A Selected Chronological Bibliography of Biology and Medicine


 Part 3B





Compiled by James Southworth Steen, Ph.D.

Delta State University


Dedicated to my loving family


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


Please forward any editorial comments to: James S. Steen, Ph.D., Professor Emeritus, DSU Box 3262, Cleveland, MS 38733. jsteen08@bellsouth.net



"Far and away the best prize that life offers is the chance to work hard at work worth doing." Theodore Roosevelt (1839).


"The supreme qualities of all science are honesty, reliability, and sober, healthy criticism." Niels Ryberg Finsen (871).


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) used the term biochemistry, defining it as science concerned with the chemical basis of life. Ref

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 (1760).


Henry Lord Wheeler (US) and Treat Baldwin Johnson (US) synthesized cytosine (2335).


Felix Ehrlich (DE) isolated the amino acid isoleucine from nitrogenous substances in beet-sugar molasses (644).


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 (750; 751). 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 (92). Later it was he who synthesized the dye indigo.

Heinrich Hörlein (DE), in 1911, at F. Bayer & Co. synthesized phenobarbital (Luminal). It has excellent hypnotic action and anticonvulsant activity. It was patented by F. Bayer & Co. under DE 247952.

Alfred Hauptmann (DE) discovered the antiepileptic properties of Luminal (phenobarbital) by accident when studying the anxiolytic effects of various drugs (810; 979).

Manipulations of the side chain at position 5 have resulted in amobarbital (Amytal) in 1923, pentobarbital (Nembutal) in 1930, 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. Sodium pentothal has been called the “truth serum” because it gives its recipient a good feeling when being forthright.


Samuel Rideal (GB) and J.T. Ainslie Walker (GB) developed the original method for determining the phenol coefficient (1810).

The Hygienic Laboratory Method (1921) is a modification of the Rideal-Walker Method (1).

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


Theobald Smith (US), in 1903, noted that guinea pigs used for 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 (1697).


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 (62).

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 leukocytes (PMNs) phagocytize and rapidly degrade antigen-antibody complexes but are themselves largely responsible for the inflammation and necrosis (432).


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 (1132).

Georg Schöne (DE) coined the phrase transplantation immunity to distinguish it from reactions resulting from injections of foreign materials (1943; 1944).


Nicholas Senn (CH-US) was the first to use röntgen rays to treat leukemia (1953).


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 (1989).

Edmund Weil (AT) and Arthur Felix (PL-GB) would designate these as the O and H antigens respectively (2314; 2315).


Louis Lapicque (FR) introduced several 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 (1299). 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 (962).


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 victuals for) (2430; 2431). 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 (1109).


Paul Ambroise Remlinger (FR), Riffat Bey Frasheri (AL), 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 (1786; 1787). Note: the first rhabdovirus


Amédée Borrel (FR) discovered the sheep pox and goat pox virus (249). Note: One virus is thought to cause both.


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 (1611-1614). 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 (248).

Vilhelm Ellermann (DK) and Oluf Bang (DK) showed that by injecting bacteria-free tissue filtrates from infected chickens into healthy chickens they could transmit leukemia in chickens. This implied a viral origin of the leukemia, i.e., oncogenic viruses (659; 660; 1964). Note: the first leukemia virus

Francis Peyton Rous (US) demonstrated that an agent, which passed through filters that stopped 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 one of the first of the tumor viruses to be demonstrated (1848-1852). Note: first solid tumor virus

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 (626; 627).


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 (1945).


W.K. Stefansky (RU) and George A. Dean (GB) discovered Mycobacterium lepraemurium, the etiological agent of rat leprosy (555; 2033).


John Fleetezelle Anderson (US) described Rocky Mountain spotted fever as a new disease and suggested the wood tick as a possible carrier (48).

Louis B. Wilson (US) and William M. Chowning (US) discussed history, location, season, previous conditions of the patient, sex and age, types of disease, symptoms, prognosis, morbid anatomy, morbid histology, etiology, inoculation experiments, mode of infection, possible hosts, diagnosis, preventive measures, and treatment as they applied to pyroplasmosis hominis ("spotted fever" or "tick fever" of the Rocky Mountains) (2395).

