A Selected Chronological Bibliography of Biology and Medicine — Part II

Ca. 1810 — 1884

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

Dedicated to my loving family

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

Please forward any editorial comments to:

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

ca. 1810

John James Audubon (FR-US) was possibly the first to study the migration of birds by banding (ringing) them (1834).

Mary Anning (GB) was celebrated as the outstanding fossil collector of her time. Among the many fossils collected and prepared by her are the first ichthyosaur skeleton and the first pleisosaur skeleton known to the English community. The ichthyosaur fossil was probably discovered sometime between 1809 and 1811, when Mary was only 10 to 12 years old. And while Mary did find the majority of the remains, her brother had discovered part of the animal twelve months earlier. The majority of Mary's finds ended up in museums and personal collections without credit being given to her as the discoverer of the fossils (3369).


William Hyde Wollaston (GB) isolated cystic oxide (cystine) from unusual kidney stones (2227, 3795). This was the second amino acid to be discovered.

Jöns Jakob von Berzelius (SE) named it cystine (Gk. cystine, bladder) (3511).

Karl Axel Hampus Mörner (SE) was the first to isolate cystine from a protein hydrolysate (animal horn) (2387).

Richard August Carl Emil Erlenmeyer, Jr. (DE) was the first to synthesize cystine (1040, 1041).

Louis Antoine Planche (FR) observed that extracts of plant roots would turn alcoholic solutions of guaiac resin a blue color. The agent responsible for this change was found to be water-soluble and thermolabile (2758, 2759). This represents an early account of enzymatic activity.

Joseph Louis Gay-Lussac (FR) found that grape juice preserved for over a year by the Appert method would upon opening ferment within a few days. An unopened control bottle of Appert’s grape juice remained unchanged.

Finding that bottles of Appert’s preserves showed no oxygen Gay-Lussac concluded that this gas must play a vital part in the fermentation process. He introduced some small and intact grapes into a bell jar standing over mercury. He filled the jar several times with hydrogen gas to displace any oxygen and he then ruptured the grapes by means of an iron rod and watched the effect. For twenty-five days no fermentation had taken place, but it soon occurred when he admitted into the bell jar some bubbles of oxygen. The oxygen introduced was soon proved to have disappeared while carbon dioxide was evolved. From this Gay-Lussac concluded that oxygen was necessary to start fermentation but not for its continuance. Grape juice, which had been preserved and poured into a fresh bottle, could be re-preserved by subsequent heating. These results obtained with grape juice were also found to apply to preserved meat, fish, and mushrooms (1285).

Robert Brown (GB) was the first to demonstrate that the gymnosperms (conifers, ginkgo, and cycads) are a group apart from the angiosperms (flowering plants) and distinguished from these in having naked ovules. He was the first to explain the floral morphology and pollination in the Asclepiadaceae (Milkweed family) (476).

Phillip Parker King (GB) quotes Brown, “It would entirely remove the doubts that may exist respecting the point of impregnation, if cases could be produced where the ovarium was either altogether wanting, or so imperfectly formed, that the ovulum itself became directly exposed to the action of the pollen…such, I believe, is the real explanation of the structure of Cycadeae, of Coniferae, of Ephedra, and even of Gnetum.” (1806

Henry Hickman (GB) used nitrous oxide to anesthetize animals. 

Gaspard Laurent Bayle (FR) pointed out that tubercles might be present in patients before symptoms appear and correlated tubercles with cavity formation. He described acute miliary tuberculosis, tubercular laryngitis, lymphadenitis and enteritis, and insisted that tuberculosis was a specific disease, not a condition brought on by another disease (145).

Franz Joseph Gall (DE-FR) and Johann Gaspar Spurzheim (DE) were the first to point out that the nerve tissue we call gray matter is important in higher thought processes while the white matter represents connecting nerves. They demonstrated that the cranial nerves issue from the medulla oblongata and not the cerebral hemisphere. They also promoted the belief that character traits and mental aberrations are organic, inborn, god given; espousing the idea that a careful study of the external appearance of the skull could be used to predict the talents and mental characteristics of the possessor (phrenology) (1249, 1250).

Thomas Copeland (GB) wrote the first English book on general colo-rectal surgery (690).


“ On laying bare the roots of the spinal nerves, I found that I could cut across the posterior fasciculus of nerves which took its origin from the posterior portion of the spinal marrow without convulsing the muscles of the back, but that, on touching the anterior fasciculus with the point of the knife, the muscles of the back were immediately convulsed.” Charles Bell (157)

Georges Léopold Chrétien Frédéric Dagobert Cuvier (FR) and Alexandre-Théodore Brongniart, Jr. (FR) concluded from their studies of sedimentary rock strata in the Paris Basin that the relative position of a layer is an indication of its relative age (469, 746, 747).

Lorenzo Romano Amedeo Carlo Avogadro (IT) proposed that two equal volumes of gases of any type, if kept at the same pressure and temperature, contain equal numbers of molecules. This became known as Avogadro’s law (79).

Joseph Louis Gay-Lussac (FR) and Louis Jacques Thénard (FR) determined the elementary composition of sugar for the first time (1284).

Henri Braconnot (FR) isolated d-mannite, the sweet principle of manna, from Agaricus mushrooms. He claimed that it was non-fermentable (389, 390). The manna that is used as an agreeable food in the East, and as a purgative for children in the West is caused to flow from the Tamarix mannifera shrub, by the punctures of a small insect, Coccus maniparus.

Henri Braconnot (FR), working with mushrooms, discovered fungine (chitin), the earliest known polysaccharide (388).

Antoine Odier (FR) in his survey of the insect cuticle renamed fungine as chitine (meaning tunic in Greek) (2552). It is spelled chitin in German and English.

Charles Marie Benjamin Rouget (FR) isolated chitosan (2975).

Louis Odier (CH) discovered greatly enlarged and very painful nerves, which he named neuromes (neuroma) (2553).

William Wood (GB) observed and described neuromas in 24 amputation stumps (3796). 

Caspar Wistar (US) wrote the first systematic treatise on anatomy to be published in North America (3779). His friend Thomas Nuttall (GB) named the wisteria vine for him.

Peter Cullen (GB) defined a case of splenitis acutus with unexplainable milky blood (732).

Alfred-Armand-Louis-Marie Velpeau (FR) described a 63-year-old florist who developed an illness characterized by fever, weakness, urinary stones, and substantial enlargement of the liver and spleen. Velpeau noted the blood of this patient had a consistency "like gruel", and speculated the appearance of the blood was due to white corpuscles (3452).

Alfred Donné (FR) detected a maturation arrest of the white blood cells (878).

John Hughes Bennett (GB) used the term leucocythemia to describe this pathological condition (169).

Rudolf Ludwig Carl Virchow (DE) coined the term leukemia and was the first to describe the abnormal excess of white blood cells in patients with the clinical syndrome described by Velpeau and Bennett (3475). Acute lymphoblastic leukemia (ALL) or acute lymphoid leukemia is an acute form of leukemia, or cancer of the white blood cells, characterized by the overproduction of cancerous, immature white blood cells—known as lymphoblasts.

Elisha North (US) wrote an essay concerning the epidemic of spotted fever in New England.  This is the first book on cerebrospinal meningitis; in it North recommended the use of the clinical thermometer, not in general use until the time of Wunderlich (2529).

Gaspard Vieusseux (CH), in 1810, was the first to describe lateral medullary infarction, noting, "Vertigo, unilateral facial numbness, loss of pain and temperature appreciation in the opposite limbs, dysphasia [sic] and hoarseness, minor tongue involvement, hiccups (cured by taking up the habit of a morning cigarette) and a drooped eyelid” (2226).

Adolf Wallenberg (DE) provided a very detailed description of the clinical signs of lateral medullary infarction with accurate localization of the lesion in the lateral medulla supplied by the posterior inferior cerebellar artery (PICA). He later proved this at postmortem (3655-3657). This condition is often called Wallenberg’s syndrome.

John Syng Dorsey (US) successfully ligated the external iliac artery (885).


Karl Friedrich Gauss (DE) wrote Theoria Combinationis Observationum Erroribus Minimis Obnoxia [Theory of Least Squares] (1283). This is basic to the statistical evaluation of data.

Joseph von Fraunhofer (DE), in 1812, invented an achromatic objective consisting of two different lenses in contact with one another. He and Pierre Louis Guinand (CH) developed ways to free optical glass of imperfections. They continued to improve lenses and prisms with additional inventions (1647).

Joseph von Fraunhofer (DE) invented the spectroscope and discovered the 574 dark lines in the solar spectrum. These lines were later named for him. He also measured the wavelength of sodium light by means of diffraction grating (3528).

Konstantin Sigizmundovich Kirchhof; Gottlieb Sigismund Constantin Kirchhof (DE-RU) obtained the hydrolysis of starch to sugars in dilute acids (sulfuric, nitric, oxalic, etc.) (1811).

Johann Jacob Paul Moldenhawer (DE) had the idea that vascular bundles are complex structures composed of xylem and phloem (2369).

Louis Nicolas Vauquelin (FR) discovered phospholipids while studying material extracted from brain tissue. He also noted that the medulla oblongata and the spinal cord contain more fatty material and less protein than grey matter (3450).

William Charles Wells (US-GB), in an often-ignored study, applied the principle of natural selection to the evolution of man (3713). 

Napoleon's army was attacked again by typhus and dysentery (the "bloody flux") during his invasion of Russia, both on the march eastward and again on the return, where disease was exacerbated by severe cold and starvation. It is estimated that only about 30,000 survived of the nearly 600,000 troops that began the campaign (1863).

René-Joachim-Henri Dutrochet (FR) was one of the first to place the rotifers in their own separate natural group, the class Rotifera (951). They are in the phylum Aschelminthes (or Nemathelminthes).

Kaspar Friedrich Wolff; Caspar Frederick Wolff) (DE-RU) described the embryonic development of the intestines in the chick (3789-3791). 

Guillaume Dupuytren (FR) was the first to successfully excise the lower jaw, in 1812 (939).

Antonio Scarpa (IT) pinned an authoritative work on hernia, from which are derived the eponyms Scarpa's fascia and Scarpa's triangle of the thigh (3050).

Georges Léopold Chrétien Frédéric Dagobert Cuvier (FR) was the first to extend the system of classification to fossils. He suggested that fossils found in the area around Paris are thousands of centuries old. This casual observation pushed the age of the earth well beyond its commonly accepted limits. Cuvier also published a paper explaining that the fossil animals he studied bore no resemblance to anything still living. In short, Cuvier proposed the theory of extinction. He coined the word pterodactyl (wing-finger). For his discoveries related to fossils he is considered the founder of paleontology (739-741, 743, 745, 2994). Through the rigorous application of his correlation theory Cuvier was able to correctly identify entire animals from a few bones and demonstrate that these animals were indeed extinct, e.g. he identified pterosaurs as flying reptiles. His conclusions represented the foundation of modern paleontology, yet they would be largely ignored for many years (742).

The New England Journal of Medicine was founded (2138).

Proceedings of the Royal Academy of Sciences of Amsterdam was founded.


"But these are deeds which should not pass away,

And names that must not wither." George Gordon (Lord Byron) (1374)

David Brewster (GB) suggested that viewing would be improved if the front element of a microscope’s objective lens could be immersed in the liquid in which the object of study was mounted. It is he who recommended that oil immersion would improve achromatic viewing (416).

Jöns Jakob Berzelius (SE) established that the elements in inorganic substances are bound together in definite proportions by weight (the law of constant proportions) (230, 231). 

Bernard Courtois (FR) was the first to prepare iodine when he observed purple vapors rising from kelp ashes that he had acidified with sulfuric acid and heated. The purple vapors condensed on a cold surface, forming nearly black crystals (713). Note: He actually performed this experiment in 1811.

Joseph Louis Gay-Lussac (FR) reported that the substance he calls iode is likely an element (1286). Later he is confidant it is a new element (1287). 

Humphrey Davy (GB) tested the substance Courtois had discovered and pronounced it a new element, which he named iodine (788).

Michel-Eugène Chevreul (FR) was the first to report the participation of water during the saponification process (605).

Michel-Eugène Chevreul (FR) was the first to isolate the following acids: margaric (a mixture of palmitic and stearic acids), butyric, caproic, capric, and isovaleric (acide phocénique), along with stearic (stearine), palmitic, and oleic, the three most common and important constituents of fats and oils. He determined that spermaceti, the wax-like substance from the head of the sperm whale, when boiled with alkali, produced soap, later identified as potassium palmitate, but did not yield glycerol as a residue. The residue was insoluble in water but soluble in alcohol and ether. He called it cetin, which was later identified as cetyl alcohol. He was the first lipid specialist to discover the concept of fatty acids and clearly demonstrate that fats have the structure of ethereal salts and are a combination of glycerol and fatty acids, easily separated by saponification (604, 608).

Jean Vincent Félix Lamouroux (FR) provided an important advance in the study of the algae when he became the first to propose a system of classification into major taxa based in part on color. He proposed a general classification for the marine algae, which he divided into Fucaceae, Florideae, Dictyoteae, Ulvaceae, Alcyonideae, and Spongodieae. Except for the last two, these groups have been maintained in present classifications. He discovered two distinct types of reproduction among the Florideae 1) tubercles called seeds (cystocarps) and 2) capsules called tetrasporocysts. Lamouroux described many new genera of algae (1953, 1954).

Frederick Pursh; Frederick Traugott Pursh (DE) described plants from some forty European collections along with some brought back from "The Lewis and Clark Expedition", or "Corps of Discovery Expedition" (1804–1806) in his Flora Americae Septentrionalis (2821). He is honored by the genus Purshia (Rosaceae).

Augustin Pyramus de Candolle (CH), in his book Théorie Élémentaire de la Botanique, introduced the word taxonomy to mean the classification of plants on the basis of their gross anatomy (808). He was the first to perceive the major trends of floral evolution in the angiosperms. In 1824, he initiated the monumental Prodromus Systematis Naturalis Regni Vegetabilis, which proposed to classify and describe every species of known seed plant including its ecology, phytogeography, and evolution. De Candolle produced the first seven volumes; the remaining 10 were completed under editorship of his son. His system of plant classification is largely in use today (809, 810).

Thomas Bateman (GB) described papular urticaria, calling it lichen urticus. He said that its first appearance was in the form of irregular inflamed wheals, so closely resembling the spots excited by the bites of insects as almost to deceive the observer. The inflammation subsides in a day or two leaving small, elevated, itching papules. The old wheals subside while new ones appear in succession until the whole body and limbs are spotted with papules which here and there become confluent in small patches. Both the wheals and the papules are accompanied by intense itching (132). Note: This condition, as of the year 2016, is considered to be a hypersensitive reaction to insect bites.

Francois Magendie (FR) and Gilbert Breschet (FR) observed that rabies could be induced in healthy dogs using the saliva from rabid humans and that it could be transmitted from carnivores to herbivores. Although they did this work together around 1813-1820 Magendie published in 1821 and Breschet waited until 1840 (88, 411, 2193).

Francois Magendie (FR) proved that the stomach is passive rather than active in vomiting. This was essentially correct; however he did fail to observe the active role of the pyloric end of the stomach (2201).

Francois Magendie (FR) showed that the epiglottis is not necessary for swallowing, which disproved the accepted doctrine that the epiglottis was necessary to cover the glottis to prevent food from entering the trachea (2190).

Antonio Scarpa (IT) presented the first illustrations of arteriosclerosis (3048).

Felix Vicq d'Azyr (FR) discovered the claustrum, a thin layer of grey matter outside the external capsule of the brain, dividing it from the white matter of the insula (3460).

Conrad Johann Martin Langenbeck; Conrad von Langenbeck (DE), in 1813, is credited with performing the first carefully planed successful vaginal hysterectomy. It was to remove a cancer (1962).

Walter Burnham (US), on 26 June 1853, performed the first operation for removal of the uterus by abdominal section (hysterectomy) that resulted in recovery (528).

Henry M. Onderdonk (US), in 1813, successfully ligated the femoral artery (2569). 


J.J. Colin (FR), Henri-Francois Gaulthier de Claubry (FR), and Friedrich Strohmeyer (DE) independently discovered that iodine reacts with starch to form a blue color (664, 3284).

Francois-Vincent Raspail (FR) introduced the starch-iodine reaction into botanical microtechnique. He described the distribution of starch in flower, fruit, and embryo of the Gramineae. He also introduced the frozen section technique (101, 2849).

D. Weighton (GB) suggested a mixture of sulfur with lime to treat mildew on fruit trees, later called lime-sulfur (3702).

In 1906, A.B. Corley (US) recommended lime-sulfur spray as a preventive for apple scab. Ref

Benjamin Collins Brodie (GB) reported, “Respecting the functions of the stomach, I divided these nerves [the vagi] in the neck of a dog, for the purpose of ascertaining the influence which they possess on the secretion of the gastric juice…. We may conclude that the suppression of the secretions…sufficiently demonstrate, that the secretions of the stomach and intestines are very much under the control of the nervous system” (462).

Karl Frederich Burdach (DE) observed that, …”in the frog, the little ovum freed from the ovary is carried to the far distant orifice of the oviduct; in birds, however, and in mammals, as in man, the tube is connected to the ovary and, having encircled that, takes that fluid into itself; this movement next is accomplished through the swelling of the tube and the filling of its vessels.” He further noted, “The fetus just produced freely swims in the amniotic liquid” and “…the amnion, in fact, rolled around the umbilicus and investing the fetus, is seen to form the skin” (522, 2320). Amnion comes from the Greek amnos, meaning lamb; named no doubt, in some ancient sheepfold when the ewes were giving birth.

Robert C. Graham (GB) first described a clinical condition later to be called Leriche syndrome (1387).

René Leriche (FR) described a constellation of symptoms in male patients, which became known as Leriche syndrome or aortoiliac occlusive disease. The syndrome consists of the following triad: (a) absent or diminished femoral pulses; (b) intermittent claudication with pallor, coldness and diffuse muscle atrophy of both the lower extremities; and (c) impotence. Leriche believed that segmental atherosclerosis caused this syndrome and proposed that restoration of the blood supply could be curative. He suggested in the 1920s that resection of the obliterated segment and repair with a vascular graft would be the ideal treatment for this syndrome (2029, 2030). 

Jean Kunlin (FR) realized Leriche’s prediction when in 1947 he successfully performed the first end-to-side anastomosis using an autogenous venous graft (1931, 1932). Note: because of fibrotic conditions end-to-end anastomoses could not be done on the patient in the 1951 paper. Kunlin had no other choice but end-to-side implantations of the venous graft into the femoral artery above and below the resected area. Thus the bypass graft procedure was born by serendipity.

Jacques Oudot (FR) was the first to resect the terminal aorta for the Leriche syndrome. He replaced the aorta with a preserved 24-day-old homologous aortic graft using end-to-end anastomoses. Six months later, because of thrombosis of the right iliac limb of the graft, Oudot placed a crossover graft from the left distal external iliac to the right external iliac—the first extra-anatomic bypass graft (2596).

Abraham Colles (IE) wrote a paper on treatment of fracture of the carpal extremity of the radius, which was so masterful that this fracture came to be known as a Colles fracture. He treated the fracture with tin splints to stabilize the wrist after closed reduction of the fracture (665).


"Why has not anyone seen that fossils alone gave birth to a theory about the formation of the earth, that without them, no one would have ever dreamed that there were successive epochs in the formation of the globe?" Léopold Chrétien Frédéric Dagobert Cuvier (744)

William Prout (GB) speculated that the atomic weights of all the elements are exact multiples of that of hydrogen or half that of hydrogen (2805).

Jean Baptiste Biot (FR) showed that when organic compounds are liquid or in solution they might, in effect, rotate polarized light either clockwise or counterclockwise. He suggested that this was due to an asymmetry that might exist in the molecules themselves (264). This represents the origin of stereochemistry.

Jean Baptiste Biot (FR) and Jean-Francois Persoz (FR) gave the name dextrin to the sugar solution produced when starch is hydrolyzed with mineral acids because the resulting solution rotates polarized light to the right (265).

Heinrich August Vogel (DE) discovered that glucose reduces heavy metals dissolved in alkaline solution causing deposition of the metal and oxidation of the glucose. This phenomenon would later be used as the basis for a number of tests for sugars (3486).

Carl A. Trommer (DE) introduced alkaline copper sulfate solution as a sensitive test for glucose (3394).

Hermann Christian Fehling (DE) greatly improved on the sensitivity of Trommer’s test for glucose with his aqueous solution of copper sulfate, sodium tartrate, and sodium hydroxide (1069).

Friedrich August Kekulé von Stradonitz (DE) interpreted this reaction to indicate that glucose is an aldehyde. Ref

Rudolf Fittig (DE) stated that the simple sugars contain aldehyde groups (1149).

Heinrich Kiliani (DE) proved this to be correct (1801).

Konstantin Sigizmundovich Kirchhof; Gottlieb Sigismund Constantin Kirchhof (DE-RU) preformed an experiment, which converted four parts of water, two parts of starch, and malt into a starch paste. This paste began to liquefy into sweet syrup. His results showed that gluten had the capacity to convert a larger quantity of starch into sugar. Thus, Kirchhoff laid the foundation for the discovery of amylase (1810).

Michel-Eugène Chevreul (FR) demonstrated that the sugar from the urine of a diabetic is identical with grape sugar (glucose). This was an important step in recognizing that diabetes is a disease of sugar metabolism (606). 

Abraham Colles (IE) was the first to tie the subclavian artery (666).

Charles Aston Key (GB) successfully ligated the subclavian artery for aneurysm at the axilla (1796).

Johann Friedrich Meckel (called the Younger) (DE) produced a teratology, which was the first comprehensive, analytical description of human congenital birth defects. He was one of the first to recognize that certain defects represent merely the persistence of anatomical conditions that are normal at an earlier stage of the embryo, e.g. cleft palate and ectopia cordis (abnormally superficial position of the heart). Other defects he attributed to local disturbances of growth during embryonic development (2280, 2282).

Francisco Romero (ES), in the opinion of some, became the first heart surgeon when, in 1801, he performed an open pericardiostomy to treat a pericardial effusion. The patient was a 35-year-old farmer named Antonio de Mira from whom five pounds of bloody fluid was drained after which he made a good recovery; going back to work in 4 months. Three years after the operation his only complaint was pain in the incision. Romero presented his work at the Society of the School of Medicine in Paris in 1815 (55, 3237).

Henry C. Dalton (US) sutured a pericardial wound. The operation took place on September 6, 1891 (754).

Daniel Hale Williams (US), on 9 July, 1893, treated a stab wound victim by sewing up a tear in the pericardium but leaving the heart muscle itself alone, allowing a small nick there — about one tenth of an inch in length — to heal on its own (3751). This does not qualify as open-heart surgery.

Benjamin Winslow Dudley (US), a remarkable surgeon in “rural” Kentucky, performed 225 lithotomies, the first 100 without death, successfully trephinated the skull in five patients, and successfully ligated the subclavian artery for axillary aneurysm and the common carotid for an intracranial aneurysm.

While Dudley was professor of anatomy and surgery in the medical department of Transylvania University in Lexington, it was considered equal to the best medical schools in the east. As a youth he managed to study with a local practitioner on the Kentucky frontier then graduate with an M.D. degree from the University of Pennsylvania, in 1806. After a brief period of practice in Kentucky he raised the funds to send himself to Europe where he studied with many of the medical luminaries of his time before returning to Lexington, Kentucky (919, 2213).

Guillaume Dupuytren (FR) successfully ligated the external iliac, 1815 (940).

Jacques Lisfranc (FR) devised an operation for partial amputation of the foot at the tarsometatarsal articulation (2092).

Jean Etienne Dominique Esquirol (FR) distinguished between “petit mal” and “grand mal” (1042).


John Vaughan Thompson (IE), in 1816, trailed a fine muslin hoop net in the seas off Madagascar to collect small life forms. See, Thompson, 1829.

John Cranch (GB) almost simultaneously used fine nets to collect small aquatic life forms during the James Kingston Tackey expedition to the river Zaire (Congo) (2007). Thompson and Cranch were possibly the first to collect and describe plankton.

Jean Vincent Félix Lamouroux (FR) described marine hydrozoa and bryozoa (1954).

William Jackson Hooker (GB) wrote British Jungermanniae, which established hepaticology (the study of liverworts) as an independent discipline (1625). He became director of Royal Botanic Gardens, Kew, in 1841. An energetic director, he and his son, Joseph Dalton Hooker, oversaw a rapid growth in the garden's library and land holdings taking it to a world-famous status. Joseph Dalton Hooker became director in 1865.

William Prout (GB) showed that the urine of a boa constrictor contains 90 percent uric acid (2806).

William Prout (GB) discovered that uric acid reacts with ammonia to yield murexide, which has a violet color. This color reaction became the basis for a delicate test for uric acid (2807).

René-Joachim-Henri Dutrochet (FR) demonstrated the analogy between the fetal envelopes in ovipara and vivipara suggesting a unity of the main features in the development of animals (952).

Karl Ferdinand von Graefe (PL-DE), in 1816, and Philbert Roux (FR), in 1819, independently performed the first closure of congenital cleft soft palate (3255, 3543).

Marie-Jules-César Lelorgne de Savigny (FR) established the homology of the jaws with other appendages of all insects whether biting or sucking (826).

Martin Heinrich Rathke (DE) in a paper on the isopod, Asellus, then on many other invertebrates, recognized that antennae, jaws, and feet exhibit developmental homology (2862, 2864).

John King (US), in 1816, operated for abdominal pregnancy, saving both mother and child (1805). 


The first great cholera pandemic of the 19th century swept Asia, probably originating near Calcutta and spreading from there throughout Southeast Asia, Japan and China. The death toll from this outbreak is not known, however, based on the 10,000-recorded deaths among British troops, researchers estimate that hundreds of thousands across India succumbed to the disease. In 1820, 100,000 people died on the Indonesian island of Java alone. Although it spread as far as Southern Russia and the Middle East, an exceptionally cold winter in 1823-24 kept it from reaching Western Europe (1863).


“Nature has neither core nor shell; she is everything at once.” Johann Wolfgang von Goethe (3534)

Pierre-Jean Robiquet (FR) was the first to note the chemical nature of narcotine and isolate it in a pure state (2953).

Francois Magendie (FR) isolated emetine (2192).

Edward Bright Vedder (US) was the first to demonstrate the value of emetine in the treatment of amoebic dysentery (3451). 

Leonard Rogers (GB) established the clinical use of emetine in the treatment of amoebic dysentery (2959, 2960). 

Pierre-Joseph Pelletier (FR) and Joseph-Bienaimé Caventou (FR) isolated and named chlorophyll (chlorophyll, Greek, green leaf) (2712).

Amos Eaton (US) wrote his Manual of Botany for the Northern States, which was an important predecessor of Gray's Manual (964). 

Leopold Gmelin (DE) described the bile acids and developed the Gmelin Test for detecting the presence of bile pigments (3353). He was also the first to apply the names ester and ketone to two classes of organic compounds. His most notable contribution, however, was the Handbuch der Chemie, first published in a 2-volume version in 1817 and 1819 and later enlarged to 13 volumes. The work was translated into English as Handbook of Chemistry (19 vol., 1848-71) (1314).

Thomas Bateman (GB) and Robert Willan (GB) first described and later assigned a name to molluscum contagiosum, a cutaneous and mucosal eruption of a contagious nature (133, 134).

William Henderson (GB) and Robert Paterson (GB) described the intracytoplasmic inclusion bodies now known as molluscum bodies or Henderson-Paterson bodies (482, 1537, 2697).

Max Juliusburg (DE), Udo J. Wile (US), and Lyle B. Kingery (US) were able to extract filterable virus from lesions of molluscum contagiosum and show transmissibility (1762, 3743).

Ernest William Goodpasture (US) later described the similarities of molluscum and vaccinia (1367).

Henry Jacob Bigelow (US) compiled a survey of the medicinal plants of the United States. It was one of the first two books in America to include plates printed in color (252). Bigelow also co-authored the first national pharmacopoeia in 1820. 

Alexander John Gaspard Marcet (CH-GB) found xanthine in kidney stones—naming it xanthic oxide (2227).

Karl Friedridi Philipp Martius (DE) was the first to describe the hyphomycetes (2251).

Christian Heinrich Pander (LV), from his study of over a thousand chick eggs announced the trilaminar structure of the chick blastoderm, a terminology that he coined. He suggested that developing chick embryos contain three germ layers. The delamination of the blastoderm (young embryo) results in the formation of the mucous membrane (endoderm) and the serous membrane (ectoderm). The serous membrane undergoes delamination, giving rise to a third layer, the vascular membrane (mesoderm) (2628, 2629).

Francois Magendie (FR) wrote the first modern physiology textbook in which the importance of nitrogenous foods (protein) in the diet of mammals was demonstrated (2191).

James Parkinson (GB) wrote a little known medical monograph entitled Observations on the Nature and Cure of Gout, however, his Essay on the Shaking Palsy gained him immortality in the annals of medicine. He described what became known as Parkinson’s disease thus, “Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards, and to pass from a walking to a running pace: the senses and intellect being uninjured” (2642, 2643).

Jean-Martin Charcot (FR) and Edme Félix Alfred Vulpian (FR), four decades later, added rigidity to Parkinson's excellent clinical description and attached the name la maladie de Parkinson [Parkinson's disease] to the syndrome (597, 598).

Edouard Brissaud (FR) and Henry Meige (FR) suggested that paralysis agitans (Parkinson’s) might be due to a vascular lesion in the substantia nigrans of the mid-brain (454).

Constantin Trétiakoff (FR) provided pathological evidence, which supported Brissaud’s suggestion (3388).

Charles Foix (FR) and Jean Nicolesco (FR) showed that the specific lesions in Parkinson’s disease are in the substantia nigra of the mid-brain (1177, 1178).

Herbert Ehringer (AT) and Oleh Hornykiewicz (AT) showed that brain dopamine is lower than normal in Parkinson's disease patients (986).

Walther Birkmayer (AT) and Oleh Hornykiewicz (AT) injected Parkinson’s disease patients with L-DOPA thereby producing a spectacular improvement of all motor deficits of the patients (269).

Oleh Hornykiewicz (AT) proved the existence of a nigro-striatal dopamine pathway in the human brain (1637).

George Constantin Cotzias (GR-US), Paul S. Papavasiliou (US), and Rosemary Gellene (US) demonstrated the effectiveness of accommodating patients to large daily dosages of L-DOPA in the treatment of Parkinson's disease (706, 707).

Jan J. Korten (NL), Antoine Keyser (NL), Ed M.G. Joosten (NL), Fons J.M. Gabreëls (NL), and Eileen Critchley (GB) introduced the use of carbidopa (Sinemet) as a treatment for Parkinson's disease (3, 723, 1872).

Eric Olaf Backlund (SE), Per-Ola Granberg (SE), Bertil Hamberger (SE), Evert Knutsson (SE), Anders Martensson (SE), Göran C. Sedvall (SE), Ake Sieger (SE), and Lars Olson (SE) surgically transplanted parts of the adrenal medulla autologously into the brain of a patient with severe Parkinson's disease (87). The results have been promising.

Mihael H. Polymeropoulos (GR-US), Christian Lavedan (US), Elizabeth Leroy (US), Susan E. Ide (US), Anindya Dehejia (US), Amalia Dutra (US), Brian Pike (US), Holly Root (US), Jeffrey Rubenstein (US), Rebecca Boyer (US), Edward S. Stenroos (US), Settara Chandrasekharappa (IN-US), Aglaia Athanassiadou (GR), Theodore Papapetropoulos (GR), William G. Johnson (US), Alice M. Lazzarini (US), Roger C. Duvoisin (US), Giuseppe Di Iorio (IT), Lawrence I. Golbe (US), and Robert L. Nussbaum (US) discovered a mutation in the alpha-synuclein gene identified in families with Parkinson's disease (2772). 

Thomas Bateman (GB) and Robert Willan (GB) described the nature of recurrent herpes simplex virus infection accurately as “a restricted group of localized vesicles with a short, self-limited course”. This publication was particularly important because it contained descriptions of herpes iris (now known as erythema multiforme) and eczema due to external irritation. It also contained descriptions of molluscum contagiosum (134).

M. Houssard (FR) described chronic subdural hematoma which he thought was of inflammatory origin (1645). Chronic subdural hematoma had been recognized by Wepfer in 1657.

The first issue of the Journal of the Academy of Natural Sciences of Philadelphia was published. It is the first natural history journal from North America.


Jöns Jakob Berzelius (SE) discovered selenium (232).

Pierre-Joseph Pelletier (FR) and Joseph-Biènaimé Caventou (FR) reported the isolation of pure strychnine from the beans of Strychnos ignatii (Saint Ignatius’s bean) and Strychnos nux vomica (2713, 2714).

Michel-Eugène Chevreul (FR) identified what he called cholestérine (cholesterol) (Gk. Chole, bile + stereos, solid) as an unsaponifiable fat (607).

Georg August Goldfuss (DE) coined the name Protozoa (Gk, protos, first, zoon, animal) but he did not restrict it just to the protozoa as we know them today (1323).

Giovanni Battista Amici (IT) described circulating protoplasm in Chara cells (41).

Pieter de Riemer (NL) appears to have been the first to freeze tissues in order to permit fine sectioning and to use anatomical sections for anatomical illustration (825).

Thomas Nutall (GB), while in North America, worked on the Torrey and Gray Flora of North America, and three volumes of an updated version of F. Andrew Michaux's North American Sylva. His Genera of North American Plants and a Catalogue of the Species of the Year 1817 was the first of its kind prepared by an on-the-spot American botanist (1713, 2539).

Étienne Geoffroy Saint-Hilaire (FR) wrote Philosophie Anatomique, in which he asked the question: "Can the organization of vertebrated animals be referred to one uniform type?" The answer for Geoffroy was yes: he saw all vertebrates as modifications of a single archetype, a single form. Vestigial organs and embryonic transformations might serve no functional purpose, but they indicated the common derivation of an animal from its archetype. Geoffroy spent much time drawing up rules for deciding when structures in two different organisms were variants of the same type -- in modern terminology, when they were homologous. He observed the way embryos develop in different animals and that the central nervous system of an insect lies along its belly while that of a human lies along its back. From this he theorized that they represented two lineages from a common ancestor (3017). This work provided important evidence, which Darwin used in his On the Origin of Species by Means of Natural Selection

Christian Gottfried Ehrenberg (DE) while studying Syzygites megalocarpus (Sporodina grandis) described the fungal zygospore for the first time. This was the first recognition of sex in the fungi (981).

John Cheyne (GB) and William Stokes (IE) described what came to be called Cheyne-Stokes respiration. This is characterized by breathing with rhythmical variations in intensity, i.e., occurring in cycles (610, 3272).

Camille Biot (FR) described an abnormal pattern of breathing characterized by groups of quick, shallow inspirations followed by regular or irregular periods of apnea. In common medical practice, Biot's respiration is often clinically equivalent to Cheyne-Stokes respiration (263). Note: This breathing pattern is seen in medullary compression of the brain, the Biot sign.

Valentine Mott (US) was the first to ligate the innominate artery for aneurysm. The patient was a fifty-seven year old sailor at New York Hospital. The anesthesia administered was a drink containing seventy drops of tincture of opium. The patient survived for twenty-five days (2398).

Elias S. Cooper (US) removed the medial end of the clavicle and a portion of the upper end of the sternum to improve the exposure to the innominate artery, this being the first time this valuable maneuver was employed during ligation of the innominate. The patient was treated for a combined aneurysm of the common carotid and subclavian arteries. He survived for nine days postoperative (689).

Andrew Woods Smyth (US) was the first surgeon to report long-term survival after ligation of the innominate artery. The operation took place at the Charity Hospital in New Orleans on 15 May 1864. Dr. Smyth ligated the right common carotid and the innominate for an aneurysm of the right subclavian artery in a 32 year-old mulatto man. The patient survived for eleven years (3207).

Astley Paston Cooper (GB) successfully ligated the common carotid and the external iliac arteries for aneurysms. In 1817, he performed the first recorded case of ligation of the aorta for aneurysm. The patient's right leg remained viable, but the left leg was totally ischemic, livid, and cold, and the patient died 40 hours later. Cooper’s fascia (the fascia transversalis) and Cooper’s hernia (retroperitoneal hernia) are named to commemorate him. He developed widely followed methods of treating dislocations and fractures (682-688).

Guillaume Dupuytren (FR) was the first to successfully treat aneurysm by compression (937).


Theodor von Grotthuss; Theodor Christian Johann Dietrich von Grotthuss (DE) was the first to recognize that light can bring about some chemical reactions as it is absorbed by molecules (3545).

 John William Draper (GB-US) rediscovered that light could bring about some chemical reactions as molecules absorb it (894). The Draper-Grotthuss law is an expression of their discovery.

Nicolas Clement (FR) and Charles Desormes (FR) performed experiments between 1819-1824) which led to the introduction of the term calorie for the unit of heat (29). Their calorie was a kg-calorie (modern kcal). It was defined as the quantity of heat to raise a kg of water by 1 degree C. About 1929 this definition was superseded when a committee of the British Academy of Sciences proposed the g-calorie as an alternate unit of energy (2032).

Henri Braconnot (FR) boiled various plant products such as sawdust, linen, and bark with acid and from the process obtained glucose (391). This had previously been obtained by the boiling of starch with acid. See, Kirchhof, 1815.

It was easy to decide that the molecule of starch was built up out of glucose units and that in many plants there must be some nonstarch material that was also built up out of glucose units. It was this nonstarch material that he was breaking down.

Louis Jacques Thénard (FR) is credited with the discovery of hydrogen peroxide, the enzyme catalase, and being the first to analyze an enzymatic reaction quantitatively (3313).

Oscar Loew (US) is also credited with the discovery of catalase. See, Oscar Loew, 1901.

James Batcheller Sumner (US) and Alexander L. Dounce (US) crystallized catalase (3289).

Joseph Louis Proust (FR) was the first to isolate leucine. It came from among the fermentation products of milk. He called it oxyde caséique (2804).

Henri Braconnot (FR) isolated and named leucine (Gk. leukos, white) from muscle tissue and wool (392).

Gerardus Johannes Mulder; Gerrit Jan Mulder (NL) was the first to secure leucine in relatively pure form and assign to it a correct formula (2416, 2418). Leucine was proved to be aminoisocaproic acid in 1891.

Pierre-Joseph Pelletier (FR) and Joseph-Bienaimé Caventou (FR) isolated the alkaloids brucine and veratrine (2715).

Simon Rudolph Brandes (DE) isolated atropine in a much purer form (397).

Philipp Lorenz Geiger (DE) and H.F. Mein (DE) purified atropine from belladonna (Atropa belladonna) roots and hyoscyamine from henbane (1296, 2285). Atropine is used to treat thirty plus ailments from hay fever to the tremors of Parkinson’s disease (paralysis agitans). Belladonna gets its name from the fact that at one time ladies used it in eye drops to make their eyes sparkle. It blocks acetylcholine in the musculature of the iris resulting in dilation.

Simon Rudolph Brandes (DE) isolated an impure sample of atropine, an alkaloid, from Atropa belladonna a member of the Solanaceae. He tested its effects on himself and birds (398).

Alfred Ladenburg (DE) isolated the alkaloid hyoscine (scopolamine) from the Solanaceae. It is similar in structure to atropine and hyoscyamine and also blocks acetylcholine (1948).

Louis Adelbert von Chamisso; Louis Charles Adélaiede de Chamissot (DE) used the phrase alteration of generations (metagenesis) when he described the life cycle of tunicates (benthic invertebrates) (3522). 

Johannes Japetus Smith Steenstrup (DK) explained how alternation of asexual and sexual generations occurs among the coelenterates, trematodes, and tunicates (3251, 3252). He is commemorated by Steenstrupia Forbes, 1846; Onchnesoma steenstrupi Koren & Danielssen, 1875; Lepidophyllum steenstrupi Odhner, 1902; Melinnacheres steenstrupi Bresciani & Lützen, 1961; Prionospio steenstrupi Malmgren, 1867; Myxicola steenstrupi Krøyer, 1856; Mimonectes steenstrupii Bovallius, 1885; Hesione steenstrupii de Quatrefages, 1866.

Karl Asmund Rudolphi (SE-DE) was the first to describe dicroceliasis in man. This is an infection, usually of the biliary duct, by the trematode fluke Dicrocoelium dendriticum, which Rudolphi named (2992, 2993).

Arthur Looss (DE) discovered D. hospos (2127).

Wendell H. Krull (US) and Cortland R. Mapes (US) published the full life cycle in a series of papers from 1951-1953 detailing their observations and experiments. It was known that D. dendriticum affected sheep, but everything else was a mystery. The first link in the chain was the discovery of the first intermediate host, the land snail Cochlicopa lubrica (synonym: Cionella lubrica). Next came the discovery that the slime balls coughed up by the snails could be a potential method of transfer of the parasite. Shortly thereafter, the ant, Formica fusca was found to be the second intermediate host by which sheep were infected (1912).

Charles Turner Thackrah (GB) found that blood collected after flowing over tissues, say in an open wound, coagulated more quickly than if the blood had been drawn directly from the blood vessel (3308, 3309). This was the first reported evidence for what William Henry Howell (US) would name tissue factor and Pierre Nolf (FR) would name thromboplastic substance (1649, 1650, 2524).

John Bostock (GB) gave an excellent clinical description of hay fever (summer catarrh) (332).

René-Théophile-Hyacinthe Laënnec (FR) was the first to realize that damage in the lungs and small grey nodules scattered throughout the body are both manifestations of pulmonary tuberculosis. In 1816, he invented the stethoscope (Gk. the chest, to look at), an instrument whose use for listening to the chest was popularized by Nikolai Sergeievich Korotkoff (RU). Laënnec coined words like rales, bronchophony, pectoriloquy, and egophany. He described the symptomology, the clinical course, the physical findings, and the pathological anatomy of pneumonia, apoplexy of the lungs, gangrene, emphysema, cysts of the lung, tuberculosis, pleurisy, pleural effusion, pneumo-thorax, edema of the lungs, pulmonary tuberculosis, pulmonary abscess and gangrene, bronchiectasis, infarction, vesicular and bronchial breathing, amphoric and cracked-pot resonance, metallic tinkling, presystolic thrill which he described but misunderstood, and alcoholic cirrhosis of the liver which he described and christened. He was the first to recognize the unity of the tuberculosis condition, which had previously been thought to be a number of different diseases. He noted variations in the heart’s contractions with or without palpable pulse reflecting atrial fibrillation (1949-1951).

Karl Frederich Burdach (DE) named the globus pallelus or globus pallidus (pale clump) and the putamen (shell), and described in detail the fasciculus gracilis. He will be remembered as a neuroanatomist with his name associated as in Burdach’s fiber, fissure, nucleus, and tract. He named claustrum, brachium conjunctivum (superior cerebellar peduncle), and the cuneus. Finally, he localized vision in the posterior part of the brain and assigned the sensation of consciousness to the thalamic region of the brain (523).

William Benjamin Carpenter (GB) would take this idea further when he linked the thalamus with the cerebral cortex by saying, “The Sensory Ganglia constitute the seat of consciousness not merely for impressions on the Organ of Sense, but also for changes in the cortical substance of the cerebrum so that until the latter have reacted downwards upon the Sensorium, we have no consciousness either of the formation of ideas, or of any intellectual process of which these may be the subjects” (562).

George N. Thompson (US) and Johannes M. Nielsen (US) “concluded that the engramme system essential to crude consciousness is located where the mesencephalon, subthalamus, and hypothalamus meet” (3324).

Philbert-Joseph Roux (FR) performed the first staphylorrhaphy (surgical closure of a cleft palate) in 1819 (2979).

Guillaume Dupuytren (FR) successfully ligated the subclavian artery (938).

The American Journal of Science was founded.


Eleven physicians meet in Washington, D.C., to establish the U.S. Pharmacopeia, the first compendium of standard drugs for the United States. Only 217 drugs that met the criteria of “most fully established and best understood” were admitted.

Pierre-Joseph Pelletier (FR) and Joseph-Bienaimé Caventou (FR) isolated and purified the alkaloid colchicine, which they extracted from meadow saffron (Colchicum autumnale), also called autumn crocus (2716).

John Want (GB) discovered that colchic (colchicine) from Colchicum autumnalis was the secret ingredient in “medicinal water” used to treat gout (3674). 

Alfred Houdé (FR), in 1884, obtained a crystallized preparation of colchicine (1644).

Friedlieb Ferdinand Runge (DE) isolated an alkaloid stimulant from mocha beans and named it caffeine (2995).

Pierre-Joseph Pelletier (FR) isolated caffeine from coffee beans (2710).

Hermann Emil Fischer (DE) and Lorenz Ach (DE) synthesized caffeine (1141).

Henri Braconnot (FR) isolated what he called sucre de gélatine (later named glycocolle, then glycine) by heating gelatin in the presence of dilute sulfuric acid. Initially he thought glycine was a sugar because of its sweet taste (392). This was the first instance in which a pure amino acid was obtained from a protein by acid hydrolysis. Glycine is also called aminoacetic acid.

Auguste Laurent (FR) determined the correct empirical formula for the amino acid glycine (1990).

William Henry Perkin (GB) and Baldwin F. Duppa (GB) synthesized glycine by treating bromoacetic acid with ammonia. This was the first amino acid to be manufactured (2720).

Robert Brainard Corey (US) and Gustav Albrecht (US) determined the structure of the amino acid, glycine. This was the first amino acid structure solved (693).

Frederick Christian Accum (DE), working in England, wrote a treatise in which he described the numerous kinds of food adulteration practiced at the time and the various methods available to detect them. This treatise had an impact on most of the civilized world and spawned a generation of books on the subject in England, the United States, and Europe. Ultimately, it resulted in the modern era of food regulatory statutes (8). Thomas Wakeley (GB), Member of Parliament and founder and editor of The Lancet, set up a sanitary commission whose findings led to the passage of the Adulteration Act and Sale of Food and Drugs Act. 

Christian Friedrich Nasse (DE) formulated Nasse's law: hemophilia occurs only in males and is passed on by unaffected females (2471).

Johann Lukas Schönlein (DE) coined the term hemophilia (3093). 

William Norris (GB) noted that fungoid disease (melanoma), a pigmented skin cell cancer, was especially prevalent in one family under study. This of course suggested a familial influence on the appearance of the cancer (2528).

Charles Robert Harington (GB) and George Barger (GB) determined the structure of thyroxine and synthesized it (1488).

Martin Heinrich Rathke (DE) reported on the embryonic development of the genital and urinary organs (2855, 2860).

Robert Gooch (GB) described postpartum psychosis (1365).


Stephen Elliott (US) authored the remarkable, A Sketch of the Botany of South Carolina and Georgia (1008). He is commemorated by the genus Elliottia.

Johann Friederich Meckel (called the Younger) (DE) proposed that higher animals, during their development, pass through the stages of lower animals, through which periodical and class differences can be traced (2281).

Jean-Antoine Colladon (CH) observed what is now recognized as dominance when he crossed grey and white mice and found that their offspring were always either grey or white, but never intermediates. He continued these experiments as far as the third generation and it is evident that what he was doing was to make back-crosses between heterozygous grey mice and homozygous recessive white mice; but the absence of blending, itself a discovery, led him to conclude that grey mice and white mice were different species (805, 824). Some consider this the discovery of the law of hybridization.

Pierre-Fidèle Bretonneau (FR) proposed the general theory that different diseases are due to different specific causes. He said, “The specificity of diseases is proved by such a mass of facts, and there is probably no truth better demonstrated and more fruitful.” This concept is often referred to as the doctrine of etiological specificity. In 1821, he read a paper before the Paris Académie de Médecine in which he concluded that a sizable epidemic of throat distemper which occurred in and about Tours, France in 1819 was due to a specific disease, characterized by the formation of a false membrane in the respiratory tract. He asserted that croup, malignant angina, and scorbutic gangrene of the gums were all the same malady, a specific disease, for which he proposed the name diphtheritis, because of the unique membrane in the throat, clearly differentiating it from other afflictions of the throat. Diphtheritis is derived from two Greek words, one meaning skin or membrane and the other meaning inflammation. Later the designation was changed to diphtheria, the term by which the disease is known today. Bretonneau said, “it is vain to deny that contagion, if not the source of epidemics, is the source of most epidemics.” He also demonstrated the typical ulcers on Peyer’s patches in cases of typhoid fever and differentiated these from tuberculous lesions (412, 413).

Antonio Scarpa (IT) provides a classic description of sliding hernia, or hernia of the large bowel (3049).

Valentine Mott (US), in 1821, excised the right side of the lower jaw, after ligating the carotid artery (2399).

Charles Waterton (GB) opened the world's first nature reserve on the grounds of his estate at Walton Hall near Wakefield, England.

Le Journal de Physiologie Expérimentale was founded. It is the first periodical devoted exclusively to physiology (2213).


Bernard Gaspard (FR) thoroughly investigated the process of putrefaction in animals. At this time, putrefaction was believed to be intimately associated with the development of septicemia, pyemia, putrid infection, and putrid intoxication. It was supposed that these conditions were due to the absorption of putrid substances into the blood stream. The injection of putrid matter into an animal invariably led to illness or death (1276, 1277). Note: The modern definition of putrefaction is the enzymatic decomposition of organic matter, especially proteins, by anaerobic microorganisms, with formation of malodorous substances such as indole, skatole, cadaverine, and putrescine. Pyemia is the disease state due to the presence of pyogenic microorganisms in the blood and the formation, wherever these organisms lodge, of embolic or metastatic abscesses. Septicemia, or septicemia, is a severe bacteremic infection usually involving invasion of the bloodstream. Sepsis is the poisoning of an individual by products of putrefaction, or a severe toxic febrile state resulting from infection with pyogenic microbes, with or without septicemia.

Francois Magendie (FR) introduced to medicine the effects and uses of morphine, veratrine, brucine, piperine, emetine, as well as quinine, and strychnine (2194, 2197).

Herbert Mayo (GB) assigned the motor nerve fibers of the face muscles to the VIIth nerve, the facial nerve, and common sensibility to the Vth nerve, the trigeminus (2269).

Pierre Salomon Ségalas d'Etchepare (FR) found that polyuria follows an injection of urea (3157).

Friedrich Wöhler (DE) was the first to introduce the idea that the role of the kidney is to keep in equilibrium the blood content of water and of those substances, which appear in the urine. He observed that the blood is alkaline while the urine is acid; the urine becomes alkaline after the ingestion of the salts of organic acids; the solutes of the urine are excreted independently of one another; and an excess of solute in the urine entails an increased excretion of water (3782). This work is the origin of the concept of osmotic diuresis.

Charles Chossat (FR) found a connection between urinary water excretion and the excretion of “animal substances,” that is, those containing nitrogen (614). 

Friedrich G. Goll (CH), Karl Friedrich Wilhelm Ludwig (DE), and Max Hermann (AT) showed that urine flow could be stopped by lowering the blood pressure by either bleeding, compression of the renal artery, stimulation of the vagus, or by cutting the spinal cord and that diuresis results from a rise of blood pressure (1359, 1558).

Charles Robert Richet (FR) and Robert Mustard-Martin (FR) revealed that: intravenous lactose, saccharose, levulose, and dextrose each caused the immediate appearance of the sugar in the urine, followed by an increase in urine flow within the first minute (2924, 2925); the polyuria was dependent on the amount of sugar that was injected and not on its concentration (2926).

Charles Eduard Hédon (FR) and J. Arrous (FR) discovered that the diuretic response to the intravenous injection of the same weight of various sugars is proportional to their molar concentration (1517).

Emile Charles Achard (FR) and Joseph Castaigne (FR) developed a urinary test using methylene blue dye to examine kidney function. The criterion used was to find the percentage of dye, injected subcutaneously, that showed up in the urine within a 24-hour period (9).

Hermann Strauss (DE), Georges Fernand Isidore Widal (FR), André Lemierre (FR), and Adolphe Javal (FR) concluded that edema is due solely to the urinary retention of sodium chloride and introduced the low sodium diet for congestive heart failure (3281, 3282, 3736-3739).

Leo Ambard (FR) provided a way to globally evaluate renal function by using the ratio plasma urea/urine urea output. This Ambard's Constant is the initial step of the concept of clearance (40).

Karl Friedrich Burdach (DE), in 1822, named the cingular gyrus (the collosal convolution) and distinguished lateral and medial geniculate (knee -like bends) (523).

Jean Zuléma Amussat (FR) was one of the inventors of lithotripsy (43).

James Carson (GB) discussed the value of induced pneumothorax for the treatment of a diseased lung (565).

Carlo Forlanini (IT) proposed that ablation of the lung or artificial pneumothorax could be a positive contribution to the therapy of phthisis (tuberculosis) (1187).

William Cayley (GB) used artificial pneumothorax induced by pleural incision to treat intractable hemoptysis (573).

Samuel Jackson (US) mentions what later became known as Korsakoff’s psychosis in a review of the peripheral neuritis of alcoholism (1719).

 Sergei Sergeievich Korsakoff; Sergei Sergeyevich Korsakov (RU) emphasized the association of alcoholic polyneuropathy with a specific pattern of mental disturbance— Korsakoff’s psychosis— as follows: "This mental disorder appears at times in the form of sharply delineated irritable weakness of the mental sphere, at times in the form of confusion with characteristic mistakes in orientation for place, time and situation, and at times as an almost pure form of acute amnesia, where the recent memory is most severely involved, while the remote memory is well preserved . . . Some have suffered so widespread memory loss that they literally forget everything immediately.” This syndrome is characterized by a severe memory defect, especially for recent events, for which the patient compensates by confabulation (1869). Korsakoff wrote on paranoia (paranoia hyperphantastica as he described it in his textbook) and classified psychiatric illnesses (1870). Known as a humanitarian, he improved conditions in mental institutions. He was the first great psychiatrist in Russia. He is considered a moral genius, as were Philippe Pinel (FR) and Jean-Martin Charcot (FR).

Alexandre-Francois Ollivier (FR) produced experimental hospital gangrene by autoinfection (2566).

Jean-Baptiste-Julien d' Omalius d'Halloy (BE) first used the term Terrain Cretace (Cretaceous Period) to describe chalk and greensand of Northern France (2567, 2568). The Cretaceous is usually noted for being the last portion of the Age of Dinosaurs, but that does not mean that new kinds of dinosaurs did not appear then.

William Daniel Conybeare (GB) and William Phillips (GB) named the Carboniferous Period in their book Outlines of Geology of England and Wales (678).

William Buckland (GB) published an account of how ancient hyenas lived and fed, based on their fossil remains. This is one of the first descriptions of living habits based on fossil evidence (509).

Gideon Algernon Mantell (GB), although an amateur paleontologist, discovered and described from Cretaceous England many fossilized animals including: Megalosaurus, Iguanodon, Pelorosaurus— the first discovered brachiosaur—and Hylaeosaurus (2223, 2224).

The German scientific society Versammlungen Deutscher Naturforscher und Ärzte was founded at Leipzig.


Johann Wolfgang Döbereiner (DE) discovered that powdered platinum greatly accelerates certain chemical reactions (866).

Jöns Jakob von Berzelius (SE) was to later name this phenomenon katalytische kraft (catalytic power) (3513-3516). The term is coined on page 243 of the 1836b article. See, Fulhame, 1794

Joakim Frederik Schouw (DK) wrote Grundzüge einer Allgemeinen Pflanzengeographie in which he divided the vegetation of Europe into twenty-two botanical regions, and, thereby became a co-founder of scientific phytogeography (3096).

Thomas Stewart Traill (GB) made the first attempt to determine the fat content of human blood. He found 4.5% of liquid fat in his sample (3375). Audubon named the Traill's Flycatcher after him.

Herbert Mayo (GB) discovered that the optic tubercles and the crura of the brain give the pupillary reflex when the stump of the optic nerve is irritated (2270).

Alexander John Gaspard Marcet (CH-GB) gave the earliest description of a case of what would later be called alcaptonuria. It was in a male infant 17 months of age. The child’s diaper was stained a deep purple color immediately after birth. The urine turned black soon after being voided and exposed to the air. It exhibited rapid blackening with alkalies and a failure of acids to restore the original color (2228).

Léon Rostan (FR) suggested that cerebral softening might be caused by defective arterial supply to the brain. He said, “…this change in the brain seems often to be a senile degeneration, showing great similarity to the gangrene of old age. As in the latter disease cerebral softening appears to be a disorganization in which the vessels designed to bring blood and life to the affected organs are ossified…by the process of old age.” He pointed out that cerebral softening may be confined to the cortex of the brain and that this malady is accompanied by loss of memory, loss of voluntary movement, mental derangement, senile dementia, and finally by complete coma (2972).

Charles-Édouard Brown-Séquard (FR) proved that cerebral activity is dependent on oxygen provided by circulating blood (488).

Guillaume Dupuytren (FR) was the first to treat wry neck by subcutaneous section of the sternomastoid muscle, 1822 (77). See, Valentine Mott, 1818.

George James Guthrie (GB) wrote the first systematic English textbook on ophthalmic surgery (1451).

William Buckland (GB) found within the Paviland Cave on the south coast of the Gower peninsula, South Wales a human skeleton covered with red ocher and ceremonially buried, with ivory ornaments and perforated seashells, the circumstances hinting at a ritual or shamanic use of the site. He thought it dated from the Roman occupation and called it the Red Lady (510). It would later be identified as Cro-Magnon and dated from roughly 30,000 - 20,000 years ago, the Early Upper Paleolithic (Early Stone Age).

The medical journal The Lancet was founded (2138).


James Edward Smith (GB), William Jackson Hooker (GB), and Miles Joseph Berkeley (GB) published their book, The English Flora, to which Berkeley contributed 155 fungus genera, 1,360 species, many of them new (3202).


Nicolas Léonard Sadi Carnot (FR) was the first to consider quantitatively the manner in which heat and work are interconnected. He was thus the founder of thermodynamics (559).

Hugo von Mohl (DE) provided a clear account of the monocot vascular bundle. In doing so, he concluded that the tissues in the vascular bundles are the same as in dicots; the difference is only in that they are arranged differently (3604, 3609). 

René-Joachim-Henri Dutrochet (FR) described the movement of vesicular globules (leukocytes) from the vascular lumen to the extravascular space in the transilluminated tadpole tail (953).

Julius Friedrich Cohnheim (DE) suggested that endothelial cells participated in this process and that the migrated leukocytes form pus at the site of injury (657).

John Goss (GB) observed segregation of a recessive trait in peas, but failed to note numerical ratios. In the same year, Alexander Seton (GB) published similar observations (1376, 3162).

Moritz Herold (DE) was the first to do considerable original work on the embryonic development of a division of the invertebrates—the aranea (spiders) (1559).

James Scarth Combe (GB) was the first to describe a case of what would later be called pernicious anemia (669).

Thomas Addison (GB) and Hermann Lebert (DE) independently described idiopathic or pernicious anemia based on single cases. Addison called it melasma suprarenale (13-15, 2009).

Michael Anton Biermer (DE) provided the classic description of pernicious anemia (pernicious because no remedy could be found) characterized by anemia, general languor and debility, remarkable feebleness of the heart's action, irritability of the stomach, and a peculiar change of the color in the skin resulting from the deterioration of the adrenal cortex (249, 250).

William Gardner (CA) and William Osler (CA) wrote a thorough and classic account of pernicious anemia (1261). This is the first complete account of pernicious anemia and beyond question the first major achievement of clinical endocrinology.

George Richards Minot (US) and William Parry Murphy (US) demonstrated that adding liver to their diet could successfully treat patients suffering from pernicious anemia. They suspected that a dietary deficiency of some vitamin was the root cause of the disease (2354, 2452).

William Bosworth Castle (US) and Thomas Hale Ham (US) showed that the substance responsible for preventing pernicious anemia arises from the combination of an intrinsic factor in the gastric juice and an extrinsic factor in the diet. This antianemic factor is stored in the liver (569, 570). Castle called the essential gastric secretion "intrinsic factor" because it is formed in the body.

Lucy Wills (GB) described treatment of pernicious anemia of pregnancy and tropical macrocytic anemia, with special reference to yeast extract (folic acid) as a curative agent (3755).

Tom Douglas Spies (US), Carl F. Vitter (US), Mary B. Koch (US), Margaret H. Caldwell (US) experimentally proved that folic acid from yeast extract is the curative agent for macrocytic anemia (3233).

Lionel Berk (US), William Bosworth Castle (US), Arnold D. Welch (US), Robert W. Heinle (US), Rudolf Anker (US) and Martin Epstein (US) found that absence of gastric juice carrying intrinsic factor would fail to activate and protect vitamin B12 thus leading to pernicious anemia (180). 

This intrinsic factor was subsequently found to be a glycoprotein with which vitamin B12 (cyanocobalamin) must combine to be absorbed by the gut. Intrinsic factor is secreted by parietal cells of the gastric glands in the stomach, where it binds with the vitamin. Thus bound, intrinsic factor protects vitamin B12 from digestion as it passes through the gastrointestinal tract. See, Grasbeck, 1965.

Horace Albert Barker (US), Herbert Weissbach (US), and R.D. Smyth (US) isolated several forms of the B12 coenzyme in pure form and showed that it contained the elements of adenine and a pentose linked to the corrinoid (123).

Mary Shaw Shorb (US) showed that there is a direct relationship between the ability of liver extracts to cure pernicious anemia and their ability to stimulate the growth of the microorganism Lactobacillus lactis Dorner. Thus, a bioassay method was established for what would later prove to be vitamin B12 (3169, 3170).

Edward Lawrence Rickes (US), Norman G. Brink (US), Frank R. Koniuszy (US), Thomas R. Wood (US), and Karl August Folkers (US) were the first to purify, crystallize, and characterize the vitamin B12 (cyanocobalamin) molecule, which surprisingly contains a cyanide group and a cobalt atom (2927). Randolph West (US) clinically verified the ability of the crystalline preparation to arrest Addisonian pernicious anemia (3726).

P. Galen Lenhert (US) and Dorothy Mary Crowfoot Hodgkin (GB) demonstrated by X-ray diffraction analysis that the coenzyme form of B12 was formed by the direct ligation of C-5 of 5′-deoxyadenosine to the Co atom at the center of the corrinoid ring of vitamin B12. This was the first demonstration of the existence of a biologically stable and functional carbon-metal bond (2028).

D. Schuette (DE) was possibly the first to recommend cod liver oil as a treatment for rickets (wrickken = to twist) (2272, 3100). In 1650, Francis Glisson (GB) recommended rachitis—Greek for spine—as the medical term now used (1313).

Pierre Paul Broca (FR) described rickets as a nutritional disease (457).

William Prout (GB) discovered that the stomachs of dogs, rabbits, horses, cats, hares, and humans contain free hydrochloric acid (2808).

Friedrich Heinrich Bidder (LV-DE) and Carl Ernst Heinrich Schmidt (LV-DE), by quantitative analyses of the gastric juice collected by means of a fistula created in different species of live fasting animals, proved that the acid of gastric juice is exclusively hydrochloric acid (247). 

William Frédéric Edwards (GB-FR) studied minimum and maximum temperatures compatible with life; heat production in young animals and adults; resistance of young animals to cold and oxygen deprivation; the importance of humidity, pressure, and movement of air in the loss of heat by transpiration; and the role of light in the development of batrachians (frogs, toads, and newts) (976, 977).

Henry Hill Hickman (GB) used carbon dioxide to anesthetize animals prior to surgery and suggested it use on man (567, 1582).

Jean Civiale (FR), by modifying the primitive lithotrite of Albucasis, introduced a trilable, grasping and fragmenting instrument in 1824. This can be considered the beginning of the use of lithotriptors and ‘endourology’ in stone fragmentation. Henry Bigelow (), in 1874, developed a stronger and harder lithotrite, which was introduced into the bladder with the help of anaesthesia. He filled the bladder, crushed the stones, and evacuated the fragments. This was called litholopaxy. Suddenly, the mortality rate dropped from 25% to 2.4%.

William Buckland (GB) published Notice on the Megalosaurus or giant fossil lizard of Stonesfield. This was the first time a dinosaur fossil was described and named (the term dinosaur did not yet exist). In the same science meeting where he described Megalosaurus Buckland also announced the first fossil mammal from the Age of Reptiles (511). Note: In 1822, Gideon Algernon Mantell (GB) found the fossilized tooth of a Cretaceous animal he would characterize as herbivorous, reptilian, and tens of feet long; he would name it Iguanodon. After he prepared a paper reporting Iguanodon for the Royal Society the aforementioned William Buckland urged Mantell to delay, consequently it was Buckland not Mantell who first published on a dinosaur discovery.  

The Annales des Sciences Naturelles was founded.


Albert Policard (FR) and A. Paillot (FR) were among the first to use epi-illumination fluorescence microscopy (vertically incident exciting light) (2768).

Johan Sebastiaan Ploem (NL) developed epi-illumination with narrow band blue and green light (2764, 2765).

Johan Sebastiaan Ploem (NL) and Hans J. Tanke (NL) popularized epi-illumination using fluorescence microscopy (2766).

Michael Faraday (GB) reported that benzene reacted with chlorine in sunlight to give a solid body and dense, viscous fluid. This was undoubtedly the first sample of technical benzene hexachloride (BHC). He knew nothing of its biological activity (1057).

Teunis van der Linden (NL) was the first to isolate and describe γ-hexachlorcyclohexane (3438). Giovanni Battista Amici The gamma isomer came to be known as lindane in his honor. Lindane (gamma-hexachlorocyclohexane) has been widely used as an antiscabetic and a pediculicidal agent with reasonably good efficacy. Bender mentions the insecticidal properties of hexachlorocyclohexane (HCH) in a patent paper in 1933. HCH was first patented in the 1940s. It should not be confused with benzene hexachloride (BHC), a mixture of various isomers and by-products. Note: Lindane is a nerve poison that interferes with GABA neurotransmitter function.

Augustin Pyramus de Candolle (CH) wrote Mémoires sur la Famille des Léguminenses, the beginning of phylogenetic interpretation of this family (811).

Robert E. Grant (GB) created the name Porifera "pore-bearer" from (L. porus - pore; ferre - to bear) for the sponges. He began his work in 1825, becoming the first great student of the morphology and physiology of the sponges (1396).

Henri-Marie Ducrotay de Blaineville (FR) proposed that Malacozoa replace the name Mollusca. Although this was not adopted the term malacologist survived as the name of one who studies mollusks (806).

Pierre André Latreille (FR) elevated the batrachians (frogs, toads, and newts) into a separate class, the amphibians (1987).

Johannes Evangelista Purkinje; Jan Evangelista Purkyne (CZ) discovered the germinal vesicle (nucleus of the oocyte) in the germ-disk of birds. He was the first to describe the blastula of a fertilized animal egg (bird) (2814, 2816).

Karl Ernst von Baer (EE-DE-RU) discovered the mammalian ovum (3499).

Jean Jacques Marie Cyprien Victor Coste (FR), Jacques Matthieu Delpech (FR), and Thomas Wharton Jones (GB) independently discovered the germinal vesicle (nucleus of the oocyte) in mammals (704, 1755).

Rudolph Wagner (DE) discovered an important formation in the ovum of several species of mammals, which he called the macula germinativa – later known as the nucleolus (3645).

Martin Heinrich Rathke (DE) discovered embryonic precursors of gills in the embryos of higher animals that lack gills as adults (2856, 2857). He found branchial clefts and branchial arches in the embryos of birds and mammals then worked out the detailed homologies of the gill arches and hyoid in the higher vertebrates. He followed the embryological history of these structures and found that the branchial clefts disappear eventually and that the blood vessels adapt themselves to the lungs. He held that the upper jaw develops from the first visceral arch as a process independent of the lower jaw (2860, 2861, 2863).

Karl Bogislaus Reichert (DE) described the fate of the first and second visceral arches in Anura and Urodela (2893).

William Beaumont (US), over a period of several years, observed the responses of the stomach of his famous patient, Alexis St. Martin, who had a permanent fistula into his stomach as the result of a gunshot wound. He extended the work of others on digestion by making clear the physiological responses of the gastric mucosa to chemical and mechanical stimuli. He established the presence of a “chemical principal” in the gastric juice and demonstrated that an empty stomach is devoid of acid; the presence of stomach acid is induced by the presence of food (149, 150, 2142). See, Helm, 1801

Ernst Heinrich Weber (DE) and Wilhelm Eduard Weber (DE) were the first to make a detailed application of hydrodynamic principles to the study of the circulation of the blood (3689).

Francois Magendie (FR) later gave an excellent description of cerebrospinal fluid and identified the median aperture (also known as the medial aperture, and foramen of Magendie) which drains cerebrospinal fluid from the fourth ventricle into the cisterna magna (2195, 2196, 2200).

J.-J.-A.-Ernest Faivre (FR) and Hubert Luschka (DE) provided microscopic studies, which gave origin to the hypothesis that the choroid plexuses of the cerebral ventricles elaborate the cerebrospinal fluid (1052, 2162).

Auguste Pettit (FR) and Joseph Girard (FR) reported an increase in volume of the choroidal cytoplasm after injections of muscarin, pilocarpine, etc., chemicals known to increase the production of cerebrospinal fluid (2732).

Lewis Hill Weed (US) presented evidence that the perivascular spaces of the central nervous system also pour a small amount of fluid into the subarachnoid space (3692).

Lewis Hill Weed (US) and Harvey Williams Cushing (US) recorded the outflow of cerebrospinal fluid from a catheter inserted into the third ventricle through the aqueduct of Sylvius thus demonstrating an intraventricular source of the fluid (3693).

Walter J. Meek (US) confirmed the work of Pettit and Girard (2283).

Louis Barkhouse Flexner (US) and Hyman Winters (US) found that the cerebrospinal fluid is passed by the cells of the choroid plexuses, which do work in the process, in small amount into the neural cavities (1160, 1161).

 See, Domenico Felice Antonio Cotugno, 1770

Morris Simmonds (DE) described a previously healthy woman who fell ill with a severe puerperal sepsis, developed a septic necrosis of the pituitary resulting in: menopause, muscle weakness, dizziness and attacks of unconsciousness, anemia, and premature senility. The remaining intact fragments of the pituitary tended to atrophy in the surrounding fibrotic tissue. The gland became completely insufficient and the woman died in coma. The autopsy revealed as the only cause of death an almost complete dwindling of the hypophysis. This is the first description of hypopituitarism or as it was later called, Simmonds disease (3175).

Pierre Charles Alexandre Louis (FR) is considered by many to be the founder of medical statistics. He emphasized the careful collection of facts that had been well and completely observed followed by an equally careful analysis of the facts. He called this the numerical method. In his book, Recherches Anatomico-Pathologiques sue la Phthisie, he reported on 123 cases of phthisis (pulmonary tuberculosis) carefully reporting the symptoms, lesions in the various organs, and clinical course of each patient. In his book, Recherches Anatomiques Pathologiques et Therapeutiques sur la Maladie Conne sous les noms de Fièvre Putride, Adynamique, Ataxique, Typhoide, etc., he reported on 138 patients suffering from typhoid using his same careful methodology. In his Recherches sur les Effets de la Saigéee dans Quelques Maladies Inflammatoires, et sur l’Action de l’Emetique et des Vesicatoires dans la Pneumonie, he presented statistical evidence that venesection (bloodletting) never arrested an attack of pneumonia and appeared to have no beneficial effect (2139-2141).

Johannes Evangelista Purkinje; Jan Evangelista Purkyne (CZ) discovered what later was called the Purkinje shift or Purkinje effect. Blue objects became brighter than yellow objects when they were placed in dim light. This was later explained, as the rods, which are responsible for vision in dim light, are more sensitive to short wavelengths than to long wavelengths (2815).

John Edward Gray (GB) proposed the family name Hominidae for members of the zoological family of man (1411).


Dengue fever spread from Savannah, Georgia, to other cities along the southeastern coast of the United States, and through the Caribbean (1863).


The second cholera pandemic of the 19th century, and the most devastating one, began in Bengal and spread through India in 1826. It reached Afghanistan in 1827, and spread further into central Asia and the Middle East. By late 1830 it had reached Moscow, and from there spread westward into Europe in 1831. It reached England on a ship from Hamburg in October 1831 and spread throughout the British Isles; in England alone 22,000 died. Irish immigrants, fleeing poverty and the potato famine, carried the disease from Europe to North America. On their arrival in the summer of 1832, 1,220 died in Montreal and another thousand across Quebec. The disease then entered the U.S. through Detroit and New York, and reached Latin America by 1833. Another outbreak across England and Wales began in 1848, killing 52,000 over two years (1863).


René-Joachim-Henri Dutrochet (FR) discovered and named the phenomenon of osmosis, the free passage of water through a membrane that may restrict the movement of substances in solution. He measured osmotic pressure and determined that the pressure related directly to the concentration of dissolved solute. Dutrochet realized that this explained how roots take up water, the movement of water within the plant, and turgor (954-956). See, Jean Antoine Nollet, 1748.

Wilhelm Friedrich Philipp Pfeffer (DE) discovered that if he placed a protein solution inside a semipermeable membrane immersed in water the internal pressure of the bag would rise. The process is osmosis and Pfeffer showed how one might measure the osmotic pressure resulting. He was the first to measure osmotic pressure. Pfeffer also showed that the pressure depended upon the size of the molecules dissolved within the bag. This meant that, from osmotic pressure, the molecular weight of specific proteins could be determined. In this way Pfeffer was able to make the first reasonably reliable measurements of the size of giant molecules (2735). 

Burton Edward Livingston (US) gave an excellent presentation of the current state of knowledge regarding diffusion and osmosis in plants (2107).

Per Fredrik Thorkelsson Scholander (SE-NO-US) proposed the solvent tension theory of osmosis (3087).

Augustin Sageret (FR) experimentaly crossed muskmelons and cantelopes. He noticed that his parent forms differed from one another in characters that could be contrasted in pairs: flesh white or yellow, seeds white or yellow, flavor acid or sweet. He observed that some of these characters were dominant over others and that the F1 generation was uniform, and he concluded that a hybrid did not show fusion of parental characters, but a 'distribution.' This, however, was not equivalent to a discovery of segregation of unit factors (805, 3014). In this paper Sageret canonized the concept of dominance, the genetic term still in use.

Friedrich Tiedemann (DE) and Leopold Gmelin (DE) demonstrated that digestion is, in fact, a complicated series of processes, involving a number of organs (previously it was thought to be a simple dissolution process). They found that some substances are transformed during digestion, e.g., starch to glucose. They showed that various digestive juices have discrete properties, e.g., secretions of the pancreas can digest proteins, and saliva cannot. They discovered that some biliary substances are purely excretory, e.g., bile pigments, while others play important physiological roles, e.g., absorption of fats. They also discovered shortly after William Prout (GB) and independently of him that the stomach produces hydrochloric acid. Gmelin’s nitric acid test for the presence of bilirubin in chyle, blood serum, and urine is contained here (3352, 3353).

William Kirby (GB), William Spence (GB) and Agostino Bassi (IT) were among the first to suspect that fungi could infect insects (127, 128, 1809).

Leblanc (FR) described in cattle what he mistakenly thought was a tumor, so he named it osteosarcoma tumors (lumpy jaw), the most prominent symptoms being swelling and suppuration of the jaw (552, 2010). Incomplete ref

William Dick (GB) treated ‘clyers’ (lumpy jaw) of cattle with iodine as early as 1839. Ref

Otto Bollinger (DE) described a series of pathologic processes of the jaws and throats of cattle, which had previously been considered as osteosarcoma, bone cancer and wooden tongue. He demonstrated the granulomatous nature of the condition and described detritus containing granulation cells, leukocytes, and opaque, yellow granular bodies, which he regarded as true fungi (325).

Carl Otto Harz (DE) was the first to call the infectious agent ray fungus, or actinomycosis (1504). 

Charles Bell (GB) recognized what he termed a sixth sense, which later was characterized as proprioceptive function (158).

Johannes Petrus Müller (DE) showed that sensory nerves could interpret an impulse in but one way, e.g., the optic nerve, however stimulated, records a flash of light whether light is involved or not. In his honor this is called Müller’s law or Muller’s doctrine of specific nerve energies. He discovered the Müllerian duct; worked out the finer structure of glands, bones, and cartilage; described the uriniferous capsule (also described by Bowman); discovered the lymph heart in the frog; discovered the Müllerian duct; and worked out the microscopic anatomy of the glandular and cartilaginous tissues. He isolated chondrin and glutin and emphasized, based on his microscopic studies, that there is considerable histological variation among tumors. He started the journal, Archiv für Anatomie und Physiologie, also called Müller’s Archiv. His book, Handbuch der Physiologie des Menschen fur Vorlesungen (Handbook of Human Physiology for Lectures) was monumental (2433-2442). He was an inspiring teacher as witnessed to by his many famous pupils including: Theodor Ambrose Hubert Schwann (DE), Friedrich Gustav Jacob Henle (DE), Emil Heinrich du Bois-Reymond (CH-DE), Karl Vierordt (DE), Rudolph Ludwig Karl Virchow (DE), and Hermann Ludwig Ferdinand von Helmholtz (DE). 

René-Théophile-Hyacinthe Laënnec (FR) coined the term cirrhosis during a discussion of liver disease, “This type of growth [of the liver] belongs to the group of those which are confused under the name of scirrhus. I believe we ought to designate it with the name of cirrhosis, because of its color. Its development in the liver is one of the most common causes of ascites, and has the peculiarity that…the tissue of the liver is absorbed, and it ends often…by disappearing entirely” (1949).

Jean-Nicolas Marjolin (FR) first described cancer-like ulcers such as those occasionally seen in chronically irritated or scarred skin (2240). In 1850, Robert William Smith (GB), a professor of surgery at Trinity College in Dublin, in his essay Observations upon the Warty Ulcers, first linked Marjolin’s name to the phenomenon he described.

Antoine Lembert (FR) introduced a suture, which ensures that during suture of the intestine (enterorrhaphy) serous surface is applied to serous surface when suturing the intestine. This technique laid the foundation of all modern gastric and intestinal surgery (2027).

Johann Friedrich Dieffenbach (DE) was the first to successfully apply Lembert’s suture when he performed the first resection of the small intestine, in a patient with a gangrenous segment of the bowel (857).

Christian Albert Theodor Billroth (DE) performed a number of bowel resections, which are here recounted by Ernst Hauer (DE) (1508).

Guillaume Dupuytren (FR) gave the first clear pathological description of congenital dislocation of the hip joint. He distinguished this syndrome caused by failure of fetal development of the acetabulum from deformities due to tuberculosis and pyoarthrotic disease of the hip joint (941).

Johann Friedrich Dieffenbach (DE) achieved the first surgical closure of the hard palate (854, 855, 3071).

Carl Friedrich Benedictus Quittenbaum (DE), in 1826, is credited with the first elective splenectomy. The patient only lived six hours postoperatively (2832, 3712).

Jules Emile Péan (FR) reported the first successful splenectomy. He described his operation on a 20-year-old woman who he believed had a large ovarian or uterine tumor (2706).

Bernard Delaitre (FR), Bruno Maignien (FR), Philippe Icard (FR), Brendan J. Carroll (US), Edward H. Phillips (US), Chester J. Semel (US), Moses J. Fallas (US), and Leon Morgenstern (US) almost simultaneously reported the first laproscopic splenectomy (563, 837).

The journal Bijdragen Tot de Natuurku`ndige Wetenschappen was founded.


There is an epidemic of acrodynia (epidemic erythema) in France. Acrodynia means pain of the extremities. Karl Petren (SE) notes that the so-called epidemic of acrodynia may have been due to arsenical poisoning. Arsenic was used in the French wine districts for destroying the parasites that attack the grape vines (254, 2727).


"I have never yet examined the body of a patient dying with dropsy attended coagulable urine, in whom some obvious derangement was not discovered in the kidneys.... In all the cases in which I have observed the albuminous urine, it has appeared to me that the kidney has itself acted a more important part, and has been more deranged both functionally and organically than has generally been imagined." Richard Bright (422)

Auguste Arthur Plisson (FR) was the first to isolate aspartic acid. It came from an extract of the root of the marshmallow plant (Althaea officinalis) (2763). Plisson named it.

Karl Heinrich Leopold Ritthausen (DE) described the isolation of proteins from plant seeds in a long series of experiments. He also isolated the long known aspartic acid from hydrolysates of legumin and conglutin (2944, 2945). Aspartic acid is also known as aminosuccinic acid.

William Prout (GB) was the first to divide the components of foodstuffs into saccharinous, oleaginous, and albuminous (a historic designation since they correspond to later carbohydrates, fats, and proteins). He recognized fat as an important nutrient in the diet along with protein and carbohydrate. He also determined the composition of urea and lithic acid (uric acid) (2809-2811).

Pierre-Jean-François Turpin (FR), an outstanding artist, reports and illustrates his observations of cell division in algae (3407). 

John James Audubon (FR-US), an artist of birds without peer, began the publication of his four-volume work, The Birds of America (73). This elephant folio is over three feet high and contains 435 hand-colored aquatint plates. This is the most famous of all ornithological works. His five-volume Ornithological Biography followed in 1831. It contains the bird descriptions for The Birds of America (74). 

Thomas Hodgkin (GB) and Joseph Jackson Lister (GB) described for the first time the true microscopic structure of a range of tissues, e.g., striated muscle and biconcave blood cells. Some science historians consider this paper the origin of animal histology (1604).

Augustin Sageret (FR) made crosses of the so-called “cantaloupe” and “chaté” varieties of melons, which have different grooves and netting. He studied the combination of these characters in hybrids (3015). Sageret cited unit characters in human eye color, and used the term dominant.

John Creery Ferguson (IE) was the first in the British Isles to auscultate a fetal heart tone. He had obtained his fetal stethoscope from Jacques Kergeradec (FR) in Paris during 1827.

Karl Ernst von Baer (EE-DE-RU) was the first to point out that the ovarian follicle contains the mammalian egg. He made it clear that mammalian development (including man’s) is not fundamentally different from that of other animals. He regarded the sperm cells as entozoa, i.e., parasites, and named them spermatozoa (3499, 3500, 3502, 3503).

Francois Magendie (FR) discovered the median aperture in the roof of the fourth ventricle connecting it with the subarachnoid space. This later became known as the foramen of Magendie (2200).

Hubert Luschka (DE) described the paired lateral foramina in the meningeal roof of the fourth ventricle (Luschka’s foramen). They drain the fourth ventricle into the subarachnoid space at the cerebellopontine angle. Ref ca. 1863

Nathan Smith (US) gave this early and important description of “necrosis” which today we would call osteomyelitis (3203). Note: In New England at this time it was known as fever-sore.

Richard Bright (GB) gave an excellent description of a syndrome characterized by dropsy (edema), sclerosis of the kidney, albuminous urine, cardiac hypertrophy, and an increase in blood urea. In his honor it has been called Bright’s disease (glomerulonephritis) or Morbus Brightii. With nothing more sophisticated than a candle and a silver spoon, he discovered protein in urine, the diagnostic characteristic of Bright's disease of the kidneys. He was the first to suggest a connection between a large heavy heart and contracted kidneys.

Bright also wrote on cerebral lesions, acute yellow atrophy of the liver, nephritis, condensation of the lung in whooping cough, pathologic lesions in typhoid fever, paralysis and tetanus, cerebral hemorrhage, laryngeal phthisis (pulmonary tuberculosis), acute otitis, pancreatic diabetes, unilateral convulsions, and status lymphaticus (333, 419-453).

Robert M. Kark (ZA-GB-US), Conrad L. Pirani (US), Victor E. Pollak (US), Robert C. Muehrcke (US), and John D. Blainey (US) perfected the technique of renal biopsy in the prone position. They biopsied patients and diagnosed many cases of nephritic syndromes, and toxemia of pregnancy (1770). 

John Rhea Barton (US) performed a femoral osteotomy between the greater and lesser trochanters to secure motion in an ankylosed hip. He performed a subtrochanteric osteotomy of the femur for a severe flexion-adduction deformity of the hip (126). This has been called the first successful arthroplasty.

Ludwig van Beethoven (DE) was a 56-year-old man who presented with fever and chills associated with ascites, abdominal pain and a hacking cough with scant hemoptysis. Another dominant feature of his medical history was deafness, which had its onset at the age of 28. Hemoptysis and epistaxis became more frequent and Beethoven eventually developed anuria, became comatose, and died.

Michael S. Donnenberg (US), Michael T. Collins (US), R. Michael Benitez (US), and Philip A. Mackowiak (US) support the cause of death as pneumonia, possibly complicated by bacterial peritonitis; tertiary syphilis with gummatous cirrhosis, luetic otitis, and luetic iridocyclitis (resolved); and irritable bowel syndrome (883, 2186).

Collin S. Karmody (US) and Edgar S. Bachor (US) offered a diagnosis of inflammatory bowel disease (IBD) to provide a single entity that explains most of Beethoven's symptoms and was finally the cause of his death. They concluded that Beethoven's sensorineural hearing loss was an immunopathy associated with IBD (1771).

Valentine Mott (US) was the first to ligate the common iliac artery at its origin. This was during an operation for aneurysm (2400, 2401).

The Medical Gazette was founded in London.

The American Journal of the Medical Sciences was founded.

The Western Journal of the Medical and Physical Sciences was founded.


Robert Brown (GB) reported that under the microscope pollen grains in water, jiggled around irregularly. He tried nonliving particles of about the same size and found the same type of motion. This became known as Brownian movement or Brownian motion (477, 478).

Albert Einstein (CH-US) and Jean Perrin (FR) later supported Brown’s concept (1003, 1004, 2721). See, Jan Ingen-Housz (Ingenhousz), ca. 1790. Note: Brownian motion provided the first incontrovertible evidence of the existence of atoms/molecules.

Friedrich Wöhler (DE) was the first person to accomplish the in vitro synthesis of an organic compound from inorganic compounds. He reacted lead cyanate or silver cyanate with ammonia to produce urea crystals (3518, 3783).

Antoine Béchamp (FR) obtained urea in vitro by protein oxidation (151).

Francois-Vincent Raspail (FR), in 1828, noted that plant proteins and sugars together give a purplish-red color when treated with strong sulfuric acid, thus providing the basis of the aldehyde test for the amino-acid tryptophan nearly fifty years before it was introduced (2850).

Francois-Vincent Raspail (FR) applied chemical tests to the protoplasm of Chora, which form the bases of three reactions that are still widely used in the laboratory for the identification of proteins, the xanthoproteic reaction, Liebermann's test and the aldehyde reaction. He tested the reaction of protoplasm with a blue dye obtained from a species of sun spurge, found in the Mediterranean, which turned pink in acid solution (2850, 2851). This actually anticipated the Voisenet-Fürth reaction.

Count Karl Axel Hampus Mörner (SE) quantified the xanthoproteic reaction (2388).

Francois-Vincent Raspail (FR) used hydrochloric acid to detect carbohydrates (furfural or Liebermann reaction). In 1829, he applied the natural acid-base indicator, turnsole, to living cells and determined that the cell interior is acidic. In the same year he proved the presence or absence of various metals in cells by incinerating them and analyzing the ashes and demonstrated by what became known as the xanthoproteic, Liebermann, and aldehyde tests the presence of albuminous matter in the cytoplasm (he called it sap) of plant cells (2852). He is also credited with determining the agent of scabies (the mite Sarcoptes scabiei). See, Giovan Cosimo Bonomo, 1687.

Christian Gottfried Ehrenberg (DE) coined the term bacterium as a representative name for some bacterial types. The word comes from the Greek meaning “small stick” (985).

T.A. Konishi (JP) described a disease of rice, now called bakanae (foolish seedling), characterized by tall thin plants dramatically overgrowing their neighbors (3299). Later it was discovered that this is due to an infecting fungus, Gibberella fujikuroi, producing gibberellins. See, S. Hori, 1898.

Adolphe-Théodore Brongniart (FR) recognized four successive periods of vegetation on earth, each characterized geologically. Three were particularly well characterized: the first, extending to the end of the Carboniferous, dominated by the vascular cryptogams; the third, covering the Jurassic and the Cretaceous, dominated by ferns and the gymnosperms; the fourth, which was the Tertiary, dominated by the dicotyledons.

He also divided the vegetable kingdom into six classes: Agame (thallophytes), cellular cryptogams (liverworts and mosses, i.e., Hepaticae and Muscae), vascular cryptogams, and three classes of phanerogams: gymnosperms, monocotyledonous angiosperms, and dicotyledonous angiosperms.

