A Selected Chronological Bibliography
of Biology and Medicine
c. 1948 — 1956
Compiled by James Southworth Steen, Ph.D.
Delta State University
Dedicated to my loving family
This document celebrates those
secondary authors and laboratory technicians without whom most of this great
labor of discovery would have proved impossible.
Please forward any editorial comments to: James S. Steen, Ph.D., Professor
Emeritus, DSU Box 3262, Cleveland, MS 38733. firstname.lastname@example.org
Hyman (US-GB) discovered that cyclopentadiene reacts with acetylene to give
bicyclo [2.2.1] hepta-2, 5-diene (norbornadiene) as a stable product. It was
then reacted with hexachlorocyclopentadiene (hex) to yield aldrin (1417).
“The surgeon who is his own physician, though
he often has a fool for a colleague, has the happiness of working in an
atmosphere of mutual confidence and admiration.” William
Heneage Ogilvie (1338).
has become apparent over a period of years that even when a histologic
diagnosis of malignant melanoma has been made in children the clinical behavior
rarely has been that of a malignant tumor. The disparity in behavior of the
melanomas of adults and children, despite the histologic similarity of the
lesions occurring in the different age groups, is obviously a matter of
fundamental importance …” Sophie Spitz (1690).
Wilhelm Kaurin Tiselius (SE) was awarded the Nobel Prize in Chemistry for his
research on electrophoresis and adsorption analysis, especially for his
discoveries concerning the complex nature of the serum proteins.
Hermann Müller (CH) was awarded the Nobel Prize in Physiology or Medicine for
his discovery that dichloro-diphenyl-trichloroethane (DDT), also called 2,2-di
(4-chlorophenyl)-1,1,1-trichloroethane, is a potent insecticide.
T. Aldrich (US) and Alfred Otto Carl Nier (US) provided absolute confirmation
that 40Ar is the decay product of 40K when they measured significantly
increased 40Ar/36Ar ratios on argon extracted from potassium-rich minerals
relative to the atmospheric 40Ar/36Ar ratio (15). This set the stage for the rapid
development of the K-Ar dating method. This
dating technique is most useful between 10,000 and 3 billion years.
Leonard Horecker (US) and Arthur J. Kornberg (US) determined the precise
extinction coefficients of both reduced diphosphopyridine nucleotide (DPNH) (cozymase I) and reduced
triphosphopyridine nucleotide (TPNH) (reduced coenzyme II) at 340 nanometers. The values proved to be identical (875). This work made
possible quantitative spectrophotometric measurements in reactions involving
the pyridine nucleotides and became one of the most frequently cited papers in
biochemical literature. Note: DPN
became NAD and TPN became NADP.
Mary Crowfoot-Hodgkin (GB) and Jack D. Dunitz (CH) determined the structure of
calciferol (vitamin D) (377).
Zhu (US) and William H. Okamura (US) synthesized vitamin D (1957).
Bernard Beryl Brodie (US) and Julius Axelrod
(US) investigated the fate of acetanilide in the human body and concluded that
its analgesic actions through N-acetyl-p-aminophenol (now known as acetaminophen) (226). In the early 1970s Johnson
& Johnson marketed N-acetyl-p-aminophenol as Tylenol.
C. Pease (US) and Richard Freligh Baker (US) reliably prepared thin sections
(0.1 to 0.2 micrometers thick) of biological material (80; 1397; 1398).
Eugene Moore (US) described how radioactive di-iodofluorescein
could be used to diagnose and localize brain tumors (1265).
Carl Pauling (US) proposed the principle of transition-state stabilization to
explain enzyme catalysis (1380).
Moore (US) and William Howard Stein (US) introduced partition chromatography on
starch gel columns (1269). This
technique was quickly modified using an ion-exchange resin (sulfonated
cross-linked polystyrene), in 1951, and an automatic recording assembly to
detect chemicals (amino acids) as they emerged from the column (1272; 1684). This apparatus for the first time allowed
the complete amino acid analysis of protein hydrolysates.
H. Lack (GB) reported that several workers had reported the lysis of
fibrin clots by staphylococci, and this has been assumed to be due to a fibrinolysin
produced by the bacteria (1033). Note: This fibrinolysis it turns out was
due to staphylokinase.
Luzon Morris (US) discovered that a solution of anthrone in 95% sulfuric acid
produces a characteristic blue color when added to twice its volume of a water
solution of carbohydrates. The depth of color can be used for quantitative
determination of sugars and polysaccharides even when these are chemically
combined. The effective range is from 20-500 micrograms. Prior hydrolysis to
convert sugars to the free state is not needed; thus, the reagent can be used
for the quick determination of total carbohydrates in a mixture in terms of
their glucose equivalent. Glycogen, starch, sucrose and other glucosides have
been accurately measured (1277).
Abraham Kabat (US) and Manfred Martin Mayer (DE-US) wrote Experimental Immunochemistry, the first great text in
immunochemistry (943). They revised it in 1961 to include, among
other things, Mayer’s discoveries concerning the complement cascade.
G. Albaum (US), and Milton Kletzkin (US) established conclusively the presence
in Drosophila melanogaster adults of
an ATP with the same physical, chemical, and physiological properties as
vertebrate ATP (14).
Kunitz (RU-US) described the isolation of deoxyribonuclease
in crystalline form from beef pancreas (1028).
Friedkin (US) and Albert Lester Lehninger (US) provided experimental proof that
electron transport from NADH to oxygen is the direct source of the energy used
for the coupled phosphorylation of ADP. Pure NADH was incubated aerobically
with water-treated mitochondria, phosphate, and ADP in the absence of
tricarboxylic acid cycle intermediates or any other added organic metabolite.
(The hypotonic water treatment was necessary to make the mitochondria permeable
to NADH.) The NADH was rapidly oxidized to NAD+ at the expense of
molecular oxygen; simultaneously, up to three molecules of ATP were formed from
ADP and phosphate. Such experiments indicated that at three points in the chain
of electron carriers leading from NADH to oxygen, oxidation-reduction energy is
transformed into phosphate-bond energy (629; 1072).
Minge Duggar (US) discovered and introduced Aureomycin
(chlortetracycline), the first of the
tetracycline antibiotics. It is produced by Streptomyces
aureofaciens (501). The tetracyclines block binding of aminoacyl-tRNA
to the A-site of the ribosome in prokaryotes only.
L. Grafflin (US), Dina E. Green (US), W. Eugene Knox (US), Betty N. Noyce (US),
and Victor H. Auerbach (US) discovered that the process of beta-oxidation of
fatty acids is localized in mitochondria (688; 994).