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 (1805; 1806).

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 (1807). 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 (2420).

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) (90).


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 (1664).


William Ernest Castle (US) wrote the first paper on Mendelism in America (363).


William Ernest Castle (US) was probably the first to recognize the relationship between allele and genotype frequencies (362). Note: In this work Castle anticipated what has now become known as the Hardy–Weinberg law. Formulated in the terms "as soon as selection is arrested the race remains stable at the degree of purity then attained."


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 (1491; 1492).

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 (1424; 2250-2252).

Charles Mantoux (FR) popularized Mendel’s test, thus the Mendel-Mantoux Tuberculin Test (1424).


Nicholas Senn (US) was the first to use röntgen rays to treat leukemia (1953).


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 (333).


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 (1137; 1138; 1733). He introduced the terms and defined the concepts of gene, phenotype, genotype, and selection (1139; 1140).

Richard Woltereck (DE) would confirm this restriction on natural selection as it applies to animals using parthenogenic freshwater crustaceans of the genus Daphnia (2427).


Emily Arensen (NO) presented information on the geographical distribution of sponges (59).


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 (57; 638; 639; 662; 663; 1144).


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 (899; 1777).


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 (1878).


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 (1127).


Ettore Marchiafava (IT) and Amico Bignami (IT) described a neurological disorder consisting of tremor, convulsions, and coma related to alcohol intake (1429; 1430). This is a progressive neurological disease of alcoholism, characterized by corpus callosum demyelination, necrosis, and subsequent atrophy.


William Gibson Spiller (US), John Herr Musser (US), and Edward Martin (US) described inflammation of the spinal canal (arachnoiditis) in a patient as meningitis circumscripta spinalis (2016).


Georges Fernand Isidore Widal (FR) found that blood in cerebrospinal fluid was diagnostic of meningeal hemorrhage (2348).


Georges Froin (FR) described inflammation of the meninges with obstruction of the spinal subarachnoid space associated with a coagulable state of the cerebrospinal fluid (Froin syndrome) (807). Note: This condition is typically caused by meningeal irritation (e.g. during spinal meningitis) and CSF flow blockage by tumor mass or abscess.


William Osler (CA) was the first to associate a renal affection or one affecting the central nervous system with cases of lupus erythematosus (1687; 1688).


Alfred Wolff-Eisner (DE) trephined the tibia and femur of experimental animals and suggested biopsy of bone marrow as a clinical procedure (2424).


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 the Bloch-Mikulicz operation (2248).


Maximilian Carl-Friedrich Nitze (DE) became the first to develop a cystoscope for examining the bladder and the bladder neck; a feat accomplished using his and Joseph Leiter’s (AT) invention (1652). In 1891 Nitze initiated endoscopic surgery with a newly modified cystoscope. He operated by using a loop which could be combined with cautery. The loop was put around a tumor, tightened, and the galvanocautery was turned on. The hot loop cut and coagulated the tissue thus controlling bleeding. Nitze used this method for the treatment of 150 patients and recorded only one death (1653).

Maximilian Carl-Friedrich Nitze (DE) developed a ureteral occlusion catheter to block the ureter of the diseased kidney so that the urine of the healthy kidney could be collected separately (1654).

Karl Otto Ringleb (DE) improved the cystoscope with his “orienting cystoscope,” a breakthrough in 1908 (1815; 1816). Suprapubic prostatectomy had a mortality rate of 50% prior to the introduction of Ringleb-Berlin’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 (175).

Leo Buerger (US) constructed a universal urethroscope with two optical systems, direct or indirect viewing, and used for catheterizing and operating respectively. It was both a cystoscope and urethroscope (316).

Maximilian Stern (DE-US), with Reinhold Wappler’s assistance, created the first instrument that used an electric loop to cut prostatic tissue (2041).