Adolphe-Théodore Brongniart (FR) made the first attempt at a synthesis of paleobotany: the inventory of fossil genera as a whole and the place of these genera in natural classification. He is considered to be one of the founders of paleobotany (466, 468).

Gottfried Reinhold Treviranus (DE) was the first to accurately draw the rods of the retina, which he called cylinders. He saw these rods in the retinas of birds, mammals, amphibians, and fish. Treviranus associated these structures and their terminal papillae with the optic nerve and with the reception of light (3389, 3391). He incorrectly thought that the rods faced the vitreous chamber.

Friedrich Heinrich Bidder (LV-DE) was the first to recognize the inverted nature of the retinal receptors (244).

Heinrich Müller (DE) identified and numbered the principle layers of the retina (2426, 2427).

Rudolf Albert von Kölliker (DE) described two distinct types of nerve endings in the retina (rods and cones) (3580, 3581).

Maximillian Johann Sigismund Schultze (DE) described the inner and outer segments of the photoreceptors and other elements of the retina, including bipolar cells. He detailed all 10 layers of the retina and proposed that rods are responsible for colorless night vision, whereas cones are necessary for daylight color vision and high-resolution spatial vision. Schultze noted that there is a strong correlation between the peak period of an animal’s activity and the ratio of rods to cones in its retina (3110-3112).

Henri Parinaud (FR) and Augustin Charpentier (FR), independently of Schultze, postulated two classes of photoreceptors (rods and cones), one sensitive to dim light, and the other to daylight. Parinaud wrote that night blindness (hemeralopia) is due to a defect in the rods (599, 2637).

Wilhelm Friedrich Kühne (DE) recognized that stimulation of the cones of the retina actually mediated the sensation of color while the rods conveyed light or darkness (1189).

Santiago Ramón y Cajal (ES) showed conclusively that in the vertebrate retina there are not only independent receptors and retinal ganglion cells but also bipolar cells between them (2842).

Johannes Adolf von Kries (DE) formulated the modern "duplicity" or "duplexity" theory of vision mediated by rods at low light levels and three types of cones at higher light levels (3588).

Karl Ernst von Baer (EE-DE-RU) wrote On Developmental History of Animals, which marks the beginning of modern scientific embryology and contains his strong opposition to preformationism. His publications between 1828 and 1838 described the germ layers of the developing embryo (he thought there were four layers) and how the early stages of the development of vertebrate embryos were quite similar even among creatures that in the end were quite dissimilar. This implies that development proceeds from the sculpturing of general features to the chiseling of fine details, which give the species its distinctive characteristics. He worked out the genesis of all the principal organs from the germ layers. His work led him to conclude that relationships among animals could be deduced more properly by comparing embryos than by comparing adult structure (the origin of comparative embryology). Von Baer was able to show that embryonic notochords appear among vertebrates and some non-vertebrates. This feature-in-common led to their being placed together in the phylum Chordata (3500-3503). See, Pander 1817

Karl Ernst von Baer (EE-DE-RU) theorized that, "The eye seems to be an outgrowth of the neural tube, which protrudes through the muscle layer as far as the skin layer, and the outer parts of the eye are changes in the skin evoked as a result" (3501).

Hans Spemann (DE) performed experimental analysis of lens formation in the frog. He cauterized the prospective retina arrangement in the neurula stage of Rana fusca. A few days later, Spemann observed that both the eye and the lens were missing on the operated side of the tadpole. In those cases where the retinal rudiment had not been totally destroyed, the ability to form lenses appeared to correlate with the ability of the remnant to contact the overlying ectoderm. Spemann claimed that contact of the optic vesicle with the overlying ectoderm was needed to turn that ectoderm into a lens, but he did not know whether or not it was a sufficient cause. Moreover, he did not know yet whether the optic cup instructed the ectoderm to form a lens or merely acted as a trigger to permit a pre-existing potency to become expressed (3222).

Warren Harmon Lewis (US) provided stringent experimental proof of lens induction following displacement of optic vesicles (which he had pushed caudally underneath the skin). He also achieved heteroplastic lens induction, by placing Rana sylvatica epidermis over the denuded optic vesicle of R. palustris, where it produced a lens (2061).

Helen Dean King (US) found that if the optic cup and the overlying ectoderm are from the same species, lens induction is more likely to be successful (1804).

Ross Granville Harrison (US) obtained experimental induction of the lens by transplanting the optic cup (1493).

Martin Heinrich Rathke (DE) described the embryonic development of lungs and air sacs in birds (2858).

Armand Juillet (FR) published a comprehensive treatise embracing the anatomical, embryological, histological, and comparative study of the bird's lung (1761).

Léopold Chrétien Frédéric Dagobert Cuvier (FR) and Achille Valenciennes (FR) wrote Histoire Naturelle des Poissons [Natural History of the Fishes] which summarized and logically organized everything known about fishes up to that time. It included 11,253 pages of text and 650 plates in 22 volumes issued between 1828 and 1849. The work described 4,514 species of fish, 2,311 of these new to science. By studying fish skeletons and internal organs Cuvier separated out spiny-ray finned fishes (acanthopterygians) and realized the importance of whether the pelvis is attached skeletally to the bony structure, not just its relative placement (748).

Charles Alexandre Lesueur (FR) was a student of Cuvier. He made a cabinet of fish dwelling within the Great Lakes and Saint Lawrence River regions. 

Leon Dufour (FR) established the generic name Gregarina and considered them to be worms (now known to be sporozoans). He observed them in association with insects (921). Filippo Cavolini (IT), in 1787, described a gregarine from the glandular appendages of the stomach of the crustacean Pachygraspus marmoratus Stim. He thought it to be a tapeworm (572).

Rudolf Albert von Kölliker (CH) reported gregarines in the intestine of barnacles, and characterized them from the intestine of Balanus pallidus as Gregarina balani. He noted the unicellular nature of gregarines and added considerably to our knowledge of the frequent occurrence and wide distribution of these organisms (3576).

Norman Dion Levine (US) and Virginia Ivens (US) renamed them to the phylum Apicomplexa (2052).

James Annersley (GB) wrote, Researches into the Causes, Nature and Treatment of the More Prevalent Diseases of India and of Warm Climates Generally, which is regarded as containing the first accurate descriptions of both intestinal and hepatic amoebiasis (49).

George Budd (GB) made the connection between amoebic dysentery and liver abscesses (513).

Friedrich Alekshandrevitch Lösch; Fedor Lesh (DE) discovered the amoeba, Amoeba coli (Entamoeba histolytica), in 1873 in Russia, and established the relationship between the parasite and the disease in dogs experimentally infected with amoebae from humans (2134, 2135).

Stephanos Kartulis (GR) found Entamoeba histolytica in intestinal ulcers of Egyptian patients suffering from dysentery. He noted that he never found amoebae from nondysenteric cases (1776, 1777).

Heinrich Hermann Robert Koch (DE) and Georg Theodor August Gaffky (DE) found Entamoeba histolytica in sections of human intestine (1854).

Stephanos Kartulis (GR) also showed that cats could be infected with amoebae per rectum and thus develop dysentery (1778).

William Thomas Councilman (US) and Henri Amadée Lafleur (US), while working at the Johns Hopkins Hospital, authored a paper which represented a definitive statement of what was known about the pathology of amoebiasis at the end of the 19th century, and much of it is still valid today (709).

Heinrich Irenaeus Quincke (DE) and Ernst Roos (DE) distinguished Entamoeba histolytica from Enatamoeba coli (2831).

Fritz Richard Schaudinn (DE) was one of the first to show that dysentery can be caused by the amoeba he named Entamoeba histolytica. He distinguished it from the harmless Entamoeba coli (3053).

Alexandre Joseph Emilé Brumpt (FR) proposed two species to distinguish pathogenic and non-pathogenic infections: E. dysenteriae and E. dispar (498).

Based on DNA evidence it has been established that two distinct species exist within what was originally known as Entamoeba histolytica. These are E. dispar and E. histolytica, for the nonpathogenic and pathogenic forms, respectively.

Thomas Hodgkin (GB) discovered aortic insufficiency (1601).

Dominic John Corrigan (GB) described the typical pulse of aortic insufficiency, since commonly known as the Corrigan pulse (697). 

Jean Léonard Marie Poiseuille (FR) demonstrated that blood pressure rises during expiration and falls during inspiration. He also discovered that at each heartbeat the dilatation of an artery is about 1/23 of normal (2767). Poiseuille accurately measured blood pressure using his hemodynamometer. Mercury was layered over potassium carbonate (anticoagulant) in a tube. The end containing the potassium carbonate was connected directly to the blood stream.

Jacques Mathieu Delpech (FR) made one of the most significant discoveries of operative orthopedics, namely subcutaneous tenotomy. He also established the tuberculous nature of Pott’s disease, established the true function of the ligaments, and presented a complete list of human physical deformities (838-840).

James Syme (GB) performed one of the most remarkable operations of the 19th century. He removed, without anesthesia, a four and one-half pound tumor from the lower jaw of Robert Penman. The patient not only survived the operation, but also remained in excellent health for many years afterwards. The operation was performed with the patient sitting in an ordinary chair, and in all took twenty-four minutes with the loss of seven or eight ounces of blood (3294).

Valentine Mott (US) excised the left clavicle for osteosarcoma (2402).

S. Pomeroy White (US) successfully ligated the internal iliac artery (3732).

John Abercrombie (GB) wrote Pathological and Practical Researches on Diseases of the Brain and Spinal Cord, regarded as the first textbook in neuropathology (7).

Boston Medical and Surgical Journal was founded.

Glasgow Medical Journal was founded.

Lancette Francaise (Gazette des Hopitaux) was founded.


In the Pacific Northwest, malaria (the ague) killed an estimated 150,000 Native Americans. Other diseases may have contributed to the death toll, but contemporary writing describes symptoms that closely correspond to those of malaria. The disease was probably introduced in February 1829 by a ship reaching Oregon after coming from Chile, carrying infected mosquitoes in water tanks onboard ship. The Columbia River was flooded at the time, creating stagnant water in which the mosquitoes could breed (1863).


During late 1829 an influenza epidemic began in China, then spread from there to the Philippines in September 1830, to Indonesia in January 1831, through the Malay Peninsula and into Asia in 1832. The disease also broke out in Moscow and St. Petersburg in the winter of 1830-31 and spread westward overland through the summer of 1831. By November it had reached the U.S., and continued to spread there in 1832. Another outbreak of influenza spread through Asia and Europe during 1836-37 but except for a single Canadian focus did not reach North America (1863).


"Animals have no habits but those that result from the structure of their organs; if the latter varies, they vary in the same manner all their springs of action, all their faculties and all their actions." Étienne Geoffroy Saint-Hilaire (51)

Thomas Graham (GB) discovered that the rate of diffusion of a gas is inversely proportional to the square root of its molecular weight. He also showed that the various forms of phosphoric acid differed in their hydrogen content. This introduced chemists to the idea of polybasic acids (1388, 1389).

Louis René Le Canu (FR) isolated and correctly characterized cholesterine (cholesterol) from an extract of hen egg yolk (2001).

Johann Friedrich Gustav von Eschscholtz (EE-RU-DE) created the orders Ctenophorae, Discophorae (all medusae), and Siphonophorae (3523). 

Von Eschscholtz was one of the first and most important scientists in the exploration of the Pacific, Alaska, and California. Among his publications were the System der Akalephen (1829), and the Zoologischer Atlas (1829–1833). Von Eschscholtz was the first naturalist to describe the acorn worm (Balanoglossus), which he encountered in the Marshall Islands in 1825(3523, 3524). He is commemorated by the plant genus Eschscholzia.

Joseph Claude Recamier (FR) coined the term metastasis to describe the transfer of disease from one organ or body area to another to which it is not directly connected (2881).

John Stevens Henslow (GB) was a botanist, a vicar of the church, a professor of mineralogy and botany at Cambridge University, and the teacher of Charles Darwin who recommended that he serve as a naturalist aboard H.M.S. Beagle (1554, 1555). He began teaching at Cambridge in 1826.

Martin Heinrich Rathke (DE) found confirmation of the germ-layer theory of Pandar and von Baer in the embryonic development of the invertebrate crayfish (2859).

Léon Jean Baptiste Cruveilhier (FR) in his lavish pathological atlases, among other things, described and illustrated cysts, colic diverticulosis, fibrous bodies of the breast, diffuse cerebral sclerosis, gelatinous disease of the peritoneum, dilation of the veins of the abdominal wall, and disseminated (multiple) sclerosis for the first time. He also gave an early description of progressive muscular atrophy, and gastric ulcer (670, 730, 731). His description of enteric ulcer follows: “There is first an erosion of the mucosa…. The erosion or inflammation becomes an ulcer…. Simple ulcer…does not present other than a gross resemblance to cancerous ulcer… The best proof, however, that these ulcerations are not cancerous is their curability…. The [principal] symptoms are…loss of appetite or bizarre appetite, insurmountable distress, difficult digestion…heavy pains in the epigastrium, and sometimes epigastric pain extremely sharp during the process of digestion or indeed when there is no food in the stomach…. The patient has the sensation of an enemy who is always present.”

Friedrich Theodor von Frerichs (DE) provided an exhaustive description of the pathological and clinical findings of multiple sclerosis. He named this affliction brain sclerosis, “hirnsklerose” and was the first to diagnose it in a living patient, which was confirmed by autopsy years later (3529).

Gabriel Andral (FR) recognized a direct correlation between the pathology of the blood and that of the organs and tissues. He urged chemical analysis of the blood, especially in morbid conditions. He discussed the role of the blood in plethora, anemia, pyrexia, and so-called organic diseases such as cardiac hypertrophy (47).  

Michael Sars (NO) and John Graham Dalyell (GB) worked out the life cycle of Aurelia aurita and, more generally, of scyphozoans; demonstrating the relationship between the polyploid and medusoid stages (755, 3039, 3040, 3043).

John Vaughan Thompson (IE) published the first records of the vast community of planktonic life. He correctly described barnacles as crustaceans and was the first to describe the planktonic stages of crabs (3326, 3327, 3329-3332, 3335).

Hermann Burmeister (AR) also saw the larval stages of barnacles and realized that they should be placed with the crustaceans and not with the mollusks (525).

Johann Friedrich Georg Christian Martin Lobstein (DE-FR) coined the term arteriosclerosis (2109).

Benjamin Guy Babington (GB) invented the laryngoscope, which he called a glottiscope (84). His colleague, W. Thomas Hodgkin (GB), later suggested the name laryngiscope.

Alfred Kirstein (DE) learned of an inadvertent tracheal insertion of an esophagoscope, and proceeded to develop a rigid laryngoscope with transmitted light for direct observation. This consisted of a lamp within the handle, focused on a lens and redirected through the scope by a prism (1815).

Dominique Jean Larrey (FR) performed the first successful surgery on the pericardium, the patient died within a month (1980).

Johann Friedrich Dieffenbach (DE) is considered the founder of modern plastic surgery. He performed the first successful closure of both hard and soft palate; made early references to tenotomy, myotomy, otoplasty, early rhinoplasty, and blepharoplasty. Between 1829 and 1845 Dieffenbach wrote important texts on surgery such as Die Operative Chirurgie (859, 3826).

Valentine Mott (US) ligated the carotid during operation for an aneurysm of the arteria innominata (2401, 2403).

Valentine Mott (US) ligated the carotid during operation for anastomosing aneurysm in a three-month old infant (2404).

Isidore Geoffroy Saint-Hilaire (FR) suggested that in some apes and man certain infantile characteristics such as large brain and great possibility for adaptation persist into adulthood (3020). This was long before Louis Lodewijk Bolk (NL) enunciated the theory of neoteny. See, Bolk, 1918.

Alexandre-Théodore Brongniart, Jr. (FR) named the Jurassic Period in geologic history for the extensive marine limestone exposures of the Jura Mountains, in the region where Germany, France and Switzerland meet (467). Note: Today this represents the middle Jurassic.

Jules Pierre Desnoyers (FR) was the first to apply the term Quaternary to a geological time when he discussed Tertiary sediments of the Seine River Valley (he was incorrect) (848).

Henri P.I. Reboul (FR) redefined the period from approximately 2 Ma to the present (2880).


Cholera overruns Russia and invades Western Europe (1265).


“There is nothing in a caterpillar that tells you it’s going to be a butterfly.” Yisrael ben Gedalyah Lipschutz (2091)

Charles Lyell (GB) wrote Principles of Geology, a three volume book on geology, in which he popularized and amplified the Huttonian view that geological change is gradual over eons of time and that the forces for change are the same today as in the past, namely heat and erosion (uniformitarianism). Emphasis on the immensity of geological time was his greatest contribution to or understanding of the earth’s history. It was he who first named the Eocene, Miocene, and Pliocene geological epochs (2168-2170). This new view of the geological past suggested that the question about man’s own antiquity was capable of an empirical answer.

David Brewster (GB) discovered the laws governing polarization of light by refraction (417).

Joseph Jackson Lister (GB), a London wine merchant, discovered the principle of aplanatic foci then subsequently developed the modern type of compound microscope free of chromatic and spherical aberrations. Only from this time can modern microscopy be said to date. He was the father of Joseph, Lord Lister, the surgeon (2102).

Johann Justus Liebig (DE) discovered the compound he named hippuric (from equine urine) acid. In contrast to benzoic acid it contains nitrogen (2070).

Jöns Jakob von Berzelius (SE) was the first to formally define the concept of isomerism. “By isomeric substances I understand those which possess the same chemical composition and the same atomic [molecular] weight, but different properties.” He coined the terms isomer and isomerism (3510). He named the phenomenon isomeria.

Louis René Le Canu (FR) was the first to prepare blood hematin (iron protoporphyrin) in pure form. He determined that the iron in blood is associated with the hematin pigment (2002, 2003).

Friedrich Tiedemann (FR) prepared blood hematin (iron protoporphyrin) in crude form (3351). Porphyrin comes from the Greek meaning purple.

Johann Joseph Scherer (DE) described a purple-red iron-free residue that he had extracted from blood using concentrated sulfuric acid (3056).

Gerardus Johannes Mulder; Gerrit Jan Mulder (NL) called Scherer's purple-red extract “iron-free hematin” (2419).

Johann Ludwig Wilhelm Thudichum (DE-GB) recognized the “splendid blood-red” fluorescence of Scherer's hematin, which he purified and called “cruentine” (3344).

Ernst Felix Immanuel Hoppe-Seyler (DE) called the purple substance found in iron-free hematin hemato-porphyrin, in other words “purple-blood” (1631, 1632).

Diederich Franz Leonhard von Schlechtendal (DE), Christian Julius Wilhelm Schiede (DE), Ferdinand Deppe (), and Louis Adelbert von Chamisso (FR-DE) described many of the most important plants of Mexico (3621).

William Sharpey (GB) wrote on cilia and ciliary motion. “In the course of some investigations on the development of the tadpole, in which I was lately engaged, I was accidentally led to observe, that the surface of the animal possessed the power of exciting currents of water contiguous to it, in a constant and determinate direction” (3164).

John Vaughan Thompson (IE) was the first to recognize the class Polyzoa (3328).

Christian Gottfried Ehrenberg (DE) introduced the name Bryozoa (moss-like animals), which replaced Polyzoa (985).

Christian Gottfried Ehrenberg (DE) coined the genus name Euglena in 1830 but it was not diagnosed until 1838 (982, 983).

Etienne Geoffroy Saint-Hilaire (FR) originated the concept of parallel evolution in which both the evolution of the phyla and their adaptive convergences are allowed for during classification (3018). 

Friedrich Schlemm (DE) discovered the corneal nerves (3069).

William MacKenzie (GB) presented a classic description of the symptomatology of glaucoma, and was probably the first to draw attention to the increase of intra-ocular pressure as a characteristic of the condition (2185).

John Conolly (GB) practiced the doctrines of Philippe Pinel (FR) and introduced the non-restraint treatment of the insane (674). “Restraint and neglect are synonymous. They are a substitute for the thousand attentions needed by a disturbed patient” (675).


Samuel Guthrie (US), Eugène Soubeiran (FR), and Johann Justus Liebig (DE), independently and very near the same time, are all credited with being the first to prepare chloroform. Liebig also synthesized chloral hydrate by chlorinating ethanol (1452, 2072, 2073, 3218).

Jean Baptiste André Dumas (FR) determined the composition of and named chloroform (928).

Mathias Eugenius Oscar Liebreich (DE) was the first to use choral hydrate as a sedative-hypnotic (2087). It is infamous as “Knock out drops” or the "Mickey Finn" but has only had legitimate medical use as a sedative in minor surgery and as a topical analgesic (1282).

Johann Justus Liebig (DE) described a novel apparatus for measuring the carbon content of organic materials upon combustion. It was based on trapping carbon dioxide in a five-bulb trap filled with potash (KOH) (2071).

Heinrich Wilhelm Ferdinand Wackenroder (DE), in 1831, isolated beta-carotene from carrot roots (Daucus carotus) (3825).

Eduard Schwarz (AT), a ships doctor, knew that night blindness was a recurring problem among sailors on long sea voyages. The wisdom of traditional liver therapy was largely being ignored. On one voyage (1857-1859) he deprived the sailors of liver, 75 of the 352 men developed the condition. Every evening when dusk came, they lost their vision and had to be led about like the blind. Schwartz fed them ox or pork liver and found that the night vision in all of the afflicted was restored (3134, 3788).

Richard Martin Willstätter (DE) and Walter Mieg (DE) established the empirical formula of beta-carotene as C40H56 (3756). 

Harry Steenbock (US), Erwin G. Gross (US), Paul W. Boutwell (US), and Mariana T. Sell (US) observed that yellow foods are good sources of vitamin A (retinol), whereas white foods and red foods are not (3246-3249).

Elisabeth von Euler-Chelpin (DE), Hans Karl August Simon von Euler-Chelpin (DE-SE), Harry Hellström (SE), and Thomas Moore (GB) offered proof that carotene is provitamin A (2378-2381, 3525).

Paul Karrer (RU-CH), A. Helfenstein (CH), Hansuli Wehrli (CH), and Albert Wettstein (CH) determined the chemical structure of beta-carotene (1773).

Paul Karrer (RU-CH), Rudolph Morf (CH), and Kurt Schöpp (CH) worked out the constitutional formula for vitamin A (retinol) and proved that it is related to carotenoids in structure; showing that beta-carotene consists of two vitamin A molecules end to end minus two water molecules (1774, 1775).

Otto Isler (CH), W. Huber (CH), A. Ronco (CH), and Max Kofler (CH) synthesized vitamin A (1714).

Paul Karrer (RU-CH) and Conrad Hans Eugster (CH) synthesized beta-carotene (1772).

Hans Herloff Inhoffen (DE), Ferdinand Bohlmann (DE), Käthe Bertram (DE), Günter Rummert (DE), and Horst Pommer (DE) synthesized beta-carotene (1711).

Nicholas A. Milas (US), Pauls Davis (), Igor Belic (), and Dragutin A. Fles (HR) synthesized beta-carotene (2346).

John E. Dowling (US) and George Wald (US) reported that the general tissue functions of vitamin A that support growth and maintenance in the rat are served also by vitamin A acid; but since this substance is not reduced, it forms neither the alcohol, the form in which vitamin A is stored, nor the aldehyde (retinene) needed for the synthesis of visual pigments. For this reason, rats maintained on vitamin A acid, though growing normally and otherwise in good condition, become extremely night-blind, and eventually blind. The failure to form visual pigments also has specific anatomical consequences: the outer segments of the visual cells deteriorate, followed by the loss of almost all the cells themselves, in an otherwise normal retina. These anatomical changes resemble those observed in certain hereditary forms of blindness and in human retinitis pigmentosa (887). 

Masamitsu Kanai (US), Amiram Raz (US), and DeWitt S. Goodman (US) isolated and characterized retinol-binding protein: the transport protein for vitamin A (retinol) in human plasma (1767).

Friedrich Tiedemann (DE) and Leopold Gmelin (DE) reported a color test for the presence of protein. They treated the proteins with chlorine water. The proteins had usually been at least partially broken down by harsh treatment (3353).

Erhard Friedrich Leuchs (DE) described the hydrolysis of starch by saliva, due to the presence of an enzyme in saliva (ptyalin or salivary amylase) (2039, 2040).

Anselme Payen (FR) and Jean-François Persoz (FR) isolated an amylase complex from germinating barley and named it diastase (2704).

Jöns Jakob von Berzelius (SE) named it ptyalin (to spit) (3512).

Louis Mialhe (FR) purified what he called animal diastase (salivary amylase or alpha amylase) by precipitating it with alcohol (2338, 2339).

Alexander Jakulowitsch Danilewsky; Alexander Jakulowitsch Danielewski (RU) separated pancreatic amylase from trypsin (759).

Robert Brown (GB) published a paper in England describing the microscopic structure of the reproductive organs of the Orchideae and Asclepiadeae. This study established the nucleus as a constant feature of plant cells and as fundamental unit of cells. It was Brown who coined the term nucleus, meaning little nut. “In each cell of the epidermis of a great part of the family, especially of those with membranous leaves, a single circular areola, generally somewhat more opaque than the membrane of the cell, is observable…only one areola belongs to each cell…This areola, or nucleus of the cell as perhaps it might be termed, is not confined to the epidermis, being also found not only in the pubescence of the surface particularly when jointed, as in Cypripedium, but in many cases in the parenchyma or internal cells of the tissue…The nucleus of the cell is not confined to the Orchideae but is equally manifest in many other Monocotyledonous families; and I have found it, hitherto however in very few cases, in the epidermis of Dicotyledonous plants” (479, 480). Brown is also credited with being among the first to recognize the significance of pollen in fertilization.

Lorenz Oken (DE) reasoned that growth and development of both plants and animals is driven by the multiplication and specialization of the primary vesicles (cells). He states that the process of differentiation between the primary vesicles produces vessels through which sap runs (2561).

William Brooke O’Shaughnessy (IE) used intravenous potassium and sodium to successfully treat the loss of these ions in cholera patients (2544).

O’Shaughnessy noted electrolyte imbalance in cholera cases. “The blood drawn in the worst of cases of the cholera is unchanged in its anatomical or globular structure…. It has lost a large proportion of its water, 1000 parts of…serum having but the average of 860 parts of water…. It has lost also a great proportion of its neutral saline ingredients…. Of the free alkali contained in healthy serum, not a particle is present in some…cases, and barely a trace in others…. All the salts deficient in the blood…are present in large quantities in the peculiar white dejected matters” (2543).

Thomas Latta (GB) introduced the practice of intravenous infusion of saline solution to patients suffering from shock associated with cholera. "I at length resolved to throw the fluid immediately into the circulation. In this, having no precedent to direct me, I proceeded with much caution." His first patient was an ‘aged female’, and he used the basilic vein. The result was remarkable, "Ounce after ounce was injected ... when six pints had been injected, she expressed in a firm voice that she was free from all uneasiness" (1988).

Robert Lewins (GB), Thomas Craigie (GB), and John Macintosh (GB) used the same technique at very near the same date (2053).

William Edmonds Horner (US) found that the rice-water stools in cases of Asiatic cholera consist of epithelium stripped from the small intestine (1635, 1636).

Frank Macfarlane Burnet (AU), and Joyce D. Stone (AU) reported on how Vibrio cholerae damages the epithelial lining of the gastrointestinal tract (526, 527).

Robert A. Phillips (US) with Taiwanese associates demonstrated that cholera is a disease of extracellular fluid depletion due to reverse sodium transport in the gut. Their treatment of this disease with massive intravenous salt and water repletion resulted in prevention of shock and avoidance of death (2746).

Salomon Levi Steinheim (DE) and Jean Baptiste-Hippolyte Dance (FR) were the first to describe the clinical symptoms of tetany (756, 3254).

Francois Remy Lucien Corvisart (FR) coined the term tetanie (tetany) in his thesis (699).

Lothar von Frankl-Hochwart (AT) performed detailed work on tetany then published the first comprehensive monograph dealing with this disease (3527).

James Syme (GB) penned a booklet detailing cases where joint excision could be used instead of amputation for diseased joints, as in tuberculosis, and injured joints. In 1842, Syme described an amputation at the ankle. This amputation bears his name, as it replaced a portion of below knee amputations, which were ordinary practice at that time (3295, 3296).

Guillaume Dupuytren (FR) described the condition now known as Dupuytren’s contracture (contracture of palmar fascia) and cured it by operation (942, 945).

Felix Platter (CH) was the first to described flexion contracture deformity of the fingers (Dupuytren’s contracture). This work also contains the first known report of death from hypertrophy of the thymus in an infant (2762).

Patrick Matthew (GB) predates Charles Robert Darwin (GB) in the proposal of a theory of natural selection. In his book, On Naval Timber and Arboriculture, he wrote, “As nature, in all her modifications of life, has a power of increase far beyond what is needed to supply the place of what falls by Time's decay, those individuals who possess not the requisite strength, swiftness, hardihood, or cunning, fall prematurely without reproducing -- either a prey to their natural devourers, or sinking under disease, generally induced by want of nourishment, their place being occupied by the more perfect of their own kind, who are pressing on the means of subsistence. There is more beauty and unity of design in this continual balancing of life to circumstance, and greater conformity to those dispositions of nature which are manifest to us, than in total destruction and new creation. It is improbable that much of this diversification is owing to commixture of species nearly allied, all change by this appears very limited, and confined within the bounds of what is called species; the progeny of the same parents, under great differences of circumstance, might, in several generations, even become distinct species, incapable of co-reproduction” (2261).

The H.M.S. Beagle put to sea on a cartographic voyage with Charles Robert Darwin (GB) aboard as naturalist.


William Frédéric Edwards (GB-FR) and Balzac (FR) were the first to declare that gelatin alone could not replace albuminous bodies in animal nutrition (978). At this time gelatin referred to a substance formed by boiling meat, tendons, etc. with water, rather than the product of deep-seated hydrolysis as would occur with Papin’s digestor.

Bartolomeo Bizio (IT) made a study of ‘blood spots’ on communion wafers, and found them to consist of a bacterium, which he named Serratia marcescens. He used bread as a growth medium (277).

Barthélemy Charles Joseph Dumortier (BE) was the first to observe cell division in a multicellular organism, Conferva aurea (alga), and to conclude from direct experimental evidence that the growth of the organism as a whole was determined by this mechanism alone (933). See, Lorenz Oken, 1831

Augustin Pyramus de Candolle (CH) theorized that all plants liberate substances into the soil adjacent to them. These excreted chemicals may be beneficial to some neighboring plants and harmful to others. He observed that the movements of the stem and leaves in response to light produce differential growth effects on their opposite sides and coined the term tropism to connote this movement of a plant towards a source of light (heliotropism) (812). Taxis is often used in reference to tropic behavior in animals.

Étienne Geoffroy Saint-Hilaire (FR) originated modern experimental teratology when he produced abnormal development in chick embryos by varying their environment. These results were reported by his son Isidore Saint-Hilaire and provided an argument against preformation (3021).

Johann Lukas Schönlein (DE) and Edward Heinrich Henoch (DE) described allergic non-thrombocytopenic purpura (Schönlein-Henoch purpura) and made the connection between purpura and abdominal pains (1553, 3092).

William Heberden (GB) had been the first to report this condition (Heberden-Willan disease) (1514).

William Osler (CA) was the first to suggest the relationship of the condition to allergy (2591).

This syndrome is an allergic reaction to bacteria (especially ß-hemolytic streptococci), food or drugs; it is a form of anaphylactoid (allergic) or non-thrombopenic purpura, which is the most common connective-tissue disorder in children.

Thomas Hodgkin (GB) described the malignant lymphoma which bears his name—Hodgkin’s disease (1602, 1603). See, Marcello Malpighi, 1666.

Samuel Wilks (GB), a fellow physician, also described this lymphoma disease and named it for Hodgkin (3747).

William Osler (CA) mentions chemotherapy for lymphoma (Fowler's solution - arsenic containing medicinal) (2589).

Carl Sternberg (AT) and Dorothy Reed (US) independently described the giant cells associated with Hodgkin’s lymphoma (2884, 3257). They are now called Reed-Sternberg cells.

Paul Chevalier (FR) and Jean Jacques Robert Bernard (FR) gave the first description of the use of high dosage radiotherapy in the treatment of Hodgkin's disease (602).

Louis S. Goodman (US), Maxwell M. Wintrobe (US), William Dameshek (US), Morton J. Goodman (US), Alfred Gilman (US) and Margaret T. McLennan (US) reported on nitrogen mustard therapy. They used methyl-bis(beta-chloroethyl)amine hydrochloride and tris(beta-chloroethyl)amine hydrochloride to treat Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders (1366). This could be first phase I/II trial on record.

Franziska Jundt (DE), Nina Raetzel (DE), Christine Muller (DE), Cornelis F. Calkhoven (DE), Katharina Kley (DE), Stephen Mathas (DE), Andreas Lietz (DE), Achim Leutz (DE), and Bernd Dorken (DE) determined the mechanism that causes normal B-lymphocytes to mutate into the cancerous cells in Hodgkin's lymphoma (1764).

Jason S. Knight (US), Nikhil Sharma (US), and Erle S. Robertson (US) determined the link between Epstein-Barr Virus (EBV) and several cancers including Hodgkin's lymphoma via molecular elimination of the retinoblastoma protein (Rb) (1832).

Jean Victor Audouin (FR) and Henri Milne-Edwards (FR) discussed the correlation between the increasing degree of exposure to air from low to high-tide levels and the pattern of distribution of organisms in narrow horizontal zones (72). Today this is referred to as vertical zonation.

Pierre-Louis Alphée Cazenave (FR) gave the first good clinical description of what he named lupus erythemateaux (lupus erythematosus) (574-576). His teacher Laurent-Théodore Biett (CH-FR) had identified a special variety within the erythema genus, the centrifugal erythema; and the variety of lupus that destroys on the surface (251). See, J. Darier 1916-1917.

William Osler (CA) also described lupus at a slightly later date, calling it erythema exudativum multiforme (2590).

James Hope (GB) described aortic valve murmurs (1627).

Johann Friedrich Dieffenbach (DE) was the first to attempt cardiac catheterization on a human, performed during an unsuccessful attempt to obtain blood from a patient suffering from cholera (856).

Valentine Mott (US) ligated both carotid arteries simultaneously (at an interval of 15 minutes) during an operation for carcinoma of the parotids. Death occurred within 24 hours with the patient in a state of coma (2405).

Guillaume Dupuytren (FR) gave lectures covering the entire surgical panorama of that day, often casuistically disposed with anamnesis, pathological anatomy, differential diagnostics, therapy, postoperative course and unfortunate cases closed with an autopsy report (943, 944).

Johann Justus Liebig (DE) established the journal Annalen der Pharmazie, later renamed the Annalen der Chemie und Pharmazie.

The Proceedings of the Royal Society of London was founded.


"The external world is all-powerful in alteration of the form of organized bodies… these [modifications] are inherited, and they influence all the rest of the organization of the animal, because if these modifications lead to injurious effects, the animals which exhibit them perish and are replaced by others of a somewhat different form, a form changed so as to be adapted to the new environment." Étienne Geoffroy Saint-Hilaire (3019

Karl Ludwig Reichenbach (DE) discovered creosote (2892).

Joseph Louis Gay-Lussac (FR) and Théophile Jules Pelouze (FR) determined the elemental composition of lactic acid (1289).

Joseph Louis Gay-Lussac (FR) proposed that all plant seeds contain nitrogen (1288).

Hugo von Mohl (DE) demonstrated that sporangia of pteridophytes (ferns, horsetails, and club-mosses) and the pollen-producing organs of the phanerograms (seed plants) are analogous (3605).

Francois-Vincent Raspail (FR) used microincineration to demonstrate that leaves and other parts of plants can be calcined and reduced to ashes, losing all traces of organic matter, without the loss of general structural characters (2853). The next notable advance was made when R.E. Liesegang (DE) modified the technique to deal with sections of animal tissues, which were calcined on slides for the purpose of microchemical analysis (2089).

Ferdinand Rose (DE) observed that a green precipitate developed when a protein solution (e.g., egg white or ox serum) was treated with copper sulfate. In the alkaline range, the precipitate became soluble and formed a deep blue-violet color (2963).

Gustav Heinrich W. Wiedemann (DE) showed that the blue-violet color resulting from the reaction of albumins with a solution of alkaline copper sulfate is due to the substance he called biuret (biuret had been identified as a product of the prolonged heating of urea at high temperatures). This is the origin of the famous Biuret Test for proteins (3740).

Karl Heinrich Leopold Ritthausen (DE) and R. Pott (DE) first applied the biuret reaction to the study of proteins (2946).

Anselme Payen (FR) and Jean-Francois Persoz (FR) isolated and purified a substance from malt extract, which hastened the conversion of starch to sugar and was destroyed by boiling. They called it diastase (Gk. diastasis, separation). This enzyme, which today we call amylase, was the first enzyme to be purified. Its name set the fashion of using the suffix -ase to name enzymes (2733).

Theodor Ambrose Hubert Schwann (DE) conducted similar experiments in 1836 (3125). These organic catalysts were not yet called enzymes—a name invented by Wilhelm Friedrich Kühne (DE) (1920).

Alfons Wendt (CZ), under the direction of Johannes Evangelista Purkinje; Jan Evangelista Purkyne (CZ), discovered the sudoriferous (sweat) glands of the skin with their excretory ducts (3716).

Armand Trousseau (FR) and Amédée Bonnet (FR) reported 200 cases of diphtheria treated with tracheostomy (3396, 3399).

William Wallace (IE), in 1833, originally described the disease known variously as lymphogranuloma venereum (LGV), lymphogranuloma inguinale, lymphopathia venerea, Durand-Nicolas-Favre disease, tropical bubo, climatic bubo, strumous bubo, and poradenitis inguinales (3653).

N. Joseph Durand (FR), Joseph Nicolas (FR), and Maurice Favre (FR) defined it as a clinical and pathological entity (946). The causative agent is Chlamydia trachomatis (serologic type L1, L2, or L3).

Wilhelm Siegmund Frei (DE) developed a skin test for lymphogranuloma venereum. It consists of intracutaneous administration of heated pus from an infected bubo, a positive reaction being indicated by the development of an inflamed necrotic area (1210).

Sven Curt Alfred Hellerström (SE) and Erik Wassen (SE) transmitted lymphogranuloma venereum to monkeys by intracerebral inoculation (1536).

Murray Sanders (US), and Geoffrey Rake (US), Clara M. McKee (US), and Morris F. Schaffer (US) successfully cultivated the agent of lymphogranuloma venereum in tissue culture and chick embryos respectively (2841, 3032).

John Hilton (GB) gave the first macroscopic description of parasitic cysts of Trichina in human muscle (1584).     

Richard Owen (GB) named the organism Trichina spirilis. Louis Joseph Alcide Railliet (FR) later changed the name to Trichinella spirilis (2597, 2839).

Joseph Leidy (US) discovered the cyst of the human parasite Trichina spiralis in pork (2015, 2020).

Rudolf Ludwig Karl Virchow (DE) was the first to describe the adult form of the Trichina worm (3478).

Friedrich Albert Zenker (DE) noted the intestinal and muscular forms of trichinosis and concluded that eating raw pork infected humans (3828).

Karl Georg Friedrich Rudolf Leuckart (DE) and Friedrich Albert Zenker (DE) found that Trichina spiralis causes trichonosis in man (2042, 2044, 3827).

James Paget (GB) and Samuel Wilks (GB) gave the first microscopic description of Trichina cysts in human muscle (2616, 2617).

Gilbert Breschet (FR) traced human fetal development from conception until birth. He described embryonic and fetal development, which lead to parturition and birth defects (409).

Evory Kennedy (IE) gave the first detailed account of fetal heart tones (1788).

Valentine Mott (US) ligated the right subclavian artery within the scaleni during an operation for aneurysm (2406). 

Carl von Rokitansky (CZ-AT) practiced as a pathologist in Vienna at the Allgemeines Krankenhaus from 1833 to 1875. During this time he either personally performed or supervised 59,786 autopsies (of which at least 25,000 were medico-legal) reporting the effects of disease on the tissues and organs. This was a novel approach and paved the way for treating patients to halt the anatomical changes occurring during a disease state rather than treating the symptoms, as was common practice. For centuries the accepted method of attempting a cure had been treatment of symptoms, e.g., lower a fever by wrapping the patient in cold towels and placing ice in the mouth.

Rokitansky was one of the first to recognize a relationship between the brain and digestive tract function by pointing out that infectious lesions involving the base of the brain were commonly associated with gastric hemorrhage and perforations of stomach and duodenum. He was the first to differentiate between lobar and lobular pneumonia, gave the first pathological account of spondyloisthesis, the first accurate description of acute yellow atrophy of the liver, and the correct classification of patent ductus arteriosis as a congenital lesion (3088, 3617).


A pandemic of influenza occurs in Europe (733).

1834 - 1854 

André Marie Constant Duméril (FR) and Gabriel Bibron (FR) authored Erpétologie Générale; ou, Histoire Naturelle Complète des Reptiles, a ten volume work representing a major summary of the field of herpetology. It gives a comprehensive scientific account of the reptiles in general (including the amphibians as the distinct order Batrachia), as to their structure and physiology as well as their systematics, together with an historical account of the literature of the subject (931). Note: Auguste H. A. Dumeril (FR), son of the senior author, aided in the preparation of volumes 7 and 9 after the death of Bibron.


There is a dysentery (the "bloody flux") pandemic in Central Europe (2).


Michael Faraday (GB) in his report On Electrochemical Decomposition introduced terms suggested to him by William Whewell (GB), and still used today (e.g., anode, cathode, electrolyte, ion, anion, cation) (1058, 3753).

Friedlieb Ferdinand Runge (DE) obtained carbolic acid (now called phenol) from coal tar (2996).

Friedlieb Ferdinand Runge (DE) discovered that coal tar contains several interesting compounds. One of these gave a beautiful bright red color on contact with hydrochloric acid. He called it pyrrole after the Greek word for ‘fiery red oil’ (2997). Aniline blue or its constituents are used to stain collagen as the fiber stain in Masson's trichrome, as well as to reveal callose structures in plant tissues. It can be used in the Mallory's connective tissue stain and Gömöri trichrome stain. It is used in differential staining.

Thomas Anderson (GB) obtained pyrrole in a pure state from ivory oil. He transformed it into its potassium salt then hydrolyzed and distilled it to yield pure pyrrole (45).

Johann Friedrich Wilhelm Adolf Baeyer (DE) and Adolf Emmerling (DE) suggested the structure of pyrrole (94).

Chichester Alexander Bell (GB) and Edwin Lapper (GB) synthesized pyrrole (159).

Ludwig Knorr (DE) and Carl Ludwig Paal (DE) developed synthetic methods for producing derivatives of pyrrole (1833, 2611).

Hans Fischer (DE) synthesized naturally occurring pyrrolic pigments (1101, 1104, 1107, 1108, 1110, 1115-1117, 1119, 1121, 1125).

Leon Pavel Teodor Marchlewski (PL), in collaboration with Wilhelm Marceli Nencki (PL) proved that hemin and chlorophyll are structurally related (1106, 2235). These are the tetrapyrrolic pigments of life.

Hans Fischer (DE) showed that the urine and feces of a case of congenital porphyria, a disease then recently discovered, contained uroporphyrin and coproporphyrin (1101, 1103, 1117).

Hans Fischer (DE) discovered porphyrin syntheses then subsequently synthesized over 130 isomers (1101, 1104, 1119).

Hans Fischer (DE) introduced iron into protoporphyrin thus synthesizing hemin indistinguishable from natural hemin obtained from hemoglobin (1105).

Paula Sachs (DE) found that urine from patients with acute porphyria gives a positive Ehrlich reaction, which is characteristic for pyrrole and its derivatives (3012).

Gerry H. Cookson (GB) and Claude Rimington (GB) characterized the component responsible for the positive Ehrlich reaction as porphobilinogen, the precursor of all tetrapyrrolic pigments known (680).

Hans Fischer (DE) developed the techniques necessary to synthesize biliverdin and bilirubin (1100, 1102, 1109, 1111-1114, 1118, 1120). Note: In the spleen heme is converted to biliverdin, which is converted to unconjugated bilirubin. Unconjugated bilirubin enters the blood prior to being converted to conjugated bilirubin in the liver. It then enters the small intestine in bile. Conjugated bilirubin is converted to urobilinogen in the small intestine then transported to the kidneys via the blood. In the kidney urobilinogen is converted to urobilin, which is excreted in the urine. 

Hans Fischer (DE) put forward his formula for the structure of chlorophyll a. He found that the formula for chlorophyll b is the same as that for chlorophyll a, except that in the former a formyl group replaces the methyl group in pyrrole ring II of the latter (1122-1124). At his death Fischer had nearly completed the synthesis of chlorophyll. Note: See, Woodward 1960 for the synthesis of chlorophyll.

Hans Fischer (DE) discussed the relationship between hemin and chlorophyll (1106).

Johann Justus Liebig (DE) and Eilhardt Mitscherlich (DE) established the elementary composition of uric acid (2074, 2361).

Carl Julius Fritsche (DE) correctly described the structure of starch granules (1234).

R.T. Guérin-Varry (FR) fractionated starch from wheat (Triticum spp.) into an integumentary part and two soluble parts, which he called amidon and amylin. When he analyzed these soluble fractions he discovered that they contained hydrogen and oxygen in the same ratio as occurred in water (1436-1438).

Anselme Payen (FR), in 1834, purified cellulose from plant tissue and named it. The name cellulose started the trend of using the -ose suffix in naming sugars (2701).

Ludovici Davidis de Schweinitz; Lewis David von Schweinitz (US) described over 3,000 species of fungi, more than half of which were species new to science (827). De Schweinitz was considered a world authority on the cryptogamia. 

Johann Nepomuk Eberle (DE) showed that an acidic extract of the gastric mucosa causes the dissolution of coagulated egg white (965).

Theodor Ambrose Hubert Schwann (DE) showed that glandular structures in the gastric mucosa of the stomach are responsible for the properties of gastric juice. He also discovered that corrosive sublimate (mercuric chloride) formed a precipitate in such extracts, and that on converting the mercury to its insoluble sulfide and filtering, the filtrate possessed a high degree of digestive power. The active substance thus precipitated he called pepsin (Gk. pepsis, cooking, digestion). This paper constitutes the first mechanistic enzyme study. “Free acid is…essential in digestive action [but is] however not the only active element…. Since [another substance] active in very small amounts carries on the digestion of the most important animal nutrients, one might with justice apply to it the name pepsin” (3125, 3126). See, Beaumont, 1825.

Francois Remy Lucien Corvisart (FR) used pepsin therapeutically to improve digestion (700, 701).

Karl Gotthelf Lehmann (DE), in 1853, gave the name peptone to the end product of pepsin-hydrochloric acid action on proteins (2013).

Rudolf Peter Heinrich Heidenhain (DE) noticed in the stomach three types of cells in the gastric glands and showed that one, the chief or zymogenic cells, secret the enzyme pepsin, a second type the parietal cells secrete hydrochloric acid, and the third type is the epithelial cell (1521, 1523).

Nikolai Nikolaevich Lubavin (RU-CH-DE) observed that the action of pepsin on proteins results in the uptake of water and cleavage, with the formation of peptones and later leucine and tyrosine (2144).

Joseph Dalton Hooker (GB), Eugen Franz von Gorup-Besánez (AT-DE) and H. Will (DE) concluded that carnivorous plants produce an enzyme like pepsin (1624, 3536).

John Howard Northrop (US) was the first to crystallize the enzyme pepsin. He demonstrated that it is a protein (2530, 2531).

Joseph Stewart Fruton (PL-US) and Max Bergman (DE-US) produced a synthetic polypeptide that they cleaved with purified pepsin, thus demonstrating that pepsin hydrolyzes peptide bonds (179, 1237). 

Karl Friedrich Wilhelm Ludwig (DE), in 1834, pointed out that some innervations of blood vessels serve to maintain blood vessel tonus and thus blood pressure. Ref

Robert Bentley Todd (IE-GB) defined peripheral neuritis and described the sensory element in sphincter control (3361).

Friedrich August von Alberti (DE) first used the term Triassic when he recognized the unity of the three characteristic strata that compose the sedimentary deposits of the Triassic period in Northern Europe. The three-division sequence consists of variegated Bunter sandstone, Muschelkalk (shell) sandstone, and Keuper sandstone (3496). The Triassic Period of the Mesozoic Era was a time of transition and follows the largest extinction event in the history of life, and so is a time when the survivors of that event spread and recolonized. 

The organisms of the Triassic can be considered to belong to one of three groups: holdovers from the Permo-Triassic extinction, new groups which flourished briefly, and new groups which went on to dominate the Mesozoic world. The holdovers included the lycophytes, glossopterids, and dicynodonts. While those that went on to dominate the Mesozoic world include modern conifers, cycadeoids, and the dinosaurs.

Rocks rich in Triassic fossils include: the Moenkopi Formation, Arizona; Ischigualasto Badlands, Argentina; Newark Supergroup, Eastern U.S.; Djadochta, Mongolia; and the Chinle Formation, Arizona.

The journal Müller’s Archiv (Archiv für Anatomie und Physiologie) was founded.

Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, Paris was founded. It was subdivided into series A, B, and C in 1966.

India Journal of Medical Sciences was founded.

ca. 1835

Ernst Heinrich Weber (DE) discovered that the minimum difference in intensity that the brain can distinguish between two sensations of identical kind maintains a constant relationship to the total intensity of sensation (3687).

John Hunter (GB) advised in cases of breast cancer, “We should examine, for example, the glands in the groin or axilla, to ascertain if they are thickened or swoln, and also the course of the absorbents; for if these are sound and movable, then the disease may be safely removed. But if they are deep or fixed as not to admit of removal, then we must consider whether the whole limb can be removed, above the consequent tumours; and if not, we ought to do nothing.” In cases of the cancerous testicle Hunter remarks, “but when I recollected that the scrotum was affected, I knew it to be owing to the lymphatics of the scrotum, which pass through the groin” (868, 1665). This illustrates his appreciation of lymphatic involvement in malignant disease. Note: John Hunter died in 1793, so the original manuscript was written some time earlier.

John Hunter (GB) was the first to clearly describe the pathological details of the formation of sequestra in chronic osteomyelitis. “Exfoliation. —This is the separation of a dead bone from the living, and is not generally understood … When a piece of bone becomes absolutely dead, it is then to the animal machine as any other extraneous body, and adheres only by the attraction of cohesion to the machine. The first business of the machine, therefore, is to get rid of this cohesion and discharge it …” (1665). Note: John Hunter died in 1793, so the original manuscript was written some time earlier.

John Hunter (GB) was the first to present a satisfactory theory of the mechanism of referred pain. “This delusion of the senses makes disease seem where it really is not, from the different seat of the symptoms and of the diseased part…When the trunk of the nerve is injured, the pain is referred to the termination of it, as, after amputation of the leg, pain is felt in the toes” (1665). Note: John Hunter died in 1793, so the original manuscript was written some time earlier.

S. Martyn (GB) discussed the concept of referred pain (2252).

John Hilton (GB) discussed a case for referred pain and described the synovial membrane as a serous membrane endowed with secreting and absorbing powers (1586).

John Hunter (GB) offered an explanation for accommodation by the eye. “I saw no power that could adapt the eye to the various distances … unless we suppose the crystalline humour [lens] to be varied in figure” (1665). Note: John Hunter died in 1793, so the original manuscript was written some time earlier.

John Hunter (GB) observed that the organ of hearing in Mollusks (Cephalopods) is of different construction from that in fishes. He suggested a progression from the invertebrates through the vertebrates, with the Mollusks lacking a semicircular canal, the Cyclostomes having one semicircular canal, the lamprey two, the cartilaginous and bony fishes three (1665). Note: John Hunter died in 1793, so the original manuscript was written some time earlier.


Typhus fever is epidemic in Scotland (714).


Lambert Adolphe Jacques Quetelet (BE) showed the importance of statistical analysis for biologists and laid the foundation of biometry (2825, 2826)

Michel-Eugène Chevreul (FR) discovered creatine (Gk. kreas, flesh) in muscle tissue (609).

Pierre-Jean Robiquet (FR) made the dye rufigallol (668).

Pierre-Joseph Pelletier (FR) refined his procedure for fractioning opium and separated codeine, paramorphine (thebaine), and pseudo-morphine (oxydimorphine, dehydromorphine). The latter was found to be non-poisonous and to contain less carbon and more oxygen than morphine (2711). 

Johann Justus Liebig (DE) proved that the first step in the oxidation of alcohol by organisms is the formation of an aldehyde (2075, 2076).

Friedrich Gustav Jacob Henle (DE) was among the first authors to use the term cell in its modern biological context. Writing in volume 13 of Encyclopädisches Wörterbuch der Medicinischen Wissenschaften he described the microscopic anatomy of the prismatic epithelium of the gall bladder saying, “If they are turned upward under the microscope, these surfaces appear more or less angular and like cells” (1541).

Athanase Peltier (FR) and Félix Dujardin (FR) demonstrated that the spermatozoa are produced in the lining of the seminiferous tubules of the testis (924, 925, 2719).

Rudolf Albert von Kölliker (CH), in 1847, demonstrated the true development of the spermatozoa, showing that they are not extraneous bodies, but originate in testicular cells and fertilize the ovum (3575).

Hugo von Mohl (DE), for the first time, carefully described some details of mitosis in plants including the appearance of the cell plate between daughter cells. He remarked, "Cell division is everywhere easily and plainly seen in Confervae, Mycelia, Chara and also in terminal buds and root tips of Phanerogams." He described and drew quadripartition by furrowing in the pollen-mother-cells of Cucurbita (3606).

Wilhelm Friedrich Benedikt Hofmeister (DE) used Tradescantia and other species of plants to provide the first accurate descriptions of all stages of mitosis. He was able to describe the loss of the nuclear membrane prior to cell division. He also presented evidence of cell division leading to the formation of tetrads within pollen (meiosis) but did not grasp its significance (1613).

Friedrich Anton Schneider (DE) published one of the first reasonably accurate descriptions of what Walther Flemming (DE) later named mitosis. His material was the dividing egg of Mesostomum ehrenbergii, one of the platyhelminths. He observed prophase, metaphase, and the formation of a spindle. He did not name them (3086). He discovered the connection between the adult and larva of phoronids and is commemorated by Spirinia schneideri Villot, 1875 and Protodrilus schneideri Langerhans, 1880) (3085).

Otto Bütschli (DE) and Hermann Fol (CH) independently described complex nuclear changes which occurred during cell division and which are now termed mitosis (544, 1179).

Édouard-Gérard Balbiani (FR) was the first to recognize the mechanical significance of the mitotic events. He noted that narrow little sticks (chromosomes) were divided into two groups then partitioned between the two daughter cells (103).

W. Schleiclier (DE) had named this type of cell division karyokinesis (3065, 3066).

Walther Flemming (DE) was a pioneer in applying stains to cells. The nucleus had strong affinity for one of the dyes he used so he called the nuclear material chromatin (Greek, color) and speculated that it might be synonymous with nuclein. When he dyed a section of growing tissue, cells were caught at different stages of cell division and he could sort out the successive stages through which the chromatin material passed. As the process of cell division began, the chromatin coalesced into short threadlike objects that eventually came to be called chromosomes (colored bodies). Because these thread-like chromosomes were so characteristic a feature of cell division, Flemming named the process mitosis, from a Greek word for thread. He chose the epithelial cells of salamander larvae for his studies.

As cell division proceeded, the chromosomes doubled in number. After that came what seemed the crucial step. The chromosomes, entangled in the fine threads of a structure that Flemming named the aster (star), were pulled apart along their length, half going to one end of the cell, half to the other. The cell then divided and the two daughter cells, each left with an equal supply of the chromatin material. And, because of the doubling of the chromosomes before the division, each daughter cell had as much chromatin as the original undivided cell (1154-1157, 1159).

W. Schleiclier (DE) working with frog and cat tissue was one of the first to describe mitosis in animal cells. He coined the term karyokinesis to describe the nuclear events during mitosis (3065, 3066).

Eduard Adolf Strasburger (PL-DE) accurately described the processes of mitotic cell division and demonstrated that cells are formed directly from previously existing cells (3274, 3275).

Walther Flemming (DE) studied amphibian oocytes, described their giant nucleus or germinal vesicle, and discovered their unusual lampbrush chromosomes, and multiple, peripheral nucleoli. He coined the terms chromatin, mitosis, and spireme (1157).

Wilhelm Pfitzner (DE) coined the term chromomeres to name the granules that may appear along a chromosome (2740).

Giulio Cesare Bizzozero (IT), in 1883, made drawings of cells in various stages of mitosis in spleen tissue from the Triton (large sea snail) (2271).

Wilhelm Roux (DE) hypothesized that mitosis is a devise, which ensures that the qualitative properties of the cell nucleus are equally distributed to the two daughter cells. He proposed that each of the chromosomes carries a different genetic load (2981, 2984).

Eduard Adolf Strasburger (PL-DE) coined the terms prophase, metaphase, and anaphase (3277).

Karl Rabl (DE), from his work with Salamandra maculata und Proteus, theorized that the chromosomes retain their individuality in all stages of the cell cycle. He conjectured that the threads of chromatin into which a given chromosome dissolves when the nucleus enters the resting stage condense again into the same chromosome at the next mitosis. He insisted on constancy in the number of chromosomal filaments characteristic of a given tissue (2833, 2834).

Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) coined the word chromosome to refer to the chromatin staves (3631).

Theodor Boveri (DE) observed that chromatin is the substance that transforms into chromosomes during mitosis (376).

David Paul Hansemann (DE) described in detail the mitotic figures of 13 different carcinoma samples. In every case, he found examples of aberrant mitotic figures. These included multipolar mitoses and anaphase figures that showed asymmetric distribution of 'chromatin loops' (or chromosomes). He postulated that these aberrant cell divisions were responsible for the decreased or increased chromatin content found in cancer cells (3547). This is called the aneuploidy theory of cancer development.

Henrik Lundegardh (SE) coined the term interphase as it applies to mitosis (2160).

Theodor Boveri (DE) suggested that aberrant mitoses lead to the unequal distribution of chromosomes, which, in most cases, are detrimental. Yet, on occasion, a "particular, incorrect combination of chromosomes" will generate a malignant cell endowed with the ability of unlimited growth (schrankenloser vermehrung), which will pass the defect on to its progeny. He foretold the existence of cell-cycle checkpoints (hemmungseinrichtungen), tumor-suppressor genes (teilungshemmende chromosomen) and oncogenes (teilungsfoerdernde chromosomen). He further envisaged that poisons (including nicotine), radiation, physical insults, pathogens, chronic inflammation and tissue repair might all be linked to the development of cancer by indirectly promoting aberrant mitoses or other events that cause chromosome imbalances. Boveri applied his model further to explain the emergence of different tumor types within one tissue, and anticipated the clonal origin of tumors, the allelic loss of recessive chromosome elements, the heritability of cancer susceptibilities, the similarity of the steps that initiate tumorigenesis and those responsible for cancer progression, and the sensitivity of cancer cells to radiotherapy (369, 378).

Gottfried Reinhold Treviranus (DE) asserted that spermatozoa are analogous to the pollen of plants (3390). 

Agostino Bassi (IT), a lawyer by trade and amateur scientist by love, demonstrated that a fungus—later named Botrytis bassiana in his honor—is the causative agent of calcinaccio, a devastating disease of silkworms (the English called it muscardine). This was the first demonstration that an infectious animal disease was due to a microbe. William Bulloch (GB), the historian, says, “He is justly regarded as the real founder of the doctrine of pathogenic microorganisms of vegetable origin" (517).

Bassi also wrote on the use of germicides such as heat, alcohol, acids, alkalies, sulfur, chlorine, calcium chloride, and potassium nitrate. For cholera he recommended immediate isolation of the patient followed by disinfection of their clothes and excreta. When vaccinating children in series he strongly recommended sterilizing the needle between each vaccination so as to prevent complications or the transference of diseases other than vaccinia (128, 130, 517).

Felix Dujardin (FR) associated the sarcode (protoplasm) of protozoa with life processes and placed the foraminiferans among the rhizopods (923).

Johannes Evangelista Purkinje; Jan Evangelista Purkyne (CZ) and Gabriel Gustav Valentin (DE-CH) discovered ciliary movements on epithelial cells within the multicellular animal body (2820).

Michael Sars (NO) was a pioneer in studies of development, metamorphosis and metagenesis of several marine animal groups, like Scyphozoa, Mollusca, Asteroida, and Annellida. Along with Sven Lovén (SE) he found and described the trochophore larvae (annelid). He was the first to describe the veliger larvae of mollusks (1837, 1840) and the bipinnaria larvae (1835), which he later identified as a stage in development of sea stars (3040-3042).

Andrew Buchanan (GB) concluded that the coagulant power of a "washed clot" on ascetic fluid, serum from the chest, and hydrocele fluid was because the clot produced a coagulum similar to that, which separates spontaneously from blood (504, 505, 507).

Andrew Buchanan (GB) concluded that coagulation of pleural, peritoneal, pericardial, serous testicular, and hydrocele fluids was not the result of the spontaneous coagulation of fibrin but rather that, …”like albumin and casein, fibrin often coagulates under the influence of suitable reagents: and that the blood and most other liquids of the body which appear to coagulate spontaneously, only do so in consequence of their containing at once fibrin and substances capable of reacting upon it and so occasioning coagulation” (506).

Rudolf Ludwig Karl Virchow (DE) was the first to use the term thrombin (3406).

Prosper Sylvain Denis (FR) published two monographs in 1856 and 1859 which validated and extended Panum’s technique of fractionating complex materials like egg albumin and blood plasma into distinct proteins by salting out. Upon the salting out of blood plasma it yielded a precipitate, which was not soluble in water but was soluble in a dilute salt solution. The salt soluble fraction possessed properties of a precursor to fibrin. Denis gave the name plasmine to this precursor of fibrin (844).

Benjamin Guy Babington (GB) had already named this fibrin precursor fibrinogen. See, Babington, 1830.

Hermann Adolf Alexander Schmidt (DE) separated plasmine into its two constituents, both proteids of the globulin class to which he gave the names fibrinogen and fibrino-plastic substance (3076). The later constituent was called para-globulin by Wilhelm Friedrich Kuhne (DE) and serum globulin by Theodor Weyl (DE) (1918, 3730).

Hermann Adolf Alexander Schmidt (EE-DE) repeated the experiments described by Buchanan and called the activity fibrin ferment (thrombin). He found that fibrin ferment could be precipitated by addition of alcohol to fresh serum. Schmidt later concluded that since the presence of thrombin in the circulation did not allow blood to remain fluid it must have a precursor, prothrombin. At first, therefore, prothrombin was hypothetical (3077-3079). Prothrombin activation occurs due to the presence of "zymoplastic substances" in the tissues.

Olof Hammarsten (SE) and Karl Friedrich Wilhelm Ludwig (DE) showed that fibrinogen is the sole precursor of fibrin and that fibrin is the consequence of a reaction between thrombin and fibrinogen (1476-1478).

William Dobinson Halliburton (GB) concluded that coagulation of the blood is due to the formation of fibrin from fibrinogen which was previously dissolved in the blood-plasma; that this change is brought about by the fibrin ferment; and that the fibrin ferment is one of the products of the disintegration of the white blood-corpuscles that occurs when the blood is shed (1471).

Nicolas Maurice Arthus (FR), Calixte Pages (FR) and L. Sabbatini (FR) observed that precipitation of calcium inhibits coagulation, and that this effect is reversed when sufficient calcium is re-added. Calcium is not required for the reaction of thrombin with fibrinogen, but is required for the conversion of the hypothetical prothrombin to thrombin (65, 2827, 3000).

Joseph Lister (GB) maintained that the blood has no spontaneous tendency to clot but that it only clots when brought into contact with a foreign body (2101).

Paul Morawitz (DE) called these “zymoplastic substances” thrombokinase, and William Henry Howell (US) later denominated them "tissue thromboplastins" (factor III) (1649, 2382).

Paul Morawitz (DE) synthesized various observations into one of the first formulations of the biochemistry of blood coagulation: prothrombin, he hypothesized, was converted into the enzyme thrombin by “thrombokinase” (tissue factor) in the presence of calcium; thrombin, in turn, converted fibrinogen to fibrin (2382).

John H. Ferguson (US) discovered the presence of intrinsic thromboplastin under the name of tryptase (1071).

Jean Baptiste Bouillaud (FR) used experiments as well as controlled clinical and autopsy findings, to confirm the view of Gall, that the center for articulate speech is located in the anterior lobes of the brain. He further pointed out the difference between the ability to create words and the ability to articulate them—internal and external language.

Bouillaud was an outstanding cardiologist, being the first to name and describe accurately the endocardium and endocarditis. He realized that endocarditis usually began with exudation and terminated with cicatrisation (scaring) and deformity of the valves. He pointed out the association between endocarditis and acute articular rheumatism (rheumatic heart disease). See, Baillie, 1793. He elucidated the mechanism and significance of the normal heart sounds, described the positive venous pulse in the neck, stressed its value in the diagnosis of tricuspid insufficiency, and described the bruit du diable, gallop rhythm, the double sound at the apex in mitral stenosis, the friction in pericarditis, extrasystoles, and auricular fibrillation (343-345).

Pierre-Carl-Èdouard Potain (FR) determined that the “Gallop rhythm" [bruit de galop] results from the abruptness with which the dilation of the ventricle takes place during the pre-systolic period…. It appears to be an indirect consequence of the excessive arterial tension which interstitial nephritis produces (2777).

Jean-Baptiste Bouillaud (FR) coined and defined the terms endocarditis and valvular endocarditis (342).

Samuel Wilks (GB) discussed bacterial endocarditis as a source of pyemia in peripheral circulation (3748).

James Young Simpson (GB) wrote on diseases of the placenta (3179), peritonitis in the fetus (3181), hernia in the fetus (3182), and hermaphrodism (3180).

Wilhelm Friedrich von Ludwig (DE) described Ludwig's angina, otherwise known as angina ludovici; a serious, potentially life-threatening cellulitis or connective tissue infection, of the floor of the mouth, usually occurring in adults with concomitant dental infections and if left untreated, may obstruct the airways, necessitating tracheotomy (3600).

Cellulitis is a diffuse inflammation of connective tissue, caused by bacteria, with severe inflammation of dermal and subcutaneous layers of the skin. Cellulitis can be caused by normal skin flora or by exogenous bacteria. Erysipelas is the term used for a more superficial infection of the dermis and upper subcutaneous layer that presents clinically with a well-defined edge.

Jean Zuléma Amussat (FR) presented his method for alleviating hemorrhages of the arteries (44).


"The great rule is, to avoid everything which obviously deranges the stomach." Richard Bright (433)

Auguste Laurent (FR) advanced the hypothesis that the structural grouping of atoms within molecules determines how the molecules combine in organic reactions (2538).

Gerardus Johannes Mulder; Gerrit Jan Mulder (NL), a pioneer in the investigations of molecules associated with living tissue, analyzed silk, egg albumin, serum albumin, blood fibrin, casein, gelatin from several sources, and other substances of similar properties. He concluded that they all contained a common radical which, at the suggestion of von Berzelius, he called protéine, later protein (Gk. proteios, primary) (2410-2415, 2417, 2420). Six years later he wrote, “There is present in plants and animals a substance which … performs an important function in both. It is one of the very complex substances, which under various circumstances may alter their composition and serves … for the regulation of chemical metabolism … It is without doubt the most important of the known components of living matter, and it would appear that, without it, life would not be possible. The substance has been named protein.” Ref

Jöns Jakob von Berzelius (SE) demonstrated that the hydrolysis of starch is catalyzed more efficiently by malt diastase than by sulfuric acid and published the first general theory of chemical catalysis (3513-3516). Note: The 1836b paper contains the first definition of catalysis.

Jöns Jakob von Berzelius (SE) coined the term catalysis to name a force involved in the decomposition of hydrogen peroxide. “The catalytic force is reflected in the capacity that some substances have, by their mere presence and not by their own reactivity, to awaken activities that are slumbering in molecules at a given temperature.” “I shall also call catalysis the decomposition of bodies by this force” (3513-3516).

Jöns Jakob von Berzelius (SE) attributed fermentation to the catalytic force doctrine, which says that yeasts serve as catalysts setting off the fermentation process. Fermentation itself is purely chemical, not requiring living things to carry it out (3514).

Charles Giles Bridle Daubeny (GB) investigated the efficiency of different parts of the visible light spectrum in photosynthesis (774).

Franz Joseph Andreas Nicolas Unger (AT) proposed the chemical concept of plant distribution, i.e., that mineral content of rocks and soils is the major edaphic influence on substrate-specific plant distribution (3416).

Franz Schulze (DE) proved that when a solution containing animal or vegetable matter is boiled, no putrefaction sets in provided that all air, which is allowed to have access to the liquid, is previously passed through strong sulfuric acid. Heating the air gives the same result. He also found that boiling would stop a wine fermentation that is in progress. The wine fermentation will remain inactive as long as air contacting it is treated as above (3118).

Asa Gray (US) championed Darwin’s theory of evolution and authored several important botanical works including: Darwinana; Elements of Botany; Flora of North America; How Plants Grow; Field, Forrest, and Garden Botany; and Manual of Botany of the Northern United States (1403-1408). The Manual of Botany of the Northern United States is now called Gray’s Manual of Botany. It has for many years been the most important and influential book dealing with the Northern American flora.

Merritt Lyndon Fernald (US) authored the eighth edition of Gray's Manual of Botany, the standard for plant identification in North America (1072).

William Henry Harvey (IE) was the first to subdivide the algae into four divisions based on the dominant pigment in their thallus: the Chlorospermeae (green algae), Rhodospermeae (red algae), Melanospermeae (brown algae) and Diatomaceae (diatoms and desmids) (1503). Today these are called Rhodophyta, Heterokontophyta, Chlorophyta, and Diatomaceae.

Constantine Samuel Rafinesque (TR-FR-IT-US), a brilliant eccentric self-taught polymath, published 6,700 binomial names of plants, many of which have priority over more familiar names (317, 2309).

In his Flora Telluriana he details 2,000 new species of plants (2836, 2837).

Rafinesque was the first to declare earthworks, primarily from the Ohio Valley, as the "Ancient Monuments of America." He listed more than 500 such archaeological sites in Ohio and Kentucky (3681).

John Vaughan Thompson (IE) was the first to describe the barnacle, Sacculina, and its parasitism of the shore crab, Carcinus maenas (3334).

Alfred Francois Donné (FR), while examining women with abnormal vaginal discharge, discovered and named Trichomonas vaginalis. He at first believed it to be the infectious agent in gonorrhea. He later determined it to be a normal inhabitant of the female genital tract. Donné was, by this work, the first to describe living organisms in pathological conditions, as observed by modern methods (879).

John Le Couteur (GB) published a summary of his work on wheat breeding. This summary has been the basis and origin of variety testing (2005).

Patrick Sheriff (GB), ca. 1850, improved cereals by deliberately selecting individual ears of great excellence and segregating their progeny from mingling with mediocre stock. He became a celebrated breeder and originator of desirable varieties (832). “A good variety may be safely regarded as the forerunner of a better one” (3167).

Richard Bright (GB) and Thomas Addison (GB) gave a very accurate description of appendicitis (453). Appendicitis had been described as early as 30 B.C.E. See, Aulus Cornelius Celsus. 

John Vaughan Thompson (IE) discovered the Pentacrinus europaeus, and showed that it is the larval form of the feather-star Antedon (Comatula) (3333).

Gilbert Breschet (FR) discovered the rete mirabile (marvelous network), the organ that enables whales and dolphins to survive at great depths (410). The rete mirabile exchanges heat, ions, or gases between vessel walls so that the two bloodstreams within the rete maintain a gradient with respect to temperature, or concentration of gases or solutes.

Charles Dickens (GB), the novelist, described his character Joe the Fat Boy as loud snoring, hypersomnambulant, obese, with a bizarre personality, polycythemia, and congestive heart failure (851). Doubtless what is today called obstructive sleep apnea syndrome.

Albert G. Bickelmann (US), C. Sydney Burwell (US), Eugene Debs Robin (US), and Robert D. Whaley (US) described a medical case, which they named Pickwickian Syndrome. Their patient, a 51-year-old business executive who stood 5 feet 5 inches and weighed over 260 pounds entered the hospital because of obesity, fatigue, and somnolence (243). The name was chosen because the symptoms are the same as those of the fat boy, Joe, described by Charles Dickens in his The Posthumous Papers of the Pickwick Club, 119 years earlier.

Joseph Honoré Simon Beau (FR) was one of the first to characterize myocardial insufficiency and inability of the heart to perform a complete systole. This incomplete contraction involves the ventricles primarily (148).

Philippe Frédéric Blandin (FR) wrote the first general treatise on plastic surgery, including a review of the history of plastic surgery (297).

Christian Jurgensen Thomsen (DK) studied the characteristics of the tools from different periods of prehistory. On the basis of the predominant materials of which these tools were made, he divided early human history into the Stone Age, the Bronze (Brass) Age, and the Iron Age (3339). Note: The three-age system actually originated with Lucretius, however, this work popularized the concept in a practical way.

Thomsen’s work led to the Law of Association, which deduces that objects placed in a grave as part of a burial generally consist of things in use at the time of interment.

John Lubbock (GB) further subdivided the Stone Age into Paleolithic and Neolithic periods (2145). Late in the nineteenth century, the Mesolithic period was conceived.

Adam Sedgwick (GB), while working in central Wales, proposed the existence of a separate system below the Silurian, which he named the Cambrian -- commemorating Cambria, the Latin name for Wales (3152). This represents the discovery of the Cambrian Period of the Paleozoic Era. The system was not fully recognized until the faunas were described by Frederick Mac Coy (IE)-AU) and John W. Salter (GB) (3029, 3151).


England experiences an epidemic of smallpox (red plague) and typhus fever.


An epidemic of cerebrospinal meningitis spreads out over Europe from Bayonne, France.


"It is quite impossible for any man to gain information respecting acute disease, unless he watch its progress. Day after day it must be seen; the lapse of eight and-forty hours will so change the face of disease.... Acute disease must be seen at least once a-day by those who wish to learn; in many cases twice a-day will not be too often." Richard Bright. Address delivered at the Commencement of a Course of Lectures on the Practice of Medicine (439).

Giovanni Battista Amici (IT) developed very high-powered achromatic lenses for the compound microscope (42). See, Beeldsnijder, 1791.

Johann Justus Liebig (DE) detailed the constitution of organic compounds and described the modern method of chemical analysis. His conviction that vital activity could be explained in physicochemical terms was an important one for investigators interested in the nature of life (2077, 2081-2083, 2086).

Johann Justus Liebig (DE) showed that aldehyde is an intermediary product in the oxidation of alcohol to acetic acid (2078, 2079).

Friedrich Wöhler (DE) and Johann Justus Liebig (DE) isolated the enzyme emulsin from almond extract (3786).

Charles Cagniard-Latour; Cagniard de la Tour (FR) stated that the non-motile globular yeasts of beer are organized bodies probably belonging to the vegetable kingdom. He found that wines contain similar yeast globules which can survive cooling to -5°C in liquid carbon dioxide. He believed that yeast activity formed carbonic acid and alcohol from sugar. Latour observed yeast budding and stated that yeast is a mass of globular bodies capable of reproduction and therefore organized. He stated that yeast are not a simple chemical substance, as had been supposed (550, 551).

Theodor Ambrose Hubert Schwann (DE) examined beer yeast with a microscope and described granules, which were often arranged in rows resembling a segmented fungus. He concluded that yeast is without doubt a plant and clearly connected the yeast plant with the fermentation process. He observed that yeast budding, gas development, and fermentation are frequently concurrent events and noted that when the process is at an end the yeast sink to the bottom. He pointed out the differences between the yeasts of beer and wine and spoke of the yeast plant as Zuckerpilz (sugar fungus), from which the term Saccharomyces was later derived. Schwann also noted the requirement of a nitrogenous substance during the yeast fermentation. 

He carried out experiments that led him to conclude that putrefaction is brought about by microorganisms (3127-3129).

Friedrich Traugott Kützing (DE) described the microbial nature of the scum called mother of vinegar that grows on alcohol, which is being converted to vinegar. 

He was clearly of the opinion that yeast was not a chemical substance but a living thing, and in a discussion on the terms organic and inorganic he developed the idea that all fermentation is vital. Kützing was possibly the first investigator to suggest that different fermentations were due to physiologically different organisms (1942).

August Carl Joseph Corda (CZ) produced a large body of work on the fungi in which he used the microscope to add thousands of new microscopic species (692).

Joseph-Henri Léveillé (FR), Ferdinand Moritz Ascherson (DE), August Carl Joseph Corda (CZ), Johann Friedrich Klotsch (DE), P. Phoebus (DE) and Miles Joseph Berkeley (GB) each independently described the structure of the fungal basidium. Léveille’s paper is best known, for in it he coined the terms basidium and cystidium (66, 181, 184, 692, 2051). Need Klotsch and Phoebus refs

Friedrich Gustav Jacob Henle (DE) was the first to describe the epithelia of the skin and intestines, defined columnar and ciliated epithelium, and pointed out that this tissue constitutes the true lining membrane of all free surfaces of the body and the inner lining of its tubes and cavities (1542).

Pierre-François-Olive Rayer (FR) was the first to describe glanders in man (2876). He demonstrated the transmissibility of glanders (a bacterial disease primarily of solipeds) by infecting a horse with material from a case of glanders in a human subject (2877).

Étinne-Guillaume La Fosse (FR) wrote a treatise on the cause of glanders in horses (1944).

Friederich August Johannes Löffler (DE) and Johann Wilhelm Schütz (DE) discovered that the bacterium Pseudomonas mallei (Burkholderia mallei) is the cause of glanders. This is primarily a disease of horses, mules, and the ass (2118, 2119). 

John W. Nelson (GB), Catherine J. Doherty (GB), P.H. Brown (GB), Andrew P. Greening (GB), Mary E. Kaufmann (GB), and John R.W. Govan (GB) found that Burkholderia cepacia (Pseudomonas cepacia) is an important pathogen of pulmonary infections in people with cystic fibrosis (CF) (2486).

Matthias Jakob Schleiden (DE) published detailed observations on the origin and development of the plant ovule. He confirmed that the pollen tube grows to the ovule and observed that it enters the ovule through the micropyle (3067).

René-Joachim-Henri Dutrochet (FR) reported that stomata communicate with lacunae in deeper plant tissue, that only cells containing green pigment can absorb carbon dioxide and transform light energy to chemical energy, and demonstrated that mushrooms are in fact the fruiting bodies of the mycelium, detected heat from an individual plant and from an insect muscle (957).

Alfred Francois Donné (FR) reported the presence of globules and granular bodies in human milk (880). Some of these were very likely to have been cells.

Hugo von Mohl (DE) discovered chloroplasts in plant cells, calling them Chlorophyllkörnern (chlorophyll granules) (3239, 3607, 3610).

Theodor Ludwig Wilhelm Bischoff (DE), in 1837, published a study on respiration, in which he proved that free carbonic acid and oxygen coexisted in blood. Ref

Louis René Le Canu (FR) found that cholesterol is a constituent of normal human blood (2003, 2004).

Ernst Friedrich Burdach; Karl Friedrich Burdach (DE) published a book on microscopic anatomy of the nervous system (524).

Heinrich Gustav Magnus (DE) discovered that blood, whether from artery or from vein, contains large amounts of both oxygen and carbon dioxide, that the carbon dioxide released in the lungs is not formed locally by oxidation but has been carried there by the blood, and that more oxygen and less carbon dioxide is contained in arterial than in venous blood. All of this suggested that carbon dioxide might facilitate the release of oxygen from the blood and that combustion takes place in the capillaries rather than in the lungs (2204, 2207).

Heinrich Gustav Magnus (DE) was the first to postulate that oxygen and carbon dioxide cross the alveolar-capillary membrane of the lungs by diffusion (2205).

John Gould (GB) was recruited by Charles Darwin to identify his bird specimens collected during the voyage of the Beagle. It was Gould who identified Darwin's Galapagos finches as separate species, thus providing one of the crucial insights in the development of Darwin's theory. Today these unique finches are known as Darwin's finches or Galapagos finches.

George Newport (GB) reported that there is a correlation between activity and elevated body temperature in a moth, a bumblebee, and a beetle (2496).

Marius Nielsen (DK) showed that human body temperature rises during strenuous activity, and is then regulated at a high level corresponding to work output (2505).

Schack August Steenberg Krogh (DK) and Eric Zeuthen (DK) concluded that the temperature of an insect's flight muscle during pre-flight warm-up determines its maximal rate of work output during flight. They demonstrated that wing movements during both pre-flight shivering and flight, are associated with a steady rise in muscle temperature until temperatures approaching human body temperature are reached. The butterfly Venessa could fly when its muscle temperature was as low as 25 degrees C. Their observations of flight muscle temperature in the bumblebee Bombus horti found that the bumblebee's temperatures paralleled those of the butterfly; the thoracic muscles heated up to at least 30°C before flight. In the large lamellicorn beetle, Geotrupes stercorarius, the flight muscles were active even though the wings did not move. When insect subjects stopped exercising they cooled rapidly to their initial body temperatures, and from the cooling curve Krogh and Zeuthen calculated the insects' energy expenditures. They concluded that the heating process during insect pre-flight warm-up is unlikely to be an adaptation for the discharge of nervous impulses from the ganglia to the muscles. Instead, they state that it is "required to allow the muscular engine to develop the energy expenditure for flight" (1910).

Isidore Geoffroy Saint-Hillarie (FR), in 1837, lectured at the Athena in Paris on animal behavior. He coined the word ethologic (ethnology), meaning the study of the relationships of organized beings in the family and society, in the aggregate and the community, and teratology, meaning the study of abnormal individuals (3022). Ethnology and ethnology (the study of human groups) are so close in spelling that confusion often arises. 

Smallpox (red plague) appeared in a Sioux tribe in Missouri, June 1837, then spread to Blackfoot and other tribes in Montana and Saskatchewan. The last previous outbreak among the Blackfoot had been in 1781, so by 1837 most of the population was susceptible (1863).

William Lonsdale (GB), in 1837, suggested from a study of the fossils of the South Devon limestones that they would prove to be of an age intermediate between the Carboniferous and Silurian systems. It was Lonsdale who coined the term Devonian, commemorating Devon county, England (2124).

Adam Sedgwick (GB) and Roderick Impey Murchison (GB) presented researches on certain rocks in Devonshire, England, which had a distinctive fossil assemblage that led them to propose a new division of the geological time scale -- the Devonian. Sedgwick and Murchison first used Devonian in a publication (3153). This represents the discovery of the Devonian Period—408 Ma to 360 Ma—of the Paleozoic Era.


Jöns Jakob von Berzelius (SE) gave the name organic to substances of living or once-living tissue (3517).

Anselme Payen (FR) discovered and determined the chemical composition of cellulose (2701).

Alexandre-Théodore Brongniart, Jr. (FR), Théophile-Jules Pelouze (FR), and Jean-Baptiste-André Dumas (FR), in their report to the French national Academy, coined the terms glucose and cellulose. They defined cellulose as the major constituent of wood, related chemically to starch. They defined it as “ ... a compound which fills the cells and which makes up the substance of the wood itself” (470). As the group’s recorder, Dumas was most likely the person who actually coined these words.

Jean Baptiste Joseph Dieudonné Boussingault (FR) found evidence that nitrogen enters legume plants by some unknown mechanism, but not the non-legumes (355).

Jean Baptiste Joseph Dieudonné Boussingault (FR) carried out greenhouse experiments, which clearly showed that leguminous plants could fix atmospheric nitrogen (358).

J. Lachmann (DE), in 1858, studied the nodules in the roots of legumes and observed bacteria (1946).

Albert B. Frank (DE) showed that the root nodules in legumes are formed due to infection by the organism he named Schinzia leguminosarum believing it to be a fungus (1201).

Martinus Willem Beijerinck (NL) isolated symbiotic nitrogen-fixing bacteria (Rhizobium) from root nodules of leguminous plants by using an enrichment culture medium minus nitrogen containing compounds. He speculated but could not prove that these bacteria fixed nitrogen (154).

Albert B. Frank (DE) realized that the infectious agent in the root nodules of legumes is a bacterium. He names it Rhizobium leguminosarum (1202).

Perry William Wilson (US), E.W. Hopkins (US), Edwin Broun Fred (US), Carl E. Georgi (US), Fred S. Orcutt (US), M.R. Salmon (US), Joseph C. Burton (US), V.S. Bond (US), Wayne William Umbreit (US), P.M. West (US), Sylvan B. Lee (US), George Bond (US), and Robert Harza Burris (US) established: 1) growth substance requirements for rhizobia, 2) the effects of carbon dioxide and light intensity on nitrogen fixation, 3) the pN2 function and the pO2 function in nitrogen fixation, 4) the Michaelis constant for nitrogen fixation in Red Clover, 5) that by using heavy nitrogen they could collect data supporting ammonia as a key intermediate in nitrogen fixation, and 6) that hydrogen is a specific and competitive inhibitor of nitrogen fixation in free living Azotobacter vinelandii and in the rhizobia of red clover (533, 1207, 1301, 3725, 3764-3775).

Robert F. Fisher (US), Thomas T. Egelhoff (US), John T. Mulligan (US), and Sharon Rugel Long (US) discovered that legumes release a flavonoid, which penetrates the rhizobial cells and stimulates a gene-activating protein. The activated bacterial genes produce a Nod factor, which leads to nodule formation by triggering cell division in the legume (1148).

Patrice Lerouge (FR), Philippe Roche (FR), Catherine Faucher (FR), Fabienne Maillet (FR), Georges Truchet (FR), Jean Claude Promé (FR), Jean Dénarié (FR), and Frédéric Debelle (FR) purified NodRm-1 (a sulfated beta-1, 4-tetrasaccharide of D-glucosamine), the major alfalfa specific signal from Rhizobium meliloti, which causes root hair deformation and forecasts nodular formation (2031, 2956).

Christian Gottfried Ehrenberg (DE) described the first observations of wave-shaped flagella, which he thought were probably necessary for motility (984).

George Owen Rees (GB) described a method for isolating sugar from diabetic blood serum (2888).

Eugène-Melchior Péligot (FR) determined that the sugar in diabetic urine is grape sugar (glucose) (2709).

Johannes Evangelista Purkinje; Jan Evangelista Purkyne (CZ), in 1837, discovered the pear shaped cells in the cerebellar cortex which bear his name (2817).

Tradition has it that Purkinje was the first to use the microtome, Canada balsam, glacial acetic acid, potassium dichromate, and the Drummond limelight in the study of tissues.

Theodor Ambrose Hubert Schwann (DE) described ganglion-globules in the gray matter of the brain and spinal cord that contain nuclei and nucleoli, also the double-contoured white substance, which forms the sheath around white nerve fibers (the sheath of Schwann), even noting that the sheath material was fat-like in nature and responsible for the white color of the fibers. It is he for whom the Schwann cells that make up the nerve sheaths are named (3130, 3131, 3133).

Christian Gottfried Ehrenberg (DE) proposed that all bacteria be placed in the class Infusoria. He put the study of microorganisms on a systematic basis and was able to establish a number of groups by clearly recognizing fundamental morphological distinctions, such as those differentiating the spirochetes from certain of the protozoa with which others had grouped them. Some of the names he used, such as bacterium and spirillum, are still used today. It was he who first used the generic term Spirochaeta for the large free-living forms he was observing. He describes the use of indigo and carmine to reveal the stomachs [food vacuoles] of infusorians (983).

John Torrey (US), professor of botany at what is now Columbia University, coauthored A Flora of North America with Asa Gray and authored A Flora of the State of New York (3370, 3371). He is commemorated by the genus Torreya (a rare Florida gymnosperm).

George Johnston (GB) coined the term hydroida as it applied to animals (1751).

Robert Remak (PL-DE) mentions that nonmyelinate, sympathetic fibers, "are covered with small, oval or rounded, but more rarely irregular, corpuscles, which exhibit one or more nuclei, in size almost equal to the nuclei of the ganglion globules [nerve cells]," thus most likely referring to "Schwann cells" of nonmyelinated fibers. He suggested that nerve fiber and nerve cell are joined and demonstrated that the neurofibers originated in the ganglionic cells (2898). See, Ross Granville Harrison, 1907.

