozoa, Polystomella crispa a foraminiferan (1977).

David Bruce (GB) and Mary Elizabeth Steele Bruce (GB) while investigating an outbreak of nagana, a disease similar to surra, in cattle in Zululand, were looking for a bacterial cause and found trypanosomes in the blood of diseased cattle; they demonstrated experimentally that these caused nagana in cattle and horses and also infected dogs. They also observed that infected cattle had spent some time in the fly-infested "tsetse belt" and that the disease was similar to that in humans called negro lethargy and fly disease of hunters (451-454). 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 (2321).

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 (928, 929, 1150).

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 (537).

Frederick George Novy (US) and Ward J. MacNeal (US) successfully established in vitro cultures of Trypanosoma brucei (2383).

Friedrich K. Kleine (DE) demonstrated the essential role of the tsetse fly (Glossina palpalis) in the life cycle of trypanosomes (1772).

John William Watson Stephens (GB) and Harold Benjamin Fantham (GB) described Trypanosoma brucei rhodesiense, the cause of Rhodesian or acute sleeping sickness (2995).

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 (2689).

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) (1643, 2490). 

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 (718, 3223, 3224).

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 (3081). 

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 (355-357).

Wilhelm His (CH) was the first to accurately describe the hypothalamus, which he named (1537).

Jean-Martin Charcot (FR) and Jean Albert Pitres (FR) conclusively proved the existence of cortical motor centers in man (572).

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 (740).

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 (732).

Jules Emile Péan (FR) is believed to have performed the first surgery to correct diverticula of the bladder (2489). 

Josef Breuer (DE) and Sigmund Freud (CZ-AT) discovered the subconscious mind and introduced psychoanalysis using hypnosis and free-association (413, 414). 

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 (1680).

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" (3376).

Ismar Isidor Boas (DE) founded Archiv für Verdauungs-Krankheiten, the first journal devoted to the subject of gastroenterology.


“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 (150).

“Chemistry has taken possession of medicine, and will not let go." Pierre Émile Duclaux (903).

Antoine Henri Becquerel (FR) discovered radioactivity. He planned to place a silver coin between uranium salts and a photographic plate wrapped in thick black paper, exposing the entire package to the sun. To his amazement, he discovered the coin’s shadow on the plate despite the fact that it had not been exposed to light. He concluded that this new radiation was an atomic property of uranium (245-247). During his studies of uranium salts found in pitchblende he concluded that it was more radioactive than could be accounted for by its uranium content and therefore might contain another more powerfully radioactive substance. He encouraged Pierre and Marie Curie to look into the matter.

Wilhelm Friedrich Ostwald (DE) made the first electrometric measurement of hydrogen ion concentration by the potential on a platinum electrode in solutions saturated with hydrogen gas (2424). 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 (693).

Fritz Habër (DE) and Zygamunt Klemensiewicz (PO-GB-PO), in 1909, constructed and studied glass H+ electrodes (1354).

Karl Albert Hasselbalch (DK) and Christen Lundsgaard (DK) produced a modified Ostwald platinum electrode with which they measured blood pH at body temperature (1436).

Heinrich Dannneel () discovered the reaction of oxygen with a negatively charged metal (cathode), the basis of oxygen polarography, later developed by Jaroslav Heyrovsky (CZ) (1520).

Phyllis Tookey Kerridge (GB) constructed the first blood glass pH electrode (1742).

Poul Bjørndahl Astrup (DK) designed an apparatus with which it was possible to determine the acid-base imbalance in a patient (109).

Richard W. Stow (US), Richard F. Baer (US), and Barbara F. Randall (US) conceived of an electrode for measuring PCO2 (3035).

Leland C. Clark, Jr. (US) developed and perfected a PO2 electrode (591).

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 (2879).

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 (2108).

Scipione Riva-Rocci (IT) introduced the mercury sphygmomanometer in its modern form (for determining arterial blood pressure) (272, 2558, 2657, 2727).

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 (2319).

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 conststuent, 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, on the whole, 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) (3511).

Sakugaro Hirase (JP) and Seiichiro Ikeno (JP) were the first to prove the existence of motile spermatozoids in gymnosperms (1530, 1531, 1613, 1614).

Herbert John Webber (US) reported that one of the higher plants, Zamia, produces swimming sperm (3391-3396). 

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 (2977).

John Richard Pappenheimer (US) and Armando Soto-Rivera (VE) confirmed Starling’s findings (2463).

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 (2462). 

Theobald Smith (US) published papers on differences in virulence in tubercle bacilli from several sources. The tubercle bacilli which he isolated from the udder or other affected organs of tuberculous cattle and cultivated on artificial media were definitely more pathogenic for rabbits, as well as for cattle, than were organisms isolated from human sputum or affected human lungs at postmortem. Later, the designation human and bovine as applied to different strains of the tuberculosis bacillus became widely accepted (2934, 2935).

Johann Petruschky (DE) appears to be one of the first to have isolated Alcaligenes faecalis (Bacterium faecalis alcaligenes) (2519). He originated litmus milk as a bacterial culture medium. Ref

Emile M. P. van Ermengem (BE) isolated and named Clostridium botulinum, the etiological agent of botulism (L.botulus, sausage). He called it Bacillus botulinas. The source was pickled ham, which had made a large number of people ill (3191, 3192).

P. Tessmer Snipe (US) and Hermann Sommer (US) purified botulinus toxin (2946). 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 (474).

Alan B. Scott (US) and Edward J. Schantz (US) were the first to work on a standardized botulinum toxin preparation for therapeutic purposes (887, 2885).

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) (2785, 2858, 2859).

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 (118, 2242). 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 (15).

Benjamin Minge Duggar (US) described toxic septicemia of the squash bug, Anasa tristis DeG., and assigned the bacterium Bacillus entomotoxicon as the etiological agent (910). It was later decided that the agent is Bacterium entomotoxicon.

Henry Koplik (US) found that red skin spots with a minute bluish-white center (Koplik spots) are absolutely diagnostic of measles (rubeola) (1817).

Robert Almer Harper (US) discovered the ascospore and sexual reproduction in the Ascomycetes (1414).

Rudolf Albert von Kölliker (CH) gave the name axon to the axis cylinder of the nerve cell (3298). 

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 (3093). 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” (3094).

Josef Jadassohn (DE) introduced the concept of the Patch Test to dermatology and immunology (1645).

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 (1326, 1543).

Thor Stenbeck (SE), in 1899, initiated the treatment of a 49-year-old woman's basal-cell carcinoma of the skin of the nose, delivering over 100 treatments in the course of 9 months. The patient was living and well 30 years later (2993). At the same time, Tage Anton Ultimus Sjörgen (SE) and Edvard Sederholm (SE) cured a squamous cell epithelioma with fifty treatments over 30 months (2924).

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 (3486).

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 (772).

Robert Abbe (US) used radium as a surgical adjuvant in treating cancer (6).

Pierre Curie (FR), Charles Bouchard (FR), and Victor Balthazard (FR) studied the effect of radium on animals and discovered that it could destroy diseased cells. It cured tumors and certain kinds of cancer (721). 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 (1793).

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 (2566).

Vaughn Pendred (GB) was the first to draw attention to the association of goiter with deaf-mutism (2498).

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 (46).

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 (3227-3229)

Henri-Jules-Marie Rendu (FR) gave a clinical description of hereditary hemorrhagic telangiectasia (2613).

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 (2095).

William Pringle Morgan (GB) was the first to publish a report describing a congenital word-blind (dyslexia) patient (2260).

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 (2599). 

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 (1845).

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 (123). 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 (124, 125, 129, 131).

George Thomas Beatson (GB) found that inoperable breast tumors regressed following surgical removal of the ovaries (oophorectomy) and ingestion of thyroid tablets (243). This represents the first suggestion of a linkage between breast cancer and hormones (or hormone-secreting tissue).

Ludwig Wilhelm Carl Rehn (DE) was possibly the first surgeon to successfully suture the heart. This occurred following a knife stab wound in the right ventricle. Quoting Rehn, “I decided to suture the heart wound. I used a small intestinal needle and silk suture. The suture was tied in diastole. Bleeding diminished remarkably with the third suture, all bleeding was controlled. The pulse improved. The pleural cavity was irrigated. Pleura and pericardium were drained with iodoform gauze. The incision was approximated, heart rate and respiratory rate decreased and pulse improved post-operatively.” The patient made a complete recovery (1678, 2606, 2607). Some consider this the origin of cardiac surgery.

Journal of Experimental Medicine was founded.

American Journal of Physiology was founded.

The Paul-Ehrlich-Institut was founded as Institut für Serumforschung und Serumprüfung (Institute for Serum Research and Serum Testing) at Steglitz near Berlin as a test and research institution.


“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 (1158).

"Hypotheses come and go, but data remain" Santiago Ramón y Cajal (2592).

"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" (2592).

Joseph John Thomson (GB) announced the existence of negatively charged particles smaller than an atom (3107, 3108). They were then called cathode rays but were later named electrons by George Johnstone Stoney (GB), in 1891 (3028).

Karl Ferdinand Braun (DE) invented the oscilloscope (408).

David T. Day (US) described the separation of petroleum fractions upon percolation through an adsorbent, a form of column chromatography (785).

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 (822).

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 (461, 462). Note: the yeast extract was produced for use in animal experiments, but underwent change so rapidly that sugar was added as a preservative. The action of the extract upon this added sucrose drew Buchner’s attention to the fact that fermentation was proceeding in the absence of yeast cells.

This work is seminal: first, because it discounted long held and popular vitalistic theories that consider cellular processes as fundamentally different from other principles of chemistry; secondly, it introduced a methodology that would allow scientists to break down biochemical processes into their individual steps; and, finally, the discovery of cell-free fermentation opened the doors to one of the most important concepts in biochemistry- the enzymatic theory of metabolism.

In 1897, oil of citronella (plant genus Cymbopogon) was first used as an insect repellent (2879). 

Herbert Spencer Jennings (US) and J.H. Crosby (US) began their pioneering studies on reactions to stimuli in unicellular organisms. This led to such concepts as the trial-and-error behavior and many important concepts concerning various forms of tropisms and taxes (1662-1668).

Filippo Bottazzi (IT) and Léon Frédéricq (BE) found that most marine invertebrates are isotonic with the ocean (370, 371, 1180). 

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 (7-9).

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 (1849). It is known as Kulchitsky’s cell.

B. Moore (GB), D.P. Rockwood (GB), Heinrich Otto Wieland (DE), and Hermann Sorge (DE) proposed that bile acids somehow form polymolecular complexes with fatty acids (2235, 3477).

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 (1863). 

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 (365). 

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 (1548).

Alan F. Hofmann (US) and Bengt Borgström (SE)) isolated the micellar phase from small intestinal content during fat digestion (1549).

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) (221, 1592, 1969, 2011, 2578, 2832, 2833). 

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 (2479-2481).

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 (3595).

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 (1841).

George Neil Stewart (US) reported on the blood circulation time course and on the influences, which affect it (3009).

Eugen Rehfisch (DE) established the paradigm that micturition is initiated and sustained by active primary relaxation of the sphincter (2604).

Walter Migula (DE) introduced the order Thiobacteria for those microbes, which Winogradsky had called sulfur bacteria (2204).

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 (1931).

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 (2559, 2772). 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) (2915).

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 (644, 3512).

Adolf Wallenberg (DE), Cornelius Ubbo Ariëns-Kappers (NL), and Willem Frederik Theunissen (NL) related the olfactory system to recognition and taste for food (86, 87, 3356).

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 (359, 1833).

Jacques Oudin (FR) modified this procedure by adding a small amount of agar to the anti-serum forming a gel in a tube. When this was over-layed with antigen a series of rings appeared in the gel corresponding to the number of specific antigens and antibodies in the materials (2435).

Örjan Ouchterlony (SE) adapted the analysis of precipitin reactions to gel plates. This greatly increased the precision of the analysis (2432-2434).

Masanori Ogata (JP) injected crushed fleas from rats dead of plague into two mice, one of which died after three days. On the basis of this meager evidence he correctly suggested that suctorial insects such as mosquitoes and fleas transmit plague (2388).

Alexandre Émile Jean Yersin (CH) developed an antiserum to protect against the bubonic plague bacillus (3598).

Alessandro Lustig (IT) and Gino Galeotti (IT) were the first to isolate a toxin from Yersinia pestis (2028).

Paul-Louis Simond (FR) found organisms morphologically indistinguishable from plague bacilli in the stomach of fleas, which had fed upon rats and mice dying of plague. He succeeded in infecting a mouse by injecting an extract of crushed fleas taken from a plague rat. Simond found that in the absence of fleas the plague was not transmitted from sick or dead rats to healthy rats in close proximity, but in at least two incidents he observed transmission when fleas were present. He concluded incorrectly that contaminated flea feces was being introduced at the site of fleabites (2916). This and Ogata’s work above represents the discovery that fleas vector the plague.

Heinrich Hermann Robert Koch (DE) demonstrated that the bubonic plague is transmitted by means of a body louse that infests rats. Ref

Robert H. Pollitzer () concluded, “Pulex irritans plays the main role in the spread of human plague" (2552). 

Paul Ehrlich (DE) discovered that antibodies act by combining with the substances, which incited their production and observed that the plant poison ricin caused mouse erythrocytes to agglutinate and that he could prevent this agglutination in vitro and in vivo with anti-ricin serum provided that the ratio of ricin to anti-ricin was proper. He discovered that if non-immune mice were given anti-ricin serum it could protect them from the effects of ricin. Finding that there is a direct union of ricin and anti-ricin in vitro, Ehrlich concluded that it was necessarily a chemical process. 

He discovered that the union of antitoxin and toxin is accelerated by mild heat and retarded by cold. He also demonstrated that the reaction took place more quickly in concentrated than in dilute solutions.

In trying to determine what proportions of antitoxin and toxin produced the optimum reaction Ehrlich discovered that toxins are unstable and have a tendency to deteriorate into less potent versions he called toxoids. Although these toxins slowly lose their toxicity he found that their ability to stimulate an immune response remained relatively constant over time. Based on these observations he theorized that a toxin consists of two portions, one of which, the haptophore, brings about the union with the antitoxin, whereas the other—the toxophore—is, as its name implies, the carrier of the toxic action. He studied a number of different samples of diphtheria toxin and from them laid down the principles for the accurate standardization of antitoxic sera.

Ehrlich improved Behring's diphteria antitoxin and established an international standard for this and other antitoxins. The first exposition of his side-chain theory of immunity also appeared in the 1897b paper (961-963).

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 (3578).

Almroth Edward Wright (GB) and Frederick Smith (GB) devised an Agglutination Test for the diagnosis of undulant fever (3579).

Ronald Ross (GB) while a medical officer in India uncovered the remarkable relationship existing between man, the Anopheles mosquito, and the malarial parasite. He then shifted his attention to bird malaria and was the first to demonstrate the mosquito cycle in bird malaria. Ross worked out the relationship between bird, malarial parasite, and mosquito (Culex). He proved transmission of Plasmodium by mosquitoes using Plasmodium relictum in sparrows (2683-2688). Note: in 1898 Ronald Ross (GB) convinced Patrick Manson (GB) that mosquitoes could possibly transmit malaria. To test this theory Manson actually allowed Anopheles mosquitoes which had fed on a tertian malaria patient to bite his own son and his son came down with malaria! He then went with some friends to the Roman Compagna near Ostia, which was notorious for malaria, and lived in a mosquito-proof hut from July to October; he and his friends remained in perfect health. These experiments established clearly that mosquitoes carry malaria.

William George MacCallum (US) and Eugene Lindsay Opie (US) discovered that the plasmodium of malaria goes through a sexual cycle in the blood of its victim (2038, 2039, 2399). Its asexual behavior was already known. 

Giovanni Battista Grassi (IT), Amico Bignami (IT), and Giuseppe Bastianelli (IT) were able to report their demonstration of the development of human plasmodium malarial parasites on the gut wall of Anopheles claviger (198, 312, 1301-1303).

Giovanni Battista Grassi (IT) and Amico Bignami (IT) showed that the plasmodium undergoes its sexual phase only in the Anopheles mosquito (1304). 

These works led to the preventative measure of protecting people from mosquitoes.

Alexandre Joseph Emilé Brumpt (FR) reported the existence of Plasmodium gallinaceum (458). 

Étienne Sergent (FR) and Edmond Sergent (FR) used attenuated sporozoites of Plasmodium relictum to successfully immunize canaries against mosquito-borne malaria (2877).

Sydney P. James (GB) and Parr Tate (IE) discovered extra-erythrocytic stages of malaria with an avian plasmodium (1650).

Charles R. Anderson (US) achieved in vitro culture of the blood stages of avian Plasmodium (65).

Alon Warburg (IL) and Louis H. Miller (US) achieved the first in vitro culture of the mosquito stage of any malaria parasite, using Plasmodium gallinaceum (3358).

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 (3584).

Waldemar Mordecai Wolff Haffkine (RU-CH-FR) used killed plague microorganisms as a vaccine against the plague (1360).

George Frederick Still (GB) identified the three categories of juvenile chronic arthritis. The systemic form is now often referred to as Still's Disease (3012).

Wilhelm Theodor Engelmann (DE) was the first to distinguish the four types of activity of the heart nerves: inotropic, bathmotropic, chronotropic, and dromotropic (1025).

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 (3315, 3316).

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 (1526). 

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” (1819).

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 (2015). 

Edward Flatau (PL) reported that the greater the length of the fibers in the spinal cord the closer they are situated to the periphery (1119).

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” (2287). This is one of the earliest examples of vascular surgery.

Cesar Roux (CH) attached the small intestine to the stapled off upper third of the stomach and joined it in a Y formation to the now quiescent exit from the lower two thirds of the stomach (2703). This is called a Roux-en-Y operation in his honor.

Carl B. Schlatter (CH), in 1897, performed the first successful complete gastrectomy (2827).

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.


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 (722, 723). Marie also presented this discovery in her doctoral thesis (720).

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 (704, 3214).

Joseph H. Kastle (US) and Arthur S. Loevenhart (US) demonstrated the reversibility of enzymes using lipase (1717).

Arthur Croft-Hill (GB) announced the first enzymatic synthesis, that of isomaltose (704). 

Frank George Edmed (GB) determined the structure of oleic acid (948).

Carl Benda (DE) coined the name fädenkörner or mitochondrien (from the Greek meaning thread granule) to identify rod-like structures found in cytological preparations by Richard Altmann (DE). Altmann had called them bioblasts and regarded them as microorganisms; Benda recognized them as cell organs (53, 275). Today we call them mitochondria (sing. mitochondrium). Benda developed a staining technique using crystal violet and alizarin, which was especially good at demonstrating mitochondria (276).

Leonor Michaelis (DE-US) discovered that mitochondria could be stained selectively and supravitally with a dilute solution of Janus green, the method of choice until 1952 (2198).

Margaret Reed Lewis (US) and Warren Harmon Lewis (US) described and pondered the location of mitochondria within cells (Lewis and Lewis 1915).

Frantisek Vejdovsky (CZ) and Alois Mrazek (CZ) are credited with the discovery of the centrosome in animal cells. They called it the periplast (3218).

Thomas Harrison Montgomery Jr. (US) performed comparative cytological studies, with especial regard to the morphology of the nucleolus (2233).

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 (3126). Renin would later be found to promote the release of angiotensin, a powerful pressor agent.

Edward Lee Thorndike (US) described his puzzle box and began work, which led to his proposed psychological law of effect. In full it reads: "Of several responses made to the same situation those which are accompanied or closely followed by satisfaction to the animal will, other things being equal, be more firmly connected with the situation, so that, when it recurs, they will be more likely to recur; those which are accompanied or closely followed by discomfort to the animal will, other things being equal, have their connections to the situation weakened, so that, when it recurs, they will be less likely to occur. The greater the satisfaction or discomfort, the greater the strengthening or weakening of the bond." His works include Psychology of Learning and The Measurement of Intelligence (3111-3116, 3572).

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 (2769).

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 (1569-1571).

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 (1853).

Teijiro Yabuta (JP) and Yusuke Sumiki (JP) isolated the bakanae factor, crystallized it, and named it gibberellin (3590, 3591).

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) (2369). 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 (835).

Monroe D. Eaton (US), Gordon Meikeljohn (US), and William Van Herick (US) isolated and cultivated the causative agent of atypical pneumonia in man (934).

Maurice C. Shepard (US) discovered the so-called T strains (tiny colonies 15 to 20µ) which appeared to produce nongonococcal urethritis in man (2890).

Robert Merritt Chanock (US), Leonard Hayflick (US), and Michael F. Barile (US) were the first to cultivate Mycoplasma pneumoniae on an artificial medium (568).

Robert Merritt Chanock (US) named the agent Mycoplasma pneumoniae (567). 

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 (2899-2901).

Walther Kruse (DE) found the dysentery bacillus during an epidemic of dysentery in the Ruhr area (1846). This bacterium is often referred to as the (Shiga-Kruse bacillus).

Adrien Veillon (FR) and A. Zuber (FR) found Bacteroides fragilis in 22 cases of appendicitis (3216). 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 (2811). 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 (786-789).

Sporothrix schenckii was renamed Sporotrichum beurmanni.

Michael Siedlecki (PL-DE) published the first complete life cycle of a gregarine (Adelea ovata living in Lithobius forticatus) (2914).

Justin Jolly (FR) made a detailed in vitro study of the behavior of different kinds of leucocytes and ultimately succeeded in keeping the leucocytes of the newt (Triton) alive for one month (1681-1684).

Carl August Ljunggren (SE) demonstrated that human skin could still be successfully grafted after being stored for weeks in ascitic fluid (1982).

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 (358, 977, 978).

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 (2530).

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 (507).

Montoya (CO) and J.B. Flores (CO) were the first to definitely report tinea nigra as a disease state. They called it Caraté noir (2234). 

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 (555).

Paulo Parreiras Horta (BR) named the fungal agent Cladosporium wernickii (1577).

John McFadyean (GB) and Frederick Hobday (GB), in dogs, reported the first cell-free transmission of papillomas (2145).

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 (2520).

Paul Frosch (DE) confirmed the suggestion of Petruschky (1196, 1197).

Karl Wilhelm von Drigalski (DE) found that apparently healthy individuals might pass typhoid bacilli in their feces, i.e., healthy carriers (3253).

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 (2408). 

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 (2309).

Patrick Manson (GB) established tropical medicine as a specialty and founded a school of tropical medicine in London. He was among the first to suggest that mosquitoes might be the agents for spreading malaria (2081, 2082).

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 (162, 163, 165).

Francis Galton (GB) presented his ancestoral law of heredity (1212). Ronald Aylmer Fisher (GB) later found this law to be the natural consequence of Mendelian inheritance for polygenic traits. See, Fisher, 1918.

Charles Scott Sherrington (GB) described decerebrate (removal of the cerebrum) rigidity in the cat (2893).

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 (2892).

Henry Head (GB) and Alfred Walter Campbell (GB) showed herpes zoster to be a hemorrhagic inflammation of the posterior nerve roots and the homologous spinal ganglia. They made a map of human dermatomes. Patients with herpes zoster provided valuable information to the development of this map (1447, 1449).

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 (1138).  

William Henry Howell (US) showed that the pituitary’s blood pressure lowering activity resides in the posterior lobe (1581).

John Newport Langley (GB) and William I. Dickinson (GB) coined the phrase autonomic nervous system, and the term parasympathetic (1897). 

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 (3424, 3425).

John Hay (GB) discovered the form of second-degree AV block currently known as type 2 block or Mobitz type 2 auriculoventricular block (1441).

Woldemar Mobitz (DE) provided electrocardiographic proof of Hay’s discovery (2223).

Georges Hayem (FR) gave the first adequate description of acquired hemolytic jaundice (Hayem-Widal’s disease) (1443).

John Benjamin Murphy (US) announced his technique of treating tubercular lungs by intentional pneumothorax (2288, 2289).

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 (2227).

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 (1748).

Leonardo Gigli (IT) developed a safe method for temporary cranial resection using a grooved probe and a wire saw (1245).

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) (917).

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 (2880). 

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 (891, 892).

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.


“The good physician treats the disease; the great physician treats the patient who has the disease.” William Osler. ca. 1899-1905 (2555).

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 (3453).

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 (2461, 3182)

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 considered to be the origin of the analysis of the regulation of protein synthesis (904). 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 (630).

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 (834).

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 (1716).

Marjory Stephenson (GB) and John Yudkin (GB) demonstrated the adaptation of bacteria to different biochemical environments (2996, 3606, 3607).

Jacques Lucien Monod (FR) observed that when Bacillus subtilis or Escherichia coli are grown on a mixture of two particular sugars, growth occurs in two distinct phases separated by a lag time. During the first phase only one of the two sugars is metabolized, and the second begins to be degraded only when the first sugar has totally disappeared. Glucose was found to be in the first category and lactose in the second (2228, 2229).

Jacques Lucien Monod (FR) christened this phenomenon diauxie, in bacteria. Diauxie is from a Greek root meaning double growth (2230, 2231).

Jacques Lucien Monod (FR) would relate enzymatic adaption to genetics and cellular differentiation (2232).

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 (3299).

Noël Bernard (FR) established that orchid seed germination requires a mycorrhizal relationship (292, 293).

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 (943-945).

Theobald Smith (US) determined the thermal death time of Mycobacterium tuberculosis in milk to be 15 minutes at 60°C (2936).

Maurice Nicolle (FR) and Adil-Bey/Adil Mustafa () discovered that the etiological agent of rinderpest or cattle plague is a virus (2354-2356).

Richard Edwin Shope (US) developed a vaccine to rinderpest, which was grown and attenuated in hen’s eggs (2905).

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 (2154). 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 Sydney Rowland (GB) were the first to test the effect of extremely low temperatures on the viability of bacteria (2047).

Harvey Williams Cushing (US) reports that a vaginal gonococcus infection can ultimately lead to acute diffuse peritonitis (729).

Hugh Hampton Young (US) performed nearly all 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 (660, 661, 667, 3003).

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 (707). Note: obviously he did not choose organisms like some reptiles where the incubation temperature influences sex.

Lucien Claude Jules Cuénot (FR) proposed that armadillos from the same litter are true twins born of polyembryony (707).

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 (2012).

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 (359).

Stabsarzt Slawyk (DE) isolated and cultured the influenza bacillus (Haemophilus influenzae) from the blood and spinal (lumbar puncture) fluid of a child with meningitis (2925).

Martha Wollstein (US) demonstrated the transmissibility of Haemophilus influenzae infection and the capacity of this organism to cause purulent meningitis (3569). She drew attention to the marked tendency for Haemophilus 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 Haemophilus influenzae type b meningitis (1159).

Max Freudweiler (CH) made the connection that uric acid crystals cause gout (1184).

Wilhelm His, Jr. (CH) and Max Freudweiler (CH) clearly showed that urate crystals cause inflammation (1185, 1540).

Wilhelm Ebstein (DE) found that localized death of tissue (necrosis) is a primary event in gout (938).

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 (343).

George Washington Crile (US) documented the results of his extensive experimental studies on shock and hypertension (697, 699).

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 (702).

Max Wilms (DE) described a case of nephroblastoma—Wilms tumor. He performed a successful nephrectomy but the cancer returned and the patient died (3507).

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 (2565).

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 (679-681).

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" (3077). 

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 (5, 2910). See, Audubon, 1810.

Robert Kirk (GB) produced sensitization to Primrose (Primula obconica) tissue by applying the plant repeatedly to irritated skin under occlusive dressings (1757).

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 (336, 337).

N.S.Wedroff (RU) experimentally sensitized humans to 2:4 dinitrochlorobenzene (DNCB) through the skin (3400). 

Rudolf L. Mayer (DE) sensitized humans and guinea pigs to p-phenylenediamine using salve (2125).

Marin-Théodore Tuffier (FR) developed an extradural (epidural) anesthetic technique (3157).

Jean Athanse Sicard (FR) described injecting dilute solutions of cocaine through the sacral hiatus to treat patients suffering from severe intractable sciatic pain or lumbago (2911).

Fernand Cathlin (FR) gave sacral injections of cocaine (549, 550).

Fidel Pagés (ES) described a lumbar approach to epidural anesthesia (2445). 

Eugene Aburel (RO) injected chinocaine through a silk ureteral catheter to block the lumboaortic plexus of laboring women (13).

Archile Mario Dogliotti (IT) performed abdominal surgery with single-shot lumbar epidural anesthesia (855).

Alexandr Petrovich Karpinsky (RU) recorded his classic work on Paleozoic fossil sharks of the family Edestidae (1713, 1715).

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 (3347).

Károly Gorjanović-Kramberger (HR), between 1899 and 1905, discovered Homo sapiens neanderthalensis (Homo neanderthalensis) fossil remains at a site near the Krapinica River at Krapina, Croatia. The find consisted of 13 men, women and children. The remains are dated to ca. 125,000 B.P (1290-1293).

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 (646, 1884).

The First International Congress of Genetics was held in London.   

ca. 1900

“Do not confuse biology and religion—one is a science to be proved or disproved, the other is a life to be lived,” Quinton Hogg (1555).

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.


“That we are in the presence of a new principle of the highest importance is, I think, manifest. To what further conclusions it may lead us cannot be foretold.” William Bateson commenting on the work of Johann Gregor Mendel (202).

“The general problems of embryology, heredity, and evolution are indissolubly bound up with those of cell structure.” Edmund Beecher Wilson (3513).

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 (2543).

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 (1826).

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 (1106, 3501).

Auguste Fernbach (FR) and Louis Hubert (FR) invented phosphate buffers for the purpose of controlling the acidity of a protease from malt and introduced the term tampon. Sørensen later called these solutions puffer; they became buffer in English (1082).

Erich Tschermak (AT), unaware of Johann Gregor Mendel’s (Moravian-CZ) earlier work, independently discovered the laws of genetics (3151).

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 (798).

Hugo Marie de Vries (NL) introduced the concept of segregation to genetics. He referred to it as spaltung (splitting) (799).

Carl Franz Joseph Erich Correns (DE) associated the segregation of alleles with the reduction division in meiosis (661).

Ernst Moro (DE) isolated Lactobacillus acidophilus from the feces of infants. It is a natural inhabitant of the infantile intestine and important in making certain sour milk products (2262). 

Henry Tissier (FR) isolated Bacillus bifidus communis (Lactobacillus bifidus) (Bifidobacterium) from the feces of breast-fed infants (3131).

Henry Tissier (FR) advocated intentional consumption of Bifidobacterium to improve one’s health (3132). 

Hugo Schottmüller (DE) used the specificity of bacterial agglutination reactions to separate the paratyphoid fevers (2845).

Simon Flexner (US) while working in the Philppines isolated a new and different species of dysentery bacillus now called Shigella flexnerii (1134).

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 (916).

Charles Franklin Craig (US) was probably the first to recognize a fourth type of human malaria; that caused by Plasmodium ovale. He described a malaria parasite which he found in the blood of American soldiers, returned from the Philippines, and noted especially its tertian fever pattern plus certain peculiar morphological characteristics not found in P. vivax (684-686).

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 (607). 

A. Mayer (FR) found that serum osmolality is increased during thirst (2121).

Erich Leschke (DE) found that intravenous injections of hypertonic saline cause thirst in man (1934).

Avery Veryl Wolf (US) was the first to suggest that osmosensitive centers for thirst are located in the brain (3561).

Peter Arundel Jewell (GB) and Ernest Basil Verney (GB) localized the osmoreceptor to the anterior hypothalamus (1673).

Paul Ehrlich (DE) presented his general theory of immunity, which, under the name of the side-chain or receptor theory, had for many years an enormous vogue. In this theory he visualized mammalian cells as possessing various specific receptors for all sorts of foreign chemical groups. When exposed to a foreign substance, the substance and its specific receptor would combine and thus stimulate the cell to produce more of these receptors some of which would spill into the blood. The combination of the receptor with the foreign substance would have a tendency to neutralize any harmful effect the foreign substance might have. In the absence of the foreign substance the blood level of receptors would slowly drop (964).

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” (979). 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" (980).

Karl Landsteiner (AT-US) discovered that there are two types of erythrocyte agglutinins in human sera (alpha and beta) as well as two kinds of erythrocyte agglutinogens (A and B) on the cells. Cells were characterized as either A, B, or C. C was later changed to O (1878, 1879).

Alfred von Decastello (US) and Adriano Sturli (US) discovered that some erythrocytes possess both A and B agglutinogens, type AB (3250). The A,B,O blood types were the first known human polymorphism.

Georges Fernand Isidore Widal (FR), M. Paul Ravaut (FR) and Arthur Sicard (FR) introduced cytodiagnosis, the examination of the cellular elements suspended in the fluid of any serous cavity, as a tool to diagnose disease (3457, 3460). 

John M’Fadyean (GB) examined the etiological agent of African horse-sickness and found it to be filterable (2033).

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 (1286).

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 (741).

Rudolph Matas (US) was the first to use positive pressure in thoracic surgery and introduced endotracheal anesthesia much as it is used today (2114).

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 (3435-3437). See, Wilhelm Alexander Freund, 1878.

Henry Charlton Bastian (GB) believed the muscles provided a considerable amount of sensory information and that this information was used by the brain to coordinate motor acts (196). He later introduced the phrase kinaesthetic sense to describe this relationship (197). This gave way to Sherrington’s new term proprioception (2896).

Charles Scott Sherrington (GB) stated that the cerebellum is head ganglion of the proprioceptive system, holding that it functions as a whole because it deals with the musculature of the body as a whole rather than with individual muscles (2894). 

Graham Steell (GB) described the murmur of high-pressure in the pulmonary artery later called Graham Steell murmur (2985). The observation took place in 1888.

Mathieu Jaboulay (FR), in 1900, performed the first vagotomy on a human (45, 1632).

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 (1901).

Lester Reynold Dragstedt (US) and Frederick W. Owens, Jr. (US) recommended vagotomy with pyloroplasty, for treatment of duodenal ulcer. This soon became the standard treatment (885).

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 (1182, 1183). 

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 (265). He described two patients with a significant memory deficit who, on autopsy, were found to have softening of hippocampal and adjacent cortical tissue.

Brenda Milner (US) would present experimental evidence to support Bekhterev (2212).

Dukinfield Henry Scott (GB) wrote two significant books on paleobotany (2860, 2861).

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 (4, 143, 762, 2030, 2882).

Randolph T. Major (US) found that resistance of Ginkgo biloba L. to pests accounts in part for the longevity of this species (2071).

Thomas Chrowder Chamberlain (US) was the first to suggest a continental freshwater origin of vertebrates during the Silurian and Devonian time (561). Currently most scholars support a marine origin for vertebrates.


"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 (2417).

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."

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 (1106, 1109, 1110, 1112).

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) (44, 3066, 3067). 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 (389). The drug is derived from plants of the genus Ephedra and is most commonly used to prevent mild or moderate attacks of bronchial asthma. Unlike epinephrine, ephedrine is slow to take effect and of mild potency and long duration. It is a bronchodilator and decongestant.

Takamine also isolated a starch-hydrolyzing diastase from rice (Oryza sativa).

Friedrich Wolfgang Martin Henze (DE) was the first to crystallize hemocyanin. He obtained it from octopus blood (1481).

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 (2320). The derivative was identified as methylpropylpyrrol.

Leonor Michaelis (DE-US) established the chemical principles of staining fat with various oil-soluble dyes (2199).

Count Karl Axel Hampus Mörner (SE) introduced the Nitroprusside Test, a rather specific test for sulfhydryl groups (2261).

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 (1994).

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 (631-634).

E. Wildiers (BE) discovered that yeast require trace amounts of a growth factor before they will produce alcohol from inorganic salts and glucose. The growth factor was later found to be a B vitamin (3484).

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 (1926, 1927).

Paul Theodor Uhlenhuth (DE) built on the earlier work of Jules Bordet (BE) and developed the preciptin test, which can show whether a bloodstain is human or animal in origin (3171-3173). The first forensic application of his new technique was in the case of two murdered and dismembered children in the town of Göhren on the Baltic island of Rügen. The suspect in the case, Ludwig Tessnow claimed that the stains on his clothing were either cattle's blood or wood stain from a carpentry project. They were able to prove otherwise.

Hans Horst Meyer (DE) and Charles Ernest Overton (GB) reported the striking correlation between the solubility of general anesthetics in olive oil and their ability to anesthetize/immobilize tadpoles. As a result of these observations, it was proposed that anesthetic agents interfered with the structural and dynamic properties of the nerve cell membrane and, in so doing, altered the function of the neuron (2186, 2441).

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 (1190).

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 (2745-2751).

Thomas Hunt Morgan (US) and Eugene Korschelt (DE) pioneered studies on regeneration and transplantation in salamanders (1822, 2249).

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 (2135, 2136). 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) (800, 802).

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 (362).

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” (1552).

Martinus Willem Beijerinck (NL) announced that the blue-green algae (cyanobacteria), the free-living aerobic bacterium Azotobacter, and other microorganisms are capable of using atmospheric nitrogen as their sole source of nitrogen. He was the discoverer of Azotobacter.

“I shall call oligonitrophilic microbes those which in free competition with other microbes grow in nutrient solution where one has not willingly introduced nitrogen-containing substances but from which one has not removed the last traces of these compounds. They have the property of fixing free atmospheric nitrogen either alone or in symbiosis with other microbes” (258).

Newton Barris Pierce (US) described Xanthomonas juglandis as the cause of blight of walnuts (2537).

Martinus Willem Beijerinck (NL) was a master practitioner of what is referred to as the enrichment culture technique. One of his early papers uses this methodology to isolate a bacterium capable of utilizing urea (257).

Charles Louis Alphonse Laveran (FR) received a number of blood-smears—made by Arnold Theiler (CH-ZA)—from horses suffering with biliary fever (piroplasmosis). Laveran recognized intra-corpuscular parasites, which he named Piroplasma equi (Babesia equi) (Theilera equi) (1907).

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 (3097, 3098).

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 (802).

Lucien Claude Jules Cuénot (FR) defined the sexual cycle of the Gregarina (708).

Theodor Boveri (DE) found that polarity in sea urchin eggs is associated with particular qualities of the cytoplasm. When he compared the development of isolated upper and lower portions of ova, he observed that the isolated upper portion could not gastrulate, while the lower could do so and could also differentiate primary mesenchyme. Boveri thought of the lower portion as a privileged region: “here differentiation began, and from here all other regions are influenced in their differentiation” (380, 381).

Albert Schütze (DE) working with iso-immunization of rabbits produced the first evidence of homospecific antigens in the serum of mammals (2856, 2857).

Russell W. Cumley (US) and M.R. Irwin (US) demonstrated the existence of intraspecies genetically determined differences in certain serum proteins (heterogeneity), comparable to genetic variations in blood type, eye color, and other hereditary traits (716, 1621).

Sarane Thompson (US), Joseph F. Foster (US), John W. Gowen (US), and Oscar E. Tauber (US) confirmed the work of Cumley and Irwin (3105).

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 (2436, 2437). 

Sarturnin Arloing (FR) and Paul Courmont (FR) developed a test for agglutinating antibodies in cases of tuberculosis (90).

William Henry Howell (US) demonstrated the importance of inorganic salts in regulating heart rate (1582).

Charles Sedgwick (US) described marrow sinusoids (2216).

Gaston Milian (FR) was the first to study bleeding time course (2205-2207).

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 (913).

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 (2923).

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 (580, 581, 1066).

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” (2400).

Alfred Fröhlich (AT) is remembered for his classic description of dystrophia adiposogenitalis or Fröhlich syndrome (1193).

Leo Loeb (US) described the transplantation of tumors (1991).

Max Wilms (DE) was the first to carry out full excision of burnt tissue, and sometimes grafted excised areas (3508).

Franz Kuhn (DE) introduced orotracheal intubation (1848).

Samuel James Meltzer (DE-US) and John Auer (US) perfected a method of intra-tracheal intubation to give “continuous respiration without respiratory movement” (1005, 1006, 2161). The clinical introduction of Kuhn’s, and Meltzer and Auer's methods mark the beginning of modern endotracheal anesthesia.

James H. Sequeira (GB) saw in epithelial cells of a cancer treated by irradiation a “lysis” of both nucleus and protoplasm and a fatty degeneration (2, 2875, 2876).

Georg Clemens Perthes (DE) was the originator of deep Röntgen-therapy and a prime mover of the treatment of cancer by irradiation (2504).

The Rockefeller Institute for Medical Research was founded with Simon Flexner (US) as its first director (2714).

Smallpox had its last major outbreak in the urban Northeast U.S., beginning in New York and spreading through other major cities (1803).

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 (2886).

The Journal of Hygiene was founded.

Biometrika was founded.


"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.

"The type of condensation described here through formation of —CO—NH—CH= groups may thus explain both the building up of protein substances in the organism, as well as their breakdown in the intestinal tract and in the tissues. On the basis of these given facts one may therefore consider the proteins as for the most part arising by condensation of alpha-amino acids, whereby the linkage through the group —CO—NH—CH= has to be regarded as the regularly recurring one." Franz Hofmeister (1553).

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 (2737, 2738).

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 (2729).

William Thomson (Lord Kelvin) (GB) introduced the concept of the electron (3110).

Richard Adolf Zsigmondy (AT-DE) and Heinrich Friedrich Wilhelm Siedentopf (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 (2913, 3623).

Eugen Baumann (DE) discovered cysteine as a product of the reduction of cystine (232).

Carl Alexander Neuberg (DE-US) discovered cysteine (2330). 

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 (595).

Hermann Emil Fischer (DE) isolated the amino acid hydroxyproline from gelatin hydrolysate (1107). 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 (1108, 1553). 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 (2719).

Adolf Magnus-Levy (DE) was one of the first to suggest that acetylaldehyde is an intermediate product in various fermentations of sugar (2070). 

Adrian J. Brown (GB) and Victor Henri (FR) separately discovered that the rate of hydrolysis of cane sugar by saccharase was independent of the sugar concentration over a wide range, although it depended on the enzyme concentration. Brown for the first time deduced the formation of the enzyme-substrate complex from careful rate measurements that indicated the initial rate of cane-sugar hydrolysis, except for very dilute solutions, to be independent of the concentration of the cane sugar used. He concluded that mass action is concealed in the case of this substrate-independent rate by a time course factor associated with molecular combination. Henri derived a hyperbolic rate equation for a single-substrate enzymatic reaction and showed that his rate equation predicted the catalytic rate to be proportional to the substrate concentration at low, and independent of it at high substrate concentrations (443, 444, 1476).

Leonor Michaelis (DE-US) and Maud Leonora Menten (CA) would later revive and extend this as the Henri-Michaelis-Menten theory. See Michaelis and Menten, 1913.

Charles Ernest Overton (GB) found that extracellular sodium ions are required for nerve excitability, and suggested that a sodium-potassium exchange is involved in signal conductance (2442). 

Ernest Henry Starling (GB) and Rudolf Magnus (NL) reported that pituitary extracts cause expansion of the kidney and a marked and often prolonged diuresis. This was the first indication that the hypophysis plays a part in the regulation of urine secretion (2980).

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 (1355).

"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" (1355).

Hans Lohmann (DE) discovered nanoplankton while studying tunicate stomachs (2006).

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 (209). The proposal was declined.

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 (582).

Fred Neufeld (DE) described the Quellung phenomenon, which consists of apparent capsular swelling when pneumococci are mixed with undiluted antiserum to the capsular polysaccharide (2344).

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 (2346).

Fred Neufeld (DE) and R. Etinger-Tulczynska (IL) applied the Quellung reaction to practical diagnosis (2345). 

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 (3254).

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 (1962).

Paul Ravaut (FR) and Pierre-Ernest Pinoy (FR) reported the first incidence of actinobacillosis in man (2597).

Richard May (DE) and Ludwig Grünwald (DE) developed a stain for peripheral blood film and bone marrow (2120). 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 (1243, 1244, 3580).

Andre Huot (FR) discovered that some fish (lophobranchs) have aglomerular kidneys, proving that renal tubules can secrete and resorb substances (1597). 

William Maddock Bayliss (GB) reported on the local reactions of the arterial wall to changes of internal pressure (237).

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 (240, 241).

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 (2978).

Otto Loewi (DE-US) demonstrated that protein digested outside the body to the point that it would not give a positive Biuret Test could be fed to an animal and substitute for all of its food protein. This suggested that dietary proteins are cleaved to amino acids in the gastrointestinal tract, taken into the blood, and later oxidized or used to synthesize new proteins (1995).

Theodor Boveri (DE) proved the hypothesis that the physical basis of inheritance resides in the chromosomes by creating sea urchin embryos with abnormal chromosome sets. He also determined that every cell in the sea urchin embryo must have the normal set of 36 chromosomes if development is to be normal. In the 1902 article he gave his views on the importance of interaction between nucleus and cytoplasm as, “It appears to me that the quite peculiar interaction of the cytoplasm with its simple structure and differential division and the nucleus with its complex structure and manifold total multiplication may still achieve what Weismann and Roux attempted to explain with the help of differential nuclear division. When the primitive differences of the cytoplasm, as expressed in the existence of layers, are transferred to the cleaved egg without any change in the relationships of the layers, they affect the originally equal nuclei unequally by unfolding (activating) or suppressing certain nuclear qualities, as may be visualized directly in the cleavage of Ascaris. The inequalities of the nuclei, in some cases perhaps of temporary nature only, lend different potencies to the cytoplasm that to begin with was differentiated only by degrees. Thus new cytoplasmic conditions are created which again release in certain nuclei the activation or suppression of certain qualities thus imprinting on these cells in turn a specific character and so on, and so on. In short: a continually increasing specification of the originally totipotent complex nuclear structure, and consequently, indirectly, of the cytoplasm of the individual cells, appears conceivable on the basis of physico-chemical events once the machine has been set in motion by the simple cytoplasmic differentiation of the egg. In this same article he speculated that multipolar mitosis might cause tumors and that mitotic aberrations might be caused by physical and chemical agents.” The 1904a paper states that chromatin is the substance that transforms into chromosomes during mitosis (382, 384, 386, 3494).

William Bateson (GB) showed the validity of Johann Gregor Mendel’s (Moravian-CZ) principle of segregation in animals (poultry) (203, 2568).

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 (1220-1223). 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 (203, 214).

William Bateson (GB) introduced the term epistasis (the masking effect of one mutant gene pair over another mutant gene pair) into genetics (207).

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) (546, 709-714, 1978). 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 (663).

Paul Portier (FR), Charles Robert Richet (FR), and Georges Richard (FR) discovered the remarkable fact that certain poisons of animal origin evoke a condition of hypersusceptibility instead of immunity, and that as a result of this hypersusceptibility death may ensue from a dose of the poison which is otherwise ineffective. By maceration of the tentacles of certain sea anemones (Actinia eqnina, Anemone sulcata) they obtained a poisonous fluid which, injected intravenously into dogs in a dose of 0.2 gm. per kilo, produced hypothermia, diarrhea, and death in two or three days, doses smaller than 0.2 gm. produced only transient symptoms. If, however, several weeks after the injection of such a dose a second sub-lethal dose was administered, violent symptoms of poisoning set in and were sometimes followed by death of the animal in an hour but mostly in 12 to 24 hours. Richet coined the word anaphylaxis (Greek, removal of protection) to describe this reaction. It was intended to convey the idea of the opposite of prophylaxis (Greek, favoring protection) (2556, 2631-2633).

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 (2679).

James MacKenzie (GB) began a systematic study of cardiac patients in 1883, devised a polygraph to study irregularities of the pulse, and wrote, The Study of the Pulse, followed by Diseases of the Heart. He classified irregularities of the pulse as the youthful type (sinus irregularity), the adult type (extra-systole), and the dangerous type (auricullar fibrillation) (2049, 2050).

J. Strasburger (DE) estimated the daily output of fecal microorganisms by humans to be eight grams (3036).

George Frederic Still (GB), England’s first professor of childhood medicine, described attention-deficit disorder (ADD) (3013).

Charles E. Gray (ZW) and William Robertson (ZW) recorded East Coast Fever in Africa (1307). 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) (3096).

Richard Gonder (ZA) identified the apicomplexan parasite Theileria parva as the cause of East Coast fever in South Africa (1281).

Emil von Dungern (DE) was the first to give evidence for local antibody production in the antigenically stimulated eye (3255).

Max Bielschowsky (DE) developed several stains that are still commonly used in diagnosing Alzheimer’s disease (304, 305).

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 (730, 731).

John William Ballantyne (GB) wrote Manual of Antenatal Pathology and Hygiene, the most complete history of teratology in English (152).

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 (2691).

William Richard Gowers (GB) was the first to describe a muscular disorder later called distal myopathy of Gowers (1296).

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 (523-525, 531-533, 648). 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.

A.E. Polya (DE) and Emerich von Navratil (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 (2553).

Hugh Hampton Young (US) devised and performed the first perineal prostatectomy, in 1902 (3601).

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 (130) and wrote a book on cerebrospinal fluid. He made intensive study on nerve fibers, anatomic and degenerative in nature. He did considerable clinical and chemical research on the myelin sheath. He also did considerable work on connective tissue.

Harris Hawthorne Wilder (US) pioneered comprehensive studies of the methodology, inheritance, and racial variation of palmer and planter papillary ridge patterns as well as fingerprints. These represented the first serious study of palmer and plantar dermatoglyphics (3482, 3483).

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") (1843).


"The supreme qualities of all science are honesty, reliability, and sober, healthy criticism." Niels Ryberg Finsen (1295).

Antoine Henri Becquerel (FR) in recognition of the extraordinary services he had rendered by his discovery of spontaneous radioactivity and Pierre Curie (FR) and Marie Sklodowska Curie (PL-FR) in recognition of the extraordinary services they have rendered by their joint researches on the radiation phenomena discovered by Professor Henri Becquerel were awarded the Nobel Prize in Physics.

Svante August Arrhenius (SE) was awarded the Nobel Prize in Chemistry for his doctoral dissertation work in which he hypothesized ionic dissociation.

Niels Ryberg Finsen (DK) was awarded the Nobel Prize in Physiology or Medicine "in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science."

Carl Alexander Neuberg (DE-US) introduced the term biochemistry. Ref 1903

Carl Alexander Neuberg (DE-US) introduced the term phosphorylation in 1910. Ref

Thomas Purdie (GB) and James Colquhoun Irvine (GB) introduced an important methodology for the analysis of carbohydrate structure. Free hydroxyl groups were methylated followed by acid hydrolysis. The nature of the resulting monosaccharides could then be determined (2569).

Henry Lord Wheeler (US) and Treat Baldwin Johnson (US) synthesized cytosine (3441).

Felix Ehrlich (DE) isolated the amino acid isoleucine from nitrogenous substances in beet-sugar molasses (954). 

Hermann Emil Fischer (DE) and Joseph von Mering (DE) were the first to synthesize a therapeutically active "barbiturate" by substituting two ethyl groups for two hydrogens attached to carbon in barbituric acid; the result was diethyl barbituric acid or diethylmalonylurea. It is frequently called (barbital or veronal). When they administered this new barbiturate to human subjects, the compound was found to induce sleep (1114, 1115). The term for a drug that causes sleep induction is a somnolent or a hypnotic.

Johann Friedrich Wilhelm Adolf Baeyer (DE), in 1864, had synthesized barbiturhaltige säure (malonylurea) from a reaction of urea with malonic acid, a chemical found in apples. Malonylurea became known as barbituric acid, parent compound of well-known sleeping pills of today (136). Later it was he who synthesized the dye indigo. 

In 1911-1912, two independent teams of German chemists synthesized what became known as Luminal, or phenobarbital with excellent hypnotic action and anticonvulsant activity. Ref

Alfred Hauptmann (DE) reported on the use of Luminal as a treatment for epilepsy (1439).

Manipulations of the side chain at position 5 have resulted in amobarbital (Amytal) in 1923, pentobarbital (Nembutal) in1930, and secobarbital (Seconal) in 1930. These drugs have become widely known as drugs of abuse. Changes in position 2 have resulted in the short-acting barbiturates: hexobarbital (Evipal), thiopental (Pentothal) and methohexital (Brevital). Valium and Halcion are also barbiturates. Refs

Samuel Rideal (GB) and J.T. Ainslie Walker (GB) developed the original method for determining the phenol coefficient (2641).

The Hygienic Laboratory Method (1921) is a modification of the Rideal-Walker Method (3).

The Food and Drug Administration Test (1931) is a combination of the best features of both of the above (1931).

Theobald Smith (US), in 1903, noted that guinea pigs used for the purpose of diphtheria anti-toxin testings frequently succumbed rapidly to a second injection of diphtheria, i.e., anaphylaxis. This phenomenon was not reported by Smith but communicated by him to Paul Ehrlich (2431).

Nicolas Maurice Arthus (FR) described a type of allergic reaction brought on by repeated injection of horse serum into rabbits. The reaction was characterized by a localized, acute necrotizing vasculitis. Later it became known as the Arthus reaction (94).

