A Selected Chronological Bibliography
of Biology and Medicine
1964 — 1970
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.
can and should devote ourselves with truly religious devotion to the cause of
ensuring greater fulfillment for the human race in its future destiny. And this
involves a furious and concerted attack on the problem of population; for the
control of population is…a prerequisite for any radical improvement in the
human lot.” Julian Sorell Huxley (815).
wish I had the voice of Homer
sing of rectal carcinoma,
kills a lot more chaps, in fact,
were bumped off when Troy was sacked.” John Burdon Sanderson Haldane (690).
Mary Crowfoot-Hodgkin (GB) was awarded the 1964 Nobel Prize in Chemistry for
her determinations by x-ray techniques of the structures of important
Emil Bloch (US) and Feodor Felix Konrad Lynen (DE) were awarded the Nobel Prize
in Physiology or Medicine for their discoveries concerning the mechanism and
regulation of the cholesterol and fatty acid metabolism.
David W. Menzel (US) and Ralph F. Vaccaro (US)
reported that organic carbon in aqueous solution may be measured with a
precision of ± 0.1 mg C/l using persulfate as an oxidant. Oxidation is
accomplished in sealed ampules. The evolved CO2 is quantified with an infrared
A. Yphantis (US) introduced the
‘meniscus depletion’ (a.k.a. ‘high speed’ and ‘Yphantis’) technique to
equilibrium ultracentrifugation of dilute solutions. This method required
spinning the sample at a rotor speed high enough to deplete the meniscus of
Andrews (GB) developed a way to determine the molecular weights of proteins
using Sephadex gel-filtration (38).
Ornstein (US) and Baruch J. Davis (US) introduced the use of synthetic
polyacrylamide gels in disc (discontinuous) electrophoresis (386; 1277).
Alfred Zettner (US) and David Seligson (US)
were the first to use atomic absorption spectrophotometry to measure serum
David L. Trudeau (US) and Esther F. Freier
(US) first described the use of lanthanum in the measurement of calcium in
biological fluids (1687).
Henry N. Wagner, Jr. (US), David C. Sabiston,
Jr. (US), Masahiro Iio (US), John G. McAfee (US), Jon K. Meyer (US), and James
K. Langan (US) developed an isotope tracer technique whih allowed them to
determine regional pulmonary blood flow in man (739).
E. Pearson Murphy (CA) and Chauncey J. Patee (CA) described a simple, rapid
method for the determination of serum thyroxine, which is based on the specific
binding properties of thyroxine-binding globulin (TBG). One-half ml of the test
sample is deproteinized and the thyroxine thus freed is measured according to
its competition with a fixed amount of thyroxine-I131 for a fixed amount of TBG
Arne Dahlqvist (SE)
described a simple method for testing disaccharidase activity. It has now been
used for numerous clinical investigations, especially for peroral biopsies of
the small intestinal mucosa (372; 373).
Gerald Kessler (US) and Morris Wolfman (US)
provided the first auto analyzer
method for the simultaneous measurement of calcium and phosphorus without
preliminary sample treatment (928).
G. Duncombe (GB) devised a method useful in a variety of applications in which
the concentration of long-chain fatty acids extracted from biological materials
was required. Long-chain fatty acids dissolved in chloroform will form chloroform-soluble
copper soaps. The reaction of these with a chromogenic reagent for copper is
the basis for the determination described (462).
Henry N. Wagner, Jr. (US), David C. Sabiston, Jr.
(US), John G. McAfee (US), Donald Tow (US), and Howard S. Stern (US) developed
a way to use radioiodine labeled macroaggregates of albumin in the rapid
diagnosis of acute pulmonary embolism (1728).
Federico Leloir (AR), Carlos Eugenio Cardini (AR), Jose M. Olavarría (AR), Sara
H. Goldemberg (AR), and Hector Carminatti (AR) discovered that glycogen can be
synthesized by a process in which the reactive intermediate uridine diphosphate
glucose (UDP-glucose) transfers glucose to the growing glycogen chain. They
found that galactose is broken down to yield glucose in a similar pathway. They
identified the enzyme glucose1-phosphate
kinase acting in a separate glycogen synthesis. The product of this
reaction, glucose 1,6-diphosphate, is a coenzyme of the glycolysis pathway
enzyme, phosphoglucomutase. They went
on to identify galactokinase and
discovered that the product, galactose 1-phosphate, is converted into glucose 1-phosphate (1009-1012).
Moritz Kalckar (DK-US), Beatriz Braganea (DK), and Agnete Munch-Petersen (DK)
had presented direct evidence that the synthesis of UDP galactose does occur in
extracts of the yeast Saccharomyces
fragilis, catalyzed by galactose-1-P
uridyl transferase (880).
Daniel Lane (US), Karl L. Rominger (DE), David L. Young (US), and Feodor Felix
Konrad Lynen (DE), using Propionibacterium
shermanii, showed that the synthetase
catalyzed a two-step reaction. The first step involved the ATP-dependent
formation of biotinyl-5'-AMP and pyrophosphate after which the biotinyl group
was transferred from the AMP derivative to the appropriate lysyl epsilon-amino group of the apotranscarboxylase (982). Synthetase had been shown to catalyze biotin loading onto the apoenzyme.
