A Selected Chronological Bibliography of Biology and Medicine
Part 3B
1903—1924
Compiled by
James Southworth Steen, Ph.D.
Delta State
University
Dedicated to
my loving family
This document celebrates those secondary authors and laboratory technicians
without whom most of this great labor of discovery would have proved
impossible.
Please
forward any editorial comments to: James S. Steen, Ph.D., Professor Emeritus,
jsteen08@bellsouth.net
1903
"The
supreme qualities of all science are honesty, reliability, and sober, healthy
criticism." Niels Ryberg Finsen (907).
Antoine Henri Becquerel (FR) in recognition of the extraordinary
services he had rendered by his discovery of spontaneous radioactivity and
Pierre Curie (FR) and Marie Sklodowska Curie (PL-FR) in recognition of the
extraordinary services they have rendered by their joint researches on the
radiation phenomena discovered by Professor Henri Becquerel were awarded the
Nobel Prize in Physics.
Svante August Arrhenius (SE) was awarded the Nobel Prize in
Chemistry for his doctoral dissertation work in which he hypothesized ionic
dissociation.
Niels Ryberg Finsen (DK) was awarded the Nobel Prize in Physiology
or Medicine "in recognition of his contribution to the treatment of
diseases, especially lupus vulgaris,
with concentrated light radiation, whereby he has opened a new avenue for
medical science."
Carl Alexander Neuberg (DE-US) used the term biochemistry,
defining it as science concerned with the chemical basis of life. Ref
Carl Alexander Neuberg (DE-US) introduced the term phosphorylation
in 1910. Ref
Thomas Purdie (GB) and James Colquhoun Irvine (GB) introduced an
important methodology for the analysis of carbohydrate structure. Free hydroxyl
groups were methylated followed by acid hydrolysis. The nature of the resulting
monosaccharides could then be determined (1837).
Henry Lord Wheeler (US) and Treat Baldwin Johnson (US) synthesized
cytosine (2442).
Felix Ehrlich (DE) isolated the amino acid isoleucine from
nitrogenous substances in beet-sugar molasses (666).
Hermann Emil Fischer (DE) and Joseph von Mering (DE) were the
first to synthesize a therapeutically active "barbiturate" by
substituting two ethyl groups for two hydrogens attached to carbon in
barbituric acid; the result was diethyl barbituric acid or diethylmalonylurea.
It is frequently called (barbital or veronal). When they administered this new
barbiturate to human subjects, the compound was found to induce sleep (775; 776). The term
for a drug that causes sleep induction is a somnolent or a hypnotic.
Johann Friedrich Wilhelm Adolf Baeyer (DE), in 1864, had
synthesized barbiturhaltige säure (malonylurea) from a reaction of urea with malonic acid, a
chemical found in apples. Malonylurea became known as barbituric acid, parent
compound of well-known sleeping pills
of today (93). Later it was he who synthesized
the dye indigo.
Heinrich Hörlein (DE), in 1911, at F. Bayer & Co. synthesized
phenobarbital (Luminal). It has excellent hypnotic action and anticonvulsant
activity. It was patented by F. Bayer & Co. under DE 247952.
Alfred Hauptmann (DE) discovered the antiepileptic properties of Luminal
(phenobarbital) by accident when studying the anxiolytic effects of various
drugs (835; 1022).
Manipulations of the side chain at position 5 have resulted in
amobarbital (Amytal) in 1923, pentobarbital (Nembutal) in 1930, and
secobarbital (Seconal) in 1930. These drugs have become widely known as drugs
of abuse. Changes in position 2 have resulted in the short-acting barbiturates:
hexobarbital (Evipal), thiopental (Pentothal) and methohexital (Brevital). Valium and Halcion are also
barbiturates. Sodium pentothal has been called the “truth serum” because it
gives its recipient a good feeling when being forthright.
Samuel
Rideal (GB) and J.T. Ainslie Walker (GB) developed
the original method for determining
the phenol coefficient (1892).
The Hygienic
Laboratory Method (1921) is
a modification of the Rideal-Walker
Method (1).
The Food
and Drug Administration Test (1931) is
a combination of the best
features of both above.
Theobald Smith (US), in 1903, noted that guinea
pigs used for diphtheria anti-toxin
testings frequently succumbed rapidly to a second injection of diphtheria, i.e., anaphylaxis.
This phenomenon was not reported by Smith but communicated by him to Paul
Ehrlich (1772).
Nicolas Maurice Arthus (FR) described a type of allergic reaction
brought on by repeated injection of horse serum into rabbits. The reaction was
characterized by a localized, acute necrotizing vasculitis. Later it became
known as the Arthus reaction (63).
Charles G. Cochrane (US), William O. Weigle (US), and Frank James
Dixon (US) showed that this reaction is caused by the formation of relatively
large amounts of antigen-antibody precipitates in the vessel walls. They found
that polymorphonuclear leukocytes (PMNs) phagocytize and rapidly degrade
antigen-antibody complexes but are themselves largely responsible for the
inflammation and necrosis (447).
Carl Oluf Jensen (DK) was the first to do experiments in transplantation immunity. He found that
tumors, which arose spontaneously in mice, could sometimes be propagated by
grafting them from one mouse to another. He passed one tumor through nineteen
generations of grafting. Jensen recognized that mice of different races were not all equally susceptible
to the growth of the tumors and spoke of an active
immunity. This report discredited the theory of the infectivity of cancer (1181).
Georg Schöne (DE) coined the phrase transplantation immunity to distinguish it from reactions
resulting from injections of foreign materials (2033; 2034).
Nicholas Senn (CH-US)
was the first to use röntgen rays to treat leukemia (2049).
Theobald Smith (US) and Arthur L. Reagh (US) noted that there are
two types of antigens present in the
Salmonella group, one associated with the cell substance and the other with
the flagella (2087).
Edmund Weil (AT) and Arthur Felix (PL-GB) would designate these as
the O and H antigens respectively (2421; 2422).
Louis Lapicque (FR) introduced several terms to describe
excitability of nerve and muscle. Rheobase
(lowest point of current) was defined as, “the intensity of a constant current
of abrupt onset and prolonged duration which gives the threshold of
excitability.” Chronaxie (value of
time) was defined as, “the duration of constant current of abrupt onset which
attains the threshold of stimulation with an intensity equal to double that of
the rheobase, i.e., with a voltage of
double that of the rheobase” (1357). This work
was begun in 1903.
Ross Granville Harrison (US) discovered
the mode of embryonic origin of the lateral line sense organs of aquatic
vertebrates. He demonstrated that the growth cones of sensory neurites accompany
the primordium, thereby, establishing a physical link between the cranial
ganglion and the body neuromasts (1004).
Almroth Edward Wright (GB) and Stewart R. Douglas (GB) showed that
substances exist in immune serum, which by their action render the microbe more
susceptible to phagocytosis. They called these substances opsonins (Greek, I prepare victuals for) (2539; 2540). Today we
know that opsonins are antibodies.
Dmitrii Iosifovich Ivanowski; Dmitrii Iosifovich Iwanowsky;
Dmitrii Iosifovich Ivanovski (RU) described inclusion bodies caused by tobacco
mosaic virus in tobacco plants (1156).
Paul Ambroise Remlinger (FR), Riffat Bey Frasheri (AL), and their
assistant Hamdi Efendi (TR) mixed a fixed rabies virus homogenate with a rather
virulent culture of the fowl cholera agent (Pasteurella multocida), put
the mixture through a Berkefeld V Filter and this mixture was then inoculated
intracerebrally in rabbits. While the absence of Pasteurella among the
inoculated animals confirmed the success of filtration, their death from rabies
after displaying paralysis symptoms within 8-10 days made clear that the rabies
agent could pass the Berkefeld V Filter. Remlinger went on to repeat the same
experiment by using both fixed and street viruses and filtrating the agent
through less and less permeable Berkefeld and Chamberland filters and was thus
able to demonstrate that the rabies virus could pass through the porcelain
filters. He
therefore not only confirmed Pasteur’s hypothesis that the rabies agent was a
filterable virus, but at the same time demonstrated that it was not a parasitic
protozoan as some had suggested (1868; 1869). Note:
the first rhabdovirus
Amédée Borrel (FR) discovered the sheep pox and goat pox virus (255). Note: One virus is
thought to cause both.
Adelchi Negri (IT) described the characteristic inclusion bodies
found in the brain cells of animals infected with rabies. They are found most
frequently in the pyramidal cells of Ammon's horn, and the Purkinje cells of
the cerebellum. He mistakenly thought them to be protozoa (1686-1689). These
inclusion bodies were later found to be rabies viruses and named Negri bodies
in his honor.
Amédée Borrel (FR) proposed the virus theory of cancer (254).
Vilhelm Ellermann (DK) and Oluf Bang (DK) showed that by injecting
bacteria-free tissue filtrates from infected chickens into healthy chickens
they could transmit leukemia in chickens. This implied a viral origin of the
leukemia, i.e., oncogenic viruses (681; 682; 2062). Note:
the first leukemia virus
Francis Peyton Rous (US) demonstrated that an agent, which passed
through filters that stopped bacteria, caused a spindle-cell sarcoma in
Plymouth Rock chickens. Rous was reluctant to pronounce it a virus. Today this
virus is called the Rous sarcoma virus and was one of the first of the tumor viruses to be demonstrated (1934-1938). Note:
first solid tumor virus
Francisco Duran-Reynals (ES-US) proved that
the Rous sarcoma - the cell-destroying virus of chicken cancer - was not
confined to chickens but could leap the so-called species barrier and incite
cancers in ducks and turkeys. Indeed, the virus sometimes gained virulence as
it passed from one species to another. He showed how a virus could lie dormant
for many years before inciting cancer (648; 649).
Hugo Schottmüller (DE) was the first to use blood agar for
determining hemolytic properties of bacteria. He proposed that different
varieties of streptococci be classified based on their capacities to hemolyze
erythrocytes (2035).
W.K. Stefansky (RU) and George A. Dean (GB) discovered Mycobacterium lepraemurium, the
etiological agent of rat leprosy (571; 2132).
John Fleetezelle Anderson (US) described Rocky Mountain spotted fever as a new disease and suggested the
wood tick as a possible carrier (48).
Louis B. Wilson (US) and William M. Chowning (US) discussed
history, location, season, previous conditions of the patient, sex and age,
types of disease, symptoms, prognosis, morbid anatomy, morbid histology,
etiology, inoculation experiments, mode of infection, possible hosts,
diagnosis, preventive measures, and treatment as they applied to pyroplasmosis
hominis ("spotted fever"
or "tick fever" of the
Rocky Mountains) (2503).
Howard Taylor Ricketts (US) demonstrated
tick transmission of Rocky Mountain
spotted fever to guinea pigs. He found that the etiologic agent is present
in blood from infected humans and demonstrated that it can be removed via
filtration (1887; 1888).
Howard Taylor Ricketts (US) demonstrated that a bipolar-staining
bacillus of minute size and transmitted by the bite of the wood tick (Dermacentor occidentalis) is the
causative agent of Rocky Mountain spotted
fever (1889). This
bacterium would later be called Rickettsia
rickettsia in his honor and Simeon Burt Wolbach (US) would offer final
proof that Rickettsia rickettsia is
the etiological agent (2529).
Frederick George Novy (US) and Ward J. McNeal (US) took blood from
rats and succeeded in cultivating the trypanosome of rats, Trypanosoma lewisi, on blood agar (1740).
James Homer Wright (US) demonstrated syphilitic spirochetes in
cases of aortitis providing definitive proof of the nature of syphilitic
aortitis (2541).
William Ernest Castle (US) wrote the first paper on Mendelism in
America (374).
William Ernest Castle (US) was probably the first to recognize the
relationship between allele and genotype frequencies (373). Note:
In this work Castle anticipated what has now become known as the Hardy–Weinberg
law. Formulated in the terms "as soon as selection is arrested the
race remains stable at the degree of purity then attained."
Felix Mendel (DE) described his method for intracutaneous testing
for tuberculin sensitivity. Within 24 to 72 hours the injected area becomes
hard (indurated) and red in a person who is infected with tuberculosis or has
been immunized with BCG vaccine (1562; 1563).
Clemens Peter Pirquet von Cesenatico; Clemens Peter von Pirquet
(AT) used tuberculin in a diagnostic skin scratch test and Charles Montoux (FR)
used it to perform an intradermal test (1492; 2355-2357).
Charles Mantoux (FR) popularized Mendel’s test, thus the
Mendel-Mantoux Tuberculin Test (1492).
Nicholas Senn (US) was the first to use röntgen rays to treat leukemia (2049).
Alfred Walter Campbell (AU-GB) successfully studied the
cytoarchitecture of the anthropoid cerebral cortex with the aim of establishing
a correlation between physiologic function and histologic structure (342).
Wilhelm Ludwig Johannsen (DK) demonstrated in plants that natural
selection could only influence evolutionary change if there is a source
containing multiple genotypes. Therefore, genetically pure lines (homozygous)
would not lend themselves to natural selection (1186; 1187; 1810). He
introduced the terms and defined the concepts of gene, phenotype, genotype, and selection (1188; 1189).
Richard Woltereck (DE) would confirm this restriction on natural
selection as it applies to animals using parthenogenic freshwater crustaceans
of the genus Daphnia (2536).
Emily Arensen (NO) presented information on the geographical
distribution of sponges (60).
Ludwig
Edinger (DE), Adolf Wallenberg (DE), Gordon Morgan Holmes (GB), Grafton
Elliot-Smith (AU-GB), John B. Johnston (US), Cornelius Ubbo Ariëns-Kappers
(NL), Gotthelf Carl Huber (US), and Elizabeth Caroline Crosby (US) established
the anatomy of the avian brain. They suggested that the major subdivisions of
the avian telencephalon correspond to different components of the mammalian
basal ganglia with the avian spinal cord, midbrain, and thalamus being
homologous to those of mammals, but that nearly all of the avian telencephalon
corresponds to mammalian basal ganglia (58; 660; 661; 684; 685; 1193).
Pietro Grocco (IT) and Karl
Andreyevich Rauchfuss (RU) described the triangular area of dullness (Grocco’s triangle or Grocco-Rauchfuss triangle) on the
patient’s back, on the side opposite to that on which a pleural effusion had occurred. Most
commonly seen in children and adolescents (935; 1857).
Adam
Rydel (PL-DE) and Friedrich Wilhelm Seiffer (DE) found that vibratory sense and
proprioceptive sense are closely related and that both senses are carried in
the posterior columns of the spinal cord (1965).
Pierre Marie Félix Janet (FR) and Fulgence Raymond (FR) described psychasthenia for the first time (a
neurosis marked by stages of pathologic fear or anxiety, obsessions, fixed
ideas, tics, feelings of inadequacy, and self-accusation), i.e., obsessive
compulsive disorder. Here bulimia is
described in medical terms for the first time (1175).
Ettore Marchiafava (IT) and Amico Bignami (IT) described a
neurological disorder related to alcohol intake. It consisted of tremor,
convulsions, and coma (1497; 1498). This is a
progressive neurological disease of alcoholism, characterized by corpus
callosum demyelination, necrosis, and subsequent atrophy.
William Gibson Spiller (US), John Herr Musser (US), and Edward
Martin (US) described inflammation of the spinal canal (arachnoiditis) in a
patient as meningitis circumscripta
spinalis (2114).
Georges Fernand Isidore Widal (FR) found that blood in
cerebrospinal fluid was diagnostic of meningeal hemorrhage (2455).
Georges Froin (FR) described inflammation of the meninges with
obstruction of the spinal subarachnoid space associated with a coagulable state
of the cerebrospinal fluid (Froin syndrome) (832). Note: This condition is typically caused by meningeal irritation
(e.g. during spinal meningitis) and CSF flow blockage by tumor mass or abscess.
William Osler (CA) was the first to associate a renal affection or
one affecting the central nervous system with cases of lupus erythematosus (1763; 1764).
Alfred Wolff-Eisner (DE) trephined the tibia and femur of
experimental animals and suggested biopsy of bone marrow as a clinical
procedure (2533).
Oscar Thorvald Bloch (DE) and Jan Mikulicz-Radecki; Johannes
von Mikulicz-Radecki (PL-AT) developed a two-stage operation for resection of tumors
of the rectum. This operation is known as the Bloch-Mikulicz operation (2353).
Maximilian
Carl-Friedrich Nitze (DE) developed a ureteral occlusion catheter to block the
ureter of the diseased kidney so that the urine of the healthy kidney could be
collected separately (1730).
Karl Otto
Ringleb (DE) improved the cystoscope with his “orienting cystoscope,” a
breakthrough in 1908 (1897; 1898).
Suprapubic prostatectomy had a mortality rate of 50% prior to the introduction
of Ringleb-Berlin’s new method, after which the rate went down to 10%.
Edwin Beer (US) devised a new method for surgical treatment of
bladder tumors employing
high frequency (Oudin) currents through a catheterizing cystoscope (178).
Leo
Buerger (US) constructed a universal urethroscope with two optical systems,
direct or indirect viewing, and used for catheterizing and operating
respectively. It was both a cystoscope and urethroscope (324).
Maximilian
Stern (DE-US), with Reinhold Wappler’s assistance, created the first instrument
that used an electric loop to cut prostatic tissue (2140).
S.W.
Goldberg (RU) and Efim Semenovich London (RU) described the use of radium to
treat two patients with basal cell
carcinoma of the skin. The disease was eradicated in both patients (885).
Ivan Petrovich Pavlov; Ivan Petrovic Pavlov (RU) reported in 1901
how he used salivary gland fistulas in dogs to demonstrate two types of
reflexes—one inherited, the other developed from specific or psychic stimuli by
training and association. The discovery of the second type, the conditioned reflex had a dramatic effect
on the fields of physiology and psychology (1794-1797).
Ivan Mikhailovich
Sechenov (RU) wrote Reflexes of the Brain,
which Pavlov acknowledged as the single most important theoretical inspiration
for his work on conditioning (1798; 2041-2043).
Ivan Petrovich Pavlov; Ivan Petrovic Pavlov (RU) and
Vladimir Mikhailovich Bekhterev;
Vladimir Mikhailovich Bechterev (RU) independently developed a theory of
conditioned reflexes which describes
automatic responses to the environment. What Bekhterev called association reflex is called the conditioned reflex by Pavlov, although
the two theories are essentially the same. John Watson discovered the
salivation research completed by Pavlov and incorporated it into his famous theory of behaviorism, making Pavlov a
household name. While Watson used Pavlov’s research to support his behaviorist
claims, closer inspection shows that in fact, Watson’s teachings are better
supported by Bekhterev’s research (186).
William Osler (CA) was the first to recognize polycythemia vera as a definite clinical entity (1762).
August Karl Gustav Bier (DE) introduced artificial active and passive hyperemia as an adjuvant to surgical
therapy (212).
Vincent B. Nesfield (GB) developed the technique of purification
of drinking water by use of compressed liquefied chlorine gas (1699).
Die
Neue Generation was founded.
1904
Ivan Petrovich Pavlov; Ivan Petrovic Pavlov (RU) received the
Nobel Prize in Physiology or Medicine "in recognition of his work on the
physiology of digestion, through which knowledge on vital aspects of the
subject has been transformed and enlarged."
Thomas Chrowder Chamberlin (US) and Forest Ray Moulton (US)
developed the planetesimal hypothesis for the origin of the Earth and other
planetary bodies, i.e., the planets formed from the coalescing of
rocky fragments ranging in size from boulders to asteroids called planetesimals (388; 1644).
Hantaro
Nagaoka (JP), in 1904, proposed an atomic model with electrons rotating in
rings about a central nucleus. “The system, which I am going to discuss, consists
of a large number of particles of equal mass arranged in a circle at equal
angular intervals and repelling each other with forces inversely, proportional
to the square of distance. At the center of the circle, place a particle of
large mass attracting the other particles according to the same law of force.
If these repelling particles be revolving with nearly the same velocity about
the attracting center, the system will generally remain stable, for small
disturbances provided the attracting force be sufficiently great” (1681).
Ernest Rutherford (New Zealand-GB) proposed the theory of the
nuclear atom. He maintained that the atom contains a very tiny nucleus at its
center which is positively charged, and which contains all the protons of the
atom and therefore nearly all of its mass. In the outer reaches of the atom are
the negatively charged electrons which are very light, and which interpose no
detectable barrier to the passage of alpha particles. This theory was deduced
from experiments where gold foil was bombarded with alpha particles and their
behavior observed (1955).
August Karl Johann Valentin Köhler (DE) and Moritz von Rohr
(PL-DE) developed quartz monochromatic microscope objectives (quartz-fluorite)
for working in the ultraviolet at 275 and 280 nm and designed the first
ultraviolet microscope (1294; 1295). They found that cell nuclei
absorb ultraviolet light strongly.
Friedrich Stolz (DE) and Henry Drysdale Dakin (US) determined the
chemical formula for both epinephrine (adrenaline) and norepinephrine
(noradrenaline) and achieved a total chemical synthesis of both substances (532; 2154). Note:
This was the first synthetic production of a hormone.
Albert Einhorn (DE) synthesized and patented procaine
hydrochloride (Novocaine) in 1904.
Heinrich Braun (DE) was the first to report its existence as Novocaine (280). It
supplanted cocaine as the local anesthetic of choice.
Potassium cyanide powder was advocated for the control of ants (2050).
Marshall Albert
Barber (US) invented the technique for making glass capillary micropipettes and
manipulating them in the field of a compound microscope (122; 2198).
He developed
this method initially to clone bacteria and to confirm the germ theory of Koch
and Pasteur. Later, he refined his approach and was able to manipulate nuclei
in protozoa and to implant bacteria into plant cells. Continuous improvement
and adaptation of this method to new applications dramatically changed experimental
embryology and cytology and led to the formation of several new scientific
disciplines including animal cloning as one of its latest applications.
Joseph Everett Dutton (GB) and John Lancelot Todd (CA) working in
the Congo and independently Philip Hedorland Ross (GB) and Arthur Dawson Milne
(GB) working in Uganda discovered that human
tick disease is caused by a spirochete (Borrelia
duttonii) transmitted by the African soft-shelled or argasid tick, Orhithodoros moubata (653-655; 1931).
Heinrich Hermann Robert Koch (DE), in 1904, confirmed the role of Orhithodoros moubata and was the first
to demonstrate that spirochetes are transmitted via eggs (transovarial
transmission) to the progeny of the infected female ticks (1285; 1286).
Henri Vallé (FR) and Henri Carré (FR) proved the viral etiology of
equine infectious anemia (2265). Note: the first
retrovirus
William Thomas Councilman (US), George B. Magrath (US), and Walter
R. Brinckerhoff (US) gave an excellent clinical characterization of the
pathological anatomy and histology of smallpox (variola) (481; 482).
Thomas Renton Elliott (GB) was the first to express the idea of
chemical neurotransmission, but he did not support it experimentally.
“Adrenalin (epinephrine) might then be the chemical stimulant liberated on each
occasion when the impulse arrives at the periphery” (686; 687). This was
one of the earliest statements of the neurotransmitter hypothesis. More years
later von Euler showed that noradrenaline is the principal neurotransmitter in
the post-ganglionic sympathetic nerves. See,
von Euler 1933a, 1946, and 1948.
Henry Edward Crampton (US), a graduate student in Edmund Beecher
Wilson’s laboratory, performed an experiment, which suggested that there is an
association between a region of egg cytoplasm and a particular type of
development. He removed the polar lobe from cleaving eggs of the mollusk Dentalium and found that larvae showed a
deficiency for the post-trochal and other regions. This effect was not seen
when other regions of equivalent size were removed (2494).
Thomas Hunt Morgan (US) was the first to formulate the concept of
cytoplasmic determination (1631).
Karl Illmensee (US) and Anthony P. Mahowald (US) clearly
established this relationship when they were able to transform animal pole
cells of a Drosophila embryo into
gametes by transferring polar cytoplasm from the posterior to the anterior end
of an egg (1145).
Lorenz Hiltner (DE) introduced the concept of the rhizosphere (1084).
Cornelius Johan Koning (NL) suggested that fungi play an important
role in the decomposition of organic matter and the formation of humus (1300).
Albrecht Karl Ludwig Martin Leonard Kossel (DE) and Henry Drysdale
Dakin (US) discovered the enzyme arginase,
which splits arginine into ornithine and urea (1307; 1308).
Antonino Clementi (IT) found that arginase is absent from the livers of animals, which do not excrete
urea (e.g., birds and reptiles) (422).
George Henry Falkiner Nuttall (US-GB) investigated the serological
relationships of animals by the precipitin reaction (1741).
Franz Schardinger (AT) isolated aerobic bacteria capable of
producing industrial chemicals such as acetone, ethanol, and acetic acid (1987).
Karl Pearson (GB) correctly generalized the principle of
segregation showing that the F2 ratio ¼
AA: ½ Aa: ¼ aa should maintain itself indefinitely in a large, random-breeding
population. This was an explicit statement of the equilibrium principle for a
single locus, and its application to multiple loci could have been inferred
from this (1800). Note: this work precedes that of Hardy
and Weinberg in 1908.
Roland H. Biffen (GB) reported the first proof that disease
resistance in plants may be inherited in a Mendelian manner when he found that
resistance to yellow rust in wheat is inherited as a simple Mendelian recessive
to susceptibility (213).
Carl Franz Joseph Erich Correns (DE) had previously found that in
the four o’clock plant, Mirabilis jalapa,
a gene determined a localized disease in the palisade cells called Sordago (473; 474).
Theodor Boveri (DE) predicted what later became known as genetic linkage: “When in continued
breeding experiments two characters either always appear together, or disappear
together, the conclusion may be drawn with the greatest probability that the
factors for the two characters are located on the same chromosome.” He also
predicted that if in continued breeding experiments combinations in which
traits appear is larger than the number of possible combinations, this might be
the result “of an exchange of parts between homologous chromosomes” (260). See, Sutton, 1903.
Martinus Willem Beijerinck (NL) was the first to obtain the
sulfur-oxidizing bacterium, Thiobacillus
denitrificans in axenic culture (180). Note:
Under anaerobic conditions it uses carbon dioxide as a source of carbon.
Albert Francis Blakeslee (US) analyzed mating type determination
in the fungus Mucor and found that
mating (conjugation) occurs between mycelia of opposite mating types,
designated plus (+) and minus (-). The resulting sporangia produce either + or
- spores, never both (227).
Hans Burgeff (DE) demonstrated that dissimilar nuclei could be
associated in the vegetative hyphae of Phycomyces
nitens, a condition he called heterokaryosis
(326; 327).
Karl Johannes Kniep; Hans Kniep (DE) developed a technique called
tetrad analysis. It is commonly used in fungal genetics (1271).
Mathilde Bensaude (FR) discovered that the clamp connection
structure in the basidiomycetes is used to ensure the production of cells, each
of which contains two complementary nuclei (194; 195).
Leonard Doncaster (GB) explained the inheritance of tortoiseshell,
which is sex-linked, and related colors in cats (616).
Friedrich Meves (DE) discovered mitochondria in plants (the
tapetal cells of Nymphae anthers) (1574).
Anton Julius Carlson (SE-US) proved that the heartbeat in the Limulus crab is neurogenic by section of
the cardiac nerve (357). This was
soon shown to be inapplicable to the hearts of amphibia and mammals.
William Philipps Dunbar (US) proposed that hay fever is a disease
caused by vegetable poisons contained in the pollen of certain plants. These
substances were connected with the proteid of the pollen grain and of a highly
specific character. He developed methodologies for testing patients'
sensitivity to certain pollens by minuscule exposure to pollen via their eyes
or nasal passages. Dunbar determined that it was the dried cat saliva on cat
hair that caused the allergic reaction. About grass pollen, Dunbar identified
the albumin fraction as the active toxin, discovered changes in the blood that
accompanied exposure to the pollen, and was able to grade individuals' relative
susceptibility to each type of pollen (645; 646).
Charles Scott Sherrington (GB) and Edward George Tandy Liddell
(GB) investigated spinal reflexes such as the knee-jerk. They discovered
reciprocal innervation of motor areas, i.e., when one set of muscles is
stimulated, muscles working against the activity of the first will be inhibited
(Sherrington’s law). The proprioceptive
system, i.e., the brain can judge the tensions upon the muscles and joints
and thereby possess a sense of position and equilibrium. They formulated the
concepts of the final common pathway,
i.e., “The reflex arcs (of the synaptic system) converge in their course so as
to impinge upon links possessed by whole varied groups in common paths. This arrangement culminates in the convergence of
many separately arising arcs upon the efferent-root neuron. This neuron thus
forms a final common path for many different reflex arcs and acts. It is
responsive in various rhythm and intensity, and is relatively unfatigable,” and
the integrative action of the nervous
system. Also, they will be remembered for their contributions to the
physiology of perception, reaction and behavior. They also discovered the stretch reflex (1413; 2058-2060).
Georg Franz Knoop (DE) fed dogs the sodium salts of various
straight-chain fatty acids in which the carbon atom farthest from the carboxyl
group was linked to a phenyl group. Based on the urinary products he deduced
that oxidative degradation of fatty acids occurs by oxidation at the
beta-carbon thereby releasing two carbons at a time from the fatty acid. This
became known as the beta-oxidation theory (533; 1274-1276). This
represents one of the first experiments in which a metabolite was labeled in
such a way that end products could provide evidence of how physiological
conversions had occurred.
Gustav Georg Embden (DE) discovered that glycogen was converted to
lactic acid, but he also showed that lactic acid could be converted to glucose.
That is, Embden showed that glucose and lactic acid could be interconverted
with each other in laboratory animals. This interconversion observation would
become one of the most important biochemical pathways for muscle contraction in
all living animals. Ref
Gershom Franklin White (US) reported the isolation of Bacillus X in honeybee (Apis mellifera Linn.) larvae suffering
from American foulbrood (2447). White then
renamed the organism Bacillus larvae (2448; 2449).
William Bateson (GB), Edith Rebecca Saunders (GB), and Charles C.
Hurst (GB) discovered intermediate (blended) inheritance in the mint genus
Salvia. In this same article they reported, for the first time, that one
character or trait (comb shape in chickens) could be controlled by more than
one gene. Further research by various geneticists was to show that this is the
general rule rather than the exception. Most characters are controlled by more
than one gene (153; 1836).
Ross Granville Harrison (US) contributed to our knowledge of the
relation of the nervous system to muscle differentiation in the embryo, and the
development and regeneration of peripheral nerves (1005; 1006).
William Thomas Councilman (US), George B. Magrath (US), and Walter
R. Brinckerhoff (US) observed round or oval acidophilic intranuclear inclusion bodies in Variola infected cells of man and monkeys (482; 1473).
Léon Ambard (FR), Eugene Beaujard (FR) and André-Simon Weill (FR)
discovered the link between salt and high blood pressure in hypertensive
patients studied weeks under different schemes providing very different amounts
of sodium chloride (42-44).
Paul Emil
Flechsig (DE) evolved a map of cortical function that appeared in a report of
1904 to the Central Committee for Brain Research
(782).
Karl Albert Ludwig Aschoff (DE) discovered granuloma in the
myocardium specific for rheumatic fever (67).
Ernst Ferdinand Sauerbruch (DE) introduced a low-pressure surgical
cabinet for preventing lung collapse during thoracic surgery and is credited
with the first operation on the open chest (1981).
Ludolph Brauer (DE) invented the airtight mask that could be
fitted over the face and connected with an oxygen container under the desired
hyperpressure. The oxygen also passed through a bottle of ether, so that both
the anesthetic and oxygen could be given under higher than atmospheric
pressure. This method replaced the cabinet (274).
Felix Jacob Marchand (DE) coined the term atherosclerosis because arteriosclerosis is not sufficient to
include the entire disease processes of the primary fatty and atheromatous
degeneration intimately involved in the sclerosing processes within the blood
vessels. He suggested that atherosclerosis
is responsible for nearly all obstructive processes in the arteries. The Greek athero refers to gruel (1496).
Giuseppe Gradenigo (IT) reported a triad of symptoms consisting of
periorbital unilateral pain related to trigeminal nerve involvement, diplopia
due to sixth nerve palsy and persistent otorrhea, associated with
bacterial otitis media with apex involvement of the petrous part of the
temporal bone (petrositis) (909; 910). It was
later named Gradenigo’s syndrome.
Julius Donath (AT) and Karl Landsteiner (AT-US) were the first to
describe an autoimmune disease, paroxysmal
hemoglobinuria. This disease is characterized by the discharge of massive
amounts of hemoglobin, not intact erythrocytes, into the urine. It results from
an antibody of the IgG class directed against the P blood group antigen and is
associated with syphilis and viral
infections and is responsible for paroxysmal
cold hemoglobinuria (615).
Eduard Hitzig (DE) noted that electrical stimulation of a region
in front of the pre-central gyrus in the dog caused combined movements of the
head and eyes (1089).
Thomas Grainger Stewart (GB) and Gordon Morgan Holmes (IE) wrote a
paper about precise localization of destructive lesions in the cerebellum. This
paper contains a description of the Stewart-Holmes
syndrome (epileptic
fits, manifested by jerking movements of one arm) and the first
description of the rebound phenomenon (2144).
Edward Albert Schäfer (GB) described a method for administering
artificial respiration. It was especially effective with a person in danger of
drowning (1985).
Kristian Igelsrud (NO) was the first to perform open-chest cardiac
massage in 1901, but William Williams Keen, Jr. (US) did not report this until
a few years later (1227).
Harvey Williams Cushing (US) gave the first report of using a
tourniquet with pneumatic pressure of a measurable degree. This inflatable cuff
was the forerunner of the modern technique used generally in surgery (515).
Max Askanazy (DE-CH) was the first to link osteitis fibrosa cystica with parathyroid
tumors (73).
Paul Charles Dubois (CH) is known for the introduction of
"persuasion therapy", a process that employed a rational approach for
treatment of neurotic disorders. Within this discipline, he developed a
psychotherapeutic methodology that was a form of Socratic dialogue, using the
doctor-patient relationship to persuade the patient to change his/her behavior.
He believed it was necessary to appeal to a patient's intellect and reason in
order to eliminate negative and self-destructive habits. He also maintained it
was necessary for the physician to convince the patient of the irrationality of
his/her neurotic feelings and thought processes (635; 636).
Joseph Grinnell (US) wrote, “two species of approximately the same
food habits are not likely to remain long evenly balanced in numbers in the
same region” (929). Grinnell
connected the idea of competitive
exclusion to the term niche when
he asserted that “no two species regularly established in a single fauna have
precisely the same niche relationships” (930; 931). He was the
first to use the word niche to refer
to an animal’s ecological position in the world by defining the ecological or environmental niche as the ultimate distributional unit of one
species or subspecies (932). Grinnell
more fully developed the idea when he wrote “…the concept of the ultimate
distributional unit, within which each species is held by its structural and
instinctive limitations, these being subject only to exceedingly slow
modification down through time” (933).
Georgi Frantsevitch Gause (RU) proposed what has come to be one of
the laws of ecology when he wrote, “It is admitted that as a result of
competition two similar species scarcely ever occupy similar niches, but
displace each other in such a manner that each takes possession of certain peculiar
kinds of food and modes of life in which it has an advantage over its
competitor” (857-860). It is
known as the competitive exclusion
principle.
Francis Wall Oliver (AU) and Dunkinfield Henry Scott (GB)
discovered evidence for the seed of Lyginodendron,
which led to the removal of the Cycadofilices from the Pteridophyta (ferns,
horsetails, and club-mosses), and their inclusion with the gymnosperms (1746). “We now know that the true
ferns were only present in the coal measures in small and archaic forms
(Coenopteridales) very unlike living ferns and that probably all the
conspicuous fernlike leaves of that era belonged to seed plants” (1491).
Charles H. Sternberg (US) discovered the fossil remains of a
creature showing both amphibian and reptilian characteristics. Ferdinand Broili
(DE) would name it Seymouria baylorensis
for Seymour, Texas in Baylor County (304).
The Journal of Experimental
Zoology was founded.
1905
"Ludwig
was absolutely unselfish. He loved his science and rejoiced in the scientific
achievements of his students. He freely gave to every earnest worker from the
vast store of his physiological knowledge, and his experience in experimental
methods. He became at once the friend of each of his pupils, making him feel
that he had a personal interest in him and in his work. This feeling spread
throughout the laboratory, where good-fellowship reigned, each man becoming
interested not only in his own problem, but glad to lend a helpful hand to
every other, rejoicing when a research was successful and sorry when the
problem baffled. I can recall Ludwig’s enthusiastic, joyous shout, as he called
all who could leave their work to come and witness some physiological process revealing
itself in its true light for the first time, or some unusually suggestive
histological or anatomical preparation. Hearty congratulations followed, all
rejoicing in the new discovery. And then came one of those delightful talks,
leading us forward to the borderland of science, and giving us glimpses into
that fascinating, mysterious land—the unknown." Warren P. Lombard (US)
speaking of Karl Friedrich Wilhelm Ludwig (DE) the great physiologist and his
former teacher (1436).
More than two hundred and fifty men from a dozen countries came to study under
this great master.
"In the
Vertebrates we meet with two great categories of white corpuscles, of which one
group resembles those of the invertebrates in that they also possess a single
large nucleus and an amoeboid protoplasm. These are the macrophages of the
blood and of the lymph, and are intimately connected with the macrophages of
such organs as the spleen, lymphatic glands, and bone marrow. Another group of
white corpuscles in the Vertebrata is made up of small amoeboid cells, which
are distinguished by having a nucleus, which, although single, is divided into
several lobes. These are the microphages [neutrophils]. Phagocytosis is
exhibited not only by the macrophages but also, in a high degree, by the
microphages which stand out as the defensive cells par excellence against
microorganisms [… ]. The microphages, on the other hand, appear to play their
part, specially, in acute infections." Élie Metchnikoff (RU-FR) (1571).
"Science is built up
of facts, just as a house is built up of stones; but an accumulation of facts
is no more a science than a heap of stones is a house." Henri Poincaré (1827).
"Nothing is constant but change! All existence is a perpetual
flux of ‘being and becoming’! That is the broad lesson of the evolution of the
world." Ernst Heinrich Philipp August Haeckel; Ernst Heinrich Philipp
August Häcke; Ernst Heinrich Philipp August Heckel (954).
Johann Friedrich Wilhelm Adolf von Baeyer (DE) was awarded the
Nobel Prize in Chemistry for his advancement of organic chemistry and the
chemical industry, through his work on organic dyes and hydroaromatic
compounds.
Heinrich Hermann Robert Koch (DE) was awarded the Nobel Prize in
Physiology or Medicine "for his
investigations and discoveries in relation to tuberculosis."
William Weber Coblentz (US), between 1903-1905, pioneered infrared
spectrophotometry as a method for determining the presence of specific atomic
groupings. He was the first to show that different atomic and molecular
groupings absorbed specific and characteristic wavelengths in the infrared
region (442; 443).
Richard Adolf Zsigmondy (AT-DE) applied the centrifuge to the
study of colloids, making a more detailed understanding of protoplasmic
constituents possible (2569).
Vladimir Sergeyevich Gulewitsch (RU) and R.P. Krimberg (RU) isolated
a new compound from meat extracts. They named it carnitine from carnos
(meat) (947).
Masaji Tomita (JP) and Yuzo Sendju (JP)
determined the chemical structure of carnitine to be 3-hydroxy-4-trimethylamino
butyric acid (2227).
Cornelis Adrianus Pekelharing (NL) found that very minute
quantities of a substance in the whey of milk are as capable as whole milk of
promoting health in mice receiving adequate protein from some other source (1804; 2271).
Valdemar Henriques (NL) and C. Hansen (NL) demonstrated that
autolyzed (self-digested) pancreas or mucosa not only supplied rats with amino
acids for their protein synthesis but also supplied them with something of
necessity in their diet other than amino acids, carbohydrates, fats, and salts (1046).
Richard Anton Burian (CS) discovered xanthine oxidase, which catalyzes the conversion of xanthine to
uric acid and hypoxanthine to xanthine (329).
Arthur Harden (GB) and William John Young (GB-AU) showed that the
enzymes were not consumed during the breakdown of sugar by yeast, however the
reaction slowed down even when there was ample sugar and enzyme present. If
they added inorganic phosphate the reaction speeded up again. This was
initially a puzzling finding because phosphorus is neither present in sugar,
nor alcohol, nor carbon dioxide, nor enzyme. Their search for the fate of the
added phosphate led them to discover that phosphorylated sugars are being
manufactured. They isolated a hexose diphosphate (the Harden-Young ester) from
the fermentation mix (985; 991-994; 2555). Note: They realized that fermentation requires
the presence of both a heat-labile component they called “zymase” and a low
molecular weight, heat-stable fraction called “cozymase.” (It was later shown
that zymase contains several enzymes
whereas cozymase consists of metal ions, ATP, ADP, and coenzymes such as NAD.)
They presented an equation for overall alcoholic fermentation in 1908.
Phoebus Aaron Theodor Levene (RU-US) and Albert L. Raymond (US)
characterized the structure of the Harden-Young ester as
fructose-1,6-diphosphate (1394).
Leonid Aleksandrovich Ivanov (RU) had independently discovered
that organic phosphates are produced during alcoholic fermentation (1155).
Arthur Harden (GB) made another important set of observations
revealing that in the presence of the inhibitor, fermenting yeast extracts
showed an accumulation of two phosphate esters, 3-phosphoglycerate and
2-phosphoglycerate. On the other hand, the inhibitor iodoacetate caused an
accumulation of fructose-1,6-diphosphate. Once these intermediates were
identified, it became possible to study the enzymatic reactions by which they
were formed and utilized. Harden’s work marks the beginning of the study of intermediary
metabolism. Ref
The first version of International
Rules (Code) of Botanical Nomenclature (ICBN) was approved in Vienna,
Austria.
Frederick Frost Blackman (GB) and Gabrielle Louise
Caroline
Matthaei (GB) proposed that photosynthesis consists of a light-dependent
reaction (the 'light' reaction) and a temperature-dependent reaction (the
'dark' reaction). Both these reactions are going on simultaneously. The 'light'
reaction feeds something to the 'dark' reaction. As the intensity of
illumination is increased, the rate of photosynthesis (as measured, for
example, by the volume of oxygen produced each minute) does not increase
indefinitely but approaches a saturation state in which a further increase of
light intensity has no effect. This suggests a two-stage process in which only
one stage can be accelerated by light (226; 1522).
Otto Heinrich Warburg (DE) later called the process of limiting
the rate of carbon assimilation at high intensities of illumination the Blackman reaction (2389).
John Sidney Edkins (GB) showed that extracts of the gastric antral
mucosa stimulate secretion of acid by the oxyntic mucosa, and postulated that
his extracts contained a hormone, which he called gastrin (662; 663).
Helen R. Gregory (GB), Roderic Alfred Gregory (GB), Paul Martin
Hardy (GB), Duncan S. Jones (GB), George Wallace Kenner (GB), Robert Charles
Sheppard (GB) and Hilda J. Tracy (GB) determined the structure of gastrin (926; 927).
John Christopher Anderson (GB), Moira A. Barton (GB), Roderic
Alfred Gregory (GB), Paul Martin Hardy (GB), George Wallace Kenner (GB), John
Keith MacLeod (GB), Jean Preston (GB), Robert Charles Sheppard (GB) and John
Selwyn Morley (GB) described their synthesis of gastrin (47).
William Henry Howell (US) discovered the remarkable hypotensive
effect of acetylcholine (1114).
John Newport Langley (GB) introduced the concept of receptor substance or synaptic substance, “probably not in the
nerves, but in the cells in which they end.”
Langley said, “I conclude that in all cells two constituents at
least must be distinguished, (1) substances concerned with carrying out the
chief functions of the cells, such as contraction, secretion, the formation of
special metabolic products and (2) receptive substances especially liable to
change and capable of setting the chief substances in motion. Further, that
nicotine, curare, atropine, pilocarpine, strychnine, and most other alkaloids,
as well as the effective material of internal secretions produce their effects
by combining with the receptive substance...” (1355).
Nettie Maria Stevens (US) and Edmund Beecher Wilson (US)
independently discovered the existence of the so-called sex chromosomes. Stevens worked with the beetle Tenebrio while Wilson worked with
several genera of hemipteran insects, including Anasa tristis (2143; 2495-2498). This was
not the first time that sex determination was associated with a chromosome, but
it was the first proof. See, Henking,
1891 and McClung, 1901. Thomas Harrison Montgomery, Jr. is credited with
coining heterochromosomes in 1904 and
autosomes in 1906 (1613; 1614).
William Bateson (GB), Edith Rebecca Saunders (GB), Reginald
Crundall Punnett (GB), and Charles Chamberlain Hurst (GB) discovered linkage and genetic interaction (154; 156). Punnett
has two species of marine worms named for him, Cerbratulus punnetti, Punnettia
splendia.
William Bateson (GB), Edith Rebecca Saunders (GB), and Reginald
Crundall Punnett (GB) discovered that two genes behaving in a recessive
epistatic mode control flower color in Lathyrus (sweet peas) and Matthiola
(stocks) (155; 1836).
William Bateson (GB) first suggested using the word
"genetics" (from the Greek gennō, γεννώ;
"to give birth") to describe the study of inheritance and the science
of variation in a personal letter to Adam Sedgwick (1854–1913, zoologist at
Cambridge, not the Adam Sedgwick (1785–1873) who had been Darwin's professor),
dated 18 April 1905 (144).
William Curtis Farabee (US) determined that brachydactyly in
humans can be explained by Mendelian principles (741).
The first human pedigree was published. It showed the inheritance
of shortened hands and fingers in a Norwegian village (1206).
William Bateson (GB) and Reginald Crundall Punnett (GB) made
several reports to the Evolution Committee of the Royal Society of London from
1905 to 1908 in which they related the discovery of two new genetic principles:
gametic coupling and gene interaction. They studied poultry
comb form, demonstrating significant departure from Mendelian ratios for some
gene pairs (150-152; 1836).
Thomas Hunt Morgan (US) proposed
that the frequency with which recombinants took place was related to the
physical distance separating the genes on the chromosome and further proposed
that this could be used for mapping the positions of genes relative to each
other. This phenomenon was clarified and called gene linkage (1626).
Alfred Henry Sturtevant (US), based on his work with Morgan,
created the first genetic map (2169). See Sutton, 1903.
John Burdon Sanderson Haldane (GB), Alexander Dalzell Sprunt (GB),
and Naomi Mitchison Haldane (GB) were the first to demonstrate linkage of genes
in the mouse (968).
Lucien Claude Jules Cuénot (FR) discovered a lethal allele, the
yellow coat color allele in mice, even though he did not interpret it correctly (508).
William Ernest Castle (US) and Clarence Cook Little (US) proved
that the yellow allele has two expressions: a dominant one on coat color, and a
recessive one on viability, since yellow homozygotes died early in the
embryonic state (377).
William B. Kirkham (US) later discovered that the homozygous
yellow embryos died in utero (1258).
Konstantin Sergejewitsch Mereschkowsky (RU) proposed the theory of
the symbiotic origin of the eukaryotic cell and introduced the term symbiogenesis to signify the emergence
of new species with identifiably new physiologies and structures as a
consequence of stable integration of symbionts. It stated that the chloroplast
and mitochondria of eukaryotic cells had their origins from endosymbiotic
cyanobacteria and aerobic bacteria, respectively, whose ancestors were once
captured and incorporated by a primitive, anaerobic, heterotrophic host. Many
others would later refine this theory (381; 382; 1250; 1251; 1504; 1567).
Robert K. Trench (US), Richard W. Greene (US), Barbara G. Bystrom
(US), Merriley E. Trench (US), and Leonard Muscatine (US) found contemporary
organisms that offer some striking examples of symbiotic relationships with a
similar history (2232; 2233).
The last yellow fever epidemic on the North American
continent occurred in New Orleans, Louisiana. The epidemic ended in the fall
after a large-scale mosquito eradication program (1559).
Stamen Grigoroff (BG) isolated Lactobacillus
bulgaricus from Bulgarian fermented milk (928).
Alfred T. MacConkey (GB) used bile salts to select for lactose
fermenting bacteria in fecal samples (1463; 1464).
M. Casimir Wize (PL) found that a chytridiaceous fungus was
parasitizing the larvae and pupae of Cleonus and Anisolplia (Coleoptera). He
named the fungus Olpidiopsis
ucrainica
(2526).
Fritz Richard Schaudinn (DE) and P. Erich Hoffman (DE) used a
special staining technique to demonstrate the spirochaete causing syphilis in serum obtained from a
genital lesion by Hoffmann. They named it Spirochaeta
pallida (2009; 2010). The
organism is now called Treponema pallidum.
Aldo Castellani; Count of Chisiamaio (IT) discovered, Treponema pertenue, the spirochete
causing yaws (370).
Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj
Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) noted that mononuclear phagocytes from
animals resistant to certain bacterial infections had increased competence for
ingesting and killing these microbes. This phenomenon became known as
macrophage activation (1571).
Sergei Nikolaevich Winogradsky (RU) and Martinus Willem Beijerinck
(NL) observed that the reason microbiologists so often succeed in isolating
specific microbes from a given sample of soil or water is due to a
methodological principle called the ecological approach, often designated as
the principle of elective or enrichment culture. Its application depends on a
well-considered selection of the conditions in a primary culture medium, thus
causing preferential growth of a certain kind of germ, ultimately leading to a
predominance of the conditionally fittest. Typically, these enrichment cultures
offer the microbe a single simple carbon compound as the sole source of carbon (184).
Ludvig Hektoen (US) demonstrated by subcutaneous injections of
volunteers with blood taken from measles patients that the measles (rubeola)
virus circulates in the blood during the initial thirty hours of the rash (1033). Hektoen
was also the first to grow blood cultures from living patients (1032).
Martinus Willem Beijerinck (NL) published little concerning his
original concepts and approaches, however, upon being awarded the Leeuwenhoek
medal by the Koninklijke Akademie van Wetenschappen in Amsterdam he said, “I am
happy to note the way in which I approach microbiology has the approval of the
best judges. This approach can be concisely stated as the study of microbial
ecology, i.e., of the relation between environmental conditions and the special
forms of life corresponding to them. It is my conviction that, in our present
state of understanding, this is the most necessary and fruitful direction to
guide us in organizing our knowledge of that part of nature which deals with
the lowest limits of the organic world, and which constantly keeps before our
mind the profound problem of the origin of life itself. Therefore, it is a
great satisfaction to me that the Academy apparently wishes to honor the
experimenter who exploits this field.
In an experimental sense the ecological approach to microbiology
consists of two complementary phases, which give rise to an endless number of
experiments. On the one hand it leads to investigating the conditions for the
development of organisms that have for some reason or other, perhaps
fortuitously, come to our attention; on the other hand to the discovery of
living organisms that appear under predetermined conditions, either because
they alone can develop, or because they are the more fit and win out over their
competitors. Especially, this latter method, in reality nothing but the
broadest application of the elective culture method, is fruitful and truly
scientific, and it is no exaggeration to claim that the rapid and surprising
advances in general microbiology are due to this methodology. Nevertheless, and
this in spite of the fact that Leeuwenhoek, more than two hundred years ago,
already used this aspect of micro-ecology in some of his studies, and that
Pasteur was enabled to make most of his great discoveries because he was guided
by the same principle, the number of conscious exponents has so far remained
very small. And I feel that I certainly may be reckoned among them because of
the enthusiasm that is in me to contribute to the grand task can here be
accomplished” (2269; 2438).
Cornelis Bernardus Kees van Niel (NL) remarked, “Beijerinck’s
major contributions can be considered as the first direct experimental
investigations of Darwin’s principle of natural selection. In the enrichment
cultures the experimentally defined environmental conditions are the selecting
agent, and the outcome of the cultures can provide an unambiguous answer to the
question as to what organisms among the many types present in the inoculum are
best fit to cope with the environment” (2273).
Shigetane Ishiwata (JP) discovered that the Sotto-Kin disease of silkworms is caused by a new species of
bacterium, which he named Sotto-Bacillen.
This organism would later be named Bacillus
thuringiensis (1150).
Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj
Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) and Pierre Paul Émile Roux (FR)
demonstrated that syphilis may be transmitted to anthropoid apes, such as the
chimpanzee and gibbon, and, with less certainty to monkeys (1573).
Louis Joseph
Alcide Raillet (FR) and Albert Henry (FR) described six female immature Oesophagostomum brumpti
(nematode) worms that Alexandre Joseph Emilé Brumpt (FR) found
in tumors of the caecum and colon, in 1902, when he
performed autopsy on a 30-year old African man, who had been living near the
River Omo, East-Africa (317;
318; 1845).
William Bateson (GB) coined the term genetics to denote the science of heredity, but the word had been
used earlier (145; 146).
Count Grafen Emmerich Festetics (HU), a prominent sheep breeder
from Hungary, wrote Genetic Laws. It
included the observation that progeny inherit traits from their parents, and
that traits of grandparents can reappear in the offspring of their offspring (757; 758).
Hugo Marie de Vries (NL), while studying the genetics of the
evening primrose, Oenothera lamarckiana,
found an unusual variant among his plants. O.
lamarckiana has a chromosome number of 2N = 14. The variant had a
chromosome number of 2N = 28. He found that he was unable to breed this variant
with O. lamarckiana. He named this
new species O. gigas (569).
Anne Mae Lutz (US) proved that the gigas mutation in the evening primrose contains twice the usual
chromosome number. This led to the analysis and artificial production of
polyploidy (1456).
Lettice Digby (GB) observed that the primrose species Primula verticillata and P. floribunda can cross to produce a
sterile hybrid. This hybrid was called the Kew primrose (P. kewensis) and possessed 18 chromosomes. Digby observed that
these sterile hybrids occasionally gave rise to fertile Kew primroses. Using
microscopic analysis, she proved that the fertile hybrid was a polyploid
containing 36 chromosomes. This was the first documented case of a polyploid hybrid (596).
Øjvind Winge (DK), unaware of Digby's results, speculated that
speciation could occur by interspecific hybridization followed by chromosome
doubling. Winge believed that hybrid sterility was caused by unbalanced chromosome
sets. He reasoned that upon doubling, a proper pairing partner would be
available to each chromosome resulting in fertility (2515).
Roy Elwood Clausen (DK-US) and Thomas Harper Goodspeed (US) used Nicotiana tabacum to experimentally demonstrate Øjvind Winge’s hypothesis of
the origin of species by amphidiploidy.
George D. Karpchenko (RU) did the same using radish and cabbage (414; 415; 1220; 1221). It was
soon realized that allopolyploids—hybrid species that contain two or more
diploid sets of parental genomes—are common in nature.
W.C. Frank Newton (GB) and Caroline Pellew (GB) noted that
spontaneous hybrids of Primula
verticillata and P. floribunda
set tetraploid seed on at least three occasions during 1905, 1923 and 1926 (1718).
Rowland H. Biffen (GB) was the first to breed crops for disease
resistance in cereal rusts using Mendelian principles. But variability in the
pathogen was not fully appreciated (214).
Elvin Charles Stakman (US) and Frank Joseph Piemeisal (US), in
1917, reported that stem rust in cereals and grasses comprised six biological
forms. These forms were distinguished from each other morphologically and
parasitically and were differentiated on selected cereal and grass hosts (2122). Note: This led to research on variation and variability of plant
pathogens, and subsequently of all microorganisms, and the breeding of plants for
resistance to specific races. Races became essential also in microorganisms
important in industry, e.g. in the production of acids and enzymes from
organisms, and in medicine in the development of antibiotics.
Edwin G. Conklin (US), used the ascidian Cynthia (now Steyla), for
his discovery. The mature oocytes of these animals have a large transparent
germinal vesicle. The interior consists of a mass of gray yolk and the
periphery contains a yellow pigment. When the germinal vesicle ruptures at the
onset of meiosis, it liberates a quantity of clear material. At fertilization
the sperm enters near the vegetal pole, and this starts a dramatic
rearrangement of the cytoplasm.
Conklin discovered that at the close of the first cleavage these
distinctively colored regions of the embryo have a precise relationship with
the structures that will form subsequently. The fate of the yellow crescent is
to form muscles and mesenchyme, the gray yolky cytoplasm forms endoderm, and
the clear cytoplasm of the animal hemisphere forms ectodermal structures (459).
Charles Zeleny (CZ-US) showed that removal of the eyestalk
shortened the intermolt period in crustaceans (2563).
Max Kauffmann (DE) showed that the nutritional value of various
proteins depends upon their constituent amino acids. Proteins such as gelatin
lack some necessary amino acids (1225).
Otto Knut Olof Folin (SE-US) reported, “The distribution of the
nitrogen in urine among urea and the other nitrogenous constituents depends on
the absolute amount of total nitrogen present.
The distribution of the sulfur in urine among the three chief
normal representatives — inorganic sulfates, ethereal sulfates, and neutral
sulfur — depends on the absolute amount of total sulfur present.
The absolute quantity of creatinine eliminated in the urine on a
meat-free diet is a constant quantity different for different individuals, but
wholly independent of quantitative changes in the total amount of nitrogen
eliminated.
When the total amount of protein metabolism is greatly reduced,
the absolute quantity of uric acid is diminished, but not nearly in proportion
to the diminution in the total nitrogen, and the percent of the uric acid
nitrogen in terms of the total nitrogen is therefore much increased.
With pronounced diminution in the protein metabolism (as shown by
the total nitrogen in the urine), there is usually, but not always, and
therefore not necessarily, a decrease in the absolute quantity of ammonia
eliminated. A pronounced reduction of the total nitrogen is, however, always
accompanied by a relative increase in the ammonia nitrogen, provided that the
food is not such as to yield an alkaline ash.
The absolute quantity of undetermined nitrogen decreases under the
influence of the starch and cream diet, but in percent of the total nitrogen
there is always an increase.
Urea is the only nitrogenous substance which suffers a relative,
as well as, an absolute diminution with a diminution in the total protein
metabolism” (794).
Paul Ehrlich (DE) and Hugo Apolant (DE) demonstrated change of
experimental carcinoma transplants into sarcoma (674).
Nikolai S. Korotkoff (RU) described five types of Korotkoff
sounds. The first Korotkoff sound is the snapping sound first heard at the
systolic pressure. The second sounds are the murmurs heard for most of the area
between the systolic and diastolic pressures. The third and the fourth sounds
appear at pressures within 10 mm Hg above the diastolic blood pressure, and are
described as “thumping” and “muting.” The fifth Korotkoff sound is silence as
the cuff pressure drops below the diastolic pressure (1306). Note: Traditionally, the
systolic blood pressure is taken to be the pressure at which the first
Korotkoff sound is first heard and the diastolic blood pressure is the pressure
at which the fourth Korotkoff sound is just barely audible. There has recently
been a move toward the use of the fifth Korotkoff sound (i.e., silence) as the
diastolic pressure, as this has been felt to be more reproducible. The
intensity and duration of the Korotkoff sounds can be used to appraise the
blood flow into an extremity.
John Scott Haldane (GB) and John Gillies Priestley (GB) determined
by observations on normal men that breathing is quite unaffected either by
inhalation of oxygen-rich air or by such a moderate decrease of oxygen as
occurs on first going to an altitude. On the other hand, the breathing changes
its volume automatically in such close adjustment to the amount of carbon
dioxide produced in the body that the alveolar air is kept nearly constant in
this respect. They concluded that carbon dioxide is the chief immediate
respiratory hormone and its tension in the blood is the major stimulus for the
respiratory center. They demonstrated that as carbon dioxide concentration of
alveolar air rises there is an increase in depth of breathing. There was no
alteration in frequency of ventilation until the alveolar concentration had
been increased to about five times normal (970).
Francis H.A. Marshall (GB) and William A. Jolly (GB) noted, “The
ovary is an organ providing an internal secretion which is elaborated by the
follicular epithelial cells or by the interstitial cells of the stroma. This
secretion circulating in the blood induces menstruation and heat. After
ovulation, which takes place during oestrus, the corpus luteum is formed, and
this organ provides a further secretion, whose function is essential for the
changes taking place during the attachment and development of the embryo in the
first stages of pregnancy” (1513). Note: They had performed ovarian grafts preventing uterine atrophy,
however, this statement is based on the work of others as well as theirs.
Josef von Halban (AT) deduced the endocrine function of the
placenta. He believed that lactation was controlled by active principles from
the chorionic villi of the placenta (2348).
Alfred Binet (FR) and Théodore Simon (FR) developed an
intelligence test used particularly on children aged 3 to 15 years (218).
Clemens Peter Pirquet von Cesenatico; Clemens Peter von Pirquet
(AT) and Béla Schick (HU-AT-US) described the essence of serum sickness—antibody combines with the foreign serum antigen to
form a toxic compound, which causes the disease. They observed that children
treated for diphtheria with large quantities (up to 200 mL, almost 7
ounces, or almost 1 cup) of antitoxin derived from horses often went on to
experience symptoms such as swelling, fever, rash, and joint pains(2359-2361). Note:
We now know that the human immune system mistakes the foreign antibodies in the
serum for antigens. The symptoms of serum sickness are the result of a
cascading immune reaction.
Hans Curschmann (DE), Hans Gustav Wilhelm Steinert (DE), Frederick
Eustace Batten (GB), and Harold Pace Gibb (GB) provided a clinical description
of myotonic dystrophy (Curschmann-Steinert-Batten
disease),
the most common form of muscular dystrophy (163; 514; 2133). Myotonic dystrophy (MD) is a
neuromuscular disorder with autosomal dominant inheritance, associated with
muscle weakness and myotonia, dilated cardiomyopathy, cataracts, and mental and
endocrine abnormalities.
Alfred Walter Campbell (AU) wrote Histological Studies on the Localization of Cerebral Function, a
classic. Campbell’s map of the human brain can be seen in nearly every
well-known textbook on neuroanatomy (343).
Henri Duret (FR) described brain tumors, their clinical
manifestations, the pathophysiological consequences of intracranial
hypertension and the corresponding surgical treatments (650).
Harvey Williams Cushing (US) reported a successful operative
intervention in intracranial hemorrhage of the newborn (516).
William
Arbuthnot Lane (GB) performed repair of cleft lip and palate in neonates (1350).
Hugo
Sellheim (DE), in 1905, performed the first drug induced thoracic sympathetic
block for reduction of pain during childbirth (1882).
J. Winter
(AT) used chloroform to suspend circulation and respiration in animals. He then
injected adrenaline into the left ventricle of the heart thus restoring heart
action when all other methods failed. He suggested that this technique be tried
in humans (2521).
Reinhard von
den Velden (DE) attempted intracardiac injection in humans to restore heart
action after complete cessation of heart action (2313).
Carl Boden
(US) reports that J. Winter (AT), in 1905 was the first to attempt an
intracardiac injection of adrenalin in humans (239).
Henry Fairfield Osborn (US) described the Tyrannosaurus rex, which Barnum Brown (US) discovered in 1902 in
Hell Creek, Montana (1755).
Frederic Edward Clements (US) wrote the first American textbook in
ecology, Research Methods in Ecology (423).
John Jacob Abel (US) and Christian Archibald Herter (US) founded
the Journal of Biological Chemistry.
The Journal of Experimental
Medicine initiated publication.
1906
“The true contrast between science and myth is more nearly touched
when we say that science alone is capable of verification.” George Santayana (1976).