S.W. Goldberg (RU) and Efim Semenovich London (RU) described the use of radium to treat two patients with basal cell carcinoma of the skin. The disease was eradicated in both patients (849).


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 (1719-1722).

Ivan Mikhailovich Sechenov (RU) wrote Reflexes of the Brain, which Pavlov acknowledged as the single most important theoretical inspiration for his work on conditioning (1723; 1947-1949).

Ivan Petrovich Pavlov; Ivan Petrovic Pavlov (RU) and Vladimir Mikhailovich Bekhterev; Vladimir Mikhailovich Bechterev (RU) independently developed a theory of conditioned reflexes which describes 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. John Watson discovered the salivation research completed by Pavlov and incorporated it into his 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 (183).


William Osler (CA) was the first to recognize polycythemia vera as a definite clinical entity (1686).


August Karl Gustav Bier (DE) introduced artificial active and passive hyperemia as an adjuvant to surgical therapy (208).


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 (377; 1573).


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” (1606).

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 nearly 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 (1868).


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 (1236; 1237). 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 (516; 2055). Note: This was the first synthetic production of a hormone.


Albert Einhorn (DE) synthesized and patented procaine hydrochloride (Novocaine) in 1904. Heinrich Braun (DE) was the first to report its existence as Novocaine (273). It supplanted cocaine as the local anesthetic of choice.


Potassium cyanide powder was advocated for the control of ants (1954).


Marshall Albert Barber (US) invented the technique for making glass capillary micropipettes and manipulating them in the field of a compound microscope (120; 2097). He developed this method initially to clone bacteria and to confirm the germ theory of Koch and Pasteur. Later, 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 (631-633; 1845).

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 (1227; 1228).


Henri Vallé (FR) and Henri Carré (FR) proved the viral etiology of equine infectious anemia (2160). Note: the first retrovirus


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” (664; 665). 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 (2386).

Thomas Hunt Morgan (US) was the first to formulate the concept of cytoplasmic determination (1560).

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 (1098).


Lorenz Hiltner (DE) introduced the concept of the rhizosphere (1040).


Cornelius Johan Koning (NL) suggested that fungi play an important role in the decomposition of organic matter and the formation of humus (1242).


Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Henry Drysdale Dakin (US) discovered the enzyme arginase, which splits arginine into ornithine and urea (1249; 1250).

Antonino Clementi (IT) found that arginase is absent from the livers of animals, which do not excrete urea (e.g., birds and reptiles) (407).


George Henry Falkiner Nuttall (US-GB) investigated the serological relationships of animals by the precipitin reaction (1665).


Franz Schardinger (AT) isolated aerobic bacteria capable of producing industrial chemicals such as acetone, ethanol, and acetic acid (1898).


Karl Pearson (GB) correctly generalized the principle of segregation showing that the F2 ratio ¼ AA: ½ Aa: ¼ aa 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 (1725). Note: this work precedes that of Hardy and Weinberg in 1908.


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 (209).

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 (458; 459).


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 appear is larger than the number of possible combinations, this might be the result “of an exchange of parts between homologous chromosomes” (254). See, Sutton, 1903.


Martinus Willem Beijerinck (NL) was the first to obtain the sulfur-oxidizing bacterium, Thiobacillus denitrificans in axenic culture (177). 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 (222).

Hans Burgeff (DE) demonstrated that dissimilar nuclei could be associated in the vegetative hyphae of Phycomyces nitens, a condition he called heterokaryosis (318; 319).

William B. Brierley (GB), Hi N. Hansen (?), and R.E. Smith (?) discovered and elaborated on heterokaryosis in the Ascomycetes (292; 943; 944).

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 (1214).

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 (191; 192).

John Hubert Craigie (GB) in a series of experiments with Puccinia helianthi (the sunflower rust fungus) and P. graminis (the cereal stem rust fungus), Craigie demonstrated that rust fungi 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 (475-477). He designated two different mating types as (+) and (-) and showed that aeciospores are produced only when opposite sex come into contact and fuse together. Later, he showed that a pycniospore nucleus migrates to a protoaecidium through a flexuous hypha, starting the formation of aecia and dikaryotic aeciospores (478; 479).