Gregolin (IT), Elena Ryder (VE), Robert C. Warner (US), Albrecht K.
Kleinschmidt (US), Huei-Che Chang (US), and Malcolm Daniel Lane (US) described
the molecular characteristics of chicken acetyl
coenzyme A carboxylase, including its reversible inter-conversion between
protomeric and polymeric forms. They determined that the carboxylase has a
binding site for citrate and another for acetyl-CoA and that citrate binding
might be involved in regulating the enzyme (661).
B. Guchhait (US), S. Efthimios Polakis (US), Donald Hollis (US), Catherine
Fenselau (US), and Malcolm Daniel Lane (US) used the acetyl coenzyme A carboxylase system from Escherichia coli to provide definitive evidence that the ureido-N
of biotin is the site of carboxylation (670).
Efthimios Polakis (US), Ras B. Guchhait (US), Eberhard E. Zwergel (US), Malcolm
Daniel Lane (US), and Terrance G. Cooper (US) gave a thorough analysis of the acetyl coenzyme A carboxylase system
from Escherichia coli. They define
the requirements and properties of isotopic exchange and stoichiometric
reactions representative of the two half- reactions in acetyl-CoA carboxylation
and describe studies using prosthetic group and intermediate model derivatives
as substrates to elucidate the mechanisms of the partial reactions (1340).
Chemical Company introduced the herbicide fluometuron, a substituted urea,
useful in cotton (Gossypium spp.) and
sugar cane (Saccharum officinarum). Ref
Robert Jenkins (US) presented a simple, rapid, and inexpensive method for the
extraction of nematodes from soil (839).
Clinton Edward Edgerton Ballou (US) and Yuan
Chuan Lee (TW-US-TW) determined the structures of
the family of mannosyl phosphoinositides in the mycobacteria (76; 1004).
Sune Detlof Bergström (SE), Henry Danielsson (SE), and Bengt Samuelson (SE) demonstrated the enzymatic conversion of
arachidonic acid to prostaglandin E2 (125). Because
arachidonic acid is
synthesized from linoleic acid in humans, this discovery helped establish
prostaglandins as products of the metabolism of essential fatty
P. Skipski (US), Robert F. Peterson (US), and Marion Barclay (US) described the
conversion of their previously-developed procedure for qualitative separation
of phospholipids by thin-layer chromatography to a quantitative analysis which
permitted the determination of the main known phospholipids in animal tissues (1539).
Hao Li (CN-US) and Yehudith Burk (US) isolated and purified beta-lipotropin
Hao Li (CN-US), Livio Barnafi (CL), Michel Chretien (US) and David Chung (US)
determined the amino-acid sequence of beta-LPH. They found contained within the
91 residues of beta-LPH the 18-residue sequence of melanocyte-stimulating
hormone (MSH). Beta-LPH may be viewed as a prohormone from which MSH is derived (1022).
Chretien (US) and Choh Hao Li (CN-US) isolated, purified, and characterized
gamma-lipotropin hormone from sheep pituitary glands. It consists of the first
58 residues of beta-lipotropin and contains the MSH sequence (291).
Michael Poston (US), Kazuoki Kuratomi (US), and Earl Reece Stadtman (US)
determined that methyl-B12 is involved in acetate synthesis and is the first
step in the acetyl-CoA pathway (1349). This was a major clue to unraveling the
Rodbell (US) isolated individual fat cells then showed that insulin bounds
directly to receptors on these cells and stimulates glucose metabolism (1409).
Franklin Utter (US), D. Bruce Keech (US), and Michael C. Scrutton (US)
demonstrated that acetyl-CoA regulates the activity of pyruvate carboxylase (combines CO2 with pyruvate in
glucogenesis), thus providing one of the first examples of allosteric control
of enzymes (1488; 1710).
Lee Bender (US), Ferenc J. Kézdy (US), and Claude R. Gunter (US) concluded that
the enzymatic reactivity of alpha-chymotrypsin could be accounted for by (1)
the intramolecular character of the enzymatic process and the concomitant
increase in effective concentration of the catalytic group(s); (2) general
basic catalysis by imidazole; (3) the change in rate-determining step of the
amide hydrolysis to an alcoholysis; (4) the freezing of the substrate in a
conformation resembling the transition state, and (5) the general acidic
catalysis by imidazole (117).
Szybalski (US) and Zofia Opara-Zubinska (US) concluded that DNA in which
thymidine is replaced by 5-bromodeoxyuridine (BUdR) in either or both strands
is many times more sensitive to damage by x-rays, short and medium wavelength
ultraviolet light, subcritical heat,
and hydrodynamic shear (1630).
W. Dungan (US) and Paul M. Lish (US) were the first to describe sotalol (463). Initially it was used as a beta-blocker but
was later demonstrated to have effects on the action potential (repolarization
delay), which led to its use as a class III antiarrhythmic drug (1530).
Guha (IN) and Satish C. Maheshwari (IN) obtained haploid plants of Datura innoxia Mill (Angel's trumpet)
from anther cultures (672; 673).