"The beauty and
genius of a work of art may be reconceived, though its first material
expression be destroyed; a vanished harmony may yet again inspire the composer;
but when the last individual of a race of living beings breathes no more,
another heaven and another earth must pass before such a one can be
again." …
"And the next time you raise your gun to needlessly take a
feathered life, think of the marvelous little engine which your lead will
stifle forever; lower your weapon and look into the clear bright eyes of the
bird whose body equals yours in physical perfection, and whose tiny brain can
generate a sympathy, a love for its mate, which in sincerity and unselfishness
suffers little when compared with human affection." Charles William Beebe (176).
"It is as if the Milky Way entered upon some cosmic dance.
Swiftly the brain becomes an enchanted loom, where millions of flashing
shuttles weave a dissolving pattern, always a meaningful pattern though never
an abiding one; a shifting harmony of subpatterns."Charles Scott
Sherrington (2059).
“For this general concept of the changed capacity for reaction, I
propose the term allergy. Allo denotes the deviation from the
original state, from the behavior of the normal, as in allorhythmia, allotropy.”
Clemens Peter Pirquet von Cesenatico; Clemens Peter von Pirquet (2354). Introduction of the word allergy
to the medical lexicon.
“We may have been more plastic and receptive, but I doubt it; even
our generation … had a practical demonstration of the slowness of the
acceptance of an obvious truth in the long fight for the aseptic treatment of
wounds … [It was] a long grievous battle, as many of us well know who had to
contend in hospitals with the opposition of men who could not — not who would
not — see the truth ….
In making knowledge effective we have succeeded where our masters
failed. But this last and final stage, always of slow and painful consummation,
is evolved directly from truths which cannot be translated into terms
intelligible to ordinary minds.” William Osler, 1906 in his Harveian Oration (1765).
"Intellectual beauty is sufficient unto itself, and only for
it rather than for the future good of humanity does the scholar condemn himself
to arduous and painful labors." Santiago Ramón y Cajal (ES) in his 1906
Nobel lecture (1851; 1852)
"Unfortunately, nature seems unaware of our intellectual need
for convenience and unity, and very often takes delight in complication and
diversity." Santiago Ramón y Cajal (ES) in his 1906 Nobel lecture (1851; 1852)
Bartolomeo Camillo Emilio Golgi (IT) and Santiago Ramón y Cajal
(ES) were awarded the Nobel Prize in Physiology or Medicine "in
recognition of their work on the structure of the nervous system."
Walther Hermann Nernst (DE) proposed what we refer to as the third
law of thermodynamics: entropy change approaches zero at a temperature of
absolute zero (1696-1698).
Ernest Rutherford (NZ-GB) measured the uranium and helium (helium
is an intermediate decay product of uranium) contents of uranium-bearing
minerals to calculate an age of the minerals. This is the origin of using
radioactive decay for dating objects (1953; 1954).
Bertram Borden Boltwood (US) developed the chemical uranium to
lead method. He was among the first to suggest that from the quantity of lead
in uranium ores and from the known rate of uranium disintegration, it might be
possible to determine the age of the earth’s crust. These first geochronology studies yielded the first
absolute ages from geologic material and indicated that parts of the Earth's
crust are hundreds of millions of years old. He published a list of geologic
ages based on radioactivity, which were incredibly accurate for his time (246).
Mikhail Semenovich (Semyonovich) Tswett (RU) is usually given
credit for having originated and named the technique called chromatography
(Greek, written in color) when he reported, “If a petroleum ether solution of
chlorophyll is filtered through a column of an adsorbent (I use mainly calcium
carbonate which is stamped firmly into a narrow glass tube), then the pigments,
according to their absorption sequence, are resolved from top to bottom into
various colored zones, since the more strongly adsorbed pigments displace the
more weakly adsorbed ones and force them further downwards. This separation
becomes practically complete if, after the pigment solution has flowed through,
one passes a stream of solvent through the adsorbent column. Like light rays in
the spectrum, so the different components of a pigment mixture are resolved on
the calcium carbonate column according to a law and can be estimated on it qualitatively
and quantitatively. Such a preparation I term a chromatogram and the
corresponding method, the chromatographic method.
It is self-evident that the adsorption phenomena described are not
restricted to the chlorophyll pigments, and one must assume that all kinds of
colored and colorless chemical compounds are subject to the same laws.” Twsett
separated blue chlorophyll (chlorophyll a), from yellow chlorophyll (chlorophyll b), using column
chromatography, and called them chlorophyll alpha
and beta, which later became a and b (2239; 2240). See, Goppelsröder, 1861. This
methodology was presented for the first time in 1903 to a meeting of scientists
in Warsaw, Poland.
George Barger (GB), Francis Howard Carr (GB), and Henry Hallett
Dale (GB) announced the first isolation of an active ergot alkaloid, which they
named ergotoxine (128).
Henry Hallett Dale (GB) demonstrated that ergotoxine (ergotamine)
produces effects at the end plates of the motor nerves in skeletal muscle and
some involuntary organs (536). Note:
Some consider this to be the origin of the concept later called beta-blockers.
Ergotoxine
was later
shown to be a mixture of three alkaloids.
Arthur Stoll
(CH), in 1918, isolated
ergotamine tartrate from the various alkaloids present in extracts of the sclerotia
of the fungus Claviceps purpurea
(ergot), which grow on rye and, to a lesser extent, on other grasses;
he named it Gynergen. This was the
first chemically pure ergot alkaloid. It found widespread therapeutic use in
obstetrics as an oxytocic, and internal medicine for relief of migraines (2151; 2152).
Arthur Stoll
(CH), Ernst Burckhardt (CH), M. Edward Davis (US), Fred L. Adair (US), Gerald
Rogers (US), Morris Selig Kharasch (RU-US), Romeo R. Legault (US), Harold Ward
Dudley (GB), John Chassar Moir (GB), and Marvin R. Thompson (GB) discovered ergonovine, the specific oxytocic
principle of ergot (557; 639; 2153; 2211).
Mitsumaru Tsujimoto (JP) discovered a hydrocarbon in oils from
shark liver he named squalene (2237). He later assigned the correct empirical formula C30H50 to squalene (2238).
Ernest Walker (US) was the first to use carbon disulfide as a
herbicide when he poured the liquid around the stems of sassafras and killed
them in an apple orchard (2381).
Arthur Harden (GB), Stanley G. Walpole (GB), and Dorothy Norris
(GB) found that acetoin (3-hydroxybutanone or acetylmethylcarbinol) is produced
by many bacteria (987; 988; 990).
Albert Jan Kluyver (NL), Hendrik Jean Louis Donker (NL), and F.
Visser't Hooft (NL) found that when yeast produce acetylaldehyde during the
alcohol fermentation it may be converted to acetoin if a strong hydrogen
acceptor like methylene blue or oxygen is present. The acetoin may then be
reduced to 2,3-butylene glycol (1270).
David Paretsky (US) determined the mechanism for the conversion of
2,3-butylene glycol to acetylmethylcarbinol in bacterial fermentation (1783; 1784).
Arthur Harden (GB) and William John Young (GB-AU) recognized the
existence of a heat-stable coenzyme participating in fermentation reactions
catalyzed by yeast juice. One component of this coenzyme was recognized as
adenosine triphosphate (ATP), but the structure of the other, known for many
years as cozymase remained unknown (992).
Otto Fritz Meyerhof (DE-US) perfected a technique of using muscle
extract, which was very low in carbohydrate content to study the role of
chemicals suspected of being intermediates or cofactors in the conversion of
glycogen to lactic acid. He confirmed earlier findings that phosphate promotes
the process, and that hexose diphosphate (Harden-Young
ester) is converted into lactic acid. He found that glucose is not utilized
effectively unless there is added, Harden’s heat-stable coferment and a
heat-labile factor from yeast juice which Meyerhof called hexokinase (1596).
Otto Fritz Meyerhof (DE-US) demonstrated that glycogen in muscle
is split by enzymes into two molecules of lactic acid per molecule of hexose.
He stressed the identity of the reactions of glycogen in muscle and glucose in
yeast. These experiments laid the foundation for the development of the
Embden-Meyerhof-Parnas theory of glycolysis (1593; 1594; 1596; 1597).
Hans Karl August Simon von Euler-Chelpin (DE-SE) Hjalmar Ohlsén
(SE), and Sixten Kullberg (SE) had earlier postulated that an enzyme they named
phosphatase acts upon a mixture of
phosphate and the intermediate products of alcoholic fermentation, causing the
formation of a carbohydrate ester (2324; 2326).
Hans Karl August Simon von Euler-Chelpin (DE-SE), Ragnar Vestin
(SE), Henry Albers (SE), Fritz Schlenk (SE), Erich Adler (SE), Otto Heinrich
Warburg (DE), and Walter Christian (DE) determined that nicotinic acid is an
essential part of the coenzymes NAD (also called DPN, diphosphopyridine
nucleotide, cozymase I, and coenzyme I) and NADP (also called TPN,
triphosphopyridine nucleotide, codehydrogenase II, and coenzyme II) (2021; 2320-2323; 2327; 2328; 2391). This was
the first evidence that nicotinic acid, in the form of its amide, formed a part
of the structure of a coenzyme. Absence of nicotinic acid leads to failure of
certain enzymes to function normally. The enzymes that fail are those that make
use of coenzymes with a nicotinic acid moiety.
Otto Heinrich Warburg (DE) and Walter Christian (DE) proposed the
names diphosphopyridine nucleotide (DPN) and triphosphopyridine nucleotide
(TPN) (2391).
Nicolaas Louis Söhngen (NL) discovered that some bacteria produce
methane and others can use it as both a carbon and energy source (2095).
Frederick Gowland Hopkins (GB) concluded that the necessary
precursor of epinephrine (adrenaline), a hormone that must be continuously
formed, must be derived from the diet. He did not mention tyrosine, but
apparently had this amino acid in mind as a precursor of some synthetic product
important in metabolism. Hopkins introduced the idea that hormones are derived
from digestion products of proteins (1104).
Ernst Joseph Friedmann (DE) was the first to characterize a
hormone by revealing its chemical formula (epinephrine; adrenaline) (829).
Hans Winterstein (DE) determined the capacity of the central nervous
system to consume oxygen (2522).
Robert Heath Lock (GB) and Alfred Henry Sturtevant (US) were the
first to clearly express the relationship between linkage and exchange of parts
between homologous chromosomes (1429; 2170).
Charles Scott Sherrington (GB) discovered nociceptors. In
earlier centuries, scientists believed that animals were like mechanical
devices that transformed the energy of sensory stimuli into motor responses.
Sherrington used many different experiments to demonstrate that different types
of stimulation to an afferent nerve fiber's receptive field led to different
responses. Some intense stimuli trigger reflex withdrawal, certain autonomic
responses, and pain. The specific receptors for these intense stimuli were
called nociceptors (2059).
Leonard Doncaster (GB) and Gilbert H. Raynor (GB) were the first
to discover a sex-linked character. They described a trait called lacticolor segregating among wild female
currant moths (Abraxas grossulariate)
but not among males (618).
William Bateson (GB), Reginald Crundall Punnett (GB), and Leonard
Doncaster (GB) found that the female moth is heterogametic and the male,
homogametic (149; 617).
The sex-linked, recessive inheritance of lacticolor was not understood until it was recognized that, in Abraxus and other Lepidoptera, the
female is the heterogametic sex, not the male. See, Bridges, 1916.
Craig W. Woodworth (US) was the first to breed Drosophila in quantity, and it was he
who suggested that William Ernest Castle (US) use Drosophila as experimental material for genetic studies.
William Ernest Castle (US), Frederic Walton Carpenter (US), Alonzo
Howard Clark (US), Samuel Ottmar Mast (US), and William M. Burrows (US)
performed the first genetic study using Drosophila
as an experimental animal (376). Note: Thomas Hunt Morgan
(US) would later use Drosophila melanogaster as the experimental animal
in work leading to his 1933 Nobel Prize.
Ernest Edward Tyzzer (US) observed intranuclear inclusions in
cells infected by Varicella virus (2252).
Erwin Bauer (DE) demonstrated graft transmission of abutilon
mosaic and several other viruses, which cause variegation, or infectious
chlorosis in woody plants (164; 165).
Adelchi Negri (IT) showed
that vaccinia lymph, the vaccine
for the dreaded smallpox (caused by Variola virus) passed through a
filter that held back bacteria (1690).
Émile Marchoux (FR) and Paul-Louis Simond (FR) provided evidence
to suggest that yellow fever virus could undergo transovarial transmission
within the mosquito vector, Aedes aegypti (1499).
Eduard V. de Freudenreich (DK) and Sigurd Orla-Jensen (DK)
isolated and characterized propionic acid bacteria (561).
Jules Jean Baptiste Vincent Bordet (BE) and Octave Gengou (FR)
isolated the causative agent of whooping cough, Haemophilus pertussis (now Bordetella
pertussis) and devised a method to immunize against it (252; 253).
Thorvald Johannes Marius Madsen (DK) and Bjorn Kristensen (DK)
proved that Bordetella pertussis is
the etiological agent of whooping cough (1312; 1469-1471).
Pearl Louella Kendrick (US) and Grace Eldering (US) cultured Bordetella pertussis in BG medium
containing sheep’s blood then developed a vaccine for whooping cough (1241).
Pearl Louella Kendrick (US) and Gordon C. Brown (US) combined
vaccines for diphtheria, whooping cough, and tetanus into the single DPT shot used today (310; 1240).
Thomas Lane Bancroft (GB-AU) showed that the mosquito Stegomyia fasciata (Aedes aegypti) is the carrier for the dengue-fever pathogen (109).
John Ashburton Thompson (AU) arrived at a theory of plague that
involved or necessitated transmission by fleas (2210).
The Advisory Committee of the India Plague Commission (GB)
concluded that the plague is carried from one rat to another and from (461) rat to man by Xenopsylla cheopis (Rothschild), the rat
flea (454). They also
determined that the plague bacilli multiply in the stomach of the flea (455). Early
members of the Commission were Charles Martin (GB), George Lamb (GB), William Glen
Liston (GB), George Ford Petrie (GB), Sydnet Rowland (GB), Thomas Henry Gloster
(GB), M. Kasava Pai (GB), V.L. Manker (GB), P.S. Ramachandrier (GB), and C.R.
Arvi (GB).
Mary Mallon (IE-US) came to the attention of Public Health
Officials in 1906 when she became the first identified healthy carrier of
typhoid: she carried the typhoid bacteria and spread them to others, but did
not fall ill herself. Over her lifetime, Mary was officially blamed for 10
outbreaks totaling 51 cases of typhoid fever, and three deaths from the
disease. She was given the nickname, "Typhoid Mary" (308; 2098).
Aldo Castellani; Count of Chisiamaio (IT) discovered the
spirochete of spirochetal bronchitis (Castellani’s
disease) (371).
Samuel Taylor A. Darling (US) was the first to clinically describe
the fungal disease histoplasmosis. He
thought the etiological agent was protozoal and named it Histoplasma capsalata (549-552).
Henrique da Rocha-Lima (BR) concluded from histological studies
that Darling’s agent was fungal (529). Its name
would become Histoplasma capsulatum.
Katharine Dodd (US) and Edna H. Tompkins (US) reported the first intra vitam diagnosis. The
diagnosis was made from the blood during life by finding
the characteristic parasite in the large mononuclear cells (605).
William DeMonbreum (US) described the dimorphic nature of Histoplasma capsulatum after being
surprised by the growth of a mold from patient tissues displaying yeasts (582).
Amos Christie (US) and J. Cyril Peterson (US) found that
histoplasmosis is endemic to the Ohio River Valley (403).
Chester W. Emmons (US) demonstrated that it is a soil saprophyte (708).
Chester W. Emmons (US) and Libero W. Ajello (US) discovered its
relationship to bats and avian habitats respectively (30; 709).
Maurice Nicolle (FR) and Felix Mesnil (FR) introduced the use of
trypan-blue to treat trypanosomiasis (1723).
Georgii Norbertovich Gabritschewsky; Georgii Norbertovich
Gabrichevskii (RU) used preparations of killed streptococci to vaccinate
patients against scarlet fever (842).
Friedrich Voelcker (DE) and Alexander von Lichtenberg (DE) devised
retrograde pyelography (introduction of radiopaque medium into the kidney
pelvis by way of the ureter) for the study of the urinary tract (2302).
August Paul Wasserman (DE), Albert Ludwig Siegmund Neisser (DE),
Carl Bruck (DE), Arthur J. Schucht (DE) and Felix Plaut (DE) discovered the
presence of antibodies to syphilis antigen in the serum of syphilitic monkeys;
then working with A. Schucht (DE) they demonstrated similar antibodies in the
blood of human syphilitics. This became the basis of a Complement Fixation Test
for anti-syphilitic antibodies called the Wasserman Test (2401-2403). This work
is considered to include the first isolation of what Pangborn would call cardiolipin.
Karl Landsteiner (AT-US), Rudolf Müller (AT), and Otto Pötzl (AT)
discovered the working principle of the Wassermann reaction (1346).
Mary C. Pangborn (US) coined the term cardiolipin to denote a lipid isolated from beef heart and
possessing antigenic properties in the complement-fixation test (1781).
Rudolf Müller (AT) and Moriz Oppenheim (AT) developed a complement
fixation test for serodiagnosis of gonorrhea (1657).
Alfred Wolff-Eisner (DE) coined the terms pollen disease and
pollen sensitivity. He suggested that hay fever might be a form of
hypersensitivity or anaphylaxis in the nose (2534).
The following is taken from Paul Ehrlich’s speech at the
dedication of the Georg Speyer-Haus in Frankfurt Germany. It was a privately
endowed institute dedicated entirely to the study of chemotherapy. Ehrlich was
its first director (he was simultaneously the director of the Institute for the
Investigation and Control of Sera). A portion of the address in 1906 is
repeated here so the reader can sense the working of possibly the greatest medical
mind of the nineteenth century.
“Since
throughout my whole life, my thoughts have been most intimately interwoven with
the same fundamental ideas as are now due to give a lead to the enterprises of
the Speyer-Haus, I ask for your indulgence, and hope that you will not impute
it to me as lack of modesty, if now, somewhat unconventionally, I retrace some
of my personal memories and unfold to you the story of the origin of my own
ideas. I would not have done this, had I not thought that such a developmental
presentation would be the simplest way of making clear to you the nature of the
problems, which give to this institute its special character.
It was some
33 years ago—I was then still quite a young student—when I came across a
publication on lead poisoning, by Heubel. To elucidate the nature of this
poisoning, the author had estimated quantitatively the lead content of the
liver, the kidney, and the heart, and had discovered that there were remarkable
differences in the amount of lead to be found in the various organs. When he
immersed organs of normal animals in dilute lead-solutions and subsequently
subjected the organs to chemical analysis, he believed that he obtained exactly
the same differences. This experiment seemed to me, at that time, a revelation.
The possibility emerged that this technique might be used also to ascertain the
sites of action of poisons. That lead was found to be present in certain
organs, e.g. the brain, provided merely the starting point for the
investigation. The brain is a large structure and is made up of many
constituents—cells, fibers, etc. The real problem was to determine in which of
these cells the poison was stored. The immediate effect of this idea became
almost a disaster for me, since it disrupted, more than a little, the normal
course of my studies, without bringing me any nearer to the desired goal. I had
nothing but failure from any of my attempts to detect, with the aid of the
microscope, the presence of metals applied in high dilutions, and I was not a
step further forward.
It became
necessary, therefore, to approach the task from a more general standpoint and,
first of all, to obtain some insight into the manner and the method of the
distribution of substances within the body and its cells. When we see that certain
poisons, e.g. strychnine, produce spasms which originate from the nerve cells
of the spinal cord, and when we see that the American arrow-poison, curare,
causes a paralysis of the extreme nerve-endings, which extend to the muscle,
the possibility becomes clear that these effects can be caused only through
strychnine making a direct connection with the cells of the spinal cord and
curare with the ultimate finest nerve-endings. Conclusions such as these seem
at once to be self-evident—to be, as I might express it, part of a man’s inborn
inheritance. They can be traced back into antiquity and have assumed importance
in several of the by-paths of medicine. They appear quite clearly, for example,
in a statement of a mediaeval physician, who thought that drugs must possess
spicules, by the aid of which they are able to anchor themselves in the various
organs. But these ideas, like so many axioms, were as easy to express, as they
were difficult to prove; and this may well be the reason why they were
completely ignored in the practical study of drugs and, despite their
fundamental importance, have played no role in the development of pharmacology.
If one had wished to put the storage-axiom
to the test, one would have had to demonstrate, by the use of the microscope
that the poison under consideration was, in fact, present at these minute
sites. This, however, was found to be impracticable.
It was,
therefore, necessary to begin the investigation by an entirely different line
of approach, and to utilize substances that, like dyes, are easily detected,
even by the naked eye; it would suffice to remove and examine a small piece of
an organ of an animal after it had been killed. A glance through the microscope
would then give evidence immediately, and in the finest detail, concerning the
distribution of the substance.
The fact
that a large number of dyes exists which differ widely in their constitution,
and the fact, too, that some of these dyes exhibit a high degree of toxicity,
made such endeavors all the more feasible, and thus the method originated
which, nowadays, is known briefly as vital
staining. I do not intend to dwell on the wealth of results, which this
technique has yielded, especially in microscopic anatomy, but will just refer
to the fact that the various dyes show quite characteristic differences in
their distribution and localization. Thus, for example, methylene blue causes a
really wonderful staining of the peripheral nervous system.
If a small
quantity of methylene blue is injected into a frog, and a small piece of the
tongue is excised and examined, one sees the finest twigs of the nerves
beautifully stained, a magnificent dark blue, against a colorless background.
With many
vital stains it is therefore extremely easy, almost at a glance, to ascertain their
distribution in the different parts of the body—which parts they favor, which
organs they avoid.
Of course,
staining of the dead organs and tissues has for a long time been one of the
most important tools of histological research. But staining of this kind can
only give information concerning purely the anatomical structure of the
tissues. If, however, one wishes to acquire an understanding of the properties
and functions of the living cell, then the staining reaction must be made to
take place in the body itself, i.e., one must stain the living substance. In
this way one can gain an insight into the relationship between the individual
tissues and certain dyestuffs. I have denominated this affinity of the stains
and other foreign substances by adjectives with the ending tropic, and, for example, describe a dye which stains only a single
specific tissue as monotropic, and
speak thus of neurotropic and myotropic substances, etc., while
substances which have the capacity to stain several tissues should be called polytropic. In 1866, in my early study “
On the methylene-blue reaction of the living nerve-tissue,” I had already
indicated the lines along which a further analysis of the process should
proceed. Two questions had first of all to be answered:
1. Why does
methylene blue stain nerve cells?
2. Why are
nerves stained by methylene blue?
As to the
first question, the answer, by virtue of the nature of the problem, had, of
necessity, to be in terms of pure chemistry; and I was able to prove that the
nerve-staining property of methylene blue is conditioned by the presence of
sulfur in the methylene-blue molecule. Synthetic chemistry has, in fact, given
us a dye, which, apart from the absence of sulfur, corresponds exactly in its
chemical constitution to methylene blue. This is Bindschedler’s green. With the
absence of sulfur, there is associated the inability to stain living nerves.
The interest of the second question was heightened by the circumstance that, in
higher animals, not all the nerve endings are stained by methylene blue. I have
shown it to be probable that these differences between the individual nerve
endings are not due to different degrees of avidity for methylene blue, but
rather to certain associated environmental conditions; for bluing of the nerves
is intimately associated with the degree of oxygen saturation, inasmuch as it
is precisely at those places which are best supplied with oxygen that staining
of the nerve endings by methylene blue also occurs. Further, one can easily
ascertain that the nerve fibers that stain have also an alkaline reaction; and
thus oxygen saturation and alkaline reaction provide the conditions, which make
possible the staining of nerve endings by methylene blue. Just as methylene
blue accumulates only in alkaline fibers, so one must suppose, in the light of
the investigations of Lieberkühn and Edinger, that certain other stains, such
as alizarin blue, would stain the acid regions. One is, therefore, compelled to
differentiate between alkaline, acid and also neutral fibers, and it is
evidently to such differences, in conjunction with the degree of oxygen
saturation, that the determinant role must be ascribed, in regulating the
distribution and action of injected substances among the particular regions of
the nervous system. It seemed, moreover, according to my earlier investigations
on the methylene-blue staining of the nerve fibers, that an irreversible
combination very soon takes place between dye and certain constituents of the
nerve substance, since one can see that intensely blue granules appear in the
axis cylinder, a phenomenon which may well be intimately associated with the fibrillic acid recently described by
Bethe.
Very special
conditions govern the uptake of dyes by the brain. The early anatomists,
themselves, noticed that, even in the most severe jaundice, the brain remains
snow-white, while all the other tissues are of a deep orange tint. I obtained
this same effect on introducing into animals a large number of synthetic dyes,
all of which, however, were alike in containing an acid group, such as the
sulphonic acid radicle. In contrast to this, a large number of basic dyes,
which, like the alkaloids, form salts from acids, stain the brain very
effectively. I have assumed that the reason for this behavior is that the
alkalinity of the blood plays a decisive role. On this basis, it is now
possible to look at all these phenomena from a common point of view. The difference
in the behavior of acid and alkaline dyes may accordingly be ascribed to the
fact that the former are chiefly bound in the blood in the form of salts,
whereas the latter remain free. Thus, the brain plays the same role as does the
ether in the method of recognizing poisons devised by Stas-Otto; this method,
as is well known, depends on the fact that basic substances, such as alkaloids,
are bound in acid solution and are, on that account, difficult to extract,
whereas they can easily be shaken out with ether from an alkaline solution. I
was, in fact, able to confirm this idea experimentally, for if one introduces
acid groups, e.g. the sulphonic acid radicle, into neurotropic stains, then the
neurotropic property of the resulting derivatives is immediately abolished. We
can similarly explain the fact that toxic substances are so often weakened in
their toxic properties by the introduction of a sulphonic acid radicle into the
molecule. The accumulation of the toxic agent in the central nervous system is
made impossible, merely by the introduction of this sulphonic acid radicle.
The analogy
between the roles played, respectively, by the brain and by ether, in the
storage of dyes in the one case and in the method of identifying poisons in the
ether, is further emphasized by the fact, discovered by me, that neurotropic
and lipotropic properties, as a rule, go together, i.e., that those dyes which
are taken up by the brain are also deposited in adipose tissue. This similarity
in the behavior of the adipose and nervous tissues finds a simple explanation
in the fact that the brain contains an abundance of fat-like substances—myelin
and lecithin. Fat and brain, therefore, behave in the body exactly as ether
does in the extraction of alkaloids. This theory, moreover, many years after
the publications dealing with my work on it, was taken up again by Hans Horst
Meyer and Overton, as the lipid-theory,
it plays today an important role in medicine.
These
observations, based on my work with dyes, I developed also, during the years
1886 and 1887, in relation to a series of remedies. I demonstrated that
thallin, like a large of dyestuff, is lipotropic. In order to detect thallin in
the tissues, I made use of the property that, even in very dilute solutions, it
is transformed by oxidizing agents (ferric chloride) into a dark green
dyestuff. If this is immediately fixed, in
statu nascendi, in an insoluble form, it is then easy to obtain an insight
into the distribution of the thallin. The pronounced affinity of thallin for
adipose tissue causes the thallin to be held for a long time in the body; and
this long retention of so readily oxidizable a substance is explained by my
discovery that there is no free oxygen in adipose tissue, but that this, on the
contrary, has a maximal reducing power. All these observations led me to the
view that the hitherto dualistic approach to the problem of the connection
between chemical constitution and pharmacological action has been much too
narrowly conceived, and that there exists another and, indeed, decisive element
which must be considered—the distribution in the body. My investigations have
shown that the distribution, i.e., the selective affinity for certain organs and
systems, is a function of the chemical constitution.
But the
establishment of the existence of this relationship between constitution,
distribution and action fulfilled only one part of the program, which I had
planned for myself. For an action produced on an organ, the first requirement
is the fixation of chemical substances; but the simple storage of substances of
any kind is not of itself enough to cause specific toxic effects. This requires
a second determinant factor to be present in the chemical substance. With the
alkaloids, which we will consider first, the conditions are very similar to
those, which had already been observed with the simpler dyestuffs. In these
there are two different chemical constituents, which are responsible for the
dying property, a so-called chromophore group and, further, the auxochrome
groups. In exactly the same way, one must postulate, when considering the
alkaloids, that in the constitution of these powerfully acting substances two
different factors must be distinguished: (1) a selective group which governs
distribution, and (2) a pharmacophore group which evokes the specific activity.
You will allow me, perhaps, to clarify this with an example. As is well known
to you, cocaine, which, in medicine, plays so important a role as a local
anesthetic, is the benzoyl derivative of an ecgoine ester. A large number of
chemical homologues of cocaine can be synthesized by replacing the benzoyl
radicle by those of other acids, e.g. of acetic acid or formic acid. All the
substances obtained in this way are, by virtue of their chemical nature,
homologues of cocaine, and all these different cocaines follow the same pattern
of distribution in the body, because they belong, chemically, to the same
class. But of all these substances, only one, the benzoyl-cocaine obtained from
the coca plant, acts as a local anesthetic; and from this it is immediately
obvious that the benzoic acid residue is the source of the specific action, and
thus, that the benzoyl radicle functions here as the anaesthesiophore group.
The science
of immunology provides the most striking examples of the relation between
distribution and action. It has been found in this connection that the group,
which is responsible for the distribution of bacterial poisons, which I have called
the haptophore group, is a quite separate complex, and that the toxic action is
attributable to the presence of a second group, the usually very unstable
toxophore group. A still further differentiation between the factors of
distribution and of activity is to be found if we take into consideration such
cell poisons (hemolysins and bacteriolysins) as are present even in a normal
blood serum, or are produced by immunization. For, in the case of these, each
of the two properties is connected with a special molecule, one of which,
called the amboceptor, is the carrier of the haptophore group, and the other,
called the complement, that of the toxophore group. The hemolytic action of
snake venom follows the same pattern. The factor contained in the snake venom
represents solely the distributive component, whilst the appropriate
pharmacophore group is present in lecithin. Neither snake venom nor lecithin is
able, of its own accord, to destroy the blood cells. On the other hand, the
product formed from them, the snake lecithide, corresponds, as was shown by
Kyes, to a toxin, the haptophore group of which comes from snake venom and
toxophore complex from the lecithin.
The
concepts, which have thus been developed, indicate the direction, which must be
followed in the construction of new organotropic medicaments. It will,
therefore, be one of the main tasks of the new institute to persevere along
this path; and this entails, in the first instance, the discovery of substances
and chemical groups, which have an affinity for particular organs. The
organotropic substances must then be furnished with pharmacophore groups, which
will bring about a therapeutic and pharmacological activity. We intend, as it
were, to use certain chemical complexes as vehicles to carry appropriate
pharmacophore groups to the desired types of cell. To begin with, however, the
main emphasis will be put on the haptophore group, the distributive factor. For
this represents the conditio sine qua non
for any therapeutic action.
But the
theoretical problem represents only one aspect of our objective; on the other
hand, our main effort will be directed to the discovery of new, rational,
curative remedies. As you are aware, the study of medicaments, or pharmacology,
is a long-established field of research, which has been cultivated and
developed in numerous institutes. But most pharmacological research is directed
merely to determining the effects, on animals in good health, of the
substances, which are used as remedies, and to fix the limits of their safe
administration in the clinic, by observations on their side effects and their
toxicity. Prior attentions, therefore, given to those substances (especially
alkaloids), which produce interesting and important toxic effects. These highly
toxic substances, however (if one excludes a few alkaloids such as morphine,
cocaine, atropine, etc.), are frequently quite useless in clinical practice,
and thus a large part of the research work is carried out in realms, which are
remote from any practical application in medicine. Admittedly, one obtains
information about the risks which excessive dosage and otherwise unsuitable
methods of administering particular substances involve, and this, of course, is
of the greatest importance. Application of drugs in practice must be based on
toxicological examination, and it need not be emphasized that toxicology, as
such, represents a thoroughly justified and necessary type of science, which
may even be of the greatest importance in biology and physiology—the very
foundation of our medical knowledge. But it seems to me that, with the line of
approach so predominantly in this one direction, some of the most important
tasks of pharmacology are pushed all too readily aside, and practical medicine
does not receive sufficient benefit. We must certainly be grateful to those who
have safeguarded our departure [on the voyage of discovery] with beacons
against toxic action—but they have not charted our course into the open sea of
curative medicine” (1372).
Charles Scott Sherrington (GB) coined the term proprioceptive as it refers to a sense
of position and equilibrium (2059; 2060).
Paul Carnot
(FR) and Clotilde-Camille DeFlandre (FR) proposed the idea that erythropoiesis
is regulated by hormones. After conducting experiments on rabbits subject to
bloodletting, they attributed an increase in erythrocytes in rabbit subjects to
a hemotopic factor they named hématopoïetine (haemopoietin) (360).
Eva
Bonsdorff (FI) and Eeva Jalavisto (FI) suggested that hématopoïetine be changed to erythropoietin because they found that it affects only the
erythroid series (248).
Leon Orris
Jacobson (US), Eugene Goldwasser (US), Walter Fried (US), and Louis F. Pizak (US)
detected the
production of erythropoietin by the
kidney (1168).
Toshiaki Miyake
(JP), Charles K.-H. Kung (US) and Eugene Goldwasser (US) were the first to
isolate erythropoietin;
their source was human urine (1603).
Fu-Kuen Lin
(CN-US), Sidney S. Suggs (US), Chi-Hwei Lin (US), Jeffrey K. Browne (US), Ralph
Smalling (US), Joan C. Egrie (US), Kenneth K. Chen (US), Gary M. Fox (US), Frank
Martin (US), Zippora Stabinsky (US), Sayred M. Badrawi (US), Por-Hsiung Lai (US),
and Eugene Goldwasser (US) identified the erythropoietin
(EPO) gene and cloned it (1418;
1419).
Sylvia Lee-Huang
(US) cloned and obtained expression of recombinant human erythropoietin (EPO) gene (1377).
Kirk P. Conrad
(US), Deborah F. Benyo (US), Andrea Westerhausen-Larsen (US), and Theresa M.
Miles (US) presented results suggesting a new site of erythropoietin
(EPO) expression: the trophoblast cell of the human placenta (460).
Georg Jochmann
(DE) and Simon Flexner (US) introduced serum therapy for epidemic meningitis with serum from immunized horses (787;
1185).
Simon Flexner (US) and James Wesley Jobling (US) produced a serum
that remained the best treatment for cerebral
spinal meningitis until the sulfa drugs were introduced. They determined
that antibacterial serum had to be administered directly into the fluid
encompassing the brain and spinal column so that it could reach bacteria
insulated by the blood–brain barrier (786; 788; 789).
Alfred Vogt (CH) described a form of uveomeningoencephalitis endemic in the Far East. A disease, usually
occurring in adult life, in which severe bilateral inflammation of the iris (iridocyclitis), ciliary body and choroid
of the eye is associated with relapsing
meningoencephalitis, deafness, alopecia, depigmentation of the skin and
eye, symmetrical vitilligo and poliosis (whitening of the ends of the hairs) (2303). It is
called Vogt-Koyanagi-Harada syndrome.
Robert Bárány (AT-SE) devised the caloric test for labyrinthine function. If the normal ear is
irrigated with hot water at 110° to 120° F, a rotary nystagmus is developed away from the irrigated side. There
is no nystagmus if the labyrinth is
diseased (118).
Robert Bárány (AT-SE) also developed a clinical pointing test for demonstrating the
existence of disturbances of the vestibular apparatus and its paths in the
brain. The patient is asked to point at a fixed object with a finger or a toe
with the eyes alternatively open and closed. With eyes open the patient holds his
arm upwards and then lowers it to a horizontal position, so that it points at
the investigator's index finger. In damages of vestibularis there are
disturbances of coordination and the patient points past (119-121).
Lodewijk (Louis) Bolk (NL) investigated the comparative anatomy of
the cerebellum and its nerves. He determined that muscle coordination is
localized to this portion of the brain (241; 242; 244).
Jules Joseph Déjérine (CH-FR) and Gustave Roussy (FR) described
the Déjérine-Roussy or thalamic syndrome (superficial
persistent hemianesthesia, mild hemiplegia, mild hemiataxia, complete
astereognosis, severe pains in the hemiplegic side, and choreo-athetoid
movements in the members of the paralyzed side) (577). Typically,
his condition arises following thalamic stroke.
Alois Alzheimer (DE), in 1907, wrote, “A woman, 51 years old,
showed jealousy toward her husband as the first noticeable sign…. Soon a
rapidly increasing loss of memory could be noticed. She could not find her way
around in her own apartment…. Her entire behavior bore the stamp of utter
perplexity. She was totally disoriented to time and place…. The generalized
dementia progressed…. After 4 1/2 years…death occurred…. The autopsy revealed a
generally atrophic brain without macroscopic lesions…. Scattered through
the…cortex…one found miliary foci that were caused by the deposition of a
peculiar substance.” This is from his monumental work on Alzheimer’s Disease for which he will always be remembered (38; 39).
Emil Wilhelm Magnus Georg Kraepelin (DE) named Alzheimer's disease in 1910 (1310).
Gheorghe Marinesco (RO) and Paul Oscar Blocq (FR) were the first
to describe plaques in brain tissue of senile patients (1506).
George Washington Crile (US) was the first to describe radical
neck dissection that encompasses the surgical removal of neck metastases
contained between superficial and deep fascial layers of the neck (499).
George Washington Crile (US) and David H. Dolley (US) pioneered
the use of high-dose epinephrine (adrenaline) in the resuscitation of an animal
near death from anesthetics and asphyxia (501).
Christian J. Gauss (DE) and Bernard Krönig (DE) reported their
successes with scopolamine-morphine anesthesia in obstetrics (twilight sleep) (861-863).
George Washington Crile (US), in August 1906, at St. Alexis
Hospital in Cleveland, Ohio, performed the first successful transfusion of
blood from one human to another in the United States. This was the first
human-to-human blood transfusion in which Landsteiner’s discovery of blood
types was used to match the donor and recipient (500).
Edward Konrad Zirm (AT) performed the first successful cornea
transplant in humans. The patient had sustained alkali burns. The
donor was an 11-year-old boy whose eye was enucleated because of penetrating
scleral injury (2568).
Vladimir Petrovich Filatov (RU) and M.A. Bajenova (RU), in 1912,
greatly improved the success rate in corneal transplants when he showed that
material from a fresh cadaver is just as satisfactory as that from a living
person and that eyes can be banked in
a refrigerated, sterile receptacle. He used an
egg membrane to adhere the graft (765; 766).
José Goyanes (ES) accomplished the surgical substitution of veins
for arteries (908).
Mathieu
Jaboulay (FR) carried out the first attempts at human kidney transplantation.
On January 22, he transplanted a porcine kidney to the brachial vessels of a
woman suffering from nephrotic syndrome. Three months later he repeated the
experiment with a goat kidney (1157).
Neither kidney xenograft lasted more than several hours.
Alexis Carrel (FR-US) performed a double nephrectomy followed by
transplantation of both kidneys from another animal. He noted that the
recipient animal could secrete almost normal urine and live in good health for
at least a few weeks (362).
Harold Neuhof (US) performed a xenotransplant of lamb kidney into
a human in acute renal failure. The patient survived for nine days (1716).
Yu Yu
Voronoy (UA) transplanted human kidneys (2371).
Charles A. Hufnagel (US), Ernest Landsteiner (US), and David M.
Hume (US), in 1947, performed a human renal transplant. The first patient was a
young woman in renal failure following obstetrical complications. The purpose
of the transplant was to provide temporary renal function until her kidneys
recovered from acute tubular necrosis. The donor kidney was anastomosed in the
antecubital space under local anesthesia using a cutaneous ureterostomy. The
patient died a few months later of fulminating hepatitis secondary to pooled
plasma infusions, which she had received during her treatment. The temporary
kidney transplant had been previously removed (1616).
David M. Hume (US), John Putnam Merrill (US), Benjamin F. Miller
(US), and George Widmer Miller (US) performed nine cadaveric or free kidney transplantations in humans,
eight to thigh and one to an orthotopic location. One thigh kidney transplant
functioned for five months. No immunosuppression was used (1126).
J. Hartwell Harrison (US), John Putnam Merrill (US), Joseph Edward
Murray (US), and Warren R. Guild (US), on 23 December 1954, transplanted a
kidney from a healthy twenty-four-year-old individual to his twin brother
suffering from severe renal disease (cross skin grafting established genetic
identity). This was the first time in medical history that a normal healthy
person was to be subjected to a major surgical operation not for his own
benefit. Post-operatively the transplanted kidney functioned immediately with a
dramatic improvement in the patient's renal and cardiopulmonary status. This
spectacular success was a clear demonstration that organ transplantation could
be lifesaving (1003; 1569). Some
consider this to be the first truly successful kidney transplantation.
Joseph Edward Murray (US), Stanley Lang (US), Benkamin J. Miller
(US), and Gustave J. Dammin (US) developed a reproducible renal transplant
operation in dogs using intra-abdominal vascular anastomoses and a
uretero-cystostomy for urinary drainage, placing the kidney in the lower
abdomen. This has become the universal renal transplant procedure since that
time. Complete functional studies of some of these autografted kidneys two
years after transplantation proved them to be completely normal (1672).
Joseph Edward Murray (US), John Putnam Merrill (US), Gustave J.
Dammin (US), James B. Dealy, Jr. (US), Carl W. Walter (US), Marcus S. Brooke
(US), Richard E. Wilson (US), J. Hartwell Harrison (US), and Eli A. Friedman
(US) performed a renal allograft from a human fraternal twin to a recipient
preconditioned with a sublethal total body irradiation. This was the first long
survival of an organ allograft, an objective not previously achieved in an
animal model (1568; 1674). The
patient subsequently led a full active normal life until he died of cardiac
problems 25 years later.
Joseph Edward Murray (US), John Putnam Merrill (US), Gustave J.
Dammin (US), James B. Dealy, Jr. (US), Guy W. Alexandre (US), J. Hartwell
Harrison (US), Richard E. Wilson (US), Frank J. Takacs (US), and Edward B.
Hager (US) carried out clinical trials on the efficacy of 6-mercaptopurine and
azathioprine as immunosuppressive agents to prolong the survival rates of
allograft kidney transplants. One patient, transplanted in April 1962, was
treated with azathioprine following a cadaveric renal allograft. He survived
over one year and was the world's first successful unrelated renal allograft (1570; 1673; 1675).
Jean Alban Bergonié (FR) and Louis Mathieu Frédéric Adrien
Tribondeau (FR) presented the rationale for radiotherapy as follows: “The
effect of radiations on living cells is the more intense: (1) the greater their
reproductive activity, (2) the longer their mitotic phase lasts, and (3) the
less their morphology and function are differentiated” (201).
The Congress of the United States enacted the Food and Drugs Act,
the first federal statute prohibiting the misbranding or adulteration of food (458).
Alexandr Petrovich Karpinsky (RU) reported research on Devonian
algae, the so-called charophytes. His study of the contemporary charophytes
showed their closeness to extinct Devonian forms and indicated that they likely
had a common ancestor (1222; 1223).
George Reber Wieland (US) researched plant material derived from
the Upper Jurassic and Lower Cretaceous beds of Maryland, Dakota, and Wyoming
where he discovered the hermaphrodite nature of the bennettitean flower and
recognized an affinity between the mesozoic cycadophyta and the angiosperms.
The angiosperm with which he specially compared the fossil type was the Tulip
tree (Liriodendron) and certainly
there is a remarkable analogy with the magnoliaceous flowers, and with those of
related orders such as Ranunculaceae and the water lilies (2459).
The Biochemical Journal
was founded.
The Biochemische
Zeitschrift was founded.
1907-1916
Polio turned into a major problem in the U.S., with about a
thousand cases in New York in 1907, and another outbreak in 1911. The disease
was recognized as contagious, but there was no understanding yet of exactly how
it was spread. The first widespread outbreak, seriously affecting 26 states,
occurred in 1916. About 7,000 deaths were recorded (1296).
1907
"We must not forget that the greatest engineer is not the man
who is trained merely to understand machines and apply formulas, but is the man
who, while knowing these things, has not failed to develop his breadth of view
and the highest qualities of his imagination. No creative work, whether in
engineering or in art, in literature or in science, has been the work of a man
devoid of the imaginative faculty." George Ellery Hale, first director of
the Mount Wilson Observatory (972).
Eduard Buchner (DE) was awarded the Nobel Prize in Chemistry for
his discovery that fermentation can function independently of cell structure.
Charles Louis Alphonse Laveran (FR) was awarded the Nobel Prize in
Physiology or Medicine "in recognition of his work on the role played by
protozoa in causing diseases."
Paul Ehrlich (DE) had a fascination with dye affinity for specific
cells going back to his days as a medical student at Strassburg. While there he
devised a fuchsin stain, which could demonstrate lead in the tissues. Later
this concept would reemerge in his interest in affinity of antitoxins for
toxins and drugs for target microbes, which led to his discovery of
arsphenamine (Salvarsan), a cure for
syphilis.
Ehrlich and his colleagues discovered that the dye trypan red
kills the trypanosome which causes sleeping sickness. Ehrlich kept looking for
something better. He decided that the nitrogen atom combinations it contains
cause the action of trypan red. Arsenic atoms resemble nitrogen atoms in
chemical properties and, in general, introduce a more poisonous quality into compounds.
By 1907 he and Sahachiro Hata (JP-DE) had synthesized 606 different compounds.
Number 606, dihydroxydiamino-arsenobenzene hydrochloride, did not work very
well against trypanosomes but later an assistant (H. Sachs) tested it against
syphilis and found it to be deadly. It was called arsphenamine or Salvarsan,
the latter being the name under which it was marketed. Today it is called arsphenamine. Ehrlich knew that dyes
often exhibit exquisite specificity and reasoned that it might be possible to
create a chemical which was very specific and toxic for a parasite and yet
harmless to its host. He often referred to these chemicals as magic bullets. Ehrlich’s success
represents the beginning of chemotherapy
(a word he coined) as a laboratory science (667; 669-672; 675-677; 1691).
Percival Hartley (GB), using liver tissue, was the first to
isolate arachidonic acid (1013).
Adolf Otto Reinhold Windaus (DE) and Wilhelm Vogt (DE) prepared
histamine synthetically by the
decarboxylation of histidine (2514).
Friedrich Alfred Bauer (DE), Carl Alexander Neuberg (DE-US) and Benno
Brahn (DE) discovered that inosinic acid contains a pentose (166; 1704; 1705).
A.V. Braun (DE) and Joseph Tcherniac (DE) prepared the
phthalocyanine nucleus of a new class of dyes called the phthalocyanins from
phthalimide and acetic andydride (279). These did not find use as biological
stains until 1950 when alcian blue was used to stain acid mucins (2129).
Walter Morley Fletcher (GB) and Frederick Gowland Hopkins (GB)
showed that, after being formed in muscular contraction, some lactic acid is
oxidized to furnish energy for resynthesis of glycogen from the remaining
lactic acid. They demonstrated rigorously that
muscle contraction is accompanied by the anaerobic formation of lactic acid,
which is removed aerobically, at a rate depending on the level of exposure to
oxygen (784).
Carl Franz Joseph Erich Correns (DE), gave the first experimental
evidence that sex-difference behaved as a Mendelian character. The work was
carried out using the dioecious plant, Bryonia
where he found that the pollen was of two types, half male determining, and
half female determining, while the eggs, in respect to sex, were alike. The
male was heterogametic, while the female was homogametic (475).
Erwin Baur (DE) was the first to clearly demonstrate a lethal
allele in Antirrhinum (snapdragon) (168).
Svante August Arrhenius (SE) enriched immunology by observing that
antigen-antibody reactions obey the law of mass action, emphasizing
quantification, encouraging mathematical and graphic evaluation, applying
physics and coining the term immunochemistry (61).
Eduard Pfuhl
(DE) described how he had made use of the catalytic properties of spongy
platinum to obtain anaerobic conditions for the culture of organisms (1819).
Patrick
Playfair Laidlaw (GB) suggested the use of platinized charcoal and colloidal platinum
for the same purpose (1332).
James
McIntosh (GB), Paul Gordon Fildes (GB), and William Bulloch (GB) developed the
highly successful 'McIntosh-Fildes Jar,' an anaerobic jar (1549).
John Hanna Brewer (US) and J. Howard Brown (US) devised a safe
method of accomplishing anaerobiosis for culturing microorganisms. It used an
electrically heated platinized catalyst in a closed system with illuminating
gas or hydrogen (286).
John Hanna Brewer (US) devised a bacterial culture medium to which
thioglycollate was added to maintain a reducing environment (284).
The modern
anaerobic jar is based on that originally described by J. Howard Brown (US) and
later modified by John Hanna Brewer (US), Anita A. Heer (US), C. Baxter
McLaughlin (US) and Daniel L. Aligeier (US) in which palladium is used to
catalyze the reduction of oxygen with hydrogen generated from sodium
borohydride and water (285; 287; 312).
Hans Molisch (CZ) pioneered in isolating and describing several
species of non-sulfur purple photosynthetic bacteria in pure culture. He
demonstrated conclusively that such organisms do not produce oxygen and
discovered the photoheterotrophic growth mode (1605).
Adolfo Ferrata (IT), Hans Ritz (DE), Arthur F. Coca (US), John
Gordon (GB), Hugh Robinson Whitehead (GB), Arthur Wormall (GB), Herbert Joseph
Rapp (US), A.B. Taylor (US), Myron A. Leon (US), Kusuya Nishioka (JP), William
D. Linscott (US), Kozo Inoue (US), Robert A. Nelson, Jr. (US), Joerg Jensen
(US), Irma Gigli (AR-US), Noboru Tamura (JP), Hans Joachim Müller-Eberhard
(DE-US), Irwin H. Lepow (US), George B. Naff (US), Earl W. Todd (US), Jack
Pensky (US), Carl F. Hinz, Jr. (US), and Anne L. Haines (US) made discoveries
which revealed the numerous factors of the complement system in the blood (444; 756; 905; 957; 958; 1147; 1148; 1382; 1421; 1658; 1680; 1693; 1727; 1855; 1856; 1907; 2196).
Stanislas Josef Matthias von Prowázek (CZ) demonstrated that
material from silkworms (Bombyx mori)
suffering from the polyhedral disease, which the breeders called jaundice was infectious after the
polyhedra were removed by filtration through many layers of filter paper. This
pointed the way to the eventual realization that some insect diseases are
caused by viruses. In this same paper he suggested that viruses might someday
be useful in controlling insect pests (2368). These are
now considered Baculovirus.
Giuseppe Ciuffo (IT) realized the viral nature (papillomavirus)
of genital warts when he induced warts after autoinoculation of cell-free wart
extracts (408). Note:
the first papillomavirus
Karl Bernhard Lehmann (DE) and Rudolf Otto Neumann (DE) started a
formal manual for classification of bacteria in which for the first-time
staining reactions and the formation of the highly heat resistant endospores
were considered formal diagnostic features (1379).
Raymond Jacques Adrien Sabouraud (FR) discovered that Epidermophyton inguinale can cause human
dermatomycosis (1974).
Anatole Chauffard (FR) made original contributions to the
understanding of the pathophysiology of the red cell abnormalities present in hereditary spherocytosis (393). This work led him to develop
the osmotic fragility of erythrocytes test which finally enabled physicians to distinguish hepatic and hemolytic jaundice.
RBCs from hepatic jaundice are much
more resistant to lysis than those from hemolytic
jaundice patients.
Clarence Cook Little (US) produced the first inbred strain of mice
by carrying out brother sister matings for over 20 generations. The animals
chosen carried recessive genes for dilution, brown, and nonagouti. Today this
strain is called DBA (925). He also
established the black C57BL inbred strain of mice.
It was Clarence Cook Little who, with funds from the Jackson and
Ford families, established the Jackson Laboratory at Bar Harbor, Maine during
the late 1920’s. This laboratory is one of the world’s most important sources
of inbred animals for research.
Élie Metchnikoff; Ilya Metchinikoff; Iljitj Metchnikov; Iljitj
Metschnikov; Ilya Ilyich Mechnikov; Ilja Metjnikov (RU-FR) proposed that human life could be prolonged
by introducing bacteria into the diet which would compete with the proteolytic
types present in the colon. He recommended that Bacillus bulgaricus, an organism he isolated from sour milk in
Bulgaria, be used for this purpose. He found that if this organism was
introduced in sufficient numbers it would replace the putrefactive bacteria
normally present in the colon. He also determined that its growth was promoted
by lactose (1572).
Ludwig Halberstäedter (DE-IL) and Stanislas Josef Matthias von
Prowázek (CZ) were the first to describe the inclusions
(Halberstäedter—Prowázek bodies) found in cells of a trachoma infection. They thought the organism was closely related
to the smallpox virus (964; 965).
Hideyo Noguchi (JP-US) established the etiology of trachoma when he isolated Bacterium granulosis from cases of trachoma then inoculated it into monkeys
and obtained granulomatous lesions of the conjunctiva (1736).
Tang Fei-Fan (CN), Yuan-Tung Huang (CN), Hsiao-Lou Chang (CN), and
Ko-Chien Wang (CN) were the first to isolate Chlamydia trachomatis as an etiological agent of trachoma (2194).
Erwin Frink Smith (US) and Charles O. Townsend (US) in describing Agrobacterium tumefaciens as the
causative agent of crown gall in plants wrote the following:
“For two
years the writers have been studying a tumor or gall which occurs naturally on
the cultivated marguerite, or Paris daisy. It has been difficult to isolate the
organism and to demonstrate it unmistakably in stained sections. Recently the
bacteria (seen in small numbers in the unstained tissues on the start) have
been plated out successfully. With subcultures from poured plate colonies, thus
obtained, the galls have been reproduced abundantly and repeatedly during the
last few months, the inoculations having been made by needle-pricks. From galls
thus produced the organism has been re-isolated in axenic culture and the disease reproduced, using subcultures from
some of the colonies thus obtained and puncturing with the needle as before.
More than 300 galls have been produced by puncture inoculations. Under the most
favorable conditions (young tissues) the swellings begin to be visible in as
short a time as four or five days, and are well developed in a month, but continue
to grow for several months, and become an inch or two in diameter.
In some of
our experiments one hundred percent of the inoculations have given positive
results (40 punctures out of 40 in one series; 62 punctures out of 62 in
another), while the check plants have remained free from tumors, and also, in
nearly every case, the check punctures on the same plant. In the two series
just mentioned there were 110 check punctures on the same plants, all of which
healed normally and remained free from galls. Old tissues are not very
susceptible. The tumors grow rapidly only in young fleshy organs. The organism
attacks both roots and shoots. It frequently induces abnormal growths on the
wounded parts of young cuttings. Its power to produce hyperplasia is not confined
to the marguerite. Well-developed small tumors have been produced in a few
weeks on the stems of tobacco (Nicotiana
tabacum), tomato and potato (Solanum
tuberosum) plants and on the roots of sugar beets (Beta vulgaris). More interesting economically is the fact that
galls closely resembling the young stages of crown gall have been produced on
the roots of peach trees by needle-pricks, introducing this organism. In
eighteen days these growths have reached the size of small peas, the checks
remaining unaffected. It is too early, perhaps, to say positively that the
cause of the widespread and destructive crown-gall of the peach has been
determined by these inoculations, but it looks that way. Of course, the most
that can be affirmed absolutely at this writing is that we found an organism
which when inoculated into the peach produces with great regularity galls which
in early stages of their growth can not be distinguished from crown gall. The
matured daisy galls look astonishingly like the peach gall. Numerous
experiments which ought to settle the matter definitely in the course of the
next three months are now under way. In the best series of experiments on peach
roots (that inoculated from a standard nutrient agar culture five days old) 14
groups of needle-punctures (5 in each group) were made on nine trees, 13 tumors
resulting. The fourteenth group was on a weak tree which did not leaf out, and
might therefore be left out of the count. In that case we have 100 per cent of
infections. On the roots of nine young trees from the same lot, held as checks,
75 punctures were made, using a sterile needle, but no galls resulted. In
another series of nine peach trees inoculated at the same time as the preceding
and examined on the twenty-third day, 75 per cent of the punctures had yielded
galls (9 tumors on 7 plants). These roots were inoculated by needle-pricks from
a culture believed to be rather too old (glycerin agar streak 6 days), but the
plants were set out again, and it is not unlikely that galls will finally
develop on the roots of the other two plants. The plants, inoculated and
un-inoculated, were set, immediately after making the needle-punctures, in good
greenhouse soil, in new ten-inch pots, and have been subject to the same
conditions as to light, heat and water” (2083).
Erwin Frink Smith (US), Nellie A. Brown (US), and Charles O.
Townsend (US) affirmed the 1907 paper (2082).
Albert Joyce Riker (US) discovered that Agrobacterium tumefaciens invades and multiplies within host cells
on its way to causing crown gall disease (1895; 1896).
Rudolf Massini (DE) isolated a mutant strain of Escherichia coli that he called mutabile and that, in contrast to
ordinary Escherichia coli strains,
was unable to ferment lactose. The metabolic defect of this lactose-negative
strain could be readily observed by plating the strain on a special
sugar-utilization indicator medium called EMB agar. This agar contains a
nutrient broth medium containing the dyes eosin yellow and methylene blue and
the sugar whose fermentation is to be tested. On EMB agar, a bacterium able to
ferment the sugar produces a dark red colony, whereas a nonfermenting bacterium
produces a white colony. (The red and white colors reflect alternative states
of the indicator dyes, which in turn signal the respective chemical changes
produced in the agar during bacterial growth with or without fermentation of
the test sugar.) Thus, when the lactose-negative Escherichia coli mutabile is plated on EMB-lactose agar, its
colonies are white. Upon prolonged incubation of these plates, however, isolated
dark red spots or papillae appear on the colonies. Upon picking and replating
the bacteria present in the red papillae on EMB-lactose agar, Massini found
that these bacteria had regained the capacity to ferment lactose—that is, they
had become lactose-positive Thus during the growth of the colony initiated by a
lactose-negative bacterium, mutations of the type lactose-negative
tolactose-positive had taken place, and these gave rise to subclones of
bacteria to which the capacity for lactose fermentation, characteristic of
ordinary Escherichia coli had been
restored (1515). In
Massini’s day it did not seem possible to prove conclusively the genetic nature
of these changes.
Ernest Edward Tyzzer (US) discovered Cryptosporidium, a coccidian protozoan parasite, in the gastric
mucosa of mice (1244; 2253-2255).
Freda A. Nime (US), Joe D. Burek (US), David L. Page (US), Myron
A. Holscher (US), John Howard Yardley (US), John Lawrence Meisel (US), David
Rhodes Perera (US), Criss Meligro (US), and Cyrus E. Rubin (US) reported cases
of Cryptosporidium parvum infections
in humans (1555; 1726). It affects
the intestines and is typically an acute short-term infection. It is spread
through the fecal-oral route, often through contaminated water. From 1981
onward, numerous new cases began to be recognized in AIDS patients where the
symptoms are particularly severe and often fatal.
Ross Granville Harrison (US), Milton J. Greenman (US), Franklin P.
Mall (US), and Clarence M. Jackson (US) cultivated amphibian spinal cord in a
lymph clot, thereby demonstrating that axons are produced as extensions of
single nerve cells (1007; 1008; 1010) Some people
consider this work as the origin of modern tissue culture (See Justin Jolly, 1898).
Henry V. Wilson (US) demonstrated that if cells from two different
species of sponges are teased apart then mixed together the cells recognize
their own species, congregate together, and ignore the cells of the other
species (2502).
Edward Babák (CZ) reported that the size of the external gills of
the frog are increased by prolonged hypoxia and lessened by prolonged hyperoxia
of ambient water (88).
Alfred Wolff-Eisner (DE), to explain the origin of contact-type
immune reactions, proposed that dermatological problems result from the
complexing of medications with the patient’s tissues (self) (2535). Later
experiments would prove him correct.
Béla Schick (HU-AT-US) accurately postulated the immunological
origin of the delayed sequelae to streptococcal infections, which include rheumatic fever and glomerulonephritis. Like serum
sickness, they are part of a systemic
Arthus-type reaction, and hence are diseases caused by circulating immune
complexes (2012; 2013).
Ludvig
Hektoen (US) described what would become the major and minor cross matches for
blood (1034). He later suggested that the
safety of blood transfusions might be improved by cross matching blood between
donors and patients to exclude incompatible mixtures.
Reuben Ottenberg (US) performed the first human-to-human blood
transfusion using blood typing and cross matching.
Over the next several years he successfully used the procedure in 128 cases,
virtually eliminating transfusion reactions (1768).
Reuben Ottenberg (US) observed the Mendelian inheritance of blood
groups and recognized the universal
utility of group O donors (1769).
Ivar Wickman (DE) was the first to produce evidence confirming the
infectious nature of poliomyleitis (2454).
Karl Landsteiner (AT-US) and Erwin Popper (DE) demonstrated that a
filterable agent (virus) from a human case of poliomyelitis would cause paralysis if injected intraperitoneally
into monkeys (1347; 1348). This was
considered proof that poliovirus is the etiological agent of poliomyelitis. Note: the first
enterovirus
Constantin Levaditi (RO-FR) and Karl Landsteiner (AT-US) were the
first to isolate the poliomyelitis virus and were among the first to use
monkeys in polio research (1386).
Percy Moreau Ashburn (US) and Charles F. Craig (US) showed that dengue
hemorrhagic fever or dengue fever is caused by a virus (71). Note: They showed
inconclusively that it was vectored by mosquitoes.
Wilhelm Türk (AT) provided the first case description of complete agranulocytosis (2244).
Joseph Marek (HU) described a disease in adult cockerels, which
were affected by paralysis of the legs and wings. He called it neuritis interstitialis or polyneuritis (1503). There is
little doubt that this is the first clinical description of what became known
as Marek’s disease (MD). Poultrymen call it range paralysis.
Anthony E. Churchill (GB) and Peter Martin Biggs (GB) isolated a Herpes virus associated with the disease
and proved it to be the etiological agent (405).
Maurice Ralph Hilleman (US) developed a vaccine to Marek’s disease. It became the first
practical vaccine against a tumor disease of any type in any species (1083).
Anthony E. Churchill (GB), L.N. Payne (GB), and Roger Charles
Chubb (GB) developed a vaccine against Marek’s disease using a live attenuated
virus (406).
Jean René Cruchet (FR) wrote an influential monograph on spasmodic
torticollis in which he documented 357 cases of torticollis (506).
James Ramsay Hunt (US) reported a syndrome characterized by an
acute peripheral facial neuropathy associated with erythematous vesicular rash
of the skin of the ear canal, auricle (also termed Herpes zoster oticus), and/or mucous membrane of the oropharynx (1128). This became known as Ramsay Hunt syndrome type II. The
pathophysiology of Ramsay Hunt syndrome
type II is defined as Varicella-zoster
virus infection of the head and neck that involves the facial nerve, often
the seventh cranial nerve (CN VII).
George Hoyt Whipple (US) described a disease characterized by an
accumulation of granular material in the walls of the small intestine and lymph
nodes. He called it lipodystrophia
intestinalis. Others would later name it Whipple’s disease (2444).
Whipple's disease is a
chronic, relapsing, and multisystem disease. It presents a diagnostic challenge
for both clinicians and pathologists.