Charles G. Cochrane (US), William O. Weigle (US), and Frank James Dixon (US) showed that this reaction is caused by the formation of relatively large amounts of antigen-antibody precipitates in the vessel walls. They found that polymorphonuclear leucocytes (PMNs) phagocytize and rapidly degrade antigen-antibody complexes but are themselves largely responsible for the inflammation and necrosis (626).

Carl Oluf Jensen (DK) was the first to do experiments in transplantation immunity. He found that tumors, which arose spontaneously in mice, could sometimes be propagated by grafting them from one mouse to another. He passed one tumor through nineteen generations of grafting. Jensen recognized that mice of different races were not all equally susceptible to the growth of the tumors and spoke of an active immunity. This report discredited the theory of the infectivity of cancer (1669).

Georg Schöne (DE) coined the phrase transplantation immunity to distinguish it from reactions resulting from injections of foreign materials (2843, 2844).

Nicholas Senn (CH-US) was the first to use röntgen rays to treat leukemia (2874).

Theobald Smith (US) and Arthur L. Reagh (US) noted that there are two types of antigens present in the Salmonella group, one associated with the cell substance and the other with the flagella (2940).

Edmund Weil (AT) and Arthur Felix (PL-GB) would designate these as the O and H antigens respectively (3407, 3408).

Louis Lapicque (FR) introduced a number of terms to describe excitability of nerve and muscle. Rheobase (lowest point of current) was defined as, “the intensity of a constant current of abrupt onset and prolonged duration which gives the threshold of excitability.” Chronaxie (value of time) was defined as, “the duration of constant current of abrupt onset which attains the threshold of stimulation with an intensity equal to double that of the rheobase, i.e., with a voltage of double that of the rheobase” (1899). This work was begun in 1903.

Ross Granville Harrison (US) discovered the mode of embryonic origin of the lateral line sense organs of aquatic vertebrates. He demonstrated that the growth cones of sensory neurites accompany the primordium, thereby, establishing a physical link between the cranial ganglion and the body neuromasts (1417).

Almroth Edward Wright (GB) and Stewart R. Douglas (GB) showed that substances exist in immune serum, which by their action render the microbe more susceptible to phagocytosis. They called these substances opsonins (Greek, I prepare) (3576, 3577). Today we know that opsonins are antibodies.

Dmitrii Iosifovich Ivanowski; Dmitrii Iosifovich Iwanowsky; Dmitrii Iosifovich Ivanovski (RU) described inclusion bodies caused by tobacco mosaic virus in tobacco plants (1629).

Paul Ambroise Remlinger (FR), Riffat Bey (TR), and their assistant Hamdi Efendi (TR) mixed a fixed rabies virus homogenate with a rather virulent culture of the fowl cholera agent (Pasteurella multocida), put the mixture through a Berkefeld V Filter and this mixture was then inoculated intracerebrally in rabbits. While the absence of Pasteurella among the inoculated animals confirmed the success of filtration, their death from rabies after displaying paralysis symptoms within 8-10 days made clear that the rabies agent could pass the Berkefeld V Filter. Remlinger went on to repeat the same experiment by using both fixed and street viruses, and filtrating the agent through less and less permeable Berkefeld and Chamberland filters, and was thus able to demonstrate that the rabies virus could pass through the porcelain filters. He therefore not only confirmed Pasteur’s hypothesis that the rabies agent was a filterable virus, but at the same time demonstrated that it was not a parasitic protozoan as some had suggested (2611, 2612).

Adelchi Negri (IT) described the characteristic inclusion bodies found in the brain cells of animals infected with rabies. They are found most frequently in the pyramidal cells of Ammon's horn, and the Purkinje cells of the cerebellum. He mistakenly thought them to be protozoa (2312-2315). These inclusion bodies were later found to be rabies viruses and named Negri bodies in his honor.

Amédée Borrel (FR) proposed the virus theory of cancer (369). 

Vilhelm Ellermann (DK) and Oluf Bang (DK) showed that leukemia in chickens could be transmitted by injecting bacteria-free filtrates from infected chickens into healthy chickens. This implied a viral origin of the leukemia, i.e., oncogenic viruses (997, 998, 2902).

Hugo Schottmüller (DE) was the first to use blood agar for determining hemolytic properties of bacteria. He proposed that different varieties of streptococci be classified based on their capacities to hemolyze erythrocytes (2846).

W.K. Stefansky (RU) and George A. Dean (GB) discovered Mycobacterium lepraemurium the etiological agent of rat leprosy (803, 2988).

John Fleetezelle Anderson (US) described Rocky Mountain spotted fever as a new disease and suggested the wood tick as a possible carrier (68).

Howard Taylor Ricketts (US) demonstrated tick transmission of Rocky Mountain spotted fever to guinea pigs. He found that the etiologic agent is present in blood from infected humans, and demonstrated that it can be removed via filtration (2638, 2639).

Howard Taylor Ricketts (US) demonstrated that a bipolar-staining bacillus of minute size and transmitted by the bite of the wood tick (Dermacentor occidentalis) is the causative agent of Rocky Mountain spotted fever (2640). This bacterium would later be called Rickettsia rickettsia in his honor and Simeon Burt Wolbach (US) would offer final proof that Rickettsia rickettsia is the etiological agent (3558).

Lucius F. Badger (US) and Adolph S. Rumreich (US) isolated Rickettsia rickettsii from the American dog tick (Dermacentor variabilis Say) and determined that it is a vector for the rickettsia of Rocky Mountain spotted fever (eastern type) (134).

Frederick George Novy (US) and Ward J. McNeal (US) took blood from rats and succeeded in cultivating the trypanosome of rats, Trypanosoma lewisi, on blood agar (2382).

William Ernest Castle (US) wrote the first paper on Mendelism in America (543).

William Ernest Castle (US) recognized the relationship between allele and genotype frequencies for the first time (542).

Felix Mendel (DE) described his method for intracutaneous testing for tuberculin sensitivity. Within 24 to 72 hours the injected area becomes hard (indurated) and red in a person who is infected with tuberculosis or has been immunized with BCG vaccine (2163, 2164).

Clemens Peter Pirquet von Cesenatico; Clemens Peter von Pirquet (AT) used tuberculin in a diagnostic skin scratch test and Charles Montoux (FR) used it to perform an intradermal test (2084, 3319-3321).

Charles Mantoux (FR) popularized Mendel’s test, thus the Mendel-Mantoux Tuberculin Test (2084).

Nicholas Senn (US) was the first to use röntgen rays to treat leukemia (2874).

Alfred Walter Campbell (AU-GB) successfully studied the cytoarchitecture of the anthropoid cerebral cortex with the aim of establishing a correlation between physiologic function and histologic structure (493).

Wilhelm Ludwig Johannsen (DK) demonstrated in plants that natural selection could only influence evolutionary change if there is a source containing multiple genotypes. Therefore, genetically pure lines (homozygous) would not lend themselves to natural selection. He introduced and defined the concepts of phenotype, genotype, and selection (1674, 1675, 2506).

Richard Woltereck (DE) would confirm this restriction on natural selection as it applies to animals using parthenogenic freshwater crustaceans of the genus Daphnia (3570).

Ludwig Edinger (DE), Adolf Wallenberg (DE), Gordon Morgan Holmes (GB), Grafton Elliot-Smith (AU-GB), John B. Johnston (US), Cornelius Ubbo Ariëns-Kappers (NL), Gotthelf Carl Huber (US), and Elizabeth Caroline Crosby (US) established the anatomy of the avian brain. They suggested that the major subdivisions of the avian telencephalon correspond to different components of the mammalian basal ganglia with the avian spinal cord, midbrain, and thalamus being homologous to those of mammals, but that nearly all of the avian telencephalon corresponds to mammalian basal ganglia (86, 943, 945, 1000, 1001, 1679). 

Pietro Grocco (IT) and Karl Andreyevich Rauchfuss (RU) described the triangular area of dullness (Grocco’s triangle or Grocco-Rauchfuss triangle) on the patient’s back, on the side opposite to that on which a pleural effusion had occurred. Most commonly seen in children and adolescents (1323, 2596).

Adam Rydel (PL-DE) and Friedrich Wilhelm Seiffer (DE) found that vibratory sense and proprioceptive sense are closely related and that both senses are carried in the posterior columns of the spinal cord (2744).

Pierre Marie Félix Janet (FR) and Fulgence Raymond (FR) described psychasthenia for the first time (a neurosis marked by stages of pathologic fear or anxiety, obsessions, fixed ideas, tics, feelings of inadequacy, and self-accusation), i.e., obsessive compulsive disorder. Here bulimia is described in medical terms for the first time (1654).

Alfred Wolff-Eisner (DE) trephined the tibia and femur of experimental animals and suggested biopsy of bone marrow as a clinical procedure (3566).

Oscar Thorvald Bloch (DE) and Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) developed a two-stage operation for resection of tumors of the rectum. This operation is known as Bloch-Mikulicz operation (3314).

Maximilian Carl-Friedrich Nitze (DE) became one of the first to originate the idea of examining the anterior wall of the bladder and the bladder neck in 1903; a feat accomplished using his invention of the new retrograde view cystoscopes. Nitze’s last invention was in 1905: a ureteral occlusion balloon catheter with accompanying occlusive ureterocystoscope. Refs

Otto Ringleb (DE) improved the cystoscope with his “orienting cystoscope,” a breakthrough in 1908 (2646, 2647). Suprapubic prostatectomy had a mortality rate of 50% prior to the introduction of Ringleb’s new method, after which the rate went down to 10%.

Edwin Beer (US) devised a new method for surgical treatment of bladder tumors employing high frequency (Oudin) currents through a catheterizing cystoscope (249).

Leo Buerger (US) constructed a universal urethroscope with two optical systems, direct or indirect viewing, and use for catheterizing and operating respectively. It was both a cystoscope and urethroscope (468).

Maximilian Stern (DE-US), with Reinhold Wappler’s assistance, created the first instrument that used an electric loop to cut prostatic tissue (3005).

Ivan Petrovich Pavlov; Ivan Petrovic Pavlov (RU) reported in 1901 how he used salivary gland fistulas in dogs to demonstrate two types of reflexes—one inherited, the other developed from specific or psychic stimuli by training and association. The discovery of the second type, the conditioned reflex had a dramatic effect on the fields of physiology and psychology (2482-2485).

Ivan Mikhailovich Sechenov (RU) wrote Reflexes of the Brain, which Pavlov acknowledged as the single most important theoretical inspiration for his work on conditioning (2486, 2862-2864).

Ivan Petrovich Pavlov; Ivan Petrovic Pavlov (RU) and Vladimir Mikhailovich Bekhterev; Vladimir Mikhailovich Bechterev (RU) independently developed a theory of conditioned reflexes which describe automatic responses to the environment. What Bekhterev called association reflex is called the conditioned reflex by Pavlov, although the two theories are essentially the same. Because John Watson first discovered the salivation research completed by Pavlov, this research was incorporated into Watson’s famous theory of behaviorism, making Pavlov a household name. While Watson used Pavlov’s research to support his behaviorist claims, closer inspection shows that in fact, Watson’s teachings are better supported by Bekhterev’s research (266).

William Osler (CA) was the first to recognize polycythemia vera as a definite clinical entity (2418).

August Karl Gustav Bier (DE) introduced artificial active and passive hyperemia as an adjuvant to surgical therapy (307).

Die Neue Generation was founded.


Ivan Petrovich Pavlov; Ivan Petrovic Pavlov (RU) received the Nobel Prize in Physiology or Medicine "in recognition of his work on the physiology of digestion, through which knowledge on vital aspects of the subject has been transformed and enlarged."

Thomas Chrowder Chamberlin (US) and Forest Ray Moulton (US) developed the planetesimal hypothesis for the origin of the Earth and other planetary bodies, i.e., the planets formed from the coalescing of rocky fragments ranging in size from boulders to asteroids called planetesimals (562, 2273).

Hantaro Nagaoka (JP), in 1904, proposed an atomic model with electrons rotating in rings about a central nucleus. “The system, which I am going to discuss, consists of a large number of particles of equal mass arranged in a circle at equal angular intervals and repelling each other with forces inversely, proportional to the square of distance. At the center of the circle, place a particle of large mass attracting the other particles according to the same law of force. If these repelling particles be revolving with nearly the same velocity about the attracting center, the system will generally remain stable, for small disturbances provided the attracting force be sufficiently great” (2305).

Ernest Rutherford (New Zealand-GB) proposed the theory of the nuclear atom. He maintained that the atom contains a very tiny nucleus at its center which is positively charged and which contains all the protons of the atom and therefore virtually all of its mass. In the outer reaches of the atom are the negatively charged electrons which are very light and which interpose no detectable barrier to the passage of alpha particles. This theory was deduced from experiments where gold foil was bombarded with alpha particles and their behavior observed (2732).

August Karl Johann Valentin Köhler (DE) and Moritz von Rohr (PL-DE) developed quartz monochromatic microscope objectives (quartz-fluorite) for working in the ultraviolet at 275 and 280 nm and designed the first ultraviolet microscope (1801, 1802). They found that cell nuclei absorb ultraviolet light strongly.

Friedrich Stolz (DE) and Henry Drysdale Dakin (US) determined the chemical formula for both epinephrine (adrenaline) and norepinephrine (noradrenaline) and achieved a total chemical synthesis of both substances (752, 3027).

Albert Einhorn (DE) synthesized and patented procaine hydrochloride (Novocaine) in 1904. Heinrich Braun (DE) was the first to report its existence as Novocaine (407). It supplanted cocaine as the local anesthetic of choice. Procaine is made artificially by combining two B vitamins—PABA (para amino benzoic acid) and DEAE (diethyl amino ethanol).

Richard Anton Burian (CS) discovered xanthine oxidase, which catalyzes the conversion of xanthine to uric acid and hypoxanthine to xanthine (476).

Potassium cyanide powder was advocated for the control of ants (2879). 

Cornelis A. Pekelharing (NL) found that very minute quantities of a substance in the whey of milk are as capable as whole milk of promoting health in mice receiving adequate protein from some other source (2497, 3196).

Valdemar Henriques (NL) and C. Hansen (NL) demonstrated that autolyzed (self-digested) pancreas or mucosa not only supplied rats with amino acids for their protein synthesis but also supplied them with something of necessity in their diet other than amino acids, carbohydrates, fats, and salts (1477).

Marshall A. Barber (US) invented the technique for making glass capillary micropipettes and manipulating them in the field of a compound microscope (174, 3085). He developed this method initially to clone bacteria and to confirm the germ theory of Koch and Pasteur. Later on, he refined his approach and was able to manipulate nuclei in protozoa and to implant bacteria into plant cells. Continuous improvement and adaptation of this method to new applications dramatically changed experimental embryology and cytology and led to the formation of several new scientific disciplines including animal cloning as one of its latest applications.

Joseph Everett Dutton (GB) and John Lancelot Todd (CA) working in the Congo and independently Philip Hedorland Ross (GB) and Arthur Dawson Milne (GB) working in Uganda discovered that human tick disease is caused by a spirochete (Borrelia duttonii) transmitted by the African soft-shelled or argasid tick, Orhithodoros moubata (930-932, 2682).

Heinrich Hermann Robert Koch (DE), in 1904, confirmed the role of Orhithodoros moubata and was the first to demonstrate that spirochetes are transmitted via eggs (transovarial transmission) to the progeny of the infected female ticks (1790, 1792).

Thomas Renton Elliott (GB) was the first to express the idea of chemical neurotransmission, but he did not support it experimentally. “Adrenalin (epinephrine) might then be the chemical stimulant liberated on each occasion when the impulse arrives at the periphery” (1002, 1003). This was one of the earliest statements of the neurotransmitter hypothesis. More years later von Euler showed that noradrenaline is the principal neurotransmitter in the post-ganglionic sympathetic nerves. See, von Euler 1933a, 1946, and 1948.

Henry Edward Crampton (US), a graduate student in Edmund Beecher Wilson’s laboratory, performed an experiment, which suggested that there is an association between a region of egg cytoplasm and a particular type of development. He removed the polar lobe from cleaving eggs of the mollusk Dentalium and found that larvae showed a deficiency for the post-trochal and other regions. This effect was not seen when other regions of equivalent size were removed (3514, 3521).

Thomas Hunt Morgan (US) was the first to formulate the concept of cytoplasmic determination (2257).

Karl Illmensee (US) and Anthony P. Mahowald (US) clearly established this relationship when they were able to transform animal pole cells of a Drosophila embryo into gametes by transferring polar cytoplasm from the posterior to the anterior end of an egg (1615). 

Lorenz Hiltner (DE) introduced the concept of the rhizosphere (1528).

Cornelius Johan Koning (NL) suggested that fungi play an important role in the decomposition of organic matter and the formation of humus (1812).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Henry Drysdale Dakin (US) discovered the enzyme arginase, which splits arginine into ornithine and urea (1824, 1825).

Antonino Clementi (IT) found that arginase is absent from the livers of animals, which do not excrete urea (e.g., birds and reptiles) (603).

George Henry Falkiner Nuttall (US-GB) investigated the serological relationships of animals by the precipitin reaction (2385).

Franz Schardinger (AT) isolated aerobic bacteria capable of producing industrial chemicals such as acetone, ethanol, and acetic acid (2786).

Karl Pearson (GB) correctly generalized the principle of segregation showing that the F2 ratio 1/4 AA : 1/2Aa : 1/4aa should maintain itself indefinitely in a large, random-breeding population. This was an explicit statement of the equilibrium principle for a single locus, and its application to multiple loci could have been inferred from this (2495). Note: this work precedes that of Hardy and Weinberg in 1908.

Theodor Boveri (DE) predicted what later became known as genetic linkage: “When in continued breeding experiments two characters either always appear together, or disappear together, the conclusion may be drawn with the greatest probability that the factors for the two characters are located on the same chromosome.” He also predicted that if in continued breeding experiments combinations in which traits actually appear is larger than the number of possible combinations, this might be the result “of an exchange of parts between homologous chromosomes” (384). See, Sutton, 1903.

Martinus Willem Beijerinck (NL) was the first to obtain the sulfur-oxidizing bacterium, Thiobacillus denitrificans in axenic culture (259). Under anaerobic conditions it uses carbon dioxide as a source of carbon.

Albert Francis Blakeslee (US) analyzed mating type determination in the fungus Mucor and found that mating (conjugation) occurs between mycelia of opposite mating types, designated plus (+) and minus (-). The resulting sporangia produce either + or - spores, never both (327).

Hans Burgeff (DE) demonstrated that dissimilar nuclei could be associated in the vegetative hyphae of Phycomyces nitens, a condition he called heterokaryosis (472, 473).

William B. Brierley (GB), H.N. Hansen (?), and R.E. Smith (?) discovered and elaborated on heterokaryosis in the Ascomycetes (433, 1398, 1399).

The groundwork for understanding the heterokaryotic nature of the dikaryon in the Basidiomycetes was laid by:

Karl Johannes Kniep; Hans Kniep (DE) developed a technique called tetrad analysis. It is commonly used in fungal genetics (1777).

Mathilde Bensaude (FR) discovered that the clamp connection structure in the basidiomycetes is used to ensure the production of cells, each of which contains two complementary nuclei (281, 282).

John Hubert Craigie (GB) discovered that the rusts are heterothallic, and confirmed Heinrich Anton de Bary’s findings that the pustules on Barberry and the rust on wheat (Triticum spp.) are both caused by the same organism and that the pycnospores are sperm (687, 688).

Leonard Doncaster (GB) explained the inheritance of tortoiseshell (sex-linked) and related colors in cats (868).

Friedrich Meves (DE) discovered mitochondria in plants (the tapetal cells of Nymphae anthers) (2184).

Anton Julius Carlson (SE-US) proved that the heartbeat in the Limulus crab is neurogenic by section of the cardiac nerve (521). This was soon shown to be inapplicable to the hearts of amphibia and mammals.

William Philipps Dunbar (US) proposed that hay fever is a disease caused by vegetable poisons contained in the pollen of certain plants. These substances were connected with the proteid of the pollen grain and of a highly specific character. He developed methodologies for testing patients' sensitivity to certain pollens by minuscule exposure to pollen via their eyes or nasal passages. Dunbar determined that it was the dried cat saliva on cat hair that caused the allergic reaction. With regard to grass pollen, Dunbar identified the albumin fraction as the active toxin, discovered changes in the blood that accompanied exposure to the pollen, and was able to grade individuals' relative susceptibility to each type of pollen (918, 919).

Charles Scott Sherrington (GB) and Edward George Tandy Liddell (GB) investigated spinal reflexes such as the knee-jerk. They discovered reciprocal innervation of motor areas, i.e., when one set of muscles is stimulated, muscles working against the activity of the first will be inhibited (Sherrington’s law). The proprioceptive system, i.e., the brain is able to judge the tensions upon the muscles and joints and thereby possess a sense of position and equilibrium. They formulated the concepts of the final common pathway, i.e., “The reflex arcs (of the synaptic system) converge in their course so as to impinge upon links possessed by whole varied groups in common paths. This arrangement culminates in the convergence of many separately arising arcs upon the efferent-root neuron. This neuron thus forms a final common path for many different reflex arcs and acts. It is responsive in various rhythm and intensity, and is relatively unfatigable,” and the integrative action of the nervous system. Also they will be remembered for their contributions to the physiology of perception, reaction and behavior. They also discovered the stretch reflex (1959, 2895-2897).

Franz Knoop (DE) fed dogs the sodium salts of various straight-chain fatty acids in which the carbon atom farthest from the carboxyl group was linked to a phenyl group. Based on the urinary products he deduced that oxidative degradation of fatty acids occurs by oxidation at the beta-carbon thereby releasing two carbons at a time from the fatty acid. This became known as the beta-oxidation theory (753, 1778-1780). This represents one of the first experiments in which a metabolite was labeled in such a way that end products could provide evidence of how physiological conversions had occurred.

Gustav Georg Embden (DE) showed that pancreatectomized dogs convert lactic acid to glucose. This suggested that the glycolytic reactions are reversible. Ref

Gershom Franklin White (US) reported the isolation of Bacillus X in honeybee (Apis mellifera Linn.) larvae suffering from American foulbrood (3446). White then renamed the organism Bacillus larvae (3447, 3448).

William Bateson (GB), Edith Rebecca Saunders (GB), and Charles C. Hurst (GB) discovered intermediate (blended) inheritance in the mint genus Salvia. In this same article they reported, for the first time, that one character or trait (comb shape in chickens) could be controlled by more than one gene. Further research by various geneticists was to show that this is the general rule rather than the exception. Most characters are controlled by more than one gene (215, 2568).

Ross Granville Harrison (US) contributed to our knowledge of the relation of the nervous system to muscle differentiation in the embryo, and the development and regeneration of peripheral nerves (1418, 1419).

William Thomas Councilman (US), George B. Magrath (US), and Walter R. Brinckerhoff (US) observed round or oval acidophilic intranuclear inclusion bodies in variola infected cells of man (671).

Léon Ambard (FR), Eugene Beaujard (FR) and André-Simon Weill (FR) discovered the link between salt and high blood pressure in hypertensive patients studied weeks under different schemes providing very different amounts of sodium chloride (60-62). 

Paul Emil Flechsig (DE) evolved a map of cortical function that appeared in a report of 1904 to the Central Committee for Brain Research (1128).

Karl Albert Ludwig Aschoff (DE) discovered granuloma in the myocardium specific for rheumatic fever (97).

Ernst Ferdinand Sauerbruch (CH-DE) introduced a low-pressure surgical cabinet for preventing lung collapse during thoracic surgery and is credited with the first operation on the open chest (2777).

Ludolph Brauer (DE) invented the airtight mask that could be fitted over the face and connected with an oxygen container under the desired hyperpressure. The oxygen also passed through a bottle of ether, so that both the anesthetic and oxygen could be given under higher than atmospheric pressure. This method replaced the cabinet (405).

Felix Jacob Marchand (DE) coined the term atherosclerosis because arteriosclerosis is not sufficient to include the entire disease processes of the primary fatty and atheromatous degeneration intimately involved in the sclerosing processes within the blood vessels. He suggested that atherosclerosis is responsible for nearly all obstructive processes in the arteries. The Greek athero refers to gruel (2087).

Julius Donath (AT) and Karl Landsteiner (AT-US) were the first to describe an autoimmune disease, paroxysmal hemoglobinuria. This disease is characterized by the discharge of massive amounts of hemoglobin, not intact erythrocytes, into the urine. It results from an antibody of the IgG class directed against the P blood group antigen and is associated with syphilis and viral infections and is responsible for paroxysmal cold hemoglobinuria (867). 

William Osler (CA) was the first to associate a renal affection or one affecting the central nervous system with cases of lupus erythematosus (2419, 2420).

Eduard Hitzig (DE) noted that electrical stimulation of a region in front of the pre-central gyrus in the dog caused combined movements of the head and eyes (1541).

T. Grainger Stewart (GB) and Gordon Holmes (IE) wrote a paper about precise localization of destructive lesions in the cerebellum. This paper contains the first description of the rebound phenomenon (3011). 

Edward Albert Schäfer (GB) described a method for administering artificial respiration. It was especially effective with a person in danger of drowning (2781).

Kristian Igelsrud (NO) was the first to perform open-chest cardiac massage in 1901, but William Williams Keen, Jr. (US) did not report this until a few years later (1723). 

Harvey Williams Cushing (US) gave the first report of using a tourniquet with pneumatic pressure of a measurable degree. This inflatable cuff was the forerunner of the modern technique used generally in surgery (733).

Joseph Grinnell (US) wrote, “two species of approximately the same food habits are not likely to remain long evenly balanced in numbers in the same region” (1317). Grinnell connected the idea of competitive exclusion to the term niche when he asserted that “no two species regularly established in a single fauna have precisely the same niche relationships” (1318, 1319). He was the first to use the word niche to refer to an animal’s ecological position in the world by defining the ecological or environmental niche as the ultimate distributional unit of one species or subspecies (1320). Grinnell more fully developed the idea when he wrote “…the concept of the ultimate distributional unit, within which each species is held by its structural and instinctive limitations, these being subject only to exceedingly slow modification down through time” (1321).

Georgi Frantsevitch Gause (RU) proposed what has come to be one of the laws of ecology when he wrote, “It is admitted that as a result of competition two similar species scarcely ever occupy similar niches, but displace each other in such a manner that each takes possession of certain peculiar kinds of food and modes of life in which it has an advantage over its competitor” (1228-1231). It is known as the competitive exclusion principle.

Francis Wall Oliver (AU) and Dunkinfield Henry Scott (GB) discovered evidence for the seed of Lyginodendron, which led to the removal of the Cycadofilices from the Pteridophyta (ferns, horsetails, and club-mosses), and their inclusion with the gymnosperms (2391). “We now know that the true ferns were only present in the coal measures in small and archaic forms (Coenopteridales) very unlike living ferns and that probably all the conspicuous fernlike leaves of that era belonged to seed plants” (2083).

Charles H. Sternberg (US) discovered the fossil remains of a creature showing both amphibian and reptilian characteristics. Ferdinand Broili (DE) would name it Seymouria baylorensis for Seymour, Texas in Baylor County (439).

The Journal of Experimental Zoology was founded.


“Ludwig was absolutely unselfish. He loved his science and rejoiced in the scientific achievements of his students. He freely gave to every earnest worker from the vast store of his physiological knowledge, and his experience in experimental methods. He became at once the friend of each of his pupils, making him feel that he had a personal interest in him and in his work. This feeling spread throughout the laboratory, where good-fellowship reigned, each man becoming interested not only in his own problem, but glad to lend a helpful hand to every other, rejoicing when a research was successful and sorry when the problem baffled. I can recall Ludwig’s enthusiastic, joyous shout, as he called all who could leave their work to come and witness some physiological process revealing itself in its true light for the first time, or some unusually suggestive histological or anatomical preparation. Hearty congratulations followed, all rejoicing in the new discovery. And then came one of those delightful talks, leading us forward to the borderland of science, and giving us glimpses into that fascinating, mysterious land—the unknown.” Warren P. Lombard (US) speaking of Karl Friedrich Wilhelm Ludwig (DE) the great physiologist and his former teacher (2008). More than two hundred and fifty men from a dozen countries came to study under this great master.

“Science is built up of facts, just as a house is built up of stones; but an accumulation of facts is no more a science than a heap of stones is a house.” Henri Poincaré (2548).

“Nothing is constant but change! All existence is a perpetual flux of ‘being and becoming’! That is the broad lesson of the evolution of the world.” Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (1358).

Johann Friedrich Wilhelm Adolf von Baeyer (DE) was awarded the Nobel Prize in Chemistry for his advancement of organic chemistry and the chemical industry, through his work on organic dyes and hydroaromatic compounds.

Heinrich Hermann Robert Koch (DE) was awarded the Nobel Prize in Physiology or Medicine "for his investigations and discoveries in relation to tuberculosis."

William Weber Coblentz (US), between 1903-1905, pioneered infrared spectrophotometry as a method for determining the presence of specific atomic groupings. He was the first to show that different atomic and molecular groupings absorbed specific and characteristic wavelengths in the infrared region (622, 623).

Richard Adolf Zsigmondy (AT-DE) applied the centrifuge to the study of colloids, making a more detailed understanding of protoplasmic constituents possible (3622).

W.I. Gulewitsch (RU) and R. Krimberg (RU) isolated a new compound from meat extracts. They named it carnitine from carnos (meat) (1341). 

Masaji Tomita (JP) and Yuzo Sendju (JP) determined the chemical structure of carnitine to be 3-hydroxy-4-trimethylamino butyric acid (3134).

Arthur Harden (GB) and William John Young (GB) showed that the enzymes were not consumed during the breakdown of sugar by yeast, however the reaction slowed down even when there was ample sugar and enzyme present. If they added inorganic phosphate the reaction speeded up again. This was initially a puzzling finding because phosphorus is neither present in sugar, nor alcohol, nor carbon dioxide, nor enzyme. Their search for the fate of the added phosphate led them to discover that phosphorylated sugars are being manufactured. They isolated a hexose diphosphate (fructose 1,6-diphosphate) from the fermentation mix which became known as the Harden-Young ester (1400, 1406-1409, 3605). The structure of this ester would later be characterized by Phoebus Aaron Theodor Levene (RU-US) and Albert L. Raymond (US) as fructose-1,6-diphosphate (1943).

Leonid Aleksandrovich Ivanov (RU) had independently discovered that organic phosphates are produced during alcoholic fermentation (1625).

Arthur Harden (GB) made another important set of observations revealing that in the presence of the inhibitor fluoride, fermenting yeast extracts showed an accumulation of two phosphate esters, 3-phosphoglycerate and 2-phosphoglycerate. On the other hand, the inhibitor iodoacetate caused an accumulation of fructose-1,6-diphosphate. Once these intermediates were identified, it became possible to study the enzymatic reactions by which they were formed and utilized. Harden’s work marks the beginning of the study of intermediary metabolism. Ref

The first version of International Rules (Code) of Botanical Nomenclature (ICBN) was approved in Vienna, Austria.

Frederick Frost Blackman (GB) and Gabrielle Louise Caroline Matthaei (GB) proposed that photosynthsis consists of a light-dependent reaction (the 'light' reaction) and a temperature-dependent reaction (the 'dark' reaction). Both these reactions are going on simultaneously. The 'light' reaction feeds something to the 'dark' reaction. As the intensity of illumination is increased, the rate of photosynthesis (as measured, for example, by the volume of oxygen produced each minute) does not increase indefinitely but approaches a saturation state in which a further increase of light intensity has no effect. This suggests a two-stage process in which only one stage can be accelerated by light (326, 2118).

Otto Heinrich Warburg (DE) later called the process of limiting the rate of carbon assimilation at high intensities of illumination the Blackman reaction (3361).

John Sidney Edkins (GB) showed that extracts of the gastric antral mucosa stimulate secretion of acid by the oxyntic mucosa, and postulated that his extracts contained a hormone, which he called gastrin (946, 947).

H. Gregory (GB), Roderic Alfred Gregory (GB), Paul Martin Hardy (GB), D.S. Jones (GB), George Wallace Kenner (GB), Robert Charles Sheppard (GB) and Hilda J. Tracy (GB) determined the structure of gastrin (1312, 1313).

J.C. Anderson (GB), Moira A. Barton (GB), Roderic Alfred Gregory (GB), Paul Martin Hardy (GB), George Wallace Kenner (GB), John Keith MacLeod (GB), J. Preston (GB), Robert Charles Sheppard (GB) and John Selwyn Morley (GB) described the synthesis of gastrin (67).

William Henry Howell (US) discovered the remarkable hypotensive effect of acetylcholine (1583).

John Newport Langley (GB) introduced the concept of receptor substance or synaptic substance, “probably not in the nerves, but in the cells in which they end” (1895).

Nettie Maria Stevens (US) and Edmund Beecher Wilson (US) independently discovered the existence of the so-called sex chromosomes. Stevens worked with the beetle Tenebrio while Wilson worked with several genera of hemipteran insects, including Anasa tristis (3008, 3515-3518). This was not the first time that sex determination was associated with a chromosome but it was the first proof. See, Henking, 1891 and McClung, 1901. Wilson is credited with coining the phrase X-chromosome.

Roland H. Biffen (GB) reported the first proof that disease resistance in plants may be inherited in a Mendelian manner when he found that resistance to yellow rust in wheat is inherited as a simple Mendelian recessive to susceptibility (310).

Carl Franz Joseph Erich Correns (DE) had previously found that in the four o’clock plant, Mirabilis jalapa, a gene determined a localized disease in the palisade cells called Sordago (661, 662).

William Bateson (GB), Edith Rebecca Saunders (GB), Reginald Crundall Punnett (GB), and Charles Chamberlain Hurst (GB) discovered linkage and genetic interaction (216, 218). Punnett has two species of marine worms named for him, Cerbratulus punnetti, Punnettia splendia.

William Bateson (GB), Edith Rebecca Saunders (GB), and Reginald Crundall Punnett (GB) discovered that two genes behaving in a recessive epistatic mode control flower color in Lathyrus (sweet peas) and Matthiola (stocks) (217, 2568).

William Curtis Farabee (US) determined that brachydactyly in humans can be explained by Mendelian principles (1067).

The first human pedigree was published. It showed the inheritance of shortened hands and fingers in a Norwegian village (1697).

William Bateson (GB) and Reginald Crundall Punnett (GB) made several reports to the Evolution Committee of the Royal Society of London from 1905 to 1908 in which they related the discovery of two new genetic principles: gametic coupling and gene interaction. They studied poultry comb form, demonstrating significant departure from Mendelian ratios for some gene pairs (211-213, 2568).

Thomas Hunt Morgan (US) proposed that the frequency with which recombinants took place was related to the physical distance separating the genes on the chromosome and further proposed that this could be used for mapping the positions of genes relative to each other. This phenomenon was clarified and called gene linkage (2252).

Alfred Henry Sturtevant (US), based on his work with Morgan, created the first genetic map (3041). See Sutton, 1903.

Lucien Claude Jules Cuénot (FR) discovered a lethal allele: the yellow coat color allele in mice even though he did not interpret it correctly (714).

William Ernest Castle (US) and Clarence Cook Little (US) proved that the yellow allele has two expressions: a dominant one on coat color, and a recessive one on viability, since yellow homozygotes died early in the embryonic state (546). 

William B. Kirkham (US) later discovered that the homozygous yellow embryos died in utero (1758).

Konstantin Sergejewitsch Mereschkowsky (RU) proposed the theory of the symbiotic origin of the eukaryotic cell and introduced the term symbiogenesis to signify the emergence of new species with identifiably new physiologies and structures as a consequence of stable integration of symbionts. It stated that the chloroplast and mitochondria of eukaryotic cells had their origins from endosymbiotic cyanobacteria and aerobic bacteria, respectively, whose ancestors were once captured and incorporated by a primitive, anaerobic, heterotrophic host. Many others would later refine this theory (551, 552, 1745, 1746, 2096, 2168).

Robert K. Trench (US), Richard W. Greene (US), Barbara G. Bystrom (US), Merriley E. Trench (US), and Leonard Muscatine (US) found contemporary organisms that offer some striking examples of symbiotic relationships with a similar history (3142, 3143).

Stamen Grigoroff (BG) isolated Lactobacillus bulgaricus from Bulgarian fermented milk (1315).

Alfred T. MacConkey (GB) used bile salts to select for lactose fermenting bacteria in fecal samples (2040, 2041).

M. Casimir Wize (PL) found that a chytridiaceous fungus was parasitizing the larvae and pupae of Cleonus and Anisolplia (Coleoptera). He named the fungus Olpidiopsis ucrainica (3555). 

Fritz Richard Schaudinn (DE) and P. Erich Hoffman (DE) used a special staining technique to demonstrate the spirochaete causing syphilis in serum obtained from a genital lesion by Hoffmann. They named it Spirochaeta pallida (2808, 2809). The organism is now called Treponema pallidum.

Aldo Castellani; Count of Chisiamaio (IT) discovered, Treponema pertenue, the spirochete causing yaws (538). 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) noted that mononuclear phagocytes from animals resistant to certain bacterial infections had increased competence for ingesting and killing these microbes. This phenomenon became known as macrophage activation (2177).

Sergei Nikolaevich Winogradsky (RU) and Martinus Willem Beijerinck (NL) observed that the reason microbiologists so often succeed in isolating specific microbes from a given sample of soil or water is due to a methodological principle called the ecological approach, often designated as the principle of elective or enrichment culture. Its application depends on a well-considered selection of the conditions in a primary culture medium, thus causing preferential growth of a certain kind of germ, ultimately leading to a predominance of the conditionally fittest. Typically these enrichment cultures offer the microbe a single simple carbon compound as the sole source of carbon (263).

Ludvig Hektoen (US) demonstrated by subcutaneous injections of volunteers with blood taken from measles patients that the measles (rubeola) virus circulates in the blood during the initial thirty hours of the rash (1458). Hektoen was also the first to grow blood cultures from living patients (1457).

Martinus Willem Beijerinck (NL) published little concerning his original concepts and approaches, however, upon being awarded the Leeuwenhoek medal by the Koninklijke Akademie van Wetenschappen in Amsterdam he said, “I am happy to note the way in which I approach microbiology has the approval of the best judges. This approach can be concisely stated as the study of microbial ecology, i.e., of the relation between environmental conditions and the special forms of life corresponding to them. It is my conviction that, in our present state of understanding, this is the most necessary and fruitful direction to guide us in organizing our knowledge of that part of nature which deals with the lowest limits of the organic world, and which constantly keeps before our mind the profound problem of the origin of life itself. Therefore it is a great satisfaction to me that the Academy apparently wishes to honor the experimenter who exploits this field.

In an experimental sense the ecological approach to microbiology consists of two complementary phases, which give rise to an endless number of experiments. On the one hand it leads to investigating the conditions for the development of organisms that have for some reason or other, perhaps fortuitously, come to our attention; on the other hand to the discovery of living organisms that appear under predetermined conditions, either because they alone can develop, or because they are the more fit and win out over their competitors. Especially, this latter method, in reality nothing but the broadest application of the elective culture method, is fruitful and truly scientific, and it is no exaggeration to claim that the rapid and surprising advances in general microbiology are due to this methodology. Nevertheless, and this in spite of the fact that Leeuwenhoek, more than two hundred years ago, already used this aspect of micro-ecology in some of his studies, and that Pasteur was enabled to make most of his great discoveries because he was guided by the same principle, the number of conscious exponents has so far remained very small. And I feel that I certainly may be reckoned among them because of the enthusiasm that is in me to contribute to the grand task can here be accomplished” (3195, 3430).

Beijerinck’s (NL) major contributions can be considered as the first direct experimental investigations of Darwin’s principle of natural selection. In the enrichment cultures the experimentally defined environmental conditions are the selecting agent, and the outcome of the cultures can provide an unambiguous answer to the question as to what organisms among the many types present in the inoculum are best fit to cope with the environment (3197).

Shigetane Ishiwata (JP) discovered that the Sotto-Kin disease of silkworms is caused by a new species of bacterium, which he named Sotto-Bacillen. This organism would later be named Bacillus thuringiensis (1623). 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) and Pierre Paul Émile Roux (FR) demonstrated that syphilis may be transmitted to anthropoid apes, such as the chimpanzee and gibbon, and, with less certainty to monkeys (2179).

Louis Joseph Alcide Raillet (FR) and A. Henry (FR) described six female immature Oesophagostomum brumpti (nematode) worms that Alexandre Joseph Emilé Brumpt (FR) found in tumors of the caecum and colon, in 1902, when he performed autopsy on a 30-year old African man, who had been living near the River Omo, East-Africa (457, 459, 2579). 

William Bateson (GB) coined the term genetics to denote the science of heredity, but the word had actually been used earlier (204, 205).

Count Grafen Emmerich Festetics (HU), a prominent sheep breeder from Hungary, wrote Genetic Laws. It included the observation that progeny inherit traits from their parents, and that traits of grandparents can reappear in the offspring of their offspring (1086, 1087).

Hugo Marie de Vries (NL), while studying the genetics of the evening primrose, Oenothera lamarckiana, found an unusual variant among his plants. O. lamarckiana has a chromosome number of 2N = 14. The variant had a chromosome number of 2N = 28. He found that he was unable to breed this variant with O. lamarckiana. He named this new species O. gigas (801).

Anne Mae Lutz (US) proved that the gigas mutation in the evening primrose contains twice the usual chromosome number. This led to the analysis and artificial production of polyploidy (2029).

Lettice Digby (GB) observed that primrose the species Primula verticillata and P. floribunda can cross to produce a sterile hybrid. This hybrid was called the Kew primrose (P. kewensis) and possessed 18 chromosomes. Digby observed that these sterile hybrids occasionally gave rise to fertile Kew primroses. Using microscopic analysis she proved that the fertile hybrid was a polyploid containing 36 chromosomes. This was the first documented case of a polyploid hybrid (838).

Øjvind Winge (DK), unaware of Digby's results, speculated that speciation could occur by interspecific hybridization followed by chromosome doubling. Winge believed that hybrid sterility was caused by unbalanced chromosome sets. He reasoned that upon doubling, a proper pairing partner would be available to each chromosome resulting in fertility (3537).

Roy Elwood Clausen (DK-US) and Thomas Harper Goodspeed (US) used Nicotiana tabacum to experimentally demonstrate Øjvind Winge’s hypothesis of the origin of species by amphidiploidy.

George D. Karpchenko (RU) did the same using radish and cabbage (597, 598, 1710, 1711). It was soon realized that allopolyploids—hybrid species that contain two or more diploid sets of parental genomes—are common in nature.

W.C. Frank Newton (GB) and Caroline Pellew (GB) noted that spontaneous hybrids of Primula verticillata and P. floribunda set tetraploid seed on at least three occasions. These happened in 1905, 1923 and 1926 (2349).

Edwin G. Conklin (US), used the ascidian Cynthia (now Steyla), for his discovery. The mature oocytes of these animals have a large transparent germinal vesicle. The interior consists of a mass of gray yolk and the periphery contains a yellow pigment. When the germinal vesicle ruptures at the onset of meiosis, it liberates a quantity of clear material. At fertilization the sperm enters near the vegetal pole, and this starts a dramatic rearrangement of the cytoplasm.

Conklin discovered that at the close of the first cleavage these distinctively colored regions of the embryo have a precise relationship with the structures that would form subsequently. The fate of the yellow crescent is to form muscles and mesenchyme, the gray yolky cytoplasm forms endoderm, and the clear cytoplasm of the animal hemisphere forms ectodermal structures (645).

Charles Zeleny (CZ-US) showed that removal of the eyestalk shortened the intermolt period in crustaceans (3613).

Max Kauffmann (DE) showed that the nutritional value of various proteins depends upon their constituent amino acids. Proteins such as gelatin lack some necessary amino acids (1720).

Paul Ehrlich (DE) and Hugo Apolant (DE) demonstrated change of experimental carcinoma transplants into sarcoma (973).

John Scott Haldane (GB) and John Gillies Priestley (GB) determined by observations on normal men that breathing is quite unaffected either by inhalation of oxygen-rich air or by such a moderate decrease of oxygen as occurs on first going to an altitude. On the other hand the breathing changes its volume automatically in such close adjustment to the amount of carbon dioxide produced in the body that the alveolar air is kept nearly constant in this respect. They concluded that carbon dioxide is the chief immediate respiratory hormone and its tension in the blood is the major stimulus for the respiratory center. They demonstrated that as carbon dioxide concentration of alveolar air rises there is an increase in depth of breathing. There was no alteration in frequency of ventilation until the alveolar concentration had been increased to about five times normal (1378).

Alfred Binet (FR) and Théodore Simon (FR) developed an intelligence test used particularly on children aged 3 to 15 years (315).

Clemens Peter Pirquet von Cesenatico; Clemens Peter von Pirquet (AT) and Béla Schick (HU-AT-US) described the essence of serum sickness—antibody combines with the foreign serum antigen to form a toxic compound, which causes the disease (3323-3325).

Hans Curschmann (DE), Hans Gustav Wilhelm Steinert (DE), Frederick Eustace Batten (GB), and H.P. Gibb (GB) provided a clinical description of myotonic dystrophy (Curschmann-Steinert-Batten disease), the most common form of muscular dystrophy (227, 725, 2989). Myotonic dystrophy (MD) is a neuromuscular disorder with autosomal dominant inheritance, associated with muscle weakness and myotonia, dilated cardiomyopathy, cataracts, and mental and endocrine abnormalities.

Alfred Walter Campbell (AU) wrote Histological Studies on the Localization of Cerebral Function, a classic. Campbell’s map of the human brain can be seen in nearly every well-known textbook on neuroanatomy (494).

Harvey Williams Cushing (US) reported a successful operative intervention in intracranial hemorrhage of the newborn (734).

William Arbuthnot Lane (GB) performed repair of cleft lip and palate in neonates (1887).

J. Winter (AT) used chloroform to suspend circulation and respiration in animals. He then injected adrenaline into the left ventricle of the heart thus restoring heart action when all other methods failed. He suggested that this technique be tried in humans (3551).  Incomplete Ref

Reinhard von den Velden (DE) attempted intracardiac injection in humans to restore heart action after complete cessation of heart action (3252).

Carl Boden (US) reports that J. Winter (AT), in 1905 was the first to attempt an intracardiac injection of adrenalin in humans (341).

Henry Fairfield Osborn (US) described the Tyrannosaurus rex, which Barnum Brown (US) discovered in 1902 in Hell Creek, Montana (2409).

Frederic Edward Clements (US) wrote the first American textbook in ecology, Research Methods in Ecology (604).

John Jacob Abel (US) and Christian Archibald Herter (US) founded the Journal of Biological Chemistry

The Journal of Experimental Medicine initiated publication.


“The true contrast between science and myth is more nearly touched when we say that science alone is capable of verification.” George Santayana (2771).

"The beauty and genius of a work of art may be reconceived, though its first material expression be destroyed; a vanished harmony may yet again inspire the composer; but when the last individual of a race of living beings breathes no more, another heaven and another earth must pass before such a one can be again." Charles William Beebe (248).

"It is as if the Milky Way entered upon some cosmic dance. Swiftly the brain becomes an enchanted loom, where millions of flashing shuttles weave a dissolving pattern, always a meaningful pattern though never an abiding one; a shifting harmony of subpatterns."Charles Scott Sherrington (2896).

“For this general concept of the changed capacity for reaction, I propose the term allergy. Allo denotes the deviation from the original state, from the behavior of the normal, as in allorhythmia, allotropy.” Clemens Peter Pirquet von Cesenatico; Clemens Peter von Pirquet (3318). Introduction of the word allergy to the medical lexicon.

“ We may have been more plastic and receptive, but I doubt it; even our generation … had a practical demonstration of the slowness of the acceptance of an obvious truth in the long fight for the aseptic treatment of wounds … [It was] a long grievous battle, as many of us well know who had to contend in hospitals with the opposition of men who could not — not who would not — see the truth ….

In making knowledge effective we have succeeded where our masters failed. But this last and final stage, always of slow and painful consummation, is evolved directly from truths which cannot be translated into terms intelligible to ordinary minds.” William Osler, 1906 in his Harveian Oration (2421).

Bartolomeo Camillo Emilio Golgi (IT) and Santiago Ramón y Cajal (ES) were awarded the Nobel Prize in Physiology or Medicine "in recognition of their work on the structure of the nervous system."

Walther Hermann Nernst (DE) proposed what we refer to as the third law of thermodynamics: entropy change approaches zero at a temperature of absolute zero (2323-2325).

Ernest Rutherford (NZ-GB) measured the uranium and helium (helium is an intermediate decay product of uranium) contents of uranium-bearing minerals to calculate an age of the minerals. This is the origin of using radioactive decay for dating objects (2730, 2731).

Bertram Borden Boltwood (US) developed the chemical uranium to lead method. He was among the first to suggest that from the quantity of lead in uranium ores and from the known rate of uranium disintegration, it might be possible to determine the age of the earth’s crust. These first geochronology studies yielded the first absolute ages from geologic material and indicated that parts of the Earth's crust are hundreds of millions of years old. He published a list of geologic ages based on radioactivity, which were incredibly accurate for his time (351).

Mikhail Semenovich (Semyonovich) Tswett (RU) is usually given credit for having originated and named the technique called chromatography (Greek, written in color) when he reported, “If a petroleum ether solution of chlorophyll is filtered through a column of an adsorbent (I use mainly calcium carbonate which is stamped firmly into a narrow glass tube), then the pigments, according to their absorption sequence, are resolved from top to bottom into various colored zones, since the more strongly adsorbed pigments displace the more weakly adsorbed ones and force them further downwards. This separation becomes practically complete if, after the pigment solution has flowed through, one passes a stream of solvent through the adsorbent column. Like light rays in the spectrum, so the different components of a pigment mixture are resolved on the calcium carbonate column according to a law and can be estimated on it qualitatively and also quantitatively. Such a preparation I term a chromatogram and the corresponding method, the chromatographic method.

It is self-evident that the adsorption phenomena described are not restricted to the chlorophyll pigments, and one must assume that all kinds of colored and colorless chemical compounds are subject to the same laws.” Twsett separated blue chlorophyll (chlorophyll a), from yellow chlorophyll (chlorophyll b), using column chromatography, and called them chlorophyll alpha and beta, which later became a and b (3154, 3155). See, Goppelsröder, 1861. This methodology was presented for the first time in 1903 to a meeting of scientists in Warsaw, Poland.

George Barger (GB), Francis Howard Carr (GB), and Henry Hallett Dale (GB) announced the first isolation of an active ergot alkaloid, which they named ergotoxine (179).

Henry Hallett Dale (GB) demonstrated that ergotoxine (ergotamine) produces effects at the end plates of the motor nerves in skeletal muscle and some involuntary organs (755). Some consider this to be the origin of the concept later called beta-blockers

Ergotoxine was later shown to be a mixture of three alkaloids.

Arthur Stoll (CH), in 1918, isolated ergotamine tartrate from the various alkaloids present in extracts of the sclerotia of the fungus Claviceps purpurea (ergot), which grow on rye and, to a lesser extent, on other grasses; he named it Gynergen. This was the first chemically pure ergot alkaloid. It found widespread therapeutic use in obstetrics as an oxytocic, and internal medicine for relief of migraines (3024, 3025).

Arthur Stoll (CH), Ernst Burckhardt (CH), M. Edward Davis (US), Fred L. Adair (US), Gerald Rogers (US), Morris Selig Kharasch (RU-US), Romeo R. Legault (US), Harold Ward Dudley (GB), John Chassar Moir (GB), and Marvin R. Thompson (GB) discovered ergonovine, the specific oxytocic principle of ergot (782, 909, 3026, 3104). 

Mitsumaru Tsujimoto (JP) discovered a hydrocarbon in oils from shark liver he named squalene (3152). He later assigned the correct empirical formula C30H50 to squalene (3153).

Carbon disulfide was introduced as a herbicide and soil fumigant. Ref

Arthur Harden (GB), Stanley G. Walpole (GB), and Dorothy Norris (GB) found that acetoin; 2,3-butylene glycol; and acetylmethylcarbinol are produced by many bacteria (1402, 1403, 1405).

Albert Jan Kluyver (NL), Hendrik Jean Louis Donker (NL), and F. Visser't Hooft (NL) found that when yeast produce acetylaldehyde during the alcohol fermentation it may be converted to acetoin if a strong hydrogen acceptor like methylene blue or oxygen is present. The acetoin may then be reduced to 2,3-butylene glycol (1776).

David Paretsky (US) determined the mechanism for the conversion of 2,3-butylene glycol to acetylmethylcarbinol in bacterial fermentation (2464, 2465).

Arthur Harden (GB) and William John Young (GB) recognized the existence of a heat-stable coenzyme participating in fermentation reactions catalyzed by yeast juice. One component of this coenzyme was recognized as adenosine triphosphate (ATP), but the structure of the other, known for many years as cozymase remained unknown (1407).

Otto Fritz Meyerhof (DE-US) perfected a technique of using muscle extract, which was very low in carbohydrate content to study the role of chemicals suspected of being intermediates or cofactors in the conversion of glycogen to lactic acid. He confirmed earlier findings that phosphate promotes the process, and that hexose diphosphate (Harden-Young ester) is converted into lactic acid. He found that glucose is not utilized effectively unless there is added, Harden’s heat-stable coferment and a heat-labile factor from yeast juice which Meyerhof called hexokinase (2195).