Thorvaldur Johnson (CA) and Margaret Newton (CA) isolated new races of P. graminis by crossing two races of P. graminis tritci (1143).


Leonard Doncaster (GB) explained the inheritance of tortoiseshell, which is sex-linked, and related colors in cats (594).


Friedrich Meves (DE) discovered mitochondria in plants (the tapetal cells of Nymphae anthers) (1503).


Anton Julius Carlson (SE-US) proved that the heartbeat in the Limulus crab is neurogenic by section of the cardiac nerve (347). 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. About 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 (623; 624).


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 can 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 (1350; 1960-1962).


Georg 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 (517; 1216-1218). 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) discovered that glycogen was converted to lactic acid, but he also showed that lactic acid could be converted to glucose. That is, Embden showed that glucose and lactic acid could be interconverted with each other in laboratory animals. This interconversion observation would become one of the most important biochemical pathways for muscle contraction in all living animals. Ref


Gershom Franklin White (US) reported the isolation of Bacillus X in honeybee (Apis mellifera Linn.) larvae suffering from American foulbrood (2340). White then renamed the organism Bacillus larvae (2341; 2342).

American foulbrood is a severe bacterial disease affecting larvae of the honeybee Apis mellifera and it is caused by Paenibacillus larvae larvae, formally Bacillus larvae.

Gershom Franklin White (US) demonstrated conclusively that the bacterium Bacillus larvae was the cause of American foulbrood disease by fulfilling Koch's postulates (2343).


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 (151; 1759).


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 (963; 964).


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 and monkeys (466; 1405).


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 (42-44).


Paul Emil Flechsig (DE) evolved a map of cortical function that appeared in a report of 1904 to the Central Committee for Brain Research (758).


Karl Albert Ludwig Aschoff (DE) discovered granuloma in the myocardium specific for rheumatic fever (66).


Ernst Ferdinand Sauerbruch (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 (1892).

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 (267).


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 (1428).


Giuseppe Gradenigo (IT) reported a triad of symptoms consisting of periorbital unilateral pain related to trigeminal nerve involvement, diplopia due to sixth nerve palsy and persistent otorrhea, associated with bacterial otitis media with apex involvement of the petrous part of the temporal bone (petrositis) (873; 874). It was later named Gradenigo’s syndrome.


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 (593).


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 (1045).


Thomas Grainger Stewart (GB) and Gordon Morgan Holmes (IE) wrote a paper about precise localization of destructive lesions in the cerebellum. This paper contains a description of the Stewart-Holmes syndrome (epileptic fits, manifested by jerking movements of one arm) and the first description of the rebound phenomenon (2045).


Edward Albert Schäfer (GB) described a method for administering artificial respiration. It was especially effective with a person in danger of drowning (1896).


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 (1175).


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 (499).


Max Askanazy (DE-CH) was the first to link osteitis fibrosa cystica with parathyroid tumors (72).


Paul Charles Dubois (CH) is known for the introduction of "persuasion therapy", a process that employed a rational approach for treatment of neurotic disorders. Within this discipline, he developed a psychotherapeutic methodology that was a form of Socratic dialogue, using the doctor-patient relationship to persuade the patient to change his/her behavior. He believed it was necessary to appeal to a patient's intellect and reason in order to eliminate negative and self-destructive habits. He also maintained it was necessary for the physician to convince the patient of the irrationality of his/her neurotic feelings and thought processes (614; 615).


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” (893). 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” (894; 895). 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 (896). 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” (897).

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” (829-832). 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 (1670). “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” (1423).


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 (296).


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 (1371). More than two hundred and fifty men from a dozen countries came to study under this great master.