R. Sharp (US), Donald K. Dougall (US), and Elton F. Paddock (US) obtained
haploid plantlets and callus from immature pollen grains of tobacco (Nicotiana) and tomato (Lycopersicon) (1505).
M. Cathey (US) explained that chemical growth retardants (8 families) block
cell elongation of stems without affecting leaf formation, resulting in
compact, stress-resistant plants. With many woody plants the treated plants
initiate flowers earlier than typical for the species. Chemical growth
retardants are one of the reasons for the house plant boom in America. They
have permitted the sizing of plants to fit any space (272).
Yechiel Becker (IL) and Wolfgang Karl Joklik
(AT-AU-US) investigated the genesis of vaccinia virus specific polyribosomes.
Messenger RNAs were found to combine first with 40 S subribosomal particles (the free half-life of mRNA being
about 30 s) and then with
60 S subribosomal particles to form polyribosomes. 40 S and 60 S subribosomal particles are always
present in strictly equivalent
numbers; they are made in the nucleus and enter the cytoplasm as individual entities (112).
Abraham Marcus (US) and John Feeley (US)
analyzed the mechanism for protein synthesis in intact seeds and isolated seed
embryos. They found that the protein synthesis apparatus is functional in the
ungerminated seed, yet imbibition is necessary if sufficient messenger RNA for
germination is to be made (1097).
Wolfgang Karl Joklik (AT-AU-US) found that
uncoating of poxvirus DNA is a two-step process. Enzymes present in uninfected cells
release the viral cores and the viral inducer protein. The
second, namely the breakdown of cores to liberate the viral genome,
requires de novo synthesis of the
uncoating protein elicited by the inducer protein (859).
Losef Stopler (RO), Victoria Camuescu (RO), Mihaela Voiculescu (RO), J. Donald
Coonrod (US), Peter J. Leadley (US), and Theodore C. Eickhoff (US) successfully
isolated Bacillus cereus as the
etiological agent from cases of bronchial pneumonia. It was cultured from the
blood and pleural fluid (333; 1601). Bacillus
cereus is an opportunistic human pathogen and is occasionally associated
with infections, causing periodontal diseases and other more serious
Bacillus cereus can spread easily to many types of foods
such as plants, eggs, meat, and dairy products, and is known for causing 25% of
food-borne intoxications due to its secretion of emetic toxins and enterotoxins
M. Wijnands (NL), J.B. Dufrenne (NL), Marcel H. Zwietering (NL), and Frans M.
van Leusden (NL) reported that immunocompromised patients are susceptible to bacteremia,
endocarditis, meningitis, pneumonia, and endophthalmitis caused by Bacillus cereus (1799). Its potential to
cause systemic infections is of current public health and biomedical concerns.
Pettijohn (US) and Philip C. Hanawalt (US), using Escherichia coli strain TAU-bar, found that in
ultraviolet-resistant organisms a mechanism for repair replication exists in
which damaged single-strand regions of the chromosome can be excised and
replaced, using the undamaged DNA strand as template (1327).
N. Chatterjee (US), James Theodore Park (US), Pauline M. Meadow (GB), John S.
Anderson (US), and Jack Leonard Strominger (US) determined that the second
phase of the synthesis of bacterial cell wall material occurs in the membrane
of the cell. Here UDP-acetylmuramyl-pentapeptide and UDP-acetylglucosamine are
joined to form a linear peptidoglycan (286; 1126; 1604). The antibiotics ristocetin, vancomycin,
and bacitracin inhibit this second
phase of cell wall synthesis.
C. Michaelides (US), Roger Sherman (US), Ernst Helmreich (US), Carl Ferdinand
Cori (US), Agnes Ullmann (FR), Pindaros Roy Vagelos (FR-US), Jacques Lucien
Monod (FR), Donald L. DeVincenzi (US), and Jerry L. Hedrick (US) presented
evidence that muscle glycogen phosphorylase b is an allosteric enzyme
influenced by 5’AMP at the allosteric site (421; 732; 1143; 1702).
Burr (US) and Daniel Edward Koshland, Jr. (US) developed a technique called reporter groups to correlate function
with structure in protein molecules. A chemical group sensitive to
environmental changes and which will transmit a signal to an appropriate
detector is introduced into a specific position in the protein (231).
Tod Schimke (US) was the first to report protein degradation as a regulatory
process and thereby established a new field of biochemistry (1471).
G. Comb (US) and Solomon Katz (US) presented evidence that tRNA precursor
molecules are synthesized in the nucleolus move to the cytoplasm where base
methylation occurs and perhaps other alterations, then moves back to the
Gorini (IT-US) and Eva Kataja (US) presented evidence that streptomycin was
altering the specificity of translation via an interaction with the ribosome.
They suggested that, "the ribosomal structure could include the accuracy
of the reading of the code during translation" (639).
E. Davies (US), Luigi Gorini (US), Eva Kataja (US), Walter Gilbert (US),
Bernard David Davis (US), Theophil Staehelin (US) and Matthew Stanley Meselson
(US) determined that streptomycin and related antibiotics interfere with the
protein translation process (383-385; 638; 640; 1573).