Otto Fritz Meyerhof (DE-US) demonstrated that glycogen in muscle is split by enzymes into two molecules of lactic acid per molecule of hexose. He stressed the identity of the reactions of glycogen in muscle and glucose in yeast. These experiments laid the foundation for the development of the Embden-Meyerhof-Parnas theory of glycolysis (2193-2196).

Hans Karl August Simon von Euler-Chelpin (DE-SE) Hjalmar Ohlsén (SE), and Sixten Kullberg (SE) had earlier postulated that an enzyme they named phosphatase acts upon a mixture of phosphate and the intermediate products of alcoholic fermentation, causing the formation of a carbohydrate ester (3267, 3268). 

Hans Karl August Simon von Euler-Chelpin (DE-SE), Ragnar Vestin (SE), Henry Albers (SE), Fritz Schlenk (SE), Karl August Simon (SE), Erich Adler (SE), Otto Heinrich Warburg (DE), and Walter Christian (DE) determined that nicotinic acid is an essential part of the coenzymes NAD (also called DPN, diphosphopyridine nucleotide, cozymase I, and coenzyme I) and NADP (also called TPN, triphosphopyridine nucleotide, codehydrogenase II, and coenzyme II) (2829, 3263-3266, 3269, 3270, 3367). This was the first evidence that nicotinic acid, in the form of its amide, formed a part of the structure of a coenzyme. Absence of nicotinic acid leads to failure of certain enzymes to function normally. The particular enzymes that fail are those that make use of coenzymes with a nicotinic acid moiety.

Otto Heinrich Warburg (DE) and Walter Christian (DE) proposed the names diphosphopyridine nucleotide (DPN) and triphosphopyridine nucleotide (TPN) (3367).

Nicolaas Louis Söhngen (NL) discovered that some bacteria produce methane and others can use it as both a carbon and energy source (2950).

Frederick Gowland Hopkins (GB) concluded that the necessary precursor of epinephrine (adrenaline), a hormone that must be continuously formed, must be derived from the diet. He did not mention tyrosine, but apparently had this amino acid in mind as a precursor of some synthetic product important in metabolism. Hopkins introduced the idea that hormones are derived from digestion products of proteins (1565).

Ernst Joseph Friedmann (DE) was the first to characterize a hormone by revealing its chemical formula (epinephrine; adrenaline) (1191).

Paul Julius Mobius (DE), who found that the blood of a sheep that has suffered operative removal of the thyroid gland can neutralise the action of the thyroid hormone.

Hans Winterstein (DE) determined the capacity of the central nervous system to consume oxygen (3552).

Robert Heath Lock (GB) and Alfred Henry Sturtevant (US) were the first to clearly express the relationship between linkage and exchange of parts between homologous chromosomes (1984, 3042).

Leonard Doncaster (GB) and Gilbert H. Raynor (GB) were the first to discover a sex-linked character. They described a trait called lacticolor segregating among wild female currant moths (Abraxas grossulariate) but not among males (870). 

William Bateson (GB), Reginald Crundall Punnett (GB), and Leonard Doncaster (GB) found that the female moth is heterogametic and the male, homogametic (210, 869).

The sex-linked, recessive inheritance of lacticolor was not understood until it was recognized that, in Abraxus and other Lepidoptera, the female is the heterogametic sex, not the male. See, Bridges, 1916.

Craig W. Woodworth (US) was the first to breed Drosophila in quantity, and it was he who suggested that William Ernest Castle (US) use Drosophila as experimental material for genetic studies.

William Ernest Castle (US), Frederic Walton Carpenter (US), Alonzo Howard Clark (US), Samuel Ottmar Mast (US), and William M. Burrows (US) performed the first genetic study using Drosophila as an experimental animal (545). 

Edward Ernest Tyzzer (US) observed intranuclear inclusions in cells infected by varicella virus (3167). 

Erwin Bauer (DE) demonstrated graft transmission of abutilon mosaic and several other viruses, which cause variegation, or infectious chlorosis in woody plants (228, 229).

Adelchi Negri (IT) showed that vaccinia virus, the vaccine for the dreaded smallpox caused by variola virus, is filterable (2316).

Eduard V. de Freudenreich (DK) and Sigurd Orla-Jensen (DK) isolated and characterized propionic acid bacteria (790).

Jules Jean Baptiste Vincent Bordet (BE) and Octave Gengou (FR) isolated the causative agent of whooping cough, Haemophilus pertussis (now Bordetella pertussis) and devised a method to immunize against it (363, 364).

Thorvald Johannes Marius Madsen (DK) and Bjorn Kristensen (DK) proved that Bordetella pertussis is the etiological agent of whooping cough (1834, 2056-2058).

Pearl Louella Kendrick (US) and Grace Eldering (US) cultured Bordetella pertussis in BG medium containing sheep’s blood then developed a vaccine for whooping cough (1739).

Pearl Louella Kendrick (US) and Gordon C. Brown (US) combined vaccines for diphtheria, whooping cough, and tetanus into the single DPT shot used today (445, 1738). 

Thomas Lane Bancroft (GB-AU) showed that the mosquito Stegomyia fasciata (Aedes aegypti) is the carrier for the dengue-fever pathogen (154).

John Ashburton Thompson (AU) arrived at a theory of plague that involved or necessitated transmission by fleas (3103).

The Advisory Committee of the India Plague Commission (GB) concluded that the plague is carried from one rat to another and from (649) rat to man by Xenopsylla cheopis (Rothschild), the rat flea (638). They also determined that the plague bacilli multiply in the stomach of the flea (639). Early members of the Commission were Charles Martin (GB), George Lamb (GB), William Glen Liston (GB), George Ford Petrie (GB), Sydnet Rowland (GB), Thomas Henry Gloster (GB), M. Kasava Pai (GB), V.L. Manker (GB), P.S. Ramachandrier (GB), and C.R. Arvi (GB).

Aldo Castellani; Count of Chisiamaio (IT) discovered the spirochete of spirochetal bronchitis (Castellani’s disease) (539).

Samuel Taylor A. Darling (US) was the first to clinically describe the fungal disease histoplasmosis. He thought the etiological agent was protozoal and named it Histoplasma capsalata (774-777).

Henrique da Rocha-Lima (BR) concluded from histological studies that Darling’s agent was fungal (749). Its name would become Histoplasma capsulatum.

Cecil James Watson (US) described the first case of disseminated histoplasmosis reported in the continental United States (3386).

Katharine Dodd (US) and Edna H. Tompkins (US) reported the first intra vitam diagnosis. The diagnosis was made from the blood during life by finding the characteristic parasite in the large mononuclear cells (853).

William DeMonbreum (US) described the dimorphic nature of Histoplasma capsulatum after being surprised by the growth of a mold from patient tissues displaying yeasts (816).

Amos Christie (US) and J. Cyril Peterson (US) found that histoplasmosis is endemic to the Ohio River Valley (584).

Chester W. Emmons (US) demonstrated that it is a soil saprophyte (1019).

Chester W. Emmons (US) and Libero W. Ajello (US) discovered its relationship to bats and avian habitats respectively (40, 1020).

Maurice Nicolle (FR) and Felix Mesnil (FR) introduced the use of trypan-blue to treat trypanosomiasis (2357).

Georgii Norbertovich Gabritschewsky; Georgii Norbertovich Gabrichevskii (RU) used preparations of killed streptococci to vaccinate patients against scarlet fever (1206).

Friedrich Voelcker (DE) and Alexander von Lichtenberg (DE) devised retrograde pyelography (introduction of radiopaque medium into the kidney pelvis by way of the ureter) for the study of the urinary tract (3234).

August Paul Wasserman (DE), Albert Ludwig Siegmund Neisser (DE), Carl Bruck (DE), Arthur J. Schucht (DE) and Felix Plaut (DE) discovered the presence of antibodies to syphilis antigen in the serum of syphilitic monkeys; then working with A. Schucht (DE) they demonstrated similar antibodies in the blood of human syphilitics. This became the basis of a Complement Fixation Test for anti-syphilitic antibodies called the Wasserman Test (3380-3382). This work is considered to include the first isolation of what Pangborn would call cardiolipin.

Karl Landsteiner (AT-US), Rudolf Müller (AT), and Otto Pötzl (AT) discovered the working principle of the Wassermann reaction (1881).

Mary C. Pangborn (US) coined the term cardiolipin to denote a lipid isolated from beef heart, and possessing antigenic properties in the complement-fixation test (2455).

Rudolf Müller (AT) and Moriz Oppenheim (AT) developed a complement fixation test for serodiagnosis of gonorrhea (2283).

Alfred Wolff-Eisner (DE) coined the terms pollen disease and pollen sensitivity. He suggested that hay fever might be a form of hypersensitivity or anaphylaxis in the nose (3567).

The following is taken from Paul Ehrlich’s speech at the dedication of the Georg Speyer-Haus in Frankfurt Germany. It was a privately endowed institute dedicated entirely to the study of chemotherapy. Ehrlich was its first director (he was simultaneously the director of the Institute for the Investigation and Control of Sera). A portion of the address is repeated here so the reader can sense the working of the greatest medical mind of the nineteenth century. 

“Since throughout my whole life, my thoughts have been most intimately interwoven with the same fundamental ideas as are now due to give a lead to the enterprises of the Speyer-Haus, I ask for your indulgence, and hope that you will not impute it to me as lack of modesty, if now, somewhat unconventionally, I retrace some of my personal memories and unfold to you the story of the origin of my own ideas. I would not have done this, had I not thought that such a developmental presentation would be the simplest way of making clear to you the nature of the problems, which give to this institute its special character.

It was some 33 years ago—I was then still quite a young student—when I came across a publication on lead poisoning, by Heubel. In order to elucidate the nature of this poisoning, the author had estimated quantitatively the lead content of the liver, the kidney, and the heart, and had discovered that there were remarkable differences in the amount of lead to be found in the various organs. When he immersed organs of normal animals in dilute lead-solutions and subsequently subjected the organs to chemical analysis, he believed that he obtained exactly the same differences. This experiment seemed to me, at that time, a revelation. The possibility emerged that this technique might be used also to ascertain the sites of action of poisons. That lead was found to be present in certain organs, e.g. the brain, provided merely the starting point for the investigation. The brain is a large structure and is made up of many constituents—cells, fibers, etc. The real problem was to determine in which of these cells the poison was stored. The immediate effect of this idea became almost a disaster for me, since it disrupted, more than a little, the normal course of my studies, without bringing me any nearer to the desired goal. I had nothing but failure from any of my attempts to detect, with the aid of the microscope, the presence of metals applied in high dilutions, and I was not a step further forward.

It became necessary, therefore, to approach the task from a more general standpoint and, first of all, to obtain some insight into the manner and the method of the distribution of substances within the body and its cells. When we see that certain poisons, e.g. strychnine, produce spasms which originate from the nerve cells of the spinal cord, and when we see that the American arrow-poison, curare, causes a paralysis of the extreme nerve-endings, which extend to the muscle, the possibility becomes clear that these effects can be caused only through strychnine making a direct connection with the cells of the spinal cord and curare with the ultimate finest nerve-endings. Conclusions such as these seem at once to be self-evident—to be, as I might express it, part of a man’s inborn inheritance. They can be traced back into antiquity and have assumed importance in several of the by-paths of medicine. They appear quite clearly, for example, in a statement of a mediaeval physician, who thought that drugs must possess spicules, by the aid of which they are able to anchor themselves in the various organs. But these ideas, like so many axioms, were as easy to express, as they were difficult to prove; and this may well be the reason why they were completely ignored in the practical study of drugs and, despite their fundamental importance, have played no role in the development of pharmacology. If one had wished to put the storage-axiom to the test, one would have had to demonstrate, by the use of the microscope that the poison under consideration was, in fact, present at these minute sites. This, however, was found to be impracticable.

It was, therefore, necessary to begin the investigation by an entirely different line of approach, and to utilize substances that, like dyes, are easily detected, even by the naked eye; it would suffice to remove and examine a small piece of an organ of an animal after it had been killed. A glance through the microscope would then give evidence immediately, and in the finest detail, concerning the distribution of the substance.

The fact that a large number of dyes exists which differ widely in their constitution, and the fact, too, that some of these dyes exhibit a high degree of toxicity, made such endeavors all the more feasible, and thus the method originated which, nowadays, is known briefly as vital staining. I do not intend to dwell on the wealth of results, which this technique has yielded, especially in microscopic anatomy, but will just refer to the fact that the various dyes show quite characteristic differences in their distribution and localization. Thus, for example, methylene blue causes a really wonderful staining of the peripheral nervous system.

If a small quantity of methylene blue is injected into a frog, and a small piece of the tongue is excised and examined, one sees the finest twigs of the nerves beautifully stained, a magnificent dark blue, against a colorless background.

With many vital stains it is therefore extremely easy, almost at a glance, to ascertain their distribution in the different parts of the body—which parts they favor, which organs they avoid.

Of course, staining of the dead organs and tissues has for a long time been one of the most important tools of histological research. But staining of this kind can only give information concerning purely the anatomical structure of the tissues. If, however, one wishes to acquire an understanding of the properties and functions of the living cell, then the staining reaction must be made to take place in the body itself, i.e., one must stain the living substance. In this way one can gain an insight into the relationship between the individual tissues and certain dyestuffs. I have denominated this affinity of the stains and other foreign substances by adjectives with the ending tropic, and, for example, describe a dye which stains only a single specific tissue as monotropic, and speak thus of neurotropic and myotropic substances, etc., while substances which have the capacity to stain several tissues should be called polytropic. In 1866, in my early study “ On the methylene-blue reaction of the living nerve-tissue,” I had already indicated the lines along which a further analysis of the process should proceed. Two questions had first of all to be answered:

1. Why does methylene blue stain nerve cells?

2. Why are nerves stained by methylene blue?

As to the first question, the answer, by virtue of the nature of the problem, had, of necessity, to be in terms of pure chemistry; and I was able to prove that the nerve-staining property of methylene blue is conditioned by the presence of sulfur in the methylene-blue molecule. Synthetic chemistry has, in fact, given us a dye, which, apart from the absence of sulfur, corresponds exactly in its chemical constitution to methylene blue. This is Bindschedler’s green. With the absence of sulfur, there is associated the inability to stain living nerves. The interest of the second question was heightened by the circumstance that, in higher animals, not all the nerve endings are stained by methylene blue. I have shown it to be probable that these differences between the individual nerve endings are not due to different degrees of avidity for methylene blue, but rather to certain associated environmental conditions; for bluing of the nerves is intimately associated with the degree of oxygen saturation, inasmuch as it is precisely at those places which are best supplied with oxygen that staining of the nerve endings by methylene blue also occurs. Further, one can easily ascertain that the nerve fibers that stain have also an alkaline reaction; and thus oxygen saturation and alkaline reaction provide the conditions, which make possible the staining of nerve endings by methylene blue. Just as methylene blue accumulates only in alkaline fibers, so one must suppose, in the light of the investigations of Lieberkühn and Edinger, that certain other stains, such as alizarin blue, would stain the acid regions. One is, therefore, compelled to differentiate between alkaline, acid and also neutral fibers, and it is evidently to such differences, in conjunction with the degree of oxygen saturation, that the determinant role must be ascribed, in regulating the distribution and action of injected substances among the particular regions of the nervous system. It seemed, moreover, according to my earlier investigations on the methylene-blue staining of the nerve fibers, that an irreversible combination very soon takes place between dye and certain constituents of the nerve substance, since one can see that intensely blue granules appear in the axis cylinder, a phenomenon which may well be intimately associated with the fibrillic acid recently described by Bethe.

Very special conditions govern the uptake of dyes by the brain. The early anatomists, themselves, noticed that, even in the most severe jaundice, the brain remains snow-white, while all the other tissues are of a deep orange tint. I obtained this same effect on introducing into animals a large number of synthetic dyes, all of which, however, were alike in containing an acid group, such as the sulphonic acid radicle. In contrast to this, a large number of basic dyes, which, like the alkaloids, form salts from acids, stain the brain very effectively. I have assumed that the reason for this behavior is that the alkalinity of the blood plays a decisive role. On this basis, it is now possible to look at all these phenomena from a common point of view. The difference in the behavior of acid and alkaline dyes may accordingly be ascribed to the fact that the former are chiefly bound in the blood in the form of salts, whereas the latter remain free. Thus, the brain plays the same role as does the ether in the method of recognizing poisons devised by Stas-Otto; this method, as is well known, depends on the fact that basic substances, such as alkaloids, are bound in acid solution and are, on that account, difficult to extract, whereas they can easily be shaken out with ether from an alkaline solution. I was, in fact, able to confirm this idea experimentally, for if one introduces acid groups, e.g. the sulphonic acid radicle, into neurotropic stains, then the neurotropic property of the resulting derivatives is immediately abolished. We can similarly explain the fact that toxic substances are so often weakened in their toxic properties by the introduction of a sulphonic acid radicle into the molecule. The accumulation of the toxic agent in the central nervous system is made impossible, merely by the introduction of this sulphonic acid radicle.

The analogy between the roles played, respectively, by the brain and by ether, in the storage of dyes in the one case and in the method of identifying poisons in the ether, is further emphasized by the fact, discovered by me, that neurotropic and lipotropic properties, as a rule, go together, i.e., that those dyes which are taken up by the brain are also deposited in adipose tissue. This similarity in the behavior of the adipose and nervous tissues finds a simple explanation in the fact that the brain contains an abundance of fat-like substances—myelin and lecithin. Fat and brain, therefore, behave in the body exactly as ether does in the extraction of alkaloids. This theory, moreover, many years after the publications dealing with my work on it, was taken up again by Hans Horst Meyer and Overton, as the lipid-theory, it plays today an important role in medicine.

These observations, based on my work with dyes, I developed also, during the years 1886 and 1887, in relation to a series of remedies. I demonstrated that thallin, like a large of dyestuff, is lipotropic. In order to detect thallin in the tissues, I made use of the property that, even in very dilute solutions, it is transformed by oxidizing agents (ferric chloride) into a dark green dyestuff. If this is immediately fixed, in statu nascendi, in an insoluble form, it is then easy to obtain an insight into the distribution of the thallin. The pronounced affinity of thallin for adipose tissue causes the thallin to be held for a long time in the body; and this long retention of so readily oxidizable a substance is explained by my discovery that there is no free oxygen in adipose tissue, but that this, on the contrary, has a maximal reducing power. All these observations led me to the view that the hitherto dualistic approach to the problem of the connection between chemical constitution and pharmacological action has been much too narrowly conceived, and that there exists another and, indeed, decisive element which must be considered—the distribution in the body. My investigations have shown that the distribution, i.e., the selective affinity for certain organs and systems, is a function of the chemical constitution.

But the establishment of the existence of this relationship between constitution, distribution and action fulfilled only one part of the program, which I had planned for myself. For an action produced on an organ, the first requirement is the fixation of chemical substances; but the simple storage of substances of any kind is not of itself enough to cause specific toxic effects. This requires a second determinant factor to be present in the chemical substance. With the alkaloids, which we will consider first, the conditions are very similar to those, which had already been observed with the simpler dyestuffs. In these there are two different chemical constituents which are responsible for the dying property, a so-called chromophore group and, further, the auxochrome groups. In exactly the same way, one must postulate, when considering the alkaloids, that in the constitution of these powerfully acting substances two different factors must be distinguished: (1) a selective group which governs distribution, and (2) a pharmacophore group which evokes the specific activity. You will allow me, perhaps, to clarify this with an example. As is well known to you, cocaine, which, in medicine, plays so important a role as a local anesthetic, is the benzoyl derivative of an ecgoine ester. A large number of chemical homologues of cocaine can be synthesized by replacing the benzoyl radicle by those of other acids, e.g. of acetic acid or formic acid. All the substances obtained in this way are, by virtue of their chemical nature, homologues of cocaine, and all these different cocaines follow the same pattern of distribution in the body, because they belong, chemically, to the same class. But of all these substances, only one, the benzoyl-cocaine obtained from the coca plant, acts as a local anesthetic; and from this it is immediately obvious that the benzoic acid residue is the source of the specific action, and thus, that the benzoyl radicle functions here as the anaesthesiophore group.

The science of immunology provides the most striking examples of the relation between distribution and action. It has been found in this connection that the group, which is responsible for the distribution of bacterial poisons, which I have called the haptophore group, is a quite separate complex, and that the toxic action is attributable to the presence of a second group, the usually very unstable toxophore group. A still further differentiation between the factors of distribution and of activity is to be found if we take into consideration such cell poisons (hemolysins and bacteriolysins) as are present even in a normal blood serum, or are produced by immunization. For, in the case of these, each of the two properties is connected with a special molecule, one of which, called the amboceptor, is the carrier of the haptophore group, and the other, called the complement, that of the toxophore group. The hemolytic action of snake venom follows the same pattern. The factor contained in the snake venom represents solely the distributive component, whilst the appropriate pharmacophore group is present in lecithin. Neither snake venom nor lecithin is able, of its own accord, to destroy the blood cells. On the other hand, the product formed from them, the snake lecithide, corresponds, as was shown by Kyes, to a toxin, the haptophore group of which comes from snake venom and toxophore complex from the lecithin.

The concepts, which have thus been developed, indicate the direction, which must be followed in the construction of new organotropic medicaments. It will, therefore, be on of the main tasks of the new institute to persevere along this path; and this entails, in the first instance, the discovery of substances and chemical groups, which have an affinity for particular organs. The organotropic substances must then be furnished with pharmacophore groups, which will bring about a therapeutic and pharmacological activity. We intend, as it were, to use certain chemical complexes as vehicles to carry appropriate pharmacophore groups to the desired types of cell. To begin with, however, the main emphasis will be put on the haptophore group, the distributive factor. For this represents the conditio sine qua non for any therapeutic action.

But the theoretical problem represents only one aspect of our objective; on the other hand, our main effort will be directed to the discovery of new, rational, curative remedies. As you are aware, the study of medicaments, or pharmacology, is a long-established field of research, which has been cultivated and developed in numerous institutes. But most pharmacological research is directed merely to determining the effects, on animals in good health, of the substances, which are used as remedies, and to fix the limits of their safe administration in the clinic, by observations on their side effects and their toxicity. Prior attentions, therefore, given to those substances (especially alkaloids), which produce interesting and important toxic effects. These highly toxic substances, however (if one excludes a few alkaloids such as morphine, cocaine, atropine, etc.), are frequently quite useless in clinical practice, and thus a large part of the research work is carried out in realms, which are remote from any practical application in medicine. Admittedly, one obtains information about the risks which excessive dosage and otherwise unsuitable methods of administering particular substances involve, and this, of course, is of the greatest importance. Application of drugs in practice must be based on toxicological examination, and it need not be emphasized that toxicology, as such, represents a thoroughly justified and necessary type of science, which may even be of the greatest importance in biology and physiology—the very foundation of our medical knowledge. But it seems to me that, with the line of approach so predominantly in this one direction, some of the most important tasks of pharmacology are pushed all too readily aside, and practical medicine does not receive sufficient benefit. We must certainly be grateful to those who have safeguarded our departure [on the voyage of discovery] with beacons against toxic action—but they have not charted our course into the open sea of curative medicine” (1918).

Karel Frederik Wenckebach (NL-AT) discovered the cardiac anatomical structure named for him: the Wenckebach bundle. It is the median bundle of the conductive system of the heart leading to the atrioventricular node (3426, 3427).

Charles Scott Sherrington (GB) coined the term proprioceptive as it refers to a sense of position and equilibrium (2896, 2897).

Henry Hallett Dale (GB) discovered the oxytocic or uterine-contracting effect of the posterior pituitary extract (755, 756).

Paul Carnot (FR) and Catherine DeFlandre (FR) proposed the idea that erythropoiesis is regulated by hormones. After conducting experiments on rabbits subject to bloodletting, they attributed an increase in erythrocytes in rabbit subjects to a hemotopic factor they named hématopoïetine (haemopoietin) (522).

Eva Bonsdorff (FI) and Eeva Jalavisto (FI) suggested that hématopoïetine be changed to erythropoietin because they found that it affects only the erythroid series (353).

Allan Jacob Erslev (DK-US) concluded that plasma from rabbits rendered anemic by bleeding contains a factor (erythropoietin) capable of stimulating red cell production (1035).

Leon Orris Jacobson (US), Eugene Goldwasser (US), Walter Fried (US), and Louis F. Pizak (US) detected the production of erythropoietin by the kidney (1644).

Takaji Miyake (JP), Charles K. Kung (US) and Eugene Wasserman (US) were the first to isolate erythropoietin; their source was human urine (2221).

Fu-Kuen Lin (CN-US) identified the erythropoietin (EPO) gene (1970, 1971).

Sylvia Lee-Huang (US) cloned and obtained expression of recombinant human EPO gene (1922).

Alfred Vogt (CH) described a form of uveomeningoencephalitis endemic in the Far East. A disease, usually occurring in adult life, in which severe bilateral inflammation of the iris (iridocyclitis), ciliary body and choroid of the eye is associated with relapsing meningoencephalitis, deafness, alopecia, depigmentation of the skin and eye, symmetrical vitilligo and poliosis (whitening of the ends of the hairs) (3236). It is called Vogt-Koyanagi-Harada syndrome.

Robert Bárány (AT-SE) devised the caloric test for labyrinthine function. If the normal ear is irrigated with hot water at 110° to 120° F, a rotary nystagmus is developed away from the irrigated side. There is no nystagmus if the labyrinth is diseased (170).

Robert Bárány (AT-SE) also developed a clinical pointing test for demonstrating the existence of disturbances of the vestibular apparatus and its paths in the brain. The patient is asked to point at a fixed object with a finger or a toe with the eyes alternatively open and closed. With eyes open the patient holds his arm upwards and then lowers it to a horizontal position, so that it points at the investigator's index finger. In damages of vestibularis there are disturbances of coordination and the patient points past (171-173).

Lodewijk (Louis) Bolk (NL) investigated the comparative anatomy of the cerebellum and its nerves. He determined that muscle coordination is localized to this portion of the brain (345, 346, 348).

Jules Joseph Déjérine (CH-FR) and Gustave Roussy (FR) described the Déjérine-Roussy or thalamic syndrome (superficial persistent hemianesthesia, mild hemiplegia, mild hemiataxia, complete astereognosis, severe pains in the hemiplegic side, and choreo-athetoid movements in the members of the paralyzed side) (807).

Alois Alzheimer (DE), in 1907, wrote, “A woman, 51 years old, showed jealousy toward her husband as the first noticeable sign…. Soon a rapidly increasing loss of memory could be noticed. She could not find her way around in her own apartment…. Her entire behavior bore the stamp of utter perplexity. She was totally disoriented to time and place…. The generalized dementia progressed…. After 4 1/2 years…death occurred…. The autopsy revealed a generally atrophic brain without macroscopic lesions…. Scattered through the…cortex…one found miliary foci that were caused by the deposition of a peculiar substance.” This is from his monumental work on Alzheimer’s Disease for which he will always be remembered (55, 56).

Emil Wilhelm Magnus Georg Kraepelin (DE) named Alzheimer's disease in 1910 (1831).

George Washington Crile (US) was the first to describe radical neck dissection that encompasses the surgical removal of neck metastases contained between superficial and deep fascial layers of the neck (700).

George Washington Crile (US) and David H. Dolley (US) pioneered the use of high-dose epinephrine (adrenaline) in the resuscitation of an animal near death from anesthetics and asphyxia (703).

Christian J. Gauss (DE) and Bernard Krönig (DE) reported their successes with scopolamine-morphine anesthesia in obstetrics (twilight sleep) (1232-1234).

George Washington Crile (US), in August 1906, at St. Alexis Hospital in Cleveland, Ohio, performed the first successful transfusion of blood from one human to another in the United States. This was the first human-to-human blood transfusion in which Landsteiner’s discovery of blood types was used to match the donor and recipient (701).

Edward Konrad Zirm (AT) performed the first successful cornea transplant in humans. The patient had sustained alkali burns. The donor was an 11-year-old boy whose eye was enucleated because of penetrating scleral injury (3620).

Vladimir Petrovich Filatov (RU) and M.A. Bajenova (RU), in 1912, greatly improved the success rate in corneal transplants when he showed that material from a fresh cadaver is just as satisfactory as that from a living person and that eyes can be banked in a refrigerated, sterile receptacle. He used an egg membrane to adhere the graft (1097, 1098).

Mathieu Jaboulay (FR) carried out the first attempts at human kidney transplantation. On January 22, he transplanted a porcine kidney to the brachial vessels of a woman suffering from nephrotic syndrome. Three months later he repeated the experiment with a goat kidney (1633). Neither kidney xenograft lasted more than several hours.

Alexis Carrel (FR-US) performed a double nephrectomy followed by transplantation of both kidneys from another animal. He noted that the recipient animal could secrete almost normal urine and live in good health for at least a few weeks (526).

Harold Neuhof (US) performed a xenotransplant of lamb kidney into a human in acute renal failure. The patient survived for nine days (2347).

Yu Yu Voronoy (UA) transplanted human kidneys (3335). 

Charles A. Hufnagel (US), Ernest Landsteiner (US), and David M. Hume (US), in 1947, performed a human renal transplant. The first patient was a young woman in renal failure following obstetrical complications. The purpose of the transplant was to provide temporary renal function until her kidneys recovered from acute tubular necrosis. The donor kidney was anastomosed in the antecubital space under local anesthesia using a cutaneous ureterostomy. The patient died a few months later of fulminating hepatitis secondary to pooled plasma infusions, which she had received in the course of her treatment. The temporary kidney transplant had been previously removed (2237).

David M. Hume (US), John Putnam Merrill (US), Benjamin F. Miller (US), and George Widmer Miller (US) performed nine cadaveric or free kidney transplantations in humans, eight to thigh and one to an orthotopic location. One thigh kidney transplant functioned for five months. No immunosuppression was used (1594).

J. Hartwell Harrison (US), John Putnam Merrill (US), Joseph Edward Murray (US), and Warren R. Guild (US), on 23 December 1954, transplanted a kidney from a healthy twenty-four-year-old individual to his twin brother suffering from severe renal disease (cross skin grafting established genetic identity). This was the first time in medical history that a normal healthy person was to be subjected to a major surgical operation not for his own benefit. Post-operatively the transplanted kidney functioned immediately with a dramatic improvement in the patient's renal and cardiopulmonary status. This spectacular success was a clear demonstration that organ transplantation could be life saving (1416, 2172). Some consider this to be the first truly successful kidney transplantation.

Joseph Edward Murray (US), Stanley Lang (US), Benkamin J. Miller (US), and Gustave J. Dammin (US) developed a reproducible renal transplant operation in dogs using intra-abdominal vascular anastomoses and a uretero-cystostomy for urinary drainage, placing the kidney in the lower abdomen. This has become the universal renal transplant procedure since that time. Complete functional studies of some of these autografted kidneys two years after transplantation proved them to be completely normal (2299).

Joseph Edward Murray (US), John Putnam Merrill (US), Gustave J. Dammin (US), James B. Dealy, Jr. (US), Carl W. Walter (US), Marcus S. Brooke (US), Richard E. Wilson (US), J. Hartwell Harrison (US), and Eli A. Friedman (US) performed a renal allograft from a human fraternal twin to a recipient preconditioned with a sublethal total body irradiation. This was the first long survival of an organ allograft, an objective not previously achieved in an animal model (2171, 2301). The patient subsequently led a full active normal life until he died of cardiac problems 25 years later.

Joseph Edward Murray (US), John Putnam Merrill (US), Gustave J. Dammin (US), James B. Dealy, Jr. (US), Guy W. Alexandre (US), J. Hartwell Harrison (US), Richard E. Wilson (US), Frank J. Takacs (US), and Edward B. Hager (US) carried out clinical trials on the efficacy of 6-mercaptopurine and azathioprine as immunosuppressive agents to prolong the survival rates of allograft kidney transplants. One patient, transplanted in April 1962, was treated with azathioprine following a cadaveric renal allograft. He survived over one year and was the world's first successful unrelated renal allograft (2173, 2300, 2302).

Jean Alban Bergonié (FR) and Louis Mathieu Frédéric Adrien Tribondeau (FR) presented the rationale for radiotherapy as follows: “The effect of radiations on living cells is the more intense: (1) the greater their reproductive activity, (2) the longer their mitotic phase lasts, and (3) the less their morphology and function are differentiated” (287).

The Congress of the United States enacted the Food and Drugs Act, the first federal statute prohibiting the misbranding or adulteration of food (643).

Alexandr Petrovich Karpinsky (RU) reported research on Devonian algae, the so-called charophytes. His study of the contemporary charophytes showed their closeness to extinct Devonian forms and indicated that they likely had a common ancestor (1714, 1715). 

George Reber Wieland (US) researched plant material derived from the Upper Jurassic and Lower Cretaceous beds of Maryland, Dakota, and Wyoming where he discovered the hermaphrodite nature of the bennettitean flower and recognized an affinity between the mesozoic cycadophyta and the angiosperms. The angiosperm with which he specially compared the fossil type was the Tulip tree (Liriodendron) and certainly there is a remarkable analogy with the magnoliaceous flowers, and with those of related orders such as Ranunculaceae and the water lilies (3462).

Charles William Andrews (GB), in 1900, discovered numerous early higher primate fossils in the Fayum Depression region east of Cairo, Egypt. These Eocene and Oligocene fossils include protomonkeys believed to be ancestral to Old World monkeys and thus in the lineage to hominids (73).

The Biochemical Journal was founded.

The Biochemische Zeitschrift was founded.


Polio turned into a major problem in the U.S., with about a thousand cases in New York in 1907, and another outbreak in 1911. The disease was recognized as contagious, but there was no understanding yet of exactly how it was spread. The first widespread outbreak, seriously affecting 26 states, occurred in 1916. About 7,000 deaths were recorded (1803).


Eduard Buchner (DE) was awarded the Nobel Prize in Chemistry for his discovery that fermentation can function independently of cell structure.

Charles Louis Alphonse Laveran (FR) was awarded the Nobel Prize in Physiology or Medicine "in recognition of his work on the role played by protozoa in causing diseases."

Paul Ehrlich (DE) had a fascination with dye affinity for specific cells going back to his days as a medical student at Strassburg. While there he devised a fuchsin stain, which could demonstrate lead in the tissues. Later this concept would reemerge in his interest in affinity of antitoxins for toxins and drugs for target microbes, which led to his discovery of arsphenamine (Salvarsan), a cure for syphilis.

Ehrlich and his colleagues had discovered that the dye trypan red killed the trypanosome, which causes sleeping sickness. Ehrlich kept looking for something better. He decided that the nitrogen atom combinations it contains cause the action of trypan red. Arsenic atoms resemble nitrogen atoms in chemical properties and, in general, introduce a more poisonous quality into compounds. By 1907 he and Sahachiro Hata (JP-DE) had synthesized 606 different compounds. Number 606, dihydroxydiamino-arsenobenzene hydrochloride, did not work very well against trypanosomes but later an assistant (H. Sachs) tested it against syphilis and found it to be deadly. It was called arsphenamine or Salvarsan, the latter being the name under which it was marketed. Today it is called arsphenamine. Ehrlich knew that dyes often exhibit exquisite specificity and reasoned that it might be possible to create a chemical which was very specific and toxic for a parasite and yet harmless to its host. He often referred to these chemicals as magic bullets. Ehrlich’s success represents the beginning of chemotherapy (a word he coined) as a laboratory science (965, 967-971, 974-976). 

Percival Hartley (GB), using liver tissue, was the first to isolate arachidonic acid (1427). 

Adolf Otto Reinhold Windaus (DE) and W. Vogt (DE) prepared histamine synthetically by the decarboxylation of histidine (3535). 

Friedrich Alfred Bauer (DE), Carl Alexander Neuberg (DE-US) and Benno Brahn (DE) discovered that inosinic acid contains a pentose (230, 2332, 2333).

A.V. Braun (DE) and Joseph Tcherniac (DE) prepared the phthalocyanine nucleus of a new class of dyes called the phthalocyanins from phthalimide and acetic andydride (406). These did not find use as biological stains until 1950 when alcian blue was used to stain acid mucins (2984).

Walter Morley Fletcher (GB) and Frederick Gowland Hopkins (GB) showed that, after being formed in muscular contraction, some lactic acid is oxidized to furnish energy for resynthesis of glycogen from the remaining lactic acid. They demonstrated rigorously that muscle contraction is accompanied by the anaerobic formation of lactic acid, which is removed aerobically, at a rate depending on the level of exposure to oxygen (1133).

Carl Franz Joseph Erich Correns (DE), gave the first experimental evidence that sex-difference behaved as a Mendelian character. The work was carried out using the dioecious plant, Bryonia where he found that the pollen was of two types, half male determining, half female-determining, while the eggs, in respect to sex, were alike. The male was heterogametic, while the female was homogametic (664).

Erwin Baur (DE) was the first to clearly demonstrate a lethal allele in Antirrhinum (snapdragon) (234). 

Svante August Arrhenius (SE) enriched immunology by observing that antigen-antibody reactions obey the law of mass action, emphasizing quantification, encouraging mathematical and graphic evaluation, applying physics and coining the term immunochemistry (92).

Eduard Pfuhl (DE) described how he had made use of the catalytic properties of spongy platinum to obtain anaerobic conditions for the culture of organisms (2532).

Patrick Playfair Laidlaw (GB) suggested the use of platinized charcoal and colloidal platinum for the same purpose (1864).

James McIntosh (GB), Paul Gordon Fildes (GB), and William Bulloch (GB) developed the highly successful 'McIntosh-Fildes Jar,' an anaerobic jar (2150).

John Hanna Brewer (US) and J. Howard Brown (US) devised a safe method of accomplishing anaerobiosis for culturing microorganisms. It used an electrically heated platinized catalyst in a closed system with illuminating gas or hydrogen (417).

John Hanna Brewer (US) devised a bacterial culture medium to which thioglycollate was added to maintain a reducing environment (415).

The modern anaerobic jar is based on that originally described by J. Howard Brown (US) and later modified by John Hanna Brewer (US), Anita A. Heer (US), C. Baxter McLaughlin (US) and Daniel L. Aligeier (US) in which palladium is used to catalyze the reduction of oxygen with hydrogen generated from sodium borohydride and water (416, 418, 447).

Hans Molisch (CZ) pioneered in isolating and describing a number of species of non-sulfur purple photosynthetic bacteria in pure culture. He demonstrated conclusively that such organisms do not produce oxygen and discovered the photoheterotrophic growth mode (2225).

Adolfo Ferrata (IT), Hans Ritz (DE), Arthur F. Coca (US), John Gordon (GB), Hugh Robinson Whitehead (GB), Arthur Wormall (GB), Herbert Joseph Rapp (US), A.B. Taylor (US), Myron A. Leon (US), Kusuya Nishioka (JP), William D. Linscott (US), Kozo Inoue (US), Robert A. Nelson, Jr. (US), Joerg Jensen (US), Irma Gigli (AR-US), Noboru Tamura (JP), Hans Joachim Müller-Eberhard (DE-US), Irwin H. Lepow (US), George B. Naff (US), Earl W. Todd (US), Jack Pensky (US), Carl F. Hinz, Jr. (US), and Anne L. Haines (US) made discoveries which revealed the numerous factors of the complement system in the blood (624, 1085, 1288, 1363, 1364, 1618, 1619, 1932, 1973, 2284, 2304, 2318, 2362, 2594, 2595, 2656, 3080).

Stanislas Josef Matthias von Prowázek (CZ) demonstrated that material from silkworms (Bombyx mori) suffering from the polyhedral disease, which the breeders called jaundice was infectious after the polyhedra were removed by filtration through many layers of filter paper. This pointed the way to the eventual realization that some insect diseases are caused by viruses. In this same paper he suggested that viruses might someday be useful in controlling insect pests (3328). These are now considered Baculovirus.

Giuseppe Ciuffo (IT) realized the viral nature of genital warts when he induced warts after autoinoculation of cell-free wart extracts (590).

Karl Bernhard Lehmann (DE) and Rudolf Otto Neumann (DE) started a formal manual for classification of bacteria in which for the first time staining reactions and the formation of the highly heat resistant endospores were considered formal diagnostic features (1925).

Raymond Jacques Adrien Sabouraud (FR) discovered that Epidermophyton inguinale could cause human dermatomycosis (2761).

Anatole Chauffard (FR) made original contributions to the understanding of the pathophysiology of the red cell abnormalities present in hereditary spherocytosis (574). This work led him to develop the osmotic fragility of erythrocytes test which finally enabled physicians to distinguish hepatic and hemolytic jaundice. RBCs from hepatic jaundice are much more resistant to lysis than those from hemolytic jaundice patients.

Clarence Cook Little (US) produced the first inbred strain of mice by carrying out brother sister matings for over 20 generations. The animals chosen carried recessive genes for dilution, brown, and nonagouti. Today this strain is called DBA (1311). He also established the black C57BL inbred strain of mice.

It was Clarence Cook Little who, with funds from the Jackson and Ford families, established the Jackson Laboratory at Bar Harbor, Maine during the late 1920’s. This laboratory is one of the world’s most important sources of inbred animals for research.

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) proposed that human life could be prolonged by introducing bacteria into the diet which would compete with the proteolytic types present in the colon. He recommended that Bacillus bulgaricus, an organism he isolated from sour milk in Bulgaria, be used for this purpose. He found that if this organism was introduced in sufficient numbers it would replace the putrefactive bacteria normally present in the colon. He also determined that its growth was promoted by lactose (2178).

Ludwig Halberstäedter (DE-IL) and Stanislas Josef Matthias von Prowázek (CZ) were the first to describe the inclusions (Halberstäedter—Prowázek bodies) found in cells of a trachoma infection. They thought the organism was closely related to the smallpox virus (1370, 1371).

Hideyo Noguchi (JP-US) established the etiology of trachoma when he isolated Bacterium granulosis from cases of trachoma then inoculated it into monkeys and obtained granulomatous lesions of the conjunctiva (2374).

Tang Feifan (), Yung T. Huang (), H.L. Chang (), and K.C. Wong () were the first to isolate Chlamydia trachomatis as an etiological agent of trachoma (3074).

Erwin Frink Smith (US) and Charles O. Townsend (US) in describing Agrobacterium tumefaciens as the causative agent of crown gall in plants wrote the following: 

“For two years the writers have been studying a tumor or gall which occurs naturally on the cultivated marguerite, or Paris daisy. It has been difficult to isolate the organism and to demonstrate it unmistakably in stained sections. Recently the bacteria (seen in small numbers in the unstained tissues on the start) have been plated out successfully. With subcultures from poured plate colonies, thus obtained, the galls have been reproduced abundantly and repeatedly during the last few months, the inoculations having been made by needle-pricks. From galls thus produced the organism has been reisolated in axenic culture and the disease reproduced, using subcultures from some of the colonies thus obtained and puncturing with the needle as before. More than 300 galls have been produced by puncture inoculations. Under the most favorable conditions (young tissues) the swellings begin to be visible in as short a time as four or five days, and are well developed in a month, but continue to grow for several months, and become an inch or two in diameter.

In some of our experiments one hundred percent of the inoculations have given positive results (40 punctures out of 40 in one series; 62 punctures out of 62 in another), while the check plants have remained free from tumors, and also, in nearly every case, the check punctures on the same plant. In the two series just mentioned there were 110 check punctures on the same plants, all of which healed normally and remained free from galls. Old tissues are not very susceptible. The tumors grow rapidly only in young fleshy organs. The organism attacks both roots and shoots. It frequently induces abnormal growths on the wounded parts of young cuttings. Its power to produce hyperplasia is not confined to the marguerite. Well-developed small tumors have been produced in a few weeks on the stems of tobacco (Nicotiana tabacum), tomato and potato (Solanum tuberosum) plants and on the roots of sugar beets (Beta vulgaris). More interesting economically is the fact that galls closely resembling the young stages of crown gall have been produced on the roots of peach trees by needle-pricks, introducing this organism. In eighteen days these growths have reached the size of small peas, the checks remaining unaffected. It is too early, perhaps, to say positively that the cause of the widespread and destructive crown-gall of the peach has been determined by these inoculations, but it looks that way. Of course, the most that can be affirmed absolutely at this writing is that we found an organism which when inoculated into the peach produces with great regularity galls which in early stages of their growth can not be distinguished from crown gall. The matured daisy galls look astonishingly like the peach gall. Numerous experiments which ought to settle the matter definitely in the course of the next three months are now under way. In the best series of experiments on peach roots (that inoculated from a standard nutrient agar culture five days old) 14 groups of needle-punctures (5 in each group) were made on nine trees, 13 tumors resulting. The fourteenth group was on a weak tree which did not leaf out, and might therefore be left out of the count. In that case we have 100 per cent of infections. On the roots of nine young trees from the same lot, held as checks, 75 punctures were made, using a sterile needle, but no galls resulted. In another series of nine peach trees inoculated at the same time as the preceding and examined on the twenty-third day, 75 per cent of the punctures had yielded galls (9 tumors on 7 plants). These roots were inoculated by needle-pricks from a culture believed to be rather too old (glycerin agar streak 6 days), but the plants were set out again, and it is not unlikely that galls will finally develop on the roots of the other two plants. The plants, inoculated and uninoculated, were set, immediately after making the needle-punctures, in good greenhouse soil, in new ten-inch pots, and have been subject to the same conditions as to light, heat and water” (2931).

Rudolf Massini (DE) isolated a mutant strain of Escherichia coli that he called mutabile and that, in contrast to ordinary Escherichia coli strains, was unable to ferment lactose. The metabolic defect of this lactose-negative strain could be readily observed by plating the strain on a special sugar-utilization indicator medium called EMB agar. This agar contains a nutrient broth medium containing the dyes eosin yellow and methylene blue and the sugar whose fermentation is to be tested. On EMB agar, a bacterium able to ferment the sugar produces a dark red colony, whereas a nonfermenting bacterium produces a white colony. (The red and white colors reflect alternative states of the indicator dyes, which in turn signal the respective chemical changes produced in the agar during bacterial growth with or without fermentation of the test sugar.) Thus when the lactose-negative Escherichia coli mutabile is plated on EMB-lactose agar, its colonies are white. Upon prolonged incubation of these plates, however, isolated dark red spots or papillae appear on the colonies. Upon picking and replating the bacteria present in the red papillae on EMB-lactose agar, Massini found that these bacteria had regained the capacity to ferment lactose—that is, they had become lactose-positive Thus during the growth of the colony initiated by a lactose-negative bacterium, mutations of the type lactose-negative tolactose-positive had taken place, and these gave rise to subclones of bacteria to which the capacity for lactose fermentation, characteristic of ordinary Escherichia coli had been restored (2111). In Massini’s day it did not seem possible to prove conclusively the genetic nature of these changes.

Edward Ernest Tyzzer (US) discovered Cryptosporidium, a coccidian protozoan parasite, in the gastric mucosa of mice (1743, 3168-3170).

F.A. Nime (), J. D. Burek (), David L. Page (US), Myron A. Holscher (US), John Howard Yardley (US), John Lawrence Meisel (US), David Rhodes Perera (US), Criss Meligro (US), and Cyrus E. Rubin (US) reported cases of Cryptosporidium parvum infections in humans (2157, 2361). It affects the intestines and is typically an acute short-term infection. It is spread through the fecal-oral route, often through contaminated water. From 1981 onward, numerous new cases began to be recognized in AIDS patients where the symptoms are particularly severe and often fatal.

Ross Granville Harrison (US), Milton J. Greenman (US), Franklin P. Mall (US), and Clarence M. Jackson (US) cultivated amphibian spinal cord in a lymph clot, thereby demonstrating that axons are produced as extensions of single nerve cells (1420, 1421, 1423) Some people consider this work as the origin of modern tissue culture (See Justin Jolly, 1898). 

Henry V. Wilson (US) demonstrated that if cells from two different species of sponges are teased apart then mixed together the cells recognize their own species, congregate together, and ignore the cells of the other species (3524).

Edward Babák (CZ) reported that the size of the external gills of the frog are increased by prolonged hypoxia and lessened by prolonged hyperoxia of ambient water (119).

Alfred Wolff-Eisner (DE), in an attempt to explain the origin of contact-type immune reactions, proposed that dermatological problems result from the complexing of medications with the patient’s tissues (self) (3568). Later experiments would prove him correct.

Béla Schick (HU-AT-US) accurately postulated the immunological origin of the delayed sequelae to streptococcal infections, which include rheumatic fever and glomerulonephritis. Like serum sickness, they are part of a systemic Arthus-type reaction, and hence are diseases caused by circulating immune complexes (2815, 2816).

Ludvig Hektoen (US) described what would become the major and minor crossmatches for blood (1459). He later suggested that the safety of blood transfusions might be improved by crossmatching blood between donors and patients to exclude incompatible mixtures.

Reuben Ottenberg (US) performed the first human-to-human blood transfusion using blood typing and crossmatching. Over the next several years he successfully used the procedure in 128 cases, virtually eliminating transfusion reactions (2427).

Reuben Ottenberg (US) observed the Mendelian inheritance of blood groups and recognized the universal utility of group O donors (2428).

Ivar Wickman (DE) was the first to produce evidence confirming the infectious nature of poliomyleitis (3454).

Wilhelm Türk (AT) provided the first case description of complete agranulocytosis (3159).

Joseph Marek (HU) described a disease in adult cockerels, which were affected by paralysis of the legs and wings. He called it neuritis interstitialis or polyneuritis (2093). There is little doubt that this is the first clinical description of what became known as Marek’s disease (MD). Poultrymen call it range paralysis.

Anthony E. Churchill (GB) and Peter Martin Biggs (GB) isolated a herpes virus associated with the disease and proved it to be the etiological agent (586, 587).

Maurice Ralph Hilleman (US) developed a vaccine to Marek’s disease. It became the first practical vaccine against a tumor disease of any type in any species (1527).

Simon Flexner (US) and James Wesley Jobling (US) produced a serum that remained the best treatment for cerebral spinal meningitis until the sulfa drugs were introduced (1135-1137).

George Hoyt Whipple (US) described a disease characterized by an accumulation of granular material in the walls of the small intestine and lymph nodes. He called it lipodystrophia intestinalis. Others would later name it Whipple’s disease (3443).

Chevalier Jackson (US) introduced the bronchoscope into the practice of medicine (1635). The introduction probably took place ca. 1899.

Arthur Robertson Cushny (GB) and Charles Wallis Edmunds (US) published the first case report of atrial fibrillation. The patient was 3 days post-operative following surgery on an "ovarian fibroid" when she developed a "very irregular" pulse at a rate of 120 - 160 bpm (743).

Friedrich Jamin (DE) and Hermann Merkel (DE) published the first röntgenographic atlas of the human coronary arteries. It contained a study of 29 hearts in which the coronary arteries were injected with a suspension of red lead in gelatin (1652).

Thomas Peel Dunhill (AU) performed his first thyroid lobectomy under local anesthesia for toxic goiter. He advocated a bilateral attack on the thyroid and thyroidectomy in the thyrocardiac patient (920).

Anton von Eiselsberg (AT) performed the first operation on a patient with adiposogenital syndrome (3262).

William Arbuthnot Lane (GB) introduced the ‘no-touch technique’ in open reduction and plating of long bone fractures by “Lane's steel plates” (1888).

Anton von Eiselsberg (AT) and Otto Marburg (AT) performed the first successful resection of an intramedullary spinal cord tumor in 1907 (3261).

Alexander G. Ruthven (US) wrote a pioneering paper in ecology based on field studies in the American Southwest (2739).

Charles Henry Turner (US) was the first to prove that insects can hear and distinguish pitch and that cockroaches learn by trial and error (3160-3165).

Alfred Adler (AT) introduced the concept of inferiority complex and the method of compensation needed to overcome it (27).

Lightner Witmer (US) coined the phrase clinical psychology (3554).

USDA's Pure Food and Drug Act became effective. The Pure Food and Drug Act of June 30, 1906, is a United States federal law that provided federal inspection of meat products and forbade the manufacture, sale, or transportation of adulterated food products and poisonous patent medicines (1310).

Archiv für Geschichte der Medizin was founded.

Gesellschaft für Morphologie und Physiologie was founded


“Treasure your exceptions! When there are none the work gets so dull that no one cares to carry it further. Keep them always uncovered and in sight. Exceptions are like the rough rock work of a growing building which tells that there is more to come and shows where the next construction is to be.” - William Bateson (206).

Ernest Rutherford (NZ-England) was awarded the Nobel Prize in Chemistry for his investigations into the disintegration of the elements, and the chemistry of radioactive substances.

Ilya Ilyich Mechnikov (RU-FR) and Paul Ehrlich (DE) were awarded the Nobel Prize in Physiology or Medicine "in recognition of their work on immunity."

William Sealy Gosset (GB) derived the statistical method that came to be known as Student’s t test. The test consists of rejecting a hypothesis if, and only if, the probability (derived from t) of erroneous rejection is small. Gosset published all his papers under the pseudonym Student (2491, 3040).

