A Selected Chronological Bibliography of Biology and Medicine


Part 3A





Compiled by James Southworth Steen, Ph.D.

Delta State University


Dedicated to my loving family


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


Please forward any editorial comments to: James S. Steen, Ph.D., Professor Emeritus, jsteen08@bellsouth.net



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


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


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


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

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

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

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

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

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


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


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

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


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

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

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

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


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

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

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

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

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


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


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


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


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

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

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

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


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


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


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

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


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


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


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


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


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


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


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


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


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


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

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

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

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


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


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


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

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


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


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


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


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

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

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


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


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


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


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

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

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

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

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


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


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


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


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


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

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

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


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

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


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


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


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


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


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



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


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


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


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

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


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


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


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


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


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


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

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


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


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


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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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


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


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

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

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

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


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


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

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


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


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


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


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


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


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


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

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

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


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

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

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


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


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


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

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

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

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

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

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

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

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


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


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


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


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

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

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

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


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


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

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

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

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

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

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



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


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


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


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

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


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



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


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



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


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

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

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


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

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


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


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

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

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

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

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

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

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


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

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

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


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


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


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


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


Enrique Paschen (DE) rediscovered these elementary bodies (1266). They were