Wilhelm Joseph Holtz (DE) and Hans-Joachim
Schümann (DE) were the first to report the production of norepinephrine
(noradrenaline) in the adrenal medulla (871).
Stanley Cohen (US) found that the nucleic acid of T2 phage is exclusively of
the DNA type and that within 7-10 minutes following its infection of an Escherichia coli cell the metabolic
activity of the host cell is directed to production of virus DNA in large
amounts. He also found that the phosphorus contained within the newly
synthesized viral DNA is largely derived from inorganic phosphorus in the
culture medium (330-332).
H. Doermann (US) discovered that with bacteriophages the infectivity associated
with the original parental phage is lost at the outset of the reproductive process,
since no infective phages whatsoever were found in any of the infected bacteria
lysed artificially within the first ten minutes following infection. The time
course that elapses between infection and the first intracellular reappearance
of infective phage particles is called the eclipse
B. Lewis (US) studied position pseudoallelism in Drosophila (1109-1112).
Sherry (US), William Smith Tillet (US), and L. Royal Christensen (US)
discovered that some strains of hemolytic streptococci produce a streptococcal deoxyribonuclease that
they named streptodornase (1618; 1766).
Lucien Monod (FR), Madeleine Jolit (FR), and Anne-Marie Torriani (FR) isolated lactase (beta-galactosidase) and amylomaltase
from Escherichia coli strain ML (1260).
A. Krasnovsky (RU) discovered that in the presence of appropriate chemical
reagents, chlorophyll a in solution
is reversibly reduced in light (1023).
Moore (US), William Howard Stein (US), Christophe Henri Werner Hirs (US),
Christian Boehmer Anfinsen, Jr. (US), Robert R. Redfield (US), Darrel H.
Spackman (US), Derek G. Smyth (US), Warren L. Choate (US), Juanita Page (US),
William R. Carroll (US), John Thomas Potts, Jr. (US), Arieh Berger (US), and
Juanita Cooke (US) determined the primary structure for ribonuclease. This was the first enzyme to have its primary
structure solved (36; 836-838; 1270; 1271; 1429; 1487; 1662; 1663; 1685; 1708; 1709).
Kartha (US), Jake Bello (US), and David Harker (US) determined the tertiary
structure of ribonuclease (953).
W. Wyckoff (US), Karl D. Hardman (US), Norma M. Allewell (US), Tadashi Inagami
(US), Louise N. Johnson (GB), Frederic Middlebrook Richards (US), William D.
Carlson (US), Byungkook Lee (US), and Yukio Mitsui (JP) determined the tertiary
structure of ribonuclease-S at 3.5
angstrom resolution (1500; 1940).
Pacy Cohen (US) and Santiago Grisolia (CL) demonstrated the fixation of carbon
into the carbonyl group of citrulline and into urea and concluded that
citrulline is an obligate intermediate in the urea synthesis cycle (323).
Pacy Cohen (US) and Santiago Grisolia (CL) concluded that in the synthesis of
citrulline from ornithine, carbamyl-L-glutamic acid is an intermediate (322; 324).
Guzman Barron (US) and Theodore N. Tahmisian (US) provided sufficient evidence
to establish that the Krebs cycle is present in the tissues of insects (97).
Koloman Laki (HU-US) and Laszlo Lorand
(HU-US) partially purified the plasma protein that became known
as the Laki-Lorand factor or fibrin-stabilizing factor, and
presently as factor XIII (1036).
Renne Chen (US) and Russell F. Doolittle (US)
found that the stabilization of fibrin clots by activated factor XIII involves two different sets of cross-linked chains (300).
C. Schneider (US) developed a method for separating the various subcellular
fractions by homogenizing tissues in isotonic sucrose and subjecting the
homogenate to differential centrifugation (1591).
J. Walter Wilson (US) and Elizabeth H. Leduc
(US) discovered the occurrence and formation of binucleate and multinucleate
cells and polyploid nuclei in the mouse liver (1909).
John Fenner (AU) studied the
pathogenesis of ectromelia virus in mice (in which it causes fatal hepatitis) (578; 579). This
work became a classic and has served as a model for such
studies ever since.
Markham (GB), Richard Ellis Ford Matthews (NZ), and Kenneth M. Smith (GB)
purified and characterized an isometric plant virus, Turnip yellow mosaic
virus. They showed that its infectivity depends on the presence of viral RNA,
thus concluding that nucleic acid is essential for virus multiplication. For
the first time RNA was shown to be capable of genetic behavior independent of
David Davis (US), Joshua Lederberg (US), and Norton David Zinder (US) developed
methodology for direct selection of bacterial auxotrophs (403; 405; 1070).
Andreevna Kuprianova (RU) illuminated the pollen morphology of the
Alfred Borthwick (US), Sterling Brown Hendricks (US), and Marion Wesley Parker
(US) found that the action spectrum for floral induction in winter barley, a
long-day plant, is very similar to that for the prevention of floral induction
in soybean and cocklebur. In all three plants the active portion of the
spectrum lies between 600 and 660 nm. The spectral sensitivity and energy
requirements for stem elongation are very similar suggesting that the formation
of flowers and stem elongation are linked to and dependent upon one another.
They speculated that a light absorbing pigment is common to these processes (197). Sterling Brown Hendricks constructed an
absorption curve for C-phycocyanin and found it to be remarkably like the
action spectra for floral initiation and leaf growth (1370).
Alfred Borthwick (US), Sterling Brown Hendricks (US), Marion Wesley Parker
(US), Eben Henry Toole (US), and Vivian Kearns Toole (US) showed that the
photoreceptor is very likely a photoreversible pigment in which absorption of
red light (R) converts it into a form which absorbs far red light (FR) and vice
versa. The wavelengths to which the seeds were last exposed, either R or FR,
determine whether they were induced to germinate or inhibited (198).
Herman Heinze (US), Albert Aloysius Piringer (US) and Harry Alfred Borthwick
(US) determined that the photoperiodic pigment controls skin coloring in
tomatoes (785; 1416).
Alfred Borthwick (US), Sterling Brown Hendricks (US), Eben H. Toole (US), and
Vivian Kearns Toole (US) discovered that the action spectra for promotion and
inhibition of germination of Grand Rapids lettuce seeds seemed to be identical
to the one that controlled flowering and stem and leaf growth. Maximum
induction was at 660 nm with maximum inhibition at 710-750 nm (199). According to Hendricks, “One could hardly
believe such an astounding result, showing that the control by light of a
phenomenon at the start and termination of plant growth—the germination of the
seed and the eventual flowering of the plant—were the same not only in a
qualitative sense but on an absolute basis as well” (790).