Ernest Rutherford (NZ-GB), Johannes (Hans) Wilhelm Geiger (DE), and Thomas Royds (GB) proved that alpha particles are the equivalent of helium nuclei. They used a scintillation counter to determine that one gram of radium emits 37 million alpha particles per second. This quantity of alpha particles per second is now referred to as a curie (2734-2736). One million emissions per second is a rutherford.

Lawrence Joseph Henderson (US) formulated the theory of acid-base equilibrium in animal tissues (1466). Henderson later explained the respiratory function of the blood and demonstrated the quantitative relationships of eight blood variables (1468). 

Svante August Arrhenius (SE) pointed out that carbon dioxide in the atmosphere serves as a heat-trap, for it allows the high frequency sunlight to penetrate freely to the earth’s surface but is opaque to the low frequency infrared radiation which the earth reradiates at night. He also theorized that life began on earth when living spores had reached it across the emptiness of space (panspermia) (93).

Richard Martin Willstätter (DE) and Arthur Stoll (CH) worked out the way in which the magnesium atom is placed in the chlorophyll molecule and showed that the iron atom is held in similar fashion in heme, the colored portion of the hemoglobin molecule. They determined the chemical composition of blue-greenish chlorophyll a as 137 atoms (C55H72N4O5Mg), and yellowish-green chlorophyll b as 136 atoms (C55H70N4O6Mg) (3504, 3506).

Richard Martin Willstätter (DE) and Ernst Hug (DE) were the first to separate chlorophyll a, chlorophyll b, carotin (carotene), and xanthophyll (3503).

Richard Martin Willstätter (DE) and Arthur Stoll (CH) discovered and named phytol (the major esterifying alcohol of chlorophyll at position 7 of the macrocycle), pheophorbide (chlorophyllide without the central Mg-atom), chlorophyllase (the enzyme that de-esterifies chlorophyll) and allomerization (3505).

Hans Fischer (DE) and Adolf Stern (DE) proposed a correct structure of chlorophyll, except for the position of the two extra hydrogens, which are now recognized to be located on ring IV at positions 7 and 8 of the macrocycle (1102, 1103).

Hans Fischer (DE) and Hermann Wenderoth (DE) correctly assigned the two extra hydrogens of chlorophyll to positions 7 and 8 on ring IV (1104).

K. Noack (DE) and E. Schneider (DE) started the study of bacteriochlorophyll (2365).

Hans Fischer (DE), Robert Lambrecht (DE), and Hellmuth Miittenzwei (DE) established the chemical relationship of bacteriochlorophyll to chlorophyll by the preparation of common derivatives (1100, 1101). 

Phoebus Aaron Theodor Levene (RU-US) and Walter Abraham Jacobs (US) showed that the five-carbon sugar D-ribose is to be found in inosinic acid, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid. They established unequivocally that the arrangement of the three components of inosinic acid, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid is nitrogenous base-ribose-phosphate with the purine or pyrimidine connected to the sugar by a glycosidic linkage and the phosphate attached to the carbon 5 of the ribose by an ester linkage. They also discovered that mild hydrolysis of adenylic acid, cytidylic acid, uridylic acid, and guanylic acid yielded adenosine, cytosine, uridine, and guanosine. They named compounds such as inosinic acid, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid nucleotides, and compounds such as hypoxanthine, adenosine, cytosine, uridine, and guanosine, nucleosides They concluded (incorrectly) that intact nucleic acid is composed of the four nucleotides, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid in equivalent proportions to form a tetranucleotide. They demonstrated in 1909 that guanosine, a ‘simple nucleoside’ could, like guanylic acid, form gels (1937-1940).

Charles Jules Henry Nicolle (FR) and Louis Manceaux (FR) discovered a protozoan organism in the tissues of a hamster-like rodent known as the gundi, Ctenodactylus gundi. They named it Toxoplasma gondii, a reference to its morphology (Toxo, from Greek τόξον (toxon); arc, bow, and πλάσμα (plasma); i.e., anything shaped or molded) and the host in which it was discovered, the gundi (gondii). The same year that Nicolle and Mancaeux discovered T. gondii, Alfonso Splendore (BR) identified the same organism in a rabbit. 

Helen Dean King (US) saw the accumulation of amplified ribosomal RNA during pachytene in the American toad Bufo lentiginosus (= B. americanus) and its subsequent migration to the nuclear periphery as nucleoli (1751). Helen Dean King (US) led the development and production of the first line of standardized laboratory rats, known as Wistar Rats, produced between 1906 and 1940.

San Jose scale insect resistance to lime-sulfur was reported from orchards in the Pacific Northwest. Ref

Daniel Trembly MacDougal (US) wrote Botanical Features of North American Deserts, which contains geology, geography, physiology, ecology, the dominant flora, adaptive mechanisms of desert plants, and superb illustrations (2043). 

Charles Edward Spearman (GB) and G. Kärber (DE) developed a nonparametric procedure for computing an ED50 estimate (and fiducial limits) during drug research (1709, 2960). This became known as the "Spearman-Karber estimator", which is frequently used in drug screening.

 Julius Wohlgemuth (DE) described a method for measuring the concentration of amylase (diastase) in the serum, thereby introducing the potential for diagnosing acute pancreatitis prior to laparotomy or autopsy (3557).

Karl Landsteiner (AT-US) and Erwin Popper (DE) demonstrated that a filterable agent (virus) from a human case of poliomyelitis would cause paralysis if injected intraperitoneally into monkeys (1882, 1883). This was considered proof that poliovirus is the etiological agent of poliomyelitis.

Constantin Levaditi (RO-FR) and Karl Landsteiner (AT-US) were the first to isolate the poliomyelitis virus and were among the first to use monkeys in polio research (1935).

Robert Doerr (DE) reported that the virus of pappataci fever, also called sand-fly fever, phlebotomus fever, or three-day fever is transmitted by sand flies that have fed on the blood of patients with the fever (854).

Clemens Peter Pirquet von Cesenatico; Clemens Peter von Pirquet (AT) noted that the tuberculin skin test response of immune individuals is transiently depressed during the course of acute measles (rubeola) virus infection, from just prior to the rash until 7-20 or more days following its appearance (3322). This phenomenon is called virus-induced immunosuppression.

Martinus Willem Beijerinck (NL) demonstrated that Azotobacter is capable of fixing atmospheric nitrogen when it is grown in axenic culture (260).

Jules Brunel (CA) related the antibacterial properties of the Penicillia through an anecdote told by Doctor A.E. Cliffe, a biochemist from Montreal. …”It was during a visit through Central Europe in 1908 that I came across the fact that almost every farmhouse followed the practice of keeping a moldy loaf on one of the beams in the kitchen. When asked the reason for this I was told that this was an old custom and that when any member of the family received an injury such as a cut or bruise, a thin slice from the outside of the loaf was cut off, mixed into a paste with water and applied to the wound with a bandage. I was assured that no infection would then result from such a cut” (460). 

George Harrison Shull (US) used a Mendelian interpretation to explain the phenomenon of hybrid vigor and its association with plant productivity in corn (Zea mays). This represents the introduction of the concept of heterosis (superiority of heterozygotes) although the word was not used until 1914. George Harrison Shull (US) showed that self-pollination in corn, a naturally cross-pollinating plant, results in the isolation of inbred strains that are uniform and true breeding. Following Johanssen he called these pure lines. They are much less vigorous than the open-pollinated varieties from which they are derived. However, when two such lines are crossed, the F1 hybrids are uniform, like their inbred parents, but much more vigorous and in some cases more productive than the original open-pollinated varieties. There is only one shortcoming: The hybrid seed is borne on the weak, unproductive plants of the inbred strains used as the female (2907-2909).

Donald Forsha Jones (US) solved this problem in 1917 when he invented the double-cross method of hybrid seed production. He crossed the single cross of two strains of Chester’s Leaming with a single cross of two strains of Burr White. Grown in 1918, this double cross yielded more than the best open-pollinated varieties (1686-1690) 

Donald Forsha Jones (US) made a significant contribution to hybrid corn production when he employed fertility-restoring genes to overcome cytoplasmic male sterility. This method employs hereditary factors in the cytoplasm to make male corn flowers sterile when sterility is an asset and uses heredity factors on the chromosomes to make it fertile when fertility is essential (1691-1693). A patent on using genetic restorers in hybrid-seed corn production was issued to Jones in 1956. It was the first patent on a genetic technique to be granted in the United States. Ref

Marcus Morton Rhoades (US) was the first to describe cytoplasmic male sterility in corn. This represented the first instance in plants where a phenotype other than chlorophyll variegation was shown to be determined by cytoplasmic factors (2623).

Godfrey Harold Hardy (GB), and Wilhelm Weinberg (DE), independently formulated the theorem that in the absence of mutation and selection, the frequency of a gene in any large, randomly mating population will reach equilibrium in one generation and remain in equilibrium thereafter regardless of whether the gene is dominant or recessive. Also, the genotypic frequencies of a population in equilibrium with two alleles with frequencies p and q are given by the formula p2 + 2pq + q2. This theorem forms the mathematical basis for population genetics (392, 1410, 2506, 2999, 3413). See, Karl Pearson, 1904.

Paul Jaccard (FR) devised the Jaccard index (Jaccard similarity index; Jaccard coefficient; coefficients of association) which provides numerical expression of taxonomic similarity based on presence-absence of species. It directly expresses the percentage of taxa shared between two collections (1634).

Carlo Moreschi (IT) observed that incubation of typhoid bacteria with a diluted (goat) anti-thyphoid serum did not lead to agglutination. However, bacterial agglutination could be induced by the addition of anti-goat serum, thus documenting the antiglobulin reaction, which would later be explained by Coombs, et al (2243, 2244). See, Coombs, 1945. Although Moreschi did not realize it he had discovered weak or incomplete antibodies.

Vladimir Mikhailovich Bekhterev (Bechterev) (RU) described the superior nucleus of the vestibular nerve (Bekhterev's nucleus). Ref

Note: In 1927 Bekhterev diagnosed Joseph Stalin with “grave paranoia.” Later that day Bekhterev suddenly died, causing speculation that Stalin as revenge for the diagnosis killed him. Moreover, after Bekhterev’s death, Stalin had Bekhterev’s name and all of his works removed from textbooks.

Korbinian Brodmann (DE) described 52 discrete cortical areas. He is responsible for establishing the basis upon which the present day science of comparative cytoarchitectonics of the mammalian cortex rests. All confusion of brain area nomenclature disappeared with Brodmann’s contribution (438).

Konstantin von Economo; Konstantin Baron Economo von San Serff (AT) and Georg N. Koskinas (AT) revised Brodmann's cortical nomenclature of the cerebral cortex (3259).

Leonid Abgarovich Orbeli (RU) showed that a change in the intensity of light could serve as a conditioned stimulus for a dog, even though the dog could not distinguish the color (2403).

John Mellanby (GB) described the inhibition of blood coagulation by oxalate and citrate (2158). This finding would prove to be immensely valuable for subsequent studies. Citrate is used for preservation of blood for transfusion.

Yandell Henderson (US) suggested that acapnia, or deficiency of carbon dioxide in the blood and tissues, is an important factor contributing to the depression of respiratory and circulatory activity, which accompanies operation and anesthesia (1469).

Yandell Henderson (US), Felix Percy Chillingworth (US), and James Ryle Coffey (US) showed that acapnia (diminished carbon dioxide in the blood) might induce acute disturbance of the heart and failure of the peripheral circulation. These conditions resemble the functional depression of shock in patients after prolonged anesthesia and major operations. On the other hand it was found that if the carbon dioxide content of the body is conserved by partial rebreathing, the vitality of an animal, even under prolonged and extensive operation and trauma, is but little depressed (1470, 1472).

Yandell Henderson (US), Howard W. Haggard (US) and Raymond C. Coburn (US) carried their observations to the clinic and found that when inhalations of carbon dioxide (8%) in air were administered to patients after major surgical operations under open ether anesthesia, the effects were strikingly beneficial. With the return of deep breathing, the cyanosis then common after anesthesia disappeared. The cutaneous circulation improved. The skin changed in color and temperature, from blue-gray and cold to pink and warm. The volume of the pulse, previously thready, rapidly became full; and arterial pressure was restored to normal. Owing to the increased volume of breathing, the anesthetic (ether) was rapidly ventilated out of the blood and consciousness returned within a few minutes, even after profound anesthesia. Nausea and vomiting were either greatly reduced or entirely absent and after the inhalation the patient dropped off to sleep. In continuation of these observations, White found that when slow hemorrhage occurs after operations upon the brain, the rate of breathing gradually decreases until death is imminent. In several such cases life was saved by stimulation of respiration with inhalation of carbon dioxide (1473, 1474).

Yandell Henderson (US) pointed out the importance of acapnia, showed that fatal apnea could result from excessive forced breathing, and recommended the administration of carbon dioxide in conditions of shock, particularly in collapse due to anesthesia. He also pointed out that high altitude flying could produce decompression sickness or caisson disease (1471). Atelectasis of a lobe, or even a massive collapse of an entire lung, may develop.

Pol N. Coryllos (US) and George L. Birnbaum (US), on the basis of bronchoscopic investigations on dogs, considered lobar pneumonia to be a “pneumococcal atelectasis,” caused by an obstruction of a bronchus by the production of an excessive and sticky secretion. They demonstrated experimentally that pneumonia might develop if pathogenic organisms happen to be present because they find in an atelectatic lung conditions favorable to their growth (668-670).

Percy Theodore Herring (GB) thoroughly described hyaline or colloid masses (Herring bodies) scattered throughout the posterior lobe of the pituitary gland in both mammals and nonmammals. These nerve-end organs had first been reported by Harry J. Berkley (US) (288, 1493).

Leo Buerger (US) described thromboangiitis obliterans (Buerger disease), a recurring inflammation and thrombosis (clotting) of small and medium arteries and veins of the hands and feet (467).

George Coats (GB) described an exudative vasculopathy, which became known as Coat’s Disease. It is neither inherited nor associated with systemic vascular abnormalities, but ocular disorders, such as retinitis pigmentosa, may be seen with retinal telangiectasia (621).

Franklin Paine Mall (US) wrote A Study of the Causes Underlying the Origin of Monsters. Third Contribution to the Study of the Pathology of Human Embryos in which he concluded that every human egg has the possibility of becoming an abnormal embryo if the environment is unfavorable at critical times in its development. By monsters he simply meant embryos that had failed to develop in a normal way (2075, 2076).

Noël Fiessinger (FR) elucidated the histogenesis of cirrhosis. Showing that the course of the destruction is the same whatever the conditions, pathological or otherwise, which determine it (1093).

William Halse Rivers Rivers (GB) and Henry Head (GB) set up experiments based on Head’s submitting to the division of his own left radial and external cutaneous nerves. Their findings of the loss and restoration thus brought about, led to a reclassification of the sensory pathways (2659).

Friedrich Trendelenburg (DE) described his first unsuccessful pulmonary embolectomy in a human (3144). This operation became famous and is known as the Trendelenburg operation.

Martin Kirschner (DE) (Trendelenburg’s student) surgically treated pulmonary embolism with more success (1759).

Victor Alexander Haden Horsley (GB) and Robert H. Clarke (GB) developed the Horsley-Clarke system and apparatus for performing the so-called stereotactic surgery of the brain, whereby a set of precise numerical coordinates are used to locate each brain structure (1575).

Lars Leksell (SE) improved this apparatus considerably when he introduced his stereotactic instrument for human functional neurosurgery (1930).

Harvey Williams Cushing (US) developed surgical temporal decompression to relieve cerebral contusion and edema (735).

Robert Mearns Yerkes (US) and John D. Dodson (US) found in their studies of the mouse that: 1) the rapidity of learning increases as the amount of difference in the brightness of the electric boxes between which the mouse is required to discriminate is increased, 2) the relation of the strength of electrical stimulus to rapidity of learning or habit-formation depends upon the difficultness of the habit, 3) the rapidity of learning increases as the strength of the electrical stimulus is increased from the threshold of stimulation to the point of harmful intensity, 3) when task discrimination is extremely difficult the rapidity of learning at first rapidly increases as the strength of the stimulus is increased from the threshold, but, beyond an intensity of stimulation which is soon reached, it begins to decrease, 5) as the difficultness of task discrimination is increased the strength of that stimulus which is most favorable to habit formation approaches the threshold (3594). 

Karl Grobben (AT) proposed a division of the animal kingdom into two great stems determined by the fate of the blastopore in the earliest stages of development. These two stems were Protostomia (annelids, arthropods, and molluscs) and the Deuterostomia (chordates, hemichordates, and echinoderms). He proposed the name Aschelminthes (Gk. ascos, cavity, helminth, worm) to replace Nemathelminthes (1322).

Amédée Bouyssonie (FR), Jean Bouyssonie (FR) and Louis Bardon (FR) found skeletal remains of Homo sapiens neanderthalensis; Homo neanderthalensis near the village of La Chapelle-aux-Saints in France (375). The remains are dated at ca. 60K B.P.

Otto Schoetensack (DE) described and named archaic forms of Homo sapiens uncovered by gravel pit workers in 1907 near Heidelberg in Germany. Estimated age is between 400,000 and 700,000 B.P. This find consisted of a lower jaw with a receding chin and all its teeth. The jaw is extremely large and robust, like that of Homo erectus, but the teeth are at the small end of the erectus range. They were named Homo heidelbergensis (2842). 

Arthur Smith Woodward (GB) described a more complete skull from the Broken Hill Mine, Kabwe, Zambia and named it Homo rhodesiensis: Homo sapiens rhodesiensis (3571). It is dated at late Middle Pleistocene, ca. 300,000 B.P.

George Henry Falkiner Nuttall (US-GB) founded and edited the journal Parasitology.


“There is no alleviation for the sufferings of mankind except veracity of thought and action, and the resolute facing of the world as it is, when the garment of make-believe, by which pious hands have hidden its uglier features, is stripped off.” Thomas Henry Huxley (1610).

Emil Theodor Kocher (CH) was awarded the Nobel Prize in Physiology or Medicine for his investigations on physiology, pathology, and surgery of the thyroid gland. He was one of the first surgeons to resect and unite the intestines.

Søren Peder Lauritz Sørensen (DK) suggested that chemists express hydrogen ion concentration as the negative logarithm (pH) of the molar concentration of the ion. A chemist, instead of speaking of a hydrogen ion concentration of 10-7 moles per liter, would speak of a pH of 7. This represents the introduction of the quantitative formulation of the concept of pH (2954).

Søren Peder Lauritz Sørensen (DK) pointed out the effect of pH on enzyme activity (2953).

Lawrence Joseph Henderson (US) was the first to understand and express quantitatively the buffering effect of carbon dioxide and bicarbonate interacting with hydrogen ions in blood. Later Karl Albert Hasselbalch (DK) converted Henderson’s dissociation equations to the logarithmic form using the pH concept of Sørenson (1435, 1467). Lawrence Joseph Henderson (US) rewrote the laws of mass action for weak acids and their salts (1468).

Otto Wallach (DE) proposed the isoprene rule which states that chemicals can be considered terpenes if their molecular formulas have a carbon to hydrogen ratio of 5:8 (3354, 3355).

Leopold Stefan Ruzicka (HR-CH), Jules Meyer (CH), Max Stoll (CH) and M. Mingazzini () demonstrated that isoprene is a structural unit of the terpenes. This was a reintroduction of the isoprene rule and helped in the understanding of the structure of turpentine oil, sesquiterpenes, diterpenes, triterpenes, squalene, cholesterol, and the bile acids (2741-2743).

Leopold Stefan Ruzicka (HR-CH), Albert Eschenmoser (CH), Oskar Jeger (CH), and Duilio Arigoni (CH) further refined the concept of the isoprene rule (1036, 2740).

Federico Battelli (IT) and Lina Salomonovna Stern (LT-CH-RU) reported their discovery that animal liver material can oxidize ethanol to acetaldehyde and acetic acid (and possibly other volatile acids). This represents the discovery of alcohol dehydrogenase (222-224).

Elmer Verner McCollum (US), in work with laying hens, found that all organic forms of phosphorus of biological importance could be synthesized in the animal body from orthophosphates in the food (2138). 

Archibald Vivian Hill (GB) and William Hartree (GB), using delicate thermocouples, discovered that contracting frog leg muscle fibers produce heat in two phases. Heat is first produced quickly as the muscle contracts. Then, after the initial contraction, further heat is evolved more slowly but often-in greater amounts. Hill also showed that molecular oxygen is consumed after the work of the muscles is over but not during muscular contraction. Hill and C.L. Evans (GB) deduced that the heat liberated in the presence of contraction and recovery are not sufficient for the complete combustion of the lactic acid formed (1042, 1521-1524).

Wallace Osgood Fenn (US) studied the production of heat by muscle. In particular he showed that there is a fairly good quantitative relation between the heat production of muscles and the work which they perform, and that a muscle, which does work, liberates, ipso facto, an extra supply of energy which does not appear in any isometric contraction. (Archibald Vivian Hill (GB) referred to this as the Fenn effect.) Fenn’s heat data showed first of all that if a muscle shortens, no matter how little and no matter how lightly loaded, it produces more heat than during an isometric contraction over the same period. He then showed that this extra heat production is proportional to the external work done by the muscle. It was clearly not determined by load alone, or by the change in length. This was the first evidence, and remains today the best evidence, that shortening is an active process and that muscle is not simply a prestretched spring shortening passively (1075, 1076).

Stanley Rossiter Benedict (US) developed Benedict’s reagent to test for reducing sugars (279).

Otto Neubauer (DE) showed that in normal animal tissues amino acids are deaminated to their corresponding keto acids (e.g., alanine to pyruvic acid) (2326).

A.I. Ignatowski (RU) observed a possible relation between cholesterol-rich foods and experimental atherosclerosis (1612). See, Felix Jacob Marchand, 1904.

Adolf Otto Rheinhold Windaus (DE) showed that atheromatous lesions contain six times as much free cholesterol as a normal arterial wall and twenty times more esterified cholesterol (3528).

Nikolai Nikolaevich Anichkov; Nikolai Nikolajewitsch Anitschkow (RU-DE-RU) and Semen Sergejewitsch Chalatov (RU), using cholesterol-fed rabbits to produce experimental atherosclerosis, demonstrated that it was cholesterol alone that caused atherosclerotic changes in the rabbit intima (77). English translation found in: Arteriosclerosis, 1983, 3: 178-182.

Jean de Meyer (BE) suspected, but did not prove, that a hormone was produced by the pancreatic islets of Langerhans. He suggested naming it insuline from the Latin word for island (795).

Edward Albert Schäfer (GB) predicted that the islands of Langerhans must secrete a substance, which controls carbohydrate metabolism (2782).

Klaus Peter (DE) reported that the loops of Henle are present in the kidney of mammals only, and that they are proportionally more developed in species living in a dry habitat and producing concentrated urine (2505).

Keith Lucas (GB) and Edgar Douglas Adrian (GB) published work on the all-or-none principle in nerve stimulation (32, 33, 2018).

Carl Franz Joseph Erich Correns (DE) and Erwin Baur (DE) independently and in the same year proposed that inheritance of leaf color in Pelargonium zonale (geranium) and Mirabilis jalapa (the four-o’clock) respectively is due to genes carried in the maternal cytoplasm (non-Mendelian), perhaps in the chloroplasts. This was the first indication that mitochondria and chloroplasts may have their own genetic systems. Baur favored the idea that the plastids were the genetic determinants—the Plastom theory— while Correns favored the idea that the inheritance was carried by nonparticulate cytoplasmic material—non-Plastom theory (235, 665, 666).

Wilhelm Ludwig Johannsen (DK) suggested that Johann Gregor Mendel’s factors of inheritance be called genes from a Greek word meaning to give birth to by dropping the first syllable of the pangene of Darwin and De Vries and suggested that the genes “…may be tentatively considered to be chemical factors of various kinds….” Johannsen also introduced other terms such as phenotype and genotype (1676, 1677).

William Ernest Castle (US) and John C. Phillips (US) performed an experiment, which was important to the demise of the concept of acquired characteristics and the notion that the genotype of body cells might in some way influence the genotype of germ cells. They transplanted the ovary from a pure line of black (recessive) guinea pigs into an albino recipient. The albino foster mother when mated to an albino male bore three litters consisting entirely of fully black offspring. No influence of the albino foster mother, in whose body the eggs had been produced, could be seen (547). 

Muriel Wheldale (GB) was the first to attempt to understand the events relating gene to phenotypic expression. She investigated flower color mutants and the pigments produced in several species (3442).

Hubert Dana Goodale (US) demonstrated that the barred plumage pattern of Plymouth Rock fowls is inherited in a sex-linked mode (1282).

Nils Herman Nilsson-Ehle (SE) analyzed the inheritance of color in wheat and found that three different gene pairs R1r1, R2r2, and R3r3 were segregating, each pair acting in the same way on the same quality, seed-coat color. The effects of the different pairs were additive R1R1R2R2r3r3 being redder than R1R1r2r2r3r3 (2360).

This work along with that of Edward M. East (US) showed that continuous hereditary variation could be explained by discontinuous genetical variations (i.e., genes altered by mutation) (933).

Richard Woltereck (DE) performed experiments, which probed the interaction of genotype and environment. He studied quantitatively varying and readily measurable characters, chiefly head form within and between pure lines of the micro-crustacean, Daphnia (3570). 

Albert A. Epstein (US) and Reuben Ottenberg (US) pointed out that the human blood groups (A, B, O) are inherited in accord with Mendelian principles (1028).

Emil von Dungern (DE) and Ludwik Hirszfeld (PL) proposed that the heredity of the ABO blood group system depends on two independently segregating loci with allele pairs A, a and B, b respectively (3256).

Lewis Ralph Jones (US) demonstrated bacterial pectolytic exoenzymes for the first time (1694). This led to an understanding of bacterial soft rot.

Paul Ehrlich (DE) was the first to propose that immune mechanisms are involved in protection against aberrant cells from within the organism itself when he said, “I am convinced that during development and growth malignant cells arise extensively and frequently but that in the majority of people they remain latent due to the protective action of the host. I am also convinced that this natural immunity is not due to the presence of antimicrobial bodies but is determined purely by cellular factors. These may be weakened in the older age groups in which cancer is more prevalent” (966, 1529). This can be considered the origin of immune surveillance. See Lewis Thomas, 1959.

Richmond T. Prehn (US) and Joan M. Main (US) showed that tumors induced by chemical carcinogens in mice can stimulate tumor-specific responses that are able to reject those same tumors on challenge. They concluded that tumor immunity was induced by antigens unique to the chemically induced tumor, but found that spontaneously arising tumors were not rejected when tested in the same experimental manner (2564).

Ludwik Gross (US), Edgar J. Foley (US), Richmond T. Prehn (US) and Joan M. Main (US) demonstrated that mice could be rendered resistant to tumor transplantation by preimmunization with the same tumor (1140, 1324, 2564).

Osias Stutman (US) reported that athymic mice do not have an increased frequency of tumors induced by a chemical carcinogen, implying that the concept of immune surveillance providing protective immunity was incorrect (3048).

Harold B. Hewitt (GB), E.R. Blake (GB), and A.S. Walder (GB) summarized data in support of the idea that naturally arising tumors are not immunogenic (1510).

Aline van Pel (BE) and Thierry Boon (BE) reported that vaccinating mice with mutagenized tumor cells could induce specific immunity to spontaneous tumors. Their study showed that spontaneous tumors are not inherently deficient in tumor antigens, but instead failed to stimulate an effective immune response (3198).

Pierre van der Bruggen (BE), Catia Traversari (IT), Patrick Chomez (BE), Christophe Lurquin (BE), Etienne De Plaen (BE), Benoit Van den Eynde (BE), Alex Knuth (DE), and Thierry Boon (BE) reported the first identification of a tumor-specific antigen recognized by cytolytic T cells in humans, reinforcing the idea that tumor antigens can elicit a detectable tumor-specific response (3188).

Gerald Willimsky (DE) and Thomas Blankenstein (DE) found that sporadic immunogenic tumors avoid destruction by inducing T-cell tolerance.

Ward J. McNeal (US), Lenore L. Latzer (US), and Josephine E. Kerr (US) investigated the bactericidal effects of gastric juice and found that it killed nearly all bacteria, which pass through the stomach (2152).

Max Einhorn (PL-US) invented the duodenal tube for aspirating contents of the intestine below the pylorus (985, 986).

Janus von Bókay (AT) proposed that there is a relationship between varicella (chickenpox) and herpes zoster (shingles) (3248).

Karl Kundratitz (DE) demonstrated that the same infectious agent causes varicella (chickenpox) and herpes zoster (shingles) (1851).

Joseph Garland (US) hypothesized that herpes zoster might become manifest as immunity to the varicella-zoster-virus (VZV) waned (1216).

Thomas Huckle Weller (US) and Marguerite B. Stoddard (US) isolated viruses from chickenpox and herpes zoster to confirm this relationship (3421).

R. Edgar Hope-Simpson (GB), after studying numerous cases of varicella and zoster, supported Garland’s hypothesis (1564). 

Sigurd Orla-Jensen (DK) emphasized the importance of physiological characteristics in a logical classification of bacteria. Organisms were assigned to genera using a combination of morphological and physiological characters (2407). 

John McFadyean (GB) and Stewart Stockman (GB) discovered that the microaerophilic campylobacters (formerly Vibrio fetus) could cause abortion in cattle and sheep (2146).

Charles Jules Henri Nicolle (FR) and Louis Herbert Manceaux (FR) discovered and described Toxoplasma gondii as the causative agent of a disease in the Gondi (Ctenodactylus gondi), a small North African rodent. They named it toxoplasmosis. Toxaplasma is from the Greek toxón, a bow or arc, and gondii from the name of the rodent (2353).

Alfonso Splendore (BR) described the same disease the same year in laboratory rabbit (2969, 2970). 

Josef Janku (CZ) was the first to definitively recognize the parasite, Toxoplasma gondii, in humans (1656, 1657).

Arne Wolf (US) and David Cowen (US) established that an association exists between Toxoplasma gondii and human congenital disease (3560). This association was followed by the realization that T. gondii rarely causes disease even though it is a very common parasite of adults but that in pregnant women the parasite can cross the placenta and can damage the fetus.

William McPhee Hutchison (GB), J. Findlay Dunachie (GB), J. Chr Siim (DK), and Kresten Work (DK) worked out the life cycle of Toxoplasma gondii and the role of the domestic cat in transmission of toxoplasmosis (1604-1606).

J.P. Dubey (US), Nancy L. Miller (US), and Jack K. Frenkel (US) reported that T. gondii is capable of infecting virtually all warm-blooded animals. In humans, it is one of the most common parasites with a lifecycle which can be broadly summarized into two components: 1) a sexual component that occurs only within cats (felids, wild or domestic), and 2) an asexual component that can occur within virtually all warm-blooded animals, including humans, cats, and birds. The existence of oocysts was discovered in cat feces, and the fecal-oral route of infection via oocysts was demonstrated. Ingestion of oocysts by humans or other warm-blooded animals is one of the common routes of infection (896, 897, 3415).

Theobald Smith (US) discovered that immunity to diphtheria could be generated in guinea pigs by giving them a mixture of diphtheria toxin and antitoxin (antibodies to the toxin). The toxin alone is so potent that only trace amounts are harmful to the animals (2937).

Karl Bogislaus Reichert (DE) determined optimum conditions for visualizing moving flagella and described them in great detail (2609).

Benjamin Minge Duggar (US) wrote Fungous Diseases of Plants, with Chapters on Physiology, Culture Methods and Technique, which was the first plant pathology text, published in America (911).

Ernst Lowenstein (AT) discovered that formaldehyde treatment could be used to convert toxins into relatively inert but still antigenic toxoids (2014).

Richard Richter (DE) was the first to publish concerning an intrauterine device (IUD). The device he inserted was a ring made of silkworm gut, with 2 ends, which protruded from the cervical os enabling him both to check the device and remove it (2637).

Herbert McLean Evans (US) determined that during embryonic development in vertebrates the aorta, cardinal and umbilical veins, and other large blood vessels begin as a network of capillaries (1043).

Simeon Burt Wolbach (US) and Tadasu Saiki (JP) have shown that anaerobic bacteria are almost always present in aseptically removed dog livers. They mention that the presence of these bacteria may account for many of the changes occurring in so-called autolysis of aseptically removed liver. These pathogenic anaerobic bacteria are typically of the Bacillus welchii (Clostridium welchii) type (3559).

Frank Charles Mann (US) noted, in 1923, that if these fragments were allowed into the peritoneal cavity during surgery that a serious peritonitis was likely to follow. Ref

James C. Ellis (US) and Lester Reynold Dragstedt (US) proved that Mann was correct (883, 1004).

Lester Reynold Dragstedt (US), H.E. Haymond (US), and James C. Ellis (US) demonstrated that the pancreas contains the pathogenic anaerobic Clostridium welchii (884).

Léon Charles Albert Calmette (FR), Jean-Marie Camille Guérin (FR), Benjamin Weill-Hallé (FR), Alfred Bouquet (FR), Leopold Nègre (FR), Wilbert (FR), Marcel Léger (FR), and Raymond Turpin (FR) developed a bovine strain of tubercle bacillus, which was rendered completely avirulent by 230 transfers over 18 years (1906-1924) on bile-glucose-potato medium. This strain is designated as BCG (Bacille-Calmette-Guérin) and is widely used outside the U.S.A. as a vaccine for tuberculosis in cattle and man (488-492).

Carlos Ribeiro Justiniano Chagas (BR) gathered preliminary evidence that South American trypanosomiasis or Chagas’ disease is caused by Schizotrypanosome (Trypanosoma) cruzi and transmitted by the Reduviid bug of the genus Triatoma. He proved it in 1916 then broadened his studies on the acute phase of the disease and, in 1922, he and Eurico de Azevedo Villela (BR) described the chronic heart form, thereby completing their clinical studies on the disease(557, 559, 560).

Alexandre Joseph Emilé Brumpt (FR) demonstrated transmission of South American trypanosomiasis or Chagas’ disease via the fecal route of the Reduviid bug (456).

Fritz Köberle (AT-BR) established the links between infection with Trypanosoma cruzi and the various signs of Chagas' disease, such as distended colon and esophagus and cardiac failure (1786).

Carlos Ribeiro Justiniano Chagas (BR) and Antonio Carini (IT-BR) described Pneumocystis from humans but mistook it as a stage in the life cycle of a trypanosome. Chagas placed it in a new genus, Schizotrypanum (519, 558).

Antonio Carini (IT-BR) observed cysts in rats with experimental trypanosomiasis, but suspected the cysts were from an unknown organism. He sent samples to his colleague, Charles Louis Alphonse Laveran (FR), for further examination. In 1912, Laveran's students, Pierre Delanoe (FR) and Maria Delanoe (FR), found similar cysts restricted to the lungs of trypanosoma-free sewer rats, and named the new organism Pneumocystis carinii (811).

J. Wätjen (DE) was the first to render a clinical description of the pulmonary pneumocystosis associated with Pneumocystis carinii (3385).

Otto Ammich (DE) and Everett Smith Beneke (US) established pulmonary pneumocystosis as a definite clinicopathologic entity (63, 280).

M.G. van der Meer (NL) and S. Li Brug (NL) described Pneumocystis carinii as the infecting organism in a 3-month-old infant with congenital heart disease and in 2 of 104 autopsy cases (a 4-month-old infant and a 21-year-old adult). This paper contains the first light microscopy photographs of Pneumocystis trophic and cystic forms in human beings (3189).

Christian Georg Schmorl (DE) showed that the first sign of healing in rachitic children is the reformation of the provisional zone of calcification on the epiphyseal side of the metaphysis (2839).

Karl Bruno Stargardt (DE) described familial juvenile macular degeneration (Stargardt macular dystrophy) which is the most frequently encountered juvenile onset macular degeneration (2976).

Thomas Lewis (GB) described atrial fibrillation in considerable detail. He also discussed pulsus alternans, the alternating pulse, which usually meant death was close at hand (1950-1953).

Charles Rupert Stockard (US) studied the effects of chemicals on embryologic development and produced cyclopia and other monstrosities by the use of lithium and other agents (3017, 3018).

Harvey Williams Cushing (US) was the greatest neurosurgeon of the twentieth century and the first to devote himself entirely to surgery of the brain. He authored The Pituitary Body and its Disorders. His contributions to neurosurgery were numerous, among which was his analysis of the function of the human brain by stimulating motor and sensory areas while patients were under local anesthesia. These studies provided for the first time direct evidence that irritation of the post-central gyrus gives rise to sensations like those that precede epileptic attacks. He distinguished between excess function of the anterior lobe of the pituitary (as in gigantism and acromegaly) and deficiency of its function (as in dwarfism and Frohlich's asexual adiposity) (736, 738, 739).

Philip Edward Smith (US), Herbert McLean Evans (US), Miriam E. Simpson (US), Karl Meyer (US), Frederick L. Reichert (US), Alexander J. Szarka (US), Richard I. Pencharz (US), Robert E. Cornish (US), and Paul R. Austin (US), working with rats and dogs, found that the anterior pituitary gland produces a substance or substances which stimulate sleletal growth with weight increase, increase the size of the viscera(somatotropin or growth hormone/GH), and promote activity of the adrenal cortex (adrenocorticotropic hormone/ACTH), thyroid gland (thyrotropic stimulating hormone/TSH), and gonads (luteinizing hormone/LH or interstitial cell-stimulating hormone/ICSH and follicle stimulating hormone/FSH) (1048, 1051, 1052, 2932).

Carl Richard Moore (US) and Dorothy Price (US) discovered that a substance from the anterior pituitary lobe stimulates the gonads (luteinizing hormone/LH or interstitial cell-stimulating hormone/ICSH and follicle stimulating hormone/FSH) and in turn the gonads produce a substance that depresses the production of the pituitary substance (2236). This is historically one of the earliest known examples of a biologic feedback mechanism.

James Bertram Collip (CA), Evelyn Mary Anderson (CA), and David Landsborough Thomson (GB-CA) had by 1933 found that separate substances from the anterior pituitary regulate the adrenal cortex (adrenocorticotropic hormone/ACTH) and the thyroid gland (thyroidstimulating hormone/TSH). See Collip, 1933.

Fuller Albright (US), William Parson (US), and Esther Bloomberg (US) unraveled the pathogenesis of Cushing’s syndrome (42, 43).

Wilder Graves Penfield (US-CA), Lyle Gage (CA) and Edwin Boldrey (CA) confirmed Cushing’s studies on electrical stimulation of the brains of epileptics (2499, 2500).

Hermann Oppenheim (DE), and Fedor Krause (DE), in1908, were the first to successfully remove an intervertebral disc from a human (2401).

Anton von Eiselsberg (AT) and Julius Hochenegg (AT) founded the world's first model emergency rooms.

Wilfred Hudson Osgood (US) and Clinton Hart Merriam (US) provided a revision of the mice of the American genus Peromyscus. For this work they used over 27,000 specimens (2414).

John Jacob Abel (US) founded the Journal of Pharmacology and Experimental Therapeutics.

Albert J. Cook (US) founded the Journal of Entomology, which became the Journal of Entomology and Zoology in 1913.


"Enough has been advanced here to make it extremely probable that the inorganic composition of the blood plasma of vertebrates is an heirloom of life in the primeval ocean." Archibald Byron Macallum (2035).

Johannes Diderik van der Waals (NL) was awarded the Nobel Prize in Physics for his work on the equation of state for gases and liquids.

Albrecht Karl Ludwig Martin Leonard Kossel (DE) was awarded the Nobel Prize in Physiology or Medicine in recognition of the contributions to our knowledge of cell chemistry made through his work on proteins, including the nucleic substances.

H. Lehmann (DE) developed a filter which when placed in front of an iron arc lamp produced a beam rich in ultraviolet light. Lehmann knew of the more primitive nitrosodimethylaniline dye UV filter made by Robert Wood (US) in 1903 (1924).

Siegfried Ruhemann (GB) produced triketohydrindene hydrate (ninhydrin) then discovered its reaction with amines to form the colored reaction product known as Ruhemann's purple (2726). The reaction of amines, amino acids, peptides and related compounds with ninhydrin has found extensive use in the qualitative and quantitative analysis of such compounds in chemistry and biochemistry.

George Barger (GB) and Henry Hallett Dale (GB) derived and isolated histamine from ergot by the chemical decarboxylation of the amino acid histidine. They found that beta-phenylethanolamine derivatives simulated the effects of sympathetic nerve stimulation with varying degrees of intensity and precision, and they coined the term sympathomimetic amines (181). Amphetamine, methamphetamine, and mescaline are well known sympathomimetic amines.

Henry Hallet Dale (GB) and Patrick Playfair Laidlaw (GB) in their studies on the effects of histamine on the circulation observed the similarity between the physiological effects of histamine and the symptoms of anaphylaxis (758).

Henry Hallet Dale (GB) and Alfred Newton Richards (US) found that histamine affects blood pressure by causing dilatation of peripheral capillaries and small arterioles (760).

Jakub (Jacob) Karol Parnas (PL) reported that an aldehyde mutase present in animal tissues can catalyze the conversion of an aldehyde into the corresponding alcohol and acid, indicating that this dismutation involves a process in which one molecule of the aldehyde is acting as the hydrogen acceptor (to form the alcohol) and the other as the hydrogen donor (to form the acid). This concept was rapidly accepted as an explanation for some of the molecular behavior in alcoholic fermentation (2472).

Ivar Christian Bang (NO) was the first to describe the puzzling behaviour of guanylic acid in which the self-association of guanosine at millimolar concentrations was characterized by the ready formation of polycrystalline gels (156).

Martin Gellert (US), Marie N. Lipsett (US), and David R. Davies (US) identified the structure of helical guanylic acid-quadruplexes (1238). 

Gustav Georg Embden (DE) discovered that if a dog’s liver is perfused with alpha-keto acids and ammonia it converts them to the corresponding amino acids. This provided evidence of a metabolic linkage between proteins, carbohydrates, and fats. Ref

Graham Lusk (US) showed that the animal body could convert glycine, alanine, glutamic acid, and aspartic acid into glucose (2027).

Francis Gotch (GB) described a refractory phase between nerve impulses (1294). 

Schack August Steenberg Krogh (DK) proved that the physical forces of diffusion uniquely explain the mechanism of gas exchange in the lungs (1835, 1839).

Jean Eugene Bataillon (FR) discovered that it is possible to trigger the frog's egg development by pricking it with a needle dipped in serum (199).

Archibald Byron Macallum (CA) found a close resemblance between the ionic composition of blood sera and that of sea water and suggested that tissue cells can only live within a relatively narrow range of physiochemical conditions—conditions which represent those of the ancient ocean in which cells of ancestral organisms arose (2035, 2036). 

Gustav Georg Embden (DE) and Hermann Tachau (DE) discovered the presence of free amino acids in human sweat when they isolated serine from this secretion (1012).

Léon Ambard (FR) defined his law of urea output. With the urinary urea concentration constant, the output of urea varies directly as the square of the concentration of the blood urea. With the blood urea concentration constant, the output of urea varies inversely as the square root of the urinary concentration (59).

Samuel James Crowe (US), Harvey Williams Cushing (US), and John Homans (US) provided the first experimental evidence of the relationship between the pituitary gland and the reproductive system (706).

Kurt Goldstein (DE-US) charted the course of the lateral spinothalamic tract to its termination and demonstrated the phylogenetic development of the diencephalon (1274). Ref on diencephalon

Harry B. Shaw (US) provided the first known example of insect transmission of a plant virus when he found that the beet leafhopper (Euttetix tenellus) is an insect vector for sugar beet (Beta vulgaris) curly-top virus (2888). 

Nathan Edwin Brill (US) described 221 cases of what was probably recrudescent epidemic typhus in the New York area (436). This has been called Brill’s disease, as though it were a new entity.

William D. Frost (US) presented arguments in favor of the use of dehydrated media to culture microorganisms. This is the earliest reference, in America, to the preparation and use of dehydrated media (1198).

Dankwart Ackermann (DE), using defined media, showed that bacteria could produce putrescine from ornithine and cadaverine from lysine (16-18, 3489).

Ronald Ross (GB) and David Thomson (GB) demonstrated antigenic variation in African trypanosomes (2690).

John E. Donelson (US) and Mervyn J. Turner (GB) determined how antigenic variation is accomplished by the trypanosomes (871).

Aldo Castellani; Count of Chisiamaio (IT) discovered that Endodermophyton concentricum can cause human dermatomycosis (540).

Helmut Bruchmann (DE) was the first to obtain spore germination leading to mature prothalli in a species of Lycopodium (455).

Ernst Küster (DE) demonstrated the ability of onion epidermal protoplasts to fuse upon de-plasmolysis (1854).

Theodor Boveri (DE) demonstrated the direct influence of the cytoplasm on the nucleus in Ascaris. Either by dispermy or by centrifugation of eggs and shifting the plane of the spindle through 90 degrees, he brought two nuclei, instead of only one, into the proximity of a particular part of the cytoplasm. The result was that the chromosomes exhibited a peculiar visible behavior at one pole and not at the other (387). 

Ludwig Plate (DE) is credited with coining the term pleiotropy, i.e., a single gene or allele which may produce two or more characters (traits) which are not obviously related (778, 2544). This was the 4th edition.

Thomas Hunt Morgan (US) initiated the use of the fruit fly, Drosophila melanogaster (black-bellied honey lover) for genetic research and described the important discovery of a sex linked character in these animals as follows: “In a pedigree culture of Drosophila which had been running for nearly a year through a considerable number of generations, a male appeared with white eyes. The normal flies have brilliant red eyes. 

The white-eyed male, bred to his red-eyed sisters, produced 1,238 red-eyed offspring, (F1), and three white-eyed males. The occurrence of these three white-eyed males (F1) (due evidently to further sporting) will, in the present communication be ignored.

The F1 hybrids, inbred, produced: 2,459 red-eyed females, 1,011 red-eyed males, and 782 white-eyed males. No white-eyed females appeared. The new character showed itself therefore to be sex limited in the sense that it was transmitted only to the grandsons.” It was in his 1910 review that Morgan articulated the view that chromosomes consisted of linear arrangements of genes in an order that could be mapped by experimental breeding methods (2250, 2259).

Calvin Blackman Bridges (US) is given credit for discovering the white-eyed Drosophila mutant in Morgan’s laboratory (2238).

Erwin Baur (DE) described the first sex-linked plant gene. It was a mutant of Silene alba (Melandrium album) with narrow leaves. He could prove that this feature is sex-linked (236).

Montrose Thomas Burrows (US) was the first to grow chick embryo tissue in cell culture by placing explants in hen plasma clot hanging drops where connective tissue, muscle cells, and nerve cells were observed to proliferate (478).

Alexis Carrel (FR-US) and Montrose Thomas Burrows (US) grew a variety of adult tissues taken from a variety of species in cell culture. They observed that initially the new cells were differentiated and represented the tissue types of origin, however, as the tissues aged they eventually contained dividing cells of only two types, one resembling connective tissue cells, and the other epithelial cells (528).

Alexis Carrel (FR-US) and Montrose Thomas Burrows (US) were the first to grow tumor tissue in vitro. The tissue was Rous sarcoma (529).

Francis Peyton Rous (US) demonstrated that an agent, which passed through filters stopping bacteria, caused a spindle-cell sarcoma in Plymouth Rock chickens. Rous was reluctant to pronounce it a virus. Today this virus is called the Rous sarcoma virus and was the first of the tumor viruses to be demonstrated (2694-2697). See Ellermann and Bang, 1908.

Francisco Duran-Reynals (ES-US) proved that the Rous sarcoma - the cell-destroying virus of chicken cancer - was not confined to chickens but could leap the so-called species barrier and incite cancers in ducks and turkeys. Indeed, the virus sometimes gained virulence as it passed from one species to another. He showed how a virus could lie dormant for many years before inciting cancer (921, 922).

John Zahorsky (US) was the first to recognize exanthem subitum (roseola infantum, roseola subitum) as a separate clinical entity, which occurs almost exclusively in infants and young children (3609).

Koichi Yamanishi (JP), Kimiyasu Shiraki (JP), Toshio Kondo (JP), Toshiomi Okuno (JP), Michiaki Takahashi (JP), Yoshizo Asano (JP), and Takeshi Kurata (JP) isolated a virus from the peripheral blood lymphocytes of patients with exanthem subitum (sixth disease). It was shown to be antigenically related to human herpesvirus-6 (HHV-6). This and other results strongly suggest that the newly isolated virus is identical or closely related to HHV-6 and the causal agent for exanthem subitum (3593).

Arvid Afzelius (SE) reported on a severe bulls-eye shaped skin rash that followed bites of the tick Ixodes ricinus (34, 35). There is little doubt that the condition he named erythema chronicum migrans is synonymous with Lyme disease. It has also been called Afzelius’s disease. Borrelia afzelii, one of the borrelia species that is an agent of Lyme disease, is named in his honor

James Bryan Herrick (US) gave the first description of sickle cell anemia when he found "peculiar, elongated and sickle-shaped red blood corpuscles" in the blood of a 20-year-old black patient with symptoms of severe anemia. He did not use the phrase sickle cell anemia (1491).

Isaac Ott (US) and John C. Scott (US) discovered that an extract from the posterior pituitary gland could behave as a galactogogue (an agent that promotes the flow of milk or lacteal secretion) (2425).

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 (2426).

Alfred Fröhlich (AT) and Lothar von Frankl-Hochwart (AT) concluded that obstetricians and urologists could consider pituitrin (a proprietary preparation of the posterior lobe of the pituitary gland) as essentially non-toxic and safe to use in therapeutically stimulating the contraction of the uterus (1194).

Walter Lee Gaines (US) discovered that pituitrin causes contraction of smooth muscle of the milk passages in the mammary gland (1207).

Noël Fiessinger (FR) and Pierre-Louis Marie (FR) demonstrated the existence of enzymes in the white cells of the blood, and showed that these cells, according to their type, contain either protease or lipase. The presence of protease accounts for the dissolution of internal blood clots or purulent collections, while lipase weakens the lipidic membrane of the Koch bacilli, thus permitting their attack by the protease-carrying white cells (1094, 1095).

John Auer (US) and Paul Adin Lewis (US) gave the first adequate account of the physiological reactions leading to fatal anaphylactic shock (112).

Corrado Donato da Fano (GB) and James B. Murphy (US) gave experimental evidence that the destruction of a graft of foreign tissue is carried out by the hostile activities of the recipient’s lymphoid cells (748, 2290-2292, 2294).

Samuel James Meltzer (DE-US) concluded that bronchial asthma is due to anaphylaxis, although he did not appreciate that all cases of asthma are so caused (2160).

Berkeley George Andrew Moynihan (GB) offered a methodology to distinguish duodenal from gastric ulcer, “In the differentiation from gastric ulcer there is, as a rule, no great difficulty. If pain after food does not appear for two hours or more, it may be said with reasonable confidence that the ulcer is in the duodenum…. If pain appears early, within an hour or so, the ulcer is certainly in the stomach, probably on the lesser curvature…. The period of relief from pain conferred by the taking of a meal is then the first and a chief point to be considered in the differential diagnosis” (2274).

Samuel J. Mixter (US) and Robert Bayley Osgood (US) performed the first successful surgical stabilization of atlanto-axial (C1-C2) instability (2219).

Alexis Carrel (FR-US) reported a series of experiments that constitute the earliest forms of direct coronary artery bypass, by anatomizing the innominate artery of one dog into distal coronary of another and also by using a free carotid autograft between descending thoracic aorta and distal coronary artery. This was presented before the American Surgical Association in 1910 where he stated; unfortunately the operation was too slow. Three minutes after the interruption of the circulation, fibrillary contraction appeared, but the anastomoses took five minutes. By massage the dog was kept alive, but he died two hours later. His experiments with animals were the precursor to the bypass operations of modern human surgery, including the Blalock-Taussig shunt (527).

Hans Christian Jacobaeus (SE) described his endoscopic investigations of the abdominal cavity of man (1639-1641).

Marc Armand Ruffer (GB) found Schistosoma haematobium eggs in two Egyptian mummies dating from the 20th dynasty, 1250 to 1000 B.C.E. (2721). This finding is generally regarded as the beginning of paleoparasitology.

Max Schlosser (DE) conducted further excavations of Oligocene primate remains from the Fayum of Egypt (2831). 

The Rockefeller Institute Hospital opened its doors, becoming the first clinical research hospital in the United States.

The regulation of pesticides by the United States federal government began in 1910 with the passage of the Federal Insecticide Act by Congress. This act was passed in response to concerns from the United States Department of Agriculture (USDA) and farm groups about the sale of fraudulent or substandard pesticide products. Congress subsequently enacted the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) of 1947 that broadened the federal government's control of pesticides. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) of 1972 was later enacted.

The Journal of Genetics was founded.


Marie Sklodowska Curie (PL-FR) was awarded the Nobel Prize in Chemistry in recognition of her services to the advancement of chemistry by the discovery of the elements radium and polonium, by the isolation of radium and the study of the nature and compounds of this remarkable element.