Bernard La Scola (FR), Florence Fenollar (FR), Pierre-Edouard
Fournier (FR), Martin Altwegg (CH), Marie-Noelle Mallet (FR), and Didier Raoult
(FR) identified the organism responsible for the disease to be a member of the
order Actinomycetes designated Tropheryma whipplei (1326).
Chevalier Jackson (US) introduced the bronchoscope into the
practice of medicine (1159). Note:
The introduction probably took place c. 1899.
Arthur Robertson Cushny (GB) and Charles Wallis Edmunds (US)
published the first case report of atrial
fibrillation. The patient was 3 days post-operative following surgery on an
"ovarian fibroid" when she developed a "very irregular"
pulse at a rate of 120 - 160 bpm (524).
Friedrich Jamin (DE) and Hermann Merkel (DE) published the first
röntgenographic atlas of the human coronary arteries. It contained a study of
29 hearts in which the coronary arteries were injected with a suspension of red
lead in gelatin (1174).
Thomas Peel Dunhill (AU) performed his first thyroid lobectomy
under local anesthesia for toxic goiter. He advocated a bilateral attack on the
thyroid and thyroidectomy in the thyrocardiac patient (647).
Anton von
Eiselsberg (AT) performed the first operation on a patient with adiposogenital syndrome
(2319).
Arthur
Edward James Baker (IE-GB) published a full description of spinal analgesia in
100 cases by injecting stovaine (amylocaine,
the first synthetic local anesthetic). In the following year a further series
exhibited improvement by the addition of 5 per cent glucose to increase the
density and limit the spread of the fluid (103; 104).
William
Arbuthnot Lane (GB) introduced the ‘no-touch technique’ in open reduction and
plating of long bone fractures by “Lane's steel plates” (1351).
Anton von
Eiselsberg (AT) and Otto Marburg (AT) performed the first
successful resection of an intramedullary
spinal cord tumor in 1907 (2318).
Alexander G. Ruthven (US) wrote a pioneering paper in ecology
based on field studies in the American Southwest (1960).
Charles Henry Turner (US) was the first to prove that insects can
hear and distinguish pitch and that cockroaches learn by trial and error (2245-2250).
Alfred Adler (AT) introduced the concept of inferiority complex and the method of compensation needed to
overcome it (18).
Lightner Witmer (US) coined the phrase clinical psychology (2525).
USDA's Pure Food and Drug Act became effective. The
Pure Food and Drug Act of June
30, 1906, is a United States federal law that provided federal inspection of
meat products and forbade the manufacture, sale, or transportation of
adulterated food products and poisonous patent medicines (923).
Archiv
für Geschichte der Medizin was founded.
Gesellschaft für Morphologie und
Physiologie was founded
1908
“Inborn errors of metabolism are due to the failure of a step in
the metabolic sequence due to loss or malfunction of an enzyme.” Although the
significance of this deduction remained dormant for many years, and is still
not fully appreciated, it is now recognised as the foundation of medical
genetics. Archibald Edward Garrod (854).
“Treasure
your exceptions! When there are none the work gets so dull that no one cares to
carry it further. Keep them always uncovered and in sight. Exceptions are like
the rough rock work of a growing building which tells that there is more to
come and shows where the next construction is to be.” - William Bateson (147).
“The law of
progress is this: —The race is not to the swift, nor to the strong, but to the
wise—the secret of evolutionary success is the development of a superior
brain.”—Walter Holbrook Gaskell (855).
Ernest Rutherford (NZ-England) was awarded the Nobel Prize in
Chemistry for his investigations into the disintegration of the elements, and
the chemistry of radioactive substances.
Ilya Ilyich Mechnikov (RU-FR) and Paul Ehrlich (DE) were awarded
the Nobel Prize in Physiology or Medicine "in recognition of their work on
immunity."
William Sealy Gosset (GB) derived the statistical method that came
to be known as Student’s t test. The
test consists of rejecting a hypothesis if, and only if, the probability
(derived from t) of erroneous rejection is small. Gosset published all his papers
under the pseudonym Student (1799; 2168).
Ernest Rutherford (NZ-GB), Johannes (Hans) Wilhelm Geiger (DE),
and Thomas Royds (GB) proved that alpha particles are the equivalent of helium
nuclei. They used a scintillation counter to determine that one gram of radium
emits 37 million alpha particles per second. This quantity of alpha particles
per second is now referred to as a curie (1957-1959). One
million emissions per second is a rutherford.
Lawrence Joseph Henderson (US) formulated the theory of acid-base
equilibrium in animal tissues (1036). Henderson
later explained the respiratory function of the blood and demonstrated the
quantitative relationships of eight blood variables (1038).
Svante August Arrhenius (SE) pointed out that carbon dioxide in
the atmosphere serves as a heat-trap,
for it allows the high frequency sunlight to penetrate freely to the earth’s
surface but is opaque to the low frequency infrared radiation which the earth
reradiates at night. He also theorized that life began on earth when living
spores had reached it across the emptiness of space (panspermia) (62).
Richard Martin Willstätter (DE), Max Benz (DE), and Arthur Stoll
(CH) worked out the way in which the magnesium atom is placed in the
chlorophyll molecule and showed that the iron atom is held in similar fashion
in heme, the colored portion of the hemoglobin molecule. They determined the
chemical composition of blue-greenish chlorophyll a as 137 atoms (C55H72N4O5Mg), and yellowish-green chlorophyll b as
136 atoms (C55H70N4O6Mg) (2488; 2492).
Richard Martin Willstätter (DE) and Ernst Hug (DE) were the first
to separate chlorophyll a,
chlorophyll b, carotin (carotene),
and xanthophyll (2490).
Richard Martin Willstätter (DE) and Arthur Stoll (CH) discovered
and named phytol (the major esterifying alcohol of chlorophyll at position 7 of
the macrocycle), pheophorbide (chlorophyllide without the central Mg-atom), chlorophyllase (the enzyme that
de-esterifies chlorophyll) and allomerization (2491).
Hans Fischer (DE) and Adolf Stern (DE) proposed a correct
structure of chlorophyll, except for the position of the two extra hydrogens,
which are now recognized to be located on ring IV at positions 7 and 8 of the
macrocycle (771; 772).
Hans Fischer (DE) and Hermann Wenderoth (DE) correctly assigned
the two extra hydrogens of chlorophyll to positions 7 and 8 on ring IV (773).
K. Noack (DE) and E. Schneider (DE) started the study of
bacteriochlorophyll (1731).
Hans Fischer (DE), Robert Lambrecht (DE), and Hellmuth Miittenzwei
(DE) established the chemical relationship of bacteriochlorophyll to
chlorophyll by the preparation of common derivatives (769; 770).
Phoebus Aaron Theodor Levene (RU-US) and Walter Abraham Jacobs
(US) showed that the five-carbon sugar D-ribose is to be found in inosinic
acid, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid. They
established unequivocally that the arrangement of the three components of
inosinic acid, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid
is nitrogenous base-ribose-phosphate with the purine or pyrimidine connected to
the sugar by a glycosidic linkage and the phosphate attached to the carbon 5 of
the ribose by an ester linkage. They also discovered that mild hydrolysis of
adenylic acid, cytidylic acid, uridylic acid, and guanylic acid yields
adenosine, cytosine, uridine, and guanosine. They named compounds such as inosinic
acid, adenylic acid, cytidylic acid, uridylic acid, and guanylic acid nucleotides, and compounds such as
hypoxanthine, adenosine, cytosine, uridine, and guanosine, nucleosides They concluded (incorrectly) that intact nucleic acid
is composed of the four nucleotides, adenylic acid, cytidylic acid, uridylic
acid, and guanylic acid in equivalent proportions to form a tetranucleotide.
They demonstrated in 1909 that guanosine; a ‘simple nucleoside’ could, like
guanylic acid, form gels (1388-1391).
Helen Dean King (US) saw the accumulation of amplified ribosomal
RNA during pachytene in the American toad Bufo
lentiginosus (= B. americanus)
and its subsequent migration to the nuclear periphery as nucleoli (1256). Helen Dean
King (US) led the development and production of the first line of standardized
laboratory rats, known as Wistar Rats, produced between 1906 and 1940.
Axel Leonard Melander (US) noted in 1908 that lime-sulfur washes
failed to kill the San Jose scale insect on apples in the Clarkston,
Washington, area. This is one of the first known examples of insect resistance
to chemicals (1556).
Daniel Trembly MacDougal (US) wrote Botanical Features of North American Deserts, which contains
geology, geography, physiology, ecology, the dominant flora, adaptive
mechanisms of desert plants, and superb illustrations (1465).
Julius
Wohlgemuth (DE) described a method for measuring the concentration of amylase (diastase) in the serum, thereby introducing the potential for
diagnosing acute pancreatitis prior
to laparotomy or autopsy (2528).
Robert Doerr (DE) reported that the virus of pappataci fever,
also called sand-fly fever, phlebotomus fever, or three-day
fever is transmitted by sand flies that have fed on the blood of patients
with the fever (606). Note:
first phleboviruses
Clemens Peter Pirquet von Cesenatico; Clemens Peter von Pirquet
(AT) noted that the tuberculin skin test response of immune individuals is
transiently depressed during acute measles (rubeola) virus infection, from just
prior to the rash until 7-20 or more days following its appearance (2358). This phenomenon is called virus-induced
immunosuppression.
Martinus Willem Beijerinck (NL) demonstrated that Azotobacter can fix atmospheric nitrogen
when it is grown in axenic culture (181).
Jules Brunel (CA) related the antibacterial properties of the
Penicillia through an anecdote told by Doctor A.E. Cliffe, a biochemist from
Montreal. …” It was during a visit through Central Europe in 1908 that I came
across the fact that almost every farmhouse followed the practice of keeping a
moldy loaf on one of the beams in the kitchen. When asked the reason for this I
was told that this was an old custom and that when any member of the family
received an injury such as a cut or bruise, a thin slice from the outside of
the loaf was cut off, mixed into a paste with water and applied to the wound
with a bandage. I was assured that no infection would then result from such a
cut” (319).
George Harrison Shull (US) used a Mendelian interpretation to
explain the phenomenon of hybrid vigor
and its association with plant productivity in corn (Zea mays). This represents the introduction of the concept of heterosis (superiority of heterozygotes)
although the word was not used until 1914. George Harrison Shull (US) showed
that self-pollination in corn, a naturally cross-pollinating plant, results in
the isolation of inbred strains that are uniform and true breeding. Following
Johanssen he called these pure lines.
They are much less vigorous than the open-pollinated varieties from which they
are derived. However, when two such lines are crossed, the F1 hybrids are
uniform, like their inbred parents, but much more vigorous and in some cases
more productive than the original open-pollinated varieties. There is only one
shortcoming: The hybrid seed is borne on the weak, unproductive plants of the
inbred strains used as the female (2066-2068).
Donald Forsha Jones (US) solved this problem in 1917 when he
invented the double-cross method of hybrid seed production. He crossed the
single cross of two strains of Chester’s Leaming with a single cross of two
strains of Burr White. Grown in 1918, this double cross yielded more than the
best open-pollinated varieties (1194; 1195; 1197; 1198)
Donald Forsha Jones (US), Paul C. Mangelsdorf (US), Harry Theodore
Stinson, Jr. (US), and Uheng Khoo (MY-US) made a significant contribution to
hybrid corn production when they employed fertility-restoring genes to overcome
cytoplasmic male sterility. This method employs hereditary factors in the
cytoplasm to make male corn flowers sterile when sterility is an asset and uses
heredity factors on the chromosomes to make it fertile when fertility is
essential (1199-1201). A patent
on using genetic restorers in hybrid-seed corn production was issued to Jones
and the “Research Corporation”in 1956. This was the first patent on a genetic
technique to be granted in the United States.
Marcus Morton Rhoades (US) was the first to describe cytoplasmic
male sterility in corn. This represented the first instance in plants where a
phenotype other than chlorophyll variegation was shown to be determined by
cytoplasmic factors (1874).
John C. Stephens (US) and Robert F. Holland (US) utilized the
hybrid of two breeds found in Africa to create the high production seeds for
sorghum (2137).
Yuan Longping (CN), in 1966, found a particularly important
species of wild rice that he ended up using for the creation of a high-yield
hybrid rice species (1439). Note: In 1973, in
cooperation with others, he was finally able to establish a complete process
for creating and reproducing this high-yield hybrid rice species (2544).
Godfrey Harold Hardy (GB), and Wilhelm Weinberg (DE),
independently formulated the theorem that in the absence of mutation and
selection, the frequency of a gene in any large, randomly mating population
will reach equilibrium in one generation and remain in equilibrium thereafter
regardless of whether the gene is dominant or recessive. Also, the genotypic
frequencies of a population in equilibrium with two alleles with frequencies p
and q are given by the formula p2 + 2pq + q2. This theorem forms the mathematical
basis for population genetics (264; 995; 1810; 2138; 2427). See, Karl Pearson, 1904.
Paul Jaccard (FR) devised the Jaccard index (Jaccard similarity index;
Jaccard coefficient; coefficients of association) which
provides numerical expression of taxonomic similarity based on presence-absence
of species. It directly expresses the percentage of taxa shared between
two collections (1158).
Charles P.
Sigerfoos (US); Theodor Mortensen (DK); Guiseppe Mazzarelli (IT); Thurlow
Nelson (US); and Douglas P. Wilson (US) all played significant roles in the
discovery of delayed metamorphosis among invertebrate larval forms (1526; 1638; 1694; 1695; 2071; 2493).
Carlo Moreschi (IT) observed that incubation of
typhoid bacteria with a diluted (goat) anti-thyphoid serum did not lead to
agglutination. However, bacterial agglutination could be induced by the
addition of anti-goat serum, thus documenting the antiglobulin reaction, which would later be
explained by Coombs, et al (1619; 1620). See, Coombs, 1945. Although Moreschi did
not realize it he had discovered weak or incomplete antibodies.
Vladimir Mikhailovich Bekhterev (Bechterev) (RU), in
1885, described
the superior nucleus of the vestibular nerve (Bekhterev's nucleus). Ref
Korbinian Brodmann (DE) described 52 discrete cortical areas. He
is responsible for establishing the basis upon which the present-day science of
comparative cytoarchitectonics of the mammalian cortex rests. All confusion of
brain area nomenclature disappeared with Brodmann’s contribution (303).
Leonid Abgarovich Orbeli (RU) showed that a change in the
intensity of light could serve as a conditioned stimulus for a dog, even though
the dog could not distinguish the color (1751).
Victor Henri Hutinel (FR) and Oscar M. Schloss (US) reported on
cases of allergy to common foods. These represent some of the earliest
contributions on food sensitivity of the immunologic category (1139; 2022).
Yandell Henderson (US) suggested
that acapnia, or deficiency of carbon
dioxide in the blood and tissues, is an important factor contributing to the
depression of respiratory and circulatory activity, which accompanies operation
and anesthesia (1039).
Yandell Henderson (US), Felix Percy Chillingworth (US), and James
Ryle Coffey (US) showed that acapnia
(diminished carbon dioxide in the blood) might induce acute disturbance of the
heart and failure of the peripheral circulation. These conditions resemble the
functional depression of shock in patients after prolonged anesthesia and major
operations. On the other hand, it was found that if the carbon dioxide content
of the body is conserved by partial rebreathing, the vitality of an animal,
even under prolonged and extensive operation and trauma, is but little
depressed (1040; 1042).
Yandell Henderson (US), Howard W. Haggard (US) and Raymond C.
Coburn (US) carried their observations to the clinic and found that when
inhalations of carbon dioxide (8%) in air were administered to patients after
major surgical operations under open ether anesthesia, the effects were
strikingly beneficial. With the return of deep breathing, the cyanosis then common
after anesthesia disappeared. The cutaneous circulation improved. The skin
changed in color and temperature, from blue-gray and cold to pink and warm. The
volume of the pulse, previously thready, rapidly became full; and arterial
pressure was restored to normal. Owing to the increased volume of breathing,
the anesthetic (ether) was rapidly ventilated out of the blood and
consciousness returned within a few minutes, even after profound anesthesia.
Nausea and vomiting were either greatly reduced or entirely absent and after
the inhalation the patient dropped off to sleep. In continuation of these
observations, White found that when slow hemorrhage occurs after operations
upon the brain, the rate of breathing gradually decreases until death is
imminent. In several such cases life was saved by stimulation of respiration
with inhalation of carbon dioxide (1043; 1044).
Yandell Henderson (US) pointed out the importance of acapnia, showed that fatal apnea could result from excessive forced
breathing, and recommended the administration of carbon dioxide in conditions
of shock, particularly in collapse due to anesthesia. He also pointed out that
high altitude flying could produce decompression sickness or caisson disease (1041).
Atelectasis of a lobe, or even a massive collapse of an entire lung, may
develop.
Pol N. Coryllos (US) and George L. Birnbaum (US), based
on bronchoscopic investigations on dogs, considered lobar pneumonia to be a
“pneumococcal atelectasis,” caused by an obstruction of a bronchus by the
production of an excessive and sticky secretion. They
demonstrated experimentally that pneumonia might develop if pathogenic
organisms happen to be present because they find in an atelectatic lung
conditions favorable to their growth (478-480).
Percy Theodore Herring (GB) thoroughly described hyaline or
colloid masses (Herring bodies) scattered throughout the posterior lobe of the
pituitary gland in both mammals and nonmammals. These nerve-end organs had
first been reported by Harry J. Berkley (US) (202; 1058).
Leo Buerger (US) described thromboangiitis
obliterans (Buerger disease), a
recurring inflammation and thrombosis (clotting) of small and medium arteries
and veins of the hands and feet (323).
George Coats (GB) described an exudative
vasculopathy, which became known as Coat’s
Disease. It is neither inherited nor associated with systemic vascular
abnormalities, but ocular disorders, such as retinitis pigmentosa, may be seen with retinal telangiectasia (437).
Franklin Paine Mall (US) wrote A
Study of the Causes Underlying the Origin of Monsters. Third Contribution to
the Study of the Pathology of Human Embryos in which he concluded that
every human egg has the possibility of becoming an abnormal embryo if the
environment is unfavorable at critical times in its development. By monsters he
simply meant embryos that had failed to develop in a normal way (1482; 1483).
Noël Fiessinger (FR) elucidated the histogenesis of cirrhosis.
Showing that the course of the destruction is the same whatever the conditions,
pathological or otherwise, which determine it (762).
William Halse Rivers Rivers (GB) and Henry Head (GB) set up
experiments based on Head’s submitting to the division of his own left radial
and external cutaneous nerves. Their findings of the loss and restoration thus
brought about, led to a reclassification of the sensory pathways (1909).
Friedrich Trendelenburg (DE) described
his first unsuccessful pulmonary embolectomy in a human (2234). This operation
became famous and is known as the Trendelenburg operation.
Martin Kirschner (DE) (Trendelenburg’s student) surgically treated
pulmonary embolism with more success (1259).
Walther Spielmeyer (DE) showed that amaurotic familial idiocy was
the result of a disturbed lipid metabolism and demonstrated primary
degeneration of the posterior columns and cerebral changes (2111).
Gordon Morgan Holmes (IE-GB) described an inheritable disease
characterized by cerebellar ataxia due to a degeneration of the cerebellar
olivary nucleus. This condition was later given the name Holmes’ syndrome I (1096).
Victor Alexander Haden Horsley (GB) and Robert H. Clarke (GB)
developed the Horsley-Clarke system
and apparatus for performing the so-called
stereotactic surgery of the brain, whereby a set of precise numerical
coordinates are used to locate each brain structure (1110).
Lars Leksell (SE) improved this apparatus considerably when he
introduced his stereotactic instrument for human functional neurosurgery (1381).
Harvey Williams Cushing (US) developed surgical temporal
decompression to relieve cerebral contusion and edema (517).
Archibald Donald (GB) presented his operation for cases of
complete prolapse (613). Note: Prolapse is a
condition where organs fall down or slip out of place. It is used for organs
protruding through the vagina, rectum, or for the misalignment of the valves of
the heart.
Giuseppe Dagnini (IT) and Bernhard Aschner (AT-US) independently
described what became known as the oculocardial
reflex. It is characterized by a slowing of the pulse following pressures
applied to the eyeball or the carotid sinus. It is sometimes used to slow the
heart during attacks of a supraventricular tachycardia. It may also be used as
a diagnostic test for angina pectoris.
Slowing of the heart produced by this reflex may relieve anginal pain (64; 531).
Greenfield Sluder (US) described a syndrome of neuralgia of the
lower half of the face, nasal congestion, and rhinorrhea secondary to a lesion
in the pterygo-palatine ganglion (pterygopalatine
syndrome) (2079).
Alban Köhler (DE) described a clinical condition in which, the
navicular bone temporarily loses its blood supply. As a result, tissue in the
bone dies and the bone collapses (1293). Note: called Köhler disease
Edouard Brissaud (FR) and Jean-Marie-Athanase
Sicard (FR) described a
hemiparesis and contralateral hemifacial spasm resulting from a pontine lesion (302). Later it was named Brissaud-Sicard syndrome.
Robert Mearns Yerkes (US) and John D. Dodson (US) found in their
studies of the mouse that: 1) the rapidity of learning increases as the amount
of difference in the brightness of the electric boxes between which the mouse
is required to discriminate is increased, 2) the relation
of the strength of electrical stimulus to rapidity of learning or
habit-formation depends upon the difficultness of the habit, 3) the rapidity of
learning increases as the strength of the electrical stimulus is increased from
the threshold of stimulation to the point of harmful intensity, 3) when task
discrimination is extremely difficult the rapidity of learning at first rapidly
increases as the strength of the stimulus is increased from the threshold, but,
beyond an intensity of stimulation which is soon reached, it begins to
decrease, 5) as the
difficultness of task discrimination is increased the strength of that stimulus
which is most favorable to habit formation approaches the threshold (2551).
Karl Grobben (AT) proposed a division of the animal kingdom into
two great stems determined by the fate of the blastopore in the earliest stages
of development. These two stems were Protostomia
(annelids, arthropods, and molluscs) and the Deuterostomia (chordates, hemichordates, and echinoderms). He
proposed the name Aschelminthes (Gk. ascos,
cavity, helminth, worm) to replace
Nemathelminthes (934).
The first continuous use of chlorine in
the United States for disinfection took place in 1908 at Boonton Reservoir (on
the Rockaway River), which served as the supply for Jersey City, New Jersey (1369). Chlorination was achieved by controlled additions of dilute solutions
of chloride of lime (calcium hypochlorite) at doses of 0.2 to 0.35 ppm.
The technique of purification of
drinking water by use of compressed liquefied chlorine gas was developed by a
British officer in the Indian Medical Service, Vincent B. Nesfield, in 1903.
Amédée Bouyssonie (FR), Jean Bouyssonie (FR) and Louis Bardon (FR)
found skeletal remains of Homo sapiens
neanderthalensis; Homo
neanderthalensis near the village of La Chapelle-aux-Saints in France (259). Note:
The remains are dated at c. 60K B.C.E.
Otto Schoetensack (DE) described and named archaic forms of Homo sapiens uncovered by gravel pit
workers in 1907 near Heidelberg in Germany. Estimated age is between 400K and
700K B.C.E. This find consisted of a lower jaw with a receding chin and all its
teeth. The jaw is extremely large and robust, like that of Homo erectus, but the teeth are at the small end of the erectus
range. They were named Homo
heidelbergensis (2032).
Arthur Smith Woodward (GB) described a more complete skull from
the Broken Hill Mine, Kabwe, Zambia and named it Homo rhodesiensis: Homo
sapiens rhodesiensis (2537). It is
dated at late Middle Pleistocene, c. 300K B.C.E.
George Henry Falkiner Nuttall (US-GB) founded and edited the
journal Parasitology.
1909
“There is no alleviation for the sufferings of mankind except
veracity of thought and action, and the resolute facing of the world as it is,
when the garment of make-believe, by which pious hands have hidden its uglier
features, is stripped off.” Thomas Henry Huxley (1141).
Emil Theodor Kocher (CH) was awarded the Nobel Prize in Physiology
or Medicine for his investigations on physiology, pathology, and surgery of the
thyroid gland. He was one of the first surgeons to resect and unite the
intestines.
Søren Peder Lauritz Sørensen (DK) suggested that chemists express
hydrogen ion concentration as the negative logarithm (pH) of the molar
concentration of the ion. A chemist, instead of speaking of a hydrogen ion
concentration of 10-7 moles per liter, would speak of a pH of 7.
This represents the introduction of the quantitative formulation of the concept
of pH (2099). See, Arrhenius 1884 for definition of acid
Søren Peder Lauritz Sørensen (DK) pointed out the effect of pH on enzyme activity (2099; 2100).
Lawrence Joseph Henderson (US) was the first to understand and
express quantitatively the buffering effect of carbon dioxide and bicarbonate
interacting with hydrogen ions in blood.
Later Karl Albert Hasselbalch (DK) converted Henderson’s dissociation
equations to the logarithmic form using the pH concept of Sørenson (1020; 1037). Lawrence
Joseph Henderson (US) rewrote the laws of mass action for weak acids and their
salts (1038).
Otto Wallach (DE) proposed the isoprene
rule which states that chemicals can be considered terpenes if their
molecular formulas have a carbon to hydrogen ratio of 5:8 (2383; 2384).
Leopold Stefan Ruzicka (HR-CH), Jules Meyer (CH), Max Stoll (CH)
and M. Mingazzini () demonstrated that isoprene is a structural unit of the
terpenes. This was a reintroduction of the isoprene
rule and helped in the understanding of the structure of turpentine oil,
sesquiterpenes, diterpenes, triterpenes, squalene, cholesterol, and the bile
acids (1962-1964).
Leopold Stefan Ruzicka (HR-CH), Albert Eschenmoser (CH), Oskar
Jeger (CH), and Duilio Arigoni (CH) further refined the concept of the isoprene
rule (718; 1961).
Alexander I. Ignatowski (RU) observed a possible relation between
cholesterol-rich foods and experimental atherosclerosis (1144). See, Felix
Jacob Marchand, 1904.
Adolf Otto Rheinhold Windaus (DE) showed that atheromatous lesions
contain six times as much free cholesterol as a normal arterial wall and twenty
times more esterified cholesterol (2509).
Nikolai Nikolaevich Anichkov; Nikolai
Nikolajewitsch Anitschkow (RU-DE-RU) and Semen
Sergejewitsch Chalatov (RU), using cholesterol-fed rabbits to produce experimental atherosclerosis, demonstrated that it
was cholesterol alone that caused atherosclerotic changes in the rabbit intima (54; 55). English translation found in: Arteriosclerosis,
1983, 3: 178-182. Note: This was the first experimental production of
atherosclerosis.
Federico Battelli (IT) and Lina Salomonovna Stern (LT-CH-RU) reported
their discovery that animal liver material can oxidize ethanol to acetaldehyde
and acetic acid (and possibly other volatile acids). This
represents the discovery of alcohol
dehydrogenase (157-159).
Elmer Verner McCollum (US), in work with laying hens, found that
all organic forms of phosphorus of biological importance could be synthesized
in the animal body from orthophosphates in the food (1535).
Archibald Vivian Hill (GB) and William Hartree (GB), using
delicate thermocouples, discovered that contracting frog leg muscle
fibers produce heat in two phases. Heat is first produced quickly as the muscle
contracts. Then, after the initial contraction, further heat is evolved more
slowly but often-in greater amounts. Hill also showed that molecular oxygen is
consumed after the work of the muscles is over but not during muscular
contraction. Hill and C. Lovatt Evans (GB) deduced that the heat liberated in
the presence of contraction and recovery are not sufficient for the complete
combustion of the lactic acid formed (723; 1077; 1079-1081).
Wallace Osgood Fenn (US) studied the production of heat by muscle.
He showed that there is a fairly good quantitative relation between the heat
production of muscles and the work which they perform, and that a muscle, which
does work, liberates, ipso facto, an
extra supply of energy which does not appear in any isometric contraction.
(Archibald Vivian Hill (GB) referred to this as the Fenn effect.) Fenn’s heat data showed first that if a muscle
shortens, no matter how little and no matter how lightly loaded, it produces
more heat than during an isometric contraction over the same period. He then
showed that this extra heat production is proportional to the external work done
by the muscle. It was clearly not determined by load alone, or by the change in
length. This was the first evidence, and remains today the best evidence, that
shortening is an active process and that muscle is not simply a prestretched
spring shortening passively (748; 749).
Stanley Rossiter Benedict (US) developed Benedict’s reagent to test for reducing sugars (192).
Otto Neubauer (DE) showed that in normal animal tissues amino
acids are deaminated to their corresponding keto acids (e.g., alanine to
pyruvic acid) (1700).
Jean de Meyer (BE) suspected, but did not prove, that a hormone
was produced by the pancreatic islets of Langerhans. He suggested naming it insuline from the Latin word for island (567).
Edward Albert Schäfer (GB) predicted that the islands of
Langerhans must secrete a substance, which controls carbohydrate metabolism (1986). See,
Laguesse, 1894.
Klaus Peter (DE) reported that the loops of Henle are present in
the kidney of mammals only, and that they are proportionally more developed in
species living in a dry habitat and producing concentrated urine (1809).
Keith Lucas (GB) and Edgar Douglas Adrian Adrian (GB) published
work on the all-or-none principle in
nerve stimulation (22; 1447; 1448).
Carl Franz Joseph Erich Correns (DE) and Erwin Baur (DE)
independently and in the same year proposed that inheritance of leaf color in Pelargonium zonale (geranium) and Mirabilis jalapa (the four-o’clock) respectively is due to genes carried in
the maternal cytoplasm (non-Mendelian), perhaps in the chloroplasts. This was
the first indication that mitochondria and chloroplasts may have their own
genetic systems. Baur favored the idea that the plastids were the genetic
determinants—the Plastom theory—
while Correns favored the idea that the inheritance was carried by
nonparticulate cytoplasmic material—non-Plastom
theory (169; 476; 477). Note: Non-Mendelian inheritance, while
rare, is accepted in such cases as the female-biased sex ratios in several
species of Drosophila, biased
inheritance of alleles at the autosomal t-locus of mice, and meiotic drive
(segregation distortion) of sex chromosomes in several genera and species.
Wilhelm Ludwig Johannsen (DK) suggested that Johann Gregor
Mendel’s factors of inheritance be called genes
from a Greek word meaning to give birth
to by dropping the first syllable of the pangene of Darwin and De Vries and
suggested that the genes “…may be tentatively considered to be chemical factors
of various kinds….” Johannsen also introduced other terms such as phenotype and genotype (1188; 1189).
William Ernest Castle (US) and John Charles Phillips (US)
performed an experiment, which was important to the demise of the concept of
acquired characteristics and the notion that the genotype of body cells might in
some way influence the genotype of germ cells. They transplanted the ovary from
a pure line of black (recessive) guinea pigs into an albino recipient. The
albino foster mother when mated to an albino male bore three litters consisting
entirely of fully black offspring. No influence of the albino foster mother, in
whose body the eggs had been produced, could be seen (378).
Muriel Wheldale (GB) was the first to attempt to understand the
events relating gene to phenotypic expression. She investigated flower color
mutants and the pigments produced in several species (2443).
Rollins Adams Emerson (US) and Edward Murray East (US) discovered
multiple allelomorphism in maize and in beans (699-707).
Hubert Dana Goodale (US) demonstrated that the barred plumage
pattern of Plymouth Rock fowls is inherited in a sex-linked mode (900).
Nils Herman Nilsson-Ehle (SE) analyzed the inheritance of color in
wheat and found that three different gene pairs R1r1, R2r2, and R3r3 were
segregating, each pair acting in the same way on the same quality, seed-coat
color. The effects of the different pairs were additive R1R1R2R2r3r3 being
redder than R1R1r2r2r3r3 (1725).
This work along with that of Edward M. East (US) showed that
continuous hereditary variation could be explained by discontinuous genetical
variations (i.e., genes altered by mutation) (656).
Richard Woltereck (DE) performed experiments, which probed the
interaction of genotype and environment. He studied quantitatively varying and
readily measurable characters, chiefly head form within and between pure lines
of the micro-crustacean, Daphnia (2536).
Albert A. Epstein (US) and Reuben Ottenberg (US) pointed out that
the human blood groups (A, B, O) are inherited in accord with Mendelian
principles (712).
Emil von Dungern (DE) and Ludwik Hirszfeld (PL) proposed that the
heredity of the ABO blood group system depends on two independently segregating
loci with allele pairs A, a and B, b respectively (2314).
Lewis Ralph Jones (US) demonstrated bacterial pectolytic
exoenzymes for the first time (1202). This led
to an understanding of bacterial soft rot.
Paul Ehrlich (DE) was the first to propose that immune mechanisms
are involved in protection against aberrant cells from within the organism
itself when he said, “I am convinced that during
development and growth malignant cells arise extensively and frequently but
that in the majority of people they remain latent due to the protective action
of the host. I am also convinced that this natural immunity is not due to the
presence of antimicrobial bodies but is determined purely by cellular factors.
These may be weakened in the older age groups in which cancer is more
prevalent” (668; 678). This can be considered the origin of the immune surveillance theory. See
Lewis Thomas, 1959.
Richmond T. Prehn (US) and Joan M. Main (US) showed
that tumors induced by chemical carcinogens in mice can stimulate
tumor-specific responses that are able to reject those same tumors on
challenge. They concluded that tumor immunity was induced by antigens unique to
the chemically induced tumor but found that spontaneously arising tumors were
not rejected when tested in the same experimental manner (1834).
Ludwik Gross (US), Edgar J. Foley (US), Richmond T. Prehn (US) and
Joan M. Main (US) demonstrated that mice could be rendered resistant to tumor
transplantation by preimmunization with the same tumor (793; 939; 1834).
Osias Stutman (US) reported that athymic mice do not have an
increased frequency of tumors induced by a chemical carcinogen, implying that
the concept of immune surveillance providing protective immunity was incorrect (2177).
Harold B. Hewitt (GB), Eileen R. Blake (GB), and Angela S. Walder
(GB) summarized data in support of the idea that naturally arising tumors are
not immunogenic (1066).
Aline van
Pel (BE) and Thierry Boon (BE) reported that vaccinating mice with mutagenized
tumor cells could induce specific immunity to spontaneous tumors. Their study
showed that spontaneous tumors are not inherently deficient in tumor antigens,
but instead failed to stimulate an effective immune response (2274).
Pierre van
der Bruggen (BE), Catia Traversari (IT), Patrick Chomez
(BE), Christophe Lurquin (BE), Etienne De Plaen (BE), Benoit Van den Eynde
(BE), Alex Knuth (DE), and Thierry Boon (BE) reported the
first identification of a tumor-specific antigen recognized by cytolytic T
cells in humans, reinforcing the idea that tumor antigens can elicit a
detectable tumor-specific response (2267).
Gerald Willimsky (DE) and Thomas Blankenstein (DE) found that
sporadic immunogenic tumors avoid destruction by inducing T-cell tolerance.
Ward J. McNeal (US), Lenore L. Latzer (US), and Josephine E. Kerr
(US) investigated the bactericidal effects of gastric juice and found that it
killed nearly all bacteria, which pass through the stomach (1552).
Max Einhorn
(PL-US) invented the duodenal tube for aspirating contents of the intestine below
the pylorus (679; 680).
János von Bókay (HU-AT) proposed that there is a relationship
between Varicella (chickenpox) and Herpes zoster (shingles) (2312).
Karl Kundratitz (DE) demonstrated that the same infectious agent
causes Varicella (chickenpox) and Herpes zoster (shingles) (1321).
Joseph Garland (US) hypothesized that Herpes zoster might become manifest as immunity to the Varicella-zoster-virus (VZV) waned (850).
Thomas Huckle
Weller (US) and Marguerite B. Stoddard (US) isolated viruses from chickenpox and Herpes zoster to confirm this relationship (2434).
R. Edgar Hope-Simpson (GB), after studying numerous cases of Varicella and zoster, supported Garland’s hypothesis (1102).
Sigurd Orla-Jensen (DK) emphasized the importance of physiological
characteristics in a logical classification of bacteria. Organisms were
assigned to genera using a combination of morphological and physiological
characters (1754).
John McFadyean (GB) and Stewart Stockman (GB) discovered that the
microaerophilic campylobacters (formerly Vibrio
fetus) can cause abortion in cattle and sheep (1545).
Charles Jules Henri Nicolle (FR) and Louis Herbert Manceaux (FR)
discovered and described Toxoplasma
gondii as the causative agent of a disease in the Gondi (Ctenodactylus gondi), a small North African rodent. They named it toxoplasmosis. Toxaplasma is from the Greek toxón,
a bow or arc, and gondii from the
name of the rodent (1722).
Alfonso Splendore (BR) described the same disease the same year in
laboratory rabbit (2115; 2116).
Josef Janku (CZ) was the first to definitively recognize the
parasite, Toxoplasma gondii, in
humans (1178; 1179).
Arne Wolf (US) and David Cowen (US) established that an association
exists between Toxoplasma gondii and
human congenital disease (2531). This
association was followed by the realization that T. gondii rarely causes disease even though it is a very common
parasite of adults but that in pregnant women the parasite can cross the
placenta and can damage the fetus.
William McPhee Hutchison (GB), J. Findlay Dunachie (GB), J. Chr
Siim (DK), and Kresten Work (DK) worked out the life cycle of Toxoplasma gondii and the role of the
domestic cat in transmission of toxoplasmosis (1136-1138).
Jitender P. Dubey (US), Nancy L. Miller (US), and Jack K. Frenkel
(US) reported that T. gondii is capable of infecting virtually all
warm-blooded animals. In humans, it is one of the most common parasites with a
lifecycle which can be broadly summarized into two components: 1) a sexual
component that occurs only within cats (felids, wild or domestic), and 2) an
asexual component that can occur within virtually all warm-blooded animals,
including humans, cats, and birds. The existence of oocysts was discovered in
cat feces, and the fecal-oral route of infection via oocysts was demonstrated.
Ingestion of oocysts by humans or other warm-blooded animals is one of the
common routes of infection (633; 634; 2430).
Theobald Smith (US) discovered that immunity to diphtheria can be generated in guinea
pigs by giving them a mixture of diphtheria
toxin and antitoxin (antibodies to the toxin). The toxin alone is so potent
that only trace amounts are harmful to the animals (2085).
Karl Bogislaus Reichert (DE) determined optimum conditions for
visualizing moving flagella and described them in detail (1865).
Lennart von Post (SE) initiated the modern discipline of
palynology when he reported on almost perfectly preserved pollen grains from
anaerobic sediments of peat bogs in Sweden. The pollen in the layered sediments
recorded a sequence of change in the dominant plant genera from the end of the
last glacial period to the present (2362-2367).
Otto Gunnar Elias Erdtman (SE) published works important to the expansion
of palyonology into an internationally accepted science (713; 714).
Harold A. Hyde (US) and David A. Williams (US) coined the term palynology
based on the Greek words paluno meaning 'to sprinkle' and pale
meaning 'dust' (and thus similar to the Latin word pollen). They defined
it as ‘the study of pollen and other spores and their dispersal, and
applications thereof’ (1142).
Benjamin Minge Duggar (US) wrote Fungous Diseases of Plants, with Chapters on Physiology, Culture
Methods and Technique, which was the first plant pathology text, published
in America (641).
Ernst Lowenstein (AT) discovered that formaldehyde treatment can
be used to convert toxins into relatively inert but still antigenic toxoids (1445).
Richard Richter (DE) was the first to publish concerning an
intrauterine device (IUD). The device he inserted was a ring
made of silkworm gut, with 2 ends, which protruded from the cervical os
enabling him both to check the device and remove it (1886).
Herbert McLean Evans (US) determined that during embryonic
development in vertebrates the aorta, cardinal and umbilical veins, and other
large blood vessels begin as a network of capillaries (724).
Simeon Burt Wolbach (US) and Tadasu Saiki (JP) have
shown that anaerobic bacteria are almost always present
in aseptically removed dog livers. They
mention that the presence of these
bacteria may account for many of the changes
occurring in so-called autolysis of aseptically
removed liver.
These pathogenic anaerobic bacteria are typically of the Bacillus welchii (Clostridium
welchii) type (2530).
Frank Charles Mann (US) noted, in 1923, that if these fragments
were allowed into the peritoneal cavity during surgery that a serious
peritonitis was likely to follow. Ref
James C. Ellis (US) and Lester Reynold Dragstedt (US) proved that
Mann was correct (628; 688).
Lester Reynold Dragstedt (US), Harold E. Haymond (US), and James C.
Ellis (US) demonstrated that the pancreas contains the pathogenic anaerobic Clostridium welchii (629).
Léon Charles Albert Calmette (FR), Jean-Marie Camille Guérin (FR),
Benjamin Weill-Hallé (FR), Alfred Bouquet (FR), Leopold Nègre (FR), Wilbert
(FR), Marcel Léger (FR), and Raymond Turpin (FR) developed a bovine strain of
tubercle bacillus, which was rendered completely avirulent by 230 transfers
over 18 years (1906-1924) on bile-glucose-potato medium. This strain is
designated as BCG (Bacille-Calmette-Guérin) and is widely used outside the U.S.A.
as a vaccine for tuberculosis in cattle and man (337-341).
Carlos Ribeiro Justiniano Chagas (BR) gathered preliminary
evidence that South American
trypanosomiasis or Chagas’ disease
is caused by Schizotrypanosome
(Trypanosoma) cruzi and transmitted by the Reduviid bug of the genus Triatoma. He proved it in 1916 then broadened his studies on the acute phase of the
disease and, in 1922, he and Eurico de Azevedo Villela (BR) described the
chronic heart form, thereby completing their clinical studies on the disease(384; 386; 387).
Alexandre Joseph Emilé Brumpt (FR) demonstrated
transmission of South American
trypanosomiasis or Chagas’ disease
via the fecal route of the Reduviid bug (316).
Alexandre Joseph Emilé Brumpt (FR), in 1912, introduced
the xenodiagnosis technique into
parasitological research and extensively studied such diseases as bilharzia, Chagas' disease, onchocerciasis and leishmaniasis. Note: An
example of xenodiagnosis is a method
of diagnosing acute or early Trypanosoma
cruzi infection (Chagas disease) in humans. Infection-free
(laboratory-reared) triatomine bugs are fed on the patient's tissue and the
trypanosome is identified by microscopic examination of the bug's intestinal
contents after an incubation period.
Cezar Guerreiro (BR) and Astrogildo Machado (BR) introduced the
Bordet and Gengou reaction as a diagnostic procedure in Chagas' disease (946).
Fritz Köberle (AT-BR) established the links between infection with
Trypanosoma cruzi and the various
signs of Chagas' disease, such as distended colon, distended esophagus, and
cardiac failure (1282-1284).
Carlos Ribeiro Justiniano Chagas (BR) and Antonio
Carini (IT-BR) described
Pneumocystis from humans but mistook it as a stage in the life cycle of a
trypanosome. Chagas placed it in a new genus, Schizotrypanum (356; 385).
Antonio Carini (IT-BR) observed cysts in rats with experimental trypanosomiasis, but suspected the cysts
were from an unknown organism. He sent samples to his colleague, Charles Louis
Alphonse Laveran (FR), for further examination. In 1912, Laveran's students,
Pierre Delanoë (FR) and Maria Delanoë (FR), found similar cysts restricted to
the lungs of trypanosoma-free sewer rats, and named the new organism Pneumocystis carinii (578).
J. Wätjen (DE) was the first to render a clinical description of
the pulmonary pneumocystosis
associated with Pneumocystis carinii (2407).
Otto Ammich (DE) and Everett Smith Beneke (US) established pulmonary pneumocystosis as a definite
clinicopathologic entity (45; 193).
M.G. van der
Meer (NL) and S. Li Brug (NL) described Pneumocystis
carinii as the infecting organism in a 3-month-old infant with congenital
heart disease and in 2 of 104 autopsy cases (a 4-month-old infant and a
21-year-old adult). This paper contains the first light microscopy photographs
of Pneumocystis trophic and cystic
forms in human beings (2268).
Jeffrey C. Edman (US), Joseph A. Kovacs (US), Henry Masur (US), Daniel
V. Santi (US), Hille J. Elwood (US), and Mitchell L. Sogin (US) used
phylogenetic analysis of Pneumocystis
16S-like rRNA to demonstrate that Pneumocystis carinii is a member of the Fungi. Note: Small subunit ribosomal RNAs (16S-like rRNAs) are
well-suited for this purpose because they have the same function in all
organisms and contain sufficient information to estimate both close and distant
evolutionary relationships. Phylogenetic frameworks based upon such comparisons
reveal that the plant, animal and fungal lineages are distinct from the diverse
spectrum of protozoan lineages (2094).
James R. Stringer (US), Charles B. Beard (US), Robert F. Miller (GB), and
Ann E. Wakefield (GB) renamed Pneumocystis
carinii as Pneumocystis
jirovecii. This causative organism of Pneumocystis pneumonia is an important human pathogen, particularly among
immunocompromised hosts (2166).
Alexander A. Maximow (RU-US) introduced the unitarian theory of
hematopoiesis, upon which, the modern concept of blood cell origin and
differentiation is based. He postulated that hematopoiesis is organized as a
cellular hierarchy derived from a common precursor, a “hematopoietic stem cell”
(HSC) (1523).
Cécile
Mugnier Vogt (FR-DE) described the myelocytoarchitecture of the thalamus. This
work helped to subdivide the different parts of the thalamus into discrete
areas (2304).
Christian Georg Schmorl (DE) showed that the first sign of healing
in rachitic children is the reformation of the provisional zone of
calcification on the epiphyseal side of the metaphysis (2028).
Karl Bruno Stargardt (DE) described familial juvenile macular degeneration (Stargardt macular dystrophy) which is the most frequently
encountered juvenile onset macular degeneration (2124).
Thomas Lewis (GB) described atrial fibrillation in considerable detail. He also discussed pulsus alternans, the alternating pulse,
which usually meant death was close at hand (1402-1405).
Charles Rupert Stockard (US) studied the effects of chemicals on
embryologic development and produced cyclopia and other monstrosities using
lithium and other agents (2146; 2147).
Harvey Williams Cushing (US) was the greatest neurosurgeon of the
twentieth century and the first to devote himself entirely to surgery of the
brain. He authored The Pituitary Body and
its Disorders. His contributions to neurosurgery were numerous, among which
was his analysis of the function of the human brain by stimulating motor and
sensory areas while patients were under local anesthesia. These studies
provided for the first time direct evidence that irritation of the post-central
gyrus gives rise to sensations like those that precede epileptic attacks. He
distinguished between excess function of the anterior lobe of the pituitary (as
in gigantism and acromegaly) and deficiency of its function (as in dwarfism and
Frohlich's asexual adiposity) (518; 520; 521).
Philip Edward Smith (US), Herbert McLean Evans (US), Miriam E.
Simpson (US), Karl Meyer (US), Frederick L. Reichert (US), Alexander J. Szarka
(US), Richard I. Pencharz (US), Robert E. Cornish (US), and Paul R. Austin
(US), working with rats and dogs, found that the anterior pituitary gland
produces a substance or substances which stimulate skeletal growth with weight
increase, increase the size of the viscera (somatotropin or growth hormone/GH),
and promote activity of the adrenal cortex (adrenocorticotropic hormone/ACTH),
thyroid gland (thyrotropic stimulating hormone/TSH), and gonads (luteinizing
hormone/LH or interstitial cell-stimulating hormone/ICSH and follicle
stimulating hormone/FSH) (728; 731; 732; 2084).
Carl Richard Moore (US) and Dorothy Price (US) discovered that a
substance from the anterior pituitary lobe stimulates the gonads (luteinizing
hormone/LH or interstitial cell-stimulating hormone/ICSH and follicle stimulating
hormone/FSH) and in turn the gonads produce a substance that depresses the
production of the pituitary substance (1615). This is
historically one of the earliest known examples of a biologic feedback
mechanism.
James Bertram Collip (CA), Evelyn Mary Anderson (CA), and David
Landsborough Thomson (GB-CA) had by 1933 found that separate substances from
the anterior pituitary regulate the adrenal cortex (adrenocorticotropic
hormone/ACTH) and the thyroid gland (thyroid stimulating hormone/TSH). See Collip, 1933.
Fuller Albright (US), William Parson (US), and Esther Bloomberg
(US) unraveled the pathogenesis of Cushing’s syndrome (31; 32).
Wilder Graves Penfield (US-CA), Lyle Gage (CA) and Edwin Boldrey
(CA) confirmed Cushing’s studies on electrical stimulation of the brains of
epileptics (1805; 1806).
Rudolph Matas (US) experimented—with great success—using numerous
selective anesthetic blocks for surgery. In a 1909 article, he details how to
perform these blocks, including knowledge of regional anesthesia of nerves as
small as the digital nerves of the hand to as large as blockade of the brachial
plexus for amputation of the arm (1516).
Hermann Oppenheim (DE), and Fedor Victor Krause (DE), in1908, were
the first to successfully remove an intervertebral disc from a human (1749).
Ludwik
Rydygier; Ludwig Anton Rydygier von Ruediger (PL-DE) introduced
techniques for diagnosing and treating ureteral narrowing (1966).
Hans Eppinger (AT) and Carl Julius Rothenberger (AT) found that a
large amount of the free wall of the ventricle could be destroyed with
relatively little change in the electrocardiogram compared with the effect of
small lesions in the region of the ventricular septum. They suspected that
damage in the region of the septum resulted in electrocardiographic changes due
to injury of the bundle branches, and the following year they confirmed this (710; 711). These are the first
experimental studies of the electrocardiographic changes in bundle-branch
block.
Jósef Polikarp Brudzínski (PL) reported
Brudziński’s neck sign or Brudziński's symptom which is a clinical
sign observed when forced flexion of the neck elicits a reflex flexion of the
hips. It is found in patients with meningitis,
subarachnoid haemorrhage and possibly
encephalitis (314).
Jósef Polikarp Brudzínski (PL) reported
a phenomenon that is a sign of meningitis:
pressure on the cheek below the cheekbone elicits a reflexive rising and a
simultaneous flexion of the lower arm (Brudzinski’s cheek phenomenon).
Brudziński’s symphyseal sign, pressure over the symphysis pubis leading to
knee, hip flexion and leg abduction is analogous but in the lower limbs (315).
Carl Julius Peter Behr (DE) described
degeneration of the macula lutea and optic nerve, associated with ataxia (179). Called Behr syndrome it is
caused by an autosomal recessive gene.
Anton von Eiselsberg (AT) and Julius
Hochenegg (AT) founded the world's first model emergency rooms.
Wilfred Hudson Osgood (US) and Clinton Hart Merriam (US) provided
a revision of the mice of the American genus Peromyscus. For this work they used over 27,000 specimens (1761).
John Jacob Abel (US) founded the Journal of Pharmacology and Experimental Therapeutics.
Albert J. Cook (US) founded the Journal of Entomology, which became the Journal of Entomology and Zoology in 1913.
1910
"....[Medicine] tinges the whole philosophy of life and
furnishes the whole basis of thought. The healthy skepticism which medical
training induces, the desire to prove every fact, and only to reason from such
proved facts--these are the finest foundations for all thought. And then the
moral training to keep a confidence inviolate, to act promptly on a sudden
call, to keep your head in critical moments, to be kind and yet strong--where
can you, outside medicine, get such a training as that?...And then there is
another way in which it acts. It sets a very high standard of strenuous work.
You may not consider this altogether an advantage while you do it, but it
remains a precious heritage for life. To the man who has mastered Grey's
Anatomy, life holds no further terrors...All work seems easy after the work of
a medical education." From Conan Doyle's talk "The Romance of
Medicine", which he gave to the students at St. Mary's Hospital, London,
in 1910: Arthur Conan Doyle (626)
"Enough has been advanced here to make it extremely probable
that the inorganic composition of the blood plasma of vertebrates is an
heirloom of life in the primeval ocean." Archibald Byron Macallum (1460).
Johannes Diderik van der Waals (NL) was awarded the Nobel Prize in
Physics for his work on the equation of state for gases and liquids.
Albrecht Karl Ludwig Martin Leonard Kossel (DE) was awarded the
Nobel Prize in Physiology or Medicine in recognition of the contributions to
our knowledge of cell chemistry made through his work on proteins, including
the nucleic substances.
Hans Moritz Lehmann (DE) developed a filter which when placed in
front of an iron arc lamp produced a beam rich in ultraviolet light. Lehmann
knew of the more primitive nitrosodimethylaniline dye UV filter made by Robert
Wood (US) in 1903 (1378).
Siegfried Ruhemann (GB) produced triketohydrindene
hydrate (ninhydrin)
then discovered its reaction with amines to form the colored reaction
product known as Ruhemann's purple (1950). The reaction of amines, amino
acids, peptides and related compounds with ninhydrin has found extensive use in
the qualitative and quantitative analysis of such compounds in chemistry and
biochemistry.
Federico Battelli (IT) and Lina Salomonovna Stern (LT-CH-RU), and
Torsten Ludvig Thunberg (SE) discovered malate
dehydrogenase (160; 2216).
Kalman Pandy
(HU) devised a new test for the level of albumin in the cerebrospinal fluid (1780).
George Barger (GB) and Henry Hallett Dale (GB) derived and
isolated histamine from ergot by the chemical decarboxylation of the amino acid
histidine. They found that beta-phenylethanolamine derivatives
simulated the effects of sympathetic nerve stimulation with
varying degrees of intensity and
precision, and they coined the term sympathomimetic
amines (130). Amphetamine,
methamphetamine, and mescaline are well known sympathomimetic
amines.
Henry Hallet Dale (GB) and Patrick Playfair Laidlaw (GB) in their
studies on the effects of histamine on the circulation observed the similarity between
the physiological effects of histamine and the symptoms of anaphylaxis (538).
Henry Hallet Dale (GB) and Alfred Newton Richards (US) found that
histamine affects blood pressure by causing dilatation of peripheral
capillaries and small arterioles (540).
Otto Heinrich Warburg (DE) concluded that in cells “…the oxidative
processes stand in closest connection with the physical state of the lipids” (2387).
Jakub (Jacob) Karol Parnas (PL) reported that an aldehyde mutase present in animal
tissues can catalyze the conversion of an aldehyde into the corresponding
alcohol and acid, indicating that this dismutation
involves a process in which one molecule of the aldehyde is acting as the
hydrogen acceptor (to form the alcohol) and the other as the hydrogen donor (to
form the acid). This concept was rapidly accepted as an explanation for some of
the molecular behavior in alcoholic fermentation
(1789).
Archibald Vivian Hill (GB) gave the first description of
cooperative binding to a multisite protein. He drew on observations of oxygen
binding to hemoglobin and the idea that cooperativity arose from the
aggregation of hemoglobin molecules, each one binding one oxygen molecule, Hill
suggested a phenomenological equation that has since been named for him (1078).
Ivar Christian Bang (NO) was the first to describe the puzzling
behavior of guanylic acid in which the self-association of guanosine at
millimolar concentrations was characterized by the ready formation of
polycrystalline gels (110).
Martin Gellert (US), Marie N. Lipsett (US), and David R. Davies
(US) identified the structure of helical guanylic acid-quadruplexes (868).
Franz Knopp (DE) succeeded in separating from the urine of a dog
fed with alpha-keto acid the corresponding alpha amino acid (1277).
Gustav Georg Embden (DE) discovered that if a dog’s liver is
perfused with alpha-keto acids and ammonia it converts them to the
corresponding amino acids. This provided evidence of a metabolic linkage
between proteins, carbohydrates, and fats (695; 696).
Ed Verschaffelt (NL) demonstrated that sinigrin regulates host selection of the cabbage caterpillars
(Pieris spp.) providing the classical example of a chemical 'sign stimulus' —
the taste or odor of a constituent unique to the host plants and essential to
recognition and acceptance by an insect species (2295).
Robert Arnold Wardle (GB-CA) proposed that certain simple
nutrients, ubiquitous in plants, suffice to induce certain larvae to feed. No
sign stimulus for feeding exists rather the food plant range is determined
solely by a highly specific tolerance for a few potentially inhibitory plant
constituents (2396).
Asgeir Jonas Thorsteinson (CA) showed that glucosinolates, e.g.,
sinigrin or sinalbin, are essential to induce larval feeding by the
oligophagous insect, the diamond-back moth. Since the botanical distribution of
glucosinolates is congruent with the host plant range of this insect, its host
selection mechanism is explained (2213).
Graham Lusk (US) showed that the animal body could convert
glycine, alanine, glutamic acid, and aspartic acid into glucose (1455).
Francis Gotch (GB) described a refractory
phase between nerve impulses (906).
Schack August Steenberg Krogh (DK) proved that the physical forces
of diffusion uniquely explain the mechanism of gas exchange in the lungs (1313; 1317).
Jean Eugene Bataillon (FR) discovered that it
is possible to trigger the frog's egg development by pricking it with a needle
dipped in serum
(143).
Archibald Byron Macallum (CA) found a close resemblance between
the ionic composition of blood sera and that of sea water and suggested that
tissue cells can only live within a relatively narrow range of physiochemical
conditions—conditions which represent those of the ancient ocean in which cells
of ancestral organisms arose (1460; 1461).
Gustav Georg Embden (DE) and Hermann Tachau (DE) discovered the presence
of free amino acids in human sweat when they isolated serine from this
secretion (697).
Léon Ambard (FR) defined his law of urea output. With the urinary
urea concentration constant, the output of urea varies directly as the square
of the concentration of the blood urea. With the blood urea concentration
constant, the output of urea varies inversely as the square root of the urinary
concentration (41).
Samuel James Crowe (US), Harvey Williams Cushing (US), and John
Homans (US) provided the first experimental evidence of the relationship
between the pituitary gland and the reproductive system (505).
Franz Julius Keibel (PL-DE) and Franklin P. Mall (DE) produced a
two volume landmark publication devoted exclusively to the human embryo, it widely
referenced many publications that were available at that time, and presented
new topics such as the formation of the integument, coelom, and diaphragm (1228).
Kurt Goldstein (DE-US) charted the course of the lateral
spinothalamic tract to its termination and demonstrated the phylogenetic
development of the diencephalon (899). Ref on diencephalon
Harry B. Shaw (US) provided the first known example of insect
transmission of a plant virus when he found that the beet leafhopper (Euttetix tenellus) is an insect vector
for sugar beet (Beta vulgaris)
curly-top virus (2053).
Nathan Edwin Brill (US) described 221 cases of what was probably recrudescent epidemic typhus in the New York
area (301). This has
been called Brill’s disease, as
though it were a new entity.
William D. Frost (US) presented arguments in favor of the use of
dehydrated media to culture microorganisms. This is the earliest reference, in
America, to the preparation and use of dehydrated media (833).
Dankwart Ackermann (DE), using defined media, showed that bacteria
could produce putrescine from ornithine and cadaverine from lysine (8-10; 2482; 2483).
Ronald Ross (GB) and David Thomson (GB) demonstrated antigenic
variation in African trypanosomes (1932).
John E. Donelson (US) and Mervyn J. Turner (GB) determined how
antigenic variation is accomplished by the trypanosomes (619).
Aldo Castellani; Count of Chisiamaio (IT) discovered that Endodermophyton concentricum can cause
human dermatomycosis (372).
Helmut Bruchmann (DE) was the first to obtain spore germination
leading to mature prothalli in a species of Lycopodium (313).
Ernst Küster (DE) demonstrated
the ability of onion epidermal protoplasts to fuse upon de-plasmolysis (1323).
Theodor Boveri (DE) demonstrated the direct influence of the
cytoplasm on the nucleus in Ascaris.
Either by dispermy or by centrifugation of eggs and shifting the plane of the
spindle through 90 degrees, he brought two nuclei, instead of only one, into
the proximity of a particular part of the cytoplasm. The result was that the
chromosomes exhibited a peculiar visible behavior at one pole and not at the
other (261).
Ludwig Plate (DE) is credited with coining the term pleiotropy, i.e., a single gene or
allele which may produce two or more characters (traits) which are not
obviously related (553; 1823). This was the 4th edition.
Thomas Hunt Morgan (US) initiated the use of the fruit fly, Drosophila melanogaster (black-bellied
honey lover) for genetic research and described the important discovery of a
sex linked character in these animals as follows: “In a pedigree culture of Drosophila which had been running for
nearly a year through a considerable number of generations, a male appeared
with white eyes. The normal flies have brilliant red eyes.
The white-eyed male, bred to his red-eyed sisters, produced 1,238
red-eyed offspring, (F1), and three white-eyed males. The occurrence
of these three white-eyed males (F1) (due evidently to further
sporting) will, in the present communication be ignored.
The F1 hybrids, inbred, produced: 2,459 red-eyed
females, 1,011 red-eyed males, and 782 white-eyed males. No white-eyed females
appeared. The new character showed itself therefore to be sex limited in the
sense that it was transmitted only to the grandsons.” It was in his 1910 review that Morgan articulated the view that
chromosomes consisted of linear arrangements of genes in an order that could be
mapped by experimental breeding methods (1624; 1633).
Calvin Blackman Bridges (US) is given credit for discovering the
white-eyed Drosophila mutant in
Morgan’s laboratory (1617).
Erwin Baur (DE) described the first sex-linked plant gene. It was
a mutant of Silene alba (Melandrium album) with narrow leaves. He
could prove that this feature is sex-linked (170).
Montrose Thomas Burrows (US) was the first to grow chick embryo
tissue in cell culture by placing explants in hen plasma clot hanging drops where
connective tissue, muscle cells, and nerve cells were observed to proliferate (332).
Alexis Carrel (FR-US) and Montrose Thomas Burrows (US) grew a
variety of adult tissues taken from a variety of species in cell culture. They
observed that initially the new cells were differentiated and represented the
tissue types of origin, however, as the tissues aged they eventually contained
dividing cells of only two types, one resembling connective tissue cells, and
the other epithelial cells (364).
Alexis Carrel (FR-US) and Montrose Thomas Burrows (US) were the
first to grow tumor tissue in vitro.
The tissue was Rous sarcoma (365).
John Zahorsky (US) was the first to recognize exanthem subitum (roseola
infantum, roseola subitum) as a
separate clinical entity, which occurs almost exclusively in infants and young
children (2558).
Koichi Yamanishi (JP), Kimiyasu Shiraki (JP), Toshio Kondo (JP),
Toshiomi Okuno (JP), Michiaki Takahashi (JP), Yoshizo Asano (JP), and Takeshi
Kurata (JP) isolated
a virus from the peripheral blood lymphocytes of patients with exanthem subitum (sixth disease). It was
shown to be antigenically related to human
Herpesvirus-6 (HHV-6). This and other results strongly suggest that the
newly isolated virus is identical or closely related to HHV-6 and the causal
agent for exanthem subitum (2549).
Arvid Afzelius (SE) reported on a severe bulls-eye shaped skin
rash that followed bites of the tick
Ixodes ricinus (24; 25). There is little doubt that the
condition he named erythema chronicum
migrans is synonymous with Lyme
disease. It has also been called Afzelius’s
disease. Borrelia afzelii, one of
the borrelia species that is an agent of Lyme disease, is named in his honor.
Emanuel Libman (US) and Herbert L. Celler (US) by bringing
together clinical and laboratory observations of patients with endocarditis
were definitive in showing that bacteria, most often streptococci that produced
alpha or gamma hemolysis on blood agar (the viridans streptococci), and
occasionally other organisms, were responsible for the clinical syndrome
identified as subacute infective
endocarditis (1412).