Lee Butler (US), Karl H. Norris (US), Harold William Siegelmann (US), and
Sterling Brown Hendricks (US) worked out methods for detection, assay, and
preliminary purification of the pigment controlling photoresponsive development
of plants. They named the R-absorbing form of the pigment P655 and the
FR-absorbing form P735 (256). Shortly thereafter the pigment was named phytochrome (Greek=plant color) with the
R-absorbing form called Pr and the
FR-absorbing form called Pfr (196; 1795).
Pressman (US) and Geoffrey Keighley (US) attempted to create radiolabeled
Pressman (US) and Leonhard Korngold (US) demonstrated that antibodies could be
artificially complexed with a toxic material then act as a carrier of the toxin
to a target cell. They showed that labeled antibodies against Wagner
osteosarcoma were concentrated in vivo
in these tumors (1014; 1434).
Pressman (US), Eugene D. Day (US), and Monte Blau (US) introduced the paired
labeling method in which both antibodies and a control preparation of IgG, each
labeled with a different isotope are injected simultaneously into the same
tumor-bearing animal. The measurement of radioactivity from each isotope in a
dual channel scintillation counter allows one to distinguish the specific
localization of antibodies in a tumor from the nonspecific accumulation of
normal IgG, which is known to occur in the inflammatory and necrotic regions of
the tumor (1432).
Stanley Holt (US) and Charles Stacy French (US) showed the isotopic composition
of oxygen liberated by the Hill reaction from 18O-enriched water to
follow that of water—thus proving that this reaction is a photochemical
oxidation of water (870).
Wayne Kielley (US) and Otto Fritz Meyerhof (DE-US) were the first to isolate
sarcoplasmic reticulum as particulate material. It was found to possess ATPase activity stimulated by magnesium
ions and inhibited by calcium ions (978).
F. Loomis (US) and Fritz Albert Lipmann (DE-US) were the first to discover a
chemical that will allow electron flow in oxidative phosphorylation but
uncouple it from the phosphorylation of ADP to ATP. The uncoupling agent was
2,4 dinitrophenol (1142).
Ezra Mirsky (US), Hans Ris (CH-US), André Félix Boivin (FR), Roger Vendrely
(FR), and Colette Vendrely (FR) reported that the amount of DNA per set of
chromosomes is in general constant in different cell types of an organism.
Moreover, the DNA content per chromosome set is a characteristic of each
species and the DNA content of haploid and diploid nuclei is roughly in the
ratio of 1:2 (188; 1239; 1506; 1813; 1814).
Gerald C. Mueller (US) and James A. Miller
(US) were the first to demonstrate the oxidative metabolism of a carcinogen, 4-dimethylaminoazobenzene
(DAB), in a cell-free system containing rat
liver microsomes/ribosomes (1287).
Julius Axelrod (US) discovered a new class of
enzymes, later called cytochrome P450
dependent monooxygenases (CYPs), which exert a profound influence in many
areas of research, including metabolism of drugs, metabolism of normally
occurring compounds, and investigations of carcinogenesis (67-73).
Allan H. Conney (US), Elizabeth C. Miller
(US), and James A. Miller (US) provided the first evidence that certain
carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), can promote their
own metabolism through induction of microsomal proteins (345).
Tsuneo Omura (JP) and Ryo Sato (JP), David Y.
Cooper (US), Otto Rosenthal (US), and Ronald W. Estabrook (US) discovered
cytochrome P450 and suggested that
this hemoprotein functions in the oxidation of certain chemicals (1341-1344). Note:
Martin Klingenberg published a paper
reporting the presence of a redox pigment in liver
microsomes/ribosomes in 1958.
Anthony Y.H. Lu (US) and Minor Jesser Coon
(US) determined that cytochrome P450
dependent monooxygenases (CYPs) are associated with an NADPH-dependent reductase (1151).
Masayuki Katagiri (JP), Bimal Naresh Ganguli
(IN), and Irwin Clyde Gunsalus (US) were able to separate the methylene hydroxylase system from Pseudomonas putida into three fractions:
a putidaredoxin reductase,
putidaredoxin (an iron-sulfur protein), and a soluble cytochrome P-450 (P-450cam). The three enzymes were shown to
function together to catalyze the hydroxylation of methylene carbon 5 of
Chang-An Yu (US), Irwin Clyde Gunsalus (US),
Masayuki Katagiri (JP), Katsuko Suhara (JP), and Shigeki Takemori (JP) purified
and crystallized cytochrome P-450cam and reported some of its general
Eventually, Gunsalus and his colleagues published the amino acid sequence of
bacterial cytochrome P-450 and solved its three-dimensional structure.
David A. Haugen (US) and Minor Jesser Coon
(US) established beyond doubt the presence of at least two P-450 isoforms in
CYP enzymes mainly catalyze the initial step during conversion of organic
xenobiotics into hydrophilic and excretable derivatives. Nucleophilic or
chemically inert compounds such as aromatic and heterocyclic amines, aminoazo
dyes, PAHs, N -nitrosamines, halogenated
olefins, and others represent the great majority of human carcinogens. As these
chemicals do not react directly with cellular constituents—they require
enzymatic conversion into their ultimate carcinogenic forms—they are termed procarcinogens.
W. Pohl (DE) was the first to demonstrate a circadian rhythm in a unicellular
organism, Euglena gracilis. The
recorded variables were photo accumulation in a beam of light, cell motility,
and cell division (1419).
R. Roth (US), E. Richard Toole (US), and George Henry Hepting (US) determined
that littleleaf disease in Southern
pines results from a progressive deficiency of nitrogen brought about by
complex interaction among certain soil conditions, feeder-root pathogens, land
use practices, and stand density (1526).
William Berliner (US) and Thomas J. Kennedy, Jr. (GB), in the normal dog,
reported a constant rate of potassium excretion, dissociated from filtered
load, occurring after salyrgan administration suggested a tubular secretory
mechanism located, presumably, in the distal tubule. The presence of such a
mechanism has been demonstrated by the intravenous administration of hypertonic
potassium chloride solutions which yielded rates of potassium excretion
considerably above the rates of filtration of potassium at the glomerulus (138).
H. Vincke (BE) and Marcel Lips (BE) isolated the first known rodent malarial
parasite, Plasmodium berghei. It was
found in the blood of a thicket rat in Katanga (now Zaire) Africa (1817).
D. M. Paton (GB) and Eleanor J. Ziamis (GB) while developing muscle relaxants
using anesthetized cats and rabbits discovered that decamethonium produces
neuromuscular block, and hexamethonium produces ganglionic block. Hexamethonium, is the first effective
drug for the treatment of high blood pressure. Although this ganglionic blocker
is effective in reducing blood pressure in humans it has undesirable side
effects because of its action on many different nerve reflexes (1373).