Andrew Ferguson-Smith (GB) discovered that the pattern of multiple associations
suggests that three long and two short chromosomal bivalents are capable of
forming terminal nucleoli during pachytene. The evidence suggests that these
five bivalents are the five pairs of satellited chromosomes in the human
mitotic ideogram (524).
R. Warner (US) and Alexander Rich (US) found that each ribosome possesses two
tRNA binding sites. They postulated that the two binding sites are adjacent.
One of them they called the A site, which binds aminoacyl tRNA, and the other
the P site, which binds peptidyl tRNA (1752).
Geigenmuller (DE) and Knud H. Nierhaus (DE) postulated the existence of a third
tRNA binding site on the surface of the ribosome, the E site (Exit). When the tRNA
from the P site has had its peptide chain transferred to the adjacent tRNA, it
does not leave the ribosome promptly. Rather, it delays slightly at the E site (595).
B. Arlinghaus (US), Joseph Schaeffer (US), Richard S. Schweet (US), Joanne M.
Ravel (US), Jean Lucas-Lenard (US), Anne-Lise Haenni (US), Richard W. Erbe
(US), and Philip Leder (US) found that the so-called T factor, together with
GTP, participates in the attachment of aminoacyl tRNAs to ribosomes (45; 502; 1062; 1379).
Chang (US) and Louis Weinstein (US) report that the antibiotic cephalothin inhibits cell wall
peptidoglycan synthesis (283).
Leslie Ada (AU), Gustav Joseph Victor Nossal (AU), John Pye (AU), and Andrew
Abbot (AU) described the preparation and physical and chemical properties of
the monomeric protein flagellin and
of the formation in vitro of
polymerized forms which appear similar in appearance to the parent flagella
particles from Salmonella adelaide (4).
Bernard Lurie (LT-US) discovered that macrophages must be
activated to digest cells of Mycobacterium
A. Rose (US), Jessie V.B. Warms (US), and Edward L. O’Connell (US) observed
that during glycolysis inorganic phosphate counteracts the glucose-6-phosphate
inhibition of hexokinase (1419).
Moore (US) and Berton Charles Pressman (US) presented evidence that the
antibiotic valinomycin acts as an
ionophore that transports potassium ions down its electrochemical gradient and
across the cell membrane. It is an energy dependent accumulation of potassium
ions in mitochondria (1182).
Nathans (US) demonstrated that puromycin
inhibits protein synthesis by being incorporated into the growing polypeptide
chain, resulting in premature termination of translation (1208).
Max Pappenheimer, Jr. (US), R. John Collier (US), Ronald S. Goor (US),
Elizabeth Ames (US), D. Michael Gill (US), Robin Brown (US), James T. Kurnick
(US), Tasuku Honjo (JP), Yasutomi Nishizuka (JP), Osamu Hayaishi (JP), Iwao
Kato (JP), Tsuyoshi Uchida (JP), and Annabel A. Harper (US) demonstrated that
diphtheria toxin acts by inhibiting protein synthesis. It specifically
inactivates elongation factor 2 (EF-2) by an ADP-ribosylation reaction in the
presence of nicotinamide adenine dinucleotide (NAD) (316; 618; 631-633; 786; 1293; 1699).
Fernández-Morán (VE), Takuzo Oda
(JP), Paul V. Blair (US), and David Ezra Green (US) demonstrated the presence
of thousands of elementary particles (EP) embedded within the inner membrane of
mitochondria from various sources. Each EP was composed of: (1) a head (80-100
angstroms), (2) a cylindrical stalk (about 50 angstroms long and 30-40
angstroms wide), and (3) a base piece (40 X 110 angstroms) (525).
E. Varner (US), G. Ram Chandra (US), and Maarten J. Chrispeels (US) discovered
that the plant hormone gibberellin
regulates the expression of alpha-amylase
in barley aleurone cells at the level of the gene (292; 293; 1718).
C. Ledbetter (US), Keith R. Porter (US), David M. Phillips (US), Lewis G.
Tilney (US), Joseph Bryan (US), Doris J. Bush (US), Keigi Fujiwara (US), Mark
S. Mooseker (US), Douglas B. Murphy (US), and Daniel H. Snyder (US) described
the 13-protofilament structure of microtubules which they found to be
widespread among many organisms (996; 1329; 1664).
Miller (DE) and George Emil Palade (RO-US) carried out one of the first
examples of combined cytochemistry and electron microscopy. They found that
enzymes and substrates colocalize in lysosomes (1151).
L. Gowans (GB), E. Julie Knight (GB), and Vincent T. Marchesi (US) showed that
lymphocytes recognize post-capillary high-walled endothelial venule (HEV) cells
that are present under normal circumstances only in lymphoid tissues. These
lymphocytes when taken from a lymphoid site tend to return, or home back to the same site when
reinjected, suggesting that they possess homing receptors (649; 1094).