Simon Flexner (US) and Paul A. Lewis (US) discovered the nature of
the virus in spontaneous poliomyelitis, ascertained many of its
properties, established some of its immunity effects, elucidated the clinical
and pathological peculiarities of the disease, and secured a basis on which to
develop measures of prevention (790).
James Bryan Herrick (US) gave the first description of sickle cell anemia when he found "peculiar,
elongated and sickle-shaped red blood corpuscles" in the blood of a
20-year-old black patient with symptoms of severe anemia. He did not use the
phrase sickle cell anemia (1054).
Isaac Ott (US) and John C. Scott (US) discovered that an extract
from the posterior pituitary gland can behave as a galactogogue (an agent that
promotes the flow of milk or lacteal secretion) (1767).
Alfred Fröhlich (AT) and Lothar von Frankl-Hochwart (AT) concluded
that obstetricians and urologists could consider pituitrin (a proprietary preparation of the posterior lobe of the
pituitary gland) as essentially non-toxic and safe to use in therapeutically
stimulating the contraction of the uterus (831).
Walter Lee Gaines (US) discovered that pituitrin causes contraction of smooth muscle of the milk passages
in the mammary gland (843).
Noël Fiessinger (FR) and Pierre-Louis Marie (FR) demonstrated the
existence of enzymes in the white cells of the blood, and showed that these
cells, according to their type, contain either protease or lipase. The presence
of protease accounts for the dissolution of internal blood clots or purulent
collections, while lipase weakens the lipidic membrane of the Koch bacilli,
thus permitting their attack by the protease-carrying white cells (763; 764).
John Auer (US) and Paul Adin Lewis (US) gave the first adequate
account of the physiological reactions leading to fatal anaphylactic shock (81).
Corrado Donato da Fano (GB) and James B. Murphy (US) gave
experimental evidence that the destruction of a graft of foreign tissue is
carried out by the hostile activities of the recipient’s lymphoid cells (528; 1660-1662; 1664).
James B. Murphy (US) and Arthur W.M. Ellis (US) demonstrated the
role of lymphocytes in the defensive mechanism against tuberculosis (1665).
James B. Murphy (US) and John J. Morton (US) demonstrated the role
of lymphocytes in the resistance to the growth of inoculated tumor cells (1666).
James B. Murphy (US) and Ernest Sturm (US) demonstrated that
immunized rabbits, x-rayed in doses sufficient to reduce the amount of lymphoid
tissue without damaging bone marrow, showed a deficiency in production of
precipitins, bacterial agglutinins, and protective antibodies. Conversely,
rabbits subjected to dry heat sufficient to increase activity of lymphoid
organs developed antibodies in larger quantities than control non-immunized
rabbits (1667).
Philip D. McMaster (US) and Stephen S. Hudack (US) demonstrated
the early appearance of specific antimicrobial antibodies to corresponding
antigens only in regional cervical lymph nodes homolateral to intradermally
injected mouse ears; later identification of antibodies in contralateral nodes
was attributed to systemic circulation (1551).
Arnold Rice Rich (US) pointed to the spleen as one of the main
organs where antibody production occurred (1875).
Tzvee N. Harris (US), Elizabeth
A. Grimm (US), Elizabeth Mertens (US), and William E. Ehrich (US) identified
specific antibodies in the efferent fluid of popliteal lymph nodes within days
after injecting rabbit hind food pads with either typhoid antigen or sheep
erythrocytes. Subsequently, they extended their findings, clearly demonstrating
that the lymphocytes within these nodes produced, rather than absorbed, the
antibodies contained in the fluid (665; 1000).
Mogens Bjørneboe (DK), Harald Gormsen (DK), and Frank Lundquist
(DK) were the first to publish a close correlation between antibody production
and plasma cell proliferation, especially in the spleen and the liver. They
further confirmed that plasma cells were antibody producers, which could be
found in nonlymphoid tissues such as adipose tissue or renal sinus (223; 224).
Albert Hewett Coons (US), Elizabeth H. Leduc (US), and Jeanne M. Connolly
(US) used immunofluorescent staining to detect antigen in tissues and to show
that plasma cells contained antibodies. They showed that antibodies against the
antigen were present in groups of plasma cells in the red pulp of the spleen,
the medullary areas of lymph nodes, the sub-mucosa of the ileum, and the
portal-connective tissues of the liver. They also found that the secondary
response was accompanied by a far larger number of stained cells (463; 1375).
Samuel James Meltzer (DE-US) concluded that bronchial asthma is
due to anaphylaxis, although he did not appreciate that all cases of asthma are
so caused (1558).
Ernest Fuchs (AT) reported 13 cases of central corneal clouding,
loss of corneal sensation and the formation of epithelial bullae, which he
labeled dystrophia epithelialis corneae.
It was characterized by late onset, slow progression, decreased visual acuity
in the morning, lack of inflammation, diffuse corneal opacity, intense
centrally, and roughened epithelium with vesicle-like features (834).
Henri Verger (FR), Joseph Jules Dejerine (FR), J. Manson (FR),
Gordon Morgan Holmes (IE-GB), and George Riddoch (GB) described a disorder of
space perception caused by brain injuries and characterized by the inability to
localize a stationary or moving object in the three planes of space because of
lack of ability to estimate distance and improper judgment of size and length
of objects (576; 1097; 1891; 2292). This
condition is referred to as Holmes’
syndrome II, Verger-Dejerine syndrome,
and Dejerine’s syndrome.
Berkeley George Andrew Moynihan (GB) offered a methodology to
distinguish duodenal from gastric ulcer, “In the differentiation from gastric
ulcer there is, as a rule, no great difficulty. If pain after food does not
appear for two hours or more, it may be said with reasonable confidence that
the ulcer is in the duodenum…. If pain appears early, within an hour or so, the
ulcer is certainly in the stomach, probably on the lesser curvature…. The
period of relief from pain conferred by the taking of a meal is then the first
and a chief point to be considered in the differential diagnosis” (1645).
Samuel J. Mixter (US) and Robert Bayley Osgood (US) performed the
first successful surgical stabilization of atlanto-axial (C1-C2) instability (1601).
Alexis Carrel (FR-US) reported a series of experiments
that constitute the earliest forms of direct coronary artery bypass, by
anatomizing the innominate artery of one dog into distal coronary of another
and by using a free carotid autograft between descending thoracic aorta and
distal coronary artery. This was presented before the American Surgical
Association in 1910 where he stated; unfortunately, the operation was too slow.
Three minutes after the interruption of the circulation, fibrillary contraction
appeared, but the anastomoses took five minutes. By massage the dog was kept
alive, but he died two hours later. His experiments with animals were the precursor to the bypass
operations of modern human surgery, including the Blalock-Taussig shunt (363).
Hans Christian Jacobaeus (SE) described his endoscopic
investigations of the abdominal cavity of man (1164-1166).
Marc Armand Ruffer (FR-GB) discovered and identified Shistosoma hematobium
bilharzia-calcified eggs in the kidneys of Egyptian mummies dating from 1250 to
1000 BC, revealing for the first time the existence of schistosomiasis in
ancient Egypt (1946; 1949). Note: This finding is
generally regarded as the beginning of paleoparasitology.
Grafton Elliot Smith (GB), Marc Armand Ruffer (FR-GB), and Karl
Sudhoff (DE) described Pott's disease (a kind of tuberculous arthritis of the
intervertebral joints) in another Egyptian mummy, opening the debate about the
occurrence of tuberculosis in ancient times (2178).
Max Schlosser (DE) conducted further excavations of Oligocene
primate remains from the Fayum of Egypt (2023).
The Rockefeller Institute Hospital opened its doors, becoming the
first clinical research hospital in the United States.
The regulation of pesticides by the United States federal
government began in 1910 with the passage of the Federal Insecticide Act by
Congress. This act was passed in response to concerns from the United States
Department of Agriculture (USDA) and farm groups about the sale of fraudulent
or substandard pesticide products. Congress subsequently enacted the Federal Insecticide, Fungicide, and
Rodenticide Act (FIFRA) of 1947 that broadened the federal government's
control of pesticides. The Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) of 1972 was later enacted.
The Journal of Genetics
was founded.
1911
Marie Sklodowska Curie (PL-FR) was awarded the Nobel Prize in
Chemistry in recognition of her services to the advancement of chemistry by the
discovery of the elements radium and polonium, by the isolation of radium and
the study of the nature and compounds of this remarkable element.
Allvar Gullstrand (SE) was awarded the Nobel Prize in Physiology
or Medicine for his work on the dioptrics of the eye. He elucidated how the eye
accomplishes intracapsular accommodation.
Frederick Soddy (GB) introduced the term isotope and the concept that it represents a variation on the
common atom of an element. The isotope possessing a number of neutrons
different from that found in the atom most common to the element (2092; 2093).
Radioactive isotopes have proved to be of great importance in biological
research because they make it possible to trace the course of various elements
in living organisms.
Fritz Pregl (Slovenian-AT) developed techniques and equipment,
which laid the foundation of microchemistry (1833).
Oskar Heimstädt (DE) and Hans Moritz Lehmann (DE) constructed the
first successful fluorescence microscope (1031).
Max Haitinger (AT) together with other scientists developed the
technique of secondary fluorescence, which involved applying exogenous
fluorescent chemicals to samples. Haitinger also coined the term 'fluorochrome'
(959).
Philipp Ellinger (DE) and August Hirt (DE), in 1929, developed the
prototype of the epi-fluorescence microscope. In what they called an
'intravital microscope' the excitation light passed through a series of filters
before the right wavelength hit the objective lens and triggered emission of
fluorescent light in the observed tissue (683).
Albert Hewett Coons (US), Hugh J. Creech (US), and R. Norman Jones
(US) invented a method that could localize specific classes of proteins in cells
by chemically attaching fluorescein to an antibody, which subsequently adhered
to its cellular antigen, i.e., immunofluorescence (462).
E.M. Brumberg (), in 1959, and Johan Sebastiaan Ploem (NL), in
1967, are closely associated with the development of dichromatic beamsplitters,
or dichromatic mirrors and described incident vertical illumination with
dichromatic mirrors (1824). Dichromatic mirrors made it
possible for the epi-fluorescence microscope to gain widespread use in modern
biology.
Carl Alexander
Neuberg (DE-US) and Ladislaus Karczag (DE), in 1910, discovered that
pyruvic acid is broken down into carbon dioxide and acetaldehyde
by all yeasts that ferment hexoses as well
as by the enzyme preparations (decarboxylase) prepared from the former (1708). Note: This is the first
success in the search for intermediary
products.
Otto Neubauer (DE) and Konrad Fromherz (DE), from their studies on
yeast, postulated that the deamination of alanine would yield pyruvic acid, whose
decarboxylation would yield acetylaldehyde, which might be reduced to ethanol.
They proposed that pyruvic acid might be intermediate in the alcoholic
fermentation (1701).
Carl Alexander Neuberg (DE-US), Arnold Hildesheimer (DE), and L.
Tir (DE) isolated the enzyme pyruvate decarboxylase,
which catalyzes the decarboxylation of pyruvic acid to acetylaldehyde and
carbon dioxide (1706; 1715).
Auguste Fernbach (FR) and Moise Schoen (FR) were the first to
demonstrate that pyruvic acid is present during the alcoholic fermentation
process (754; 755; 2031).
Aleksandr Nikolaevich Lebedev; Lebedew (RU) showed that D-fructose
1,6-biphosphate is formed during fermentation of dihydroxyacetone (1371).
Arthur Harden (GB) and William John Young (GB-AU) found that two
fractions of yeast extracts are required for alcoholic fermentation to take
place, a heat-labile fraction, called zymase,
presumably containing the enzymes required for the process, and a heat-stable
fraction (cozymase) required for the activity of zymase (994). The
heat-stable fraction was later shown to contain two essential components, the
oxidation-reduction coenzyme nicotinamide adenine dinucleotide, or NAD, and a
mixture of the adenine nucleotides ADP and ATP (986). Note: Over the years Harden and Young’s
cozymase has been called: co-ferment, Koenzym, cozymase, codehydrase,
codehydrogenase, coenzyme I (Co I); diphosphopyridine nucleotide (DPN); and
nicotinamide adenine dinucleotide (NAD).
Carbon tetrachloride was recommended as a substitute for carbon
disulfide in fumigation of grain. From this first use of carbon tetrachloride
as an insecticide came its later use as a control of hookworm; the latter
discovery was acclaimed one of world's most outstanding accomplishments (2050).
Hubert Dana Goodale (US) introduced vital staining of the
amphibian embryo as a method of tracing the fate of embryonic parts (901; 902).
Edwin B. Hart (US), Elmer Verner McCollum (US), Harry Steenbock
(US), and George C. Humphrey (US) performed a long experiment with cattle, the
results of which provided the first clear evidence that the nutritive value of
a diet depends on factors other than its content of protein, a few minerals,
and energy sources (1012).
Horace Middleton Vernon (GB) showed that oxidation of indophenol
blue in cerebral tissue is due to the enzyme indophenol oxidase (cytochrome
oxidase) which is especially abundant in grey matter and other respiring
tissues (2294).
Gheorghe Marinesco (RO) demonstrated that grey matter could easily
be distinguished from white matter when treated in vitro with Ehrlich’s indophenol reagent. The sharp delineation
being due to the presence of indophenol
oxidase in the cell bodies and dendrites (plentiful in grey matter) and
absent from axons (plentiful in white matter). This paper also indicated that
the cerebral area is very rich in dendrites (1505).
Gheorghe Marinesco (RO) was also the first to suggest that indophenol oxidase is located in the
mitochondria (1812).
Arend Lourens Hagedoorn (NL) expressed the concept that the gene
is autocatalytic (955).
Edmund Beecher Wilson (US) surmised that the heredity factor
causing color-blindness in humans is linked to the X chromosome (2499). This was
the first gene assigned to a human chromosome.
Thomas Hunt Morgan (US) proposed that the genes for white eyes, yellow
body, and miniature wings in Drosophila are
linked together on the X chromosome (1625).
Thomas Hunt Morgan (US) provided incontrovertible evidence of
recombination between sex-linked genes in Drosophila
thus supporting Franciscus Alphonsius Janssens’ (BE) cytological evidence of
crossing over (1626).
Walter Stanborough Sutton (US) had already predicted linkage in
1903. He and Morgan both worked at Columbia University just down the hall from
one another in 1903. See, Sutton,
1903.
Richard Benedikt Goldschmidt (DE-US) summarized his theory of sex
determination as a matter of the rate of developmental expression for
sex-determining genes. This was based on his study of intersexual forms in
moths (895).
Schack August Steenberg Krogh (DK) studied the hydrostatics of the
air bladder of Corethra larvae during 1896. He demonstrated that these organs
function like diving tanks of a submarine (1314). This is a
type of gnat whose larvae are often fed upon by fish.
Henry Bryant Bigelow (US) wrote a paper on the Siphonophorae,
which was at that time one of the most important reports ever written on this
group (215). These are
in the phylum Cnidaria.
Thomas Burr Osborne (US) and Lafayette Benedict Mendel (US)
reported that the coprophagy exhibited by rats benefits their health and growth (1758).
Margaret Reed Lewis (US) and Warren Harmon Lewis (US) were the
first to culture eukaryotic cells on cover slips in vitro. They were also the first to attempt in vitro cultivation of eukaryotic cells using simple salt
solutions (1401; 1402).
Marshall Albert Barber (US) proposed a new technique—the microinjection
technique. He developed this method initially to clone bacteria and to confirm
the germ theory of Koch and Pasteur (123). Later, he refined his approach and
was able to manipulate nuclei in protozoa and to implant bacteria into plant
cells.
George Lester Kite (US) used microsurgical techniques to study the
fine structure of cells. He found that protoplasm exists in the
form of sols and gels of varying consistency with that of plants generally of a
lower viscosity. That the nucleus contains a gel of high viscosity and that the
membrane of the nucleus is a definite morphological structure belonging to the
nucleus (1260-1262).
Anton Julius
Carlson (US) and Fred M. Drennan (US) removed the pancreas from pregnant
bitches and in one of these animals observed that sugar did not appear in the
urine until after the pups were born. Carlson inferred that in the intervening
period the internal secretion of the pancreas of the pups had secured access to
the maternal circulation and prevented diabetes in the mother until
parturition. Undoubtedly this experiment stimulated subsequent research on the
pancreas, and it is of interest that Ernest L. Scott, one of Carlson's pupils,
made extracts of the pancreas by a method similar to that later found effective
in the production of insulin and concluded that these extracts were beneficial
in the treatment of the diabetes of depancreatized dogs (359).
Arnold Lang (DE)
observed that the lop-eared phenotype in rabbits is likely due to the multiple
factor hypothesis which had been formulated by Nilsson-Ehle based on his
studies of quantitative characters in oats and wheat (1354).
William Ernest
Castle (US) and Sheldon C. Reed (US) supported Lang's conclusion that lop-ears
in rabbits is inherited in a multiple factor pattern (379).
Alexis Carrel (FR-US) and Montrose Thomas Burrows (US)
successfully explanted malignant cells from Rous sarcoma, Ehrlich and Jensen
rat sarcomas, a canine breast carcinoma, a primary human breast carcinoma, and
a human sarcoma of the tibia into in
vitro cell culture (366).
Frederick P. Gay (US) coined the word immunology (864).
Magnus John Karl August Forssman (SE) discovered the
"Forssman antigen", defined as a glycolipid heterophile antigen found
on tissue cells of many animal species. It was first described for ovine red
cells. It is not present in human, rat, rabbit, porcine or bovine cells (808).
Walter Bradford Cannon (US) and Daniel de la Paz (PH) argued that
strong emotions stimulated the sympathetic nerves and thence the secretion of
epinephrine (adrenaline); all the varied effects of the hormone on the body
could be seen as quick preparations for "fight or flight" (345; 346; 348; 349). Note:
“Fight or flight” was coined in the 1915 reference.
Henry Head (GB) and Gordon Morgan Holmes (GB) gave the first
systematic account of the functions of the thalamus and its relationship to the
cerebral cortex (1027).
Francis Peyton Rous (US) and James B. Murphy (US) were the first
to use embryonated eggs to grow a virus (1940).
Joseph Goldberger (SK-US) and John Fleetezelle Anderson (US)
established the viral etiology of measles
(rubeola) when filtered respiratory
tract secretions of measles patients
were inoculated into macaque monkeys resulting in measles-like symptoms in
these animals (49; 889).
Hideyo Noguchi (JP-US) used an in
vitro mixture of serum water containing fresh rabbit kidney or testicle to
grow Treponema pallidum under
anaerobic conditions (1733).
Hideyo Noguchi (JP-US) developed a serum diagnosis for syphilis
and established the presence of Treponema
pallidium in the lesions of syphilis in the central nervous system (1734).
George W. McCoy (US) and Charles W. Chapin (US) reported that they
had recovered the organism responsible for tularemia from fleas (Diamanus montanus Baker = Ceratophyllus acutus Baker) taken from
sick or dead ground squirrels and tested in guinea pigs (1540). This is
the first scientific paper on tularemia,
which gets its name from Tulare County, California where it was first known as
a plague-like disease of rodents (1541).
Edward Francis (US) proved that the disease known in Utah as deer fly fever is tularemia and is transmitted from infected rabbits to man by the
bite of the fly Chrysops discalis. He
would later show that Pasteurella
tularensis (now Francisella
tularensis) was present in rabbits at the market place and that rabbit
fever was not infrequent among humans in contact with rabbits (818-821).
Hachiro
Ohara (JP) discovered the Japanese form of tularemia, Ohara's disease. It is also called yato-byo, meaning rabbit fever (1742).
Alberto Ascoli (IT) presented his thermo
precipitation test for the diagnosis of anthrax using a tissue extract and
anthrax antiserum. This test is used for detection of anthrax bacilli in animal
hides and meat (70).
Charles Manning Child (US) formulated his axial gradient theory of embryonic development, proposing that
certain regions of the developing embryo dominate others and mold them into
subsidiary forms. He showed that these gradients are physiological in various
ways by demonstrating that regions with different rates of growth differ in
their susceptibility to poisons and narcotics that interfere with respiration
and other functions of living cells (395-397). Though
present knowledge views his theory as incorrect, in its time, it represented an
early approach to understanding functional organization within organisms
Leland Ossian Howard (US) and William F. Fiske (US) were
entomologists who recognized clearly that, of the numerous factors, which
influence the morphology and natality of insects, only those, which act with
increasing severity as populations become larger, can adjust populations to
their environments (1113). Other
biologists would later refer to these factors, which operate with increasing
intensity as a population grows as density-dependent
factors, and those, which do not do so as density-independent factors.
Leonard Noon
(GB) and John Freeman (GB) helped establish the basis for immunotherapy or
allergy shots, i.e., allergen-specific
immunotherapy (SIT) (825; 1737).
Immunotherapy involves injecting the allergy sufferer with small, gradually
increasing amounts of the substance that is causing the reaction. The idea is
that over a time course, the body's immune system will become less sensitive to
the substance and the allergy symptoms will be reduced or eliminated.
Hans Günther (DE) described acute
porphyria (porphyrinuria) and
noted that the signs and symptoms include red porphyrins in the urine, periodic
attacks of abdominal pain, and mental disorder similar to schizophrenia or paranoia (948).
Thomas Chalmer Addis (GB) made his claim that the fault in hemophilic blood is due to an inherited
qualitative defect in the prothrombin (16).
Ethel Browne Harvey (US) described the changes that take place in
the cortical region of an egg during fertilization. For example, the granules
near the surface disappear in a wavelike manner around the egg (1018). These
granules release material during their breakdown that promotes formation of the
fertilization membrane.
Gordon R. Ward (GB) diagnosed human fascioliasis by finding eggs in feces (2395).
Rupert Waterhouse (GB) and Carl
Friderichsen (DK) described Waterhouse–Friderichsen
syndrome
(WFS) or hemorrhagic adrenalitis
or fulminant meningococcemia as a most severe form of meningococcal septicemia. The onset of the
illness is nonspecific with fever, rigors, vomiting, and headache. Soon a rash
appears; first macular, not much different from the rose spots of typhoid, and
rapidly becoming petechial and purpuric with a dusky gray color. Low blood
pressure (hypotension) develops and rapidly leads to septic shock. The cyanosis
of extremities can be extreme, and the patient is very prostrated or comatose (828; 2405). Note: The bacterial infection
leads to massive hemorrhage into one or (usually) both adrenal glands. It is
characterized by overwhelming infection (bacteremia or viremia) leading to
massive blood invasion, organ failure, coma, low blood pressure and shock,
disseminated intravascular coagulation (DIC) with widespread purpura, rapidly
developing adrenocortical insufficiency and death.
Felix Jacob Marchand (DE), Arthur
Francis Voelcker (GB), and Ernest Gordon Graham Little (GB) reported cases of
WFS but did not describe them as a medical entity (1428; 1495; 2301).
Erich Lexer (DE) stated that homografts (allografts) are
invariably unsuccessful, even when transplanted from parent to child and vice
versa (1409; 1410).
Hans Winterstein (DE) suggested that CO2
stimulated breathing by acidifying extracellular
fluid near the "respiratory centers” (2523).
Thomas
Chalmer Addis (US), Erich Frank (DE-TR), E. Hartmann (DE), Arthur J. Patek, Jr.
(US) and Richard P. Stetson (US) observed that plasma, presumably largely
depleted of platelets, was as effective as whole blood in correcting the in vitro and in vivo clotting defects in hemophilia. This meant that platelets
did not contain the therapeutic agent necessary for clotting hemophilic blood (16; 824; 1791; 1792).
Rudolph Matas (US) wrote a landmark article in which
he described a challenge test to assess the degree and efficacy of the
collateral circulation in patients under consideration for permanent occlusion
of a major vessel. Matas studied the feasibility of such a test by temporarily
occluding the carotid and femoral arteries in dogs for variable periods of
time. In the introduction to his seminal article on the subject, he stated that
"the chief object of this inquiry has been to determine whether the large
arteries can be occluded long enough to make it possible to observe the effect
of the arrested circulation in the territory supplied by the occluded vessel,
without irreparably damaging the artery during the period of observation" (1517). See, Celsus, 30 B.C.E. and John Hunter, 1793b.
William
Arbuthnot Lane (GB) performed resection of the cervical esophagus for cancer
and reconstruction by skin graft (1352).
Harvey
Williams Cushing (US) developed techniques to control bleeding in operations
for brain tumors where ligature was not possible
(519).
Cécile
Mugnier Vogt (FR-DE) defined the so-called corpus
striatum syndrome (2305).
Cécile
Mugnier Vogt (FR-DE) and Oskar Vogt (DE) described a condition characterized by
athetosis, emotional liability, and rhythmic oscillation of the limbs due to a
lesion in the corpus striatum. It became known as Vogt syndrome (2307).
Charles Doolittle Walcott (US) discovered a rich assemblage of
algae and invertebrate fossils from the Middle Cambrian Period of the Paleozoic
Era in the Burgess shale located in Yoho National Park in the Rocky Mountains,
near Field, British Columbia, Canada (2376). Note:
The word Cambrian is taken from a Latin form of the Welsh name for Wales. Other
fossil rich Cambrian sites include Chengjiang, China, the Wheeler Formation in
Utah, and the Croixan Series in Minnesota-Wisconsin. (Shale is rock formed by
condensation of layers of clay or mud, along with phytoplankton and other
debris, sedimented at the bottoms of lakes or ocean basins.)
Samuel Wendell Williston (US) and Ermine Cowles Case (US)
described Seymouria and other
labyrinthodont amphibian and reptile fossils from the Permian beds of Texas and
New Mexico (369; 2485-2487).
Louis Capitan (FR) and Denis Peyrony (FR) found a fossil remains
of Homo sapiens neanderthalensis; Homo neanderthalensis dated at c. 38 K
BP. The site was near La Ferrassie, France (355).
1912
"A path is opened in order to wheel the patient in. The
professor reads the history; displays on the lackboard a temperature chart;
then in quick clear fashion explores the patient, pointing out what he
finds,discoursing on its significance, suggesting alternative suggestions,
until he settles down on the most probable diagnosis. This furnishes the topic
for development and further illustration. The etiology, the pathology, the
therapeutics, of the condition are set forth with wonderful vigor and lucidity.
My notes abound in accounts of similar discourses. The effort made to prepare
for a complete exposition is everywhere striking. …A master mind at work is
exhibited daily to two hundred students or more." Reflections by Abraham
Flexner (US) on lectures given by Friedrich von Müller (DE), Medical Professor
in Munich, Germany (785).
"Diagnosis," says Friedrich von Müller (DE), "is
the peculiar art of the physician." "This does not mean that the
physician's interest ceases when he has worked out his problem and given it a
name: in a sense, he is then just ready to begin. But correct diagnosis means
intelligent control; it means a fight in the open. The ground is firm beneath
the doctor's feet. He has still, indeed, his fight to make, —to win the battle
or postpone defeat. And one battle, at least, he will sooner or later
inevitably lose." Abraham Flexner (US) reflecting on the art of diagnosis
and treatment (785).
Alexis Carrel (FR-US) was awarded the Nobel Prize in Physiology or
Medicine in recognition of his work on vascular suture and the transplantation
of blood vessels and organs. He was the first American to receive the prize in
physiology and medicine.
Max Theodor Felix von Laue (DE) theorized that it might be
possible to determine the wavelength of x-rays —known to be extremely short—by
using crystalline lattices as diffraction gratings (2349-2352).
Walther Friedrich (DE), Paul Knipping (DE), and Max Theodor Felix
von Laue (DE) were the first to obtain x-ray diffraction patterns. They passed
x-rays through a crystal of zinc sulfide. Laue had theorized that it might be
possible to determine the wavelength of x-rays —known to be extremely short—by
using crystalline lattices as diffraction gratings. However, because the
crystal had lines of atoms in various
directions, the results would be complicated. There would be beams located at
varying distances and angles from the center, those distances and angles
depending on the structure of the crystal. By beginning with a crystal of known
structure, and measuring the amount of diffraction, the wavelength of the
x-rays could be calculated. See,
Braggs, 1915. Second, by using x-rays of known wavelength it was possible to
deduce the structure of a crystal from the patterns produced on x-ray film.
This was the beginning of x-ray crystallography (830).
William C. Piper (US) developed calcium arsenate as a replacement
for Paris Green and lead arsenate. It soon became important for controlling the
boll weevil on cotton in the United States. Ref
William Küster (DE) proposed a correct formula for the ring system
of porphyrins in which four pyrrole rings are linked together into a macrocycle
by 4 methine bridges (1324). Porphyrin
comes from the Greek meaning purple.
Henry Hallett Dale (GB) and Patrick Playfair Laidlaw (GB) prepared
very active solutions of the hormone secretin (539).
Gunnar Agren (SE), Einar Hammarsten (SE), and Olof Wilander (SE),
crystallized secretin (28).
Paul Mayer (DE) was the first to demonstrate that pyruvic acid is
often reduced to lactic acid in various tissues. He also showed that pyruvic
acid could be converted to glucose in fasting rabbits (1525).
Gustav Georg Embden (DE) and Max Oppenheimer (DE) confirmed
Mayer’s findings (694).
Gustav Georg Embden (DE), Karl Baldes (DE), and Ernst Schmitz (DE)
noted that yeast juice and working muscle produced the same intermediate, which
they believed to be glyceraldehyde (689).
Donald Dexter van Slyke (US) described a procedure for the direct
determination of amino acid (alpha-amino) nitrogen in protein hydrolysates and
in extracts of animal tissues, in the presence of various other organic
nitrogenous compounds, which occur in animal tissues (2275).
Donald Dexter van Slyke (US) and Gustav M. Meyer (US) were the
first to determine that amino acids, liberated during digestion in the
intestine, are absorbed into the bloodstream, that they are removed from the
blood by the other tissues, and that the liver alone possesses the ability to
convert the amino acid nitrogen to urea (2276; 2282; 2284-2286).
Otto Knut Olof Folin (SE-US) and Willey Glover Denis (US), by
direct chemical analysis, proved that it is amino acids rather than more
complex intermediary products of protein digestion, which are absorbed by the
intestine and enter the blood. They determined that ammonia is present in
excessive amounts only in blood, which had just passed through the walls of
parts of the colon in which putrefaction of fecal residues is in progress. They
proved that ammonia is absorbed in fairly large quantities from such fecal
putrefaction (795-798; 801). Note:
While at Harvard University Folin became the First Professor of Biological
Chemistry in the United States.
Casimir Funk (PL-GB-FR-US) suggested that the chemicals required
in small quantities to prevent diseases such as beriberi, scurvy, pellagra, and rickets be called vitamines (838). This name
occurred to him when he was investigating Christiaan Eijkman’s anti-beriberi
factor and found it to contain an amine group. He assumed that all these
factors required in small quantities contained an amine group (837-839). When it
was discovered that this was incorrect Jack Cecil Drummond (GB) suggested
dropping the final e producing
vitamin. “The suggestion is now advanced that the final "-e" [of
Funk's "vitamine"] be dropped, so that the resulting word Vitamin is
acceptable under the standard scheme of nomenclature adopted by the Chemical
Society…. It is recommended that the somewhat cumbrous nomenclature introduced
by McCollum (Fat-soluble A, Water-soluble B), be dropped, and that the
substances be spoken of as Vitamin A, B, C, etc.” (631). The
anti-beriberi factor was called vitamine B1 (thiamine) because it was the first
water soluble vitamin characterized. It is also called the antineuritic vitamin
because the deficiency syndrome is predominantly neurological. Funk also
isolated nicotinic acid from rice (Oryza
sativa) polishings but failed to discover its relationship to pellagra.
Agnes Robertson Arber (GB), Bruce Rogers (GB), and Pforzheimer
Rogers (GB) authored The Herbals, Their
Origin and Evolution, which has remained the basic reference for the
herbals (57).
Julien Tournois (FR) discovered that in the Japanese hop, Humulus japonicus, a decrease in
day-length during the normal growth period provokes some floral reproduction.
After obtaining similar results with another species of hop and hemp, he
concluded that young plants flower when exposed to short days from germination
onward. And he deduced that night-length, rather than the brevity of the day,
was the determining factor (2229; 2230). These
papers represent the origin of the study of photoperiodism.
Georg Albrecht Klebs (DE), from his studies of the houseleek (Sempervivum funkii), reached a similar
conclusion in 1918 (1264).
Wightman Wells Garner (US) and Harry Ardell Allard (US) performed
extensive experiments with three strains of tobacco (Nicotiana tabacum), four varieties of soybean (Glycine max) beans from Peru and Bolivia, radish (Raphanus sativus), carrot (Daucus carotus), lettuce (Lactuca sativa), cabbage (Capitata),
wild aster (Symphyotrichum),
climbing hempweed (Mikania scandens), ragweed (Ambrosia
artemisiifolia), hibiscus, wild violet (Viola papilionacea), and goldenrod (Solidago). They
concluded that of the various factors of the environment, which affect plant,
life the length of the day is unique in its action on sexual reproduction.
Unlike temperature, rainfall, or light intensity, daylight is “the only
consistently rhythmic feature of the external environment.” They coined and
defined the terms short-day plants
(SDP), long-day plants (LDP), intermediate plants, and indeterminante or day-neutral plants. Their terminology is descriptive of the length
of the period of continuous illumination to which the plants are exposed during
each 24-hour period. Garner also introduced the term photoperiodism for the response of organisms to relative length of
night and day (851; 852).
Karl C. Hamner (US) and James Frederick Bonner (US) proved that
Tournois was correct. The length of night is more important to short-day plants
than length of day in floral initiation. They found that the cocklebur (Xanthium strumarium) must have
about 8.5 hrs. of uninterrupted night for flowering, this was the discovery of
the night-break phenomenon (981).
Alexei F. Kleshnin (RU) concluded, “It is only the amount of
energy absorbed by some acceptor of the leaf that is important…” “For every
region of the spectrum there is a definite threshold of radiation intensity
below which this region is perceived as darkness in the photoperiodical
process; this threshold is different for different plants” (1267).
Hans Jean Chrysostome de Winiwarter (BE) made the earliest
systematic observations on the human karyotype, concluding the chromosome number
as 47 in the human testis and 48 in the ovary, concluding that man has an XX-XO
sex chromosome constitution (570).
Edgar
Douglas Adrian (GB) published a study on the effects of the block of nerve
conduction induced by application of alcohol vapors to small segments of nerves
from which he derived the conclusion that nerve signals regenerate along the
nerve fiber during the conduction process (21).
Torald Hermann Sollmann (US) and Edgar Dewight Brown (US) found
that caudal traction upon the central end of a divided carotid artery produced
cardiac slowing in animals (2097).
Heinrich Ewald Hering (AT) gave the first description of the
afferent nerve fibers leading from the carotid sinus by way of the
glossopharyngeal nerve to the brain, innervating the baroreceptors in the wall
of the carotid sinus and the chemoreceptors in the carotid body. They respond
to changes in blood pressure that reflexly control heart rate. An increase in pressure
diminishes heart rate (1049-1051).
Oil barriers were recommended for control of chinch bugs (genus
Blissus). They are considered pests that feed on stems of turfgrass.
Paradichlorobenzene
was first used in the U. S. as an insecticide: used for clothes moth control.
Eugenol
derivatives were first noted as entomological attractants.
Nicotine
insecticides were developed for control of onion thrips.
The U.
S. Public Health Service adopted hydrocyanic acid gas as a standard fumigant (2050).
Friedrich Richard Baltzer (CH) reported the first valid case of
environmental sex determination in nature. He observed in the marine Bonellia (Echiuridae) that if a larva
finds a suitable substrate, it would settle and most probably develop into a
female. However, if it is picked up by the proboscis of an adult female, the
larva will attach itself to the proboscis with the help of an "underwater
glue" and develop into a male (107; 108).
Oscar M. Schloss (US) proposed cutaneous tests (skin test or
scratch) in the diagnosis of the food allergy {Schloss 1912; Schloss 1915).
Fritz B. Talbot (US) used the scratch test, to associate asthma to
a food "intoxication" by egg {Talbot, 1918 #14530}.
Jost Frederick Gudernatsch (DE) caused a female frog to ovulate in
September, some seven months before the normal breeding period, by
subcutaneously implanting six pituitary glands from adult female donors. The
eggs were artificially inseminated. When the tadpoles developed hindlimb buds,
minute amounts of thyroxin (bits of horse thyroid) were added to the water. In about three weeks, the treated
tadpoles reabsorbed their swimming tails, grew hindlimbs and then forelimbs,
lost their horny teeth (used for plant feeding), shortened their intestinal
tracts in preparation for carnivorous feeding, modified their respiratory and
integumentary systems for terrestrial environments, and emerged as normal but
miniature air-breathing adult frogs.
Since thyroxin initiated the metamorphic changes long before they
would normally occur, the resulting froglets
are about one-third the size of those metamorphosing in nature.
Thyroid-ectomized tadpoles never metamorphose, but grow to giant size (943; 944).
Wilbur Willis Swingle (US) reproduced Gudernatsch's results on
metamorphosis in frogs by providing or withholding inorganic iodine (2187).
Martinus Willem Beijerinck (NL) was possibly the first person to
recognize that bacterial variation might reflect the occurrence of gene
mutation (182).
Thomas Hunt Morgan (US) reported the first sex-linked recessive
lethal gene. It was in Drosophila (1627).
Thomas Hunt Morgan (US) and Clara J. Lynch (US) were the first to
publish a case of autosomal linkage. The subject was Drosophila (1632).
Montrose Thomas Burrows (US) devised a perfusion chamber, which,
for the first time, allowed cells grown in
vitro to be continuously supplied with fresh medium (333).
Charles Louis Alphonse Laveran (FR) and Félix Étienne Pierra Mesnil
(FR) discovered that trypanosomes can be maintained indefinitely in rats and
mice by serial passages (1363).
Christian Champy (FR) noted that eukaryotic cells grown in vitro often lost some of the specific
features that characterized them in their normal in vivo habitat. He denominated the process dedifferentiation (389; 390).
Robert A. Lambert (US) was the first to describe the formation of
multinucleated cells in vitro (1333).
Charles C. Bass (US) and Foster M. Johns (US) succeeded in the in vitro culturing of the malarial
protozoan (142).
Allan Kinghorn (CA) and Warrington Yorke (GB) found that Glossina morsitans (a tsetse fly) can
transmit human trypanosomes and that human trypanosomes occur in game animals (1257).
Measles became a nationally notifiable disease in the United
States, requiring U.S. healthcare providers and laboratories to report all
diagnosed cases. In the first decade of reporting, an average of 6,000
measles-related deaths were reported each year.
At about this time it became routine to record the four vital
signs (temperature, respiration, pulse rate, blood pressure) on all patients’
charts. See, Cushing, 1895.
Isaac A. Adler (GB) was the first to link lung cancer to
cigarettes (19).
Franz H.
Müller (DE) indicated that non-smokers were more common in healthy populations
than among lung cancer patients (1652).
Ernest Ludwig Wynder (US) and Evarts Ambrose Graham (US) observed
a relationship between lung cancer and smoking. Together they performed the
most systematic and detailed survey to date showing links between smoking and
cancer (2548).
William Richard Shaboe Doll (GB), Austin Bradford Hill (GB), and
Richard Peto (GB) almost simultaneously reached the same conclusions. They were
also able to show that stopping smoking immediately reduces the risk of cancer (607-611).
E. Cuyler Hammond (US) and Daniel Horn (US) issued their report
entitled: Smoking and
death rates: report on forty-four months of follow-up of 187,783 men.
They announced a link between cigarettes and both lung cancer and heart
disease. Regular cigarette smokers were reported to be ten times more likely to
die from lung cancer than non-smokers. They revealed that the chances of heart
attack were seventy percent higher for smokers than for non-smokers (978-980)
The United
States Surgeon General concluded that "Cigarette smoking is causally
related to lung cancer in men; the magnitude of the effect of cigarette smoking
far outweighs all other factors" (2262).
Mikhail F.
Denissenko (US), Annie Pao (US), Moon-shong Tang (US), and Gerd P. Pfeifer (US)
found the first direct biological link between cigarette smoking and lung
cancer. DNA mutations caused by the cigarette smoke by-product benzo[a]pyrene
in the tumor suppressor gene p53 were found to be the same as those found in
lung cancer cells (584).
See, von Sömmerring, 1795.
William Richard Shaboe Doll (GB), Richard Petro (GB), Jullian
Boreham (GB), and Isabelle A. Sutherland (GB) reported that a substantial
progressive decrease in the mortality rates among non-smokers over the past
half century (due to prevention and improved treatment of disease) has been
wholly outweighed, among cigarette smokers, by a progressive increase in the
smoker to non-smoker death rate ratio due to earlier and more intensive use of
cigarettes. Among the men born around 1920, prolonged cigarette smoking from
early adult life tripled age specific mortality rates, but cessation at age 50
halved the hazard, and cessation at age 30 avoided almost all of it (612).
Roger I. Lee
(US) and Paul Dudley White (US) developed the Lee-White clotting time course
test. Lee demonstrated that it is safe to give group O blood to patients of any
blood group, and that blood from all groups can be given to group AB patients.
The terms "universal donor" and "universal recipient" are
coined (1376).
Hakaru Hashimoto (JP) described four patients with a chronic
disorder of the thyroid, which he termed
struma lymphomatosa (Hashimoto’s
thyroiditis). The thyroid glands of these patients were characterized by
diffuse lymphocytic infiltration, fibrosis, parenchymal atrophy, and an
eosinophilic change in some of the acinar cells (1019). It is now
appreciated that the progressive enlargement of the thyroid gland is due to
autoimmunization against the patient’s own thyroglobulin circulating in the
blood.
Louis Édouard Octave Crouzon (FR) described craniofacial dystosis
(misplaced) and hypertelorism (abnormal width), due to autosomal dominant
inheritance (Crouzon’s disease) (503; 504).
Wilhelm Weinberg (DE) made a detailed study of the dwarfism trait,
achondroplasia, which he knew to be
inherited as a Mendelian dominant. Specifically, he noted that an affected
child born from normal parents tended to be among the last-born children in the
sibship. From this he suggested that these were new mutations (2428).
Lionel Sharples Penrose (GB) relates achondroplasia to advanced paternal age and spontaneous mutation in
the male gamete that has experienced many divisions (1807; 1808).
Samuel
Alexander Kinnier Wilson (GB) reported on progressive
lenticular degeneration (Wilson’s disease):
A familial nervous disease associated with cirrhosis of the liver. Wilson’s
1911 medical thesis introduced the term "extrapyramidal" into neurology and
focused attention upon the importance of the basal ganglia (2505-2507). Note:
this
hepatolenticular degeneration is due to abnormality in copper metabolism.
Karl Friedrich Otto Westphal (DE) and Ernst
Adolf Gustav Gottfried von Strümpell (DE) had previously described Westphal-Strümpell's pseudosclerosis but
they failed to discuss the lenticular or hepatic aspects, thus they failed to
recognize the two major signs of the disorder (2370; 2441).
Friedrich
Heinrich Lewy (DE-US) first
described the inclusion bodies named after him as he saw them in Parkinson’s disease (‘paralysis agitans’) (1091; 1408). Note: Dementia with Lewy bodies is a common disorder of a-synuclein
metabolism and is characterized by the development of abnormal cytoplasmic
inclusions, called Lewy bodies, throughout the brain.
Haruo
Okazaki (US), Lewis E. Lipkin (US), and Stanley M. Aronson (US) described two
patients with parkinsonism and
dementia with (262)cortical
Lewy body like eosiophilic inclusions (1743).
Gleb von Anrep (LB-GB) discovered a regulatory mechanism of the
heart whereby cardiac performance improves as the afterload (aortic pressure)
is increased. It is called homeometric autoregulation because it is independent
of muscle length (2310).
Anton Julius Carlson (US) characterized the movements of the empty
stomach in man, including illumination with electric lights in order to observe
digestion (358).
Arthur Läwen (DE) used curare to relax the abdomen during surgery
keeping the patient alive by artificial ventilation (1364).
Wilfred
Harris (GB) treated trigeminal neuralgia
by injecting alcohol through the foramen ovale into the Gasserian ganglion (1001).
Hürter (DE)
made the first arterial punctures
in humans. He was able
to show that the arterial oxygen saturation in four normal
subjects was between 93% and 100% (1132).
William Christopher Stadie (US) is believed to have been the first
to introduce arterial puncture into clinical medicine where he used it to
compare the oxygen content of air inhaled with that in arterial blood. He demonstrated
that cynosis is due to arterial anoxemia (2119).
William Christopher Stadie (US) treated cases of cynosis in hyperbaric oxygen rooms he
developed (2120).
Frizt Bleichroeder (DE), Ernst Unger (DE), and Walter Loeb (DE)
were among the first to perform human vascular catheterization. They inserted
catheters into the blood vessels without x-ray visualization. After
numerous experiments on dogs without any accident, Bleichroeder successfully
catheterized the heart of Joseph Portmann, laboratory technician at the
hospital. Bleichroeder's approach to the heart was from the femoral vein. The
procedure was done with a ureteral catheter (235).
Ernst Unger (DE)
inserted ureteric catheters transcubital into the axillary vein, through the
femoral vein into the inferior vena cava, and through the femoral artery into
the abdominal aorta, and, through the
ulnar artery into the arch of the aorta (235;
2258).
Werner Theodor Otto Forssmann (DE), a surgical trainee, was the
first to document right heart catheterization in humans using radiographic
techniques. Forssmann said, “After the experiments in the cadavers had been
successful, I undertook the first experiments in living man by experimenting on myself…. I carried out
under local anesthesia a venesection in my left elbow and introduced the
catheter without resistance in its whole length of 65 cm…. I checked the position of the catheter in the röntgen
picture and I observed the forward advance of the catheter in a mirror held
in front of the fluoroscope screen by a nurse…. The method…has opened numerous
prospects for metabolic studies and for studies of cardiac activity” (809; 810). In return,
he was fired from his position at the hospital and won the Nobel Prize in 1956.
See, Claude Bernard, 1844.
Otto Klein (DE) published 11 successful experiments on humans in
which he catheterized and measured cardiac output (1265).
George P. Robb (US) and Israel Steinberg (US) successfully
performed cardiac catheterization (introduction of a small tube into the heart
by way of veins or arteries) on humans and were able to visualize the chambers
of the heart on x-ray film (1910).
André Frédéric Cournand (FR-US) and Hilmert A. Ranges (US)
inserted a catheter into the right atrium of a human and measured cardiac
output. They found that the catheter could be left in place for considerable
periods of time without harm (487). See Forssmann, 1929.
André Frédéric Cournand (FR-US), Richard L. Riley (US), Stanley E.
Bradley (US), Ernest S. Breed (US), Robert P. Noble (US), Henry D. Lauson (US),
Magnus I. Gregersen (US), and Dickinson Woodruff Richards, Jr. (US)
investigated traumatic shock in man and found: 1) that with a deficit of 40 to
50 percent in blood volume, there is a critical depression in cardiac output
and in return of blood to the right heart worsening as shock continues
unrelieved, 2) that peripheral resistance tends to be maintained in hemorrhage
and skeletal trauma, and greatly increases in severe burns, 3) that peripheral
blood flow is reduced particularly in the kidneys, and 4) that whole blood
offers great advantages over plasma as sustaining therapy (488; 1881).
André Frédéric Cournand (FR-US) demonstrated the feasibility of
making accurate measurements of cardiac output in man under physiological
conditions. He reached the conclusion that the quantity of oxygen absorbed by
the body per minute must be equal to that taken up at the lungs, which would in
turn be equal to the total pulmonary blood flow multiplied by the difference in
oxygen concentration between the blood entering and leaving the lungs (483).
Dickinson Woodrruff Richards (US) measured cardiac output by
catheterization (1879).
Richard A. Bloomfield (US), Henry D. Lauson (US), André Frédéric
Cournand (FR-US), Ernest S. Breed (US), and Dickinson Woodruff Richards (US)
used cardiac catheterization to record right heart pressures in normal subjects
and in patients with chronic pulmonary disease and various types of
cardiocirculatory disease (236).
André Frédéric Cournand (FR-US), Janet S. Baldwin (US), and Aaron
Himmelstein (US) were among the first to apply cardiac catheterization to the
diagnosis of congenital heart lesion (485; 486).
André Frédéric Cournand (FR-US) and Dickinson Woodruff Richards
(US) continued to develop venous catheterization
(484; 1880).
John A. Hartwell (US), Joseph P. Hoguet (US), and Fenwick Beekman
(US) concluded from experiments on dogs that death following
experimental intestinal obstruction is due, first, to a dehydration or loss of
water from the tissues as a result of the excessive drain into the lumen of the
intestine and vomiting, and, second, to the presence of a toxin in the
circulating blood. They demonstrated that duodenojejunal obstruction in dogs
responds well to liberal intravenous administration of saline (1014-1017).
Edward Flatau (PL) wrote a classic monograph on migraine (781).
Janet Elizabeth Lane-Claydon (GB) published a groundbreaking study
of two cohorts (groups) of babies, fed cow's milk and breast milk respectively.
Lane-Claypon found that those babies fed breast milk gained more weight, and
she used statistical methods to show that the difference was unlikely to occur
by chance alone. She also investigated whether something other than the type of
milk could account for the difference, an effect known as
"confounding" (1353). This study may have been the
first epidemiologic implementation of a retrospective (historical) cohort
study, the first modern description of "confounding" with an
accompanying analysis, and the first use of Student’s t test to assess the
difference of means in small samples. Lane-Claydon credits Major Greenwood for
his help in the statistical analysis of her data.
Theodore B. barringer (US) and Mortimer Warren (US) reported that
assessment for urinary casts became a routine part of clinical assessment and
was recognised very early on as being associated with increased cardiovascular
death, such as this report in 1912 of almost 400 otherwise healthy men from New
York (136).
James Bryan Herrick (US) was the first observer to identify and
describe the clinical features of sudden obstruction of the coronary arteries,
i.e., coronary thrombosis (1055). Note:
At this time transient episodes of nonfatal chest pain were attributed to
indigestion or other non-cardiac causes.
William Gibson Spiller (US), Edward Martin (US), Williams B.
Cadwalader (US), and Joshua E. Sweet (US) demonstrated that persistent pain of
organic origin in the lower part of the body could be successfully treated by
division of the anterolateral column of the spinal cord (335; 2113).
Rudolf
Magnus (NL) and Adriaan de Kleijn (NL) found that standing, walking, and bodily
balance in general, are reflexes that are affected, partly by the position of
the head in space and partly by its position in relation to the neck. Both
groups, which can reinforce or weaken each other according to a definite
pattern, have been combined under the name of attitudinal or standing reflexes
since they enable the animal to stand up. They discovered a special group of
‘righting reflexes’ which are elicited, partly by the vestibular apparatus in
the inner ear, and the neck, partly by the eyes, and, partly, by the trunk of
the body. It is these complex reflexes that enable a cat always to land on its
feet (1476; 1480; 1481).
Rudolf Magnus (NL) gives a clear definition of tonic reflexes.
These reflexes are called tonic, because they last as long as the head keeps a
certain position; and that not only for minutes and hours, but also for days,
months and even years. He was aware of two classes of tonic reflexes, those
that originate in the labyrinthine and depend solely on head position in space.
These can be contrasted to the neck tonic reflexes, which depend only upon the
position of the head on the neck and are independent of body position in space. Magnus also showed that there is a
shift in excitation, so that a reflex evoked with the head straight can be much
different than when the neck is flexed. The classic picture of the anencephalic
infant with its head turned to the side, with the viewed limb
extended, and the contralateral limb flexed, is the epitome of the neck
reflexes that underlie normal posture. Magnus also showed that the neck
reflexes cause the forelimbs to extend when the head is flexed back and the
forelimbs to be flexed when the neck is flexed forward. Finally, he and his
group demonstrated that processing for the neck reflexes is in the upper
cervical segments, whereas the vestibulospinal reflexes are processed in the medulla (1477-1479).
Eugen
Bircher (CH) reported the use of the laproscope for arthroscopy of the knee
joints of 18 paptients (220).
Henri Charles Jules Claude (FR) and Marie Loyez (FR) described a form of brainstem
stroke syndrome (Claude’s syndrome)
characterized by the presence of an ipsilateral oculomotor nerve palsy,
contralateral hemiparesis, contralateral ataxia, and contralateral hemiplegia
of the lower face, tongue, and shoulder. Claude's
syndrome affects occulomotor nerve, red nucleus and brachium conjunctivum (413).
Marin-Théodore Tuffier (FR), in 1912, performed the first
operation to open a stenotic (narrowed) heart valve. Using his finger, he
attempted to push the wall of the aorta near the heart through the stenotic
aortic valve and dilate the valve (2241). The
patient recovered and improved. Note: Tuffier was also the first to
transport a wounded soldier by airplane.
Elliott Cutler (US) and Samuel A. Levine (US) used a tenotome (a
tendon-cutting instrument) to successfully relieve a patient’s mitral stenosis
(a narrowing of the mitral valve between the upper and lower chambers of the
left side of the heart). The patient was a 12-year-old girl whose mitral valve
had been narrowed by rheumatic fever (525). This was a
very dangerous operation, which was soon abandoned because of its low rate of
success.
Henry Sessions Souttar (GB) performed the first successful
transauricular mitral valvotomy. It was on a 15-year-old girl. He approached
the valve from the left auricular appendage and used a finger as the basic
instrument to dilate the stenotic mitral valve. He passed his finger through
the mitral valve orifice into the left ventricle and did not cut the valve
cusps. The patient made an excellent recovery (2104).
Dwight Emary Harken (US), Laurence B. Ellis (US), Paul F. Ware
(US), Leona R. Norman (US), Charles Philamore Bailey (US), Charles Baker (GB),
Russell C. Brock (GB), and John Maurice Hardman Campbell (GB) reported on a
daring procedure to correct mitral stenosis. Harken had first performed this on
WWII shrapnel victims by cutting a small hole in the side of a beating heart
then inserting a finger and very carefully widening the narrowed valve (94; 95; 105; 998). Charles P.
Bailey (US) was the first to perform this operation, June 10, 1948. Russel C.
Brock (GB) performed the same operation just months later.
Just Marie Marcelin Lucas-Championnière (FR) described Neolithic
human skulls from nearly all parts of the world with disks of bone removed.
This process, called trephining,
represents the first evidence of man’s intervention in an attempt to heal his
fellow man. This surgical procedure was likely done to release confined demons
associated with epilepsy, infantile convulsions, headache, and various cerebral
diseases (1449).
Jacques Loeb (DE-US) wrote The
Mechanistic Conception of Life: Biological Essays (1430).
John Murray (GB), Johan Hjört (NO), Jakob Johan Adolf Appellöf (SE),
Haaken Hasberg Gran (NO), and Bjørn Helland-Hansen (NO) wrote, The Depths of the Ocean, a pioneering
work in oceanography (1671).
Charles Dawson (GB), Arthur Smith Woodward (GB), and Elliot Smith
(GB) reported to the Geographical Society of London announcing their discovery
of the fossil remains of Piltdown man (558). This
became the most infamous hoax in the history of paleontology.
1913
“There is no harder scientific fact in the world than the fact
that belief can be produced in practically unlimited quantity and intensity,
without observation or reasoning, and even in defiance of both, by the simple
desire to believe founded on a strong interest in believing.” George Bernard
Shaw (2052).
“Corpora non
agunt nisi fixata” [a substance
is not (biologically) active unless it is "fixed" (bound
by a receptor)]. Paul Ehrlich (673).
"In its most primitive form, life is, therefore, no longer
bound to the cell…life is like fire, like a flame borne by the living
substance—like a flame which appears in endless diversity and yet has
specificity in it." Martinus Willem Beijerinck (185). Note: In a speech discussing viruses
"The controversy over phagocytosis could have killed me, or
permanently weakened me sooner. Sometimes, (I remember such attacks of Lubarsch
in 1889, and those of Pfeiffer in 1894) I was ready to get rid of life." Élie
Metchnikoff (RU-FR) (380)
Charles Robert Richet (FR) was awarded the Nobel Prize in
Physiology or Medicine for his work on anaphylaxis.
Niels Henrik David Bohr (DK) produced a theory of the energy
status of the atom (in particular, the hydrogen atom) that showed its structure
to be mathematical. He assumed that the electrons could revolve about the
nucleus in definite orbital paths, and he then established a rigorous
mathematical theory to account for all those possible states. While the
electrons remained in their predicted paths they emitted no energy, but when
one would jump spontaneously from an outer to an inner orbit, it would emit
energy as a quantum of light (240).
Joseph John Thomson (GB), using equipment he calls a
"positive-ray" apparatus, observed that neon atoms have two different
atomic weights (20 and 22). The existence of isotopes is confirmed (2212).
Arthur Holmes (GB) concluded that the breakdown of radioactive
isotopes in igneous rocks could be used to determine when the rocks solidified.
The ability to determine the absolute ages of rocks enables scientists to
better date fossils. Using his quantitative time scale and other factors, he
made an estimate of Earth's age that was far older than anyone had suggested
until then – at least 3 billion years. His initial estimates of Earth's eras
have held up remarkably well over time: For example, he placed the beginning of
the Cambrian period at around 600 million years ago; today 590 million years is
the time frame largely accepted (1095).
Charles Marie Paul Auguste Fabry (FR) and Henri Buisson (FR) used
spectrographic techniques to demonstrate that the principal atmospheric
location of ozone is in the stratosphere. They noted that it is important for filtering out ultraviolet
radiation (735).
Eduard Riehm (DE) discovered that organo-mercurial treatment of
cereal seed will protect it from fungal attack. It was used to prevent a
disease called bunt in wheat (1893).
Leonor Michaelis (DE-US) and Maud Leonora Menten (CA) used the
rules of chemical kinetics to propose an equation, which describes how the rate
of an enzyme-catalyzed reaction varies with the concentration of the substrate.
They postulated that a complex is formed between an enzyme and its substrate,
which complex then decomposes to yield free enzyme and the reaction product.
The rate at which this occurs determines the overall rate of substrate-product
conversion. The velocity of such a reaction is greatest when all the sites at
which catalytic activity can take place on the enzyme molecules (active sites)
are filled with substrate; i.e., when the substrate concentration is very high.
These relationships provide the basis for all kinetic studies of enzymes and
have been applied to investigations of the effects of carriers upon the
transport of substances through cell membranes (1599). This work
was influenced by the work of Victor Henri (FR) (1045).
Kurt Guenter Stern (US) spectroscopically demonstrated the
existence of an intermediate enzyme-substrate complex for the enzyme catalase, thus confirming the
Henri-Michaelis-Menten hypothesis (2139).
Torsten Ludvig Thunberg (SE) and Heinrich Otto Wieland (DE)
maintained, because of their experiments over a number of years, that the
crucial reaction in living tissue is dehydrogenation (removal of hydrogen atoms
from foodstuffs, two at a time). It is this, they maintained, and not the
addition of oxygen, that is enzymatically catalyzed. They discovered the rapid
oxidation of the salts of acids, such as lactate, succinate, fumarate, malate,
citrate, and glutamate (2214; 2215; 2219; 2221; 2222; 2462-2464).
Otto Heinrich Warburg (DE) was opposed to this view while
maintaining it is the addition of oxygen that is crucial, and that this
reaction is catalyzed by enzymes containing iron atoms. He wrote, “… that the
oxygen respiration in the egg [sea-urchin] is an iron catalysis; that the
oxygen consumed in the respiratory process is taken up initially by dissolved
or adsorbed ferrous ions.” He postulated a
respiratory enzyme for the activation of oxygen, discovered its inhibition by
cyanide, and showed the requirement of iron in respiration(2388).
As it turned out both were correct. Together they made a good
start toward working out the respiratory chain in tissues, the route by which
the body converts organic molecules to water and carbon dioxide, releasing
energy in the process.
Santiago Ramón y Cajal (ES) developed gold chloride-mercury stain
to show astrocytes (1850).
Georg Albrecht Klebs (DE), from a thorough study of the houseleek, Sempervivum funkii, deduced that light
operates perhaps not as a nutritive factor, but on the contrary, more
catalytically (1263).
Henry Drysdale Dakin (US) and Harold Ward Dudley (US) discovered
the enzyme glyoxalase, which is
widely distributed in nature and catalyzes the interconversion of methyl
glyoxal and lactic acid (534).
Carl Alexander Neuberg (DE-US) and Johannes Kerb (DE) while
researching alcoholic fermentation by yeast, proposed an interpretation of this
process as the net result of a series of consecutive step reactions (pathway),
each one chemically conceivable and simple in nature, i.e., glycolysis (1709). Glycolysis
occurs (with some variations) in nearly all organisms, both aerobic and
anaerobic.
Robert Chodat (CH) was one of the first to obtain axenic cultures of algae (399).
Peter Boysen-Jensen (DK) working with coleoptiles of barley
seedlings established the existence of phytohormones
or auxins (Greek, to increase) which
are responsible for the chemical transmission of growth responses of higher
plants. He demonstrated that the phototropic influence is a chemical agent,
since it can cross an incision, but cannot pass through a mica barrier (265; 266).
Frits Warmolt Went (NL-US) hypothesized, as had others, that a
plant’s growing tip is a source of substances promoting the growth of cells
lower down the organ. His creative innovation was to collect such growth
hormones by allowing them to diffuse from the cut surface of the excised tip
into gelatin blocks. When applied symmetrically to the subapical tissue, these
gelatin blocks promoted elongation of the decapitated coleoptile, and when
applied asymmetrically, they caused curvature in a dose-dependent manner. This
experiment, which succeeded in the spring of 1926, was the first unequivocal
demonstration of the existence of a growth-promoting hormone (later named auxin) in plant tissues (2439).
Fritz Kögl (NL), between 1931-1935, extracted minute quantities of
plant growth promoters from the urine of man and other animals. He named them auxins which were later identified as
auxin a and auxin b. Kögl identified auxin b as
3-indoleacetic acid (1288).
Fritz Kögl (NL), Arie Jan Haagen-Smit (NL-US), and Hanni Erxleben
(NL) isolated auxin a from human
urine (1289).
Fritz Kögl (NL), Arie Jan Haagen-Smit (NL), Hanni Erxleben (NL), Désiré
George Florent Rudolphe Kostermans (NL), Kenneth Vivian Thimann (GB-US), and Joseph B.
Koepfli (US) identified the first known plant hormone, indoleacetic acid (IAA) (1290; 1292; 2207).
Fritz Kögl (NL), Arie Jan Haagen-Smit (NL-US), and Hanni Erxleben
(NL) isolated auxins and characterized them chemically (1291).
George Robert Sabine Snow (GB) found that indoleacetic acid (IAA)
stimulates cambial activity (2091).
James Frederick Bonner (US) and Samuel G. Wildman (US)
demonstrated that indolacetic acid is a principal native auxin of higher plants (247).
Harry Federley (FI) proposed that mules are sterile due to a
failure of normal sperm production by meiosis, the type of cell division that
gives rise to germ cells. Specifically, the failure occurs at the stage of
synapsis, when the homologous chromosomes of maternal and paternal origin come
together (742).
William Ernest Castle (US) made significant contributions toward
simplifying genetic terminology and formulae (375).
Elbert Thomas Bartholomew (US) studied potato black heart where he
elucidated the effects of abnormal environmental conditions on the metabolism
of the host cells. This study showed how environment could bring on disease (140; 141).
Howard P. Barss (US) was the first to describe bacterial blight of
hazelnuts (Corylus avellana) (137).