Perry Ahlquist (US) graded the reaction of a series of six sympathomimetic
amines on vasoconstriction, the pupil, heart, gut and uterus. He found their
action to be inhibitory or excitatory depending on the site of action. He
concluded that the relative density and location of two types receptors (alpha
and beta) determined opposing responses at different locations (10). Ahlquist conceived the theory that there
must be two types of receiving mechanisms, or sites, in the cardiovascular
system—one type prevailing in the heart, and the other in the blood vessels.
These receptors, which receive "messages" from the sympathetic
nervous system, were classified and named by him, alpha and beta. Because they
are receptors for adrenaline and adrenaline-like substances, they are known as "adrenergic"
receptors. Ahlquist further postulated that the predominant adrenergic
receptors in the heart are of the beta type, and affect its contraction, its
rate and its rhythm. See James Whyte
A. Owen, Jr. (US) and Jesse L. Bollman (US) discovered what would later be
called factor VII of the blood clotting mechanism (1348).
Koller (CH), Emil A. Loeliger (NL) and Francois Henri Duckert (CH) identified
the same factor, which they named factor VII (1003).
Brian Medawar (GB) found that the brain performs quite poorly when challenged
to set up a primary immune response to a locally introduced antigen, i.e., the
brain is an immunologically privileged
M. Schmidt-Nielsen (DK-US), Knut Schmidt-Nielsen (DK-US), Adelaide Brokaw (US),
Howard Schneiderman (US), Humio Osaki (US), Herschel V. Murdaugh, Jr. (US), and
Roberta O'Dell (US) suggested that urea must be actively secreted. At this time
their studies could not determine the precise nephron segment where the
secretion takes place (1294; 1578; 1579; 1583; 1586).
Kawamura (JP), Juha P. Kokko (US), Akihiko Kato (US), and Jeff M. Sands (US)
found in subsequent tubule perfusion studies conclusive evidence that urea was
actively secreted in two different nephron segments: first, in the straight
segment of the rabbit proximal tubule; and second, in the terminal portion of
the rat inner medullary collecting duct (955; 956).
Solomon Kety (US) and Carl F. Schmidt (US) reported that the brain, which
comprises only 2% of the body weight of man, receives for its nutrition
one-sixth of the heart’s output of blood and consumes one-fifth of the oxygen
utilized by the body at rest (976).
Davies Snell (US) studied tissue transplantation among inbred strains of mice
and coined the term histocompatibility
antigens to describe those gene
products responsible for tissue compatibility. The genes that code for these
antigens he called histocompatibility
A. Gorer (GB), Stewart D. Lyman (GB), and George Davies Snell (US) discovered
the major histocompatibility complex in mice; later named the H-2 locus (683).
Macfarlane Burnet (AU) and Frank John Fenner (AU), based on Ray David Owen’s
observations and on studies of lymphocytic choriomeningitis virus by Erich
Traub, postulated that immunological self-recognition is not genetically
determined but rather is learned by the immune system during the organism’s
embryonic stages, i.e., immunological tolerance develops during embryonic life.
They predicted that antigen introduced prior to maturity of the immune
mechanism would be mistaken for self then and throughout the life of the
Anderson (GB), Rupert Everett Billingham (GB-US), G.H. Lampkin (GB), and Peter
Brian Medawar (GB) demonstrated mutual tolerance to skin grafts by freemartin
cattle twins and speculated that actively
acquired tolerance was responsible (30).
Everett Billingham (GB-US) and Peter Brian Medawar (GB) produced a primer to
skin grafting in mammals. The impact of the paper has been greatly amplified in
that it facilitated the later discovery of
actively acquired tolerance and the definition of the principal
laws of transplantation tolerance (168).
Rupert Everett Billingham
(GB-US), G.H. Lampkin (GB), Peter Brian Medawar (GB), and H.L.L. Williams (GB)
while examining the fate of skin allografts in young cattle, with the objective
of devising a test for distinguishing between fraternal and identical twins,
found that skin grafts transplanted from one twin to the other were accepted,
irrespective of the origin of the twins (167). Note: Cattle fetuses share a placenta, with the
effect that the two blood systems communicate with each other and a free
exchange of blood between the twins is possible.
Baptiste Gabriel Joachim Dausset (FR) and André D. Nenna (FR) discovered isoagglutinins for the human leukocyte during a search for an
immunologic etiology of leukopenia (400).
Brian Medawar (GB) was the first to point out the immunologically privileged
nature of the fetal allograft (1211).
Hasek (CZ), in 1953, produced actively acquired donor specific tolerance
to skin allografts in chickens by deliberately twinning chick embryos: using
two embryonated hen's eggs he joined them by connecting their circulatory
systems, ie., created a vascular bridge between them. When the chicks grew up he
observed that they had lost the ability to form antibodies against the
erythrocytes of their parabiotic partners . Note: This strongly
supported Burnet's theory above.
Everett Billingham (GB-US), Leslie Brent (GB), and Peter Brian Medawar (GB)
produced actively acquired donor specific tolerance to skin allografts
in mice injected during late fetal life with donor hematolymphopoietic cells (164). Note: This strongly supported
Burnet's theory above.
Baptiste Gabriel Joachim Dausset (FR) reported the observation that the sera
from 60 patients contained antibodies, which agglutinated lymphocytes from
certain individuals. He noted that 90% of these patients had received multiple
transfusions. Dausset concluded that transfusion was responsible for creating
antibodies against leukocytes because of an immune response toward the donor (397).
Everett Billingham (GB-US), Leslie Brent (GB), and Peter Brian Medawar (GB)
concluded that in mice the transplantation antigens are developed many days
before birth (166).
Everett Billingham (GB-US), Leslie Brent (GB), and Peter Brian Medawar (GB)
proposed that all the nucleated cells of different tissues of an individual
have exactly the same antigenic make-up and that neonatal mice given foreign
tissue would later treat it as self— immunological
tolerance— whereas older mice which had never experienced the same foreign
material would treat it as non-self and respond immunologically (165).
Joseph van Rood (NL), J. George Eernisse (NL), Adriana van Leeuwen (NL), Rose
Payne (US), and Mary R. Rolfs (US) found that pregnant mothers can be
stimulated by their unborn child to produce human leukocyte agglutinins (HLA
antibodies). The child and the mother must differ from one another in a
leukocyte membrane antigen inherited from the father by the fetus (1396; 1804). Note: In 1967 the World Health
Organization (WHO) named these human leukocyte antigens (HLA).