Carlo Matteucci (IT) discovered that the frog’s heart, upon contraction, produces an electric current (2258, 2260).

George Gulliver (GB), Friedrich Gustav Jakob Henle (DE), Julius Vogel (DE), and William Hewson (GB) indicated that leukocytes are components of the pus found in suppurating wounds (1445, 1543, 1579, 3487). 

Johannes Petrus Müller (DE) was the first to describe multinucleate cells in vertebrate tissue. He was studying tumor tissue at the time. Müller was a distinguished physiologist and considered the founder of scientific medicine in Germany (2440).

Martin Heinrich Rathke (DE) worked on the embryonic development of the vertebrate skull and among other things found that the two lobes of the pituitary gland have separate embryologic origins. A portion of the roof of the pharynx pushes upward towards the floor of the brain forming the anterior pituitary (adenohypophysis, pars distalis, pars tuberalis, pars intermedia). Where it meets a portion of the brain pushing downward forming the posterior pituitary (neurohypophysis, pars nervosa). Rathke's pouch eventually looses its connection with the pharynx (1560, 2865, 2866, 2868).

Phillippe Ricord (FR) established syphilis and gonorrhea as separate and distinct diseases. He classified the symptoms of syphilis as 1) Primary symptom (accident primitif), chancre from the direct action of the virus which it produces, and by means of which it propagates itself, 2) Secondary symptoms, or symptoms of general infection, and 3) Tertiary symptoms, (accidents tertiares) occurring at indefinite periods, but generally long after the cessation of the primary affection.

He warns that when gonorrheal matter is in the conjunctive of the eyes one must always insist on quick application of silver nitrate to preserve sight (2928).

Jean Etienne Dominique Esquirol (FR) was the first to clinically describe what later became known as Down’s syndrome (1043).

Édouard Séguin (FR) also described the Down’s syndrome (3158).

John Langdon Haydon Down (GB) described the syndrome that bears his name, but did not discover its cause (888-890).

Jérôme Jean Louis Marie LeJeune (FR), Marthe Gautier (FR), Raymond Alexandre Turpin (FR), Patricia A. Jacobs (GB), Albert Gordon Baikie (GB-AU), William Michael Court-Brown (GB), and John A. Strong (GB) were the first to associate a genetic disease in humans with a chromosomal abnormality. They found that Down’s syndrome patients possess an extra small acrocentric chromosome number 21 (1739, 2023, 2024). Down’s syndrome is one of the most common causes of mental retardation.

Edward Selleck Hare (GB), Publio Ciuffini (IT), Henry Khunrath Pancoast (US), and José W. Tobías (AR) described the medical condition later known as Hare’s syndrome or Ciuffini-Pancoast-Tobías syndrome or Pancoast’s disease or superior pulmonary sulcus tumor (1487, 2626, 2627, 3360). 

Karl Wigand Maximilian Jacobi (DE) presented the first formulation of the concept and intent of psychosomatic medicine (an attempt to integrate psychopathology with biology and physiology) (1738).

Isaac Ray (US) wrote the first treatise on the medical jurisprudence of insanity (2875). 

Pierre-Francois Verhulst (BE) developed the logistic model of population to describe the self-limiting growth of a biological population (3458, 3459).

Raymond Pearl (US) and Lester James Reed (US) rediscovered the S-shaped logistic curve when they found that human population growth over time seemed to follow this curve (2708).

Vito Volterra (IT) used the logistic equation to construct a nonlinear differential equation model of competition between two species and developed a model of predation in a two-species system, if prey increase, predators will also until prey decrease. As the predators starve, the prey increases. The two populations fluctuate out of phase with each other due to the length of the gestation period delaying the population peaks; i.e., the predator population is still growing after the prey population has begun to decline (3495).

Alfred James Lotka (US) anticipated Volterra with a mathematical model of two-species predation (2137). Today these are known as the Lotka-Volterra equations.

Alexander John Nicholson (AU) and Victor Albert Bailey (AU) tried to improve on the Lotka-Volterra predation model by taking into account the effects of competition from members of the same species, as well as delays caused by age distribution of the populations (2500).

Thomas Bell (GB), Charles Robert Darwin (GB), Thomas Campbell Eyton (GB), George Scharf (GB), and George Robert Waterhouse (GB) published The Zoology of the Voyage of H.M.S. Beagle, Under the Command of Captain Fitzroy, R.N., During the Years 1832 to 1836. : Published With the Approval of the Lords Commissioners of Her Majesty's Treasury (162).

Charles Robert Darwin (GB) published the second edition of The Voyage of the Beagle in 1845 (765). 

The United States Exploring Expedition, an exploring and surveying expedition, was launched to the Pacific Ocean and surrounding lands by the United States from 1838 to 1842. The expedition was of major importance to the growth of science in the United States, in particular the then-young field of oceanography (3242).

Jacques Boucher De Crèvecouer De Perthes (FR) found near Abbeville, France, the first evidence of Stone Age man. He determined that they were from the Pleistocene epoch. De Perthes was the first to develop the idea that prehistory could be measured on the basis of periods of geologic time (340, 341).


“Every mentally ill person is also physically ill.” Johannes Baptista Friedreich (DE) (1226)

"The elementary parts of all tissues are formed of cells in an analogous, though very diversified manner, so that it may be asserted, that there is one universal principle of development for the elementary parts of organisms, however different, and that this principle is the formation of cells." Theodor Ambrose Hubert Schwann (3131)

Michael Faraday (GB) showed that the laws of definite and multiple proportions hold not only for chemical elements, but also for electricity (1059).

Johann Wolfgang Döbereiner (DE) introduced a test whereby the amount of fermentable sugar present could be determined by the amount of carbon dioxide released by yeast placed in the unknown mixture (867).

Anselme Payen (FR) isolated from plants a compound that he recognized as a carbohydrate and which he termed cellulose because it was derived from cell membranes of plants. Payen considered cellulose to be an isomer of starch and dextrine and ascribed the different properties of the three compounds to different states of aggregation (2702, 2703).

Pierre-Jean Robiquet (FR) predicted that there is a relationship between an animal’s surface area and its food requirements (2954).

Charles Thornton Coathupe (GB) reported that the amount of carbon dioxide in air expired by humans varied between 3.63% and 4.37% (634).

Theodor Ambrose Hubert Schwann (DE) introduced the term metabolic (Gk. metabolikon, disposed to cause or suffer change) to denote the chemical transformations undergone by cell constituents and surrounding material (2303).

Bernard Rudolf Konrad von Langenbeck (DE) discovered that a yeast-like organism was associated with the white patches of thrush in the mouth, pharynx, and esophagus in a case of typhoid fever (3591). Note: He is perhaps best known today as the "father of the surgical residency."

Fredrik Theodor Berg (SE) recognized the etiological agent of thrush as a mold-like fungus (173).

David Gruby (HU-FR) found Candida albicans in thrush and demonstrated its fungal nature (1431).

John Hughes Bennett (GB) reported a cryptogram as the cause of buccal thrush in infants (168). 

Fredrik Theodor Berg (SE) independently discovered that a fungus (Candida albicans) causes thrush in man (174).

J. Stuart Wilkinson (GB) described vulvovaginal candidiasis for the first time (3745).

Charles-Philippe Robin (FR) named the causative agent Oïdium albicans (Candida albicans) (2952).

Max B. Burchardt (DE) published experimental, microscopical observations of the thrush fungus. He studied its growth in epithelial preparations on microscope slides over 2 or 3 days and observed septate, branched filaments bearing lateral buds, some filaments growing by the lengthening of terminal buds. These filaments were pseudohyphae, which he described and illustrated (521).

David Haussmann (FR) demonstrated that the causative organism in both vulvovaginal candidiasis and oral candidiasis was Oïdium albicans (Candida albicans) (1509, 2172).

Raymond Jacques Adrien Sabouraud (FR) would rediscover Gruby’s findings in 1894.

Christine Marie Berkhout (NL) later proposed the genus name Candida for this yeast-like fungus (186).

Johann Justus Liebig (DE) was convinced that fermentations are of a purely chemical nature and not associated with life forms. His prestige made it difficult for those who espoused that microorganisms caused fermentations to be heard. He demonstrated that the source of animal heat is really the consumption of the fuel taken in through the stomach and lungs (2080).

Johann Justus von Liebig (DE) strongly defends his abiotic chemical explanation for fermentation even in the face of the growing evidence for a biotic explanation (3598, 3599).

Louis Pasteur (FR), in response to von Liebig, brilliantly presses home the case for a biotic theory of fermentation (2677).

Benno Müller-Hill (DE) says, "Pasteur was right with his experiments, but Liebig was right with his intuition that fermentation was simple chemistry" (2447).

P. Sarrus (FR) and J.-F.Rameaux (FR) proposed what was called the “surface law”. They suggested that the heat production of different-sized species should be related to their surface area rather than their body masses if they were to maintain the same body temperature (3037). Note: D’Arcy Wentworth Thompson (GB) reminds us, “we are taught by elementary mathematics—and by Archimedes himself—that in similar figures the surface increases as the square, and the volume as the cube, of the linear dimensions.” Thompson then describes the implications of size for both structure and function of animals and plants (3323).

Max Rubner (DE), in 1883, demonstrated the “surface law” in accurate respiration trials on dogs (2988).

Max Kleiber (CH-US) supported the concept that the basal metabolism of animals differing in sex is nearly proportional to their respective body surfaces, i.e., the surface law (1828, 1829).

Victor Regnault (FR) and Jules Reiset (FR) developed an innovative respirometer (one that provided oxygen at the rate it was consumed) and measured the metabolic rates of a number of animals (including rabbits, dogs, fowl, ducks, finches, sparrows, frogs, salamanders, lizards and beetles). Because their measurements were carried out at temperatures ranging from ~15 °C to ~23 °C (average ~18 °C), and generally on animals feeding, these were not measurements of basal metabolism. However, they did report a number of seminal findings: (i) mammals and birds of the same size had similar mass-specific rates of oxygen consumption; (ii) the mass-specific oxygen consumption of the small bird species (average mass ~23 g) was more than 8-fold greater than the larger birds (average mass ~1.4 kg); and (iii) there was a huge difference in the metabolic rates of the endotherms (mammals and birds) compared to the ectothermic vertebrates (amphibians and reptiles). For example, with respect to this last point, although they were approximately the same size, the mass-specific oxygen consumption rates of the small bird species was ~135 times that of the amphibians and reptiles.

Interestingly, Regnault and Reiset also showed that when they kept rabbits and dogs in an atmosphere that had 2–3 times normal oxygen levels they had exactly the same metabolic rates as those in normal atmospheric oxygen. In other words, metabolic rate seemed to be an intrinsic characteristic of the species and was not limited by the supply of oxygen. In this way it differed from combustion (2890).

Schack August Steenberg Krogh (SE) showed that: (i) the Standard Metabolic Rate of cold-blooded animals (measured at the same temperature as each other) and expressed relative to body mass increased with decreasing body size; and (ii) even when compared at the same temperature that the “oxidative energy of the tissues is greater in the warm-blooded than in the cold-blooded organism” (1909).

Martin Heinrich Rathke (DE) described the embryonic development of the snake (2866, 2867).

Martin Heinrich Rathke (DE) and Henry James Clark (US) described the embryonic development of the turtle (622, 2870).

Martin Heinrich Rathke (DE) described the embryonic development of the crocodile (2871).

Johann Lukas Schönlein (DE) discovered that favus (honeycomb) of the human scalp, a disease long known, is due to a parasitic fungus (later named Achorion schoenleinii then Trichophyton schoenleinii) growing at the roots of the hair (3093). Note: this was the first infectious disease the etiology of which was scientifically explained. The citation’s title contains the term impetigo, which at this time meant an inflammatory skin disease characterized by isolated pustules.

David Gruby (HU-FR) described the fungi associated with four of the common types of ringworm in man. He conclusively proved for the first time, that a microbial organism could cause disease in man. Culturing the fungus of favus (honeycomb disease) of the scalp he reproduced the disease by reinoculating the fungus into normal areas of the skin, thereby fulfilling what became famous forty years later as Koch’s postulates, in the study of anthrax (1429, 1430). This experiment proved, for the first time, that a microorganism was the cause of a human disease. See, Schönlein, 1839.

Robert Remak (PL-DE) cultured the etiologic agent of favus on apple slices, induced the infection in himself and validly described it as Achorion schoenleinii, in honor of his colleague Schönlein (2902).

Johann Lukas Schönlein (DE) is also attributed with naming the disease, Tuberculosis (3093). Prior to Schönlein's designation, Tuberculosis had been called "consumption".

Jean Baptiste Joseph Dieudonné Boussingault (FR) and Louis Frédéric Le Bel (FR) quantitatively studied the balance between the elementary constitution of the maintenance ration of a cow and that of the excretions and the milk (367).

Francois Magendie (FR) was possibly the first experimenter to induce anaphylaxis. He found that rabbits that tolerated an initial injection of egg albumin often died upon receiving a second injection (2198).

Alfred-Armand-Louis-Marie Velpeau (FR) described hidradenitis suppurativa, a chronic acneiform infection of the cutaneous apocrine glands that also can involve adjacent subcutaneous tissue and fascia (3453).

Bogislaus Palicki (CZ), in his dissertation directed by Johannes Evangelista Purkinje (Jan Evangelista Purkyne) (CZ), discovered Purkinje fibers in heart muscle (2623, 2624). 

Wilhelm Kaspar (CZ), in 1839, in his dissertation directed by Johannes Evangelista Purkinje (Jan Evangelista Purkyne) (CZ), discovered Purkinje fibers in the wall of the uterus (1779).

Johannes Evangelista Purkinje (CZ) reports the discovery of Purkinje fibers (2819).

James Hope (GB) described mitral regurgitation and discussed why it is undesirable. He also discussed how to diagnose pulmonary stenosis (1628).

Isaac E. Taylor (US) and James Augustus Washington (US), in 1839, administered a solution of morphine in an Anel syringe. This was one of the earliest subcutaneous injections of an anesthetic (54).

Eduard Caspar Jacob von Siebold (DE) wrote the first and arguably the most important history of obstetrics (3623). 

Samuel David Gross (US), an outstanding surgeon, wrote Elements of Pathology and Anatomy, the first exhaustive treatise on pathological anatomy in the English language. In 1854, he wrote A Practical Treatise on Foreign Bodies in the Air-Passages, the first systematic treatise on this subject and, in 1859, finished System of Surgery, published in two volumes totaling 2,360 pages. Gross became world famous being honored by Oxford University with the D.C.L. degree and Cambridge University with the L.L.D. degree (1423-1425).

Richard Owen (GB) announced one of his most important discoveries: his identification of the bones of a giant bird from New Zealand. The Moa now ranks among the world's most famous extinct birds (2598).

Roderick Impey Murchison (GB), while studying the rocks of Wales, documented rock strata containing a distinctive set of fossils, one in which very few fish were found, but that included numerous different types of trilobites, brachiopods, and other such fossils. Murchison named the system of rocks containing such fossils the Silurian, commemorating the Silures, a Celtic tribe living in the Welsh Borderlands at the time of the Romans (2450). This represents the discovery of the Silurian Period of the Paleozoic Era.


There was a pandemic of cholera.


“Race after race resigned their fleeting breath— The rocks alone their curious annals save.” Timothy Abbott Conrad (676)

Germain Henri Hess (CH-RU) measured the heats evolved in various reactions and was able to demonstrate that the quantity of heat produced in going from substance A to substance B was the same no matter by what chemical route the reaction proceeded or in how many stages (1574).

Christian Friedrich Schönbein (CH) discovered and named ozone (Gk. ozein, to smell). He found that it forms during electrical discharges (3089).

Sydney Chapman (GB) published the theory of ozone formation and depletion. The reactions are still valid and called the 'Chapman cycle' or the 'Chapman reactions'. Oxygen and ozone are transformed into each other. The bonds are broken by photolysis due to solar radiation. In order to break the bond in O2 the energy of the sunlight has to be higher (wavelength shorter than 240 nm), than for ozone (wavelength shorter than 900 nm). Formation and depletion are in equilibrium and the net result is a 'zero' reaction: Oxygen absorbs in the highly energetic UV-C range, ozone in the slightly less energetic UV-B range. Longer wavelengths partially pass the atmosphere and reach the Earth surface (587).

Richard S. Stolarski (US) and Ralph J. Cicerone (US) proposed that chlorine coming from rocket fuel in supersonic transport (SST) aircrafts could destroy ozone (3273).

Mario J. Molina (MX-US) and F. Sherwood Rowland (US) published an article highlighting the threat to the ozone layer posed by chlorofluorocarbons (CFCs) used as refrigerants, aerosol sprays, and in making plastic foams (2371).

Joseph C. Farman (GB), Brian G. Gardiner (GB), and Jonathan D. Shanklin (GB) reported a 40% decrease in ozone over the Antarctic between 1977 and 1984 (1061).

Johann Justus Liebig (DE) and Friedrich Wöhler (DE) attributed decomposition, eremacausis (Gk. erema, quietly + causis, burning), putrefaction, and fermentation to chemical instability of certain substances which were able to communicate their instability to other substances in succession. Liebig asserted that animalcules are the result, not the cause of fermentation and further that “if agitated in a vessel filled with a solution of sugar the molecules of yeast communicate their condition to the particles of sugar, the result being the formation of alcohol and carbon dioxide, compounds in which the constituents are retained in combination with a greater force than in sugar. In contact with sugar, yeast disappears and none is reproduced, but when added to the gluten (albumin) contained in vegetable juices new yeast is formed. Yeast, therefore, is produced from gluten”.

Johann Justus Liebig (DE) introduced the concept of metabolism and was the first to realize that the addition of a single fertilizer will increase crop yield only if a particular soil can deliver all the other necessary nutrients. Depending on the circumstances, therefore, any of the essential minerals (nitrates, phosphates, potassium, etc.) might become the controlling factor. This generalization became known as Liebig's "Law of the Minimum" and it remains today a central concept in agriculture (2081). Note: Thanks to Felicjan Odrowąż Sypniewski's (PL-DE) notes and observations - Karl Phillip Sprengel (DE) formulated his "Theorem of minimum" (commonly known as Liebig's "Law of the Minimum", because it was Johann Justus Liebig who later popularized this theorem and was mistakenly attributed it's authorship (3238)).

Jean Louis Rodolphe Agassiz (CH-US) wrote a large five-volume work on fossil fishes. He was the first to come to the conclusion—from his studies of glaciers— that there had been an Ice Age. He borrowed the phrase ice age (Eiszeit) from a poem by his friend Karl Schimper (26-28, 2236). He is commemorated by Phascolosoma agassizii Keferstein, 1867, Polydora agassizi Claparède, 1969, Linvillea agassizi (McCrady, 1857), and Aglauropsis agassizi Fr. Müller, 1865.

James Croll (GB) was the first to suggest that variations in the Earth’s orbit might have initiated ice ages (725).

Milutin Milankovitch; Milutin Milankovic (Serbian), in 1930, found that for Croll’s theory to be a more accurate predictor of ice ages it must consider that over long periods of time the Earth tilts, pitches, and wobbles relative to the Sun (2345).

Johannes Evangelista Purkinje; Jan Evangelista Purkyne (CZ) was one of the first to use a mechanical microtome to prepare thin sections of tissue for microscopic analysis, introducing glacial acetic acid, potassium dichromate and Canada balsam in the preparation of tissue samples for microscopic examination. He was aware of the cellular nature of the skin and other animal organs. He coined the word protoplasm in reference to the living embryonic material in the egg and together with Hugo von Mohl (DE) who applied the term protoplasm to the living content of plant cells, established the protoplasm concept (2818, 3285, 3608).

Ferdinand Julius Cohn (DE) unified the concept of protoplasm by applying it equally to both plant and animal cells (642).

René-Joachim-Henri Dutrochet (FR) detected heat production by a plant and by an insect’s muscles during movement (958).

Friedrich Gustav Jacob Henle (DE), one of the most celebrated anatomists of the world and the greatest histologist of his time, was one of Heinrich Hermann Robert Koch’s teachers. He wrote, Von den Miasmen und Contagien und von den Miasmatisch-Contagiösen Krankheiten (On Miasmas and Contagions and Concerning Miasmatic-Contagious Diseases), a monograph in which he lays the foundation for Koch’s postulates and stated, “The material of contagions is not only organic but a living one and is indeed endowed with a life of its own, which is, in relation to the diseased body, a parasitic organism.” He insisted that in order to claim a given microbe caused a disease (1) there be constancy in the association of a given disease and its supposed parasitic cause, as well as its absence in other diseases, (2) isolation and separation from other microbes, and finally, (3) proof of the power of the isolated germ to produce disease (1550).

He was the first to describe the epithelium of the skin and intestines, to define columnar and ciliated epithelium, and to point out the importance of epithelium as the lining membrane of all free surfaces of the body and of its tubes and cavities. His Allgemeine Anatomie was the first systematic treatise on microscopic anatomy. In it, for the first time, he described the presence of smooth muscle in the endothelial lining of small arteries, a finding critical to the later understanding of the vasomotor mechanism. The 1866-1871 citation contains the first logical account and nomenclature of the axes and planes of the body. The sections on ligaments, the muscles, the viscera, and the nervous system are very important (1544, 1545, 1547, 1549). The loop of Henle in the nephritic unit of the kidney is named for him. He described these tubular loops as running perpendicular to the kidney surface, and penetrating at a variable depth in the medulla. The descending portion of these loops had a small outer diameter (thin limb) as compared to that of the ascending portion located in the outer medulla (thick limb) (1548).

Rudolf Albert von Kölliker (CH) confirmed Henle’s finding of smooth muscle in the endothelial wall of arteries (3574).

Henle and Karl von Pfeufer (DE) established the journal, Zeitschrift für Rationelle Medizin.

Friedrich Ludwig Hünefeld (DE) reported seeing brick red, sharp edged crystals of blood pigment in dried menstrual blood of humans and swine, which had been placed between glass plates in a desiccator (1663).

William Bowman (GB) published his paper on the minute structure and functions of the striated, voluntary muscle. He coined the term sarcolemma (381, 382). 

M. Doyère (FR), Wilhelm Friedrich Kühne (DE), Charles Marie Benjamin Rouget (FR), and Louis-Antoine Ranvier (FR) demonstrated that motor nerves end on muscle fiber at a specialized structure, the plaque terminale, or endplate. There, the nerve loses its myelin sheath and branches on top of a cytoplasmic eminence of the muscle fiber particularly rich in nuclei (892, 1915, 2847, 2976, 2977).

Carlo Mattecci (IT) had demonstrated the electrical negativity of a cross section of muscle and proceeded to show the electrical oscillations in a tetanized muscle (2259).

Benedikt Stilling (DE) was the first to investigate vasomotor nerves (3265).

Frederick William Hope (GB) coined myiasis to refer to diseases of humans originating specifically with dipterous larvae (e.g., botfly, blowfly, fleshfly, and screwfly), as opposed to those caused by insect larvae in general, scholechiasis, which was coined by William Kirby (GB) and William Spence (GB) (1626, 1809).

William S. Baer (US), an orthopedic surgeon at Johns Hopkins Medical School during the late 1920s, used maggot therapy to treat a series of patients with osteomyelitis, an infection of bone or bone marrow. The idea was based on an experience in World War I in which two soldiers presented to him with broken femurs after having lain on the ground for seven days without food and water. Dr. Baer could not figure out why neither man had a fever or signs of sepsis. He observed: “On removing the clothing from the wounded part, much was my surprise to see the wound filled with thousands and thousands of maggots, apparently those of the blow fly. The sight was very disgusting and measures were taken hurriedly to wash out these abominable looking creatures.” However, he then saw that the wounds were filled with “beautiful pink granulation tissue” and were healing well (89).

Throughout recorded history maggots have been used therapeutically to clean out necrotic wounds, an application known as maggot therapy. Maggot therapy – also known as maggot debridement therapy (MDT), larval therapy, larva therapy, or larvae therapy – is the intentional introduction by a health care practitioner of live, disinfected green bottle fly maggots (larvae) into the non-healing skin and soft tissue wound(s) of a human or other animal for the purpose of selectively cleaning out only the necrotic (dead) tissue within a wound in order to promote wound healing. Although maggot therapy has been used in the US for the past 80 years, the FDA approved it as a “medical device” only in 2004 (along with leeches in the same year). Maggots are approved for treating neuropathic (diabetic) foot ulcers, pressure ulcers, venous stasis ulcers, and traumatic and post-surgical wounds that are unresponsive to conventional therapies (2987). The American Medical Association and Centers for Medicare and Medicaid Services recently clarified the reimbursement guidelines to the wound care community for medicinal maggots, and this therapy may soon be covered by insurance (23).

Jules-Gabriel-François Baillarger (FR), while engaged in clinicopathological correlations with simple methodology, divided the cerebral cortex into six layers of alternate white and grey lamina. He was able to satisfy himself that the white lines seen by Francisco Gennari in the occipital area could be traced in all parts of the cortex, although they were far less conspicuous anteriorly than posteriorly. This continuation of Gennari's line has therefore come to be known as the "external line or white stripe of Baillarger". He discussed the connections between gray matter of the cerebral cortex and the internal white matter. He also demonstrated that the surface of the human brain in comparison to its own volume is less than that in smaller animals and that as a compensatory measure larger brains undergo greater fissuration than smaller ones – in short that the difference in external form of lissencephalic and gyrencephalic brains is explicable on the basis of the geometric law of volumes, that the volume increases as the cube of the diameter while the surface increases as the square (96).

Robert Remak (PL-DE) used microscopic observations to confirm Baillarger’s 6-layered cortex of the brain. He was the first to illustrate these layers (2901).

Pierre Adolphe Piorry (FR) and Sébastien Didier L’Héritier (FR) coined the term uraemia (uremia) to describe the condition in renal failure patients characterized by retention of products of urine in the blood (289, 2749).

Friedrich Theodor Frerichs (DE) described the clinical uremic syndrome and accepted a toxic mechanism as its etiology (1213).

Joseph Picard (FR) developed a sensitive method to detect blood in urea. He was able to detect a 40% fall in urea concentration occurring between renal artery and vein (2747). This work along with Frerichs’ made popular the concept and the term uremia.

Victor-Timothée Feltz (FR) and Eugene Ritter (FR) declared that retained potassium is the uremic poison (1070).

Moritz Heinrich Romberg (DE) wrote the first systematic treatise in neurology and a milestone in the development of clinical neurology. It included a classic on achondroplasia (congenital rickets). He and Peter Frank were pioneers in the study of the spinal cord. He described the classic, Romberg sign (swaying of the body with the feet close together and the eyes closed: a sign of locomotor ataxia) and stated that no ataxic can stand still with eyes shut. Patients with the tabes dorsalis of syphilis typically sway or loose their balance. He described Romberg's sign as: "The gait begins to be insecure... he puts down his feet with greater force...The individual keeps his eyes on his feet to prevent his movements from becoming still more unsteady. If he is ordered to close his eyes while in the erect posture, he at once commences to totter and swing from side to side; the insecurity of his gait also exhibits itself more in the dark" (2961, 2962).

Jonathan Mason Warren (US) was one of the first surgeons to use free skin grafts. Small, entirely detached pieces of skin were taken from the arm or thigh to fill in gaps in a wound (3679).

Richard Owen (GB), beginning in 1840, produced works of the highest importance in paleontology (2599, 2601, 2604, 2608, 2609).

John Phillips (GB), a nephew of William Smith (GB), proposed the geologic eras: Paleozoic (ancient life), Mesozoic (middle life), and Kainozoic which became (Cenozoic) (recent life) (2744). See, Smith in 1799.


Rudolf Albert von Kölliker (CH) traced the histogenesis of the spermatozoa in invertebrates and proved that they are differentiated tissue cells and not parasites as thought by some. He also concluded that the physical basis of inheritance must be the chromosomes (3571).

Rudolf Albert von Kölliker (CH) demonstrated that spermatozoa of higher organisms are cellular products of the organism. He also extended this finding to the ovum, from which the organism is derived by cell division (3573).

Robert Remak (PL-DE) provided experimental evidence that only the division of pre-existing cells produces body cells of animals. He was probably the first to describe division of the cell nucleus and to observe the multiplication of vertebrate cells outside the body (2899, 2900, 2908, 2910).

Franz Joseph Andreas Nicolas Unger (AT) concluded that the growth of all parts of the plant is normally driven by meristematic cell division (3417, 3418).

The Magendie Commission (FR) reported, based on experiments using dogs, that no extract of bone could replace meat in the diet. Gelatin, albumen, and fibrin, taken separately, nourish animals for a very limited period. The seasoning of foods did not improve their nutritional value. Normal muscular flesh with its attendant gelatin, albumen, fibrin, fats, and salts supply sufficient nutrients for prolonged survival (later proved incorrect). Raw bones supply sufficient nutrients for prolonged survival but must be eaten in large quantities. Harsh treatment of meat and bone with high temperatures or acids substantially reduces their nutritive value. Gluten of wheat (Triticum spp.) or maize (Oryza sativa) supported prolonged survival (later proved incorrect). Fats alone cannot sustain life over a prolonged period of time (2199).

Alexander Ure (GB) performed the first human metabolic study when he administered benzoic acid to himself and to volunteers. He succeeded in isolating large quantities of hippuric acid from their urine. Ure thus must be given the credit of being the first one to discover a biotransformation of a foreign compound. He proposed the use of benzoic acid for the treatment of gout (3422).

Friedrich Wöhler (DE) and Friedrich Theodor Frerichs (DE) confirmed this work using dogs (3784, 3785).

Gabriel Gustav Valentin (DE-CH) made the first observation of a trypanosome in the blood. The host animal was a trout (3425).

Friedrich Gustav Jacob Henle (DE), E. Berger (FR), and A. Tulk () independently discovered Demodex folliculorum, the mite of hair follicles (175, 1546, 3405).

Johannes Petrus Müller (DE) and Friedrich Gustav Jacob Henle (DE) made a thorough study of the cyclostomata, which they placed among the fishes. This work established the outline of elasmobranch taxonomy for the remainder of the 19th century (2445).

Martin Heinrich Rathke (DE) was the first to describe the lancet fish (Amphioxus lanceolatus). It had been considered to be the larvae of a mollusk (2869).

Johannes Petrus Müller (DE), Anders Adolf Retzius (SE), and Gustaf Magnus Retzius (SE) carefully studied and described Branchiostoma lanceolatum (Amphioxus lanceolatus, i.e., the lancelet) (2443, 2444, 2915).

Johann Lukas Schönlein (DE) described purpura rheumatica including petechies and the associated joint troubles - Schönlein's purpura (3094).

Johann Friedrich Dieffenbach (DE) reported on 140 cases of tenotomy for treatment of clubfoot (858).

Valentine Mott (US), in 1841, removed a large fibrous growth from the nostril by dividing the nasal and maxillary bones (2407).

Richard Owen (GB), in his report to the Eleventh Meeting of the British Association for the Advancement of Science, coined the word dinosaur. “The combination of such characters, some, as the sacral ones, altogether peculiar among reptiles, others borrowed, as it were, from groups now distant from each other, and all manifested by creatures far surpassing in size the largest of existing reptiles, will, it is presumed, be deemed sufficient ground for establishing a distinct tribe or sub-order of Saurian reptiles, for which I would propose the name Dinosauria.” He put together two Greek words: deinos meaning terrible and sauros meaning lizard. The result has been a favorite of paleontologists and children ever since. The original dinosaurs of this new group were Megalosaurus, Iguanodon and Hylaeosaurus (2600, 3368). See, Gideon Algernon Mantell, 1822 and William Buckland, 1824.

Although Richard Owen (GB) was an outstanding anatomist and museum curator he was not above pirating the work of others such as Gideon Algernon Mantell (503). 

Roderick Impey Murchison (GB) defined the Permian Period in geological history; named after the strata of the Perm region in Russia (2451).


Scotland experiences an epidemic of relapsing fever.


Julius Robert Mayer (DE) was a brilliant theorist who presented the mechanical theory of heat. James Prescott Joule (GB) later received credit for this concept because of his many elegant experiments (1759). Julius Robert Mayer also presented a logical argument for the conservation of energy in his law of the equivalence of heat and work. Hermann Ludwig Ferdinand von Helmholtz (DE) later received credit for this idea because of his experiments in which he proved mathematically that all forms of energy, such as heat, light, electricity, and chemical phenomena, can be transformed from one form to another but are indestructible as well as impossible of creation. He said that this conservation of energy is a fundamental principle of physics (3555). Mayer included living phenomena in the realm of energy conservation.

Julius Robert Mayer (DE) suggested that solar energy is the ultimate source of all energy on the earth, both living and non-living. He proposed that solar energy is derived from the slow contraction of the sun or from the fall of meteors into the sun. In either case kinetic energy was being converted into radiant energy. Hermann Ludwig Ferdinand von Helmholtz (DE) and William Thomson (Lord Kelvin) (GB) received credit for this idea (2266-2268, 3601).

Karl Friedrich Mohr (DE) was the first to record the concept of the conservation of energy (2368).

Johann Justus Liebig (DE) noted that, “The blood corpuscles contain an iron compound. From the invariable presence of iron in red blood it must be concluded that it is absolutely essential for animal life, and… there can be no doubt that they (corpuscles) assume a role in the respiratory process.” He discussed the tendency of some iron compounds to take up oxygen, and for the products to be reduced through the loss of oxygen… He called attention to the fact that in Prussian blue (ferrocyanide and ferricyanide) iron is present in combination “with all the organic constituents of the animal body: hydrogen and oxygen (water), carbon and nitrogen (cyanogen)” and concluded that… “blood corpuscles of the arterial blood contain iron compound that is saturated with oxygen, and in which the living blood loses its oxygen during the passage through the capillary vessels; the same occurs when blood is taken from the body and begins to decompose (begins to putrefy); the oxygen-rich compound is transformed by the loss of oxygen (reduction) into a less-oxygenated compound. One of the resultant products of oxidation is carbonic acid.” He helped establish the view that body heat and vital activity arise out of energy derived from the oxidation of foodstuffs within the body, and declared fats and carbohydrates—rather than carbon and hydrogen—the fuels of the body. He introduced the concept of stoffwechsel (metabolism) (2082, 2083). This book is regarded as the first formal treatise on organic chemistry as applied to physiology and to pathology.

Eilhard Mitscherlich (DE) used a parchment filter to divide a sugar solution into two compartments, one in contact with yeasts the other deprived of contact with yeast cells. Fermentation only took place where yeasts were in contact with sugar. He also found that yeast extract could convert cane sugar into a levorotatory sugar (2362).

Augustin Pierre Dubrunfaut (FR) then showed the levorotatory sugar to be a mixture of glucose and fructose (906).

John Edwards Holbrook (US), with the publication of North American Herpetology, became the leading American zoologist (1616).

John Gill (GB), while working in the Madura region of India, in 1842, was the first to describe mycetoma, which later became known as Madura foot or maduromycosis (659, 1310).

Alexandre Joseph Emilé Brumpt (FR) showed that several different fungi could cause the same clinical picture. He originated the Genus Madurella at this time (497).

Albert J. Chalmers (GB) and John B. Christopherson (GB) coined the term maduromycoses to refer to mycetomas of fungal etiology (582).

David Gruby (HU-FR) described ectothrix (Trichophyton ectothrix) invasion of the beard and scalp causing the disease Sycosis barbae (Barber's itch) (1432). This organism would later be named Trichophyton mentogrophytes.

David Gruby (HU-FR) gave the first accurate description of Microsporon audouinii, the fungus of Willan's porrigo decalvans, tinea tonsurans, and Gruby's disease (1433).

David Gruby (HU-FR) described endothrix hair invasion by Herpes (Trichophyton) tonsurans (1434). This is called Tinea capitis (Ringworm of the scalp).

Hermann Ludwig Ferdinand von Helmholtz (DE) discovered that the nerve fibers originate in the ganglion cells. For the first time the connection between nerve fibers and nerve cells was established (3554). This represents the origin of the histological basis of nervous physiology and pathology.

Rudolph Wagner (DE) demonstrated the link between the ganglion cells of the brain and the peripheral nerve fibers (3646).

Charles Chossat (FR) studied the effect of diet on bone formation in pigeons. He found that birds on a wheat (Triticum spp.) only diet did not produce normal bones. If calcium carbonate was added to the wheat diet their bones were normal (615, 616).

Henry Bence Jones (GB) asserted that sodium chloride is indispensable in the human diet (1753).

Jean Baptiste Joseph Dieudonné Boussingault (FR) used oxen to prove experimentally what man had known empirically for centuries, that is, that animals require sodium chloride in their diet (360-362).

Friedrich Heinrich Bidder (LV-DE) and Alfred Wilhelm Volkmann (DE) showed the sympathetic nervous system to consist largely of small, medullated fibers originating from the sympathetic and spinal ganglia (248).

William Bowman (GB) published his theory of urinary secretion and described the capsule which surrounds the “bare or naked system of capillaries,” called the Malpighian body (glomerulus), and is continuous with the uriniferous tubule (383). This capsule now bears his name as Bowman’s capsule.

Karl Friedrich Wilhelm Ludwig (DE) also discovered glomerular filtration (2149).

William Addison (GB) discovered the emigration of polymorphonuclear leukocytes from circulation into tissues, and that this movement increased during inflammation (17, 18).

Augustus Volnay Waller (FR-GB) independently discovered the emigration of polymorphonuclear leukocytes in inflammation (3660).

Thomas Wharton Jones (GB) reported for the first time the ameboid movements of leukocytes. Jones differentiated the leukocytes into non-granular, finely granulated, and coarsely granulated types; later to be called lymphocytes, neutrophils, and eosinophils, respectively (1756).

Casimir Joseph Davaine (FR) and Nathanael Lieberkühn (DE) observed leukocyte ameboid movement (775, 2067).

Ernst Heinrich Philipp August Haeckel (DE) described the ability of molluscan leukocytes to ingest India ink particles (1453).

Maximilian Johann Sigismund Schultze (DE) observed ingestion of particles by mammalian polymorphonuclear leukocyte blood cells (3107).

Albert von Recklinghausen (DE) described granular cells in the frog mesentery; later named mast cells by Paul Ehrlich. He noted translocational locomotion of leukocytes for the first time and observed ingestion of particles by mammalian polymorphonuclear blood cells (3613).

William Peyer (GB) and Maximilian Johann Sigismund Schultze (DE) gave descriptions of translocational locomotion and phagocytosis, which are nearly as complete as any made today (2734, 3109).

Julius Arnold (DE) mentioned that leukocytes pass through specialized openings between endothelial cells via “para-cellular” migration, which he referred to as diapedesis (58).

Julius Friedrich Cohnheim (DE) showed that the essential feature of inflammation is the passage of white blood cells through the walls of capillaries (diapedesis), and that pus and pus-cells are formed in this way from blood. These experiments traced the migration of stained leukocytes to the center of inflammation in the cornea (656).

Karl Ewald Konstantin Hering (DE), in 1868, found that leukocytes became adherent to blood vessels near sites of injury (2318).

Christian Albert Theodor Billroth (DE-AT) noted that connective tissue destruction appeared to be associated with leukocyte collections in inflamed sites (258).

Alfred Francois Donné (FR) was the first to describe blood platelets or "globulins" (881). At the time he thought that globulins originated from lymph (les globulins du chyle) and in the late 1800s scientists described platelets variously as being precursors or disintegration products of erythrocytes, leukocytes, or fibrin and even as bacteria.

Maximillian Johann Sigismund Schultze (DE) was the first to describe the four different types of blood leukocytes corresponding to what we now recognize as the lymphocyte, the monocyte, the eosinophil, and the neutrophil. He also provided a description of the blood platelet (3109).

Carl Heitzmann (HU-AT-US) was one of the first to describe blood platelets as hematoblasts, thinking them to be precursors of erythrocytes (1531).

Georges Hayem (FR) reported the first accurate platelet counts. The platelet numbers he reported do not differ significantly from those reported as normal today (1065, 1510, 1511).

Giulio Cesare Bizzozero (IT) was the first to describe platelets as distinct blood elements referring to them as petites plaques. Because he used living animals for his studies, he was able to indicate the relationship of platelets to thrombosis and he described the changes platelets underwent when activated as "viscous metamorphosis." He said that in a blood clot, there is first the platelet thrombus followed by the more massive fibrin thrombus (285, 286).

Carl Joseph Eberth (DE) and Curt Schimmelbuch (DE) induced thrombus formation in mesenteric vessels of animals and regarded platelet agglutination as the initial phase of thrombosis (971).

James Homer Wright (US) described megakaryocytes as the cell of origin of platelets—he called them “cell plates” (3799).

William Waddell Duke (US) proposed that the bleeding time is closely correlated to platelet number and described a method for determining the bleeding time and coagulation time (926, 927). See, Milian, 1901.

James Homer Wright (US) and George Richards Minot (US) found that platelet viscous metamorphosis may occur before fibrin formation (3800).

Karl Albert Ludwig Aschoff (DE) classified the etiopathogenic components of thrombosis into three groups: parietal factors, hemostasis, and blood dyscrasia disorders (67).

Karl Friedrich Wilhelm Ludwig (DE) presented his physical theory of urine secretion by which a significant amount of liquid is removed from the blood by pressure in the glomerulus then partially recaptured by endo-osmotic flow from the urinary canals into the surrounding blood vessels. “The glomerular filtrate is driven…into the urinary vessels and thereby comes in contact with the blood which is flowing in the narrow vessels…and…has originated from the glomerulus [and] would draw water from the urinary canals into the blood vessels whereby the urine would become concentrated” (2148, 2150).

Theodor Ludwig Wilhelm Bischoff (DE) provided the most comprehensive research into the history of the development of the ovum in Mammalia, which had been done so far. He specifically studied ovum development in man, dogs, guinea-pigs, and roe-deer (270-274).

William E. Clark (US), in January 1842, used ether to anesthetize a patient whose tooth was then extracted by doctor Elijah Pope (US) (2171). This is the first recorded use of ether as an anesthetic.

Crawford Williamson Long (US) was the first physician to use ether as an anesthetic in surgery. “Since '42, I have performed one or more surgical operations annually, in patients in a state of etherization…. From one [patient] I removed three tumours the same day…. I amputated two fingers of a negro boy” (2122).

Charles Thomas Jackson (US) is one of the people who claimed to have been the first to use ether as an anesthetic. Jackson's claims for priority were substantially as follows: He had already experimented on the anesthetic properties of chloroform and of nitrous-oxide gas, and previous to the winter of 1841-'2, having received some perfectly pure sulfuric ether, he tried its effects upon himself, administering it with a mixture of atmospheric air, and inhaled it to such an extent as to lose all consciousness, without suffering any of the dangerous or disagreeable consequences that had hitherto attended the inhalation of impure sulfuric ether unmingled with atmospheric air. In 1852 a memorial was presented to congress, signed by 143 physicians of Boston and its vicinity, ascribing the discovery exclusively to Dr. Jackson. Jackson never published.

Charles Oscar Waters (US) described a form of chorea (magrums), including an accurate description of its progression, and the strong heredity of the disease (935). This later became known as Huntington's disease.

Johan Christian Lund (NO) was the first to describe setesdalsrykkja or rykkja, i.e., “jerking disease” (Huntington’s disease) (2158, 2159).

George Huntington (US) wrote his classic paper in which he diagnosed hereditary chorea (now called Huntington’s disease). He noted the familial nature of the disorder and provided a graphic description of it (1666).

William Bateson (GB) used the pedigrees of affected families to establish that Huntington's disease did have an autosomal dominant inheritance pattern (141). This was the first human genetic disease inherited in the autosomal dominant mode to be uncovered.

Alois Alzheimer (DE) recognized cortical loss in Huntington’s, but emphasized that it was striatal damage that caused the motor disturbances (39).

James F. Gusella (US), Nancy S. Wexler (VZ), P. Michael Conneally (US), Susan L. Naylor (US), Mary Anne Anderson (US), Rudolph E. Tanzi (US), Paul C. Watkins (US), Kathleen Ottina (US), Margaret R. Wallace (US), Alan Y. Sakaguchi (US), Anne B. Young (VZ), Ira Shoulson (VZ), Ernesto Bonilla (VZ), and Joseph B. Martin (US) of The US–Venezuela Huntington's Disease Collaborative Research Project discovered the approximate location of a causal gene for Huntington's disease (1448, 1449).

Marcy E. MacDonald (US), Christine M. Ambrose (US), Mabel P. Duyao (US), Richard H. Myers (US), Carol Lin (US), Lakshmi Srinidhi (US), Glenn Barnes (US), Sherryl A. Taylor (US), Marianne James (US), Nicolet Groot (US), Heather MacFarlane (US), Barbara Jenkins (US), Mary Anne Anderson (US), Nancy S. Wexler (US), James F. Gusella (US), Gillian P. Bates (GB), Sarah Baxendale (GB), Holger Hummerich (GB), Susan Kirby (GB), Mike North (GB), Sandra Youngman (GB), Richard Mott (GB), Gunther Zehetner (GB), Zdenek Sedlacek (GB), Annemarie Poustka (GB), Anna-Maria Frischauf (GB), Hans Lehrach (GB), Alan J. Buckler (US), Deanna Church (US), Lynn Doucette-Stamm (US), Michael C. O'Donovan (US), Laura Riba-Ramirez (US), Manish Shah (US), Vincent P. Stanton (US), Scott A. Strobel (US), Karen M. Draths (US), Jennifer L. Wales (US), Peter Dervan (US), David E. Housman (US), Michael Altherr (US), Rita Shiang (US), Leslie Thompson (US), Thomas Fielder (US), John J. Wasmuth (US), Danilo Tagle (US), John Valdes (US), Lawrence Elmer (US), Marc Allard (US), Lucio Castilla (US), Manju Swaroop (US), Kris Blanchard (US), Francis S. Collins (US), Russell Snell (GB), Tracey Holloway (GB), Kathleen Gillespie (GB), Nicole Datson (GB), Duncan Shaw (GB) and Peter S. Harper (GB) discovered the precise causal gene for Huntington's disease at 4p16.3, making this the first autosomal disease locus found using genetic linkage analysis (2177).

Domenico Antonio Rigoni-Stern (IT) examined the death records of the city of Verona for the years of 1760 to 1839. He found that cancer of the cervix of the uterus was rare in nuns, but the nuns were afflicted with a veritable epidemic of breast cancer. Housewives had breast cancer far less frequently than nuns, but cancer of the cervix was widespread among them (2929, 2930).

Dimitrios Trichopoulos (GR-US), Brian MacMahon (US), and Philip Cole (US) compared the reproductive experience of women with breast cancer with that of women of comparable ages who did not have it. They found that a woman who had a live born infant at an early age was afforded considerable protection against breast cancer when compared to women who had not delivered such an infant while they were young. They also showed that a woman who had never given birth to a full term, live born infant was twice as likely to develop breast cancer as a woman who had borne one at any age (3392).

Norman Chevers (GB) described aortic subvalvular stenosis (603).

James Syme (GB) performed his first innovative ankle disarticulation (3031).

Pierre Michel Toussant de Serres (FR) wrote the first scientific study of animal migrations (828).

Johannes Japetus Smith Steenstrup (DK) discovered the possibility of using the subfossils (not yet truly fossilized) of the post glacial as a means of interpreting climate changes and correlated vegetation change, which he called succession in the recent past (715, 3250).

Archiv für Physiologische Heilkunde was founded.

Zeitschrift für Rationelle Medicin was founded.


“The plant cell, like the animal cell, is a type of laboratory of cellular tissues that organize themselves and develop within its innermost substance; its imperforate walls, to judge from our strongest magnifying instruments, have the property of drawing out by aspiration from the ambient liquid the elements necessary for its elaboration. Thus they have the property of acting as a sorter, of admitting certain substances and preventing the passage of others, and consequently of separating the elements of certain combinations in order to admit only a portion of them. 

Since disease originates in the elementary cell, the organization and microscopic functions of which reproduce the general organization exactly and in all its relationships, nothing is more suited to simplifying the work of classification and of systematic division than to take the elementary cell as the basis of division.” Francois-Vincent Raspail (FR) (2854)

With thinking such as this Raspail helped point the way to the cell theory and to cellular pathology.

Adolph Wilhelm Hermann Kolbe (DE) carried out the second "total synthesis" of an organic compound (acetic acid) from truly inorganic precursors. Carbon disulfide was the starting material (1864, 1865).

Jean Baptiste André Dumas (FR) published the empirical formula for glucose (929).

Joseph Redtenbacher (CZ) distilled glycerol with a small addition of phosphorus pentoxide and obtained acrolein (acrylic aldehyde), which he identified with the highly irritating vapors formed when fats are heated to decomposition. This odor formation was subsequently employed as a qualitative test for fats (2883).

Johann Justus Liebig (DE) surmised that organic acids might be the intermediate sub- stances on the path of carbon from carbon dioxide (CO2) to carbohydrates. He proposed that various organic acids, such as oxalic, malic, tartaric and citric acids, were the intermediates in the stepwise reduction of CO2 to carbohydrates (2085, 2501, 2698). 

Johann Justus Liebig (DE) proposed that carbohydrates could serve as precursors to fats. He suggested this based on his observation that farmers fattened their cattle by feeding them grains. He noted that to make fat from sugar would simply require the removal of oxygen from sugar molecules (2084).

DeWitt Stetten, Jr. (US) and George E. Boxer (US) concluded from their experiments that in animals fed a high carbohydrate diet, fatty-acid formation is a more important pathway in glucose utilization than glycogenesis (3260).

Julius Vogel (DE) showed that cholesterol is present in atherosclerotic plaques (3488).

George Busk (GB), in 1843, was the first to describe a clinical case of fasciolopsiasis (giant intestinal fluke). He found 14 flukes in the duodenum of a sailor from eastern India during an autopsy. The discovery was not published. 

George Budd (GB) described Fasciolopsis buski as the trematode fluke causing fasciolopsiasis (512, 1064).

Angelo Dubini (IT), in 1838, observed a “new human intestinal worm” following the dissection of the corpse of a peasant woman who had “died of croupous pneumonia”. This hookworm is the agent causing ankylostomiasis, the hookworm disease. He named the hookworm, Ancylostoma duodenale (903, 904).

Theodor Maximillian Bilharz (DE) proposed a connection between hookworms (Ancylostoma) and Egyptian chlorosis (255).

Wilhelm Griesinger (DE) recognized Ancylostoma as the cause of Egyptian chlorosis (1415, 1416).

R.J. Lee (GB) was the first to describe cutaneous larva migrans (CLM) which he called "the creeping eruption" (2012). Today, it is one of the most common helminth (hookworm) infections (usually caused by Ancylostoma braziliense) acquired from subtropical and tropical regions of the world.

Camillo Bozzolo (IT) introduced thymol as a treatment for hookworm infestation (386).

Arthur Looss (DE), working in Egypt, was dropping cultures of hookworm larvae into the mouths of guinea pigs when he spilled some of the culture onto his hand. He noticed that it produced an itching and redness and wondered if infection would occur this way. He began examining his feces at intervals and, after a few weeks, found that he was passing hookworm eggs. He elucidated the entire life cycle of the parasitic hookworm nematode called Ancylostoma duodenale (2125-2127).

Gabriel Andral (FR) wrote this first monograph on hematology and one of the most important works in the history of hematology. Here he first uses the terms anemia and hyperanemia and clearly describes a number of diseases of the blood including lead poisoning, septicemia and polycythaemia (48).

James Braid (GB) coined the terms hypnosis, hypnotism, hypnotize, and hypnotist (396).

Jean Louis Rodolphe Agassiz (CH-US) completed Recherches sur les Poissons Fossiles… describing the fossil fish of the world. This single monograph increased tenfold the formally described vertebrates known to science (25).

Pierre-Joseph van Bénéden (BE) founded the first marine biological laboratory. It was located at Ostend, Belgium.


Johann Justus Liebig (DE) wrote Bemerkungen uber das Verhaltniss der Thierchemie zur Thier -Physiologie, which united the fields of chemistry and physiology (2086).

Heinrich Gustav Magnus (DE) and Julius Bodo Unger (DE) isolated guanine from the guano of birds. This was forty years prior to its recognition as a nucleic acid constituent (2206, 3419, 3420). 

Johann Florian Heller (AT) devised the Ring Test for albumin (1532).

Johann Florian Heller (AT) devised the caustic Potash Test for sugar in urine (1533).

Théophile Jules Pelouze (FR), et al. were the first to describe the synthesis of a natural neutral lipid, tributyrin, by reacting butyric acid with glycerine in the presence of concentrated sulfuric acid (2717).

Nicolas-Theodore Gobley (FR) described the isolation from egg yolk of a substance, which contained both nitrogen and phosphorus in addition to glycerol and fatty acids. He called it lecithin (Gk. lekithos, egg yolk) (1315-1317, 1319).

Ernst Felix Immanuel Hoppe-Seyler (DE) rediscovered lecithin, a fat (phospholipid) containing nitrogen and phosphorus (1630).

Carl Schmidt (DE) coined the term kohlenhydrate, i.e., carbohydrate to include sugars, starches, and other natural products whose precipitates contained carbon plus hydrogen and oxygen in the same ratio as in water (CH2O) (3072). Schmidt was the first to demonstrate the presence of sugar in the blood

Karl Friedrich Gaertner (DE) distinguished spores from seeds, and endosperm from cotyledons. He noted the distinction between the uniformity of the first hybrid generation and the diversity of later generations, and reported hybrid vigor (1244-1246).

Jean Baptiste Joseph Dieudonné Boussingault (FR) performed experiments, which showed that animals couldn’t live on beetroots or potatoes (Solanum tuberosum) alone without sustaining a weight loss. He concluded that animals could not use nitrogen from the atmosphere to supplement inadequate protein in their diet (357).

Jean Baptiste Joseph Dieudonné Boussingault (FR) and Jean-Francois Persoz (FR) offered experimental proof that animals can synthesize fat from carbohydrate (356, 2724).

Eduard Friedrich Wilhelm Pflüger (DE) recognized that hypoxia stimulates ventilation of the lungs (2741).

Max Josef Pettenkofer (DE) devised a qualitative test for bile salts (cholic acid) (2728).

Max Josef Pettenkofer (DE) discovered kreatinin (creatinine) in human urine then devised a qualitative test for it (2729).

Agostino Bassi (IT) suggested that parasites were the causes of various diseases (including plague, smallpox (red plague), syphilis, and cholera) and advocated methods of prevention. He became the founder of the doctrine of parasitic microbes (129).

Robert Remak (PL-DE) was the first to describe the intrinsic nerve ganglia of the heart (Remak’s ganglia). This helped explain the relatively autonomous nature of the heart beat (2901).

Robert Remak (PL-DE) discovered the nerve ganglion located in the sinus venosus of the frog’s heart (2903).

Karl Friedrich Wilhelm Ludwig (DE) discovered the ganglion cells of the interauricular ganglion of the heart (Ludwig's ganglion) (2152).

Friedrich Heinrich Bidder (LV-DE) discovered two large masses of ganglion cells at the juncture of the auricles and ventricles of the heart (245).

Rudolf Albert von Kölliker (CH) demonstrated the relative independence of the sympathetic nervous system (3572).

Claude Bernard (FR), in one of the earliest cardiac catheterizations, inserted a mercury thermometer into the carotid artery of a horse and advanced it through the aortic valve into the left ventricle to measure blood temperature. He adapted this experiment over the next forty years for measuring intracardiac pressures in a variety of animals. It was Bernard who coined the phrase cardiac catheterization (2409). 

Horace Wells (US) and Gardner Q. Colton (US), in 1844, administered nitrous oxide gas and performed the operation of extracting a tooth painlessly (53). This predates Morton’s use of ether by two years but postdates the use of ether by William E. Clark in 1842.

James Young Simpson (GB), in 1844, introduced into obstetrical practice dilatation of the cervix uteri for diagnostic purposes (3183, 3189, 3192). He was the first to use chloroform in obstetrics and the first in Britain to use ether (3186). Simpson introduced the terms ovariotomy and coccydynia (3192).

Auguste Nélaton (FR) placed alcohol-soaked dressings on open wounds and reported a decreased infection rate (2484).

Theodor Ambrose Hubert Schwann (DE), using an artificial biliary fistula in a dog, established that bile from the liver and gall bladder is indispensable to digestion (3132).

Karl Moritz Gottsche (DE), Johann Bernhard Wilhelm Lindenberg (DE), and Christian Godfried Daniel Nees von Esenbeck (DE) brought together in one publication the descriptions of the world’s known hepatics (liverworts); some 1,600 species (1379).

Hermann Schlegel (NL) was the first to use a third name—ternary nomenclature—added to the Linnean binomial when he used it to designate geographic variants among birds (3172).

Friedrich A. Puchelt (DE) gave the first clinical report describing astereogenesis or failure to identify the form of an object being held (2812).

Arthur L. Wigan (GB) wrote philosophically about each hemisphere of the brain housing its own distinct mind. Wigan wrote that the two minds ordinarily worked in a unified, highly adaptive manner, but also possessed the ability to function independently (3741).

Walter Edward Dandy (US) argued that no symptoms follow splitting of the corpus collosum (757). 

Roger Wolcott Sperry (US), Ronald Myers (US), Joseph E. Bogen (US), Philip J. Vogel (US), and Michael S. Gazzaniga (US) reported on cases of cerebral commissurotomy (brain splitting) in cats, monkeys and epileptic patients in whom the corpus callosum — the bundle of axons fibers that connects the two brain hemispheres — had been severed to prevent seizures. A number of tests revealed how the two brain hemispheres hold independent streams of conscious awareness, perceptions, thoughts, and memories and, importantly, that neuronal connections are formed and maintained with a high degree of precision (318, 319, 2458, 3229, 3232).

Roger Wolcott Sperry (US) reported that under controlled testing conditions, the left hemisphere showed that it is much more verbal than the right, as well as more analytic and more rational. The right hemisphere, in turn, came out being more holistic, emotional, impulsive, and artistic (3230, 3231).

Michael S. Gazzaniga (US) later wrote, “Results accumulated over a period of six years demonstrated that the cortical commissures were critical to the inter-hemispheric integration of perceptual and motor function. These studies also revealed that the mute right hemisphere was specialized for certain functions that deal with nonverbal processes, while, not surprisingly, the left hemisphere was dominant for language. For the first time in the history of brain science the specialized functions of each hemisphere could be positively demonstrated as a function of which hemisphere was asked to respond” (2037). This work forms the basis of human developmental neurobiology and psychobiology.

Ernst Maria Johann Karl von Feuchtersleben (AT), in 1844, introduced the term psychosis in its modern context during lectures on psychiatry (3526).

Robert Chambers (GB), first writing anonymously and then under the pseudonym Samuel Richard Bosanquet, introduced the idea of evolution to the wider public in a popular book. He argued for an ancient solar system begun in fire, then coalescing under gravity as it cooled and geological processes, violent at first, then gradually subsiding over eons. He reasoned that life arose by a natural and material process with simple forms gradually giving rise to more complex forms. Man was seen as a product of this process (1, 331).

ca. 1845

Rudolf Buchheim (EE), in Dorpot, Estonia, set up the world’s first laboratory devoted to the study of the actions of drugs (677).


" What exact relation disease of the kidney bears to hypertrophy of the heart, we do not know even yet. But the two are too often coincident in the same subjects for them not to bear some, and that a very important, relation to each other." Peter Mere Latham (1986)

Alfred Francois Donné (FR) produced the first engravings from photomicrographs, in this case, daguerreotypes (882). He had shown these photomicrographs to the French Academy of Science in 1839.

Raffaelle Piria (IT) described salicin (salicyl alcohol glucoside) from willow bark (2750).

Raffaelle Piria (IT) showed that aspartic acid is converted to malic acid upon treatment with nitrous acid (2751).

V. Dessaignes (FR) made aspartic acid from malic acid or fumaric acid (849).

John F.W. Herschel (GB) described the fluorescent properties of quinine sulfate ushering in the 'modern' period for observing fluorescence and realizing its nature (1561).

George Gabriel Stokes (GB) described a vast collection of fluorescent substances, from quinine sulfate to Oporto wine. It was he who coined the word fluorescence to describe light emission induced during excitation (3268).

Johann Friedrich Wilhelm Adolf Baeyer (DE) synthesized the first fluorescent dye, fluorescein (92, 93).

Carl Schmidt (DE) discovered that the tunicates contain cellulose (3073). This was unexpected since cellulose was thought to be unique to plants.

Nicolas-Theodore Gobley (FR) described in egg yolk and brain the presence of a phosphorus-containing fraction, which gave by hydrolysis oleic acid, margaric acid, and phosphoglyceric acid (1318, 1320, 1321). This represents the discovery of phospholipids.

Johannes Ludwig Wilhelm Thudichum (DE-GB) coined the term phosphatide to designate phosphorus-containing lipids (3345).

Julius Robert Mayer (DE) was the first to state that the fundamental physical function of photosynthesis is the conversion of light energy into chemical energy saying: "Nature has put itself the problem of how to catch in flight light streaming to the Earth and to store the most elusive of all powers in rigid form. The plants take in one form of power, light; and produce another power, chemical difference” (2267).

Apollinaire Bouchardat (FR) and Claude M.S. Sandras (FR) detected a diastase in the pancreas but were unsure of their findings (339).

Ernst Heinrich Weber (DE) and Eduard Friedrich Wilhelm Weber (DE) shared the discovery of the inhibitory power of the vagus nerve upon the beating of the heart in frogs, fish, birds, cats, dogs, and rabbits (3685, 3688).

Robert Dundas Thomson (GB) was the first to show that after a meal rich in fat, the blood level of fat will rise (3340).

Robert Dundas Thomson (GB) and Friedrich Knapp (DE) are credited with devising a method for determining animal rations, using data from chemical analysis of foods and excreta (3341).

Miles Joseph Berkeley (GB) insisted that a fungus, Botrytis, (later names Phytophthora infestans [Mont.] De Bary) was responsible for the potato blight which attacked the crops of Great Britain and Ireland in 1845. He did not, however, prove this. Berkeley was a leader in taxonomic mycology in England where he named approximately six thousand new species of fungi (181-185, 3202).

Heinrich Anton de Bary (DE) and Mikhail Stepanowitsch Woronin (DE) showed that the potato blight was caused by the fungus Phytophthora infestans (798, 804).

Bernhard Rudolf Konrad von Langenbeck (DE), in 1845, was the first to report a case of what would later be called human actinomycosis. It occurred in a patient with vertebral caries and was attributed to a fungus. James Adolf Israel (DE) later reported Langenbeck’s discovery (1715).

Otto Bollinger (DE) was the first to recognize tumors (lumpy jaw of cattle) caused by Actinomyces bovis as a specific parasitic disease. At this time the organism had neither been named nor classified (326, 327).

Karl Otto Harz (DE), at the suggestion of Otto Bollinger (DE), studied parasitic material isolated from osteosarcomic tumors, lumpy jaw, in cattle and gave it the name Actinomyces bovis because of the ray-like structure of its growth in the tissues (1504).

James Adolf Israel (DE) and Emil Ponfick (DE) discovered granules in human autopsy material and described actinomycosis in humans. Thoracic actinomycoses was described for the first time in the 1882 reference (1715-1717, 2774, 2775).

James Adolf Israel (DE) described human cases of actinomycosis very similar to lumpy jaw in cattle (1715). 

Max Wolff (DE) and James Adolf Israel (DE) delineated the anaerobic nature of actinomyces (Actinomyces israelii), obtained axenic cultures of Actinomyces israelii from man, and proved their pathogenicity by animal inoculations (3792).

Selman Abraham Waksman (RU-US) showed that actinomyces is actually a gram-positive bacteria (3649).

John Leconte (US) described the nervous system of the alligator (2011).

Johann Franz Simon (DE) performed clinical trials for the treatment of chlorosis (green sickness, a peculiar anemia most likely to affect young girls about the time of puberty) by iron administration. He monitored the patient’s progress and the success of the treatment by analyzing the blood for hematin (iron protoporphyrin) content (3178). Chlorosis is very likely the equivalent of what is today called iron deficiency anemia.

Knud Helge Faber (DK) gave a clinical description of achylia gastrica (atrophic gastritis) which is very suggestive of iron deficiency anemia (1048).

Karl Theodor Ernst von Siebold (DE) and Hermann Friedrich Stannius (DE) were the first to introduce the taxa Arthropoda, Rhizopoda, and define the taxon Protozoa in their present sense. They made it quite clear that protozoa are single cell life forms and established Protozoa as the basic phylum of the animal kingdom. They were the first to study cilia, and showed that they could be used for locomotion (3624, 3625).

John Goodsir (GB) established that cells are the active structures involved in glandular secretion, and observed that bone-forming properties reside with certain corpuscles (cells) found within osseous tissue. This represents the foundation of the study of osteogenesis, as distinct from descriptive osteology. He determined that the cell nucleus must be regarded as the central organelle of the cell (1368, 1369). Rudolf Virchow dedicated his 1859 book, Cellularpathologie, to Goodsir because of his advances of knowledge at the cellular level.

Hermann Lebert (DE) wrote Physiologie Pathologique, one of the earliest and most important atlases of pathological histology. This work played an important role in introducing the idea of cellular pathology (2008).

Robert Bentley Todd (IE-GB), by inductive reasoning and not experiment, was the first to call attention to the functions of the posterior columns of the spinal cord. “The posterior columns of the spinal cord may be in part commissural between the several segments of the cord, serving to unite them and harmonize them in their various actions, and in part subservient to the function of the cerebellum in regulating and coordinating the movements necessary for perfect locomotion” (3363).

Charles-Édouard Brown-Séquard (FR) proved by experiment the truth of Todd’s view. See, Brown-Séquard, 1855.

Robert Bentley Todd (IE-GB) discussed the role of the cerebral cortex in mentation (the thinking process), corpus striatum in movement, and midbrain in emotion (3363). Verify

Karl Wilhelm Ludwig Bruch (DE) wrote his dissertation on rigor mortis (493).

John Hughes Bennett (GB) and Rudolph Ludwig Karl Virchow (DE) were the first to describe chronic myeloid leukemia. Virchow’s description was post-mortem and it was he who coined the word leukemia (169, 3467).


Sweden experiences an epidemic of cerebrospinal meningitis.


"We must assume also that the organization of this substance is the process that inaugurates the formation of new cells. It therefore seems justifiable for me to propose a name that refers to its physiological function: I propose the word protoplasma." Hugo von Mohl (3608)

Auguste Laurent (FR) developed at length the difference between an atom and a molecule (1991).

Johann Justus von Liebig (DE) produced crystals of the amino acid tyrosine (Gk. tyros, cheese) by treating casein with alkali (3594, 3595).

Friedrich Bopp (DE), a colleague of von Liebig’s, studied tyrosine much more carefully (328).

Claude Bernard (FR) isolated lipase from pancreatic juice (196). Note: The publication lagged the discovery by ten years.

Augustin Pierre Dubrunfaut (FR) discovered maltose as a major product of the breakdown of starch by diastase (amylase) and described it as a disaccharide (905). He determined that acid would convert cane sugar into a mixture of sugars called invert sugar. He later showed that the invert sugar mixture included dextrose (glucose) and levulose (fructose) (906).

Hugo von Mohl (DE) studied the contents of plant cells and used the word protoplasm (coined by Purkinje), to designate the physical basis of life (3608). See, Purkinje, 1839.

Eben Norton Horsford (US) developed a method for the quantitative estimation of plant fiber (1638).

Jean Baptiste Joseph Dieudonné Boussingault (FR) performed experiments, which allowed him to calculate the minimum amount of dietary calcium phosphate necessary for normal skeletal development in the pig (359).

Max Josef Pettenkofer (DE) produced one of the earliest pieces of evidence that food has a determining influence on the composition of urine (2730). Verify

Golding Bird (GB) weighed and determined the specific gravity of 24-hour urine collections. From these values and a formula, he calculated the quantity of solids in 1000 grains of urine. He also used nitric acid to test for bile in urine (a green color), and a simple polariscope or alkaline copper reagent for glycosuria (267).

Heinrich Freidrich Link (DE) presented a classification of inflorescence types and determined that filaments of lichens and fungi consist of cells (3833).

The first Hereford Herd Book was published and later adopted by the 'Hereford Herd Book Society', founded in 1878. 

John James Audubon (US) and John Bachman (US) authored Viviparous Quadrupeds of North America, which, among other things, gave the first substantial report on the mammals of North America (75).

Karl Friedrich Wilhelm Ludwig (DE) invented the kymograph (cymograph). Ludwig made his first tracing on December 12th, 1846 (2151). Physiologists first used kymographs for recording blood pressure. The detailed study of blood pressure made possible in this way showed that blood circulation could be explained in terms of ordinary mechanical forces. This machine represents one of the first graphic methods employed in experimental physiology. Ludwig by simultaneously recording the pulse wave and respiratory pattern became the first to described sinus arrhythmia in 1847. 

Peter Ludwig Panum (DK) is responsible for our modern understanding of the epidemiology of measles. Having been sent by the Danish government to study an outbreak of the disease on the remote Faeroe Islands in the North Atlantic he demonstrated that measles is contagious, discerned both the length of the incubation period, and the establishment of a lifelong immunity in those who recovered from this infection.

 “ If among 6,000 cases of which I myself observed and treated about 1,000, not one was found in which it would be justifiable, on any grounds whatever, to suppose a miasmatic origin of measles, because it was absolutely clear that the disease was transmitted from man to man and from village to village by contagion, whether the latter was received by immediate contact with a patient, or was conveyed to the infected person by clothes, or the like, it is certainly reasonable at least to entertain a considerable degree of doubt as to the miasmatic nature of the disease…. It is beyond doubt that the surest means of hindering the spread of the disease, is to maintain quarantine” (2635). Note: This is a republishing of Panum’s classic paper in 1846.

Cenci (IT), in 1901, described passive immunization of individuals exposed to measles (rubeola) by using convalescent serum. ref

Charles Nicolle (FR) and Ernest Conseil (FR) confirmed the effectiveness of the passive immunization procedure for measles (rubeola) (2504).

Carl Ferdinand Eickstedt (DE) discovered that Tinea versicolor is the cause of Pityriasis versicolor, a superficial dermatomycosis in man (999).

Theodorus Slyter (DE) made the same discovery (3198).

Henri Baillon (FR) named the causative agent Malassezia furfu (98).

William Thomas Greene Morton (US) successfully anesthetized a patient by the administration of ether while Dr. John Collins Warren (US) removed a tumor from the patient’s neck. This operation received widespread recognition and although it postdates William E. Clark’s and Crawford Williamson Long’s anesthetic use of ether by five years it is nevertheless considered the inauguration of the era of painless surgery (253, 3677, 3678).

Oliver Wendell Holmes (US) wrote Morton suggesting that the word anesthesia be used to refer to the process of inducing insensibility in the patient. Holmes did not coin this word; it was used by the ancient Greeks (Gk. no pain) (2213).

John Hutchinson (GB) developed the spirometer for measuring capacity of the lungs (1667).

F. Wild (DE) and Karl Friedrich Wilhelm Ludwig (DE) were the first to establish an isolated heart preparation; they connected the aorta of a killed animal with the carotid artery of a living donor animal, thus maintaining perfusion of the coronary arteries of the recipient heart. This was an empty, beating, nonejecting mammalian heart preparation. Regular beating could be maintained for a very long period of time if blood clotting was prevented (3742).

Elie de Cyon (LT-DE-RU-FR) and Karl Friedrich Wilhelm Ludwig (DE) were the first to excise a heart (frog) and to keep it in this completely isolated perfused state for a long period of time. They used it to make the first report on the effects of temperature changes on the function of the isolated (frog) heart (813).

Henry Newell Martin (GB-US), using the dog, was the first to devise a mammalian heart-lung preparation from which the systemic circulation was cut off and replaced by an artificial system (2250).

Oscar Langendorff (DE), using cats, rabbits and dogs, was the first to excise a mammalian heart, perfuse it, and keep it alive for several hours (1964, 1965).

Stanley J. Sarnoff (US), Eugene Braunwald (AT-US), George H. Welch, Jr. (US), Robert B. Case (US), Wendell N. Stainsby (US), and Radi Macruz (BR) used a novel blood-perfused preparation consisting of an isolated dog heart supported by a donor dog. This preparation maintained cardiac performance, allowing critical evaluation of the effect of varying heart rate, aortic pressure, and preload on oxygen consumption in the left ventricle (3036).

James R. Neely (US), H. Liebermeister (DE), Edward J. Battersby (US), and Howard E. Morgan (US), using the rat, converted the Langendorff heart into a working mode. They were able to conduct experiments for up to 3 h without deterioration in function, while manipulating ventricular pressure development, filling pressure, and heart rate and observing the effect on oxygen consumption and flow (2480). Various laboratories for studies on cardiac metabolism and coronary regulation, applying conventional chemical methods and nuclear magnetic resonance techniques, have used this preparation.

Both Sarnoff and Neely identified the importance of the tension-time index (average ejection pressure of the left ventricle multiplied by the duration of ejection) and peak systolic pressure as strong correlates of oxygen consumption, while changes in cardiac output and work were not.

Willard Parker (US), in 1846, performed cystotomy to relieve inflammation and rupture of the bladder (2641).

The third great pandemic of Asiatic cholera began (517).

Rudolf Ludwig Karl Virchow (DE) and Benno Ernst Heinrich Reinhardt (DE), founded a new journal, Archiv für Pathologische Anatomie und Physiologie und für Klinische Medizin [Archives of Pathological Anatomy and Physiology and of Clinical Medicine]. Later it became Virchow’s Archiv.


A dysentery (the "bloody flux") epidemic occurs in the United States.


"One cannot say that, again with the help of the press, "the truth" can overcome the lie and the error. O, you who say this, ask yourself: Do you dare to claim that human beings, in a crowd, are just as quick to reach for truth, which is not always palatable, as for untruth, which is always deliciously prepared, when in addition this must be combined with an admission that one has let oneself be deceived! Or do you dare to claim that "the truth" is just as quick to let itself be understood as is untruth, which requires no previous knowledge, no schooling, no discipline, no abstinence, no self-denial, no honest self-concern, no patient labor!" Søren Kierkegaard (1800)

Lambert Heinrich Joseph von Babo (DE) discovered that the vapor pressure of a liquid is lowered by dissolving a substance in it, and that the relative lowering of the vapor pressure is proportional to the concentration of the solution (3498).

Marie-Jean-Pierre Flourens (FR) found that chloroform has a similar anesthetic effect to ether (1173). See, Samuel Guthrie, 1831.

Johann Justus von Liebig (DE) isolated and named inosinic acid (Gk. inos, muscle or sinew). He obtained it from muscle extracts (3595).

Franz Haiser (DE) discovered that inosinic acid yielded hypoxanthine on acid hydrolysis, suggesting its relationship to the nucleic acids, and that it contains phosphorus as phosphate. He also concluded that there was a third component which he did not identify (1465).

Apollinaire Bouchardat (FR) cleaved inulin and from it purified levulose (fructose) (1236).

Johann Florian Heller (AT) was the first to note the retention of chlorides in pneumonic urine (1534).

Johann Justus von Liebig (DE) discovered that the blood and lymph have a relatively high concentration of sodium and a low concentration of potassium while in the extravascular tissues the reverse is true (3596).

C. Blondeau (FR) made a study of various fermentations other than the vinous. He examined the lactic, butyric, acetic, urea, and what he called fatty fermentations. Blondeau concluded that they were all caused by vegetable growths, and suggested that different fungi caused different fermentations (308).

George Henry Kendrick Thwaites (GB) discovered conjugation in the diatoms and was the first to regard conjugation as a sexual process without qualification. He considered the diatoms to be algae (3349, 3350).

Rudolf Albert von Kölliker (CH) reported that involuntary nonstriated muscle fibers in the walls of blood vessels are actually elongated nucleated cells and noted that this type of cell has wide distribution within the body (3574).

Joseph Lister (GB) observed such cells in the arterioles of the frog's web and confirmed Kölliker’s findings. Lister also showed that these cells occur in mammals as well as amphibians (2093).

Friedrich Stein (DE) made a histological study of the female reproductive organs of beetles. This represents the beginning of the modern study of the insect ovary (3253).

Karl Bogislaus Reichert (DE) observed cell division of zygotes in the nematode Strongylus auriculatus and noted that the nuclear membrane disappeared prior to division. He introduced the cell theory into embryology, proving that the segments of the fertilized ovum in the mulberry stage develop into cells and that all the organs develop from these cells (2894).

Heinrich Frey (DE) and Karl Georg Friedrich Rudolf Leuckart (DE) separated the coelenterates from the echinoderms emphasizing that although both displayed radial symmetry they were not closely related. Leuckart denied the existence of taxons founded on negative character states and established the taxon Coelenterata (Gk. koilos, cavity, enteron, intestine). It included sponges and ctenophores (1219, 1220). Leuckart is commemorated by Leuckartiara Hartlaub, 1913; Podon leuckartii G.O. Sars, 1862; Protohydra leuckarti Greeff, 1870; Mesocyclops leuckarti (Claus, 1857); Sphaeronella leuckartii Salensky, 1868; Arachnomysis leuckartii Chun, 1887; Protodrilus leuckartii Hatschek, 1882; Chromadorita leuckarti (de Man, 1876); and Sabelliphilus leuckarti Kossmann, 1877.

Karl Georg Lucas Christian Bergmann (DE) and Joel Asaph Allen (US) independently proposed very similar rules in zoology. Bergmann’s rule states that body weight tends to a minimum in warmer regions, increases to a certain threshold as temperature declines, and then falls off again as temperature falls further. Birds and mammals in cold regions have been observed to be bulkier than individuals of the same species in warm regions. It was proposed to account for an adaptive mechanism to conserve or to radiate body heat, depending on climate. Allen’s rule states that animals adapted to cold have smaller and shorter limbs and other protruding body parts (35, 178).

Jean Jacques Marie Cyprien Victor Coste (FR) in his studies of various mammals, birds, and fishes discovered that partial division of the ovum begins during its descent through the oviduct (703). 

Daniel Cornelius Danielssen (NO) and Carl Wilhelm Boeck (NO) published Om Spedalskhed (About Leprosy) which became the foundation of the modern medical history of leprosy (758).

Dairo Fujii (JP), in 1847, properly recorded Katayama disease (a schistosomiasis caused by Schistosoma japonicum). The report did not become available until 1909 (1239).

E. Mashima (JP) discovered the pathogenic agent of Japanese schistosomiasis when he found the ova of Schistosoma japonicum in the liver at autopsy (2256).

Tokuho Majima (JP) found schistosome eggs in patients with Katayama disease and associated the pathological changes with the presence of the schistosome eggs (2212).

Fujiro Katsurada (JP) discovered, described, and named this parasitic trematode Schistosoma japonicum (1780, 1781).

Keinosuke Miyairi (JP) and M. Suzuki (JP) discovered that snails are the intermediate host of Schistosoma japonicum (2365, 2366).

Joseph Hyrtl (AT) published his Handbuch der Topographischen Anatomie (Handbook of Topographic Anatomy), the first textbook of applied anatomy of its kind ever issued. Other important anatomy books by him include Lehrbuch der Anatomie des Menschen, Handbuch der Praktischen Zergliederungskunst als Anleitung zu den Sectionsubungen und zur Ausarbeitung, Anatomischer Praparate, and Onomatologia Anatomica. While Chair of Anatomy at the University of Vienna he achieved worldwide fame as a teacher (1705-1708).

Ernst Wilhelm Brücke (DE) discovered a ciliary muscle later named for him (495).

Alexander Ecker (CH) described erythrocytes inside of rabbit spleen cells. He speculated that the red cells might have been "jammed" into the larger cells by circulatory forces (972).

 Kranid Slavjansky () reported the presence of coal dust within alveolar macrophages from miners’ lungs (3197).  

Nathanael Lieberkühn (DE) showed that leukocytes could ingest erythrocytes (2068).

Felix Victor Birch-Hirschfeld (DE) found that leukocytes might take up bacterial cocci injected into the blood stream (266).

William Osler (CA) found erythrocyte-containing leukocytes in the blood of humans with various diseases (2586).

Giulio Cesare Bizzozero (IT) described the clearance of carbon particles by cells of lymph nodes and also the internalization of small leukocytes by larger leukocytes in the spleen (281). Verify

Giulio Cesare Bizzozero (IT) described the process of efferocytosis in an experimental model performed in the inflamed anterior chamber of the eye of rabbits. He described the pus: “If one investigates the exudate, it is possible to detect, in addition to the white blood suppurative cells, different bigger cellular elements (30–50 μm) and containing in addition to the nucleus a variable number (from 1 to 20 and more) of round corpuscles, which in terms of morphology and chemical reaction look exactly like the other suppurative cells” (282).

He concluded his second report by stating: “In summary, my observation showed the presence of big cells able to engulf white blood suppurative cells or red blood cells in their contractile protoplasms. This represents a way through which the pus or blood is absorbed from the anterior chamber” (283). See, Bizzozero in 1847

James Young Simpson (GB) and Jacob Bell (GB) introduced the use of chloroform as an anesthetic in obstetrics. After testing it on themselves it was given to a woman during childbirth (3184, 3185, 3187).

Jean-Marc Dupuy (FR) and Nikolai Ivanovich Pirogov; Nicholas Ivanovich Pirogoff; Nikolai Iwanowitsch Pirogow (RU) discovered rectal anesthesia (936, 2753, 2803).

Daniel Molière (FR) and Alex Iversen (DK) reintroduced rectal anesthesia (2370).

Robert Bentley Todd (IE-GB), in 1847, invented locomotor ataxy (tabes dorsalis), by which he began the separation and classification of spinal diseases. Prior to this all spinal diseases were labeled paraplegias

“Two kinds of paralysis may be noticed in the lower extremities, the one consisting simply in the impairment or loss of voluntary motion, the other distinguished by a diminution or total loss of the power coordinating movement. In he later form, while considerable voluntary motion remains, the patient finds great difficulty in walking and his gait is so tottering and uncertain that his centre of gravity is easily displaced… In two examples of this variety of paralysis I ventured to predict disease of the posterior columns, the diagnosis being founded upon the views of their functions which I now advocate, and this was found to exist on a postmortem inspection; and in looking through the accounts of recorded cases in which the posterior columns were the seat of the lesion, all seem to have commenced by evincing more or less disturbance of the locomotive powers, sensation being affected only when the morbid change of structure extended to and more or less involved the posterior roots of the spinal nerves” (3362).

Jaques Francois Édouard Hervieux (FR) reported on autopsies of 44 jaundiced infants. His descriptions of pathoanatomical findings were very detailed and systematic. A number of his clinical observations are still thought to be accurate today, such as the essentially benign nature of neonatal jaundice in most cases, the appearance of neonatal jaundice during the first 2 to 4 days of life as well as its disappearance within 1 to 2 weeks, and the cephalocaudal progression of jaundice. He described jaundice of the brain in 31 of his 44 autopsied cases, with variable intensity of staining (1572). Christian George Schmorl (DE) would name this yellow staining of certain areas of the brain kernicterus (3083).

Golding Bird (GB) and John Hilton (GB) recorded the first operation for intestinal strangulation of the small intestine. No anesthetic was used; the patient died nine hours afterward (268).

Moritz Schiff (DE) investigated the effects of section of the vagus on respiration (3060).

Hundreds of Cayuse Indians in the Pacific Northwest were killed by measles. This tribe had never been exposed to measles previously, and missionaries were blamed for introducing it. One missionary near present-day Walla Walla tried to provide them with food and medicine, but the Indians thought he was making it worse, and killed him, his wife and twelve others at the mission, and took a number of others hostage. Several years of conflict followed (1863).

Archiv für Pathologische Anatomie was founded.

The American Medical Association was founded then reorganized in 1901 (2213).

David Jones Peck (US) was the first African-American man to receive the Doctor of Medicine degree from a United States medical school (Rush Medical College).


Auguste Laurent (FR) and Charles Frédéric Gerhardt (FR) indicated that leucine and glycine have very similar chemical properties and they considered both to be part of a homologous series having the composition CnH2n+1NO2 (1992).

Benjamin Collins Brodie, Jr. (GB) determined that beeswax consists primarily of the solid alcohols: cerotic, myricine, and ceroleine (463-465). This work proved the existence of solid alcohols that were homologous with known liquid alcohols, and it had important implications for the understanding of animal metabolism.

Louis Pasteur (FR), while professor of physics in Dijon, made the discovery that formed the starting point for all of his later brilliant studies in bacteriology, viz., that by means of fermentation he could produce, then separate, the two varieties of tartaric acid distinguished by their capacity to rotate a plane of polarized light in opposite directions. He had already separated these types on a crystallographic basis (1844). One form, he found, was destroyed by fermentation, the other not. This discovery opened the way for a more exact understanding of the essential nature of ferment action. From this he developed an intense interest in the subject of fermentation in general (2649-2651).

Rudolf Albert von Kölliker (DE) proved the act of phagocytosis beyond doubt when he observed the heliozoan, Actinophrys sol. in the act of ingesting another protozoan (3577).

Per Henrik Malmsten (SE) discovered that Trichophyton tonsurans causes a human dermatomycosis (2216).

Claude Bernard (FR) and Charles-Louis Barreswil (FR) suggested that the production of glucose by the liver (glycogenesis) is a characteristic of mammalian life and occurs independently of whether glucose is in the diet. They concluded that “like plants, animals can create and destroy sugar physiologically” (187, 192-194, 212). 

Bernard suggested, based on experiments with the hypothalamus, that glucose homeostasis is regulated by a balance of opposing influences originating in the central nervous system (190).

Lawrence A. Frohman (US), Lee L. Bernardis (US), Errol B. Marliss (CA), Lucien Girardier (CH), Josiane Seydoux (CH), Claes B. Wollheim (CH), Yasunori Kanazawa (JP), Lelio Orci (CH), Albert Ernst Renold (CH), and Daniel Porte, Jr. (US) showed that while Bernard was not completely correct the islets of Langerhans are richly endowed with autonomic nerve endings containing both adrenergic and cholinergic synaptic vesicles, and gap junctions between nerve endings and islet cells have been observed. Stimulation of the ventromedial nucleus of the hypothalamus and of the sympathetic nerve to the pancreas causes an outpouring of glucagon and limits insulin secretion, as does the administration of catecholamines. Appropriate adrenergic blocking agents block these effects. The effect of adrenergic stimulation is to lower the insulin: glucagon ratio, thereby increasing hepatic glucose production and glycemia (1235, 2241). 

Richard Owen (GB) coined the word homology in its biological context, defining it as “the same organ in different animals under every variety of form and function” and elaborated between homology (homologous) and analogy (analogous) as applied to the anatomical features of animals. He emphasized that all vertebrates have a similar structure, which has adapted in different ways but was not "aimed" in a linear way at man (2602, 2603, 2607).

Johann Florian Heller (AT) invented the ureometer for determining specific gravity of urine samples (1265).

Emil Heinrich du Bois-Reymond (CH-DE) refined old instruments and devised new ones with which he detected the passage of tiny currents in nerve and muscle (e.g., nerve galvanometer). He was able to show that the nerve impulse is accompanied by a change in the electrical condition of the nerve (900).

Carl Müller (DE) brought together in one publication the entire world’s mosses, which had been described. It included 2,400 species of Mucsi and only 25 species of Sphagnum (2421).

Joseph Dalton Hooker (GB) realized that planktonic diatoms are plants, and suggested that they play the same ecological role in the sea that green plants do on land (1623).

Matthias Jakob Schleiden (DE) published Die Pflanze und ihr Leben, a book that dramatically changed the approach to botany. Microscopic examination was exalted, giving it an importance equivalent to that of systematics. Inductive reasoning was elevated in importance to exceed that of philosophical theorizing (3068).

Henri Milne Edwards (FR), based upon respiratory organs, divided the gastropoda into Pulmonés, Opisthobranches, and Prosobranches, now rendered Pulmonata, Opisthobranchia, and Prosobranchia (975). Johann Wilhelm Spengel (DE), based upon their nervous system, divided the gastropoda into Strepyoneura and Euthyneura. Streptoneura is equivalent to Prosobranchia; Euthyneura embraces Opisthobranchia and Pulmonata (3227). He is commemorated by Edwardsia de Quatrefages, 1841; Edwardsiella Andres, 1883; Henricia J.E. Gray, 1840; Autolytus edwardsi de Saint-Joseph, 1887; Lophoura edwardsi Kölliker, 1853; Plesiopenaeus edwardsianus (Johnson, 1867); Plesionika edwardsii Brandt, 1851; Dynamene edwardsi Lucas, 1849; Grapsicepon edwardsi Giard & Bonnier, 1888; Glossocephalus milneedwardsi Bovallius, 1887; Onisimus edwardsii Krøyer, 1846; Diastylis edwardsi Krøyer, 1841; Neoamphitrite edwardsii de Quatrefages, 1866; Colpaster edwardsi Perrier, 1882; Milnesium Doyère, 1840; Jasus edwardsii (Hutton, 1875), Odontozona edwardsi (Bouvier, 1908), Milneedwardsia Bourguignat, 1877, Boeckosimus edwardsii (Krøyer, 1846), Lithophyllon edwardsi (Rosseau, 1850), and Goniastria edwardsi Chevalier, 1971. Phascolosoma spengeli, and Spengelia Willey, 1898, commemorate Spengel.