Shiro Tashiro (JP-US) discovered that the production of the nerve
impulse depends upon the metabolic activity of the nerve fiber (cell) (2195).
Antonio Berlese (IT) theorized that the insect larva
is a free-living, feeding embryo. He believed that the larval stage is
equivalent to the pro-nymph stage of more primitive insects with incomplete
metamorphosis, like grasshoppers (203).
Vilém
Laufberger (CZ) demonstrated that desiccated cattle thyroid glands could induce
the metamorphosis of the amphibian Amblyostoma
mexicanum (Siredon mexicanum)
from its neotenic form to the adult form, which is not found in nature (20; 1361).
Julian
Sorell Huxley (GB), unaware of Laufbergers work, performed the same experiment
on the axolotl (1140).
William Bateson (GB) discovered that dominance, in a genetic
context, is not always absolute (148). As a
result, terminology such as partial dominance, incomplete
dominance, codominance, lack or absence of dominance, intermediate dominance,
imperfect dominance, egalitarian dominance, and transdominance came into use.
Alfred Henry Sturtevant (US) and Thomas Hunt Morgan (US)
discovered that despite their physical linkage some recombination does take
place between genes on the same chromosome. They reasoned that the mechanism
responsible is crossing over between homologous chromosomes. By measuring the
frequency with which linked genes segregate Morgan and Sturtevant were able to
construct a genetic map of the four chromosomes of Drosophilia; a map which turned out to be linear (1630; 2169).
Alfred Henry Sturtevant (US) and George Wells Beadle (US)
postulated that the genes are arranged in a manner like beads strung on a loose
string (2175).
Gershom Franklin White (US) showed the cause of sacbrood in honeybees, Apis mellifera Linn., to be a filterable
agent, i.e., virus (2451).
Alexander Ivanovitch Petrunkevitch (RU-US) began what became an
important group of monographs on fossil arachnids (1813-1817).
Fujiro Katsurada (JP) described metagonimiasis when he first observed eggs of Metagonimus
yokagawai in feces (date is disputed in various studies) (1224). M. takahashii was
described later first by Suzuki in 1930 and then M. Miyatai was
described in 1984 by Saito. Metagonimiasis is a disease caused
by an intestinal trematode, most commonly Metagonimus yokagawai, but
sometimes by M. takashii or M. miyatai. The metagonimiasis
causing flukes are one of two small flukes called the heterophyids.
John Murray (GB) and Johan Hjört (NO) led the Michael Sars
deep-sea expedition. This expedition greatly expanded knowledge about deep-sea
animals, including ecological patterns (1670). Michael Sars was a Norwegian zoologist (1805-1869).
Alfred Whitmore (GB) described melioidosis,
a glanders-like disease of rodents, transmissible to man, occurring in India,
the Malay states, and Indo-China, caused by Burkholderia pseudomallei (Malleomyces pseudomallei) (2453). It is also
called Whitmore's disease.
Nicolaas Louis Söhngen (NL) reported that the presence of a solid
phase could influence a diversity of bacterial processes, such as nitrogen
fixation, alcohol oxidation, nitrification, and denitrification (2096).
Eduard Riehm (DE) at I.G. Farbenindustrie A.-G. introduced a
chlorophenol-mercury compound called Uspulun for seed treatment against wheat
bunt (fungal disease) (1894).
Albert Francis Blakeslee (US) discovered that copulation between
two fungal thalli of opposite mating types precedes the formation of zygospores
in Rhizopus (228).
Victor Ernest Shelford (US) studied
succession in dune environments; this included his famous relating of
variations in tiger beetle coloration to their presence in different
successional stages, and in turn to a law
of tolerance that related presence/absence to limiting factors in the
environment (2054). Note: also called the law of
ecologic tolerance
Charles C. Adams (US) and Victor Ernest Shelford (US) wrote two of
the earliest books dealing with animal ecology (15; 2054).
Carl A. Kling (DE) worked out the viral etiology of Varicella (chickenpox) (1268).
Edna Steinhardt (US), Clara Israeli (US), and Robert A. Lambert
(US) were the first to cultivate virus in tissue culture —vaccinia virus on
pieces of rabbit cornea (2135).
Emil Adolf von Behring (DE) reported the successful use of
toxin-antitoxin mixtures in the immunization of children against diphtheria. The vaccine proved
unreliable and only gave consistent results after Paul Ehrlich standardized it (2311).
William Hallock Park (US) studied the use of diphtheria
toxin-antitoxin mixtures to produce active immunity in animals and then in
humans. He adjusted the amounts of the substances until he achieved a balance
between lasting immunity and reactions to the mixture (1785; 1786).
Béla Schick (HU-AT-US) developed the Schick Test, a practical method for distinguishing non-immune
individuals from those already immune to diphtheria.
It consists of injecting into the skin a very low dose of diphtheria toxin and observing the local reaction. In those whose
blood serum contains no antitoxin, a characteristic reddish swelling develops
at the site of injection, i.e., the Römer reaction. In those who are immune,
the antitoxin already present in the circulation neutralizes the injected toxin
and prevents the reaction from occurring (2014).
James Cecil Mottram (GB) showed that in both plant and animal
tissues (the tips of bean shoots and ova of Ascaris
megalocephala) cells are more vulnerable to damage by beta and gamma
radiation when they are in process of division than in the resting stage, and
that the metaphase is the most vulnerable stage. This damage results in
profound nuclear changes affecting chromatin (1642).
Claude Gordon Douglas (GB),
John Scott Haldane (GB), Yandell Henderson (US), Edward C. Schneider (US),
Gerald B. Webb (US), and J. Richards (US) demonstrated that at a given carbon
dioxide pressure, oxygenated blood takes up less carbon dioxide than
deoxygenated blood (623).
Mabel Purefoy Fitzgerald (GB) provided the first demonstration of
the extraordinary sensitivity of the hypoxia pathway to ambient oxygen levels (780).
Donald Dexter van Slyke (US) and Gustave M. Meyer (US) showed that
amino acids are absorbed from the blood by the tissues, without undergoing any
immediate chemical change. The amino acids of the blood appear to be in
equilibrium with those of the tissues. The process by which the amino-acids are
taken up and held by the tissues cannot be wholly osmotic, because the normal
concentration of amino nitrogen in the tissues is five to ten times that in the
blood (2283).
Eli Kennerly Marshall, Jr. (US) developed a rapid (urease) method for the quantitative
determination of urea in urine and blood (1509-1511).
Roger I. Lee (US) and Paul Dudley White (US) reported on a
clinical study of the coagulation time course of blood (1376).
Frank Rattray Lillie (US) hypothesized the existence of a
substance in the jelly coat of eggs, which causes sperm cells to clump
together. He coined the name fertilizin
for this substance (1415).
Lillie elaborated on his thoughts in a follow-up paper (1416).
Jules Jean Baptiste Vincent Bordet (BE) and Léon Delange (BE)
described a lecithin rich activator (cytozyme)
in an alcohol extract of blood platelets (251).
William Henry Howell (US) discovered that Bordet’s cytozyme (thromboplastic
substance, or tissue fibrinogen) is a cephalin (phosphatidylethanolamine) rather than a lecithin (1115; 1117).
Hans Berger (DE) made the
first human electroencephalogram (EEG) recordings in 1924 and published in 1929.
He discovered the alpha wave rhythm which is a type of brainwave (198; 199).
Edgar Douglas Adrian (GB) and Bryan Harold Cabot Matthews (GB)
confirmed the observations of Berger (23).
George Hoyt Whipple (US) reported the absence of prothrombin in a
case of melena neonatorum in a
3-day-old infant who developed melena
and other hemorrhagic symptoms (2445). He also
described abnormal hemorrhage associated with prothrombin deficiency in a
patient with obstructive jaundice. In
this paper Whipple describes the first known method for determining
prothrombin-time (2446). See,
Quick, 1935.
Aldred Scott Warthin (US) discovered a relationship between heredity
and carcinoma as shown by the study of the cases examined in the pathological
laboratory of the University of Michigan, 1895-1913 (2399).
Aldred Scott Warthin (US) gave the classic
description of pulmonary fat embolism (2400).
Ivan Whiteside Magill (IE-GB) and Edgar Stanley Rowbotham (GB), c.
1913, developed a technique of placing a breathing tube into the windpipe, and
endotracheal anesthesia was born. This was driven by the immense difficulties
of administering "standard" anaesthetics such as chloroform and ether
to men with severe facial injury using masks; they would cover the operative
field (1474; 1944).
Chevalier Jackson (US), in 1911, developed the first laryngoscope
used to visualize the larynx and insert an endotracheal tube. He combined this
endoscopic proficiency with open surgical techniques (1161).
Arthur Ernest Guedel (US) and Ralph M. Waters (US) discovered the
cuffed endotracheal tube in 1928. This advance allowed the use of
positive-pressure ventilation into a patient’s lungs (945).
John Jacob Abel (US), Leonard George Rowntree (CA-US), and
Benjamin Bernard Turner (US) invented the artificial kidney when they developed
a device for vivi-diffusion of blood of small animals. This was like a
shell-and-tube heat exchanger. A series of handmade nitrocellulose tubes of 8
mm inside diameter was connected by glass manifolds and enclosed in a glass
shell. Blood flowed through the collodion tubes, while isotonic saline solution
flowed around the tubes. To prevent clotting of the blood in the extracorporal
circuit, hirudin, obtained by crushing the heads of leeches, was used as an
anticoagulant.
The authors noted the potential of this invention when they
stated, “There are numerous toxic states in which the eliminating organs of the
body, more especially the kidneys, are incapable of removing at an adequate
rate the natural or unnatural substances whose accumulation is detrimental to
life. In hope of providing a substitute … a method has been devised by which
the blood of a living animal may be submitted to dialysis outside the body” (4; 5).
William Thalhimer (US), Donald Y. Solandt (US), and Charles
Herbert Best (US-CA) contributed to the evolution of hemodialysis with the
demonstration that commercially available cellophane tubing could be used for in vivo dialysis (2200-2202).
Willem Johan Kolff (NL-US), Henrick T. J. Berk (NL), Maria ter
Weele (NL), A.J.W. van der Ley (NL), Evert C. van Dijk (NL), and Jacob van
Noordwijk (NL) invented the artificial kidney for use with humans. It
was a rotating drum artificial kidney, made by winding 100 feet of cellophane
in a spiral pattern around a large horizontal drum, which revolved in an enamel
tube containing a rinsing fluid. Gravity drew blood in the cellophane to the
lowest point, and as the drum turned, the blood worked its way from one end of
the cellophane tube to the other, releasing its impurities into the surrounding
fluid as it traveled (1299).
Willem Johan Kolff (NL-US) demonstrated that in vivo dialysis could replace all known excretory functions of the
kidney and regulate the electrolyte pattern of the blood plasma water in
patients (1298).
Abraham Albert Hijmans van den Bergh (NL) and Isidore Snapper
(NL-US) reported, relative to jaundice, that it was suspected that bilirubin
passes into the urine once its blood level passes a threshold value. The
threshold value was not known. They devised a test to
detect the presence of bilirubin in blood serum or plasma (2266).
Guido
Banti (IT) concluded that the leukemias are systematic diseases arising from
hemopoietic structures, lymph glands, and bone marrow, and that they are the
consequence of limitless proliferative power of staminal blood cells (113). This
is still the basic definition of leukemia.
Albert
Salomon (DE) reported,“Roentgen photographs of excised breast specimens give a
demonstrable overview of the form and spread of cancerous tumors” (1975).
Otto Kleinschmidt
(DE) gave the first description of the clinical use of mammography on a patient
(1266).
Edmond
Barthe de Sandfort (FR) developed keritherapy,
the treatment of burns by using the
paraffin-resin solution ambrine (138).
Edmond
Barthe de Sandfort (FR) advocated keritherapy
in the treatment for rheumatism by plunging of the whole body or the parts
affected into heated paraffin (139).
Hugh Morriston Davies (GB) performed a
hilar dissection and ligation of individual pulmonary arteries and veins and
sutured the bronchial stump closed in a patient with lung cancer (556).
Evarts Ambrose Graham (US) and Jacob Jesse Singer (US) removed a
whole lung for cancer, performing a simultaneous thoracoplasty to avert the
high risk of empyema (912). The
patient, a doctor, was still alive at the time of Graham's death in 1957 (1684).
Paul Ferdinand Schilder (AT-US), Charles Foix (FR), and Julien
Marie (FR) described intracerebral
centrolobular sclerosis or diffuse myelinoclastic sclerosis (Schilder’s disease) a rare, progressive and invariably fatal disease of
the central nervous system characterized by adrenal atrophy and diffuse
cerebral demyelination (792; 2015).
Ludwig Wilhelm Carl Rehn (DE) and Ernst Ferdinand Sauerbruch (DE)
independently performed the first pericardial resection in which an inflamed
pericardium was partially excised because it constricted the movement of the
heart. A left anterolateral thoracotomy approach
was used (1864; 1982).
Edward Delos
Churchill (US) was the first in the U.S.A. to perform decortication of the
heart to relieve adhesive pericarditis (407).
Edmond
Delorme (FR) had been the first to suggest that an operation to relieve
adherent pericardium, i.e. restrictive pericarditis, had a likelihood of
success (580).
Ludwig Rehn (DE) first performed this operation in 1913 (1863).
Hermann Oppenheim (DE) and Fedor Victor Krause (DE) performed the
first successful removal of a pineal gland tumor
(1750).
John Broadus Watson (US) founded the behaviorist school of
psychology, which emphasized the study of observable behavior rather than
conscious and unconscious mental processes (2411; 2412).
Vladimir Mikhailovich Bekhterev (RU) played a pivotal role in the
psychiatric examination during the Beilis trial, which entered the history of
science as the first forensic psychological psychiatric examination. Menahem
Mendel Beilis was a Russian Jew accused of ritual murder in Kiev in the Russian
Empire in a notorious 1913 trial.
Albert
Schweitzer (DE) opened a hospital for the leprous
in Lambaréné, located in West Africa.
1914
“All the evidence points to the nuclear germ-plasm as the
essential carrier of hereditary characters. We are thus compelled, on the
mechanistic hypothesis, to attribute to the germ-plasm, or germinal nuclear
substance, a structure so arranged that in presence of suitable pabulum and
stimuli it produces the whole of the vast and definitely ordered assemblage of
mechanisms existing in the adult organism.” John Scott Haldane (969).
“[...] there is no more difficult art to acquire than the art of
obser- vation, and for some men it is quite as difficult to record an
observation in brief and plain language.” - Sir William Osler (1766).
Max Theodor Felix von Laue (DE) was awarded the Nobel Prize in
Physics for obtaining the first x-ray diffraction patterns by passing x-rays
through a crystal of zinc sulfide.
Robert Bárány (AT-SE) was awarded the Nobel Prize in Physiology or
Medicine for his work on the physiology and pathology of the vestibular
apparatus.
Leonor Michaelis (DE) wrote Die Wasserstoffionenkonzentration;
Ihre Bedeutung für die Biologie und die Methoden Ihrer Messung [The hydrogen
ion concentration; Their significance for biology and the methods of their
measurement]; the authority on pH and buffers for over a decade (1598). Note: Michaelis
discovered Janus green as a supravital stain for mitochondria and the Michaelis–Gutmann
body in urinary tract infections (1902). He found that thioglycolic acid could
dissolve keratin, a discovery that would come to have several implications in
the cosmetic industry, including the permanent wave ("perm").
Hermann Emil Fischer (DE), Burckhardt Helferich (DE), and Kálmán
V. Fodor (HU) became the first to synthesize a nucleotide (774).
Yotako Koga (JP) and Ryo Ohtake (JP) isolated citrulline from
watermelon (Citrullus
vulgaris)
juice (1287).
Mitsunori Wada (JP) coined the term citrulline from watermelon (Citrullus vulgaris) then proved
through chemical synthesis that it is synonymous with delta-ureido-ornithine or
alpha-amino-delta carbamido-n-valeric acid (2375).
Arthur James Ewins (GB) isolated the neurotransmitter
acetylcholine (734).
Phoebus Aaron Theodor Levene (RU-US) and Frederick B. LaForge (US)
correctly identified the structure of hexosamine, which they called
chondrosamine (now called galactosamine) (1392; 1393).
Phoebus Aaron Theodor Levene (RU-US) was the first to obtain
sphingomyelin in pure form and determine its structure (1387).
John Charles Grant Ledingham (GB) and William James Penfold (GB)
discussed the mathematics of the lag phase and log phase of bacterial growth (1373).
Donald Dexter van Slyke (US) and Glenn E. Cullen (US) developed a
gasometric method of quantitatively determining urea concentration in blood and
urine (2280).
Herbert McLean Evans (US) and Werner Schulemann (DE) introduced
the use of the acid dis-azo dyes for use in vital staining. Among the best
known of these vital dyes are trypan red, trypan blue, vital red, and Evans
blue (729; 730).
Henry Hallett Dale (GB) showed the obvious relation of
acetylcholine’s action on the parasympathetic system to that of epinephrine
(adrenaline) on the true sympathetic
system. He found that of all the various choline esters (natural and
synthetic) active on striated muscle, acetylcholine was the most potent one (537). Dale
coined the terms adrenergic and cholinergic systems.
Stanislaus Josef Mathias von
Prowázek (CZ) introduced the use of fluorescent dyes for the staining of cells
and tissues in animal physiology. He used fluorescent dyes to enhance the
auto-fluorescence of cells (2369).
Robert Joachim Feulgen (DE) applied the aldehyde reaction of Hugo
Schiff (fuchsin sulfurous acid) to thymic nucleic acid (apurinic acid) (DNA)
and reported that a neutralized acid hydrolysate of thymic nucleic acid
restores the color of a fuchsin solution previously decolorized by sulfur
dioxide (759).
Petroleum oils were introduced as herbicides for use along
drainage ditches in the Western United States and as a selective herbicide in
carrots (Daucus carotus).
Arthur Harden (GB) and Robert Robison (GB) found hexose
monophosphate in a carbohydrate fermentation mixture (989). Robert
Robison (GB) later determined that it was a mixture of isomeric hexose
monophosphates, probably those of glucose and fructose (1915).
Gustav Georg Embden (DE) and Fritz Oscar Laquer (DE) showed that
when hexose diphosphate was added to muscle extract lactic acid production was
increased (690).
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 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 (1579-1591).
Hans Karl August Simon von Euler-Chelpin (DE-SE) and Karl David
Reinhold Myrbäck (SE) suggested the role of coenzymes as hydrogen carriers (2325).
Gustav Georg Embden (DE) and Margarete Zimmerman
(DE) isolated a hexose monophosphate, Embden
ester, from muscle (698). Embden
ester turned out to be a mixture of hexose monophosphates that were
subsequently identified: fructose-6–P (Neuberg
ester), glucose-6–P (Robison ester),
and eventually glucose-1–P (Cori ester)
(466; 1703; 1915).
Robert Robison (GB) and Earl Judson King (CA-GB) isolated glucose
monophosphate (Robison ester) from a
carbohydrate fermentation mixture (1918; 1919). This Robison ester would prove to be
glucose-6-phosphate.
Robert Robison (GB) isolated the Newberg ester (D-fructose 6-phosphate) from yeast juice
fermentation (1917).
Calvin Blackman Bridges (US) presented papers on nondisjunction
offering the final and conclusive proof that genes are parts of chromosomes (288; 289; 293).
Hiram Bentley Glass (US) presented data illustrating the
nondisjunction of chromosomes (873; 874).
Karl von Frisch (AT), Herbert Heran (DE), and Martin Lindauer (DE)
studied communication in the honeybee, Apis
mellifera Linn. They performed
pioneering and imaginative studies, which led eventually to an understanding of
some of the ways in which honeybees communicate with one another. Through a dance (usually performed on the comb)
workers can communicate the direction and distance to food. They also
discovered that bees have the ability to discriminate some colors (they cannot
see red but can see ultraviolet) and orient themselves by direction of light
polarization in the sky (2332-2347).
Edmund M. Walker (CA) discovered that rock crawlers/ice bugs
(Grylloblattodea), are a new order of insects. They inhabit cold areas, often
in mountains, under rocks and in litter in forests, and in caves. During summer
the North American species feed at night on insects frozen on the surface of
snowfields; they are somewhat omnivorous. Their range includes Western North
America, Japan, Korea, China, and Siberia (2382). (Gryll =
cricket, blatta = cockroach)
P.P. Awrorow (RU) and Alexander D. Timofejewskij (RU) concluded
that the lymphocyte is the stem cell from which arises the enlarged mononudear
cell and from it develop the other types of transformed cells found in their
plasma cultures; i.e., the wandering cell, spindle-shaped cell, phagocytic
cell, giant cell, and the cell which these observers call the
"Auslauferzele." (85)
Florence Rena Sabin (US), Robert S. Cunningham (US), Charles
Austin Doan (US), and Claude E. Forkner (US) introduced the technique of supravital staining—staining of living
cells with dyes—which made it possible to distinguish certain types of cells
from others for the first time in living tissue. The supravital staining
research, in turn, led them to a study of cells (monocytes) involved in immune
reactions, especially against the tuberculosis bacillus. They were able to
watch cellular growth in the hanging drop
preparations and to see under the microscope the development of the earliest
blood cells in explanted bits of the blastoderm of the chick embryo. They
reported that on the second day of incubation of such cultures only red cells
could be seen coming from the endothelial walls of the blood vessels. By the
third day white cells appeared arising partly from new cells that
differentiated from mesenchyme without becoming part of the vessel's lining.
They differentiated the various types of blood cells and attempted to group
them in accordance with their origin(511; 600; 1967-1973).
Margaret Reed Lewis (US) observed, "the transformation and
growth of the leucocytes into macrophages, epithelioid cells, and giant cells
in the blood of the chick embryo, young chicken, adult hen, mouse, guinea-pig
and dog, and in human blood. In every kind of blood examined there developed
first large wandering cells, several times larger than any of the normal leucocytes,
which were phagocytic for red blood cells, melanin granules, carbon particles,
dead granulocytes, and tuberde bacilli. Somewhat later there appeared a cell
more like a primitive mesenchyme cell, and still later the epitheloid cell was
formed. This cell was sometimes binudeate and in some instances a typical
multinucleated giant cell (Lagahans giant cell) was formed. Since the
transformation and growth of the leucocytes were much the same in the different
bloods examined, only the details of the phenomenon in avian and human blood
only will be described." (1400)
Eliot R. Clark (US) and Eleanor Linton Clark (US) made the first in vivo demonstration, in which
monocytes became macrophages (409).
Robert Higgins Ebert (US) and Howard Walter Florey (AU-GB)
verified the authenticity of change from blood monocyte to tissue macrophage in
mammals (659).
Lewis Hill Weed (US) discovered that the cranial end of the
central nervous system provides the greatest area of absorption of
cerebrospinal fluid. Most of the absorption occurs by way of cranial arachnoid
villi, those projections of arachnoid directly beneath the endothelial walls of
the dural venous channels. A slow accessory absorption of the fluid occurs into
the lymphatic system of the body. This secondary pathway seemed to be through
perineural spaces for a limited distance outward along the spinal and cranial
nerves, and then an indirect passage through tissue spaces into the adjacent
lymphatic vessels (2415-2417).
Lewis Hill Weed (US) deduced that factors, which might play a role
in the process of absorption of cerebrospinal fluid, included the colloid
osmotic pressure of the blood and the hydrostatic pressure-difference between
the subarachnoid pressure and the intracranial venous pressure (2418).
Walther Kruse (DE) passed nasal washings from individuals with the
common cold (acute viral rhinopharyngitis; acute
coryza) through Berkefeld filters, then used these to inoculate healthy
individuals. Successful transmission of the common cold to these healthy human
volunteers strongly suggested that the etiological agent is a virus (1320).
George B. Foster, Jr. (US) performed a very similar experiment
during 1916-17 (811; 812).
Peter K. Olitsky (US), James E. McCartney (US), Alphonse Raymond
Dochez (US), Gerald S. Shibley (US), Katherine C. Mills (US), Yale Kneeland,
Jr. (US), Commission on Acute Respiratory Diseases (US), Christopher Howard
Andrewes (GB), Donna M. Chaproniere (GB), Annette E.H. Gompels (GB), Helio
Gelli Pereira (BR), A. Tony Roden (GB), Harry F. Dowling (US), George Gee
Jackson (US), Tohru Inouye (US), Irwin G. Spiesman (US), Harold G. Spiesman
(US), and Arthur V. Boand, Jr. (US) established definitively that common colds may be caused by agents
with the properties of viruses (50; 51; 53; 599; 602; 604; 624; 625; 1162; 1163; 1745).
Jacob Traum (US) was the first to describe brucellosis in swine. It was in a swineherd in Indiana (2231).
Alice Catherine Evans (US) confirmed these results and those of
earlier work on Malta fever and cattle abortion (719).
Irwin F. Huddleson (US) identified and named as a separate species
the Brucellae causing swine brucellosis
(Brucella suis) (1122).
Marshall A. Barber (US) observed the relationship of Staphylococcus albus to acute
gastrointestinal upsets associated with drinking milk from a cow with mastitis (124).
Arthur William Bacot (GB) and Charles James Martin (GB) determined
that humans are infected with the plague bacillus when a flea carrying the
bacillus regurgitates during a blood meal (90).
Albert Hustin (BE) showed that addition of citrate can prevent
blood from clotting and that citrated blood can be safely transfused into the
dog. He then used citrated blood to transfuse a human (1133; 1134).
Luis Agote (AR) discovered that sodium citrate, when added to
freshly drawn blood, prevents clotting. This meant that donors could go home
rather than being present during transfusion. He performed a
successful blood transfusion in humans using sodium citrate as an anticoagulant (26; 27).
Richard Lewisohn (US) determined the maximum amount of citrate
that can be transfused into dogs without toxicity and thus determined the
optimum concentration that can be added to blood for the best anticoagulant
effect (1407).
Henry M. Thomas (US) and Kenneth Daniel Blackfan (US) detailed a
case of a boy who died of lead poisoning
after ingesting white lead paint from the railings of his crib (2208).
Otto Knut Olof
Folin (SE-US) and J.L. Morris (US) adapted Jaffe's reaction into a clinical
procedure (800; 801). Note:
Folin used
a Duboscq colorimeter for measurement precision, and is credited for
introducing colorimetry into modern biochemical analysis.
Arthur Robertson
Cushny (GB) and co-workers advocated the filtration-reabsorption theory of
kidney function (522; 523).
Poul Kristian Brandt Rehberg (DK) developed
a reliable clearance method for determining the glomerular filtration rate
(GFR) based on the substance creatinine. With his method, he was able to show that
GFR in adults is about 180 L / day. Creatinine clearance is still a worldwide
standard clinical method for assessing renal function. Rehberg presented the
theory that
urinary excretion occurs by an ultrafiltration of the blood into the kidney's
ventricles ( glomeruli ) with subsequent re-uptake of fluid and
nutrients into the renal tubules ( tubules ) (1862).
Carl Voegtlin (US) provided the earliest study, which proved that
human pellagra is unquestionably
caused by dietary deficiency (2299).
Joseph Goldberger (SK-US), Clarence H. Waring (US), David G.
Willets (US), George A. Wheeler (US), William F. Tanner (US), Ralph Dougall
Lillie (US), and L. M. Rogers (US) discovered that pellagra is caused by a dietary deficiency of a vitamin belonging
to the B-complex and is not infectious (886-888; 890-892).
Tracy Neil Spencer (US) was the first to call attention to the
similarity between the symptoms of a spontaneous canine disease known to
veterinarians as black-tongue and
those of human pellagra (2109).
Joseph Goldberger (SK-US)
and William F. Tanner (US) learned which foods are rich in the P-P (pellagra-preventive) factor, as they
called it, and thus they could prevent pellagra
by diet modification (893).
William Boog Leishman (GB) developed a vaccine against typhoid fever. It was a
whole vaccine killed by heat at 53°C. and preserved with 0.25 per cent
tricresol (1380).
Malaria control by
fluctuating water levels was first observed (2050).
Erich Schmidt (DE) measured high serum cholesterol levels in
patients with xanthomatosis making
this the first time that an essential
hypercholesterolemia was recognized (2024).
Alfred Fabian Hess (US) and Mildred Fish (US) noted numerous
petechial hemorrhages of the skin or mucous membranes as one of the earliest
signs of infantile scurvy. Fruit juices, orange peel, and potato all were excellent
antiscorbutic agents. Normal infants could withstand a blood-band pressure of
90 for three minutes with no ill effects whereas blood vessels would give way
and form petechial hemorrhages in infants with scurvy (1064).
Albert Niemann (DE) was the first to describe what is now known as
Niemann-Pick disease, type A (1724).
Ludwig Pick (DE) described the pathology of Niemann-Pick disease (1821).
Note: Niemann-Pick disease is a group of
inherited severe metabolic disorders that allows sphingomyelin to accumulate in
lysosomes (membrane-bound organelles in cells).
Walter E. Garrey (US) noted that persistence of cardiac
fibrillation is, other conditions being equal, directly proportional to the
size of the tissue masses involved whether the pieces are cut from hearts
already fibrillating or are faradically stimulated to start the process in
them.
Experiments support the block hypothesis and suggest that the
blocks probably result in intramuscular ring-like circuits with resulting “
circus contractions ” which are fundamentally essential to the fibrillary
process. Such ring circuits can exist in large masses but not in sufficiently
small ones (853).
Franz Volhard (DE) and Karl Theodor Fahr (DE) gave the first full
description of pure nephrosis,
relating clinical features to morbid anatomy. They differentiated between
degenerative (nephroses), inflammatory (nephritides) and arteriosclerotic
(scleroses) diseases. Nephrosclerosis was divided into the benign and malignant
form, of which the latter stood the test of time as a new disease entity. Fahr
further divided benign nephrosclerosis into the compensated and decompensated
form – depending on the presence or absence of glomerular injury. In the
pathogenesis of malignant nephrosclerosis, Volhard stressed the decisive role
of severe blood pressure elevation, while Fahr postulated an inflammatory
mechanism, a concept later confirmed by Adalbert Bohle for at least a minority
of patients. A very far reaching concept of Franz Volhard was his idea that
pale (renal) hypertension results from a pressor substance released from
ischaemic kidney(s) contributing – via a vicious circle – to a further rise in
blood pressure with subsequent renovascular injury and aggravation of
hypertension (2308). Note: The consequent detection of the
renin angiotensin system was the final confirmation of Volhard’s postulated
renal pressor substance. See, Tigerstedt,
1898 and Ruyter,
1925
Karel Frederik Wenckebach (NL-AT) published his classic book on
cardiac arrhythmias. Here he described the effect of quinine on atrial
fibrillation, when he was able to rid a patient of tachycardia with a dosage of
one gram of quinine (2437).
Walter Frey (CH) proved that quinidine, an optical isomer of
quinine, is the most effective of all quinine derivatives against atrial
flutter (827).
Richard Clarke Cabot (US), following an analysis of 600 cases of
heart disease divided them all into four categories. He
reported that 93% of the cases were of rheumatic, atherosclerotic, syphilitic,
or nephritic etiology (334).
Walter Edward Dandy (US) and Kenneth Daniel Blackfan (US) produced
a classic account of the pathogenesis and management of hydrocephalus. They produced hydrocephalus
experimentally and explained that various types of hydrocephalus are due to obstruction of the aqueduct of Silvius, obstruction of the foramina of Magendie and Luschka, and devised surgical operations
for the relief of the different varieties (545).
Joseph Jules
François Félix Babinski (PL-FR) described and named anosognosia
(Babinski-Anton syndrome). When the right hemisphere of the brain is damaged, there is
usually complete paralysis of the left side of the body. Patients with anosognosia obstinately insist that
their left arm is not paralyzed even though they are mentally lucid in other
respects. They may even deny ownership of their left arm, asserting that it
belongs to someone else (56; 89).
Charles Alfred Balance (GB) performed nerve grafting for facial
palsy (106).
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 (2072).
Lucien Claude Jules Cuénot (FR) proposed the theory of preadaptation: the empty
space or ecological niche is
populated with mutants already showing characteristics adapted to the
conditions of the empty space (509).
David Meredith Seares Watson (GB) provided the first evidence that
mammals evolved from reptiles. This conclusion was based on the fossilized
remains of primitive reptiles and mammals he collected on trips to South Africa
and Australia during 1911-1914 (2410).
Hans Reck (DE) discovered rich deposits of early mammalian fossils
including Stone Age artifacts at Olduvai Gorge in East Africa. Among other
fossils he unearthed a fully human Late Pleistocene skeleton
on the northern slope of the gorge; naming it Olduvai Hominid 1 (OH 1) (1859; 1860).
c. 1915
Konstantin von Economo; Konstantin Alexander Economo von San Serff
(RO-AT) started his monumental studies on encephalitis
lethargica (lethargic encephalitis),
an epidemic disease of the central nervous system marked mainly by pronounced
somnolence (lethargy), myalgias, fever, stupor, ophthalmoplegia, and paresis (2315; 2316). The
disease, sometimes called type A
encephalitis is now considered extinct. The etiological agent was never
identified.
Jean René Cruchet (FR), J. Moutier (FR), and A. Calmettes (FR)
also described encephalitis lethargica at
this time (507).
1915
William Henry Bragg (GB) and his son William Lawrence Bragg (GB)
shared the Nobel Prize in Physics for their formulation of the mathematical
equations needed to calculate wavelength of the x-rays from the scattering
pattern. They also used the x-ray diffraction patterns to deduce molecular
structure of crystals. William Lawrence Bragg, at age twenty-five, was the
youngest Nobel laureate ever. This coincidentally gave striking confirmation of
the tetrahedral nature of the carbon atom (268-272).
Richard Martin Willstätter (DE) was awarded the Nobel Prize in
Chemistry for his researches on plant pigments, especially chlorophyll.
Chaim Weizmann (RU-GB-IL) discovered a way to produce acetone via
bacterial fermentation. He modified the process slightly and got the bacteria
to produce butyl alcohol (2432; 2433).
Gustav Georg Embden (DE) and Fritz Oscar Laquer (DE) discovered a
compound formed from glycogen (fructose-1, 6-diphosphate) as a metabolic
intermediate in muscle. They named it lactacidogen (691; 692).
Gustav Georg Embden (DE) and Fritz Oscar Laquer (DE) discovered
that if the hexose diphosphate from a yeast alcoholic fermentation is added to
press juice from muscle that lactic acid is produced. This strongly suggested
that the pathways of carbohydrate breakdown in the alcoholic fermentation by
yeast and the lactic acid glycolysis by muscle are very similar (691; 693).
Charles Robert Harington (GB) and George Barger (GB) were able to
synthesize thyroxine (996; 997).
Rosalind Pitt-Rivers (GB), Jack Gross (CA), and West R. Trotter (GB)
synthesized tri-iodothyronine (the T3 hormone) which was biologically more
active than thyroxine (936-938).
Alfred
Franklin Burgess (US) oversaw moth work in the United States through the Plant
Quarantine and Control Administration. They used lead arsenate for control of the
gypsy moth (Lymantria dispar) in
Massachusetts, US (328).
Edna Steinhardt (US) and Marie Grund (US) neutralized the growth
of vaccinia on rabbits' skin using convalescent serum (2134).
Thomas Lewis (GB) and Marcus A. Rothschild (GB) described how the
excitatory process in the dog's heart first reveals itself in the region of the
sino-auricular node then spreads from this node in every direction, progressing
to all the margins of the musculature (1406).
Alexander Forbes (US) and Alan Gregg (US) made a systematic
analysis of nerve impulses originating from the central nervous system and
compared them with those evoked by artificial stimulation of a peripheral nerve.
Their conclusion was that nerve impulses are always of the same nature
regardless of their origin (803).
Francis Arthur Bainbridge (GB) demonstrated that an increase in
pressure on the venous side of the heart results in an increase of heart rate
due to the inhibition of vagal influences and the excitation of some accelerator
mechanisms (102).
Arnold Theiler (CH-ZA), Henry H. Green (ZA), and Philip Rudolph
Viljoen (ZA) were the first to assert that the nutritive requirements of the
ruminants are quite different from the omnivores and carnivores. They stated,
“We … think it is at least possible that the vitamin requirements of cattle are
so low that they may even be covered indirectly by synthesis carried out by the
extensive bacetrial flora of the intestines” (2206).
Otto Knut Olof Folin (SE-US) and Willey Glover Denis (US)
developed excellent methodology for the determination of phenols and conjugated
phenols. They concluded from their studies of blood and urine that by no means
can all the phenols formed in the colon and absorbed into the blood be
conjugated and detoxified (799).
Mac H. McCrady (US) developed the most probable number, multiple-tube fermentation technique as a
quantitative approach for analyzing water samples for coliforms (1542).
Richard Benedikt Goldschmidt (DE-US) was the first to successfully
grow insect cells in vitro (896; 897).
Paradichlorobenzene was first recommended in the U. S. for control
of clothes moth and carpet beetles (2050).
Constantine Janicki (PL) coined the term karyomastigont to refer to a conspicuous organellar system he
observed in certain protists: the mastigont (“cell whip”, eukaryotic flagellum,
or undulipodium, the [9 (2) +(2)] microtubular axoneme underlain by its [9 (3)
+ 0] kinetosome) attached by a nuclear connector or rhizoplast to a nucleus. He
observed this structure in highly motile trichomonad symbionts in the
intestines of termites where karyomastigonts dominate the cells (1177).
Joel B. Dacks (CA) and Rosemary J. Redfield (CA) reported that the
karyomastigont is an ancestral
feature of eukaryotes present in early branching protists (530).
Thomas Hunt Morgan (US), Alfred Henry Sturtevant (US), Calvin
Blackman Bridges (US), and Hermann Joseph Muller, Jr. (US) had their book, The Mechanism of Mendelian Heredity,
published (1633).
Calvin Blackman Bridges (US), in 1915, accidently discovered the mutant bithorax (bx) in Drosophila.
The fly halteres (the second pair of fly 'wings' , very tiny structures,
evolutionary remnants of a 4-winged ancestor) are transformed into full-fledged
wings. This mutation was coined 'homeotic', William Bateson's word for a
malformation that substitutes the pattern of a region for that of a different
one such as changing sepals into petals in a flower. Bridges' discovery
was first reported by Dan L. Lindsley (US) and Ellsworth H. Grell (US) (1420).
Thomas Hunt Morgan (US) and his colleagues settled decisively the
mechanism of sex determination in Drosophila
and based on evidence concerning eye color control in Drosophila they hypothesized the possibility that genes could have
multiple alleles (1633).
James Allen Nelson (US) made an extensive study of the embryology
of the honeybee, Apis mellifera Linn (1692).
Frederick William Twort (GB) discovered a transmissible, and
filterable agent that destroys bacteria producing a phenomenon on agar plates
he called glassy transformation. He
speculated that this agent might be virus or an enzyme (2251). At about
this same time Félix Hubert d’Herelle (CA) observed this same filterable disease of bacteria while in
Mexico studying diarrhea of locusts (527). Two years
later bacterial viruses were independently discovered by Félix Hubert d’Herelle
(CA) and he named them bacteriophage (from the Gk. phagein, to devour) (526).
André Gratia (BE) published his work on phages of Staphylococcus and E. coli (914; 915).
André Gratia (BE) and Sara Dath (BE) demonstrated that cultures of
organisms designated as Streptothrix,
now known to be actinomycetes, are capable of dissolving living and dead
bacterial cells (918).
André Gratia (BE) developed a therapeutically effective
preparation that Maurice Welsch (BE) named actinomycetin (917; 2436). Actinomycetin turned out to be a mixture
of bacterial wall dissolving enzymes.
André Gratia (BE) described colicin V, the first among the
bacteriocins, a class of antibiotics shown to be related to bacteriophages (916).
Hideyo Noguchi (US) found that vaccinia virus freed from all
associated bacteria by means of suitable disinfecting agents could be
propagated in a pure state in the testicles of rabbits and bulls (1735).
Ernst Berliner (DE) described a sporeforming bacterium, which he
named Bacillus thuringiensis,
isolated from diseased larvae of the Mediterranean flour moth, Ephestia kühniella Zell (204).
David Shepherd (US) was the first to use this bacterium as a
natural control of an insect pest, the slender-horned flour beetle, Echocerus cornutus (2055).
John Henry Porteus Graham (GB) described trench fever in the medical literature for the first time. He
characterized it as relapsing
febrile illness of unknown origin (913).
George H. Hunt (GB) and Alan C. Rankin (CA) dubbed it trench fever less than two months later (1127). It has
also been called five-day fever, quintan fever, and urban trench fever.
John William McNee (GB), Arnold Renshaw (GB), E.H. Brent (GB), and
Wilmot Herringham (GB) described human experimentation on enlisted volunteers
and showed that trench fever is transmitted by whole blood, but not by serum,
and is most likely carried "by one of the common flies or parasites found
in the trenches” (1553).
J. William Vinson (US), Henry S. Fuller (US), Gerardo Varela (MX),
and Claudio Molina-Pasquel (MX) demonstrated that trench fever is transmitted
by the body louse and caused by the bacterium Rickettsia quintana (2289; 2297; 2298).
Erich August Hübener (DE), Hans Conrad Julius Reiter (DE), Paul
Theodor Uhlenhuth (DE), Walther Fromme (DE), Ryokichi Inada (JP), Yutaka Ido
(JP), Rokuro Hoki (JP), Renjiro Kaneko (JP), and Hiroshi Ito (JP) discovered
the spirochete Spirochaeta icterohaemorrhagiae
to be the etiological agent of infectious
jaundice, also called Weil’s disease.
They found that it is usually transmitted to man from infected rats (1121; 1146; 2257).
Ido Yutaka (JP), Rokuro Hoki (JP), Hayozo Ito (JP), and Hidetsune
Wani (JP) found that rats are the carriers of Leptospira icterohaemorrhagiae (2556).
The first director of the International Health Board of the
Rockefeller Foundation, Wickliffe Rose (US) appointed William Crawford Gorgas
(US) to head the Yellow Fever Commission.
Gorgas would effectively eliminate malaria and yellow fever in the Panama Canal
Zone by eradicating the Aëdes and Anopheles mosquitoes.
Francis Peyton Rous (US) and Joseph R. Turner (US) developed the
simple finger-prick method of cross matching blood, which enables one to
determine within a few minutes whether the blood of a donor is suitable for
transfusion (1941).
Richard Weil (US) demonstrated the feasibility of refrigerated
storage of anticoagulated blood. He found that it could be stored for 2 days
and still be effective when transfused into guinea pigs and dogs, which had
lost blood (2423).
Francis Peyton Rous (US) and Joseph R. Turner (US) used rabbits to
demonstrate that, with certain additives and proper treatment, citrated blood
can be stored for 14 days and still be successfully transfused (1942).
William Maddock Bayliss (GB) expressed the view which eventually
prevailed. Hormones are produced in particular organs, carried in the blood
current, act as chemical messengers, and influence cell processes in distant
organs. They provide chemical coordination of the organism, working side by
side with the nervous system (171).
Abbie E.C.
Lathrop (US) and Leo Loeb (US) reported the influence of internal secretions
from the corpus luteum (ovarian
follicles) on the development of spontaneous tumors in mice. Their study showed
that tumor incidence was delayed and reduced from 60–90% to 9% in female mice
castrated before 6 months of age. As it was already known that the corpus luteum secreted an
uncharacterized substance that induced growth of the breast during pregnancy,
the authors speculated that this chemical might be involved in tumor formation (1359).
William S.
Murray (US) supported the findings of Lathrop and Loeb (1676; 1677).
Edgar V. Allen (US) and Edward Adelbert Doisy (US) demonstrated in
mice and rats that ovarian follicles influence the estrous cycle by releasing a
hormone, which they called oestrin
(estrogen) (36).
Edgar V. Allen (US) reported that “menstruation is a catabolic
process due to the temporary absence of ovarian follicular hormone or its
decrease below a subliminal amount after its anabolic influence has induced the
growth of a certain amount of genital tissue” (35).
Elwood
Vernon Jensen (US) discovered the estrogen receptor (ER). He devised an
apparatus that tagged it with tritium — a radioactive form of hydrogen — at an
efficiency level that had not previously been achieved. This innovation allowed
him to detect a trillionth of a gram of estradiol (1182).
Elwood
Vernon Jensen (US), George E. Block (US), Sylvia Smith (US), Kay Alvin Kyser (US), and Eugene R.
DeSombre (US) studied the effect of adrenalectomy on human breast cancer. They
found that breast tumors fall into two categories — ER-rich and ER-poor — and
patients who had tumors with a high level of ER expression were more responsive
to hormone-ablative therapy. This led Jensen to propose that the ER status of a
tumor could predict the response to therapy (1183).
Virgil Craig
Jordan (US) and Tim Jaspan (US) showed that long-term tamoxifen treatment targeted to the estrogen receptor (ER) could
successfully treat and prevent rat mammary cancer (1209).
Bernard
Fisher (US), Joseph P. Costantino (US), D. Lawrence Wickerham (US), Carol K.
Redmond (US), Maureen Kavanah (US), Walter M. Cronin (US), Victor Vogel (US),
André Robidoux (US), Nikolay Dimitrov (US), James Atkins (US), Mary Daly (US),
Samuel Wieand (US), Elizabeth Tan-Chiu (US), Leslie Ford (US), Norman Wolmark
(US), and other National Surgical Adjuvant Breast and Bowel Project
Investigators found that tamoxifen
decreases the incidence of invasive
and noninvasive breast cancer. Despite side effects
resulting from administration of tamoxifen, its use as a breast cancer
preventive agent is appropriate in many women at increased
risk for the disease (777).
Maud Slye
(US), in controlled breeding experiments with mice, found that certain mice are
more susceptible to cancer whereas others are not. She attempted to extrapolate
her mouse results to humans (2080; 2081).
Frédéric Justin Collet (FR) described a disorder he called glossolaryngoscapulopharyngeal hemiplegia,
which was later to be named Collet's
syndrome. It results from a lesion of cranial nerves IX, X, XI, and XII,
resulting in paralysis of the vocal cords, palate, trapezius muscle and
sternocleidomastoid muscle. It also results in anesthesia of the larynx,
pharynx and soft palate. This condition is sometimes referred to as Collet-Sicard syndrome, named in
conjunction with Jean-Marie-Athanase Sicard, who provided a description of the
disorder independent of Collet (453; 2069).
Jules Tinsel (FR) discovered Tinel's sign, which is a way to detect
irritated nerves. It is performed by lightly tapping (percussing) over the
nerve to elicit a sensation of tingling or "pins and needles " in the
distribution of the nerve (2224-2226). Note: Although most frequently
associated with carpal tunnel syndrome Tinel's sign is a generalized term and
can also be positive in ulnar nerve impingement at the wrist (Guyon's canal
syndrome), where it affects the other (ulnar) half of the fourth digit and the
fifth digit.
Bertram Welton Sippy (US) developed a method for medical care of
gastric and duodenal ulcers by accurately protecting the ulcer from gastric
juice corrosion until healing of the ulcer takes place (2077).
Henry McIlree Williamson Gray (GB) offered a methodology for early
treatment of war wounds (920).
Thomas Clifford Allbutt (GB) proved that angina is caused by narrowing of the coronary artery (33).
William Edward Fothergill (GB) performed
an anterior colporrhaphy and its combination with amputation of the cervix as a
single operation (813). Note: Colporrhaphy
is a surgical procedure in humans that repairs a defect in the wall of the
vagina.
Booker Taliaferro Washington (US) died of systemic
"hypertension so severe and so protracted that by the time of his final
hospitalization, it had destroyed his kidneys, damaged his heart and brain and
would shortly take his life." Born into slavery in 1856, he died as a
famous, influential, and greatly admired American who had guided the creation
and maturation of the Tuskegee Institute from 1881 until his death in 1915 (1467). He was cared for by some of
America's best physicians who had the tools but lacked the knowledge to
effectively manage hypertension. It was not until 1946 that pentaquine; the first drug shown to have
anti-hypertensive activity was available.
Otto Ludwig Binswanger (DE), during the conflict of WW I, tried to
identify risk factors for the disorder we now know as
post-traumatic-stress-disorder (PTSD) (219).
Charles S. Myers (GB) kept a diary during World War I, which became
the basis of the first systematic investigation of combat-related neurosis. It
was Myers who coined the phrase "shell shock" to call attention to
the importance of the physical effects of bursting shells in creating the
disorder (1678; 1679).
Charles William Beebe (US) hypothesized that the ancestors of
birds passed through what he referred to as a “Tetrapteryx stage”, with wings
on both their front and hind limbs. Beebe based this theory on his observation
that the hatchlings and embryos of some modern birds possess long quill
feathers on their legs, which he regarded as an atavism; he also noticed vestiges
of leg-wings on one of the specimens of Archaeopteryx (177). Note: In 2003, Beebe's
Tetrapteryx hypothesis was supported by the discovery of Microraptor gui,
a small feathered dinosaur which possessed asymmetrical flight feathers on both
its front and hind limbs (1835).
The Proceedings of the
National Academy of Sciences of the United States of America was first
published.
1916
Karol Mayer (PL) described the principles and
practical uses of tomography (1524).
Andre-Edmund-Marie Bocage (FR) applied for a patent on a machine
in which both x-ray source and film were moved reciprocally and
proportionately, i.e., tomography. He had designed a linear device,
pluri-directional device and a curvilinear device (237).
Allan MacLeod Cormack (ZA-US) developed mathematical theory and
built machines to achieve two-dimensional x-ray image reconstruction, i.e.,
axial tomagraphy (468; 469).
Gilbert Newton Lewis (US) was the first to suggest that a bond
between two elements can be formed not only through the transfer of electrons,
but also through the sharing of electrons. Each bond in an organic compound
represents the sharing of one pair of electrons, the result being that all
atoms achieve the stable electronic configuration of the inert gas atom (1398).
Alfred Stock (DE) and Karl Somieski (DE) were the first to use the
term ligand (ligare L.). It was in
relation to silicon chemistry (2145).
Carl Alexander Neuberg (DE-US) coined the term hydrotropy to
describe the increase in the solubility of a solute by the addition of fairly high
concentrations of alkali metal salts of various organic acids. However, the
term has been used in the literature to designate non-micelle-forming
substances, either liquids or solids, capable of solubilizing insoluble
compounds (1702).
Heinrich Otto Wieland (DE), Hermann Sorge (DE), Hedwig Stender
(DE), Albert Kulenkampff (DE), Franz Adickes (DE), Werner Mothes (DE), Gustav
Reverey (DE), and Richard Jacobi (DE) studied the three bile acids which had
been isolated and showed how closely related they are in basic structure and
the detailed way they differ. The molecular skeleton they showed to be
steroid—term not yet coined— in nature, related to the well-known molecule,
cholesterol (2460; 2463-2466; 2468-2476).
Heinrich
Otto Wieland (DE) later suggested a structure for cholic acid (2467).
Fédérico Battelli (IT), Lina Salomonovna Stern (LT-CH-RU), and
Torsten Ludvig Thunberg (SE) demonstrated that anaerobic suspensions of minced
animal tissues catalyze the transfer of hydrogen atoms from certain organic
acids known to occur in cells—especially succinic, malic, and citric acids—to
the reducible dye methylene blue, giving its colorless reduced form. Enzymes
catalyzing such reactions were named dehydrogenases (157; 161; 162; 2217; 2218). In later
years several investigators using manometric measurement of the
oxygen-utilization rate of minced-tissue suspensions found that succinate,
fumarate, malate, and citrate are rapidly oxidized to carbon dioxide by
molecular oxygen (2390).
Heinrich Otto Wieland (DE) had named these enzymes dehydrogenases (2461).
Leon Popielski (PL) discovered the role of histamine
(beta-imidazolylethylamine) as an agent increasing the secretion of gastric
hydrochloric acid (1829).
Harold Ackroyd (GB) and Frederick Gowland Hopkins (GB) concluded
that a rat’s diet must contain either arginine or histidine (11).
William Cumming Rose (US) and Gerald J. Cox (US) discovered that
histidine is an essential amino acid in rats (1925).
Elliott Proctor Joslin (US) and Francis Gano Benedict (US), in 1908,
carried out extensive metabolic balance studies examining fasting and feeding
in patients with varying severities of diabetes. They noted a 20 percent
decrease in the mortality of patients after instituting a program of diet and
exercise (1210).
William Beecroft Bottomly (GB) noted that incubation of peat with
a mixed culture of aerobic soil bacteria resulted in stimulation of wheat
seedling's growth in this peat (257).
August J.P. Pacini (US) and Dorothy Wright Russell (US)
demonstrated the formation of a bacterial substance capable of stimulating
animal growth. They showed that a water extract of the typhoid bacillus
produced a marked growth response in rats ingesting a "vitamin B"-
deficient ration (1774). These two papers offer evidence
that microorganisms produce factors beneficial to the nutrition of plants and
animals.
Walter Abraham Jacobs (US) was the first to observe the germicidal
properties of quaternary ammonium compounds (1167).
Søren Peder Lauritz Sørensen; Søren Peer Lauritz Sørensen (DK),
Margrethe Høyrup (DK), S. Goldschmidt (DK), and S. Palitzsch (DK), during
1916-17, published a series of papers in which they reported the molecular
weights of various proteins based on measurements of osmotic pressure. Although
they underestimated their size their work pointed the way to visualizing
proteins as having molecular weights in the 10s of thousands (2101; 2102).
Jay McLean (US) found that certain phosphatides and fat-soluble
extracts from fresh brain, heart, and liver tissues accelerated blood clotting,
but after storage for some months they lost their coagulant activity, and
indeed were now acting as anticoagulants. Many consider this to represent the
discovery of heparin (1550).
William Henry Howell (US) and L. Emmett Holt, Jr. (US) coined the
term heparin to denote the presence
of a fat-soluble anticoagulant in the liver (Gk. hepar) (1118).
William Henry Howell (US) later claimed to isolate heparin in such a way that it could not
be the same substance as those isolated in either 1916 or 1918 (1116). Priority
of discovery has yet to be settled, however, James A. Marcum in a very
scholarly article credits Howell with the discovery (1502).
D.W. Gordon Murray (CA), Louis B. Jaques (CA), Thomas Stewart
Perrett (CA), and Charles Herbert Best (CA), beginning in 1934, conducted a
series of tests on heparin in dogs for both "the prevention of venous
thromboembolism" and also "for its use in vascular surgery,"
thereby becoming the first to demonstrate that such procedures could be
performed with the assistance of heparin. They used heparin prophylactically
against deep-vein thrombosis following surgery in humans (1668; 1669).
Erik Jorpes (SE) and Clarence Crafoord (SE) conducted similar
experiments in the Karolinska Institute in Stockholm (489; 490).
George Henry Alexander Clowes (US) suggested that watery and
lipoidal phases might exist together in a cell membrane by the action of
balanced ions; postulating phase-reversal such as one can obtain in oil-water
emulsions by modifying the critical balance of sodium and calcium ions, or
other monovalent and divalent cations (436).
Henry Josef Quayle (US) reported resistance to cyanide fumigation
in the California red scale, Aonidiella
aurantii. This is the first known case of insect resistance to chemicals (1840-1842).
Charles C. Macklin (CA) showed that when two nuclei in a
binucleate heterokaryon enter mitosis together, the two sets of chromosomes
commonly join a single metaphase plate and are then systematically distributed
to two mononucleate daughter cells each of which can subsequently be shown to
contain within a single nucleus the chromosomes of both parents (1466).
Hermann Joseph Muller (US) reported his definitive work on
crossing over among chromosomes (1653).
Frank Rattray Lillie (US) demonstrated that sex hormones are
concerned in the embryonic differentiation of sex characters among vertebrates.
He showed that when the fetal membranes of male and female calf embryos become
united in the uterus, so that the blood vessels of the two are continuous, the
female embryo is modified in the male direction, forming the so-called
freemartin (1417).
Kenzo Futaki (JP), Ftsuma Takaki (JP), Tenji Tangiguchi (JP), and
Shimpachi Osumi (JP) discovered that Spirillum
minor is the etiological agent of rat-bite
fever or sodoku (841).
Hans Conrad Reiter (DE) described a disease he called spirochetosis arthritica. Currently it
is called Reiter syndrome (1867).
Francis Peyton Rous (US) and Frederick S. Jones (US) were the
first to liberate individual cells from plasma clot cell culture — using the
enzyme, trypsin — with the objective
of growing the individual cells in vitro (1939).
James B. Murphy (US) appears to have been the first to observe a graft-versus-host reaction. He was
inoculating the chorioallantoic membranes of 7-day embryos with adult chicken
spleen and bone marrow. He did not correctly interpret the phenomenon (1663). This has
also been called runt disease.
William J. Dempster (GB), Morten Simonsen (DK), J. Buemann (DK), Allan
Gammeltoft (DK), F. Jensen (DK), and K. Jorgensen (DK) were the first to
correctly interpret the graft-versus-host
reaction as the graft mounting a response to the host (583; 2073; 2075).
David W.H. Barnes (GB), Michael J. Corp (GB), John Freeman Loutit
(GB), and Frank E. Neal (GB) described graft-versus-host
disease (GVHD) in mice (131).
Morten Simonsen (DK), Rupert Everett Billingham (GB-US), and
Leslie Brent (GB) independently demonstrated graft-versus-host disease (GVHD)
in chick embryos (manifested as pancytopenia)
and mice (runt disease) after
intravenous injection of adult spleen cells (217; 2074).
Alan G. Cock (GB) and Morten Simonsen (DK) introduced the phrase graft-versus-host reaction to describe
the direction of the immunological damage caused by introduction of
immunologically competent cells into an immunocompromised host (448).
Rupert Everett Billingham (GB-US) proposed 3 conditions required
for the development of GVHD, as follows: (1) the graft must contain
immunologically competent cells, (2) the host must possess important transplant
alloantigens that are lacking in the donor graft so that the host appears foreign
to the graft, and (3) the host itself must be incapable of mounting an
effective immunological reaction against the graft (216).
Henry Edward Crampton (US) described geographical races of the
snail Partula in Tahiti. Beginning around 1916, he studied this snail over a
period of 50 years, concluding (1) that the variation in the
color, banding, and chirality of the shells was Mendelian in nature, (2) that
these characters are unaffected by selection, and (3) that active evolution was
demonstrable in the short time between his successive samples. Although the
second and third of these conclusions appear to be badly flawed, the Partula
studies nevertheless exerted an important influence on the modern synthesis of
evolutionary biology (496). Note: The last member of the snail species Partula turgida died at the London Zoo in 1996. Also known as the
Polenesian Tree Snail, it was wiped out in the wild in a bungled attempt to
control a nuisance snail with an introduced species.
George Edward Nicholls (AU) discovered that the vertebral column
is important in classifying Salientia (frogs, toads, and tree toads) (1719).
Edward Sylvester Morse (US), George H. Hudson (US), and John B.
Buck (US) were among the first to report synchronous flashing by fireflies. In
1988 Buck defined this behaviour (321; 322; 1123; 1637).
Frederic Edward Clements (US) stated his ecological theory, that
when a geographical area is newly vacated it becomes occupied by a succession
of species gradually leading to a climax community and the plant community can
be treated as a complex organism undergoing a life cycle and evolutionary
history analogous to the individual organism (424; 425). See, Cowles, 1899.
Delafield du Bois (US) and Eugene F. du Bois (US) introduced a
formula to estimate the approximate surface area of the body if height and weight
are known (632).
Arthur Isaac
Kendall (US) has shown that the total abstinence from food for thirty-one days
did not eliminate the bacteria from the lower intestine of man (1233).
Jerry Edward Wodsedalek (US) was the first to provide an
explanation of the male mule's sterility. He studied the testes of a number of
mules and concluded that there was a block in meiosis due to an incompatibility
between the paternal (donkey) and maternal (horse) chromosomes (2527).
Francis Peyton Rous (US) and Joseph R. Turner (US) determined that
rabbit blood cells could be useful in transfusion after storage for a long time in vitro. They suggested that kept
human cells could be profitably employed in the same way (1943).
Joannes Gregarius Dusser de Barenne (NL-US) did considerable work on
posture and was a pioneer in demonstrating the major functional subdivisions of
the sensory cortex. His contributions to the knowledge of the analysis of the
interaction of various cortical and subcortical regions of the brain were
considerable (651; 652).
Ferdinand-Jean Darier (FR) was the first
to describe erythema anulare centrifugum,
a skin lesion that consists of redness (erythema) in a ring form (anulare),
which spreads from the center (centrifugum) (548).
James
Walker Dawson (GB) provides the greatest pathological account of multiple
sclerosis in the English language. After summarizing the literature—and the
debate, which went on then as now, about whether the disease is “inflammatory”
or “developmental” (degenerative)—Dawson reviews the histology of nine personal
cases. Illustrating the text with 22 colour and 434 black-and-white
figures in 78 plates, Dawson describes the form, symmetry, distribution,
and histological features of several types of lesions and provides an analysis
of changes in each cellular element of the nervous system—nerve cells and their
axons, neuroglia, blood vessels, and lymphatics. Dawson then attempts a
clinicopathophysiological correlation. (Weakness in the legs is consistent with
the extensive spinal cord gliosis, for example.) He also characterizes old and
acute lesions. Dawson summarizes his ideas on plaque formation around brain
inflammation to include a sequence of events that, although not disease
specific, produces recognizable clinical characteristics (559).
Harris
Peyton Mosher (US) initiated the modern method of trephining and draining
inflammatory processes of the brain (1641).
Maurice Villaret (FR) described a retroparotid space syndrome
that combined ipsilateral paralysis of the last four cranial nerves (IX, X, XI,
XII) and Horner syndrome (enophthalmos, ptosis, miosis) (2296). This was
later named Villaret’s syndrome.
The first record of carbolineum being used for control of poultry
parasites appears (a heavy oily substance distilled from an anthracene-oil or
creosote-oil fraction of coal tar and used as a wood preservative,
disinfectant, or insecticide). Calcium arsenate was discovered effective for control
of the boll weevil. Sodium fluoride was discovered to be effective for control
of lice on poultry (2050).
Michel Weinberg (FR) and Pierre Séguin (FR) discovered Bacillus histolyticus (Clostridium histolyticum) in war wounds.
This organism can liquefy living tissue to a remarkable degree (2425; 2426).
George Harrison Shull (US) founded the journal Genetics.
1917-1919
The most lethal influenza pandemic ever recorded killed an
estimated 20 to 40 million people worldwide. An estimated
675,000 Americans died of influenza during the pandemic, ten times as many as in the world war. Of the U.S. soldiers who
died in Europe, half of them fell to the influenza virus and not to the enemy
(Deseret News). Its spread was facilitated by troop movements in the closing
months of World War I. Mortality rates were unusually high for flu, especially
among young, otherwise healthy adults. Deaths occurred both from the flu itself
and from secondary pneumonia (1296). This was
the worst epidemic since the Middle Ages. It was called the Spanish Flu because
of where it was first properly reported.