Baptiste Gabriel Joachim Dausset (FR) introduced the first human
histocompatibility antigen, MAC, named after the initials of three donors whose
leukocytes did not agglutinate the test sera. This antigen is also known as
HLA-A2. He showed that monozygotic twins exhibited identical agglutination
patterns while dizygotic twins did not, which led him to hypothesize that
leukocyte antigens are genetically controlled (398).
Joseph van Rood (NL) and J. George Eernisse (NL) discovered additional
leukocyte antigens which they designated antigens 2 and 3 (1803).
Joseph van Rood (NL) and Adriana van Leeuwen (NL) were the first to use
computers to make sense of the complex reactions produced by human antibodies,
allowing identification of antigens currently known as HLA-B4 and 6, as well as
leukocyte antigen grouping (1805).
Ceppellini (IT), Emilia Sergio Curtoni (IT), Pier Luigi Mattiuz (IT), Vincenzo Miggiano (IT), Guido Scudeller (IT), and
Antonio Serra (IT) coined the word haplotype
to indicate the chromosomal combination of HLA alleles (283).
from a workshop in Torino during 1967 provided the first evidence that
leukocyte antigens are the products of closely linked genes located on the same
chromosome (283; 399; 1806).
Bernard Amos (US), and Fritz H. Bach (US) showed that the mixed leukocyte
culture reaction was detecting the HLA-D locus (28).
Richard Batchelor (GB) and Valerie C. Joysey (GB) analyzed the effect of graft
incompatibility with respect to antigens of the HL-A system in 52 cases of
cadaveric renal transplantation. It was concluded that prospective HL-A-antigen
typing of donors and recipients should be carried out whenever possible, so
that multiple incompatibilities can be avoided making graft survival more
Baptiste Gabriel Joachim Dausset (FR), Felix T. Rapaport (FR), Liliane Legrand
(FR), Jacques Colombani (FR), and Aline Marcelli-Barge (FR) demonstrated the
importance of HLA compatibility for the survival of skin grafts in unmodified
human volunteers (401).
Earl Starzl (US), Kendrick Arthur Porter (US), Giuseppe A. Andres (US), Charles
G. Halgrimson (US), Richard Hurwitz (US), Geoffrey Giles (US), Paul Ichiro
Terasaki (US), Israel Penn (US), Gerhard T. Schroter (US), John R. Lilly (US),
Selby John Starkie (GB), Charles W. Putnam (US), Max Ray Mickey (US), Miguel
Kreisler (ES), Ekkehard D. Albert (US), and N. Tanaka (US) found that zero-HLA
mismatching gives human kidney allografts their best chance for function, good
histologic appearance, and least dependence on immunosuppression (1226; 1703).
van Leeuwen (DK), H. Riek Schuit (DK), and Johannes Joseph van Rood (NL)
identified the first sera that could be used for HLA-DR typing. This formed the
basis on which HLA-DR serology developed (1802). Note: HLA-DR is an MHC class II
cell surface receptor encoded by the human leukocyte antigen complex on
chromosome 6 region 6p21.31
P.M. Jongsma (NL), Harry van Someren (NL), Andries Westerveld (NL), Ann
Hagemeijer (NL), and Peter Pearson (NL) located the HLA genes on chromosome
number 6 (940).
Bradford Hill (GB) suggested that a statistical method of randomization be used to determine which treatment group each
patient should be placed into in the streptomycin trial. It is because of
Hill's efforts that the streptomycin trial is often cited as the first randomized controlled trial (RCT) in
medical history; and that 1948 is celebrated as marking the beginning of a new
era in modern medicine. See, Johannes
Andreas Grib Fibiger, 1898.
Britain, during the inter-war period, the Medical Research Council (MRC)
collaborated with drug licensing bodies to systematize a methodology for making
fair and reliable judgments about the efficacy of therapeutic interventions. By
1950 this methodology had evolved into the randomized controlled trial
(RCT). It involved comparing different therapeutic interventions by casting
lots to determine which patients would be assigned to which treatment groups.
The MRC's Streptomycin Trial Committee was chaired by Philip D'Arcy Hart with
Marc Daniels as Vice-Chairman and Austin Bradford Hill the statistician on the
Committee (360; 816).
Estrade (MG) was the first to successfully treat pneumonic plague (Yersinia pestis) patients. He used
E. Smadel (US), Theodore E. Woodward (US), C. Russell Amies (US), Kenneth
Goodner (US), Fred R. McCrumb, Jr. (US), S. Mercier (), Jean-Marie Robic (FR) and
M. Bouillot () successfully treated bubonic and pneumonic plague (Yersinia pestis) patients with the
antibiotics chloramphenicol and terramycin (oxytetracycline) (1197; 1652).
McCallum Hargraves (US), Helen Robinson (US), Robert J. Morton (US) described
the lupus erythematosus cell which led to the subsequent discovery of
antinuclear antibodies (758) and better
understanding of the disease as one where immune complex deposition played a
major role in tissue pathology and disease manifestations (741).
Farber (US), Louis Klein Diamond (US), Robert D. Mercer (US), Robert F.
Sylvester (US), and James A. Wolff (US) described the temporary remission of
acute leukemia in children following treatment with aminopterin (570).
Howieson Gibson (GB-US) was able to identify the pathway involved in the
reduction of methemoglobin, thereby describing the first hereditary disorder
involving an enzyme deficiency. As a result, the disease was named
"Gibson’s syndrome" (664).
Schneider (US), Edgar J. Poth (US), and William C. Levin (US) found that
nitrogen mustard hydrochloride (mechlorethamine) has an antineoplastic effect
in Hodgkin's lymphoma (1590).
Frei, III (US), Emil J. Freireich (US), James F. Holland (US), and Donald
Pinkel (US) were pioneers in the use of combination chemotherapy (Total Therapy
V protocol), and supportive care of patients receiving combination chemotherapy
for lymphoma and acute leukemia (623; 624; 864; 1413; 1414). Note:
By the mid 1970s the cure rate for acute lymphoblastic leukemia (ALL) at
St. Jude Children’s Hospital approached 90%.
Frei III (US), Vincent T. DeVita, Jr. (US), John H. Moxley, III (US), Arthur A.
Serpick (US), Paul P. Carbone (US), Robert C. Young (US), Bruce A. Chabner
(US), Susan P. Hubbard (US), George P. Canellos (US), Brian J. Lewis (US), Dan
L. Longo (US), Susan M. Hubbard (US), Margaret N. Wesley (US), Richard I.
Fisher (US), Elaine S. Jaffe (US), and Costan Berard (US) made outstanding contributions
to the concept of combination therapy in the treatment of Hodgkin’s lymphoma.