"In the Vertebrates we meet with two great categories of white corpuscles, of which one group resembles those of the invertebrates in that they also possess a single large nucleus and an amoeboid protoplasm. These are the macrophages of the blood and of the lymph, and are intimately connected with the macrophages of such organs as the spleen, lymphatic glands, and bone marrow. Another group of white corpuscles in the Vertebrata is made up of small amoeboid cells, which are distinguished by having a nucleus, which, although single, is divided into several lobes. These are the microphages [neutrophils]. Phagocytosis is exhibited not only by the macrophages but also, in a high degree, by the microphages which stand out as the defensive cells par excellence against microorganisms [… ]. The microphages, on the other hand, appear to play their part, specially, in acute infections." Élie Metchnikoff (RU-FR) (1500).


 "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 (1750).


"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 (917).


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 (427; 428).


Richard Adolf Zsigmondy (AT-DE) applied the centrifuge to the study of colloids, making a more detailed understanding of protoplasmic constituents possible (2458).


Fritz Haber (DE) and Carl Bosch (DE) developed the Haber process for making ammonia, a milestone in industrial chemistry with deep consequences in agriculture. The Haber process, or Haber-Bosch process, combined nitrogen and hydrogen to form ammonia in industrial quantities for production of fertilizer and munitions (250; 916). Note: As of the early 21st century, the food production for half the world's current population depends on this method for producing fertilizer.


Vladimir Sergeyevich Gulewitsch (RU) and R.P. Krimberg (RU) isolated a new compound from meat extracts. They named it carnitine from carnos (meat) (910).

Masaji Tomita (JP) and Yuzo Sendju (JP) determined the chemical structure of carnitine to be 3-hydroxy-4-trimethylamino butyric acid (2124).


Cornelis Adrianus 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 (1727; 2166).

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 (1002).


Richard Anton Burian (CS) discovered xanthine oxidase, which catalyzes the conversion of xanthine to uric acid and hypoxanthine to xanthine (321).


Arthur Harden (GB) and William John Young (GB-AU) 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 (the Harden-Young ester) from the fermentation mix (945; 951-954; 2444). Note: They realized that fermentation requires the presence of both a heat-labile component they called “zymase” and a low molecular weight, heat-stable fraction called “cozymase.” (It was later shown that zymase contains several enzymes whereas cozymase consists of metal ions, ATP, ADP, and coenzymes such as NAD.) They presented an equation for overall alcoholic fermentation in 1908.

Phoebus Aaron Theodor Levene (RU-US) and Albert L. Raymond (US) characterized the structure of the Harden-Young ester as fructose-1,6-diphosphate (1333).

Leonid Aleksandrovich Ivanov (RU) had independently discovered that organic phosphates are produced during alcoholic fermentation (1108).

Arthur Harden (GB) made another important set of observations revealing that in the presence of the inhibitor, 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 photosynthesis 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 (221; 1453).

Otto Heinrich Warburg (DE) later called the process of limiting the rate of carbon assimilation at high intensities of illumination the Blackman reaction (2283).


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 (640; 641).

Helen R. Gregory (GB), Roderic Alfred Gregory (GB), Paul Martin Hardy (GB), Duncan S. Jones (GB), George Wallace Kenner (GB), Robert Charles Sheppard (GB) and Hilda J. Tracy (GB) determined the structure of gastrin (890; 891).

John Christopher Anderson (GB), Moira A. Barton (GB), Roderic Alfred Gregory (GB), Paul Martin Hardy (GB), George Wallace Kenner (GB), John Keith MacLeod (GB), Jean Preston (GB), Robert Charles Sheppard (GB) and John Selwyn Morley (GB) described their synthesis of gastrin (47).


William Henry Howell (US) discovered the remarkable hypotensive effect of acetylcholine (1068).


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.”

Langley said, “I conclude that in all cells two constituents at least must be distinguished, (1) substances concerned with carrying out the chief functions of the cells, such as contraction, secretion, the formation of special metabolic products and (2) receptive substances especially liable to change and capable of setting the chief substances in motion. Further, that nicotine, curare, atropine, pilocarpine, strychnine, and most other alkaloids, as well as the effective material of internal secretions produce their effects by combining with the receptive substance...” (1297).