René Dujarric de la Rivière (FR), Charles Jules Henri Nicolle (FR), Charles Lebailly (FR), H. Graeme Gibson (GB),
F.B. Bowman (GB), J.I. Connor (GB), Aristides Marques da Cunha (BR), Octavio de
Magalhaes (BR), Olympio da Fonseca (BR), Hugo Selter (DE), T. Yamanouchi (JP),
K. Skakami (JP), S. Iwashima (JP), John Rose Bradford (GB), E.F. Bashford (GB),
and J.A. Wilson (GB) proposed that the causative agent was a virus,
based on properties of infectious
extracts from diseased patients (267; 510; 566; 870; 1720; 1721; 2047; 2550). Noteworthy,
is the work of Nicolle and Lebailly in Paris. They filtered out the bacteria
from bronchial expectoration of an influenza patient and injected the filtrate
into the eyes and nose of two monkeys. The monkeys developed a fever and a marked
depression. The filtration was later administered to a volunteer subcutaneously
who developed typical signs of influenza. They reasoned that the inoculated
person developed influenza from the filtrate since no one else in their
quarters developed influenza. Note: These scientists followed Koch's
postulates as they isolated the causal agent from patients with the illness and
used it to reproduce the same illness in animals. Most medical authorities at
the time thought bacteria caused the disease influenza.
1917
Frederick B. La Forge (US) and Clause S. Hudson (US) isolated
sedoheptulose from Sedum spectabile, an
ornamental plant (1325).
Hermann Staudinger (DE), in a 1917 lecture to the Swiss Chemical
Society, speculated for the first time that "high molecular
compounds" consist of covalently bonded long-chain molecules, and first
proposed the idea that polymers are giant molecules whose small-molecule
constituents are linked together in long chains by chemical bonds no different
from chemical bonds in ordinary organic compounds.
He postulated that rubber and similar materials are composed of
very large molecules, called macromolecules, that they are held together by
chemical bonds — the same forces that hold smaller, lighter molecules together
and that the unusual strength and elasticity of polymers is due to their great
length and high molecular weight. A very radical idea at the time (2127).
Hermann Staudinger (DE) and Jakob Fritschi (DE) proposed that
materials such as rubber and cotton are composed of long chain-like molecules
containing thousands of atoms, joined together by the same type of covalent
bonds that joined the atoms of smaller molecules. They introduced the concept
of macromolecules (a term which they coined) and polymerization (2128).
Karl Landsteiner (AT-US) described antigens as distinct,
recognizable atomic groups (1345).
Laszlo (Ladislaus) Berczeller (AT-HU), E. Szegö (HU) and M. Seiner
(HU) were probably the first to point out the significance of surface tension
in the inactivation of biological substances (196; 197).
James N. Currie (US) developed a method of producing large
quantities of citric acid by growing Aspergillus
niger in a growth-limiting medium rich in iron (513).
Martinus Willem Beijerinck (NL) proposed that genetic characters
function by way of controlling the formation of enzymes (183).
Thomas Hunt Morgan (US) presented his theory of the gene (1628).
Harold H. Plough (US) showed that crossing over in Drosophila occurs during the early
synaptic stage (zygotene) (1825).
Otto Renner (DE) suggested that many of the oenotheras (evening
primroses) are permanent heterozygotes persisting in this condition because of
balanced lethal factors (1870-1873).
Ralph Erskine Cleland (US) discovered the presence of ring
chromosome formation during meiosis in Oenothera
(the evening primrose) (418-420).
John Belling (US) explained the formation of ring chromosomes in Datura stramonium (Jimson weed) as due
to a reciprocal translocation between two nonhomologous chromosomes. He
determined that a plant possessing two original chromosomes and two that had
interchanged segments, would exhibit a circle of four chromosomes because of
their pairing requirements (190). This led
quickly to an understanding of the puzzling genetic behavior exhibited by these
organisms with ring chromosomes.
Ralph Erskine Cleland (US) summarized his and his colleagues’ work
on Oenothera in his book, Oenothera:
Cytogenetics and Evolution (421).
Charles Benedict Davenport (US) reported that apparent blending
inheritance of stature is due merely to the presence of multiple factors (554).
Else Hirschberg (DE) and Hans Winterstein (DE) discovered that
nervous tissue requires glucose (1085).
Calvin Blackman Bridges (US) began a series of studies in which
phenotypes within Drosophila were
related to translocations or deficiencies of parts or of whole chromosomes.
Eventually it became possible to associate each of the four groups of linked
genes with one of the four pairs of chromosomes, and in some cases, to narrow
the location of particular genes to small segments of chromosome (290; 292; 295).
Charles-Edward Amory Winslow (US), Jean Broadhurst (US), Robert
Earl Buchanan (US), Charles Krumwiede, Jr. (US), Lore Alford Rogers (US), and
George H. Smith (US) described the bacterial genus Erwinia. The genus is named in honor of Erwin Frink Smith (2520).
Stefan Kopec (PL) suggested that the brain of the gypsy moth (Lymantria dispar L.) caterpillars
produces a hormone that initiates pupation and maintains pupal development.
This represents the first time that insect development was associated with
hormones (1302-1304). Today this
is called prothoracicotropic hormone or PTTH. It stimulates a paired thoracic
endocrine organ, the prothoracic gland, to synthesize and release ecdysone (a molting hormone). Ecdysone is the steriod hormone in insects,
which is indispensable for insect development.
Leonhard Hess Stejneger (NO-US) authored Check List of North American Amphibians and Reptiles, which had a
profound positive impact on the study of herpetology in North America (2136).
Warren R. Sisson (US) reported that under normal conditions of
health duodenal contents contain very few live microorganisms (2078).
Charles Rupert Stockard (US) and George Nicholas Papanicolaou
(Greek-US), by applying cytological methods to vaginal scrapings, established
criteria for the determination of the various phases of the estrous cycle in
guinea pigs (2148).
Joseph Abraham Long (US) and Herbert McLean Evans (US) used
vaginal scrapings from the albino rat to elaborate many of the details of the
estrous cycle and its associated phenomena (1437).
George Nicholas Papanicolaou (Greek-US) used vaginal smears to
reveal the sexual cycle in the human female (1782).
This work, along with the earlier work in guinea pigs by Stockard
and Papanicolaou, directed attention to the ovarian-uterine cycle as a general
phenomenon, which is predictable, thus allowing the identification of the
various phases of the cycle in animals whose sexual rhythm was unknown.
André Fouchet (FR) developed a method for demonstrating the
presence of bilirubin in feces, urine, and serum
(814).
Alice Hamilton (US) wrote Industrial
Poisons Used or Produced in the Manufacture of Explosives and Industrial Poisons in the United States.
These books were an outgrowth of her pioneering studies of industrial diseases
and industrial toxicology (973; 974).
Donald Dexter van Slyke (US), Glenn E. Cullen (US), Reginald Fitz
(US), Edgar Stillman (US), William Christopher Stadie (US), Walter W. Palmer
(US), Julius Sendroy, Jr. (US), and S. Seelig (US) published papers on acidosis
from 1917-1934. Van Slyke reasoned that if incomplete oxidation of fatty acids
in the body leads to the accumulation of acetoacetic and beta-hydroxybutyric
acids in the blood then a reaction would result between these acids and the
bicarbonate concentration in blood plasma. They devised a volumetric glass
apparatus that allowed the quantitative determination of bicarbonate in the
blood. This permitted early diagnosis and therapy of patients with diabetes.
The 1921 paper is a landmark in which chemical terms are used to describe
normal and abnormal variations in the acid-base balance of the blood (2278; 2281). This
apparatus was quickly adapted for the determination of blood oxygen and
percentage saturation of blood hemoglobin (2277).
Henry Drysdale Dakin (US), Walter Estell Lee (US), Joshua E. Sweet
(US), Byron M. Hendrix (US), and Robert G. LeConte (US) reported the
outstanding success of treating many different types of infected war wounds with
dichloramin-T (535). Note: The proper use of dichloramin-T was called the Carrel-Dakin
treatment because Alexis Carrel described the surgery that should preceed its
use.
Aaron S. Green (US) and Louis D. Green (US) reported excellent
success when using dichloramin-T as an antiseptic on the ocular conjunctiva (924).
Franz Ernest Christian Neumann (DE) was the first to postulate a
common stem cell for all hematopoietic cells. "It is evident, that a
continuing transformation of lymphoid cells into colored blood cells takes
place in the bone marrow during the whole life" (1717).
George Howard Parker (US) and Anne P. van Heusen (US) studied
behavioral responses of the brown bullhead catfish, Ameiurus nebulosus, to
metallic and non-metallic rods in water. They demonstrated these fish respond
to galvanic currents generated at the interface between metal and aquarium
water. Parker and van Heusen did not realize they were studying the
electrosensitivity of fishes that have—as we now know— distinct
electroreceptors (1788).
Hans Werner Lissmann (RU-DE-GB) studied electric discharges by Gymnarchus niloticus and other weakly
electric fish. He proposed that their discharges allowed them to locate nearby
objects of an electrical conductivity different from that of the surrounding
water by appreciating the distortion it causes to their electric field (1422).
Sven Dijkgraaf (NL), Adrianus
J. Kalmijn (NL-US),
Robert C. Peters (NL) and Frédéric van Wijland (NL) discovered that many fishes
not equipped with electric organs of any kind nevertheless have electrical
sensitivities equaling or even exceeding those of species specialized for
electrical orientation (597; 1218; 1811).
Adrianus J. Kalmijn (NL-US) performed experiments clearly
demonstrating that the shark Scyliorhinus
canicula and the ray Raja clavata
make biologically significant use of their electrical sensitivity. Therefore,
we are justified in accrediting these animals with an electric sense and in
designating the ampullae of Lorenzini as electroreceptors (1218). See, Lorenzini, 1678.
R. Eustace Montgomery (GB) discovered the Nairobi sheep disease
virus in Kenya (1611). Note: the first
nairovirus, the first tick-borne virus
C.N. Dandawate (IN) and K.V. Shah (IN) in north east India
isolated the Ganjam virus, which turned out to be a different strain of
the Nairobi sheep disease virus (542).
Cecil Charles Worster-Drought (GB) and Alex Mills Kennedy (GB)
described death due to circulatory disturbance and neural damage resulting from
fulminating meningococcal septicemia (2538).
Charles Morley Wenyon (GB) and Francis William O'Connor (GB)
described their inquiry into some problems affecting the spread and incidence
of intestinal protozoal infections among British troops and natives in the Near
East, with special reference to the carrier question, diagnosis and treatment
of amoebic dysentery and an account of three new human intestinal protozoa
including Endolimax nana (2440).
Arthur Robertson Cushny (GB) presented what he called the modern theory of renal secretion in
which he stated, “… the constituents of the plasma which I have termed
Threshold Bodies… are taken up by the cells of the tubules and return to the
blood, while the No-threshold substances, such as urea, are rejected and can
only escape by the ureter. Further, the threshold bodies are not absorbed
indiscriminately but in definite proportions, which are determined by their
normal values in the plasma; otherwise the kidney would eliminate waste
products but would fail to regulate the concentration of the threshold bodies
in the plasma. The cells lining the tubules thus absorb from the glomerular
filtrate a slightly alkaline fluid containing sugar, amino-acids and other
similar food substances, and chloride, sodium, and potassium in approximately
the proportions in which they are present in normal plasma, or in the
artificial mixtures which have been introduced for the perfusion of surviving
organs” (522).
Elmer Verner McCollum (US), Nina Simmonds (US), and Helen T.
Parsons (US) showed that xerophthalmia
in rats is due to lack of a fat-soluble substance which they named vitamin A (1537; 1538).
George Riddoch (GB) described a pathological condition in which
inattention to objects in one-half of the visual field was accompanied by
inability to recognize these objects (1890). This condition became known as Riddoch syndrome.
Charles Hunter (CA) and Gertrud Hurler (AT) described a hereditary
disturbance of mucopolysaccharide metabolism (1129; 1130). Later this became known as Hunter-Hurler syndrome with Hunter’s
syndrome X-linked while Hurler syndrome is autosomal recessive.
Thomas Chalmer Addis (GB-US) developed the concept of clearance
(the amount of blood “freed” from urea per unit time) (17). Note: Some consider this work to be the birth of modern renal
physiology.
Augustus Désiré Waller (FR-GB) published the first report of a
recording of cardiac electricity on the body’s surface; he called the recording
a cardiograph. Among his
contributions were the variability of the electrogram, the dipole concept that
led to isopotential mapping, and the vector concept (2385). This work
was first presented in 1887, at the International Congress of Physiology in
London.
Kanematsu Sugiura (US) and Gioacchino
Failla, (US) developed the first external-beam radium therapy device, known as
a “radium element pack.” It was used to treat cancers located in the chest,
brain, and abdomen (1176; 2179).
Henry Harrington Janeway (US) described the use of interstitial
irradiation for operable breast cancer instead of mastectomy. He stated,
"The use of radium can be offered to those patients who dread and refuse
operation and it should also be useful in cases where the wisdom of using the
knife is doubtful" (1560). Geoffrey Langdon Keynes (GB)
and Stamford Cade (GB) substituted high voltage x-rays for the radium needles (1245).
René Leriche (FR), in 1917, performed the first
periarterial sympathectomy, which resulted in the patient experiencing dramatic
relief 15 days later. The patient had complained of permanent and painful
paresthesia in the hand following a gunshot wound to the right axilla (1383). Sympathectomy was subsequently
found to be effective in various vasomotor disorders, Raynaud’s disease and
scleroderma.
D'Arcy Wentworth Thompson (GB) wrote On
Growth and Form, which led the way for the scientific explanation of morphogenesis,
the process by which patterns and body structures are formed in plants and
animals. Thompson's description of the mathematical beauty of nature and the
mathematical basis of the forms of animals stimulated many scientists (2209).
On February 3, the U.S. Congress established a National
Leprosarium in Carville, Louisiana.
Journal de Physiologie et de Pathologie Générale
was founded.
Annals of Medical History (New
York) was founded.
1918
Max Karl Ernst Ludwig Planck (DE) was awarded the Nobel Prize in
Physics in recognition of the services he rendered to the advancement of
physics by his discovery of energy quanta.
Carl Alexander Neuberg (DE-US) showed that a mild acid hydrolysis
of hexose diphosphate (Harden-Young ester)
yielded hexose monophosphate (Neuberg
ester). This hexose monophosphate was easily fermented by yeast juice and
would prove to be fructose-6-phosphate (1703).
Carl
Alexander Neuberg (DE-US) and Elsa Reinfurth (DE) found that by adding sodium
bisulfite to an actively fermenting culture of Saccharomyces they could cause
the yeast to excrete glycerol rather than ethanol (1713). Their process was the first
example of the large-scale manipulation of fermentation using a steering agent. The added
sodium bisulfite fixes to acetaldehyde blocking its use as electron acceptor.
The yeasts adapt by using dihydroxyacetone phosphate (DHAP) as electron
acceptor, producing glycerol-3-phosphate, then glycerol as waste product.
Otto Fritz Meyerhof (DE-US) discovered that the co-ferment (nicotinamide adenine
dinucleotide phosphate) (NADP) of yeast alcoholic fermentation is also present
in animal tissues. He defined co-ferment
as heat-stable, dialyzable, and a participant in the oxidation of
carbohydrates. This finding suggested that alcoholic fermentation and muscle
glycolysis might proceed along the same metabolic pathway (1577; 1578). See, Harden and Young, 1905.
Meyerhof found that the glycolytic system of muscle requires a co-ferment similar to the material
obtained from yeast (1593; 1595).
Carl Alexander Neuberg (DE-US), Elsa Reinfurth (DE), Julius Hirsch
(DE), Maria Kobel (DE), and Max Scheuer (DE), between 1918 and 1931, determined
that the yeast fermentation may be one of four types based on the major end
products: 1) ethanol, carbon dioxide, 2) glycerol, acetylaldehyde, carbon
dioxide, 3) glycerol, acetic acid, ethanol, carbon dioxide, 4) pyruvate,
glycerol (1280; 1281; 1707; 1710-1714).
Colin K. Watanabe (US) described the hypoglycaemic properties of
guanidine (2404).
Friedrich Meves (DE) proposed that mitochondria carry hereditary
material (1575).
Elvin Charles Stakman (US), John H. Parker (US), and Frank Joseph
Piemeisel (US) began the process of destroying the popular bridging host theory, which was believed to explain how many plant
parasites adapt to new hosts. They also set in motion studies that led to the
reduction of black wheat stem rust of wheat from a major plague of wheat
throughout the world to a relatively minor problem (2121).
Thomas Burr Osborne (US), Lafayette Benedict Mendel (US), Edna L.
Ferry (US), and Alfred J. Wakeman (US) discovered that the liver is the
principal storage organ for vitamin A (retinol) (1760).
Sewall Green Wright (US) used equilibrium principles in rejecting
a one-gene hypothesis for the inheritance of blue eye color in man (2542).
Ronald Aylmer Fisher (GB-AU) mathematically analyzed data on human
stature and other measurements and concluded that inheritance is better
explained as particulate rather than blending. He was the first to point out
that for natural selection to work inheritance had to be particulate and not blending. Polymorphic traits had been widely
viewed as a result of blending. In the 1930 reference he defined the true cost
of making a child as being measured in lost opportunities to make other
children. This opportunity cost he named parental
expenditure (778; 779).
Robert L. Trivers (US) used the same idea to elucidate sexual
selection, calling it parental investment (2235).
Johann Gregor Mendel (Moravian-CZ) was the first to demonstrate
that inheritance is particulate (1564-1566).
Nikolai Ivanovich Vavilov (RU), in 1918, stressed the importance
of biologic centers of origin such as China and India as reservoirs of
desirable genes, which can be incorporated into cultivated strains derived from
those regions (452; 467; 2290; 2291).
Rich Ege (SE) pointed out that when the oxygen in the air film of
diving insects and spiders is removed by diffusion into the trachea, additional
oxygen replaces it by diffusion from the water. Metabolic carbon dioxide leaves
by the reverse route, and thus we might have a permanent and adequate
underwater lung. However, the nitrogen pressure in the film must therefore
increase and the nitrogen diffuse into the water until the surface area becomes
reduced to such size that it can no longer support the metabolic demands of the
creature. It must now return to the surface, not to replenish it oxygen supply
but to replenish its nitrogen (664).
Lodewijk Bolk; Louis Bolk (NL) proposed the fetalization or neoteny theory which states that there are
evolutionary advantages to carrying certain infantile characteristics into
adulthood. An example found among the apes and man is the large brain to body size
ratio (243-245).
Edmund Beecher Wilson (US) said that Theodor Boveri (DE), “By the
slow and painstaking process of observation, experiment and analysis,
accomplished the actual amalgamation between cytology, embryology and
genetics—a biological achievement which … is not second to any of our time” (2500).
Ernest Henry Starling (GB) stated the law of the heart as follows, “In the first place, provided the
inflow remains constant, it seems to be immaterial to the heart whether it has
to contract against a resistance of 44 mm. Hg, or 208 mm. Hg. In each case it
puts out as much blood as it receives, so that the total outflow remains
constant whatever the arterial pressure. Of course, there is a limit which must
not be exceeded… The second fact, which results from this experiment, is that
the fraction of the total output of blood, which passes through the coronary vessels,
rises steadily with the height of the arterial pressure. This means that the
more work the heart has to do, the better it is supplied with blood, i.e., with
the oxygen and nutriment necessary to furnish it with energy…Within
physiological limits the larger the volume of the heart, the greater are the
energy of its contraction and the amount of chemical change at each
contraction… the energy of contraction, however measured, is a function of the
length of the muscle fibre” (2125).
J. S. Szymanski (DE) showed that animals can maintain 24-hour
activity patterns in the absence of external cues such as light and
temperature. These are now known as circadian
rhythms, or the biological clock (2189).
Franz Halberg (US), Maurice Bolks Visscher (US), and John J.
Bittner (US) along with Jürgen Aschoff (DE) developed an explanation of the
role that environmental factors play in the functioning of internal biological
clocks. Aschoff called these environmental factors zeitgeber, meaning time giver (65; 963).
Aaron B. Lerner (US), James D. Case (US), Yoshiyata Takahashi
(US), Teh H. Lee (US), and Wataru Mori (JP) succeeded in
isolating from bovine pineal glands the compound named melatonin (5-methoxy, N-acetyltryptamine). It was given this name
because of its blanching effect on melanophores in the skin of tadpoles (1385). See, Fiske, 1941.
Franz Halberg (US), Erna Halberg (US), Cyrus P. Barnum (US), and
John J. Bittner (US) were the first to use the term circadian to describe time rhythms in living creatures (derived
from circa meaning about and dies meaning day) (961; 962). These
environmental factors act to keep biological cycles in phase with periodic
fluctuations in the environment. In the absence of environmental cues, the
cycles continue to run but tend to drift.
Colin S. Pittendrigh (GB-US), Victor G. Bruce (US), Norton S.
Rosensweig (US), and Martin L. Rubin (US) discovered circadian rhythm in fungi.
It manifested as periodic conidiation that provided a permanent record as bands
formed along a growth continuum (1822).
Jürgen Aschoff (DE) found that beyond certain narrow limits, the
presence or absence of environmental cues has no effect on biological rhythms (66).
Julius
Axelrod (US), Herbert Weissbach (US), and Betty G. Redfield (US) determined
that serotonin is converted to melatonin in the pineal gland as follows:
serotonin—N-acetylserotonin—melatonin (86; 2431).
Curt Paul Richter (US), in his studies of biological rhythms,
discovered that circadian rhythms (and longer-term endogenous clocks) influence
behavior. He demonstrated that the circadian clock is not dependent on learning
or upon external stimuli for its expression. Richter
then discovered that a marked disruption in activity rhythms can be produced by
damage to the anterior region of the hypothalamus (1884).
Malcolm L. Sargent (US) and Winslow R. Briggs (US) found that
resetting the circadian clock in Neurospora
is mediated by a blue-light photoreceptor (1977).
Ronald J. Konopka (US), Seymour Benzer (US), Aimita Sehgal (US),
Jeffrey L. Price (US), Bernice Man (US), Michael W. Young (US), Leslie B.
Vosshall (US), and Lino Saez (US) determined that the generation of circadian
rhythms in Drosophila requires the
activity of two genes, period (per) and timeless (tim) (1301; 2044; 2372).
Central to the timekeeping mechanism of the body and mind are suprachaismatic nuclei or SCN. The SCN
is the master clock – the circadian rhythm that controls all other rhythms of
the body.
Milton H. Stetson (US) and Marcia Watson-Whitmyre (US) found
that destruction of the suprachiasmatic
nuclei in the golden hamster by bilateral radiofrequency lesions abolishes
three well-documented circadian rhythms--locomotor activities, estrous
cyclicity, and photoperiodic photosensitivity (2141).
Jon M.
Kornhauser (US), Dwight E. Nelson (US), Kelly E. Mayo (US), and Joseph S.
Takahashi (US) found that light is carried from the eye to the suprachiasmatic nuclei (SCN) in mammals.
The effect of this information has been found to induce the expression of the
genes, c-fos and jun-B in SCN cells. These genes control the expression of
other genes (1305).
Robert Y.
Moore (US), Margaret M. Moga (US), Rehana K. Leak (US), and J. Patrick Card
(US) localized the site of the mammalian suprachiasmatic nucleus (SCN) to a small cluster of cells just
above the optic chiasm (1368; 1604; 1618).
Farhan H. Zaidi (GB), Joseph T. Hull
(GB), Stuart N. Peirson (GB), Katharina Wulff (GB), Daniel Aeschbach (GB), Joshua
J. Gooley (GB), George C. Brainard (GB), Kevin Gregory-Evans (GB), Joseph F.
Rizzo 3rd (GB), Charles A. Czeisler (GB), Russell G. Foster (GB), Merrick J.
Moseley (GB), and Steven W. Lockley (GB) presented data showing that
photosensitive retinal ganglion cells (pRGCs) contribute to both circadian
physiology and rudimentary visual awareness in humans and challenge the
assumption that rod- and cone-based photoreception mediate all "visual"
responses to light (2561). Note: These photoreceptors have nothing to do with
vision but exist simply to detect brightness—to know when it is daytime and
when night. They pass this information on to two tiny bundles of neurons within
the brain, roughly the size of a pinhead, embedded in the hypothalamus and
known as suprachiasmatic nuclei. These two bundles (one in each hemisphere)
control our circadian rhythms. This third type of receptor functions completely
independent of sight.
Samer Hattar
(US), His-Wen Liao (US), Motoharu Takao (US), David M. Berson (US), and
King-Wai Yau (US) reported that the retinal ganglion cells containing the
photosensitive pigment melanopsin are
connected through the retinohypothalamic
nerve tract to the suprachiasmatic nucleus, the
primary circadian pacemaker of the brain. Then the suprachiasmatic nucleus
sends its signal to the superior cervical
ganglia, which in turn innervates the pineal gland via
norepinephrine-containing (sympathetic)
nerves (1021).
Thus, light influences the flux of melatonin in the pineal gland.
Percy Heath Hobart Gray (CA), Henry Brougham Hutchinson (GB), Aage
Christian Thaysen (GB) and Nagendra Nath Sen-Gupta (IN) demonstrated that soil
bacteria are capable of destroying phenol, cresol, toluene, and napthalene, and
that the rate of destruction increases with successive dosages applied to the
soil plot (921; 1135; 2048).
Karel Kruis (CZ), Jan Satava (CZ), and Øjvind Winge (DK)
demonstrated that standard vegetative cells of the yeast Saccharomyces cerevisiae are diploid, being produced by copulation
of two spores or gametes derived from spores. The diploid nuclei undergo
reduction at spore formation to produce four haploid ascospores (1319; 2518).
Magnesium arsenate was first used as an insecticide.
Paradichlorobenzene was discovered to be effective for control of peach tree
borer. The commercial use of calcium arsenate for boll weevil control started;
35,000 acres were treated (2050).
Ezra Jacob
Kraus (US) and Henry Reist Kraybill (US) proved that variations in internal
juices of plants are produced by variations in the fertilizer treatment and in
the available moisture of the soil (1311).
Donald Forsha Jones (US) showed that grain productivity and vigor
in maize is further increased by a double
cross between two hybrids, each of which is the product of two inbred lines (1196).
Walter Bradford Cannon (US), John Fraser (GB), Arthur Norman
Hooper (GB) and William Maddock Bayliss (GB) observed the human body under
hemorrhagic and traumatic stress during World War I. They observed that in
shock a concentration of the blood occurs, at least in the superficial
capillaries. From these experiences Cannon developed the notion of homeostasis; that is, the effort of the
body to maintain a stable internal environment despite fluctuations (within
reason) of the outside environment (172; 347; 350). Primarily
responsible for this were the various hormones, particularly epinephrine
(adrenaline). See, isonomy of Alcmaèon, 520 B.C.E. and milieu intérieur of Claude Bernard,
1865.
Studying the nerve endings influenced by epinephrine, Cannon
discovered that they secreted an epinephrine-resembling compound even under
normal nonemergency conditions. Since these nerve endings belonged to what was
called the sympathetic nervous system, he called the compound sympathin
(352).
Ulf Svante Hansson von Euler-Chelpin (SE) subsequently isolated
and identified noradrenaline (norepinephrine) as the neurotransmitter in the
sympathetic nervous system (2329-2331).
Ernst Franz Moro (AT-DE) explained
the embrace or startle reflex in infants under six months of age as a defensive
reflex. In response to a loud noise, passive movement of the child’s head or
striking the surface on which the infant rests, the infant draws its arms
across its chest in an embracing manner. Absence of this reflex under 6 months
of age suggests diffuse central nervous system damage and asymmetric responses
are seen with all forms of palsies - its presence after 6 months of age
suggests cortical disturbance (1634).
Margaret W. Jepps (GB) and Clifford Dobell (GB) gave the first
description of Dientamoeba fragilis (1184). Patients infected with this
protozoan frequently suffer from acute intestinal signs such as explosive
diarrhea, severe abdominal pain, cramps, nausea, vomiting, mild fever, and
general fatigue.
Eighty-five years after its first description, although D.
fragilis is accepted as a true pathogen in some countries and infected
patients are treated, it is still struggling to gain acceptance as a legitimate
pathogen in many others.
Robert Sanno Fåhraeus (SE) discovered the decrease in apparent
viscosity of blood that occurs when it flows through a vessel of smaller
diameter than about 1.5 mm (738-740).
Chevalier Jackson (US) insufflated bismuth through a bronchoscope
to visualize the bronchi radiologically (1160).
Jean-Marie-Athanase Sicard (FR) and Jacques Forestier (FR) are
credited with the introduction of radiopaque poppy seed oil (Lipiodol) for the
exploration of the lower respiratory tract (2070).
Walter Edward Dandy (US) introduced a method for diagnosis of
cerebral tumors (543). He
injected air into the ventricles (liquid-filled cavities) of the brain to
increase their contrast in x-ray.
May Tweedy Mellanby (GB) discover that the onset of dental caries
is determined partly by the deficiency of certain substances in the diet,
particularly salts of calcium and phosphorus. She also found that the onset of
caries is influenced by the structure of the teeth, which is determined largely
by the diet during development (1557).
Anton Breinal (AU), John Burton Cleland (AU), Alfred W. Campbell
(AU), and Burton Bradley (AU) showed that Murray Valley encephalitis is
caused by a virus (282; 417). Note:
prior to 1951 it was called Australian X disease.
Eric L. French (AU) found that the causative virus of Murray
Valley encephalitis was an arbovirus (826). Note: the virus
reservoir appears to be birds in Northern Australia, the vector being
mosquitoes
Francis Bertody Sumner (US) studied geographic variation in Peromyscus
(deer mice) and convinced himself that the apparently continuous variability is
Mendelian in nature. He concluded
that the evolution of species is the result of minute genetic changes largely
of an adaptive nature (2181).
Edward
Glanzmann (CH) reported on hereditary
hemorrhagic thrombasthenia as a condition characterized by prolonged
bleeding time and poor clot retraction in the presence of a normal platelet
count (872).
This paper ushered in the era of platelet function studies.
The concern over the rate of venereal disease infection in
American military recruits in the First World War I was a major factor in the
establishment of a Division of Venereal Diseases in the United States Public
Health Service through the Chamberlain-Kahn Act in 1918.
Joseph Barrell (US) published a Phanerozoic time scale based on chemical ages produced by Arthur Holmes
(1911), and interpolations involving less quantitative methods. The divisions
in the time scale fall close to today's accepted values. For example, Barrell
placed the Cenozoic-Mesozoic (Cretaceous-Tertiary) boundary at 55-65 million
years ago (today's value: 65 million years ago), and the base of the Cambrian
at 360-540 million years ago (today's value: 570 million years ago) (133).
1919
“Paradoxical though it may sound, the more skillfully a
demonstration experiment is performed the less from it do some students learn.”
Charles Scott Sherrington (2061).
Jean Baptiste Vincent Bordet (BE) was awarded the Nobel Prize in
Physiology or Medicine for his discovery of complement fixation and studies in
bacterial immunology.
Francis William Aston (GB) made a significant contribution to
atomic science with the invention of the mass spectrograph. The device is
capable of separating isotopes by measuring the minute differences in their
masses. Using the mass spectrograph, Aston discovered a third isotope of neon
with atomic weight 21, then successfully identified 212 of the 287 naturally
occurring isotopes (76; 77; 79; 80). The
invention also prompted him to devise his famous Whole Number Rule which states, "the mass of the oxygen
isotope being defined, all the other isotopes have masses that are very nearly
whole numbers” (78). The rule
became crucial to future developments in nuclear energy technology.
Hugh Hampton Young (US), Edwin C. White (US), and Ernest O. Swartz
(US) reported on the germicidal efficiency of
2,7-dibromohydroxymercurifluorescein-disodium salt, in a 2% aqueous solution,
known as Mercurochrome or merbromin (2553; 2554). It was the best known and most widely
used antiseptic in the world until banned by the Food and Drug Administration
(FDA) in 1998 as not being safe and effective.
Jack Cecil Drummond (GB) proposed calling the antiscorbutic
substance vitamin C (630).
Thomas Burr Osborne (US), Lafayette Benedict Mendel (US), Edna L.
Ferry (US) developed a method of expressing numerically the growth-promoting
value of proteins (1759).
Arpad Paál (HU) showed that when the tip of a plant shoot is cut
off and replaced to one side, the growth of the base is greater on this side.
This signaled the occurrence of a growth substance, produced in the tip, that
somehow regulated the positive curvature of oat coleoptiles, the distinctive
feature of the phototropism (1773).
James Howard Brown (US) introduced the terms alpha, beta, and gamma to describe the three types of
hemolytic reactions produced by bacteria on blood agar plates (311).
Ludwik Hirszfeld (PL) and Hanka Hirszfeld (PL) were the first to
describe racial variation in ABO blood-group frequencies and thereby introduce
serological genetics into anthropology (1087; 1088). Their
discovery of blood-group gene polymorphism and of regular geographic clines of
changing frequency (e.g., blood group B increasing from west to east across
Europe and Asia) prepared the way for the most extensive genotypic description
of geographic populations which is available for any species.
Ludwik Hirszfeld (PL) discovered the bacillus Salmonella
paratyphi C, today called Salmonella hirszfeldi (1086).
Winfred Ashby (US) developed a differential agglutination method,
which she used to determine survival rates of erythrocytes in the human body,
and thus became the first person to establish the correct life span of
erythrocytes (approximately 30 days) (72).
Schack August Steenberg Krogh (DK) observed that in resting tissue
not all capillaries are open at any one time but rather there is a shifting
back and forth by any given capillary, open at one time closed at another, the
demands of surrounding tissues obviously influencing the degree of dilation (1315; 1318). Note: Salomon Stricker (AT), in 1865, observed irregular and
spontaneous contractions and relaxations of capillaries in the nictitating
membrane of the frog (2165).
Schack August Steenberg Krogh (DK) observed that in striated
muscles the capillaries are arranged with such regularity along the muscle
fibers that each capillary can be taken to supply a definite cylinder of tissue
the average cross-section of which can be determined by counting the
capillaries in a known area of the transverse section.
A formula is given which allows the calculation of the oxygen
pressure head, which is necessary and sufficient to supply the muscle with
oxygen from the capillaries.
The number of capillaries per square mm. of the transverse section
of striated muscle appears to be a function of the intensity of the metabolism,
being higher in small mammals than in larger forms.
The necessary oxygen pressure head deduced from the total number
of capillaries is in all cases extremely low (1316).
Selig Hecht (PL-US) introduced the idea that in photosensory
systems a photosensitive substance S is decomposed by light into P and A (light
adaptation) and that in the dark, P and A combine to reform S (dark adaptation) (1028).
Thomas Hunt Morgan (US) authored The Physical Basis of Heredity, a summary of the rapidly growing
findings in genetics (1629).
Calvin Blackman Bridges (US) discovered chromosomal duplications
in Drosophila (291).
Calvin Blackman Bridges (US) and Otto L. Mohr (NO) showed that in Drosophila melanogaster the character vortex is dependent upon or is modified
by four mutant genes. The grade of the vortex
character and the proportion of flies showing that character is higher in the
females than in males of the same genetic constitution (299).
Pio del Rio-Hortego (ES) perfected an ammonical silver carbonate
staining technique with which he announced that Cajal’s third element consisted of 2 types of cells, which he named microglia (mononuclear phagocytes that
reside within the central nervous system) and oligodendroglia (form the myelin sheath around axons in the central
nervous system). Later he published his classic work on histogenesis of microglia
(1899-1905).
William Ford Robertson (GB) had introduced the term microglia but did not study the cell
type in any detail (1913; 1914). Santiago
Ramón y Cajal (ES) referred to these cells as the third element (1850).
Pio del Rio-Hortega (ES) demonstrated that microglial cells are
reticuloendothelial cells (1906).
Clifford Dobell (US) wrote Amoebe
Living in Man in which he clarified the taxonomy of the parasitic amoebae
by classifying them into four genera (601).
Carl C. Speidel (US) discovered neurosecretion in spinal cord
cells of the skate (2105).
Ernst Scharrer (DE-US) confirmed neurosecretion when he found
secretory droplets in certain hypothalamic neurons of the European minnow, Phoxinus laevis. He called them nerve gland cells and proposed that they
secreted substance in the same manner as endocrine cells (2006). This was a revolutionary idea
at the time. The current scientific dogma was that cells could either conduct
electrical impulses or secrete hormones, not both. Scharrer’s work represents
the origin of neuroendocrinology.
Berta Vogel Scharrer (DE-US) described neurosecretory cells in the
opisthobranch snail, Aplysia, in the
polychete worm, Nereis, in the
cockroach, and in the horseshoe crab,
Limulus polyphemus (1988-1991).
Berta Vogel Scharrer (DE-US) determined the function of
neuroglandular bodies in the head of the South American woodroach, Leucophaea maderae, including especially
the corpus allatum and corpus cardiacum. She found that removal
of the corpus allatum severely
effects development due to hormonal imbalance. Nymphs undergo premature
metamorphosis and egg development is abnormal. Removal of the corpus cardiacum has no observable
effect. She concluded that the corpus
cardiacum is a storage depot for hormones from the corpus allatum and that these hormones are shipped from the corpus cardiacum out to the body by
neurosecretory cells, the secretory granules traveling down the nerve axon
prior to release at the axon’s terminus. Surprisingly she noted that when these
neurosecretory cells are severed tumors develop in their distal tissues.
Ernst Albert Scharrer (DE-US) and Berta Vogel Scharrer (DE-US) noted
many interesting parallels between the corpus
allatum-corpus cardiacum system of insects and the hypothalamo-hypophyseal system of vertebrates (1992-1994; 2004; 2005; 2007).
Berta Vogel Scharrer (DE-US) revealed the ultrastructure of the
insect neurosecretory cell, showing that neurosecretory granules originated in
the endoplasmic reticulum and Golgi apparatus of these cells then passed down
the axon to be released at the axon terminals (1995-1999; 2008).
Berta Vogel Scharrer (DE-US) formulated a comprehensive theory of
the evolutionary origins of neurosecretory cells. She suggested that
neurosecretory communication of the type seen in insects preceded specialized
endocrine and synaptic systems (2000; 2001).
Berta Vogel Scharrer (DE-US) showed that invertebrate
neurosecretory cells and neuropeptides participate in regulation of the immune
system (2002; 2003).
Ernest Adolf Spiegel (AT) and H. Zweig (AT) recognized a nuclear
mass dorsal to the optic chiasma which they called the suprachiasmatic
nucleus (SCN) (2110).
Nobuo Ibuka (JP) and Hiroshi Kawamura (JP) observed that lessions
in the suprachiasmatic
nucleus caused a loss of circadian rhythm in the sleep-wakefulness cycle of the
rat (1143).
Benjamin Rusak (CA) and Irving Zucker (CA) confirmed the
central role which the SCN plays in coordinating mammalian circadian rhythms (1951).
Ralph Lydic (US) and Martin C. Moore-Ede (US) extended
studies of SCN structure and function to the squirrel monkey (Saimiri sci-
ureus). Ablation of the SCN eliminates circadian rhythmicity in activity,
feeding, and drinking, whereas other circadian rhythms such as body temperature
persist. Thus, the SCN acts as one of the key pacemakers in the multioscillator
circadian timing system of this diurnal primate (1458).
Joseph Arthur Arkwright (GB), Arthur William Bacot (GB), and F.
Martin Duncan (GB) supplied strong circumstantial evidence that the etiological
agent of trench fever is rickettsial
and that body lice carry it (59). The etiological agent was named
Rickettsia pediculi and later Rochalimea quintana or Rickettsia quintan. Currently it is
called Bartonella quintana.
Ernest William Goodpasture (US) described a progressive, rare, and
usually fatal autoimmune disorder affecting primarily the kidney and lung. It
is characterized by glomerulonephritis and intra-alveolar hemorrhage (903). Goodpasture’s syndrome
Cécile Mugnier Vogt (FR-DE) and Oskar Voigt (DE) described over
200 cortical areas of the brain (2306).
William Healey Dall (US), a naturalist who specialized in
malacology (describing over 5,300 species) but also made contributions in
ornithology, zoology in general, anthropology, oceanography, and paleontology
published over 1,600 papers, reviews, and commentaries. He is commemorated by Dallina Beecher, 1895 and Dalliella Cossman, 1895.
Theobald Smith (US) and Marian S. Taylor (US) observed that the
bacterium Vibrio fetus is the cause
of fetal membrane disease in cattle (2088).
Arnold Löwenstein (DE) isolated the herpes simplex 1 virus
from fever blisters in humans (1444).
Wilhelm Gruter (DE) initiated a series of animal studies that
demonstrated unequivocally the infectious nature of Herpes simplex virus (HSV). He showed how HSV could be transmitted serially
from rabbit to rabbit, and it is he who is usually given credit for the
isolation of HSV (941; 942). This work was done between 1911
and 1914.
Christopher Howard Andrewes (GB) and E. Arnold Carmichael (GB)
observed that recurrent infections of Herpes
occurred only in adults who carried neutralizing antibodies – an occurrence in
sharp contrast to the behavior of other known infectious agents at that time (52).
Frank Macfarlane Burnet (AU) and Stan W. Williams (AU) provided
the first accurate description of the biology of Herpes simplex virus infections in humans (331).
Frank Macfarlane Burnet (AU), Dora Lush (AU), and Alan V. Jackson
(AU) grew Herpesvirus type 1 on the
chorioallantoic membrane of chick embryos (330).
Karl Edward Schneweis (DE) presented evidence that orolabial and
genital herpes are caused by two different strains of human Herpes simplex virus (2030).
Gary S. Hayward (US), Robert J. Jacob (US), Samuel C. Wadsworth
(US), and Bernard Roizman (US) determined the organization of the Herpes simplex virus genome (1025).
Rebecca Craighill Lancefield (US), Oswald Theodore Avery (CA-US),
and Alphonse Raymond Dochez (US) used the precipitin test to differentiate the
beta-hemolytic streptococci into a number of immunological groups designated by
the letters A through O. Most strains causing human infections were found to
belong to group A (83; 1334-1344).
Dudley H. Morris (US) and Frederick D. Bullock (US), using rat
plague bacillus in animal studies, established the importance of the spleen in
resistance to infection (1635).
Harold King (US) and Harris B. Shumacker, Jr. (US) were the first
to firmly establish an association between fulminant bacterial sepsis and
splenectomy in humans. They reported on five cases where bacterial sepsis
followed splenectomy in infants (1255).
Kurt Huldschinsky (DE) found that sunlight or a quartz lamp aided
in the cure of rickets (1125).
Harry Goldblatt (GB) and Katherine Marjorie Soames (GB) clearly
identified that when 7-dehydrocholesterol (a precursor to vitamin D) is
irradiated with sunlight or ultraviolet light, a substance equivalent to the
fat-soluble vitamin is produced (894).
Alfred Fabian Hess (US) confirmed the dictum that "light
equals vitamin D". He excised a small portion of skin, irradiated it with
ultraviolet light, and then fed it to groups of rachitic rats. The skin that
had been irradiated provided an absolute protection against rickets, whereas
the unirradiated skin provided no protection whatsoever; clearly, these animals
were able to produce adequate quantities of "the fat-soluble vitamin",
suggesting that it was not an essential dietary trace constituent (1063).
Harry Steenbock (US), Arthur J. Black (US), and Mariana T. Nelson
(US) obtained similar results when they found that rat food irradiated with
ultra violet light also acquired the property of being antirachitic (2130; 2131).
Adolf Otto Rheinhold Windaus (DE) and Alfred Fabian Hess (US)
discovered that vitamin D consists of a steroid molecule in which a bond is
broken by the action of sunlight. This provided the rationale for the
irradiation process whereby the vitamin D content of such foods as milk and
bread are increased by exposure to ultraviolet light (2511).
Sigmund Otto Rosenheim (GB) and Thomas Arthur Webster (GB)
identified ergosterol (isolated from oil of ergot, the fungus) as being
synonymous with provitamin D. Irradiation with ultraviolet light transformed
ergosterol into the vitamin (1926).
Robert Benedict Bourdillon (GB), Catherine Fischmann (GB), Robert G.C.
Jenkins (GB), and Thomas Arthur Webster (GB) confirmed the theory suggested
previously that the ultra-violet irradiation of ergosterol produces three
substances in succession. Of these, the first shows intense absorption for
wavelengths between 2500 A. and 2900 A., and great, anti-raehitie power. The
second shows intense absorption at 2400 A., and no antirachitic power. The
final product (or products) has little or no appreciable absorption and no
antirachitic power. They became convinced that the first substance is vitamin D (258).
Frederic
Anderton Askew (GB), Robert Benedict Bourdillon (GB), Hilda Margaret
Bruce (GB), Robert G.C. Jenkins (GB), Thomas Arthur Webster (GB), and Henry Hallett
Dale (GB) isolated and crystallized what they thought to be pure vitamin
D (75).
Adolf Otto Rheinhold Windaus (DE), Otto Linsert (DE), Arthur
Luttringhaus (DE), and G. Weidlich (DE) crystallized and chemically
characterized vitamin D2 (ergocalciferol) which could be produced by
ultraviolet irradiation of ergosterol (2512).
Adolf Otto Reinhold Windaus (DE), Friedrich
Schenck (DE), and Fritz von Werder (DE) isolated and identified the structure
of vitamin D3 (cholecalciferol) (2513). Verify
Adolf Otto Reinhold Windaus (DE) and Franklin W. Bock (DE) proved
that the provitamin D in hog skin is 7-dehydrocholesterol (2510). See Blunt, 1968.
Solomon Eberhard Henschen (SE) surveyed
specific disorders of calculation following brain damage and named the disorder
acalculia (without calculation),
today it is called dyscalculia (disordered
calculation) (1047).
Lewis Hill Weed (US) and Paul S. McKibben (US) used intravenous
injections of hypertonic saline solutions in patients with intracranial
pathologies to treat
cerebral edema and elevated intracranial pressure. These
solutions lowered the pressure of the cerebrospinal fluid and produced a
definite shrinking of the brain (2419; 2420).
Walter
Edward Dandy (US) reported eight pneumencephalographies after lumbar air
insufflation (544).
Bordeaux mixture was demonstrated effective for control of potato
leafhopper (2050).
1920
“And though much has been written foolishly about the antagonism
of science and religion, there is, indeed, no such antagonism. What all these
world religions declare by inspiration and insight, history as it grows
clearer, and science as its range extends, display, as a reasonable and
demonstrable fact, that men form one universal brotherhood, that they spring
from one common origin, that their individual lives, their nations and races,
interbreed and blend and go on to merge again at last in one common human
destiny upon this little planet amidst the stars.” Herbert George Wells (2435).
“Phases of real intellectual progress in any community seem to be
connected with the existence of a detached class of men, sufficiently free not
to be obliged to toil or worry exhaustively about mundane needs, and not rich
and powerful enough to be tempted into extravagances of lust, display, or
cruelty. They must have a sense of security, but not a conceit of superiority.
This class, we have further insinuated, must be able to talk freely and
communicate easily. It must not be watched for heresy or persecuted for any
ideas it may express.” Herbert George Wells (2435).
“Even our digestion is governed by angels," said Blake; and
if you will resist the trivial inclination to substitute "bad
angels," is there really any greater mystery than the process by which
beef is turned into brains, and beer into beauty?” Richard Le Gallienne (1367).
Hermann Walther Nernst (DE) was awarded the Nobel Prize in Chemistry
for his proposal of the third law of thermodynamics.
Schack August Steenberg Krogh (DK) was awarded the Nobel Prize in
Physiology or Medicine for his discovery of the capillary motor regulating
mechanism.
Ernest Rutherford (New Zealand-GB) was the first man ever to
change one element into another as a result of his own manipulations. He did
this by bombarding nitrogen atoms with alpha particles. Occasionally one of the
nitrogen nuclei had one of its protons knocked out, changing it into an oxygen
atom (this was detected using a scintillation counter). This is also the first
man-made nuclear reaction.
He found that the nitrogen nucleus has
hydrogen nuclei in it. That meant the hydrogen nucleus is an elementary
particle. Rutherford named it the proton, from the Greek word protos, meaning first (1956).
Rutherford,
in 1920, predicted the neutron which James Chadwick (GB) later discovered (383).
Wendell
Latimer (US) and Worth H. Rodebush (US) proposed hydrogen bonds, defining them
as secondary interatomic links, weaker than valence bonds (1360).
Reginald Oliver Herzog (DE) and Willi Jancke (DE) used x-ray
crystallography (diffractometry) to provide
strong evidence that silk fibroin contains polypeptide chains in
the extended configuration (1061).
Gilbert T. Morgan (GB) and Harry Dugald Keith Drew (GB) introduced
the term chelate to chemistry when
they stated: "The adjective chelate,
derived from the great claw or chela
(chely- Greek) of the lobster or
other crustaceans, is suggested for the caliper like groups which function as
two associating units and fasten to the central atom so as to produce
heterocyclic rings" (1621).
Otto Knut Olof Folin (SE-US) and Hsien Wu (CN-US) developed a
system for testing sugar content of the blood. Folin had hit upon
phosphotungstic-phosphomolybdic acid complexes as sensitive color producing
reagents, applicable to a number of substances, phenols, tyrosine, uric acid,
glucose, etc., under appropriate conditions. Also he found that tungistic acid
was a simple and effective way to precipitate completely at about neutral
reaction all of the proteins of blood without absorbing the non-protein
constituents. In tungstic acid filtrates, sugar, non-protein nitrogen, urea,
uric acid, creatinine and creatin, amino acids, chlorides and other substances
could be determined by the sort of micro-methods Folin had devised (802).
Torsten Ludvig Thunberg (SE) was among the first to suggest that
the protein portion of an enzyme possesses both substrate specificity and
catalytic power. His comments were in reference to dehydrogenases (2219).
Carl Voegtlin (US), Mather H. Neill (US), and Andrew Hunter (US)
reported that pellagra could be cured
by daily doses of 15-30 grams of dried yeast, or by 15 grams of a water extract
of yeast (2300).
Ellen Marion Delf (GB) and Alfred Fabian Hess (US) independently
showed that oxidizing agents and air easily
inactivate vitamin C (579; 1062).
Johann Ernst Oswald Schmiedeberg (DE) coined the name
chondroitinschwefelsäure (chondroitin sulfuric acid) derived from chondros
(cartilage, and deduced composition: acetate, sulfate, glucuronic acid, and
hexosamine (2026).
Torsten Ludvig Thunberg (SE) was the first to recognize l (-)
alpha-hydroxyglutaric acid (2-hydroxyglutarate) as a substrate of the
intermediary metabolism of animal tissues (2219).
Hans Weil-Malherbe (DE-GB-US) found that 2-hydroxyglutarate is
oxidized by a hydroxyglutaric dehydrogenase (2-hydroxyglutarate dehydrogenase)
in animal tissues (2424).
Walter Jennings Jones (US) described an enzyme from the swine
pancreas as relatively heat-stable and capable of digesting yeast nucleic acid
(RNA) but failing to digest thymic nucleic acid (DNA) (1207).
René Jules Dubos (US) and Robert H.S. Thompson (US) named this
enzyme ribonuclease (637).
Hans Karl Albert Winkler (DE) introduced the term genome into genetics. It is an irregular
hybrid of gene and the suffix ome meaning “the entire collectivity of
units”. Both parents are Greek (2519). From page
165 of his book, "I propose the expression Genome for the haploid chromosome set, which, together with the
pertinent protoplasm, specifies the material foundations of the species...”
Alfred Henry Sturtevant (US) discovered that some mutations
restore the wild-type character to a mutant phenotype without having restored
the mutant gene to its pristine, wild type state. Sturtevant gave the name suppressor to such mutations (2171).
George Wells Beadle (US) and Boris Ephrussi (RU-FR) further
contributed to the understanding of gene suppression (173).
Franz Schrader (DE-US) proved for the first time that sex may be
determined by haploidy or diploidy of the zygote; that fertilized females can
produce male progeny parthenogenetically; and that these males, unlike their
sisters, are fatherless, for their single set of chromosomes comes from their
mother (2036).
Johan Schmidt (DK), Tatuo Aida (JP), and Øjvind Winge (DK) were
the first to demonstrate Y-linked inheritance in animals. Their subjects were
the fish Lebistes reticulatus (guppy)
and Aplocheilus latipes (killifish).
Aida’s work includes the first demonstration of crossing over between an X- and
a Y-chromosome (29; 2025; 2516; 2517).
Clarence Cook Little (US) and Leonell C. Strong (US) established
the existence of multiple genes for susceptibility and resistance to tumor
transplants in mice. These genes would later be called histocompatibility genes
(1425-1427).
Sears P. Doolittle (US) demonstrated that Aphis gossypii Glov., and the cucumber beetles Diabrotica vittata and
Diabrotica duodecimpunctata Oliv. act as vectors of the cucumber mosaic
virus (620).
Elmer Walker Brandes (US) demonstrated that Aphis maidis acts as a vector of sugar cane (Saccharum officinarum) mosaic virus (273).
Edward John Russell (GB) indicated that fungi of the genera, Verticillium, Fusarium, and Pythium are
injurious root pathogens (1952).
David Keilin (PL-GB) made the first adequate description of yeast
(ascomycete) infection of insects. The host was the larvae of the biting midge,
Dasyhelea obscura Winnertz, and the
yeast Monosporella unicuspidata Keil (1229).
Alexandrino Pedroso (BR) and José Maria Gomes (BR) were the first
to observe the fungal infection which Fernando Terra (BR), Magarinos Torres
(BR), Olympio Oliveiro da Fonseca (BR), and Antonio Eugenio de Area Leao (BR)
would later call chromoblastomycosis (1803; 2197). The term chromoblastomycosis refers to pigmented
fungal infections of the subcutaneous tissue.
C. Guy Lane (US) and Edgar M. Medlar (US) reported the fungus Phialophora verrucosa as a cause of this
disease (1349; 1554).
Alexandre Joseph Emilé Brumpt (FR) renamed the fungus Hormodendrum pedrosi (317).
Arturo L. Carrión (PR) reported that Hormodendrum compactum could also be the etiological agent (368). The
disease has been called verrucous
dermatitis and chromomycosis.
Jose Paulo Smith Nóbrega (BR), Sergio Rosemberg (BR), Ana Maria
Adami (BR), Elizabeth Maria Heins-Vaccari (BR), Carlos da Silva Lacaz (BR), and
Thales de Brito (BR) reported the first human culture-proven case of brain
abscesses due to Fonsecaea pedrosoi (Hormodendrum compactum) in Brazil (1732).
Joseph Francis Charles Rock (AT-US) discovered that oil from the
seeds of Hydnocarpus wightiana and Hydnocarpus anthelmintica is the
legendary chaulmoogra oil (hydnocarpus oil) which for centuries has been used
to successfully treat the early stages of leprosy (1920).
Irving Widmer Bailey (US) demonstrated for the first time how the
single cell-layered cambrial cylinder could increase the circumference of the
ever-expanding stem or root of the plant (96-98).
Harry Webster Graybill (US) and Theobald Smith (US) determined
that fatal blackhead in turkeys resulted from feeding them embryonated eggs of
the nematode parasite Heterakis papillosa
(922).
Paul Saxl (AT) and Robert Heilig (AT) reported the diuretic effect
of merbaphen (Novasurol) which
contains mercury in a complex organic form. It was originally introduced as an
antisyphilitic agent (1984).
Jean R. Camus (FR) and Gustave Roussy (CH-FR) discovered in dogs
that, puncturing the hypothalamus but leaving the pituitary intact, produced
polyuria (344).
Percival B. Bailey (US), Frédéric Bremer (US) and Stephen Walter
Ranson (US) described a supraoptico-hypophyseal tract in animals that connects
the hypothalamic supraoptic nuclei to the posterior pituitary and showed that
an injury to this tract produced diabetes insipidus (101; 1854).
Hans H. Forssman (SE) found that diabetes insipidus can be
derived not only from autosomal genes but also from two different types of sex-linked
genes (807).
Antonio J. Waring (US), Laslo Kajdi (US) and Vivian Tappan (US)
described patients with “an unusual syndrome” that presented shortly after
birth, characterized by polyuria, polydipsia, fever, and constipation vomiting,
high serum Na and Cl, rapid dehydration, and inability to excrete hypertonic
urine. They concluded that the condition was caused by “a specific defect in
tubular reabsorption of water” and appeared more frequently in boys. This
description is consistent with what we know today to be the congenital form of
the X-linked nephrogenic diabetes insipidus (2397).
Robert H. Williams (US) and Cole Henry (US) introduced the term nephrogenic
diabetes insipidus for the congenital syndrome characterized by polyuria
and renal concentrating defect resistant to vasopressin (2481).
Joseph Luder (GB) and Dorothy Burnett (GB) reported the presence
of the biologically active antidiuretic hormone arginine vasopressin
(AVP) in the urine of nephrogenic diabetes insipidus (NDI) patients (1451).
Malcolm A. Holliday (US), Charles Burstin (US), and Jean Harrah
(US) found active AVP in the blood of nephrogenic diabetes insipidus patients
(1092).
Hans H. Bode (US) and John D. Crawford (US) presented “The
Hopewell Hypothesis,” that most cases of nephrogenic diabetes insipidus
in America could be traced to descendants of Ulster Scots who arrived in Novia
Scotia, in 1761, on the ship Hopewell (238).
Gary L. Robertson (US) and James A. Scheidler (US) provided
evidence of a variant of familial nephrogenic diabetes insipidus characterized
by partial resistance to vasopressin (1912).
Nine V.A.M. Knoers (NL), H. van der Heyden (NL), Bernard A. van
Oost (NL), Hilger H. Ropers, (NL), Leo A.H. Monnens (NL), and J. Willems (NL) localized
the gene that, when mutated, caused the most common type of inherited nephrogenic
diabetes insipidus (NDI). This was the vasopressin-2 receptor (V2R)
gene (1273).
Daniel G. Bichet (CA), Mohammad Razi (US), Marie-Francoise Arthus
(CA), Michele Lonergan (CA), Pauline Tittley (CA), Robert K. Smiley (CA), Gail
Rock (CA), and David J. Hirsch (CA) determined that nephrogenic diabetes
insipidus patients were not responding to dDAVP, a synthetic analog of arginine
vasopressin (AVP) (209).
Mariel Birnbaumer (US), Anita Seibold (US), Stephanie Gilbert (US),
Masami Ishido (JP), Claude Barberis (FR), Anaid Antaramian (US), Phillippe
Brabet (US), and Walter Rosenthal (US) isolated the gene and the cDNA for the vasopressin-2
receptor (221).
Stephen J. Lolait (US), Anne-Marie O'Carroll (US), O. Wesley McBride
(US), Monica Konig (US), Alain Morel (FR), and Michael J. Brownstein
(US) cloned a vasopressin V2 receptor of a rat and suggested its connection to nephrogenic
diabetes insipidus (1435).
Walter Rosenthal (US), Anita Seibold (US), Anaid Antaramian (US),
Michele Lonergan (CA), Marie-Francoise Arthus (CA), Geoffrey N. Hendy (CA),
Mariel Birnbaumer (US), and Daniel G. Bichet (CA) provided biochemical proof
that a mutated vasopressin V2 receptor is the cause of X-linked NDI (1929).
Anita Seibold (US), Phillippe Brabet (US), Walter Rosenthal (US),
and Mariel Birnbaumer (US) deduced the primary structure of the human vasopressin
V2 receptor (2045).
Kiyohide Fushimi (JP), Shinichi Uchida (JP), Yukichi Hara (JP), Yukio
Hirata (JP), Fumiaki Marumo (JP), and Sei Sasaki (JP) isolated the
vasopressin-regulated water channel (AQP2) cDNA in the rat (840).
Anita Seibold (US), Walter Rosenthal (US), Daniel G. Bichet (CA),
and Mariel Birnbaumer (US) confirmed that the V2 receptor cDNA and gene mapped to
the same region of the X chromosome to which nephrogenic diabetes insipidus
had been previously mapped by genetic linkage analysis (2046).
Walter Rosenthal (US), Anita Siebold (US), Anaid Antaramian (US),
Stephanie Gilbert (US), Mariel Birnbaumer (US), Daniel G. Bichet (CA),
Marie-Francoise Arthus (CA), and Michele Lonergan (CA), between 1992 and 1994, identified
the first mutations in the V2 receptor gene in individuals affected with nephrogenic
diabetes insipidus that had been clinically characterized by Dr. Daniel G. Bichet
(CA), and confirmed biochemically that a receptor bearing those mutations did not
function in vitro as the normal receptor does. This joint effort of
medicine, molecular biology and biochemistry established the receptor mutations
as the most common cause of nephrogenic diabetes insipidus (1927; 1928).
Sei Sasaki (JP), Kiyohide Fushimi (JP), Hidehiko Saito (JP),
Fumiko Saito (JP), Shinichi Uchida (JP), Kenichi Ishibashi (JP), Michio
Kuwahara (JP), Tatsuro Ikeuchi (JP), Ken-ichi Inui (JP), Kiichird Nakajima (JP),
Tohru Watanabe (JP), and Fumiaki Marumo (JP) isolated the human cDNA for the
aquaporin 2 water-channel gene (AQP2) and its chromosomal localization
was assigned to 12q13 (1980; 2256).
Angenita F. van Lieburg (NL), Marian A.J. Verdijk (NL), Nine V.A.M.
Knoers (NL), Anthonie J. van Essen (NL), Willem Proesmans (NL), Rudolf Mallmann
(NL), Leo A.H. Monnens (NL), Bernard A. van Oost (NL), Carel H. van Os (NL), Peter
M.T. Deen (NL), and Be Wieringa (NL) isolated the human cDNA for the AQP2
water channel gene and identified mutations of the AQP2 gene as a cause
of the recessive form of nephrogenic diabetes insipidus (574; 2272).
Peter M.T. Deen (NL), Daniel Olde Weghuis (NL), Richard J. Sinke
(NL), Ad Geurts van Kessel (NL), Be Wieringa (NL), and Carel H. van Os (NL) mapped
the human AQP2 gene to the long arm of chromosome 12 (575).
David Marples (DK), Sten Christensen (DK), Erik Ilso Christensen (DK),
Peter D. Ottosen (DK), and Soren Nielsen (DK) were the first to demonstrate
changes in the aquaporin 2 water-channel gene (AQP2) in association with
nephrogenic diabetes insipidus (1507)
Peter M.T. Deen (NL), Huib Croes (NL), Remon A.M.H. van Aubel (NL),
Leo A. Ginsel (NL), and Carl H. van Os (NL) provided cell biological proof that
mutant AQP2 proteins, coded for by patients with recessive nephrogenic
diabetes insipidus, are impaired in their transport to the plasma membrane (export
from the endoplasmic reticulum) (573).
Sabine M. Mulders (NL), Daniel G. Bichet (NL), Johann P.L. Rijss
(NL), Erik-Jan Kamsteeg (NL), Marie-Francoise Arthus (NL), Michele Lonergan
(NL), T. Mary Fujiwara (NL), Kenneth Morgan (NL), Richtje Leijendekker (NL),
Peter van der Sluijs (NL), Carl H. van Os (NL), and Peter M.T. Deen (NL) provided
the first evidence that autosomal dominant nephrogenic diabetes insipidus
(NDI) is also caused by a mutation in the AQP2 gene and that this form
of NDI is also caused by an impaired transport of the mutant AQP2 protein to
the plasma membrane (retained in the Golgi Complex) (1649).
Katsumi Goji (JP), Michio Kuwahara (JP), Yong Gu (JP), Masafumi Matsuo
(JP), Fumiaki Marumo (JP), Sei Sasaki (JP) identified two new mutations in the AQP2
gene causing nephrogenic diabetes insipidus .