Malnic (US), Ruth M. Klose (US), Gerhard Giebisch (US), Cristobal G. Duarte
(US), Francoise Chomety (US), Margarida de Mello Aires (BR), Fred S. Wright
(US), Nikolaus Strieder (US), and Nicole B. Fowler (US) perfected the method of
performing micropuncture and microperfusion studies on the distal tubule of the
nephron. They unequivocally demonstrated that potassium is reabsorbed by the
proximal tubule and the loop of Henle, that potassium reabsorption by these
nephron segments is constant in a variety of experimental and metabolic
conditions, and that it is the distal tubule that primarily determines the
amount of potassium excreted in the urine by either continuing potassium
reabsorption, or by secreting potassium into the tubular fluid. Furthermore,
they provided the first insight into the cellular mechanisms of potassium
transport by the distal tubule (455; 1086-1089; 1832).
Francis Addison Woodruff (GB) and James L. Boak (GB) demonstrated that animals
experience a stimulation of their immune system and an inhibition of
transplantable tumors when injected with species of Corynebacterium parvum (1823).
S. Edgar (US) and Ilga Lielausis (US) isolated temperature sensitive mutants of
T4 bacteriophage and showed that its linkage map had no ends, and so could be
drawn as a circle (478).
Warren Nirenberg (US), and Philip Leder (US) announced their technique by which
artificially synthesized RNA trinucleotides cause specific tRNAs to bind to the
surface of ribosomes. These tRNAs each carry a specific amino acid called for
by the one-word codon in the synthetic trinucleotide. Using this methodology,
they rapidly determined many of the codons used by the cell to specify amino
acids. These became part of what is now called the RNA dictionary (437; 717; 997; 1229; 1230; 1322).
Dewey Watson (US), Yasutomi Nishizuka (JP), Fritz Albert Lipmann (US), Julian
Gordon (CH), Jean Lucas-Lenard (US), and Maxwell E. Gottesman (US), proposed
that GTP and the G (ribosome-linked
GTPase) factor are involved in messenger RNA movement and, simultaneously,
in translocation of the newly synthesized peptidyl-tRNA from the aminoacyl to
the peptidyl site (1046; 1232; 1757).
Jacob (FR), Agnes Ullmann (FR), and Jacques Lucien Monod (FR) discovered the
element in the genetic mechanism of control in microorganisms at which
molecules of the enzymes that make messenger RNA must attach to start
transcribing from DNA into RNA. They named this element the promoter (830).
Farnes (US), Barbara E. Barker (US), L.E. Brownhill (US), and Herbert Fanger
(US) discovered that the extract of pokeweed is mitogenic to lymphocytes of
peripheral blood (519).
G. Coon (US) and Robert D. Cahn (US) were the first to obtain in vitro clones of euploid cells that
retained their specialized function. They also showed that this specialized
function could be stabilized (330-332).
Sachs (IL) and Kenneth Vivian Thimann (GB-US) showed that the growth of
axillary buds, which remain dormant in the presence of terminal buds, could be
initiated by the exogenous application of cytokinins. Thus, one could induce
the release of lateral buds on a growing shoot with an intact terminal bud by
growing the shoot in a medium containing cytokinin. This would release buds
from apical dominance (1442).
E. Reif (US) and Joan M.V. Allen (US) discovered the theta—later changed to thy—antigenic
marker for thymus-derived (T) lymphocytes and found it to be specific for
lymphocytes of thymic origin (1386).
N. Eisen (US), Gregory W. Siskind (US), and Baruj Benaceraff (US) discovered
that a feature of the immune response to T cell-dependent antigens is an
increase in the average affinity of antigen-specific antibody during the
response (493; 1531).
D. Beck (US), Nancy J. Alexander (US), John L. Shane (US), and Irene B. Colvin
(US) investigated whether the hormone
proctodone, which they discovered and named, plays a role during diapause
development in insects. They proposed a two-oscillator model to explain the
interaction between the secretion of proctodone and the secretion of
prothoracicotropic hormone from the cerebral neurosecretory system. This model
suggested that an eight-hour subcircadian proctodone rhythm is phase set by the
onset of darkness, and that an eight-hour cerebral neurosecretory rhythm is
phase set by the onset of illumination. They concluded that proctodone
activates the neurosecretory system under long days, when the two rhythms are
in phase, but this does not occur under short days, when the two rhythms are
out of phase (105; 109-111).
Jacobus Hoedemaeker (NL), Jules J. Abels (NL), J.J. Wachters (NL), Albertus
Arends (NL), and Hendrik Omgo Nieweg (NL) determined the site of intrinsic
factor production to be parietal cells of the stomach in man, monkey, rabbit,
guinea pig, cat, and ox; peptic cells in the rat and mouse, and pyloric
duodenal cells in the hog (767; 768).
Gräsbeck (FI), Kai Lennart Simons (DE), and Irma Sinkkonen (FI) isolated
intrinsic factors from human gastric juice and determined it to be a 60K Da
glycoprotein (653; 654).
B. Jones (US), Sidney P. Kent (US) and Charles E. Butterworth, Jr. (US)
determined the chemical and biological properties of fractions derived from hog
intrinsic factor concentrate by disc electrophoresis (863).
Kurt J. Isselbacher (US) and Norton J. Greenberger
(US) reported that alcohol has many effects on hepatic, carbohydrate, protein,
and lipid metabolism. Many of the actions of alcohol on the liver cell are of a
direct or toxic nature. Other effects are indirect and the result of changes in
the redox state of the hepatocyte secondary to ethanol oxidation. Their
knowledge of the metabolic actions of alcohol has provided insight into the
mechanism of alcohol-induced hyperlipidemia, hyperuricemia, and hypoglycemia (825).