Allvar Gullstrand (SE) was awarded the Nobel Prize in Physiology or Medicine for his work on the dioptrics of the eye. He elucidated how the eye accomplishes intracapsular accommodation.

Frederick Soddy (GB) introduced the term isotope and the concept that it represents a variation on the common atom of an element. The isotope possessing a number of neutrons different from that found in the atom most common to the element (2948, 2949). Radioactive isotopes have proved to be of great importance in biological research because they make it possible to trace the course of various elements in living organisms. 

Fritz Pregl (Slovenian-AT) developed techniques and equipment, which laid the foundation of microchemistry (2563).

Oskar Heimstädt (DE) and Hans Moritz Lehmann (DE) constructed the first successful fluorescence microscope (1456).

Max Haitinger (AT) together with other scientists developed the technique of secondary fluorescence, which involved applying exogenous fluorescent chemicals to samples. Haitinger also coined the term 'fluorochrome' (1365).

Philipp Ellinger (DE) and August Hirt (DE), in 1929, developed the prototype of the epi-fluorescence microscope. In what they called an 'intravital microscope' the excitation light passed through a series of filters before the right wavelength hit the objective lens and triggered emission of fluorescent light in the observed tissue (999).

Albert Hewett Coons (US), Hugh J. Creech (US), and R. Norman Jones (US) invented a method that could localize specific classes of proteins in cells by chemically attaching fluorescein to an antibody, which subsequently adhered to its cellular antigen, i.e., immunofluorescence (650).

E.M. Brumberg (), in 1959, and Johan Sebastiaan Ploem (NL), in 1967, are closely associated with the development of dichromatic beamsplitters, or dichromatic mirrors and described incident vertical illumination with dichromatic mirrors (2545). Dichromatic mirrors made it possible for the epi-fluorescence microscope to gain widespread use in modern biology.

Carl Alexander Neuberg (DE-US) and Ladislaus Karczag (DE), in 1910, discovered that pyruvic acid is broken down into carbon dioxide and acetaldehyde by all yeasts that ferment hexoses as well as by the enzyme preparations (carboxylase) prepared from the former (2336). Note: This is the first success in the search for intermediary products.

Otto Neubauer (DE) and Konrad Fromherz (DE), from their studies on yeast, postulated that the deamination of alanine would yield pyruvic acid, whose decarboxylation would yield acetylaldehyde, which might be reduced to ethanol. They proposed that pyruvic acid might be intermediate in the alcoholic fermentation (2327).

Carl Alexander Neuberg (DE-US), Arnold Hildesheimer (DE), and L. Tir (DE) isolated the enzyme pyruvate carboxylase, which catalyzes the decarboxylation of pyruvic acid to acetylaldehyde and carbon dioxide (2334, 2343).

Auguste Fernbach (FR) and Moise Schoen (FR) were the first to demonstrate that pyruvic acid is present during the fermentation process (1083, 1084, 2841).

Arthur Harden (GB) and William John Young (GB) found that two fractions of yeast extracts are required for alcoholic fermentation to take place, a heat-labile fraction, called zymase, presumably containing the enzymes required for the process, and a heat-stable fraction (cozymase) required for the activity of zymase (1409). The heat-stable fraction was later shown to contain two essential components, the oxidation-reduction coenzyme nicotinamide adenine dinucleotide, or NAD, and a mixture of the adenine nucleotides ADP and ATP (1401).

Federico Battelli (IT) and Lina Salomonovna Stern (LT-CH-RU), and Torsten Ludvig Thunberg (SE) discovered malate dehydrogenase (225, 3119).

Carbon tetrachloride was recommended as a substitute for carbon disulfide in fumigation of grain. From this first use of carbon tetrachloride as an insecticide came its later use as a control of hookworm; the latter discovery was acclaimed one of world's most outstanding accomplishments (2879).

Hubert Dana Goodale (US) introduced vital staining of the amphibian embryo as a method of tracing the fate of embryonic parts (1283, 1284).

Edwin B. Hart (US), Elmer Verner McCollum (US), Harry Steenbock (US), and George C. Humphrey (US) performed a long experiment with cattle, the results of which provided the first clear evidence that the nutritive value of a diet depends on factors other than its content of protein, a few minerals, and energy sources (1424).

Otto Heinrich Warburg (DE) came to the conclusion that in cells “…the oxidative processes stand in closest connection with the physical state of the lipids” (3359).

Horace Middleton Vernon (GB) showed that oxidation of indophenol blue in cerebral tissue is due to the enzyme indophenol oxidase (cytochrome oxidase) which is especially abundant in grey matter and other respiring tissues (3219).

Gheorghe Marinescu (RO) demonstrated that grey matter could easily be distinguished from white matter when treated in vitro with Ehrlich’s indophenol reagent. The sharp delineation being due to the presence of indophenol oxidase in the cell bodies and dendrites (plentiful in grey matter) and absent from axons (plentiful in white matter). This paper also indicated that the cerebral area is very rich in dendrites (2101).

Gheorghe Marinescu (RO) was also the first to suggest that indophenol oxidase is located in the mitochondria (2512).

Arend Lourens Hagedoorn (NL) expressed the concept that the gene is autocatalytic (1361).

Edmund Beecher Wilson (US) surmised that the heredity factor causing color-blindness in humans is linked to the X chromosome (3519). This was the first gene assigned to a human chromosome.

Thomas Hunt Morgan (US) proposed that the genes for white eyes, yellow body, and miniature wings in Drosophila are linked together on the X chromosome (2251).

Thomas Hunt Morgan (US) provided incontrovertible evidence of recombination between sex-linked genes in Drosophila thus supporting Franciscus Alphonsius Janssens’ (BE) cytological evidence of crossing over (2252).

Walter Stanborough Sutton (US) had already predicted linkage in 1903. Interestingly enough these two men both worked at Columbia University just down the hall from one another in 1903. See, Sutton, 1903.

Schack August Steenberg Krogh (DK) studied the hydrostatics of the air bladder of Corethra larvae during 1896. He demonstrated that these organs function like diving tanks of a submarine (1836). This is a type of gnat whose larvae are often fed upon by fish.

Henry Bryant Bigelow (US) wrote a paper on the Siphonophorae, which was at that time one of the most important reports ever written on this group (311). These are in the phylum Cnidaria.

Thomas Burr Osborne (US) and Lafayette Benedict Mendel (US) reported that the coprophagy exhibited by rats benefits their health and growth (2412).

Margaret Reed Lewis (US) and Warren Harmon Lewis (US) were the first to culture eukaryotic cells on cover slips in vitro. They were also the first to attempt in vitro cultivation of eukaryotic cells using simple salt solutions (1949, 1950).

Marshall Albert Barber (US) proposed a new technique—the microinjection technique. He developed this method initially to clone bacteria and to confirm the germ theory of Koch and Pasteur (175). Later on, he refined his approach and was able to manipulate nuclei in protozoa and to implant bacteria into plant cells.

George Lester Kite (US) used microsurgical techniques to study the fine structure of cells. He found that protoplasm exists in the form of sols and gels of varying consistency with that of plants generally of a lower viscosity. That the nucleus contains a gel of high viscosity and that the membrane of the nucleus is a definite morphological structure belonging to the nucleus (1764-1766).

A. Lang (DE) observed that the lop-eared phenotype in rabbits is likely due to the multiple factor hypothesis which had been formulated by Nilsson-Ehle on the basis of his studies of quantitative characters in oats and wheat (1891).

William Ernest Castle (US) and Sheldon C. Reed (US) supported Lang's conclusion that lop-ears in rabbits is inherited in a multiple factor pattern (548).

Alexis Carrel (FR-US) and Montrose Thomas Burrows (US) successfully explanted malignant cells from Rous sarcoma, Ehrlich and Jensen rat sarcomas, a canine breast carcinoma, a primary human breast carcinoma, and a human sarcoma of the tibula into in vitro cell culture (530).

Frederick P. Gay (US) coined the word immunology (1236).

Walter Bradford Cannon (US) and Daniel de la Paz (PH) argued that strong emotions stimulated the sympathetic nerves and thence the secretion of epinephrine (adrenaline); all the varied effects of the hormone on the body could be seen as quick preparations for "fight or flight" (508, 509, 511, 512). “Fight or flight” was coined in the 1915 reference.

Henry Head (GB) and Gordon Morgan Holmes (GB) gave the first systematic account of the functions of the thalamus and its relationship to the cerebral cortex (1448).

Francis Peyton Rous (US) and James B. Murphy (US) were the first to use embryonated eggs to grow a virus (2699).

Joseph Goldberger (SK-US) and John Fleetezelle Anderson (US) established the viral etiology of measles (rubeola) when filtered respiratory tract secretions of measles patients were inoculated into macaque monkeys resulting in measles-like symptoms in these animals (69, 1260).

Hideyo Noguchi (JP-US) used an in vitro mixture of serum water containing fresh rabbit kidney or testicle to grow Treponema pallidum under anaerobic conditions (2370).

Hideyo Noguchi (JP-US) developed a serum diagnosis for syphilis and established the presence of Treponema pallidium in the lesions of syphilis in the central nervous system (2371).

George W. McCoy (US) and Charles W. Chapin (US) reported that they had recovered the organism responsible for tularemia from fleas (Diamanus montanus Baker = Ceratophyllus acutus Baker) taken from sick or dead ground squirrels and tested in guinea pigs (2140). This is the first scientific paper on tularemia, which gets its name from Tulare County, California where it was first known as a plague-like disease of rodents (2141).

Edward Francis (US) proved that the disease known in Utah as deer fly fever is tularemia and is transmitted from infected rabbits to man by the bite of the fly Chrysops discalis. He would later show that Pasteurella tularensis (now Francisella tularensis) was present in rabbits at the market place and that rabbit fever was not infrequent among humans in contact with rabbits (1167-1170).

Hachiro Ohara (JP) discovered the Japanese form of tularemia, Ohara's disease. It is also called yato-byo, meaning rabbit fever (2389).

Alberto Ascoli (IT) presented his thermo precipitation test for the diagnosis of anthrax using a tissue extract and anthrax antiserum. This test is used for detection of anthrax bacilli in animal hides and meat (100).

Charles Manning Child (US) formulated his axial gradient theory of embryonic development, proposing that certain regions of the developing embryo dominate others and mold them into subsidiary forms. He showed that these gradients are physiological in various ways by demonstrating that regions with different rates of growth differ in their susceptibility to poisons and narcotics that interfere with respiration and other functions of living cells (577-579). Though present knowledge views his theory as incorrect, in its time, it represented an early approach to understanding functional organization within organisms

Leland Ossian Howard (US) and William F. Fiske (US) were entomologists who recognized clearly that, of the numerous factors, which influence the morphology and natality of insects, only those, which act with increasing severity as populations become larger, are capable of adjusting populations to their environments (1580). Other biologists would later refer to these factors, which operate with increasing intensity as a population grows as density-dependent factors, and those, which do not do so as density-independent factors.

Leonard Noon (GB) and John Freeman (GB) helped establish the basis for immunotherapy or allergy shots, i.e., allergen-specific immunotherapy (SIT) (1181, 2375). Immunotherapy involves injecting the allergy sufferer with small, gradually increasing amounts of the substance that is causing the reaction. The idea is that over a time course, the body's immune system will become less sensitive to the substance and the allergy symptoms will be reduced or eliminated.

Hans Günther (DE) described acute porphyria (porphyrinuria) and noted that the signs and symptoms include red porphyrins in the urine, periodic attacks of abdominal pain, and mental disorder similar to schizophrenia or paranoia (1347).

Thomas Chalmer Addis (GB) made his claim that the fault in hemophilic blood is due to an inherited qualitative defect in the prothrombin (26).

Ethel Browne Harvey (US) described the changes that take place in the cortical region of an egg during fertilization. For example, the granules near the surface disappear in a wavelike manner around the egg (1432). These granules release material during their breakdown that promotes formation of the fertilization membrane.

Gordon R. Ward (GB) diagnosed human fascioliasis by finding eggs in feces (3373).

Erich Lexer (DE) stated that homografts (allografts) are invariably unsuccessful, even when transplanted from parent to child and vice versa (1956, 1957).

Hans Winterstein (DE) suggested that CO2 stimulated breathing by acidifying extracellular fluid near the "respiratory centers” (3553).

Thomas Chalmer Addis (US), E. Frank (DE), E. Hartmann (DE), Arthur J. Patek, Jr. (US) and Richard P. Stetson (US) observed that plasma, presumably largely depleted of platelets, was as effective as whole blood in correcting the in vitro and in vivo clotting defects in hemophilia. This meant that platelets did not contain the therapeutic agent necessary for clotting hemophilic blood (26, 1176, 2477, 2478).

Rudolph Matas (US) wrote a landmark article in which he described a challenge test to assess the degree and efficacy of the collateral circulation in patients under consideration for permanent occlusion of a major vessel. Matas studied the feasibility of such a test by temporarily occluding the carotid and femoral arteries in dogs for variable periods of time. In the introduction to his seminal article on the subject, he stated that "the chief object of this inquiry has been to determine whether the large arteries can be occluded long enough to make it possible to observe the effect of the arrested circulation in the territory supplied by the occluded vessel, without irreparably damaging the artery during the period of observation" (2116). See, Celsus, 30 B.C.E. and John Hunter, 1793b.

William Arbuthnot Lane (GB) performed resection of the cervical esophagus for cancer and reconstruction by skin graft (1889).

Harvey Williams Cushing (US) developed techniques to control bleeding in operations for brain tumors where ligature was not possible (737). 

Charles Doolittle Walcott (US) discovered a rich assemblage of algae and invertebrate fossils from the Middle Cambrian Period of the Paleozoic Era in the Burgess shale located in Yoho National Park in the Rocky Mountains, near Field, British Columbia, Canada (3348). The word Cambrian is taken from a Latin form of the Welsh name for Wales. Other fossil rich Cambrian sites include Chengjiang, China, the Wheeler Formation in Utah, and the Croixan Series in Minnesota-Wisconsin. (Shale is rock formed by condensation of layers of clay or mud, along with phytoplankton and other debris, sedimented at the bottoms of lakes or ocean basins.)

Samuel Wendell Williston (US) and Ermine Cowles Case (US) described Seymouria and other labyrinthodont amphibian and reptile fossils from the Permian beds of Texas and New Mexico (536, 3497-3499).

Louis Capitan (FR) and Denis Peyrony (FR) found a fossil remains of Homo sapiens neanderthalensis; Homo neanderthalensis dated at ca. 38,000 years old. The site was near La Ferrassie, France (518).


Alexis Carrel (FR-US) was awarded the Nobel Prize in Physiology or Medicine in recognition of his work on vascular suture and the transplantation of blood vessels and organs. He was the first American to receive the prize in physiology and medicine.

Max Theodor Felix von Laue (DE) theorized that it might be possible to determine the wavelength of x-rays —known to be extremely short—by using crystalline lattices as diffraction gratings (3300-3303).

Walther Friedrich (DE), Paul Knipping (DE), and Max Theodor Felix von Laue (DE) were the first to obtain x-ray diffraction patterns. They passed x-rays through a crystal of zinc sulfide. Laue had theorized that it might be possible to determine the wavelength of x-rays —known to be extremely short—by using crystalline lattices as diffraction gratings. However, because the crystal had lines of atoms in various directions, the results would be complicated. There would be beams located at varying distances and angles from the center, those distances and angles depending on the structure of the crystal. By beginning with a crystal of known structure, and measuring the amount of diffraction, the wavelength of the x-rays could be calculated. See, Braggs, 1915. Second, by using x-rays of known wavelength it was possible to deduce the structure of a crystal from the patterns produced on x-ray film. This was the beginning of x-ray crystallography (1192).

William C. Piper (US) developed calcium arsenate as a replacement for Paris Green and lead arsenate. It soon became important for controlling the boll weevil on cotton in the United States. Ref

William Küster (DE) proposed a correct formula for the ring system of porphyrins in which four pyrrole rings are linked together into a macrocycle by 4 methine bridges (1856). Porphyrin comes from the Greek meaning purple.

Henry Hallett Dale (GB) and Patrick Playfair Laidlaw (GB) prepared very active solutions of the hormone secretin (759).

Gunnar Agren (SE), Einar Hammarsten (SE), and Olof Wilander (SE), crystallized secretin (38).

Paul Mayer (DE) was the first to demonstrate that pyruvic acid is often reduced to lactic acid in various tissues. He also showed that pyruvic acid could be converted to glucose in fasting rabbits (2124). 

Gustav Georg Embden (DE) and Max Oppenheimer (DE) confirmed Mayer’s findings (1011). 

Gustav Georg Embden (DE), Karl Baldes (DE), and Ernst Schmitz (DE) noted that yeast juice and working muscle produced the same intermediate, which they believed to be glyceraldehyde (1007).

Donald Dexter van Slyke (US) described a procedure for the direct determination of amino acid (alpha-amino) nitrogen in protein hydrolysates and in extracts of animal tissues, in the presence of various other organic nitrogenous compounds, which occur in animal tissues (3199).

Elmer Verner McCollum (US), James Garfield Halpin (US), A.H. Drescher (US), and Gustav Fingerling (DE) showed that the body requires no dietary phosphorus-containing organic materials, simple inorganic forms are sufficient (1099, 2139).

Donald Dexter van Slyke (US) and Gustav M. Meyer (US) were the first to determine that amino acids, liberated during digestion in the intestine, are absorbed into the bloodstream, that they are removed from the blood by the other tissues, and that the liver alone possesses the ability to convert the amino acid nitrogen to urea (3200, 3206-3209).

Otto Folin (SE-US) and Willey Glover Denis (US), by direct chemical analysis, proved that it is amino acids rather than more complex intermediary products of protein digestion, which are absorbed by the intestine and enter the blood. They determined that ammonia is present in excessive amounts only in blood, which had just passed through the walls of parts of the colon in which putrefaction of fecal residues is in progress. They proved that ammonia is absorbed in fairly large quantities from such fecal putrefaction (1141-1144, 1146).

Casimir Funk (PL-GB-FR-US) suggested that the chemicals required in small quantities to prevent diseases such as beriberi, scurvy, pellagra, and rickets be called vitamines (1202). This name occurred to him when he was investigating Christiaan Eijkman’s anti-beriberi factor and found it to contain an amine group. He assumed that all of these factors required in small quantities contained an amine group (1201-1203). When it was discovered that this was incorrect Jack Cecil Drummond (GB) suggested dropping the final e producing vitamin. “The suggestion is now advanced that the final "-e" [of Funk's "vitamine"] be dropped, so that the resulting word Vitamin is acceptable under the standard scheme of nomenclature adopted by the Chemical Society…. It is recommended that the somewhat cumbrous nomenclature introduced by McCollum (Fat-soluble A, Water-soluble B), be dropped, and that the substances be spoken of as Vitamin A, B, C, etc” (894). The anti-beriberi factor was called vitamine B1 (thiamine) because it was the first water soluble vitamin characterized. It is also called the antineuritic vitamin because the deficiency syndrome is predominantly neurological. Funk also isolated nicotinic acid from rice (Oryza sativa) polishings, but failed to discover its relationship to pellagra.

Agnes Robertson Arber (GB), Bruce Rogers (GB), and Pforzheimer Rogers (GB) authored The Herbals, Their Origin and Evolution, which has remained the basic reference for the herbals (85).

Julien Tournois (FR) discovered that in the Japanese hop, Humulus japonicus, a decrease in day-length during the normal growth period provokes some floral reproduction. After obtaining similar results with another species of hop and hemp, he concluded that young plants flower when exposed to short days from germination onward. And he deduced that night-length, rather than the brevity of the day, was the determining factor (3136, 3137). These papers represent the origin of the study of photoperiodism.

Georg Albrecht Klebs (DE), from his studies of the houseleek (Sempervivum funkii), reached a similar conclusion in 1918 (1769).

Wightman Wells Garner (US) and Harry Ardell Allard (US) performed extensive experiments with three strains of tobacco (Nicotiana tabacum), four varieties of soybean (Glycine max) beans from Peru and Bolivia, radish (Raphanus sativus), carrot (Daucus carotus), lettuce (Lactuca sativa), cabbage (Capitata), wild aster (Symphyotrichum), climbing hempweed (Mikania scandens), ragweed (Ambrosia artemisiifolia), hibiscus, wild violet (Viola papilionacea), and goldenrod (Solidago). They concluded that of the various factors of the environment, which affect plant, life the length of the day is unique in its action on sexual reproduction. Unlike temperature, rainfall, or light intensity, daylight is “the only consistently rhythmic feature of the external environment.” They coined and defined the terms short-day plants (SDP), long-day plants (LDP), intermediate plants, and indeterminante or day-neutral plants. Their terminology is descriptive of the length of the period of continuous illumination to which the plants are exposed during each 24-hour period. Garner also introduced the term photoperiodism for the response of organisms to relative length of night and day (1217, 1218).

Karl C. Hamner (US) and James Frederick Bonner (US) proved that Tournois was correct. The length of night is more important to short-day plants than length of day in floral initiation. They found that the cocklebur (Xanthium strumarium) must have about 8.5 hrs. of uninterrupted night for flowering, this was the discovery of the night-break phenomenon (1397). 

Alexei F. Kleshnin (RU) concluded, “It is only the amount of energy absorbed by some acceptor of the leaf that is important…” “For every region of the spectrum there is a definite threshold of radiation intensity below which this region is perceived as darkness in the photoperiodical process; this threshold is different for different plants” (1773).

Edgar Douglas Adrian (GB) published a study on the effects of the block of nerve conduction induced by application of alcohol vapors to small segments of nerves from which he derived the conclusion that nerve signals regenerate along the nerve fiber during the conduction process (31).

Oil barriers were recommended for control of chinch bugs (genus Blissus). They are considered pests that feed on stems of turfgrass. Paradichlorobenzene was first used in the U. S. as an insecticide: used for clothes moth control. Eugenol derivatives were first noted as entomological attractants. Nicotine insecticides were developed for control of onion thrips. The U. S. Public Health Service adopted hydrocyanic acid gas as a standard fumigant (2879).

Friedrich Baltzer (DE) reported the first valid case of environmental sex determination in nature. He observed in the marine Bonellia (Echiuridae) that if a larva finds a suitable substrate, it would settle and most probably develop into a female. However, if it is picked up by the proboscis of an adult female, the larva will attach itself to the proboscis with the help of an "underwater glue" and develop into a male (153).

Oscar M. Schloss (US) proposed cutaneous tests (skin test or scratch) in the diagnosis of the food allergy (Schloss 1912; Schloss 1915).

Fritz B. Talbot (US) used the scratch test, to associate asthma to a food "intoxication" by egg (3069).

Alfred Erich Frank (DE) showed that the posterior lobe of the pituitary gland produces an antidiuretic hormone (vasopressin) which controls diabetes insipidus (1174).

Jost Frederick Gudernatsch (DE) caused a female frog to ovulate in September, some seven months before the normal breeding period, by subcutaneously implanting six pituitary glands from adult female donors. The eggs were artificially inseminated. When the tadpoles developed hindlimb buds, minute amounts of thyroxin (bits of horse thyroid) were added to the water. In about three weeks, the treated tadpoles reabsorbed their swimming tails, grew hindlimbs and then forelimbs, lost their horny teeth (used for plant feeding), shortened their intestinal tracts in preparation for carnivorous feeding, modified their respiratory and integumentary systems for terrestrial environments, and emerged as normal but miniature air-breathing adult frogs.

Since thyroxin initiated the metamorphic changes long before they would normally occur, the resulting froglets are about one-third the size of those metamorphosing in nature. Thyroid-ectomized tadpoles never metamorphose, but grow to giant size (1336, 1337).

Wilbur Willis Swingle (US) reproduced Gudernatsch's results on metamorphosis in frogs by providing or withholding inorganic iodine (3059).

Martinus Willem Beijerinck (NL) was possibly the first person to recognize that bacterial variation might reflect the occurrence of gene mutation (261).

Thomas Hunt Morgan (US) reported the first sex-linked recessive lethal gene in Drosophila (2253).

Thomas Hunt Morgan (US) and Clara J. Lynch (US) were the first to publish a case of autosomal linkage in Drosophila (2258).

Montrose Thomas Burrows (US) devised a perfusion chamber, which, for the first time, allowed cells grown in vitro to be continuously supplied with fresh medium (479).

Charles Louis Alphonse Laveran (FR) and Félix Mesnil (FR) discovered that trypanosomes could be maintained indefinitely in rats and mice by serial passages (1908).

Christian Champy (FR) noted that eukaryotic cells grown in vitro often lost some of the specific features that characterized them in their normal in vivo habitat. He denominated the process dedifferentiation (563, 564).

Robert A. Lambert (US) was the first to describe the formation of multinucleated cells in vitro (1866).

Charles C. Bass (US) and Foster M. Johns (US) succeeded in the in vitro culturing of the malarial protozoan (194).

At about this time it became routine to record the four vital signs (temperature, respiration, pulse rate, blood pressure) on all patients’ charts. See, Cushing, 1895.

Isaac A. Adler (GB) was the first to link lung cancer to cigarettes (28).

Franz H. Müller (DE) indicated that non-smokers were more common in healthy populations than among lung cancer patients (2279).

Ernest Ludwig Wynder (US) and Evarts Ambrose Graham (US) observed a relationship between lung cancer and smoking. Together they performed the most systematic and detailed survey to date showing links between smoking and cancer (3587).

William Richard Shaboe Doll (GB), Austin Bradford Hill (GB), and Richard Peto (GB) almost simultaneously reached the same conclusions. They were also able to show that stopping smoking immediately reduces the risk of cancer (856-860).

E. Cuyler Hammond (US) and Daniel Horn (US) issued their report entitled: Smoking and death rates: report on forty-four months of follow-up of 187,783 men. They announced a link between cigarettes and both lung cancer and heart disease. Regular cigarette smokers were reported to be ten times more likely to die from lung cancer than non-smokers. They revealed that the chances of heart attack were seventy percent higher for smokers than for non-smokers (1394-1396)

The United States Surgeon General concluded that "Cigarette smoking is causally related to lung cancer in men; the magnitude of the effect of cigarette smoking far outweighs all other factors" (3179).

Mikhail F. Denissenko (US), Annie Pao (US), Moon-shong Tang (US), and Gerd P. Pfeifer (US) found the first direct biological link between cigarette smoking and lung cancer. DNA mutations caused by the cigarette smoke by-product benzo[a]pyrene in the tumor suppressor gene p53 were found to be the same as those found in lung cancer cells (818). See, von Sömmerring, 1795.

William Richard Shaboe Doll (GB), Richard Petro (GB), Jullian Boreham (GB), and Isabelle A. Sutherland (GB) reported that a substantial progressive decrease in the mortality rates among non-smokers over the past half century (due to prevention and improved treatment of disease) has been wholly outweighed, among cigarette smokers, by a progressive increase in the smoker to non-smoker death rate ratio due to earlier and more intensive use of cigarettes. Among the men born around 1920, prolonged cigarette smoking from early adult life tripled age specific mortality rates, but cessation at age 50 halved the hazard, and cessation at age 30 avoided almost all of it (861).

Roger I. Lee (US) and Paul Dudley White (US) developed the Lee-White clotting time course test. Lee demonstrated that it is safe to give group O blood to patients of any blood group, and that blood from all groups can be given to group AB patients. The terms "universal donor" and "universal recipient" are coined (1921).

Hakaru Hashimoto (JP) described four patients with a chronic disorder of the thyroid, which he termed struma lymphomatosa (Hashimoto’s thyroiditis). The thyroid glands of these patients were characterized by diffuse lymphocytic infiltration, fibrosis, parenchymal atrophy, and an eosinophilic change in some of the acinar cells (1434). It is now appreciated that the progressive enlargement of the thyroid gland is due to autoimmunization against the patient’s own thyroglobulin circulating in the blood.

Wilhelm Weinberg (DE) made a detailed study of the dwarfism trait, achondroplasia, which he knew to be inherited as a Mendelian dominant. Specifically, he noted that an affected child born from normal parents tended to be among the last-born children in the sibship. From this he suggested that these were new mutations (3414).

Lionel Sharples Penrose (GB) relates achondroplasia to advanced paternal age and spontaneous mutation in the male gamete that has experienced many divisions (2502, 2503).

Samuel Alexander Kinnier Wilson (GB) reported on progressive lenticular degeneration (Wilson’s disease): A familial nervous disease associated with cirrhosis of the liver. Karl Friedrich Otto Westphal (DE) and Ernst Adolf Gustav Gottfried von Strümpell (DE) had previously described Westphal-Strümpell's pseudosclerosis but they failed to discuss the lenticular or hepatic aspects, thus they failed to recognize the two major signs of the disorder (3330, 3439, 3525, 3526).

Gleb von Anrep (LB-GB) discovered a regulatory mechanism of the heart whereby cardiac performance improves as the afterload (aortic pressure) is increased. It is called homeometric autoregulation because it is independent of muscle length (3241).

Arthur Läwen (DE) used curare to relax the abdomen during surgery keeping the patient alive by artificial ventilation (1909).

Hürter (DE) made the first arterial punctures in humans. He was able to show that the arterial oxygen saturation in four normal subjects was between 93% and 100% (1599).

William Christopher Stadie (US) is believed to have been the first to introduce arterial puncture into clinical medicine where he used it to compare the oxygen content of air inhaled with that in arterial blood. He demonstrated that cynosis is due to arterial anoxemia (2972).

William Christopher Stadie (US) treated cases of cynosis in hyperbaric oxygen rooms he developed (2973).

Frizt Bleichroeder (DE), Ernst Unger (DE), and Walter Loeb (DE) were among the first to perform human vascular catheterization. They inserted catheters into the blood vessels without x-ray visualization. After numerous experiments on dogs without any accident, Bleichroeder successfully catheterized the heart of Joseph Portmann, laboratory technician at the hospital. Bleichroeder's approach to the heart was from the femoral vein. The procedure was done with a ureteral catheter (335).

Ernst Unger (DE) inserted ureteric catheters transcubital into the axillary vein, through the femoral vein into the inferior vena cava, and through the femoral artery into the abdominal aorta, and, through the ulnar artery into the arch of the aorta (335, 3176).

Werner Theodor Otto Forssmann (DE), a surgical trainee, was the first to document right heart catheterization in humans using radiographic techniques. Forssmann said, “After the experiments in the cadavers had been successful, I undertook the first experiments in living man by experimenting on myself…. I carried out under local anesthesia a venesection in my left elbow and introduced the catheter without resistance in its whole length of 65 cm…. I checked the position of the catheter in the röntgen picture and I observed the forward advance of the catheter in a mirror held in front of the fluoroscope screen by a nurse…. The method…has opened numerous prospects for metabolic studies and for studies of cardiac activity” (1154, 1155). In return, he was fired from his position at the hospital and won the Nobel Prize in 1956. See, Claude Bernard, 1844.

Otto Klein (DE) published 11 successful experiments on humans in which he catheterized and measured cardiac output (1771).

George P. Robb (US) and Israel Steinberg (US) successfully performed cardiac catheterization (introduction of a small tube into the heart by way of veins or arteries) on humans and were able to visualize the chambers of the heart on x-ray film (2661).

André Frédéric Cournand (FR-US) and Hilmert A. Ranges (US) inserted a catheter into the right atrium of a human and measured cardiac output. They found that the catheter could be left in place for considerable periods of time without harm (676). See Forssmann, 1929.

André Frédéric Cournand (FR-US), Richard L. Riley (US), Stanley E. Bradley (US), Ernest S. Breed (US), Robert P. Noble (US), Henry D. Lauson (US), Magnus I. Gregersen (US), and Dickinson Woodruff Richards, Jr. (US) investigated traumatic shock in man and found: 1) that with a deficit of 40 to 50 percent in blood volume, there is a critical depression in cardiac output and in return of blood to the right heart worsening as shock continues unrelieved, 2) that peripheral resistance tends to be maintained in hemorrhage and skeletal trauma, and greatly increases in severe burns, 3) that peripheral blood flow is reduced particularly in the kidneys, and 4) that whole blood offers great advantages over plasma as sustaining therapy (677, 2627).

André Frédéric Cournand (FR-US) demonstrated the feasibility of making accurate measurements of cardiac output in man under physiological conditions. He reached the conclusion that the quantity of oxygen absorbed by the body per minute must be equal to that taken up at the lungs, which would in turn be equal to the total pulmonary blood flow multiplied by the difference in oxygen concentration between the blood entering and leaving the lungs (672).

Dickinson Woodrruff Richards (US) measured cardiac output by catheterization (2628). 

Richard A. Bloomfield (US), Henry D. Lauson (US), André Frédéric Cournand (FR-US), Ernest S. Breed (US), and Dickinson Woodruff Richards (US) used cardiac catheterization to record right heart pressures in normal subjects and in patients with chronic pulmonary disease and various types of cardiocirculatory disease (338).

André Frédéric Cournand (FR-US), Janet S. Baldwin (US), and Aaron Himmelstein (US) were among the first to apply cardiac catheterization to the diagnosis of congenital heart lesion (674, 675).

André Frédéric Cournand (FR-US) and Dickinson Woodruff Richards (US) continued to develop venous catheterization (673, 2629).

John A. Hartwell (US), Joseph P. Hoguet (US), and Fenwick Beekman (US) concluded from experiments on dogs that death following experimental intestinal obstruction is due, first, to a dehydration or loss of water from the tissues as a result of the excessive drain into the lumen of the intestine and vomiting, and, second, to the presence of a toxin in the circulating blood. They demonstrated that duodenojejunal obstruction in dogs responds well to liberal intravenous administration of saline (1428-1431).

Edward Flatau (PL) wrote a classic monograph on migraine (1120).

James Bryan Herrick (US) was the first observer to identify and describe the clinical features of sudden obstruction of the coronary arteries, i.e., coronary thrombosis (1492).

Henri-Charles-Jules Claude (FR) and Marie Loyez (FR) described syndromes of lesions in the brain stem. The Claude syndrome of ipsilateral oculomotor nerve paralysis and asynergia on the other side together with dysarthria is a major contribution as is Claude’s Hyperkinesis where there are reflex movements of paretic muscles elicited by painful stimuli (596). Need Hyperkinesis Ref

Rudolf Magnus (NL) and Adriaan de Kleijn (NL) found that standing, walking, and bodily balance in general, are reflexes that are affected, partly by the position of the head in space and partly by its position in relation to the neck. Both groups, which can reinforce or weaken each other according to a definite pattern, have been combined under the name of attitudinal or standing reflexes since they enable the animal to stand up. They discovered a special group of ‘righting reflexes’ which are elicited, partly by the vestibular apparatus in the inner ear, and the neck, partly by the eyes, and, partly, by the trunk of the body. It is these complex reflexes that enable a cat always to land on its feet (2063, 2067, 2068). 

Rudolf Magnus (NL) gives a clear definition of tonic reflexes. These reflexes are called tonic, because they last as long as the head keeps a certain position; and that not only for minutes and hours, but also for days, months and even years. He was aware of two classes of tonic reflexes, those that originate in the labyrinthine and depend solely on head position in space. These can be contrasted to the neck tonic reflexes, which depend only upon the position of the head on the neck and are independent of body position in space. Magnus also showed that there is a shift in excitation, so that a reflex evoked with the head straight can be much different than when the neck is flexed. The classic picture of the anencephalic infant with its head turned to the side, with the viewed limb extended, and the contralateral limb flexed, is the epitome of the neck reflexes that underlie normal posture. Magnus also showed that the neck reflexes cause the forelimbs to extend when the head is flexed back and the forelimbs to be flexed when the neck is flexed forward. Finally, he and his group demonstrated that processing for the neck reflexes is in the upper cervical segments, whereas the vestibulospinal reflexes are processed in the medulla (2064-2066). 

Marin-Théodore Tuffier (FR), in 1912, performed the first operation to open a stenotic (narrowed) heart valve. Using his finger he attempted to push the wall of the aorta near the heart through the stenotic aortic valve and dilate the valve (3158). The patient recovered and improved. Tuffier was also the first to transport a wounded soldier by airplane.

Elliott Cutler (US) and Samuel A. Levine (US) used a tenotome (a tendon-cutting instrument) to successfully relieve a patient’s mitral stenosis (a narrowing of the mitral valve between the upper and lower chambers of the left side of the heart). The patient was a 12-year-old girl whose mitral valve had been narrowed by rheumatic fever (744). This was a very dangerous operation, which was soon abandoned because of its low rate of success.

Henry Sessions Souttar (GB) performed the first successful transauricular mitral valvotomy. It was on a 15-year-old girl. He approached the valve from the left auricular appendage and used a finger as the basic instrument to dilate the stenotic mitral valve. He passed his finger through the mitral valve orifice into the left ventricle and did not cut the valve cusps. The patient made an excellent recovery (2958).

Dwight Emary Harken (US), Laurence B. Ellis (US), Paul F. Ware (US), Leona R. Norman (US), Charles Philamore Bailey (US), Charles Baker (GB), Russell C. Brock (GB), and John Maurice Hardman Campbell (GB) reported on a daring procedure to correct mitral stenosis. Harken had first performed this on WWII shrapnel victims by cutting a small hole in the side of a beating heart then inserting a finger and very carefully widening the narrowed valve (138, 139, 149, 1413). Charles P. Bailey (US) was the first to perform this operation, June 10, 1948. Russel C. Brock (GB) performed the same operation just months later.

Janet Elizabeth Lane-Claydon (GB) published a groundbreaking study of two cohorts (groups) of babies, fed cow's milk and breast milk respectively. Lane-Claypon found that those babies fed breast milk gained more weight, and she used statistical methods to show that the difference was unlikely to occur by chance alone. She also investigated whether something other than the type of milk could account for the difference, an effect known as "confounding" (1890). This study may have been the first epidemiologic implementation of a retrospective (historical) cohort study, the first modern description of "confounding" with an accompanying analysis, and the first use of Student’s t test to assess the difference of means in small samples. Lane-Claydon credits Major Greenwood for his help in the statistical analysis of her data.

Just Marie Marcelin Lucas-Championnière (FR) described Neolithic human skulls from nearly all parts of the world with disks of bone removed. This process, called trephining, represents the first evidence of man’s intervention in an attempt to heal his fellow man. This surgical procedure was likely done to release confined demons associated with epilepsy, infantile convulsions, headache, and various cerebral diseases (2019).

Jacques Loeb (DE-US) wrote The Mechanistic Conception of Life: Biological Essays (1989).

John Murray (GB) and Johan Hjört (NO) wrote, The Depths of the Ocean, a pioneering work in oceanography (2298).

Charles Dawson (GB), Arthur Smith Woodward (GB), and Elliot Smith (GB) reported to the Geographical Society of London announcing their discovery of the fossil remains of Piltdown man (783). This became the most infamous hoax in the history of paleontology.


“There is no harder scientific fact in the world than the fact that belief can be produced in practically unlimited quantity and intensity, without observation or reasoning, and even in defiance of both, by the simple desire to believe founded on a strong interest in believing.” George Bernard Shaw (2887).

Corpora non agunt nisi fixata” [a substance is not (biologically) active unless it is "fixed" (bound by a receptor)]. Paul Ehrlich (972).

Charles Robert Richet (FR) was awarded the Nobel Prize in Physiology or Medicine for his work on anaphylaxis.

Niels Henrik David Bohr (DK) produced a theory of the energy status of the atom (in particular, the hydrogen atom) that showed its structure to be mathematical. He assumed that the electrons could revolve about the nucleus in definite orbital paths, and he then established a rigorous mathematical theory to account for all those possible states. While the electrons remained in their predicted paths they emitted no energy, but when one would jump spontaneously from an outer to an inner orbit, it would emit energy as a quantum of light (344). 

Joseph John Thomson (GB), using equipment he calls a "positive-ray" apparatus, observed that neon atoms have two different atomic weights (20 and 22). The existence of isotopes is confirmed (3109).

Arthur Holmes (GB) concluded that the breakdown of radioactive isotopes in igneous rocks could be used to determine when the rocks solidified. The ability to determine the absolute ages of rocks enables scientists to better date fossils. Using his quantitative time scale and other factors, he made an estimate of Earth's age that was far older than anyone had suggested until then – at least 3 billion years. His initial estimates of Earth's eras have held up remarkably well over time: For example, he placed the beginning of the Cambrian period at around 600 million years ago; today 590 million years is the time frame largely accepted (1557).

Charles Marie Paul Auguste Fabry (FR) and Henri Buisson (FR) used spectrographic techniques to demonstrate that the principal atmospheric location of ozone is in the stratosphere. They noted that it is important for filtering out ultraviolet radiation (1060). 

E. Riehm (DE) discovered that organo-mercurial treatment of cereal seed would protect it from fungal attack. It was used to prevent a disease called bunt in wheat (2642).

Leonor Michaelis (DE-US) and Maud Leonora Menten (CA) used the rules of chemical kinetics to propose an equation, which describes how the rate of an enzyme-catalyzed reaction varies with the concentration of the substrate. They postulated that a complex is formed between an enzyme and its substrate, which complex then decomposes to yield free enzyme and the reaction product. The rate at which this occurs determines the overall rate of substrate-product conversion. The velocity of such a reaction is greatest when all the sites at which catalytic activity can take place on the enzyme molecules (active sites) are filled with substrate; i.e., when the substrate concentration is very high. These relationships provide the basis for all kinetic studies of enzymes and also have been applied to investigations of the effects of carriers upon the transport of substances through cell membranes (2200). This work was influenced by the work of Victor Henri (FR) (1476).

Kurt G. Stern (US) spectroscopically demonstrated the existence of an intermediate enzyme-substrate complex for the enzyme catalase, thus confirming the Henri-Michaelis-Menten hypothesis (3000).

Torsten Ludvig Thunberg (SE) and Heinrich Otto Wieland (DE) maintained, as a result of their experiments over a number of years, that the crucial reaction in living tissue is dehydrogenation (removal of hydrogen atoms from foodstuffs, two at a time). It is this, they maintained, and not the addition of oxygen, that is enzymatically catalyzed (3118, 3122, 3124, 3125, 3465-3467). They were opposed by Otto Heinrich Warburg (DE) who, as a result of his own experiments, maintained that it is the addition of oxygen that is crucial and that this reaction is catalyzed by enzymes containing iron atoms. He wrote, “ … that the oxygen respiration in the egg [sea-urchin] is an iron catalysis; that the oxygen consumed in the respiratory process is taken up initially by dissolved or adsorbed ferrous ions” (3360).

As it turned out both were correct. Together they made a good start toward working out the respiratory chain in tissues, the route by which the body converts organic molecules to water and carbon dioxide, releasing energy in the process.

Santiago Ramón y Cajal (ES) developed gold chloride-mercury stain to show astrocytes (2590).

Georg Albrecht Klebs (DE), from a thorough study of the houseleek, Sempervivum funkii, deduced that light operates perhaps not as a nutritive factor, but on the contrary, more catalytically (1768).

Henry Drysdale Dakin (US) and Harold Ward Dudley (US) discovered the enzyme glyoxalase, which is widely distributed in nature and catalyzes the interconversion of methyl glyoxal and lactic acid (754).

Carl Alexander Neuberg (DE-US) and Johannes Kerb (DE) while researching alcoholic fermentation by yeast, proposed an interpretation of this process as the net result of a series of consecutive step reactions (pathway), each one chemically conceivable and simple in nature, i.e., glycolysis (2337). Glycolysis occurs (with some variations) in nearly all organisms, both aerobic and anaerobic.

Robert Chodat (CH) was one of the first to obtain axenic cultures of algae (583).

Peter Boysen-Jensen (DK) working with coleoptiles of barley seedlings established the existence of phytohormones or auxins (Greek, to increase) which are responsible for the chemical transmission of growth responses of higher plants. He demonstrated that the phototropic influence is a chemical agent, since it can cross an incision, but cannot pass through a mica barrier (393, 394).

Frits Warmolt Went (NL-US) hypothesized, as had others, that a plant’s growing tip is a source of substances promoting the growth of cells lower down the organ. His creative innovation was to collect such growth hormones by allowing them to diffuse from the cut surface of the excised tip into gelatin blocks. When applied symmetrically to the subapical tissue, these gelatin blocks promoted elongation of the decapitated coleoptile, and when applied asymmetrically, they caused curvature in a dose-dependent manner. This experiment, which succeeded in the spring of 1926, was the first unequivocal demonstration of the existence of a growth-promoting hormone (later named auxin) in plant tissues (3431).

Fritz Kögl (NL), between 1931-1935, extracted minute quantities of plant growth promoters from the urine of man and other animals. He named them auxins which were later identified as auxin a and auxin b. Kögl identified auxin b as 3-indoleacetic acid (1795).

Fritz Kögl (NL), Arie Jan Haagen-Smit (NL-US), and Hanni Erxleben (NL) isolated auxin a from human urine (1796).

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) (1797, 1799, 3101).

Fritz Kögl (NL), Arie Jan Haagen-Smit (NL-US), and Hanni Erxleben (NL) isolated auxins and characterized them chemically (1798).

George Robert Sabine Snow (GB) found that indoleacetic acid (IAA) stimulates cambial activity (2947).

James Frederick Bonner (US) and Samuel G. Wildman (US) demonstrated that indolacetic acid is a principal native auxin of higher plants (352).

Harry Federley (FI) proposed that mules are sterile due to a failure of normal sperm production by meiosis, the type of cell division that gives rise to germ cells. Specifically the failure occurs at the stage of synapsis, when the homologous chromosomes of maternal and paternal origin come together (1069).

William Ernest Castle (US) made significant contributions toward simplifying genetic terminology and formulae (544).

Elbert Thomas Bartholomew (US) studied potato black heart where he elucidated the effects of abnormal environmental conditions on the metabolism of the host cells. This study showed how environment could bring on disease (191, 192).

Howard P. Barss (US) was the first to describe bacterial blight of hazelnuts (Corylus avellana) (188).

Shiro Tashiro (JP-US) discovered that the production of the nerve impulse depends upon the metabolic activity of the nerve fiber (cell) (3078).

Antonio Berlese (IT) theorized that the insect larva is a free-living, feeding embryo. He believed that the larval stage is equivalent to the pro-nymph stage of more primitive insects with incomplete metamorphosis, like grasshoppers (289). 

Vilém Laufberger (CZ) demonstrated that desiccated cattle thyroid glands could induce the metamorphosis of the amphibian Amblyostoma mexicanum (Siredon mexicanum) from its neotenic form to the adult form, which is not found in nature (29, 1905).

Julian Sorell Huxley (GB), unaware of Laufbergers work, performed the same experiment on the axolotl (1608). 

William Bateson (GB) discovered that dominance, in a genetic context, is not always absolute (208). As a result, terminology such as partial dominance, incomplete dominance, codominance, lack or absence of dominance, intermediate dominance, imperfect dominance, egalitarian dominance, and transdominance came into use. 

Alfred Henry Sturtevant (US) and Thomas Hunt Morgan (US) discovered that despite their physical linkage some recombination does take place between genes on the same chromosome. They reasoned that the mechanism responsible is crossing over between homologous chromosomes. By measuring the frequency with which linked genes segregate Morgan and Sturtevant were able to construct a genetic map of the four chromosomes of Drosophilia; a map which turned out to be linear (2256, 3041).

Alfred Henry Sturtevant (US) and George Wells Beadle (US) postulated that the genes are arranged in a manner similar to beads strung on a loose string (3047). 

Rollins Adams Emerson (US) and Edward Murray East (US) discovered multiple allelomorphism in maize and also in beans (1014, 1015).

Gershom Franklin White (US) showed the cause of sacbrood in honeybees, Apis mellifera Linn., to be a filterable agent, i.e., virus (3449).

Alexander Ivanovitch Petrunkevitch (RU-US) began what became an important group of monographs on fossil arachnids (2514-2518).

Fujiro Katsurada (JP) described metagonimiasis when he first observed eggs of Metagonimus yokagawai in feces (date is disputed in various studies) (1718). M. takahashii was described later first by Suzuki in 1930 and then M. Miyatai was described in 1984 by Saito. Metagonimiasis is a disease caused by an intestinal trematode, most commonly Metagonimus yokagawai, but sometimes by M. takashii or M. miyatai. The metagonimiasis causing flukes are one of two small flukes called the heterophyids.

John Murray (GB) and Johan Hjört (NO) led the Michael Sars deep-sea expedition. This expedition greatly expanded knowledge about deep-sea animals, including ecological patterns (2297). Michael Sars was a Norwegian zoologist (1805-1869). 

Alfred Whitmore (GB) described melioidosis, a glanders-like disease of rodents, transmissible to man, occurring in India, the Malay states, and Indo-China, caused by Burkholderia pseudomallei (Malleomyces pseudomallei) (3452). It is also called Whitmore's disease.

Nicolaas Louis Söhngen (NL) reported that the presence of a solid phase could influence a diversity of bacterial processes, such as nitrogen fixation, alcohol oxidation, nitrification, and denitrification (2951). 

Chlorophenol was introduced as a fungicide. Ref

Albert Francis Blakeslee (US) discovered that copulation between two fungal thalli of opposite mating types precedes the formation of zygospores in Rhizopus (328).

Rollins Adams Emerson (US) discovered and analyzed variegated pericarp, a highly mutable gene in maize and an example of multiple allelomorphism. With this work he provided evidence that mutations can arise in somatic cells contrary to the prevailing opinion that they occurred only in germinal tissue (25).

Victor Ernest Shelford (US) studied succession in dune environments; this included his famous relating of variations in tiger beetle coloration to their presence in different successional stages, and in turn to a law of tolerance that related presence/absence to limiting factors in the environment (2889).

Charles C. Adams (US) and Victor Ernest Shelford (US) wrote two of the earliest books dealing with animal ecology (23, 2889).

Carl A. Kling (DE) worked out the viral etiology of varicella (chickenpox) (1774).

Emil Adolf von Behring (DE) reported the successful use of toxin-antitoxin mixtures in the immunization of children against diphtheria. The vaccine proved unreliable and only gave consistent results after Paul Ehrlich standardized it (3243).

Béla Schick (HU-AT-US) developed the Schick Test, a practical method for distinguishing non-immune individuals from those already immune to diphtheria. It consists of injecting into the skin a very low dose of diphtheria toxin and observing the local reaction. In those whose blood serum contains no antitoxin, a characteristic reddish swelling develops at the site of injection, i.e., the Römer reaction. In those who are immune, the antitoxin already present in the circulation neutralizes the injected toxin and prevents the reaction from occurring (2817).

James Cecil Mottram (GB) showed that in both plant and animal tissues (the tips of bean shoots and ova of Ascaris megalocephala) cells are more vulnerable to damage by beta and gamma radiation when they are in process of division than in the resting stage, and that the metaphase is the most vulnerable stage. This damage results in profound nuclear changes affecting chromatin (2271).

 Claude Gordon Douglas (GB), John Scott Haldane (GB), Yandell Henderson (US), Edward C. Schneider (US), Gerald B. Webb (GB), and J. Richards (GB) demonstrated that at a given carbon dioxide pressure, oxygenated blood takes up less carbon dioxide than deoxygenated blood (876).

Reinhard von den Velden (DE), A. Farini (IT), and B. Ceccaroni (IT) discovered the antidiuretic effect of posterior lobe pituitary gland extract (vasopressin). Each had patients with disease or damage to the pituitary accompanied by polyuria and, interpreting this to be due to the gland’s impaired function, they easily controlled the excessive water loss by administration of extracts of the posterior lobe (1068, 3251). See Frank, 1912

Eli Kennerly Marshall, Jr. (US) developed a rapid (urease) method for the quantitative determination of urea in urine and blood (2104-2106).

Roger I. Lee (US) and Paul Dudley White (US) reported on a clinical study of the coagulation time course of blood (1921).

Frank Rattray Lillie (US) hypothesized the existence of a substance in the jelly coat of eggs, which causes sperm cells to clump together. He coined the name fertilizin for this substance (1965).

Lillie elaborated on his thoughts in a follow-up paper (1966).

Jules Jean Baptiste Vincent Bordet (BE) and Léon Delange (BE) described a lecithin rich activator (cytozyme) in an alcohol extract of blood platelets (361).

William Henry Howell (US) discovered that Bordet’s cytozyme (thromboplastic substance, or tissue fibrinogen) is a cephalin (phosphatidylethanolamine) rather than a lecithin (1584, 1586).

George Hoyt Whipple (US) reported the absence of prothrombin in a case of melena neonatorum in a 3-day-old infant who developed melena and other hemorrhagic symptoms (3444). He also described abnormal hemorrhage associated with prothrombin deficiency in a patient with obstructive jaundice. In this paper Whipple describes the first known method for determining prothrombin-time (3445).

Aldred Scott Warthin (US) discovered a relationship between heredity and carcinoma as shown by the study of the cases examined in the pathological laboratory of the University of Michigan, 1895-1913 (3377).

Aldred Scott Warthin (US) gave the classic description of pulmonary fat embolism (3378).