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 (2044; 2387-2390). 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. Thomas Harrison Montgomery, Jr. is credited with coining heterochromosomes in 1904 and autosomes in 1906 (1542; 1543).


William Bateson (GB), Edith Rebecca Saunders (GB), Reginald Crundall Punnett (GB), and Charles Chamberlain Hurst (GB) discovered linkage and genetic interaction (152; 154). 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) (153; 1759).


William Bateson (GB) first suggested using the word "genetics" (from the Greek gennō, γεννώ; "to give birth") to describe the study of inheritance and the science of variation in a personal letter to Adam Sedgwick (1854–1913, zoologist at Cambridge, not the Adam Sedgwick (1785–1873) who had been Darwin's professor), dated 18 April 1905 (142).


William Curtis Farabee (US) determined that brachydactyly in humans can be explained by Mendelian principles (715).


The first human pedigree was published. It showed the inheritance of shortened hands and fingers in a Norwegian village (1157).


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 (148-150; 1759).

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 (1555).

Alfred Henry Sturtevant (US), based on his work with Morgan, created the first genetic map (2070). See Sutton, 1903.

John Burdon Sanderson Haldane (GB), Alexander Dalzell Sprunt (GB), and Naomi Mitchison Haldane (GB) were the first to demonstrate linkage of genes in the mouse (931).


Lucien Claude Jules Cuénot (FR) discovered a lethal allele, the yellow coat color allele in mice, even though he did not interpret it correctly (492).

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 (366).

William B. Kirkham (US) later discovered that the homozygous yellow embryos died in utero (1202).


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 (370; 371; 1194; 1195; 1436; 1496).

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 (2128; 2129).


The last yellow fever epidemic on the North American continent occurred in New Orleans, Louisiana. The epidemic ended in the fall after a large-scale mosquito eradication program (1488).


Stamen Grigoroff (BG) isolated Lactobacillus bulgaricus from Bulgarian fermented milk (892).


Alfred T. MacConkey (GB) used bile salts to select for lactose fermenting bacteria in fecal samples (1396; 1397).


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 (2417).


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 (1920; 1921). The organism is now called Treponema pallidum.


Aldo Castellani; Count of Chisiamaio (IT) discovered, Treponema pertenue, the spirochete causing yaws (359).


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 (1500).


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 (181).


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 (989). Hektoen was also the first to grow blood cultures from living patients (988).


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” (2164; 2331).

Cornelis Bernardus Kees van Niel (NL) remarked, “Beijerinck’s 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” (2167).


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 (1103).


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 (1502).


Louis Joseph Alcide Raillet (FR) and Albert 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 (309; 310; 1767).


William Bateson (GB) coined the term genetics to denote the science of heredity, but the word had been used earlier (143; 144).

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 (732; 733).


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 (553).

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 (1390).

Lettice Digby (GB) observed that the primrose 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 (574).

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 (2406).

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 (399; 400; 1168; 1169). 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 during 1905, 1923 and 1926 (1642).


Rowland H. Biffen (GB) was the first to breed crops for disease resistance in cereal rusts using Mendelian principles. But variability in the pathogen was not fully appreciated (210).

Elvin Charles Stakman (US) and Frank Joseph Piemeisal (US), in 1917, reported that stem rust in cereals and grasses comprised six biological forms. These forms were distinguished from each other morphologically and parasitically and were differentiated on selected cereal and grass hosts (2024). Note: This led to research on variation and variability of plant pathogens, and subsequently of all microorganisms, and the breeding of plants for resistance to specific races. Races became essential also in microorganisms important in industry, e.g. in the production of acids and enzymes from organisms, and in medicine in the development of antibiotics.


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 will 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 (444).


Charles Zeleny (CZ-US) showed that removal of the eyestalk shortened the intermolt period in crustaceans (2452).


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 (1173)