T. Shahidi (US), David G. Nathan (US), and Louis K. Diamond (US) during
examination of two sibling patients discovered an error in iron metabolism
characterized by massive hepatic iron deposition and absent stainable bone
marrow iron stores. The association of this discrepancy with the chronic
hypochromic anemia present in these two siblings is unique (1498).
E. Phillips (CA) demonstrated that active ion transport occurs
in the locust rectum. The coupling of metabolic energy to the movement of
compounds across the epithelium is vital for osmoregulation and for the
retention of ions, water and nutrients. Microelectrode measurements showed that
chloride transport set up an electrical gradient that facilitated the movement
of sodium and potassium from the lumen into the hemolymph. The most startling
and significant finding was that water could be transported from the rectum to
the hemolymph when the rectum was filled with a solution of 800-mOsm xylose,
even though the hemolymph remained at a lower concentration of about 400-mOsm.
He demonstrated that rectal capacity for ion and water transport exceeds the
rate at which ions and water enter the rectum in the urine. His results
provided a mechanistic explanation for the observation that the fecal pellets
of Schistocerca are in equilibrium with a very concentrated solution, but
essentially devoid of sodium, potassium and chloride ions. Phillips had
simultaneously shown how ions and water were retained in the locust under
desiccating conditions and clarified the mechanisms by which highly
concentrated feces were produced (1330-1332).
Thomas Puck (US) carried out experiments in which he demonstrated that the
large variation in the apparent radiosensitivity of different organs is due
essentially to regional differences in the rate of cell turnover (1357).
Lubínska (PL) showed that axonal transport is not a simple flow of axoplasm.
She described in nerve fibers the retrograde and anterograde movements of
radioactive acetylcholinesterase (1061).
Hagiwara (JP-US), Ken-ichi Naka (JP), Shiko Chichibu (JP), and Charles Edwards
(US) described ionic mechanisms in active membranes and especially calcium
channels. They discovered blocking ions, flux saturation, and that
intracellular calcium blocks calcium channels. All this work was done in muscle
fibers of the giant barnacle (484; 687-689).
Hoyle (US) and Thomas Smyth, Jr. (US) had discovered the giant muscle fibers in
the North Pacific barnacle (796).
MacPherson (GB) and Luc Montagnier (FR) demonstrated that with polyoma virus
there is a systematic relationship between dose of virus and number of
transformed colonies of cells (1078).
William F.H. Jarrett (GB), William B. Martin (GB), George W.
Crighton (GB), Roger G. Dalton (GB), Mary F. Stewart (US-GB), Elizabeth M.
Crawford (GB), and F. Davie (GB) showed feline leukemia to be transmissible
experimentally in cats using cell-free extracts of lymphosarcoma tissue from a
spontaneous field case. Type C virus particles were demonstrated in the
experimentally induced tumor and in cells cultured from it. This was the first
transmission of a spontaneous mammalian leukemia (836; 837).
W. Littlefield (US) introduced HAT medium
(hypoxanthine, aminopterin, and thymidine) for the selective growth of somatic cell
Together with the technique of cell fusion, this made somatic-cell genetics
Adrian Marcker (DK) and Frederick Sanger (GB) discovered that when protein
synthesis occurs in Escherichia coli
the first amino acid in every new polypeptide is N-formylmethionine brought to
the ribosome by N-formyl-tRNAf (1095).
Guthrie Catcheside (GB-AU), Adrienne P. Jessop (GB), and Brian R. Smith (GB)
discovered rec genes in Neurospora. These are unlinked or
nonadjacent genes, which influence local recombination frequencies (269).
Brisco Ford (GB) coined ecological
genetics to refer to the study of evolution in action by a mixture of
laboratory and fieldwork (556).
Edwin T. Mertz (US), Oliver Evans Nelson, Jr.
(US), Lynn S. Bates (US), and Olivia A. Vernon (US) demonstrated that the opaque 2 and floury 2 mutants of maize (Zea
mays L.) produce seed containing elevated concentrations of two essential
amino acids, lysine and tryptophan, that are deficient in normal corn seed (1137; 1138).
B. Abeles (US) and Bernard Rubinstein (US) found that auxin stimulated ethylene
production, and that it was the gas which promoted abscission after the ability
of auxin to delay aging was lost. This paper provided experimental proof for
the principle that ethylene could act as a second messenger in some of the
effects of auxin on plant growth and development (3).
L. Craig (US) and Elizabeth Buckley Shull Russell (US) demonstrated that in
mice embryonic hemoglobins are expressed only in the large nucleated
erythrocytes from the yolk sac while adult hemoglobins are produced in the
fetal liver (355). This finding supported arguments that
differential gene expression is dependent on factors intrinsic to ontogenic
H. Labrec (US), Herman Schneider (US), Thomas J. Magnani (US), and Samuel B.
Formal (US) found that the essential step in the pathogenesis of bacillary
dysentery (Shigella flexneri) is the
invasion of the colonic mucosa (973).