They demonstrated that MOPP (mechlorethamine, Oncovin [vincristine],
procarbazine, and prednisone) chemotherapy could cure advanced Hodgkin's
lymphoma (452; 622; 1108; 1141; 1951).
V. Simone (US), Rhomes J.A. Aur (US), H. Omar Hustu (US), Manuel Verzosa (US),
Donald Pinkel (US), Lorrie Furman (US), Bruce M. Camitta (US), Norman Jaffe
(US), Stephen E. Sallan (US), J. Robert Cassady (US), Demetrius Traggis (US),
Pearl Leavitt (US), David G. Nathan (US), and Emil Frei, III (US) combined
chemotherapies in different phases and based on different toxicities, and
including radiotherapy, developed a regimen that prolonged remission in 80% of
patients with acute lymphocytic leukemia (642; 1636). Note: Collectively
these papers—1964-1984— describe a major milestone in the modern chemotherapy
era as they show the first demonstrations that a previously incurable advanced
disease could be cured by combination chemotherapy and provided the rationale
for the use of combination chemotherapy in medical oncology. This type of
therapy became the standard drug regimen used to treat advanced lymphoma
and acute leukemia.
de F. Baldwin (US), André Frédéric Cournand (FR-US), and Dickinson Woodruff
Richards, Jr. (US) studied a large number and variety of cases of chronic
pulmonary disease in man. The cases were found to fall into broad categories of
pulmonary insufficiency: 1) the gross ventilatory, with restrictive or
obstructive aspects, 2) the alveolar-capillary, with primary disturbances in
respiratory gas exchange, 3) pulmonary emphysema, with various combinations of
these factors, and 4) diffusional insufficiency or alveolar-capillary block,
with the major interference at the alveolar-capillary interface (82-84).
W. Stewart (US) and Norman Treves (US) reported a rare secondary malignancy in
6 cases of angiosarcoma in post-mastectomy lymphedema. They recognized that an
edematous arm after radical mastectomy for breast cancer may suggest recurrent
breast cancer, but that long-standing chronic edema without recurrent cancer
may occasionally produce "a heretofore unrecognized and unreported sequel...
long after the malignant breast neoplasm has apparently been arrested... a new
specific tumor" (1721). The term Stewart-Treves syndrome is broadly applied to an angiosarcoma that
arises in a chronically lymphedematous region due to any cause, including
congenital lymphedema and other causes of secondary lymphedema unassociated
with mastectomy. Lymphangiosarcoma is a misnomer because this malignancy seems
to arise from blood vessels instead of lymphatic vessels. A more appropriate
name is hemangiosarcoma.
Ward S. Fowler (US) measured physiological
dead space in lungs by simultaneous and continuous measurement of volume flow
and nitrogen content of gas expired following the change from breathing air to
breathing 99.6% oxygen. The average volume of the physiological dead space in
45 healthy males at rest was 156 cc. The volume of physiological dead space is
affected by, a) anatomical volume of the bronchial tree, and b) gas diffusion
between terminal bronchioles and alveolar spaces and variation in the rate of
inspiratory volume flow (605).
Ernest Denny-Brown (NZ-GB-US) described bronchogenic carcinoma associated with
primary degeneration of the dorsal root ganglion cells with primary
degeneration of the muscles (447).
H. Patey (GB) and Walter H. Dyson (GB) developed the modified radical
mastectomy for breast cancer. This surgical procedure is less disfiguring than
the radical mastectomy and eventually replaced it as the standard surgical
treatment for breast cancer (1372).
National Heart Institute, in 1948, initiated a study begun in Framingham,
Massachusetts, known as the Framingham
Study. This investigation involved 1,980 men and 2,421 women aged 30 to 62
who showed no signs of heart disease. Every two years, the participants
underwent a complete physical examination. The study showed that high blood
pressure, smoking, and high cholesterol levels are major factors in heart
disease. Fifty years’ worth of data collected from the residents of Framingham
has produced over 1,000 scientific papers; introduced the concepts of biologic,
environmental, and behavioral risk factors; identified major risk factors
associated with heart disease, stroke, and other diseases; created a revolution
in preventive medicine; and forever changed the ways in which the medical
community and the general population view the genesis of disease.
R. Dawber (US), William B. Kannel (US), Nicholas Revotskie (US), Joseph Stokes
III (US), Abraham Kagan (US), and Tavia Gordon (US) Thomas R. analyzed several
factors within the Framingham Study for possible association with the
development of coronary heart disease. During the six years of follow-up of the
population there was an inverse association with educational status, the
incidence of new CHD being less at higher educational levels. There was no
association between national origin and the risk of CHD. A suggestively low CHD
incidence was noted in one of the eight Framingham precincts. This precinct
differed from the others in some respects, but no explanation of this finding
can yet be offered.
was associated with an increased incidence of nonfatal myocardial infarction
and of death from CHD in men 45-62. It was not associated with an increased
incidence of angina pectoris. Cholesterol levels were higher among cigarette
smokers than among non-smokers and higher among those who had smoked and
stopped than among those who had never smoked. Neither relative weight nor
blood pressure showed a similar association with smoking.
consumption per se was not associated with CHD although heavy alcohol intake
was associated with heavy smoking (409).
B. Kannel (US), Thomas R. Dawber (US), Abraham Kagan (US), Nicholas Revotskie
(US), and Joseph Stokes, III (US) reported
additional results from the Framingham study (948).
Ernest Denny-Brown (NZ-GB-US) discovered bronchogenic carcinoma associated with
primary degeneration of the dorsal root ganglion cells with primary
degeneration of the muscles (447). This was named
Denny-Brown’s syndrome II.
Franklin Bland (US) and Richard Harwood Sweet (US) performed the first pulmonary-azygos shunt operation for
relief of mitral stenosis (174).
Hancock (GB) performed the first recorded successful operation for peritonitis
due to abscess in the appendix (735).
Thomas Holmes Sellors (GB) performed the first successful
pulmonary valvulotomy in humans (1608).
B. Schumacker, Jr. (US) reported
the excision of a small descending thoracic aortic aneurysm with reanastomosis of the
Dexter van Slyke (US) reported that in the first, circulatory phase of shock
kidney, renal failure is attributable chiefly to decreased renal blood flow. In
the 2d, organic damage, phase renal failure appears to be attributable to
tubular reabsorption of glomerular filtrate. Means that may be taken during shock
to forestall organic renal damage, and after shock to favor recovery from such
demand are discussed (1809).
David H. Patey (GB) and Walter H. Dyson (GB) modified
Halsted’s mastectomy operation by keeping the great pectoral muscle. The
surgery is less traumatic and is followed by less postoperative complications
(axillary retractable scar, painful syndrome, lymphedema, upper limb mobility
limitation). Lymphedema was not constant, and the postoperative outcome was
better with the preservation of the great pectoral and by changing the type of
incision, which was oblique or transverse, and circumscribed the breast as an
ellipse with poles on the xiphoid medial breast and axillary (1372).