William Sharpey (GB) described Sharpey's fibers (bone fibers, or perforating fibers) as a matrix of connective tissue consisting of bundles of collagenous fibers connecting periosteum to bone. They are part of the outer fibrous layer of periosteum, entering into the outer circumferential and interstitial lamellae of bone tissue (2822). Note: Clementi (IT) claimed priority in this discovery.

Hermann Ludwig Ferdinand von Helmholtz (DE) demonstrated that heat production accompanies contraction in muscle (3556).

Henry Bence Jones (GB) discovered an unusual protein in the urine of patients with multiple myelomas (1754).

Charles Freeman Geschickter (US) and Murray Marcus Copeland (US) found a myeloma protein in serum and distinguished it from the urinary Bence Jones proteins (1303).

Alfred Baring Garrod (GB) noted the link between gout and hyperuricaemia (1266).

Josiah Clark Nott (US) advanced the hypothesis that yellow fever is unique and that insects vector it from person to person (2537).

Johann Ferdinand Martin Hayfelder (DE-RU) was the first German surgeon to use an anesthetic, performing many operations using ether or chloroform. He discovered the anesthetic properties of ethyl chloride (1580).

Pinckney W. Ellsworth (US), in 1848, amputated the leg of Henry A. Goodale, age 14, as Horace Wells (US) anesthetized him with nitrous oxide (3343).

John M. Harlow (US) reports a singular incident, which was to change our understanding of the relation between mind and brain. Phineas P. Gage, a 25-year-old railroad foreman, was excavating rock. In preparation for blasting he was tamping powder into a drill hole when a premature explosion drove the tamping iron—1.1m long, 6 mm in diameter, and weighing 6 kg—through his left cheek and out of the vault of his skull with such force that it threw him on his back and fell several rods behind, “smeared with brain.” Despite his injuries he remained conscious and only a few minutes later was sitting in an ox cart writing in his workbook. He recognized and reassured Dr. Harlow, who had been summoned to the scene. The wound continued to bleed for two days; then followed a virulent infection that rendered Gage semiconscious for a month. His condition was so poor that a coffin had been prepared. Nevertheless, Dr. Harlow continued treatment, and by the fifth week the infection had resolved and Gage had regained consciousness.

He later developed epilepsy, and in May 1861, 12 years after the injury, he died in status epilepticus.

Immediately after physical recovery Dr. Harlow described Gage as follows: “Remembers passing and past events correctly, as well before as since the injury. Intellectual manifestations feeble, being exceedingly capricious and childish, but with a will as indomitable as ever; is particularly obstinate; will not yield to restraint when it conflicts with his desires.” Dr Harlow reports that Gage’s employers, “who regarded him as the most efficient and capable foreman ... considered the change in his mind so marked that they could not give him his place again.... He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires.... A child in his intellectual capacity and manifestations, he has the animal passions of a strong man.... His mind was radically changed, so decidedly that his friends and acquaintances said he was ‘no longer Gage (1490, 1491).

Emil Heinrich du Bois-Reymond (CH-DE), using a sensitive galvanometer, described an "action potential" accompanying muscular contraction. He detected the small voltage potential present in resting muscle (resting currents) and noted that this diminished with contraction of the muscle (899).

The American Association for the Advancement of Science established Science Magazine, which would become one of the world's foremost science journals.

Zeitschrift für Wissenschaftliche Zoologie was founded.


Charles Adolphe Würtz (FR) discovered the aliphatic amines by the action of alkali on cyanic and cyanuric esters (2647).

Eugène Auguste Nicolas Millon (FR) introduced a color test for the presence of protein, which bears his name. The reagent was prepared by dissolving mercury in fuming nitric acid and diluting with water. When the reagent was heated in the presence of most proteins it gave a brick-red precipitate (2348).

Otto Nasse (DE) discovered that a positive Millon Test is not confined to proteids and to tyrosine, but is a general reaction to all aromatic bodies in which a hydroxyl group is connected with the benzol ring (2475, 2476).

Wilhelm Friedrich Karl August Fürst zu Salm-Horstmar (DE) developed a totally inert soil by charring crystalline sugar and demonstrated that normal plants could be grown on this soil provided they were supplied the proper inorganic salts (3024-3026).

Alexander Carl Heinrich Braun (DE) helped modify the cell theory by insisting that the plant cell wall is in fact a structure, which entombs the true living part of the cell where physiological activities take place. The wall must give way if the cell is to rejuvenate (reproduce) itself (404, 405, 1539).

Henri Victor Regnault (FR) and Jules Reiset (FR) were the first to devise a closed system for respiration studies with which they refined Lavoisier’s experiments on measuring the oxygen uptake and carbon dioxide production of animals and calculated the first accurate ratios of carbonic acid gas given off divided by oxygen absorbed. This relationship became known as the respiratory quotient (2889).

Claude Bernard (FR) discovered that pancreatic juice and bile performs some function, which is indispensable for the digestion and absorption of fat. This he conceived to be digestion of fat into glycerol and fatty acid, the latter forming soaps, soluble in water and capable of passing the water-permeated membrane of the intestinal villi (188, 189, 196, 197, 199).

Arpad Bokay (HU) gave the first indication of the existence of enzymes in pancreatic juice hydrolyzing lecithin into glycerophosphoric acid, fatty acids and choline (321).

Claude Bernard (FR) is credited with originating and applying the phrase internal secretion as it applied to the liver liberating glucose into the bloodstream (194). See, Brown-Séquard, 1856.

Heinrich R. Göppert (DE) and Ferdinand Julius Cohn (DE) used carmine and madder (Galium, Ladies’ broomstraw; contains alizarin) with the intention of making the internal contents of Nitella flexilis (alga) more visible (1373).

Rudolf Albert von Kölliker (CH) showed that nerve fibers are elongated portions of nerve cells (3578). See, Robert Remak, 1838.

Hermann Ludwig Ferdinand von Helmholtz (DE) declared nervous transmission to be a material process capable of being measured—invented the myograph—then using the frog made the first measurement of the conduction velocity of a motor nerve axon, finding it to be about one-tenth the speed of sound (3557, 3559).

Julius Bernstein (DE) confirmed the work of Helmholtz by measuring the time course of the action potential (a phrase coined by him) and producing the first plot of the action potential with the wave moving in both directions from the point of stimulation and with an overshoot (214).

Thomas Addison (GB) described patients showing clinical features attributable to adrenal insufficiency: anemia, debility, feebleness of the heart, irritability of the stomach, and changes in skin color. This would become known as Addison's disease (13-15).

Armand Bronze Trousseau (FR) suggested that the disease should bear Addison's name (3400). The condition is commonly called adrenocortical insufficiency or Addison’s disease to this day. Causes of adrenal insufficiency can be grouped by the way they cause the adrenals to produce insufficient cortisol.

Franz Antoine Pollender (DE), in 1849, observed the microorganism now known as Bacillus anthracis (Gr. anthrakos, meaning coal and referring to the black escher in the cutaneous form of the disease) in the blood and organs of infected animals. He thought they were of a vegetable nature. He did not report his finding until 1855 (2770).

Pierre-Francois-Olive Rayer (FR) inoculated sheep with blood of other sheep dead of anthrax. Microscopically he saw the anthrax bacillus in the blood of the inoculated sheep (2878).

Casimir Joseph Davaine (FR) reasoned that bacteria must be the cause of anthrax because they are consistently present in the disease, the disease can be transmitted by inoculation, and when the bacteria are absent there is no anthrax (778-782, 784, 785, 787).

Heinrich Hermann Robert Koch (DE) traveled to Breslau, Germany to share his discovery of the complete life cycle of the anthrax bacillus, Bacillus anthracis, with Ferdinand Julius Cohn and other prominent German scientists reasoning that the facts about anthrax suggested the possibility of spore formation. Studying the disease in small animals and under primitive conditions in his home he had found that it was transmissible from mouse to mouse in a series of twenty generations, and that the lesions in each member of the series were identical. He worked out the distribution of the bacilli in the bodies of different animals. Placing minute particles of fresh anthrax spleens in drops of sterile blood serum or aqueous humor, he set himself to watch, hour after hour, what took place. His technique was simplicity itself; his apparatus was homemade. After twenty hours he saw the anthrax rods grow into long filaments especially at the edge of the cover glass, and, as he watched, he saw rounded and oval granular bodies appear in the filaments. The bodies became clearer and stood out in the filaments. He realized that they were spores, which had not been seen before. He determined accurately the optimal thermal conditions for spore formation. He succeeded in showing that under suitable conditions the spores again grew into typical anthrax rods. He described and correctly interpreted germination of spores, and determined that they are highly resistant to adverse conditions. He realized the epidemiological significance of the resistant spores. He studied septicemia and demonstrated that it and anthrax are different processes. In putrid infusions of vitreous humor he found a bacillus almost identical in appearance as in spore production with the true anthrax bacillus, but showed that it does not produce anthrax. From facts such as these he concluded, “Only one kind of bacillus is in position to induce the specific morbid process whereas other schizophytes are not, or, if pathogenic, they act in a manner different from anthrax.” He tried to induce anthrax in mice by having them ingest the organism but was unsuccessful. He confirmed Brauell’s observation that the young of pregnant animals, dead from anthrax, are non-infective, and he studied the general pathology of experimental anthrax in a complete and masterly manner. He showed that the septicemic stage is reached only very late in anthrax of mice. Dogs, partridges, and sparrows were not susceptible to the disease (517, 1841).

Heinrich Hermann Robert Koch’s (DE) culturing of the anthrax bacillus on the aqueous humor of an ox’s eye, description of its life history, and reproduction of the disease state with an axenic culture of the microorganism is one of the most significant events in the history of biology and medicine. It represents among other things the first proof that a specific disease, anthrax, can be caused by a specific microorganism.

Heinrich Hermann Robert Koch (DE) purified anthrax by passing it through a series of otherwise healthy animals (1841).

Heinrich Hermann Robert Koch (DE) found that when dealing with non-pigmented organisms and pathogens, broths based on fresh beef serum or meat extracts (bouillions) gave the best bacterial growth (1841). 

John Snow (GB) came to the conclusion that fecal pollution and transfer of the unknown specific agents from the sick to the well through direct contact and through drinking water were responsible for the spread of cholera. His cholera experience began at the age of eighteen years during the first pandemic of the disease, when he saw the miners brought up from some of the coal-pits of Northumberland in the winter of 1831-32, after having profuse discharges from the stomach and bowels, and when fast approaching a state of collapse. In answer to Snow’s inquiry, a relative connected with a colliery near Leeds wrote: “The pit is one huge privy and of course the men,” who spend eight to nine hours in the pits, “always take their victuals with unwashed hands.” He came to his conclusion through care of patients, painstaking follow-up of case after case, searching for the unknown contacts with earlier cases, and from statistical studies.

The culmination of his studies in the disease came as a result of the Broad Street pump epidemic in London in 1854. There were cases of cholera in London during the year but few in this area until the latter part of August. Within 250 yards of the pump in a two-week period from August 31, upwards of five hundred fatal cases of Asiatic cholera occurred. By laborious questioning Snow found that most of the cases were among people in the habit of drinking from the Broad Street pump and that few of those in the neighborhood who used other water acquired the disease. Further studies gave convincing evidence: the brick work both of the well and nearby cesspool—only 2 feet 8 inches away! —was in a badly decayed condition and the well was at a lower level showing drainage from cesspool to the well. It is in this work that he originated the concept of the well carrier (3209, 3210, 3212).

Heinrich Hermann Robert Koch (DE) while studying cholera in Egypt demonstrated the importance of the concept of the well carrier first proposed by John Snow (1853).

G. Gros (RU) discovered a parasitic amoeba in the tartar of the teeth (likely Endamoeba gingivalis). This possibly represents the first discovery of a parasitic amoeba in man (1422).

Thomas Henry Huxley (GB) wrote one of the first scholarly papers on the medusa. He noted: a lack of blood and blood vessels, a body plan composed of two tissue layers (ectoderm and endoderm) physiologically analogous to the serous and mucous layers in a typical embryo, that the Medusae, Hydroids, and Sertularian polyps possess body plans similar enough to justify their being grouped together, and that some of these Coelenterata are complicated colonial forms of typical medusae double-membrane structures, i.e., Portuguese man-of-war (1669, 1693).

Arnold Adolph Berthold (DE) observed that the atrophy of a rooster’s comb, which normally follows castration, could be prevented if the testes were transplanted to another location in the rooster. Berthold realized that there was some type of gonadal secretion involved, “…. so it follows that the interaction in question is exerted through the productive relationship of the testes, that is, through their action on the blood and next through a consequent action of the blood on the organism as a whole…” (227). The real significance of testicular secretion into the blood became evident and thus Berthold should be viewed as the founder of the concept of endocrine function. See, Théophile de Bordeu, 1775.

Robert Bentley Todd (IE-GB), in 1849, described epileptic hemiplegia, which came to be called Todd's paralysis (3365).

Charles Emmanuel Sédillot (FR) performed the first successful gastrostomy (creation of an artificial gastric fistula). The patient died within a few hours (3154).

Edgar Allan Poe (US) most likely died of complications brought on by severe alcoholism (2186).

The third major pandemic of cholera, again starting in Bengal, reached Europe and the U.S. in 1848-49. In 1854, the worst year, 23,000 died in Britain alone. In that same year, British physician John Snow succeeded in identifying contaminated water as the transmitter of the disease, a breakthrough in eventually bringing cholera under control (1863, 2498).

Elizabeth Blackwell (GB-US) was the first woman in the modern era to receive a medical degree. Blackwell pursued medical studies independently beginning in 1844. In 1847, she began studying under the tutelage of Dr. Samuel H. Dickson, a professor at Charleston Medical College. Although she applied to more than 25 medical schools, only Geneva Medical School (now Hobart and William Smith Colleges) accepted her. She endured much ridicule and prejudice but still graduated at the head of her class in 1849. Blackwell established a practice in New York but by 1869, she had decided to settle permanently in England (3757).

William Bowman (GB) authored the first work to include a sound description of the microscopic anatomy of the eye and the ciliary ('Bowman's') muscle (384).

Henry Willard Williams (US), in 1849, introduced the use of sutures for cataract surgery by using a shortened sewing needle threaded with a strand of fine glover's silk (3752).

Ludwig Traube (DE) and Friedrich Wilhelm Felix von Bärensprung (DE), in 1849 or 1850, introduced measurement of body temperature as a routine clinical examination method (3379).

Guillaume Benjamin Amand Duchenne de Boulogne (FR) and Francois-Amilcar Aran (FR) described a condition— Aran-Duchenne spinal muscular atrophy— characterized by chronic progressive wasting of muscles with subsequent weakness and paralysis (52, 907, 908).

Jules Bernard Luys (FR) later found this condition to be caused by degeneration of the anterior horn cells of the spinal cord (2166).

Luther V. Bell (US) reported an affliction characterized by wild delirium, general disturbances of the psychic functions and of the motor functions and fever. He found slight cerebral and meningeal engorgements on autopsy (161). Note: Called acute peripheral encephaliys, phrenitis mania gravis, typhomania, acute delirium, delirium grave, and Bell’s disease it is caused by acute hyperemia and subsequent inflammatory changes in the cerebral cortex.

Robert William Smith (IE) wrote a treatise on cases of generalized neurofibromatosis (von Recklinghausen’s disease) 33 years before Recklinghausen’s account (3205).

Friedrich von Recklinghausen (DE) reported on cases of multiple fibroma and multiple neuroma (3614). Note: Ribera (IT) may have been the first to observe neurofibromatosis. Johann Gotfried Rheinhardt (DE) in1793, observed neurofibromatosis. 

James Young Simpson (GB) introduced into obstetrical practice the long obstetrical forceps (3188), and the use of iron wire sutures (3190).

ca. 1850

Emmanuel Geoffroy (FR) isolated nicouline (rotenone) from a specimen of Robinia nicou, now called Lonchocarpus nicou, while traveling in French Guiana. This was posthumously published in 1895 (1299).

The earliest recorded insecticidal use of rotenone was against leaf-cutting caterpillars in 1848 (3030, 3676).

Kazuo Nagai (JP) isolated the active principle from Derris chinensis and named it rotenone (2460).

Frederick B. La Forge (US), Herbert L. Haller (US), and Lloyd E. Smith (US) determined the chemical structure of rotenone (1943).

Youssef Hatefi (US) found that rotenone works by interfering with the electron transport chain in mitochondria. Specifically, it inhibits the transfer of electrons from iron-sulfur centers in complex I to ubiquinone. This prevents NADH from being converted into usable cellular energy in the form of ATP (1505).

The third plague pandemic began in China in the 1850s and spread slowly until it reached the seaports in the 1880s, then spread more rapidly around the world, striking particularly hard in India, Egypt and North Africa, and South America. The continental U.S. was largely spared, but Hawaii suffered a severe outbreak in 1899, and San Francisco was affected in 1900-1904, and again in 1907-1909. The second outbreak in San Francisco was exacerbated by unsanitary conditions following the earthquake of 1906. Sporadic outbreaks continued worldwide for years, and officially this pandemic was not considered over until 1959 (1863).


“There rolls the deep where grew the tree,

O Earth what changes hast thou seen!

There where the long street roars, hath been

The stillness of the central sea.” In Memoriam by Alfred Lord Tennyson

Rudolf Julius Emanuel Clausius (PL-DE) noted that heat is destructible, and examined how it can be converted to work with the flow of heat from a warm body to a cold one. He concluded that entropy, a concept he introduced, must inevitably increase in the universe (625-627, 2202).

Harry Stephen Meysey Thompson (GB) and John Thomas Way (GB) invented ion-exchange chromatography and ion chromatography methods when they treated various clays with ammonium sulfate or carbonate in solution to extract the ammonia and release calcium (3325, 3683). In 1927, the first zeolite mineral column was used to remove interfering calcium and magnesium ions from solution to determine the sulfate content of water.

Edward R. Tompkins (US), Joseph X. Khym (US), Waldo E. Cohn (US), Warren C. Johnson (US), Laurence L. Quill (US), and Farrington Daniels (US) initiated the modern era of ion-exchange chromatography and ion chromatography in their quest to purify radioisotopes and rare earths for the Manhattan Project. A technique was required to separate and concentrate the radioactive elements needed to make the atom bomb. Researchers chose adsorbents that would latch onto charged transuranium elements, which could then be differentially eluted. Ultimately, once declassified, these techniques made available new ion exchange resins to develop the systems that are often used today for specific purification of biologicals and inorganics (1750, 3366).

Waldo E. Cohn (US) then applied the technique to separation of mononucleotides (654). 

Ludwig Ferdinand Wilhelmy (DE) described the first measurements of the velocity of a chemical reaction in a homogeneous medium; he polarimetrically determined the rate of inversion of cane sugar in the presence of various acids (3744).

Adolf Friedrich Ludwig Strecker (DE) synthesized alanine via the cyanohydrin reaction from acetylaldehyde. He proposed the term alanine, which contains the first syllable of the word aldehyde (3283). Alanine is also called aminopropionic acid.

Paul Schützenberger (FR) was the first to find alanine in proteins (silk and ovalbumin) (3120, 3121).

Theodor Weyl (DE), in 1888, isolated alanine from acid hydrolysis of silk fibroin (3731).

Jean Baptiste Joseph Dieudonné Boussingault (FR) was the first to devise a methodology whereby nitrogen of ammonia salts and nitrogen as urea could be distinguished in urine (363).

Charles Adolphe Würtz (FR) obtained methylamine by treating casein with alkali (3811).

Johann Joseph Scherer (DE) isolated and named sarkin (hypoxanthine) from the pulp of the spleen and heart muscle (3057). Hypoxanthine was later shown to be a secondary product formed by the deamination of adenine. 

Franz Leydig (DE) discovered the interstitial cell in the seminiferous tubules and in the mediaseptum and connective tissue septa of the testes (2063, 2065). These cells, called Leydig’s cells, are believed to produce the male hormone testosterone, which determines male secondary sexual characteristics. 

Augustus Volnay Waller (FR-GB) and Julius Budge (DE) contrasted degenerating nerves with unaffected nerves and demonstrated that when nerve fibers are cut the distal portions of the fiber degenerate. This made it possible to trace the course of fibers through the nervous system and demonstrated the importance of the nucleus in the regeneration of fibers. He also found that healthy nerve cells swell in water while damaged cells lost this power (possibly the first account of the loss of semi-permeability in a damaged cell) (3661-3663, 3667, 3669, 3670).

Georg Liebig (DE) published a study on isolated frog muscle activity under aerobic and anaerobic conditions in which he concluded… “in the process of respiration the blood really acts only as a means to effect the transport of gases to the capillaries and back, and that in the capillaries there occurs not the formation of carbonic acid, but only the exchange through the walls of the blood vessels of that already formed for the oxygen of the blood … [T]he formation of carbonic acid from a part of the respiratory oxygen … proceeds in the body not within the capillary vessels, but outside them in the muscle tissue” (2069).

Karl Friedrich Wilhelm Ludwig (DE) and Friedrich Wilhelm Noll (DE) proposed that lymph is formed by the diffusion of fluids from the blood vessels through the vessel walls into the surrounding tissues, the motor power being the capillary blood pressure. The ultimate cause of the lymph flow must be looked for in the energy of the heart’s contraction (2525).  

Claude Bernard (FR) showed that curare destroys the communication between nerve and muscle but that the muscle still responds to stimuli (191, 2718). He went on to show that curare selectively abolishes the action of the motor nerves by stopping the transmission of impulses from motor nerves to voluntary muscles but has no effect on the sensory nerves (198, 200).

Edme Félix Alfred Vulpian (FR) demonstrated that curare interrupts the communication between the nerve fibers and the muscle fibers and does not act on the central nervous system (3640).

Franz Leydig (DE) reported intracellular microorganisms within the cells of aphids and scale insects (actually he did not realize what they were). This was the first study of this type (2063, 2064). These intracellular collections of microorganisms have been called symbiotic organs, pseudovitelli, green bodies, bacteriosomes, mycetoms, and mycetomes.

F. Blochmann (DE) was the first to be convinced that mycetomes contain bacteria (305-307).

Paul Buchner (DE) recognized that the bacteria of mycetomes are symbiotic with their host (508).

Ferdinand Julius Cohn (DE) described the developmental and sexual cycles of the algae Protococcus pluvialis (1850), Stephanosphaera pluvialis (1856), Sphaeroplea annulina (1855), and Volvox globator (1875) and of the lower fungi Pilobolus crystallinus and Empusa (Entomophthora) muscae (642, 643, 645, 646, 651, 653)

Pierre-Joseph van Bénéden (BE) deduced that bladderworms (cystici), which had hitherto been regarded as a separate class of helminths, were simply larval tapeworms. He coined the terms scolex and strobila in reference to tapeworms (3431). 

Maximillian Johann Sigismund Schultze (DE) was the first to render a correct account of the general anatomical features of the nemertines. Schultze knew the use of the proboscis, distinguished between the armed and unarmed types of proboscis, discovered the nephridia, and defined the nemertines—which he called Rhynchocoela or Nemertina—as turbellarians with an anus and an eversible proboscis (3103). These animals are commonly called ribbon worms.

Robert Remak (PL-DE) described the role of different embryonic germ layers for organogenesis and reduced von Baer’s four germ layers to three and named them: ectoderm (outer skin), mesoderm (middle skin), and endoderm (inner skin) (2904).

Moritz Hoffa (DE) and Karl Friedrich Wilhelm Ludwig (DE) described strange unregulated actions of the ventricles (later called ventricular fibrillation) during experiments with strong electrical currents across the hearts of dogs and cats. They demonstrated that a single electrical pulse could induce fibrillation (1605).

Ernst Heinrich Weber (DE) described the role of elasticity and resistance in the vascular system as a determinant of the distribution and rate of flow of blood throughout the body (3686). In 1827, he had described the effect of the elasticity of blood vessels in transforming the pulsatile movement of the blood in the aorta into a continuous flow of blood in arterioles and capillaries. He demonstrated that the pulse wave traveled at 9.24 meters per second and arrived in the feet a fraction of a second after it reached the jaw.

Marshall Hall (GB) coined the phrase spinal shock (1466).

Daniel Drake (US) wrote, A Systematic Treatise, Historical, Etiological and Practical, on the Principal Diseases of the Interior Valley of North America, as they Appear in the Caucasian, African, Indian, and Esquimaux Varieties of its Population, one of the unique medical treatises of the 19th century (893). Drake is considered one of the greatest American teachers of medicine.

Lamuel Shattuck (US), Nathaniel Banks, Jr. (US), and Jehiel Abbott (US) presented their Report of the Sanitary Commission of Massachussetts: Report of a General Plan for the Promotion of Public and Personal Health. The report, based on a sanitary survey of Boston in 1845, contains such far reaching recommendations as: We recommend that provision be made for obtaining observations on the atmospheric phenomena, on a systematic and uniform plan at different stations within the Commonwealth. We recommend that measures be taken to prevent, as far as practicable, the smoke nuisance. We recommend that, in laying out new towns and villages and in extending those already laid out, ample provision be made for a supply, in purity and abundance, of light, air, and water; for drainage and sewerage, for paving, and for cleanliness.

The report also contains far-reaching recommendations relative to housing, schools, occupational health, and adulterated food and drugs, and recommended that persons be specially educated in sanitary science (3166). In 1948, Charles-Edward Amory Winslow (US) called the Shattuck Report, as it is popularly called, “Perhaps the most significant single document in the history of public health… I know of no single document in the history of that science quite so remarkable in its clarity and completeness and in its vision of the future.” 

Pierre Paul Broca (FR) described the venous spread of cancer independently of Carl von Rokitansky (CZ-AT) (455, 3617, 3619).

William MacIntyre (GB) was the first to describe multiple myeloma (2183).

William Detmold (US) opened the lateral sinus of the brain for abscess (850).

Alcide Dessalines d’Orbigny (FR) is considered the founder of the science of micropaleobotany. His most important work was the founding of the science of stratigraphical paleontology based on observations of exposed fossil-bearing strata in the Paraná Basin of South America between 1826 and 1834. He studied small marine fossils, pollen, grain and spores found in sedimentary rocks for the purpose of dating stages. Like his mentor Cuvier, he found that some fossils occurred only in certain layers of a geological formation. He used these fossils to subdivide what we today call the Jurassic into twenty-seven stratigraphic stages, each with its particular fossils (752, 753).

An extensive epidemic of dengue fever began in Charleston, SC, and then spread to Savannah, Augusta, New Orleans, Mobile, Galveston, and other southern coastal cities (1863).


Alexander William Williamson (GB) was the first person to formulate the concept of chemical reactions reaching an equilibrium state; introducing the phrase dynamic equilibrium. He was also the first person to clearly demonstrate that a specific intermediate compound formed in a catalyzed reaction. This was the formation of ethyl sulfate when sulfuric acid catalyzed the conversion of ethyl alcohol to ethyl ether (3754).

Francois Verdeil (FR) suggested a relationship between chlorophyll and heme upon chemical conversion of chlorophyll to a red pigment (3456).

Peter Ludwig Panum (DK) found that protein separated from serum and egg white on dilution and the addition of acid. The blood serum gave a precipitate, which would redissolve in water while the egg albumin gave no precipitate. This was one of the first clues that proteins may exist in various chemical types (2631, 2632).

Louis René Tulasne (FR), Charles Tulasne (FR) and Heinrich Anton de Bary (DE) described the life history of certain fungi and developed the doctrine of ‘alternation of generations’. They used the terms pleomorphism or heteromorphism to express the observed fact that one and the same fungus appeared in several forms, not only as regards the vegetative but also the fructifying organs, and it was soon shown that this is a widespread type of development, especially among the fungi which cause disease in cereals (797, 801, 803, 3401).

Wilhelm Friedrich Benedikt Hofmeister (DE) authored Vergleichende Untersuchungen [Comparative Researches], which represented the beginning of modern work with the Bryophyta (liverworts and mosses) and Pteridophyta (ferns, horsetails, and club-mosses). Here for the first time was a general account of the life histories and reproductive structures of the main types of Bryophyta and Pteridophyta together with some reference to the gymnosperms. Descriptions of prothalli, sex organs, developmental stages in many ferns, and alternation of sexual and asexual generations in plants was here described for the first time. Hofmeister explained how seeds are formed: the megaspore is not released from the megasporangium, but germinates there. The pollen grains correspond to the spores of vascular cryptogams (1614).

"It was to Hofmeister, working as a young man, an amateur and enthusiast, in the early morning hours of summer months, before business, at Leipzig in the years before 1851, that the vision first appeared of a common type of Life-Cycle, running through Mosses and Ferns to Gymnosperms and Flowering Plants, linking the whole series in one scheme of reproduction and life-history." Arthur Harry Church (2173).

Theodor Hartig (DE) furnished the first exact description of the descending sap flow in the 1851 edition of his father’s book, Lehrbuch für Forster und die es Werden Wollen (1494).

Theodor Hartig (DE) discovered and described sieve tubes in plants (1495).

Carl Vogt (DE) recognized the leeches as annelids, placed the nematodes, gordiaceans, acanthocephalans, and gregarines under the class Nematelmia and the true flatworms plus the nemertines under the class Platyelmia (3489).

Karl Gegenbaur (DE) altered Vogt’s names to Platyelminthes and Nemathelminthes. His Platyelminthes contained three groups: Turbellaria (including nemertines), Trematoda, and Cestoda (1294).

Ernst Ehlers (DE) put the nemertines in their own group, the Nemertina (980).

Charles Sedgwick Minot (US) then removed the nemertines and placed them in their own phylum (2353).

Libbie Henrietta Hyman (US) emphasized that the etymologically correct form Platyhelminthes (Gk. platys, flat, helminthes, worms) should be used (1703). 

Heinrich Müller (DE) discovered what he characterized as a red pigment in the retina (rhodopsin, or visual purple). He thought it likely to be hemoglobin (2425).

Franz Christian Boll (DE), Wilhelm Friedrich Kühne (DE), and Carl Anton Ewald (DE) independently discovered the visual pigment (rhodopsin) and described the effect of light on this visual pigment found in rod cells of the eye. They showed that light bleaches the visual pigment first to a visual yellow then to a visual white. Kühne solubilized visual pigment (rhodopsin) and suggested that it is a protein (322-324, 1651, 1922, 1923, 1928). Boll called the pigment sehrot (visual red). Ewald and Kühne coined the term sehpurpur (visual purple) and gave the pigment its present name, rhodopsin (1045, 1925).

Selig Hecht (PL-US) and Edward G. Pickels (US) formally identified visual purple (rhodopsin) as a protein (1515).

Carl Ferdinand Arlt (AT) presented the proof that shortsightedness is normally a consequence of an elongation of the sagittal axis of the eye (56).

Ernst Reissner (LV) discovered the membrane in the cochlea that now bears his name (2897). This discovery allowed the cochlea to be divided into three scalae (media, tympani, and vestibularis).

Alfonso Giocomo Corti (IT) described the cochlear receptor organ in the inner ear (organ of Corti) and in the process discovered the hair cells, the rods (arches) of Corti, and the tectorial membrane (Corti’s membrane) and discussed methods for fixing and staining mammalian epithelial cells of the cochlea. He used chromic acid, ether, acetic acid and alcohol as fixatives with a water/alcohol/carmine mixture as his stain (698).

Gustaf Magnus Retzius (SE) observed the nerve ending on the hair cells (2913).

Rafael Lorente de Nó (ES) showed that each inner hair cell is innervated by one or two nerve fibers and that each nerve fiber branches to innervate only a few hair cells (2129).

Hermann Ludwig Ferdinand von Helmholtz (DE) pioneered the scientific study of perception. In 1850, he invented an ophthalmoscope to see within the eye, an ophthalmometer to measure the curvature of the eye, and in 1852 the phakoscope for studying the changes in lens during accommodation, revived and expanded Young’s three-color vision theory (there are three fundamental color sensations—red, green, and blue), and advanced the theory that the ear detects differences in pitch through the action of the cochlea in the inner ear (3558, 3562, 3563). He discovered that light that impinges directly on the optic nerve does not give rise to any sensation, but that it must fall on a nerve ending in the retina before it can be perceived.

Thomas Henry Huxley (GB) confirmed that the life cycle of Salpa goes through an alternation of solitary and chain-like colonial generations. He discovered that the solitary form is the product of the sexual generation and the colonial form results from budding (asexual). He determined that the tail of Appendicularia is a retained larval feature lost by most adult ascidians. He named the phylum Coelenterata (1540, 1670, 1672-1674, 1676, 1694, 1695, 1697, 1699).

Thomas Henry Huxley (GB) popularized the phrase describing protoplasm as the physical basis of life. See, Hugo von Mohl, 1846. Huxley was the greatest champion of Darwin’s theory of evolution (1701).

Josef von Gerlach (DE) was the first to show that human skin uses oxygen from ambient air (3531). 

Friedrich Theodor von Frerich (DE) theorized that uremic intoxication results from the action of a plasma enzyme on the increased amount of urea thus leading to the release of ammonium carbonate (3530).

Franciscus Cornelis Donders (NL) introduced the use of cylindrical and prismatic glasses in impaired vision. He investigated the differentiation of presbyopia and hyperopia, along with the movements of the eye and the accommodation of the pupil. He devised sets of letters of different sizes for testing a patient’s visual acuity. 

In his book, On the Anomalies of Accommodation and Refraction of the Eye, Donders separated the errors of refraction (the bending of light) from those of accommodation (the change in the shape of the lens of the eye to maintain focus). He described the errors in refraction as constant, resulting from light being focused at a constant point either behind or in front of the retina, depending on the shape of the eye. Errors in accommodation, he discovered, result from defects in the eye’s focusing machinery, such as weak ciliary muscles (the muscles that change the shape of the lens) or a hardening of the lenses. These achievements labeled Donders as one of the first scientists who explored the physical field of the eye (871, 872, 875, 876).

Karl Friedrich Wilhelm Ludwig (DE), Emil Becher (DE), and Conrad Rahn (DE) discovered innervation of the submaxillary gland and showed that its secretion is not dependent on blood pressure but rather the gland cells respond like muscle cells to special nerves (152, 2153, 2838). In 1856, Ludwig found that stimulation of the lingual-chorda tympani would cause secretion by the submaxillary gland (2154).

Pierre Paul Broca (FR) described muscular dystrophy as a primary affliction of muscle (456).

Ernst Gustav Benjamin von Bergmann (DE), beginning around 1851, popularized aseptic surgery as an outgrowth of the growing appreciation of the importance of infected persons as the primary source of sepsis. This was an important transition from the clumsy antiseptic technique to the more practical aseptic technique (3509).

Hand washing and preoperative surgical scrubbing became part of the system of aseptic surgery introduced in 1882 by Trendelenburg, von Bergmann, and Schimmelbusch in Germany and by Halstad in the United States.

Hermann Kümmell (DE) devised the routine of scrubbing up for surgery. Ref

William Stewart Halsted (US) had rubber gloves specially made for operating. This article makes the first mention of their use in an operating room (1473).

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) described the use of sterilized linen gloves and a mouth covering of gauze during surgery (3603).

Jean-Pierre Falret (FR) described a condition he called la folie circulaire (circular insanity), of which a patient would experience cycles of manic excitement and cycles of depression. Falret's description is considered to be the earliest documented diagnosis of what today is known as a bipolar affective disorder (1053, 1054).

Jules-Gabriel-François Baillarger (FR) described a psychiatric disorder involving both manic and depressive episodes in the same individual, a condition that he referred to as folie à double forme (dual-form insanity) (97).

The journal Wiener Medicinische Wochenschrift was founded.


"Fear not! Life still
 leaves human effort scope.

But, since life teems with ill,

Nurse no extravagant hope".
 Mathew Arnold

Edward Frankland (GB) was the first to study and synthesize organometallic molecules. During his reading of a paper to the Royal Society on organic metallic compounds he made the empirical observation that elements possess fixed combining powers, or “only room, so to speak, for attachment of a fixed and definite number of the atoms of other elements” (1203). This is considered to be the theory of valence, although the term valence or valency began to be used only after 1865.

Alexander Crum-Brown (GB) developed a system of graphic formulation of compounds which is essentially identical with that used today. His formulae were the first to show clearly both the valency and the linking of atoms in organic compounds (728).

Carl Hermann Wichelhaus (DE) introduced the term valenz (valence) to denote what had been termed saturating capacity or atomicity (3735).

Richard Wilhelm Heinrich Abegg (PL-DE) proposed that a chemical reaction became the transfer of electrons and that chemical bonds became the attraction between opposite electric charges. (It turned out that he was correct for ionic bonding but not for covalent bonding.) He suggested that the outer electron shell governs the chemical properties of an atom. Noting that the inert gases (neon, argon, krypton, xenon, and radon) all have eight electrons and are especially stable, he proposed what become known as Abegg's rule: the difference of the maximum positive and negative valence of an element tends to be eight (6).

Walther Kossel (DE) and Gilbert Newton Lewis (US) independently proposed the electronic theory of valency and brought the new atomic physics to bear on chemical problems. In particular, this theory led organic chemists and biologists to consider reactions in their domain as involving electronic mechanisms. Lewis developed a theory that focused on the significance of valence electrons (electrons in the outer shell) in chemical reactions and in bonding. Lewis’s theory of the cubical atom layed the groundwork for Irving Langmuir’s (US) octet rule, in which atoms form bonds by losing, gaining, or sharing enough electrons to have the same number of valence electrons (eight) as the nearest noble gas in the Periodic Table. The bond formed is ionic or covalent depending on whether the electrons are transferred or shared between atoms (1892, 1972, 1973, 2054, 2625).

Erich Armand Arthur Joseph Hückle (DE) proposed the molecular orbital theory (1654-1659).

Rudolph Pariser (US), Robert Ghormley Parr (US), and John Anthony Pople (GB) presented the Pariser-Parr-Pople method of molecular orbital computation (2638-2640, 2776).

Roald Hoffmann (PL-US) developed the extended Hückel method, a molecular orbital scheme which allowed the calculation of the approximate sigma- and pie- electronic structure of molecules, and which gave reasonable predictions of molecular conformations and simple potential surfaces (1611). 

Raffaelle Piria (IT) described populin (benzoyl salicin) from the bark and leaves of the poplar tree (2752).

Ludwig T. Stawiarski Teichmann (PL) isolated an iron-containing molecule from the blood of various animal types. He named it haemin (3307). Today we know this was hemoglobin and that he demonstrated it contains iron. 

Charles Naudin (FR) compared the origin of species in nature with that of varieties under cultivation. “We do not believe that, when nature created species, it acted in a way any different from the way we act to create varieties; in plain words, we have transposed nature’s processes into our practice. What is this process? It is to attune each member with the whole by assigning to it the function it must carry out in the general organism of nature, a function that is its raison d’etre” (2478).

 Augustus Volnay Waller (FR-GB) confirmed Fontana’s discovery that cut nerve cells could regenerate by demonstrating that regeneration begins proximally to the point of the cut and not distally to it then concluded that the cell body was necessary for cell survival and regeneration (3663). Franz Nissl (DE) would experimentally support this finding (2515).

Waller established that all nerve fibers are filiform cellular processes connected with cell bodies (ganglionic corpuscles) and that the fibers degenerate if separated from their cell bodies (3664).

He expressed his concept of the nutritive influence of nerve cell bodies on the whole fiber and concluded that the nutritive cell bodies for the sensory fibers are in the spinal ganglia, while, for the motor fibers, the nutritive cell bodies are in the anterior horns of the spinal cord (3665).

He obtained experimental evidence for a perennial intraneuronal equilibrium between anabolism and catabolism (3666).

Hermann Friedrich Stannius (DE) performed experiments on animals, which indicated that the heartbeat can be inhibited by the vagus nerve and that the heart contains a pacemaker. He tied ligatures between the sinus venosus and the atrium, and between the atrium and the ventricles of a frog heart, and demonstrated that the sinus is the pacemaker of the heart, yet the atria and ventricles are capable of independent, spontaneous contractions (3240, 3241). See, Ernst Heinrich Weber and Eduard Friedrich Weber, 1845.

Ludwig Traube (DE) also found that if the vagus nerve is cut, the speed of the pacemaker—consequently heart contractions— can not be slowed (3376, 3377, 3379).

Ludwig Traube (DE), in 1852, produced the first graphic presentation of a fever course with simultaneous recording of pulse and respiratory frequency (3379).

Friedrich Heinrich Bidder (DE) and Carl Schmidt (DE) showed the importance of bile in emulsifying fat in the intestine (246).

Karl Vierordt (DE) invented the first quantitative method of counting erythrocytes. He found that man averages 5,714,400 erythrocytes per cubic centimeter (3461-3463).

Hermann Welcker (DE), in 1853, counted white blood cells in man and reported 12,133/ cubic millimeter (630).

Hermann Welcker (DE), in 1854, counted the cells in a patient with chlorosis (an old word for what is probably our modern iron-deficiency anemia) and found that an anemic patient had significantly fewer erythrocytes than a normal person (3423).

Hermann Welcker (DE), ca. 1854, made hemoglobin estimates (630).

Antony Cramer (NL) introduced dilution and counting chambers for blood cells (717).

Magnus Gustaf Blix (SE), in 1885, offered an alternative to counting erythrocytes. He suggested the use of centrifugal force to pack the red cells together and to estimate their number by measuring their volume (2969).

Pierre Carl-Joseph Potain (FR), in 1867, invented the blood-diluting pipette (630).

Georges Hayem (FR) reported the first accurate platelet counts. The platelet numbers he reported do not differ significantly from those reported as normal today (1510).

William Richard Gowers (GB) invented the modern hemocytometer (1380).

William Richard Gowers (GB) developed a method for determining the quantity of hemoglobin in a blood sample (1383). 

Sven Gustaf Hedin (SE) developed a machine for measuring packed erythrocytes—the "hämatokrit"(hematocryte) (1516).

Leon L. Blum (US) laid down certain principles of turbidometry, which led to the use of light transmission as a method of counting blood cells (310-312).

Rudolf Albert von Kölliker (CH) wrote, Handbuch der Gewebelehre des Menschen, fur Aerzte und Studirende, the first textbook of histology. Many of his descriptions have never needed correction (3579). Here he found that more than one nucleus occurs in the giant cells (polykaryocytes) of bone marrow and in certain nerve cells.

Rudolph Wagner (DE) and Georg Meissner (DE) discovered the encapsulated receptors for touch located in the connective tissue papillae of the skin. They conceived the stimulation of these tactile corpuscles as pressure changes in the skin, which in turn triggered neural responses (2287, 3647). In their honor these touch receptors are called Wagner’s corpuscles and Meissner’s corpuscles.

George Meissner (DE) gave the first description of Tinea ungium with detection of fungi in the nail material as the etiologic cause (2288).

Rudolf Virchow (DE) named this disease onychomycosis (3470).

Rudolph Ludwig Karl Virchow (DE) became convinced that connective tissue cells secreted fibrillar intercellular substance (3468).

Robert Remak (PL-DE) argued that proliferation of cells to form tissues is accomplished by cell division and that pathological new growths in animals represent cells arising from previously existing cells (2905, 2907, 2908).

Clemens Heinrich Lambert von Babo (DE) demonstrated the rapid separation of blood-corpuscles from the serum by centrifugation (3497).

Maximilian Perty (DE) created Ciliata for the ciliated forms of protozoa (2725).

Thomas Henry Huxley (GB) grouped all the free-swimming tunicates he had studied into the same group, Ascidiacea (sea squirts), based upon their typical structure (1671, 1696).

Rudolf Albert von Kölliker (CH) described how motor nerves originate from the neurons in the nucleus glossopharyngei (anterior horn) of the spinal cord (3579).

Karl Friedrich Wilhelm Ludwig (DE) and Adolf Beutner (DE), in 1850, were the first to measure blood pressure in the pulmonary artery. They used cats, rabbits, and dogs in which they opened the left pleural cavity then inserted a manometer directly into the pulmonary artery (239).

Karl Friedrich Wilhelm Ludwig (DE) was the first to carry out in hemodynamics the differentiation between measurements of lateral versus retrograde pressure. Ref

Charles-Édouard Brown-Séquard (FR) foreshadowed Claude Bernard's discovery of the vasomotor system by showing in the rabbit that stimulation of the cervical sympathetic causes blanching of the ear (483-485).

Auguste Nélaton (FR) first described a disease characterized by sensory disorders of the lower extremities, leading to perforating ulceration of the feet and destruction of the underlying bones (2485). This disease would be called Nélaton's syndrome.

Eric Perrin Hicks (GB) reported a family as having hereditary perforating ulcer of the foot. Derek Ernest Denny-Brown (NZ-GB-US) reported on this same family and called the disease hereditary sensory radicular neuropathy. It is today called hereditary sensory neuropathy type 1 (HSN1) and recognized as the most common dominantly inherited degenerative disorder of sensory neurons (845, 1583). 

Karl Theodor Ernst von Siebold (DE) first identified Hymenolepis nana syn. Rodentolepis nana, the dwarf tapeworm, as a human parasite in 1852 (2189).

Charles Wardell Stiles (US) identified an identical parasite with a rodent host and named it Hymenolepis fraterna syn. Rodentolepis fraterna (3262).

Hymenolepis is a genus of cyclophyllid tapeworms responsible for hymenolepiasis. They are parasites of humans and other mammals.

Edward Meryon (GB) was the first to give a definite description of what is called Duchenne-Griesinger disease. He reported on four affected brothers whom he had studied for several years. He took pains to conduct postmortem microscopic examinations of muscle tissue from the brothers observing the utter destruction of muscle fibers, as well as, the breakdown of the surrounding muscle sheath, a feature that Duchenne would fail to note (2310). Also known as: Duchenne de Boulogne muscular dystrophy, Duchenne's muscular dystrophy (DMD), Duchenne's myodystrophy, Duchenne's pseudohypertrophic muscular dystrophy, Duchenne's syndrome, and Griesinger's disease or syndrome. DMD was the first well-characterized muscular dystrophy.

Wilhelm Griesinger (DE) and Guillaume Benjamin Amand Duchenne (FR) described a condition—Duchenne-Griesinger disease— characterized by weakness and pseudohypertrophy of the affected muscles. The disease begins in childhood, usually between 2 and 6 years, is progressive, and affects the shoulder and pelvic girdle muscles (912, 1417). In the 1868 article he mentions his use of a biopsy procedure to obtain tissue from a living patient for microscopic examination. Duchenne constructed a biopsy needle (Duchenne’s trocar), which made possible percutaneous muscle biopsies without anesthesia.

William Richard Gowers (GB) recognized that only boys are affected, and that the disease is transmitted through healthy mothers to their sons (1382). See, Broca, 1851.

Thomas Addison (GB) and William Whitey Gall (GB) described hypercholesterolemia (FH) (16).

Thomas Addison (GB) described a case of xanthoma diabeticorum as follows: “an eruption somewhat suddenly appeared on the arms…. It consisted of scattered tubercles of various sizes, some being as large as a small pea…. When incised with a lancet they were found to consist of firm tissue…. They were of a yellowish colour, mottled with a deepish rose-tint…. [At the beginning of March] many of the tubercles began to subside” (3749).

C. Hilton Fagge (GB) described a case of xanthomastosis with cardiovascular symptoms (1051).

Julius Ehrmann (DE) described xanthomas and lipomas (997).

Georg Lehzen (DE), and Karl Knauss (DE) reported the case of an 11-year-old girl presenting with the steadily growing xanthomas, accompanied by cardiovascular symptoms. She died suddenly and the post-mortem study revealed exanthomatous deposits in the aorta, with the narrowing isthmus, as in other large arteries. Later, her sister manifested similar skin changes, highlighting this case to be an early report on homozygous familial hypercholesterolemia (2014).

Carl von Rokitansky (CZ-AT) wrote his excellent monograph on diseases of the arteries in which he described, but did not name, polyarteritis nodosa in a 23-year-old man with a 5-day history of fever and diarrhea (3618). 

Carl Philipp Adolf Konrad Kussmaul (DE) and Rudolf Maier (DE) were the first to use the phrase periarteritis nodosa and provide its classic description, the prototype of systemic necrotizing vasculitis (1941).

William Senhouse Kirkes (GB) discussed embolia as follows: “The effects produced and the organs affected will be…determined by the side of the heart from which the fibrinous masses have been detached; for if the right valves have furnished the source of the fibrine, the lungs will bear the brunt of the secondary mischief, displaying it in coagula in the pulmonary arteries…but if…the left valves are affected, the mischief…may fall on any systemic part, but especially…the brain, spleen, and kidneys” (1813).

Rudolph Ludwig Karl Virchow (DE) demonstrated that masses in the blood vessels resulted from thrombosis (a term he coined) and that portions of a thrombus could become detached to form an embolus (also his term). An embolus set free in the circulation might eventually be trapped in a narrower vessel and lead to a serious lesion in the neighboring parts. He also explained the genesis of thrombophlebitis and was one of the first to recognize lung-and cerebral embolisms (3476, 3479, 3485).

Nikolai Ivanovich Pirogov; Nicholas Ivanovitch Pirogoff (RU) produced the first significant publication on the technique of frozen sections. He thought he had invented the technique, not realizing that Pieter de Riemer (NL) had priority. See, Pieter de Riemer, 1818.

This is also a major work on topographical anatomy and laid a firm foundation for that field as a special area of science having great practical significance for surgery (2754).

James Marion Sims (US), in 1845, surgically repaired vesicovaginal fistula used lateral positioning of the patient, invention of a special curved speculum, and use of silver sutures and a silver catheter to operate successfully for vesicovaginal fistula, a frequent and distressing complication of childbirth seen particularly among the poor (3193).

John Simon (GB) performed the first uretero-intestinal anastomosis, an operation for directing the orifices of the ureters into the rectum (3177).


“Never, in any circumstances, is an optically active compound produced by a non-living body, while almost all the substances elaborated by nature in vegetable organisms are asymmetrical, in the manner of tartaric acid.” Louis Pasteur (2652)

Charles Frédéric Gerhardt (FR) coined the word glyceride in reference to simple compounds forming fats and oils (1302).

Patrick J. Duffy (GB) found that crystallized tristearin, a triacylglycerol, has three melting points (920).

Johann Justus von Liebig (DE) isolated and named kynurenic (Gk. kynos, dog + ouron, urine) acid from dog’s urine (3597).

Ludwig Karol Teichmann- Stawiarski (PL) showed that hemin could be crystallized from dried blood using sodium chloride and hot glacial acetic acid (3306). By 1857 this had been introduced into forensic chemistry as a test for blood.

Johannes Petrus Müller (DE) and Ferdinand Julius Cohn (DE) independently separated out the flagellated protozoa into their own group, Flagellata (644).

Karl Moritz Diesing (AT) suggested the name Mastigophora to replace Flagellata (860).

Gustave Adolphe Thuret (FR) and Joseph Decaisne (FR) showed that in Fucus, a brown marine alga, the eggs had to be activated by sperms before they could germinate, i.e., microgonidia (or spermatozoids) attach themselves to the macrogonidia (or egg cell). This represents the discovery of sexual reproduction among the cryptogams (3346-3348).

Ferdinand Julius Cohn (DE) described the life history of the alga Sphaeroplea annulina (645).

Nathanael Pringsheim (DE) confirmed sexuality in the alga and demonstrated alternation of generations using Vaucheria, Oedogonium, Coleochaete, and Pandorina (2790-2802). Pringsheim is honored with the genus Pringsheimiella.

Ladislav Josef Celakovsky (CZ) proposed his "antithetic theory", according to which a regular alternation of generations occurs in the higher cryptograms only through the interpolation of a new, nonhomologous generation (the sporophyte) arising from the division and progressive sterilization of the zygote of a primitive, sexually reproducing plant (577, 578).

Louis René Tulasne (FR) and Charles Tulasne (FR) demonstrated that a species of fungal rust produces more than one type of spore and that some rusts had three spore forms, which we now call urediospores, teliospores, and sporidia (basidiospores) (3402-3404). 

Philipp Bruch (DE), Wilhelm Philip Schimper (DE), and Theodor Gümbel (DE) authored Bryologia Europea, one of the most important bryological floras ever published. It set the standard in illustration and description for all subsequent works (494).

John Snow (GB) presented the intellectual framework on which his discoveries of the decade or two later were to be built. His most notable application of this framework was his work on the epidemiology of cholera (3211). 

Thomas Henry Huxley (GB), based on comparative anatomy and comparative embryology (largely from Karl Ernst von Baer), concluded that the Cephalopoda, Gastropoda, and Lamellibranchiata are all members of a larger common group (1675, 1698).

Edme Félix Alfred Vulpian (FR) reported on the origins of cranial nerves III to X (3638).

Ernst Adolf Coccius (DE) was the first to describe a break in the retina of the eye and subsequently made the association with retinal detachment (637).

Jules Gonin (CH) was the first to observe the importance of retinal tears in the development of retinal detachments (1361, 1362).

Jules Gonin (CH) pioneered the procedure of ignipuncture and thermocautery, the first successful surgery for the treatment of retinal detachments (1363, 1364).

Karl Vierordt (DE) invented a non-invasive sphygmograph for recording the pulse (3465). It was presented at a meeting in 1853.

Karl Vierordt (DE) established the modern method of estimating blood pressure by adding weights to a sphygmograph (sphygmos is Greek for pulse) (3464, 3465).

Samuel Siegfried Karl von Basch (CZ), in 1881, invented the sphygmomanometer. His device consisted of a water-filled bag connected to a manometer. The manometer was used to determine the pressure required to obliterate the arterial pulse (3505).

Augustus Volnay Waller (FR-GB) discovered the vasoconstrictor action of the sympathetic nervous system (3668).

Smallpox (red plague) was introduced to Hawaii by a ship arriving from San Francisco. At least 2500 people died, possibly as many as 5,000 (1863).


Sweden and Germany experienced an epidemic of cerebrospinal meningitis.


“Dans les champs de l’observation, le hasard ne favorise que les esprits préparés [In the fields of observation, chance favors only the prepared minds]”. Louis Pasteur (3427

Pierre Eugène Marcellin Berthelot (FR) described glycerol as a tribasic alcohol and successfully combined it with fatty acids to yield mono- di- and triacylglycerols (222).

Richard G. Jensen (US), Joseph Sampugna (US), R.L. Pereira (US), Ramesh C. Chandan (US), and Khem M. Shahani (US) described for the first time the synthesis of mixed acid triacylglycerols (1748).

Rudolf Ludwig Carl Virchow (DE) was the first to use the term amyloid to name the tissue condition other pathologists had called lardaceous or cholesterin disease (Speck- oder Cholesterin-krankheit), wax-spleen (Wachs-milz), sago spleen, and lardaceous spleen (2279, 3471, 3472).

Alan S. Cohen (US) and Evan Calkins (US) discovered that amyloid has a precise fibrous ultra- structure (641).

Alan S. Cohen (US) layed out the basic pathobiologic, immunologic, and biochemical factors involved in the genesis of amyloidosis, as well as, the clinical behavior of the disease. This has led to a clearer understanding of its manifestations. The description of the various clinical types including an analysis of the increasing numbers of heredofamilial amyloidoses has led to a greater awareness of their presence and greater interest in their diagnosis (638-640). 

Pierre Eugène Marcellin Berthelot (FR) was among the first to accomplish in vitro synthesis of fats, formic acid, methyl alcohol, ethyl alcohol, methane, benzene, and acetylene. He was the first to synthesize organic substances, which did not occur in nature (222, 223). He coined partition coefficient, explosion wave, saccharose, and acetylene. He was the first to use the word synthesis to mean the production of organic compounds from their elements.

Hermann Welcker (DE) was the first to determine the total blood volume and the size, number, surface area, and volume of the normal blood cells (3709-3711).

John Bennett Lawes (GB) and Joseph Henry Gilbert (GB) used animal feeding experiments to clearly demonstrate that proteins from cereal and legume seeds differed in nutritive value (1997).

The first recorded recommendation of sodium chloride as an herbicide occurred in Germany (3359).

The first documented insecticide in the United States was a sulfur-tobacco dip employed to control sheep scab in 1854. The sheep mite, Psoroptes communis causes sheep scab (3161). The inventor is unknown. The Department of Agriculture was not established until 1862.

Wilhelm Reuling (DE) used logwood (hematoxylin) paper indicator to show that ammonia is not excreted through the lungs during breathing (2916).

Nathanael Pringsheim (DE) noticed that solutions of salts, acids, and sugar caused the zellinhalt (cell contents) to collapse inwards away from the cell wall (2789).

Karl Wilhelm Nägeli (CH) discovered that many plant cells respond to a hypertonic solution by retracting their contents. He attributed this to a semi-permeable cell membrane allowing water to leave the cytoplasm (2464).

Hugo Marie de Vries (NL) named and defined plasmolysis as the detachment of the living protoplasm from the cell wall through the action of aqueous solutions. He realized that the membrane responsible for this osmotic phenomenon is at the boundary of the vacuole, and since it was involved in the maintenance of turgor, he named it the tonoplast (829, 830).

Theodor Hartig (DE), while observing sieve plates, in 1837, was probably the first to see plasmodesmata or connective strands that sometimes connect cells (1499).

Eduard Adolf Strasburger (PL-DE) introduced the name of plasmodesmen (singular plasmodesma) (3279), The Greek plural, plasmodesmata, became the preferred term (3279).

Heinrich Georg Schroeder (DE) and Theodor von Dusch (DE) heated an infusion and the air over it in a flask. The flask was connected to both a sterile tube containing sterile cotton wool and a vacuum tank called a gasometer where the vacuum was produced by lowering the water level. Once the infusion and all associated apparatus cooled the vacuum tank was used to draw fresh air through the cotton wool and into the infusion flask. Meat infusions and malt broths treated this way remained free of putrefaction for approximately one month. If the cotton wool was not in place a similarly treated infusion became putrid by the second week. These two scientists were the first to use cotton plugs to prolong the sterility of culture flasks and tubes. They were not successful, however, in preventing contamination of milk or of meat, without the addition of water, even when the air entering the flask had been filtered through cotton wool (3097, 3098).

Filippo Pacini (IT), during the cholera epidemics in Florence 1854-1855, microscopically examined the blood and feces of those afflicted with the disease as well as the changes of the intestinal mucosa of cholera corpses. This work was done with the support of his assistant, Francesco Magni (IT). These investigations proved the presence of millions of rod-shaped corpuscles, which he considered to be microbes, and so named them. He stated that cholera is a contagious disease characterized by destruction of the intestinal epithelium, followed by extreme loss of water from the blood (for which condition he later recommended, in 1879, the therapeutic intravenous injection of saline solution). Pacini went on to declare that the intestinal injuries common to the disease were caused by living microorganisms - which he called "vibrions"; he further provided drawings of the vibrions that he had observed microscopically in abundance in the intestine of cholera victims (2612, 2613).

Heinrich Hermann Robert Koch (DE) later isolated the cholera vibrio from cases of cholera in Egypt. Then, while in the Orient as the head of the German Cholera Commission, he discovered the cholera vibrio in the intestinal discharges of cholera patients, thereby providing a ready and successful means of quarantine control of the disease (1848, 1850-1852). This microorganism has gone by various names including: Spirillum cholerae asiaticae (Koch), Spirillum cholerae, Vibrio cholerae, the comma bacillus, and Vibrio comma (Bergey). In 1965 the international committee on nomenclature adopted Vibrio cholerae Pacini 1854 as the correct name of the cholera-causing organism.

George Newport (GB) and George Viner Ellis (GB) proved that it was the sperm cells, not the fluid, in semen, which fertilized frog eggs. He also found that the point of sperm entry determines the plane of the first cleavage and the axis of the developing embryo (2497).

Robert Remak (PL-DE) was the first to use hardening agents to improve definition of histological preparations (2906).

Theodor Hartig (DE) reported on staining plant chlorogen granules (chlorophyll) and other parts of the cell using gamboge, carmine, cinnabar, copper sulfate, litmus, and ink (1496-1498).

Rudolf Ludwig Karl Virchow (DE) discovered the neuroglia (3469).

John Simon (GB) was a physician and public health reformer of great importance in the 19th century. The eight annual reports that Simon presented to the Corporation of London are the most famous health reports ever written. They led directly to the Sanitary Act of 1866 and the great Public Health Act of 1875. The latter provided a complete sanitary code upon which the present system is still founded. The good public health infrastructure in western countries is his legacy.

Maximilianus Carolus Augustus Flinzer (DE) introduced the use of silver stain in his study of the cornea (1172).

Bartolomeo Camillo Golgi (IT) discovered the silver nitrate stain for nerve cells (1356). See, Golgi, 1873

Louis-Antoine Ranvier (FR), and Santiago Ramón y Cajal (ES) popularized the use of silver stains in neurological histology (2844, 2845)}.

Louis Pierre Gratiolet (FR) deduced that the two sides of the brain control movement of the opposite sides of the body. He decided that the progression on intellect was clear from lower vertebrates to cats to dogs to monkeys and to man (1400).

William Stokes (IE) wrote, The Diseases of the Heart and the Aorta, which contains a very early account of aortic valve stenosis, paroxysmal tachycardia and a description of Cheyne-Stokes respiration. In 1846 he described bradycardia, Cannon waves, and heart block, since known as Adams-Stokes disease (3271, 3272).

Giovanni Battista Morgagni (IT), Thomas Spens (GB), and Robert Adams (IE) had previously described cases of Adams-Stokes disease; the description by Adams being the most scientific (12, 2384, 3228).

Rudolf Peter Heinrich Heidenhain (DE) demonstrated that the vagus nerve functions to regulate heart activity; the automatic activity seemed to him to originate in the ganglia of the heart (1519).

Nikolai Ivanovich Pirogov; Nicholas Ivanovitch Pirogoff (RU) pioneered the medical use of plaster casts during the Sevastopol campaign of the Crimean War in 1854. He conceived the idea while observing the work of a sculptor (2756, 2757).

Nikolai Ivanovich Pirogov; Nicholas Ivanovitch Pirogoff (RU) invented an osteoplastic foot amputation at the ankle, removing a portion of the os calcis. The foot is severed so that part of the heel bone is left in the stump to give added support to the lower ends of the leg bones (2755).

Gabriel Colin (FR), to explore the psychology and physiology of the horses' feeding process, experimented with various foods and chemicals (663).

Ferdinand Vandiveer Hayden (US) made the first discovery of dinosaur remains in North America during his exploration along the Judith River in the Nebraska Territory (2016).

Aerztliches Intelligenz-Blatt was founded. It became Müncher Medicinsche Wochenschrift in 1886.

Archiv für Ophthalmologie was founded; later renamed Albrecht von Graefe’s Archiv für Ophthalmologie, then Graefe's Archive for Clinical and Experimental Ophthalmology.

Europe experiences a pandemic of dysentery (the "bloody flux").


"For researches [on circulatory changes] the Frog—that arch-martyr to science—affords the most convenient subject." Carl Wedl (3691)

Eugen Franz von Gorup-Besánez (AT-DE) was the first to isolate valine (it was not named at the time). The source was pancreas extract (3535). By 1878 valine was shown to be alpha-aminovaleric acid.

Hermann Emil Fischer (DE) isolated valine from casein and determined its structural formula (1138). Fischer named it valine from the Latin validus meaning healthy (1139).

Charles Adolphe Würtz (FR) proposed the correct formula for glycerol (3812).

Friedrich Gaedcke (DE) announced that he had isolated the active alkaloid ingredient from coca (Erythroxylum coca) leaves. He named it erythroxyline (cocaine) (1243). 

Albert Niemann (DE) is also credited with isolating cocaine from coca plant tissue in 1859 and coining the name cocaine (2506, 2507).

In 1855, Germany introduced sulfuric acid as a herbicide in cereals and onions (3832).

Gottleib Carl Haubner (DE) was the first to conduct digestion trials and to discover that fiber (cellulose) is, in fact, partly digestible (1507).

Wilhelm Henneberg (DE) and Friedrich Stohmann (DE), 1860-1864, conducted trials to determine the digestibilities of all the proximate constituents for a variety of feeds. In 1864, they showed, among other things, that in some cases the crude fiber was more digestible than the nitrogen-free extract (NFE), and that the indigestible portion of the NFE was a noncarbohydrate constituent called lignin (1551).

Wilhelm Henneberg (DE) and Fridrich Strohmann (DE) studied the fate of cellulose in the food of herbivores and found it to have a high nutritional value. They speculated that microbial action converted cellulose into organic acids, and methane (1552).

Hans Pringsheim (CZ-GB) demonstrated that certain cellulose-digesting bacteria liberate simple sugars, and disaccharides (2788).

William Senhouse Kirkes (GB) published a study of apoplexy in Bright's disease. He pointed clearly to the role of raised intra-arterial tension in the causation of arterial disease (1814).

Ludwig Traube (DE) discovered that hypertension often contributes to advanced kidney disease as do fluid and electrolyte disturbances (3378).

F.M. von Heymann (DE) described the optic changes of malignant hypertension (3566). Later called hypertensive neuroretinopathy by Fishberg and Oppenheimer in 1930.

Frederick Henry Horatio Akbar Mahomed (GB) was also one of the originators of the concept that high blood pressure could damage the kidneys and blood vessels (2210, 2211).

Theodor Hartig (DE) described aleurone grains and discovered the nucleus in aleurone cells and was the first to describe it as the basic component of cells (1500, 1501).

Karl Gotthelf Lehmann (DE) reported that fats taken in during a meal are unaltered in the stomach then passed across the intestinal wall of the duodenum where they appear as fat globules in the lacteals. He was mystified as to how fats crossed the membranes of cells in the vicinity of the lacteals (2013).

Richard Ladislaus Heschl (AT) described the transverse gyri in the temporal lobe (Heschl's gyri) (1573). This anatomical structure processes incoming auditory information.

Richard Liebreich (DE) was the first to describe central retinal vein occlusion (2088).

John Russell Reynolds (GB) described the symptomology of tabes dorsalis (locomotor ataxia) (2918).

Heinrich Adolf Rinne (DE) developed a hearing test (Rinne test) conducted with a tuning fork that is used to test and compare a patients' hearing via air conduction (normal process) or by way of bone conduction (sound to the inner ear through the mastoid). He reasoned that if a person hears a sound for a longer period of time through bone conduction than through air conduction, a disease is present somewhere in the conduction apparatus (2942).

Auguste Louis Jules Millard (FR) and Adolphe-Marie Gubler (FR) described Millard–Gubler syndrome with symptoms that result from the functional loss of several anatomical structures of the pons, including the sixth and seventh cranial nerves and fibers of the corticospinal tract. Paralysis of the abducens (CN VI) leads to diplopia, internal strabismus (i.e., esotropia), and loss of power to rotate the affected eye outward), and disruption of the facial nerves (CN VII) leads to symptoms including flaccid paralysis of the muscles of facial expression and loss of the corneal reflex. Disruption of the corticospinal tract leads to contralateral hemiplegia of the extremities (1435).  Need 1855 Millard ref

Guillaume Benjamin Amand Duchenne (FR) developed a meticulous neurological examination to which he added electrical stimulation as a diagnostic test in localization. In 1855, he localized the lesion in polio to the anterior horn cells. His great book in 1867 was a kinesiology of the entire muscular system (911, 913, 915).

William Smellie (GB), Guillaume Benjamin Amand Duchenne (FR) and Wilhelm Erb (DE) described Erb's or Erb–Duchenne palsy as a form of brachial plexus palsy most common in dystocia, an abnormal or difficult childbirth or labor (915, 1033, 3199).

Christian Albert Theodor Billroth (DE-AT) wrote a monograph on colonic polyps recognizing the relationship between adenomatous polyps and colorectal cancers (256). He was the first surgeon to excise a rectal cancer and by 1876 he had performed 33 such operations.

Matthew Fontaine Maury (US) wrote the first textbook on oceanography (2263).


A pandemic of diphtheria spreads into Europe, North America, and Australia. It coincides with a deficiency of rain in these regions (2499). 


William Henry Perkin (GB) patented the aniline dye tyrian purple (mauve) (621).

Jakub Natanson (PL) heated aniline in the presence of chloride of ethylene resulting in a mixture that took on a rich blood-red color. This was most likely the dye rosaniline (basic fuchsine or magenta I) (2477).

François-Emmanuel Verguin (FR), between 1858 and 1859, found that reaction of aniline with stannic chloride gave a fuchsia, or rose-colored dye, which he named fuchsin (magenta or roseine) (2824). Fuchsine is still in use as a biological stain, especially in the periodic acid-Schiff's reagent for detecting aldehydes.

Edward Chambers Nicholson (GB) discovered a better route to the red in which arsenic acid was employed in the oxidative condensation of commercial aniline. He called this dye roseine (1612).

Henry Medlock (GB), in 1860, patented a process for making roseine almost identical to that of Nicholson.

Georg Christian August Wilhelm Hofmann (DE) obtained fuchsine by the reaction of carbon tetrachloride with aniline. Later he isolated rosaniline, and from it, produced a series of violet dyes including aniline blue (triphenyl rosaniline) (3567).

Charles Girard (FR) and Georges de Laire (FR), in 1860, produced spirit-soluble blue (aniline blue or Lyon blue) by heating magenta with aniline (24).

Jean Baptiste Joseph Dieudonné Boussingault (FR) showed that nitrates are the most suitable form of nitrogen supply for plants (364). He was commemorated by the genus Boussingaultia.

Leon Semenowitj Cienkowski (PL-RU) convincingly demonstrated that morphological and physiological processes on the border of animals and plants coincide and no clear characters, delimitating the two kingdoms, can be found (617).

Arnold Cloetta (CH) discovered inosite, taurin, leucin, and uric acid in animal lung tissue (632, 633).

Francois Remy Lucien Corvisart (FR), in 1856, was the first to prove the digestion of proteins by pancreatic juice (trypsin) (702).

Alexander Jakovlevich Danilevsky; Alexander Jakovlevich Danielewski (RU) experimentally separated trypsin from pancreatic amylase by differential adsorption (759).

Wilhelm Friedrich Kühne (DE) coined the term enzyme (Greek énzymos = leavened) to describe the pancreatic protease (trypsin). He also coined the name trypsin (1920, 1921).

Wilhelm Friedrich Kühne (DE) found that an alkaline environment does, in fact, aid the proteolytic action of trypsin (1924).

John Howard Northrop (US) and Moses Kunitz (RU-US) were the first to crystallize the enzyme trypsin (2532-2536).

John William Draper (US) was one of the first to produce photomicrographs, taking pictures of what he saw under a microscope and reproducing them in a book on physiology (895).

Angelo Malestri (IT) and Emilio Cornalia (IT) were the first to describe inclusion viruses. They found the inclusion bodies in diseased silkworms (694, 2214).

Peter Ludwig Panum (DK) discovered bacterial endotoxin (2633, 2634).

Claude Bernard (FR) discovered the presence of a starch-like substance in the mammalian liver, which he called animal starch (glycogen). He identified animal starch as the source of endogenous glucose and noted that it is converted into maltose by the action of salivary enzyme, pancreatic juice, malt extract, and yeast cells (195, 201-203). 

William Starling Sullivant (US) and Leo Lesquereux (CH-US) wrote two important books on North American mosses (3287, 3288).

George Engelmann (DE-US) produced two outstanding monographs on the Cactaceae of the Southwestern United States and adjacent Mexico (1012, 1013).

Maximillian Johann Sigismund Schultze (DE) localized mammalian olfactory receptors high in the nasal cavity in a small area in the superior turbinated bone where there resided special cells with hair-like processes. Because the area has a distinctive yellow color in humans it was given the name locus luteus (3104).

Bartolomeo Camillo Golgi (IT) identified the endings of the olfactory fibers, the granular cells, and the large mitral cells, along with the arborizations within each glomerulus (1329, 1330, 1354).

David Ferrier (GB) concluded from experiments in monkeys that lesions in the temporal lobes often affected the sense of smell (1080).

Santiago Ramón y Cajal (ES) found that the olfactory tract projects back without crossing to end primarily in the temporal prepyriform cortex and in the corticomedial nuclei of the amygdala (2844).

Charles-Édouard Brown-Séquard (FR) proved that removal of both suprarenal (adrenal) glands from dogs invariably led to an exaggerated Addison’s disease and inevitably death. This argued for ductless glands and the doctrine of internal secretion (486, 487).

Eduard Jäger von Jaxtthal (AT) was the first to report diabetic macular changes in the form of yellowish spots and extravasations that permeated part or the whole thickness of the retina (3570).

Edward Nettleship (GB) provided the first histopathological proof of "cystoid degeneration of the macula" in patients with diabetes (2487).

Wilhelm Manz (DE) described the proliferative changes occurring in diabetic retinopathy and the importance of tractional retinal detachments and vitreous hemorrhages (2225).

Arthur James Ballantyne (GB) and A. Lowenstein (IL) provided more evidence suggesting that diabetic retinopathy represents a unique vasculopathy (113).

F.M. von Heymann (DE) was the first to describe retinal cytoid bodies (in collaboration with Zenker in a case of Bright’s disease) thinking that they were degenerate ganglion cells (3565).

Heinrich Müller (DE) correctly claimed that retinal cytoid bodies were swollen varicose nerve fibers (2429).

Rudolf Albert von Kölliker (CH) and Heinrich Müller (DE) were the first to demonstrate that an electrical current accompanies each heartbeat. They measured the current by applying a galvanometer to the base and apex of an exposed ventricle of a frog’s heart. They also applied a nerve-muscle preparation to the ventricle and observed that a twitch of the muscle occurred just prior to ventricular systole and also a much smaller twitch after systole (124, 3586). These twitches would later be recognized as being caused by the electrical currents of the QRS and T waves.

Edme Félix Alfred Vulpian (FR) applied a solution of ferric chloride to slices of the adrenal glands and noted that the medulla stained green while the cortex did not. He also noted that the same reaction was given by samples of venous blood leaving the adrenal, but not by arterial blood entering the gland. To account for these observations, he assumed that the medulla synthesized a substance that was liberated into the circulation (3639). That substance turned out to be epinephrine (adrenaline).

Berthold Werner (PL) reported a histochemical reaction associated with the adrenal medulla, the chromaffin reaction, named so for a relatively specific reaction to chromate salts, observed as a brownish deposit after fixation in chromic acid or dichromate salts (3719).

Alfred Kohn (CZ) coined the phrases chromaffin reaction and chromaffin cell (1862).

Heinrich Anton de Bary (DE), in 1856, while studying the fungus Sclerotina, demonstrated the action of exoenzyme on the host, and postulated the influence of the host substrate on pathogenicity (802).

Rudolph Ludwig Karl Virchow (DE) reported a case of pulmonary aspergillosis (3474).

Robert Remak (DE) discovered the motor points—the entry points of the nerves into the muscles – essential for stimulating the muscles by electricity (2909).

Jakob Ernst Arthur Böttcher (DE) described the nerve ganglion around the cochlear nerve within the internal auditory meatus (335).

Adolf Eugen Fick (DE) wrote Die Medizinische Physik, the first book in the world dedicated to medical physics (1086).

Rudolph Ludwig Karl Virchow (DE) proposed the term erregbarkeit (excitability) for the cell’s capacity to respond to altered nutritive action and reizbarkeit (irritability) for the cells capacity to exhibit contraction, secretion, and conduction (3473).

William Budd (GB) published his first paper on typhoid fever. He concluded that the specific element was furnished in the excreta of affected individuals. “The first thing to attract attention after the disorder had become rife in North Tawton, was the strong tendency it showed, when once introduced into a family, to spread through the household.” By his studies, Budd showed a high probability that the specific element was in the intestinal discharges from the fever patients and fresh cases occurred through contact with the feces. 

In another series, “kept in strict separation from one another, as far as their persons were concerned, the common privy was almost the only connecting link left between them. Neither dirt nor rotting manure cause the fever but some specific element breeding and multiplying in the body and passing to well individuals by various routes.” It was not the aesthetically objectionable and disagreeable rotting feces that were responsible for the spread of typhoid but some specific element in the stools from a previous case (514-516).

Austin Flint (US) was an exceptional teacher and medical diagnostician. Through his teaching and writing he had a profound positive influence on medicine in America. His books included: Physical Exploration and Diagnosis of Diseases Affecting the Respiratory Organs, Compendium of Percussion and Auscultation, A Manual of Percussion and Auscultation, A Practical Treatise on the Diagnosis, Pathology, and Treatment of Diseases of the Heart, and A Treatise on the Principles and Practice of Medicine (1162, 1164-1167).

William Withey Gull (GB) was one of the first to describe the pathological lesions in tabes dorsalis (failure of muscular coordination) and intermittent hemoglobinuria. He and Henry Gawen Sutton (GB) described arterio-capillary fibrosis in chronic nephritis, called Gull-Sutton disease (1444). See, Romberg, 1840.

In 1856, a specimen of Homo sapiens neanderthalensis; Homo neanderthalensis was discovered in the Neander River Valley near Düsseldorf, Germany by quarrymen who gave the bones to a local school teacher and amateur naturalist, Johan Karl Fuhlrott (1238). William King, an Irish anatomist, gave them the name “Neanderthal Man” in 1864. He named them for the Neander River Valley (tal = river in German) (1807, 1808). This specimen probably lived around 80,000 B.P.


“Disease is from of old and nothing about it has changed. It is we who change, as we learn to recognize what was formerly imperceptible.” Jean-Martin Charcot (588).

“It may be considered as a general fact, very likely to be more fully illustrated as investigations cover a wider ground, that the phases of development of all living animals correspond to the order of succession of their extinct representatives in past geological times. As far as this goes, the oldest representatives of every class may then be considered as embryonic types of their respective orders or families among the living.” Jean Louis Rodolphe Agassiz (28).

Claude-Félix-Abel Niepce de Saint-Victor (FR) noticed a fogging of silver chloride emulsions by uranium salts. He reported that the blackening of the emulsions occurred even when they were separated from the uranium salts by thin sheets of paper. He did not appreciate the true nature of the phenomenon that probably represents the first observation of radioactivity (2508-2511).

Eduard Schweizer (CH) developed a solution of cupric oxide in ammonia, which would dissolve cellulose without decomposing it (3137).

Franz Leydig (DE) was the first person to state in unequivocal terms that the cell wall is not a necessary constituent of the cell. “ . . . not all cells are of bladder-like nature; a membrane separable from the contents is not always distinguishable. For the morphological idea of a cell one requires a more or less soft substance, primitively approaching a sphere in shape, and containing a central body called a kernel (nucleus). The cell-substance often hardens to a more or less independent boundary-layer or membrane, and the cell then resolves itself, according to the terminology of scholars, into membrane, cell contents, and kernel” (2065).

Charles Edward Isaacs (US) discovered that, “… the Malpighian tuft or coil is covered by oval, nucleated cells, which are differently affected by chemical reagents from those which line the capsule, and consequently have a different organization. The Malpighian tuft is evidently, then, a glandular structure, every way adapted for the separation of the proximate elements of the urine…” (1712). Note: Malpighian tuft or coil = glomerulus

Georg Meissner (DE) discovered the submucosal nervous plexus consisting of small aggregations of ganglion cells, innervating the submucosa of the alimentary tract (2289). These became known as Meissner’s plexus.

Karl Wilhelm Nägeli (CH) introduced the term Schizomycetes (fission fungi) as a collective designation for the bacteria (2462).

Louis Pasteur (FR) produced fermentation in a solution, which did not contain gluten (albumin). He showed that in a solution of pure sugar with a small quantity of ammonium phosphate and chalk, cloudiness appears and gas was evolved. As the fermentation proceeded the ammonia disappeared, phosphates and calcium salts were dissolved, lactate of calcium was formed, and lactic yeast settled to the bottom. He showed that in all probability the lactic ferment came from the air, for when he used sterile solutions of the various ingredients and allowed only heated air to enter, neither lactic fermentation nor lactic acid nor infusoria appeared; the fluid remained barren. He also showed that some of the sugar was incorporated into cellular material (2653, 2655).

Jean Baptiste Payer (FR) wrote an outstanding treatise on floral anatomy (2705). His work along with that of van Tieghem below represents the origin of the scholarly treatment of floral anatomy.

Philippe Edouard Léon van Tieghem (FR) defined the plant as having three distinct parts, the stem, the root, and the leaf. He studied the origin and differentiation of each type of plant tissue. He studied the gross anatomy of the phanerogams (plants with reproductive organs) and the cryptogams (plants without reproductive organs), such as mosses and ferns. Van Tieghem created a plant anatomy founded on the homologies of tissues and on their origin from the initial cells (3007, 3442-3446).

Franz Leydig (DE) described a large secretory cell, found in the epidermis of fishes and larval amphibians. This mucous cell is peculiar in that it does not pour its secretion over the surface of the epithelium. Leydig believed that its function was to lubricate the skin; the cell now bears his name (2065).

Karl Wilhelm Nägeli (CH) described spores that were probably Nosma bombycis, a microsporidian, when he investigated an outbreak of a disease called pébrine in the silkworm, Bombyx mori (2461).

Édouard-Gérard Balbiani (FR) placed Nosema bombysis, the causative agent of pébrine a disease of silkworms, in the class Sporozoa (105).

Friedrich August Brauell (DE), a professor of veterinary medicine, carried out a number of inoculations to demonstrate the transmissibility of anthrax to sheep by means of human or horse anthrax blood. Dogs and fowl were found to resist infection. He found rod shaped objects in the anthrax bloods but did not regard them as unique to anthrax (401, 402).

W.F. Wade (GB) and Julius Jacobson (DE) characterized cases of syphilitic retinitis (1740, 3643).

Charles Locock (GB), obstetrician to Queen Victoria, was reported to have commented that during the past 14 months he had used potassium bromide to successfully stop epileptic seizures in all but one of 14 or 15 women with hysterical or catamenial epilepsy at a meeting of the Royal Medical and Chirurgical Society in London on Tuesday 11 May 1857. Edward H. Sieveking (GB) had just previously presented 52 cases of epilepsy (3173).

Claude Bernard (FR) found that glucose production continued in diabetic cases where glycogen stores had been depleted. This was the first recognition of the process of gluconeogenesis (201).

Friedrich Wilhelm Ernst Albrecht von Graefe (DE) justified iridectomy for glaucoma as follows: “It seemed to me that all the characteristic symptoms [of glaucoma] tended to one point—increase of the intra-ocular pressure…. Supported by these facts and considerations, I considered myself perfectly justified in performing iridectomy in glaucoma; for I knew the favorable action of the operation on the condition of the choroid in regard to its circulation” (3537). In his short career von Graefe performed more than 10,000 eye operations. He died at 42 as undoubtedly the most important ophthalmologist of the 19th century.

Nikolaus Friedreich (DE) gave the first description of acute leukemia (1227).

Thomas Henry Huxley (GB) insisted that as suggestive as they are, comparisons of adult structures are insufficient for the demonstration of homology in animals. Only by studying the embryonic development of the various structures from their earliest stages and determining that they follow the same path of development can we say with certainty that they are homologous (1677).

Per Henrik Malmsten (SE) described the parasitic ciliated protozoan Balantidium coli, which was later named by Friederich von Stein (DE) (2217, 3626). Balantidium is the only ciliated protozoan known to infect humans. Balantidiasis is a zoonotic disease and is acquired by humans via the fecal oral route from the normal host, the pig, where it is asymptomatic.

Marshall Hall (GB) devised a method of artificial respiration. The subject was first placed in the prone position and pressed upon the back, causing an active expiration. He was then turned over on his side, with the shoulder raised, to bring about an active inspiration (1467, 3213).

Henry Robert Silvester (GB) developed a new method of resuscitating stillborn children, and for restoring persons apparently drowned or dead. The patient lies on his or her back, with arms raised to the sides of the head, held there temporarily, then brought down and pressed against the chest. Movement repeated 16 times per minute (3174).

Edward Albert Sharpey-Schafer (GB) developed a method for artificial respiration of those who were apparently drowned. Place patient prone and face down turning their head to the side. Kneel across the patient’s waist placing both hands flat on the patient’s lower back. Gradually throw your weight forward onto the patient. Immediately thereafter the operator raises his body slowly so as to remove the pressure leaving his hands in place. This forward and backward motion is repeated every four to five seconds (3165).

Robert Bentley Todd (IE-GB) was the first to describe hypertrophic cirrhosis of the liver accurately, sometimes called Todd’s Disease (3364).

Rocco Gritti (IT) described knee disarticulation using the patella as a protective flap (3031).

In 1856, bones were discovered in a cave in the Neander River Valley near Düsseldorf, Germany by quarrymen who gave them to a local schoolteacher and amateur naturalist, Johan Karl Fuhlrott. Fuhlrott identified them as human and thought them to be very old. He recognized them to be different from the usual bones of humans and showed them to the Professor of Anatomy at the University of Bonn, Hermann Schaaffhausen. Fuhlrott and Schaaffhausen presented papers on the fossils and the geology of the Feldhofer Cave at a meeting of the Niederrheinische Gesellschaft für Natur- und Heilkunde (Lower Rhine Medical and Natural History Society) in Bonn in 1857. They published indepently at a later date (1238, 3051).

William King, professor of geology at Queens College in Galway, Ireland, presented a paper in 1864 where he argued the Neanderthal fossils of Fuhlrott and Schaaffhausen belonged to an extinct species of early human that he named Homo neanderthalensis (Homo sapiens neanderthalensis). He named them for the Neander River Valley (tal = river in German) (1807, 1808). This specimen probably lived around 80k B.P.

The journal Jahrbücher für Wissenschaftliche Botanik was founded.


Stanislao Cannizzaro (IT) demonstrated the validity of Avogadro's number (554).

Friedrich August Kekulé (DE) was the first to suggest that carbon is tetravalent, with the ability to bond with up to three other elements and possessing the ability to bond with one, two, three, or even four other carbon atoms. Kekulé also allowed for double and triple bonds (1785). 

Archibald Scott Couper (GB), contributed significantly when he suggested that the chemical bonds could be represented as dashes, assumed carbon to have a combining power of four, and the ability to combine with itself (710, 711).

Kekulé structures quickly became the most popular way of representing molecules. Kekulé along with Johann Friedrich Wilhelm Adolf Baeyer (DE) pioneered the concepts of structural organic chemistry.

Karl Friedrich Wilhelm Ludwig (DE) defined what would come to be known as molecular biology. “Whenever the body of an animal is subdivided to its ultimate parts, one always finally arrives at a limited number of chemical atoms…. One draws the conclusion in harmony with this observation, that all forms of activity arising in the animal body must be a result of the simple attractions and repulsions which would be observed in the coming together of those elementary objects” (2155).

Johann Peter Griess (DE) discovered the diazo compounds that are so important in the chemistry of dyestuffs (1418). 

Josef von Gerlach (DE) while experimenting with solutions of carmine and leaving a section of brain tissue in a dilute carmine solution overnight, reported good differential staining of the nucleus and nuclear granules compared with little or no staining of the cytoplasm and intercellular substance. He concluded that previous staining solutions had been too concentrated, and also noted that the dye was absorbed by specific cellular elements and could not be washed out. He is regarded as the originator of controlled and standardized methods of staining in histology (3532, 3533).

Johann Florian Heller (AT) developed the caustic Potash Test for blood in the urine (1535).

O. Maschke (DE) succeeded in extracting the reserve protein of the Brazil nut and crystallizing it in his laboratory. Later this protein was called excelsin (2253, 2255).

Moritz Traube (PL) proposed that catalytic power in tissues resides in proteins and that biological oxidations are based on the activation of molecular oxygen by intracellular enzymes (3381, 3383-3385).

Louis Pasteur (FR) reported that during the tartaric acid fermentation he had observed an organism (probably Penicillium) to use only the dextrorotatory ammonium tartrate when grown in a mixture of dextrorotatory and levorotatory ammonium tartrate. Thus he developed a practical method for separating compounds, which are identical except for the spatial arrangement of the substituent group (2654, 2656).