Henry Head (GB) defined two basic subtypes of sensation. He
characterized epicritic sensibility
as the ability to make fine discrimination of touch and temperature sensations,
as well as the ability to localize and discriminate sensation. He characterized
protopathic sensation as changes in
temperature and pressure without the ability to localize an abnormality (1026).
George
Linius Streeter (US) wrote, Weight, sitting height, head size, foot length
and menstrual age of the human embryo, accompanied by six charts. This is
the classical account of human prenatal growth, to which every embryologist
goes when it is necessary to ascertain the age of a fetus or late embryo from
its dimensions (2162; 2163).
Mieczyslaw
Minkowski (CH) determined the pattern of termination of optic tract fibers in
the lateral geniculate nucleus (LGN),
the thalamic relay for vision. He did so using studies of transneuronal atrophy
and degeneration. Cells in the LGN that are deprived of their input from the
eye shrink or die (1600).
Bernard
Brouwer (NL), Willem Pieter Cornelis Zeeman (NL), and Wilfred E. le Gros Clark
(GB) confirmed that there is an orderly projection from the retina to the LGN
and from the LGN to the visual cortex. Neighboring points in the visual fields
are represented at neighboring points on the cerebral cortex (309; 410).
Isadore Clinton Rubin (US) described insufflation as a test of tubal
patency, which allows the diagnosis of tubal disease without diagnostic
laparotomy (1945).
Hans Gerhard Creutzfeldt (DE) described a rare human dementia. He thought it was inherited (497; 498).
Alfons Maria Jakob (DE) diagnosed cases of the same disease (1170-1172). This
disease, a form of senile dementia,
became known as Creutzfeldt-Jakob disease
(CJD).
Jacques Jean Lhermitte (FR) described a rare syndrome of ocular
palsy with nystagmus and paralysis of adduction during attempted lateral
deviation of the eyes (1411). Max Bielschowsky (DE), in 1902,
first reported the clinical features that were subsequently described by
Lhermitte in 1922. Ref
Henry C. Sherman (US), Lucy H. Gillett (US), and Emil Osterberg
(US) suggested that grain products in the diet be supplemented by milk
products, and it is clear that in providing for needs of growing children and
of pregnant or nursing mothers the proportion of milk in the diet should be
more liberal than it need be when only maintenance is concerned; this both
because of the superior amino-acid make-up of the milk proteins and to provide
amply for the mineral elements and vitamins as well (2057).
Charles W. Hooper (US), Harry P. Smith (US), Arthur E. Belt (US)
and George Hoyt Whipple (US) developed a reproducible dye dilution method for
quantitative estimation of plasma volume (1100).
Georges Fernand Isidore Widal (FR)
defined hemoclasia as a leukocyte
phenomenon: In some people, following a meal containing white of egg (albumin)
there occurs a significant reduction in leukocytes and an increase in the
refracto-motor value of the serum (2456).
Solomon Eberhard Henschen (SE) found that isolated
damage to the left superior temporal gyrus (Wernicke's area) of the brain
probably does not produce multimodal language comprehension deficits and that disorders
of language and calculation abilities can occur independently (1048). Wernicke's area is one of the two parts of the cerebral cortex linked since the
late nineteenth century to speech.
Emile Holman (US), in 1920, performed experiments that hinted at
the first signs of what would become the concept of tissue rejection. He
transplanted the skin of a mother onto a badly burnt child. The subsequent
grafting of more skin onto the child a few days later resulted in the
inflammation of both the mother and the child’s own skin, the implications of
immunogenicity from this experiment were noted by Holman (960; 1094).
Karl Bauer (DE) performed a successful skin allograft between
identical twins and the skin on the twins stayed on indefinitely (167; 1459). See, Medawar 1944.
Georges Bardet (FR) described a medical condition characterized by
obesity, retinitis pigmentosa, polydactyly and hypogonadism (126; 127).
Arthur Biedl (HU) described two sisters who had retinitis
pigmentosa, polydactyly, hypogonadism as well as obesity (210; 211). Note: This condition is now referred to as Bardet-Biedl syndrome; inherited as an autosomal recessive.
Oil-soaked sawdust was first recommended for mosquito control.
Paris green was first rated as a mosquito larvicide (2050).
The Society of Neurological Surgeons was founded.
1921
Anonymous Poem on Syphilis from the 1920s
"There was a young man from Back Bay, Who thought syphilis
just went away. He believed that a chancre
Was only a canker,
That healed in a week and a day. But now he has `acne vulgaris'
(Or whatever they call it in Paris); On his skin it has spread
From his feet to his head
And his friends want to know where his hair is. There's more to his terrible
plight,
His pupils won't close in the light,
His heart is cavorting,
His wife is aborting,
And he squints through his gun-barrel sight. Arthralgia cuts into his slumber,
His aorta is in need of a plumber,
But now he has tabes
And sabre-shinned babies,
While of gummas he has quite a number.
He's been treated in every known way,
But his spirochaetes grow day by day;
He's developed paresis,
Has long talks with Jesus,
And thinks he's the Queen of the May."
Michael Polanyi (DE) showed that forces associated with adsorption
could lower the energy of decomposition of a reactant (1828).
Frederick Gowland Hopkins (GB) discovered and named glutathione isolated from yeast. He
characterized it as a dipeptide containing glutamic acid linked to a sulfur
compound (1106). He later
crystallized glutathione and concluded
that it is a tripeptide composed of glutamic acid, cysteine, and glycine, the
structure being gamma-glutamyl-cysteinyl-glycine
(1107).
Edward Calvin Kendall (US), Bernard F. McKenzie (US), and Harold
L. Mason (US) independently crystallized glutathione and identified it as a
tripeptide of glutamic acid, cysteine, and glycine (1238; 1239).
John Addyman Gardner (GB), Francis William Fox (GB), Hans
Beumer (DE), F.R. Lehmann (DE), Siegfried J. Thannhauser (DE), Hans Schaber
(DE), Harold John Channon (GB), F.S. Randles (US), and Arthur Knudson (US)
demonstrated that cholesterol is synthesized in the animal body (207; 391; 848; 849; 1853; 2203).
Ernest Francois Auguste Fourneau (FR) and his colleagues extended
Paul Ehrlich’s work by introducing stoxvarsol
(acetarsone; spirozid) the first antisyphilitic arsenical compound that could be
taken orally (815; 1372). It was
introduced to treat intestinal amebiasis, necrotizing ulcerative gingivitis,
and topically in trichomonas vaginitis. Also used as an antihelmintic in
veterinary cases.
Rudolf Lieske (DE) observed that some actinomycetes could bring
about the lysis of some bacteria as well as antagonize their growth (1414).
Harvey P. Barret (US) and Nancy Yarbrough (US) succeeded with in vitro
cultivation
of Balantidium coli through
eleven transplants over a period of thirty-two days (135).
Harvey P. Barret (US) and Nannie M. Smith (US) were the first to
obtain in vitro cultures of parasitic
amoeba. They grew Endamoeba barreti
from the turtle (134).
Theophilus Shickel Painter (US) described the Y chromosome in man (1775).
Marin Molliard (FR) cultivated fragments of plant embryos with
limited success (1606).
James L. Johnson (US) developed controlled growth chamber
environments to study factors such as temperature that influence plant growth
and disease (1190; 1191).
Lewis R. Jones (US) also emphasized the role of environment in
causing disease in plants (1203).
Neil Everett Stevens (US) described how Stewart's disease in corn
caused by Aplanobacter stewartii (now Pantoea stewartii) does not
occur when the sum of the mean temperatures from December through February is
below 90 but is destructive when the sum exceeds 100, based on 35 years of data
(2142). Note: This fostered an appreciation of environmental factors,
especially temperature, in the epidemiology of plant disease.
Aleksandr Fedorovich Lebedev (RU) suggested that all cells can fix
carbon dioxide. What set apart the photosynthetic group was its use of light as
a source of energy for the process. This view was so far ahead of its time that
it had little impact (1370).
David Keilin (PL-GB) was the first to identify a blastocladiaceous
(phycomycete) fungus as parasitic for insects. He isolated it from the mosquito
larvae of Aëdes alboptictus Skuse,
i.e., Stegomyia scutellaris Walker (1230).
Auguste-Henri Forel (CH) wrote his great masterpiece, Le Monde
Social des Fourmis du Globe Comparé à Celui de l’Homme [The Social World of the Ants of the Globe Compared to that of Man] (804).
Paul Galpin Shipley (US), Edwards A. Park (US), Elmer Verner
McCollum (US), and Nina Simmonds (US) demonstrated the therapeutic value of
sunlight in the treatment and prevention of rickets (2063; 2064).
Thomas Palmer Nash, Jr. (US) and Stanley Rossiter Benedict (US)
determined that ammonia excreted in human urine is produced in the kidney (1682; 1683).
Herbert McLean Evans (US) and Joseph Abraham Long (US) found that removal
of the anterior lobe of the pituitary gland inhibited growth in young rats and
repressed their sexual development. This strongly suggested that the anterior
lobe of the pituitary gland produced a growth hormone (somatotropic hormone/STH) and gonadotropic
hormones (follicle stimulating
hormone/FSH and luteinizing hormone/LH) (726). When they
injected an alkaline extract of ox pituitaries into young rats, they produced
such enhanced growth that some of the treated animals grew far heavier than the
largest untreated rats in the colony. This work also strongly suggested that
the anterior pituitary gland contains a growth hormone (somatotropic hormone/STH) (727). These
works represent the first direct experimental demonstration of the action of
the anterior pituitary on the gonads.
Otto Loewi (DE-US) elegantly demonstrated that while the nerve
impulse is electrical in nature it is also chemical in nature. Working with the
nerves attached to the frog’s heart, he showed that chemical substances are set
free when the nerve is stimulated. The fluid containing the substance can be
used to stimulate (slow down) another heart directly without the intervention
of nerve activity. Loewi called the substance Vagusstoff (acetylcholine), meaning vagus material, because he
obtained it by stimulating the vagus nerve. Because Loewi used animals in which
the cardiac branch is a mixed nerve containing parasympathetic and sympathetic
fibers, he also found that vagus stimulation on occasion produced an
accelerating substance, Acceleransstoff (1431; 1432).
Walter Bradford Cannon (US) and Joseph E. Uridil (US)
independently made the same discovery (353). These
works strongly supported the concept of chemical neurotransmission. See, du Bois-Reymond, 1877.
Anton W. Kibjakow (RU) developed a method, which demonstrated that
Otto Loewi’s Vagusstoff and
acetylcholine are identical (1252).
Wilhelm Siegmund Feldberg (DE-GB) and John Henry Gaddum (GB)
confirmed his results (743).
Ross Granville Harrison (US) solved one
of the most difficult problems in embryology, the origin of bilateral symmetry,
which is a basic morphological attribute of vertebrates (1009).
Hans Spemann (DE) and Hilda Proescholdt Mangold (DE) removed the
dorsal lip from one embryo and grafted it onto another embryo. The dorsal lip
cells removed from the donor embryo and grafted into a host embryo, if they are
able to invaginate, form a nerve tube, which is produced from the overlying
presumptive ectoderm of the host. The results indicated that the presumptive
neural plate cells of the early gastrula do not possess an inherent capacity to
form neural tissue. Instead, the presumptive neural plate cells become
determined as a result of stimulation by the presumptive notochordal cells of
the archenteron roof. The notochord, therefore, although of transitory
importance as a skeletal element, is part of the basic organization of the
vertebrate embryo. It is present in all vertebrates because it is necessary if
the embryo is to get past the gastrula stage. This is an example of why some
structures must be recapitulated
during embryonic development. The notochord while not necessary as a skeletal
support is necessary as an organizer.
Out of this and other work grew the hypothesis that one part of an
embryo, the organizer, can influence
(induce) the differentiation of another part, the reacting tissue (1488; 2106-2108). Mangold
died in a house fire shortly after this work; she was 26 years old.
Johannes Friedrich Karl Holtfreter (DE-US) further established the
distinction between self-differentiating and induced organs when he treated the
gastrula of the axolotl with chemical solutions which did not interfere with
cell proliferation, but which prevented the normal invagination of blastomeres.
The organizer was thus kept distant
from the overlying ectoderm and the nerve tube failed to develop (1099). The organizer came to be called, the evocator.
Vivian F. Irish (US), William M. Gelbart (US), F. Michael Hoffmann
(US) and Walter Goodman (US) found that the decapentaplegic
(dpp) gene is required for dorsal-ventral patterning of the Drosophila embryo. It favors
dorsalization (1090; 1149).
Horst Grunz (DE) and Lothar Tacke (DE) found in Xenopus laevis that the absence, not the
presence, of an intercellular signal is necessary for neural differentiation.
Neural fate might indeed be the 'default' fate of ectodermal cells (940).
William C. Smith (US) and Richard M. Harland (US) developed an
assay to identify m-RNAs that coded for proteins that could induce a neural
plate in ventralized Xenopus embryos.
They generated and systematically screened a library of m-RNAs derived from
hyperdorsalized gastrula-stage embryos. They isolated noggin, a novel m-RNA
that could not only induce a neural plate (and complete dorso–ventral axis)
without requiring the presence of mesoderm, but also was expressed
appropriately in the dorsal lip and in the notochord (2090).
Edwin L. Ferguson (US) and Kathryn V. Anderson (US) found that the
short gastrulation gene (sog) product
normally blocks dpp activity ventrally helping to establish a dorsal-ventral
axis in the embryo, i.e., it favors ventralization (750).
Ali Hemmati-Brivanlou (US) and Douglas A. Melton (US) reported
that inhibition of the activin II receptor could, by itself, induce neural
differentiation in the absence of the notochord (1035).
Yoshiki Sasai (JP), Bin Lu (US), Herbert Steinbeisser (DE),
Douglas Geissert (US), Linda K. Gont (US), and Edward Michael de Robertis (US)
found that in Xenopus the chordin
molecule is a potent dorsalizing factor that is expressed at the right time and
in the right place to regulate cell-cell interactions in the organizing centers
of head, trunk, and tail development (1979).
Yoshiki Sasai (US), Bin Lu (US), Herbert Steinbeisser (DE),
Stefano Piccolo (IT), and Edward Michael de Robertis (US) identified chordin,
another new dorsal lip protein that could directly induce a neuraxis. They also
showed that bone morphogenetic protein-4 (BMP-4) a growth factor related to
activin, inhibited the neuralizing activity of both chordin and noggin in
Xenopus embryos. The same group soon found that chordin directly binds and
inactivates BMP4, and Harland and colleagues reported a similar function for
noggin (1820; 1978).
The genetic text of decapentaplegic
reads very much like that of BMP4
while that of short gastrulation reads like
chordin. It would appear that arthropods and vertebrates are upside-down
versions of each other. Sometime in the distant past here was a common ancestor
from which one line of descendants started walking on their stomachs and the
other line started walking on their backs.
Lyle B. Zimmerman (US), José M. De Jesus-Escobar (US), and Richard
M. Harland (US) reported that in amphibians neural induction and mesoderm
dorsalization are antagonized by bone morphogenetic proteins (BMPs), which
induce epidermis and ventral mesoderm instead (2565).
Andrea Streit (US), Alyson J. Berliner (US), Costis Papanayotou
(US), Andrés Sirulnik (US), Claudio D. Stern (US), Hiroki Kuroda (US), Oliver
Wessely (US), and Edward Michael de Robertis (US) reported that the neural
ectoderm is specified in the blastula before the Spemann organizer even forms. Fibroblast growth factor (FGF) signaling
is required at this stage to enable later neural differentiation. In Xenopus
at least, the anterior — but not the posterior — neural ectoderm is specified
at the blastula stage, through a mechanism that already involves noggin and
chordin (1322; 2164).
J. Harold Austin (US), Edgar Stillman (US), and Donald Dexter van
Slyke (US) showed that when the urine volume is above a certain limit, there is
a direct ratio between the blood urea content and the urea excretion rate. They
called this the augmentation limit (82).
Paul Galpin Shipley (US), Edwards A. Park (US), Elmer Verner
McCollum (US), and Nina Simmonds (US) showed that diets in which the calcium is
deficient, but in which the phosphate content is near the optimum, cause injury
to young rats, interfering with growth and causing characteristic disturbances
in the growth and ossification of the skeleton. Butterfat, even in liberal
amounts, fails to be very effective in protecting the animals against this
injury due to calcium deficiency. Cod liver oil, on the other hand, is
remarkably effective in promoting growth under the experimental conditions
described, and in protecting young animals against the harmful effects of
partial calcium starvation (2065).
John Belling (US) was the first person to apply the chromosome
squash technique to both plant and animal tissues. Belling improved the method
for making chromosomal preparations and staining them with his iron
acetocarmine stain (187-189).
John H. Gerould (US) may have been the first to report an example
of the selective elimination of a mutant gene (autosomal recessive) from a
population by a predator (869).
Calvin Blackman Bridges (US) presented evidence that sex
determination in Drosophila melanogaster
is the result of interactions between genes in the X chromosomes and those in
the autosomes. The autosomal genes have a net male-forming tendency and the X
chromosomes a net female-forming tendency (292; 294; 297).
Franz Schrader (US) introduced the term "imprinting" to
describe events in the insect Pseudococcus nipae (2037). Note: In Pseudococcids (mealybugs)
(Hemiptera, Coccoidea) both the male and female develop from a fertilised egg.
In females, all chromosomes remain euchromatic and functional. In embryos
destined to become males, one haploid set of chromosomes becomes heterochromatinised
after the sixth cleavage division and remains so in most tissues; males are
thus functionally haploid.
Jules Jean Baptiste Vincent Bordet (BE) and Gheorghe Ciuca (RO)
gave one of the first descriptions of what they called lysogenic behavior in bacteria. The lysogenic bacteria released something (bacteriophage) that gave
rise to lysis of sensitive bacteria (250). The true
nature of this phenomenon was not appreciated for many years.
Hermann Joseph Muller, Jr. (US), in a famous bit of logic, deduced
that d´Herelle substances (bacteriophages) behave like genes. “That two
distinct kinds of substances—the d´Hérelle substances and the genes—should both
possess this remarkable property of heritable variation or mutability, each working by a totally different mechanism, is quite
conceivable…yet it would seem a curious coincidence indeed. It would open the
possibility of two totally different kinds of life, working by different
mechanisms. On the other hand, if these d´Hérelle bodies were really genes,
fundamentally like our chromosome genes, they would give us an utterly new
angle from which to attack the gene problem. They are filterable, to some
extent insoluble, can be handled in test tubes, and their properties, as shown
by their effect on bacteria, can then be studied after treatment. It would be
very rash to call these bodies genes, and yet at present we must confess that
there is no distinction between the genes and them. Hence, we cannot categorically
deny that perhaps we may be able to grind genes in a mortar and cook them in a
beaker after all. Must we geneticists become bacteriologists, physiological
chemists, simultaneously with being zoologists and botanists? Let us hope so.” In
this remarkably prescient analysis, Muller lays out the paradoxical nature of
the genetic material. It is apparently both autocatalytic (i.e., directs
its own synthesis) and heterocatalytic (i.e., directs the synthesis of
other molecules), yet only the heterocatalytic function seems subject to
mutation. With this, he defines the key problems that must be solved for a
successful chemical model of the gene (1654; 1655).
Hermann Joseph Muller, Jr. (US), Benjamin Minge Duggar (US), and
Joanne Karrer Armstrong (US) suggested that there are many analogies between
viruses, and genes that have broken loose from their moorings (642; 1457; 1655).
Ivan C. Jagger (US) demonstrated that the green peach aphid, Myzus persicae Sulz., acts as a vector
for lettuce mosaic virus (1169).
R. Eustace Montgomery (GB) discovered Africian swine fever virus
in Kenya during 1921, as a new disease causing high mortalities in recently
imported European pigs (1612). Note: the only
asfarvirus
Winston A. Malmquist (US), working in Kenya with David Hay (GB), discovered
the hemadsorption and cytopathic effects in buffy coat and bone marrow culture
of African swine fever virus (1485-1487). Note:
Wart-hogs are a major reservoir with ticks being the primary vector.
Joseph Arthur Arkwright (GB) described the development and
persistence of rough and smooth bacterial colony types. He coined
the terms smooth and rough to describe the forms of the colonies produced by
the intestinal group of microorganisms, and
the application of these terms
to the colony forms of other species (Arkwright 1921).
Paul Henry de Kruif (US) analyzed the changes in virulence in the
bacillus of rabbit septicemia (Streptococcus) and observed that the
colony morphologies on agar plates (smooth and rough) correlated with the
pathogenicity in animals. He also showed that a “pure” culture of virulent
organisms (smooth) could give rise to avirulent variants (rough). De Kruif’s
experiments were the first to explain this phenomenon, called microbic dissociation, within the
framework of genetic mutation in bacteria (565).
Reuben Ottenberg (US) established the medico-legal application of
human blood grouping (1770; 1771).
Hans Zinsser (US) was the first to formulate clearly the
distinction between the tuberculin type of allergic reaction and classic
anaphylactic shock (2566).
Alexander Thomas Glenny (GB) and H.J. Südmerson (GB) discovered
the primary and secondary immune response. In the same paper they described the
properties of diphtheria toxoid (877).
Otto Carl Prausnitz (DE-GB) and Heinz Küstner (DE) demonstrated
that hypersensitivity (allergy) to a food (cooked fish) could be passively
transferred to a healthy nonallergic human by intradermal injection of serum
from the allergic person (1830; 1831). Food
sensitivity, hay fever, asthma, and allergy to animal dander naturally occur in
only some 10 percent of humans. Other individuals cannot acquire these
disorders, which are categorized under atopy
(strangeness).
Arthur F. Coca (US) and Ella F. Grove (US) were the first to refer
to the antibodies of these allergies as atopic
reagins (445).
Kimishige Ishizaka (US), Teruko Ishizaka (US), and Margaret
M. Hornbrook (US) discovered the immunoglobulin epsilon (IgE) class of
antibodies and linked their function with immediate hypersensitivity, i.e.,
reagin or atopic antibodies (1152-1154). Note: These atopic reagins were now classified as immunoglobulin class E (IgE). Skin
tests using patch application, scratching in, or intradermal injections of sets
of antigens (allergens) are called P-K tests to commemorate Prausnitz and Küstner.
Jacques Forestier (FR) and Jean-Marie-Athanase Sicard (FR)
introduced positive contrast myelography with iodized oil (lipiodol). They
x-rayed the spinal canal then shortly thereafter the bronchial tree (805; 806). This technique was so being used to
diagnose ruptured intravertebral disks, nerve root compression or when
posterior fossa neural structures are
suspected.
Hermann Rorschach (CH) developed the Ink Blot Test for use in
psychodiagnosis (1923; 1924).
Charles Haskell Danforth (US) was the first to demonstrate that
the presence of hair on the middle phalanx (mid-digital hair) of man is
genetically determined, the presence of hair being dominant (546).
Alexandre-Achille Souques (FR) documented the importance of encephalitis lethargica as a cause of Parkinsonism (2103). Note: encephalitis
lethargica
is a form of encephalitis caused by a virus and characterized by headache and
drowsiness leading to coma.
Luis Barraquer y Roviralta (ES) was the first to describe the
“grasp reflex” (hemiplegic spasticity) of the foot (132).
John Newport Langley (GB) described the autonomic nervous system. He described three parts to this system:
the sympathetic (fight or flight),
the parasympathetic (eat and sleep)
and the enteric (second brain) (1356). Note:
The chemical modulator for the sympathetic
NS is norepinephrine (noradrenaline). The chemical modulator for the parasympathetic NS is acetylcholine
(ACh). The chemical modulator of the enteric
NS (ENS) is primarily serotonin (5-HT) and secondarily substance P.
Carl John Wiggers (US) saw that, ". . . by aligning such a
galvanometer with optical recorders for pressure, muscular contraction and
heart sounds, the interrelations of electric and contractile events in the
heart could be determined more accurately than before. This problem was— and
remains—one of cardiologic as well as scientific interest, for it is basic to
the usefulness of electrocardiographic interpretation of impulse
conduction." He collected the data necessary to produce a graphic summary
that correlated the dynamic, mechanical, acoustic, and electrocardiographic
events during the normal cardiac cycle, lasting approximately 0.9 seconds. As a
chart this summary became a standard textbook figure and was reprinted in
reviews and books dealing with physiology, electrocardiography, and cardiology
in general. It is still used as a diagram upon which new data, such as
single-cell membrane action potentials, can easily be added. Wiggers also
confirmed the independence of electrical and mechanical reactions in the
mammalian heart (2477-2480).
Frederic Bremer (BE) and Percival Bailey (US) found
that without touching the pituitary, puncture of the hypothalamic infundibulum
provoked adiposogenital dystrophy and
diabetes insipidus, and they
attributed this result to disturbance of hypothalamic innervations of the
pituitary (100).
Claude Regaud (FR) and Alexander Schmincke (DE) were the first to
describe nasopharyngeal carcinoma
(NPC) as a separate entity. This is a tumor arising from the epithelial cells
that cover the surface and line the nasopharynx (1861; 2027).
James Taylor Gwathmey (US) and James Greenough (US) introduced
synergistic anesthesia (949).
John Martin Munro Kerr (GB) was the first in the United Kingdom to
realize that the lower uterine segment incision for caesarean section is
superior (1243).
George Herman Monrad-Krohn (NO) presented the first edition of The Clinical Examination of the Nervous
System, which made him world famous (1610).
Alois Alzheimer (DE) together with Franz Nissl (DE) established
the pathologic anatomy of mental illness (40).
Ralph Milton Waters (US) introduced a resuscitation technique,
which today goes by the name of cardiopulmonary
resuscitation (CPR) (2406).
Carl Gustav Jung (CH) developed the concept of the autonomous and
unconscious complex and the technique of free association. Jung explained human
behavior as a combination of four psychic functions: thinking, feeling,
intuition and sensation. He coined the term "synchronicity," the
coincidence of causally unrelated items having identical or similar meanings.
He used this as an explanation for extrasensory events traditionally thought to
be occult (1212).
Lead arsenate spray was developed and recommended for control of apple
maggot.
The value of
arsenic as a mosquito larvicide was first noted (2050).
Arthur John Evans (GB) unearthed the palace of Knossos on the Greek
island of Crete. Based on the structures and artefacts found there and
throughout the eastern Mediterranean, Evans found that he needed to distinguish
the Minoan civilization Mycenaean Greece. Evans was also the first to define
Cretan scripts Linear A and Linear B, as well as an earlier pictographic
writing (720-722). Michael George
Francis Ventris (GB), in 1952, deciphered the Minoan Linear B script and showed
it to be Greek in its oldest known form; the Linear A script is yet to be
deciphered. Note: The Minoans flourished between 2000 and 1500 B.C.E.
Marc Armand Ruffer (FR-GB) studied the anatomy of Egyptian mummies
and concluded that one of the most prevalent diseases of ancient Egypt was
osteo-arthritis. His examination of the internal organs found that
arteriosclerosis with calcification was also common (1947-1949).
Marc Armand Ruffer (FR-GB) analyzed the mummified remains of
Rhamses (Ramses) V, Egyptian pharoah from 1153-1157 B.C.E., and found that he
suffered from smallpox (red plague) (2; 1103; 1508; 1947; 1949). Note:
Ruffer originated paleopathology
Arthur Smith Woodward (GB) described a skull from the Broken Hill
Mine, Kabwe, Zambia and named it Homo
rhodesiensis: Homo sapiens
rhodesiensis (2537). It is
dated at late Middle Pleistocene, circa 300,000 B.C.E.
1922
“Besides the ordinary proteins, carbohydrates, lipoids, and
extractives, of their several types, there are present within the cell
thousands of distinct substances—the ‘genes’; these genes exist as ultramicroscopic
particles.” Hermann Joseph Muller, Jr. (1655).
Francis William Aston (GB) was awarded the Nobel Prize in
Chemistry for his discovery, by means of his mass spectrograph, of isotopes in
a many non-radioactive elements and for his enunciation of the whole-number
rule.
Archibald Vivian Hill (GB), for his discovery relating to the
production of heat in the muscle, and Otto Fritz Meyerhof (DE-US), for his
discovery of the fixed relationship between the consumption of oxygen and the
metabolism of lactic acid in the muscle, shared the Nobel Prize in physiology
and medicine.
Friedrich Dessauer (DE), Marietta Blau (DE), and Kamillo
Altenburger (DE) postulated the hit
theory of radiobiology. According to this view, the shape of the
dose-effect curve following exposure of a homogeneous population to ionizing
radiation is due to the fact that absorption of radiation is not continuous but
a quantized process, which follows the statistical principle, that bears the
name of Poisson. The effect occurs when a minimal number of absorption events
(called hits) have happened to an
individual (233; 585).
John Augustus Larson (CA) and Leonard Keeler (US) developed the
polygraph (the lie detector) (1358).
John Howard Mueller (US) discovered the amino acid methionine
while working on nutritional requirements of some streptococci (1646).
John Howard Mueller (US) described the properties of a pure sample
of methionine (1647; 1648).
George Barger (GB) and Frederick Philip Coyne (GB) determined the
structure of methionine (129).
Richard Martin Willstätter (DE), Johanna Graser (DE), Richard Kuhn
(DE), and Walter Wassermann (DE) described the existence of a prosthetic group
combined with a larger carrier molecule to form an enzyme (2489).
Donald Dexter van Slyke (US) put the concept of buffer value of
weak electrolytes on a mathematically exact basis (2279).
William Jacob Robbins (US) and Walter Kotte (DE) succeeded in
culturing plant roots by starting with tissue that was already meristematic as
an explant source. Kotte worked with excised root tips such as pea and maize
placing these in a variety of nutrients which contained the salts of Knop's
solution, glucose and several nitrogen compounds such as asparagine, alanine
and meat extract. Kotte obtained growth of root tips for periods of up to 2
weeks, but he did not subculture. Robbins on the other hand maintained maize
roots in vitro for longer periods by
subculturing but with time the growth of the cultures decreased, and the
cultures were lost. Robbins used yeast extract in his cultures (1309; 1911).
Lewis Knudson (US) accomplished the asymbiotic
germination of orchid seeds (1278).
Lewis
Knudson (US) accomplished the symbiotic germination of orchid seeds (1279).
Karl Sax (US) and Hitoshi Kihara (JP) analyzed meiosis in wheat
species and hybrids and were the first to establish the basic chromosome
number of seven and document polyploidy in the wheat group (1253; 1983).
Katherine Scott Bishop (US) and Herbert McLean Evans (US) found
that rats raised on certain diets became totally sterile over a period of two
generations. Fertility could be reinstated by the administration of certain
foods (222). They
demonstrated that the substance X was
not any known nutrient (725). Barnett Sure (US) came to the same conclusion
and named substance X, vitamin E (2182).
Frank Charles Mann (US) and Thomas B. Magath (US) found that dogs
lose consciousness after removal of the liver because of rapid depletion of
glucose from the blood. Consciousness was regained following administration of
glucose (1489; 1490).
Frederick Grant Banting (CA), Charles Herbert Best (US-CA), James
Bartram Collip (CA), John James Richard Macleod (GB), and Edward Clark Noble (CA) discovered
that injection of insulin may cause similar hypoglycaemic coma in rabbits (117). The
obvious conclusion was that glucose is an essential nutrient for the brain.
Alexander Fleming (GB) reported the occurrence of a bacteriolytic
principle in egg white, tears, and other animal fluids. He named this principle
lysozyme (783).
L.K. Wolff (DE) precipitated and purified lysozyme from egg white (2532).
Karl Meyer (US), Richard Thompson (US), John W. Palmar (US), and
Devorah Khorazo (US) showed that lysozyme
is a protein giving some of the typical reactions noted by Fleming and Meyer's
group above (1576).
Edward Penley Abraham (GB) and Robert Robinson (GB) crystallized lysozyme (7).
W. Charles Dorner (CH) published his method for staining bacterial
endospores (621; 622).
Reuben Leon Kahn (US) developed a simple quantitative
precipitation test for syphilis. He found that by adjusting the temperature,
salt concentration, and serum dilution used in his test, the reaction could
indicate the presence of the agents of tuberculosis, malaria, or leprosy in the
blood sample. He therefore called it the universal serological reaction (1213-1216).
Albert Francis Blakeslee (US), John Belling (US), and Marshall E.
Farnham (US) analyzed all the 12 possible trisomic aneuploids possible in the
Jimson weed (Datura stramonium) with
variation in seed capsules being the most obvious phenotypic expression (229-232).
William Porter MacArthur (GB) was the first to recognize a ciliate
pathogenic for an insect. He found Glaucoma
pyriformis parasitizing living and dead larvae of the mosquito Culiseta annulata Schrank=Theobaldia annulata Schrank (1462).
Karl Albert Ludwig Aschoff (DE) coined the phrase reticulo-endothelial system (RES) to
include phagocytic cells in diverse tissues active in the defense of the body.
He excluded lymphocytes (68; 69).
Albert H. Ebeling (US) and Alexis Carrel (FR-US) showed that
eukaryotic cells can grow for long periods in culture provided they are fed
regularly under aseptic conditions. They kept a strain of fibroblasts, obtained
from the heart of a chick embryo, alive and growing for over ten years before
it was deliberately terminated. They also reported long-term cultures of
chicken blood (367; 657).
Herbert Spencer Gasser (US) and Joseph Erlanger (US) published the
first paper in which nerve potentials were recorded with the oscillograph (856). This paper
had a profound effect on the study of nerve physiology.
Norbert Oscar Jean Goormaghtigh (BE) demonstrated that the zona fasciculata of the adrenal cortex
is a source of corticosteroids while the medulla is adrenergic (904).
Theophilus Shickel Painter (US) examined the spermatogenesis of
the opossum (Didelphys virginiana)
and became the first to elucidate sex determination in a marsupial. He found
that it is of the XX/XY type with the male producing sperm, which carry either
the X or the Y chromosome (1776).
Theophilus Shickel Painter (US) was the first to provide evidence
that sex in humans is associated with an X, Y system. He pointed out that
humans contain one pair of chromosomes which do not completely pair with one
another and that segregate at the first maturation division, the X going to one
pole and the Y to the other. He concluded (erroneously) that females are 48 XX,
and males 48 XY (1777). Painter
went on to examine the sex determination mode and chromosome number in many
other marsupial and placental mammals, finding that all exhibit the XX/XY mode.
Ernest Gustav Anderson (US), Calvin Blackman Bridges (US) and
Lilian Vaughan Morgan (US) determined that regarding genetic recombination: (1)
exchange occurs pair-wise among the four homologs. (2) Each pair of alleles
segregates in a ratio of 2:2 among the four meiotic products, regardless of the
number or distribution of exchanges. That is, recombination is reciprocal. (3)
All four homologs of a tetrad may recombine (46; 298; 1622; 1623).
Frederick Grant Banting (CA), Charles Herbert Best (US-CA), and
John James Richard McLeod (GB) isolated insulin from the Islets of
Langerhans in the pancreas of dogs and went on to prove that the purified insulin
could restore a diabetic dog to normal (114). Note:
Nicolae Constantin Paulescu (RO) had 8 months prior to Banting and Best's paper
reported the discovery of a pancreas extract (named: 'pancrein'), which lowered
the blood glucose level (1793).
Frederick Grant Banting (CA), Charles Herbert Best (US-CA), James
Bertram Collip (CA), Walter R. Campbell (CA), Almon A. Fletcher (CA), John
James Richard McLeod (GB), and Edward Clark Noble (CA) successfully treated
seven cases of diabetes mellitus in
humans by giving subcutaneous injections of insulin. Walter R. Campbell and
Almon A. Fletcher supervised the experiment (115; 116).
Theobald Smith (US) and Ralph Bulkley Little (US) demonstrated
that the mother’s colostrum provides new borne calves with immunity to
infectious diarrhea. They attributed the specific role of colostrum to be the
transfer of immune bodies to the calves (2086).
Gerald H. Stott (US), David B. Marx (US), Barry Eugene Menefee
(US), and Gene Thomas Nightengale (US) found that in calves as the interval
following birth to the start of colostrum consumption increases, the ability to
absorb colostral immunoglobulins decreases. Calves fed colostrum after birth
had a closure time for IgG absorption at 21 hours, IgM 23 hours and IgA 23
hours. Calves not ingesting colostrum by 12 hours of age are subject to gut
closure before any Ig absorption takes place (2158-2160).
Donald Baker Parrish (US), George H. Wise (US), Floyd W. Atkeson
(US), and Josiah S. Hughes (US) showed that colostrum transfers large amounts
of vitamin A (retinol) to the new borne calf (1790).
Lewis Lunsford, Jr.
(US), Harold F. Deutsch (US), and Folke Nordbring (SE) established that human
milk whey contains material that reacts with anti-gamma globulin (1454; 1738). Later
other investigators would find IgA, IgG, and IgM in precolostrum, colostrum,
and mature milk.
Edgar V. Allen (US) presented a detailed description of the
cellular changes in primary and secondary sex organs over the course of a
complete reproductive cycle in a female mouse (34).
George Washington Corner (US) reported the whole sequence of
uterine changes occurring in the swine during the reproductive cycle as well as
those occurring in the corpus luteum (470).
Gaston Ramon (FR) observed the formation of a precipitation within
a diphteric mixture of toxin and its antitoxin. He noticed that this
flocculation becomes more intense as the mixture of toxin and antitoxin
approach mutual saturation. This observation was used as a basis for the method
of “proportioning per flocculation” which made it possible to titrate in vitro the diphteric antitoxin that,
before, could be done only by the test in
vivo, on experimental animals (1846).
Verne R. Mason (US), William Hay Taliaferro (US) and John Huck
(US), from a study of sickling of human erythrocytes in several black families,
erroneously concluded that the phenomenon is inherited as a single, Mendelian
dominant gene (S) (1514; 2191). Other
workers would later show that the trait exhibits an intermediate type
inheritance.
Virgil P. Sydenstricker (US), William A. Mulherin (US), and Robert
Wright Houseal (US) published the first case report of sickle cell anemia with autopsy findings (2188).
Thomas Milton Rivers (US) discovered the parainfluenzae bacillus (Haemophilus parainfluenzae) (1908).
Arthur Davies (GB) studied the intestinal contents of soldiers
with dysentery during World War I. He
discovered that stools from men with bacillary
dysentery who had reported sick 24-36 hours earlier, contained specific
agglutinins to Shigella dysenteriae,
whereas such antibodies did not appear in the serum until several days later.
He felt this was evidence that fecal antibodies were produced locally by the
inflamed bowl wall, rather than being derived from the blood (555). Many other
investigators later confirmed his conclusion.
Arthur N. Donaldson (US) studied the signs and symptoms in five
otherwise healthy men who agreed to resist the desire to defecate during a
ninety-hour period. During this time course they were placed on a liberal
lacto-ovo-vegetarian diet. They experienced coated tongue, foul breath,
impaired appetite, gas discomfort, mental sluggishness (increased reaction time
for sight, touch, and hearing), reduced attention span, depression,
restlessness, irritability, failure to be refreshed by sleep, a sense of
heaviness in the pelvis, a dull toxic
headache, an increase in basal metabolic rate, elevated blood sugar, a more
rapid onset of fatigue, and general malaise. Within one hour of having a bowel
movement all were completely normal again. Donaldson then packed the rectums of
four of his subjects, using cotton pledgets saturated with petroleum and dusted
with barium sulfate. This was done two days following the constipation
experiment. Within three hours during which the rectal packing was retained
there was a recurrence of the signs and symptoms previously recited. Donaldson
concluded that the results indicated that the signs and symptoms were not the
result of the absorption of toxins (614).
Walter C. Alvarez (US) concluded from his investigations of
gastroenterological problems that the signs and symptoms attendant to
constipation result from mechanical distention and irritation of the lower
bowel by fecal masses. They are the result of alteration of the physiological
activity of other organs and tissues brought about by the stimulation of
sensory nerves in the distended, overreacting bowel (37).
Shimesu Koino (JP) determined the life cycle of Ascaris lumbricoides in humans,
including the migration of the larval stages around the body. He infected both
a volunteer and himself and realized what was happening when he found large
numbers of larvae in his sputum (1297).
Walther Spielmeyer (DE) wrote an important book on histopathology
of the nervous system, which was the first textbook of general histopathology (2112).
Ernest Marcel Labbé (FR), Jules Tinel (FR) and E. Doumer (FR)
first described the anatomical (adrenal medullary tumor) and clinical
(paroxysmal hypertension) features of pheochromocytoma
or phaeochromocytoma (PCC) (1327).
Georges Fernand Isidore Widal (FR), Pierre Abrami (FR), and
Jacques Lermoyez (FR) were the first to describe the aspirin triad syndrome characterized by the triad of bronchial asthma, vasomotor rhinitis, with or without nasal polyps, and intolerance
to aspirin and aspirin-like medications (2457).
Carl John Wiggers (US) and Louis N. Katz (US) observed that to
maintain a normal or augmented systolic discharge (which is the case in hearts
that are in good condition) it is necessary for the velocity of ejection to
increase. When the heart fails to respond in this way, systolic ejection is
reduced (2480).
Herbert Planner (DE) and Franz Remenovsky (DE) described a
recurrent systemic disease characterized by uveitis with hypopyon, recurrent
ulceration of the mucous membranes of the mouth and pharynx, and ulceration of
the genitalia. It became known as Bechet's
syndrome in honor of Hulusi Bechet (TR) who later described it and first
recommended that this triad be considered an entity (174).
Rudolf Schindler (DE) was using a gastroscope for interpreting
pictures of disease conditions, which formerly could not be diagnosed at all,
e.g. different forms of chronic gastritis
and ventricular polyposis (2017).
Rudolf Schindler (DE) introduced the semi-rigid endoscope (2018).
Charles Foix (FR) described an ophthalmoplegic disease picture
originating in processes secondary to intracranial aneurysms or thrombosis of
the cavernous or lateral sinuses, sometimes associated with trigeminal
neuralgia. There is paralysis of the third, fourth, fifth, and sixth cranial
nerves and the ophthalmic branch of the fifth cranial nerve, together with
proptosis and edema of the eyelids. There may also be trigeminal neuralgia (791).
Remington Kellogg (US) wrote Pinnipeds
from Miocene and Pleistocene Deposits of California which remains the base
upon which modern research on fossil pinnipeds begins (1231).
Curt Paul Richter (US) devised ways to measure the spontaneous
activity of rats. He described how running behavior varied during the day and
night and discovered gender differences in the expression of this behavior,
e.g. the ovarian cycle influences the female rat’s running activity (1883). In
association with his behavioral studies Richter invented the Richter tube for
measuring fluid intake, the running wheel for measuring activity rhythms, and
new ways to measure sweating, salivation, and nest building.
Nicotine became available commercially as an insecticide for
control of cotton aphids. Bordeaux mixture was first suggested as a control for
leafhoppers. Rotenone-bearing insecticides were reported effective for control
of cattle grub and cattle louse. Mexican bean beetle control by use of calcium
arsenate was reported. Magnesium arsenate was developed for control of Mexican
bean beetle. Calcium cyanide dust was first suggested as an insecticidal
fumigant (2050).
The Journal of Biochemistry was founded.
1923
“The edifice of science is akin to
a cathedral built by the efforts of a few architects and many
workers.” Gilbert Newton Lewis and Merle Randall (1399).
“Be kind and tender to the Frog,
And do not call him names,
As ‘Slimy skin’, or ‘Poly-wog’,
Or likewise ‘Ugly James’,
Or ‘Gape-agrin’, or ‘Toad-gone-wrong’,
Or ‘Billy Bandy-knees’:
The Frog is justly sensitive
To epithets like these.
No animal will more repay
A treatment kind and fair;
At least so lonely people say
Who keep a Frog (and, by the way,
They are extremely rare).” Joseph Hilaire Pierre Belloc (191).
Fritz Pregl (AT) was awarded the Nobel Prize in Chemistry for
developing techniques and equipment, which laid the foundation of
microchemistry.
Frederick Grant Banting (CA) and John James Richard Macleod (GB)
were awarded the Nobel Prize in Physiology or Medicine for their discovery of
insulin.
Johannes Nicolaus Brønsted (DK) and Thomas Martin Lowry (GB)
independently suggested a slightly broader definition of acids and bases. In
their definitions: acid = any compound that donates a proton, base = any
compound that accepts a proton. One particularly important feature of their
definitions is the recognition that the anion of a weak acid acts as a base
when it accepts a proton from water, and the cation of a weak base (such as
ammonium) acts as an acid when it transfers a proton back to water. They called
these ions conjugate acids and bases (306; 1446).
The oxidation-reduction potential was standardized as “… the
normal hydrogen electrode. This is defined as a platinized platinum electrode
held under one atmosphere of hydrogen and immersed in a solution normal with
respect to the hydrogen ions. The potential difference at such an electrode is
assigned the arbitrary value of zero” (411).
Peter Joseph William Debye (DE) and Erich Hückel (DE) described
the behavior of an ion in relation to its charge, radius, other ions in
solution, and the dielectric properties of the medium (572).
Sodium chlorate was introduced in France as a soil sterilant and
herbicide in 1923 (2564).
Robert Joachim Feulgen (DE) and Heinrich Rossenbeck (DE)
introduced a test in which a pine shaving impregnated with a solution of
hydrolyzed nucleic acid was exposed to moist hydrogen chloride vapor. With thymus
nucleic acid, a green color appeared; in the presence of ammonia, the pine
splinter turned red. These reactions were not given by the nucleic acids from
yeast or wheat germ, known to contain ribose units, and provided the basis for
a distinction between ribonucleic acids and desoxyribonucleic acids (760; 761).
Feulgen demonstrated the presence of DNA in plant nuclei thus
disposing of the belief that DNA was found only in cell nuclei of animal cells (760).
C.P. Kimball (US) and John R. Murlin (US) noted that pancreatic
extracts contained a hyperglycemic factor, which they named glucagon (1254).
Earl Wilbur Sutherland, Jr. (US) and Christian Rene de Duve
(GB-BE-US) showed that glucagon is
made by no other tissue than the pancreas except the gastric mucosa and certain
other parts of the digestive tract. They obtained evidence suggesting that
pancreatic glucagon is probably a
hormone made in the endocrine islets by cells different from the
insulin-producing beta cells; presumably the alpha cells (2183).
Charles A. Vuylsteke (BE), G. Cornelis (BE), and Christian Rene de
Duve (GB-BE-US) found
compelling evidence that the pancreatic islet alpha cells produce glucagon in significant quantities (2373; 2374).
Alfred Staub (US), Leroy Sinn (US), and Otto K. Behrens (US)
purified then crystallized glucagon (2126).
William W. Bromer (US), Leroy Sinn (US), Alfred Staub (US), and
Otto K. Behrens (US) determined the amino acid sequence of porcine glucagon (305).
Lawrence E. Mallette (US), John H. Exton (US), Charles R. Park
(US), Dennis J. Mackrell (US), and Joseph E. Sokal (US) were the first to
demonstrate the biological antagonisms of insulin
and glucagon (1468; 1484).
Roger Harold Unger (US) postulated that this antagonism underlies
the concept that the relative concentrations of these two polypeptides
perfusing their common target organ at any one moment determine the magnitude
and direction of the metabolic response (2259).
Roger Harold Unger (US), Akira Ohneda (JP), Eugenio Aguilar-Parada
(MX), and Anna M. Eisentraut (US) found that following a release of insulin the extracellular glucose
concentrations are kept relatively constant by a coupled release of glucagon to stimulate hepatic glucose release (2261).
Otto Heinrich Warburg (DE) and Erwin Paul Negelein (DE) reported
the first measurements on the quantum efficiency of photosynthesis. This work led
to the conclusion that four quanta are needed to produce one molecule of oxygen (2392).
Hans Christian Hagedorn (DE) and B. Norman Jensen (DE) developed a
method for determining blood sugar in small volumes of blood (956).
Hugh McGuigan (US) and Hans Paul Kaufmann (DE) reported the
antibacterial activity of furan compounds, specifically furfural and furoic
acids (1226; 1548). This led
eventually to the production of the nitrofurans, which are antimicrobials, used
to treat urinary tract infections.
George Charles de Hevesy; Georg
Charles von Hevesy (HU-DE-SE-DE) was able to follow the absorption of lead in detail
by watering plants with a radioactive isotope of lead-212. The principle of
isotope tracers was thus established (562).
Jens Anton Christiansen (DK), George Charles de Hevesy; Georg
Charles von Hevesy (HU-DE-SE-DE) and Svend Lomholt (DK) performed the first
radiotracer studies in animals. They used lead-210 and bismuth-210 (401; 402).
George Charles de Hevesy; Georg
Charles von Hevesy (HU-DE-SE-DE) and Erich Hofer (DK) showed that phosphorus was
taken up and released by the skeleton, indicating for the first time that the
bone is an active organ (563).
Ole Chievitz (DK) and George Charles de Hevesy; Georg
Charles von Hevesy (HU-DE-SE-DE) used radioactive phosphorus to study phosphorus
metabolism in rats (394).
Joseph Gilbert Hamilton (US) and Robert Spencer Stone (CA), in
1936, administered sodium-24 to a leukemia patient (976).
John Hundale Lawrence (US), L.W. Tuttle (US), K.G. Scott (US), and
C.L. Connor (US) did pioneering work on phosphorus-32 to treat leukemia, first
in rats and shortly after, in humans (1365; 1366).
Torsten Ludvig Thunberg (SE) was the first to hypothesize that
photosynthesis is an oxidation-reduction (redox) reaction in which carbon
dioxide is reduced and water is oxidized (2220). He also
studied the oxidative degradation of foodstuffs in animals.
René Wurmser (FR) also advanced the concept of photosynthesis as a
redox reaction (2545; 2546).
James L. Gamble (US), Gary S. Ross (US), and Frederick F. Tisdall
(US) gave the first demonstration of the need to replace extracellular, as well
as, intracellular fluid and electrolytes in those subjected to extreme loss of
food and water (844; 845).
Malcolm A. Holliday (US) and William E. Segar (US) devised the Holliday-Segar
equation which remains the standard method for calculating maintenance fluid
requirements (1093). Note: The Holliday-Segar
method actually estimates kilocalories lost. It is estimated that a loss of 1
kilocalorie requires 1 mL in replacement. To estimate the daily fluid
requirements of a 9-year-old boy who weights 32 kg, 10*100 + 10*50 + 12*20 =
1740 kcal per day. At a 1 kcal / 1 mL conversion, the daily H20
requirements would therefore be 1740 mL.
Joseph Barcroft (GB), Jonathan C. Meakins (GB), Harold Whitridge
Davies (GB), James Matthews Duncan Scott (GB), and W.J. Duncan Fetter (GB)
demonstrated that the body alters its blood volume as part of its temperature
regulating mechanism (125).
James Cecil Mottram (GB) and William S. Cramer (GB) published the
first known report concerning the male antifertility factor of gonadal origin,
which D. Roy McCullagh (US) later named inhibin (1543; 1643).
Milislav L. Demerec (Yugoslavian-US) working with maize seed stocks,
which were segregating white and normal seedlings, demonstrated 15:1 ratio
segregations in two stocks and later obtained two pedigrees, which segregated in
63:1 ratios. The former condition indicates that two factors act as duplicate
genes producing white seedlings in the double recessive only, while in the
latter case, possibly three duplicate genes are present (581).
Robert Robison (GB) found that ossifying cartilage contains a “bone phosphatase” which promotes the
deposition of calcium phosphate (1916).
Honor Bridget Fell (GB) and Robert Robison (GB) found that phosphatase is synthesized by cartilage,
by the hypertrophic cells found in the preliminary stage of ossification. They
showed that the developing osteoid tissue and hypertrophic cartilage cannot at
once acquire the complete calcifying mechanism but that this mechanism is
gradually developed during tissue differentiation (744-746).
Donald Dexter van Slyke (US), Hsien Wu (CN-US), and Franklin C.
McLean (US) developed equations to predict the change in distribution of water
and diffusible ions between blood plasma and blood cells when there is a change
in pH of the oxygenated blood (2288).
George Washington Corner (US) recovered from a Macacus rhesus (monkey), autopsied on
the 14th day of the menstrual cycle, an ovum in the oviduct, en route from the
ruptured ovarian follicle to the uterus. This was the first such finding in a
primate and confirmed the monkey’s time of ovulation. He also discovered the
phenomenon of anovulatory menstruation seen in young female monkeys and humans (471; 472).
Alfred Henry Sturtevant (US) and Thomas Hunt Morgan (US) proposed
that the same genetic material may have different effects on the phenotype when
its position is altered, the position
effect (2172).
Alfred Henry Sturtevant (US) worked out the phenomenon of unequal
crossing over at the Bar locus in Drosophila,
a position effect (2174). Note:
The discovery of the Bar gene in Drosophila was first reported by
Sabra Colby Tice (US) (2223).
Calvin Blackman Bridges (US), Hermann Joseph Muller, Jr. (US),
Aleksandra Alekseevna Prokofyeva-Belgovskaya (RU), and K.V. Kossikov (RU)
showed that the Bar mutation is itself a tandem duplication of seven
bands, and double-Bar is a tandem triplication, rather than a
duplication, for those bands (296; 1656).
Barbara McClintock (US) proposed that the striking color
variations in the leaves and kernels of Indian corn (Zea mays), are caused by the movement of controlling elements from one chromosomal location to another. This
theory contradicted the paradigm that genes are immutably fixed along the
length of chromosomes. Transposition is now accepted as a major way in which
genes are activated and expressed during development. McClintock also suggested
that induction of gene instability by transposable elements may provide a
mechanism to reorganize the genome rapidly in response to stress and thus may
play an important role in generating diversity (1527-1534). This was
the discovery of what would later be called transposable
elements or transposons or jumping genes.
Edward B. Lewis (US) reported that transposition of
heterochromatin or other chromosomal elements could inhibit the action of
nearby genes (1395).
Charles Haskell Danforth (US) presented his method of estimates of
mutation rates for dominants. This is the first paper to point out the
possibility of using the principle of equilibrium in calculating human mutation
rates (547).
Arthur Edwin Boycott (GB) and Cyril Diver (GB) described “delayed” Mendelian
inheritance controlling the direction of the coiling of the shell in the snail Limnea peregra (263).
Alfred Henry Sturtevant (US) suggests that the character of the
ooplasm, which is in turn controlled by the mother’s genotype, determines the
direction of coiling (2173).
Gershom Franklin White (US) first described hornworm septicemia in
the larvae of two species of insects, Protoparce
sexta Johan. (tobacco hornworm) and Protoparce
quinquemaculata Haw. (tomato hornworm) (2452).
Lemuel Roscoe Cleveland (US) discovered the symbiotic relationship
between intestinal flagellates and termites. This was the first instance in
which a mutualistic relationship between internal microorganisms and their
metazoan host was clearly proved (426-434).
Lemuel Roscoe Cleveland (US), S.R. Hall (US), Elizabeth P.
Saunders (US), and Jane Collier (US) established that the wood roach, Crypotocercus punctulatus, like the
termite, depends on its intestinal flagellates for the ability to utilize
cellulose as its principal food (435). Cleveland is commemorated by Clevelandina reticulitermitidis, a large
wood eating spirochete symbiotic in the gut of cockroaches and termites.
Leonid Abgarovich Orbeli (RU) and Alexandr Grigorievich Ginetsinki
(RU) observed that when the lumbar sympathetic nerve is stimulated in the frog,
the force of the fatigued skeletal muscle contracting due to electrical stimulation
recovered from the weakened tension, but not fully; the anti-fatigue effect of
sympathetic nerves (871; 1752; 1753).
Alexander Thomas Glenny (GB), Barbara E. Hopkins (GB), and Gaston
Ramon (FR) produced a vaccine to diphtheria,
which consisted of a chemically modified (formalin-treated) toxin, known as a toxoid. It is safer than the
toxin-antitoxin mixture and is the one still used today (876; 1847; 1848). This
simple and effective procedure led to the production of several highly
successful vaccines. In 1926, Glenny would later add aluminum salts to the diphtheria
toxoid as an adjuvant to increase its effeciency in stimulating antibodies.
George Frederick Dick (US) and Gladys Henry Dick (US) succeeded in
reproducing typical scarlet fever in
human volunteers by inoculation of axenic
cultures of beta-hemolytic streptococci. This established that a beta-hemolytic
streptococcus is the etiological agent of scarlet
fever (587). They,
along with Alphonse Raymond Dochez (US) and Lillian Sherman (US) discovered the
erythrogenic toxin produced by these
cocci (587; 589-593; 603).
David H. Bergey (US) and Robert Earl Buchanan (US) edited the
first edition of Bergey’s Manual of
Determinitive Bacteriology which was published by the Society of American
Bacteriologists (now the American Society for Microbiology) (200). Over the
years this most famous of modern texts on bacterial classification has
incorporated all significant advances as they have been made. It records the
discoveries of new species, new criteria for classification, and improved
schemes for classification. The current revision goes by the title, Bergey’s Manual of Systematic Bacteriology.
Marcus Eugene Jones (US) authored the monograph Revision of North-American species of
Astragalus, probably the largest genus of flowering plants in North America (1204).
Oswald Theodore Avery (CA-US) and Michael Heidelberger (US)
determined that pneumococcal capsular material is pure polysaccharide free of
protein and furthermore that this capsular material is antigenic—the first
evidence that animals can make antibodies to something other than protein (84; 1029; 1030).
Simon Marcovitch (RU-US) demonstrated that the appearance of
sexual forms of the strawberry louse in late fall is regulated by photoperiod
and not by temperature, as was previously believed. This may be the first time
that sexuality in an animal was shown to respond to a photoperiod. He had
similar findings among the Aphididae (1500; 1501).
Remington Kellogg (US) produced a paper which remained the
definitive work on the squalodonts
(fossil cetaceans with serrated teeth) until Karlheinz Rothausen’s (DE) paper
in 1968 (1232; 1933).
Eli Kennerly Marshall, Jr. (US) and John L. Vickers (US)
discovered that kidney tubules are capable of secreting substances directly
into the urine. They concluded that “the problem would appear to be definitely
settled, and satisfactory evidence would seem to exist that … filtration,
reabsorption, and secretion all play a role in the elimination of urine” (1512). This
represents the discovery of active transport. They first presented this
discovery in October 1922, at a meeting of the Johns Hopkins Medical Society in
a talk entitled, “Proof of Secretion of the Convoluted Tubules.” See, Overton, 1895.
Jacques Roskam (BE) described the presence of fibrinogen on the
platelet surface, suggesting that the fibrinogen-fibrin transition on the
platelet surface might be important (1930).
Heinrich Necheles (DE) used hirudin to perform hemodialyses in
uremic dogs employing prepared peritoneum (Goldbeater's skin) as a membrane (1685).
Georg Haas (DE) performed the first in vivo dialyses of human blood using collodion membranes and
hirudin as anticoagulant. He had very limited success (950-952).
Thomas J. Lumsden (GB) reported that the respiratory center within
the medulla couldn’t generate an autonomous rhythmicity when cut off from
efferent impulses of higher neuraxis and from afferent impulses of the vagi.
Under these circumstances it exhibited sustained inspiration, which he called apneusis. He found that there are
anatomically and functionally separate cell groups for the inspiratory and
expiratory muscles; that the rhythm of the medullary inspiratory center is
determined by another center (pneumotaxic)
in the upper part of the pons (1452; 1453).
Bernardo Alberto Houssay (AR) and Juan T. Lewis (AR) determined
that the cortex of the adrenal gland is indispensable to life; it maintains its
vital functions without the cooperation of the medulla. The chromophil tissue
of the suprarenals is not necessary to life or to normal functions (1112).
Archibald Vivian Hill (GB) and Hartley Lupton (GB) coined the
phrase oxygen deficit in reference to
exercise (1082).
Fritz de Quervain (CH) described a case of complete testicular
feminization (568).
John McLean Morris (US), after searching the literature, clearly
defined the syndrome of complete testicular feminization; the commonest form of
male pseudohermaphroditism. The main
clinical features are female external genitalia with underdeveloped labia and a
blind-ending vagina, absence of internal female genital organs, and the
presence of testes in the inguinal canal or within the abdomen. In appearance
these patients present essentially normal female characteristics with average or
juvenile type of breast development and normal fat deposits; however, large
hands and feet are usually evident with scanty or absent axillary, pubic and
vulval hair (1636). De Quervain’s syndrome
Henry Stanley Plummer (US) introduced the use of iodine in
pre-operative treatment of patients suffering from hyperthyroidism (1826).
Arno Benedict Luckhardt (US) and Jay Bailey Carter (US) introduced
ethylene as a gas anesthetic (1450).
Earl D. Osborne (US), Charles G. Sutherland (US), Albert J.
Scholl, Jr. (US), and Leonard George Rowntree (US) introduced röntgenography of
the urinary tract during excretion of sodium iodide (1757).
William Jason Mixter (US) was the first to successfully treat hydrocephalus with endoscopic third
ventriculostomy (1602).
Franz Volhard (DE) and Viktor Schmieden (DE) performed the first
complete pericardectomy for constrictive
pericarditis (2309).
Max Askanazy (DE-CH) was the first to describe a gastric neuroendocrine tumor (gastric carcinoid tumor) (74). Note: these tumors develop from enterochromaffn-like cells in the
gastric mucosa.
Arthur Sydney Blundell Bankart (GB) described an operation for
habitual dislocation of the shoulder joint. The joint capsule is sewed to the
detached labrum glenoidale, without
duplication of the subscapularis tendon (111; 112). Auguste
Broca (FR) and Georg Clemens von Perthes (DE) had previously described similar
operations but Bankart’s was recognized to be superior.
Joseph Capgras (FR) and Jean Reboul-Lachaux (FR) presented what
has come to be called Capgras syndrome.
The most striking feature of this disorder is that the patient comes to regard
close acquaintances, typically either his parents, children, spouse, or siblings,
as “imposters,” i.e., he may claim that the person in question “looks like” or
is even “identical to” his father, but really isn’t his father (354). Although
frequently seen in psychotic states, more than a third of the documented cases
have occurred in conjunction with traumatic brain lesions, suggesting that it
can have an organic origin.
James Bourne Ayer (US) punctured the cisterna magna to obtain
samples of cerebrospinal for diagnostic purposes (occipital puncture) (87).
Robert Jones (GB) and Robert W. Lovett (GB) wrote Orthopaedic Surgery, probably the first
book to deal systematically with the diagnosis and treatment of fresh fractures (1205).
Rudolph Matas (US), on April 9, 1923, for the first time in
history, successfully ligated the abdominal aorta in the treatment of an
aneurysm. The patient survived the operation but died 18 months later of
pulmonary tuberculosis (1518).
The control of screwworm by use of benzol and pine tar oil was
recommended. Geraniol was discovered as an attractant for Japanese beetles (2050).
1924
"The life of a great scientist in his
laboratory is not, as many may think, a peaceful idyll. More often it is a
bitter battle with things, with one's surroundings, and above all with oneself.
A great discovery does not leap completely achieved from the brain of the
scientist, as Minerva sprang, all panoplied, from the head of Jupiter; it is the
fruit of accumulated preliminary work. Between the days of fecund productivity
are inserted days of uncertainty, when nothing seems to succeed, and when even
matter itself seems hostile; and it is then that one must hold out against
discouragement." Marie Curie (512)
"To come back to the question what significance might be
attached to the co-enzyme common to respiration and fermentation, we may
perhaps suggest that it could possibly have a share in the esterification of
organic compounds with phosphoric acid. Doubtless some substances become more
unstable by such combination…May I make the bold hypothesis that on the one
hand the animal body makes fats and carbohydrates accessible to oxidation by
combining them with phosphoric acid, whereby they become more labile, and on
the other hand, that proteins can only burn in cells by being split up into
amino acids?" Otto Fritz Meyerhof (1592)
"The cytological discoveries of this period
(1870-1900) reached their climax in the splendid reseaches of Edouard Van
Beneden (1883-1884, 1887) on the history of the nuclei during the fertilization
of the egg of the nematode Ascaris megacephala which demonstrated that
the chromosomes of the offspring are derived in equal numbers from the nuclei
of the two conjugating germ-cells and hence equally from the two parents." Edmund
Beecher Wilson (2501).