Voino-Yasenetsky (HU), Th. N. Khavkin (HU-RU), Akio Takeuchi (US), Samuel B.
Formal (US), Eugene H. Labrec (US), and Helmuth Sprinz (US) determined that the
process of invasion by Shigella
includes penetration into epithelial cells, intracellular replication leading
to host cell death, and spreading to adjacent cells and conjunctive tissue of
intestinal villi (1634; 1722).
J. Sansonetti (FR), Dennis J. Kopecko (US), and Samuel B. Formal (US)
discovered that a plasmid within Shigella
is encoded with the information necessary to invade host cells (1457; 1458).
S. Sarabhai (IN), Anthony O.W. Stretton (US), Sydney Brenner (ZA-GB), and
Antoinette Bolle (CH), working with the T4 virus of Escherichia coli, demonstrated that nonsense codons determine the length of polypeptides to be
incorporated into the head protein of the virus. This strongly suggested that nonsense codons act as termination
signals during polypeptide synthesis (1460).
Holliday (GB) proposed that genetic recombination in yeast proceeds through two
single stranded breaks made simultaneously at the same sites on the two DNA
molecules to be recombined (the Holliday
Junction). During recombination, the nicked strands unwind then invade the
DNA of the opposite homolog by rewinding with one of its DNA chains. At this
point the rewinding structure rotates to take on a crossed configuration. In
his honor this crossed configuration is called a Holliday intermediate (784).
D. Hurst (US), Seymour Fogel (US), and Robert K. Mortimer (US) investigated the
relationship between gene conversion and crossing-over at several different
loci in Saccharomyces cerevisiae.
They demonstrated that for a given marker about 50% of conversion events are
associated with crossing-over, whereas the other 50% do not show an associated
crossing-over (812). Gene conversion
represents the nonreciprocal transfer of information between two homologous
sequences where one allele is duplicated while another is lost.
William Szostak (CA-US), Terry L. Orr-Weaver (US), Rodney J. Rothstein (US),
and Franklin W. Stahl (US) proposed the double-strand-break repair (DSBR) model
to explain tetrad data generated by Saccharomyces
cerevisiae matings (1628).
Nicolas (FR), Douglas Treco (US), Neil P. Schultes (US), Liang Cao (US), Eric
Alani (US), Nancy Kleckner (US), and Jack William Szostak (CA-US) went on to
provide strong support for this conjecture, showing that double-strand breaks
do occur at the time and place of initiation of meiotic recombination and that
genetic defects that block the appearance of double-strand breaks also block
the initiation of recombination (251; 1226).
Hunt Potter (US) and David Dressler (US-GB)
demonstrated the validity of the Holliday model of recombination (1350).
Ichiro Terasaki (US) and John D. McClelland (US) developed the
microcytotoxicity test, critical for further development and practical use of
HLA typing (1651).
H. Bach (US) and Kurt Hirschhorn (US) along with Barbara Bain (CA), Magdalene
R. Vas (CA), and Louis Lowenstein (CA) independently developed the Mixed
Lymphocyte Culture (MLC) Test of histocompatibility (59; 68).
J. Haslam (GB) observed that platelets themselves under the influence of a
suitable agent such as thrombin, release enough adenosine diphosphate (ADP) to
induce their own aggregation (712).
Gwyn MacFarlane (GB) set out for the first time the concept of blood
coagulation as a cascade of eight enzymatic reactions which culminate in the
formation of fibrin, and which involve activation of factors, as well as
biochemical amplification and negative feedback to control the process (1074).
Roger L. Lundblad (US) and Earl Warren Davie
(US) suggested that activated Christmas factor converted anti-hemophilic
factor to an active form, and it in turn converted Stuart factor
to an active form in the presence of phospholipid and calcium (1067).
Earl Warren Davie (US) and Oscar D. Ratnoff
(US) presented a blood coagulation scheme based on the concept that clotting
factors were present in blood in an inactive or precursor form and were
converted to active enzymes in a step-by- step manner most likely via limited
proteolysis they called a "waterfall sequence for intrinsic blood clotting" (382). Later the extrinsic (now called the tissue factor pathway) was added.
Payne (US) Millie Tripp (US), Joan Weigle (CH-US), Walter Fred Bodmer (GB), and
Julia Bodmer (GB) defined the allelic system now known as HLA-A 1, 2, and 3 (1305).
S. Remington (US), Kenneth L. Vosti (US), Arthur Lietze (US), A. Leonard
Zimmerman (US), Malcolm S. Artenstein (US), Joseph A. Bellanti (US), and Edward
L. Buescher (US) simultaneously reported that immunoglobulin alpha (IgA) is the
predominant immunoglobulin in normal human nasal secretions collected by lavage
of the nasal cavities with isotonic salt solution (48; 1388).
Joseph Victor Nossal (AU), Aleksander Szenberg (AU), Gordon Leslie Ada (AU),
and Caroline M. Austin (AU) observed that individual B cells can switch
immunoglobulin (Ig) class upon activation (1246).