Félix Archimède Pouchet (FR) began the presentation of a series of papers to the Academy of Sciences of Paris in which he claimed that he had proven the existence of spontaneous generation or heterogenesis. He was not of the opinion that life springs de novo from a fortuitous arrangement of molecules. He believed in the necessary existence of a vital force coming from pre-existing living matter. Like previous experimenters on the question of spontaneous generation, Pouchet admitted that the real point at issue was whether there are germs in the air or not (2778-2784).

Robert Remak (PL-DE) concluded that cells with more than one nucleus arose by failure of the cell to complete its division (2910).

Karl Wilhelm Nägeli (CH), coined the term meristem, described the function of the apical cell, explained the significance of primary meristem, and identified starch grains. He developed the distinction between meristematic tissue (bildungsgewebe) and structural parts (dauergewebe) whose cells do not multiply (2463).

Julius Gotthelf Kühn (DE) observed and described a fungus on diseased potato (Rhizoctonia solani) (1913).

Spencer Fullerton Baird (US), John Cassin (US), and George Newbold Lawrence (US) authored the most important treatise on the systematics and nomenclature of North American birds up to that time (100).

Spencer Fullerton Baird (US), John Cassin (US), and George Newbold Lawrence (US) authored the most important treatise on the systematics and nomenclature of North American mammals up to that time (99).

Louis Xavier Édouard Léopold Ollier (FR) described the inner layer of the periosteum, closest to the bone. The osteoblasts are in this layer (2563).

Heinrich Müller (DE) performed histological examinations of bone growth including a comparison of normal to abnormal bone structure. He described the healing of a ricketic lesion (2428).

Gustav Pommer (DE) carefully described the distinguishing histologic features of bone structure in rickets, osteomalacia, and osteoporosis (2773).

Heinrich Müller (DE) published descriptions of three eye muscles: the superior and inferior muscles of the tarsal plate, the muscle that bridges the inferior orbital fissure, and the innermost fibers of the circular portion of the ciliary muscle (2431, 2432).

Wilhelm Max Wundt (DE) described the isotonic curves produced by muscle under continuous and constant excitation (3809).

Rudolph Ludwig Karl Virchow (DE) confirmed Remak’s conclusion that the cells of diseased tissue descended from normal cells of ordinary tissue. There was no sudden break or discontinuity signifying the disease, but a smooth development of abnormality. Thus he helped bring disease down to the cellular level (3476, 3482). The medical historian Ralph Herman Major states that for this and his other great works Virchow “…was unquestionably the outstanding physician of his generation, a man who stands aloof in the select company of Hippocrates, Galen, Morgagni, Auenbrugger, and Laënnec. He was the creator of the modern science of pathology, in which subject he had among his precursors only one rival, Morgagni, and among his successors none” (2213).

Maximilian Johann Sigismund Schultze (DE) described the sensory epithelium in the ear of fishes as composed of basal cells and cylinder cells, with numerous nuclei between them, surrounded by protoplasm and having prolongations upwards and downwards, the former passing between the cylinder cells, and the latter between the nuclei of the basal cells. These intermediate cells he called Fadenzellen (3105).

Rudolph Ludwig Karl Virchow (DE) confirmed that syphilis is a disease, which involves all organs and tissues of the body and showed that the causal organism is transferred through the blood to the various organs and tissues (3477).

Casimir Joseph Davaine (FR) and Giovanni Battista Grassi (IT) determined that humans become infected with Ascaris lumbricoides by ingesting the eggs (776, 1397).

Ernst Leberecht Wagner (DE) presented the first important contribution to the knowledge of the gross pathology of uterine cancer (3644).

Robert Remak (PL-DE) having treated some 70 patients with galvanic current believed that it was superior to faradic current for electrotherapy (2911).

Henry Gray (GB) and Henry Vandyke Carter (GB) produced the first edition of Anatomy, Descriptive and Surgical. This would become known simply as Gray’s Anatomy, the most influential human anatomy book in history, going through many editions (1410). Gray died of smallpox at thirty-four years of age.

Johannes Hubertus van den Broek (NL) pioneered work demonstrating that many normal tissues such as blood, urine, and vegetable matter are free of microorganisms. He aseptically cut open grapes then squeezed the juice into sterile containers. Even after months the juice showed no signs of fermentation. When he introduced sterile oxygen no fermentation occurred. When he introduced yeast cells the grape juice underwent fermentation (3436, 3437).

Guillaume Benjamin Amand Duchenne de Boulogne (FR) delineated tabetic locomotor ataxia as a degeneration of the posterior roots and column of the spinal cord and the brain stem. Characterized by attacks of pain, progressive ataxia, loss of reflexes, functional disorders of the bladder, larynx, and gastrointestinal system, and impotence. It develops in conjunction with syphilis and most frequently affects middle-aged men (909, 914).

John Murray Carnochan (US) excised the superior maxillary nerve (including Meckel’s ganglion) for facial neuralgia (558).

Alfred Russel Wallace (GB), while ill in Borneo, had a brilliant insight into how natural selection works. He quickly wrote to Charles Robert Darwin (GB) expressing these thoughts. Darwin had for many years been working on the same theory. The two jointly published a paper, On the tendency of species to form varieties; and On the perpetuation of varieties and species by natural selection, in the Journal of the Proceedings of the Linnean Society expressing their thoughts on the subject. This article included Wallace's paper and excerpts from Darwin's unpublished book, as well as a letter Darwin had written to Asa Grey on the subject in 1857 (771). Darwin's monograph was published the following year (767).

Philip Lutley Sclater (GB) produced studies of the geographical distribution of birds, which resulted in the classification of the zoological regions of the world into six major categories. This was the first serious attempt to study geographical distribution of organisms (3142).

Philip and William Lutley Sclater (GB) later extended these studies to mammals, and it is still the basis for work in zoogeography (3143).

Alfred Russel Wallace (GB) gave an accounting of "what animals live where and why" which helped provide a firm foundation for the subsequent development of the field of zoogeography. Wallace’s Line separates the predominately Australian fauna from that of Asia (3651, 3652). 

Henry Darwin Rogers (US) named the Pennsylvanian period, and Alexander Winchell (US) named the Mississippian period; both these divisions were given system/period status in Geology by Thomas Chrowder Chamberlin (US) and Rollin Daniel Salisbury (US) (585, 2958, 3776).

Joseph Leidy (US) reported the finding by William Parker Foulke (US) of the first relatively complete dinosaur skeleton. Leidy named this creature found in New Jersey, Hadrosaurus foulkii (2017).

Ibis, journal of the British Ornithological Union, was founded.


“At last gleams of light have come, and I am almost convinced that species are not (it is like confessing a murder) immutable.” Charles Robert Darwin (766).

“You would be surprised at the number of years it took me to see clearly what some of the problems were which had to be solved…. Looking back, I think it was more difficult to see what the problems were than to solve them.” Letter from Charles Robert Darwin to Charles Lyell (772)

John William Dawson (CA) discovered fossil plant remains (Psilophyton princeps) in Middle and Lower Devonian rocks from the Gaspé Peninsula in Eastern Canada (789, 790).

Thore Gustaf Halle (SE), Robert Kidston (GB), and William H. Lang (GB) later found similar confirming fossils and established the order Psilophytes (1470, 1799).

Harlan Parker Banks (US) subsequently split the Psilophytes into three divisions: Rhyniophytina (Rhyniophyta), Zosterophyllophyta, and Trimerophytina (Trimerophytophyta) (122).

Jean Baptiste Joseph Dieudonné Boussingault (FR) demonstrated a spontaneous increase of nitrates in plant-free soil (365).

Charles Hanson Greville Williams (GB) made the dye safranin (668).

O. Maschke (DE) introduced the use of indigo to histology. He noted that the affinity of proteins for dyes might serve to differentiate between the different members of this group (2254).

Heinrich Müller (DE) developed a simple dichromate solution (Müllers fluid) with an indifferent salt (potassium sulfate) that was used as a primary tissue fixative. It has limited application as a preservative, but it may be used as a secondary fixative for post chroming (2430).

Wilhelm Friedrich Kühne (DE) used strong salt solutions to extract then characterize the protein he called myosin from muscle (1914, 1917, 1927).

Carl H.D. Boedeker (DE) established the biochemical basis for alcaptonuria by isolating the chemical cause for the darkening seen in the patient’s urine. The chemical is 2,5-dihydroxyphenylacetic acid or homogentisic acid; he named it alcapton then later alkapton (315, 316).

Friedrich Wilhelm Ernst Albrecht von Graefe (DE) first described central retinal artery occlusion (3538).

Edward Smith (GB) made many observations on the relationship of human activity to energy requirements. He noted that the amount of urea in the urine was determined by the amount of nitrogenous substance in the diet and not by level of activity. He observed that output of exhaled carbon dioxide rose with the level of activity (3200).

Claude Bernard (FR) reported that he was unsuccessful when he tried to acidify blood by injecting dilute solutions of acetic or lactic acid intravenously. The animal always died before the blood reached neutrality. Here he also describes some organs as secreting substances outside the blood, others as secreting substances directly into the blood, while others secrete substances both outside and into the blood (204).

Moritz Schiff (DE-FR-CH) proved that removal of the thyroid gland in dogs is fatal (3061). He later discovered that grafts or injections of thyroid extracts could prevent death (3062). Schiff used ground sheep thyroid to successfully treat patients operated on for struma, i.e., goiter. They received injections of the extract twice a week, and after a few months were cured. See, Albucasis, c. 1000.

William Withey Gull (GB) was the first to describe the idiopathic form of hypothyroidism, called Gull’s disease, and associate it with atrophy of the thyroid gland—which he regarded correctly as the adult form of cretinism (1443, 1444).

William M. Ord (GB), who worked with Gull, is credited with coining the name myxedema for the non-pitting edema he observed in patients (2572).

R. Bettencourt (PT) and J-A. Serrano (PT) reported success in implanting a sheep thyroid gland under the skin of the infra-mammary area of a woman suffering from myxedema. The operation was followed by immediate improvement (236, 237).

George Redmayne Murray (GB) postulated that extracts of thyroid glands should be effective in hypothyroidism. In July 1891 he presented at the Annual Meeting of the British Medical Association his observation of a female patient with hypothyroidism (myxedema) treated successfully with hypodermic injections of extract from the thyroid glands of sheep (2453).

Hector W.G. MacKenzie (GB) and Edward L. Fox (GB) reported respectively that oral administration of fresh sheep thyroid glands and thyroid extract were effective in reversing the signs and symptoms of hypothyroidism in a female patient (1193, 2184).

Thomas Henry Huxley (GB) compared the serous and mucous layers characterized by Christian Heinrich Pander with the ectoderm and endoderm of the Coelonterata (1678). See, Pander, 1817

Charles Robert Darwin (GB) published his book, On the Origin of Species by Natural Selection. In this book Darwin gave strong support for the new paradigm that life has had a complex, ever-changing history, i.e., evolution. He also put forward natural selection as the force propelling evolution.

Since this was such a seminal work I offer this excerpt: “A struggle for existence inevitably follows from the high rate at which all organic beings tend to increase. Every thing, which during its natural lifetime produces several eggs or seeds, must suffer destruction during some period of its life, and during some season or occasional year, otherwise, on the principle of geometrical increase, its numbers would quickly become so inordinately great that no country could support the product. Hence, as more individuals are produced than can possibly survive, there must in every case be a struggle for existence, either one individual with another of the same species, or with individuals of distinct species, or with the physical conditions of life. It is the doctrine of Malthus applied with manifold force to the whole animal and vegetable kingdoms… There is no exception to the rule that every organic being naturally increases at so high a rate, that if not destroyed, the earth would soon be covered by the progeny of a single pair.

Owing to this struggle for life, any variation, however slight and from whatever cause proceeding, if it be in any degree profitable to an individual of any species, in its infinitely complex relations to other organic beings and to external nature, will tend to the preservation of that individual, and will generally be inherited by its offspring. The offspring, also, will thus have a better chance of surviving, for, of the many individuals of any species which are periodically born, but a small number can survive. I have called this principle, by which each slight variation, if useful is preserved, by the term of Natural Selection, in order to mark its relation to man’s power of selection. We have seen that man by selection can produce great results, and can adapt organic beings to his own uses, through the accumulation of slight but useful variations, given to him by the hand of nature. But Natural Selection… is a power incessantly ready for action, and is as immeasurably superior to man’s feeble efforts, as the works of Nature are to those of Art” (767). See Anaximander, c.580 B.C.E. and Patrick Matthew, 1831.

Karl Gegenbaur (DE) emphasized that structural similarities among various animals provide clues to their evolutionary history (1294).

Albert Günther (GB) published his Catalogue of the Fishes of the British Museum. This large work contains descriptions of over 6,800 species and mentions another 1,700 (1446). 

Charles Robert Darwin (GB) performed the first experiment to strongly suggest dispersal of aquatic invasive species by movement of waterfowl (767). This phenomenon is known as epizoochory.

Jules de Guerne (FR) reported dispersal of algae by waterfowl (3820). This information came by way of a report by Zacharias.

Jules de Guerne (FR) reported dispersal of leeches by duck (816).

Florence Nightingale (GB) by training, example, will, and strength of character changed nursing forever; becoming the founder of modern nursing (2213, 2512, 2513). The first edition of her book, Notes on Nursing: What it is, and What it is Not, was published in 1859.

Starting with her service in the Crimean War in 1885 Nightingale probably suffered from not one but four disorders. She likely had an underlying bipolar personality disorder, which both magnified the post-traumatic effects of her Crimean experience and enabled her to carry on in spite of them. She very likely contracted brucellosis in the Crimea, and, almost certainly, it was the post-traumatic-stress-disorder (PTSD) that sent her to bed for thirty years after the war. She recovered from the latter only to develop a form of dementia, possibly Alzheimer's (2186).

Charles Marie Édouard Chassaignac (FR) was not the inventor of surgical drainage, but he was the first to apply India-rubber tubes to drain abscesses (600).

Iwan Michajlowitsch Setschenow; Iwan Michajlowitsch Sechenov; Iwan Michajlowitsch Secenov (RU), working with Karl Friedrich Wilhelm Ludwig (DE), described the mercurial blood-gas pump, which enabled them to separate gases from a given quantity of blood (3163). This opened the way for studying the relationships between gases and the blood.

Samuel Wilks (GB) gives the first clinical description of ulcerative colitis. The patient, a 42-year-old woman, had succumbed to an illness of diarrhea and fever, first mis-diagnosed as “arsenic poisoning.” Autopsy demonstrated a transmural inflammation of the entire colon and terminal ileum, initially labeled ulcerative colitis it was later re-classified as Crohn’s disease (1091, 3746).

Antoni Lesniowski (PL) reported this condition (2033).

Burrill Bernard Crohn (US), Leon Ginzburg (US), and Gordon D. Oppenheimer (US) described Crohn’s disease, a disease of the terminal ileum, affecting mainly young adults, characterized by a subcutate or chronic necrotizing and cicatrizing inflammation (724).

François Leuret (FR) and Louis Pierre Gratiolet (FR) pointed out that the two hemispheres of the brain develop asymmetrically: the frontal gyri are formed faster, i.e., earlier in fetal life, on the left than on the right, whereas in the occipital-sphenoidal, i.e., parietal area, the reverse occurs (2050).

Achille-Louis-Francois Foville (FR) described a syndrome (Foville’s syndrome) caused by the blockage of the perforating branches of the basilar artery in the region of the brainstem known as the pons. This produces ipsilateral horizontal gaze palsy and facial nerve palsy and contralateral hemiparesis, hemisensory loss, and internuclear ophthalmoplegia  (1191). Structures affected by the infarct are the paramedian pontine reticular formation, nuclei of cranial nerves VI and VII, corticospinal tract, medial lemniscus, and the medial longitudinal fasciculus.


Stanislao Cannizzaro (IT), at a meeting of chemists in Karlsruhe, Germany, spoke so convincingly in support of Charles Frédéric Gerhardt’s system of atomic and molecular weights that most chemists in Western Europe quickly accepted it (50, 2540).

Gustav Robert Kirchhoff (DE) and Robert Wilhelm Eberhard Bunsen (DE) introduced the technique of spectroscopy into chemical analyses (1812). 

Pierre Eugène Marcellin Berthelot (FR) prepared invertase (beta-fructofuranosidase) in dry form from yeast cells by alcoholic precipitation. Invertase converts cane sugar into glucose and fructose. Berthelot named it, ferment inversif. This ferment’s (enzyme’s) hydrolysis of sucrose contradicts the notion that fermentation requires an intrinsic vital force present only in living cells (224). Bèchamp (FR) called this enzyme zymase.

Victor Paschutin (DE) and Claude Bernard (FR) independently discovered that the epithelial cells of the mucosa of the small intestine secrete invertase (209, 2648).

Horace T. Brown (BR) and John Heron (BR) discovered invertase in the leaves of higher plants (475).

Alvan Wentworth Chapman (US) while living in virtual isolation from academic support, first in Georgia, then in Florida, produced his Flora of the Southern United States; a remarkable feat (586).

Light trap development started for insect control; chiefly for cotton leaf worm (3161).

Thomas Henry Huxley (GB) debated Bishop Samuel Wilberforce (GB) and Richard Owen (GB) under the auspices of the British Association for the Advancement of Science at Oxford, England on June 30, 1860. Their subject was the zoological position of man, i.e., Darwin’s theory of evolution. The audience numbered over one thousand. Although the debate was somewhat superficial it is one of the great turning points of human thought. The attitude of most educated people respecting our place in nature was permanently affected. Note: The debate was not recorded.

Wilhelm Krause (DE) described specialized cutaneous nerve endings, which were later named Krause end bulbs (1905-1907).

Louis Pasteur (FR) wrote that he is a staunch upholder of the view that yeast are a living organism which, in the course of its life, splits sugar not only into alcohol and carbon dioxide but also into other substances (2660, 2661).

He demonstrated that germs are not uniformly distributed in air by using a number of sterile sealed glass bulbs filled with infusion. He would break the sealed tips then re-seal them with flame a few minutes later. Flasks were opened and then re-sealed at a number of locations including: the cellars of the Paris Observatory, the road to Dole, Mount Poupet (850 meters), Mount Montanvert (1,910 meters), and the Mer de Glace (1400-2140 meters). In general, he found that the air in rural and elevated locations contained fewer germs than air from urban and low altitudes (2657-2659).

Robert Caspary (DE) discovered that light promotes the germination of certain seeds (568).

Adolph Cieslar (DE) found that some colors stimulate germination while others inhibit (619).

Lewis H. Flint (US) and Edward D. McAlister (US), using Arlington Fancy lettuce seeds, revealed that light in the violet-blue-green region is inhibitory to seed germination with 760 nm being the most inhibitory. They found that yellow-orange-red light stimulates seed germination with 670 nm being the most effective. Flint and McAlister suggested that chlorophyll, the green pigment that harnesses light energy during photosynthesis, might be the photoreceptor in seed germination (1168-1171). 

Francois Jules Lemaire (FR), on the basis of the germ theory of putrefaction, suggested that carbolic acid (phenol) be used to treat wounds. His work precedes that of Joseph Lister. Lister later applied this knowledge and organized a system of antiseptic treatment (2025, 2026).

Karl Georg Friedrich Rudolf Leuckart (DE) demonstrated that the worm-like parasite known as Linguatulidae (Pentasoma) found in the body cavity of serpents and other vertebrates are degenerate Arthropoda, probably related to the Arachnida (2041).

Theodor Ludwig Wilhelm Bischoff (DE) and Karl von Voit (DE) developed a test for studying nitrogen intake and output. By matching the nitrogen contained in the urea excreted with that contained in the protein ingested, they could tell the state of the nitrogen balance; that is whether the body was storing nitrogen, losing nitrogen, or keeping the balance even. They found that if animals were fed pure proteins such as gelatin they would waste away and die. This line of investigation led to the discovery of essential amino acids (275).

Adolph Eugen Fick (DE) proposed his method for measuring cardiac output. It is based on the principle that the total uptake of oxygen by an organ is the product of blood flow to the organ and the arteriovenous concentration difference of oxygen across the organ. Cardiac output is measured as the product of oxygen consumption of the lungs per minute and the arteriovenous oxygen difference across the lungs. If there is no intracardiac shunt, then pulmonary blood flow is nearly equivalent to systemic blood flow or cardiac output. Oxygen consumption is measured as the oxygen extracted by the lungs per minute by the polarographic method or the Douglas bag. His calculations are the basis for today's procedures of cardiac catheterization (1087).

Casimir Joseph Davaine (FR) wrote, Traité des Entozoaires et des Maladies Vermineuses de L'Homme et des Animaux Domestiques, a classic book in parasitology (777).

Rudolf Ludwig Karl Virchow (DE) noted the plasma origin of fibrin and named its precursor form fibrinogen (3479, 3481). See, Babington, 1830.

Rudolf Ludwig Carl Virchow (DE) was the first to describe the protozoan Isospora belli. He found it in the intestinal mucosa at autopsy (3480).

Charles Morley Wenyon (GB) officially named this parasite Isospora belli (3717). Isosporiasis is an uncommon diarrheal illness caused by Isospora belli. The genus Isospora is related closely to the genera Cryptosporidium, Cyclospora, and Toxoplasma. The parasite is now known as Cystoisospora belli and the infection as cystoisosporiasis.

H.M. Woodstock (GB) was the first to characterize a case of human infection (isosporiasis/ cystoisosporiasis) with Cystoisospora belli (3797).

Gustav Theodor Fechner (DE) developed Fechner's law (the intensity of a sensation produced by a varying stimulus varies directly as the logarithm of that stimulus) (1066).

Friedrich Wilhelm Ernst Albrecht von Graefe (DE) pointed out that most cases of blindness and impaired vision connected with cerebral disorders are traceable to optic neuritis rather than to paralysis of the optic nerve (3539).

Guillaume Benjamin Amand Duchenne de Boulogne (FR) described a condition he called primary labioglossolaryngeal paralysis. The onset is typically between 50 and 60 years of age and characterized by gradually increasing dysphagia, i.e., difficulty swallowing, progressive speech defect, from minor defect in articulation to the production of incomprehensible sound (laryngeal). Weakness and spasticity of the muscles of the pharynx, larynx, and tongue, spasticity of extremity muscles, hyper-reflexia, and loss of emotional control with episodes of sudden laughing and crying (910). Duchenne’s syndrome is a synonym.

Adolph Wachsmuth (EE) suggested the name progressive bulbar paralysis (3642).

Jean Martin Charcot (FR) and Alexis Joffroy (FR) contributed the description of its characteristic pathology (594). 

Bénédict Augustin Morel (FR) introduced the term démence-precoce (dementia praecox) to refer to a mental and emotional deterioration beginning at the time of puberty (2383). 

Emil Wilhelm Magnus Georg Kraepelin (DE) was the first to clinically distinguish manic-depressive psychoses and dementia praecox. He described dementia praecox as a “tangible affection of the brain, probably damage or destruction of cortical cells…which was the result of chemical disturbances” (1901, 1902).

Paul Eugen Bleuler (CH) later introduced the term schizophrenia as synonymous with dementia praecox (298).“I call dementia praecox schizophrenia because (as I hope to demonstrate) the splitting of the different psychic functions is one of its most important characteristics. For the sake of convenience, I use the word in the singular although it is apparent that the group includes several diseases” (299). See, Willis, 1664

Auguste Ambroise Tardieu (FR) first described battered-child syndrome (3302).

C. Henry Kempe (US), Frederic N. Silverman (US), Brandt F. Steele (US), William Droegemueller (US), Henry K. Silver (US), and John Patrick Caffey (US) defined the battered-child syndrome, resulting in a dramatic increase in public awareness of the impact of overt physical abuse on children (549, 1787). Also called Tardieu's syndrome or Caffey-Kempe syndrome.

John Phillips (GB) diagramed the progressive but fluctuating diversity of life on earth based on the fossil record, publishing the first Phanerozoic diversity curve (Great Britain). His work evidences massive extinctions at the end of the Paleozoic and Mesozoic, and increased diversity in each subsequent age (2745).

David M. Raup (US) showed that global records of the Phanerozoic sedimentary rock record exhibits a pattern that is nearly the reverse of Britain by itself (2873).

Berliner Medicinische Gesellschaft was founded.


The U.S. Civil War brought epidemics of dysentery, typhoid fever, hepatitis, malaria, smallpox, measles, and venereal diseases. More than three times as many soldiers died of infectious disease than died of battle wounds (1863).


"The only satisfactory method of explaining our perception of colors is to suppose that we have in our eyes several different sets of nerves, one set being most affected by one kind of light and another set by a different kind of light." James Clark Maxwell (1492)

Hermann von Meyer (DE) gave the name Archaeopteryx (Archeopteryx) to a fossil discovered in fine sandstone Jurassic strata of a quarry near Solenhofen in Bavaria. It appeared to be intermediate in character between reptiles and birds. The Natural History Section of the British Museum purchased the specimen, which was described by Richard Owen (GB) (2606). In 1876 another fossil Archaeopteryx was discovered. This fossil, which now resides in the Humboldt Museum für Naturkunde in Berlin, is of such rare quality and importance that Dr. Alan Feduccia says it, “may well be the most important natural history specimen in existence, comparable perhaps in scientific and even monetary value to the Rosetta stone” (1067, 3156).

Alexander Mikhailovich Butlerov (RU) introduced the term chemical structure in the following context: “there will be possible only one such rational formula for each substance. If then the general laws will have been derived which govern the dependence of the chemical characteristics of the substances on their structure, such a formula will express all these characteristics … Time and experience will teach us best how the new formulas will have to appear if they are to express chemical structure” (1830).

Ernst Wilhelm Brücke (DE) was the first to use adsorption methods for enzyme purification (496). 

Friedrich Goppelsröder (CH) undoubtedly originated chromatography as an analytical laboratory tool. His work employed paper chromatography to separate individual dyes from complex mixtures (1371, 1372).

Thomas Graham (GB) developed the concept of dialysis as a means of removing solute from a solution. Using parchment as the semipermeable membrane he demonstrated removal of urea from urine (1390, 1391).

Thomas Graham (GB) worked on understanding the colloidal state of matter and thus advanced the understanding of protoplasmic systems (1392).

False hellebore (Veratrum californicum ) was first recommended as a bioicide for control of imported cabbageworm (3161). It contains the alkaloid veratrine and is also a good parasiticide. The inventor is unknown. 

Adolf Friedrich Ludwig Strecker (DE) characterized a nitrogen containing substance in bile and named it choline (3119).

Gabriel Gustav Valentin (DE-CH) was the first to use polarized light in the study of plant and animal tissues (3426).

Maximilian Johann Sigismund Schultze (DE) defined a cell as, “a cell is a little lump of protoplasm, in the interior of which lies a nucleus.” The actual words are: “Eine zelle ist ein kliimpchen protoplasma, in dessen innerem ein kern liegt.” In this paper he declares that the likeness between animal and vegetable protoplasm is not only structural and chemical, but also physiologic (3106).

Louis Pasteur (FR) demonstrated that air really contains germs by creating an aspirator to draw outside air through a glass tube and pass it over a plug of gun cotton acting as a filter. After aspiration was complete the gun cotton was placed in a mixture of alcohol and ether to dissolve the gun cotton. The dust being insoluble collected at the bottom of the tube and was examined under the microscope. It showed, in addition to inorganic matter, a considerable number of small, round, or oval bodies, indistinguishable from the spores of minute plants or the ova of animalcules. The number of the bodies varied according to the temperature, moisture, and movement of the air, and the distance above the soil at which the gun cotton had been placed.

He showed that infusions could be sterilized in an open flask provided that the neck of the latter is drawn out and bent down in such a way that the germs cannot descend into the infusion. This type of experiment, previously used by H. Hoffmann, removed all criticism on the question of air, as such, activating into life an organic infusion. If the bent neck of an open flask that had long remained sterile was cut off the infusion rapidly teemed with living things (1606, 2663, 2667). See, Spallanzani, 1776.

Louis Pasteur (FR) discovered anaerobes when he studied and reported on the butyric acid fermentation. Examining a drop of fluid containing the butyric vibrio under a cover glass on a slide, he was astonished to see on the margin of the drop where it was in contact with air that the vibrios had ceased to move although they were actively motile in the center. The question immediately arose as to whether the air or oxygen was necessary to their movement and vitality. He tested this by passing a stream of oxygen through an active butyric fermenting liquid with the result that the fermentation was inhibited. He discovered other anaerobes and coined the term anaérobies (anaerobes) in 1863 (2662, 2664, 2668).

Louis Pasteur (FR) showed that acidic infusions can be sterilized with temperatures around 100°C., but alkaline infusions require temperatures above 100°C (2663).

Louis Pasteur (FR) formulated a medium for growing bacteria, which became known as Pasteur fluid. It consisted of water 100 parts, pure candy sugar 10 parts, ammonium tartrate 1 part, and 1 part of ash of yeast (2662, 2664).

Louis Pasteur (FR) demonstrated that yeast can grow and ferment in the absence of gaseous oxygen and discovered that per gram of glucose more yeast is formed in the presence of air than in its absence. It was the first demonstration that aerobic metabolism is more efficient than anaerobic metabolism and the first clue to the difference in efficiency of glycolysis and oxidative phosphorylation. Pasteur also observed that in the presence of air, glucose disappeared more slowly than in the absence of air, which pointed to the operation of a control mechanism that was later called the Pasteur effect (2662, 2665, 2673).

Otto Fritz Meyerhof (DE-US) showed that in the presence of oxygen, only one-fifth to one-fourth of the lactic acid produced during anaerobic contraction of the muscle is subsequently oxidized to carbon dioxide and water. Thus, he tied the release of energy during this particular oxidation to the reconversion of the remaining four fifths of the lactic acid back to glycogen. This confirmed Pasteur’s theory. The depression of glycolysis by respiration is sometimes referred to as the Pasteur-Meyerhof effect. This conversion of glycogen to lactic acid then back again to glycogen was the first evidence of the cyclical character of energy transformations in living cells (2324-2336).

John Bennett Lawes (GB), Joseph Henry Gilbert (GB), and Evan Pugh (GB) firmly established that green plants alone are incapable of using atmospheric nitrogen (1999).

Moritz Traube (PL) supported the idea that most respiratory activity occurs in the tissues outside the circulatory system when he wrote … “The released oxygen passes in a dissolved state through the capillary walls and forms with the muscle fiber a loose combination that is able to transfer the oxygen to other substances, dissolved in the muscle fluid, and [the muscle fiber] can then take up new oxygen. … the fact that all organs of the animal body require arterial blood indicates that not only the blood, but all organs of the body respire … What we call respiration is therefore a very complex process. It represents the sum of the consumption of all those quantities of oxygen needed by each organ, either for its nutrition or for its maintenance. Thus, there can be an increase in the respiration of the brain, or liver and spleen, or indeed individual groups of muscle, without an accelerated respiration in other organs of the body … The motive forces, however, which oxygen elicits in the muscles, nerves, spinal cord, and brain are a consequence of the characteristic construction and chemical nature of the apparatus in which the oxidative processes proceed, so that these forces do not appear in the form of heat, but in the form of their specific, as yet inexplicable, vital functions” (3384).

Max Josef Pettenkofer (DE) designed a respiratory machine large enough to accommodate a man. He and Karl Voit (DE) accurately determined the respiratory quotients of protein, carbohydrate, and fat when metabolized in the body. They were able to study man’s overall metabolic rate under various conditions and were the first to establish the basal metabolic rate. This would later help diagnose diseases like abnormal thyroid (2110).

Rudolf Albert von Kölliker (CH) authored the first work of comparative embryology, which includes the relationship of the notochord to the development of the spine skull in the adult. He was the first to interpret the development of the embryo in terms of the cell theory (3582).

Jean Louis René Antoine Édouard Claparéde (CH) discovered giant axons in annelid worms (620).

Thomas Henry Huxley (GB) wrote an essay, which was instrumental in humans being considered in zoological terms and their origin as a result of the evolutionary process (1679). He also revised much of the information concerning fishes from the Devonian Epoch (1680).

Étienne Jules Marey (FR) and Jean Baptiste Auguste Chauveau (FR) elucidated the nature of the apex beat of the heart. They simultaneously recorded the apex beat movement and pressures in the right atrium and right ventricle in an awake horse using elastic balloons attached to catheters as motion and pressure transducers. Access to the right heart chambers was by way of the external jugular vein. Each movement or pressure change generated a pulsation within the air-filled catheters and was, in turn, transmitted to a rotating smoked-drum sphygmograph. Their finding that the apical impulse is caused by early forceful ventricular contraction was the first graphic recording of intracardiac events (601, 2237).

Friedrich Wilhelm Felix von Bärensprung (DE) is credited with being the first to describe the involvement of the Gasserian ganglion of the trigeminal nerve with herpes zoster on the face (3504).

Jeffrey Allen Marston (GB) provided the first modern clinical description of brucellosis, which he termed Mediterranean gastric remittent fever (2249).

David Bruce (AU-GB) was assigned by the British military to find the cause of Malta fever, a debilitating disease long known from the Central Mediterranean and the cause of British soldiers dying on the island of Malta. He and his wife— Mary Elizabeth Steele Bruce (GB) — did so by discovering that a bacterium they named Micrococcus melitensis (later named Brucella melitensis) is the cause of this infection (later called brucellosis). This is an undulant fever like malaria, but unlike malaria it is transmitted by contaminated goat’s milk (490-492).

Bernhard Laurits Frederik Bang (DK) and Valdemar Stribolt (DK) isolated Brucella abortus and determined the etiology of contagious abortion (Bang’s disease) in cattle (121).

M. Louis Hughes (GB) suggested the name undulant fever (1660, 1661).

Themistocles Zammit (MT) discovered that the Brucellae are transmitted to man chiefly through the consumption of raw goat or cow milk (3821-3823). For this achievement he was knighted.

Bruce was an avid collector of marine copepods and is commemorated by Botrynema brucei Browne, 1908; Nicothoe brucei Kabata; Pseudomesochra brucei T. & A. Scott, 1901; and Paramphiascella brucei, T. & A. Scott, 1901.

Maybelle L. Feusier (US) and Karl Friedrich Meyer (CH-US) suggested the generic name Brucella in honor of David Bruce (AU-GB) (1085).

Hubert Luschka (DE) provided the first authentic description of polyposis of the colon (2163).

Prosper Ménière (FR) was the first to attribute the sudden onset of vertigo, tinnitus (ringing or sounds in the ears), hearing loss, nausea and vomiting to an abnormality within the inner ear. This became known as Ménière’s disease or endolymphatic hydrops (glaucoma of the ear) (2304-2306). This syndrome is easily confused with cerebral congestion of the apoplectic type.

Thomas Henry Huxley (GB) coined the term calcarine sulcus in referring to the spur shaped hippocampus minor in the black spider monkey, Ateles paniscus (1681).

Paul Louis Duroziez (FR) described the double intermittent murmur over the femoral arteries as a sign of aortic insufficiency (949).

Erastus Bradley Wolcott (US) performed the first nephrectomy. It was for renal tumor (3787).

Henri Dunant (CH) wrote, Un Souvenir de Solférino, which was inspired by his having witnessed the suffering at the Battle of Solférino in 1859 (934). The impact of his book led directly to the founding of the Red Cross by the Geneva Convention of 1864.


"Whoever, in the pursuit of science, seeks after immediate practical utility may rest assured that he seeks in vain." Hermann Ludwig Ferdinand von Helmholtz (3564). 

William Thomson; Lord Kelvin (GB) computed the age of the Earth at between 25 million years and 400 million years (3342).

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

Friedrich Wilhelm Benecke (DE) introduced the use of the aniline dyes to histology (165). Verify name

Alexander Jakovlevich Danilevsky; Danielewski (RU) was the first to use preparative enzyme separation. He used selective adsorption onto collodion to subdivide a complex mixture of enzymes into purified fractions. His starting material was pancreatin (759).

Ferdinand Gustav Julius Sachs (DE) showed that plants like animals respond to their environments and documented plant tropisms; worked out plant transpiration and proved that chlorophyll in plant cells is confined to certain discrete green plastid bodies within the cell and produced experimental evidence that starch is a product of photosynthesis. He originated the Simple Iodine Test for the presence of starch (3005, 3006, 3011).

Andreas Franz Wilhelm Schimper (DE) later named these green plastids chloroplasts (3063). See, von Mohl, 1837, concerning chloroplasts.

Louis Pasteur (FR) discovered that the acetic acid fermentation is due to the activity of microorganisms in the genus Mycoderma (2666).

George Bentham (GB) and Joseph Dalton Hooker (GB) undertook the ambitious task of compiling an unambiguous descriptive classification of all seed plants. They produced the monumental Genera Plantarum covering 200 "orders" (analogous to what are now known as families) with 7,569 genera, which included more than 97,200 species. The families recognized in this work are, in general, those recognized today (172).

The Congress of the United States created the Department of Agriculture and included within it a Division of Chemistry (671-673).

Henry Walter Bates (GB) observed mimicry of distasteful or poisonous species by harmless, palatable species in the lepidoptera and suggested that the mimics enjoy protection from predation because of their resemblance (135). This phenomenon is called Batesian mimicry in his honor.

Thomas Richard Fraser (GB), in 1862, discovered that when extracts of Calabar bean (Physostigma venenosum) are introduced into the eye they cause the contraction of the pupil (1205). 

Douglas Moray Cooper Lamb Argyll Robertson (GB) discovered its ability to stimulate the ciliary nerves and cause contraction of the sphincter pupillae by instilling an extract of the bean into his own eye (2950).

Douglas Moray Cooper Lamb Argyll Robertson (GB) introduced Calabar bean extract (physostigmine) as an agent to constrict the pupil. From his examinations of 5 tabetic patients he described what is known as Argyll Robertson pupil. “I could not observe any contraction of either pupil under the influence of light, but, on accommodating the eyes for a near object, both pupils contracted.” He also studied miosis (excessive contractions of the pupil) caused by various drugs, and wrote on the tonic pupil (2951).

Thomas Richard Fraser (GB) was able to counteract the effect of Calabar extract by use of atropine (1205).

Adolf Weber (DE) reported the positive therapeutic value of Calabar bean extracts in treating glaucoma (3684). 

Rudolf Albert von Kölliker (DE) and Wilhelm Friedrich Kühne (DE) discovered and described vertebrate muscle spindles (1915, 3583).

Bryan H.C. Matthews (GB) discovered that muscle spindles function as proprioceptive units (2262).

Ake B. Valbo (SE) and Karl-Erik Hagbarth (SE) made recordings from muscle spindle afferents in their own arm nerves to demonstrate the structures' natural function as tension receptors (3424).

John William Sutton Pringle (GB) discovered that the campaniform sensilla on the palps of the cockroach respond to strain and are mechanosensory proprioceptors. This paper was the first to completely describe the function of single campaniform sensilla (2787).

Herman Snellen (NL) invented the eye chart with black block shaped letters to test vision (3208).

Ernst Kohlschütter (DE) performed the first experiments to determine the depth of sleep throughout the night (1861).

Jean Baptiste Edouard Gélineau (FR) coined the term narcolepsy, defining it as an ailment characterized by a compelling need to sleep for short durations at close intervals (1297).

George Thomas White Patrick (US) and J. Allen Gilbert (US) performed the first “controlled” sleep-deprivation study on human subjects (2699).

Marie Mikhailovna de Manacéïne (RU) deprived 10 puppies of sleep for four or five days and found that it proved fatal despite the presence of food and water. The younger the puppy the more quickly it died (818, 819).

Ludwig Mauthner (HU-AT) deduced that normal sleep could be due to “fatigue” of the cells in the gray mater of the midbrain near the aqueduct of Sylvius. This fatigue could cause a functional break in the sensory pathways between the brainstem and the cerebral cortex, effectively deafferenting the cortex (2264).

Walter Rudolf Hess (CH) showed that stimulation of the gray matter surrounding the third ventricle of the brainstem caused animals to go to sleep. The animals could then be roused normally (1575, 1576).

Maurice Raynaud (FR) described local asphyxia and symmetrical gangrene of the extremities, i.e., Raynaud phenomenon (2879).

Alfred Washington Adson (US) undertook innovative neurosurgery for the treatment of glossopharyngeal neuralgia to relieve Raynaud’s Disease. Permanent relief lies in division of the glossopharyngeal nerve proximal to the superior ganglion, through an intracranial approach (22).

Claude Bernard (FR) and Johann Friedrich Horner (CH) independently described the effects of paralysis of the human cervical sympathetic nerves, a condition later called Bernard-Horner syndrome. Quoting Horner, “The pupil of the right eye is considerably more constricted than that of the left, but reacts to light; the globe has sunk inward very slightly…. Both eyes…have normal visual acuity. During the clinical discussion of the case, the right side of her face became red and warm…while the left side remained pale and cool. The right side seemed turgid and rounded, the left more sunken and angular; the one perfectly dry, the other moist. The boundary of the redness and warmth was exactly in the midline” (205, 1634).

Claude Bernard (FR) discovered that if he severed the cervical sympathetic nerve there was an accompanying rise in local skin temperature (205).

Friedrich Albert Zenker (DE) was the first to describe pulmonary fat embolism in man (3829).

Aldred Scott Warthin (US) provided a classic description of fat embolism (3682).

Richard Owen (GB) discovered the parathyroid glands while performing necropsy on a rhinoceros, which had died at the London Zoo (2605). The necropsy took place in 1850. 

Ivor Sandström (SE) described human parathyroid glands (3033).

Austin Flint (US) described a type of heart murmur that is called Flint’s Murmur or Austin Flint Murmur in his honor. It is a presystolic or late diastolic (mitral) heart murmur present in some cases of aortic insufficiency and best heard at the apex of the heart (1163).

William Withey Gull (GB) described the clinical signs of syringomyelia (abnormal liquid filled cavities within the spinal cord) (1442).

Hans Chiari (AT) coined the term syringomyelia (611).


The fourth cholera pandemic of the 19th century appeared in Bengal, India then spread to the Middle East where it killed 30,000 pilgrims to Mecca. From there it spread by way of Suez to Mediterranean ports then on to Africa, Western Europe, North America, and Russia. It arrived in New York on a ship coming from France in October 1865, and spread rapidly. Public health reform kept the death toll lower than in previous epidemics, but there were tens of thousands of deaths nonetheless. Another wave swept through the South and Midwest in 1873, hitting particularly hard in the Mississippi and Ohio valleys. It claimed 90,000 lives in Russia during 1866. In Zanzibar 70,000 people were reported to have died in 1869–70 (351, 548, 1863, 2498).


“I propose with all kinds of misgivings these new words aerobic and anaerobic, to indicate the existence of two classes [of microbe]... those which survive only in the presence of free oxygen gas, and those which can multiply without contact with free oxygen.” Louis Pasteur (2668).

Carl A. Martius (DE-GB), John Dale (GB) and Heinrich Caro (DE-GB-DE) synthesized Manchester brown (Bismarck brown), and Manchester yellow (Martius yellow). The patent for Bismarck brown is English Patent #3307 of 1863.

Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) introduced the use of logwood extract (hematoxylin) to histology (3629).

Franz Böhmer (DE) introduced the use of crystalline hematoxylin (from logwood) to histology and dramatically increased its staining power by using it in the presence of alum as a mordant. He also used hematoxylin in the presence of chromium and in the presence of copper sulfate (320). Hematoxylin is the most widely used natural dye in histotechnology. It will stain tissue components such as myelin, elastic and collagenic fibers, muscle striations, mitochondria and so on, but its most common application is as a nuclear dye in the standard hematoxylin and eosin stain, the primary staining method for tissue section analysis. Hematoxylin is obtained from the logwood tree Hematoxylon campechianum, in the order Leguminosae (Genus Eucaesalpinieae), and so named because of the reddish color of its heartwood (from the Greek hemato, blood, and xylo, wood) and young leaves.

Pierre Alain Bitot (FR) concluded that night blindness and xerophthalmia are manifestations of the same condition (276).

M. Mori (JP) discovered that both night blindness and xerophthalmia could be cured by cod-liver oil (2386). Hippocrates, ca. 400 B.C.E., recommended eating raw liver as a treatment of night blindness (2106).

Elmer Verner McCollum (US), Marguerite Davis (US), Thomas Burr Osborne (US), Lafayette Benedict Mendel (US), Edna L. Ferry (US), and Alfred J. Wakeman (US) showed that rats developed xerophthalmia on diets in which lard supplied the fat; the condition was cured by substitution of butterfat. This was an early indicator of fat-soluble vitamin A (retinol) (2273-2275, 2581, 2582, 2584).

E. Freise (DE), M. Goldschmidt (DE), and A. Frank (DE) were the first to analyze the histology of vitamin A (retinol) dietary depletion. In young rats they found that eyelashes fell out, the sclerotic coat became dry with keratomalacia, the cornea clouded and ulcerated, and their coats became rough (1211).

Carl E. Bloch (DK) was the first to study what was later identified as vitamin A (retinol) deficiency in humans. He carried out nutritional experiments with malnourished children during World War I and realized that both xerophthalmia and night blindness could be reversed by a diet including whole milk or butter (303, 304).

Edward Mellanby (GB), Elmer Verner McCollum (US), Nina Simmonds (US), J. Ernestine Becker (US), and Paul Galpin Shipley (US) demonstrated that rickets results from a deficiency in the human diet. The deficiency is in what was called fat soluble A common in cod-liver oil, butter, and suet (2276, 2292-2296). Later it was found that fat-soluble A is complex, containing among other things vitamin A (retinol) and vitamin D. Vitamin D proved to promote calcium deposition therefore, it was the antirachitic factor (2276). 

Alarik Frithjof Holmgren (SE) reported that the uptake of oxygen by blood in the lungs assists the release of carbon dioxide by blood in the lungs (1618).

Maximilian Johann Sigismund Schultze (DE) established the protoplasm concept and, after noting the essential similarity between the cell contents of protozoa, plants and animals, concluded that "the cell is an accumulation of living substance or protoplasm definitely delimited in space and possessing a cell membrane and nucleus” (3107).

Paul Ehrlich (DE) rediscovered the mast cell, and named it such, in his medical thesis entitled, Contributions to the Theory and Practice of Histological Staining (988).

Carl Joseph Eberth (DE) observed ciliated epithelium within the air-passages and later in liver cysts (966, 967).

Wilhelm Friedrich Kühne (DE) saw a nematode swimming freely within muscle fiber. In its movements, the parasite clearly passed through the striated part of the muscle, which closed again behind the nematode’s tail. He concluded that the fiber was not as solid as most people thought and reasoned that they consisted of a concentrated solution of albumins (1916).

Karl Remigius Fresenius (DE) was among the first to use a solid culture medium (potato) for culture of microorganisms. Ref See, Pier’ Antonio Micheli, 1729. 

Louis Pasteur (FR) observed the bacterial fermentation of ammonium tartrate under oil in the absence of gaseous oxygen. He used the terms aerobic and anaerobic to indicate microorganisms that live with or without free oxygen (2668).

Louis Pasteur (FR) was one of the first to realize the indispensability of decay for the maintenance of life on earth, and to state explicitly that microbes are the driving force in the process. He stated that putrefaction was definitely produced by organized ferments of the genus Vibrio, and he described the appearances in point of time of the different bacteria, aerobic and anaerobic, which bring about the putrefactive changes in organic matter. These observations stimulated many investigators to look into the role of microorganisms in putrefaction, putrid intoxication, wound infections, pyemia, and septicemia (2668).

John William Draper (GB-US) showed that plants grown in solutions of sodium bicarbonate could liberate oxygen in the light (896).

Carl Claus (DE) wrote a monograph on the marine free-living copepods. It represents a major starting point of our knowledge of these organisms (624).

Karl Georg Friedrich Rudolf Leuckart (DE) published a study on the parasites of man in which he worked out the complicated life histories of many tapeworms and flukes. He created the subphylum Sporozoa for the spore-forming parasitic protozoa. They are characterized by alternations of the asexual (schizogony) and sexual (sporogony) generations. He created the subclass Coccidia for those sporozoans requiring only one host (2043, 2045, 2049). Rudolf Ludwig Karl Virchow (DE) recorded the first instance of coccidiosis in the small intestine of man (3480).

Henry Walter Bates (GB) wrote The Naturalist on the River Amazons, perhaps the best natural history written during the nineteenth century (136).

Hermann Ludwig Ferdinand von Helmholtz (DE) proposed the resonance theory of hearing (3560).

Leopold Auerbach (DE) discovered the myenteric plexus. A plexus of sympathetic nerve fibers situated between the longitudinal (outer muscle layer) and circular (inner) muscular coat of the stomach and intestines. It is one of the nerve networks controlling intestinal movement (76).

Rudolph Ludwig Karl Virchow (DE) wrote, Die Krankhaften Geschwülste, a book on tumors in which many tumor types were named and described for the first time (3483).

Alfred Baring Garrod (GB) determined that gout results from the failure to excrete excess uric acid (1267).

John Hilton (GB) recognized how to detect a blockage in the flow of cerebrospinal fluid (1585). 

Hans Heinrich George Queckenstedt (DE) had a special interest in the physics of cerebrospinal fluid pressure, which led to his development of the Queckenstedt Test for spinal subarachnoid block (2823).

Nikolaus Friedreich (DE) performed outstanding work on hereditary spinal ataxia (Friedreich's ataxia). It is characterized by speech impairment, lateral curvature of the spine, and swaying of the body with irregular movements (1228, 1229, 1231, 1232). Note: Freidreich’s ataxia is a genetic mitochondrial disease that results from malfunction of the protein frataxin.

Albert von Bezold (DE) described a nerve ganglion (Bezold’s ganglion), located in the interauricular septum of the heart, that contains accelerator fibers (3519).

Jean-Nicolas Demarquay (FR) found parasitic microfilaria of what would later be called Wuchereria bancrofti (elephantiasis) in the hydrocele (watery fluid around the testicle) fluid from a Cuban patient (842).

Otto Henry Wucherer (BR) found the microfilaria in urine (3806).

Timothy Richards Lewis (GB) was the first to find the microfilaria of Wuchereria bancrofti in human blood; he named it Filaria sanguini (30, 2056).

Joseph Bancroft (GB-AU), in 1876, discovered a microfilarial worm in blood and tissues of a patient with elephantiasis and also described the adult worm in various patients (117-119).

Thomas Spencer Cobbold (GB) named these nematodes Filaria bancrofti in honor of Joseph Bancroft (635).

Patrick Manson (GB) discovered that the Culex pipiens quinquefasciatus mosquito is the intermediate host of Filaria bancrofti (2219).

Patrick Manson (GB) elucidated the life cycle of Filaria bancrofti (Wuchereria bancrofti) in the mosquito and demonstrated that filariasis (elephantiasis) is transmitted to man by the bite of a mosquito (2220). This was the first time that an insect was shown to be a vector of human disease.

Thomas Lane Bancroft (AU) reported the metamorphosis of the young form of Filaria bancrofti in the body of Culex ciliaris (120).

Christian Albert Theodor Billroth (DE) wrote Die Allgemeine Chirurgische Pathologie und Therapie in Fünfzig Vorlesungen: ein Handbuch für Studirende und Ärzte, a landmark in the development of modern surgery, which was translated into ten languages (257).

Thomas Henry Huxley (GB) wrote Evidence as to Man’s Place in Nature, which was the first attempt to apply evolution explicitly to the human race (1682).

Archiv fur Mikroskopische Anatomie was founded.

Berliner Klinische Wochenschrift was founded.

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


Peter Waage (NO) and Cato Maximilian Guldberg (NO) put forward the idea that the direction taken by a chemical reaction is dependent not merely on the mass of the various components of the reaction, but rather the mass per unit volume (concentration), i.e., the Law of Mass Action (3641).

Hugo Josef Schiff; Ugo Josef Schiff (DE) discovered the condensation products of aldehydes and amines, later known as Schiff bases. In 1866, he introduced the Fuchsine Test for aldehydes, which distinguishes aldehydes from ketones (3058, 3059). This test is used to detect polysaccharides, DNA and proteins. It is variously called the aldehyde reaction and the nucleal reaction.

Maximilian Johann Sigismund Schultze (DE) stained the luminous organs of the male of the European glow-worm (Lampyris splendidula) using osmic acid (3108).

George Gabriel Stokes (GB) suggested that venous blood must be oxidized during its time course in the lungs (3269).

George Gabriel Stokes (GB) made the observation that green leaves contain both chlorophyll a and chlorophyll b; the pigments were separated using partition methods (3270).

Louis Pasteur (FR) published papers detailing his studies of the acetic acid fermentation (2669).

Heinrich Anton de Bary (DE) wrote the first important book on the slime molds (myxomycetes) in which he reported the actual formation of multinucleate cells by fusion of single cells (795).

Jean Baptiste Joseph Dieudonné Boussingault (FR) determined the ratio of oxygen evolved to carbon dioxide taken up (the photosynthetic quotient) to be close to 1.0 (366). 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) created and named the taxon Gastrotricha, separating them from the rotifers (2311).

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) discovered alternation of generations in the nematodes (2312).

Édouard Placide Duchassaing de Fonbressin (FR) and Giovanni Michelotti (IT) produced Spongiaires de la Mer Caraibe, the first work containing water colors of sponges made from specimens fresh from the water (815).

Alexander Ecker (DE) and Robert Wiedersheim (DE) produced Die Anatomie des Frosches [The Anatomy of the Frog], one of the most outstanding descriptive works of its time (973, 974).

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) outlined the essential elements of modern zoological classification and coined many words commonly used by biologists today, such as phylum, phylogeny, gastrula, coelom and ecology. In his book of 1866 he designated the third living kingdom, the Protista, the first living creatures. They included the “Protozoa” and “Protophyta” as well as “Protista Neutralia,” those ancestral to neither plant nor animal. Haeckel placed the bacteria in the order Moneres (later Monera) at “the lowest stage of the protist kingdom.” Bacteria were unique, he argued, because unlike other protists, they possessed no nucleus. Haeckel believed that the term ecology was needed to refer to the study of the multifaceted struggle for existence that Darwin had discussed in his 1859 treatise On the Origin of Species (1454-1456).

Organisms named in Haeckel’s honor include: Haeckelia Carus, 1863, [Ctenophora]; Asteropus haeckeli Dendy, 1905, [Porifera]; Leucetta haeckeliana Polejaeff, 1883, [Porifera]; Pilochrota haeckeli Sollas, 1886, [Porifera]; Margelopsis haeckeli Hartlaub, 1897, [Cnidaria: Hydrozoa]; Pantachogon haeckeli Maas, 1893, [Cnidaria: Hydrozoa]; Lucernaria haeckeli Antipa, 1892, [Cnidaria: Scyphozoa]; Protiara haeckeli Hargitt, 1902, [Cnidaria: Hydrozoa]; Pseudorhiza haeckeli Haacke, 1884, [Cnidaria: Scyphozoa]; Colobomatus haeckeli Richiardi, 1877, [Arthropoda]; Actinostephanus haeckeli Kwietniewski C. R., 1897, [Cnidaria].

August Friedrich Leopold Weismann (DE) was the first to fully recognize the function and significance of the imaginal discs (3703). See, Lyonet, 1762

Friedrich Leopold Goltz (DE) showed that paralysis of the abdominal sympathetic plexus causes widespread venodilatation, which in turn induces syncope owing to the accompanying failure in venous return (1360).

Rudolf Peter Heinrich Heidenhain (DE) found that the total energy output (heat and mechanical work) of muscle increases with increasing load (increasing active tension), an unexpected result. It showed that muscle liberates more energy when the resistance to its contraction is greater—that there is a kind of self-regulation of the energy expenditure in the working muscle—and thus that the muscle’s work is very economical (1520).

James Augustus Grant (GB), in his book A Walk Across Africa (1864), describes how his leg became grossly swollen and stiff with later a copious discharge. This was almost certainly the severe edematous form of Buruli ulcer, and is the first known description of the infection (1395).

Albert Cook (GB), a British physician, at Mengo Hospital in Kampala, Uganda identified Buruli ulcer disease (679). Peter MacCallum (AU), J.C. Tolhurst (AU), G. Buckle (AU), and H.A. Sissons (AU) wrote a detailed description of the disease while treating patients from the Bairnsdale district, near Melbourne, Australia. They were the first to identify Mycobacterium ulceans as the pathogen causing it. The disease was so named after Buruli County in Uganda (now called Nakasongola district, because of the many cases that occurred there in the 1960s (2174).

Silas Weir Mitchell (US), William Williams Keen, Jr. (US), and George R. Morehouse (US) wrote, Gunshot Wounds and Other Injuries of Nerves, an important work on nerve and related injuries and causalgia (2360). Mitchell did research and reporting on post-paralytic chorea, and described for the first time causalgia (a neuralgia characterized by intense local sensation as of burning pain) and erythromelalgia (acromelalgia or Weir Mitchell’s disease), and cerebellar function (2358, 2359). William Williams Keen, Jr. was the first brain surgeon in the United States.

James Young Simpson (GB) introduced acupressure; a new method of arresting surgical hemorrhage and of accelerating the healing of wounds (3191).

Andrew Woods Smyth (US) performed, on 15 May 1864, the first recorded operation of successfully tying the arteria innominata for subclavian aneurism. His success was attributed to ligating—where secondary hemorrhage had occurred—the vertebral artery, which prevented regurgitant hemorrhage (3206).

Herbert Spencer (GB) formulated Social Darwinism, the idea that poverty and wealth are inevitable as they represent the biological rules, which govern society. He also coined the phrase the survival of the fittest and the word evolution in its biological sense (3223-3226).

George Perkins Marsh (US) wrote a book that was an important influence on the conservation movement in America (2242).

Edouard Lartet (FR) and Henry Christy (GB), in 1864, discovered an engraved mammoth tusk at La Madeleine, France showing a drawing of a woolly mammoth. This piece gave strong evidence that man coexisted with Pleistocene animals (3013).

Zoological Record was founded.

Archiv für Mikroskopische Anatomie was founded.

Berliner Klinische Wochenschrift was founded.

Journal de l’Anatomie et de la Physiologie Normales et Pathologiques de l’Homme et des Animaux was founded.

ca. 1865

“Destiny has conferred upon us professors the favor of helping the responsive heart of youth to find the right path. In the seemingly insignificant vocation of the Schoolmaster there is enclosed a high, blessed calling. I know no higher.” Karl Friedrich Wilhelm Ludwig (DE) in a letter to Warren P. Lombard (2121).


The Mendel paper "is one of the triumphs of the human mind…it presents facts in a conceptual scheme which gives them general meanings…it is a supreme example of scientific experimentation and profound penetration of data." Kurt Guenter Stern and Eva R. Sherwood (3256).

“When the observed evidence is opposed to a theory prevailing at the moment, one must accept the data and give up the theory, even when it is supported by famous names and widely accepted.” Claude Bernard (206).

“The application of mathematics to natural phenomena is the aim of all science.” Claude Bernard (206).

“Liebig first recognized the importance of chemical transformation in the body. Thanks to the interaction between the organic components, foodstuffs, and oxygen, a series of chemical permutations took place with the formation of metabolic products. Thus, as a result of these activities and motions, there was life. Liebig clearly recognized the relationship between chemical decomposition and its effects, ascribing all animal motion and heat to such chemically induced breakdowns. …Thus Liebig came to the momentous separation between the nitrogenous and non-nitrogenous nutrients and their role in organic functions. Nitrogen-containing products replaced the used bodily matter and allowed motions, while the materials without nitrogen served for the production of animal heat.” Carl Voit (DE) speaking of Johann Justus von Liebig (DE) (2974).

“The theory is confirmed that the pea hybrids form egg and pollen cells which, in their constitution, represent in equal numbers all constant forms which result from the combination of the characters united in fertilization…The constant characters which appear in the several varieties of a group of plants may be obtained in all the associations which are possible according to the [mathematical] laws of combinations, by means of repeated artificial fertilization.” Johann Gregor Mendel (2297).

Alarik Frithiof Holmgren (SE) reported that the resting current between electrodes at the front and the back of the eye swing in a cornea-positive direction at both onset and cessation of illumination of the (frog) eye and thus discovered the retina’s electrical response to light, i.e., today’s electroretinogram. This begins the use of electrophysiological methods for studying visual systems (1619, 1620).

Friedrich August Kekulé (DE) indicated the correct structure of benzene in a paper communicated to the Paris Chemical Society in 1865. In doing so, he presented the idea that carbon atoms can join in rings thus explaining the structure of such chemicals (1786).

Carl Wilhelm Kupffer (DE) described macrophages lining the walls of the hepatic sinusoids (1933, 1934). To honor him these are called Kupffer cells. Note: He initially suggested that this type of cell belonged to a group of perivascular cells of the connective tissues or to the adventitial cells (pericytes). Two decades later (1898), he revised his earlier analysis, stating that the cells form an essential component of the vascular walls and correlate to the specific cells of endothelium, capable of phagocytising foreign materials. Shortly afterwards, pathologist Tadeusz Browicz (PL) correctly identified them as macrophages.

Emil Cramer (DE) isolated the amino acid hydroxylalanine from hydrolyzed silk thinking it was serikos (serine) (718).

Franz Schweigger-Seidel (DE) and Adolf Johann Hubert von La Valette-St. George (DE) proved that a spermatozoon is a cell possessing a nucleus and cytoplasm (3136, 3590).

Claude Bernard (FR) discovered that certain nerves govern dilatation of blood vessels and others their constriction, i.e., vasomotor system. In this way the body is able to control the distribution of heat within itself. He found by performing cardiac catheterism that blood within the right ventricle always proved to be warmer than that in the left. He also showed that it is the erythrocytes of the blood, which transport oxygen from lungs to tissues. He was the first to advance the idea that the body mechanisms act as though they are striving to maintain a constant inner environment despite the outer environment. To do so, the various organs had to be under a tight and integrated central control. He called this concept milieu intérieur and Walter Bradford Cannon was later to name it homeostasis. Bernard also did important work on the physiology of smooth muscle. In 1865, Bernard authored Introduction to the Study of Experimental Medicine, one of the greatest medical books in history (206, 208, 211). “…we must therefore seek the true foundation of animal physics and chemistry in the physical-chemical properties of the inner environment. The life of an organism is simply the result of all its innermost workings. All of the vital mechanisms, however varied they may be, have always but one goal, to maintain the uniformity of the conditions of life in the internal environment. The living organism does not really exist in the milieu extérieur (the atmosphere, if it breathes air; salt or fresh water, if that is its element), but in the liquid milieu intérieur formed by the circulating organic liquid which surrounds and bathes all the tissue elements; this is the lymph or plasma, the liquid part of the blood, which in the higher animals is diffused through the tissues and forms the ensemble of the intracellular liquids and is the basis of all local nutrition and the common factor of all elementary exchanges.

The stability of the milieu intérieur is the primary condition for freedom and independence of existence; the mechanism which allows of this is that which ensures in the milieu intérieur the maintenance of all the conditions necessary to the life of the elements” (211). See, isonomy of Alcmaèon, 520 B.C.E. and homeostasis of Walter Bradford Cannon, 1926.

Karl Friedrich Wilhelm Ludwig (DE) developed perfusion techniques for keeping animal organs alive while they were separated from the general circulation. He did this to study the metabolism of an isolated organ while keeping it alive by artificially circulating defibrinated blood through it (2156). Dr. Sczelkow (UA) was a helper during these studies.

Louis Pasteur (FR) interrupted his fermentation studies to study the diseases of silk worms, which at that time, were dying at a rate sufficient to threaten the French silk industry (2671).

Christian Herman Ludwig Stieda (DE) described sporogony of the coccidia in the rabbit (3261).

Johann Gregor Mendel (Moravian-CZ) initiated the science of genetics when he published his experiments in plant hybridization. Most of his experiments started with true-breeding varieties of garden peas that were then used to generate hybrids. The hybrids themselves and the offspring resulting from selfing these hybrids were analyzed for the frequency of expression of various traits. Mendel established that seed contain two factors or elemente as he called them. These elemente were inherited in such a way as to produce predictable patterns among the offspring. He noted that some of these elemente behaved in a dominant fashion, others in a recessive fashion (140, 2297-2299). See, Knight 1799 and Colladon, 1821.

Madan K. Bhattacharyya (GB), Allison M. Smith (GB), T.H. Noel Ellis (GB), Cliff Hedley (GB), and Cathie Martin (GB) identified the protein difference that distinguishes round (RR or Rr) from wrinkled (rr) peas. The functional R allele encodes a form of starch-branching enzyme, which normally links sugars into longer carbohydrates. Developing seeds (peas) of rr plants lack this enzyme, so they contain many free sugars. This draws water into the cells, which swells the seeds. When the pea matures, the water exits the cells, and the seeds wrinkle. Peas of genotype rr also have less protein and more lipid than Rr or RR peas (242).

Diane R. Lester (AU), John J. Ross (AU), Peter J. Davies (AU), and James B. Reid (AU) identified the product of the Le gene, which determines stem length, and therefore whether a pea plant is short or tall. The functional allele encodes an enzyme necessary for synthesis of gibberellin, a plant hormone that causes stems to elongate between nodes. A change in the gene (a mutation) replaces one amino acid with another in the encoded enzyme product at its active site, impairing its function. With the enzyme disabled, gibberellin is in short supply, and the plant is stunted (2035).

Wilhelm His (CH) presented a new classification of tissues based on histogenesis. He put forth the basic concepts of tissue embryology. Using serial sections and three-dimensional models to illustrate his theories, he showed that the serous spaces in the embryo are mesodermal in origin and that they are lined by the special layer which he was the first to term endothelial (1589).

Claude Bernard (FR) found that herbivores, which normally void turbid alkaline urine, if fasted would void clear acidic urine. He interpreted this to mean that a fasting herbivore was consuming its own flesh and metabolizing like a carnivore (206).

Otto Friedrich Karl Deiters (DE) differentiated dendrites from axons and described the lateral vestibular nucleus (Deiter’s nucleus) of the 8th cranial nerve (835). The names axon and dendrite would be coined at a later date, dendrite by Wilhelm His (CH) (1592); neuron by Heinrich Wilhelm Gottfried von Waldeyer-Hartz (3632), and axon by Rudolf Albert von Kölliker (3585).

Otto Friedrich Karl Deiters (DE) and Max Johann Sigismund Schultze probably provided the first image of an astrocyte from the brain (834).

Vladimir Mikhailovich Bekhterev (RU) distinguished between the anterior and posterior roots of the eighth cranial nerve (155, 156).

Enriei Sertoli (IT) described supporting elongated cells of seminiferous tubules (tubuli seminiferi contorti). They provide nourishment to the sperm cells for the duration of spermatogenesis until the mature spermatozoa are formed. These Sertoli cells form the blood-testis barrier (3160).

Max Josef Pettenkofer (DE) was the first professor of hygiene at any university (2272).

Elizabeth Garrett Anderson (GB) was the first English woman to qualify in medicine. Unable to attend medical school she studied privately and was licensed by the Society of Apothecaries in London in 1865.

Sydney Ringer (GB) studied the use of body temperature as a diagnostic indicator (2931).

Karl Thiersch (DE) demonstrated the epithelial origin of cancer and reported that there is a relationship between skin carcinomas and exposure to sunlight (3314).

Jules Bernard Luys (FR), Johann Bernhard Aloys von Gudden (DE), and Constantin von Monakow (RU-CH) established the identity and independence of the brain’s thalamic nuclei, thus laying the foundation on which rests the specificity of thalamic projections to the cortex (2167, 3546, 3611).

George Harley (GB) described paroxysmal hematuria (1489).

Armand Trousseau (FR) gave the first description of hemochromatosis (3397). 

Friedrich Daniel von Recklinghausen (DE) coined the term hemochromatosis (3615).

William Howship Dickinson (GB) described paroxysmal hemoglobinuria (852).

Friedrich Wilhelm Ernst Albrecht von Graefe (DE) improved the treatment of cataract by the modified linear extraction, which dramatically reduced the loss of the eye (3540-3542).

Significant numbers of cases of yellow fever and Russian cattle plague occur in England.

Zeitschrift für Biologie was founded.


Karl Heinrich Leopold Ritthausen (DE) was the first to isolate glutamic acid, which he named. The source was the acid hydrolysate of wheat gluten (2943). Glutamic acid is also called aminoglutaric acid.

Friedrich August Kekulé (DE) changed the name of glucose to dextrose because it rotates plane polarized light to the right. Ref

Ferdinand Julius Cohn (DE) was the first to stress the importance of microorganisms in transforming organic and inorganic substances on earth, with the result that these may be used over and over again to sustain life of other organisms. He discussed the role of bacteria in the cycling of elements in nature and modified Mayer’s fluid medium for culture of bacteria. Cohn’s fluid did not contain sugar but was rather a salt solution to which various carbon sources could be added. The formula was as follows: potassium phosphate, 0.5 gm.; magnesium sulfate, 0.5 gm.; calcium phosphate, 0.05 gm.; ammonium tartrate, 1 gm.; and distilled water, 100 gm (647).

John Bennet Lawes (GB) and Joseph Henry Gilbert (GB) demonstrated that animals could convert both sugar and protein into fat. They also concluded that during exercise of ordinary and extraordinary muscular force, an animal requires non-nitrogenous rather than nitrogenous food (1998).

Emerich Meissl (DE) and Fritz Strohmer (DE) provided definite proof that carbohydrates can be converted into fat within the animal body (2286).

Adolf Eugen Fick (DE), Johannes Adolf Wislicenus (DE), and Edward Frankland (GB) independently concluded that muscular energy comes principally from the oxidation of non-nitrogenous materials (1090, 1204).

Edward Frankland (GB) was the first to use a combustion calorimeter to study foods for the quantitative energy values, which they yielded on combustion (1204).

Max Josef Pettenkofer (DE), Carl von Voit (DE), and Hermann Lossen (DE) performed experiments, which led them to the conclusion that foodstuffs do not combine directly with oxygen to form carbon dioxide and water. Rather, they undergo a long chain of reactions during which a succession of intermediate products are evanescently formed with carbon dioxide and water being formed along the way (2136, 2731, 3628).

Julius Friedrich Cohnheim (DE) stained peripheral nerve endings with gold salts and thus introduced their use in histology (655).

Elie de Cyon (LT-DE-RU-FR) and Karl Friedrich Wilhelm Ludwig (DE) discovered the nervus depressor when they stimulated the central end of the depressor nerve and found a reflexive fall of blood pressure and bradycardia. They suggested that the afferent depressor nerves serve to brake the cardiac rate and to lower the peripheral resistance when the blood pressure is unduly high (814).

Louis Pasteur (FR) published work, which dealt with diseases of wines due to wild yeasts, and bacteria, which invade the wine and alter its chemical and physical properties. He pointed out that heating wine at 50 to 60°C (pasteurization) solved the spoilage problem (2670).

Leon Coze (DE) and Victor Feltz (DE) were the first to purify bacteria by inoculating a healthy animal with a mixture containing the pathogen desired, removing some of its blood and subsequently using it to inoculate another healthy animal and so on through a series of animals (716). Davaine was to later call this ‘passing’ through the animal (‘en passant si je puis ains dire dans l’économie d’un animal vivant’) (786).

Heinrich Hermann Robert Koch (DE), in 1876, used this "passing" technique to purify anthrax material (1841).

Heinrich Anton de Bary (DE) discovered that the pustules on barberry (Aecidium berberidis) and the rust on wheat (Triticum spp.) are both caused by the same organism. He even recognized that the pycnospores are sperm. He worked out the complex life cycle of Puccina graminis and was the first to recognize the Pyrenomycetes as a coherent group (796).

August Heinrich Rudolf Grisebach (DE) coined the term geobotanik (geobotany) and extended the system of physiognomic plant types (vegetative forms) founded by Friedrich Wilhelm Heinrich Alexander von Humboldt (DE) to comprise fifty-four forms (1419). 

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU) and Karl Georg Friedrich Rudolf Leuckart (1865) found, in diptera, that cellular descendants of germ-cell segregation during the early cleavage stage migrate into the body cavity of the embryo to become the sex cell (2313).   

Aleksandr Onufriyevich Kovalevsky; Alexander Kowalewski; Alexander Kovalevski; Alexander Kowalewsky (RU) extended the germ layer concept of Christian Heinrich Pander (LV) and Karl Ernst von Baer (EE-DE-RU) to include the invertebrates, establishing an important embryologic unity in the animal kingdom. He demonstrated the similarity between Amphioxus and the larval stages of tunicates and established the chordate status of the tunicates (1893-1896).

William Bateson (GB) showed that the acorn-worm, Balanoglossus, possesses a notochord, gill-slits, and a dorsal nerve chord. Based on his knowledge that vertebrates also contain a notochord during embryonic development he proposed that hemichordates are so like chordates that they should be included in the chordate phylum (139). Later the hemichordates were placed in their own phylum (1704).

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) published Generelle Morphologie der Organismen (General Morphology of Organisms), the first detailed genealogical tree relating all known organisms, incorporating the principles of Darwinian evolution. This work contains Haeckel’s first expression of his law of organic development (biogenetic law). This law proposes that ontogeny recapitulates phylogeny. It is here that he formulated the kingdom Protista to represent one of the three primary lines of descent (the others being the Plantae and the Animalia) and hypothesizes that the nucleus of a cell transmits its heredity information (1455). See, Meckel, 1821.

Karl Ernst von Baer (EE-DE-RU) suggested that embryos of higher and lower forms resemble each other more the earlier they are compared in their development, and not that embryos of higher forms resemble the adults of lower organisms; a more conservative and sounder statement of the biogenetic law (3501). 

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) in his book, Riddle of the Universe at the Close of the Nineteenth Century, writes, "I established the opposite view, that this history of the embryo (ontogeny) must be completed by a second, equally valuable, and closely connected branch of thought - the history of race (phylogeny). Both of these branches of evolutionary science are, in my opinion, in the closest causal connection; this arises from the reciprocal action of the laws of heredity and adaptation... ontogenesis is a brief and rapid recapitulation of phylogenesis, determined by the physiological functions of heredity (generation) and adaptation (maintenance),” i.e., an organism, in developing from the ovum, goes through the same changes as did the species in developing from the lower to the higher forms of animal life. This is often referred to as the law of recapitulation and is usually abbreviated as ontogeny recapitulates phylogeny. Although a strict form of recapitulation is not correct, phylogeny and ontogeny are intertwined, and many biologists are beginning to both explore and understand the basis for this connection (1455, 1457, 1462, 1463).

James Marion Sims (US) reported important and pioneering work on the treatment of infertility, including analysis of the conditions essential to conception, and the record of a successful artificial insemination (3194).

Ivan Mikhailovich Sechenov (RU) wrote a major classic, Refleksy Golovnogo Mozga (Reflexes of the Brain). He contended that all actions, conscious and unconscious alike, originate as reflexes, and the mental or psychic reflexes are based on physiologic phenomena and provide evidence of a hierarchic organization of brain function (3145-3147). This work had a profound effect on the thinking of Pavlov.

John Hughlings Jackson (GB) postulated that seizures are caused by "occasional, sudden, excessive, rapid, local discharges of grey matter". He described a seizure pattern, Jacksonian Epilepsy, and formulated concepts, even principles, that explain paroxysmal seizures of all types. He also postulated truly evolutionary levels of the sensori-motor-mechanisms: the lowest being the spinal cord, medulla and pons, the middle, being the rolandic region, and the highest level being the prefrontal lobes. As a neurologist, he published some 300 papers mostly in obscure journals (1720-1722, 1725-1737).

John Zachariah Laurence (GB) and Robert Charles Moon (GB-US) described a rare disorder associated with retinitis pigmentosa, polydactyly, spastic paraplegia, hypogonadism, and mental retardation (1989). This presentation was later named the Laurence-Moon syndrome and inherited as an autosomal recessive.


“When it had been shown by… Pasteur that the septic property of the atmosphere depended…on minute organisms suspended in it…it occurred to me that decomposition in the injured part might be avoided…by applying as a dressing some material capable of destroying the life of the floating particles…. The material, which I have employed, is carbolic…acid…. Since the antiseptic treatment has been brought into full operation…my wards…have completely changed…so that during the last nine months not a single instance of pyemia, hospital gangrene, or erysipelas has occurred.” Joseph Lister (2096).

Henry Clifton Sorby (GB) invented the microspectroscope (3216).

Moritz Traube (PL) developed artificial semipermeable membranes by precipitating ferrocyanide in a thin-layer over porous porcelain (3382). 

Charles Lauth (FR) made the dye methyl violet (1993). Note: Crystal violet is one of the components of methyl violet. 

An impure copper acetoarsenite, [(CH3COO)2Cu.3Cu(AsO2)2], called Paris Green was introduced for control of Colorado potato beetle, Leptinotarsa decemlineata (Say) in the state of Mississippi. This is the first general use of an insecticide. Paris Green was used so successfully as a plant protectant that orchardists next adopted it in their fight against the codling moth. Paris Green became so popular that by 1900 its use became widespread in the US and Europe (147, 3161). 

By 1872, Paris green was recommended for the control of cankerworms and cotton leaf worm. Petroleum was first recommended in U. S. for insect bites and stings (3161).

In 1878, Paris green was discovered to be effective for control of codling moth (3161).

Carl Huber (DE) crystallized salts of an organic acid he named nicotinic acid (niacin; vitamin B3). He also determined its elemental composition (1652).

Friedrich Wilhelm Adolf Baeyer (DE) synthesized acetylcholine (90).

Eduard Schwarz (AT) introduced differentiation to histology by using the double stain technique. He stained with ammonium carminate followed by picric acid (3135).

Louis-Antoine Ranvier (FR) simplified the double stain technique by combining the two stains in one solution (2845). 

Rudolf Albert von Kölliker (CH) described yellowish-pigmented granules inside neurons located beside the nucleus (3584).

H. Rosin (DE) in 1896 suggested that they contain fatty substance and called them lipofuscin (2971).

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

Wilhelm Friedrich Benedikt Hofmeister (DE) established the regularity of the “dissolution” of the nucleus prior to division of the maternal cell, and the appearance of new nuclei in daughter cells (1615).

Federigo Delpino (IT) was a botanist who made early studies on pollination (841). He is commemorated by the genus Delphinium.

Simon Schwendener (CH-DE) proposed that the green cells in lichens are themselves true algae parasitized and imprisoned by fungal hyphae, and that the two separate and unrelated organisms live together by obligate symbiosis (3138-3141). This was proven to be true by Max Ferdinand Friedrich Rees (GB) in 1871, [Jean-Baptiste] Édouard Bornet (FR) in 1872, and Heinrich Anton De Bary (DE) in 1873.

Andrey S. Famintsyn (RU), and Josif O. V. (or W.) Baranetsky (UA) studied a cross-section of a lichen thallus and observed green cells (then called gonidia, now, phycobionts) fall out, and they cultured them separately and concluded that they completely resemble the alga Cystococcus (1055, 1056).

Bruce Fink (US) wrote a paper that was the earliest attempt to assess the influence of environmental factors on lichen colonization, therefore this was the first paper to consider lichen ecology (separate from considering symbiosis between fungus and alga) (1092). 

Thomas Henry Huxley (GB) wrote what is probably the first comprehensive, comparative study of a single avian organ system (skeleton) (1683).

Albert Charles Lewis Gotthilf Günther (DE-GB) discovered that the New Zealand tuatara is not a lizard but a living representative of an otherwise extinct order of reptiles, the Rhynchocephalia (1447).

Paul Bert (FR) observed that the blood of cuttlefish turned from colorless to blue when exposed to air (218).

Léon Frédéricq (BE) was the first to realize the functional relationship between the hemocyanins of invertebrates and the hemoglobins. He coined the words hemocyanin and oxyhemocyanin and proposed that copper is a normal constituent of hemocyanin (1208).

Ludimar Hermann (CH), in 1867, proposed that digestion consists of a series of hydrolytic breakdowns that facilitated resorption. In turn, the products of these chemical separations enabled the body to make new and multiple syntheses, in a fashion ‘like letters of dissolving sentences in a book could be reassembled in order to make new ones’ (1557).

Albert von Bezold (DE) and Ludwig Hirt (DE) injected rabbits with veratrine causing bradycardia, hypotension, and apnea (3520). This represents the discovery of a cardiovascular decompressor reflex involving a marked increase in vagal (parasympathetic) efferent discharge to the heart, elicited by stimulation of chemoreceptors, primarily in the left ventricle. This causes a slowing of the heartbeat (bradycardia) and dilatation of the peripheral blood vessels with resulting lowering of the blood pressure.

Adolf Jarisch, Jr. (DE) rediscovered this effect after which it was named the Bezold-Jarisch reflex (1746).

Corneille Jean Francois Heymans (BE) and Eric Neil (BE) investigated the Bezold-Jarisch reflex and discovered both chemoreceptors and pressoreceptors in the region of the internal carotid artery (1581).

Domingo M. Aviado, Jr. (US) reported that nicotine has the same effect on the Bezold-Jarisch reflex as veratine (78).

Thomas Lauder Brunton (GB) discovered that amyl nitrite is useful in the relief of angina pectoris (502).

Norman Brachfeld (US), John Bozer (US), Richard Gorlin (US), Morris H. Smith (US), and Elin Alexanderson (US) presented evidence that although treatment with nitroglycerin produces coronary vasodilatation; it appears to be secondary to an increase in myocardial oxygen consumption. Hemodynamic observations revealed a general decrease in pressures in both peripheral and pulmonary circuits; caution is urged concerning the occasional severe hypotensive effects of nitroglycerin (387).

Joseph Lister (GB), on 12 August 1865, for the first time used carbolic acid in the treatment of an 11-year-old boy with a compound fracture of his tibia. In 1867, Lister presented to the British Medical Association that the use of carbolic acid had prevented wound infections and in 1869 he first described the use of a carbolic spray to the wound and the atmosphere around an operation. At this time most physicians felt that copious suppuration of wounds was a desirable effect. Lister showed that measures to prevent the development of microbes in wounds and surgical procedures in general prevented suppuration and likewise permitted healing with a minimum of scarring and distress and danger to the life of the patient. From this start came our modern aseptic surgery (2094-2098). In 1883 he was made a baronet and in 1897 became Baron Lister of Lyme Regis. He was the first physician to sit in the House of Lords and succeeded William Thomson (Lord Kelvin) as president of the Royal Society.

Richard Payne Cotton (GB) published on observations of unusually rapid action of the heart (705).

Léon Bouveret (FR) observed patients with paroxysmal supraventricular tachycardias (paroxysmal tachycardia), naming the condition tachycardie essentielle paroxystique (368).

August Hoffmann (DE) described observations of paroxysmal tachycardia over a period of many years (1607).

Louis-Benedict Gallavardin (FR) differentiated the following: Paroxysmal tachycardia (maladie de Bouveret); tachycardie paroxystique a center excitable; extrasystoles a paroxysmes tachycardiques; and terminal tachycardia (1251-1253). 

Louis Xavier Édouard Léopold Ollier (FR) used experimental animals to show that the periosteum and the subperiosteal osteogenetic layer allowed joint excision to be performed underneath the periosteum or underneath the capsule and periosteum, in cases of severe inflammation of the joints, which, in those days, would either be fatal or require amputation to save the patient's life (2564).

Georg Axhausen (DE) showed that the survival and osteogenic property of the periosteum varied between different types of grafts: they were highest in autografts; significantly less so in allografts and null in xenografts (80-83).

Dallas Burton Phemister (US) performed a series of experiments in dogs to further investigate osteogenesis. His findings showed that other than the periosteum, the endosteum, and the contents of the Haversian canals also had the capacity for osteogenesis (2743). Note: Phemister proved that Axhausen’s claim that osteogenesis did not occur from transplanted bone devoid of periosteum and endosteum was incorrect. 

John Eric Erichsen (GB) defined postconcussion syndrome or railway spine (shell-shocked) (1037, 1038).

Wilfred Batten Lewis Trotter (GB) studied post-head injury status remarking, “seriously disabling headache is a common sequel to head injuries of an apparently minor kind, in which evidence of any direct local injury of the brain has been altogether lacking” (3395). Note: The historical notion of functional impairment in the absence of structural change as a sine qua non for concussion no longer rang true.

Dorothy Gronwall (NZ) stated, “Cerebral concussion is a closed head injury that represents a usually transient alteration in normal consciousness and brain processes as a result of traumatic insult to the brain. The alterations may include loss of consciousness, amnesia, impairment of reflex activity, and confusion regarding orientation. Although most symptoms resolve within a few days in the majority of cases, some physical symptoms such as headache, and cognitive symptoms such as memory dysfunction, may persist for an undetermined time” (1421).

Thomas A. Gennarelli (US), Nancy C. Kupina (US), Megan R. Detloff (US), Walter F. Bobrowski (US), Bradley J. Snyder (US), and Edward D. Hall (US) using studies in animals of experimentally induced concussion have uncovered a variety of histological changes—some reversible, some not (1298, 1935).

Ferdinand Julius Cohn (DE) proposed that Phycochromaceae (Cyanophyceae) were early inhabitants of the earth because of their ability to adapt to extreme habitats, their simple way of reproduction, and the fossil records (648).

The Canadian Medical Association was organized.


Smallpox outbreaks hit New York, Philadelphia and other cities, and it was discovered that many children had not been vaccinated. The New York City Board of Health recommended that all residents be vaccinated in 1870, but there was widespread public resistance, since the vaccine itself was not without risk, and people perceived the campaign as creating a panic situation and allowing doctors to profit from it (1863).

ca. 1868

Thomas Jonathan Burrill (US) offered a course in bacteriology at Illinois Industrial University (later to become the University of Illinois). This very likely was the first offering of a bacteriology course in America (1312).


Gustavus Detlef Hinrichs (US) and Julius Lothar Meyer (DE) were the first to conceive the so-called law of octaves, which later was explained fully by Dimitri Ivanovich Mendeléev under the title of the periodic law (1587, 2321).

Climent Arkad´evitch Timiriazeff; Climent Arkad´evitch Timiryazev; Climent Arkad´evitch Timirjazeff (RU) established the red maximum of the absorption spectrum of chlorophyll and showed that this absorbed red light is the most efficient in promoting photosynthesis. He proposed that this absorbed light causes chemical transformations leading to photosynthesis (3355-3358).

Theodor Wilhelm Engelmann (DE), at roughly this same time, also discovered that red light is absorbed by plants and promotes photosynthesis (1022, 1023, 1026, 1029).

Carl Bernhard Wilhelm Scheibler (DE) was the first to isolate arabinose. He obtained it by acid hydrolysis of beet pulp and believed it to be an isomer of glucose (3054, 3055).

Heinrich Kiliani (DE) proved arabinose to be a pentose (1802).

Thomas Henry Huxley (GB) was the first to propose that birds originated from dinosaurs. All dinosaurs he examined had strong ornithic characteristics in the tetraradiate arrangement of the ilium, ischium, pubis, and femur. He combined the reptiles and birds into Sauropsida (1684, 1685, 1687).

John Harold Ostrom (US) proposed that birds descended from theropods (dinosaurs) (2592).

Robert T. Bakker (US) proclaims that birds are descendants of the dinosaurs (102).

Casimir Joseph Davaine (FR) demonstrated that anthrax could result from the inoculation of as little as one-millionth of a drop of anthrax blood into a healthy animal (783).

Michael Sars (NO) and Georg Ossian Sars (NO) collected living stalked crinoids (sea lilies) off the coast of Norway. These organisms were believed to have become extinct during the Mesozoic (3038, 3044).

Edwin Ray Lankester (GB) made clear morphological distinctions between the different orders of invertebrates. He distinguished between the hemocoel (blood containing cavity) in Mollusca and Arthropoda and the coelom (fluid-filled cavity) in worms and vertebrates for the first time, showing that while functionally similar they have different origins. He coined the words homoplasy and blastopore (1974-1978).

Thomas Henry Huxley (GB) incorporated geographical distribution into his taxonomy while considering the gallinaceous birds (grouse, quail, and turkey) (1686).

Johann Bernard Theodor Altum (DE) originated the concept of territory among birds. He concluded that territory reduced competition for food among members of the same species and the function of song was to threaten other males and to invite females (38).