Willem Einthoven (NL) was awarded the Nobel Prize in Physiology or
Medicine for his discovery of the mechanism of the electrocardiogram.
Harold Jeffreys (GB) was the first credible scientist to propose
that the Earth-moon system is four billion years old, not tens of millions (1180).
Albert Jan Kluyver (NL) presented the concept of unity of biology at the molecular level
and pointed out that life on earth without microbes would not be possible (1269).
Alexander Ivanovich Oparin (RU) postulated that a long chemical
evolution in the oceans preceded the appearance of life on Earth (1747; 1748).
John Burdon Sanderson Haldane (GB-IN), Harold Clayton Urey (US)
and John Desmond Bernal (GB) also forwarded this concept (205; 967; 2264). Note:
Analysis
of light transmitted or reflected by the atmospheres of other planets in our
solar system or by dust clouds in interstellar space revealed that they
contained reduced gases, e.g., methane and ammonia, thus supporting the
Oparin-Haldane hypothesis.
Antoine Marcellin Bernard Lacassagne (FR) and
Jeanne Lattès (FR) developed the first autoradiographic method to localize
radioactive polonium in biological specimens (1328-1331).
Theodor Svedberg (SE), and Herman Rinde (SE), Robin Fåhraeus (SE),
and
James Burton Nichols (US) developed the first analytical ultracentrifuge for forcing colloidal particles to
settle out of solution. From the rate of settling, the size of the particles
and even the shape could be deduced, while a mixture of two different types of
particles could be separated (It was they who coined the word ultracentrifuge). They used the analytical ultracentrifuge to estimate
the molecular weight of myoglobin as 17,600, hemoglobin as 67,000, and snail
hemocyanin as 6,680,000 (2184-2186).
Gilbert Smithson Adair (US) used osmotic pressure in dilute
solutions to very accurately determine the molecular weight of hemoglobin as
67,000 (12; 13). He
reasoned that each molecule had four heme groups and four iron atoms with the
iron atoms taking on oxygen sequentially rather than simultaneously. When he
expressed this sequential uptake in the form of a biochemical equation, with
four constants, he could generate the sigmoid curve for oxygen dissociation
known to apply to hemoglobin (14).
Juda Hirsch Quastel (GB-CA) and Margaret Dampier Whetham (GB) were
the first to measure the oxidation-reduction potential of a biological system
and the first to study competitive inhibition of an enzyme by a structural
analogue of its substrate. They studied the succinic
dehydrogenase of Escherichia coli
as it catalyzed the reaction: succinate + methylene blue = fumurate +
leuco-methylene blue (1838; 1839).
Juda Hirsch Quastel (GB-CA) and Margaret Dampier Whetham (GB)
discovered that some bacteria when centrifuged out of culture, washed with
saline, and resuspended as a washed
suspension of resting cells retain many of the activities of the cells in
culture. The breakdown of substances by such suspensions could be studied under
simple conditions in the absence of cell growth (1839).
Otto Heinrich Warburg (DE) and Tsunao Uyesugi (JP) showed that
photosynthesis has two classes of reactions: light and dark reactions (2394).
Otto Heinrich Warburg (DE), Karl Posener (DE), and Erwin Negelein
(DE) hypothesized that cancer, malignant growth, and tumor growth are caused by
the fact that tumor cells mainly generate energy (as e.g. adenosine
triphosphate /ATP) by non-oxidative breakdown of glucose (glycolysis). This contrasts
with "healthy" cells, which mainly generate energy from oxidative
breakdown of pyruvate. Pyruvate is an end-product of glycolysis and is oxidized
within the mitochondria. Hence, they surmised, the driver of cancer cells
should be interpreted as stemming from a lowering of mitochondrial respiration.
They reported a fundamental difference between normal and cancerous cells to be
the ratio of glycolysis to respiration; this observation is also known as the
Warburg Effect (2393).
Sidney Weinhouse (US), Otto Heinrich Warburg (DE), Dean Burk (US),
and Arthur L. Schade (US) confirmed the work Warburg, Posener, and Negelein
reported in 1924 above (2429).
Donald Dexter van Slyke (US) and James Maffett Neill (US) devised
a method for determining gases in blood and other solutions by vacuum
extraction and manometric measurement (2287).
Einar Hammarsten (SE) was one of the first to show that
DNA is a macromolecule (977).
Ernst Ludwig Bresslau (DE) and Luigi Scremin (IT) found that
mitochondria stain positively with the Feulgen stain. This strongly suggested
that they contained DNA (283).
Joseph Erlanger (US) and Herbert Spencer Gasser (US) determined
how different nerve fibers (cells) conducted their impulses at different rates.
All else being equal, the velocity of the impulse varies directly with the
thickness of fiber (716).
John B. Hursh (US) also experimented with conduction velocity as
it relates to diameter of nerve fibers (1131).
Helmut Kerkhof (DE) stated that one of the functions of the
vomeronasal organ, or Jacobson’s organ, is chemoreception (1242).
Felix Bernstein (DE) demonstrated that it is possible to mathematically
derive reliable conclusions about the transmission system of heredity from the
proportions of phenotypes in a random-breeding population (206).
John Burdon Sanderson Haldane (GB-IN) presented algebraic analyses
of the effects of selection (966).
Liberty Hyde Bailey, Jr. (US) wrote The Manual of Cultivated Plants (99). The 2nd
edition of 1949 runs to 1,116 pages.
Albert H. Ebeling (FR) showed that iris epithelial cells grown in vitro would cease to produce pigment
when grown on rich medium only to return to pigment production when transferred
to a nutritionally poor medium. This implied that the reacquisition of
differentiated traits by cells, which had lost them, was mediated by a
regulatory process and not by mutation (658).
Philipp Stöhr, Jr. (DE) cultivated a fragment of mesoderm from the
ventral wall of an embryonic newt’s trunk, and watched it develop into a
four-chambered heart which began to beat rhythmically (2149). This
suggested that heart-inducing potency is in the anterior endoderm.
Johannes Friedrich Karl Holtfreter (DE-US) found that the newt
gastrula is divided into future head and trunk regions, each region capable of
undergoing self-differentiation even if separated from adjacent regions (1098).
William Hay Taliaferro (US), Lucy Graves Taliaferro (US), and Anna
B. Fisher (US) infected rats with Trypanosoma
lewisi to study the variability of the parasite during the infection. They
discovered that the rat produces antibodies to the parasite. They called these
antibodies, ablastin (2190; 2192; 2193).
Joseph Treloar Wearn (US) and Alfred Newton Richards (US)
presented experimental proof that under normal circumstances protein does not
leave the blood and pass into glomerular filtrate; however, both sodium
chloride and glucose pass from the blood into the glomerular filtrate only to
be reabsorbed from the kidney tubule (1876; 2413). Their 1924
paper ranks as one of the greatest advances in 20th century renal physiology.
Hermann Braus (DE) coined the term nephron to refer to a functional unit of the kidney (281).
George William Marshall Findlay (GB) demonstrated the toxic action
of manganese on the liver (767).
J. Kilian Clarke (GB) isolated Streptococcus
mutans and associated it with the initial enamel lesion leading to dental caries (412).
Harold Haydon Storey (GB) discovered the cause of mealie variegation to be a virus (2155; 2157). He named
it maize streak virus (MSV). The virus is obligately transmitted by the
leafhopper Cicadulina mbila (Naudé)
(Homoptera: Cicadellidae) (2155; 2156).
Brian D. Harrison (GB), Hugh Barker (GB), Kenneth R. Bock (KE),
E.J. Guthrie (KE), Gina Meredith (GB), and Mark A. Atkinson (GB) designated MSV
as the type virus of the newly described group taxon Geminivirus (1002).
Claude Fuller (AU) gave the first written description of this
disease (836).
Marshall
Hertig (US) and Simeon Burt Wolbach (US) discovered and identified the
bacterium Wolbachia in Culex pipientis (1060).
Marshall
Hertig (US) provided a complete description of Wolbachia pipientis (1059).
Wolbachia is widespread in
arthropods, infecting about 25-70% of species of insects.
Walter M. Boothby (US) and Irene Sandiford (US) discovered that
thyroxine is the chief active principle of the thyroid gland (249).
William Waddell Duke (US) and Oren C. Durham (US), allergists,
authored a pioneering survey of hay fever inducing plants in the Kansas City,
MO area (643; 644).
Olaf Blegvad (DK) found that night blindness is a symptom of
vitamin A (retinol) deficiency (234).
George Frederick Dick (US) and Gladys Henry Dick (US) described
the erythrogenic toxin usually produced by the streptococci causing scarlet fever. They showed that the
filtrate of cultures that had produced experimental scarlet fever, when injected intracutaneously in the proper
dilution, gave a distinct local reaction in the skin of a large proportion
(41.6%) of persons who had no history of scarlet fever, while all the
convalescent scarlet fever patients
tested showed negative or only slightly positive reactions. It was further
found that the action of the filtrate on the skin was inhibited by small
quantities of convalescent scarlet fever
serum mixed with the filtrate before injection. This became known as the Dick test
(588).
Eli
Moschowitz (US) was the first to describe a case of what would later be named thrombotic thrombocytopenic purpura. The
patient was a 16-year-old girl who presented with an abrupt onset of petechiae
and pallor followed rapidly by paralysis, coma, and death. Upon pathologic
examination, the small arterioles and capillaries of the patient were found to
have thrombi consisting mostly of platelets (1639; 1640).
George Baehr
(US), Paul Klemperer (US), and Arthur Schiffrin (US) defined the disease
picture clinically and morphologically and distinguished it from other forms of
purpura (92).
Karl Singer (US), Frederick P. Bornstein (US), and Simon A. Wile
(US) named the disease thrombotic
thrombocytopenic purpura (2076).
Viktor Theodor Adolf Georg Schilling (DE) emphasized the value of
a differential leukocyte count of peripheral blood. He divided
polymorphonuclear neutrophil cells into four categories according to number and
arrangement of the nuclei in the cells. The so-called Schilling’s hemogram indicates the different developmental stages
and an increase in juvenile forms indicates the presence of acute infection or
of immature bone marrow as in leukemia (2016).
Augustus R. Felty (US) was the first to perceive that the
association of leukopenia with splenomegaly and chronic arthritis might
constitute a distinct clinical disorder; one which now bears his name, Felty’s syndrome (747).
Walter Bradford Cannon (US), Monroe A. McIver (US), and Sidney W.
Bliss (US) pointed out that the mechanism protecting the body from dangerous
hypoglycemia probably operates in two stages-a primary stage in which
sympathetic activity with adrenal secretion occurs and mobilizes sugar from the
liver; and, if this proves to be inadequate, a secondary stage in which the
activities of the first stage are intensified and augmented in convulsive seizures.
This is an example of automatic adjustments within the organism
when there is a disturbance endangering its equilibrium (351).
Evarts Ambrose Graham (US) and Warren H. Cole (US) developed cholecystography
(x-ray technique for viewing the gall bladder) (911).
Samuel
Alexander Kinnier Wilson (GB) wrote on pathological laughing and crying (2508).
Aladár Petz (HU) invented the surgical stapler.
“The idea stemmed from the need that the surgeon has to open the digestive
tract with its highly contaminated lumen, thereby, risking consequent
peritonitis with its associated increase in mortality” (1818).
Richard Hesse (DE) authored Ecological
Animal Geography, which provided an ecological framework for studies of
animal distribution (1065).
Thorlief Schjelderup-Ebbe (NO) described social dominance
hierarchies (pecking orders) in birds (2019; 2020).
Henry Fairfield
Osborn (US) designated the skull and claw (which he assumed to come from the
hand) from a fossil collected in Mongolia as the type specimen of a new genus, Velociraptor.
This name is derived from the Latin words velox ('swift') and raptor
('robber' or 'plunderer') and refers to the animal's cursorial nature and
carnivorous diet. Osborn named the type species V. mongoliensis after
its country of origin (1756).
2. 1991.
Earliest known victim of small pox? Nurs.
RSA 6:40
7. Abraham EP,
Robinson R. 1937. Crystallization of lysozyme. Nature 140:24
15. Adams CC.
1913. Guide to the Study of Animal
Ecology. New York: Arno Press. 183 pp.
16. Addis TC.
1911. The pathogenesis of hereditary haemophilia. J. Pathol. Bacteriol. 15:427-52
22. Adrian ED.
1914. The all-or-none principle in nerve. J.
Physiol. (London) 47:460-74
33. Allbutt TC.
1915. Diseases of the Arteries: Including
Angina Pectoris. London: Macmillan and Co.
34. Allen EV.
1922. The estrous cycle in the mouse. Am.
J. Anat. 30:297-371
37. Alvarez WC.
1919. Origin of the so-called auto-intoxication symptoms. JAMA 72:8-13
50. Andrewes CH.
1949. The natural history of the common cold. Lancet 253:71-4
51. Andrewes CH.
1953a. The common cold. Br. Med. Bull.
9:206-7
60. Arnesen E.
1903. Spongien von der Norwegischen
Küste. II, Monaxonida, Halichondrina. 30 pp.
67. Aschoff KAL.
1904. Zur myocarditisfrage [To ask myocarditis]. Verh. Dtsch. Ges. Pathol. 8:46-53
76. Aston FW.
1919a. The constitution of the elements. Nature
104:393
77. Aston FW.
1919b. A positive ray spectrograph. Phil.
Mag. Series 6 38:707-14
78. Aston FW.
1920. Isotopes and atomic weights. Nature
105:617
79. Aston FW.
1922. Isotopes. London: Edward
Arnold. 152 pp.
80. Aston FW.
1933. Mass Spectra and Isotopes.
London: Edward Arnold. 248 pp.
100. Bailey P,
Bremer F. 1921. Experimental diabetes insipidus. Arch. Intern. Med. 28:773-803
101. Bailey PB,
Bremer F. 1921. Experimental diabetes insipidus. Arch. Intern. Med. 28:773-803
109. Bancroft TL.
1906. On the etiology of dengue fever. Australas
Med. Gaz. 25:17-8
113. Banti G. 1913a.
Le leucemie [The leukemia]. Sperimentale
67:Supplement 10.9
114. Banting FG,
Best CH. 1922b. The internal secretion of the pancreas. J. Lab. Clin. Med. 7:251-66
122. Barber MA.
1904. New method of isolating microorganisms. J. Kans. Med. Soc. 4:489-94
128. Barger G, Carr
FH, Dale HH. 1906. An active alkaloid from ergot. Br. Med. J. 2:1792
140. Bartholomew ET.
1913. Black heart of potatoes. Phytopathology
3:180-2
144. Bateson W.
1905. Dear Sedgwick. ed. A Sedgwick. Cambridge, UK: University of Cambridge
145. Bateson W.
1905b. Letter. ed. A Sedgwick: John Innes Centre
149. Bateson W,
Punnett RC. 1908a. The heredity of sex. Science
27:785-7
163. Batten FE, Gibb
HP. 1909. Myotonia atrophica. Brain
32:187-205
171. Bayliss WM.
1915. Principles of General Physiology.
pp 706-734. London: Longmans Green
176. Beebe CW. 1906.
The Bird, Its Form and Function. New
York: H. Holt and Company. 496 pp.
177. Beebe CW. 1915.
A tetrapteryx stage in the ancestry of birds. Zool. 2:39-52
184. Beijerinck MW.
1921. Verzamelde Geschriften [Collected
Writings]. Gravenhage: Nijhoff
187. Belling J.
1921. On counting chromosomes in pollen-mother cells. Am. Nat. 55:573-4
189. Belling J.
1927a. The number of chromosomes of cancerous and other human tumors. JAMA 88:396
191. Belloc JHP.
1923. The Bad Child's Book of Beasts.
London: Duckworth. 47 pp.
192. Benedict SR.
1909. A reagent for the detection of reducing sugars. J. Biol. Chem. 5:485-7
202. Berkley HJ.
1894. The nerve elements of the pituitary gland. Johns Hopk. Hosp. Rep. 4:117-27
205. Bernal JD.
1951. The Physical basis of Life.
London: Routledge and Kegan Paul. 80 pp.
211. Biedl A. 1995.
A pair of siblings with adiposo-genital dystrophy. 1922. Obes. Res. 3:404
214. Biffen RH.
1905. Mendel's laws of inheritance and wheat breeding. J. Agric. Sci. Camb. 1:4-48
215. Bigelow HB.
1911. The Siphonophorae. Mem. Mus. Comp.
Zool. Harvard 38:175-402
216. Billingham RE.
1966-1967. The biology of graft-versus-host reactions. Harvey Lect. 62:21-78
220. Bircher E.
1921. Die arthroendoskopie [The arthroendoscope]. Zentralbl. Chir. 48:1460-1
225. Black LM. 1950.
A plant virus that multiplies in its insect vector. Nature 166:852-3
226. Blackman FF.
1905. Optima and limiting factors. Ann.
Botany 19:281-95
227. Blakeslee AF.
1904. Sexual reproduction in the Mucorineae. Proc. Am. Acad. Arts Sci. 40:205-319
228. Blakeslee AF.
1913. Mutations in Mucors. Year B.
Carnegie Inst. Wash. 12:104-5
229. Blakeslee AF.
1922. Variations in Datura due to
changes in chromosome number. Am. Nat.
56:16-31
230. Blakeslee AF.
1934. New Jimson weeds from old chromosomes. J. Hered. 25:80-108
237. Bocage A-E-M.
1921. France Patent No. 536,464
239. Boden C. 1923.
The intracardiac injection of adrenalin. Lancet
201:586-90
243. Bolk L. 1918. Hersenen en Cultuur [Brains and Culture].
Amsterdam: Scheltema en Holkema. 63 pp.
244. Bolk L. 1924. Collected Papers.
249. Boothby WM,
Sandiford I. 1924. Basal metabolism. Physiol.
Rev. 4:69-162
255. Borrel A. 1903.
Etude experimentale de la clavelee. Ann.
Inst. Pasteur (Paris) 17:123-7
256. Bosch C. 1908. United States
264. Boyer SH, IV.
1963. Papers on Human Genetics.
Englewood Cliffs, NJ: Prentice-Hall, Inc. 305 pp.
268. Bragg WH, Bragg
WL. 1915. X-Rays and Crystal Structure.
London: G. Bell and Sons. 228 pp.
269. Bragg WH, Bragg
WL. 1934. The Crystalline State. New
York: Macmillan
272. Bragg WL. 1937.
Atomic Structure of Minerals. Ithaca:
Cornell University Press. 292 pp.
273. Brandes EW.
1920. Artificial and insect transmission of sugarcane mosaic. J. Agr. Res. 19:131-8
275. Braun AC. 1941.
Crown gall production by bacteria-free tumor tissue. Science 94:239-41
281. Braus H. 1924. Anatomie des Menschen [Human Anatomy].
Berlin: Springer-Verlag. 697 pp.
284. Brewer JH.
1940. Clear liquid mediums for the ‘aerobic’ culture of anaerobes. JAMA 115:598-600
290. Bridges CB.
1917. Deficiency. Genetics 2:445-65
291. Bridges CB.
1919a. Duplication. The Anatomical Record
15:357-8
292. Bridges CB.
1921a. Triploid intersexes in Drosophila
melanogaster. Science 54:252-4
296. Bridges CB.
1936. The Bar ‘gene’: A duplication. Science
83:210-1
307. Brooks B. 1924.
Intra-arterial injection of sodium iodide. Preliminary report. JAMA 82:1016-9
308. Brooks J. 1996.
The sad and tragic life of Typhoid Mary. C.M.A.J.
154:915-6
312. Brown JH. 1922.
Modification of an improved anaerobic jar. J.
Exp. Med. 35:467
321. Buck JB. 1935.
Synchronous flashing of fireflies experimentally induced. Science 81:339-40
322. Buck JB. 1988.
Synchronous flashing of fireflies II. Q.
Rev. Biol. 63:265-89
324. Buerger L.
1910. A cysto-urethroscope. JAMA
54:1045-6
331. Burnet FM,
Williams SW. 1939a. Herpes simplex: A new point of view. Med. J. Aust. 1:637-40
334. Cabot RC. 1914.
The four common types of heart disease. JAMA
63:1461-3
342. Campbell AW.
1903. Histological studies on cerebral localization. Proc. R. Soc. Lond. 72:488-92
347. Cannon WB.
1918b. A consideration of the nature of wound shock. JAMA 70:611-7
362. Carrel A.
1908b. Transplantation in mass of the kidneys. J. Exp. Med. 10:98-140
370. Castellani A.
1905. Further observations on parangi (yaws). Br. Med. J. 2:1330-1
374. Castle WE.
1903b. The heredity of sex. Bull. Mus.
Comp. Zool. 11:189-218
375. Castle WE.
1913. Simplified Mendelian formulae. Am.
Nat. 47:307-11
377. Castle WE,
Little CC. 1910. On a modified Mendelian ratio among yellow mice. Science 32:868-70
379. Castle WE, Reed
SC. 1936. Studies on inheritance in lop-eared rabbits. Genetics 21:297-309
383. Chadwick J.
1932. Possible existence of neutron. Nature
129:312
388. Chamberlin TC,
Salisbury RD. 1904-1906. Geology. New
York: H. Holt and Company
391. Channon HJ.
1925. Cholesterol synthesis in the animal body. Biochem. J. 19:424-32
392. Chapelle G,
Peck LS. 1999. Polar gigantism dictated by oxygen availability. Nature 399:114-5
405. Churchill AE,
Biggs PM. 1967. Agent of Marek's disease in tissue culture. Nature 215:528-30
410. Clark WElG.
1932. The structure and connections of the thalamus. Brain 55:406-70
411. Clark WM. 1923.
Studies on oxidation-reduction. Introduction. Public Health Reports 38:443-55
421. Cleland RE.
1972. Oenothera: Cytogenetics and
Evolution. London: Academic Press. 370 pp.
425. Clements FE.
1936. Nature and structure of the climax. J.
Ecol. 24:252-84
440. Cobb NA. 1919.
The orders and classes of nemas. Contrib.
Sci. Nematol. 8:213-6
443. Coblentz WW.
1949. Early history of IR spectroradiometry. Sci. Mon. 58:102-7
451. Cockayne L.
1923. Hybridism in the New Zealand flora. New
Phytol. 22:105-27
454. Committee A.
1906. Reports on plague investigations in India. J. Hyg. (Lond) 6:425-34
471. Corner GW.
1923. Ovulation and menstruation in Macacus
rhesus. Contrib. Embryol.
15:73-101
490. Crafoord C,
Jorpes E. 1941. Heparin as a prophylactic against thrombosis. JAMA 116:2831-5
491. Craigie JH.
1927a. Experiments on sex in rust fungi. Nature
120:116-7
492. Craigie JH.
1927b. Discovery of the function of the pycnia of the rust fungi. Nature 120:765-7
502. Crisp DJ. 1961.
Territorial behaviour in barnacle settlement. J. Exp. Biol. 38:429-46
509. Cuénot LCJ.
1914. Théorie de la préadaptation [Theory of preadaptation]. Scientia 16:60-73
512. Curie MS. 1924.
Pierre Curie. Paris: Payot. 111 pp.
513. Currie JN.
1917. The citric fermentation of Aspergillus
niger. J. Biol. Chem. 31:15-37
522. Cushny AR.
1917. The Secretion of Urine. London
and New York: Longmans, Green and Co. 241 pp.
523. Cushny AR.
1926. The Secretion of Urine. London;
New York: Longmans, Green. 288 pp.
527. d'Herelle FH.
1949. The bacteriophage. Sci. News
14:44-59
529. da Rocha-Lima
H. 1912. Histoplasmosis [German]. Arch.
Schiffs. Tropen Hyg. 16:79-85
536. Dale HH. 1906.
On some physiological actions of ergot. J.
Physiol. (London) 34:163-206
546. Danforth CH.
1921. Distribution of hair on the digits of man. Am. J. Phys. Anthropol. 4:189-204
553. Darlington CD,
Mather K. 1950. The Elements of Genetics.
London: Allen & Unwin. 446 pp.
554. Davenport CB.
1917. Inheritance of stature. Genetics
2:313-89
556. Davies HM.
1913. Recent advances in the surgery of the lung and pleura. B.J.S. 1:228-58
559. Dawson JW.
1916. The histology of disseminated sclerosis. Trans. R. Soc. Edinb. 50:517-740
563. de Hevesy GC,
Hofer E. 1934. Elimination of water from the human body. Nature 134:879
581. Demerec ML.
1923. Inheritance of white seedlings in maize. Genetics 8:561-93
583. Dempster WJ.
1953. Kidney homotransplantation. B.J.S.
40:447-65
587. Dick GF, Dick
GH. 1923. Experimental scarlet fever. JAMA
81:1166-7
588. Dick GF, Dick
GH. 1924a. A skin test for susceptibility to scarlet fever. JAMA 82:265-6
589. Dick GF, Dick
GH. 1924b. Scarlet fever toxin in preventive immunization. JAMA 82:544-5
590. Dick GF, Dick
GH. 1924c. Etiology of scarlet fever. JAMA
82:301-2
597. Dijkgraaf S.
1968. Electroreception in the catfish, Amiurus
nebulosus. Experientia 24:187-8
601. Dobell C. 1919.
Amoebae Living in Man. London: J.
Bale and Danielsson. 155 pp.
613. Donald A. 1908.
Operation in cases of complete prolapse. J.
Obstet. Gynaecol. Br. Emp. 13:195-6
614. Donaldson AN.
1922. Relation of constipation to intestinal intoxication. JAMA 78:884-8
619. Donelson JE,
Turner MJ. 1985. How the typanosome changes its coat. Sci. Am. 252:44-51
620. Doolittle SP.
1920. The mosaic disease of cucurbits. Bull
U.S. Dept. Ag. No.879:1-69
622. Dorner WC.
1930. The negative staining of bacteria. Biotech.
Histochem. 5:25-7
628. Dragstedt LR,
Ellis JC. 1930. Liver autolysis in vivo.
Arch. Surg. 20:8-16
646. Dunbar WP.
1913. The present state of knowledge of hay fever. J. Hyg. (Lond) 13:105-48
657. Ebeling AH.
1922. A ten year old strain of fibroblasts. J.
Exp. Med. 35:755-9
663. Edkins JS.
1906. The chemical mechanism of gastric secretion. J. Physiol. (London) 34:133-44
673. Ehrlich P.
1913. Address in pathology, on chemiotherapy. Br. Med. J. 2:353-9
687. Elliott TR.
1905. The action of adrenalin. J.
Physiol. (London) 32:401-67
688. Ellis JC,
Dragstedt LR. 1929. Effects of liver autolysis in vivo. Exp. Biol Med.
26:304-5
699. Emerson RA.
1909a. Factors for mottling in beans. Amer.
Breed. Assoc. Rep. 5:368-76
701. Emerson RA.
1910. Latent colors in corn. Amer. Breed.
Assoc. Rep. 6
702. Emerson RA.
1913b. The possible origin of mutations in somatic cells. Am. Nat. 47:375-7
705. Emerson RA.
1918. A fifth pair of factors, Aa, for aleurone color in maize, and its
relation
to the Cc and Rr pair. Cornell Ag. Exp. Sta. Bull. 16
708. Emmons CW.
1949. Isolation of Histoplasma capsulatum
from soil. Public Health Reports 64:892-6
709. Emmons CW.
1958. Association of bats with histoplasmosis. Public Health Reports 73:590-5
715. Ereky K. 1918.
Biotechnológia. MMÉE Közlöny,
Budapest 52:337-9
717. Erslev AJ.
1953. Humoral regulation of red cell production. Blood 8:349-57
733. Ewing JR. 1921.
Diffuse endothelioma of bone. Proc. New
York Pathol. Soc. 21:17-24
734. Ewins AJ. 1914.
Acetylcholine, a new active principle of ergot. Biochem. J. 8:44-9
738. Fåhraeus R.
1921. The suspension-stability of the blood. Acta Med. Scand. 55:3-228
740. Fåhraeus RS.
1929. The suspension stability of blood. Physiol.
Rev. 9:241-74
753. Fernald ML.
1926. The antiquity and dispersal of vascular plants. Q. Rev. Biol. 1:212-45
765. Filatov VP.
1935. Transplantation of the cornea. Arch.
Ophthalmol. 13:321-47
776. Fischer HE, von
Mering J. 1904. Über veronal [About veronal]. Ther. Ggw. 45:145-6
781. Flatau E. 1912.
Die Migräne [Migraine]. Berlin: J.
Springer. 253 pp.
784. Fletcher WM,
Hopkins FG. 1907. Lactic acid in amphibian muscle. J. Physiol. (London) 35:247-308
790. Flexner S,
Lewis PA. 1910. Monkeys. J. Exp. Med.
12:227-55
794. Folin OKO.
1905. Laws governing the chemical composition of urine. Am. J. Physiol. 13:66-115
801. Folin OKO, Wu H.
1919. A system of blood analysis. J.
Biol. Chem. 38:81-110
807. Forssman HH.
1945. On hereditary diabetes insipidus. Acta
Med. Scand. Suppl. 121
820. Francis E.
1923. Public Health Reports. Rep. 38 pg.
1391, 1396
821. Francis E.
1925. Tularemia. JAMA 84:1243-50
823. Francis T, Jr.
1940. A new type of virus from epidemic influenza. Science 92:405-8
828. Friderichsen C.
1918. Nebennierenapoplexie bei kleinen kindern. Jahrb. Kinderheilk. 87:109-25
833. Frost WD. 1910.
The Society of American Bacteriologists. Science
31:554
834. Fuchs E. 1910.
Dystrophia epithelialis corneae. Graefes
Arch. Clin. Exp. Ophthalmol. 76:478-508
835. Fuchs W. 1914.
Epilepsie und Luminal [Epilepsy and Luminal]. Munch. Med. Wochenschr. 61:873
836. Fuller C. 1901.
First Report of the Government Entomologist 1899-1900, Natal.
843. Gaines WL.
1915. A contribution to the physiology of lactation. Am. J. Physiol. 38:285-312
850. Garland J.
1943. Varicella following herpes zoster. N.
Engl. J. Med. 228:336-7
855. Gaskell WH.
1908. The Origin of Vertebrates.
London: Longmans, Green
857. Gause GF. 1934.
The Struggle for Existence.
Baltimore: Williams and Wilkins. 163 pp.
859. Gause GF. 1936.
The principles of biocoenology. Q. Rev.
Biol. 11:320-36
860. Gause GF. 1937.
Experimental populations of microscopic organisms. Ecology 18:173-9
875. Gleason HA.
1924. Age and area from the viewpoint of phytogeography. Am. J. Bot. 11:541-6
877. Glenny AT,
Südmerson HJ. 1921. Notes on immunity to diphtheria toxin. J. Hyg. (Lond) 20:176-220
888. Goldberger J.
1922. The relation of diet to pellagra. JAMA
78:1676-80
898. Goldschmidt RB.
1916b. Genetic factors and enzyme reactions. Science 43:98-100
900. Goodale HD.
1909. Sex and its relation to the barring factor in poultry. Science 29:1004-5
901. Goodale HD.
1911. On blastospore closure in Amphibia. Anat.
Anz. 38:275-9
907. Gøtzche P.
2004. Niels Finsen's treatment for lupus
vulgaris. James Lind Library. www.jameslindlibrary.org/trial_records/19th_Century/finsen/finsen_commentary.html
913. Graham JHP.
1915. A note on a relapsing febrile illness of unknown origin. Lancet 186:703-4
915. Gratia A.
1921b. Studies on the d’Hérelle phenomenon. J.
Exp. Med. 34
920. Gray HMW. 1915.
Treatment of gunshot wounds by excision and primary suture. Br. Med. J. 2:317
924. Green AS, Green
LD. 1918. Dakin’s dichloramin-T solution for ocular infections. JAMA 70:1212-3
931. Grinnell J.
1917b. The niche-relationships of the California Thrasher. The Auk 34:427-33
932. Grinnell J.
1924. Geography and evolution. Ecology
5:225-9
933. Grinnell J.
1928. Presence and absence of animals. Univ.
Calif. Chron. 30:429-50
945. Guedel AE,
Waters RM. 1928. A new intratracheal catheter. Anesth. Analg. 7:238-9
procedure in Carlos Chagas' Disease]. Braz. Med. 27:225-6
953. Haber F. 1905. Thermodynamik Technischer Gasreaktionen.
Paderborn: Salzwasser Verlag
967. Haldane JBS.
1929. The origin of life. Rationalist
Ann. 148:3-10
968. Haldane JBS,
Sprunt AD, Haldane NM. 1915. Reduplication in mice. J. Genet. 5:133-5
972. Hale GE.
1958-1959. California Institute of
Technology Catalog 1958-1959. pp 12.
974. Hamilton A.
1929. Industrial Poisons in the United
States. New York: The Macmillan Co. 590 pp.
983. Hansen HN.
1942. Heterokaryosis and variability. Phytopathology
32:639-40
985. Harden A.
1911b. Alcoholic Fermentation.
London: Longmans, Green and Co. 128 pp.
986. Harden A. 1932.
Alcoholic Fermentation. London and
N.Y.: Longmans, Green & Co. 243 pp.
995. Hardy GH. 1908.
Mendelian proportions in a mixed population. Science 28:49-50
1009. Harrison RG.
1921. On relations of symmetry in transplanted limbs. J. Exp. Zool. 32:1-136
1014. Hartwell JA.
1913. Intestinal obstruction. J. Exp.
Med. 18:139-48
1026. Head H. 1920. Studies in Neurology. London: Hodder
& Stoughton
1027. Head H, Holmes GM.
1911. Sensory disturbances from cerebral lesions. Brain 34:102-254
1033. Hektoen L. 1905.
Experimental measles. J. Infect. Dis.
2:238-55
1056. Herrick JB.
1919. Thrombosis of the coronary arteries. JAMA
72:387-90
1062. Hess AF. 1920. Scurvy, Past and Present. Philadelphia:
J.B. Lippincott Company. 279 pp.
1063. Hess AF. 1922.
Influence of light on the prevention and cure of of rickets. Lancet 200:367-70
1086. Hirszfeld L.
1919. A new germ of paratyphoid. Lancet
193:296-7
1095. Holmes A. 1913. The Age of the Earth. London, New York:
Harper and Brothers. 195 pp.
1096. Holmes GM. 1908.
A form of familial degeneration of the cerebellum. Brain 30:466-89
1097. Holmes GM. 1918.
Disturbances of visual orientation. Br.
J. Ophthalmol. 2:449-68; 506-16
1104. Hopkins FG.
1906. The analyst and the medical man. Analyst
31:385-424
1106. Hopkins FG.
1921. On an auto-oxidizable constituent of the cell. Biochem. J. 15:286-305
1107. Hopkins FG.
1929. On glutathione: a reinvestigation. J.
Biol. Chem. 84:269-320
1117. Howell WH. 1935.
Theories of blood coagulation. Physiol.
Rev. 15:435-70
1123. Hudson GH. 1918.
Concerted flashing of fireflies. Science
48:573-5
1129. Hunter C. 1917.
A rare disease in two brothers. Proc. R.
Soc. Med. 10:104-16
1131. Hursh JB. 1939.
Conduction velocity and diameter of nerve fibers. Am. J. Physiol. 127:131-9
1140. Huxley JS. 1920.
Metamorphosis of axolotl caused by thyroid feeding. Nature 104:435
1141. Huxley TH. 1909.
Autobiography and Selected Essays.
Boston, New York Houghton Mifflin. 138 pp.
1142. Hyde HA,
Williams DA. 1944. The right word. Pollen
Analy. Circ. 8:2-3
1161. Jackson C. 1938.
The Life of Chevalier Jackson—An
Autobiography. pp 105. New York: Macmillan
1169. Jagger IC. 1921.
A transmissible mosaic disease of lettuce. J.
Agr. Res. 20:737-41
1173. Jakob GW. 2014.
The evolution of vision. Wiley
Interdiscip. Rev. Dev. Biol. 3:1-40
1189. Johannsen WL.
1911. The genotype conception of heredity. Am.
Nat. 45:129-59
1191. Johnson JL.
1928. Constant temperature and humidity chambers. Phytopathology 18:227-38
1195. Jones DF. 1918b.
Bearing of heterosis upon double fertilization. Bot. Gaz. 65:324-33
1197. Jones DF. 1919.
Hybrid vigor and its meaning. Sci. Am.
121:230-1
1203. Jones LR. 1924.
The relation of environment to disease in plants. Am. J. Bot. 11:601-9
1205. Jones R, Lovett
RW. 1923. Orthopaedic Surgery. New
York: William Wood. 699 pp.
1210. Joslin EP. 1916.
The Treatment of Diabetes Mellitus.
Philadelphia: Lea & Febiger
1217. Kalmijn AJ.
1966. Electro-perception in sharks and rays. Nature 212:1232-3
1218. Kalmijn AJ.
1971. The electric sense of sharks and rays. J. Exp. Biol. 55:371-83
1223. Karpinsky AP.
1912. Collected papers. 1 v. pp.
1226. Kaufmann HP.
1923. Antiseptic action of pyromucic acid. Ber.
Dtsch. Pharm. Ges. 33:132-9
1246. Keys A. 1970.
Coronary heart disease in seven countries. Circulation
41:1-211
1256. King HD. 1908.
The oögenesis of Bufo lentiginosus. J. Morphol. 19:369-438
1258. Kirkham WB.
1919. The fate of homozygous yellow mice. J.
Exp. Zool. 28:125-35
1277. Knopp F. 1910. Z. Physiol. Chem. 68:489-
1278. Knudson L. 1922.
Asymbiotic germination of orchid seeds. Bot.
Gaz. 73:1-25
1282. Köberle F. 1959.
Cardiopathia parasympathicopriva. Munch.
Med. Wochenschr. 101:1308-10
1283. Köberle F. 1963.
Enteromegaly and cardiomegaly in Chagas disease. Gut 41:399-405
1296. Kohn GC. 1995. Encyclopedia of Plague and Pestilence.
New York: Facts on File Inc. 408 pp.
1310. Kraepelin EWMG.
1910. Psychiatrie [Psychiatry].
Leipzig: J. Barth
1312. Kristensen B.
1933. Occurrence of the Bordet Gengou bacillus. JAMA 101:204-6
1332. Laidlaw PP.
1915. Some simple anaerobic methods. Br.
Med. J. 1:497-8
1333. Lambert RA.
1912. The production of foreign body giant cells in vitro. J. Exp. Med.
15:510-6
1350. Lane WA. 1905. Cleft Palate and Hare Lip. London: The
Medical Publishing Co, Ltd. 63 pp.
1351. Lane WA. 1907.
Clinical remarks on the operative treatment of fractures. Br. Med. J. 1:1037-8
1356. Langley JN.
1921. The Autonomic Nervous System.
Cambridge: W. Heffer & Sons, Ltd. 80 pp.
1367. Le Gallienne R.
1920. The Quest of the Golden Girl.
New York: J. Lane. 307 pp.
1380. Leishman WB.
1914. Anti-typhoid inoculation. J. R.
Army Med. Corps 22:365-77
1384. Lerner AB, Case
JD. 1960. Melatonin. Fed. Proc.
19:590-2
1387. Levene PAT.
1914a. On sphingomyelin, second paper. J.
Biol. Chem. 18:453-62
1391. Levene PAT,
Jacobs WA. 1912. On the structure of thymus nucleic acid. J. Biol. Chem. 12:411-20
1392. Levene PAT,
LaForge FB. 1914b. On chondroitin sulfuric acid. J. Biol. Chem. 18:123-30
1393. Levene PAT,
LaForge FB. 1915. On chondrosamine. Proc.
Natl. Acad. Sci. U. S. A. 1:190-1
1394. Levene PAT,
Raymond AL. 1928. Hexose diphosphate. J.
Biol. Chem. 80:633-8
1395. Lewis EB. 1950.
The phenomenon of position effect. Adv.
Genet. 3:73-115
1396. Lewis EB. 1978.
A gene complex controlling segmentation in Drosophila. Nature 276:565-70
1398. Lewis GN. 1916.
The atom and the molecule. J. Am. Chem.
Soc. 38:762-85
1407. Lewisohn R.
1915. Blood transfusion by the citrate method. Surg. Gynecol. Obstet. 21:37-47
1410. Lexer E. 1911b.
On free transplantations. Verh. Deutsch.
Ges. Chir. 40:386
1415. Lillie FR. 1913.
The mechanism of fertilization. Science
38:524-8
1417. Lillie FR. 1916.
The theory of the free-martin. Science
43:611
1418. Lin F-K. 1984. United States
1423. Lissmann HW.
1963. Electric location by fishes. Sci.
Am. 208:50-9
1426. Little CC.
1924a. The genetics of tissue transplantation in mammals. J. Cancer Res. 8:75-95
1436. Lombard WP.
1905. A review of the life of Ludwig. Physician
Surgeon 27:481-93
1439. Longping Y.
1966. A preliminary report on male sterility in rice. Sci. Bull. 17:322
1441. Lotka AJ. 1925. Elements of Physical Biology. Baltimore:
Williams & Wilkins Company. 460 pp.
1442. Lotka AJ. 1956. Elements of Mathematical Biology. New
York: Dover. 465 pp.
1443. Lotsy JP. 1916. Evolution by Means of Hybridization. The
Hague: Martiinus Njhoff. 166 pp.
1446. Lowry TM. 1923.
The uniqueness of hydrogen. J. Soc. Chem.
Indust. 42:43-7
1450. Luckhardt AB,
Carter JB. 1923. Ethylene as a gas anesthetic. Curr. Res. Anesth. Analg. 2:221-9
1451. Luder J, Burnett
D. 1954. A congenital renal tubular defect. Arch.
Dis. Child. 29:44-7
1452. Lumsden TJ.
1923a. The regulation of respiration. Part I. J. Physiol. (London) 58:81-91
1454. Lunsford L, Jr.,
Deutsch HF. 1957. Human milk whey proteins. Exp.
Biol Med. 96:742-4
1455. Lusk G. 1910.
The fate of the amino acids in the organism. J. Am. Chem. Soc. 32:671-80
1461. Macallum AB.
1926. The paleochemistry of the body fluids and tissues. Physiol. Rev. 6:316-57
1463. MacConkey AT.
1905. Lactose-fermenting bacteria in faeces. J. Hyg. (Lond) 5:333-79
1466. Macklin CC.
1916. Binucleate cells in tissue culture. Contrib.
Embryol. 4:69-106
1470. Madsen TJM.
1933. Vaccination against whooping cough. JAMA
101:187-8
1474. Magill IW. 1928.
Endotracheal anaesthesia. Proc. R. Soc.
Med. 22:83-8
1477. Magnus R. 1924. Körperstellung [Body Posture]. Berlin:
Springer. 740 pp.
1478. Magnus R. 1925.
Croonian Lecture: Animal posture. Proc.
R. Soc. Lond. B Biol. Sci. 98:339-53
1499. Marchoux É,
Simond P-L. 1906. Etudes sur la fievre jaune. Ann. Inst. Pasteur (Paris) 20:16-40
1500. Marcovitch S.
1923. Plant lice and light exposure. Science
58:537-8
1511. Marshall EK, Jr.
1913c. The determination of urea in urine. J.
Biol. Chem. 15:495-6
1514. Mason VP. 1922.
Sickle cell anemia. JAMA 79:1318-20
del periodo larva [Notes on the biology of
the Oyster (Ostrea edulis L.) I.
Birth and duration of larvc of the larva period]. Boll. Soc. Nat. Napoli 34:151-9
1528. McClintock B.
1947-1948. Mutable loci in maize. Year B.
Carnegie Inst. Wash. 47:155-69
1531. McClintock B.
1953. Induction of instability at selected loci in maize. Genetics 38:579-99
1535. McCollum EV.
1909. Nuclein synthesis in the animal body. Am.
J. Physiol. 25:120-41
1540. McCoy GW. 1911.
A plague-like disease of rodents. Public
Health Bull. (Wash. DC) No. 43:53-71
1543. McCullagh DR.
1932. Dual endocrine activity of the testis. Science 76:19-20
1544. McDonald S.
1908. Pathology: Acute yellow atrophy of the liver. Edinb. Med. J. 1:83-8
1548. McGuigan H.
1923. The action of furfural. J.
Pharmacol. Exp. Ther. 21:65-75
1550. McLean J. 1916.
The thromboplastic action of cephalin. Am.
J. Physiol. 41:250-7
1556. Melander AL.
1914. Can insects become resistant to sprays? J. Econ. Entomol. 7:167-72
1558. Meltzer SJ.
1910. Bronchial asthma as a phenomenon of anaphylaxis. JAMA 55:1021-4
1561. Mencken HL.
1918. In Defense of Women. New York:
A.A. Knopf. 218 pp.
1566. Mendel JG. 1901.
Experiments on plant hybridization. J.
Hortic. Soc. 26:1-32
1591. Meyerhof OF.
1923. The physico-chemical mechanism of cell respiration. Lancet 201:322-5
1592. Meyerhof OF.
1924. Chemical Dynamics of Life Phenomena.
Philadelphia: Lippincott. 110 pp.
1597. Meyerhof OF.
1930b. The chemistry of muscular contraction. Lancet 216:1415-22
1601. Mixter SJ,
Osgood RB. 1910. Traumatic lesions of the atlas and axis. Ann. Surgery 51:193-207
1606. Molliard M.
1921. Cultivation of fragments of plant embryos. C.R. Soc. Biol. 84:770-2
1617. Moore JA. 1993. Science as a Way of Knowing. Cambridge,
MA: Harvard University Press. 530 pp.
1622. Morgan LV. 1922.
Non-criss-cross inheritance in Drosophila
melanogaster. Biol. Bull.
42:267-74
1624. Morgan TH. 1910.
Sex limited inheritance in Drosophila. Science
32:120-2
1626. Morgan TH.
1911b. Random segregation versus coupling in Mendelian inheritance. Science 34:384
1627. Morgan TH.
1912a. The explanation of a new sex ratio in Drosophila. Science 36:718-9
1628. Morgan TH. 1917.
The theory of the gene. Am. Nat.
51:513-44
1629. Morgan TH. 1919.
The Physical Basis of Heredity.
Philadelphia: J.B. Lippincott. 305 pp.
1630. Morgan TH. 1926.
The Theory of the Gene. New Haven:
Yale University Press. 343 pp.
1631. Morgan TH. 1934.
Embryology and Genetics. New York:
Columbia University Press. 258 pp.
1637. Morse ES. 1916.
Fireflies flashing in unison. Science
43:169-70
1641. Mosher HP. 1916.
The wire gauze brain drain. Surg.
Gynecol. Obstet. 23:740-1
1644. Moulton FR. 1905.
On the evolution of the solar system. Astrophys.
J. 22:165-81
1645. Moynihan BGA.
1910. Duodenal Ulcer. Philadelphia:
W.B. Saunders. 379 pp.
1650. Müller C. 1938.
Xanthoma, hypercholesterolemia, angina pectoris. Acta Med. Scand. 95:75-84
1651. Müller C. 1939.
Angina pectoris in hereditary xanthomatosis. Arch. Intern. Med. 64:675-700
1658. Müller-Eberhard
HJ. 1966. Complement Workshop, La Jolla, California. Immunochemistry 3:495-505
1676. Murray WS. 1927.
Ovarian secretion and tumor incidence. Science
66:600-1
1677. Murray WS. 1928.
Ovarian secretion and tumor incidence. Cancer
Res. 12:18-25
1683. Nash TP, Jr.,
Benedict SR. 1922. Note on the ammonia content of blood. J. Biol. Chem. 51:183
1694. Nelson TC. 1924.
The attachment of oyster larva. Biol.
Bull. 46:143-51
1702. Neuberg CA.
1916. Hydrotropic phenomena. I. Biochem.
Z. 76:107-76
1704. Neuberg CA,
Brahn B. 1907. Über die inosinsäure [About inosinic acid]. Biochem. Z. 5:438-50
1716. Neuhof H. 1923. The Transplantation of Tissues. New
York: Appleton. 297 pp.
1718. Newton WCF,
Pellew C. 1929. Primula kewensis and
its derivatives. J. Genet. 20:405-67
1729. Nitze MC-F.
1891. Das operationscystoskop. Zentralblatt
für Chirurgie 51:15
1736. Noguchi H.
1928b. The etiology of trachoma. J. Exp.
Med. 48, Suppl. 2:1-53
1737. Noon L. 1911.
Prophylactic inoculation against hay fever. Lancet
177:1572-3
1748. Oparin AI. 1938.
The Origin of Life. New York: The
Macmillan Co. 270 pp.
1766. Osler W. 1914b. Aequanimitas. pp 475. Philadelphia: P.
Blakiston’s Son & Co.
1770. Ottenberg R.
1921. Medicolegal application of blood grouping. JAMA 77:682-3
1771. Ottenberg R.
1922. Medicolegal application of blood grouping. JAMA 78:873-7
1775. Painter TS.
1921. The Y chromosome in mammals. Science
53:503-4
1784. Paretsky D,
Werkman CH. 1950. The bacterial metabolism of glycine. Arch. Biochem. 25:288-98
1797. Pavlov IP. 1928.
Lectures on Conditioned Reflexes. New
York: International Publishers
1798. Pavlov IP. 1955.
Selected Works. Moscow: Foreign
Languages Publishing House. 653 pp.
1807. Penrose LS.
1955. Parental age and mutation. Lancet
266:312-3
1808. Penrose LS.
1957. Parental age and achondroplasia and mongolism. Am. J. Hum. Genet. 9:167-9
1810. Peters JA, ed.
1959. Classic Papers in Genetics. Englewood
Cliffs: Printice-Hall. 282 pp.
1813. Petrunkevitch
AI. 1913. Arachnida of North America. Trans.
Conn. Acad. Arts Sci. 18:1-137
1815. Petrunkevitch
AI. 1942. A study of amber spiders. Trans.
Conn. Acad. Arts Sci. 34:119-464
1827. Poincaré H.
1905. Science and Hypothesis. New
York: Science Press. 196 pp.
1828. Polanyi M. 1921.
On adsorption catalysis. Z. Elektroch.
27:142-50
1835. Prum RO. 2003.
Dinosaurs take to the air. Nature
421:323-4
1837. Purdie T, Irvine
JC. 1903. The alkylation of sugars. J.
Chem. Soc., Trans 83:1021-37
1840. Quayle HJ. 1916.
Are scales becoming resistant to fumigation? Univ. Calif. J. Agr. 3:333-58
1866. Reid AF, Keston
AS. 1946. Long-life radio-iodine. Phys.
Rev. 70:987-8
1874. Rhoades MM.
1931. Cytoplasmic inheritance of male sterility in Zea mays. Science
73:340-1
1880. Richards DW.
1957. Right heart catheterization. Science
125:1181-5
1882. Richardson J,
Lönnqvist PA. 1998. Thoracic paravertebral block. Br. J. Anaesth. 81:230-8
1891. Riddoch G. 1935.
Visual disorientation in homonymous half fields. Brain 58:376-82
1892. Rideal S, Walker
JTA. 1903. The standardization of disinfectants. J. R. Sanit. Inst. 24:424-41
1896. Riker AJ. 1927.
Cytological studies of crown gall tissue. Am.
J. Bot. 14:25-37
1909. Rivers WHR, Head
H. 1908. A human experiment in nerve division. Brain 31:323-450
1917. Robison R. 1932.
Hexosemonophosphoric esters: mannose-monophosphate. Biochem. J. 26:2191-202
1918. Robison R, King
EJ. 1929. Hexosemonophosphoric esters. Biochem.
J. 23:517-23
1919. Robison R, King
EJ. 1931. Hexosemonophosphoric esters. Biochem.
J. 25:323-38
1926. Rosenheim SO,
Webster TA. 1927. The parent substance of vitamin D. Biochem. J. 21:389-97
1931. Ross PH, Milne
AD. 1904. Tick Fever at Uganda. Br. Med.
J. 2:1453-4
1938. Rous FP. 1920. Observations on Chicken Tumors Caused by
Filterable Agents. New York. 152 pp.
1940. Rous FP, Murphy
JB. 1911a. Tumor transplantation in the developing embryo. JAMA 56:741-2
1950. Ruhemann S.
1910. Triketohydrindene hydrate. J. Chem.
Soc., Trans 97:2025-31
1951. Rusak B, Zucker
I. 1979. Neural regulation of circadian rhythms. Physiol. Rev. 59:449-526
1952. Russell EJ.
1920. The partial sterilization of soils. J.
Hortic. Soc. 45:237-46
1953. Rutherford E.
1906. Radioactive Transformations.
New York: Scribners. 287 pp.
1954. Rutherford E.
1907. Some cosmical aspects of radioactivity. J. R. Astron. Soc. Can. 1:145-65
1971. Sabin FR. 1922.
On the origin of the cells of the blood. Physiol.
Rev. 2:38-69
1987. Schardinger F.
1904. Bacillus macerans. Centralbl. Bakteriol. Abt. 2 14:772
2003. Scharrer BV.
1992. Recent progress in comparative neuroimmunology. Zoolog. Sci. 9:1097-100
2007. Scharrer E,
Scharrer BV. 1945b. Neurosecretion. Physiol.
Rev. 25:171-81
2018. Schindler R.
1935. Gastroscopy with a flexible gastroscope. Am. J. Dig. Dis. 2:656-63
2022. Schloss OM.
1912. A case of allergy to common foods. Am.
J. Dis. Child. 3:342-62
2037. Schrader F.
1921. The chromosomes of Pseudococcus
nipae. Biological Bulletin 40
2041. Sechenov IM.
1866. Refleksy Golovnogo Mozga [Reflexes
of the Brain]. St. Petersburg. 186 pp.
2043. Sechenov IM.
1965. Reflexes of the Brain.
Cambridge, MA: M.I.T. Press. 149 pp.
2048. Sen-Gupta NN.
1921. Dephenolisation in soil. J. Agr.
Sci. 11:136-58
2061. Sherrington CS.
1919. Mammalian Physiology.
Oxford/London. 156 pp.
2063. Shipley PG.
1922. Faulty diet and Its relation to the structure of bone. JAMA 79:1563-4
2066. Shull GH. 1908.
The composition of a field of maize. Amer.
Breed. Assoc. Rep. 4:296-301
2067. Shull GH. 1909.
A pure line method of corn breeding. Amer.
Breed. Assoc. Rep. 5:51-9
2068. Shull GH. 1910.
Hybridization Methods in Corn Breeding. American
Breeders Magazine 1:98-107
2078. Sisson WR. 1917.
Experimental studies of the intestinal flora. Am. J. Dis. Child. 13:117-27
2080. Slye M. 1916.
Cancer and heredity. Science 43:135-6
2081. Slye M. 1928.
Cancer and heredity. Ann. Intern. Med.
1:951-76
2083. Smith EF,
Townsend CO. 1907. A plant-tumor of bacterial origin. Science 25:671-3
2084. Smith PE. 1930.
Hypophyectomy and replacement therapy in the rat. Am. J. Anat. 45:205-73
2091. Snow GRS. 1935.
Activation of cambial growth by pure hormones. New Phytol. 34:347-60
2092. Soddy F. 1911.
The chemistry of mesothorium. J. Chem.
Soc., Trans 99:72-83
2093. Soddy F. 1913.
Intra-atomic charge. Nature
92:399-400
2098. Soper GA. 1939.
The curious career of Typhoid Mary. Bull.
N.Y. Acad. Med. 15:698-712
2103. Souques A-A.
1921. Rapport sur les syndromes parkinsoniens. Rev. Neurol. 28:534-73
2104. Souttar HS.
1925. The surgical treatment of mitral stenosis. Br. Med. J. 2:603-6
2107. Spemann H, ed.
1938. Embryonic Development and Induction.
New Haven, CN: Yale University.
2109. Spencer TN.
1916. Is black tongue in dogs pellagra? Am.
J. Vet. Med. 11:325
2129. Steedman HF.
1950. Alcian blue 8GS; a new stain for mucin. Q. J. Microsc. Sci. s3-91:477-9
2138. Stern C. 1943b.
The Hardy-Weinberg law. Science
97:137-8
2151. Stoll A. 1918. Switzerland
2155. Storey HH. 1924.
The transmission of a new plant virus disease by insects. Nature 114:245
2168. Student. 1908.
The probable error of a mean. Biometrika
6:1-25
2171. Sturtevant AH.
1920. The vermillion gene and
gynandromorphism. Exp. Biol Med.
17:70-1
2173. Sturtevant AH.
1923b. Inheritance of the direction of coiling in Limnaea. Science
58:269-70
Alfred Töpelmann. Number of.
2180. Sullivan JWN.
1923. Aspects of Science. London: R.
Cobden-Sanderson. 190 pp.
2191. Taliaferro WH,
Huck J. 1923. The inheritance of sickle-cell anemia in man. Genetics 8:594-8
2210. Thompson JA.
1906. On the epidemiology of plague. J.
Hyg. (Lond) 6:537-69
2212. Thomson JJ.
1913. Rays of positive electricity. Proc.
R. Soc. Lond. A Math. Phys. Sci. 89:1-20
2223. Tice SC. 1914. A
new sex-linked character in Drosophila.
Biol. Bull. 26:221-30
2225. Tinel J. 1917. Nerve Wounds. London: Baillére, Tindel
and Cox
2234. Trendelenburg F.
1908. Operative management of pulmonary emboli. Verh. Deutsch. Ges. Chir.:89
2236. Troland LT.
1917. Biological enigmas and the theory of enzyme action. Am. Nat. 31:321-50
2245. Turner CH.
1907a. Do ants form practical judgements? Biol.
Bull. 13:333-43
2247. Turner CH. 1908.
The homing of the burrowing-bees (Anthophoridae). Biol. Bull. 15:247-58
2249. Turner CH.
1923a. The homing of the hymenoptera. Trans.
Acad. Sci. St. Louis 24:27-45
2250. Turner CH.
1923b. Tropisms in insect behavior. Trans.
Acad. Sci. St. Louis 24:19-26
2251. Twort FW. 1915.
An investigation of the nature of ultra-microscopic viruses. Lancet 186:1241-3
2252. Tyzzer EE. 1906.
The histology of skin lesions in varicella. J.
Med. Res. 14:361-92
2264. Urey HC. 1952. The Planets. New Haven, CN: Yale
University Press. 291 pp.
2271. van Leersum EC.
1926. The discovery of vitamines. Science
64:357-8
2290. Vavilov NI.
1926. The Centers of Origin of Cultivated
Plants.
2293. Vernadsky VI.
1929. La Biosphère [The Biosphere].
Paris: Felix Alcan. 231 pp.
2299. Voegtlin C.
1914. he treatment of pellagra. JAMA
63:1094-8
2301. Voelcker AF.
1894-1895. Abstract of post mortem report, no title. Middlesex Hosp. Repts. 278
2315. von Economo K.
1917. Encephalitis lethargica. Wien.
Klin. Wochenschr. 30:581-5
2320. von
Euler-Chelpin HKAS. 1936a. Die cozymase
[The cozymase]. Ergeb. Physiol. 38:1-30
2334. von Frisch K.
1946. Die tanze der bienen [The dance of the bees]. Öst. Zool. Zeitschr. 1:1-48
2341. von Frisch K.
1954a. The Dancing Bees. London:
Methuen & Company. 183 pp.
2352. von Laue MTF.
1913c. Röntgenstrahlinterferenzen [X-ray interference]. Physik. Z. 14:1075-9
2354. von Pirquet CP.
1906. Allergie [Allergy]. Munch. Med.
Wochenschr. 53:1457-8
2359. von Pirquet CP.
1911. Allergy. Arch. Intern. Med.
7:259-88
2361. von Pirquet CP,
Schick B. 1951. Serum Sickness.
Baltimore: Williams & Wil;kins. 130 pp.
2368. von Prowázek
SJM. 1907. Chlamydozoa II. Jaundice of silkworms. Arch. Protistenkunde 10
2376. Walcott CD.
1911. Report of the Director, Smithsonian Institution, Washington, DC
2383. Wallach O. 1909.
Terpene und Campher. Leipzig: Veit
& Co. 576 pp.
2395. Ward GR. 1911.
Hepatic distomiasis (sheep rot) in man. Br.
Med. J. 1:931-5
2405. Waterhouse R.
1911. A case of suprarenal apoplexy. Lancet
177:577-8
2411. Watson JB. 1913.
Psychology as the behaviorist views it. Psychol.
Rev. 20:158-77
2412. Watson JB,
Rayner R. 1920. Conditional emotional reactions. J. Exp. Psychol. 3:1-14
2418. Weed LH. 1938.
Meninges and cerebrospinal fluid. J.
Anat. 72:181-215
2420. Weed LH,
McKibben PS. 1919b. Experimental alteration of brain bulk. Am. J. Physiol. 48:531-58
2423. Weil R. 1915.
Sodium citrate in the transfusion of blood. JAMA
64:425-6
2426. Weinberg M,
Séguin P. 1918. La Gangrene Gazeuse [The
Gaseous Gangrene]. Paris. 444 pp.
2432. Weizmann C. 1915a.
Great Britain Patent No. 845
2433. Weizmann C.
1915b. United States of America
2452. White GF. 1923.
Hornworm septicemia. J. Agr. Res.
26:477-86
2455. Widal GFI.
1903d. [Diagnosis of meningeal haemorrhage]. Presse Med.
2459. Wieland GR.
1906. American Fossil Cycads.
Washington, DC: Carnegie Institution of Washington
2486. Williston SW.
1912. Primitive reptiles: a review. J.
Morphol. 23:637-66
2499. Wilson EB. 1911.
The sex chromosomes. Arch. Mikrosk. Anat.
Entwicklungsmech. 77:249-71
2525. Witmer L. 1907.
Clinical psychology. Psychol. Clin.
1:1-9
2527. Wodsedalek JE.
1916. Causes of sterility in the mule. Biol.
Bull. 30:1-36
2529. Wolbach SB.
1919. Studies on Rocky Mountain spotted fever. J. Med. Res. 41:1-198
2537. Woodward AS.
1921. A new cave man from Rhodesia, South Africa. Nature 108:371-2
2538. Worster-Drought
CC, Kennedy AM. 1917. Pneumococcal meningitis. Br. Med. J. 2:481-3
2547. Wurtman R. 2011.
Physiology and clinical use of melatonin. UpToDate
19.3
2558. Zahorsky J.
1910. Roseola infantilis. J. Pediatr. 22:60-4
2559. Zahorsky J.
1920. Herpetic sore throat. South. Med.
J. 13:871-2
2560. Zahorsky J.
1924. Herpangina: A specific infevtious disease. Arch. Pediatr. 41:181-4
2563. Zeleny C. 1905.
Compensatory regulation. J. Exp. Zool.
2:1-102
2564. Zimdahl R. 2012.
Fundamentals of Weed Science.
Academic Press. 464 pp.
2567. Zinsser H. 1922.
The etiology and epidemiology of influenza. Medicine
1:213-304