John Jacob Abel (US), Leonard George Rowntree (CA-US), and Benjamin Bernard Turner (US) invented the artificial kidney when they developed a device for vivi-diffusion of blood of small animals. This was similar to a shell-and-tube heat exchanger. A series of handmade nitrocellulose tubes of 8 mm inside diameter was connected by glass manifolds and enclosed in a glass shell. Blood flowed through the collodion tubes, while isotonic saline solution flowed around the tubes. To prevent clotting of the blood in the extracorporal circuit, hirudin, obtained by crushing the heads of leeches, was used as an anticoagulant. 

The authors noted the potential of this invention when they stated, “There are numerous toxic states in which the eliminating organs of the body, more especially the kidneys, are incapable of removing at an adequate rate the natural or unnatural substances whose accumulation is detrimental to life. In hope of providing a substitute … a method has been devised by which the blood of a living animal may be submitted to dialysis outside the body” (10, 11).

William Thalhimer (US), Donald Y. Solandt (US), and Charles Herbert Best (US-CA) contributed to the evolution of hemodialysis with the demonstration that commercially available cellophane tubing could be used for in vivo dialysis (3086-3088).

Willem Johan Kolff (NL-US), Henrick T. J. Berk (NL), Maria ter Weele (NL), A.J.W. van der Ley (NL), E.C. van Dijk (NL), and Jacob van Noordwijk (NL) invented the artificial kidney for use with humans. It was a rotating drum artificial kidney, made by winding 100 feet of cellophane in a spiral pattern around a large horizontal drum, which revolved in an enamel tube containing a rinsing fluid. Gravity drew blood in the cellophane to the lowest point, and as the drum turned, the blood worked its way from one end of the cellophane tube to the other, releasing its impurities into the surrounding fluid as it traveled (1806).

Willem Johan Kolff (NL-US) demonstrated that in vivo dialysis could replace all known excretory functions of the kidney and regulate the electrolyte pattern of the blood plasma water in patients (1805).

Abraham Albert Hijmans van den Bergh (NL) and Isidore Snapper (NL-US) reported, relative to jaundice, that it was suspected that bilirubin passes into the urine once its blood level passes a threshold value. The threshold value was not known. They devised a test to detect the presence of bilirubin in blood serum or plasma (3187).

Guido Banti (IT) concluded that the leukemias are systematic diseases arising from hemopoietic structures, lymph glands, and bone marrow, and that they are the consequence of limitless proliferative power of staminal blood cells (164). This is still the basic definition of leukemia.

Edmond Barthe de Sandfort (FR) developed keritherapy, the treatment of burns by using the paraffin-resin solution ambrine (189).

Edmond Barthe de Sandfort (FR) advocated keritherapy in the treatment for rheumatism by plunging of the whole body or the parts affected into heated paraffin (190).

Hugh Morriston Davies (GB) performed a hilar dissection and ligation of individual pulmonary arteries and veins and sutured the bronchial stump closed in a patient with lung cancer (781). 

Evarts Ambrose Graham (US) and Jacob Jesse Singer (US) removed a whole lung for cancer, performing a simultaneous thoracoplasty to avert the high risk of empyema (2310).

Paul Ferdinand Schilder (AT-US), Charles Foix (FR), and Julien Marie (FR) described intracerebral centrolobular sclerosis (1139, 2818).

Ludwig Wilhelm Carl Rehn (DE) and Ernst Ferdinand Sauerbruch (CH-DE) independently performed the first pericardial resection in which an inflammed pericardium was partially excised because it constricted the movement of the heart. A left anterolateral thoracotomy approach was used (2608, 2778).

Edward Delos Churchill (US) was the first in the U.S.A. to perform decortication of the heart to relieve adhesive pericarditis (588).

Edmond Delorme (FR) had been the first to suggest that an operation to relieve adherent pericardium, i.e. restrictive pericarditis, had a likelihood of success (814). Ludwig Rehn (DE) first performed this operation in 1913 (2605).

Hermann Oppenheim (DE) and Fedor Krause (DE) performed the first successful removal of a pineal gland tumor (2402).

John Broadus Watson (US) founded the behaviorist school of psychology, which emphasized the study of observable behavior rather than conscious and unconscious mental processes (3388, 3389).

Albert Schweitzer (DE) opened a hospital for the leprous in Lambaréné, located in West Africa.


“All the evidence points to the nuclear germ-plasm as the essential carrier of hereditary characters. We are thus compelled, on the mechanistic hypothesis, to attribute to the germ-plasm, or germinal nuclear substance, a structure so arranged that in presence of suitable pabulum and stimuli it produces the whole of the vast and definitely ordered assemblage of mechanisms existing in the adult organism.” John Scott Haldane (1376).

Max Theodor Felix von Laue (DE) was awarded the Nobel Prize in Physics for obtaining the first x-ray diffraction patterns by passing x-rays through a crystal of zinc sulfide. 

Robert Bárány (AT-SE) was awarded the Nobel Prize in Physiology or Medicine for his work on the physiology and pathology of the vestibular apparatus.

Hermann Emil Fischer (DE), Burckhardt Helferich (DE), and Kálmán V. Fodor (HU) became the first to synthesize a nucleotide (1111).

Yotako Koga (JP) and Ryo Ohtake (JP) isolated citrulline from watermelon (Citrullus vulgaris) juice (1794).

Mitsunori Wada (JP) coined the term citrulline from watermelon (Citrullus vulgaris) then proved through chemical synthesis that it is synonymous with delta-ureido-ornithine or alpha-amino-delta carbamido-n-valeric acid (3340).

Phoebus Aaron Theodor Levene (RU-US) and Frederick B. LaForge (US) correctly identified the structure of hexosamine, which they called chondrosamine (now called galactosamine) (1941, 1942).

Phoebus Aaron Theodor Levene (RU-US) was the first to obtain sphingomyelin in pure form and determine its structure (1936).

John Charles Grant Ledingham (GB) and William James Penfold (GB) discussed the mathematics of the lag phase and log phase of bacterial growth (1919).

Donald Dexter van Slyke (US) and Glenn E. Cullen (US) developed a gasometric method of quantitatively determining urea concentration in blood and urine (3204). 

Herbert McLean Evans (US) and Werner Schulemann (DE) introduced the use of the acid dis-azo dyes for use in vital staining. Among the best known of these vital dyes are trypan red, trypan blue, vital red, and Evans blue (1049, 1050).

Henry Hallett Dale (GB) showed the obvious relation of acetylcholine’s action on the parasympathetic system to that of epinephrine (adrenaline) on the true sympathetic system. He found that of all the various choline esters (natural and synthetic) active on striated muscle, acetylcholine was the most potent one (757). Dale coined the terms adrenergic and cholinergic systems.

Stanislaus Josef Mathias von Prowázek (CZ) introduced the use of fluorescent dyes for the staining of cells and tissues in animal physiology. He used fluorescent dyes to enhance the auto-fluorescence of cells (3329).

Robert Joachim Feulgen (DE) applied the aldehyde reaction of Hugo Schiff (fuchsin sulfurous acid) to thymic nucleic acid (apurinic acid) (DNA) and reported that a neutralized acid hydrolysate of thymic nucleic acid restores the color of a fuchsin solution previously decolorized by sulfur dioxide (1088).

Petroleum oils were introduced as herbicides for use along drainage ditches in the Western United States and as a selective herbicide in carrots (Daucus carotus). Ref

Gustav Georg Embden (DE) and Fritz Oscar Laquer (DE) discovered a compound formed from glycogen (fructose-1, 6-diphosphate) as a metabolic intermediate in muscle. They named it lactacidogen (1008, 1009).

Gustav Georg Embden (DE) and Fritz Oscar Laquer (DE) discovered that if the hexose diphosphate from a yeast alcoholic fermentation is added to press juice from muscle that lactic acid is produced. This strongly suggested that the pathways of carbohydrate breakdown in the alcoholic fermentation by yeast and the lactic acid glycolysis by muscle are very similar (1008, 1010).

Arthur Harden (GB) and Robert Robison (GB) found hexose monophosphate in a carbohydrate fermentation mixture (1404). Robert Robison (GB) later determined that it was a mixture of isomeric hexose monophosphates, probably those of glucose and fructose (2665).

Gustav Georg Embden (DE) and Margarete Zimmerman (DE) isolated a hexose monophosphate, Embden ester, from muscle (1013). Embden ester turned out to be a mixture of hexose monophosphates that were subsequently identified: fructose-6–P (Neuberg ester), glucose-6–P (Robison ester), and eventually glucose-1–P (Cori ester) (652, 2331, 2665).

Robert Robison (GB) and Earl Judson King (GB) isolated glucose monophosphate (Robison ester) from a carbohydrate fermentation mixture (2667, 2668). This Robison ester would prove to be glucose-6-phosphate.

Calvin Blackman Bridges (US) presented papers on nondisjunction offering the final and conclusive proof that genes are parts of chromosomes (419, 420, 424).

Hiram Bentley Glass (US) presented data illustrating the nondisjunction of chromosomes (1249, 1250).

Karl von Frisch (AT), Herbert Heran (DE), and Martin Lindauer (DE) studied communication in the honeybee, Apis mellifera Linn. They performed pioneering and imaginative studies, which led eventually to an understanding of some of the ways in which honeybees communicate with one another. Through a dance (usually performed on the comb) workers can communicate the direction and distance to food. They also discovered that bees have the ability to discriminate some colors (they cannot see red but can see ultraviolet) and orient themselves by direction of light polarization in the sky (3278-3293).

Edmund M. Walker (CA) discovered that rock crawlers/ice bugs (Grylloblattodea), are a new order of insects. They inhabit cold areas, often in mountains, under rocks and in litter in forests, and in caves. During summer the North American species feed at night on insects frozen on the surface of snowfields; they are somewhat omnivorous. Their range includes Western North America, Japan, Korea, China, and Siberia (3353). (Gryll = cricket, blatta = cockroach)

Walther Kruse (DE) passed nasal washings from individuals with the common cold (acute viral rhinopharyngitis; acute coryza) through Berkefeld filters, then used these to inoculate healthy individuals. Successful transmission of the common cold to these healthy human volunteers strongly suggested that the etiological agent is a virus (1847).

George B. Foster, Jr. (US) performed a very similar experiment during 1916-17 (1156, 1157).

Peter K. Olitsky (US), James E. McCartney (US), Alphonse Raymond Dochez (US), Gerald S. Shibley (US), Katherine C. Mills (US), Yale Kneeland, Jr. (US), Commission on Acute Respiratory Diseases (US), Christopher H. Andrewes (GB), Donna M. Chaproniere (GB), Annette E.H. Gompels (GB), Helio Gelli Pereira (BR), A. Tony Roden (GB), Harry F. Dowling (US), George Gee Jackson (US), Tohru Inouye (US), Irwin G. Spiesman (US), Harold G. Spiesman (US), and Arthur V. Boand, Jr. (US) established definitively that common colds may be caused by agents with the properties of viruses (70, 72, 841, 850, 852, 877, 878, 1637, 1638, 2390). 

Jacob Traum (US) was the first to describe brucellosis in swine. It was in a swineherd in Indiana (3141).

Alice Catherine Evans (US) confirmed these results and those of earlier work on Malta fever and cattle abortion (1041).

Irwin F. Huddleson (US) identified and named as a separate species the Brucellae causing swine brucellosis (Brucella suis) (1589).

Marshall A. Barber (US) observed the relationship of Staphylococcus albus to acute gastrointestinal upsets associated with drinking milk from a cow with mastitis (176).

Arthur William Bacot (GB) and Charles James Martin (GB) determined that humans are infected with the plague bacillus when a flea carrying the bacillus regurgitates during a blood meal (133).

Albert Hustin (BE) showed that addition of citrate can prevent blood from clotting and that citrated blood can be safely transfused into the dog. He then used citrated blood to transfuse a human (1600, 1601).

Luis Agote (AR) discovered that sodium citrate, when added to freshly drawn blood, prevents clotting. This meant that donors could go home rather than being present during transfusion. He performed a successful blood transfusion in humans using sodium citrate as an anticoagulant (36, 37).

Richard Lewisohn (US) determined the maximum amount of citrate that can be transfused into dogs without toxicity and thus determined the optimum concentration that can be added to blood for the best anticoagulant effect (1955).

Henry M. Thomas (US) and Kenneth Daniel Blackfan (US) detailed a case of a boy who died of lead poisoning after ingesting white lead paint from the railings of his crib (3102).

Carl Voegtlin (US) provided the earliest study, which proved that human pellagra is unquestionably caused by dietary deficiency (3232).

Joseph Goldberger (SK-US), George A. Wheeler (US), William F. Tanner (US), Ralph Dougall Lillie (US), and L. M. Rogers (US) discovered that pellagra is caused by a dietary deficiency of a vitamin belonging to the B-complex and is not infectious (1257-1259, 1261-1263).

T.N. Spencer (US) was the first to call attention to the similarity between the symptoms of a spontaneous canine disease known to veterinarians as black-tongue and those of human pellagra (2968).

 Joseph Goldberger (SK-US) and William F. Tanner (US) learned which foods are rich in the P-P (pellagra-preventive) factor, as they called it, and thus they could prevent pellagra by diet modification (1264).

William Boog Leishman (GB) developed a vaccine against typhoid fever. It was a whole vaccine killed by heat at 53 ° C. and preserved with 0.25 per cent tricresol (1929).

Malaria control by fluctuating water levels was first observed (2879).

Erich Schmidt (DE) measured high serum cholesterol levels in patients with xanthomatosis making this the first time that an essential hypercholesterolemia was recognized (2834).

Franz Volhard (DE) and Karl Theodor Fahr (DE) gave the first full description of pure nephrosis, relating clinical features to morbid anatomy (3240).

Karel Frederik Wenckebach (NL-AT) published his classic book on cardiac arrhythmias. Here he described the effect of quinine on atrial fibrillation, when he was able to rid a patient of tachycardia with a dosage of one gram of quinine (3428).

Walter Frey (CH) proved that quinidine, an optical isomer of quinine, is the most effective of all quinine derivatives against atrial flutter (1186).

Richard Clarke Cabot (US), following an analysis of 600 cases of heart disease divided them all into four categories. He reported that 93% of the cases were of rheumatic, atherosclerotic, syphilitic, or nephritic etiology (484). 

Walter Edward Dandy (US) and Kenneth Daniel Blackfan (US) produced a classic account of the pathogenesis and management of hydrocephalus. They produced hydrocephalus experimentally and explained that various types of hydrocephalus are due to obstruction of the aqueduct of Silvius, obstruction of the foramina of Magendie and Luschka, and devised surgical operations for the relief of the different varieties (765).

Joseph Jules François Félix Babinski (PL-FR) described and named anosognosia (Babinski-Anton syndrome). When the right hemisphere of the brain is damaged, there is usually complete paralysis of the left side of the body. Patients with anosognosia obstinately insist that their left arm is not paralyzed even though they are mentally lucid in other respects. They may even deny ownership of their left arm, asserting that it belongs to someone else (79, 126).

Lucien Claude Jules Cuénot (FR) proposed the theory of preadaptation: the empty space or ecological niche is populated with mutants already showing characteristics adapted to the conditions of the empty space (715).

David Meredith Seares Watson (GB) provided the first evidence that mammals evolved from reptiles. This conclusion was based on the fossilized remains of primitive reptiles and mammals he collected on trips to South Africa and Australia during 1911-1914 (3387).

Hans Reck (DE) discovered rich deposits of early mammalian fossils including Stone Age artifacts at Olduvai Gorge in East Africa. Among other fossils he unearthed a fully human skeleton on the northern slope of the gorge; naming it Olduvai Hominid 1 (OH 1) (2600, 2601).

ca. 1915

Konstantin von Economo; Konstantin Alexander Economo von San Serff (RO-AT) started his monumental studies on encephalitis lethargica (lethargic encephalitis), an epidemic disease of the central nervous system marked mainly by pronounced somnolence (lethargy), myalgias, fever, stupor, ophthalmoplegia, and paresis (3257, 3258). The disease, sometimes called type A encephalitis is now considered extinct. The etiological agent was never identified.


William Henry Bragg (GB) and his son William Lawrence Bragg (GB) shared the Nobel Prize in Physics for their formulation of the mathematical equations needed to calculate wavelength of the x-rays from the scattering pattern. They also used the x-ray diffraction patterns to deduce molecular structure of crystals. William Lawrence Bragg, at age twenty-five, was the youngest Nobel laureate ever. This coincidentally gave striking confirmation of the tetrahedral nature of the carbon atom (397-401).

Richard Martin Willstätter (DE) was awarded the Nobel Prize in Chemistry for his researches on plant pigments, especially chlorophyll.

Chaim Weizmann (RU-GB-IL) discovered a way to produce acetone via bacterial fermentation. He modified the process slightly and got the bacteria to produce butyl alcohol (3417, 3418).

Alfred Franklin Burgess (US) was in charge of moth work in the United States through the Plant Quarantine and Control Administration. They used lead arsenate for control of the gypsy moth (Lymantria dispar) in Massachusetts, US (475).

Edna Steinhardt (US) and Marie Grund (US) neutralized the growth of vaccinia on rabbits' skin using convalescent serum (2990).

Torsten Ludvig Thunberg (SE), Fédérico Battelli (IT), and Lina Salomonovna Stern (LT-CH-RU) demonstrated that anaerobic suspensions of minced animal tissues catalyze the transfer of hydrogen atoms from certain organic acids known to occur in cells—especially succinic, malic, and citric acids—to the reducible dye methylene blue, giving its colorless reduced form. Enzymes catalyzing such reactions were named dehydrogenases (226, 3120, 3121). In later years several investigators using manometric measurement of the oxygen-utilization rate of minced-tissue suspensions found that succinate, fumarate, malate, and citrate are rapidly oxidized to carbon dioxide by molecular oxygen (3365).

Thomas Lewis (GB) and Marcus A. Rothschild (GB) described how the excitatory process in the dog's heart first reveals itself in the region of the sino-auricular node then spreads from this node in every direction, progressing to all the margins of the musculature (1954).

Alexander Forbes (US) and Alan Gregg (US) made a systematic analysis of nerve impulses originating from the central nervous system and compared them with those evoked by artificial stimulation of a peripheral nerve. Their conclusion was that nerve impulses are always of the same nature regardless of their origin (1148).

Francis Arthur Bainbridge (GB) demonstrated that an increase in pressure on the venous side of the heart results in an increase of heart rate due to the inhibition of vagal influences and the excitation of some accelerator mechanisms (148).

Arnold Theiler (CH-ZA), Henry H. Green (ZA), and Philip Rudolph Viljoen (ZA) were the first to assert that the nutritive requirements of the ruminants are quite different from the omnivores and carnivores. They stated, “We … think it is at least possible that the vitamin requirements of cattle are so low that they may even be covered indirectly by synthesis carried out by the extensive bacetrial flora of the intestines” (3099).

Otto Folin (SE-US) and Willey Glover Denis (US) developed excellent methodology for the determination of phenols and conjugated phenols. They concluded from their studies of blood and urine that by no means can all of the phenols formed in the colon and absorbed into the blood be conjugated and detoxified (1145).

Mac H. McCrady (US) developed the most probable number, multiple-tube fermentation technique as a quantitative approach for analyzing water samples for coliforms (2142).

Richard Benedikt Goldschmidt (DE-US) was the first to successfully grow insect cells in vitro (1272, 1273).

Paradichlorobenzene was first recommended in the U. S. for control of clothes moth and carpet beetles (2879).

Constantine Janicki (PL) coined the term karyomastigont to refer to a conspicuous organellar system he observed in certain protists: the mastigont (“cell whip”, eukaryotic flagellum, or undulipodium, the [9 (2) +(2)] microtubular axoneme underlain by its [9 (3) + 0] kinetosome) attached by a nuclear connector or rhizoplast to a nucleus. He observed this structure in highly motile trichomonad symbionts in the intestines of termites where karyomastigonts dominate the cells (1655).

Joel B. Dacks (CA) and Rosemary J. Redfield (CA) reported that the karyomastigont is an ancestral feature of eukaryotes present in early branching protists (750).

Thomas Hunt Morgan (US), Alfred Henry Sturtevant (US), Calvin Blackman Bridges (US), and Hermann Joseph Muller, Jr. (US) had their book, The Mechanism of Mendelian Heredity, published (2259).

Thomas Hunt Morgan (US) and his colleagues settled decisively the mechanism of sex determination in Drosophila and based on evidence concerning eye color control in Drosophila they hypothesized the possibility that genes could have multiple alleles (2259).

James Allen Nelson (US) made an extensive study of the embryology of the honeybee, Apis mellifera Linn (2317).

Frederick William Twort (GB) discovered a transmissible, and filterable agent that destroys bacteria producing a phenomenon on agar plates he called glassy transformation. He speculated that this agent might be virus or an enzyme (3166). At about this same time Félix Hubert d’Herelle (CA) observed this same filterable disease of bacteria while in Mexico studying diarrhea of locusts (747). Two years later bacterial viruses were independently discovered by Félix Hubert d’Herelle (CA) and he named them bacteriophage (from the Gk. phagein, to devour) (746).

Hideyo Noguchi (US) found that vaccinia virus freed from all associated bacteria by means of suitable disinfecting agents could be propagated in a pure state in the testicles of rabbits and bulls (2372).

Ernst Berliner (DE) described a sporeforming bacterium, which he named Bacillus thuringiensis, isolated from diseased larvae of the Mediterranean flour moth, Ephestia kühniella Zell (290).

David Shepherd (US) was the first to use this bacterium as a natural control of an insect pest, the slender-horned flour beetle, Echocerus cornutus (2891). 

Major J. Graham (GB) described trench fever in the medical literature for the first time. He characterized it as relapsing febrile illness of unknown origin (1300).

George H. Hunt (GB) and Alan C. Rankin (CA) dubbed it trench fever less than two months later (1596). It has also been called five-day fever, quintan fever, and urban trench fever.

John William McNee (GB), Arnold Renshaw (GB), and E.H. Brent (GB) described human experimentation on enlisted volunteers and showed that trench fever is transmitted by whole blood, but not by serum, and is most likely carried "by one of the common flies or parasites found in the trenches” (2153).

J. William Vinson (US), Henry S. Fuller (US), Gerardo Varela (MX), and C. Molina-Pasquel (MX) demonstrated that trench fever is transmitted by the body louse and caused by the bacterium Rickettsia quintana (3215, 3230, 3231).

Erich August Hübener (DE), Hans Conrad Julius Reiter (DE), Paul Theodor Uhlenhuth (DE), Walther Fromme (DE), Ryokichi Inada (JP), Yutaka Ido (JP), Rokuro Hoki (JP), Renjiro Kaneko (JP), and Hiroshi Ito (JP) discovered the spirochete Spirochaeta icterohaemorrhagiae to be the etiological agent of infectious jaundice, also called Weil’s disease. They found that it is usually transmitted to man from infected rats (1588, 1616, 3174).

Ido Yutaka (JP), Rokuro Hoki (JP), Hayozo Ito (JP), and Hidetsune Wani (JP) found that rats are the carriers of Leptospira icterohaemorrhagiae (3608).

Harold Mellor Woodcock (GB) observed coccidian oocysts of Isospora belli in the feces of World War I soldiers overseas (1920). This coccidian is frequently found in asymptomatic immunocompetent individuals and is associated with diarrhea in AIDS patients. The clinical entity is referred to as isosporiasis.

The first director of the International Health Board of the Rockefeller Foundation, Wickliffe Rose (US) appointed William Crawford Gorgas (US) to head the Yellow Fever Commission. Gorgas would effectively eliminate malaria and yellow fever in the Panama Canal Zone by eradicating the Aëdes and Anopheles mosquitoes.

Francis Peyton Rous (US) and Joseph R. Turner (US) developed the simple finger-prick method of crossmatching, which enables one to determine within a few minute whether or not the blood of a donor is suitable for transfusion (2700).

Richard Weil (US) demonstrated the feasibility of refrigerated storage of anticoagulated blood. He found that it could be stored for 2 days and still be effective when transfused into guinea pigs and dogs which had lost blood (3409).

Francis Peyton Rous (US) and Joseph R. Turner (US) used rabbits to demonstrate that, with certain additives and proper treatment, citrated blood can be stored for 14 days and still be successfully transfused (2701).

Abbie E.C. Lathrop (US) and Leo Loeb (US) reported the influence of internal secretions from the corpus luteum (ovarian follicles) on the development of spontaneous tumors in mice. Their study showed that tumor incidence was delayed and reduced from 60–90% to 9% in female mice castrated before 6 months of age. As it was already known that the corpus luteum secreted an uncharacterized substance that induced growth of the breast during pregnancy, the authors speculated that this chemical might be involved in tumor formation (1902).

Edgar V. Allen (US) and Edward Adelbert Doisy (US) demonstrated in mice and rats that ovarian follicles influence the estrous cycle by releasing a hormone, which they called oestrin (estrogen) (51).

Edgar V. Allen (US) reported that “menstruation is a catabolic process due to the temporary absence of ovarian follicular hormone or its decrease below a subliminal amount after its anabolic influence has induced the growth of a certain amount of genital tissue” (50).

Elwood Vernon Jensen (US) discovered the estrogen receptor (ER) (1670).

Elwood Vernon Jensen (US), George E. Block (US), Sylvia Smith (US), Kay Alvin Kyser (US), and Eugene R. DeSombre (US) studied the effect of adrenalectomy on human breast cancer. They found that breast tumors fall into two categories — ER-rich and ER-poor — and patients who had tumors with a high level of ER expression were more responsive to hormone-ablative therapy. This led Jensen to propose that the ER status of a tumor could predict the response to therapy (1671).

Virgil Craig Jordan (US) and T. Jaspan (US) showed that long-term tamoxifen treatment targeted to the estrogen receptor (ER) could successfully treat and prevent rat mammary cancer (1699).

Bernard Fisher (US), Joseph P. Costantino (US), D. Lawrence Wickerham (US), Carol K. Redmond (US), Maureen Kavanah (US), Walter M. Cronin (US), Victor Vogel (US), André Robidoux (US), Nikolay Dimitrov (US), James Atkins (US), Mary Daly (US), Samuel Wieand (US), Elizabeth Tan-Chiu (US), Leslie Ford (US), Norman Wolmark (US), and other National Surgical Adjuvant Breast and Bowel Project Investigators found that tamoxifen decreases the incidence of invasive and noninvasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease (1116).

Maud Slye (US), in controlled breeding experiments with mice, found that certain mice are more susceptible to cancer whereas others are not. She attempted to extrapolate her mouse results to humans (2926, 2927).

Bertram Welton Sippy (US) developed a method for medical care of gastric and duodenal ulcers by accurately protecting the ulcer from gastric juice corrosion until healing of the ulcer takes place (2921).

Thomas Clifford Allbutt (GB) proved that angina is caused by narrowing of the coronary artery (47).

Booker Taliaferro Washington (US) died of systemic "hypertension so severe and so protracted that by the time of his final hospitalization, it had destroyed his kidneys, damaged his heart and brain and would shortly take his life." Born into slavery in 1856, he died as a famous, influential, and greatly admired American who had guided the creation and maturation of the Tuskegee Institute from 1881 until his death in 1915 (2052). He was cared for by some of America's best physicians who had the tools but lacked the knowledge to effectively manage hypertension. It was not until 1946 that pentaquine; the first drug shown to have anti-hypertensive activity was available.

Otto Binswanger (DE), during the conflict of WW I, made an effort to identify risk factors for the disorder we now know as post-traumatic-stress-disorder (PTSD) (318).  

Charles S. Myers (GB) kept a diary during World War I, which became the basis of the first systematic investigation of combat-related neurosis. It was Myers who coined the phrase "shell shock" to call attention to the importance of the physical effects of bursting shells in creating the disorder (2303).

The Proceedings of the National Academy of Sciences of the United States of America was first published.


Karol Mayer (PL) described the principles and practical uses of tomography (Mayer 1916).

Andre-Edmund-Marie Bocage (FR) applied for a patent on a machine in which both x-ray source and film were moved reciprocally and proportionately, i.e., tomography. He had designed a linear device, pluri-directional device and a curvilinear device (340). 

Allan MacLeod Cormack (ZA-US) developed mathematical theory and built machines to achieve two-dimensional x-ray image reconstruction, i.e., axial tomagraphy (653, 654).

Godfrey Newbold Hounsfield (GB) introduced computerized axial tomography (CAT scan) (1578).

Gilbert Newton Lewis (US) was the first to suggest that a bond between two elements can be formed not only through the transfer of electrons, but also through the sharing of electrons. Each bond in an organic compound represents the sharing of one pair of electrons, the final result being that all atoms achieve the stable electronic configuration of the inert gas atom (1947).

Alfred Stock (DE) and Karl Somieski (DE) were the first to use the term ligand (ligare L.). It was in relation to silicon chemistry (3016).

Heinrich Otto Wieland (DE), Bonifaz Flaschenträger (DE), Albert Rewolle (DE), Hermann Sorge (DE), Hedwig Stender (DE), Albert Kulenkampff (DE), Franz Adickes (DE), Werner Mothes (DE), Gustav Reverey (DE), and Richard Jacobi (DE) studied the three bile acids which had been isolated and showed how closely related they are in basic structure and the detailed manner in which they differ. The molecular skeleton they showed to be steroid—term not yet coined— in nature, related to the well-known molecule, cholesterol (3463, 3466-3468, 3470-3479).

Heinrich Otto Wieland (DE) later suggested a structure for cholic acid (3469).

Leon Popielski (PL) discovered the role of histamine (beta-imidazolylethylamine) as an agent increasing the secretion of gastric hydrochloric acid (2554).

Harold Ackroyd (GB) and Frederick Gowland Hopkins (GB) concluded that a rat’s diet must contain either arginine or histidine (19).

William Cumming Rose (US) and Gerald J. Cox (US) discovered that histidine is an essential amino acid in rats (2678).

Elliott Proctor Joslin (US) and Francis G. Benedict (US), in 1908, carried out extensive metabolic balance studies examining fasting and feeding in patients with varying severities of diabetes. They noted a 20 percent decrease in the mortality of patients after instituting a program of diet and exercise (1700).

William Beecroft Bottomly (GB) noted that incubation of peat with a mixed culture of aerobic soil bacteria resulted in stimulation of wheat seedling's growth in this peat (372).

August J.P. Pacini (US) and Dorothy Wright Russell (US) demonstrated the formation of a bacterial substance capable of stimulating animal growth. They showed that a water extract of the typhoid bacillus produced a marked growth response in rats ingesting a "vitamin B"- deficient ration (2444). These two papers offer evidence that microorganisms produce factors beneficial to the nutrition of plants and animals.  

Walter Abraham Jacobs (US) was the first to observe the germicidal properties of quaternary ammonium compounds (1642).

Søren Peder Lauritz Sørensen; Søren Peer Lauritz Sørensen (DK), during 1916-17, published a series of papers in which he reported the molecular weights of various proteins based on measurements of osmotic pressure. Although he underestimated their size his work pointed the way to visualizing proteins as having molecular weights in the 10s of thousands (2955-2957).  

Jay McLean (US) found that certain phosphatides and fat-soluble extracts from fresh brain, heart, and liver tissues accelerated blood clotting, but after storage for some months they lost their coagulant activity, and indeed were now acting as anticoagulants. Many consider this to represent the discovery of heparin (2151).

William Henry Howell (US) and L. Emmett Holt, Jr. (US) coined the term heparin to denote the presence of a fat-soluble anticoagulant in the liver (hepar) (1587).

William Henry Howell (US) later claimed to isolate heparin in such a way that it could not be the same substance as those isolated in either 1916 or 1918 (1585). Priority of discovery has yet to be settled, however, James A. Marcum in a very scholarly article credits Howell with the discovery (2092).

D.W. Gordon Murray (CA), Louis B. Jaques (CA), T.S. Perrett (CA), and Charles Herbert Best (CA), beginning in 1934, conducted a series of tests on heparin in dogs for both "the prevention of venous thromboembolism" and also "for its use in vascular surgery," thereby becoming the first to demonstrate that such procedures could be performed with the assistance of heparin. They used heparin prophylactically against deep-vein thrombosis following surgery in humans (2295, 2296).

Erik Jorpes (SE) and Clarence Crafoord (SE) conducted similar experiments in the Karolinska Institute in Stockholm (682, 683).

George Henry Alexander Clowes (US) suggested that watery and lipoidal phases might exist together in a cell membrane by the action of balanced ions; postulating phase-reversal such as one can obtain in oil-water emulsions by modifying the critical balance of sodium and calcium ions, or other monovalent and divalent cations (620).

Henry Josef Quayle (US) reported resistance to cyanide fumigation in the California red scale, Aonidiella aurantii. This is the first known case of insect resistance to chemicals (2572-2574).

Charles C. Macklin (CA) showed that when two nuclei in a binucleate heterokaryon enter mitosis together, the two sets of chromosomes commonly join a single metaphase plate and are then systematically distributed to two mononucleate daughter cells each of which can subsequently be shown to contain within a single nucleus the chromosomes of both parents (2051).

Hermann Joseph Muller (US) reported his definitive work on crossing over among chromosomes (2280).

Frank Rattray Lillie (US) demonstrated that sex hormones are concerned in the embryonic differentiation of sex characters among vertebrates. He showed that when the fetal membranes of male and female calf embryos become united in the uterus so that the blood vessels of the two are continuous, the female embryo is modified in the male direction, forming the so-called freemartin (1967).

Kenzo Futaki (JP), Ftsuma Takaki (JP), Tenji Tangiguchi (JP), and Shimpachi Osumi (JP) discovered that Spirillum minor is the etiological agent of rat-bite fever or sodoku (1205).

Frederic Parker, Jr. (US) and N. Paul Hudson (US) isolated Streptobacillus moniliformis as the causative agent of rat-bite fever (also known as erythema multiforme, erythema arthriticum epidemicum, and Haverhill fever) and demonstrated its serological relation to the disease (2469).

Hans Conrad Reiter (DE) described a disease he called spirochetosis arthritica. Currently it is called Reiter syndrome (2610).

Francis Peyton Rous (US) and Frederick S. Jones (US) were the first to liberate individual cells from plasma clot cell culture — using the enzyme, trypsin — with the objective of growing the individual cells in vitro (2698).

James B. Murphy (US) appears to have been the first to observe a graft-versus-host reaction. He was inoculating the chorioallantoic membranes of 7-day embryos with adult chicken spleen and bone marrow. He did not correctly interpret the phenomenon (2293). This has also been called runt disease.

William J. Dempster (GB), Morten Simonsen (DK), J. Buemann (DK), A. Gammeltoft (DK), F. Jensen (DK), and K. Jorgensen (DK) were the first to correctly interpret the graft-versus-host reaction as the graft mounting a response to the host (817, 2917, 2919).

David W.H. Barnes (GB), Michael J. Corp (GB), John Freeman Loutit (GB), and Frank E. Neal (GB) described graft-versus-host disease (GVHD) in mice (183).

Morten Simonsen (DK), Rupert Everett Billingham (GB-US), and Leslie Brent (GB) independently demonstrated graft-versus-host disease (GVHD) in chick embryos (manifested as pancytopenia) and mice (runt disease) after intravenous injection of adult spleen cells (314, 2918).

Alan G. Cock (GB) and Morten Simonsen (DK) introduced the phrase graft-versus-host reaction to describe the direction of the immunological damage caused by introduction of immunologically competent cells into an immunocompromised host (627).

Rupert Everett Billingham (GB-US) proposed 3 conditions required for the development of GVHD, as follows: (1) the graft must contain immunologically competent cells, (2) the host must possess important transplant alloantigens that are lacking in the donor graft so that the host appears foreign to the graft, and (3) the host itself must be incapable of mounting an effective immunological reaction against the graft (313).

Henry Edward Crampton (US) described geographical races of the snail Partula in Tahiti. Beginning around 1916, he studied this snail over a period of 50 years, concluding (1) that the variation in the color, banding, and chirality of the shells was Mendelian in nature, (2) that these characters are unaffected by selection, and (3) that active evolution was demonstrable in the short time between his successive samples. Although the second and third of these conclusions appear to be badly flawed, the Partula studies nevertheless exerted an important influence on the modern synthesis of evolutionary biology (689). Note: The last member of the snail species Partula turgida died at the London Zoo in 1996. Also known as the Polenesian Tree Snail, it was wiped out in the wild in a bungled attempt to control a nuisance snail with an introduced species.

George Edward Nicholls (AU) discovered that the vertebral column is important in classifying Salientia (frogs, toads, and tree toads) (2351).

Frederic Edward Clements (US) stated his ecological theory, that when a geographical area is newly vacated it becomes occupied by a succession of species gradually leading to a climax community and the plant community can be treated as a complex organism undergoing a life cycle and evolutionary history analogous to the individual organism (605, 606). See, Cowles, 1899.

Delafield du Bois (US) and Eugene F. du Bois (US) introduced a formula to estimate the approximate surface area of the body if height and weight are known (895).

Arthur Isaac Kendall (US) has shown that the total abstinence from food for thirty-one days did not eliminate the bacteria from the lower intestine of man (1735).

Jerry Edward Wodsedalek (US) was the first to provide an explanation of the male mule's sterility. He studied the testes of a number of mules and concluded that there was a block in meiosis due to an incompatibility between the paternal (donkey) and maternal (horse) chromosomes (3556). 

Francis Peyton Rous (US) and Joseph R. Turner (US) determined that rabbit blood cells could be useful in transfusion after storage for a long time in vitro. They suggested that kept human cells could be profitably employed in the same way (2702).

Richard Henneberg (DE) coined the term cataplexy for emotionally induced muscle weakness, a prominent symptom of narcolepsy. Ref

Joannes Gregarius Dusser de Barenne (NL-US) did considerable work on posture and was a pioneer in demonstrating the major functional subdivisions of the sensory cortex. His contributions to the knowledge of the analysis of the interaction of various cortical and subcortical regions of the brain were considerable (926, 927).

Georges Charles Guillain (FR), Jean-Alexandre Barré (FR), and André Strohl (FR) described two soldiers acutely ill with muscular weakening, paresthesias, and muscular pain with major pathology in the Achilles reflex and the quadriceps muscle (1339, 1340). This condition is the most common form of acquired neuropathy, most frequently affecting young adults.

H. Draganesco (FR) and J. Claudion (FR) named this condition Guillain-Barré syndrome (881).

Auguste François Chomel (FR), in 1828, was the first to give a clinical description of this condition.

Today this syndrome is recognized as the most common form of acquired neuropathy affecting both sexes, most frequently affecting young adults and believed to be a form of autoimmune disease with a delayed hypersensitivity reaction.

J. Darier (FR) was the first to describe erythema anulare centrifugum. A skin lesion that consists of redness (erythema) in a ring form (anulare), which spreads from the center (centrifugum) (773).

James Walker Dawson (GB) provides the greatest pathological account of multiple sclerosis in the English language. After summarizing the literature—and the debate, which went on then as now, about whether the disease is “inflammatory” or “developmental” (degenerative)—Dawson reviews the histology of nine personal cases. Illustrating the text with 22 colour and 434 black-and-white figures in 78 plates, Dawson describes the form, symmetry, distribution, and histological features of several types of lesions and provides an analysis of changes in each cellular element of the nervous system—nerve cells and their axons, neuroglia, blood vessels, and lymphatics. Dawson then attempts a clinicopathophysiological correlation. (Weakness in the legs is consistent with the extensive spinal cord gliosis, for example.) He also characterizes old and acute lesions. Dawson summarizes his ideas on plaque formation around brain inflammation to include a sequence of events that, although not disease specific, produces recognizable clinical characteristics (784).

The first record of carbolineum being used for control of poultry parasites appears (a heavy oily substance distilled from an anthracene-oil or creosote-oil fraction of coal tar and used as a wood preservative, disinfectant, or insecticide). Calcium arsenate was discovered effective for control of the boll weevil. Sodium fluoride was discovered to be effective for control of lice on poultry (2879).

Lennart von Post (SE) initiated the modern discipline of palynology when he reported on almost perfectly preserved pollen grains from anaerobic sediments of peat bogs in Sweden. The pollen in the layered sediments recorded a sequence of change in the dominant plant genera from the end of the last glacial period to the present (3326, 3327).

Otto Gunnar Elias Erdtman (SE) published works important to the expansion of palyonology into an internationally accepted science (1029, 1030).

H.A. Hyde (US) and D.A. Williams (US) introduced the term palynology on the basis of the Greek words paluno meaning 'to sprinkle' and pale meaning 'dust' (and thus similar to the Latin word pollen) (1611).

Michel Weinberg (FR) and Pierre Séguin (FR) discovered Bacillus histolyticus (Clostridium histolyticum) in war wounds. This organism has the ability to liquefy living tissue to a remarkable degree (3411, 3412).

George Harrison Shull (US) founded the journal Genetics.


The most lethal influenza pandemic ever recorded killed an estimated 20 to 40 million people worldwide. An estimated 675,000 Americans died of influenza during the pandemic, ten times as many as in the world war. Of the U.S. soldiers who died in Europe, half of them fell to the influenza virus and not to the enemy (Deseret News). Its spread was facilitated by troop movements in the closing months of World War I. Mortality rates were unusually high for flu, especially among young, otherwise healthy adults. Deaths occurred both from the flu itself and from secondary pneumonia (1803). This was the worst epidemic since the Middle Ages. It was called the Spanish Flu because of where it was first properly reported.

René Dujarric de la Rivière (FR), Charles Nicolle (FR), and Charles Lebailly (FR) proposed that the causative agent was a virus, based on properties of infectious extracts from diseased patients.  Specifically, Nicolle and Lebailly found that the infectious agent was filterable, not present in the blood of an infected monkey, and caused disease in human volunteers (793, 2352). Most medical authorities at the time thought bacteria caused the disease.

Perrin H. Long (US), Eleanor A. Bliss (US), and Harriet M. Carpenter (US) succeeded in producing influenza in chimpanzees using material which had passed though a filter capable of stopping bacteria (2010).

Wilson Smith (GB), Christopher H. Andrewes (GB), and Patrick Playfair Laidlaw (GB) successfully induced influenza in ferrets by inoculating them intranasally with filtrates of throat washings obtained from patients early in the course of the disease (2943). This work proved that a virus causes human influenza. Later this would be referred to as type A.

Thomas Francis, Jr. (US) and Thomas P. Magill (US) produced evidence to indicate that the influenza virus exists in distinctly different serological strains. Among others they isolated influenza type B (1171, 1172, 2062).

Joseph Stokes, Jr. (US), Aims C. McGuinness (US), Paul H. Langner, Jr. (US), and Dorothy R. Shaw (US) reported successfully immunizing human subjects to the influenza virus by subcutaneous inoculation of the vaccine (3022). Subcutaneous inoculation of man with active or formalized influenza virus increases the titer of serum antibody (3039).

Max A. Lauffer (US) and Wendell Meredith Stanley (US) purified the influenza virus then determined its biophysical properties (1906). See, more influenza references in all sections of this work.


Frederick B. La Forge (US) and Clause S. Hudson (US) isolated sedoheptulose from Sedum spectabile, an ornamental plant (1857).

Hermann Staudinger (DE), in a 1917 lecture to the Swiss Chemical Society, speculated for the first time that "high molecular compounds" consist of covalently bonded long-chain molecules, and first proposed the idea that polymers are giant molecules whose small-molecule constituents are linked together in long chains by chemical bonds no different from chemical bonds in ordinary organic compounds.

He postulated that rubber and similar materials are composed of very large molecules, called macromolecules, that they are held together by chemical bonds — the same forces that hold smaller, lighter molecules together and that the unusual strength and elasticity of polymers is due to their great length and high molecular weight. A very radical idea at the time (2982).

Hermann Staudinger (DE) and Jakob Fritschi (DE) proposed that materials such as rubber and cotton are composed of long chain-like molecules containing thousands of atoms, joined together by the same type of covalent bonds that joined the atoms of smaller molecules. They introduced the concept of macromolecules (a term which they coined) and polymerization (2983). 

Karl Landsteiner (AT-US) described antigens as distinct, recognizable atomic groups (1880).

Laszlo Berczeller (AT-HU), E. Szegö () and M. Seiner () were probably the first to point out the significance of surface tension in the inactivation of biological substances (283, 284).

Torsten Ludvig Thunberg (SE) showed that enzymes catalyze the oxidation of a large number of organic compounds such as succinic acid, each specific for its substrate (3121).

Heinrich Otto Wieland (DE) had named these enzymes dehydrogenases (3464).

James N. Currie (US) developed a method of producing large quantities of citric acid by growing Aspergillus niger in a growth-limiting medium rich in iron (724).

Martinus Willem Beijerinck (NL) proposed that genetic characters function by way of controlling the formation of enzymes (262).

Thomas Hunt Morgan (US) presented his theory of the gene (2254).

Harold H. Plough (US) showed that crossing over in Drosophila occurs during the early synaptic stage (zygotene) (2546).

Otto Renner (DE) suggested that many of the oenotheras (evening primroses) are permanent heterozygotes persisting in this condition because of balanced lethal factors (2614-2617).

Ralph Erskine Cleland (US) discovered the presence of ring chromosome formation during meiosis in Oenothera (the evening primrose) (599-601).

John Belling (US) explained the formation of ring chromosomes in Datura stramonium (Jimson weed) as due to a reciprocal translocation between two nonhomologous chromosomes. He determined that a plant possessing two original chromosomes and two that had interchanged segments, would exhibit a circle of four chromosomes as a result of their pairing requirements (270). This led quickly to an understanding of the puzzling genetic behavior exhibited by these organisms with ring chromosomes.

Ralph Erskine Cleland (US) summarized his and his colleagues’ work on Oenothera in his book, Oenothera: Cytogenetics and Evolution (602).

Charles Benedict Davenport (US) reported that apparent blending inheritance of stature is due merely to the presence of multiple factors (779).

Else Hirschberg (DE) and Hans Winterstein (DE) discovered that nervous tissue requires glucose (1532). 

Calvin Blackman Bridges (US) began a series of studies in which phenotypes within Drosophila were related to translocations or deficiencies of parts or of whole chromosomes. Eventually it became possible to associate each of the four groups of linked genes with one of the four pairs of chromosomes, and in some cases, to narrow the location of particular genes to small segments of chromosome (421, 423, 426).

Charles-Edward Amory Winslow (US), Jean Broadhurst (US), Robert Earl Buchanan (US), Charles Krumwiede, Jr. (US), Lore Alford Rogers (US), and George H. Smith (US) described the bacterial genus Erwinia. The genus is named in honor of Erwin Frink Smith (3550). 

Elvin Charles Stakman (US) and Frank J. Piemeisel (US) developed the technique of dividing the wheat rusts into strains based on their effect on different varieties of wheat (Triticum spp.) (2975).

Stefan Kopec (PL) suggested that the brain of the gypsy moth, Lymantria dispar L., caterpillars produces a hormone that initiates pupation and maintains pupal development. This represents the first time that insect development was associated with hormones (1814-1816). Today this is called prothoracicotropic hormone or PTTH. It stimulates a paired thoracic endocrine organ, the prothoracic gland, to synthesize and release ecdysone (a molting hormone). Ecdysone is the steriod hormone in insects, which is indispensable for insect development.

Leonhard Hess Stejneger (NO-US) authored Check List of North American Amphibians and Reptiles, which had a profound positive impact on the study of herpetology in North America (2992).

Warren R. Sisson (US) reported that under normal conditions of health duodenal contents contain very few live microorganisms (2922).

Charles Rupert Stockard (US) and George Nicholas Papanicolaou (Greek-US), by applying cytological methods to vaginal scrapings, established criteria for the determination of the various phases of the estrous cycle in guinea pigs (3019).

Joseph Abraham Long (US) and Herbert McLean Evans (US) used vaginal scrapings from the albino rat to elaborate many of the details of the estrus cycle and its associated phenomena (2009).

George Nicholas Papanicolaou (Greek-US) used vaginal smears to reveal the sexual cycle in the human female (2460).

This work, along with the earlier work in guinea pigs by Stockard and Papanicolaou, directed attention to the ovarian-uterine cycle as a general phenomenon, which is predictable, thus allowing the identification of the various phases of the cycle in animals whose sexual rhythm was unknown.

André Fouchet (FR) developed a method for demonstrating the presence of bilirubin in feces, urine, and serum (1160). 

Alice Hamilton (US) wrote Industrial Poisons Used or Produced in the Manufacture of Explosives and Industrial Poisons in the United States. These books were an outgrowth of her pioneering studies of industrial diseases and industrial toxicology (1390, 1391).

Donald Dexter van Slyke (US), Glenn E. Cullen (US), Reginald Fitz (US), Edgar Stillman (US), William Christopher Stadie (US), Walter W. Palmer (US), Julius Sendroy, Jr. (US), and S. Seelig (US) published papers on acidosis from 1917-1934. Van Slyke reasoned that if incomplete oxidation of fatty acids in the body leads to the accumulation of acetoacetic and beta-hydroxybutyric acids in the blood then a reaction would result between these acids and the bicarbonate concentration in blood plasma. They devised a volumetric glass apparatus that allowed the quantitative determination of bicarbonate in the blood. This permitted early diagnosis and therapy of patients with diabetes. The 1921 paper is a landmark in which chemical terms are used to describe normal and abnormal variations in the acid-base balance of the blood (3202, 3205). This apparatus was quickly adapted for the determination of blood oxygen and percentage saturation of blood hemoglobin (3201).

Florence Rena Sabin (US), Robert S. Cunningham (US), Charles Austin Doan (US), and Claude E. Forkner (US) introduced the technique of supravital staining—staining of living cells with dyes—which made it possible to distinguish certain types of cells from others for the first time in living tissue. The supravital staining research, in turn, led them to a study of cells (monocytes) involved in immune reactions, especially against the tuberculosis bacillus.

They was able to watch cellular growth in the hanging drop preparations and to see under the microscope the development of the earliest blood cells in explanted bits of the blastoderm of the chick embryo. They reported that on the second day of incubation of such cultures only red cells could be seen coming from the endothelial walls of the blood vessels. By the third day white cells appeared arising partly from new cells that differentiated from mesenchyme without becoming part of the vessel's lining (719, 848, 2752-2758).

Franz Ernest Christian Neumann (DE) was the first to postulate a common stem cell for all hematopoietic cells. "It is evident, that a continuing transformation of lymphoid cells into coloured blood cells takes place in the bone marrow during the whole life" (2348).

George Howard Parker (US) and Anne P. van Heusen (US) studied behavioral responses of the brown bullhead catfish, Ameiurus nebulosus, to metallic and non-metallic rods in water. They demonstrated these fish respond to galvanic currents generated at the interface between metal and aquarium water. Parker and van Heusen did not realize they were studying the electrosensitivity of fishes that have—as we now know— distinct electroreceptors (2471).

Hans Werner Lissmann (RU-DE-GB) studied electric discharges by Gymnarchus niloticus and other weakly electric fish. He proposed that their discharges allowed them to locate nearby objects of an electrical conductivity different from that of the surrounding water by appreciating the distortion it causes to their electric field (1974).

Sven Dijkgraaf (NL) and Adrianus J. Kalmijn (NL-US) provided the first evidence of electrosensitivity in elasmobranchs in 1935 when Dijkgraaf, working on Scyliorhinus canicula, noticed the animal's sensitivity to a rusty steel wire (840).

Hans Werner Lissmann (RU-DE-GB) and Kenneth E. Machin (GB) demonstrated that fish, which are weakly electric, could detect objects in their immediate vicinity by sensing changes in the electric fields produced by their own electric organs (1975, 1976). Electrolocation has been shown to be a remarkably refined sense, enabling fish to discern the shapes, distances and, to some extent, the composition of objects.

Theodore H. Bullock (US), Susumu Hagiwara (US), Kiyoshi Kusano (JP), Koroku Negishi (JP), and Adrianus J. Kalmijn (NL-US) reported that Hans Werner Lissmann (RU-DE-GB) in 1958 suggested, based on behavioral evidence, that a group of receptors and central processes, called the ampullae of Lorenzini, aid in the detection and analysis of electric fields by certain fish in the marine environment. Later, experimenters verified the existence of the new class of specialized receptors through physiological experiments. They named them "electroreceptors" because their adequate stimuli were electric fields (471, 1707).

Sven Dijkgraaf (NL), Adrianus J. Kalmijn (NL-US), Robert C. Peters (NL) and Frédéric van Wijland (NL) discovered that many fishes not equipped with electric organs of any kind nevertheless have electrical sensitivities equaling or even exceeding those of species specialized for electrical orientation (839, 1708, 2511).

Adrianus J. Kalmijn (NL-US) performed experiments clearly demonstrating that the shark Scyliorhinus canicula and the ray Raja clavata make biologically significant use of their electrical sensitivity. Therefore, we are justified in accrediting these animals with an electric sense and in designating the ampullae of Lorenzini as electroreceptors (1708). See, Lorenzini, 1678.