H. Eliot Howard (GB) rediscovered this concept in 1920 (1646).

Franz Ernest Christian Neumann (DE) described the presence of nucleated erythrocytes in the bone marrow of humans and rabbits. On the basis of this observation, he was the first to conclude that during postembryonic life, erythropoiesis and leukopoiesis is taking place in the bone marrow. In the 1868a article he says, " In the so-called red bone marrow of man as well as the rabbit, one can regularly find, in addition to the well-known marrow cell, certain other elements which have not been mentioned until now; namely nucleated red blood cells, in every respect corresponding to embryonic stages of the red blood cells. … It is possible to trace the origin of these elements to the marrow cells. The high content of colorless elements in the blood of the marrow makes it likely that there is a migration of contractile marrow cells into the vessels." He coined the term "myeloid" in 1869, as he was the first to recognize white blood cells were made in the bone marrow (Greek: myelos = (bone) marrow) as opposed to the spleen (2488-2490).

Giulio Cesare Bizzozero (IT) confirmed that nucleated red blood cells in the marrow evolved into nonnucleated red cells and extended these observations to include the formation of white blood cells (278-280).

Franz Ernest Christian Neumann (DE) later says, "The present work intends to demonstrate the physiologic importance of the bone marrow and that it is an important organ for blood formation which has not been recognized. It operates continually in the de novo formation of red blood cells" (2491).

Karl Friedrich Mosler (DE) introduced the technique of bone marrow examination to diagnose leukemia (2390).

William Osler (CA) Osler gave a series of three Cartwright Lectures in New York, reviewing his own work and that of others on blood platelets, coagulation, and thrombosis. The first lecture was titled “The Blood Plaque or Third Corpuscle,” in which he focused on platelet morphology and number and speculated concerning their origin. He also discussed the role of these “plaques” in disease and referred to his own observations. He stated that these plaques were increased in chronic wasting diseases, possibly the initial description of reactive thrombocytosis. He also noted that they might be elevated in some cases of leukemia and Hodgkin's disease. In the third lecture, “The Relation of the Corpuscles to Coagulation and Thrombosis,” Osler reviewed his work and that of Bizzozero and others, indicating that platelets, not leukocytes, are the initial cellular element of thrombosis. He further noted that the red corpuscles in health are constantly degenerating and constantly being reproduced. He commented that there could be no doubt that nucleated red cells originate in the bone marrow, crediting both Neumann and Bizzozero. He speculated on the process used by these cells to convert into the ordinary red disk, as he noted the “transformation of the nucleated red into the ordinary forms … by the gradual disappearance of the nucleus.” He also commented on the controversy about other possible origins of red cells, noting that the “colorless corpuscles (white blood cells) constitute separate elements with important functions quite apart from the regeneration of red cells” (2587).

William Osler (CA) noted that marrow hemorrhages in smallpox. In leukemia, “instead of fatty marrow, the medulla of the long bones may resemble the consistency of matter which forms the core of an abscess.” In pernicious anemia, the marrow resembles that of a child, predominantly red marrow secondary to cellular hyperplasia (2588).

Otto Naegeli (CH) first characterized the myeloblast, which is the malignant cell in acute myeloid leukemia (AML). He divided the leukemias into myeloid and lymphocytic (2459).

Heinrich Irenaeus Quincke (DE) noted that there is a capillary and venous pulse observable in the fingernails, hand, forearm, and foot. It is best seen in one's own fingernails at the juncture between the white, anemic area and the redder region (2828).

Carl Reinhold August Wunderlich (DE) was the first to recognize that fever is not a disease in itself but merely a sign. He was the first to insist on careful records of the fever’s progress and took such records himself. It was Wunderlich who established that 98.6°F [37°C] is the normal temperature of the human body. Wunderlich’s curve is the typical typhoid fever curve. He is considered the founder of modern clinical thermometry (3807, 3808).

Phillip A. Mackowiak (US), Steven S. Wasserman (US), and Myron M. Levine (US) took a critical look at Wunderlich’s long established 98.6°F normal body temperature of humans and concluded that normal orally measured temperature fluctuates between 96.1°F and 100.8°F [35.6°C and 38.2°C] (2187).

Paul Langerhans, Jr. (DE) described the dendritic cells in the skin, which now bear his name. Because of their morphology he believed them to be nerve cells (1966).

John G. Frelinger (US), Leroy E. Hood (US), Sharon Hill (US), Jeffrey A. Frelinger (US), Stephen I. Katz (US), Kunihiko Tamaki (US), and David H. Sachs (US) unequivocally established the hematopoietic nature of Langerhans cells (1212, 1782). Note: Strategically located at one of the body's largest interfaces with the external environment, they form the first line of defense against pathogens that breach the skin. Langerhans cells migrate from the epidermis to the skin draining lymph nodes through the lymphatic vessels, and present processed antigens to T lymphocytes.

Gustave Albert Schwalbe (DE) and Otto Christian Lovén (SE) independently discovered taste buds in rabbits, hares, man, horse, dog, pig, squirrel, and guinea pig (2143, 3123).

Guillaume Benjamin Amand Duchenne (FR) described the Duchenne-Erb palsy caused by upper brachial plexus injury during childbirth (913).

Karl Ewald Konstantin Hering (DE) and Josef Breuer (AT) showed that the mechanism of breathing is automatic and self-regulating, the distention and contraction of the lungs being, in themselves, a normal stimulus of the vagus nerve (415, 1556).

Armand Trousseau (FR) described a type of hand contraction, which became known as Trousseau sign (3398). This type of contraction is common to tetany.

Theodore Hermann Meynert (FR-AT) performed histologic analysis of the cerebral cortex, dividing the cerebrum into anterior, motor quarters and posterior, sensory quarters. He also found that over most of brain the cortex was stratified into five layers: an outer neurological layer containing a few angular nerve cells, a second layer of small pyramidal cells, a third of large pyramidal cells, a fourth of multiform or granular cells, and a fifth layer composed of large, squat pyramids and more deeply lying spindle-shape cells (2337).

Jean-Martin Charcot (FR) described what became known as Charcot’s Joints, a degenerative disease with progressive destruction of the bones and joints within the foot, resulting from neurological disorders (589).

Jean-Martin Charcot (FR) and Paul Marie Louis Pierre Richer (FR) were perhaps the first to describe multiple sclerosis: shaking, diplopia, amblyopia, nystagmus, vertigo, paretic state with rigidity, early onset in young adults, and irregular progression with periods of remission. Young women were more often affected than men (590, 596). Note: multiple sclerosis is an autoimmune disease that attacks the myelin sheath on nerve cells leaving a sclerotic product in its place.

Jean Antoine Villemin (FR) in his book, Studies on Tuberculosis, writes: “There is no other affection which has been the object of as many studies as tuberculosis…. Constant and numerous efforts having been made to throw light on this dangerous affection, one has tried to analyze it, to divide it into distinct species, in the hope that this might permit the capturing of truth by fragments. But these attempts, far from simplifying the question, have only complicated it even more and have thrown the whole history of tuberculosis into hopeless confusion… The inoculation of tuberculous material does not act by virtue of the visible and tangible matter, but because it contains a more subtle principle which escapes our senses… Tuberculosis is inoculable, this is an uncontestable fact. From now on this affection must be classified as a virulent disease, such as morve-farcin [glanders], which is its closest relative, nosologically speaking… We would be wrong to think that the affected organism has made the virus, sense if we transfer from one organism to another a drop of vaccinal serosity, a drop of variolar or syphilitic pus, a fragment of tuberculous matter, etc., one reproduces in the inoculated subject a multitude of lesions which are similar to those found in the subject from which the inoculated material had been taken…. But the organism plays only the role of a medium in which the virus multiplies as a parasite… We must establish a fundamental distinction between the virus and the substance that contains it. The organism under the prodding of the virus makes the latter. The variolar virus is contained in the pus of the pustule but the pus is not the virus” (3466).

Jean Antoine Villemin (FR) was the first to demonstrate that tuberculosis is a communicable disease. He induced the disease by using material from human tuberculous lesions and injecting it into rabbits (3466).

Johann Dogiel (LT) and Karl Friedrich Wilhelm Ludwig (DE) concluded that the first cardiac sound is chiefly due to contraction of the muscular fibers of the ventricles assisted by closure of the auriculoventricular valves (869).

Franciscus Cornelis Donders (NL) proposed a general method to measure thought processes based on a simple logic. He subtracted the time course needed to respond to a light (say, by pressing a key) from the time course needed to respond to a particular color of light. He found that discriminating color required about 50 milliseconds. In this way, Donders isolated and measured a mental process for the first time by subtracting a control state (i.e., responding to a light) from a task state (i.e., discriminating the color of the light) (873, 874).

Jules Emile Péan (FR) and Eugène Koeberlé (Alsation) both claimed to have invented the operative hemostat. Ref

John Stough Bobbs (US) was the first to perform cholecystotomy for gallstones (313, 314).

Louis Lartet (FR), in 1868, was the first to find fossil remains of Homo sapiens sapiens (Cro-Magnon man). These were located in a rock shelter site near the village of Les Eyzies in Southwestern France (458). The remains were dated to ca. 28,000 B.C.E. The name: Cro-Magnon comes from Abri Cro-Magnon, Les Eyzies, France where the remains were found. Though spelled magnon the correct pronunciation is "man yon." Louis Lartet was a geologist and son of solicitor and prehistorian Edouard Lartet (FR).

Discarded bones at their ancient campsites testify that Cro-Magnon often fed on vertebrates such as horses and reindeer (2377).

The journal Archives de Physiologie Normale et Pathologique was founded.

The journal Archiv für die Gesamte Physiologie was founded.

The journal Archiv für Psychiatrie und Nervenkrankheiten was founded.


Dmitrii Ivanovich Mendeleev; Dmitrii Ivanovich Mendelejeff (RU) published his discovery of the periodic table showing the chemical elements and their relationships to one another. Based on this table he predicted that there were elements yet to be discovered and intentionally left gaps in the table to accommodate them (1831, 2300, 2301).

Johannes Adolf Wislicenus (DE) discovered that the two forms of lactic acid, muscle and fermentation, differed only in the rather subtle way in which they behaved with respect to polarized light. Muscle acid is dextrorotatory, whereas the fermentation acid is optically inactive. He decided that there must be some subtle differences in their formulas, one that could not be displayed in the ordinary method then used to write formulas. O. Meister quotes him, “Facts like these will force us to explain the difference of isomeric molecules of equivalent structure by different positions of their atoms in space, and to look for possible ideas about these positions. Possibly an exact determination of the density of the modifications of lactic acid will bring to light a difference in the spatial materialization of molecules [molekülare Raumerfüllung], perhaps such that the optically active meat lactic acid, which the lecturer considers a modification of ethylidene lactic acid…does not contain the atoms arranged together in the smallest possible space” (2290, 3778).

Jakob Ernst Arthur Böttcher (DE) introduced the method of regressive staining—over-staining followed by de-staining, or differentiation, with alcohol (336).

Jules Raulin (FR) identified zinc as an essential trace metal in plants and animals (2872).

Gabriel Émile Bertrand (FR) and Boje Benzon (FR) were the first to determine that zinc is essential to animal nutrition (228, 229).

Giulio Cesare Bizzozero (IT), in 1869, was the first to describe giant cells of the bone marrow (281).

William Henry Howell (US) named Bizzozero’s giant bone marrow cells megakaryocytes (1648). See, Wright 1906 for their role in platelet formation.

Sebastiano Rivolta (IT) and Pietro Delprato (IT), in 1869, observed the inclusion bodies associated with a fowlpox infection (2948).

Amédée Borrel (FR) observed minute bodies in enormous numbers in scrapings from fowlpox lesions and thought them to be the causative agent of the disease (330). These would later be named Bollinger bodies in honor of Otto von Bollinger (DE).

Hermann Hoffmann (DE), in 1869, used fuchsin and carmine to stain bacteria and thus improve viewing. This is one of the earliest examples of staining bacteria (1610).

Theodor Albrecht Edwin Klebs (DE) introduced paraffin imbedding to microtechnology (1820).

Karl Ludwig Wilhelm Otto Schultzen (DE) and Marceli Nencki; Marcellus von Nencki (PL) fed glycine and leucine to a dog and observed an increase in its urea excretion. Since urea contains two nitrogen atoms and these particular amino acids possess only one nitrogen each they concluded that some type of biosynthesis must have been occurring (3113).

Francis Galton (GB) wrote Hereditary Genius: An Inquiry into its Laws and Consequences in which he claimed that intelligence is hereditary. This led the way to eugenics (1255).

Francis Galton (GB) argued that ‘inferiority’ and ‘superiority’ could be objectively measured (1258). 

Paul Thenard (FR), in 1869, proposed injecting carbon disulfide into the soil around grape vines as a means of controlling Phylloxera and then conducted experiments near Bordeaux to demonstrate its effectiveness. This is the first use of a soil fumigant and these experiments inaugurated the era of scientific agriculture (3016).

Hermann Hoffmann (DE), professor of botany in Giessen, was the first person to attempt to stain bacteria. He used aqueous tinctures of both carmine and fuchsin (1609, 1610).

Adolf Eduard Mayer (DE) improved the Pasteur fluid for growing bacteria by using chemically pure solutions of the salts found in ash of yeast (2265).

Hinrich Nitsche (DE) proposed to divide the Bryozoa into two groups, Entoprocta, and Ectoprocta with Entoprocta used as a phylum name (2516, 2517).

Hermann Beigel (DE) described white piedra, i.e., Beigel's disease; Tinea blanca; Trichosporon beigelii, a fungus infection of the hair shafts of the human scalp or beard (153).

Pedro Severiano de Magalhaes (BR) discovered a very similar fungal disease called black piedra (817). It is caused by Piedraia hortae named for Paulo Parreiras Horta (BR).

Paulo Parreiras Horta (BR) classified piedra into 2 types. The first is black piedra, which is caused by Piedraia hortae. The second is white piedra (1643). The etiological agents of white piedra, originally named Pleurococcus beigelii and later Trichosporon beigelii, are now called Trichosporon asahii and 5 other species: Trichosporon ovoides, Trichosporon inkin, Trichosporon mucoides, Trichosporon asteroides, and Trichosporon cutaneum.

Paul Langerhans, Jr. (DE), while studying the structure of the pancreas, noted specialized groups or islands of cells that are well supplied with microscopic blood vessels (1967, 1968). These would later be named the Islets of Langerhans in his honor.

Langerhans was also an avid zoologist with a keen interest in the polychaetes. He is commemorated by Langerhansia, Autolytus langerhansi Gidholm, 1967; Demonax langerhansi P. Knight-Jones, 1983; and Hyalopomatus langerhansi Ehlers, 1887.

Jean-Martin Charcot (FR) and Alexis Joffroy (FR) described amyotrophic lateral sclerosis (ALS). It is also called motor neuron disease (MND), Charcot’s disease or Lou Gehrig’s disease (591, 593, 595). ALS is an age-dependent and fatal paralytic disorder, caused by degeneration of motor neurons in the motor cortex, brain stem, and spinal cord.

Alexis Yakovlievich Kozhevnikov (RU) demonstrated that in amyotrophic lateral sclerosis the nerve degeneration in the form of corps granuleux could be followed up to the motor cortex (1897).

Teepu Siddique (US) identified mutations in the superoxide dismutase gene SOD1 as a cause of familial amyotrophic lateral sclerosis (3171).

Carl Philipp Adolf Konrad Kussmaul (DE) performed gastric intubations, “Often when I observed the patient in the wretched prodromal stage of vomiting, the thought occurred to me that I might relieve her suffering by the employment of the stomach-pump, as the removal of large masses of decomposed acid gastric contents should cause relief from agonizing burning and retching at once” (1938). Although his advocacy of gastric lavage established this method of treatment in medical practice, the instrument had already been used many years previously.

Alexander Muirhead (GB) performed the first successful recording of electrical rhythm in the human heart. He used a Thomson siphon recorder at St. Bartholomew’s Hospital, London. This equipment was originally devised to record signals passing through the transatlantic cable, which had been laid in 1866. Not published.

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

George Miller Beard (US) and Edward H. van Deusen (US) independently made observations on a form of nervous prostration, which they named neurasthenia. It had been called nervous prostration and would later be called chronic fatigue syndrome (146, 3440).

Thomas Henry Huxley (GB) founded Nature magazine, which has become one of the world’s most important journals for scientific papers. 

Joseph Leidy (US) authored The Extinct Mammalian Fauna of Dakota and Nebraska, which included a synopsis of the mammalian remains of North America (2018).

Marcelino de Santuola (ES), in 1869, discovered the Altamira Caves near Santillana del Mar, Spain. These caves contain important Paleolithic art 14,000-16,000 years old (71).

American Journal of Obstetrics was founded.


“The tragedy of science—the slaying of a beautiful hypothesis by an ugly fact.” Thomas Henry Huxley (1688). 

Paul Bert (FR) was the first to clearly view the organism as a gas exchange system (219).

Johann Friedrich Wilhelm Adolf Baeyer (DE) was the first to suggest a scheme [pathway] of chemical reactions to explain the chemical changes brought about by living organisms. He formulated the changes characteristic of the alcoholic and lactic fermentations with the intermediate stages being derived from the hydrated aldehyde formula of glucose by the successive removal and addition of the elements of water. This was an important conceptual breakthrough (91).

Johann Friedrich Wilhelm Adolf Baeyer (DE) and Rudolf Fittig (DE) determined the molecular formula for glucose (91, 1149).

Pyrethrum production started in California about this time. The first experiments conducted with crude carbolic acid emulsion as insecticide took place. Garden engine force pump appeared on U.S. market. Potash solution was recommended for the control of scale insects on shade trees and moist heat first demonstrated as means of insect control (3161).

Johannes Ludwig Emil Robert von Hanstein (DE) was the first to describe the sequence of cell divisions in the development of the plant embryo (3548).

Bartolomeo Camillo Emilio Golgi (IT) demonstrated that the glial interstitial tissue in not amorphous but contains cells rounded or lenticular or stellar and distinct from elements of the nerve tissue (1328, 1353).

Heinrich Wilhelm Gottfried von Waldeyer-Hartz (DE) discovered the germinal epithelium (the ovarian surface epithelium) (3630).

Timothy Richards Lewis (GB) was the first to describe amoebas in the stools of humans although his descriptions do not allow identification (30, 2055).

Gustav Heinrich Theodor Eimer (DE) established the pathogenicity of trophozoites from his work on Cyclospora in the intestine of the mole (1000).

Thomas Clifford Allbutt (GB) designed the medical thermometer, a short thermometer no more than six inches long, which reaches equilibrium in only five minutes. Then, and only then, did it become possible to make temperature measurements as a matter of routine and to follow the course of fever (32).

Theodor Albrecht Edwin Klebs (DE) coined the name glomerulonephritis (1821). He later described the hypercellularity in the patients dying in the acute nephritic phase of glomerulonephritis in 1875.

Theodor Langhans (DE) confirmed that glomerular hypercellularity attends glomerulonephritis (1969).

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

Adolf Eugen Fick (DE), in 1870, was the first to measure cardiac output, using what is now called the Fick principle (inverse Fick equation). Its underlying principle is that the blood flow to an organ can be calculated using an indicator material if certain perimeters are known (1088).

Franz Ernest Christian Neumann (DE) was the first to note changes in the bone marrow in leukemia, and he proposed the term myelogenous leukemia (2492).

Gustav Simon (DE) reported the first successful planned nephrectomy (kidney removal). It was prompted by a urinary tract fistula (3176).

Theodore Gaillard Thomas (US) was the first to perform vaginal ovariotomy (3322). 

Edward Drinker Cope (US) was America's greatest herpetologist. He was perhaps best known for the dinosaur wars with his rival Othniel Charles Marsh of Yale. They were paleontologists and colorful rivals in the collecting of dinosaur skeletons, which had been discovered in abundance in the Garden Park area of Colorado and at Como Bluff, Wyoming, in the late 1870s. These specimens initiated the first great dinosaur rush in North America. Cope published nearly 1,400 papers, including large monographs. The journal Copeia from the American Society of Ichthyology and Herpetology since 1913 is named for him. He is also commemorated by Xenodermichthys copei Gill, 1884.

Beiträge zur Biologie der Pflanzen was founded.

Archiv für Gynäkologie was founded.

Sammlung Klinischer Vorträge was founded.


“False facts are highly injurious to the progress of science, for they often endure long; but false views, if supported by some evidence, do little harm, for everyone takes a salutary pleasure in proving their falseness.” Charles Robert Darwin (768).

“I have recovered by treating [pus] cells…with diluted hydrochloric acid…. a fine powder…. consisting of completely clean nuclei…. I believe that from the analyses [of them] presented…the conclusion can be drawn that we are…dealing…with a chemical entity…. In favor of this is the approximate agreement in the N-context of the soluble nuclein and of the whole nuclei….” Johann Friedrich Miescher, Jr. regarding the isolation of DNA (2341).

“No, a thousand times no; there does not exist a category of science to which one can give the name applied science. There are science and the applications of science, bound together as the fruit to the tree which bears it” (2672).

Dimitri Ivanovich Mendeléev; Dimitri Ivanovich Mendeléeff (RU) predicted that the gaps in his periodic table represented elements as yet undiscovered (2302).

Johann Friedrich Wilhelm Adolf Baeyer (DE) synthesized fluorescein by the condensation of phthalic anhydride with resorcin (92, 93).

Heinrich Hlasiwetz (CZ) and Josef Habermann (CZ) predicted that asparagine and glutamine are constituents of proteins, which are normally hydrolyzed to the corresponding acids (aspartic acid and glutamic acid), in the course of protein breakdown (1597, 1598).

Ernst Felix Immanuel Hoppe-Seyler (DE) discovered that yeast extract contains invertase, an enzyme that catalyzes the conversion of sucrose to glucose and fructose (2322).

Johann Friedrich Miescher, Jr. (CH) in his investigations to uncover the chemical nature of the nucleus used the nuclei of pus cells, the yolk of hen’s eggs, and spermatozoa of the Rhine salmon. He isolated what he called nuclein. Miescher determined that it was rich in phosphorus (phosphoric acid), soluble in alkali solution, and insoluble in dilute acids. He concluded that the unknown substance was not a protein (2340-2344).

Richard Altmann (DE), a biochemist and a student of Johann Friedrich Miescher, developed a method for producing nuclein preparations, which he considered to be free of protein; he named such protein-free nucleins nucleic acids (37).

Carl Weigert (DE) was the first to stain bacteria. While studying smallpox pustules he showed that the nuclear dye carmine would stain cocci (3697).

Ernst Tiegel (DE) used a porous unburned clay filter to separate anthrax from fluids containing it. This was the first successful filtration of bacteria from a liquid medium (3354).

David Douglas Cunningham (GB) described what was probably Endamoeba coli in the stools of humans (734).

Henry Pickering Bowditch (US), using the isolated frog heart preparation, discovered the staircase, Treppe, phenomenon that is a gradual increase in the extent of muscular contraction following rapidly repeated stimulation. Furthermore, from the experiments in this study, three important phenomena were observed: the all-or-none-law, the absolute refractory period, and the origin of cardiac automaticity, which is located in the atrium and the atrioventricular area (379, 1242).

Francis Gotch (GB) determined that the nerve action potential is an all-or none phenomenon (1377).

Frederick Haven Pratt (US) would later demonstrate that skeletal muscles also follow the all-or-none principle of contraction (2786).

Wilhelm Max Wundt (DE) described reaction time course and reflex time course through the spinal cord and ganglia, and muscle sense (3810).

Nathan Zuntz (DE) and Armin Rohrig (DE) found that curarized rabbits lost the power of maintaining body temperature and that the metabolic rate decreased by half. Thus it was deduced that there was a reflex connection between skin and skeletal muscle and that one of the skin reactions to cold was to increase muscle activity to increase metabolism. A further deduction was that maintenance of muscular tonus accounted for a large part of the total maintenance energy requirement. This is the basis of what was later called chemical heat regulation (3834).

Johann Ernst Oswald Schmiedeberg (RU-DE) and Karl Friedrich Wilhelm Ludwig (DE) traced the accelerator fibers of the vagus nerve in the dog (3081).

Karl Friedrich Wilhelm Ludwig (DE), Phillip Owsjannikow (DE) and Carl Dittmar (DE) performed precise, histologically controlled lesioning experiments into the question of the location of the vasomotor center in the medulla oblongata. A small area in the ventrolateral parts of the medulla with its caudal border 3 mm cranial to the obex and an extension of 3-4 mm in cranial direction was described as the vasomotor area which has to be left intact for normal vasomotor tone and reflexes (861, 862, 2610). Although not explicit, it is very likely that Dittmar presented a guiding device for spatial localization of intracranial structures for the positioning of electrodes in the medulla oblongata in rats.

Jean Baptiste André Dumas (FR) was the first scientist to objectively report on dietary conditions, which clearly indicated that a human diet consisting only of protein, carbohydrate, fat, and salts was inadequate (930).

Franz Ernst Christian Neumann (DE) described a benign muscle tumor of the newborn, which he named congenital epulis (CE) (2493).

C. Hilton Fagge (GB) concluded that degeneration, atrophy, or loss of the thyroid gland resulted in cretinism (1050).

Charles Emile Troisier (FR) described diabetes mellitus associated with hypertrophic cirrhosis of the liver and dark brownish skin pigmentation caused by deposition of excess of melanin or iron pigment, or both, in tissues (3393).

Friedrich Daniel von Recklinghausen (DE) named the condition hemochromatosis (3615). Troisier-Hanot-Chauffard syndrome.

Gustav Simon (DE), in 1871, performed a nephrectomy for stone disease. He carried this out on an American woman who had traveled from America to Heidelberg to undergo the procedure (2372).

Jonathan Hutchinson (GB), in 1871, was the first to successfully operate on a case of intussusception, in a two year-old infant. Intussusception is the invagination or indigitation of a portion of the intestine into an adjacent portion (1668).

Karl Friedrich Otto Westphal (DE) first described agoraphobia (fear of open places) (3727).

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

Silas Weir Mitchell (US) provided a detailed account of phantom limb syndrome (2356, 2357).

George D. Pollock (GB) introduced the treating of burn patients with epidermal grafts (2771). 

Theodor Albrecht Edwin Klebs (DE), over a two-month period, autopsied 115 men who died of gun shot wounds. Of this number, 73% showed the occurrence of septicemia and pyemia. He carried out microscopic examinations in fresh and preserved specimens and found bacteria of various forms in nearly every case (1822, 1823).

William Alexander Hammond (US) and Graeme Monroe Hammond (US) was the first to distinguish athetosis or choreo-athetosis from other choreic disorders. They predicted that the responsible lesion would be found in the striatum of the brain (1479).

Hugo Mella (US) offered experimental confirmation of the importance of the striatum in athetosis (2291).

Campbell de Morgan (GB) argued, rationally and logically, that cancer arises locally and then spreads, first to the lymph nodes and then further afield (820-822).

De Morgan presented his thesis in an address to the Pathological Society of London on 3 March 1874. He fully accepted that the local development of a tumor is influenced by host susceptibility factors, that cancers occasionally undergo spontaneous regression, and that, in some cases, spontaneous regression of cancer is associated with infections and, particularly, with the onset of tuberculosis. He noted that cancer is uncommon in, and rarely coexists in, families affected by tuberculosis (823).

Paul Bruns (DE) confirmed De Morgan's observation that regressions and even complete resolutions of cancer were occasionally associated with severe infections, notably erysipelas (501). 

William B. Coley (US), using a virulent strain of Streptococcus pyogenes, successfully induced erysipelas in a patient with advanced sarcoma of the neck and the tumor disappeared completely (660). Coley later found that Bacillus prodigiosus worked just as well (661).

William B. Coley (US) experimented with bacteria-free extracts and eventually found that a mixture of extracts of Streptococcus pyogenes and Serratia marcescens (‘Bacillus prodigiosus’) was as effective as living streptococci (662).

Steven A. Rosenberg (US), Paul Spiess (US), and Rene Lafreniere (CA) issued the first report of successful immunotherapy with autologous cytotoxic lymphocytes specific for the patient's tumor antigens (2968).

Chen Dong (US) and Richard A. Flavell (US) discovered that T helper cells mature along (at least) two distinct pathways, yielding Th1 and Th2 cells (877). These T cell types produce or induce different cytokines and thereby affect a range of quite different immune reactions. Accordingly, it is now possible to analyze immune responses in detail and to design therapeutic strategies to induce protective responses and to down-regulate inappropriate ones.

Mario Clerici (IT), Enrico Clerici (IT), Gene M. Shearer (US), Takashi Nishimura (JP), Minoru Nakui (JP), Marimo Sato (JP), Kenji Iwakabe (JP), Midemitsu Kitamura (JP), Akio Ohta (JP), Toshiaki Koda (JP), Shinichiro Nishimura (JP), Michele Orditura (IT), Ciro Romano (IT), Ferdinando De Vita (IT), Gennaro Galizia (IT), Eva Lieto (IT), Stefania Infusino (IT), Giuseppe De Cataldis (IT), and Giuseppe Catalano (IT) presented evidence that Th1 reactivity mediates protection against tumors and that many common cancers are associated, as either cause or effect, with immune dysregulation leading to a drift towards Th2 reactivity (631, 2514, 2573).

Charles Robert Darwin (GB) published The Descent of Man, which cast doubt on the idea that the universe was created for man. The role of sexual selection in evolution was described for the first time (768).

Spencer Fullerton Baird (US), zoologist and ornithologist, organized expeditions aboard the Albatross, founded the U.S. National Museum (Smithsonian Institution), and the U.S. Commission of Fisheries with its first Laboratory at Woods Hole in 1871. This started the tradition at Woods Hole and in 1888 the Marine Biological Laboratory was established, followed in 1931 by Woods Hole Oceanographic Institute (WHOI) (1259).


“Perhaps few persons who are not physicians can realize the influence which long-continued and unendurable pain may have on body and mind . . . Under such torments the temper changes, the most amiable grow irritable, the bravest soldier becomes a coward, and the strongest man is scarcely less nervous than the most hysterical girl. Nothing can better illustrate the extent to which these statements may be true than the cases of burning pain, or, as I prefer to term it, causalgia, the most terrible of all tortures which a nerve wound may inflict.” Silas Weir Mitchell (US) (2357)

Otto Nasse (DE) measured the ammonia evolved when proteins were boiled with alkali (he gives R. Thiele (?) credit for originating this technique). He worked out a method to determine the “loosely bound nitrogen” of proteins with accuracy. He compared a number of proteins in terms of the ratio of ammonia nitrogen to the total nitrogen (2472-2474).

Charles Lauth (FR) and H. Baubigny (FR), in 1872, made the dye methyl green (668). In biology methyl green is used for staining a great variety of microscopic specimens including normal and infected plant tissues, bacteria, yeasts, etc. It is also used, principally in conjunction with pyronine Y, as a histochemical procedure for differential demonstration of DNA and RNA.

Nathaniel B. Kurnick (US) and Marilee Foster (US) discovered that methyl green combines with highly polymerized DNA at pH 7.5 (1936, 1937).

L. Jullien (FR) was the first to develop a stain for connective tissue. It consisted of saturated aqueous indigo carmine acidified with oxalic acid then added to saturated picric acid (1763).

Gustav Albert Schwalbe (DE) discovered Paneth cells of the duodenum (3124).

Joseph Paneth (AT) described "cellules etroites" (Paneth’s cell) of the mucosa lining the small intestine and the appendix, at the base of tube-like depressions known as Lieberkühn glands (2630). They are functionally similar to neutrophils. When exposed to bacteria or bacterial antigens, Paneth cells secrete a number of antimicrobial molecules (alpha-defensins, also known as cryptones) into the lumen of the crypt.

Theodor Albrecht Edwin Klebs (DE), in 1872, employed as culture medium of sturgeon’s glue—one of the first uses of a solid medium in bacteriology. Ref See Pier’ Antonio Micheli, 1729 and Karl Remigius Fresenius, 1863. 

Henry Charlton Bastian (GB) published his book, entitled The Beginnings of Life, in which he staunchly supported the doctrine of heterogenesis. The effect of his book was beneficial although its conclusions were incorrect. Bastian (GB) forced Louis Pasteur (FR) and others to refine their experiments to meet his objections and thereby ultimately added to their credibility. It was through Bastian’s (GB) experiments with alkalized urine that it came to be known that germs may be much more thermo-resistant than had been supposed. The practice of heating to 115°-120°C. all liquids to be sterilized dates from the repetition of Bastain’s (GB) experiments by Louis Pasteur (FR) and Charles Édouard Chamberland (FR) (131, 2674, 2675).

Ferdinand Julius Cohn (DE) published his classic paper Untersuchungen über Bacterien and launched our modern ideas in bacteriology. Cohn raised the fundamental question whether, like plants or animals, bacteria can be arranged in genera and species. His researches convinced him that they could. This is based on studies of the larger, and especially the spiral, forms of bacteria, which in his judgment and experience showed a marked constancy of form irrespective of external conditions. He clearly pointed out, however, that a purely morphological classification is insufficient, as he recognized that bacteria similar or identical in form might differ from each other in their physiological characteristics, and in their products. In this paper he coined the genus name Bacillus (649).

Ferdinand Julius Cohn (DE) suggested the division of bacteria into four groups (Tribus), each of which contained one or more genera. His classification was as follows:

Tribus I. Sphaerobacteria

Genus 1. Micrococcus

Tribus II. Microbacteria

Genus 2. Bacterium

Tribus III. Desmobacteria

Genus 3. Bacillus

Genus 4. Vibrio

Tribus IV. Spirobacteria

Genus 5. Spirillum

Genus 6. Spirochaete

Among the round or Sphaerobacteria he described chromogenic, zymogenic, and pathogenic species. Among the zymogenic species he placed Micrococcus ureae, which had become known from Pasteur’s (FR) work. His pathogenic Sphaerobacteria included Micrococcus vaccinae, discovered by Cohn (DE) himself in 1872, and cocci in diphtheritis and sepsis. The Microbacteria differed from the Sphaerobacteria in shape and motility and he recognized one genus—Bacterium.

The Desmobacteria or filamentous forms contained two genera, viz., Bacillus and Vibrio. For the straight filaments he reserved the name Bacillus, and for the wavy forms, Vibrio. In the genus Bacillus he gave a detailed description of Bacillus subtilis and recognized and figured the spore, which he correctly interpreted as the persisting form. He placed Devaine’s anthrax bacillus in the Genus Bacillus. Of the genus Vibrio he described Vibrio rugula and Vibrio serpens.

Among the spiral bacteria (Spirobacteria) Cohn placed Spirochaete with flexible screw forms and Spirillum with inflexible screw forms. Spirillum volutans was described in great detail.

Ferdinand Julius Cohn (DE) independently discovered the extremely heat resistant form of the hay bacillus, Bacillus subtilis. He worked out the life cycle of the organism including germination, vegetative phase, and light refractive spores, which he called endospores. It is in Cohn’s work where we see the beginning of bacteriological techniques such as cotton plug closures. He also discussed the relation of bacteria with allied groups of plants and concluded that they constitute a pretty close group of organisms which show no relation to yeasts or molds, but have close affinities with certain blue-green algae, i.e., cyanobacteria (649, 650, 652).

Joseph Lister (GB), in 1872, made clinical use of Penicillium saying, "Should a suitable case present, I shall endeavor to employ Penicillium glaucum and observe if the growth of the organisms be inhibited in the human tissues." Such an opportunity did arise and he reported using Penicillium to great effect on a patient injured in a road accident. Ref

John Tyndall (GB), in 1875, described to the Royal Society in London how a species of Penicillium had made several bacteria burst open and die (3409).

Ernest Duchesne (FR) described in his dissertation the effectiveness of Penicillium glaucum in animals injected with normally fatal doses of pathogenic bacteria. In a subsequent article he emphasized the therapeutic value of Penicillium (916, 917).

André Gratia (BE) and Sara Dath (BE) mentioned that a Penicillium strain exerted a highly bacteriolytic activity against anthrax-causing bacteria (1399).

Georges Papacostas (FR) and Jean Gaté (FR) used the term antibiotic and reported clinical applications of antibiotic substances (2636).

Alexander Fleming (GB) observed that some mold contaminants of his plates of Staphylococcus aureus exerted a specific antagonism toward the bacteria. He postulated that the mold Penicillium produced a potent antibacterial agent. He named the agent penicillin and noted that it killed gram-positive bacteria more effectively than gram-negative bacteria (1152).

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) established the taxonomic position of the Chordata, and proposed the Gastraea as the hypothetical ancestor to all metazoa saying, “From these identical gastrulae of representatives of the most different animal phyla, from poriferans to vertebrates, I conclude, according to the biogenetic law, that the animal phyla have a common descent from one unique unknown ancestor, which in essence was identical to the gastrula: Gastraea” (1456, 1459).

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) proposed the gastrea hypothesis of Metazoan ancestry. He speculated that the ancestor of all the Metazoa consisted of two layers (ectoderm and endoderm) similar to the gastrula stage in embryonic development, and endoderm arose as an invagination of the blastula. Thus the diploblastic stage of ontogeny is considered a repetition of this ancestral form (1459). 

Casimir Joseph Davaine (FR) found that the blood of animals suffering or dead from putrid injections is capable of inducing a similar condition when introduced into a normal animal, and it can produce a lethal effect from incredibly minute doses. He found that the virulence of such blood disappears on keeping. He also found that the minimal lethal dose varies not with the size but with the species of the animal injected. Inside a particular species, young were more susceptible than older animals (786).

Joseph Schroeter (DE) used solid media to isolate pigmented bacteria in axenic culture. His solid medias included potato (Solanum tuberosum), potato paste, flour paste, egg albumin, bread, and meat. He obtained bacteria, which were red, blue, green, orange, yellow, brown, and violet (3099).

Carl Joseph Eberth (DE) took anthrax blood and diluted it with water. After allowing the mixture to settle he demonstrated that the supernatant fraction was non-infectious, whereas, the sediment was capable of producing anthrax in a healthy animal (968).

Julius Oscar Brefeld (DE) laid down the principles that must be followed for obtaining pure fungal cultures. These principles apply equally to bacteria although with bacteria their implementation is difficult. They were: (1) that the inoculum must be as small as is practically possible, (2) the culture medium should be clear and transparent and yield optimum growth for the organism being cultivated, and (3) the culture should throughout the growth period be protected from external contamination. He was also the first to suggest the addition of gelatin or carragheen to liquid media to produce gelled media (408).

August Heinrich Rudolf Grisebach (DE) wrote one of the first comprehensive reviews of knowledge of the Earth’s vegetation (1420).

John Thomas Gulick (US) and Alfred Russel Wallace (GB) discovered that variation in the shells of several species of self-fertilizing land snails (family Achatinellinae) occurred randomly with chance leading to the preservation of certain patterns, which became fixed, into races by reproductive isolation (1439-1441).

Sewall Wright (US) would later popularize Gulick’s discovery as random genetic drift (the Sewall-Wright effect) (3801-3805).

Elliott Coues (US) authored Key to North American Birds in which he adopted the viewpoint that geographically complementary forms, which were clearly closely related, were subspecies of one species, regardless of the degree of difference between the extremes. Coues used the abbreviation var. to indicate geographical races (708).

H.M.S. Challenger , 7 December 1872 sailed from Sheerness, England on what can be characterized as the first serious attempt to study life beneath the surface of the sea. It returned to Spithead, England on 24 May 1876. Aboard were six civilian staff/scientists under the direction of Charles Wyville Thomson (GB). They included the 'naturalists' John Murray (GB), Henry N. Mosely (GB), Rudolph von Willemoes-Suhm (DE), the 'chemist/physicist' John Buchanan (GB) and the official artist J.J. Wild (GB). Challenger traversed 68,890 nautical miles, in the course of which she sampled in the North and South Atlantic and Pacific Oceans and traveled north of the limits of drift ice in the North Atlantic polar seas and south of the Antarctic Circle. Wyville Thomson reported the Challenger to have made 362 sample/observation stations "at intervals as nearly uniform as possible". 

Back at home, the scientific findings of the cruise were examined by over 100 scientists, primarily under the guidance of John Murray, who should receive the highest praise for the work's eventual publication in The Report of the Scientific Results of the Exploring Voyage of H.M.S. Challenger during the years 1873-76 occupying 50 volumes, each measuring about 13 by 10 inches and as thick as a family Bible. They appeared between 1885 and 1895. At its completion, The Report discussed with full detail of text and illustrations the currents, temperatures, depths and constituents of the oceans, the topography of the sea bottom, the geology and biology of its covering and the animal life of the abyssal waters. The Challenger cruise had laid the cornerstone of scientific oceanography and begun its introduction to the wider scientific and lay community. John Murray correctly described the findings of the cruise in 1895 as "the greatest advance in the knowledge of our planet since the celebrated discoveries of the fifteenth and sixteenth centuries" (2554).

Morrill Wyman (US) stressed family predispositions to hay cold due to pollens (3814).

Daae-Finsen Krankheit (NO) first described epidemic pleurodynia. He reported it as acute muscular rheumatism. It is also known by other names including: epidemic myalgia, Bornholm disease, epidemic muscular rheumatism, acute benign dry pleurisy, epidemic pleuritic pain, Bamble disease, and devil’s grip. The disease is acute, febrile, specific, infectious, and of limited duration. It has an affinity for children and young adults (1903). It is usually caused by one of the group B coxsackieviruses and is less often caused by a group A coxsackievirus or an echovirus

Hjalmar Heiberg (NO) quoted Øjvind Winge (DK) as having detected microorganisms in vegetations of endocarditis (1518). 

Rudolf Ludwig Karl Virchow (DE) detected microbes in endocarditis vegetations (3484).

Anton Weichselbaum (AT), in 1883, cultivated both streptococci and staphylococci from endocardial vegetations (3695).

Vladimir Wyssokowitch (DE), Johannas Orth (DE) and Moritz Wilhelm Hugo Ribbert (DE) demonstrated that various bacteria introduced into the bloodstream could cause endocarditis on heart valves previously damaged (2578, 2920, 2921, 3815).

Hugo Schottmüller (DE) presented proof of the bacterial nature of malignant endocarditis (acute and subacute endocarditis) (3095).

Frederick John Poynton (GB), Alexander Paine (GB), Carey Franklin Coombs (GB) and Alvin Franklin Coburn (US) found that reaction to hemolytic streptococci is responsible for much if not all of rheumatic heart disease (636, 681, 2785).

Charles S.F. Easmon (GB) and Janusz Jeljaszewicz (PL) state that perhaps the archetype of a cryptic and persistent bacterial infection, in which the pathogens adhere to a tissue in large microcolonies, is bacterial endocarditis. These adherent pathogens routinely produce macroscopic vegetations on the endocardium and the cells within these huge dextran-enclosed microcolonies are inherently resistant to conventional therapy even though they are fully and directly exposed to circulating blood levels of these agents (963).

When a plastic or metal prosthesis is introduced into an animal body its biologically inert surface offers a unique substratum for colonization by bacteria, whose preferential mode of growth is the formation of adherent biofilms. Once established, adherent microcolonies of bacteria are much less susceptible than their planktonic counterparts to surfactants, antiseptics, antibiotics, opsonizing antibodies, and phagocytosis (962).

The normal biofilm of microorganisms on human tissues often excludes would be pathogens from gaining a foothold (961).

Adherent microorganisms in a thick glycocalyx are significantly more resistant to chemical biocides than are their otherwise equivalent planktonic counterparts (960).

Adhesion of bacteria to phagocytes is essential to the successful function of the phagocytic defense system (959).

Ferdinand Karl Franz von Hebra (AT) and Moriz Kohn Kaposi (HU) wrote Lehrbuch der Hautkrankheiten (Textbook on Skin Diseases) and On Diseases of the Skin, Including the Exanthemata, important books on human skin diseases. They were the first to give a clinical description of scleroderma and the then rare Kaposi’s sarcoma which would years later receive much attention as one of the signs of acquired immune deficiency syndrome (AIDS) (406, 1768, 3552, 3553).

Ferdinand Karl Franz von Hebra (AT) was the first to describe impetigo herpetiformis (3551).

Moriz Kohn Kaposi (HU) completed and refined the description of impetigo herpetiformis (1769).

Ludwig Traube (DE) coined the name of Pulsus alternans. “ …it has to do with a succession of high and low pulses, in such a manner that a low pulse follows regularly a high pulse and this low pulse is separated from the following high pulse by a shorter pause than that between it and the preceding high pulse” (3380).

Emil Jacob Noeggerath (US) described the effects of latent gonorrhea in women (2522, 2523).

Christian Albert Theodor Billroth (DE-AT) performed the first resection of the esophagus in laboratory animals (259).

Vincenz Czerny (CZ-DE) performed the first successful resection of the thoracic region of the esophagus in humans (esophagectomy) (749, 2970).

Franz Torek (DE-US) performed the first successful transthoracic resection of the esophagus for carcinoma (3367).

Marc B. Orringer (US) and Herbert Sloan (US) presented their surgical technique of esophagectomy without thoracotomy (2577). This was a revival of an incidental technique carried out by George Grey-Turner (GB) in 1933 (1413).

John Harry Garlock (US) showed that it is possible to excise the esophagus and to bring the stomach up through the chest and join it to the pharynx. Lengths of colon are also used as grafts to bridge the gap (1262-1264).

Robert Battey (US) was the first to perform oöphorectomy, the excision of normal ovary or ovaries for such non-ovarian conditions as painful menstruation and neuroses (142).

Robert Lawson Tait (GB), in 1879, reported the removal of normal ovaries in 1871, 16 days prior to Battey’s operation (3297).

William Williams Keen, Jr. (US) reported three cases of removal of the ovaries and fallopian tubes (1783).

Frank Eastman Bundy (US) and William Ingalls (US), on 8 October 1872, carried out the first nephrolithotomy, a surgical procedure in which the kidney is cut to remove a stone (520).

Louis Xavier Édouard Léopold Ollier (FR) introduced split-skin grafting (2565).

Karl Thiersch (DE) improved Ollier's split-skin grafting technique in 1874 (3315).

Johann Otto Leonhard Heubner (DE) described the vascularization of the anterior part of the caudate nucleus within the brain (1577). 

Henri Duret (FR) using injections of colored gelatin, was the first to describe the distribution of supply arteries in the brainstem and then in the cortex. His descriptions correlated irrigated territories, infarcted zones and secondary neurological deficits (948).

Douglas Alexander Spalding (GB), James Mark Baldwin (US), Conwy Lloyd Morgan (US) and Henry Fairfield Osborn (US), proposed a mechanism by which learned traits could make their way into the genome: organisms that are capable of learning an advantageous behavior will survive better; the capacity to learn will thereby spread through the population; the learned behavior will pave the way for an even more advantageous heritable version of the behavior to arise; and natural selection will thus push the congenital trait to fixation (107, 108, 2385, 2579, 2580, 3220, 3221).

Douglas Alexander Spalding (GB) discovered stamping-in (imprinting) (3221).

Konrad Zacharias Lorenz (AT), one of the founders of ethology, carried out studies which led to a deeper understanding of behavior patterns in animals, notably the releaser concept and imprinting in young birds (2130-2133). In the 1937 paper Lorenz defined releaser as, “The means evolved for the sending out of key-stimuli may lie in a bodily character, as a special color design or structure, or in an instinctive action, such as posturing, dance movements and the like. In most cases they are to be found in both, that is, in some instinctive acts which display color schemes or structure that were evolved exclusively for this end. All such devices for the issuing of releasing stimuli, I have termed releasers (Auslöser), regardless of whether the releasing factor be optical or acoustical, whether an act, a structure or a color.” The 1935 and 1937 papers are the classics on imprinting.

Oscar Heinroth (DE) and his wife Magdalena also discovered imprinting (prägung): an especially rapid and relatively irreversible learning process that occurs early in the individual's life where auditory and visual stimuli from an animal's parents are needed to induce the young to follow their parents. They conducted 'deprivation experiments', raising a variety of central European bird species in isolation, deprived of all influence of their natural parents. They did so in order to discover which instinctive acts are innate in birds and which are supplemented in their development through experience or through learning. They along with their correspondent Konrad Zacharias Lorenz (AT) founded comparative ethology (study of the immediate causes of behavior in animals, including external stimulation and physiological mechanisms and states) (1525, 1526).

Charles O. Whitman (US), like Oskar Heinroth (DE) and Konrad Zacharias Lorenz (AT), was a founding father of comparative ethology. His posthumous work The Behavior of Pigeons is a particular example (3734).

Felix Anton Dohrn (DE) was a major figure in early phylogenetics. He studied the phylogenetics of arthropods using embryological and comparative anatomical data and advocated the annelid theory of vertebrate origins. At Naples, Italy he established Statzione Zoologica de Napoli, which was among the first marine biology laboratories to routinely accept visiting scientists from other countries.


Christian Karl Hoffmann (NL) compiled the first general compendium of data on the morphology of amphibians and reptiles in Heinrich Georg Bronn's (DE) publication Klassen und Ordnungen des Thierreichs (471, 1608).


Johannes Diderik van der Waals (NL) described the weakest of the electrostatic attractions between atoms of opposite charge (3439). Today these forces of attraction are named van der Waals’ forces in his honor.

Ernst Karl Abbé (DE) published his formula for calculating the resolving power of a light microscope. This immediately led to an understanding that there is a finite limit to resolving power (4). 

Casimir Joseph Davaine (FR) discovered the antimicrobial properties of iodine (833).

Kerosene, applied by paintbrush to tree limbs, was advocated for the control of woolly apple aphid. By 1875 a kerosene emulsion spray had been developed (3161).

Heinrich Hermann Hlasiwetz (HU-AT) and Josef Habermann (CZ) made the first serious attempt to account for the composition of a protein (casein) in terms of the products of the complete hydrolysis. They hydrolyzed protein using hydrochloric acid in the presence of stannous chloride to eliminate humin formation. This was a first. It also describes for the first time the isolation of glutamic acid hydrochloride directly from a concentrated hydrolysate (1599, 1600). 

Bartolomeo Camillo Emilio Golgi (IT) and Nicolò Manfredi (IT) used potassium dichromate with silver nitrate to form silver chromate, which penetrates and stains nonmyelinated nerve fibers revealing nerve cell details never before seen. This staining technique was called the "black reaction" or "response cromoargentica." With this new stain they observed two types of cerebral cortical cells—those with long processes that travel to the white matter and subcortex (type 1) and others with processes confined within the cortex (type 2). They determined that axons (a term coined by R.A. von Kölliker in 1896) are invested with co-lateral branches (1327, 1336, 1345, 1356, 1358).

Alfred Wilhelm Volkmann (DE) described the canals in bone carrying blood vessels from the periosteum (Volkmann's canals) (3491).

David Luginbühl (DE), Carl Weigert (DE) and Eduard Krauss (DE) were the first to report multinucleate cells in lesions that can with certainty be identified as of viral origin (1908, 2157, 3698).

Theodor Wilhelm Engelmann (DE) discovered that I (isotropic) bands shorten during contraction of striated muscle (1015, 1016).

John Hughlings Jackson (GB) was the first to state clearly that the brain, the organ of mind, possesses motor functions (1723, 1724).

Sebastiano Rivolta (IT) determined that epizootic lymphangitis (African glanders) is caused by the yeast Cryptococcus farciminosus (2947). In 1934 it would be renamed Histoplasma farciminosum.

Otto Hugo Franz Obermeier (DE) while examining the blood of patients with European relapsing fever discovered Borrelia recurrentis, the bacterial cause of relapsing fever (2548). This organism has been called Obermeier’s spirillum.

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

Henry Foley (FR) and Edmond Sergent (FR) suspected and later demonstrated the exclusive role played by the louse (Pediculus corporis, P. vestimenti, or P. humanus) in the transmission of relapsing fever during an important epidemic occurring at the Algerian-Moroccan border between 1907-1910 (1180).

Joseph Dutton (GB) (famous because of B. duttoni) discovered an alternative vector: the soft tick Ornithodoros moubata.

Giulio Cesare Bizzozero (IT) was also the first—10 years before Metchnikoff—to propose that the process of phagocytosis could be protective against infection:

“…this fact [ingestion of infective particles by reticular cells] is, perhaps, the cause of the stoppage of some infections to the lymphatic glands which are connected to the part covered by the infection through the lymphatic vessels” (284, 2271). See, Metchnikoff, 1883 also Bizzozero in 1847

Theodor Albrecht Edwin Klebs (DE) was the first to attempt the isolation of pathogenic bacteria in axenic culture. His technique was to inoculate liquid medium with a small inoculum. As soon as growth was obvious a small quantity was transferred to fresh medium. The process was repeated a number of times. It was hoped that any contamination would in time be eliminated, and that the organism present in the greatest quantity in the original inoculum would ultimately dominate the situation and show itself as an axenic cultivation. We do not know much about his successes (1824).

Theodor Albrecht Edwin Klebs (DE) produced tuberculosis in cattle by feeding them infected milk (1825).

Louis-Antoine Ranvier (FR) found that dark (red) muscles contract slowly, develop tetanus (lock in full contraction) at lower rates of stimulation, have relatively more sarcoplasm, have more distinct longitudinal striations, and are more resistant to fatigue (2846).

Physicians in the United States are documented, during these years 1873-1880, to have transfused milk (from cows and goats), as a blood substitute, to humans (2547).

Charles Harrison Blackley (GB) reported that the symptoms described in 1819 by John Bostock under the term of catarrhus aestivus (hay fever or hay asthma) are due to the grains of pollens. To investigate his own hay fever, he performed the first skin test, doing so by applying pollen through a small break in his skin. His experiment introduced the concept that pollen sensitivity caused hay fever. Today's skin testing methods vary in the way in which the allergen extract is introduced into the skin; however, the principle remains the same. As Blakely found, a positive reaction to a specific allergen becomes evident in about twenty minutes by the appearance of a hive like response at the tested skin site (295). 

Pierre Cyprien Oré (FR) was the first to use an intravenous anesthetic in humans. He sedated a 52-year-old man with an acute phase of tetanus using intravenous chloral hydrate injections (2574-2576).

James Paget (GB) described eczema of the nipple with subsequent mammary carcinoma, i.e., Paget’s disease of the nipple (2614).

Christian Albert Theodor Billroth (DE-AT) and Carl Gussenbauer (DE), in 1873, performed the first total laryngectomy (262, 1450, 2970).

Nikolaus Friedreich (DE) wrote a monograph on progressive muscular atrophy (1230).

Jean Joseph Emile Letievant (FR) was the first to describe cranial and peripheral neurectomy to alleviate pain (2036).

Robert Waldo Abbe (US) performed the first spinal dorsal rhizotomy, i.e., division of the roots of the spinal nerves for pain or paralysis. He describes surgery on a patient suffering from intractable brachial neuralgia. He tried nerve-stretching, amputation, and finally, division of posterior roots of the sixth, seventh, and eighth cervical. The patient improved (5).

William H. Bennett (US) completely removed acute spasmodic pain in the left lower extremity by subdural division of the posterior roots of certain spinal nerves (170).

Victor Alexander Haden Horsley (GB), James Taylor (GB), and Walter S. Colman (GB) described an operation for the treatment of trigeminal neuralgia in which the trigeminal ganglion was removed through a temporal approach (1642). This type of operation is typically performed to give patients relief from very painful facial neuralgia.

Frank Hartley (US) performed an intracranial neurectomy of the second and third divisions of the fifth nerve (1502).

Fedor Krause (DE) performed an intracranial neurectomy in the fifth nerve (1904).

Henry Head (GB), Alfred Walter Campbell (GB), and Theodore Thompson (GB) showed herpes zoster to be a hemorrhagic inflammation of the posterior nerve roots and the homologous spinal ganglia. They made a map of human dermatomes. Patients with herpes zoster provided valuable information to the development of this map (1512, 1513). 

Harvey Williams Cushing (US) reported a method of total extirpation of the Gasserian ganglion for trigeminal neuralgia, by a route through the temporal fossa and beneath the middle meningeal artery (737).

William Gibson Spiller (US) and Charles Harrison Frazier (US), using a modification of Horsley’s approach, divided a sensory root of the fifth cranial nerve, accomplished through a subtemporal approach, to relieve tic douloureux (3234).

William Gibson Spiller (US) believed that intractable lower-body pain could be cured by section of the anterolateral column of the spinal cord. He provided understanding of the location of the pain fibers and Edward Martin (US) was the first to successfully perform this operation (3235).

Charles Harrison Frazier (US) perfected the operation for the radical cure of trigeminal neuralgia (1206).

Otfrid Foerster (DE) made a thorough study of the human dermatomes, including overlap in nerve distributions. This overlapping is correct and conflicts with some of Henry Head’s conclusions. Foerster suggested the concept of gate control. This theory asserts that large nerve fibers can inhibit small nerve fibers during a painful experience. He also introduced topographical localization of function, suggesting that pain fibers are in different locations from temperature and touch fibers (1176).

Egas Moniz (FR) reported successful control of intractable pain after frontal lobotomy (2373).

David Ferrier (GB) and William Aldren Turner (GB) began reporting their neurological studies, which according to Charles Scott Sherrington (GB) in 1928 “… established the localization of the ‘motor’ cortex very much as we now know it. He located it as a region accompanying the Rolandic fissure across the lateral aspect of the hemisphere and extending thence over and upon the hemisphere’s median aspect. He pointed out that its extent was greater and its character more detailed in the ape than in any of the types less near to man. He showed that its focal movements were obtainable with such definition and precision that ‘the experimenter can predict with certainty the result of stimulation of a given region.’ He went on to determine the effects of destruction of limited portions of the cerebral cortex. He allocated regions especially concerned with vision (occipital cortex) and with hearing (superior temporal gyrus) respectively. He showed that the hemiplegias, ensuing on injuries within the motor region of the ape, were characteristically greater than those produced by similar cerebral lesions in the dog. The symptoms in the ape he stressed as being strikingly akin to those familiar in the clinic” (1074-1079, 1081-1084, 3168, 3214). 

Pierre-Joseph van Bénéden, (BE) introduced the terms commensalism and mutualism(3432). He defined a commensal individual as requiring “a simple place on his vessel, and does not partake of his provisions...animals which live on each other, without being either parasites or messmates; many of them are towed along by others; some render each other mutual services, others again take advantage of some assistance which their companions can give them; some afford each other an asylum...” (3434). 

Archives for Experimental Pathology and Pharmacology was founded.


Josiah Willard Gibbs (US) published, between 1874 and 1878, his concepts of thermodynamics as they apply to chemical reactions. In doing this he evolved the concepts of free energy and chemical potential as the driving force behind chemical reactions (1306).

Jacobus Hendricus van’t Hoff (NL) and Joseph Achille Le Bel (FR) independently advanced a three-dimensional stereochemical representation of organic molecules such as lactic acid and proposed that the carbon atom bonds in a tetrahedral fashion. This image of the carbon atom led them to propose that it can form asymmetric relationships, which would explain optical activity of organic compounds. Their description of isomerism in terms of differences in the arrangement of atoms in space (stereoisomerism) provided a convincing argument for considering structural formulas as representations of reality (2000, 3447-3449). 

Heinrich Caro (DE) synthesized the dye eosin in 1874. It is a phthalein product consisting of brominated fluorescein (217). Eosin would later prove useful for selectively staining cytoplasmic proteins. 

Max Jaffé (DE) isolated and named urocanic acid (Gk. ouro, urine + L. canis, dog) from dog’s urine (1742, 1743).

Andrew Hunter (US) determined that urocanic acid is an imidazole derivative, and a product of the deamination of the amino acid histidine (1664).

J. Piccard (DE) discovered that the hydrolysis of nucleoproteins yields the purines, guanine, and xanthine (2748).

Walther Flemming (DE) used carmine to stain the eggs of Anodonta (freshwater muscle) (1153).

Frédéric Alphonse Musculus (FR) obtained an enzyme (urease) from putrid urine, which he found capable of decomposing urea in aqueous solutions (2455, 2456).

Albert Wojciech Adamkiewicz (PL) presented his reagent, which gives a color reaction with proteins. It was later found to give a positive reaction with tryptophan (10, 11).

Richard Neumeister (DE) coined the name tryptophan for that substance which gives a color reaction with chlorine water following extensive degradation of a protein (the Adamkiewicz Test) (2495).

Frederick Gowland Hopkins (GB) and Sydney William Cole (GB) isolated tryptophan from a trypsin digest of casein and showed that some proteins did not contain it, e.g. gelatin (1629).

Alexander Ellinger (DE) and Max Geutzen (DE) found that tryptophan could act as a precursor to indole production in the intestine (1006, 1007).

Edith G. Willcock (GB) and Frederick Gowland Hopkins (GB) carried out feeding experiments with mice, which represent the earliest animal experiments in which a decisive test proved the indispensability of a specific amino acid (tryptophan) in nutrition. Willcock and Hopkins thus originated the concept that some amino acids are essential in the diet (3750). Others had shown that rats could not survive when gelatin was their sole source of amino acids.

Thomas Burr Osborne (US) and Lafayette Benedict Mendel (US) demonstrated that rats couldn’t survive on zein of corn as their sole dietary protein unless tryptophan and lysine are added. This was also an early indicator that animals might require individual amino acids (2583).

Otto Folin (SE-US) and Vintila Ciocalteu (US) developed a method of determining the tyrosine and tryptophan in proteins (1181).

Henry D. Schmidt (US) described intersegmental clefts in the myelin sheath of peripheral nerves (3080). To honor him these are called Schmidt's Clefts.

William Roberts (GB) found that when infusions of hay are carefully neutralized they could withstand three hours boiling before they are rendered sterile. He drew attention to the fact that the degree of heat required to produce sterility varies greatly according to the nature of the materials tested.

He confirmed Johannes Hubertus Van den Broek’s work suggesting that the interiors of plant tissues are sterile. Roberts tested the interior of grapes, oranges, tomatoes, turnips, and potatoes (Solanum tuberosum). His methodology consisted of heating a spot on the surface of the tissue then puncturing it with a sterile Pasteur pipette. Plant fluids were draw into the pipette after which it was sealed with a flame.

He commented that when Penicillium glaucum was growing on a medium it was very difficult to also get bacteria to grow on the same medium. This he interpreted in Darwinian terms of the drive to survive. He was the first to use antagonism in this context (2949).

William Gilson Farlow (GB) and Heinrich Anton de Bary (DE) discovered that the asexual phase can arise directly (that is, vegetatively) from the sexual phase, i.e., apogamy, in the Pteridophyta (ferns, horsetails, and club-mosses) (799, 1060).

Christian Albert Theodor Billroth (DE-AT) reported on a five-year study of the bacteria associated with putrefaction and infectious disease. He concluded (incorrectly) that all the round and rod shaped bacterial forms were but stages of a plant—he regarded it as an alga—which he called Coccobacteria septica. He did introduce many names such as micrococcus, diplococcus, streptococcus, gliacoccus, petalococcus, mesacoccus, megacoccus, ascococcus, gliabacteria, petalobacteria, and streptobacteria, some of which persist today (260).

Tadeusz Browicz (PL) was the first to describe the bacillus that causes typhoid fever, later to be known as Salmonella typhi (473).

Charles-Marie Benjamin Rouget (FR) was the first to describe a contractile, motile cell surrounding capillaries in a tunic-like fashion. In the brain these pericytes, originally called Rouget cells, are located in precapillary arterioles, capillaries and postcapillary venules where they are part of the blood-brain barrier. Pericytes are local regulatory cells that are important for the maintenance of homeostasis and hemostasis, and are a source of adult pluripotent stem cells (2978). 

Wilhelm His (CH) presented the hypothesis of germinal localization based on what he called the principle of organ-forming primordial-regions. This hypothesis suggests that in the course of normal embryonic development identifiable regions of the early embryo develop into specific structures of the older embryo (1590, 3762).

Pierre-Joseph van Bénéden (BE) was able to show through his studies of the digestive tracts of many fishes that cysticerci are larvae of intestinal worms called taeniae (adult tapeworms). His work covered a wide range of parasites in diverse animals (3433). About 1859 he began a study of fossil and recent whales, which resulted in a major work, written in collaboration with Paul Gervais (BE) (3435). He is commemorated by Tubificoides benedii d'Udekem, 1855, Vanbenedenia Malm, 1860, Nematobothrium benedeni Monticelli, 1893, Haploporus benedenii Stossich, 1887, Benedenia Diesing, 1858, Allometabenedeniella Velasquez, 1982, Metabenedeniella Yamaguti, 1958, Neobenedenia, Acanthobothrium benedenii Lönnberg, 1889, Echinobothrium benedeni Ruszkowski, 1928, Benedenipora Pergens, 1889, Barentia benedeni Foettinger, 1886, Actigia vanbenedeni Hincks, 1869, and Bougainvillia vanbenedeni Bonnevie, 1898.

Carl Erhardt (DE) recommended the administration of potassium fluoride to pregnant women and to children during the period of tooth development. His views of the relationship between sound teeth and dietary fluoride rested on meager experimental evidence from dogs (553, 1036).

Alvaro Francisco Carlos Reynoso (CU) filed a patent, Improvement in Medical Compounds, on Elixir and Sirup containing fluoride of potassium, sodium or ammonium. His "elixir", he says, is "invigorating, nutritious, and complemental to food;" "fluorated sirup" is "... for infants at the period when the bones and teeth are in process of formation (2919).

Gerhard Henrik Armauer Hansen (NO) described the rod shaped bacterium of leprosy (Mycobacterium leprae) in association with leprous lesions. This organism is sometimes called Hansen’s bacillus (1484-1486). This was the first bacterium to be implicated as the probable cause of an infectious disease in humans.

Albert Ludwig Siegmund Neisser (DE) used aniline dyes to convincingly demonstrate that Mycobacterium leprae is the etiological agent of leprosy (2482).

H. Böttcher (DE) and Maurice Letulle (FR) discovered bacteria in the floor and margins of gastric ulcers. They were the first to propose that bacteria can cause ulcer disease (334, 2038).

Walery Jaworski (PL) isolated a spiral bacterium characteristically present in stomach cancer and ulcer. He called the bacterium Vibrio rugula (1747).

Giulio Cesare Bizzozero (IT) noted spirochetes in the gastric mucosa infiltrating gastric glands and found them within the cytoplasm and vacuoles of parietal cells of dogs (287). These organisms were named Helicobacter bizzozeronii in 1996.

Berkely George Andrew Moynihan (GB) stated, “I believe that a further search should be made for an organism thriving in hydrochloric acid medium (and variations of hydrochloric acid are normal in all stomachs) as a possible factor of chronicity, if not an etiologic factor, in peptic ulcer” (2408).

John Robin Warren (AU) and Barry J. Marshall (AU) reported that there is a strong association of a Campylobacter-like organism with gastritis and peptic ulceration (2248, 3680).

Charles Stewart Goodwin (AU), John A. Armstrong (AU), Terry Chilvers (AU), Michelle Peters (AU), M. David Collins (GB), Lindsay I. Sly (AU), William McConnell (AU), and William E.S. Harper (AU) presented compelling evidence that this organism should be placed in a new genus as Helicobacter pylori (1370).

David Y. Graham (US), Ginger M. Lew (US), Peter D. Klein (US), Dolores G. Evans (US), Doyle J. Evans, Jr. (US), Zahid A. Saeed (PK-US), Hoda M. Malaty (US), International Agency for Research on Cancer (IARC), Barry J. Marshall (AU), John A. Armstrong (AU), David B. McGechie (AU), Ross James Glancy (AU), Julie Parsonnet (US), Svein Hansen (NO), Larissa Rodriguez (US), Arnold B. Gelb (US), Roger A. Warnke (US), Egil Jellum (NO), Norman Orentreich (US), Joseph H. Vogelman (US), Gary D. Friedman (US), and Walter L. Peterson (US) proved that Helicobacter pylori, a bacterium, is the etiological agent of acute or chronic gastritis, and a predisposing factor in peptic ulcer disease, gastric carcinoma and B cell mucosa-associated lymphoid tissue (MALT) lymphoma (1386, 1709, 2246, 2646, 2726).

Barry J. Marshall (AU), David B. McGechie (AU), Peter A. Rogers (AU), and Ross James Glancy (AU) associated pyloric campylobacter infection with gastroduodenal disease (2247).

Thomas J. Borody (AU), Peggy Cole (AU), Suzanne Noonan (AU), 

Anne Morgan (AU), Jennifer Lenne, Lorraine Hyland (AU), Susan Brandl (AU), Edith G. Borody (AU), and Laura L. George (AU) reported the recurrence of duodenal ulcer and Campylobacter pylori infection after eradication (329).

Laura L. George (AU), Thomas J. Borody (AU), Peter Andrews (AU), Michele Devine (AU), Deborah Moore-Jones (AU), Mary Walton (AU), and Susan Brandl (AU) described a cure of duodenal ulcer after eradication of Helicobacter pylori (1300).

Massimo Marignani (IT), Stefano Angeletti IT), Cesare Bordi (IT), F. Malagnino (IT), C. Mancino (IT), Gianfranco Della Fave (IT), and Bruno Annibale (IT) reported that Helicobacter pylori infection can be involved in unexplained cases of iron deficiency anemia in adults, and its cure can normalize the hematologic picture (2239).

Emil Heinrich du Bois-Reymond (DE) hypothesized that the transmission of the excitatory process from nerves to effector cells could take place either electrically via currents or chemically using excitatory substances liberated by nerve endings (901).

Michael Foster (GB) and Charles Scott Sherrington (GB) deduced the existence of and named the nerve cell synapse (a name suggested by the Euripidean scholar Verrall, then at Cambridge) by showing that individual nerve cells can exert integrative influences on other nerve cells by graded excitatory or inhibitory synaptic actions (1190). Absolute proof of the existence of the synapse came in 1959 with the electron micrographs of Edward George Gray (GB) (1409).

Rudolf Peter Heinrich Heidenhain (DE) and Albert Ludwig Siegmund Neisser (DE), on the basis of carefully controlled dye injection studies, provided experimental proof for the existence of proximal tubular secretion as a principal transport process involved in urine formation (1524).

William Osler (CA) was doubtless describing platelets (thrombocytes) when he reported, "Careful investigation of the blood proves that, in addition to the usual elements, there exist pale granular masses, which on closer inspection present a corpuscular appearance. In size they vary greatly from half or quarter that of a white blood corpuscle, to enormous masses. … They have a compact solid look, … while in specimens examined without any reagents the filaments of fibrin adhere to them” (2585).

Vladimir Alekseyevich Betz; Vladimir Aleksandrovich Betz (UA) published work on giant pyramidal cells (later named for him) of the brain’s central cortex. He also put forward the important concept that motor functions are represented anterior to the central sulcus (of Rolando) and sensory functions posterior to it (238).

W. Bevan Lewis (GB) and Henry Clarke (GB) published work on the giant pyramidal cells of human pre-central gyrus (2059, 2060).

Karl Gegenbaur (DE) stressed the higher value of comparative anatomy as the basis of the study of homologies, i.e., of the relations between corresponding parts in different animals, as, for example, the arm of man, with the foreleg of a horse, and with the wing of a fowl. He showed how embryonic structures, which in fish eventually come to form gills, form other organs, from Eustachian tubes to the thymus gland, in land vertebrates. He also extended the work of Rudolf Albert von Kölliker (CH) to show that not only mammalian eggs and sperm but also all eggs and sperm, even the giant eggs of birds and reptiles, are single cells. Gegenbaur applied the term syncytium to striated muscle (1295).

Johann H. Schultz (DE) and F. Baumstark (DE) made the first clinical presentations of porphyria. Baumstark named two pigments derived from the urine of his patient—urorubrohaematin and urofuscohaematin. He interpreted the source of the porphyrin pigments as an error in biosynthesis. This was the first association of this class of pigments in urine with a disease in humans (143, 3102).

Francis Galton (GB) used the phrase nature and nuture to explain heredity and environment (1256).

Hugo Kronecker (DE) and William Stirling (GB) showed that the heart muscle cannot be tetanized (1911).

Roberts Bartholow (US) was the first to electrically stimulate the human cortical tissue (125).

Karl Ludwig Kahlbaum (DE) coined the term catatonia to denote an organic illness with somatic and mental symptoms (1766). Note: It came to mean abnormality of movement and behavior arising from a disturbed mental state (typically schizophrenia). Informally it means a state of immobility and stupor.

Carl Wernicke (PL-DE) published a small volume on aphasia, which vaulted him into international fame. In it is precise pathoanatomic analysis paralleling the clinical picture. He is best known for his work on sensory aphasia and poliomyelitis hemorrhagia superior. Both of these descriptions bear his name. Further, his books on the disorders of the internal capsule and his textbooks on diseases of the nervous system perpetuate him. In this work he also relates damage to the left temporoparietal junction of the brain to loss of language comprehension (979, 3720). See Broca, 1856. Sensory aphasia is due to cortical lesions in the posterior portion of the left first temporal convolution.

Carl Philipp Adolf Konrad Kussmaul (DE) and Anton Frey (DE), his assistant, suggested the name poliomyelitis anterior acuta for acute myelitis of the anterior cornua. This affliction is more common in children. The word polio means grey in Greek and refers to the inflammed grey matter in the spinal cord. It was frequently called infantile paralysis (1216-1218).

Carl Philipp Adolf Konrad Kussmaul (DE) described a deep and labored hyperventilation, which is found in patients dying with severe diabetic ketoacidosis. It is called 'Kussmaul respirations' (or breathing) (1939).

Karl Thiersch (DE) introduced a method of split skin grafting using epidermis and a portion of the dermis. It consists of shaving thin strips of healthy skin so that the true skin is divided and then implanting these strips on granulating tissue (3315).

Abraham Groves (CA) may have been the first to sterilize surgical instruments by boiling. He removed an ovarian cancer from a 40-year-old woman with a tumor filling the whole abdomen. Careful examination of its location and physical characteristics led him to conclude that the tumor was ovarian and monocystic. Tapping yielded about 25 pints of clear fluid, but the fluid rapidly accumulated, two further aspirations bringing only transient relief. Groves operated on her on 5 May 1874. The operation, which was successful, featured the rigorous application of antiseptic principles. Groves boiled all the water, used carbolized catgut to tie the pedicle, and dressed the wound with cotton saturated with a solution of carbolic acid. To his knowledge instruments and dressings had never been sterilized by boiling before that time. This became his surgical practice from then on (1427).

Andrew Taylor Still (US) began discussing changes in medical practice, which would lead to his establishment of osteopathic medicine. In 1892, he opened the American School of Osteopathy in Kirksville, MO.

Wilhelm Philipp Schimper (DE), in 1874, recognized and named the Paleocene Epoch (65 Ma B.P.—54.9 Ma B.P.) of the Cenozoic Era based on a study of floral samples from the Paris Basin (3064).

The Botanischer Jahresbericht was founded.

ca. 1875

Georg Meissner (DE) was successful in preserving unchanged many organs and tissues aseptically removed from cats and rabbits. Whole kidneys, spleens, pancreas, and pieces of liver from these animals as well as frogs’ thighs were removed immediately after death and preserved in a dust-free atmosphere for two or three years. The exact technique employed is not given, but it is known that everything had been sterilized by heat. All glassware was plugged with cotton wool and heated to 160° C. All the water was boiled. No sponges were used, but only sterile cotton-wool swabs. The operations were carried out in a dust-proof room, and the number of assistants was reduced to a minimum. The skin of the animal was generally stripped off completely. Meissner had developed high-class aseptic surgical techniques long before they were in vogue in human surgery. His experiments showed that tissues are sterile and will not autonomously decay and putrify (2964).


Wilbur Olin Atwater (US) was instrumental in persuading the Connecticut Legislature to set up the first state agricultural research station in the United States, at Middletown. In 1887, again at his prodding, The U.S. Congress passed the Hatch Act, providing funds for agricultural experiment stations in all the states. He was the first director of the Office of Experiment Stations (1888).

Hermann Emil Fischer (DE) discovered phenylhydrazine in 1875, and then found that it reacts with simple sugars to produce crystalline substances called osazones. Osazone crystals are often characteristic of the sugar from which they were derived.

Hermann Emil Fischer (DE), Joseph Hirschberger (DE), and Julius Tafel (CH-DE) developed an extensive work on the chemical synthesis of sugars, on their isomeric forms and stereochemistry, and on the selective transformation of some of them by yeast. They were able to synthesize 5, 6, 7, 8, and 9 carbon monosaccharides, produce their phenylhydrazine derivatives, then determine the molecular structures of fructose, glucose, and many other sugars (1126, 1127, 1129-1131, 1134, 1136, 1140, 1142-1147). 

Hermann Emil Fischer (DE) applied the Le Bel-Van’t Hoff theory to the sugar series and showed how to distinguish the formulas of the 16 stereoisometric glucoses (Fischer projections). He states, “All previous observations in the sugar group are in such complete agreement with the theory of the asymmetric carbon atom that the use of this theory as a basis for the classification of these substances seems justifiable” (1132, 1133, 1140). In the course of his stereochemical research, Fischer discovered that there are two series of sugars, the D sugars and the L sugars, that are mirror images of each other. The D and L forms of mannoic acid were the first pair of enantiomorphs to be discovered in this group of sugars (1129, 1140). 

Hermann Emil Fischer (DE) related the optical activity of sugars to that of tartaric acid (1135).

Wilhelm Friedrich Kühne (DE) showed that indole appears after proteinaceous material putrifies. The protein will give a violet color when nitric acid is added (1919).

Whale oil, soap, and kerosene were advocated as insecticidal spray for numerous insect pests (3161).

André Victor Cornil (FR), using methyl aniline violet, was probably the first to stain tissue and observe a metachromatic effect. He observed that hyaline cartilage was stained in such a manner that the cells and their capsules were violet, the intracellular material red; connective tissue fibrils and elastin fibers as well as the cells and fibers of elastic cartilage stained violet (695).

Paul Ehrlich (DE) is often given credit for discovering metachromasy and explaining that it is due to certain basic dyes staining acidic cell constituents one color and other cell components another color (990).

Rudolf Arndt (DE) was the first to demonstrate chromophilic granules within cells. These are granules, which certain dyes color more intensely than the surrounding cytoplasm (57). See Franz Nissl, 1890.

Ferdinand Julius Cohn (DE) studied a group of peach-colored sulfur bacteria isolated from contaminated waters. Although they looked alike, he concluded, based on their physiology that they were separate species. He also described Cladothrix dichotoma in 1873 and Streptothrix foersteri in 1875 (650).

Jules Emile Planchon (FR) discovered the fungus Phylloxera that causes a severe disease of grapevines (2760).

Otto Bütschli (DE) was the first to identify and order sequentially the stages of nuclear division in several types of animal cells, simultaneously with Strassburger’s work on the division of plant cells and several years prior to Flemming’s studies on mitosis. Bütschli demonstrated that the polar bodies of eggs arise through atypical cell division, and in studying fertilization he was the first to describe the fertilization cone and to prove that normally only one sperm enters the egg. He clearly illustrated the fusion of male and female pronuclei in the eggs of snails. His illustrations of the zygotene “bouquet” stage and of diakinesis during the first meiotic division of spermatogonia in the roach were excellent. He suggested that in the ciliates reproduction and the sexual processes are not closely associated. Bütschli was the first to recognize this and to demonstrate that conjugation was not a reproductive process per se, but a sexual reorganization of the cell similar to fertilization (545-547).

Wilhelm August Oskar Hertwig (DE) concluded that the physical basis of inheritance must be the chromosomes. He described the intracellular events following fertilization as they occur within the egg of the roundworm Ascaris. Hertwig was one of the discoverers of meiosis (1564).

Giulio Cesare Bizzozero (IT) and Alessandro Augusto Torre (IT) produced images of mitosis as it occurs in the spleen of the triton (288).

Édouard Joseph Louis Marie van Beneden (BE) using the horse roundworm, Ascaris megalocephala, observed that in fertilization, as in cell division, continuity depends on chromosomes: the sperm’s contribution to fertilization is a set of chromosomes homologous with those present in the egg. Rather than fusing with one another the maternal and paternal chromosomes retain their identity through subsequent cell divisions. He noted that the number of chromosomes is constant for a given species and that this number is reduced in half in reproductive cells or gametes (3429). Édouard Joseph Louis Marie van Beneden (BE) is also one of those who discovered meiosis.

Emil Heuser (DE) described in the microsporocytes of Tradescantia a transverse fission of bivalent chromosomes in the first division. He thus made the important discovery that the chromatids (spalthälften) of each chromosome were exactly separated and distributed to the two opposite spindle poles (1578).

August Friedrich Leopold Weismann (DE) wrote an article, which emphasized meiosis as an exact mechanism of chromosome distribution (3705).

Walther Flemming (DE) provided the first cytological evidence that the cell divisions involved in the production of sperm differed from the normal type of mitosis. Spermatogenesis, he reported, involved two types of cell division. The first type differed little from normal mitosis, but the second, or heterotypic mitosis, seemed to be unique in two ways. First, the chromosomes appeared as knots or rings. Second, and more significantly, the number of such ringed chromosomes was half the number that appeared in tissue cells, twelve rather than twenty-four in the salamander (1158).

Theodor Boveri (DE), working with Ascaris megalocephala and Ascaris univalens, established that chromosomal individuality is stably maintained from one generation to the next. He also presented the first description of chromosome tetrads (Vierergruppen) and their behavior during reduction division. In Ascaris megalocephala var. bivalens, where the normal diploid number is four, Boveri observed two groups of chromosomes with four chromosomes in each group. The first division of the egg separated the tetrads into two dyads, one of which remained in the egg, the second of which entered the first polar body. The second division of the egg separated the two elements of each dyad, leaving a total of two chromosomes in the egg cell and two chromosomes in the second polar body. Meanwhile, the first polar body divided once. Thus the divisions produced a total of three polar bodies, each containing two chromosomes (372, 373, 377).

August Friedrich Leopold Weismann (DE) elaborated an all-encompassing theory of chromosome behavior during cell division and fertilization and predicted the occurrence of meiosis (3706).

Édouard Joseph Louis Marie van Beneden (BE) and Adolphe Neyt (BE) demonstrated chromosome reduction in gamete maturation and discovered that each species has a fixed number of chromosomes, thereby confirming August Friedrich Leopold Weismann’s predictions. They along with Theodor Boveri (DE) described the role of the centrosome in cell division and established the independent inheritance of this organelle. It was Boveri who named it centromere in 1888 (370-373, 3430).

August Friedrich Leopold Weismann (DE) made the very significant remark that since it was unlikely that the polar bodies would remove the same ids (ancestral germ plasms) each time, those retained in the germ cells also would be different. In other words, the germ nuclei were probably different from each other (3707).

August Brauer (DE) described meiosis (spermatogenesis) in Ascaris megalocephala males. The diploid chromosome number in Ascaris is four. The cells of the testis that will later form the sperm are diploid. The four chromosomes undergo synapsis then as meiosis continues each chromosome becomes shortened until it forms a tiny sphere. During this process each chromosome splits. As a result each of the two pairs of synapsed chromosomes forms a tetrad. At the first meiotic division the two tetrads enter the spindle and are divided, half of each tetrad (a dyad) going to each pole. As a result of the first meiotic division two cells are formed. Each of these contains two dyads. In the second meiotic division the dyads of the two cells are pulled apart. At the end of this division there are four cells. Each of these contains two chromosomes, the haploid number. There is no further division of these four cells and they develop directly into sperm (403).

Eduard Adolf Strasburger (PL-DE) recognized the cytological significance of an alternation of a diploid, spore-producing generation with a haploid, gamete-producing generation in the bryophytes (liverworts and mosses) and other organisms (3278).

William Austin Cannon (US), Edmund Beecher Wilson (US), and Walter Stanborough Sutton (US) pointed out the precise equivalence between the patterns of inheritance of genes and chromosomes in organisms that reproduce sexually, that is, by the union of eggs and sperm. Cannon was the first to recognize that Mendel’s results could be explained by meiosis (555, 3761).

Hans von Winiwarter (FR) reported the occurrence of synapses in early reduction division (3635).

Thomas Harrison Montgomery, Jr. (US) published his classic paper detailing sperm formation and egg formation in many species of Hemiptera (true bugs). He concluded that chromosomes are permanent structures; that they occur in homologous pairs consisting of one originally inherited from the mother and the other from the father; that synapsis during meiosis consists of the coming together of these homologous chromosomes; that in meiosis each spermatid receives one chromosome of each type. He described accessory chromosomes that later investigators were to associate with sex determination (2374, 2375).

Walter Stanborough Sutton (US), Theodor Boveri (DE), and Carl Franz Joseph Erich Correns (DE) were independently the first to relate genetics to the study of chromosome behavior and provide the basis of the chromosomal theory of heredity. Sutton analyzed chromosome movements during meiosis in the grasshopper Brachystola, and stated, “I may finally call attention to the probability that the association of paternal and maternal chromosomes in pairs and their subsequent separation during the reducing division…may constitute the physical basis of the Mendelian law of heredity. To this subject I hope to return in another place.” Boveri analyzed chromosome movements during meiosis in the roundworm Ascaris. Correns stated clearly the hypothesis of the physical mechanism of segregation of alleles which underlies the chromosome theory of heredity, stating “Each tetrad contains bodies of both kinds, those with A as well as those with a, accordingly segregation must be carried out by nuclear division, in fact by the first division of the pollen mother cells.” They all provided strong evidence that there is an exact parallel in the behavior of Mendelian hereditary units and of the chromosomes in meiosis and fertilization. The most obvious conclusion was, therefore, that the hereditary units are parts of chromosomes (374-376, 696, 3290-3293). Note: In his 1902 paper, Sutton reports cytological studies of grasshopper chromosomes that lead him to conclude that (a) chromosomes have individuality, (b) that they occur in pairs, with one member of each pair contributed by each parent, and (c) that the paired chromosomes separate from each other during meiosis.

Walter Stanborough Sutton (US) proposed the hypothesis that Johann Gregor Mendel’s results could be explained if hereditary units were parts of chromosomes. He predicted that if he were correct some non-Mendelian results could be expected because all genes on the same chromosome would have a tendency to be inherited as a unit (linkage). Sutton summarized what was known as follows:

(1) The diploid chromosome group consists of two morphologically similar chromosome sets. Each chromosome type is represented twice or, as we say today, chromosomes are in homologous pairs. Strong grounds exist for the belief that one set is derived from the father and one set from the mother at the time of fertilization.

(2) Synapsis is the pairing of homologous chromosomes.

(3) Meiosis results in a gamete receiving only one chromosome from each homologous pair.

(4) The chromosomes retain their individuality throughout mitosis and meiosis in spite of great changes in appearance.

(5) The distribution in meiosis of the members of each homologous pair of chromosomes is independent of that of each other pair. While each gamete receives one of each pair, which one, is a matter of chance (3292). See Boveri, 1904. Sutton was a 26-year-old graduate student at Columbia University when he wrote his brilliant insightful paper of 1903.

Eduard Adolf Strasburger (PL-DE) introduced the terms haploid and diploid for the gametic and somatic chromosome numbers respectively (3280).

John Bretland Farmer (GB), and John Edmund Shorec Moore (GB) showed that during reductive division half of the chromosomes are lost within the polar bodies - a process they named maiosis (meiosis) (1062). Strasburger had described meiosis in pollen mother cells and the embryo sac (3276).

Charles E. Allen (US) was the first to observe meiosis in the algae; his material was Coleochaete (33).

Franciscus Alphonsius Janssens (BE) suggested that the chiasmata observed between synaptic chromosomes could be taken as observational evidence for the phenomenon of crossing over among linked genes, although he could not prove it (1745).

Estrella Eleanor Carothers (US) used differences between members of homologous pairs of chromosomes to give direct proof of the independent assortment of members of different pairs—which Sutton had assumed as a consequence of the location of Mendelian factors in chromosomes. The evidence became overwhelming that chromosome pairs behave in meiosis like pairs of alleles (560). 

August Wilhelm Eichler (DE) produced Bluthendiagramme, a book containing analytical drawings of the flower and inflorescence structure of all Angiosperm families then known (998).

Alexander Goette (DE) authored Die Entwickelungsgeschichte der Unke (Bombinator igneus) als Grundlage Einer Vergleichenden Morphologie der Wirbelthiere which was to become the model for all later descriptive work on frog embryology (1322).

Louis-Antoine Ranvier (FR) observed that a frog’s leukocytes can engulf (phagocytize) particles of carmine which remain visible within the leukocytes as they pass through the walls of the capillaries (2847).

Bartolomeo Camillo Emilio Golgi (IT), in 1875, showed that some brain tumors contain distinctive star-shaped neuroglial cells of the brain, and he distinguished soft and hard forms of tumors (95).

Leon Semenowitj Cienkowski (PL-RU) was the first to observe the formation of multinucleated cells from single cells in invertebrates (618).