J.B. Atkins (GB), John L. Hayward (GB), David J. Klugman (GB), and A.B. Wayte
(GB), after 10 years of clinical trial, reported the superiority of radical
mastectomy over wide excision (extended tylectomy) in patients with stage-two
breast cancer (65).
John L. Madden (US), Souheil Kandalaft (US), and Roche-Andre
Bourque (US-CA) established the current standard in radical mastectomy. Their
contribution to the technique was the preservation of both pectoral muscles (1168).
Robert Edward Gross (US), in 1948, performed
of an aortopulmonary window in a 4-year-old girl who had dyspnea
with slight exertion and a cardiac murmur that was consistent
with a patent ductus (706). The patient made a satisfactory recovery.
W. Preston (US) laid the
mathematical foundation for discussions of species abundance patterns (1435-1437).
Charles Birch (AU), using the rice weevil, Calandra
oryzae, made the first comprehensive analysis of the demography of a
population growing exponentially under carefully controlled conditions (169).
Davidson (AU) and Herbert George Andrewartha (AU) used the method of partial
regression to measure the degree of association between the numbers of thrips, Thrips imarginis, present during the
spring and the weather experienced during the preceding months. The analysis
showed that 78 per cent of the variance of the population could be related to:
1) the sum of effective temperatures between the date when the break of the dry
season in autumn allows the seeds of the annual food-plants to germinate and
the end of winter (31st August), 2) the amount of rainfall during
September-October, 3) the temperature during the autumn and winter of the
preceding year (402).
Park (GB) deliberately chose two closely related species, Tribolium confusum Duval and Tribolium
castaneum Herbst, for his long-term study of interspecies competition. In
three different experiments Park found that one of the two species always
became extinct. Park’s experimental results supported the tenet that two nearly
identical species cannot coexist on a single limiting resource (1368).
World Health Organization (WHO) was founded.
curiosity remains, though, to grasp more clearly how the same matter, which in
physics and in chemistry displays orderly and reproducible and relatively
simple properties, arranges itself in the most astounding fashions as soon as
it is drawn into the orbit of the living organism. The closer one looks at
these performances of matter in living organisms the more impressive the show
becomes. The meanest living cell becomes a magic puzzle box full of elaborate
and changing molecules, and far outstrips all chemical laboratories of man in
the skill of organic synthesis performed with ease, expedition, and good
judgment of balance. The complex accomplishment of any one living cell is part
and parcel of the first-mentioned feature, that any one cell represents more an
historical than a physical event. These complex things do not rise every day by
spontaneous generation from non-living matter—if they did, they would really be
reproducible and timeless phenomena, comparable to the crystallization of a
solution, and would belong to the subject matter of physics proper. No, any
living cell carries with it the experiences of a billion years of
experimentation by its ancestors. You cannot expect to explain so wise an old
bird in a few simple words.” Max Ludwig Henning Delbrück (441).
is impossible to exaggerate the importance of the variability of the bacterial
cell or the desirability of studying the laws regulating it. Biochemically, bacterial
cells are the most plastic of living material … The bacterial cell by reason of
its small size and consequently relatively large surface, cannot develop by
maintaining a constant chemical environment, but reacts by adapting its enzyme
systems to survive and grow in changing conditions. It is immensely tolerant of
experimental meddling and offers material for the study of processes of growth,
variation and development of enzymes without parallel in any other biological
material.” Marjory Stephenson (1715).
" A recognized
fact which goes back to the earliest times is that every living organism is not
the sum of a multitude of unitary processes, but is, by virtue of
interrelationships and of higher and lower levels of control, an unbroken
unity." Walter Rudolf Hess (812).
patients . . . do not come to you to be cured; they come to be relieved of
their pains and other symptoms and to be comforted. Forced to choose, they
would usually prefer a kind doctor to an efficient one. Never forget that the
patient and his relations are usually frightened and anxious – upset in the
normal life to such an extent that they are prepared to call you into their
lives and to tell you the most intimate facts about themselves, though you may
be unknown to them except as a member of an honorable profession.” Hugh William
Bell Cairns (260).
Rudolf Hess (CH) for his discovery of the functional organization of the
interbrain as a coordinator of the activities of the internal organs and
Antonio Caetano de Abreu Freire Egas Moniz (PT) for his discovery of the
therapeutic value of lobotomy in certain psychoses shared the Nobel prize for
physiology and medicine.
Frank Libby (US), Ernie C. Anderson (US), and James R. Arnold (US) developed
the carbon-14 dating technique (1119; 1120). Carbon-14 has a half-life of 5730 years and
is especially useful for dating objects from the last 40,000 years.
is one of the most profound discoveries of the 20th century. J. Desmond Clark
(GB) wrote that were it not for radiocarbon dating, "we would still be
foundering in a sea of imprecisions sometime bred of inspired guesswork but
more often of imaginative speculation” (309).
Reuben Spies (US) and Dorris C. Chambers (US) described several variations of a
method for colorimetric analysis of unhydrolyzed proteins. The basic method was
based on fundamental studies of the behavior of free and peptide-linked
tryptophan. These studies included a method of alkaline hydrolysis which
protects tryptophan from external destruction at temperatures up to 185°C
without addition of antioxidants to the solution (1689).
Kelner (US), working with Escherichia
coli and conidia of Streptomyces
griseus, discovered that light belonging to the visible range is capable of
reactivating biological material that has been rendered inactive by ultraviolet
radiation (UV) (963-968).
This phenomenon is commonly referred to as photoreactivation.
Note: Alexander Hollaender (US) and John T. Curtis (US) made the earliest known
suggestion that there is likely to exist a natural DNA repair mechanism (863).
Dulbecco (IT-US) discovered the same phenomenon in bacteriophages associated
with their host cell (502; 503).
Stan Rupert (US), Solomon H. Goodgal (US) and Roger M. Harriott (US) confirmed
that photoreactivation really is a DNA repair process catalyzed by a specific
enzyme with a strict requirement for visible light (1538).
Stan Rupert (US) discovered an enzyme from baker’s yeast capable of catalyzing
photoreactivation of bacterial cells, which had been inactivated by ultraviolet
Beukers (NL), J. Ijlstra (NL), Wouter Berends (NL), Adolf Wacker (DE),
Hanswerner Dellweg (DE), Diether Jacherts (DE) and Dieter Weinblum (DE)
determined that ultraviolet light produces dimers of thymine, thymine-cytosine,
and cytosine in deoxyribonucleic acid (151-155; 1833-1835).