Arthur Robertson Cushny (GB) presented what he called the modern theory of renal secretion in which he stated, “… the constituents of the plasma which I have termed Threshold Bodies… are taken up by the cells of the tubules and return to the blood, while the No-threshold substances, such as urea, are rejected and can only escape by the ureter. Further, the threshold bodies are not absorbed indiscriminately but in definite proportions, which are determined by their normal values in the plasma; otherwise the kidney would eliminate waste products, but would fail to regulate the concentration of the threshold bodies in the plasma. The cells lining the tubules thus absorb from the glomerular filtrate a slightly alkaline fluid containing sugar, amino-acids and other similar food substances, and chloride, sodium, and potassium in approximately the proportions in which they are present in normal plasma, or in the artificial mixtures which have been introduced for the perfusion of surviving organs” (742). 

Augustus Désiré Waller (FR-GB) published the first report of a recording of cardiac electricity on the body’s surface; he called the recording a cardiograph. Among his contributions were the variability of the electrogram, the dipole concept that led to isopotential mapping, and the vector concept (3357). This work was first presented in 1887, at the International Congress of Physiology in London.

Henry Harrington Janeway (US) described the use of interstitial irradiation for operable breast cancer instead of mastectomy. He stated, "The use of radium can be offered to those patients who dread and refuse operation and It should also be useful in cases where the wisdom of using the knife is doubtful" (2162). Geoffrey Keynes (GB) and Stamford Cade (GB) substituted high voltage x-rays for the radium needles (1744).

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) (1506). See Luis Agote, 1914 and Sergei Sergeivitch, 1931. 

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

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 (1065).

On February 3, the U.S. Congress established a National Leprosarium in Carville, Louisiana.

Journal de Physiologie et de Pathologie Générale was founded.

Annals of Medical History (New York) was founded.


Max Karl Ernst Ludwig Planck (DE) was awarded the Nobel Prize in Physics in recognition of the services he rendered to the advancement of physics by his discovery of energy quanta.

Carl Alexander Neuberg (DE-US) showed that a mild acid hydrolysis of hexose diphosphate (Harden-Young ester) yielded hexose monophosphate (Neuberg ester). This hexose monophosphate was easily fermented by yeast juice and would prove to be fructose-6-phosphate (2331).

Carl Alexander Neuberg (DE-US) and Elsa Reinfurth (DE) found that by adding sodium bisulfite to an actively fermenting culture of Saccharomyces they could cause the yeast to excrete glycerol rather than ethanol (2341). Their process was the first example of the large-scale manipulation of fermentation using a steering agent. The added sodium bisulfite fixes to acetaldehyde blocking its use as electron acceptor. The yeasts adapt by using dihydroxyacetone phosphate (DHAP) as electron acceptor, producing glycerol-3-phosphate, then glycerol as waste product.

Otto Fritz Meyerhof (DE-US) discovered that the co-ferment (nicotinamide adenine dinucleotide phosphate) (NADP) of yeast alcoholic fermentation is also present in animal tissues. He defined co-ferment as heat-stable, dialyzable, and a participant in the oxidation of carbohydrates. This finding suggested that alcoholic fermentation and muscle glycolysis might proceed along the same metabolic pathway (2190, 2191). In 1921, he found that the glycolytic system of muscle requires a co-ferment similar to the material obtained from yeast. Ref

Carl Alexander Neuberg (DE-US), Elsa Reinfurth (DE), Julius Hirsch (DE), Maria Kobel (DE), and Max Scheuer (DE), between 1918 and 1931, determined that the yeast fermentation may be one of four types based on the major end products: 1) ethanol, carbon dioxide, 2) glycerol, acetylaldehyde, carbon dioxide, 3) glycerol, acetic acid, ethanol, carbon dioxide, 4) pyruvate, glycerol (1784, 1785, 2335, 2338-2342). 

C.K. Watanabe (US) described the hypoglycaemic properties of guanidine (3383).

Kurt Huldschinsky (DE) found that sunlight or a quartz lamp aided in the cure of rickets (1593).

Harry Goldblatt (GB) and Katherine Marjorie Soames (GB) clearly identified that when 7-dehydrocholesterol (a precursor to vitamin D) is irradiated with sunlight or ultraviolet light, a substance equivalent to the fat-soluble vitamin is produced (1269).

Alfred Fabian Hess (US) confirmed the dictum that "light equals vitamin D". He excised a small portion of skin, irradiated it with ultraviolet light, and then fed it to groups of rachitic rats. The skin that had been irradiated provided an absolute protection against rickets, whereas the unirradiated skin provided no protection whatsoever; clearly, these animals were able to produce adequate quantities of "the fat-soluble vitamin", suggesting that it was not an essential dietary trace constituent (1505).

Harry Steenbock (US), Arthur J. Black (US), and Mariana T. Nelson (US) obtained similar results when they found that rat food irradiated with ultra violet light also acquired the property of being antirachitic (2986, 2987).

Adolf Otto Rheinhold Windaus (DE) and Alfred Fabian Hess (US) discovered that vitamin D consists of a steroid molecule in which a bond is broken by the action of sunlight. This provided the rationale for the irradiation process whereby the vitamin D content of such foods as milk and bread are increased by exposure to ultraviolet light (3530).

Sigmund Otto Rosenheim (GB) and Thomas Arthur Webster (GB) identified ergosterol (isolated from oil of ergot, the fungus) as being synonymous with provitamin D. Irradiation with ultraviolet light transformed ergosterol into the vitamin (2680).

Robert Benedict Bourdillon (GB), Catherine Fischmann (GB), R.G.C. Jenkins (GB), and Thomas Arthur Webster (GB) confirmed the theory suggested previously that the ultra-violet irradiation of ergosterol produces three substances in succession. Of these, the first shows intense absorption for wavelengths between 2500 A. and 2900 A., and great, anti-raehitie power. The second shows intense absorption at 2400 A., and no antirachitic power. The final product (or products) has little or no appreciable absorption and no antirachitic power. They became convinced that the first substance is vitamin D (373).

Frederic Anderton Askew (GB), Robert Benedict Bourdillon (GB), Hilda Margaret Bruce (GB), R.G.C. Jenkins (GB), and Thomas Arthur Webster (GB) isolated and crystallized what they thought to be pure vitamin D (103).

Adolf Otto Rheinhold Windaus (DE), O. Linsert (DE), Arthur Luttringhaus (DE), and G. Weidlich (DE) crystallized and chemically characterized vitamin D2 (ergocalciferol) which could be produced by ultraviolet irradiation of ergosterol (3531).

Adolf Otto Reinhold Windaus (DE), Friedrich Schenck (DE), and Fritz von Werder (DE) isolated and identified the structure of vitamin D3 (cholecalciferol) (3532). Verify 

Adolf Otto Reinhold Windaus (DE) and F. Bock (DE) proved that the provitamin D in hog skin is 7-dehydrocholesterol (3529). See Blunt, 1968.

Friedrich Meves (DE) proposed that mitochondria carry hereditary material (2185).

Elvin Charles Stakman (US), John H. Parker (US), and Frank Joseph Piemeisel (US) began the process of destroying the popular bridging host theory, which was believed to explain how many plant parasites adapt to new hosts. They also set in motion studies that led to the reduction of black wheat stem rust of wheat from a major plague of wheat throughout the world to a relatively minor problem (2974).

Thomas Burr Osborne (US), Lafayette Benedict Mendel (US), Edna L. Ferry (US), and Alfred J. Wakeman (US) discovered that the liver is the principal storage organ for vitamin A (retinol) (2413).

Sewall Wright (US) used equilibrium principles in rejecting a one-gene hypothesis for the inheritance of blue eye color in man (3582).

Ronald Aylmer Fisher (GB-AU) mathematically analyzed data on human stature and other measurements and concluded that inheritance is better explained as particulate rather than blending. He was the first to point out that for natural selection to work inheritance had to be particulate and not blending. Polymorphic traits had been widely viewed as a result of blending. In the 1930 reference he defined the true cost of making a child as being measured in lost opportunities to make other children. This opportunity cost he named parental expenditure (1117, 1118).

Robert L. Trivers (US) used the same idea to elucidate sexual selection, calling it parental investment (3149).

Johann Gregor Mendel (Moravian-CZ) was the first to demonstrate that inheritance is particulate (2165-2167).

Nikolay Ivanovich Vavilov (RU), in 1918, stressed the importance of biologic centers of origin such as China and India as reservoirs of desirable genes, which can be incorporated into cultivated strains derived from those regions (628).

Rich Ege (SE) pointed out that when the oxygen in the air film of diving insects and spiders is removed by diffusion into the trachea, additional oxygen replaces it by diffusion from the water. Metabolic carbon dioxide leaves by the reverse route, and thus we might have a permanent and adequate underwater lung. However, the nitrogen pressure in the film must therefore increase and the nitrogen diffuse into the water until the surface area becomes reduced to such size that it can no longer support the metabolic demands of the creature. It must now return to the surface, not to replenish it oxygen supply but to replenish its nitrogen (953). 

Lodewijk Bolk; Louis Bolk (NL) proposed the fetalization or neoteny theory which states that there are evolutionary advantages to carrying certain infantile characteristics into adulthood. An example found among the apes and man is the large brain to body size ratio (347-349).

Edmund Beecher Wilson (US) said that Theodor Boveri (DE), “By the slow and painstaking process of observation, experiment and analysis, accomplished the actual amalgamation between cytology, embryology and genetics—a biological achievement which … is not second to any of our time” (3520).

Ernest Henry Starling (GB) stated the law of the heart as follows, “In the first place, provided the inflow remains constant, it seems to be immaterial to the heart whether it has to contract against a resistance of 44 mm. Hg, or 208 mm. Hg. In each case it puts out as much blood as it receives, so that the total outflow remains constant whatever the arterial pressure. Of course there is a limit which must not be exceeded… The second fact, which results from this experiment, is that the fraction of the total output of blood, which passes through the coronary vessels, rises steadily with the height of the arterial pressure. This means that the more work the heart has to do, the better it is supplied with blood, i.e., with the oxygen and nutriment necessary to furnish it with energy…Within physiological limits the larger the volume of the heart, the greater are the energy of its contraction and the amount of chemical change at each contraction… the energy of contraction, however measured, is a function of the length of the muscle fibre” (2979). 

J. S. Szymanski () showed that animals are capable of maintaining 24-hour activity patterns in the absence of external cues such as light and temperature. These are now known as circadian rhythms, or the biological clock (3063).

Franz Halberg (US), Maurice Bolks Visscher (US), and John J. Bittner (US) along with Jürgen Aschoff (DE) developed an explanation of the role that environmental factors play in the functioning of internal biological clocks. Aschoff called these environmental factors zeitgeber, meaning time giver (95, 1369).

Aaron B. Lerner (US), James D. Case (US), Yoshiyata Takahashi (US), Teh H. Lee (US), and Wataru Mori (JP) succeeded in isolating from bovine pineal glands the compound named melatonin (5-methoxy, N-acetyltryptamine). It was given this name because of its blanching effect on melanophores in the skin of tadpoles (1933). See, Fiske, 1941.

Franz Halberg (US), Erna Halberg (US), Cyrus P. Barnum (US), and John J. Bittner (US) were the first to use the term circadian to describe time rhythms in living creatures (derived from circa meaning about and dies meaning day) (1367, 1368). These environmental factors act to keep biological cycles in phase with periodic fluctuations in the environment. In the absence of environmental cues, the cycles continue to run but tend to drift.

Colin S. Pittendrigh (GB-US), Victor G. Bruce (US), Norton S. Rosensweig (US), and M.L. Rubin (US) discovered circadian rhythm in fungi. It manifested as periodic conidiation that provided a permanent record as bands formed along a growth continuum (2541). 

Jürgen Aschoff (DE) found that beyond certain narrow limits, the presence or absence of environmental cues has no effect on biological rhythms (96).

Julius Axelrod (US), Herbert Weissbach (US), and Betty G. Redfield (US) determined that serotonin is converted to melatonin in the pineal gland as follows: serotonin—N-acetylserotonin—melatonin (117, 3416). 

Curt Paul Richter (US), in his studies of biological rhythms, discovered that circadian rhythms (and longer-term endogenous clocks) influence behavior. He demonstrated that the circadian clock is not dependent on learning or upon external stimuli for its expression. Richter then discovered that a marked disruption in activity rhythms could be produced by damage to the anterior region of the hypothalamus (2635).

Malcolm L. Sargent (US) and Winslow R. Briggs (US) found that resetting the circadian clock in Neurospora is mediated by a blue-light photoreceptor (2773).

Ronald J. Konopka (US), Seymour Benzer (US), Aimita Sehgal (US), Jeffrey L. Price (US), Bernice Man (US), Michael W. Young (US), Leslie B. Vosshall (US), and Lino Saez (US) determined that the generation of circadian rhythms in Drosophila requires the activity of two genes, period (per) and timeless (tim) (1813, 2870, 3336).

Central to the timekeeping mechanism of the body and mind are suprachaismatic nuclei or SCN. The SCN is the master clock – the circadian rhythm that controls all other rhythms of the body. 

Milton H. Stetson (US) and Marcia Watson-Whitmyre (US) found that destruction of the suprachiasmatic nuclei in the golden hamster by bilateral radiofrequency lesions abolishes three well-documented circadian rhythms--locomotor activity, estrous cyclicity, and photoperiodic photosensitivity (3007).

Jon M. Kornhauser (US), Dwight E. Nelson (US), Kelly E. Mayo (US), and Joseph S. Takahashi (US) found that light is carried from the eye to the suprachiasmatic nuclei (SCN) in mammals. The effect of this information has been found to induce the expression of the genes, c-fos and jun-B in SCN cells. These genes control the expression of other genes (1818).

Robert Y. Moore (US), Margaret M. Moga (US), Rehana K. Leak (US), and J. Patrick Card (US) localized the site of the mammalian suprachiasmatic nucleus (SCN) to a small cluster of cells just above the optic chiasm (1914, 2224, 2239).

Samer Hattar (US), His-Wen Liao (US), Motoharu Takao (US), David M. Berson (US), and King-Wai Yau (US) reported that the retinal ganglion cells containing the photosensitive pigment melanopsin are connected through the retinohypothalamic nerve tract to the suprachiasmatic nucleus, the primary circadian pacemaker of the brain. Then the suprachiasmatic nucleus sends its signal to the superior cervical ganglia, which in turn innervates the pineal gland via norepinephrine-containing (sympathetic) nerves (1438). Thus light influences the flux of melatonin in the pineal gland.

Percy Heath Hobart Gray (CA), Henry Brougham Hutchinson (GB), Aage Christian Thaysen (GB) and Nagendra Nath Sen-Gupta (IN) demonstrated that soil bacteria are capable of destroying phenol, cresol, toluene, and napthalene, and that the rate of destruction increases with successive dosages applied to the soil plot (1308, 1602, 2872).

Karel Kruis (CZ), Jan Satava (CZ), and Øjvind Winge (DK) demonstrated that standard vegetative cells of the yeast Saccharomyces cerevisiae are diploid, being produced by copulation of two spores or gametes derived from spores. The diploid nuclei undergo reduction at spore formation to produce four haploid ascospores (1844, 3540).

Magnesium arsenate was first used as an insecticide. Paradichlorobenzene was discovered to be effective for control of peach tree borer. The commercial use of calcium arsenate for boll weevil control started; 35,000 acres were treated (2879).

Ezra Jacob Kraus (US) and Henry Reist Kraybill (US) proved that variations in internal juices of plants are produced by variations in the fertilizer treatment and in the available moisture of the soil (1832).

Donald F. Jones (US) showed that grain productivity and vigor in maize is further increased by a double cross between two hybrids, each of which is the product of two inbred lines (1685).

Walter Bradford Cannon (US), John Fraser (GB), Arthur Norman Hooper (GB) and William Maddock Bayliss (GB) observed the human body under hemorrhagic and traumatic stress during World War I. They observed that in shock a concentration of the blood occurs, at least in the superficial capillaries. From these experiences Cannon developed the notion of homeostasis; that is, the effort of the body to maintain a stable internal environment despite fluctuations (within reason) of the outside environment (238, 510, 513). Primarily responsible for this were the various hormones, particularly epinephrine (adrenaline). See, isonomy of Alcmaèon, 520 B.C.E. and milieu intérieur of Claude Bernard, 1865.

Studying the nerve endings influenced by epinephrine, Cannon discovered that they secreted an epinephrine-resembling compound even under normal nonemergency conditions. Since these nerve endings belonged to what was called the sympathetic nervous system, he called the compound sympathin (514). 

Ulf Svante Hansson von Euler-Chelpin (SE) subsequently isolated and identified noradrenaline (norepinephrine) as the neurotransmitter in the sympathetic nervous system (3271-3273).

Ernst Moro (DE) explained the embrace or startle reflex in infants under six months of age as a defensive reflex. In response to a loud noise, passive movement of the child’s head or striking the surface on which the infant rests, the infant draws its arms across its chest in an embracing manner. Absence of this reflex under 6 months of age suggests diffuse central nervous system damage and asymmetric responses are seen with all forms of palsies - its presence after 6 months of age suggests cortical disturbance (2263).

Margaret W. Jepps (GB) and Clifford Dobell (GB) gave the first description of Dientamoeba fragilis (1672). Patients infected with this protozoan frequently suffer from acute intestinal signs such as explosive diarrhea, severe abdominal pain, cramps, nausea, vomiting, mild fever, and general fatigue.

Eighty-five years after its first description, although D. fragilis is accepted as a true pathogen in some countries and infected patients are treated, it is still struggling to gain acceptance as a legitimate pathogen in many others.

Robert Sanno Fåhraeus (SE) discovered the decrease in apparent viscosity of blood that occurs when it flows through a vessel of smaller diameter than about 1.5 mm (1061-1063).

Chevalier Jackson (US) insufflated bismuth through a bronchoscope so as to visualize the bronchi radiologically (1636).

Jean Athanse Sicard (FR) and Jacques Forestier (FR) are credited with the introduction of radiopaque poppy seed oil (Lipiodol) for the exploration of the lower respiratory tract (2912). 

Walter Edward Dandy (US) introduced a method for diagnosis of cerebral tumors (763). He injected air into the ventricles (liquid-filled cavities) of the brain to increase their contrast in x-ray.

May Tweedy Mellanby (GB) discovered that the onset of dental caries is determined partly by the deficiency of certain substances in the diet, particularly salts of calcium and phosphorus. She also found that the onset of caries is influenced by the structure of the teeth, which is determined largely by the diet during development (2159).

Lester Reynold Dragstedt (US), Carl Albert Dragstedt (US), John Thomas McClintock (US) and Charles Sumner Chase (US) demonstrated the feasibility of total duodenectomy in dogs and pigs (882).

Francis Bertody Sumner (US) studied geographic variation in Peromyscus (deer mice) and convinced himself that the apparently continuous variability is actually Mendelian in nature. He concluded that the evolution of species is the result of minute genetic changes largely of an adaptive nature (3052).

Edward Glanzmann (CH) reported on hereditary hemorrhagic thrombasthenia as a condition characterized by prolonged bleeding time and poor clot retraction in the presence of a normal platelet count (1248). This paper ushered in the era of platelet function studies. 

Joseph Barrell (US) published a Phanerozoic time scale based on chemical ages produced by Holmes (1911), and interpolations involving less quantitative methods. The divisions in the time scale fall fairly close to today's accepted values. For example, Barrell placed the Cenozoic-Mesozoic (Cretaceous-Tertiary) boundary at 55-65 million years ago (today's value: 65 million years ago), and the base of the Cambrian at 360-540 million years ago (today's value: 570 million years ago) (185).


“Paradoxical though it may sound, the more skillfully a demonstration experiment is performed the less from it do some students learn.” Charles Scott Sherrington (2898).

Jean Baptiste Vincent Bordet (BE) was awarded the Nobel Prize in Physiology or Medicine for his discovery of complement fixation and studies in bacterial immunology.

Francis William Aston (GB) made a significant contribution to atomic science with the invention of the mass spectrograph. The device is capable of separating isotopes by measuring the minute differences in their masses. Using the mass spectrograph, Aston discovered a third isotope of neon with atomic weight 21, then successfully identified 212 of the 287 naturally occurring isotopes (104, 105, 107, 108). The invention also prompted him to devise his famous Whole Number Rule which states, "the mass of the oxygen isotope being defined, all the other isotopes have masses that are very nearly whole numbers” (106). The rule became crucial to future developments in nuclear energy technology.

Hugh Hampton Young (US), Edwin C. White (US), and Ernest O. Swartz (US) reported on the germicidal efficiency of 2,7-dibromohydroxymercurifluorescein-disodium salt, in a 2% aqueous solution, known as mercurochrome or merbromin (3603, 3604). It was the best known and most widely used antiseptic in the world until banned by the Food and Drug Administration (FDA) in 1998 as not being safe and effective.

Jack Cecil Drummond (GB) proposed calling the antiscorbutic substance vitamin C (893).

Arpad Paál (HU) showed that when the tip of a plant shoot is cut off and replaced to one side, the growth of the base is greater on this side. This signaled the occurrence of a growth substance, produced in the tip, that somehow regulated the positive curvature of oat coleoptiles, the distinctive feature of the phototropism (2443).

James Howard Brown (US) introduced the terms alpha, beta, and gamma to describe the three types of hemolytic reactions produced by bacteria on blood agar plates (446).

Ludwik Hirszfeld (PL) and Hanka Hirszfeld (PL) were the first to describe racial variation in ABO blood-group frequencies and thereby introduce serological genetics into anthropology (1534). Their discovery of blood-group gene polymorphism and of regular geographic clines of changing frequency (e.g., blood group B increasing from west to east across Europe and Asia) prepared the way for the most extensive genotypic description of geographic populations which is available for any species.

Winfred Ashby (US) developed a differential agglutination method, which she used to determine survival rates of erythrocytes in the human body, and thus became the first person to establish the correct life span of erythrocytes (approximately 30 days) (101).

Schack August Steenberg Krogh (DK) observed that in resting tissue not all capillaries are open at any one time but rather there is a shifting back and forth by any given capillary, open at one time closed at another, the demands of surrounding tissues obviously influencing the degree of dilation (1837, 1840).

Schack August Steenberg Krogh (DK) observed that in striated muscles the capillaries are arranged with such regularity along the muscle fibers that each capillary can be taken to supply a definite cylinder of tissue the average cross-section of which can be determined by counting the capillaries in a known area of the transverse section.

A formula is given which allows the calculation of the oxygen pressure head, which is necessary and sufficient to supply the muscle with oxygen from the capillaries.

The number of capillaries per square mm. of the transverse section of striated muscle appears to be a function of the intensity of the metabolism, being higher in small mammals than in larger forms.

The necessary oxygen pressure head deduced from the total number of capillaries is in all cases extremely low (1838).

Selig Hecht (PL-US) introduced the idea that in photosensory systems a photosensitive substance S is decomposed by light into P and A (light adaptation) and that in the dark, P and A combine to reform S (dark adaptation) (1451). 

Thomas Hunt Morgan (US) authored The Physical Basis of Heredity, a summary of the rapidly growing findings in genetics (2255).

Calvin Blackman Bridges (US) discovered chromosomal duplications in Drosophila (422).

Calvin Blackman Bridges (US) and Otto L. Mohr (NO) showed that in Drosophila melanogaster the character vortex is dependent upon or is modified by four mutant genes. The grade of the vortex character and the proportion of flies showing that character is higher in the females than in males of the same genetic constitution (429).

Pio del Rio-Hortego (ES) perfected an ammonical silver carbonate staining technique with which he announced that Cajal’s third element consisted of 2 types of cells, which he named microglia (mononuclear phagocytes that reside within the central nervous system) and oligodentroglia. Later he published his classic work on histogenesis of microglia (2648-2654).

William Ford Robertson (GB) had introduced the term microglia but did not study the cell type in any detail (2663, 2664). Santiago Ramón y Cajal (ES) referred to these cells as the third element (2590).

Pio del Rio-Hortega (ES) demonstrated that microglial cells are reticuloendothelial cells (2655).

Clifford Dobell (US) wrote Amoebe Living in Man in which he clarified the taxonomy of the parasitic amoebae by classifying them into four genera (849). 

Carl C. Speidel (US) discovered neurosecretion in spinal cord cells of the skate (2961).

Ernst Scharrer (DE-US) confirmed neurosecretion when he found secretory droplets in certain hypothalamic neurons of the European minnow, Phoxinus laevis. He called them nerve gland cells and proposed that they secreted substance in the same manner as endocrine cells (2805). This was a revolutionary idea at the time. The current scientific dogma was that cells could either conduct electrical impulses or secrete hormones, not both. Scharrer’s work represents the origin of neuroendocrinology.

Berta Vogel Scharrer (DE-US) described neurosecretory cells in the opisthobranch snail, Aplysia, in the polychete worm, Nereis, in the cockroach, and in the horseshoe crab, Limulus polyphemus (2787-2790).

Berta Vogel Scharrer (DE-US) determined the function of neuroglandular bodies in the head of the South American woodroach, Leucophaea maderae, including especially the corpus allatum and corpus cardiacum. She found that removal of the corpus allatum severely effects development due to hormonal imbalance. Nymphs undergo premature metamorphosis and egg development is abnormal. Removal of the corpus cardiacum has no observable effect. She concluded that the corpus cardiacum is a storage depot for hormones from the corpus allatum and that these hormones are shipped from the corpus cardiacum out to the body by neurosecretory cells, the secretory granules traveling down the nerve axon prior to release at the axon’s terminus. Surprisingly she noted that when these neurosecretory cells are severed tumors develop in their distal tissues.

Ernst Scharrer (DE-US) and Berta Vogel Scharrer (DE-US) noted many interesting parallels between the corpus allatum-corpus cardiacum system of insects and the hypothalamo-hypophyseal system of vertebrates (2791-2793, 2803, 2804, 2806).

Berta Vogel Scharrer (DE-US) revealed the ultrastructure of the insect neurosecretory cell, showing that neurosecretory granules originated in the endoplasmic reticulum and Golgi apparatus of these cells then passed down the axon to be released at the axon terminals (2794-2798, 2807).

Berta Vogel Scharrer (DE-US) formulated a comprehensive theory of the evolutionary origins of neurosecretory cells. She suggested that neurosecretory communication of the type seen in insects preceded specialized endocrine and synaptic systems (2799, 2800).

Berta Vogel Scharrer (DE-US) showed that invertebrate neurosecretory cells and neuropeptides participate in regulation of the immune system (2801, 2802). 

Joseph Arthur Arkwright (GB), Arthur William Bacot (GB), and F. Martin Duncan (GB) supplied strong circumstantial evidence that the etiological agent of trench fever is rickettsial and that body lice carry it (88). The etiological agent was named Rickettsia pediculi and later Rochalimea quintana or Rickettsia quintan. Currently it is called Bartonella quintana.

Ernest William Goodpasture (US) described a progressive, rare, and usually fatal autoimmune disorder affecting primarily the kidney and lung. It is characterized by glomerulonephritis and intra-alveolar hemorrhage (1285). Goodpasture’s syndrome

Cécile Mugnier Vogt (FR-DE) and Oskar Voigt (DE) described over 200 cortical areas of the brain (3237).

William Healey Dall (US), a naturalist who specialized in malacology (describing over 5,300 species) but also made contributions in ornithology, zoology in general, anthropology, oceanography, and paleontology published over 1,600 papers, reviews, and commentaries. He is commemorated by Dallina Beecher, 1895 and Dalliella Cossman, 1895.

Theobald Smith (US) and Marian S. Taylor (US) observed that the bacterium Vibrio fetus is the cause of fetal membrane disease in cattle (2941).

Rebecca Craighill Lancefield (US), Oswald Theodore Avery (CA-US), and Alphonse Raymond Dochez (US) used the precipitin test to differentiate the beta-hemolytic streptococci into a number of immunological groups designated by the letters A through O. Most strains causing human infections were found to belong to group A (116, 1867-1877).

Dudley H. Morris (US) and Frederick D. Bullock (US), using rat plague bacillus in animal studies, established the importance of the spleen in resistance to infection (2264).

Harold King (US) and Harris B. Shumacker, Jr. (US) were the first to firmly establish an association between fulminant bacterial sepsis and splenectomy in humans. They reported on five cases where bacterial sepsis followed splenectomy in infants (1750).

Solomon Eberhard Henschen (SE) surveyed specific disorders of calculation following brain damage and named the disorder acalculia (without calculation), today it is called dyscalculia (disordered calculation) (1478).

Lewis H. Weed (US) and Paul S. McKibben (US) used intravenous injections of hypertonic saline solutions in patients with intracranial pathologies to treat cerebral edema and elevated intracranial pressure. These solutions lowered the pressure of the cerebrospinal fluid, and produced a definite shrinking of the brain (3401).

Walter Edward Dandy (US) reported eight pneumencephalographies after lumbar air insufflation (764).

Bordeaux mixture was demonstrated effective for control of potato leafhopper (2879).


“And though much has been written foolishly about the antagonism of science and religion, there is, indeed, no such antagonism. What all these world religions declare by inspiration and insight, history as it grows clearer, and science as its range extends, display, as a reasonable and demonstrable fact, that men form one universal brotherhood, that they spring from one common origin, that their individual lives, their nations and races, interbreed and blend and go on to merge again at last in one common human destiny upon this little planet amidst the stars.” Herbert George Wells (3422).

“Phases of real intellectual progress in any community seem to be connected with the existence of a detached class of men, sufficiently free not to be obliged to toil or worry exhaustively about mundane needs, and not rich and powerful enough to be tempted into extravagances of lust, display, or cruelty. They must have a sense of security, but not a conceit of superiority. This class, we have further insinuated, must be able to talk freely and communicate easily. It must not be watched for heresy or persecuted for any ideas it may express.” Herbert George Wells (3422).

“Even our digestion is governed by angels," said Blake; and if you will resist the trivial inclination to substitute "bad angels," is there really any greater mystery than the process by which beef is turned into brains, and beer into beauty?” Richard Le Gallienne (1913).

Hermann Walther Nernst (DE) was awarded the Nobel Prize in Chemistry for his proposal of the third law of thermodynamics.

Schack August Steenberg Krogh (DK) was awarded the Nobel Prize in Physiology or Medicine for his discovery of the capillary motor regulating mechanism.

Ernest Rutherford (New Zealand-GB) was the first man ever to change one element into another as a result of his own manipulations. He did this by bombarding nitrogen atoms with alpha particles. Occasionally one of the nitrogen nuclei had one of its protons knocked out, changing it into an oxygen atom (this was detected using a scintillation counter). This is also the first man-made nuclear reaction.

He found that the nitrogen nucleus has hydrogen nuclei in it. That meant the hydrogen nucleus is an elementary particle. Rutherford named it the proton, from the Greek word protos, meaning first (2733).

Rutherford, in 1920, predicted the neutron which James Chadwick (GB) later discovered (556).

Wendell Latimer (US) and Worth H. Rodebush (US) proposed hydrogen bonds, defining them as secondary interatomic links, weaker than valence bonds (1903).

Reginald Oliver Herzog (DE) and Willi Jancke (DE) used x-ray crystallography (diffractometry) to provide strong evidence that silk fibroin contains polypeptide chains in the extended configuration (1503).

Gilbert T. Morgan (GB) and Harry Dugald Keith Drew (GB) introduced the term chelate to chemistry when they stated: "The adjective chelate, derived from the great claw or chela (chely- Greek) of the lobster or other crustaceans, is suggested for the caliper like groups which function as two associating units and fasten to the central atom so as to produce heterocyclic rings" (2246).

Torsten Ludvig Thunberg (SE) was among the first to suggest that the protein portion of an enzyme possesses both substrate specificity and catalytic power. His comments were in reference to dehydrogenases (3122).

Carl Voegtlin (US), Mather H. Neill (US), and Andrew Hunter (US) reported that pellagra could be cured by daily doses of 15-30 grams of dried yeast, or by 15 grams of a water extract of yeast (3233).

Ellen Marion Delf (GB) and Alfred Fabian Hess (US) independently showed that oxidizing agents and air easily inactivate vitamin C (812, 1504).

Johann Ernst Oswald Schmiedeberg (DE) coined the name chondroitinschwefelsäure (chondroitin sulfuric acid) derived from chondros (cartilage, and deduced composition: acetate, sulfate, glucuronic acid, and hexosamine (2836).

Torsten Ludvig Thunberg (SE) was the first to recognize l (-) alpha-hydroxyglutaric acid (2-hydroxyglutarate) as a substrate of the intermediary metabolism of animal tissues (3122).

Hans Weil-Malherbe (GB) found that 2-hydroxyglutarate is oxidized by a hydroxyglutaric dehydrogenase (2-hydroxyglutarate dehydrogenase) in animal tissues (3410).

Walter Jennings Jones (US) described an enzyme from the swine pancreas as relatively heat-stable and capable of digesting yeast nucleic acid (RNA) but failing to digest thymic nucleic acid (DNA) (1698).

René Jules Dubos (US) and Robert H.S. Thompson (US) named this enzyme ribonuclease (902).

Hans Karl Albert Winkler (DE) introduced the term genome into genetics. It is an irregular hybrid of gene and the suffix ome meaning “the entire collectivity of units”. Both parents are Greek (3543). From page 165 of his book, "I propose the expression Genome for the haploid chromosome set, which, together with the pertinent protoplasm, specifies the material foundations of the species...”

Alfred Henry Sturtevant (US) discovered that some mutations restore the wild-type character to a mutant phenotype without having actually restored the mutant gene to its pristine, wild type state. Sturtevant gave the name suppressor to such mutations (3043).

George Wells Beadle (US) and Boris Ephrussi (RU-FR) further contributed to the understanding of gene suppression (242).  

Franz Schrader (DE-US) proved for the first time that sex may be determined by haploidy or diploidy of the zygote; that fertilized females can produce male progeny parthenogenetically; and that these males, unlike their sisters, are fatherless, for their single set of chromosomes comes from their mother (2847).

Johan Schmidt (DK), Tatuo Aida (JP), and Øjvind Winge (DK) were the first to demonstrate Y-linked inheritance in animals. Their subjects were the fish Lebistes reticulatus (guppy) and Aplocheilus latipes (killifish). Aida’s work includes the first demonstration of crossing over between an X- and a Y-chromosome (39, 2835, 3538, 3539).

Clarence Cook Little (US) and Leonell C. Strong (US) established the existence of multiple genes for susceptibility and resistance to tumor transplants in mice. These genes would later be called histocompatibility genes (1979-1981).

Maurice N. Richter (US) and E. Carleton MacDowell (US) described the incidence of leukemia in an inbred strain of mice, C58. MacDowell developed this strain from crossing male 52 with female 58. Almost 90% of C58 mice developed leukemia. Richter and MacDowell showed that the tumors could be transferred by cell-grafts within the strain but not to other strains of mice (2636).

Wilhelm Gruter (DE) initiated a series of animal studies that demonstrated unequivocally the infectious nature of herpes simplex virus (HSV). He showed how HSV could be transmitted serially from rabbit to rabbit, and it is he who is usually given credit for the isolation of HSV (1333, 1334). This work was actually done between 1911 and 1914.

Christopher H. Andrewes (GB) and E. Arnold Carmichael (GB) observed that recurrent infections of herpes occurred only in adults who carried neutralizing antibodies – an occurrence in sharp contrast to the behavior of other known infectious agents at that time (71).

F.M. Barnett (AU) and S.W. Williams (AU) provided the first accurate description of the biology of herpes simplex virus infections in humans (184).

Frank Macfarlane Burnet (AU), Dora Lush (AU), and Alan V. Jackson (AU) grew herpesvirus type 1 on the chorioallantoic membrane of chick embryos (477). 

Karl Edward Schneweiss (DE) presented evidence that orolabial and genital herpes are caused by two different strains of human herpes simplex virus (2840).

Gary S. Hayward (US), Robert J. Jacob (US), Samuel C. Wadsworth (US), and Bernard Roizman (US) determined the organization of the herpes simplex virus genome (1444).

John Zahorsky (US) is credited with being the first to describe, and then name, herpangina (3610, 3611). It typically presents as papular, vesicular, and ulcerative lesions on the anterior tonsillar pillars, soft palate, tonsils, pharynx, and posterior buccal mucosa.

Gilbert Julias Dalldorf (US) and Grace M. Sickles (US) were the first to isolate the Coxsackie virus (named for Coxsackie, New York). It came from stools of two children exhibiting signs resembling poliomyelitis and was grown in newborn mice (761).

Robert Joseph Huebner (US), Roger M. Cole (US), Edward A. Beeman (US), Joseph A. Bell (US), and James H. Peers (US) showed that Coxsackie virus type A is the etiological agent of herpangina (1590). 

Carl F.T. Mattern (US) and Herman G. DuBuy (US) crystallized the Coxsackie virus (2117).

Sears P. Doolittle (US) demonstrated that Aphis gossypii Glov., and the cucumber beetles Diabrotica vittata and Diabrotica duodecimpunctata Oliv. act as vectors of the cucumber mosaic virus (873).

Elmer Walker Brandes (US) demonstrated that Aphis maidis acts as a vector of sugar cane (Saccharum officinarum) mosaic virus (403).

Edward John Russell (GB) indicated that fungi of the genera, Verticillium, Fusarium, and Pythium are injurious root pathogens (2728).

David Keilin (PL-GB) made the first adequate description of yeast (ascomycete) infection of insects. The host was the larvae of the biting midge, Dasyhelea obscura Winnertz, and the yeast Monosporella unicuspidata Keil (1725).

Alexandrino Pedroso (BR) and José Maria Gomes (BR) were the first to observe the fungal infection which Fernando Terra (BR), Magarinos Torres (BR), Olympio Oliveiro da Fonseca (BR), and Antonio Eugenio de Area Leao (BR) would later call chromoblastomycosis (2496, 3084). The term chromoblastomycosis refers to pigmented fungal infections of the subcutaneous tissue.

C. Guy Lane (US) and Edgar M. Medlar (US) reported the fungus Phialophora verrucosa as a cause of this disease (1885, 2155).

Alexandre Joseph Emilé Brumpt (FR) renamed the fungus Hormodendrum pedrosi (457).

Arturo L. Carrión (PR) reported that Hormodendrum compactum could also be the etiological agent (534). The disease has been called verrucous dermatitis and chromomycosis.

Jose Paulo Smith Nóbrega (BR), Sergio Rosemberg (BR), Ana Maria Adami (BR), Elizabeth Maria Heins-Vaccari (BR), Carlos da Silva Lacaz (BR), and Thales de Brito (BR) reported the first human culture-proven case of brain abscesses due to Fonsecaea pedrosoi (Hormodendrum compactum) in Brazil (2366).

Joseph Francis Charles Rock (AT-US) discovered that oil from the seeds of Hydnocarpus wightiana and Hydnocarpus anthelmintica is the legendary chaulmoogra oil (hydnocarpus oil) which for centuries has been used to successfully treat the early stages of leprosy (2669).

Irving Widmer Bailey (US) demonstrated for the first time how the single cell-layered cambrial cylinder could increase the circumference of the ever-expanding stem or root of the plant (140-142).

Paul Saxl (AT) and Robert Heilig (AT) reported the diuretic effect of merbaphen (Novasurol) which contains mercury in a complex organic form and was originally introduced as an antisyphilitic agent (2780).

Henry Head (GB) defined two basic subtypes of sensation. He characterized epicritic sensibility as the ability to make fine discrimination of touch and temperature sensations, as well as the ability to localize and discriminate sensation. He characterized protopathic sensation as changes in temperature and pressure without the ability to localize an abnormality (1446).

Mieczyslaw Minkowski (CH) determined the pattern of termination of optic tract fibers in the lateral geniculate nucleus (LGN), the thalamic relay for vision. He did so using studies of transneuronal atrophy and degeneration. Cells in the LGN that are deprived of their input from the eye shrink or die (2213).

Bernard Brouwer (NL), Willem Pieter Cornelis Zeeman (NL), and Wilfred E. le Gros Clark (GB) confirmed that there is an orderly projection from the retina to the LGN and from the LGN to the visual cortex. Neighboring points in the visual fields are represented at neighboring points on the cerebral cortex (442, 592). 

Isadore Clinton Rubin (US) described insufflation as a test of tubal patency, which allows the diagnosis of tubal disease without diagnostic laparotomy (2717).

Hans Gerhard Creutzfeldt (DE) described a rare human dementia. He thought it was inherited (694, 695).

Alfons Maria Jakob (DE) diagnosed cases of the same disease (1647-1649). This disease, a form of senile dementia, became known as Creutzfeldt-Jakob disease (CJD).

Charles W. Hooper (US), Harry P. Smith (US), Arthur E. Belt (US) and George Hoyt Whipple (US) developed a reproducible dye dilution method for quantitative estimation of plasma volume (1563).

Georges Fernand Isidore Widal (FR) defined hemoclasia as a leucocyte phenomenon: In some people, following a meal containing white of egg (albumin) there occurs a significant reduction in leucocytes and an increase in the refracto-motor value of the serum (3456).

Solomon Eberhard Henschen (SE) found that isolated damage to the left STG (Wernicke's area) probably does not produce multimodal language comprehension deficits and that disorders of language and calculation abilities can occur independently (1479). Wernicke's area is one of the two parts of the cerebral cortex linked since the late nineteenth century to speech.

Emile Holman (US), in 1920, performed experiments that hinted at the first signs of what would become the concept of rejection. He transplanted the skin of a mother onto a badly burnt child. The subsequent grafting of more skin onto the child a few days later resulted in the inflammation of both the mother and the child’s own skin, the implications of immunogenicity from this experiment were noted by Holman (1366, 1556). 

Karl Bauer (DE) performed a successful skin allograft between identical twins and the skin on the twins stayed on indefinitely (231, 2032). See, Medawar 1944. 

Oil-soaked sawdust was first recommended for mosquito control. Paris green was first rated as a mosquito larvicide (2879).

The Society of Neurological Surgeons was founded.


Anonymous Poem on Syphilis from the 1920s 

There was a young man from Back Bay, Who thought syphilis just went away. He believed that a chancre
Was only a canker, 

That healed in a week and a day. But now he has `acne vulgaris' ± (Or whatever they call it in Paris); On his skin it has spread 

From his feet to his head
And his friends want to know where his hair is. There's more to his terrible plight,
His pupils won't close in the light,
His heart is cavorting,
His wife is aborting,
And he squints through his gun-barrel sight. Arthralgia cuts into his slumber,
His aorta is in need of a plumber,
But now he has tabes
And sabre-shinned babies,

While of gummas he has quite a number.

He's been treated in every known way, 

But his spirochaetes grow day by day; 

He's developed paresis, 

Has long talks with Jesus,

And thinks he's the Queen of the May. 

Michael Polanyi (DE) showed that forces associated with adsorption could lower the energy of decomposition of a reactant (2549).

Frederick Gowland Hopkins (GB) discovered and named glutathione isolated from yeast. He characterized it as a dipeptide containing glutamic acid linked to a sulfur compound (1566). He later crystallized glutathione and concluded that it is a tripeptide composed of glutamic acid, cysteine, and glycine, the structure being gamma-glutamyl-cysteinyl-glycine (1567).

Edward Calvin Kendall (US), Bernard F. McKenzie (US), and Harold L. Mason (US) independently crystallized glutathione and identified it as a tripeptide of glutamic acid, cysteine, and glycine (1736, 1737).

John Addyman Gardner (GB), Francis William Fox (GB), Hans Beumer (DE), F.R. Lehmann (DE), Siegfried J. Thannhauser (DE), Hans Schaber (DE), Harold John Channon (GB), F.S. Randles (US), and Arthur Knudson (US) demonstrated that cholesterol is synthesized in the animal body (300, 566, 1214, 1215, 2593, 3089).

Ernest Francois Auguste Fourneau (FR) and his colleagues extended Paul Ehrlich’s work by introducing stoxvarsol (acetarsone; spirozid) the first antisyphilitic arsenical compound that could be taken orally (1161, 1918). It was introduced to treat intestinal amebiasis, necrotizing ulcerative gingivitis, and topically in trichomonas vaginitis. Also used as an antihelmintic in veterinary cases.

Rudolf Lieske (DE) observed that some actinomycetes could bring about the lysis of some bacteria as well as antagonize their growth (1960).

Harvey P. Barret (US) and Nancy Yarbrough (US) succeeded with in vitro cultivation of Balantidium coli through eleven transplants over a period of thirty-two days (187).

Harvey P. Barret (US) and Nannie M. Smith (US) were the first to obtain in vitro cultures of parasitic amoeba. They grew Endamoeba barreti from the turtle (186).

Theophilus Shickel Painter (US) described the Y chromosome in man (2447).

Marin Molliard (FR) cultivated fragments of plant embryos with limited success (2226).

Aleksandr Fedorovich Lebedev (RU) suggested that all cells have the ability to fix carbon dioxide. What set apart the photosynthetic group was its use of light as a source of energy for the process. This view was so far ahead of its time that it had little impact (1917).

David Keilin (PL-GB) was the first to identify a blastocladiaceous (phycomycete) fungus as parasitic for insects. He isolated it from the mosquito larvae of Aëdes alboptictus Skuse, i.e., Stegomyia scutellaris Walker (1726). 

George Washington Corner (US) reported the whole sequence of uterine changes occurring in the sow during the reproductive cycle as well as those occurring in the corpus luteum (655).

Paul Galpin Shipley (US), Edwards A. Park (US), Elmer Verner McCollum (US), and Nina Simmonds (US) demonstrated the therapeutic value of sunlight in the treatment and prevention of rickets (2903, 2904).

Thomas Palmer Nash, Jr. (US) and Stanley Rossiter Benedict (US) determined that ammonia excreted in human urine is produced in the kidney (2307, 2308).

Herbert McLean Evans (US) and Joseph Abraham Long (US) found that removal of the anterior lobe of the pituitary gland inhibited growth in young rats and repressed their sexual development. This strongly suggested that the anterior lobe of the pituitary gland produced a growth hormone (somatotropic hormone/STH) and gonadotropic hormones (follicle stimulating hormone/FSH and luteinizing hormone/LH) (1046). When they injected an alkaline extract of ox pituitaries into young rats, they produced such enhanced growth that some of the treated animals grew far heavier than the largest untreated rats in the colony. This work also strongly suggested that the anterior pituitary gland contains a growth hormone (somatotropic hormone/STH) (1047). These works represent the first direct experimental demonstration of the action of the anterior pituitary on the gonads.

Otto Loewi (DE-US) elegantly demonstrated that while the nerve impulse is electrical in nature it is also chemical in nature. Working with the nerves attached to the frog’s heart, he showed that chemical substances are set free when the nerve is stimulated. The fluid containing the substance can be used to stimulate (slow down) another heart directly without the intervention of nerve activity. Loewi called the substance Vagusstoff (acetylcholine), meaning vagus material, because he obtained it by stimulating the vagus nerve. Because Loewi used animals in which the cardiac branch is a mixed nerve containing parasympathetic and sympathetic fibers, he also found that vagus stimulation on occasion produced an accelerating substance, Acceleransstoff (1996, 1997).

Walter Bradford Cannon (US) and Joseph E. Uridil (US) independently made the same discovery (515). These works strongly supported the concept of chemical neurotransmission. See, du Bois-Reymond, 1877.

Otto Loewi (DE-US) and Ernst Navratil (DE) decided that vagusstoff is acetylcholine (1998, 1999).

Anton W. Kibjakow (RU) developed a method, which demonstrated that Otto Loewi’s Vagusstoff and acetylcholine are identical (1747).

Wilhelm Sigmund Feldberg (DE-GB) and John Henry Gaddum (GB) confirmed his results (1070).

Ross Granville Harrison (US) solved one of the most difficult problems in embryology, the origin of bilateral symmetry, which is a basic morphological attribute of vertebrates (1422).

Hans Spemann (DE) and Hilda Proescholdt Mangold (DE) removed the dorsal lip from one embryo and grafted it onto another embryo. The dorsal lip cells removed from the donor embryo and grafted into a host embryo, if they are able to invaginate, form a nerve tube, which is produced from the overlying presumptive ectoderm of the host. The results indicated that the presumptive neural plate cells of the early gastrula do not possess an inherent capacity to form neural tissue. Instead, the presumptive neural plate cells become determined as a result of stimulation by the presumptive notochordal cells of the archenteron roof. The notochord, therefore, although of transitory importance as a skeletal element, is part of the basic organization of the vertebrate embryo. It is present in all vertebrates because it is necessary if the embryo is to get past the gastrula stage. This is an example of why some structures must be recapitulated during embryonic development. The notochord while not necessary as a skeletal support is necessary as an organizer. 

Out of this and other work grew the hypothesis that one part of an embryo, the organizer, can influence (induce) the differentiation of another part, the reacting tissue (2965-2967). Mangold died in a house fire shortly after this work; she was 26 years old.

Johannes Friedrich Karl Holtfreter (DE-US) further established the distinction between self-differentiating and induced organs when he treated the gastrula of the axolotl with chemical solutions which did not interfere with cell proliferation but which prevented the normal invagination of blastomeres. The organizer was thus kept distant from the overlying ectoderm and the nerve tube failed to develop (1562). The organizer came to be called, the evocator.

Vivian F. Irish (US), William M. Gelbart (US), F. Michael Hoffmann (US) and Walter Goodman (US) found that the decapentaplegic (dpp) gene is required for dorsal-ventral patterning of the Drosophila embryo. It favors dorsalization (1546, 1620).

Horst Grunz (DE) and Lothar Tacke (DE) found in Xenopus laevis that the absence, not the presence, of an intercellular signal is necessary for neural differentiation. Neural fate might indeed be the 'default' fate of ectodermal cells (1332).

William C. Smith (US) and Richard M. Harland (US) developed an assay to identify m-RNAs that coded for proteins that could induce a neural plate in ventralized Xenopus embryos. They generated and systematically screened a library of m-RNAs derived from hyperdorsalized gastrula-stage embryos. They isolated noggin, a novel m-RNA that could not only induce a neural plate (and complete dorso–ventral axis) without requiring the presence of mesoderm, but also was expressed appropriately in the dorsal lip and in the notochord (2944).

Edwin L. Ferguson (US) and Kathryn V. Anderson (US) found that the short gastrulation gene (sog) product normally blocks dpp activity ventrally helping to establish a dorsal-ventral axis in the embryo, i.e., it favors ventralization (1077).

Ali Hemmati-Brivanlou (US) and Douglas A. Melton (US) reported that inhibition of the activin II receptor could, by itself, induce neural differentiation in the absence of the notochord (1465).

Yoshiki Sasai (JP), Bin Lu (US), Herbert Steinbeisser (DE), Douglas Geissert (US), Linda K. Gont (US), and Edward Michael de Robertis (US) found that in Xenopus the chordin molecule is a potent dorsalizing factor that is expressed at the right time and in the right place to regulate cell-cell interactions in the organizing centers of head, trunk, and tail development (2776).

Yoshiki Sasai (US), Bin Lu (US), Herbert Steinbeisser (DE), Stefano Piccolo (IT), and Edward Michael de Robertis (US) identified chordin, another new dorsal lip protein that could directly induce a neuraxis. They also showed that bone morphogenetic protein-4 (BMP-4) a growth factor related to activin, inhibited the neuralizing activity of both chordin and noggin in Xenopus embryos. The same group soon found that chordin directly binds and inactivates BMP4, and Harland and colleagues reported a similar function for noggin (2533, 2775).

The genetic text of decapentaplegic reads very much like that of BMP4 while that of short gastrulation reads like chordin. It would appear that arthropods and vertebrates are upside-down versions of each other. Some time in the distant past here was a common ancestor from which one line of descendants started walking on their stomachs and the other line started walking on their backs.

Lyle B. Zimmerman (US), José M. De Jesus-Escobar (US), and Richard M. Harland (US) reported that in amphibians neural induction and mesoderm dorsalization are antagonized by bone morphogenetic proteins (BMPs), which induce epidermis and ventral mesoderm instead (3618).

Andrea Streit (US), Alyson J. Berliner (US), Costis Papanayotou (US), Andrés Sirulnik (US), Claudio D. Stern (US), Hiroki Kuroda (US), Oliver Wessely (US), and Edward Michael de Robertis (US) reported that the neural ectoderm is specified in the blastula, before the Spemann organizer even forms. Fibroblast growth factor (FGF) signaling is required at this stage to enable later neural differentiation. In Xenopus at least, the anterior — but not the posterior — neural ectoderm is specified at the blastula stage, through a mechanism that already involves noggin and chordin (1852, 3037).

J. Harold Austin (US), Edgar Stillman (US), and Donald Dexter van Slyke (US) showed that when the urine volume is above a certain limit, there is a direct ratio between the blood urea content and the urea excretion rate. They called this the augmentation limit (115).

John Belling (US) was the first person to apply the chromosome squash technique to both plant and animal tissues. Belling improved the method for making chromosomal preparations and staining them with his iron acetocarmine stain (267-269).

John H. Gerould (US) may have been the first to report an example of the selective elimination of a mutant gene (autosomal recessive) from a population by a predator (1240). 

Calvin Blackman Bridges (US) presented evidence that sex determination in Drosophila melanogaster is the result of interactions between genes in the X chromosomes and those in the autosomes. The autosomal genes have a net male-forming tendency and the X chromosomes a net female-forming tendency (423, 425, 427).