Oscar Lange (DE) was the first to observe the actual formation of multinucleate cells in vertebrates by fusion of single cells. He was studying blood-borne amoeboid cells in the frog (1961).

Carl Weigert (DE) considered the logic of whether the objects called bacteria, associated with many morbid conditions, were really such or whether they were by-products of tissue degeneration. He also asked the important question of what is it about a bacterium that makes it pathogenic if it is indeed pathogenic? Is it something secreted by the bacterium, or something attached to it? He attempted to show that bacteria stain differently from degenerative products. He showed that the areas of tissue damage often coincided with the area where the bacteria were concentrated. He though it unlikely that harmless bacteria would migrate to an area damaged by some other force or agent. He argued that there is no reason to suppose that because bacteria are microscopic they are necessarily all alike (3699).

Carl Weigert (DE) found during his studies of umbilical cord ulcerations in newborns that methyl violet, a product of the new aniline dye industry in Germany, was excellent for staining bacteria (probably micrococci) (3699).

Moritz Traube (PL) and Richard Gscheidlen (DE) pointed out that fresh blood resisted putrefaction. They observed that the anti-putrefactive power of the blood has limits (3385).

Thomas Henry Huxley (GB) put forward the idea that according to their embryonic development three kinds of body-cavity ought to be distinguished: (1) the enterocoelic which arises from enteric diverticula, (2) the schizocoelic which develops as a split in the embryonic mesoblast, and (3) the epicoelic which was enclosed by folds of skin and lined by ectoderm, e.g., atrial cavity of Tunicates. He proposed the group Deuterostomata for all the coelomate Bilateria, basing the name on the lack of relationship of the mouth to the blastopore. Deuterostomata was divided into three categories: Enterocoela for echinoderms, chaetognaths, and enteropneusts; Schizocoela for mollusks, polychaetes, and arthropods; and Epicoela for tunicates and Amphioxus (1689-1691, 1700).

James F.P. McConnell (GB) was the first to describe the Chinese liver fluke, Clonorchis sinensis (2277).

Harujiro Kobayashi (JP) discovered that an important food fish is the second intermediate host of Clonorchis sinensis. This is the source by which human infections are acquired. There are 12 species of fish that are mainly responsible for passing the infection to humans. Some of these fishes include Pseudorasbora parva (in the Japan region) and Ctenopharyngodon idella (in the Canton region) (1835).

Masatomo Muto (JP) recognized the snail host of Clonorchis sinensis, mainly Parafossarulus manchouricus and species from the genus Bulinus (2457).

John O’Neill (IE) gave the first description of human onchocerciasis (caused by the filarial worm Onchocerca volvulus) when he demonstrated the presence of the microfilaria in skin biopsies of an African suffering from a cutaneous disease known as craw-craw or kru kru (2542).

Alexandre Joseph Émile Brumpt (FR), in 1890, recognized that the infection occurs most commonly along riverbanks, and that the microfilariae in the skin come from deeper cutaneous nodules where adult filariae reside (499).

Patrick Manson (GB) described adult Onchocerca from material given him by Karl Georg Friedrich Rudolf Leuckart (DE) (2222).

Louis Joseph Alcide Railliet (FR) and A. Henry (FR) named it Onchocerca volvulus (2840).

Rodolfo Robles (GT), in 1915, proved that onchocerciasis is caused by a species of filaria, Onchocerca caecutiens (2955).

Jean Montpellier () and A. Lacroix () established the role of the microfilaria in causing the skin lesions (2376).

Breadablane Blacklock (GB), working in Sierra Leone, determined that Onchocerca volvulus is transmitted by black flies (Simulium damnosum) (296).

Jean Hissette (BE) discovered the part played by microfilaria in blindness (1595).

Leonard Landois (DE) reviewed 478 blood transfusions between humans and 129 transfusions between animals. Of 129 animal-to-human blood transfusions - 62 had shown no improvement or had died, 25 had dubious reports of temporary "improvement", 42 had, according to their authors, shown signs of recovery of improvement; of 347 human-to-human blood transfusions - 150 "improved", 12 had dubious reports of temporary "improvement", 180 were "unfavorable", two died, and the results for the remaining three were unknown. He showed that, if the erythrocytes of an animal belonging to one species were mixed with serum taken from an animal of another species, the red cells usually clumped and that sometimes the red cells burst, i.e., hemolyzed. Thus, the danger of transfusing blood of another species to humans was established scientifically (1957).

Richard Volkmann (DE) gave the first description of industrial tar and paraffin cancer (3492).

Carl von Rokitansky (CZ-AT) wrote his great memoir on defects in the septum of the heart (3620).

Apollinaire Bouchardat (FR) wrote what is probably the first textbook on diabetes, associating clinical observations, experimental steps and proposals for a treatment based on the patients' way of life: mainly diet and exercise. He defined urinary sugar concentration as an indication of the patient's clinical condition (338).

Claude Bernard (FR) was one of the first to advocate an adequate oxygen supply during anesthesia, as well as the first to suggest pre-anesthetic medication with morphine and other central nervous system depressants (207).

Johannes Adolf von Kries (DE) was the first to measure capillary pressure (3587).

Josef Breuer (AT), Ernst Waldfried Josef Wenzel Mach (CZ), and Alexander Crum-Brown (US), independently reached the conclusion that the semi-circular canal apparatus is a sensory organ for the perception of rotary motion and that the phenomena of rotatory vertigo is the result of abnormally strong stimulation of this sensory organ (414, 729, 2182).

Wilhelm Heinrich Erb (DE) and Karl Friedrich Otto Westphal (DE) described the knee jerk reflex, the most important reflex anomaly seen in tabes dorsalis. Absence of the knee jerk is found in central nervous system syphilis. This reflex anomaly is most pronounced in tabes dorsalis, but also occurs in other disturbances (1034, 3728).

William Howship Dickinson (GB) reported familial albuminuria (853).

Hugh Owen Thomas (GB) developed a way to immobilize a fractured thigh and hip (Thomas hip-splint) (3321).

A particularly bad epidemic of scarlet fever swept Australia, with high mortality rates (1863).

Moritz Litten (DE) reported that acute thrombo-embolic occlusion of the superior mesenteric artery (SMA) leads to abdominal catastrophe and death (2103).

Karl Wilhelm Ernst Joachim Schönborn (DE), in 1875, described the first true pharyngeal flap surgery, an inferiorly based flap surgery for velopharyngeal insufficiency (cleft palate). In 1886 he switched to a superiorly based flap operation (3090, 3091).

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

Deutsche Medicinische Wochenschrift was founded.


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

David Starr Jordan (US) and Barton Warren Evermann (US), from 1896-1900, authored The Fishes of North and Middle America (1758). 


“…we have now recognized that the most significant occurrence in fertilization is the fusion of the two cell nuclei” (1564).

"All nervous centres from the lowest to the very highest (the substrata of consciousness), are made up of nothing else than nervous arrangements, representing impressions and movements... I do not see of what other materials the brain can be made." John Hughlings Jackson (1729).

Ernst Fischer (DE) introduced the use of eosin to histology (1099).

Otto Nikolaus Witt (CH-DE) proposed the Chromophore-auxochrome theory for colored organic compounds and in the process coined the terms chromophore and auxochrome. He theorized that dyes consist of conjugated systems, called chromophores, and salt-forming groups, or auxochromes, polar substituents that modify their colors (3780).

Otto Nikolaus Witt (CH-DE), in 1876, was the first to prepare the dyestuff chrysoidine (diamino-azo-benzene) (3781).

Heinrich Caro (DE) made the dye methylene blue (668).

Charles Lauth (FR) made the dye thionin (Lauth’s violet) ( 3,7-diamino-5-phenothiazinium chloride) (668).

Johann Friedrich Miescher, Jr. (CH) was probably the first protein chemist to recognize the amphoteric properties of proteins (2344).

Louis Pasteur (FR) published his book Études sur la Bière in which he stated that fermentations are essentially the result of life without oxygen (2676).

Louis Pasteur (FR) described methods to demonstrate fermentation under anaerobic conditions (2676).

John Tyndall (GB) began publishing his studies on floating matter of the air in relation to putrefaction and infection. He had been studying radiant heat and its relation to gases, and in his experiments on air he had been impressed with the difficulty of removing particles suspended in the air. It was found that although these particles are invisible to the naked eye they could be made visible by passing a strong beam of light through the air containing them. Tyndall found that he could render air within a closed container free of these particles by burning them with the flame of an alcohol lamp. This black space free of particles Tyndall pronounced to be optically inactive.

By chance he noticed one day that a flask, which had been standing for a long time, was optically inactive. The dust particles had settled on the bottom and sides of the flask. This led him to construct a chamber suitable for experiments on optically inactive air. This chamber or case had a glass front, and the top, bottom, back, and sides were of wood. At the back was a small door, while two panes of glass were let in like windows in the sides. The top was perforated in the middle by a hole, two inches in diameter, closed air-tight by a sheet of rubber, which was pierced through the middle by a pin-hole through which was pushed a long pipette ending externally in a thistle tube. A circular tin collar two inches in diameter and one and one-half inches deep surrounded the pipette, the space between being well packed with cotton wool moistened with glycerin. Into two other small openings in the top of the chamber were inserted airtight the open ends of two narrow tubes connecting the interior of the box with the outside air. The tubes were bent up and down several times so as to trap any particles carried in the air by changes in temperature. The bottom of the chamber was pierced with holes to take a number of test tubes intended to hold the infusions, which were to be exposed to the optically inactive air. The method of experimentation was as follows. The chamber, being closed, was left untouched for several days and until a beam of light passed through the lateral windows showed that the air was optically inactive and that particles were trapped on the interior surfaces, where they were retained by a layer of glycerin with which these surfaces had previously been coated. The pipette in the top of the box being moved into position, the infusion was poured into the thistle funnel and allowed to enter the test-tubes until they were nearly filled. The tubes were then lowered into a bath of brine raised to the boiling point, and allowed to boil for five minutes. The fluids tested were urine, infusions of mutton, beef, liver, haddock, sole, cod, turbot, herring, hare, rabbit, pheasant, grouse, and vegetable infusions of turnip or hay. Tubes filled with similar infusions but exposed to air outside the box acted as controls. After some refining of his techniques Tyndall (GB) found that the protected infusions in the chambers remained unaffected even for months, and it was thereby established that the power of developing bacterial life by the atmosphere and its power of scattering light go hand in hand. He also studied the geographical distribution of aerial germs by exposing trays containing 100 tubes filled with infusions, and was able to show that the distribution of bacteria is not uniform.

Tyndall found that infusions made from old, dried hay were more difficult to sterilize than those made with new fresh hay. Following prolonged and exhaustive experimentation he reached the conclusion that bacteria have phases, one being relatively thermolabile in that it was destroyed at 100°C. in 5 minutes, whereas the other, which he regarded as the germ of the bacterium, is thermoresistant to an almost incredible extent (3409-3412, 3414, 3415).

Carl Julius Salomonsen (DK) purified bacteria of putrid blood by forcing the blood into capillary tubes (50-60 cm. X 0.5-1.0 mm.) which he was able to place under the microscope for further observation. Breaking the tubes where isolated spots occurred, he found that each spot contained only one sort of bacterium. No spots occurred in blood taken aseptically from vessels of healthy living animals (3027, 3028).

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

Thomas Casper Gilchrist (GB-US) and W.R. Stokes (US) were the first to describe American blastomycosis (oidiomycosis), a well-defined skin disease that may evolve into a systemic infection. It has been called North American blastomycosis, Gilchrist’s disease, blastomycosis, and blastomycetic dermititis. The etiological agent is a dimorphic fungus (1307, 1308).

Gilchrist and Stokes cultured the fungus and named it Blastomyces dermatitidis (1309).

Adolfo Lutz (BR) was the first to describe a case of what later became known as South American blastomycosis (2165). This disease primarily attacks areas in and around the mouth and may invade lymphatics of the neck. It has also been called paracoccidioidal granuloma and Lutz-Splendore-Almeida’s disease because Alfonso Splendore (BR) and Floriano Paulo de Almeida (BR) also contributed to defining South American blastomycosis caused by Paracoccidioides brasiliensis (791, 3236).

Jorge Lobo (BR) described lobomycosis or lacaziosis, a keloidal blastomycosis of the skin caused by Lacazia loboi (formerly named Loboa loboi) which is indigenous to South America (2108).

Édouard Joseph Louis Marie van Beneden (BE) coined the term Mesozoa to include animals intermediate in structure between Protozoa and Metazoa (3428).

Karl Wilhelm von Kupffer (DE) discovered stellate liver cells, which bear his name. However, he incorrectly believed that these cells were an integral part of the liver blood vessel's endothelium (3589).

Tadeusz Browicz (PL) correctly identified them as macrophages (474).

David Starr Jordan (US), while a high school teacher in Wisconsin, authored Manual of the Vertebrates of the Northern United States. This is a remarkable book, which became the bible of many an early naturalist (1757).

Joel Asaph Allen (US) wrote important monographs on Bison and the pinnipeds of North America (34, 36).

Joseph Marie Jules Parrot (FR) was the first to describe the primary lesion in pulmonary tuberculosis in children (Gohn’s primary focus) (2644).

Louis Alexis Normand (FR) found a novel minute worm (Strongyloides stercoralis) about 0.25 mm in length in the feces of troops who had been repatriated from Cochin-China (Vietnam) with diarrhea. He was the first to describe this parasitic nematode (1426, 2527).

Arthur Réné Jean Baptiste Bavay (FR) realized that some specimens sent to him by Normand were the adult worms of the larvae that were found in the feces (144).

Karl Georg Friedrich Rudolf Leuckart (DE) discovered the alternation of generations involving parasitic and free-living phases of Strongyloides (2048).

Paul van Durme (BE) discovered that infection occurs through the skin (3441).

Arthur Looss (DE) purposely infected himself by putting larvae of Strongyloide stercoralis on his skin and finding larvae in his feces 64 days later (2128).

Friedrich Fülleborn (DE), working with dogs, described the phenomenon of autoinfection and discovered how Strongyloides stercoralis (and also Ancylostoma spp.) migrates around the body before ending up in the intestine (1240).

Paul Emil Flechsig (DE) discovered unequal degree of crossing of the pyramidal tracts in the brain. This supported the idea that the brain possesses asymmetry in some of its internal arrangements (1151).

Étienne Jules Marey (FR) explored the nature of cardiac excitability and, in 1876, determined that the heart could be excited by an electrical stimulus only during diastole (2238). In 1896, he described the unexcitable phase of the cardiac cycle as the 'refractory period'. See, Fontana, 1780.

Giovanni Paladino (IT) reported atrial fibers descending over the AV valves and ventricular fibers ascending into the same areas and making connections with the atria. He speculated about the function of these fibers in AV valve closure and heart block. (2622).

Albert Frank Stanley Kent (GB) discovered a similar bundle, which runs from the posterior wall of the right atrium to the ventricular septum, permitting premature excitation of the ventricles by the sinus node. He concluded, “The muscular connections between the auricle and ventricle in the heart of man is not single and confined to the AV bundle but is multiple (1789-1791). The work of Paladino and Kent is the discovery of the cardiac “bundle of Kent.”

Wilhelm His, Jr. (CH-DE) researched the development of the embryonic heart during which he discovered the auriculo-ventricular bundle (bundle of His), also called the fasciculus atrioventricularis. He demonstrated that there is a muscular AV connection, and was the first to describe the function of this AV conduction system (1593).

Wilhelm His, Jr. (CH-DE) showed that following section of the A-V bundle, the auricular and ventricular beats became dissociated (1594). It would later be realized that this observation explained the Adams-Stokes syndrome (slow pulse, vertigo, and epileptoid seizures).

Karel Frederik Wenckebach (NL-AT) discovered the cardiac anatomical structure named for him: the Wenckebach bundle. It is the median bundle of the conductive system of the heart leading to the atrioventricular node (3714, 3715).

Sunao Tawara (JP) and Karl Albert Ludwig Aschoff (DE) discovered the auriculoventricular (AV) node of the heart, a small node of modified cardiac muscle that transmits the impulses originating in the sinus node down to the ventricles. It is the beginning of the auricular-ventricular bundle of His (68, 3304). Today it is called the Aschoff-Tawara node or the AV node.

Arthur Berridale Keith (GB), and Martin William Flack (GB) discovered the sinoauricular node (SA) of the heart, often called the pacemaker of the heart and noted that the auriculo-ventricular system discovered by His, Paladino, and Kent is but part of a system of fibers which extend to the whole heart and determine its rhythm (1784). It is also called the Keith-Flack node or sinus node.

Jean George Bachmann (FR-US) described the interatrial bundle (Bachmann’s bundle) as an interatrial link allowing conduction from the right to the left atrium (86).

Ivan Mahaim (BE) and A. Benatt (BE) in a series of comprehensive serial-section studies, showed that in man, dog, sheep, calf, rabbit and cat, small connections are frequently present between the bundle of His and the origin of the left branch and the septum and, occasionally, between the A-V node and the septum. In the rabbit and cat, such connections are commonly found between the beginning of the right branch and septum, but this is never found in man (2208, 2209). Note: The term “Mahaim fibers” refers to atriofascicular bypass tracts that connect the right atrium to the distal right bundle.

Thomas Naum James (US) identified bypass fibers of an internodal connection. This represents a circumvention of the AV node, originating in the atrial conduction system and running below the AV node and extending to the bundle of His and to the fascicles (1744).

Thomas John MacLagan (GB) was the first European physician to treat acute rheumatism with salicin (salicylates) (2188).

Ernst Viktor von Leyden (DE) gave the first description of myotonia congenita (delayed muscle relaxation and muscle stiffness) (3592).

Asmus Julius Thomas Thomsen (DK) gave a comprehensive description of myotonia cogenita as found in his family. He discussed 20 cases and tracked the trait through six generations of his family (3336-3338). Today it is called Thomsen’s disease.

George Armstrong Custer (US), 36 year old general and military commander at the battle of the Little Bighorn, in 1876, probably suffered from histrionic personality disorder (2215).

Karl Alfred von Zittel (DE) created a systematics of the organic fossil record in his monumental work, Handbuch der Palaeontologie. In it he discussed fossil animals from protozoa to mammals. He was the first to investigate fossil sponges by zoological methods. Zittel later wrote Geschichte der Geologie und Paläontologie, an encyclopedic historical survey of geology and paleontology (3636, 3637).

Wilhelm His, Jr. (CH) and Christian Ludwig Braune (CH) established the journal Zeitschrift für Anatomie und Entwicklungsgeschichte. It later became the anatomical part of the Archiv für Anatomie und Physiologie.


“I recall my student days and the impression made upon us by a man like Johannes Müller, the physiologist. When one feels himself in contact with a man of the first order, the entire scale of his intellectual conception is modified for life; contact with such a man is perhaps the most interesting thing life has to offer.” Hermann Ludwig Ferdinand von Helmholtz (DE), probably from Das Denken in der Medizin [On Thought in Medicine], a lecture delivered in 1877 (3561).

“Perhaps one must have witnessed the eyes of a dying patient as well as the grief and desperation which befalls the affected families in order to ask oneself the crucial question: was everything possible done to avoid the tragedy? Did, indeed, science furnish all the possible knowledge and aid in such a situation? Therefore, the theoretical questions can acquire dimensions and practical implications, which go far beyond the merely methodological issues. The theoretical investigator may smile glibly and remain detached, his imagination and pride may even flourish for a time in the isolation of his untroubled laboratory. He may even find the older prejudices interesting and excusable, labeling them as mere reflections of poetical romanticism and youthful ecstasy. Those, however, who have to struggle with the real adverse powers, cannot be indifferent or romantic. They always have to test critically what they know and are able to do, and use only the harsh light of facts, rather than entertaining pleasant illusions.” Hermann Ludwig Ferdinand von Helmholtz (DE) (3561).

Paul Ehrlich (DE) made the first systematic study of the biological staining properties of the new synthetic aniline dyes following William Henry Perkin’s discovery of mauve in 1856. Ehrlich was the first to identify mast cells and showed that eosinophil leukocytes were produced by the bone marrow(987). He realized that the nuclear region of cells had an affinity for basic dyes therefore he referred to them as basophilic.

Ralph O. Smith (US) and W. Barry Wood, Jr. (US) explained the important role of mast cells in an anti-infectious response (3204).

Earl P. Benditt (US), Joel S. Bader (US), and Phillip K.N. Lam (US) discovered the association between mast cells and histamine (164). 

Ivan Mota (US) discovered the link between mast cells and inflammation thus laying the foundations for modern research into allergy and anaphylaxis (2397).

Pierre Émile Duclaux (FR) introduced the custom of designating an enzyme by the name of the substrate on which its action was first reported and adding the suffix-ase (918).

Carbon disulfide was first recommended in the U. S. as a fumigant for insect control (3161).

Max Jaffé (DE) discovered that when he fed benzoic acid to birds they detoxified it by conjugating it with ornithine (diaminovaleric acid) (Greek ornithos, bird) which they excreted as ornithuric acid from which he prepared ornithine chloride (1741).

Nathanael Pringsheim (DE) discovered asexual reproduction and alternation of generation in the bryophytes (liverworts and mosses) (2801).

Arthur Downes (GB) and Thomas P. Blunt (GB) reported that sunlight kills bacteria, and showed that this effect is chiefly associated with the short wavelength component of the radiation (891).

Niels Ryberg Finsen (DK) discovered that light in the ultraviolet range kills bacteria. He called these waves from the blue and ultraviolet area chemical waves (1095).

Niels Ryberg Finsen (DK) used light to successfully treat certain skin diseases such as lupus vulgaris (cutaneous tuberculosis) (1096-1098).

Frederick L. Gates (US) related the effective wavelengths of ultraviolet radiation for killing bacteria to its observed absorption by nucleic acids (1278-1280).

Alexander Hollaender (US) and Chester W. Emmons (US) determined that radiation with a wavelength of 2650 angstroms appears to be the most mutagenic and fungicidal within the ultraviolet range. They noted that 2650 angstroms coincides with the high absorption coefficient of nucleic acids near this wavelength (1617). 

Carl Weigert (DE), in 1877, at a scientific meeting in Munich, showed stained sections of dog spleen, lung, and kidney infected with anthrax. The anthrax organism could be distinctly seen in contrast to the tissues (621).

John Tyndall (GB) developed a method for heat killing endospores without having to resort to extremely high temperatures. This involved heating at 100°C. on successive days until the medium was sterile. Temperatures of 100°C. kills all cells other than endospores which are stimulated to germinate by the heat and nutrients present. Once they have germinated the second round of heating will kill them. Three or more rounds may be necessary to render the sample sterile. The process is today called Tyndallization (3413).

Louis Pasteur (FR) and John Tyndall (GB), the one a chemist, the other a physicist, neither of them medical but both trained in the most exact methods of experimentation, jointly accomplished the final downfall of the doctrine of spontaneous generation (517).

Heinrich Hermann Robert Koch (DE) was the first to prepare and stain thin films of bacteria on cover glass. In his early staining methods he used methyl violet 5B, fuchsin, and aniline brown. He was the first to stain bacterial flagella. For this he employed logwood extract (hematoxylin) followed by chromic acid (1842).

Albert B. Frank (DE) coined the term “symbiotismus” (symbiosis) “ ...where two different species live on or in one another under a comprehensive concept which does not consider the role which the two individuals play but is based on the mere coexistence and for which Symbiosis is to be recommended”(1200, 3035).

Heinrich Anton de Bary (DE) adopted the term “symbiose,” defining it as “the living together of unlike named organisms” (800, 3035).

Richard Caton (GB) reported finding nerve action potentials picked up from the frontal lobe of the brain of an anesthetized rabbit when, for example, light was directed to the contra lateral retina. These were later called evoked potentials. He was thus the first to record spontaneous electrical activity from the brain (571).

Francis Gotch (GB) and Victor Haden Alexander Horsley (GB) showed that electric currents are produced in the mammalian brain, and they recorded them with a string galvanometer of the capillary electrometer (1378).

Hans Berger (DE), while studying brain generated action potentials in animals discovered that the brain develops a low-level subaudio-frequency electrical activity. This discovery led to the establishment of a neurophysiological specialty known as electroencephalography (EEGy). In 1924, he made the first elektrenkephalogram (electro-encephalogram) (EEG) of a human and reported the discovery of rhythmic 10Kz waves (which he termed 'alpha waves') in subjects with eyes closed. In addition, he observed smaller amplitude faster frequency activity, which he called 'beta waves'. This work was reported in 1929 (176, 177). Alpha waves occur in adults who have their eyes closed or who are relaxed. Beta waves mainly occur in adults who are awake, alert or focused.

Edgar Douglas Adrian (GB) and Bryan Harold Cabot Matthews (GB), in 1934, confirmed Hans Berger’s findings of alpha and beta waves then discovered delta waves. Delta waves occur mainly in infants, sleeping adults or adults with brain tumors (21).

William Grey Walter (GB) proved that, by using a larger number of electrodes pasted to the scalp, each one having a small size, it was possible to identify abnormal electrical activity in the brain areas around a tumor, and diminished activity inside it (3671, 3672).

William Grey Walter (GB) and Vivian J. Dovey (GB) discovered theta brain waves in 1943. Theta waves occur mainly in children ages 2–5 years old (3673). 

Louis Pasteur (FR) and Jules Francois Joubert (FR) were the first to identify a pathogenic species of Clostridium, Clostridium septicum or Vibrion septique (2693).

Louis Pasteur (FR) and Jules Francois Joubert (FR) were probably the first to recognize antagonism (antibiosis) between microorganisms (Bacillus anthracis and other bacteria in culture) (2694). See, William Roberts, 1874.

Jean Jacques Theophile Schloesing (FR) and Achille Muntz (FR) proved that nitrification is a biological process in the soil by using chloroform vapors to inhibit the production of nitrate. One of the greatest practical applications of this knowledge was in the treatment of sewage (3070).

Theodor Wilhelm Engelmann (DE) proposed intercellular current flow (1017, 1018).

Howard J. Curtis (US) and David M. Travis (US) gave the first direct evidence for intercellular current flow (736).

Gualtherus Carel Jacob Vosmaer (NL) separated the sponges from the coelenterates. Ref A number of sea creatures were given genus and species names in his honor.

George Engelmann (DE-US) was a plant explorer and systematist centered in St.Louis. His collections formed the basis for the Missouri Botanical Garden begun by Henry Shaw (GB-US) in 1859 (1014).

Claude Bernard (FR) found that one of the primary signs of diabetes is an excess of sugar in the blood and usually in the urine, i.e., in diabetes there is primarily glycaemia followed by glycosuria (209).

Claude Bernard (FR) found evidence for a diastase (amylase) in the liver (210). When he purified this liver diastase he found that it could convert starch and glycogen to sugars. Bernard then concluded that sugar is formed identically in animals and plants. The complicated starch he reasoned is also decomposed to the simpler sugars, which are soluble, and can be circulated and assimilated (211).

Gabriel Madeleine Camille Dareste (FR) described the successful production of developmental monstrosities by experimental means (764).

Emil Heinrich du Bois-Reymond (DE), Thomas Renton Elliott (GB), and John Newport Langley (GB) expressed the concept that the nerve impulse should not pass from nerve to muscle by an electrical discharge but by the secretion of a special substance at the end of the nerve that we presently designate as a neurotransmitter. This is the idea of chemical synaptic transmission (902, 1009, 1010, 1971).

John Newport Langley (GB) was the first to suggest the presence of receptive substances on cells (1970).

Masaharu Noda (JP), Hideo Takahashi (JP), Tsutomu Tanabe (JP), Mitsuyoshi Toyosato (JP), Yasuji Furutani (JP), Tadaaki Hirose (JP), Michiko Asai (JP), Seiichi Inayama (JP), Takashi Miyata (JP), Shosaku Numa (JP), Sho Kikyotani (JP), Hideaki Takashima (JP), Toni Claudio (US), Marc C. Ballivet (CH), James W. Patrick (US), Stephen F. Heinemann (US), L. Boas (), John Forrest (US), Holly A. Ingraham (US), Pam Mason (US), Siegfried Stengelin (US), Satashi Ueno (US), N. Davis Hershey (US), Dan J. Noonan (US), Katharine S. Mixter (US), and Norman Ralph Davidson (US) would later contribute to the nicotine receptor being the first to be sequenced, cloned, and gene-sequenced (623, 1562, 2519-2521, 2700). This can be considered the origin of neuroendocrinology.

Richard Felix Marchand (DE) and Theodor Wilhelm Engelmann (DE) were the first to present graphically the time course of the variations in electric potential of the heart of lower animals, i.e., an electrocardiogram (1019, 2229).

Augustus Désiré Waller (FR-GB) confirmed that the human heart produces an electric current on contraction. “If a pair of electrodes (zinc covered by chamois leather and moistened with brine) are strapped to the front and back of the chest, and connected with a Lippmann's capillary electrometer, the mercury in the latter will be seen to move slightly but sharply at each beat of the heart…. The electrical variation precedes the heart's beat” (3658, 3659).

Gabriel Jonas Lippmann (FR-LU) invented the capillary electrometer used by Waller in his studies (2090).

J.W. Gordon (GB) introduced the concept of ballistocardiography (1375). A ballistocardiograph is an instrument that records the motions of the body imparted to it by the heartbeat.

Yandell Henderson (US) eloquently described ballistocardiography as follows: “Under the influence of the mass-movements of the circulation, the body recoils at each heart beat feetward, headward, and again feetward. By means of a "swinging table" these movements can be magnified one hundred times and recorded in the form of a "recoil curve." The amplitude of these recoil movements…is held to be proportional to the volume of the systolic discharge of the heart” (1538).

Isaac Starr (US), Arthur Joy Rawson (US), Henry A. Schroeder (US), and Norman Ross Joseph (US) coined the term ballistocardiogram (3243).

Julius Friedrich Cohnheim (DE) and Carl Julius Salomonsen (DK) confirmed Jean Antoine Villemin’s earlier claim that tuberculosis is infectious by inoculating tuberculous material into the anterior chamber of a rabbit’s eye, where the development of the lesion could be watched from day to day (658).

Friedrich Bezold (DE) provided the first clear description of mastoiditis (240, 241).

Jean-Martin Charcot (FR) wrote Lectures on the Diseases of the Nervous System, a very important book in the history of the neurosciences. In this book he described multiple sclerosis noting that the nerves are abnormally demyelinated, yet he did not appreciate the significance of this demyelination (592).

Derek Ernest Denny-Brown (NZ-GB-US) and Charles L. Brenner (US) observed that when a damaged nerve is stimulated, it fails to pass the impulse to the connected muscle. They concluded that it is the demyelination associated with lesions on the nerve that is responsible for the block in conduction and thus the symptoms of multiple sclerosis (846).

Francis Maitland Balfour (GB) observed that the medullary region of the adrenal gland is derived from ectodermal rudiments that also give rise to parts of the sympathetic nervous system, while the cortex arises from mesodermal buds (109).

Francis Maitland Balfour (GB) wrote his monograph on the development of elasmobranch fishes (110). This was the most important addition to vertebrate embryology since Johannes Muller.

James Paget (GB) described Paget’s disease of the bone (osteitis deformans) (2615).

Karl Friedrich Otto Westphal (DE) was the first physician to provide a clinical description of narcolepsy and cataplexy (3729).

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

R. Henneberg (DE) coined the term cataplexy .

Reginald Southey (GB) introduced Southey tubes as a means of removing large amounts of dependent edema -- up to 40lbs of fluid in 2 days. These tiny tubes (each 1 inch long) were inserted subcutaneously by means of a trocar in the dorsum of the foot and the lateral aspect of the lower leg. The trocar was then removed and the Southey tubes were connected to tubing, which emptied into a bucket (3219). These tubes are helpful in treating congestive heart failure.

Carl Philipp Adolf Konrad Kussmaul (DE) characterized agnosia as “They were neither inarticulate (incapable of speech) nor illiterate (incapable of writing); but despite an acute sense of hearing they could no longer comprehend words they heard or, despite good vision, they could no longer read the words they saw” (1940).

Carl Nicoladoni (AT) performed the first operation for an esophagus diverticulum (2502). He also is the originator of the concept of a gastroenterostomy.

Anton Wölfler (AT), in 1881, was the first to perform a gastroenterostomy. He by-passed a pyloric stenosis using anastomosis of the anterior surface of the stomach with the jejunum (3793, 3794).

Ernest-Charles Lasègue (FR) and Jean-Pierre Falret (FR) diagnosed a communal psychotic disorder sometimes referred to as "Lasègue-Falret syndrome" (folie à deux). The syndrome is characterized by the coincidental appearance of psychotic symptoms in family members while living together, as well as retention of the symptoms when the individuals are separated. This syndrome can also involve a situation where a diseased family member transmits psychotic symptoms to healthy members of the family (1981).

Ernst Felix Immanuel Hoppe-Seyler (DE) founded the journal Zeitschrift für Physiologische Chemie.

Othniel Charles Marsh (US) introduced and briefly described Apatosaurus ajax, (now known to be synonymous with Brontosaurus) (2243, 2245). Two years later he described and introduced Brontosaurus, thinking they were different animals (2244). Apatosaurus means “deceptive lizard”; Brontosaurus means “thunder lizard”


"I beseech you to take interest in these sacred domains so expressively called laboratories. Ask that there be more and that they be adorned for these are the temples of the future, wealth and well being. It is here that humanity will grow, strengthen and improve. Here, humanity will learn to read progress and individual harmony in the works of nature, while humanity's own works are all to often those of barbarism, fanaticism, and destruction." Louis Pasteur (3824).

“Now that he has departed from us, he has left us a rich heritage, but inestimable good has sunk into the grave with him. The one on whom his soulful eyes rested, who listened to the flow of his thoughtful words, who felt the pressure of his hand, will always long for him. Yet not only the friend, each one who in life and in science came in contact with his power, will mourn the death of a man, in whom were mingled in complete harmony a spirit as clear as his and a nature of such richness.”  Karl Friedrich Wilhelm Ludwig’s remarks at the Gedachtnissrede (memorial service) for Ernst Heinrich Weber (2121)

“There is a true interior environment that serves as an intermediary between the external world and life itself…. It is the internal environment that provides the physical needs for life." Claude Bernard (211). In volume 1 of this work on pages 273, 278-279, Bernard performed experiments demonstrating that respiration is common to all higher life forms, both plants and animals.

"I have, on many occasions, examined normal blood and normal tissues using methods that ensure that such organisms are not overlooked, and I have never, in a single instance, found bacteria. I therefore conclude that bacteria do not occur in the blood or tissues of healthy animals or humans." Heinrich Hermann Robert Koch (461, 1843).

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

H. Baum (?) synthesized the dye orange GG (acid orange 10). The main use of Orange G is in the OG-6 Papanicolaou stain, to stain keratin, however it is also a major component of the Alexander Test for pollen staining. It is often combined with other yellow dyes and used to stain erythrocytes in the trichrome methods. Orange G can be used as a color marker to monitor the process of agarose gel electrophoresis, running approximately at the size of a 50 base pair DNA molecule, and polyacrylamide gel electrophoresis. Ref

Adolf Johann Hubert von La Valette St. George (DE), in 1878, was the first to describe the Golgi apparatus (dictyosome). He found it in the head cap of the acrosome "samenkörper" (1945).

Bartolomeo Camillo Emilio Golgi (IT) discovered the cell organelle, which bears his name, Golgi apparatus or Golgi body, while studying cells of the spinal dorsal root ganglia where he observed a characteristic filamentous structure within the cell bodies. He also found this apparatus within Purkinje cells from the cerebellum of a barn owl. Golgi and his students would eventually induce the existence of this internal reticular apparatus in all eukaryotic cells. They called it apparato reticulare interno (1327, 1345, 1355, 2562).

Gustaf Platner (DE) also gave an early description of the "nebenkern" (Golgi apparatus) in snail spermatocytes (2761).

Emil Algot Holmgren (SE) described this organelle as canaliculi and observed it in a number of cell types (1621, 1622).

Santiago Ramón y Cajal (ES) coined the name Golgi-Holmgren canals (2843).

London purple was introduced in 1878. It was used for control of the Colorado potato beetle (3161).

Wilhelm Friedrich Kühne (DE) and Carl Anton Ewald (DE) isolated rhodopsin from retinas (1045, 1922, 1925, 3490).

Arthur Gamgee GB), ca. 1878, began spectral analysis leading to the conclusion that spectroscopy can distinguish unambiguously between the various forms of hemoglobin: the reduced form; the oxygenated form bound to oxygen; the form binding carbon monoxide; and methemoglobin in which the iron of the heme group is irreversibly oxidized to the ferric state. These results occurred regardless of the species of origin (1260).

Camille Jean Marie Méhu (FR) discovered that proteins are quantitatively precipitated from their aqueous solutions upon saturation with ammonium sulfate, and that they are not coagulated by this treatment. Once precipitated the proteins could be redissolved in water or in neutral salt solution remaining unaltered from their native state (2284, 3718).

Charles Otis Whitman (US) was the first to use the term cytokinesis to denote the cytoplasmic changes occurring during cell division (3733, 3763).

Edoardo Perroncito (IT) described and isolated the bacterial agent of fowl cholera (Pasteurella multocida), a serious disease of chickens in Italy (2722, 2723). 

Jean-Joseph-Henri Toussaint (FR) also isolated the bacterial agent of fowl cholera (3372, 3373). The agent was eventually named Pasteurella multocda.

Paul Bert (FR) laid the foundation of knowledge of the physiological effects of air-pressure, both above and below atmospheric pressure. From his experiments he concluded that pressure does not affect man physically, but rather chemically by changing the proportions of oxygen in the blood. Too little creates oxygen deprivation and too much creates oxygen poisoning. He showed that pure oxygen under high pressure can be deadly and to this day Central Nervous System (CNS) oxygen toxicity is known as the ‘Paul Bert Effect’. He established the principle that it is the partial pressure of a gas-not its percentage in the atmosphere that has physiological importance. Bert reasoned that divers and caisson workers should decompress slowly and at a constant rate “for they must not only allow time for the nitrogen of the blood to escape but also to allow the nitrogen of the tissues time to pass into the blood.” When the pressure is released quickly, nitrogen boils-off producing pain (the bends) (220, 221).

Arthur E. Boycott (GB), Guybon C. Damant (GB), and John Scott Haldane (GB) were the first to apply a scientific approach to predicting decompression and their methods form the basis of the majority of modern decompression theories. They developed practical dive tables based on research that included slower ascent rates as the diver approached the surface (385).

Karl Brandt (DE), M.A. Certes (FR) and Paul Ehrlich (DE) introduced true vital staining to biology. In 1878, Brandt used bismarck brown to color granules in living Actinosphärium. Certes recommended a weak solution of cyanin for staining live infusoria, and Ehrlich used methylene blue to stain the nervelets in the intestine of the mouse. Certes also introduced the vital staining of leukocytes, using cyanine and quinolene blue for the differential staining of frog's leukocytes and noticed that they retained their motility for a short time course while taking up the dye (399, 579-581, 995).

Louis-Antoine Ranvier (FR) discovered myelin and the short specialized interruptions in the myelin sheath occurring along myelinated nerve fibers (2848). These interruptions, called the nodes of Ranvier, permit saltatory conduction.

Charles Emmanuel Sédillot (FR) coined the word microbe to refer to all living things, which cannot be seen with the unaided eye (1952, 3155).

Joseph Lister (GB), while studying the lactic acid fermentation, succeeded in obtaining an axenic culture of bacteria by diluting to the point that growth took its origin from one cell, often called dilution to extinction. He named the organism Bacterium lactis (2099). This dilution technique is also the principle underlying the Most Probable Number method for estimating the number of bacteria in a liquid. See, Theodor Albrecht Edwin Klebs, 1873.

Heinrich Hermann Robert Koch (DE) introduced the logical steps for relating a specific microorganism with a specific disease. We now habitually refer to these steps as Koch’s postulates. The 1884 paper was the first time they appeared in print (1843, 1849). He also identified staphylococci in human pus.

Louis Pasteur (FR), Jules Francois Joubert (FR), and Charles Édouard Chamberland (FR) present their germ theory of disease (2695).

Louis Pasteur (FR), Jules Francois Joubert (FR), and Charles Édouard Chamberland (FR), in 1878, credited Schwann as the real founder of the germ theory of fermentation (1209).

Timothy Richards Lewis (GB) reported that microscopic organisms found in the blood of man and other animals could cause disease (2057).

Heinrich Hermann Robert Koch (DE) isolated Erysipelothrix muriseptica from mice, which had been injected with putrefying blood (1843).

Anton Julius Friedrich Rosenbach (DE) isolated the same organism as above from erysipeloid infections in man and named it Erysipelothrix rhusiopathiae. The patient exhibited localized cutaneous lesions, thus establishing this organism as a human pathogen (2966, 2967). Erysipelothrix rhusiopathiae causes a disease known as erysipelas in animals and erysipeloid in humans. The human disease called erysipelas is not caused by E. rhusiopathiae, but by various members of the genus Streptococcus.

George Francis (AU) reported the first documented case of lethal intoxication of livestock by drinking water. The water came from Lake Alexandrina in South Australia, which was heavily infested with blue-green algal (cyanobacterial) blooms (557, 1199).

Michael Stephanovitch Woronin (DE) was the first to describe the fungus Olpidium brassicae (3798).

Patrick Geddes (FR) found that certain green planaria were in fact green because they contained symbiotic algae. He argued that the alga involved was not a parasite and the relationship was one of mutual benefit (1291-1293).

Berthold Hatschek (CZ-AT) proposed the trochophore theory which states that the trochophore is the larva of an ancestral form, the trochozoon, which was the common ancestor of most, if not all, the bilateral phyla, and which, of living forms, most nearly resembled a rotifer (1506).

Coenraad Kerbert (NL) described the lung fluke, Distoma westermanii, from the lungs of a tiger in the Amsterdam Zoo (1792). 

Sydney Ringer (GB), in 1879, was the first to report a clinical case of lung-fluke infection (human paragonimiasis, pulmonary distomiasis, endemic hemoptysis). It was from a postmortem examination of a Portuguese patient, who had died of a ruptured aortic aneurysm. At autopsy, Ringer found, in addition to the aneurysm, a parasite in the lungs (1426, 2446).

Maximillian Gustav Christian Carl Braun (DE) suggested the name Paragonimus westermani for the fluke (407).

Erwin Otto Eduard von Baelz (DE) and Patrick Manson (GB) independently recognized the eggs of Paragonimus westermani in the sputum of man. Manson also suggested that a snail might act as an intermediate host (115, 2221).

Koan Nakagawa (JP), Sadamu Yokogawa (JP), Harujiro Kobayashi (JP), and Keinosuke Miyairi (JP) reported on the whole life cycle of the lung fluke in the snail Semisulcospira (1836-1839, 2363, 2364, 2465-2470, 3816, 3817).

Fritz Müller; Johann Friedrich Theodor Müller (DE) in discussing mimicry explained that predators must learn through warning characteristics which species are palatable, and that in the process some of the prey population must be sacrificed (2422-2424). 

Adam Politzer (AT) wrote Lehrbuch der Ohrenheilkunde, the most outstanding textbook on the ear in the 19th and 20th centuries (2769).

Rudolf Peter Heinrich Heidenhain (DE) described a new technique, which he had developed to study secretion of digestive juices in dogs. The technique was named after him. Heidenhain’s pouch is a procedure in which part of the stomach is isolated from the main body of the organ (1522). One common use of the Heidenhain pouch in dogs or its equivalent in the rat, over the past fifty or so years, has been the development of drugs which reduce stomach-acid secretion. These drugs include those acting upon the histamine system such as cimetidine, or the ‘proton pump inhibitors’ like omeprazole, which act upon another stomach enzyme.

William Richard Gowers (GB) found that unilateral lesions of the spinal cord, which cause loss of sensibility of the skin, do so on the side opposite to the lesion. Painful sensations are conducted in the lateral column, those of touch in the posterior column (1381).

Martin Max Bernhardt (DE) described meralgia paraesthetica (BernhardtRoth syndrome) as a distinctive condition, more common in men than in women, characterized by paresthesia and often burning pain over the anterolateral aspect of the thigh (213). Note: Compression in the groin is the common cause.

Vladimir Karlovich Roth (RU) described the same condition, coining meralgia paraesthetica in the process (2973). 

Richard Volkmann (DE) performed the first excision of carcinoma of the rectum (3493).

Wilhelm Alexander Freund (DE) undertook the first abdominal extirpation of a cancerous uterus. It was not reported until 1885 (1215).

Pierre Paul Broca (FR) described and named the great limbic lobe of the brain (459). Limbic implies no function or theory, and has no definite shape.

Yellow fever again swept through New Orleans, Memphis, and the Mississippi and Ohio River valleys (1863).

Journal of Physiology (London) was founded.


William Crookes (GB) was the first person to confirm the existence of cathode rays (x-rays) by displaying them, with his invention of the Crookes tube, a crude prototype for all future cathode ray tubes (727).

Pierre Eugène Marcellin Berthelot (FR) coined the terms endothermic and exothermic (225).

Paul Ehrlich (DE) showed that all dyes can be described as possessing either basic, acidic, or neutral character and introduced the use of aniline dyes to stain specific granulations in white blood cells which he clearly recognized fell into three categories: acidophilic, basophilic, and neutral. He was the first to classify the blood granulocytes into the three types we know today (989-991).

Paul Ehrlich (DE) discovered the eosinophil when he stained fixed blood smears with aniline dyes (1588).

Heinrich Ferdinand Edmund Drechsel (DE) and Georg Grübler (DE) crystallized protein from Bertholletia (Brazil nuts), pumpkin seed (Cucurbita) and squash seed respectively. They allowed a warm sodium chloride solution saturated with the protein to cool slowly, whereupon crystals appeared (897, 1428).

Albrecht Karl Ludwig Martin Leonard Kossel (DE), Albert Neumann (DE), and Henry Drysdale Dakin (US) showed that the nuclein first isolated by Johann Friedrich Miescher (CH) contains a protein and a nonprotein portion. The protein portion was much like other proteins, but the nonprotein portion was unlike any other natural product known until that time. When he broke down the nonprotein part Kossel found that it contained purines and pyrimidines. He isolated two different purines (a name coined by Hermann Emil Fischer): adenine and guanine, and a total of three different pyrimidines: thymine, uracil, and cytosine. He obtained from goose erythrocytes a peptone-like substance (he named it histone) that readily combined with nuclein to form a nucleohistone. He also recognized that the nonprotein part contained a carbohydrate, but he failed to identify it (1873-1875, 1878, 1885, 1886, 1889).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) discovered that DNA contains guanine (1876, 1877).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Albert Neumann (DE) discovered that DNA contains adenine and thymine (1879-1884, 1887, 1888).

Alberto Ascoli (IT) described uracil (69).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Hermann Z. Steudel (DE) discovered that DNA contains cytosine (1890).

Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Hermann Z. Steudel (DE) discovered that DNA contains uracil (1891).

Bartolomeo Camillo Emilio Golgi (IT) and R. Rezzonico (IT) reported on the histological structure of myelin. They said that it appeared in the guise of a chain of conical funnels inserted into each other, through which passes the nerve fiber (1357, 1358).

LouisAntoine Ranvier (FR) confirmed this observation (2847).

Fredrick Schmitz (DE) reported syngamy, the fusion of the male and female gametes in plants (3082).

T. Arnold (DE) made drawings of human chromosomes in cancer cells (sarcoma) (61).

Timothy Richards Lewis (GB) found parasitic trypanosomes in the blood of healthy rats (Trypanosoma lewisi) in India (2058).

George Evans (GB) found parasitic trypanosomes (Trypanosoma evansi) in horses and camels in India (1044). 

Albert Ludwig Siegmund Neisser (DE) discovered that “If gonorrheal pus is spread out in…a layer, allowed to dry, stained by…methyl violet…a number of…masses of micrococci are seen…. They have a…characteristic, typical form…. These characteristic micrococci…appear to be a constant mark of all gonorrheal affections…” (2481). The organism was later named Neisseria gonorrhoeae. Neisser may have been the first to attribute a chronic human disease to a microorganism.

Frédéric Weiss, (FR) isolated Neisseria gonorrhoeae (3708).

Leo Leistikow (DE) isolated Neisseria gonorrhoeae (2021, 2022). 

Ernst Bumm (DE) grew axenic cultures of Neisser’s gonococcus, Neisseria gonorrhoeae, and proved by inoculations of humans that it causes gonorrhea (518, 519).

Ernst Wertheim (AT) demonstrated the existence of gonococcus in tissue of the Fallopian tubes in 1890. By 1892 he had established his theory that gonococci can ascend the female reproductive tract (3722).

Ernst Wertheim (AT) demonstrated the gonococcus in acute cystitis (3723).

Ernst Wertheim (AT) emphasized the importance of latent uterine gonorrhea (3724).

Theodor Albrecht Edwin Klebs (DE) successfully inoculated monkeys with syphilis (1826).

Pierre Victor Galtier (FR) became the first to successfully pass rabies from dogs to rabbits and then from rabbits back to dogs, confirming that rabies is some sort of infectious disease (1254).

Louis Pasteur (FR) found anthrax endospores in the soil above an anthrax carcass buried ten months previously. He and his assistants, Charles Édouard Chamberland (FR) and Pierre Paul Émile Roux (FR) concluded that the endospores in the buried anthrax carcass had been gradually brought to the surface of the soil by earthworms (2678, 2685-2687).

Erwin Otto Eduard Bälz (DE) and K. Kawakami (JP) were the first to recognize the disease known as tsutsugamushi in certain isolated river valleys in Japan (116). The etiological agent was later determined to be rickettsial.

Heinrich Gustav Adolf Engler (DE) and Karl Prantl (DE), in Das Pflanzenfamilien, worked out a plant classification scheme, which became the most influential systematic authority since Linnaeus. This system, covering the plant kingdom to the generic level, held authority until the 1970s (1030, 1031). His multi-authored Syllabus der Pflanzenfamilien was published at intervals to keep the scheme updated.

Engler founded and edited (from 1881) the periodical Botanische Jahrbücher.

Charles Edwin Bessey (US), in his The Phylogenetic Taxonomy of Flowering Plants, asserted that plants with bisexual flowers with numerous petals, sepals, etc., were the basic types from which the reduced kinds, for example, willows, oaks, and birches, representing several unrelated but superficially similar lines, were derived (233-235). This contradicted one of Engler and Prantl's basic tenants.

Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp August Häcke; Ernst Heinrich Philipp August Heckel (DE) wrote Das System der Medusen which was largely responsible for the medusa classification that we still use today (1461).

Giovanni Battista Grassi (IT), Corrado Parona (IT), and Ernesto Parona (IT) described the life cycle of Strongyloides stercoralis (a parasitic nematode) (1398). The organism was first described in 1876 in French soldiers returning from Cochin China (now Vietnam) who were suffering from intractable diarrhea.

Jean Henri Casimir Fabre (FR) wrote Souvenirs Entomologiques, a ten-volume work, which includes studies on the anatomy and behavior of wasps, bees, and many other insects (1049).

Sigmund Exner (DE) stated that reaction time course (time between stimulus and response) is often devoid of free will (1046).

Wilhelm August Oskar Hertwig (DE) and Richard Karl Wilhelm Theodor von Hertwig (DE) developed the germ theory proposed by Ernst Heinrich Philipp August Haeckel (DE), that all organs and tissues are derived variously from three basic tissue layers. What Haeckel called Gastraea-Theorie the Hertwigs would call Coelomtheorie. The Coelomtheorie suggests that development of all germ layers can be explained by the simple principle of epithelium folding (1458, 1460, 1565-1567, 1569-1571).

Ivar Victor Sandström (SE) discovered the parathyroid glands and named them glandulae parathyreoideae (3034). See, Owen, 1862.

Gerhard Engel (DE) and Friedrich Daniel Recklinghausen (DE) described osteitis cystica (primary hyperparathyroidism syndrome) (1011, 2882).

Max Askanazy (DE) was the first to associate osteitis fibrosa cystica with tumors of the parathyroid gland (70).

Jakob Erdheim (AT) demonstrated that the four parathyroid glands are enlarged in osteomalacia and in rickets, concluding correctly that this was a compensatory phenomenon. He showed that when he removed the parathyroid glands in rats, their teeth lost calcium (1035).

William George MacCallum (US) and Carl Voegtlin (US) showed that administration of calcium salts relieved the symptoms of tetany and that the parathyroid glands control calcium metabolism. They determined that an animal deprived of the parathyroids developed calcium diabetes with loss of large amounts of calcium in the urine (2175, 2176).

William Stewart Halsted (US) successfully treated patients with tetany by the administration of beef parathyroids, thus establishing the strong possibility that these glands helped regulate the blood content of calcium (1474, 1475).

James Bertram Collip (CA) isolated parathormone, the active ingredient of the parathyroid glands. It acts to prevent or control parathyroid tetany and regulate the level of blood calcium (667).

Douglas Harold Copp (CA), E. Cuthbert Cameron (CA), Barbara A. Cheney (CA), A. George F. Davidson (CA), and Kurt G. Henze (CA) discovered a hypocalcemic factor released only from the parathyroids as a result of hypercalcemia. They suggested that it be named calcitonin (691).

Henri-Louis Roger (FR) described a form of congenital heart disease which would later bear his name (Roger disease) as follows: “A developmental defect of the heart occurs from which cyanosis does not ensue in spite of the fact that a communication exists between the cavities of the two ventricles and in spite of the fact that admixture of venous blood and arterial blood occurs. This congenital defect…is even compatible with a long life” (2957).

William Murrell (GB) introduced nitroglycerin to treat angina pectoris (2454).

Heinrich Obersteiner (AT) described concussion of the spinal cord and status epilepticus (2549). He wrote an important volume on general paresis and tabes dorsalis, also a neurology text on the anatomy of the nervous system (2550). He published much on nerve fibers, granular cells of the cerebellum, and on pigment in nerve cells. With Emil Redlich (AT) he demonstrated that tabes dorsalis is a disease of the posterior roots (2551).

William Allen Sturge (GB) and Frederick Parks Weber (GB) described a congenital disorder exhibiting a port-wine nevi on the scalp along the distribution of the trigeminal nerve, combined with glaucoma and intracranial vascular abnormalities. A right-sided hemiplegia, accompanied by left-side brain lesions is also typical (Sturge-Weber syndrome) (3286, 3690).

Pierre Paul Broca (FR) was interested in the circulatory changes associated with mental activities as manifest by changes in brain temperature. He studied the effect of various mental activities, especially language, on the localized temperature of the scalp of medical students. Although such measurements might seem unlikely to yield any useful information, the reported observations, unbiased by preconceived notions of the functional anatomy of the cortex, were remarkably perceptive (460).

Angelo Mosso (IT) conceived the plethysmograph, a device that could measure cerebral blood flow variations by recording brain pulsations in patients with skull defects (2391, 2392).

Angelo Mosso (IT) developed the ‘human circulation balance’ to measure brain activity in normal patients. A delicately balanced table which could tip downwards either at the head or the foot if the weight of either end were increased. He stated that the increase in cerebral blood flow was thus proportional to the complexity of a cognitive task, and he further measured the cerebral response to emotional stimuli, both in isolation and in interaction with cognition. Mosso noticed that subjects did not react equally to the same stimulus (2393-2396).

Charles Smart Roy (GB) and Charles Scott Sherrington (GB) concluded that, “The chemical products of cerebral metabolism contained in the lymph which bathes the walls of the arterioles of the brain can cause variations of the caliber of the cerebral vessels; … in this reaction the brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with local variations of functional activity” (2986).

Henry S. Forbes (US) and Stanley Cobb (US) supported them and concluded that carbon dioxide is a major regulator of vasomotor activity in the brain (1182).

John F. Fulton (US) reported on a patient presenting with an arteriovenous malformation of the occipital cortex. Surgical removal of the malformation was attempted but was unsuccessful, leaving the patient with a bony defect over the primary visual cortex. Fulton elicited a history of a cranial sound audible to the patient whenever he engaged in a visual task. Based on this history Fulton pursued a detailed investigation of the behavior of the sound that he could auscultate and record over the occipital cortex. Remarkably consistent changes in the character of the sound could be appreciated depending upon the visual activities of the patient. Although opening the eyes produced only modest increases in the intensity of the sound, reading produced striking increases (1241). Cortical blood flow is thus related to the complexity of the visual task and the attention of the subject to that task.

Paul R. Dumke (US), Carl Frederic Schmidt (US), and Harry H. Pennes (US) made the first quantitative measurements of the cerebral blood flow in lightly anesthetized macaque monkeys and determined cerebral oxygen consumption in the same state and under deeper anesthesia as well as convulsive activity (932, 3075).

Seymour Solomon Kety (US) and Carl Frederic Schmidt (US) described a quantitative method for measuring cerebral blood flow in humans using nitrous oxide (Kety-Schmidt technique) (1794, 1795, 3074). The method is based upon the uptake by the brain of the diffusible nitrous oxide supplied by way of the arterial blood. These works led directly or indirectly to the development of current methods for the measurement of regional blood flow, metabolism, and the visualization of functional activity throughout the human brain.

Fritz A. Freyhan (US), Rachel B. Woodford (US), Seymour Solomon Kety (US), Darab K. Dastur (US), Mark H. Lane (US), Douglas B. Hansen (US), Robert N. Butler (US), Seymour Perlin (US), and Louis Sokoloff (US) concluded that cerebral circulation and oxygen consumption are not diminished in the normal elderly individual, but show a significant reduction, highly correlated with the degree of mental impairment, in senile dementia (773, 1223).

William M. Landau (US), Walter H. Freygang, Jr. (US), Lewis P. Rowland (US), Louis Sokoloff (US), and Seymour Solomon Kety (US) provided their results of quantitative changes in blood flow in the brain related directly to brain function (1793, 1956).

Renward Mangold (US), Louis Sokoloff (US), Eugene Conner (US), Jerome Kleinerman (US), Per-Olof Therman (US), and Seymour Solomon Kety (US) found that during sleep there is no decrease in oxygen consumption by the brain (2218).

Niels A. Lassen (DK), Kai Hoedt-Rasmussen (DK), S.C. Sorensen (SE), Erik Skinhøj (SE), Sten Cronquist (SE), Bengt Bodforss (SE), David H. Ingvar (SE) and Jarl Risberg (SE) were the first to directly demonstrate in normal human subjects that cerebral blood flow changes regionally during changes in brain functional activity (1710, 1984, 1985).

Vincenz Czerny (CZ-DE) performed the first total hysterectomy by the vaginal route (750).

Jules Émile Péan (FR) performed the first resection of the stomach for cancer (2707). The operation was unsuccessful.

Ludwik Rydygier (PL) was the second to perform partial stomach resection. It was to relieve a carcinomatous pylorus associated with peptic ulcer disease. His patient survived for 12 hours (2999). Rydygier introduced the technique of resection better known as the Billroth I procedure.

Christian Albert Theodor Billroth (AT) performed the first successful resection of the stomach. It was performed on a 43-year-old woman with pyloric cancer. A 14 cm portion of stomach was excised and an anastomosis of the remaining stomach to the duodenum was fashioned with about 50 carbolized silk sutures. Using chloroform anesthesia he took an hour and a half to remove the cancer (261, 2998).

Walter Hermann Heineke (DE) first described a pyelotomy (surgical incision into the renal pelvis of a kidney) for the extraction of calculi from the renal pelvis in 1879. Ref

Charles Alfred Ballance (GB), Hamilton A. Ballance (GB) and James Purves Stewart (GB), in 1895, performed the first reported facial nerve to spinal accessory nerve anastomosis for treatment of facial palsy (112). Note: there is circumstantial evidence that Thomas Drobnik (PL), in 1879, performed the first anastomosis of the proximal branch of the spinal accessory nerve to the distal branch of the facial nerve.

Jean-Louis Faure (FR) and Francis Furet (FR), in 1898, performed a faciospinal-accessory anastomosis for traumatic division of the facial nerve (1063).  

William Alvin Macewen (GB), in 1879, was the first to perform a bone allograft in humans. Using the tibia of a child with rickets, he transplanted the allograft onto the humeral shaft of a young boy whose humerus was lost through osteomyelitis. This work was described in 1881 (1752, 2179). The allograft was a success because Macewen operated under antiseptic conditions as introduced by Joseph Lister.

William Alvin Macewen (GB) originated neurosurgery when he performed exeresis of a meningioma (2180). 

Henri Judet (FR) reported a whole-joint transplantation — femur, tibia and patella — in the knee joint of man. The procedure, as he described, could be carried out to treat the trauma of infective arthritis or tuberculosis (540, 1760).

R. Geoffrey Burwell (GB), Gerald Gowland (GB) and F. Dexter (GB) showed that the bone marrow was responsible for the immune response to fresh allogenic bone and that frozen bones performed better compared to fresh allogenic bones. More significantly, their experiments shed light on the science of bone preservation and led to the development of the protocol for bone preservation we use today (534-539, 541-543).

Leif T. Ostrup (US) and John M. Frederickson (US) performed the first free vascularized bone graft (2593). 

 Charles Lapworth (GB) defined the Ordovician System of strata to resolve the Murchison-Sedgwick conflict over their overlapping claims for their Silurian and Cambrian systems (1979). The Ordovician Period of the Paleozoic Era (from the name of an ancient British tribe, the Ordovices) extended from 505 Ma until 438 Ma. At the end of the Cambrian, sea levels fell, causing extinctions. It was in the Ordovician that the first animals with backbones arose, the Agnatha, these jawless fishes were the first animals with true bony skeletons. The Ordovician is best known for the presence of its diverse marine invertebrates, including graptolites, trilobites, brachiopods, and the conodonts (early vertebrates). A typical marine community consisted of these animals, plus red and green algae, primitive fish, cephalopods, corals, crinoids, and gastropods. More recently, there has been found evidence of tetrahedral spores that are similar to those of primitive land plants, suggesting that plants invaded the land at this time. 

The Ordovician Period ended with a mass extinction. About 25% of all families did not make it into the Silurian.

Classic Fossil-Bearing Sites include: Whiterock Formation, Utah; and the Nevada Cincinnatian Series, Ohio/Indiana/ Kentucky.

Leo Lesquereux (CH-US), America’s first paleobotanist, wrote the book, which became the standard coverage of fossil flora of the carboniferous formation (2034).

Index Medicus was founded.


“Life should be made into a dream and a dream into a reality.” Pierre Curie, ca. 1880 from his diary.

"My delight may be conceived when there were revealed to me beautiful tangles, tufts and chains of round organisms in great numbers, which stood out clear and distinct among the pus cells and debris... Alexander Ogston (1005). Here Ogston is discussing his discovery of the major cause of pus.

Pierre Curie (FR) and his brother Jacques Curie (FR) discovered the piezoelectric effect in certain crystals. This became the basis for many instruments, among them ultrasound (735).

Johann Friedrich Wilhelm Adolf Baeyer (DE) synthesized indigo.

London purple (a mixture of arsenic trioxide, aniline, lime, and ferrous oxide) was first reported effective in codling moth control as the result of the first official experiments with arsenical insecticides. The presence of poisonous residues on sprayed fruit was considered at this time: the conclusion was that the quantity of poison carried over to harvest as the result of spraying was insignificant--a correct reasoning at the time when few applications were required to keep pest under control.

Lime-sulfur was first used in U. S. for the control of San Jose scale (3161).

Zdenko Hans Skraup (CZ) synthesized quinoline which can be used as an antimalarial (3196).

Emile Clément Jungfleisch (FR) and Lefranc (FR) were the first to crystallize levulose (fructose) (1765). 

Ernst Felix Immanuel Hoppe-Seyler (DE) found that heme or iron-protoporphyrin and the magnesium containing chlorophyll are structurally related (1633).

Bronislaus Radziszewski (PL) made pioneering studies of the chemiluminescence of various organic compounds and the establishment of the enzyme theory of biological oxidations (2835).

Charles Adolphe Würtz (FR) demonstrated the formation of an enzyme-substrate complex when he found that the enzyme papain (which he named) is completely removed from solution by fibrin and that the enzyme cannot be detached from the insoluble material by thorough washing (3813).

Cornelius O’Sullivan (GB) and Frederick William Tompson (GB) also presented one of the first papers concluding that an enzyme-substrate complex formed. Their evidence for this conclusion is based on the observation that invertase is more heat stable in the presence than in the absence of cane sugar, its substrate (2545).

Johannes Ludwig Emil Robert von Hanstein (DE) coined the name protoplast for the protoplasmic part of a single cell. He applied the name to the vital units of both plants and animals. The unit might secrete a wall, but he recognized that this was far from being necessary (3549).

Louis Pasteur (FR) was the first to show the presence of staphylococci in pus (2682).

Louis Pasteur (FR) examined cases of furunculosis, osteomyelitis, and puerperal fever, all of which he attributed to the development of microorganisms infecting the pus of these inflammatory conditions (2679).

Jean Joseph Henri Toussaint (FR), in July 1880, reported to the French Academy of Sciences that he had successfully protected four dogs against anthrax using a preparation of heat-killed bacilli (3374).

Louis Pasteur (FR) confirmed that fowl cholera is caused by a bacterium. He found that if the organism was grown in series in cultures the virulence for fowls was maintained, but that there were conditions in which the virulence for fowls diminished. This enfeeblement of the bacterium Pasteur called attenuation. In the same year he announced the fundamental fact that if the fowls are first inoculated with the living attenuated bacterium of chicken cholera they withstand a subsequent inoculation, which kills unprotected animals acutely. He was led to this discovery by a number of observations. He noted, for example, that the effect of chicken-cholera cultures is not always constant with fluctuations in virulence occurring. He observed that chicken cholera is not likely to reoccur if the fowl has once recovered from an attack of the disease, and that where relapses do occur they are in the inverse ratio to the severity of the first attack. In some cases inoculation produces a chronic form of the disease in certain fowls, but the transfer of the bacterium from such cases usually causes the acute form of the disease in other fowls. He noted, however, that the virulence of the culture depends on the time course, which elapses between successive cultures. As the period of time increases there are signs of progressive attenuation of the bacterium as shown by the lessened case mortality and by the delay in the development of the symptoms. If the infectious agent is transplanted from medium to medium at intervals varying from days to a month or two, no change is observed when the cultures are tested for virulence, however, if the interval between two successive transfers is extended to 3,4,5, or 8 months the scene changes. Instead of being active as judged by the mortality the latter becomes less and may disappear altogether.

It was apparently an inspiration which led Louis Pasteur (FR) to apply a virulent cholera bacterium to fowls which had come safely through an inoculation of the attenuated bacterium, and this led to his establishment of the principle of prophylaxis following the inoculation of the attenuated bacterium—a principle which he established almost at once for anthrax, swine erysipelas, and rabies. Attenuation of the fowl cholera bacterium was believed by Louis Pasteur (FR) to reside in the deleterious effect of air and particularly oxygen. Cultures in closed tubes of broth were found to maintain their virulence up to ten months (2680, 2681).

Carl Joseph Eberth (DE) was the first to describe the typhoid bacillus. First known as Eberthella typhosa, it was later named Salmonella typhi (969, 970).

Georg Theodor August Gaffky (DE) isolated the bacterial cause of typhoid, Salmonella typhosa, in axenic culture (1248).

August Gärtner (DE) isolated a bacterium from contaminated beef responsible for an outbreak of gastroenteritis, and named it Bacillus enteritidis. Today we recognize it as Salmonella enteritidis (1268). This was possibly the first clear indication that microorganisms could cause food poisoning.

James Kingston Fowler (GB) drew attention to the association of throat infection with acute rheumatism (1192).

John H. Bell (GB) gave a clinical description of cutaneous anthrax infections in man, heifers, and sheep. In man it is commonly called wool sorter’s disease (160).

George Miller Sternberg (US) published his translation of The Bacteria by Antoine Magnin (FR). This was the first textbook of bacteriology printed within the U.S.A (2203).

Charles Louis Alphonse Laveran (FR), a military surgeon working in Algiers, discovered the parasitic malarial protozoan (Plasmodium spp.) in the blood of man and associated it with the disease (1994-1996). Laveran named the parasite, Oscillaria malariae.

Ettore Marchiafava (IT), Angelo Celli (IT), and Amico Bignami (IT) gave the first accurate description of the malaria plasmodium discovered by Laveran, and named it Plasmodium malariae. They determined that malaria is transmitted by way of the blood and differentiated the malarial parasites into the three types recognized today— tertian, quartan, and aestivo-autumnal (2230, 2231, 2233, 2234).

Bartolomeo Camillo Emilio Golgi (IT) described in detail the life history of the sporozoan parasites of various forms of malaria (quartan fever caused by Plasmodium malariae, tertian fever caused by Plasmodium vivax, and aestivo-autumnal fever caused by Plasmodium falciparum) and concluded that they could be distinguished morphologically. He also showed that the malarial fever always coincides with the release of merozoites into the blood. In addition, Golgi developed effective and adequate dosages of quinine for the treatment of malaria in its various stages (1337-1343, 1348-1351).

Bartolomeo Camillo Emilio Golgi (IT) identified the parasite that causes malignant tertain fever (1344, 1352).

Cheslav Ivanovich Khentsinsky (RU) presented thorough descriptions and drawings of various forms and stages of malarial parasites in the blood, also the exflagellation of P. falciparum gametocytes and findings of P. falciparum in the liver (1797, 1798). 

Nikolai A. Sakharov (RU), in 1889, published the first comprehensive description of Plasmodium falciparum, the pathogen of aestivo-autumnal malaria, and in 1893 he described the flagellate bodies as phases in the development of plasmodia outside the human body. Ref

Nikolai A. Sakharov (RU) injected himself with intestinal contents of a leech that had fed on a patient with malaria. The result was that he developed malaria, confirming that the malarial plasmodium can survive outside the human body (3023).

Friedrich Siegmund Merkel (DE) described one form of sensory "tactile" nerve ending (2307, 2308). The eponym Merkel’s corpuscles designate them.

Bartolomeo Camillo Emilio Golgi (IT) described the musculo-tendineous organs (later to be known as the Golgi tendon organs). These are proprioceptive sense organs that are located at the insertion of skeletal muscle fibers into the tendon. This was a major contribution to the histology of proprioceptive sensitivity (1331, 1358).

Bartolomeo Camillo Emilio Golgi (IT) reported on a disease condition in which there is fusion within the neuro-muscular junction (1334, 1358).

Edmund Beecher Wilson (US) examined the embryonic development of Lumbricus (earthworm) and Nereis (polychaete marine worm) where he found that the mesoderm is formed in a spiral (mosaic) manner—that is certain cells are set aside quite early to form the mesodermal tissues. These cells begin to proliferate at the gastrula stage and all mesodermal tissues originate from them. His work suggested that spiral cleavage was probably a characteristic of all annelids (3758-3760).

Francis Maitland Balfour (GB) wrote, A Treatise on Comparative Embryology, a book which some consider the beginning of modern embryology. He suggested that all creatures possessing a notochord at some time during their life be grouped in the phylum Chordata; that suggestion was accepted (111).

Thomas Henry Huxley (GB) subdivided the Mammalia into three groups. Prototheria (monotremes), Metatheria (marsupials), and Eutheria (placentals) (1692).

Etienne Lancereaux (FR) made the distinction between fat and thin diabetes: diabete gras and diabete maigre (1955). In the pre-insulin era, most children and some adults died of diabetes within months, whereas overweight older patients often survived for years.

Wilhelm His (CH) presented the first accurate and exhaustive study of the development of the human embryo. He was the first to study the human embryo as a whole (1591).

Maximilian von Vintschgau (AT) limited the qualities of taste to: sour, sweet, salty, and bitter (3627).

Hjalmar Öhrwall (SE) supported the idea of four basic tastes. He concluded that the more basic unit of function had to be the taste bud and that while a papilla may contain a number of different types of taste buds; the taste buds themselves were probably specific to the primaries (2559, 2560).

Désiré-Magloire Bourneville (FR) provided an early description of a multi-symptom disorder that was to become known as Bourneville's syndrome, now known as tuberous sclerosis. This genetic condition may lead to mental retardation, epilepsy, a disfiguring facial rash and benign tumors in the brain, heart, kidney and other organs (352-354).  

Henry Morris (GB) performed a complete operative cure for nephrolithiasis (kidney stone disease) on a 31-year-old woman by lumbar incision and removal of the stone through the kidney parenchyma (2389).

Vincenz Czerny (CZ-DE), in 1880, performed a complete operative cure (pyelolithotomy) for a nephrolithiasis (kidney stone disease). Pyelolithotomy is the removal of a stone through the pelvic wall of the kidney. Ref

Moritz Litten (DE) found that if the abdominal aorta in rabbits is compressed for one hour a permanent paralysis of the lower limbs and incontinence of urine are common. Ref

Paul Ehrlich (DE) and Ludwig Brieger (DE) determined that in fact anterior horn cells of the spinal cord are killed by this compression (996).

Jean Baptiste Edouard Gélineau (FR) introduced the word narcolepsy (Gk. narkosis = benumbing, lepsis = to overtake) to signify the uncontrollable desire to sleep, occurring at frequent intervals (1297).

Stephen Alfred Forbes (US) did pioneering work in his analyses of food webs. He undertook detailed analyses of the food relations of insects, insects, birds, and fish within the community, believing that exact information was needed before the value of a species to society could be assessed (1183).

The Zoologischer Jahresbericht was founded.

Zeitschrift für Klinische Medizin was founded.

New York journalist John Michaels founded Science with financial support from Thomas Edison and later from Alexander Graham Bell. Science became the journal of the American Association for the Advancement of Science in 1900.


A fifth cholera pandemic was notable for the discovery of its cause, by the German physician Heinrich Hermann Robert Koch. Like its predecessors, this epidemic began in India, and spread both east and west from there. By this time improvements in sanitation kept it from affecting many European cities, and improved diagnosis and quarantine measures kept it out of the United States. A sixth pandemic began in 1899, and continued to spread through Asia over the next ten years. The United States was not affected, nor were most Western European cities (1863).


Pierre Eugène Marcellin Berthelot (FR), in 1881, introduced the bomb calorimeter for measuring heat liberated during combustions in oxygen and proposed that chemical reactions be characterized as either exothermic or endothermic, depending on whether they were accompanied by the release or uptake of heat (226). See, Berthelot, 1879.

Kerosene emulsion, the first practical contact insecticide, was recommended for control of insects affecting fruits. Pyrethrum was first advocated for control of grape leafhopper (3161).

Ernst August Schulze (CH) and Johann Barbieri (DE) identified the amino acid phenylalanine as a constituent of plant proteins from lupine (Lupinus luteus) (3115, 3116).

Friedrich Gustav Carl Emil Erlenmeyer (DE) and A. Lipp (DE) determined the constitution of phenylalanine, which they synthesized from phenylacetaldehyde, hydrogen cyanide, and ammonia (1039).

It was later determined by others that phenylalanine is the source of the benzoic acid that forms when proteins are oxidized with agents like potassium permanganate.

Eduard Zacharias (DE) showed that the characteristic material of chromosomes was either nuclein or was intimately associated with it. He demonstrated that nuclein (nucleic acid) and chromatin are the same material. This led to the conclusion that chromatin, chromosomes, and nuclein comprised one and the same substance (3819).

Édouard-Gérard Balbiani (FR) was the first to describe what later became known as polytene chromosomes. He did not understand their nature. The dipteran Chironomus was his experimental material (104). Later it was found that all diptera have these chromosomes. 

Johann Heinrich Emil Heitz (DE) and Hans Bauer (DE) described the large strands found in the nuclei of dipteran salivary gland cells as giant chromosomes (1530).

Theophilus Shickel Painter (US) discovered that the giant chromosomes found in the salivary gland cells of Drosophila are in fact composed of closely paired homologous chromosomes (polytene). In this article he introduced the acetocarmine chromosome squash technique that became so closely identified with Drosophila genetics (2618-2621). Painter quickly identified each chromosome then began to map gene loci because he found that the succession of stained bands in the salivary X chromosome of Drosophila correspond to the linear sequence of gene loci as determined by crossing over experiments.

Milislav L. Demerec (Yugoslavian -US) and Margaret E. Hoover (US) pointed out the correspondence between giant salivary gland chromosome bands and gene maps (843).

Nikolai Konstantinovich Koltzoff (RU) and Calvin Blackman Bridges (US) independently suggested that the giant chromosomes of Diptera are polytenic (418, 1868).

Johann Heinrich Emil Heitz (DE) reported that the banding pattern of polytene chromosomes is consistent (1527).

Gunther Hertwig (DE) noted that the gigantic dimensions of polytene chromosomes are achieved by real growth, i.e., by multiple doubling of the genome (1563).

Gustaf Magnus Retzius (SE) gave a detailed description of the reticular system of muscle and suggested that the T-system plays a role in the conduction of the excitation into the interior of the muscle cell. This is possibly the first definitive description of the sarcoplasmic reticulum (2912, 2914).

Gunnar Nyström (SE) provided experimental evidence for the opening of the transverse network to the extracellular space. After injection of India ink into heart muscle he observed the formation of dark lines crossing the myofibrils at spacings equal to that of the striations (2541).

Emilio Veratti (IT) used the "black reaction" of Golgi to observe a complex, delicate network of longitudinal and transverse filaments in a wide variety of muscles at different stages of development and illustrated them in beautiful drawings that accurately represent their distribution in the longitudinal and transverse plane of the muscle fiber. Veratti’s paper is a classic description and discovery of the sarcoplasmic reticulum in skeletal muscle fibers (3454, 3455).

Ebba Andersson-Cedergren (SE) described a part of the muscle cell reticulum having the form of transversely oriented tubules (T tubules) (46). These are instrumental in conducting the signal for contraction inward from the surface membrane.

Bartolomeo Camillo Emilio Golgi (IT) used histological examination to show that many nerve cells originate centrally from the spinal cord as branches of nerve fibers out of the medullary cords (1332, 1333, 1336, 1346). 

Charles Darwin (GB) and his son Francis Darwin (GB) discovered that the phototropic stimulus is detected at the tip of the plant. They found that the tip of the coleoptile is necessary for phototropism but that the bending takes place in the region below the tip. If they placed an opaque cover over the tip, phototropism failed to occur even though the rest of the coleoptile was illuminated from one side. However, when they buried the plant in fine black sand so that only its tip was exposed, there was no interference with the tropism - the buried coleoptile bent in the direction of the light (770).

Nicholas Ivanovich Lunin (RU) studied the effect of milk on the survival rate of mice feed artificial diets and concluded that milk contained some, as yet unknown, substance necessary to sustain life. That substance was not protein, fat, sugar, salts or water (2161).

Moritz Wilhelm Hugo Ribbert (DE) was the first to report inclusion bodies of cytomegalovirus. He observed these in the kidneys of a stillborn infant with syphilis in 1881. The results were not published until years later (2922).

Karl Brandt (DE) described the zusammenleben (life in common: symbiosis, in modern terms) of algae and animals, and coined the word Zoochlorella to describe the algae found in the body of Hydrae and Zooxanthella for those (yellow) living in Radiolariae (400).

Theodor Wilhelm Engelmann (DE) described the accumulation of Bacterium termo, a small, rod-shaped, polarly flagellated putrefactive bacterium, in regions of high oxygen tension surrounding cells of higher and lower plants undergoing photosynthesis. This is one of the earliest recorded examples of chemotaxis (1020).

Wilhelm Friedrich Philipp Pfeffer (DE) also discovered chemotaxis and determined that motile bacteria can exhibit a positive as well as a negative chemotaxis (2736-2738).

Julius Adler (US) proved that bacteria possess sensory devices, chemoreceptors that measure changes in concentration of certain chemicals and report the changes to the flagella (19).

Heinrich Hermann Robert Koch (DE) presented the streak plate method of isolating microorganisms in axenic culture on solid media (gelatin) in a shallow dish. This is without doubt one of the most significant papers in the history of microbiology. In this paper Koch discusses using potato slices as a medium for culturing bacteria. He prepared them by soaking the raw potato (Solanum tuberosum) in a solution of corrosive sublimate (1:1000) then sterilizing it with steam. It was split in half using a sterile knife and allowed to fall open inside a sterile covered glass vessel. The cut surface was then inoculated with the bacterial material. Here he also reports that high dilutions of mercury dichloride are bacteriostatic and bactericidal for endospores and vegetative cells of the most resistant microorganisms (1844).

Heinrich Hermann Robert Koch (DE) introduced the use of heat as a method of fixing bacterial smears (1844).

Paul Ehrlich (DE) introduced the use of methylene blue as a bacterial stain (992).

Heinrich Hermann Robert Koch (DE) and Gustav Wolffhügel (DE) determined the exact value of hot air as a sterilizing agent (1856).

Albert Ludwig Siegmund Neisser (DE) while staining the leprosy microorganism noted what would later be appreciated as its acid-fast nature (2483).

Heinrich Hermann Robert Koch (DE), Georg Theodor August Gaffky (DE), and Friederich August Johannes Löffler (DE) determined the limitations of steam at 100°C. as a sterilizing agent (1855).

Louis Pasteur (FR) observed that superheated steam is an excellent sterilizing agent. He first accomplished this by immersing sealed vials in a bath of calcium chloride heated above 100°C. Later he used Denis Papin’s (FR) digester (steam under pressure).

Heinrich Hermann Robert Koch (DE) used axenic cultures of certain bacteria to compare the antiseptic capacity of a number of chemicals. Axenic cultures were dried on small pieces of silk thread then immersed in the test chemical. After various intervals of time the impregnated threads were removed from the test chemical, washed in sterile water or sterile broth, and implanted in a medium to determine whether the bacteria had been killed or not. He was soon able to draw a distinction between the concentration of an agent that prevents a microorganism from growing (bacteriostatic), and that concentration, which kills the microorganism (bactericidal). He found that these limits may be, and usually are, far apart. Of over 70 chemicals tested, Koch found mercuric chloride to be the most antibacterial. Koch showed that mercuric chloride was superior to carbolic acid, and that live steam surpassed hot air in sterilizing power (1845).

Wilhelm Olbers Focke (DE) coined the term xenia to denote the immediate effect of pollen on the endosperm in the maize seed (1175).

Wilhelm August Oskar Hertwig (DE) and Richard Wilhelm Karl Theodor von Hertwig (DE) originated the term mesenchyme, a protoplasmic network filled with a fluid intercellular substance. It may be derived from all three germ layers, but is primarily mesodermal in origin, and gives rise to a variety of tissues: primarily connective tissue (1571).

Joseph Leidy (US) described his discovery of microorganisms in the hindgut of termites as follows: “In watching the Termites from time to time wandering along their passages beneath stones, I have often wondered as to what might be the exact nature of their food in these situations. Observing some brownish matter within the translucent abdomen of the insects, I was led to examine it with the object of ascertaining its character. On removing the intestinal canal of an individual I observed the brownish matter was contained within the small intestine, which is comparatively large and capacious. The brownish matter proved to be the semi-liquid food; but my astonishment was great to find it swarming with myriad parasites, which indeed actually predominated over the real food in quantity. Repeated examination showed that all individuals harbored the same world of parasites wonderful in number, variety and form.

If the intestine is ruptured, myriad living occupants escape, reminding one of the turning out of a multitude of persons from the door of a crowded meetinghouse. So numerous are the parasites and so varied their form, movement, and activity, that their distinctive characters cannot be seen until they become more or less widely diffused and separated” (2019).

Charles Robert Darwin (GB) was the first to report how important worms are to soil fertility (769).

Louis Pasteur (FR), Charles Édouard Chamberland (FR), Pierre Paul Émile Roux (FR), and Louis Thuillier (FR) demonstrated that rabies has an affinity for brain tissue. They discovered that the incubation period could be shortened to one or two weeks by inoculating the virus directly under the dura mater of dogs (2691, 2692).

Joseph Marie Jules Parrot (FR) mentions a pneumococcus associated with human infection (2645).

Louis Pasteur (FR), Charles Édouard Chamberland (FR), Pierre Paul Emile Roux, (FR), and Louis Thuillier (FR) isolated Streptococcus pneumoniae, or pneumococcus, from the saliva of a patient with rabies (2691).

George Miller Sternberg (US) almost simultaneously announced the discovery of the pneumococcus (3258).

Albert Fraenkel (DE) and Anton Weichselbaum (AT) grew pneumococcus (Streptococcus pneumoniae) in a pure state and established its relationship to lobar pneumonia (1194-1198, 3694, 3696).

Friederich August Johannes Löffler (DE) introduced the use of common broth or bouillon for culturing bacteria during his studies of the bacillus causing mouse septicemia. He grew this organism in a medium consisting of meat infusion, to which was added 1 percent of peptone, and 0.6 percent of common salt. The solution was made slightly alkaline with sodium monohydrogen phosphate (2114).

Carl Joseph Eberth (DE) isolated the typhoid bacillus from the mesenteric glands and the spleen of persons dying from typhoid fever (970).

Georg Theodor August Gaffky (DE) isolated Gaffkya tetragena from the pulmonary cavities of patients with phthisis (pulmonary tuberculosis) (1247).

Louis Pasteur (FR), Pierre Paul Émile Roux (FR), and Charles Édouard Chamberland (FR) developed a vaccine for anthrax. This was a difficult task because of the presence of endospores in the cultures. They found that anthrax would not grow above 45°C. but yielded abundant growth at 42-43°C. At the latter temperatures no endospores were formed. The culture had indeed become asporogenous, and in a month had ceased to grow. When a virulent anthrax culture in broth was kept at 42-43°C. for eight days it had lost a considerable part of its virulence and was innocuous when injected into guinea-pigs, rabbits, or sheep. By longer cultivation at the above temperature it became still more attenuated. They recommended this method as an anthrax prophylactic or vaccine. Louis Pasteur (FR) coined the term vaccine to honor Edward Jenner and the cowpox prophylactic treatment Jenner developed for smallpox (2683, 2687-2689).

John W. Ezzell (US), Perry Mikesell (US), Bruce E. Ivins (US), and Stephen H. Leppla (US) noted that avirulent cultures of anthrax lack a critical virulence plasmid. They point out, ironically, that Pasteur’s nonchalance about pure clone cultures, so much criticized by Koch, was the key to the success of his anthrax vaccine, which was a mixture of plasmid-deprived and still toxic (and immunogenic) plasmid-positive cells (1047). 

Alexander Ogston (GB), assistant-surgeon to the Aberdeen Royal Infirmary examined 100 abscesses, some acute and some inactive, for bacteria. No microorganisms could be found in the inactive abscesses, whereas the active ones were found to contain many micrococci. Sometimes the cocci were clumped like the roe of fish (staphylococci) and other times appeared in chains (streptococci). He showed that the difference in appearance was due to a difference in mode of fission. Using a hemocytometer he determined that the average number of cocci per cubic milliliter of pus was nearly 3 million, although in individual samples it varied between a minimum of 900 and a maximum of 45 million. He found spirilla and fusiform bacteria in alveolar abscesses. Injection of inactive abscess material into mice was without pathogenic effect. When he injected mice with material from active abscesses the results were dramatically different. Abscesses invariably developed and he traced with great clearness the symptoms and lesions, and showed by the process of counting that the cocci in the experimental lesion must have increased greatly in numbers, and that the experimental inflammatory disease with abscess formation could be propagated in series. In addition to abscesses, Ogston examined lesions associated with gonorrhea, soft chancre, sycosis, sputa from phthisis (pulmonary tuberculosis), and discharges from wounds and ulcers. Micrococci were found in all. He cultured the cocci outside the body of animals by using fresh eggs. Using cocci from these fresh egg cultures he was able to experimentally produce typical abscesses by inoculation into mice. 

Ogston concluded that micrococci produced inflammation and suppuration. There was microscopic evidence of their proliferation locally; the cocci invaded peripherally and might pass into the blood. In abscesses they were finally excluded by the formation of a delimiting wall of granulation tissue, which arrested their invasion and led to their final extrusion among the pus corpuscles (2555-2558).

Friedrich Fehleisen (DE) and Anton Julius Friedrich Rosenbach (DE) obtained axenic cultures of these microorganisms and reached similar conclusions. Anton Julius Friedrich Rosenbach (DE), adopting the term streptococcus (previously introduced by Billroth) to name Streptococcus pyogenes; the variety of organism isolated by him from suppurative lesions. Rosenbach also isolated Staphylococcus in axenic culture. He named them for the pigmented appearance of their colonies: Staphylococcus aureus, from the Latin aurum for gold, and Staphylococcus albus (now called epidermidis), from the Latin albus for white. Rosenbach was the first to show a causal relationship between the micrococci and the suppuration of wounds and osteomyelitis (1068, 2965).