Burton Setlow (US), William L. Carrier (US), Richard P. Boyce (US), Paul
Howard-Flanders (US), David Pettijohn (US), and Philip Hanawalt (US) found that
in Escherichia coli the onset of DNA
synthesis is associated with thymine dimer removal. One step in the recovery of
cells from the effects of UV may be the removal of the dimers from DNA (200; 1406; 1612).
This helped explain what was called dark
E. Rasmussen (US) and Robert B. Painter (US) presented evidence that this type
of repair also operates in mammalian cells (1479).
Burton Setlow (US), Jane K. Setlow (US), and William L. Carrier (US) determined
the action spectrum for the splitting of thymine dimers and showed that
wavelengths shorter than 254nm were most effective. Observing changes in the
absorption spectrum of DNA could thus easily follow the dimerization and
monomerization reactions in pure DNA. This simple measurement allowed them to
determine the kinetics of dimerization and monomerization as a function of
wavelength. They found that wavelengths around 280nm preferentially resulted in
the formation of dimers, whereas wavelengths around 240nm preferentially split
them (1610; 1611; 1613; 1614).
L. Wulff (US) and Claud Stan Rupert (US) went on to find evidence that both
enzyme-catalyzed photoreactivation and short-wavelength direct reactivation
operate on the same substrate, strongly suggesting that enzymatic
photoreactivation effected the monomerization of pyrimidine dimers (1936).
Howard-Flanders (US), Richard P. Boyce (US), and Lee Theriot (US) found that Escherichia coli K-12 contains three
genetic loci (uvrA, uvrB, and uvrC) that control the excision of pyrimidine dimers and certain
other mutagen products from DNA (884).
Iwatsuki (JP), Cheol O. Joe (KR), and Harold Werbin (US) purified a
photoreactivating enzyme. It is a low molecular weight, light-absorbing moiety,
flavine adenine dinucleotide, with a chromophore (918). Subsequently it was
settled that all photoreactivating enzymes have two chromophores.
Sancar (TR-US) and Claud Stan Rupert (US) cloned the E. coli phr gene, the first DNA repair gene to be cloned (1549).
B. Sancar (US), Marilyn S. Jorns (US), Gillian Payne (US), Donald J. Fluke
(US), Claud Stan Rupert (US), and Aziz Sancar (TR-US) were able to determine
that the flavin cofactor of the photoreactivating enzyme (photolyase) is fully
reduced in vivo and that, upon
absorption of a single photon in the 300 –500 nm range, the photolyase chromophore donates an
electron to the pyrimidine dimer causing its reversal to two pyrimidines (1550).
Park (US-CA), Aziz Sancar (TR-US), and Johann Deisenhofer (DE-US) solved the
crystal structure of the E. coli
photoreactivating enzyme (1361).
Levine (PL-CA-US), Maurice S. Goldstein (US), Bernice Huddlestun (US), Susan P.
Klein (US) and Samuel Soskin (US) discovered the role of insulin in glucose metabolism. Contrary to the assumption that
glucose molecules freely pass through the cell membrane, they proposed what
became known as the Levine Effect or
transport theory, in which they suggested that insulin serves as the key
regulatory factor for the transport of glucose into the cells. They theorized
that insulin stimulates the transport of glucose from blood to fat/muscle cells
and thus lowers the blood glucose level (1103-1106).
Chargaff (AT-US), Ernst Vischer (US), Ruth Doniger (US), Charlotte Green (US),
Fernanda Misani (US), and Stephen Zamenhof (US) demonstrated that contrary to
common belief the four bases in DNA are not always present in equal molar
concentrations. They discovered that the molar concentration of adenine is
always the same as that for thymine, and the molar concentration of guanine is
always the same as that for cytosine, however, the ratio of adenine to guanine
and that of cytosine to thymine vary considerably from one DNA to another (291-293; 1819).
Robert Wyatt (CA) studied the base ratios in the DNAs of wheat germ, herring
sperm, and insect viruses. His results confirmed the findings of Chargaff and
his colleagues, even though he found an unusual base, 5-hydroxymethyl-cytosine,
in the viruses. The molar ratio of cytosine plus 5-methyl-cytosine to guanine
was 1:1 in these viruses (1937).
Robert Wyatt (US) and Seymour Stanley Cohen (US) discovered
5-hydroxymethylcytosine in the DNA of T-even phages (1938; 1939).
Scatchard (US) pointed out that some proteins have attractions for small
molecules and ions (1571).
Israel Arnon (PL-US) discovered that chloroplasts of Beta vulgaris (common beet) contain an enzyme, which requires
copper as cofactor (48).
W. Kenner (GB), Harold J. Rodda (GB), and Alexander Robertus Todd (GB)
synthesized substrates for ribonuclease
H. Burchenal (US), Aaron Bendich (US), George Bosworth Brown (US), George
Herbert Hitchings (US), Cornelius P. Rhoads (US), C. Chester Stock (US), and
Gertrude Belle Elion (US) synthesized a purine that inhibited mouse leukemia.
This was the forerunner of 6-mercaptopurine (242).
Belle Elion (US), Henry Vanderwerff (US), George Herbert Hitchings (US), M. Earl Balis (US), Daniel H. Levin
(US), George Bosworth Brown (US), and Samuel Singer (US)
confirmed that diaminopurine is an adenine antagonist. Diaminopurine, thioguanine, and 6-mercaptopurine were all found to
be adenine and guanine antagonists (537; 539).
Herbert Hitchings (US), Gertrude Belle Elion (US), and Samuel Singer (US)
synthesized and developed 6-mercaptopurine (6-MP), also called purinethol, as an antitumor agent. They
quantified the synergistic effects of purine antagonists with pyrimidine and
folic acid antagonists (538; 839). Purinethol
was used to treat childhood leukemia. Elion later developed thioguanine,
also for the treatment of leukemia (536).
Gest (US) and Martin David Kamen (US) discovered light-dependent production of
hydrogen gas and nitrogen fixation by the bacterium, Rhodospirillum rubrum. The enzyme nitrogenase catalyzes both activities (659; 947).
Earl Reece Stadtman (US), Horace Alber Barker
(US), G. David Novelli (US), and Fritz Albert Lipmann (DE-US) discovered phosphotransacetylase while elucidating the role of acetyl-CoA in
fatty acid metabolism (1692-1694; 1696).
F. Speck (US) and William H. Elliott (US) demonstrated that glutamine is
synthesized by a specific enzyme, glutamine
synthetase, in the presence of glutamic acid, ATP, Mg++, and ammonia (543; 544; 1686)