Jules Jean Baptiste Vincent Bordet (BE) and Gheorghe Ciuca (RO) gave one of the first descriptions of what they called lysogenic behavior in bacteria. The lysogenic bacteria released something (bacteriophage) that gave rise to lysis of sensitive bacteria (360). The true nature of this phenomenon was not appreciated for many years.

Hermann Joseph Muller, Jr. (US), in a famous bit of logic, deduced that d´Herelle substances (bacteriophages) behave like genes. “That two distinct kinds of substances—the d´Hérelle substances and the genes—should both possess this remarkable property of heritable variation or mutability, each working by a totally different mechanism, is quite conceivable…yet it would seem a curious coincidence indeed. It would open up the possibility of two totally different kinds of life, working by different mechanisms. On the other hand, if these d´Hérelle bodies were really genes, fundamentally like our chromosome genes, they would give us an utterly new angle from which to attack the gene problem. They are filterable, to some extent insoluble, can be handled in test tubes, and their properties, as shown by their effect on bacteria, can then be studied after treatment. It would be very rash to call these bodies genes, and yet at present we must confess that there is no distinction between the genes and them. Hence we cannot categorically deny that perhaps we may be able to grind genes in a mortar and cook them in a beaker after all. Must we geneticists become bacteriologists, physiological chemists, simultaneously with being zoologists and botanists? Let us hope so.” In this remarkably prescient analysis, Muller lays out the paradoxical nature of the genetic material. It is apparently both autocatalytic (i.e., directs its own synthesis) and heterocatalytic (i.e., directs the synthesis of other molecules), yet only the heterocatalytic function seems subject to mutation. With this, he defines the key problems that must be solved for a successful chemical model of the gene (2281, 2282).

Hermann Joseph Muller, Jr. (US), Benjamin Minge Duggar (US), and Joanne Karrer Armstrong (US) suggested that there are many analogies between viruses, and genes that have broken loose from their moorings (912, 2031, 2282).

Ivan C. Jagger (US) demonstrated that the green peach aphid, Myzus persicae Sulz., acts as a vector for lettuce mosaic virus (1646).

Joseph Arthur Arkwright (GB) described the development and persistence of rough and smooth bacterial colony types. He coined the terms smooth and rough to describe the forms of the colonies produced by the intestinal group of microorganisms, and the application of these terms to the colony forms of other species (Arkwright 1921).

Paul Henry de Kruif (US) analyzed the changes in virulence in the bacillus of rabbit septicemia (Streptococcus) and observed that the colony morphologies on agar plates (smooth and rough) correlated with the pathogenicity in animals. He also showed that a “pure” culture of virulent organisms (smooth) could give rise to avirulent variants (rough). De Kruif’s experiments were the first to explain this phenomenon, called microbic dissociation, within the framework of genetic mutation in bacteria (792).

Reuben Ottenberg (US) established the medico-legal application of human blood grouping (2429, 2430).

Hans Zinsser (US) was the first to formulate clearly the distinction between the tuberculin type of allergic reaction and classic anaphylactic shock (3619).

Otto Carl Prausnitz (DE-GB) and Heinz Küstner (DE) demonstrated that hypersensitivity (allergy) to a food (cooked fish) could be passively transferred to a healthy nonallergic human by intradermal injection of serum from the allergic person (2561, 2562). Food sensitivity, hay fever, asthma, and allergy to animal dander naturally occur in only some 10 percent of humans. Other individuals cannot acquire these disorders, which are categorized under atopy (strangeness).

Arthur F. Coca (US) and Ella F. Grove (US) were the first to refer to the antibodies of these allergies as atopic reagins (625). These atopic reagins were later classified as immunoglobulin class E (IgE). Skin tests using patch application, scratching in, or intradermal injections of sets of antigens (allergens) are called P-K tests to commemorate Prausnitz and Küstner. 

Jacques Forestier (FR) and Jean Athanse Sicard (FR) introduced positive contrast myelography with iodized oil (lipiodol). They x-rayed the spinal canal then shortly thereafter the bronchial tree (1152, 1153). This technique is currently used to diagnose ruptured intravertebral disks, nerve root compression or when posterior fossa neural structures are suspected.

Hermann Rorschach (CH) developed the Ink Blot Test for use in psychodiagnosis (2675, 2676).

Charles Haskell Danforth (US) was the first to demonstrate that the presence of hair on the middle phalanx (mid-digital hair) of man is genetically determined, the presence of hair being dominant (766).

John Newport Langley (GB) described the autonomic nervous system. He described three parts to this system: the sympathetic (fight or flight), the parasympathetic (eat and sleep) and the enteric (second brain) (1896). The chemical modulator for the sympathetic NS is norepinephrine (noradrenaline). The chemical modulator for the parasympathetic NS is acetylcholine (ACh). The chemical modulator of the enteric NS (ENS) is primarily serotonin (5-HT) and secondarily substance P.

Frederic Bremer (BE) and Percival Bailey (US) found that without touching the pituitary, puncture of the hypothalamic infundibulum provoked adiposogenital dystrophy and diabetes insipidus, and they attributed this result to disturbance of hypothalamic innervations of the pituitary (147).

Claude Regaud (FR) and Alexander Schmincke (DE) were the first to describe nasopharyngeal carcinoma (NPC) as a separate entity. This is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx (2603, 2838).

James Ewing (US) described a tumor that was referred to as diffuse endothelioma of bone (1054). This tumor was later renamed Ewing sarcoma. ES is a primary malignant bone lesion usually seen in the diaphysis of long bones and in the flat bones of young patients, in the age group of five to 20 years. Characteristically the patient is ill, with low-grade fever, moderate leucocytosis and anemia. Metastases may occur to lungs and to other bones. The prognosis is poor.

James Taylor Gwathmey (US) and James Greenough (US) introduced synergistic anesthesia (1350).

Alois Alzheimer (DE) together with Franz Nissl (DE) established the pathologic anatomy of mental illness (57).

Ralph M. Waters (US) introduced a resuscitation technique, which today goes by the name of cardiopulmonary resuscitation (CPR) (3384).

Carl Gustav Jung (CH) developed the concept of the autonomous and unconscious complex and the technique of free association. Jung explained human behavior as a combination of four psychic functions: thinking, feeling, intuition and sensation. He coined the term "synchronicity," the coincidence of causally unrelated items having identical or similar meanings. He used this as an explanation for extrasensory events traditionally thought to be occult (1702).

Marc Armand Ruffer (GB) studied the anatomy of Egyptian mummies and concluded that one of the most prevalent diseases of ancient Egypt was osteo-arthritis. His examination of the internal organs found that arteriosclerosis with calcification was also common (2722).

Arthur Smith Woodward (GB) described a skull from the Broken Hill Mine, Kabwe, Zambia and named it Homo rhodesiensis: Homo sapiens rhodesiensis (3571). It is dated at late Middle Pleistocene, circa 300,000 B.P.

Lead arsenate spray was developed and recommended for control of apple maggot. The value of arsenic as a mosquito larvicide was first noted (2879).


“Besides the ordinary proteins, carbohydrates, lipoids, and extractives, of their several types, there are present within the cell thousands of distinct substances—the ‘genes’; these genes exist as ultramicroscopic particles.” Hermann Joseph Muller, Jr. (2282).

Francis William Aston (GB) was awarded the Nobel Prize in Chemistry for his discovery, by means of his mass spectrograph, of isotopes in a large number of non-radioactive elements and for his enunciation of the whole-number rule.

Archibald Vivian Hill (GB), for his discovery relating to the production of heat in the muscle, and Otto Fritz Meyerhof (DE-US), for his discovery of the fixed relationship between the consumption of oxygen and the metabolism of lactic acid in the muscle, shared the Nobel Prize in physiology and medicine.

Friedrich Dessauer (DE), Marietta Blau (DE), and Kamillo Altenburger (DE) postulated the hit theory of radiobiology. According to this view, the shape of the dose-effect curve following exposure of a homogeneous population to ionizing radiation is due to the fact that absorption of radiation is not continuous but a quantized process, which follows the statistical principle, that bears the name of Poisson. The effect occurs when a minimal number of absorption events (called hits) have happened to an individual (333, 820).

John Augustus Larson (CA) and Leonard Keeler (US) developed the polygraph (the lie detector) (1900).

John Howard Mueller (US) discovered the amino acid methionine while working on nutritional requirements of some streptococci (2275).

John Howard Mueller (US) described the properties of a pure sample of methionine (2276, 2277).

George Barger (GB) and Frederick Philip Coyne (GB) determined the structure of methionine (180).

Richard Martin Willstätter (DE), Johanna Graser (DE), and Richard Kuhn (DE) described the existence of a prosthetic group combined with a larger carrier molecule to form an enzyme (3502).

Donald Dexter van Slyke (US) put the concept of buffer value of weak electrolytes on a mathematically exact basis (3203).

William Jacob Robbins (US) and Walter Kotte (DE) succeeded in culturing plant roots by starting with tissue that was already meristematic as an explant source. Kotte worked with excised root tips such as pea and maize placing these in a variety of nutrients which contained the salts of Knop's solution, glucose and several nitrogen compounds such as asparagine, alanine and meat extract. Kotte obtained growth of root tips for periods of up to 2 weeks but he did not subculture. Robbins on the other hand maintained maize roots in vitro for longer periods by subculturing but with time the growth of the cultures decreased and the cultures were lost. Robbins used yeast extract in his cultures (1827, 2662).

Lewis Knudson (US) accomplished the asymbiotic germination of orchid seeds (1782).

Lewis Knudson (US) accomplished the symbiotic germination of orchid seeds (1783).

Herbert McLean Evans (US) and Katherine Scott Bishop (US) found that rats raised on certain diets became totally sterile over a period of two generations. Fertility could be reinstated by the administration of certain foods (1044). They demonstrated that the substance X was not any known nutrient (1045). Barnett Sure (US) came to the same conclusion and named substance X vitamin E (3053).

Frank Charles Mann (US) and Thomas B. Magath (US) found that dogs lose consciousness after removal of the liver because of rapid depletion of glucose from the blood. Consciousness was regained following administration of glucose (2078, 2079).

Frederick Grant Banting (CA), Charles Herbert Best (US-CA), James Bartram Collip (CA), John James Richard Macleod (GB), and Edward Clark Noble (CA) discovered that injection of insulin might cause similar hypoglycaemic coma in rabbits (169). The obvious conclusion was that glucose is an essential nutrient for the brain.

Alexander Fleming (GB) reported the occurrence of a bacteriolytic principle in egg white, tears, and other animal fluids. He named this principle lysozyme (1131).

L.K. Wolff (DE) precipitated and purified lysozyme from egg white (3565).

Karl Meyer (US), Richard Thompson (US), John W. Palmar (US), and Devorah Khorazo (US) showed that lysozyme is a protein giving some of the typical reactions noted by Fleming and Meyer's group above (2187). 

Edward Penley Abraham (GB) and Robert Robinson (GB) crystallized lysozyme (12).

W. Charles Dorner (CH) published his method for staining bacterial endospores (874, 875).

Reuben Leon Kahn (US) developed a simple quantitative precipitation test for syphilis. He found that by adjusting the temperature, salt concentration, and serum dilution used in his test, the reaction could indicate the presence of the agents of tuberculosis, malaria, or leprosy in the blood sample. He therefore called it the universal serological reaction (1703-1706).

Albert Francis Blakeslee (US), John Belling (US), and Marshall E. Farnham (US) analyzed all the 12 possible trisomic aneuploids possible in the Jimson weed (Datura stramonium) with variation in seed capsules being the most obvious phenotypic expression (329-332).

William Porter MacArthur (GB) was the first to recognize a ciliate pathogenic for an insect. He found Glaucoma pyriformis parasitizing living and dead larvae of the mosquito Culiseta annulata Schrank=Theobaldia annulata Schrank (2037).

Karl Albert Ludwig Aschoff (DE) coined the phrase reticuloendothelial system (RES) to include phagocytic cells in diverse tissues active in the defense of the body. He excluded lymphocytes (98, 99).

Albert H. Ebeling (US) and Alexis Carrel (FR-US) showed that eukaryotic cells can grow for long periods in culture provided they are fed regularly under aseptic conditions. They kept a piece of embryonic chicken heart alive and growing (it had to be periodically trimmed) for over thirty-four years—much longer than the life span of a chicken—before it was deliberately terminated (936).

Herbert Spencer Gasser (US) and Joseph Erlanger (US) published the first paper in which nerve potentials were recorded with the oscillograph (1227). This paper had a profound effect on the study of nerve physiology.

Norbert Oscar Jean Goormaghtigh (BE) demonstrated that the zona fasciculata of the adrenal cortex is a source of corticosteroids while the medulla is adrenergic (1287).

Theophilus Shickel Painter (US) examined the spermatogenesis of the opossum (Didelphys virginiana) and became the first to elucidate sex determination in a marsupial. He found that it is of the XX/XY type with the male producing sperm, which carry either the X or the Y chromosome (2448).

Theophilus Shickel Painter (US) was the first to provide evidence that sex in humans is associated with an X, Y system. He pointed out that humans contain one pair of chromosomes which do not completely pair with one another and that segregate at the first maturation division, the X going to one pole and the Y to the other. He concluded (erroneously) that females are 48 XX, and males 48 XY (2449). Painter went on to examine the sex determination mode and chromosome number in many other marsupial and placental mammals, finding that all exhibit the XX/XY mode.

Ernest Gustav Anderson (US), Calvin Blackman Bridges (US) and Lilian Vaughan Morgan (US) determined that with regard to genetic recombination: (1) exchange occurs pair-wise among the four homologs. (2) Each pair of alleles segregates in a ratio of 2:2 among the four meiotic products, regardless of the number or distribution of exchanges. That is, recombination is reciprocal. (3) All four homologs of a tetrad may recombine (66, 428, 2247, 2248).

Frederick Grant Banting (CA), Charles Herbert Best (US-CA), and John James Richard McLeod (GB) isolated insulin from the Islets of Langerhans in the pancreas of dogs and went on to prove that the purified insulin can restore a diabetic dog to normal (166).

Frederick Grant Banting (CA), Charles Herbert Best (US-CA), James Bertram Collip (CA), Walter R. Campbell (CA), Almon A. Fletcher (CA), John James Richard McLeod (GB), and Edward Clark Noble (CA) successfully treated seven cases of diabetes mellitus in humans by giving subcutaneous injections of insulin. Walter R. Campbell and Almon A. Fletcher supervised the experiment (167, 168).

Theobald Smith (US) and Ralph Bulkley Little (US) demonstrated that the mother’s colostrum provides new borne calves with immunity to infectious diarrhea. They attributed the specific role of colostrum to be the transfer of immune bodies to the calves (2939).

Gerald H. Stott (US), D. B. Marx (US), B. E. Menefee (US), and G. T. Nightengale (US) found that in calves as the interval following birth to the start of colostrum consumption increases, the ability to absorb colostral immunoglobulins decreases. Calves fed colostrum after birth had a closure time for IgG absorption at 21 hours, IgM 23 hours and IgA 23 hours. Calves not ingesting colostrum by 12 hours of age are subject to gut closure before any Ig absorption takes place (3032-3034). 

Donald Baker Parrish (US), George H. Wise (US), Floyd W. Atkeson (US), and Josiah S. Hughes (US) showed that colostrum transfers large amounts of vitamin A (retinol) to the new borne calf (2473).

Lewis Lunsford, Jr. (US), Harold F. Deutsch (US), and Folke Nordbring (SE) established that human milk whey contains material that reacts with anti-gamma globulin (2026, 2376). Later other investigators would find IgA, IgG, and IgM in precolostrum, colostrum, and mature milk.

Edgar V. Allen (US) presented a detailed description of the cellular changes in primary and secondary sex organs over the course of a complete reproductive cycle in a female mouse (49).

Gaston Ramon (FR) observed the formation of a precipitation within a diphteric mixture of toxin and its antitoxin. He noticed that this flocculation becomes all the more intense as the mixture of toxin and antitoxin approach mutual saturation. This observation was used as a basis for the method of “proportioning per flocculation” which made it possible to titrate in vitro the diphteric antitoxin that, before, could be done only by the test in vivo, on experimental animals (2580).

Verne R. Mason (US), William Hay Taliaferro (US) and John Huck (US), from a study of sickling of human erythrocytes in several black families, erroneously concluded that the phenomenon is inherited as a single, Mendelian dominant gene (S) (2110, 3071). Other workers would later show that the trait exhibits an intermediate type inheritance.

Virgil P. Sydenstricker (US), William A. Mulherin (US), and Robert Wright Houseal (US) published the first case report of sickle cell anemia with autopsy findings (3061).

Thomas Milton Rivers (US) discovered the parainfluenzae bacillus (Haemophilus parainfluenzae) (2658).

Arthur Davies (GB) studied the intestinal contents of soldiers with dysentery during World War I. He discovered that stools from men with bacillary dysentery who had reported sick 24-36 hours earlier, contained specific agglutinins to Shigella dysenteriae, whereas such antibodies did not appear in the serum until several days later. He felt this was evidence that fecal antibodies were produced locally by the inflamed bowl wall, rather than being derived from the blood (780). Many other investigators later confirmed his conclusion.

Arthur N. Donaldson (US) studied the signs and symptoms in five otherwise healthy men who agreed to resist the desire to defecate during a ninety-hour period. During this time course they were placed on a liberal lacto-ovo-vegetarian diet. They experienced coated tongue, foul breath, impaired appetite, gas discomfort, mental sluggishness (increased reaction time for sight, touch, and hearing), reduced attention span, depression, restlessness, irritability, failure to be refreshed by sleep, a sense of heaviness in the pelvis, a dull toxic headache, an increase in basal metabolic rate, elevated blood sugar, a more rapid onset of fatigue, and general malaise. Within one hour of having a bowel movement all were completely normal again. Donaldson then packed the rectums of four of his subjects, using cotton pledgets saturated with petroleum and dusted with barium sulfate. This was done two days following the constipation experiment. Within three hours during which the rectal packing was retained there was a recurrence of the signs and symptoms previously recited. Donaldson concluded that the results indicated that the signs and symptoms were not the result of the absorption of toxins (866).

Walter C. Alvarez (US) concluded from his investigations of gastroenterological problems that the signs and symptoms attendant to constipation result from mechanical distention and irritation of the lower bowel by fecal masses. They are the result of alteration of the physiological activity of other organs and tissues brought about by the stimulation of sensory nerves in the distended, overreacting bowel (54).

Ernest Marcel Labbé (FR), Jules Tinel (FR) and E. Doumer (FR) first described the anatomical (adrenal medullary tumor) and clinical (paroxysmal hypertension) features of pheochromocytoma or phaeochromocytoma (PCC) (1858).

M. Fernand Widal (FR), Pierre Abrami (FR), and Jacques Lermoyez (FR) were the first to describe the aspirin triad syndrome characterized by the triad of bronchial asthma, vasomotor rhinitis, with or without nasal polyps, and intolerance to aspirin and aspirin-like medications (3461).

Herbert Planner (DE) and Franz Remenovsky (DE) described a recurrent systemic disease characterized by uveitis with hypopyon, recurrent ulceration of the mucous membranes of the mouth and pharynx, and ulceration of the genitalia. It became known as Bechet's syndrome in honor of Hulusi Bechet (TR) who later described it and first recommended that this triad be considered an entity (244).

Rudolf Schindler (DE) was using a gastroscope for interpreting pictures of disease conditions, which formerly could not be diagnosed at all, e.g. different forms of chronic gastritis and ventricular polyposis (2823).

Rudolf Schindler (DE) introduced the semi-rigid endoscope (2824). 

Remington Kellogg (US) wrote Pinnipeds from Miocene and Pleistocene Deposits of California which remains the base upon which modern research on fossil pinnipeds begins (1732).

Shimesu Koino (JP) determined the life cycle of Ascaris lumbricoides in humans, including the migration of the larval stages around the body. He infected both a volunteer and himself and realized what was happening when he found large numbers of larvae in his sputum (1804).

Curt Paul Richter (US) devised ways to measure the spontaneous activity of rats. He described how running behavior varied during the day and night and also discovered gender differences in the expression of this behavior, e.g. the ovarian cycle influences the female rat’s running activity (2634). In association with his behavioral studies Richter invented the Richter tube for measuring fluid intake, the running wheel for measuring activity rhythms, and new ways to measure sweating, salivation, and nest building.

Nicotine became available commercially as an insecticide for control of cotton aphids. Bordeaux mixture was first suggested as a control for leafhoppers. Rotenone-bearing insecticides were reported effective for control of cattle grub and cattle louse. Mexican bean beetle control by use of calcium arsenate was reported. Magnesium arsenate was developed for control of Mexican bean beetle. Calcium cyanide dust was first suggested as an insecticidal fumigant (2879).

The Journal of Biochemistry was founded.


“The edifice of science is akin to a cathedral built by the efforts of a few architects and many workers.” Gilbert Newton Lewis and Merle Randall (1948).

"Whether or not it is true that the proper study of mankind is man, it is certain that he finds great difficulty in studying anything else." John William Navin Sullivan (3050).

“Be kind and tender to the Frog,

And do not call him names,

As ‘Slimy skin’, or ‘Poly-wog’,

Or likewise ‘Ugly James’,

Or ‘Gape-agrin’, or ‘Toad-gone-wrong’,

Or ‘Billy Bandy-knees’:

The Frog is justly sensitive

To epithets like these.

No animal will more repay

A treatment kind and fair;

At least so lonely people say

Who keep a Frog (and, by the way,

They are extremely rare).” Joseph Hilaire Pierre Belloc (271).

Fritz Pregl (AT) was awarded the Nobel Prize in Chemistry for developing techniques and equipment, which laid the foundation of microchemistry.

Frederick Grant Banting (CA) and John James Richard Macleod (GB) were awarded the Nobel Prize in Physiology or Medicine for their discovery of insulin.

Johannes Nicolaus Brønsted (DK) and Thomas Martin Lowry (GB) independently suggested a slightly broader definition of acids and bases. In their definitions: acid = any compound that donates a proton, base = any compound that accepts a proton. One particularly important feature of their definitions is the recognition that the anion of a weak acid acts as a base when it accepts a proton from water, and the cation of a weak base (such as ammonium) acts as an acid when it transfers a proton back to water. They called these ions conjugate acids and bases (441, 2016).

The oxidation-reduction potential was standardized as “… the normal hydrogen electrode. This is defined as a platinized platinum electrode held under one atmosphere of hydrogen and immersed in a solution normal with respect to the hydrogen ions. The potential difference at such an electrode is assigned the arbitrary value of zero” (593).

Peter Joseph William Debye (DE) and Erich Hückel (DE) described the behavior of an ion in relation to its charge, radius, other ions in solution, and the dielectric properties of the medium (805).

Sodium chlorate was introduced in France as a soil sterilant and herbicide. Ref 

Robert Joachim Feulgen (DE) and Heinrich Rossenbeck (DE) introduced a test in which a pine shaving impregnated with a solution of hydrolyzed nucleic acid was exposed to moist hydrogen chloride vapor. With thymus nucleic acid, a green color appeared; in the presence of ammonia, the pine splinter turned red. These reactions were not given by the nucleic acids from yeast or wheat germ, known to contain ribose units, and provided the basis for a distinction between ribonucleic acids and desoxyribonucleic acids (1089, 1090).

Feulgen demonstrated the presence of DNA in plant nuclei thus disposing of the belief that DNA was found only in cell nuclei of animal cells (1089).

C.P. Kimball (US) and John R. Murlin (US) noted that pancreatic extracts contained a hyperglycemic factor, which they named glucagon (1749).

Earl W. Sutherland (US) and Christian Rene de Duve (GB-BE-US) showed that glucagon is made by no other tissue than the pancreas except the gastric mucosa and certain other parts of the digestive tract. They obtained evidence suggesting that pancreatic glucagon is probably a hormone made in the endocrine islets by cells different from the insulin-producing beta cells; presumably the alpha cells (3054).

Charles A. Vuylsteke (BE), G. Cornelis (BE), and Christian Rene de Duve (GB-BE-US) found compelling evidence that the pancreatic islet alpha cells produce glucagon in significant quantities (3338, 3339).

Alfred Staub (US), Leroy Sinn (US), and Otto K. Behrens (US) purified then crystallized glucagon (2981).

William W. Bromer (US), Leroy Sinn (US), Alfred Staub (US), and Otto K. Behrens (US) determined the amino acid sequence of porcine glucagon (440).

Lawrence E. Mallette (US), John H. Exton (US), Charles R. Park (US), Dennis J. Mackrell (US), and Joseph E. Sokal (US) were the first to demonstrate the biological antagonisms of insulin and glucagon (2053, 2077).

Roger Harold Unger (US) postulated that this antagonism underlies the concept that the relative concentrations of these two polypeptides perfusing their common target organ at any one moment determine the magnitude and direction of the metabolic response (3177). 

Roger Harold Unger (US), Akira Ohneda (JP), Eugenio Aguilar-Parada (MX), and Anna M. Eisentraut (US) found that following a release of insulin the extracellular glucose concentrations are kept relatively constant by a coupled release of glucagon to stimulate hepatic glucose release (3178).

Otto Heinrich Warburg (DE) and Erwin Paul Negelein (DE) reported the first measurements on the quantum efficiency of photosynthesis. This work led to the conclusion that four quanta are needed to produce one molecule of oxygen (3368).

Hans Christian Hagedorn (DE) and B. Norman Jensen (DE) developed a method for determining blood sugar in small volumes of blood (1362).

Hugh McGuigan (US) and Hans Paul Kaufmann (DE) reported the antibacterial activity of furan compounds, specifically furfural and furoic acids (1721, 2149). This led eventually to the production of the nitrofurans, which are antimicrobials, used to treat urinary tract infections.

George Charles de Hevesy; Georg Charles von Hevesy (HU-DE-SE-DE) was able to follow the absorption of lead in great detail by watering plants with a radioactive isotope of lead. The principle of isotope tracers was thus established (791).

Torsten Ludvig Thunberg (SE) was the first to hypothesize that photosynthesis is an oxidation-reduction (redox) reaction in which carbon dioxide is reduced and water is oxidized (3123). He also studied the oxidative degradation of foodstuffs in animals.

René Wurmser (FR) also advanced the concept of photosynthesis as a redox reaction (3585, 3586).

Albert Joyce Riker (US) discovered that Agrobacterium tumefaciens invades and multiplies within host cells on its way to causing crown gall disease (2643, 2644).

Joseph Barcroft (GB), Jonathan C. Meakins (GB), Harold Whitridge Davies (GB), James Matthews Duncan Scott (GB), and W.J. Duncan Fetter (GB) demonstrated that the body alters its blood volume as part of its temperature regulating mechanism (178).

Hugo Fricke (US) measured the electrical capacitance of the surface membrane of erythrocytes, using a high-frequency alternating current bridge (1187, 1188).

James Cecil Mottram (GB) and W. Cramer (GB) published the first known report concerning the male antifertility factor of gonadal origin, which D. Roy McCullagh (US) later named inhibin (2143, 2272).

Milislav L. Demerec (Yugoslavian-US) working with maize seed stocks, which were segregating white and normal seedlings, demonstrated 15:1 ratio segregations in two stocks and later obtained two pedigrees, which segregated in 63:1 ratios. The former condition indicates that two factors act as duplicate genes producing white seedlings in the double recessive only, while in the latter case, possibly three duplicate genes are present (815).

Robert Robison (GB) found that ossifying cartilage contains a “bone phosphatase” which promotes the deposition of calcium phosphate (2666). 

Honor Bridget Fell (GB) and Robert Robison (GB) found that phosphatase is synthesized by cartilage, by the hypertrophic cells found in the preliminary stage of ossification. They showed that the developing osteoid tissue and hypertrophic cartilage cannot at once acquire the complete calcifying mechanism but that this mechanism is gradually developed during the course of tissue differentiation (1071-1073).

Donald Dexter van Slyke (US), Bishop C. Hsien Wu (US), and Franklin C. McLean (US) developed equations to predict the change in distribution of water and diffusible ions between blood plasma and blood cells when there is a change in pH of the oxygenated blood (3211).

George Washington Corner (US) recovered from a Macacus rhesus (monkey), autopsied on the 14th day of the menstrual cycle, an ovum in the oviduct, en route from the ruptured ovarian follicle to the uterus. This was the first such finding in a primate and confirmed the monkey’s time of ovulation. He also discovered the phenomenon of anovulatory menstruation seen in young female monkeys and humans (656, 657).

Alfred Henry Sturtevant (US) and Thomas Hunt Morgan (US) proposed that the same genetic material may have different effects on the phenotype when its position is altered, the position effect (3044).

Alfred Henry Sturtevant (US) worked out the phenomenon of unequal crossing over at the Bar locus in Drosophila, a position effect (3046).

Barbara McClintock (US) proposed that the striking color variations in the leaves and kernels of Indian corn (Zea mays), is caused by the movement of controlling elements from one chromosomal location to another. This theory contradicted the paradigm that genes are immutably fixed along the length of chromosomes. Transposition is now accepted as a major way in which genes are activated and expressed during development. McClintock also suggested that induction of gene instability by transposable elements may provide a mechanism to reorganize the genome rapidly in response to stress and thus may play an important role in generating diversity (2127-2134). This was actually the discovery of what would later be called transposable elements or transposons or jumping genes.

Edward B. Lewis US) reported that transposition of heterochromatin or other chromosomal elements could inhibit the action of nearby genes (1946).

Charles Haskell Danforth (US) presented his method of estimates of mutation rates for dominants. This is the first paper to point out the possibility of using the principle of equilibrium in calculating human mutation rates (767).

Arthur Edwin Boycott (GB) and Cyril Diver (GB) described “delayed” Mendelian inheritance controlling the direction of the coiling of the shell in the snail Limnea peregra (391).

Alfred Henry Sturtevant (US) suggests that the character of the ooplasm, which is in turn controlled by the mother’s genotype, determines the direction of coiling (3045).

Gershom Franklin White (US) first described hornworm septicemia in the larvae of two species of insects, Protoparce sexta Johan. (tobacco hornworm) and Protoparce quinquemaculata Haw. (tomato hornworm) (3450).

Lemuel Roscoe Cleveland (US) discovered the symbiotic relationship between intestinal flagellates and termites. This was the first instance in which a mutualistic relationship between internal microorganisms and their metazoan host was clearly proved (608-616).

Lemuel Roscoe Cleveland (US), S.R. Hall (US), Elizabeth P. Saunders (US), and Jane Collier (US) established that the wood roach, Crypotocercus punctulatus, like the termite, depends on its intestinal flagellates for the ability to utilize cellulose as its principal food (617, 618). Cleveland is commemorated by Clevelandina reticulitermitidis, a large wood eating spirochete symbiotic in the gut of cockroaches and termites.

Leonid Abgarovich Orbeli (RU) and Alexandr Grigorievich Ginetsinki (RU) observed that when the lumbar sympathetic nerve is stimulated in the frog, the force of the fatigued skeletal muscle contracting due to electrical stimulation recovered from the weakened tension, but not fully; the anti-fatigue effect of sympathetic nerves (1246, 2404, 2405).

Alexander Thomas Glenny (GB), Barbara E. Hopkins (GB), and Gaston Ramon (FR) produced a vaccine to diphtheria, which consisted of a chemically modified (formalin-treated) toxin, known as a toxoid. It is safer than the toxin-antitoxin mixture and is the one still used today (1253, 2581, 2582). This simple and effective procedure led to the production of a number of highly successful vaccines.

George Frederick Dick (US) and Gladys Henry Dick (US) succeeded in reproducing typical scarlet fever in human volunteers by inoculation of axenic cultures of beta-hemolytic streptococci. This established that a beta-hemolytic streptococcus is the etiological agent of scarlet fever (823). They, along with Alphonse Raymond Dochez (US) and Lillian Sherman (US) discovered the erythrogenic toxin produced by these cocci (823, 825-829, 851). 

David H. Bergey (US) and Robert Earl Buchanan (US) edited the first edition of Bergey’s Manual of Determinitive Bacteriology which was published by the Society of American Bacteriologists (now the American Society for Microbiology) (285). Over the years this most famous of modern texts on bacterial classification has incorporated all significant advances as they have been made. It records the discoveries of new species, new criteria for classification, and improved schemes for classification. The current revision goes by the title, Bergey’s Manual of Systematic Bacteriology.

Marcus Eugene Jones (US) authored the monoraph Revision of North-American species of Astragalus, probably the largest genus of flowering plants in North America (1695).  

Oswald Theodore Avery (CA-US) and Michael Heidelberger (US) determined that pneumococcal capsular material is pure polysaccharide free of protein and furthermore that this capsular material is antigenic—the first evidence that animals can make antibodies to something other than protein.

Simon Marcovitch (RU-US) demonstrated that the appearance of sexual forms of the strawberry louse in late fall is regulated by photoperiod and not by temperature, as was previously believed. This may be the first time that sexuality in an animal was shown to respond to a photoperiod. He had similar findings among the Aphididae (2090, 2091).

Remington Kellogg (US) produced a paper which remained the definitive work on the squalodonts (fossil cetaceans with serrated teeth) until Karlheinz Rothausen’s (DE) paper in 1968 (1733, 2693).

Eli Kennerly Marshall, Jr. (US) and John L. Vickers (US) discovered that kidney tubules are capable of secreting substances directly into the urine. They concluded that “the problem would appear to be definitely settled, and satisfactory evidence would seem to exist that … filtration, reabsorption, and secretion all play a role in the elimination of urine” (2107). This represents the discovery of active transport. They first presented this discovery in October 1922, at a meeting of the Johns Hopkins Medical Society in a talk entitled, “Proof of Secretion of the Convoluted Tubules.” See, Overton, 1895.

Jacques Roskam (BE) described the presence of fibrinogen on the platelet surface, suggesting that the fibrinogen-fibrin transition on the platelet surface might be important (2681).

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 (3239).

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 (1842).

John Loesch (AT-HU-US) induced essential hypertension in experimental animals using renal ischemia (1992, 1993).

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 (1268). They produced severe renal ischemia with a resulting syndrome, which closely simulated the malignant phase of human essential hypertension (1266-1268).

Harry Goldblatt (US) proposed the existence of a humoral mechanism due to the release of a pressor substance by the kidney (1265). 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.

Eugene F. Poutasse (US) developed renal arteriography. He discovered that in many patients with renal hypertension removing the obstruction, grafting a new vessel or removing the part of the kidney, which the diseased artery supplied, could correct it (2560).

Heinrich Necheles (DE) used hirudin to perform hemodialyses in uremic dogs employing prepared peritoneum (Goldbeater's skin) as a membrane (2311).

Georg Haas (DE) performed the first in vivo dialyses of human blood using collodion membranes and hirudin as anticoagulant. He had very limited success (1351-1353).

Thomas J. Lumsden (GB) reported that the respiratory center within the medulla couldn’t generate an autonomous rhythmicity when cut off from efferent impulses of higher neuraxis and from afferent impulses of the vagi. Under these circumstances it exhibited sustained inspiration, which he called apneusis. He found that there are anatomically and functionally separate cell groups for the inspiratory and expiratory muscles; that the rhythm of the medullary inspiratory center is determined by another center (pneumotaxic) in the upper part of the pons (2024, 2025).

Bernardo Alberto Houssay (AR) and Juan T. Lewis (AR) determined that the cortex of the adrenal gland is indispensable to life; it maintains its vital functions without the cooperation of the medulla. The chromophil tissue of the suprarenals is not necessary to life or to normal functions (1579).

Archibald Vivian Hill (GB) and Hartley Lupton (GB) coined the phrase oxygen deficit in reference to exercise (1525).

Fritz de Quervain (CH) described a case of complete testicular feminization (796).

John McLean Morris (US), after searching the literature, clearly defined the syndrome of complete testicular feminization; the commonest form of male pseudohermaphroditism. The main clinical features are female external genitalia with underdeveloped labia and a blind-ending vagina, absence of internal female genital organs, and the presence of testes in the inguinal canal or within the abdomen. In appearance these patients present essentially normal female characteristics with average or juvenile type of breast development and normal fat deposits; however, large hands and feet are usually evident with scanty or absent axillary, pubic and vulval hair (2265). De Quervain’s syndrome

Henry Stanley Plummer (US) introduced the use of iodine in pre-operative treatment of patients suffering from hyperthyroidism (2547).

Arno Benedict Luckhardt (US) and Jay Bailey Carter (US) introduced ethylene as a gas anesthetic (2023).

Earl D. Osborne (US), Charles G. Sutherland (US), Albert J. Scholl, Jr. (US), and Leonard George Rowntree (US) introduced röntgenography of the urinary tract during excretion of sodium iodide (2411).

William Jason Mixter (US) was the first to successfully treat hydrocephalus with endoscopic third ventriculostomy (2220).

Viktor Schmieden (DE) and Franz Volhard (DE) performed the first complete pericardectomy for constrictive pericarditis (2837).

Arthur Sydney Blundell Bankart (GB) described an operation for habitual dislocation of the shoulder joint. The joint capsule is sewed to the detached labrum glenoidale, without duplication of the subscapularis tendon (157, 158). Auguste Broca (FR) and Georg Clemens von Perthes (DE) had previously described similar operations but Bankart’s was recognized to be superior.

Joseph Capgras (FR) and Jean Reboul-Lachaux (FR) presented what has come to be called Capgras syndrome. The most striking feature of this disorder is that the patient comes to regard close acquaintances, typically either his parents, children, spouse, or siblings, as “imposters,” i.e., he may claim that the person in question “looks like” or is even “identical to” his father, but really isn’t his father (517). Although frequently seen in psychotic states, more than a third of the documented cases have occurred in conjunction with traumatic brain lesions, suggesting that it can have an organic origin.

Robert Jones (GB) and Robert W. Lovett (GB) wrote Orthopaedic Surgery, probably the first book to deal systematically with the diagnosis and treatment of fresh fractures (1696).

The control of screwworm by use of benzol and pine tar oil was recommended. Geraniol was discovered as an attractant for Japanese beetles (2879).


“To come back to the question what significance might be attached to the co-enzyme common to respiration and fermentation, we may perhaps suggest that it could possibly have a share in the esterification of organic compounds with phosphoric acid. Doubtless some substances become more unstable by such combination…May I make the bold hypothesis that on the one hand the animal body makes fats and carbohydrates accessible to oxidation by combining them with phosphoric acid, whereby they become more labile, and on the other hand, that proteins can only burn in cells by being split up into amino acids?” Otto Fritz Meyerhof (2192). 

Willem Einthoven (NL) was awarded the Nobel Prize in Physiology or Medicine for his discovery of the mechanism of the electrocardiogram.

Harold Jeffreys (GB) was the first credible scientist to propose that the Earth-moon system is four billion years old, not tens of millions (1661).

Albert Jan Kluyver (NL) presented the concept of unity of biology at the molecular level and pointed out that life on earth without microbes would not be possible (1775).

Alexander Ivanovich Oparin (RU) postulated that a long chemical evolution in the oceans preceded the appearance of life on Earth (2395, 2396).

John Burdon Sanderson Haldane (GB-IN), Harold Clayton Urey (US) and John Desmond Bernal (GB) also forwarded this concept (291, 1373, 3185).

Antoine Lacassagne (FR) and Jeanne Lattès (FR) developed the first autoradiographic method to localize radioactive polonium in biological specimens (1859-1862).

Theodor Svedberg (SE), and Herman Rinde (SE), Robin Fåhraeus (SE), and James Burton Nichols (US) developed the first analytical ultracentrifuge for the purpose of forcing colloidal particles to settle out of solution. From the rate of settling, the size of the particles and even the shape could be deduced, while a mixture of two different types of particles could be separated (It was they who coined the word ultracentrifuge). They used the analytical ultracentrifuge to estimate the molecular weight of myoglobin as 17,600, hemoglobin as 67,000, and snail hemocyanin as 6,680,000 (3056-3058).

Gilbert Smithson Adair (US) used osmotic pressure in dilute solutions to very accurately determine the molecular weight of hemoglobin as 67,000 (20, 21). He reasoned that each molecule had four heme groups and four iron atoms with the iron atoms taking on oxygen sequentially rather than simultaneously. When he expressed this sequential uptake in the form of a biochemical equation, with four constants, he could generate the sigmoid curve for oxygen dissociation known to apply to hemoglobin (22).

Juda Hirsch Quastel (GB-CA) and Margaret Dampier Whetham (GB) were the first to measure the oxidation-reduction potential of a biological system and the first to study competitive inhibition of an enzyme by a structural analogue of its substrate. They studied the succinic dehydrogenase of Escherichia coli as it catalyzed the reaction: succinate + methylene blue = fumurate + leuco-methylene blue (2570, 2571).

Juda Hirsch Quastel (GB-CA) and Margaret Dampier Whetham (GB) discovered that some bacteria when centrifuged out of culture, washed with saline, and resuspended as a washed suspension of resting cells retain many of the activities of the cells in culture. The breakdown of substances by such suspensions could be studied under simple conditions in the absence of cell growth (2571).

Otto Heinrich Warburg (DE) and Tsunao Uyesugi (JP) showed that photosynthesis has two classes of reactions: light and dark reactions (3372).

Otto Heinrich Warburg (DE), Karl Posener (DE), and Erwin Negelein (DE) hypothesized that cancer, malignant growth, and tumor growth are caused by the fact that tumor cells mainly generate energy (as e.g. adenosine triphosphate /ATP) by non-oxidative breakdown of glucose (glycolysis). This is in contrast to "healthy" cells, which mainly generate energy from oxidative breakdown of pyruvate. Pyruvate is an end-product of glycolysis, and is oxidized within the mitochondria. Hence, they surmised, the driver of cancer cells should be interpreted as stemming from a lowering of mitochondrial respiration. They reported a fundamental difference between normal and cancerous cells to be the ratio of glycolysis to respiration; this observation is also known as the Warburg Effect (3371).

Donald Dexter van Slyke (US) and James Maffett Neill (US) devised a method for determining gases in blood and other solutions by vacuum extraction and manometric measurement (3210).

Einar Hammarsten (SE) was one of the first to show that DNA is a macromolecule (1392).

Ernst Ludwig Bresslau (DE) and Luigi Scremin (IT) found that mitochondria stain positively with the Feulgen stain. This strongly suggested that they contained DNA (412).

Joseph Erlanger (US) and Herbert Spencer Gasser (US) determined how different nerve fibers (cells) conducted their impulses at different rates. All else being equal, the velocity of the impulse varies directly with the thickness of fiber (1032).

John B. Hursh (US) also experimented with conduction velocity as it relates to diameter of nerve fibers (1598).

Heinrich Ewald Hering (AT) gave the first description of the afferent nerve fibers leading from the carotid sinus by way of the glossopharyngeal nerve to the brain, innervating the baroreceptors in the wall of the carotid sinus and the chemoreceptors in the carotid body. They respond to changes in blood pressure that reflexly control heart rate. An increase in pressure diminishes heart rate (1484-1486).

Jean Francois Heymans (BE), Corneille Jean-Francois Heymans (BE), Jean J. Bouckaert (BE), Lucien Dautrebande (BE) and Eric Neil (BE), experimenting with anesthetized dogs, demonstrated the existence of a set of sensory organs, known as pressoreceptors, in the wall of the carotid sinus—a slight enlargement of the carotid artery, at the point where it divides into the external and internal carotids. They showed that these receptors monitor blood pressure and help to regulate heart rate and respiration. They also found near the pressoreceptors, and at the base of the aorta, a set of chemoreceptors, the glomus caroticum and glomus aorticum, that monitor the oxygen content of the blood and help to regulate breathing through the medulla, the respiratory center at the base of the brain, i.e., the reflexogenic role of the carotid-aortic and the carotid-sinus areas in the regulation of respiration (1511-1519).

Julius H. Comroe, Jr. (US) and Carl F. Schmidt (US) demonstrated that the carotid body responds to reductions in PO2 and increases in PCO2 and does not respond to changes in oxygen concentration (640, 641). 

Helmut Kerkhof (DE) stated that one of the functions of the vomeronasal organ, or Jacobson’s organ, is chemoreception (1741).

Felix Bernstein (DE) demonstrated that it is possible to mathematically derive reliable conclusions about the transmission system of heredity from the proportions of phenotypes in a random-breeding population (295).

John Burdon Sanderson Haldane (GB-IN) presented algebraic analyses of the effects of selection (1372).

Liberty Hyde Bailey, Jr. (US) wrote The Manual of Cultivated Plants (146). The 2nd edition of 1949 runs to 1,116 pages.

Albert H. Ebeling (FR) showed that iris epithelial cells grown in vitro would cease to produce pigment when grown on rich medium only to return to pigment production when transferred to a nutritionally poor medium. This implied that the reacquisition of differentiated traits by cells, which had lost them, was mediated by a regulatory process and not by mutation (937).

Philipp Stöhr, Jr. (DE) cultivated a fragment of mesoderm from the ventral wall of an embryonic newt’s trunk, and watched it develop into a four chambered heart which began to beat rhythmically (3021). This suggested that heart-inducing potency is located in the anterior endoderm.

Johannes Friedrich Karl Holtfreter (DE-US) found that the newt gastrula is divided into future head and trunk regions, each region capable of undergoing self-differentiation even if separated from adjacent regions (1561).

William Hay Taliaferro (US), Lucy Graves Taliaferro (US), and Anna B. Fisher (US) infected rats with Trypanosoma lewisi to study the variability of the parasite during the course of the infection. They discovered that the rat produces antibodies to the parasite. They called these antibodies, ablastin (3070, 3072, 3073).

Joseph Treloar Wearn (US) and Alfred Newton Richards (US) presented experimental proof that under normal circumstances protein does not leave the blood and pass into glomerular filtrate; however, both sodium chloride and glucose pass from the blood into the glomerular filtrate only to be reabsorbed from the kidney tubule (2624, 3390). Their 1924 paper ranks as one of the greatest advances in 20th century renal physiology.

Alfred Newton Richards (US), Arthur M. Walker (US), Charles L. Hudson (US), and Thomas Findley (US) developed the technique of kidney tubule micropuncture, which they used to examine tubular content in the amphibian renal tubule. They found that the chemical composition of the fluid in Bowman’s capsule corresponds closely to that of plasma filtrate, that most of the filtered glucose is reabsorbed along the proximal tubule, that creatinine concentration increases along the proximal tubule, that the osmotic pressure of the fluid remains roughly equal to that of plasma in the proximal tubule in spite of salt and water reabsorption (indicating high tubular permeability to water), and that the permeability to water is very low in the distal tubule since the osmotic pressure of the tubular fluid drops progressively along the distal segment as a result of salt reabsorption (2625, 2626, 3351).

Arthur M. Walker (US) and Charles L. Hudson (US) showed that glucose is reabsorbed from the proximal convoluted tubule, but not from the distal convoluted tubule, in both Necturus and frogs (3350). 

Arthur M. Walker (US), Phyllis A. Bott (US), Jean Redman Oliver (US), and Muriel C. MacDowell (US) used micropuncture of mammalian kidney tubules to show that the glomerular ultrafiltrate is entirely or nearly free of protein. That approximately two-thirds of the filtered fluid is reabsorbed in the proximal convolution of the renal tubule by an isosmotic process with extensive reabsorption of glucose (3349, 3352). These were the first kidney micropuncture studies on mammals (rodents).

Hermann Braus (DE) coined the term nephron to refer to a functional unit of the kidney (409).

Richard Hesse (DE) authored Ecological Animal Geography, which provided an ecological framework for studies of animal distribution (1507).

Kilian Clarke (GB) isolated Streptococcus mutans and associated it with the initial enamel lesion leading to dental caries (594).

Harold Haydon Storey (GB) discovered the cause of mealie variegation to be a virus (3029, 3031). He named it maize streak virus (MSV). The virus is obligately transmitted by the leafhopper Cicadulina mbila (Naudé) (Homoptera: Cicadellidae) (3029, 3030).

Brian D. Harrison (GB), Hugh Barker (GB), Kenneth R. Bock (KE), E.J. Guthrie (KE), Gina Meredith (GB), and Mark A. Atkinson (GB) designated MSV as the type virus of the newly described group taxon Geminivirus (1415).

Claude Fuller (AU) gave the first written description of this disease (1200).

André Gratia (BE) and Sara Dath (BE) demonstrated that cultures of organisms designated as Streptothrix, now known to be actinomycetes, are capable of dissolving living and dead bacterial cells (1306).

André Gratia (BE) developed a therapeutically effective preparation that Maurice Welsch (BE) named actinomycetin (1305, 3423). Actinomycetin turned out to be a mixture of bacterial wall dissolving enzymes.

Marshall Hertig (US) and Simeon Burt Wolbach (US) discovered and identified the bacterium Wolbachia in Culex pipientis (1497). 

Marshall Hertig (US) provided a complete description of Wolbachia pipientis (1495). Wolbachia is widespread in arthropods, infecting about 25-70% of species of insects.

Walter M. Boothby (US) and Irene Sandiford (US) discovered that thyroxine is the chief active principle of the thyroid gland (354).

William Waddell Duke (US) and Oren C. Durham (US), allergists, authored a pioneering survey of hay fever inducing plants in the Kansas City, MO area (914, 915).

Olaf Blegvad (DK) found that night blindness is a symptom of vitamin A (retinol) deficiency (334).

George Frederick Dick (US) and Gladys Henry Dick (US) described the erythrogenic toxin usually produced by the streptococci causing scarlet fever. They showed that the filtrate of cultures that had produced experimental scarlet fever, when injected intracutaneously in the proper dilution, gave a distinct local reaction in the skin of a large proportion (41.6%) of persons who had no history of scarlet fever, while all of the convalescent scarlet fever patients tested showed negative or only slightly positive reactions. It was further found that the action of the filtrate on the skin was inhibited by small quantities of convalescent scarlet fever serum mixed with the filtrate before injection. This became known as the Dick test (824).

Eli Moschowitz (US) was the first to describe a case of what would later be named thrombotic thrombocytopenic purpura. The patient was a 16-year-old girl who presented with an abrupt onset of petechiae and pallor followed rapidly by paralysis, coma, and death. Upon pathologic examination, the small arterioles and capillaries of the patient were found to have thrombi consisting mostly of platelets (2269, 2270).

George Baehr (US), Paul Klemperer (US), and Arthur Schiffrin (US) defined the disease picture clinically and morphologically and distinguished it from other forms of purpura (135).

Karl Singer (US), Frederick P. Bornstein (US), and Simon A. Wile (US) named the disease thrombotic thrombocytopenic purpura (2920).

Viktor Theodor Adolf Georg Schilling (DE) emphasized the value of a differential leucocyte count of peripheral blood. He divided polymorphonuclear neutrophil cells into four categories according to number and arrangement of the nuclei in the cells. The so-called Schilling’s hemogram indicates the different developmental stages and an increase in juvenile forms indicates the presence of acute infection or of immature bone marrow as in leukemia (2819).

Augustus R. Felty (US) was the first to perceive that the association of leukopenia with splenomegaly and chronic arthritis might constitute a distinct clinical disorder; one which now bears his name, Felty’s syndrome (1074).

Evarts Ambrose Graham (US) and Warren H. Cole (US) developed cholecystography (x-ray technique for viewing the gall bladder) (1298).

Samuel Alexander Kinnier Wilson (GB) wrote on pathological laughing and crying (3527).

Aladár Petz (HU) invented the surgical stapler. “The idea stemmed from the need that the surgeon has to open the digestive tract with its highly contaminated lumen, thereby, risking consequent peritonitis with its associated increase in mortality” (2521).

Thorlief Schjelderup-Ebbe (NO) described social dominance hierarchies (pecking orders) in birds (2825, 2826).

Henry F. Osborn (US) designated the skull and claw (which he assumed to come from the hand) from a fossil collected in Mongolia as the type specimen of a new genus, Velociraptor. This name is derived from the Latin words velox ('swift') and raptor ('robber' or 'plunderer') and refers to the animal's cursorial nature and carnivorous diet. Osborn named the type species V. mongoliensis after its country of origin (2410).

In 1924, aster yellows disease was demonstrated to be spread by aster leafhopper (2879). 

Lindsay MacLeod Black (GB-CA-US) and Karl Maramorosch (US) demonstrated that the viruses of clover club leaf and aster yellows multiply within their insect vectors (324, 2085, 2086).

Fluorine compounds were suggested as insecticides (2879).

Merritt Lyndon Fernald (US) discredited the "law of age and area" as espoused by John Christopher Willis (GB) and George Udny Yule (GB). This law stated that the area occupied by any given species (taken in groups of twenty or so) at any given time in any given country in which there occur no well-marked barriers depends upon the age of that species in that country (1078-1080, 3495).

Henry Allan Gleason (US) also discredited the "law of age and area" (1251).

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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7. Abel JJ. 1899. Über den blutdruckerrengenden bestandtheil der nebenniere, das epinephrin [About the blood pressure raising constituent of the adrenal gland, the epinephrine]. Hoppe-Seyler's Zeitschrift für Physiologische Chemie 28: 318-62

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