W. Reinhard (DE) created the class Kinorhyncha (Gr. kīneō = move + rhynchos = snout) for the genus Echinoderes. Commonly called mud dragon it is in the phylum Aschelminthes (or Nemathelminthes) (2895, 2896). These are pseudocoelomate invertebrates that are widespread in mud or sand at all depths.

Carlos Juan Finlay (CU) presented a paper at the International Sanitary Conference in Washington in which he suggested that mosquitoes of the genus Stegomyia (Aedes) might be transmitters of the unknown germ causing yellow fever (1094, 3259). While not the first to make this suggestion, he was perhaps the most zealous and enthusiastic proponent of this point of view. Finlay, an unassuming man with an international background, a Scottish father and a French mother, had much of his early training in France and other European countries, and received his medical degree at Jefferson Medical School in 1855.

Walter Reed (US) was to say, “To Dr. Carlos Juan Finlay of Havana must be given, however, full credit for the theory of the propagation of yellow fever by means of the mosquito, which he proposed in a paper read before the Royal Academy in that session of the 14th day of August, 1881 (1093). From that date to the present time, Finlay has made a number of valuable contributions to the origin and mode of transmission and the prevention of yellow fever.”

Henry Rose Carter (US) studied an outbreak of yellow fever in Mississippi and defined the limits of the extrinsic incubation period, i.e., the period of time course necessary before the surroundings of a case become infectious, as 10-15 days (566).

Walter Reed (US), James Carroll (US), Aristides Agramonte y Simoni (US), and Jesse William Lazear (US) with the American Army Commission traced the transmission of the unknown virus of yellow fever to mosquitoes of the species now known as Aedes egypti. In the course of the rigorous and heroic tests to prove the theory Carroll acquired the disease in a mild form and Lazear lost his life. John R. Kissinger (US), John J. Moran (US), and Clara Louise Maass (US) volunteered to be bitten by mosquitoes to prove its role as a vector. Ms. Maass died of yellow fever. Yellow fever was the first human disease attributed to a virus (2885-2887).

James Carroll (GB-CA-US), on the suggestion of his mentor William Henry Welch (US), embarked on research, which demonstrated that the agent of yellow fever passed through a Berkefeld infusorial bacteriological filter. This went a long way toward proving that the causative agent was a virus (564).

Adrian Stokes (GB), Johannes H. Bauer (US), N. Paul Hudson (US), Constant Mathis (FR), Andrew Watson Sellards (US), and Jean Laigret (FR), working in West Africa, proved that yellow fever is caused by a virus and transferable to monkeys (2257, 3266, 3267). Stokes died of a yellow fever infection.

Wilbur A. Sawyer (US), Stuart F. Kitchen (US), Martin M. Frobisher, Jr. (US), and Wray Lloyd (US) determined the relationship of yellow fever of the Western hemisphere to that of Africa and leptospiral jaundice (3045).

Max Theiler (ZA-US) and Hugh H. Smith (US) grew the yellow fever virus in rhesus monkeys (Macacus rhesus), and then passed it to mice. In mice, it developed as encephalitis.  They passed it from mouse to mouse, and then eventually back to the monkeys, where it produced a full immunity to the most virulent form of the virus. This attenuated strain could also be used to vaccinate man (3310, 3311).

Wilbur A. Sawyer (US) and Wray Lloyd (US) developed a serum neutralization test for the presence of yellow fever (3047).

Wilber A. Sawyer (US), Stuart F. Kitchen (US), and Wray Lloyd (US) developed a vaccine to yellow fever using the attenuated virus. The vaccine had two parts: a ten-percent suspension of mouse-brain tissue with yellow fever virus in fresh sterile human serum, and human immune serum from people recently recovered from yellow fever (3046).

Fred L. Soper (US), Elmer R. Rickard (US), and Peter J. Crawford (US) perfected the postmortem diagnosis of yellow fever by viscerotomy (histological examination of the liver) (3215). This greatly aided in field surveys of yellow fever.

Max Theiler (ZA-US), Hugh Hollingsworth Smith (US), Henrique A. Penna (BR), and Adhemar Paoliello (BR) carried out successful field trials of their yellow fever vaccine (3201, 3312).

W.T. Milles (GB) and Arthur Swayne Underwood (GB) consider that dental caries, as well as suppuration of the pulp and alveolar abscess, depends upon the presence and proliferation of microorganisms. These organisms attack first the organic material, and feeding upon it create an acid, which removes the lime-salts (2347).

Carl Wernicke (PL-DE) first diagnosed Wernicke's encephalopathy. This first diagnosis noted symptoms including paralyzed eye movements, ataxia, and mental confusion. Also noticed were hemorrhages in the gray matter around the third and fourth ventricles and the cerebral aqueduct. Brain atrophy was only found upon post-mortem autopsy. Wernicke believed these hemorrhages were due to inflammation and thus the disease was named polioencephalitis haemorrhagica superior (3721).

That this disease state was the result of a deficiency in thiamine (vitamin B-1) would be discovered in the 1930s.

Note: The condition is part of a larger group of diseases related to thiamine insufficiency, including beriberi in all its forms, and Korsakoff syndrome.

Sergei Korsakoff (RU) was studying long-term alcoholic patients and began to notice a decline in their memory function (1871). 

Alexander Crombil (GB) suggested the injection of morphine prior to the administration of chloroform to patients. This was probably the first type of preanesthetic medication (726).

Karl Siegmund Franz Credé (DE) was the first to recognize the antimicrobial properties of silver when he introduced the use of silver nitrate as a prophylactic agent against gonorrheal ophthalmia neonatorum (720, 721).

Albert Coombs Barnes (US) and Hermann Hille (DE), in 1899, developed a mild silver nitrate antiseptic solution, marketed as Argyrol, and used in the treatment of gonorrhea and as a preventative of gonorrheal blindness in newborn infants. Argyrol was first sold in 1902 (3052).

Richard Volkmann (DE) discovered that relaxation and contractures of limbs following application of tight bandages are caused by the rapid and massive deterioration of contractile substance and by…reactive and regenerative processes (3494). These are now called Volkmann ischemic contractures.

Hermann Munk (DE) placed the cerebral center for hearing in the temporal lobes of the brain (2449, 3521).

Théodule Ribot (FR) cited a number of cases from the literature to illustrate the occasional separation of procedural (ways of doing things) from declarative (factual) memory (2923).

Sanger Brown (GB) and Edward Albert Schäfer (GB) reported that damage to the temporal lobes and the underlying hippocampus may affect memory (481).

William B. Scoville (US) and Brenda Milner (US) reported on a patient in whom lesions destroyed the anterior two-thirds of the hippocampus, in addition to the parahippocampal gyrus, anterior temporal cortex, uncus, and amygdala. Declarative (factual) memory seemed to depend more upon the integrity of the hippocampus than did procedural (ways of doing things) memory (3144). 

Moritz Litten (DE) was the first physician to describe vitreous bleeding in correlation with subarachnoid hemorrhage (SAH) (2104).

William MacEwen (GB) and Joseph Lister (GB) independently found that if incisions or wounds were kept aseptic and closed with sterile catgut (sterilized with hot wax) whose loose ends had been clipped close to the tie that the catgut would be absorbed as infection free healing took place. To make the absorbable catgut antimicrobial, Lister treated it with a mixture of one part chromic acid, 4000 parts distilled water and 200 parts carbolic acid (2100, 2178).

William Holbrook Gaskell (GB) presented the results of his studies, in which he defined the five properties of cardiac muscle, viz., excitability, conductivity, tonicity, rhythmicity, and automatic contractile power (1271).

William Richard Gowers (GB) gave a classic description of epilepsy (1384).

Waren Tay (GB) and Bernard Parney Sachs (US) described amaurotic family idiocy (Tay-Sachs disease), a fatal autosomal recessive genetic disorder in which harmful quantities of a fatty substance later called ganglioside GM2 accumulate in the nerve cells in the brain (3002-3004, 3305). Note: Tay-Sachs disease occurs predominantly, but not exclusively, in Jewish children of eastern and central European (Ashkenazi) families. Patients and carriers of Tay-Sachs disease can be identified by a simple blood test that measures hexosaminidase.

Ernest-Charles Lasègue (FR) discovered a sign frequently seen in lumbar root or sciatic nerve irritation: when patient is supine with hip flexed, dorsiflexion of ankle causes pain or muscle spasm in the posterior thigh. J.J. Forst (FR), one of his pupils reported it years later (1188).

Friedrich Trendelenburg (DE) introduced the head-down tilt with pelvic elevation for abdominal surgery in 1881. This position is also favored for patients in shock. One of his students was first to report this innovation. In the 1890 paper he identified saphenofemoral incompetence in patients with varicose veins (2323, 3386, 3387).

Vincenz Czerny (CZ-DE) introduced the operation of enucleation of subperitoneal uterine fibroids by the vaginal route (751).

Nikolaus Friedreich (DE) was the first to describe paramyoclonus multiplex (1233).

Emil Wilhelm Magnus Georg Kraepelin (DE) wrote about the influence of infectious diseases on the onset of mental illness (1898, 1899).

Jan Mikulicz-Radecki; Johannes von Mikulicz-Radecki (PL-AT) was the first to use the electric esophagoscope invented by Josef Leiter (PL) in 1880, and the first gastroscope in 1881 (3602).

Moritz Litten (DE) is remembered for being the first physician to describe vitreous bleeding in correlation with subarachnoid hemorrhage (2105).

William Alvin Macewen (GB) reported the successful removal of a brain tumor of the left frontal dura mater, likely a meningioma, in a 14-year-old girl. This is considered to be the first successful surgical removal of a brain tumor (2181). The operation was performed in 1879.

Hermann Oppenheim (DE) and R. Köhler (DE) reported the successful removal of a brain tumor. Köhler was the surgeon (2570).

Francesco Durante (IT) successfully removed a cranial base meningioma. Durante performed a large left frontal craniotomy and removed an "apple-sized sarcoma." The patient recovered from the surgery without incident (947). The operation was performed in 1884.

Alexander Hughes Bennett (GB) and Rickman John Godlee (GB) diagnosed then surgically removed a cerebral tumor. The patient was a farmer, 25, who applied for advice to the Hospital for Epilepsy and Paralysis, Regent's Park, on November 3rd, 1884. His chief complaint was paralysis of the left hand and arm, which incapacitated him from work. Following surgery the patient lived only one month, dying from what was undoubtedly an infection (166, 167).

Max Schüller (DE) performed the first successful operation for non-descending testicle (3101).

Jean-Francois-Auguste Le Dentu (FR) carried out a successful nephrolithotomy (removal of kidney stones). (2006).

Richard Clement Lucas (GB), in 1879, removed a kidney with a most successful result, as the patient was shown more than twenty years afterwards (2147).

John Girdner (US) described the first allograft skin transplantation using skin from a human cadaver. Girdner procured skin from the inner thigh of a young German boy within 6 hours of his death and transplanted the skin onto the shoulder blade of a 10-year-old boy who had been struck by lightning (1311, 2546). 

Karl Semper (US) was one of the first to point out the modern ecological point of view and laid the basis for many ecological concepts of existence (3159).

The Congress of the United States passed an agricultural appropriation act establishing a divisional organization for the United States Department of Agriculture, at which time the divisions of Seed, Gardens and Grounds, and of Botany were founded. The Division of Pomology was established in 1886; the Division of Vegetable Pathology achieved independence from the Division of Botany in 1891, and became the Division of Vegetable Physiology and Pathology in 1895; in that year, the Division of Agrostology was also founded. The Section Foreign Seed and Plant Introduction was established in 1897 (1412).

Caesar Peter Møller Boeck (NO) with Skjelderup and Stabell established the journal Tidsskrift for Praktisk Medicin.

Gesellschaft für Innere Medizin was founded.

Botanische Jahrbücher was founded.


August Freund (AT) discovered and described cyclopropane (trimethylene) (1214).

George H. W. Lucas (CA) and Vilyien E. Henderson (CA) showed that cyclopropane has anesthetizing properties (2146).

John A. Stiles (US), William B. Neff (US), Emery A. Rovenstine (US), and Ralph M. Waters (US) began to use cyclopropane clinically (3263).

Ferdinand Gustav Julius Sachs (DE) suggested that nuclein carries hereditary information by pointing out that the nucleins of egg and sperm could hardly be identical—that the nuclein brought into the egg by the sperm must be different from the nuclein already there (3009, 3010).

Theodor Wilhelm Engelmann (DE) discovered that during illumination oxygen requiring motile bacteria are attracted to the surface of the eukaryotic alga Spirogyra near the chloroplast; in the absence of light they are not attracted. This provided the first direct evidence that the chloroplast is the site of oxygen production in eukaryotic organisms (1021, 1025, 1028).

White arsenic is first used to control codling moth. Napthalene is first used for insect control purposes. It is used in a cone form (3161).

Eduard Adolf Strasburger (PL-DE) coined the terms cytoplasm and nucleoplasm to describe the cell body and nucleus, respectively. Ref 

Johannes Ludwig Emil Robert von Hanstein (DE) coined the name microsome for some small granules common in the cytoplasm (3550).

Ferdinand Gustav Julius Sachs (DE), in 1882, noted that plants synthesize organ-forming substances that are typically distributed to the cell's poles (3008).

Édouard-Gérard Balbiani (FR) found that the formation of the sexual organs of the Chironomus (Diptera: Chironomidae) demonstrated that the sexual cells derive directly from the egg and are differentiated before the blastoderm appears - and that consequently they precede the individual itself. This essential fact was later observed in other species and eventually was responsible for the general theory of the autonomy of the germ cell (106).

Paul Ehrlich (DE) introduced the use of aniline water, and either methyl violet or fuchsin as a dye superior to methylene blue for staining tubercle bacilli. Aniline was shaken in water then filtered to yield aniline water. This was then saturated with either methyl violet or fuchsin in alcoholic solution. By this means the tubercle bacillus was stained deeply and the color was acid fast in that it could not be discharged by even nitric acid in a concentration of 30% in water. He counterstained with dilute blue or yellow dye. This was the first staining procedure to take advantage of the acid-fast quality of tubercle bacilli (993).

Franz Ziehl (DE) described a method for staining the tubercle bacilli. His technique did not employ a counterstain (3831).

Friedrich Carl Neelsen (DE) introduced what we may call the classic procedure for staining acid-fast bacteria (2479). Today it is referred to as the Ziehl-Neelsen method. A. Johne (DE) first mentioned it in a paper (1749).

Paul Ehrlich (DE) used the fluorescent dye uranin (a sodium salt of fluorescein) to determine the pathway of secretion of the aqueous humor in the eye of the rabbit (994). This represents the first use of a fluorescent dye in animal physiology.

Sydney Ringer (GB) introduced the use of a salt solution, which enhanced the survival rate, and function of excised animal body parts. The solution contained sodium chloride, potassium chloride, and calcium chloride. He and Dudley W. Buxton (GB) concluded that extracellular calcium ion is required to preserve the contractility of the heart but calcium, potassium, and sodium must be present in correct proportions (as in the Ringer’s solution) for normal heart activity (2932-2941). Harrington Sainsbury (GB) and Arthur G. Phear (GB) were among Ringer’s research colleagues.

Frank Spiller Locke (GB) optimized the various salt concentrations at NaCl 0.9-1.0 percent, CaCl2 0.02-0.024 percent, KCl 0.02-0.04 percent, and NaHCO3 0.01-0.03 percent. He also discovered that while each of these chlorine salts, if used individually, might be toxic to the heart they could be given together with no ill effect. The concept of antagonistic salt action was thus introduced to physiology (2111, 2112).

Percy G. Stiles (US) found that rhythmic contractions of smooth muscle in frog esophagus strips showed similar dependence on extracellular calcium ions and potassium, as did the frog heart (3264).

Hermann Tappeiner (DE) observed that although ruminants did not secrete enzymes, which digested cellulose, it nevertheless disappeared from their digestive tract. The inescapable conclusion was that microorganisms of the digestive tract were responsible for the enzymatic attack of cellulose and therefore they were absolutely necessary if the ruminant was to lead a normal life (3300, 3301).

Wilhelm Friedrich Kühne (DE), Carl Anton Ewald (DE), William C. Ayres (US), and J. Steiner (DE), in 22 articles beginning in 1877, determined that the retina (with its epithelium) acts not as a photographic plate, but actually more like a complete photographic laboratory, in which workers continuously supply new highly photosensitive material to the plate, erasing the older images. Using an alum solution as a fixative they were able to actually fix the image of a rabbit on the retina. Kühne called these optogramms. They summarized, 1) It is the function of rhodopsin to be decomposed by light; 2) the products of this photochemical reaction then stimulate the nerve impulse to the brain (722, 1926).

Bartolomeo Camillo Emilio Golgi (IT) used his "black reaction" staining technique to trace the olfactory nerves in man and other mammals (1335, 1336, 1347).

Waldemar von Schroeder (DE) perfused the liver of dogs with ammonium carbonate or ammonium formate and observed that the liver produced a significant amount of urea. This was additional evidence that urea is biosynthesized (3622).

Pier’ Andrea Saccardo (IT) with the aid of Alessandro Trotter (IT), Domenico Saccardo (IT), Giovanni Battista Traverso (IT), Paul Sydow (GB) and others produced a 25 volume work on the fungi entitled Sylloge Fungorum. This exhaustive work was begun in 1882 and ended in 1931 (3001). It spurred renewed interest around the world in describing new fungi.

Karl Wilhelm von Nägeli (CH) studied the effect on bacterial growth of various carbohydrates and proteins. He found that sugars were generally the best carbon sources and peptones were generally the best nitrogen sources (3612).

Heinrich Hermann Robert Koch (DE) introduced the use of blood serum stiffened by heat as a solid medium of great nutritive value. He used it to cultivate the tubercle bacillus (1846).

Thomas Jonathan Burrill (US) discovered and described the bacillus that causes fire blight in pears and twig blight in apples. He never grew it in axenic culture or strictly followed Koch’s postulates. Some consider this, along with Jan Hendrik Wakker’s work in 1883, to be the birth of the science of bacterial phytopathology. Burrill named the bacterium Bacillus amylovorus (529-532). See, Wakker in 1883.

Ludwig von Graff (AT) proposed the planuloid-acoeloid theory to explain how the bilateral animals evolved from radial animals (3544).

Libbie Henrietta Hyman (US) has vigorously promoted the planuloid-acoeloid theory (1702). 

George Albert Boulenger (BE-GB) was invited in 1880 to come to the British Museum to undertake a new edition of the catalogues of amphibians and reptiles. While there he oversaw the production of nine volumes, which constituted a summary of the world fauna for the classes Amphibia and Reptilia to the year 1896. He also catalogued the fishes of Africa. Notwithstanding the presence of errors this body of work represented a fundamental reform of the classification of the two great classes of vertebrates, the Amphibian and Reptilian, and was to shape zoological thinking in Europe for many years (346-350).

Harry Marshall Ward (GB) stressed the relationship of environment to the epidemiology of coffee rust in Ceylon (3675).

Joseph Jules François Felix Babinski (FR) published a treatise on typhoid fever (85). 

Heinrich Hermann Robert Koch (DE) discovered that tuberculosis is caused by a specific bacterium, Mycobacterium tuberculosis. In publishing his results he laid down the laws since considered fundamental to the science, viz., that before recognition as the cause of a disease a germ (1) must be found constantly associated with that disease, (2) must be isolated from a lesion of that disease apart from other germs, (3) must reproduce the disease in a suitable animal on inoculation with anemic culture, and finally (4) be found again in the lesions of this artificially produced disease (1846).

He described how alkaline ethylene blue penetrates the tubercle bacillus and remains there despite subsequent treatment with vesuvin or Bismarck brown. He used this technique to show the tubercle bacillus when he first worked with it (1846). Note: Tuberculosis has been called phthisis, consumption, scrofula, and the white plague.

Charles Clemens von Baumgarten (DE) independently and almost simultaneously with Heinrich Hermann Robert Koch (DE) described the tubercle bacillus (3506-3508).

Carl Friedlander (DE) discovered a bacterium, which causes pneumonia in humans and named it Bacillus pneumoniae (1224, 1225). Today it is referred to as Klebsiella pneumoniae. Occasionally it is called Freidländer’s bacillus in his honor. Friedländer contracted pulmonary tuberculosis at the age of 35 and died 5 years later (3701).

Kenneth McLeod (GB) first described Donovanosis in Madras, India as a ‘serpiginous ulcer’ (2278).

Charles Donovan (IE) described the presence of intracellular microorganisms from an oral lesion in a case of Donovanosis (884).

Max A. Goldzeiher (HU-US) and Samuel Mortimer Peck (US) provided the classical description of the disease and recognized Donovan bodies in histological sections (1326).

Edgar R. Pund (US) and Robert B. Greenblatt (US) described the pathognomonic cells of granuloma inguinale (Donovanosis) consisting of large mononuclear cells filled with intracytoplasmic cysts containing deeply staining bodies (2813). 

Donovanosis (granuloma inguinale) is caused by the obligately intracellular gram-negative bacterium Klebsiella granulomatis, previously called Calymmatobacterium granulomatis, and Donovania granulomatis.

Carle Gessard (FR) discovered that the blue or blue-green stains that sometimes appeared on surgical dressings are caused by the presence of Pseudomonas pyocyanea (Pseudomonas aeruginosa) (1304, 1305).

Alexander Ogston (GB) gave a general statement of his views on ‘micrococcus poisoning’. He considered that micrococci were of two kinds, the one arranged in chains (Streptococcus, Billroth) and the other in masses, which he named Staphylococcus (a bunch of grapes). He opposed the view that pyemia and septicemia were blood diseases, and showed that the blood was merely the vehicle which may generalize in the body what, without its aid, would be only a local process (2557).

Rudolf von Jaksch; Rudolf Jaksch von Wartenhorst (AT) identified acetoacetic acid in the urine of diabetics. It would, with the loss of carbon dioxide, break down into acetone (3568, 3569).

Heinrich Irenaeus Quincke (DE) described angioneurotic edema (2830). He also studied the mechanism of body temperature control, wrote on anosmia, traumatic brain lesions, and on hyperthermia in cord lesions.

Friedrich Daniel von Recklinghausen (DE) wrote a classic article on neurofibromatosis, Recklinghausen’s disease (3616).

Kanehiro Takaki (JP) reduced the incidence of beriberi in the Japanese navy by dietary improvements. To test his dietary theory, Takaki gave the crew of the training ship, Ryujo, a white-rice diet and gave the crew of another training ship, Tsukuba, an enriched diet of his own devising. Leaving Japan in December 1882 and in February 1884 Ryujo and Tsukuba sailed to New Zealand, along the coast of South America from Santiago to Lima, to Honolulu, and back to Japan in voyages lasting some 9 months. Of the 376 crewmen of Ryujo, all of who were eating the white-rice diet, 161 contracted beriberi and 25 died. However, only 14 of the crew of Tsukuba, who ate Takaki's enriched diet, contracted beriberi and none died. He supplemented the rice diet with milk and vegetables (561, 1718). Takaki's success came 10 years before that of Dutch hygienist Christian Eijkman.

Philippe Charles Ernest Gaucher (FR) described a case of the disease, which would later bear his name (1281).

Hans Lieb (DE) and Emil Epstein (DE) isolated a fatty substance (the cerebroside, kerasin) from the spleens of patients with Gaucher disease (1032, 2066). 

Henriette Aghion (FR) identified this fatty substance as glucocerebroside (Aghion 1934).

William Bloom (US) described the histopathology of Gaucher’s and Niemann’s diseases (309).

Roscoe O. Brady (US), Andrew E. Gal (US), Julian N. Kanfer (US), and Roy M. Bradley (US) proved that glucocerebroside collects in Gaucher cells due to the lack of an enzyme known as glucocerebrosidase (393-395).

Franz Ernst Christian Neumann (DE) postulated the law of dissemination concerning yellow and red bone marrow. In effect, he recognized a phenomenon that is sometimes referred to us as Neumann's law. It states that at birth all bones that contain marrow contain red marrow. With age, the blood producing activity contracts toward the center of the body, leaving the more peripheral bones with only fatty marrow (2494).

Ernst Ziegler (DE), in 1882, described a decrease in bone mass, which would later be called osteoporosis (3830).

Carroll A. Pfeiffer (US) and William U. Gardner (US) found that injection of estrogen into pigeons is followed by a rise in the serum calcium level and hypercalcification of the bone (2739).

Stanley Wallach (US) and Philip H. Henneman (US) conducted a 25-year retrospective study of the results of prolonged estrogen therapy in 292 post-menopausal women, which showed excellent results in the treatment of post-menopausal osteoporosis (3654).

Walter Holbrook Gaskell (GB) made many cardiac contributions including the following: 1) the recognition of certain inherent properties of cardiac muscle, which he termed “rhythmicity, excitability, contractility, conductivity and tonicity” (1272, 1273, 1275); 2) the experimental proof that led to the acceptance of the myogenic theory, as opposed to the neurogenic theory of the origin of the heartbeat (1273, 1275); 3) the mapping of the anatomy of the sympathetic nervous system (1274); 4) the understanding of the dual autonomic control of the heart (1273-1275); 5) the discovery of the vasodilating effect of sympathetic stimulation on blood flow through skeletal muscle arteries (1269, 1270); and 6) the introduction of the concept of heart block (1273, 1275).

Wilhelm August Balser (DE) and Reginald Heber Fitz (US) described acute hemorrhagic pancreatitis and some of its attendant problems (114, 1150, 2985).

Heinrich Irenaeus Quincke (PL-DE) described angioneurotic edema (or angioedema), a form of localized swelling of the deeper layers of the skin and fatty tissues beneath the skin. Hereditary angioneurotic edema (or hereditary angioedema) is a genetic form of angioedema (2829). Persons with it are born lacking an inhibitor protein (called C1 esterase inhibitor) that normally prevents activation of a cascade of proteins leading to the swelling of angioedema.

Paul Bruns (DE) formulated the general pattern of the age and the sex specific incidence of various types of human bone fractures in an impressive review of fracture epidemiology (500).

Ernst Viktor von Leyden (DE) described fatty infiltration of the heart for the first time (3593).

Eduard Albert (AT) introduced the concept of joint arthrodesis (fixation of a joint by fusion of the joint surfaces) into orthopedic surgery. This is the first description of arthrodesis of an ankle for paralytic foot (31).

Carl August Langenbuch (DE), in 1882, performed the first successful cholecystectomy (removal of the gall bladder) (1963).

Alexander von Winiwarter (AT-BE) was the first to successfully perform a cholecystoenterostomy in man (surgical anastomosis of the gallbladder and intestinal tract) (3633, 3634).

Adolf Eugen Fick (DE) introduced the concept and methodology of isotonic and isometric determination of the process of muscular contraction (1089). 

From 1882-1924 the U.S.S. Albatross, under the direction of the U. S. Fish Commission, further extended knowledge of the extent and variety of marine life.

Simon Schwendener (CH-DE) was one of the founders of the journal Deutsche Botanische Gesellschaft.


"There is something fascinating about science. One gets such wholesale returns of conjecture out of such a trifling investment of fact." Samuel Langhorne Clemens (Mark Twain) (629).

Johan Gustav Christoffer Thorsager Kjeldahl (DK) described his method for determination of nitrogen in organic materials (1818, 1819).

Jacques Louis Soret (FR) discovered an intense absorption band in the blue region of the spectrum of porphyrins and their derivatives. It became known as the Soret band (3217).

Heinrich August Bernthsen (DE) made the dye azure B (215, 216). 

Franz Hundeshagen (DE) synthesized lecithin (1662).

Max Rubner (DE) discovered that the energy supplied to the human body by foodstuffs is precisely the same in quantity as it would have been if those same foodstuffs had been consumed in a fire (once the energy content of urea was subtracted). The laws of thermodynamics, in other words, hold for living tissue. He perfected the methods of computation used in modern animal calorimetry and demonstrated that living bodies obey the law of the conservation of energy. He also established the relationship between the skin surface area of an animal and its food requirements. He showed that the heat value of metabolism in a resting animal is proportional to the area of the body surface (2988-2991).

Jacques-Louis Soret (CH) discovered a strong absorption band of hemoglobin in the violet and ultra-violet portion of the spectrum(3217).

Karl James Peter Graebe (DE) and Heinrich Caro (DE) discovered acridine orange (1385).

L. Benda (DE) synthesized acridine orange and proflavine (163).

Carl Hamilton Browning (GB) and Walter Gilmour (GB) recognized the antimicrobial properties of acriflavine (489).

Ernst August Schulze (CH) and E. Bosshard (CH) isolated the amino acid glutamine from beet juice (3117).

Ernst August Schulze (CH) established that asparagine and glutamine are important in plant metabolism (3114).

Edmund J. Mills (GB), James Snodgrass (GB), and Thomas Akitt (GB) suggested that absorption of halogen might be used to measure the degree of saturation of a fat or fatty acid (2349, 2350).

Bronislaw Lachowicz (PL) and Marceli Nencki; Marcellus von Nencki (PL) reported putrefaction under conditions in which no free oxygen could be detected even by the most sensitive tests (1947).

Hikorokuro Yoshida (JP) was the first to clearly identify an oxidative enzyme as such. The enzyme was diastatic matter, which promoted the darkening, and hardening of the latex of the Japanese lacquer tree. It catalyzes the oxidation of a plant constituent (urushiol) by atmospheric oxygen (3818).

Sydney Ringer (GB) reported that calcium ions are required in the bathing medium to maintain the contraction of an isolated frog heart (2933).

Arthur Meyer (DE) described the chloroplast as consisting of a colorless, homogeneous matrix in which grana are embedded (2319).

S. Jenny Doutreligne (NL) and Johann Heinrich Emil Heitz (DE) described chloroplasts as consisting of a lighter-colored stroma impregnated with a number of darker grana (886, 1528, 1529).

Bert Hubert (NL) and Albert Frey-Wyssling (CH) postulated that grana contain alternate proteidic and lipoidic layers with chlorophyll molecules attached (1221, 1222, 1653).

Theodor Wilhelm Engelmann (DE) discovered that Bacterium photometricum, a motile purple bacterium which metabolizes sulfur compounds is phototaxic, inhibited from motion by carbon dioxide, and does not liberate oxygen. When he illuminated the culture with a spectrum, the cells accumulated in bands at the wavelengths at which they could respond. This led to the discovery of bacteriochlorophyll a, a pigment absorbing in the near infrared, 850 nm (1024).

Heinrich Hermann Robert Koch (DE) decided that it is impossible to develop a universal medium with equal nutritional value for all bacteria. He developed an artificial solid medium by adding 2 and one-half to 5 percent gelatin to well-tried fluid medias. The sterile gelatin medium was poured onto sterile slides under a bell jar and allowed to harden. The slides were inoculated by means of a sterilized needle or platinum wire, which was drawn lightly across the surface of the gel. When growth appeared it was transferred to test tubes plugged with cotton and containing sterile nutrient gelatin, which had been set in an upright or slanted position. This technique was to revolutionize microbiology (1847).

Heinrich Hermann Robert Koch (DE) developed the pour plate method of isolating bacteria in axenic culture. A mixture of organisms was inoculated into molten nutrient gelatin, mixed thoroughly, and then poured onto cold sterile glass plates. This method for obtaining axenic cultures soon became the method of choice (1847).

Ulysse Gayon (FR) and Gabriel Dupetit (FR) isolated two strains of denitrifying bacteria in axenic culture. They found that a variety of simple and complex organics could serve as carbon sources and as reductants of nitrate (1290).

Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) reported that natural immunity depends on a cellular rather than a humoral mechanism. The cells, which possess this property, were named phagocytes by Metchnikoff, and the process phagocytosis. He first observed this phagocytic activity in starfish larvae, which he purposely irritated with rose thorns. Later he observed that the crustacean Daphnia magna used phagocytosis to defend against the parasite, Monospora bicuspidate. In frogs, lizards, turtles, guinea pigs, and rabbits he introduced a solution of anthrax under the skin or by injection into both immunized and nonimmunized animals, concluding (incorrectly) that phagocytosis was responsible for all protection (2314-2317). See, Bizzozero, 1873

Carl Claus (DE) coined the Greek equivalent to fresszellen (devouring cells), phagocyte (phagein [to eat] and kytos [cell]) (3303).

Emil Christian Hansen (DK) was the first to provide scientific evidence of the various strains of yeast. His greatly improved dilution technique allowed him to produce axenic cultures of yeast and by doing so revolutionized this aspect of the brewing industry (1480-1483).

Alphonse de Candolle (FR) wrote Origine des Plantes Cultivée that identified the geographic origin of most agronomic, horticultural, and fruit crop plants (807).

Moriz Loewit (AT) described the development of the erythrocyte from a non-hemoglobiniferous small round cell (2113).

Jan Hendrik Wakker (NL) discovered and described the microorganism causing “yellows” disease of hyacinths. Some consider this and Thomas Jonathan Burrill’s work of a year earlier to represent the birth of the science of bacterial phytopathology (3648). See, Burrill in 1882.

Theodor Albrecht Edwin Klebs (DE) announced that one type of diphtheria is caused by a bacillus which when stained with methylene blue appears to have a knob at either end of the cell. He observed that it was always present on the surface of the membranes formed in the throat, but never could be found in other tissues of diphtheria victims (1827).

Friedrich Fehleisen (DE-US) gave the first detailed account of Streptococcus erysipelatis. He induced typical erysipelas in human volunteers with streptococci from lesions of patients with the same disease (1068). In the Middle Ages erysipelas and acute ergot poisoning were both called St. Anthony’s fire.

Louis Pasteur (FR) and Louis Thuillier (FR) successfully produced a vaccine against swine erysipelas by passing the bacterium through the bodies of rabbits. Thuiller was to die later that year, at the age of 27, from cholera he was studying in Alexandria Egypt (2696).

Albert Freeman Africanus King (US) wrote a paper in which he gave 19 reasons why mosquitoes were likely to be the vector of malaria (1803).

Paul Gerson Unna (DE) recognized human transmission of herpes simplex virus infections between individuals (3421).

Victor Alexander Haden Horsley (GB) described the effects of nitrous oxide anesthesia (1639).

Wilhelm Roux (DE) worked out the timing of the determination of the main axes of the frog’s embryo and developed the first important hypothesis to explain differentiation—mosaic or determinant development—during embryonic development. This theory held that differentiation during ontogeny was caused by the qualitative nuclear division of the hereditary material during cleavage; as development progressed, cells gradually lost more and more hereditary potential in terms of the kinds of adult tissues they could form (2980, 2982).

Wilhelm Roux (DE) was the first to culture somatic cells outside the body of the organism. His objective was to observe embryonic development. He demonstrated that closure of the frog neural tube could take place without pressure from the surrounding tissues (2983).

Wilhelm Roux (DE) founded what he called entwickelungsmechanik (developmental mechanics) which became experimental embryology then analytical embryology (2571).

Magnus Gustaf Blix (SE), Johannes Karl Eugen Alfred Goldscheider (DE), and Henry Herbert Donaldson (US) discovered that a person's thermal sensations are associated with stimulation of localized sensory spots on the skin. Further investigation revealed a distinction between hot spots and cold spots; i.e., specific places in the human skin that were selectively sensitive to warm or cold stimuli (300-302, 870, 1325).

Emil Theodor Kocher (CH) showed the relationship of goiter to activity of the thyroid gland (1859). He was the first to find a way to tie off all the thyroid’s blood vessels, allowing surgery. During his professional life he performed over 2,000 thyroidectomies. In 1878, he described his early experiences with thyroidectomy for thyrotoxicosis, which he performed with a mortality of 13%. By the time he published more detailed descriptions in 1883 his operative mortality had fallen to less than 1%. He recognized myxedema after thyroidectomy, which he described as cachexia strumipriva. This occurred after 30% of thyroidectomies at that time.

His other significant contributions to surgery were descriptions of a maneuver to reduce a subluxed shoulder in1870, radical surgery for carcinoma of the tongue in1880, and an operation for inguinal hernias in 1892 (1857, 1858, 1860). He introduced the use of sterilized silk sutures into his surgical practice in 1882. His name is associated with a toothed surgical clamp, an atraumatic bowel clamp, and a curved director. A sub-costal incision for an open cholecystectomy, a percondylar humeral fracture, and a maneuver to mobilize the duodenum are also named after him.

Algernon Phillips Withiel Thomas (GB-NZ) and Karl Georg Friedrich Rudolf Leuckart (DE) independently established the life cycle of Fasciola hepatica, the liver fluke. This was the first time that a trematode life cycle was described (2046, 2047, 3316-3320). Note: at this point it was still uncertain how the encysted cercaria infected the second host.

Adolfo Lutz (BR) proved that infection of the second host is acquired by ingestion of cysts containing metacercaria (2164).

Dimitry F. Sinitsin (RU), in 1911, demonstrated the pathway of migration taken by the metacercaria in the second host. They penetrate the intestinal wall and pass into the peritoneal cavity, then attach to the liver and penetrate into biliary passages where they mature (3195).

Jaime Ferrán (ES) in a letter of 3 April 1883 to the French Academy of Sciences in Paris described how he had protected guinea pigs from an otherwise lethal dose of Vibrio cholera by previously giving them a subcutaneous injection of Vibrio cholera (1073).

Waldemar Mordecai Wolff Haffkine (RU-CH-FR) developed a vaccine for cholera, which he and his colleagues used to treat many people in India. He founded the Government Research Laboratory (now Haffkine Institute) in Bombay. Haffkine first inoculated himself to prove the safety of the vaccine before inoculating others (517, 1464). 

Francis Galton (GB) coined the term eugenic (wellborn) to refer to the breeding of members of a species in such a way as to concentrate desirable traits within offspring (1257).

Paul Albert Grawitz (DE) described renal hypernephroma, i.e., adenocarcinoma of kidney, hypernephroid tumor, clear cell carcinoma, hypernephroma, kidney adenocarcinoma, renal adenocarcinoma, renal cell carcinoma, strumasuprarenalis cystica hemorrhagicarenal cell carcinoma (1401, 1402).

Robert Lawson Tait (GB) was the first surgeon to successfully remove a ruptured ectopic pregnancy. The operation took place on March 1, 1883, in Birmingham England (1324).

H. Leyden (DE) performed the first percutaneous needle biopsy of the lung. It consisted of the examination of the consolidated right lower lobe of a moribund 48-year-old man. The specimen was stained, and bacteria and WBCs were identified. Pneumonia was diagnosed (2062).

Lloyd F. Craver (US) performed transthoracic needle biopsy of the lung at Memorial Hospital in New York City as early as 1927 (719).

Jacques-Louis Reverdin (CH) and Auguste Reverdin (CH) observed that myxedema occurred as a delayed complication when the thyroid gland was surgically removed (2917).

Robert Lawson Tait (GB) was the first to successfully surgically manage a ruptured tubal pregnancy when he performed a laparotomy and ligated the ruptured tube and the broad ligament (3298). A series of thirty-five cases with only two deaths speedily followed, and the operation took its place as a recognized method of treating a condition that had previously been looked upon as desperate.

Emil Wilhelm Magnus Georg Kraepelin (DE) attributed mental illnesses to either exogenous treatable causes or endogenous untreatable causes. In the sixth edition of his Compendium der Psychiatrie, manic-depressive psychoses were called such for the first time. He coined the terms neuroses and psychoses (1900).

O. Kobylinski (ES) describes the first reported patient with what is now called Noonan syndrome (1840).

Jacqueline A. Noonan (US) noticed that children with a rare type of heart defect, valvular pulmonary stenosis, often had a characteristic physical appearance, with short stature, webbed neck, wide spaced eyes, and low-set ears. Both boys and girls were affected. These characteristics were sometimes seen running in families but were not associated with gross chromosomal abnormalities (2526). This condition was later named Noonan syndrome.

John Cleland (GB) was the first to describe Chiari II or Arnold–Chiari malformation on his report of a child with spina bifida, hydrocephalus, and anatomical alterations of the cerebellum and brainstem (628).

Hans Chiari (AT) described the case of a 17-year-old woman with elongation of the tonsils into cone shaped projections, which accompany the medulla and are crammed into the spinal canal (612, 613).

Julius Arnold (DE) described the pathological findings in an infant dying shortly after delivery. The child had a large herniation of the spinal cord thoracolumbaly. He also described the brainstem as underdeveloped with a downward draw of some of the lower parts of the cerebellum and the 4th ventricle in the spinal canal (59).

Ernst Schwalbe (DE) and Martin Gredig (DE) described four cases of meningomyelocele and alterations in the brainstem and cerebellum, and gave the name Arnold-Chiari to these malformations (3122). Note: Arnold-Chiari malformation is a condition in which the inferior poles of the cerebellar hemispheres (cork-like protrusions) and the medulla oblongata protrude through the foramen magnum into the spinal canal, without displacing the lower brain stem.

William Keith Brooks (US) provided one of the clearest discussions of variability. Alluding to "one of the most remarkable and suggestive of the laws of variation," that parts exclusively male or of greater importance in males were "very much more variable" than parts confined to or more important in females. Brooks derived a general corollary, "that males are as a rule more variable than females." Brooks believed that he could offer a hereditary explanation for male variability in the differing functions of the sex cell. The male cell had developed "a peculiar power to gather and store up germs." Critical to this theory was the assumption that the transmission was sex-linked, so that variations accumulated exclusively in the male line. "According to this view, the male element is the originating and the female the perpetuating factor; the ovum is conservative, the male cell progressive" (472).

William Henry Flower (GB) was the first to show that lemurs are primates. He re-implanted Homo within Linnaeus’ Primates. In the almost 150 years of systematics that followed the first edition of the Systema Naturae, this was just the second time that humans were classified with the animals. Prior to Flower, only the mid-nineteenth-century French systematist Isidore Geoffroy Saint-Hilaire had been so bold (1174).

Karl August Möbius (DE) expressed the concept of community (he called it biocoenosis), however, his essay lacked the detail and impact of later papers (2367).

Stephen Alfred Forbes (US) put forth his classic description of community in its ecological context and characterized the main goal of ecological research: to analyze how harmony is maintained through the complex predatory and competitive relations of the community. This essay drew attention to the way species are bound up with others within the community (1184-1186). 

The Journal of the American Medical Association was founded (2213).

Charles Doolittle Walcott (US) identified pillar shaped masses of thinly layered limestone rock in Precambrian strata from the Grand Canyon in western North America. Although he did not understand their significance as fossils he later interpreted these and pillar like structures of limestone as fossilized reefs laid down by algae (cyanobacteria) (3650). These pillar like structures called Cryptozoon (hidden life) are now called stromatolites.

Max Josef von Pettenkofer (DE) founded the journal Archiv für Hygiene, which became Zentralblatt für Hygiene und Umweltmedizin, Journal of Hygiene and Environmental Medicine, then International Journal of Hygiene and Environmental Health.

The journal Science was founded.


“After all it is the quest after perfect truth, not its possession, that falls our lot, that gladdens us, fills up the measure of our life, nay! hallows it.” August Friedrich Leopold Weismann (3704).

Svante August Arrhenius (SE), in 1884, proposed in his doctoral dissertation that some substances when dissolved in water would behave as electrolytes and thus carry a current because they exist as charged ions in solution. Substances, which cannot behave as electrolytes, are non-ionic. He defined acids as substances that release hydrogen ions when dissolved in water to become negatively charged ions highly capable of reacting with other compounds (62-64).

Wilhelm Friedrich Ostwald (LV-DE) proffered his dissolution law (2594).

Paul Böttiger (PL-DE), in 1883, synthesized Congo red then patented it in 1884. Congo red was the first dyestuff capable of directly staining cotton without a mordant. Congo red is the essential histologic stain for demonstrating the presence of amyloidosis in fixed tissues (337).

H. Griesbach (DE), in 1886, was the first to report using Congo red to stain tissue (1414).

H. Bennhold (DE), in1922, reported that Congo red was found to bind avidly to amyloid protein (171).

Paul Divry (BE) and Marcel Florkin (BE), studying degenerative changes in aging brains, first noted the characteristic green birefringence of amyloid substance when stained with Congo red and viewed under polarized light (863-865).

Hans-Peter Missmahl (DE), Marga Hartwig (DE), Mordechai Ravid (IL), Joseph Gafni (IL), and Ezra Sohar (IL) described the “congophilic” staining of amyloid in fixed tissue with the associated apple-green birefringence when viewed under polarized light (2355, 2874). This methodology remains essential for the diagnosis of amyloidosis.

Hermann Emil Fischer (DE) began research on the purines in 1881, coined the word purine in 1884, and synthesized a purine in 1898 (1128, 1137).

Carl Weigert (DE) introduced hematoxylin stain for myelin (3700).

Hugo Marie de Vries (NL) demonstrated that solutions of substances with very similar molecular structure and at the same concentrations exert the same osmotic pressure.

He introduced a new method, which determined the osmotic value of plant cells by immersion in solutions of known concentrations of cane sugar or potassium nitrate. He determined the concentration of each solute that would bring about plasmolysis or the withdrawal of the protoplasm from the walls of the cells. He reasoned that all solutions inducing the same minimum degree of visible plasmolysis of cells must be of equal strength (829, 831).

Oscar Minkowski; Oskar Minkowsky (DE) identified b-hydroxybutyric acid in the urine of diabetics along with a decrease in blood bicarbonate leading to diabetic acidosis (2352). Minkowski also proved that diabetic coma is accompanied by a decrease in the amount of carbon dioxide dissolved in the blood, and he introduced alkali therapy to counteract it.

Johannes Ludwig Wilhelm Thudichum (DE-GB) discovered hematoporphyria and worked on the chemical constitution of the brain in which he discovered, galactose, glucose, lactic acid, cerebranic sulfatides, kephalin, and the lipoid nature of myelin (present on some CNS cells); distinguished kephalin from lecithin; introduced the terms phosphotide and sphingolipid, discovered the sphingomyelin and cerebrosides in the brain—isolating phrenosin and kerasin—and proposed that “the great diseases of the brain and spine, such as general paralysis, acute and chronic mania, melancholy and others will be shown to be connected with specific chemical changes in the neuroplasm” (3345). Thudichum is considered to be the founder of neruochemistry.

Wilhelm August Oskar Hertwig (DE) presented his kernideoplasma theory saying, “I believe that I have at least made it highly probable that nuclein is the substance that is responsible not only for fertilization but also for transmission of hereditary characteristics... Furthermore, nuclein is in an organized state before, during and after fertilization, so that fertilization is at the same time both a morphological and a physiochemical event” (1567-1569).

Heinrich Anton de Bary (DE) called for the blue-green algae (cyanobacteria) to be considered bacteria and not algae (801).

Charles T. Druery (GB) and Frederick Orpen Bower (GB) discovered apospory in the Pteridophyta (ferns, horsetails, and club-mosses) (380, 898).

Theodor Wilhelm Engelmann (DE) concluded that all plastid pigments, and not merely chlorophyll, could mediate photosynthetic oxygen evolution (1027).

Hans Christian Joachim Gram (DK) found that if bacteria are stained by Ehrlich’s aniline-water-gentian-violet, then treated with Lugol’s iodine in potassium iodide, and finally placed in alcohol, the color is discharged from certain bacteria but is retained in other bacteria. He devised this method to display bacteria in tissue sections. Gram did not use any counterstains. He actually considered the iodine as a counterstain. Neither did he appreciate the significance of the fact that some bacteria did not stain by this method. The idea of gram-positive and gram-negative bacteria was not appreciated until later. Although modified, the essence of the Gram procedure remains the differential stain most widely used in bacteriology (1393, 1394).

Agar-agar replaced gelatin as the solidifying agent of choice in bacteriological media. Angelina Fannie Hesse, the wife of Walther Hesse, one of Heinrich Hermann Robert Koch’s early co-workers, introduced it. She had obtained samples, through Dutch friends, from Batavia, where it was well known for culinary purposes and especially in the making of jam. The peculiar virtue which has established its dominance in bacteriological culture technique is that a high temperature is required to melt it, but once melted it can be cooled down to about 40°C. before it sets into a stiff and relatively transparent gel. No formal article was written describing this discovery (1596).

The Parisian engineering firm of Weisnegg produced an instrument for generating steam under pressure. It was called Chamberland’s autoclave (for Charles Édouard Chamberland) and found to be very useful in sterilizing various objects (583).

Louis Théophile Joseph Landouzy (FR) was the first to suggest the infectious nature of herpes (1958).

Émile Julien Armand Gautier (FR) introduced a bacterial filtering device made of borax, silica, and red lead. Charles Édouard Chamberland (FR) modified Gautier’s filter so that it had a candle shape with a porcelain nipple (583, 584).

Eduard Friedrich Wilhelm Pflüger (DE), by allowing frog eggs to cleave under pressure between two panes of glass, showed that the planes of cleavage are modified; nevertheless, abnormal cleavage patterns do not preclude formation of a normal embryo (2742).

Ettore Marchiafava (IT), and Angelo Celli (IT) stained diplococci in meningeal exudates from patients with meningitis (2232).

Friederich August Johannes Löffler (DE) and Theodor Albrecht Edwin Klebs (DE) stained and described Corynebacterium diphtheriae, the bacterium that causes diphtheria. They used an alkaline version of methylene blue, which is today the most popular version of this dye. This organism is sometimes called the Klebs-Löffler bacillus.

The following are excerpts from Friedrich August Löffler’s report to the German Imperial Health Office, which beautifully describe his methodology in defining his discovery that Corynebacterium diphtheriae is the etiological agent of diphtheria (Gr. coryne, club).

“Sixty years have elapsed since Bretonneau presented his classic description of diphtheria. Despite many studies, no universally acceptable explanation of the etiology of this disease has been reached. The divergence of opinions arises from the characteristics of the disease. The appearance of individual cases varies with the age of the patient, the severity and the stage of the disease. Especially significant is the frequent difficulty in deciding whether the observed lesions are due to the frequent complications or to the disease proper. Furthermore, many inflammatory diseases other than those caused by the virus of diphtheria produce pharyngeal lesions, which cannot be differentiated from diphtheria. The only significant pathognomonic differential factor is the etiological agent.

This disease is localized on a mucous membrane, which is exposed to the extensive bacterial flora of the exterior world. The numerous organisms from food and drink reaching the rugose mucous membrane of the upper respiratory tract find there a favorable medium for growth. These favorable conditions are further improved by the protein-rich inflammatory exudate induced by diphtheria. It will therefore be difficult to differentiate the primary etiological agent from the proliferating multitude of saprophytes present in the normal mouth and pharynx. The failure to define the etiological agent of diphtheria has been due to the difficulty in recognizing the essential organism in the presence of many others and to the inadequacy of methods previously available for differentiation and isolation. Koch has overcome the inadequacies of the experimental methods.

Earlier investigators sought the specific agent in the mucous exudate of the pharynx rather than the internal organs. Experience from accidental infections justified this choice in source material, since physicians and nurses aspirating exudate by mouth suction through tracheal cannulae would acquire the disease if they came in contact with it, but the disease was not acquired by contact with material from other organs and body fluids….

If, then, diphtheria is a disease caused by microorganism, three postulates must be fulfilled:

1. The organism typical in form and arrangement must be consistently demonstrated in the diseased area.

2. The organism, which by its behavior appears responsible for the pathological process, must be isolated and grown in axenic culture.

3. A specific experimental disease must be produced with the axenic culture….

An evaluation of the results of the past investigations reveals that these postulates have not been fulfilled. Previous investigators saw bacteria in pseudomembranes, but few gave detailed data regarding the types of bacteria present. The earliest investigators stated merely that molds were present. The status of bacteriology at the time did not permit more precise differentiation, technique being limited to smear preparations. Subsequently, sections were prepared which demonstrated the relationship of molds to tissue. Molds were more frequent in the upper layers of pseudomembranes. Micrococci predominated and were located in the lymph vessels. The demonstration of bacteria in internal organs was uncertain and depended upon resistance of tissue structures to the types of reagents used, acetic acid, alkali, ether, etc. Reliable investigations, utilizing stains, Abbe condensers and oil immersion, revealed the absence of bacteria in internal organs and their presence in pseudomembranes. Attempts to culture the micrococci resulted in mixed growth, since the source material was tonsillar overlay in which other bacteria were always present. Cultures of tissue from internal organs were negative.

Attempts to transmit diphtheria to animals, using a variety of infecting procedures did not lead to a truly typical diphtheria. Intramuscular injection of diphtheritic material produced a hemorrhagic inflammation. Corneal injection led to keratitis and intratrachael injection led frequently to a pseudomembranous tracheitis. Most investigators could not produce these reactions with disrupted organic materials that were used as controls, but some investigators could produce identical changes with non-diphtheritic material….

It seemed indicated, using Koch’s recently developed methods for isolation and cultivation of bacteria on solidified culture media, to reinvestigate types of bacteria associated with diphtherial tissue, to determine which might be of etiological significance, to grow these in axenic culture, and finally to perform inoculation experiments with axenic cultures in the largest possible number of animal species….

In most instances the source specimens at my disposal were not accompanied by comprehensive clinical data; acquisition of such data would have required full attendance in the hospital. However, I attempted to determine the clinical course, and especially the duration of illness, of source cases. Even though scarlatinal diphtheria was differentiated from diphtheria, the frequency of the combined disease led me to include such cases in the scope of this study.

For examining microscopic sections it was necessary to use a staining method, which would be applicable to a wide variety of bacteria. None of the available methods, namely the Weigert nuclear stain, the pico-carmine gentian-violet differential stain and the Koch-Ehrlich differential stain for tubercle bacilli were satisfactory. While studying sections of syphilitic sclerae, I found a more intense and rapid staining was achieved with a mixture of 1 cc. of concentrated alcoholic methylene blue in 200 cc. of water when 0.2 cc. of 10% potassium hydroxide was added than when such a mixture lacked potassium hydroxide. Since this weak methylene blue solution did not stain some types of bacteria adequately, I raised its concentration, and the most rapid and intense staining was achieved with 300 cc. of concentrated alcoholic methylene blue in 100 cc. of a 1-10,000 dilution of potassium hydroxide in water. The sections were immersed in the stain for several minutes and then rinsed in 0.5% acetic acid to remove excess stain and achieve differentiation of nuclei. They were then dehydrated in alcohol, treated with cedar oil and finally mounted in Canada balsam. Anthrax, rabbit and mouse septicemia bacilli, typhoid and glanders bacilli, erysipelas micrococci, Micrococcus tetragenus, spirochetes of relapsing fever, fungal mycelia, etc., were all equally well stained. This technique thus approached a universal staining method….” 

Löffler examined clinical materials from twenty-seven patients. Anatomical diagnoses were followed by a description of sections from various tissues and organs.

“ A consideration of the case material reveals that 3 types of cases may be recognized. In one type, chain-forming micrococci appear to play a major role. The mucosal surfaces are completely denuded of epithelium are greyish yellow in color and there has been a loss of tissue as a result of necrosis. Pseudomembranes are absent. The micrococci are present on the surface and penetrate into the tissues forming wedge- or tongue-like areas of necrosis marginated by a narrow unstained border followed by a layer of proliferating cells. The micrococci may thus penetrate into the lymph vessels and then spread to other organs of the body where they form plugs in the capillaries. A similar picture is seen accompanying other diseases such as smallpox, typhus fever, puerperal fever, etc., where chain-forming micrococci are known to produce complications accompanying the primary disease. Similarly these organisms are most likely a complication of primary diphtheria, thus the frequency of the occurrence of micrococci on and in mucous membrane in diphtheria should not lead to confusion regarding the true primary agent….

Another type of case offers more direct evidence of the secondary invasive role of the micrococci. True pseudomembranes are present and in addition to micrococci, a second type off organism is seen. Too few micrococci are present to account for the observed damage, but the other organism may readily account for the pseudomembrane formation. The second type of organism is Kleb’s bacillus. Unlike the micrococcus, the Kleb’s bacillus alone may be present in typical cases that are characterized by the presence of a thick pseudomembrane in the pharynx, larynx and trachea. A variety of bacteria are irregularly distributed on the surface of the pseudomembrane. Below the surface are small masses of bacilli, which stain intensely with methylene blue….

The third type of case strongly supports the hypothesis that the bacilli occurring just below the surface are the etiological agents. It can be illustrated by the case of a child who died on the third day of the disease. The pseudomembrane in the trachea, which undoubtedly was the last such element to be formed, was a thick membrane containing masses of the characteristic bacillus alone. Another child who also died on the third day of the disease with dyspnea and symptoms of lung inflammation had not only a pseudomembrane in the trachea but also masses of rods in the alveoli as well….

From the pathologico-anatomical studies it could not be determined whether the micrococci or the bacillus was the etiological agent. The only remaining course was to obtain axenic cultures of each of the two types of organisms and, by animal inoculation, to determine which could produce a disease analogous to human diphtheria.

The cases chosen for the cultural study of the coccus were those showing chain-forming micrococci either solely or in overwhelming proportion in microscopic smear preparations of tonsils and internal organs. Meat broth-peptone-gelatin was used as culture medium. Fragments from infected tonsils were incorporated into the liquified medium on slides, and the mixtures were covered with glass cover slips. The gelatin was then allowed to solidify, permitting the development of isolated colonies. The preparation of axenic cultures from internal organs was simpler. To eliminate surface contaminants, the organs were washed in 5% phenol for 10 minutes to kill vegetative forms of bacteria and in 1% bichloride of mercury for 5 minutes, to kill spores. The organs were dried on blotting paper. After the surfaces were dried, the organs were cut with a hot glowing knife and hot glowing forceps were used to tease portions of tissue for culture study. With these methods axenic cultures of chain-forming micrococci were obtained from five cases: 2 of scarlatinal diphtheria and 3 of typical diphtheria.

The chain-forming micrococci grew slowly in gelatin. After three days of growth, examination with direct light revealed small, round, grayish translucent colonies…. In reflected light the colonies were white and granular, indistinguishable from erysipelas cultures. The micrococci grew luxuriantly in meat infusion medium (meat infused with 1% peptone, 0.5% NaCl and 1% dextrose). After 24 hours of incubation at 37°C. finely threaded floccules appeared. These floccules were formed by long interweaving chains comprising up to 100 cocci. The organism grew on meat infusion broth solidified with 1% agar, but growth was more luxuriant when serum was used as gel. Pure coagulated serum was inferior to a mixture of 1 part meat infusion medium and 4 parts serum... Growth on cooked potato (Solanum tuberosum) was slow. In the various culture media, bacterial cell division was observed in both the horizontal and longitudinal plane.

Animal passage studies were performed with four axenic cultures of chain-forming cocci….”

After extensive animal experimentations with mice, guinea pigs, rabbits, birds, dogs, and apes, Löffler was finally convinced that the micrococcus could not produce a diphtherial disease in animals. He concluded:

“Since, (1) the chain-forming cocci did not produce a diphtheria-like disease in any experimental animal species, (2) the cocci were see in only a limited proportion of diphtheric cases in man, (3) they occurred in diphtherial lesions only in association with a type of bacillus to be described more fully below, and finally, (4) they were also found in internal organs in other diseases, we are justified in concluding that the chain-forming cocci are only accidental secondary invaders in diphtheria. The chain-forming micrococci may, however, produce a diphtheria-like disease when the pharynx is invaded and the organisms spread through the lymphatics to the trachea and lungs. Such was the case of an infant who had a nasal discharge and a slight pseudomembrane in the throat. After several days the infant became hoarse and a dyspnea of increasing severity set in followed by death. At autopsy the pharynx was clear, but there was a thin grey pseudomembrane on the epiglottis, trachea, and bronchi, and areas of hemorrhagic bronchopneumonia in the lungs. In sections the epithelium of the epiglottis was still intact, but the lymph vessels in the mucous membrane below were filled with micrococci. The trachea was denuded of epithelium and covered with an exudate of inflammatory cells and micrococci. Micrococci were also seen in the mucous membrane of the lungs. All other organs were normal. The disease could be interpreted as a diphtheria-like mucous membrane erysipelas.

The characteristic rods, which [had been observed previously by Klebs] were slightly bent and enlarged at the poles, and were frequently seen in smears and sections, could not be cultured on meat infusion-peptone-gelatin…. It was therefore decided to culture the material on coagulated blood serum with incubation at body temperature. Despite the possibility of rapid overgrowth with putrefying contaminants, the very first trial using this technique met with success.

Segments of organs from a dead patient were sent to me in a glass jar. The organs lay for several hours in blood that had seeped from the cut surfaces of the organs. Liver, heart, and kidney, which in smears yielded only micrococci, were washed in 5% phenol followed by 1% mercuric bichloride. Fragments of these organs were cultured on meat infusion-peptone-gelatin incubated at room temperature, coagulated beef serum incubated at 37°C. In addition, scrapings from areas of pseudomembrane of the pharynx, showing both micrococci and Kleb’s bacilli in smear preparations, were cultured on coagulated sheep serum incubated at 37°C. On the following day discrete translucent colonies were seen in all serum cultures. Most of these colonies consisted of micrococci, but occasional ones were of rods identical with the ones in the pseudomembranes. After three days of incubation the colonies of micrococci were small, yellowish and translucent, whereas the colonies of rods were large, whitish and opaque. No Kleb’s bacilli were recovered from gelatin cultures. Occasional colonies of rods were now seen in cultures of liver and kidney, which until then had revealed only micrococci. However, the presence of the rods on the peripheral areas of the internal organs is, in my estimation, a post-mortem change caused by the organs and pharynx being held in the same fluid.

For animal passage experiments loopfuls of growth from colonies of characteristic rods were suspended in 10 cc. amounts of sterile water and loopfuls of those suspensions were cultured on fresh serum slants. The organisms grew as isolated colonies. Third passage cultures prepared from isolated colonies were used for animal inoculation. Such axenic cultures were certainly free of original tissue. The medium consisted of three parts calf or sheep serum and one part veal bouillon containing 1% peptone, 1% dextrose and 0.5% NaCl. Growth on this medium was luxuriant; in 2 days a 1-mm. thickness of culture was evident and isolated colonies attained a diameter of 0.5 cm. This medium was used for subsequent cultures. Another axenic culture of rods was obtained from the tracheal pseudomembrane from another case, which in smear preparations revealed many rods.

Following the isolation of rods from autopsy material, recovery of axenic cultures of rods from living patients presented no difficulties. Axenic cultures were obtained from 4 successive living cases. Portions of membrane were removed for microscopic section and for axenic culture isolation as described above. In sections, micrococci predominated on the surface, but rods were abundant in the cellular layer immediately below the surface. The fibrinous layer was free of bacteria.

In culture, the rods appeared first followed by the micrococci. Axenic cultures of rods were obtained as before. The rods were non-motile and stained intensely with methylene blue. They were straight, or slightly bent, about as long as and twice as thick as tubercle bacilli. The larger ones were segmented with thickening at their points of junction. The ends were sometimes enlarged. Barred staining and intensified polar staining were frequent.

Treatment of methylene blue smears with dilute iodine intensified the stain in the polar granules and decolorized the remaining areas of the cells. The polar granules did not appear to be spores. They did not glisten in reflected light, they stained readily, and rods with polar granules were destroyed by heating for 30 minutes at 60°C. Cultures were viable for 3 months. The rods required temperatures above 20°C. for growth and cooked potato (Solanum tuberosum) medium did not support their growth.

Of major interest was the effect of axenic cultures of the rods in various animal species. Six axenic cultures were tested in mice, rats, guinea pigs, rabbits, apes, small birds, pigeons, and chickens. The animals were inoculated by subcutaneous route, application to traumatized and intact mucous membranes, and by inhalation.”

After having shown that mice and rats were refractory to any pernicious effect of the rods, Löffler found that the bacillus was highly pathogenic for guinea pigs. He performed pathogenicity trials, both with tube culture inocula and tissue from infected animals. Twenty-eight guinea pigs were used and all were injected by subcutaneous route. He presented the observations and results in considerable detail, and summed up as follows:

“Pairs of guinea pigs were inoculated subcutaneously with each of a series of cultures. All guinea pigs were sick on the day following injection; they were listless, coats were ruffled, and there was swelling at the site of injection. The animals died within two to seven days. There were grayish white membranes at the sites of injection, edema in the surrounding subcutaneous tissue, bloody serous exudate in the pleural cavities, and brownish red dense and atelectatic areas in the lungs. The remaining internal organs were normal. Bacilli were recoverable only at the site of injection.

I have presented the results with this series of guinea pigs in detail, first because they demonstrate that bacilli isolated from the various human cases produced the same pathology, second because they demonstrated conclusively that death resulted not from a generalized dissemination of bacilli, but from an effect induced by the bacilli at the site of injection. The hemorrhagic edema, the pleural exudate, the brownish red areas of consolidation in the lungs, where bacilli could not be demonstrated, were conclusive indications that a toxin generated at the site of injection and transmitted through the blood stream, induced severe damage to vessel walls. The toxin generated by the bacilli in the guinea pig is undoubtedly similar to the toxin of human diphtheria. The toxin in man, like that in the guinea pig, appears to act primarily on blood vessels. 

Other noteworthy observations in the guinea pig were the formation of grayish white pseudomembranes at the sites of inoculation, and the disappearance of bacilli in lesions after several days, despite the lethal outcome in the animals.

The canary, finch, siskin, etc., were more susceptible than the guinea pig, when inoculated intramuscularly…. All birds died by the third day following infection with the symptoms described above. Bacilli were recovered only from the site of inoculation and all cultures from internal organs were sterile. When birds were inoculated with nutrient broth-peptone-gelatin cultures, survival rates could be prolonged up to 5 days, but the pathological changes were the same as those obtained after injection with cultures on coagulated serum and all cultures from internal organs were sterile. As in guinea pigs, the animals died from the effects of the localized infection.

The responses of rabbits were more variable than those of guinea pigs and small birds. Cultures of the bacillus were applied on the scarified cornea or conjunctiva, injected intramuscularly in the thigh or applied on the trachea by means of a tracheotomy. Where tracheotomies were performed, both the muscle and skin wounds were closed with sutures. A small number of intravenous inoculations were also performed.”

Löffler performed an extensive series of rabbit inoculations. Twenty-five rabbits were injected with three different strains.

“The various isolates of the bacillus induced the formation of dense fibrinous membrane on the conjunctival and tracheal mucous membranes of a high proportion of the test rabbits. The pseudomembrane formation must be attributed to the bacilli because the operative procedure alone and other bacteria isolated from diphtheric material injected in the same manner did not produce these effects.

The bacilli induced the formation of pseudomembranes in experimental animals, but the bacilli in the experimental pseudomembranes were not as numerous as in human cases and were distributed differently. The membranes in animals were essentially limited to the site of inoculation and contained few bacilli. Despite the limited site of membrane formation, as in guinea pigs, the infections could lead to death. Where death occurred followed intratracheal inoculation, the mechanical obstruction caused by the intratracheal pseudomembrane possibly could be implicated as the primary cause of death but deaths following conjunctival or intramuscular inoculation must be attributed to the formation of toxin at the site of inoculation and its subsequent dissemination through the blood stream; intravenous inoculation of large numbers of bacilli in rabbits did not lead to death. The organisms seen in rabbit tissues stained poorly and showed aberrant giant forms. These forms and staining reactions were encountered in the unfavorable nutrient gelatin cultures and imply that the rabbit body is not a favorable environment for the development of the bacilli.

Since there are reports of many cases of transmission of diphtheria from man to larger birds and vice versa, it appears especially interesting to study the effect of the bacilli on pigeons and chickens.

The third serial transfer of bacilli strain No. 1 was injected under the tongue and into the gums of three pigeons; one of the three pigeons was also injected in the breast muscle. A yellowish exudate developed at the sites of injection and spread over the beak cavity. The infiltration in one animal interfered with food intake and led to death on the 11th day. In both other animals, the exudates were resorbed and the animals recovered.

Pigeons are useful for such studies because the laryngeal and tracheal mucosa is easily injected without traumatization. These areas are exposed when the beak is opened. It was thus possible to see if introduction of the rods into the untraumatized respiratory tract could induce pseudomembrane formation.

The trachea of a pigeon was streaked with the 13th serial transfer of strain No. 1 and remained well. The fifteenth passage of the same bacillus was then applied to the trachea through tracheotomy. The soft tissues of the throat became edematous on the following day and a pseudomembrane was formed on the larynx. The animal died of respiratory failure on the 7th day. At autopsy there was a yellowish fibrinous pseudomembrane at the tracheotomal wound, larynx and buccal cavity, containing a variety of bacteria including the characteristic rod.”

He then repeated the experiment with some variations, using various strains that had gone through five to twenty-three serial transfers in vitro. The variations in the route of infection involved intratracheal application through the beak cavity and through tracheotomy, injection into multiple sites in the beak cavity, and intramuscular injection. Application of the cultures through tracheotomy led to death. Injection into beak cavity or muscle was not fatal; a local lesion developed but healed in approximately two weeks. Löffler then demonstrated a similar range of pathogenic reactions in chickens with six cultures injected in a total of eleven animals. Summarizing:

“In general, these experiments demonstrated that pigeons and chicks are not nearly so susceptible as small birds, namely finches, sparrows, and canaries.

It is important at this point to discuss observations on two pigeons and one rooster. In one of the pigeons injected with strain No. 1, a weakness in the limbs and the inability to fly was evident after 4 weeks. This progressed to severe paralysis and then to eventual recovery. This animal, which had been injected in the beak cavity with an axenic culture of rods isolated from a fatal human case, had developed a pseudomembrane that regressed. The paralytic episode in the bird was reminiscent of the transitory paralysis that occurs sometimes in human diphtheria, and might be attributed to the specific organism.

This conclusion was strengthened by a similar observation on a rooster that had been infected by tracheal application on the 25th serial transfer of the same strain. After transitory pseudo membrane formation, the animal developed paralysis of the legs and wings beginning 4 weeks after injection. The paralysis did not regress. Since such a symptomatology for chickens is not described in the literature, I believed that the paralysis was due to diphtherial infection. Paralysis was also encountered in a rabbit that had received the very same inoculum.

The pigeon that had been paralyzed and had recovered was reinjected in the beak cavity and breast with the 30th transfer of strain No. 1. A transitory pseudomembrane formation was again followed by paralysis. The animal died 23 days after the second injection. Autopsy revealed pneumonia to be the cause of death and there were masses of uric acid crystals around the joints and connecting tendons. This paralytic episode therefore was not of diphtherial origin but due to a uratic arthritis. 

The rooster was then sacrificed. The entire rump musculature was atrophic, the sternum and ribs were distorted, the junctions of the ribs with the sternum were swollen, and the vertebra softened. Thus the animal was suffering from a rachitis of the rump, bones and muscles that accounted for the paralysis. Again diphtheria did not seem to be directly involved.”

Similarly, for the second pigeon in this group of three large birds that developed paralysis, the symptoms were nondiphtheritic in origin. At autopsy a myxoma was found in the lower spinal cord.

“I considered it necessary to present the information in these three birds in order to spare subsequent investigators the possibility of being misled by such observations.

There remains to be described two experiments in an ape. A long-tailed Java ape was infected by streaking and traumatizing the pharynx with a stiff brush infected with the 9th serial transfer of strain No. 3. A small transitory ulcer resulted. The animal was then injected in the conjunctiva and subcutaneously in the axilla. A transitory swelling occurred in the conjunctiva and an edematous infiltration followed by ulceration and healing occurred in the axilla. These experiments indicated that apes are not susceptible to diphtheria.

In the experiments so far discussed natural modes of infection were not used. A more natural method of infection was then tried. Three chickens, 3 pigeons, 3 rabbits and 3 guinea pigs were placed in a chamber 1 meter X 0.5 m. X 0.5 m. Three hundred cc. of a densely turbid suspension of the 6th serial transfer of bacillar strain No. 3 were then atomized into the chamber. An ape was placed in a cylindrical chamber 0.75 meters high and 0.5 meters in diameter. The cylinder was equipped with the necessary food, water and bedding. One hundred and fifty cc. of the same bacterial suspension were sprayed into the cylinder. Even though the animals were exposed to infection both by inhalation and ingestion of contaminated food, none became sick. Similarly repeated attempts to infect rabbits and guinea pigs by application of cultures to undamaged mucous membranes were unsuccessful.”

Löffler decided to try one more route of infection, the vaginal inoculation of guinea pigs. He noted that: “Recovery occurred in most animals despite severe initial symptoms of intoxication.” This recovery was due, he thought, to the fact that the animals could remove the inoculum and the membranes that might form by licking. He continued:

“Such rapid removal and subsequent recovery could not be expected to occur following subcutaneous injection of organisms.

Before further discussing the evidence regarding the implication of the bacillus as the etiological agent of diphtheria we should determine whether or not the bacillus can be found in the oral and pharyngeal secretions of healthy individuals. Children were used for this study because they are the most susceptible age group. Cultures on broth peptone sugar serum medium were taken from the oral mucous of 20 children, ages 1 to 8, and cultures from 10 adults served as controls. The cultures were examined after three days of incubation and methylene blue smears were prepared from all grayish white or white colonies. These colonies were found to consist either of micrococci or of short ovoid bacilli that were not even remotely similar to our specific rod. Axenic cultures isolated from three colonies of the short bacilli were each injected into two guinea pigs and were found to be avirulent.

In one culture from a child, bacilli morphologically similar to the diphtheric rods were observed. They were slender, the size of tubercle bacilli, showed intense polar staining and polar clubbing. After four in vitro transfers, the culture of this organism was injected subcutaneously into two guinea pigs. Both animals were sick on the day following injection and died on the third day. In one there was a grayish pseudomembrane at the site of inoculation and edema in the surrounding area. The axillary glands were swollen and hemorrhagic, the kidneys and adrenals were engorged with blood. The specific bacilli were only observed at the site of inoculation. The findings in the other guinea pig were complicated by tuberculosis. Fifth passage culture of the same organism was then injected subcutaneously into three guinea pigs. All three animals died after two days with the typical diphtheric syndrome. There could be no doubt that this organism isolated from a healthy child was the same as the bacillus isolated from cases of diphtheria.

The following facts favor designating the bacillus as the etiological agent of diphtheria: The rods were found in thirteen of twenty-seven typical cases of diphtheria with fibrinous pharyngeal exudate. The rods were present in the oldest areas of the pseudomembranes and were deeper than other organisms. Cultures of the rods were lethal when inoculated subcutaneously into guinea pigs and small birds. Whitish and hemorrhagic exudates developed at the sites of injection with diffuse edema in the surrounding tissues. As in humans, the internal organs were free of lesions. The bacilli produced pseudomembranes on the exposed tracheae of rabbits, chickens and pigeons, on the scarified conjunctivae of rabbits and on the vaginal vulvae of young guinea pigs. Another characteristic effect was severe lesions of the blood vessels as evidenced by the bloody edema, hemorrhagic lymph glands and pleural exudate. As in humans, younger animals were more susceptible than older ones.

The following points may be made against the conclusion that the bacillus is the etiological agent of diphtheria:

1. The bacilli were absent in a number of typical cases of diphtheria.

2. The bacilli in the pseudomembranes of rabbits and chickens were not arranged as in the pseudomembranes of man.

3. The bacilli did not produce disease on the untraumatized pharyngeal mucous membranes of animal species, which were susceptible when the mucous membranes were traumatized.

4. Animals surviving experimental infection did not become paralyzed.

5. Finally, a typical virulent bacillus was found in the throat of a healthy child.

The proof that the bacillus is the etiological agent of diphtheria is thus not complete. However in typical human cases where the bacilli were not found, they might have been recently eliminated, as was indicated in the experiments on vulval infection in guinea pigs. The third objection may not be important since it has been frequently observed in man that diphtheria is preceded by catarrh of the throat and air passages. The effect of sharp north or northeast winds on the incidence of such catarrhs is well known. In addition one should note that the experimental animals used in these studies did not possess an organ comparable to the human tonsil. The tonsil with its many crypts and folds offers a favorable site for growth of the organism. Paralysis was not observed in the susceptible animal species because few survived infection and, in addition, its frequency even in human diphtheria is relatively low. A maximum incidence of 11% has been reported. As far as the last objection is concerned, it is conceivable that agents, which are rarely infectious, could occasionally be found in healthy subjects.

In my estimation, the noted objections are not major ones. The future lines of study seem clear. Special emphasis should be put on the characterization of the toxin. It should be possible, in view of our knowledge of the nutritional requirements of the organism, to produce large amounts of the chemical substances that it forms. If the same specific compound occurs in the culture medium, the infected guinea pig and the diphtheria patient, it would be an important argument in support of the bacillary etiology of the disease” (2115, 2116).

Friederich August Johannes Löffler (DE) was the first to recognize Fusobacterium necrophorum as the cause of an infection, namely, calf diphtheria (2117).

Georg Schmorl (DE) was the first to describe a human infection by Streptothrix cuniculi, later named Fusobacterium necrophorum. It involved an animal strain (3084).

Jean Hallé (FR) gave the first description of the isolation from a human of what we now call F. necrophorum subsp. funduliforme as part of a Ph.D. thesis on the bacteriology of the female genital tract. He called the organism Bacillus funduliformis (1469).

Paul Courmont (FR) and A. Cade (FR) gave the first description of Lemierre's syndrome, i.e., a human postanginal septicemic infection with F. necrophorum (712). 

J.W. Long (US) first recognized a case of postanginal sepsis with internal jugular venous thrombophlebitis as caused by F. necrophorum (2123).

Louis Pasteur (FR), Charles Édouard Chamberland (FR) and Pierre Paul Émile Roux (FR) demonstrated that the virulence of the rabies virus increased up to a fixed maximum by successive passage through a host animal. It was shown that the rabies virus is attenuated for the dog, rabbit, and guinea pig, by passage through a series of monkeys (2684, 2690).

Louis Pasteur (FR), Charles Édouard Chamberland (FR), and Pierre Paul Émile Roux (FR) demonstrated that a dog can be protected from an injection of virulent rabies by first inoculating it with spinal cords of rabies infected rabbits which were dried for two weeks and ground-up in a broth (2684).

Vasili Yakovlevich Danilevskii; Vasili Yakovlevich Danilewsky (RU) discovered many of the blood parasites of birds including the parasitic malarial protozoan (Plasmodium spp.) which he associated with the disease (760-763). 

Antonio Carle (IT) and Giorgio Rattone (IT) were the first to produce tetanus in experimental animals (rabbits). They injected them with pus from a fatal human tetanus case (556). This strongly suggested that an infectious agent might be the cause.

Arthur Nicolaier (DE) was the first to describe Clostridium tetani, the etiological agent of tetanus. He did not purify it nor prove that it causes tetanus (2503). This organism is sometimes referred to as Nicolaier’s bacillus.

Shibasaburo Kitasato (JP) successfully cultivated the tetanus bacillus, Clostridium tetani, and demonstrated that it causes lockjaw. He showed that culture media in which the organism had been grown were still highly toxic for animals after the bacilli had been removed by filtration (1816). He also proved the inability of the tetanus bacillus to invade the blood stream and showed the disease to be intoxication (1817).

Edmond Isidore Étienne Nocard (FR) demonstrated the protective effect of passively transferred tetanus antitoxin in horses. The Pasteur Institute supplied the antitoxin (2518). Passive immunization in humans was used during World War I. 

Pierre A. Descombey (CA) prepared tetanus toxoid (847). The effectiveness of active immunization with tetanus toxoid was demonstrated in World War II.

Adam Sedgwick (GB), grandnephew of Adam Sedgwick (GB) the geologist, proposed the enterocoel theory, which states that the coelom is of enterocoelous origin having formed as the result of the pinching off of outpouchings of the gastric cavity (3148). His researches on the wormlike organism Peripatus, which he recognized as the zoologically important connecting link between the Annelida, or segmented worms, and the Arthropoda, such as crabs, spiders, and insects are also very important (3149, 3150).

William Bateson (GB) showed that Balanoglossus (the acorn worm), with a larval stage resembling that of echinoderms, possesses gill slits, a notochord, and a dorsal nerve chord. This established this creature as a chordate. This was the first indication that chordates are offshoots of a primitive echinoderm stock, a theory now widely accepted. Bateson also described how in Enteropneusta the coelom arises from sacs formed from a portion or portions of the primitive enteron (137, 138).

Issac Ott (US) discovered that the center for temperature regulation is located in the corpora striata region of the brain (2595). 

Greene Vardiman Black (US) was the first to routinely employ nitrous oxide for extracting teeth without pain and in 1870 invented the cord-driven dental engine. Black wrote important books on dental care such as: The Technical Procedures in Filling Teeth; The Formation of Poisons by Microorganisms; A Biological Study of the Germ Theory of Disease; A Study of the Histological Characters of the Periosteum and Peridental Membrane; Descriptive Anatomy of the Human Teeth; and A Work on Operative Dentistry. Black also perfected the use of the amalgam for filling teeth (290-294).

Ernest Charles Lasègue (FR) wrote a classic work on the cerebrum dealing with vascular disturbances of the brain. The Laségue sign is ascribed to him although there is some dispute that others preceded him in their descriptions (1982, 1983).

Karl Koller (CZ-US) was the first physician to explore the use a local anesthetic for surgery. He instilled a 2% solution of cocaine into his own eye and tested its effectiveness as a local anesthetic by pricking the eye with needles (1866, 1867). Anesthesia in the form of eye drops (cocaine) obviated the hazards of general anesthesia and its post-operative complications.

William Stewart Halsted (US), in 1884, performed the first brachial plexus block when he injected the brachial plexus in the supraclavicular region with cocaine under direct vision (1472). This is sometimes called conduction anesthesia.

Richard John Hall (US), in 1884, described how using cocaine he blocked a cutaneous branch of the ulnar nerve in his own forearm (1468).

William Stewart Halsted (US) by injecting Richard John Hall (US) discovered the technique for blocking the inferior alveolar nerve and the antero-superior dental nerve using cocaine as an anaesthetic (1472). The anaesthetic technique, described perfectly by both surgeons in 1885, has been revolutionary in the practice of odontology since its introduction, offering dentists the possibility of performing invasive interventions to the maxillary without pain.

K. Mulley (DE) developed the interscalene approach to brachial plexus block in order to avoid pneumothorax (2448).

Alon P. Winnie (US), Lennart Häkansson (SE), and Poul Buckhöj (SE) developed the modern interscalene approach using the level of the sixth cervical transverse process as the reference point for needle insertion (3777).

Harvey Williams Cushing (US) applied cocaine to the brachial plexus prior to dividing it, during a forequarter amputation for sarcoma (738).

Diedrich Kulenkampff (DE) performed the first percutaneous supraclavicular block, using himself to test the block (1929).

Diedrich Kulenkampff (DE) and M.A.Persky (US) published their experiences with a thousand blocks without apparent major complications (1930).

Alfred Einhorn (DE) and Emil Uhlfelder (DE) produced an alkamin ester of para-aminobenzoic acid, which they named procaine (1001, 1002). Procaine would later be renamed Novocaine. Einhorn was issued a U.S. patent for procaine in 1906.

Nils Löfgren (SE), in 1943, synthesized Lidocaine under the name Xylocaine. His colleague Bengt Lundqvist (SE) made the first injection anesthesia experiments on himself (2120). In addition to being a local anesthetic xylocaine has been used to prevent tachycardia, treat arrhythmias arising during heart surgery, treat post-operative arrhythmias, and treat arrhythmias resulting from myocardial infarction. It is derived from gramine which is an alkaloid found in a reed plant (Hordeum vulgare) of Central Asia. Lidocaine has now largely replaced Novocaine. Note: For spinal block see James Leonard Corning, 1885, Part III.

Ludwig Wilhelm Carl Rehn (DE) performed the first thyroidectomy for exophthalmic goiter. The operation reported was performed in 1880 (2891).

Louis A. Duhring (US) provided a description of dermatitis herpetiformis, which has remained valid to this day (922). It is also called Duhring’s disease.

Louis Théophile Joseph Landouzy (FR) and Joseph Jules Dejerine (FR) described a form of childhood progressive muscle atrophy with a characteristic involvement of facial muscles and distinct from pseudohypertrophic (Duchenne’s MD) and spinal muscle atrophy in adults (1959). 

Louis Théophile Joseph Landouzy (FR) and Joseph Jules Dejerine (FR) described progressive muscular atrophy of the scapulo-humeral type. They drew attention to the familial nature of the disorder and mentioned that four generations were affected in the kindred that they had investigated (1960).

Frank H. Tyler (US) and F.E. Stephens (US) studied 1249 individuals from a single kindred with facioscapulohumeral dystrophy traced to a single ancestor and described a typical autosomal dominant Mendelian inheritance pattern with complete penetrance and highly variable expression. The term facioscapulohumeral dystrophy is introduced (3408). Note: This condition is also called Landouzy-Dejerine dystrophy.

Moses Allen Starr (US) reported that lesions in the region of the Rolandic fissure could cause sensory disturbances in humans; typically somatosensory disturbances involved lesions posterior to the fissure of Rolando, most often in the post-central gyrus or parietal region. He noted that some cases of frontal lobe injury show deficiencies in self-control, lack of self-restraint, and undue excitability. These changes result in a change of character, which he attributed to a loss of inhibition and good judgment (3244, 3245).

Henri Verger (FR), Joseph Jules Déjérine (CH-FR), and J. Mouzon (FR) were the first to demonstrate convincingly that damage to the human parietal lobe may result in relatively minor disturbances of pain and temperature sensitivity, but clear deficits in tactile localization, postural sensitivity, and fine tactile discrimination (836, 3457).

Mieczyslaw Minkowski (CH), using monkeys, concluded that cutaneous discriminative ability is chiefly, but not exclusively, represented in the post-central gyrus of the brain (2351).

Johannes Gregorius Dusser de Barenne (NL-US) treated specific areas of the monkey cortex with strychnine and, like Minkowski, concluded that the precentral cortex has some sensory functions, but that the parietal cortex is the major projection area for cutaneous sensation (792-794).

Edgar Douglas Adrian (GB) discovered a second somatosensory cortex, just above the Sylvian fissure in the brain of the cat (20).

Joannes Gregarius Dusser De Barenne (NL-US), Clyde Marshall (US), Leslie F. Nims (US), and William E. Stone (US) found that strychnine placed on either side of the brain’s central (Rolandic) sulcus greatly exacerbated sensitivity to somatic sensory stimulation. They described the activity of the brain after strychnine application (950). 

Victor Alexander Haden Horsley (GB) induced both cretinism and myxedema in monkeys by experimentally removing the thyroid gland. He came to the conclusion that the cretinous symptoms following thyroidectomy are due to the arrest of a function of the thyroid gland (1640, 1641). Note: some of the symptoms he described are now known to have been due to removal of the parathyroid glands.

English country names and code elements taken from the International Organization for Standardization:

DZ = Algerian; US = American; AR = Argentinian; AU = Australian; AT = Austrian; AT/HU = Austro/Hungarian; BA = Bosnian-Herzegovinian; BE = Belgian; BR = Brazilian; GB = British; BG = Bulgarian; CM = Cameroonian; CA = Canadian; TD = Chadian; CL = Chilean; CN = Chinese; CO = Colombian; CR = Costa Rican; HR = Croatian; CU = Cuban; CY = Cypriot; CZ = Czechoslovakian; DK = Danish; NL = Dutch; EC = Ecuadorian; EG = Egyptian; EE = Estonian; ET = Ethiopian; FI = Finnish; FR = French; DE = German; GR = Greek; GT = Guatemalan; GU = Guamanian; HU = Hungarian; IS = Icelander; IN = Indian; ID = Indonesian; IR = Iranian; IQ = Iraqi; IL = Israeli; IE = Irish; IT = Italian; JP = Japanese; KE = Kenyan; KR = South Korean; KW = Kuwaiti ; LV = Latvian; LB = Lebanese; LT = Lithuanian; LU = Luxembourgian; MK= Macedonian; MG = Malagasy; MT = Maltese; MY = Malaysian; MX = Mexican; NA = Namibian; NZ = New Zealander; NG = Nigerian; NO = Norwegian; PK = Pakistani; PA = Panamanian; PE = Peruvian; PH = Filipino; PL = Polish; PT = Portuguese; PR = Puerto Rican; RO = Romanian; RU = Russian; SA = Saudi Arabian; SN = Senegalese; CS = Serbian-Montenegrin; SK = Slovakian; ZA = South African; ES = Spanish; LK = Sri Lankan; SE = Swedish; CH = Swiss; SY = Syrian; TW = Taiwanese; TH = Thai; TN = Tunisian; TR = Turkish; UG = Ugandan; UA = Ukrainian; UY = Uruguayan; VE = Venezuelan; ZW = Zimbabwean

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