Kataoka (JP), Toshiaki Kawakami (JP), Naoki Takahashi (JP), Tasuku Honjo (JP), and
Akira Shimizu (JP) elucidated the mechanism of immunoglobulin class switching
(class-switch recombination), whereby B cells switch
their antibody production from one antibody type to another depending
on the type of antigen with which they are presented (895; 1509).
Masamichi Muramatsu (JP), Kazuo Kinoshita
(JP), Sidonia Fagarasan (JP), Shuichi Yamada (JP), Yoichi Shinkai (JP), and
Tasuku Honjo (JP) presented results suggesting that activation-induced cytidine deaminase (AID) may be involved in regulation or catalysis of the DNA
modification step of both class switching and somatic hypermutation in
L. Hirsch (US), Donald G. McKay (US), Rosemary I. Travers (US), and Ruth K.
Skraly (US) found that hypertriglyceridemia is common during a state of
A. Rouzer (US), Anthony Cerami (US) found that defective triacylglycerol clearance
during infection is caused by systemic suppression of the enzyme lipoprotein lipase (LPL) (1430).
Karakami (JP), Anthony Cerami (US), Phillip H. Pekala (US), and Malcolm
Daniel Lane (US) found that macrophages secrete cachectin, which suppresses lipoprotein lipase activity (908; 909).
Claus Franklin (DE-US), Jerome Lowenstein (US), Bradley Bigelow (US) and Martin
Meltzer (US) were the first to report a case with gamma heavy chain disease. The patient presented with an
unexplained lymphadenopathy, fever, and a spike in the gamma fraction of serum (563).
F. Osserman (US) and Kiyoshi
Takatsuki (JP) coined the phrase gamma
heavy chain disease (1279).
Rapp (FR), Samuel B. Aronson (US), Pierre Burtin (FR), Pierre Grabar
(RU-DE-FR), Paul A. Crabbé (BE), Joseph Felix Heremans (BE), Raymond Havez
(FR), Francoise Guerrin (FR), Jean-Pierre Muh (FR), Gérard Biserte (FR), Lars
A. Hanson (SE), and Bengt G. Johansson (SE) reported that in addition to
contribution from the plasma, the gastric mucosa actively secretes four classes
of immunoglobulins—IgA, IgG, IgM, and IgD—into the gastric fluid (352; 353; 697; 721; 1377).
W. Conn (US), Edward L. Cohen (US), and David R. Rovner (US) noted that hypertension associated with overproduction of
aldosterone, the salt-active adrenal hormone, results from either an
abnormality of the adrenal gland itself or a circulatory deficiency of the
kidney. This paper demonstrates that these two causes of hypertension can be
distinguished functionally by measuring the level of plasma renin activity, subnormal in adrenal
cases and supernormal in renovascular cases (322).
Jerome W. Conn (US), Edwin L. Cohen (US),
David R. Rovner (US), and Reed M. Nesbit (US) showed that hypokalemia (deficiency of potassium in the
bloodstream) is likely a late manifestation of aldosterone
excess, if it occurs at all (323).
Rouben David (US), Salah Al-Askari (US), H. Sherwood Lawrence (US), Lewis
Thomas (US), Barry R. Bloom (US), and Boyce Bennett (US) discovered that immune
lymphoid cells stimulated by their corresponding antigen secrete a substance
that inhibits the migration of macrophages, a characteristic of delayed
hypersensitivity (148; 379; 380).
They named this substance migration
inhibitory factor (MIF). Note: This was the third cytokine
discovered. Stanley Cohen (US) coined the neologism cytokine (312).
B. West (US), Colin T. Dollery (US), and Arnold Naimark (US) determined the distribution of blood flow in isolated lung
and its relation to vascular and alveolar pressures. This is the paper that
originally described the "zones of the lung." The paper and its final
figure can be used to teach or review several physiological concepts. These
include the effects of gravity on pulmonary blood flow and pulmonary vascular
resistance; recruitment and distention of pulmonary vessels; the importance of
the transmural pressure on the diameter of collapsible distensible vessels; the
Starling resistor; the interplay of the pulmonary artery, pulmonary vein, and
alveolar pressures; and the vascular waterfall. In addition, the figure can be
used to generate discovery learning and discussion of several physiological or
pathophysiological effects on pulmonary vascular resistance and the
distribution of pulmonary blood flow (1787).
Boucher (CA), Robert Veyrat (CA), Jacques de Champlain (CA) and Jacques Genest
(CA) described an improved procedure for angiotensin isolation and
determination and also a new method for the measurement of plasma renin
Skeggs, Jr. (US),Walton H. Marsh (US), Joseph R. Kahn (US), and Norman P.
Shumway (US) found that angiotensin existed in two forms:
angiotensin I and angiotensin II. Angiotensin I was a biologically
inactive decapeptide which was converted to a highly active octapeptide by an
enzyme in the plasma (1532).
K.F. Ng (SG) and John Robert Vane (GB) discovered angiotensin converting enzyme
(ACE) in the lung of dogs (1223; 1224). Note: This work led to the development
and clinical use of angiotensin converting enzyme (ACE) inhibitors in medicine.
The discovery of the pulmonary converting enzyme and its inhibition by
Bradykinin Potentiating Factor (BPF) led to the synthesis of captopril (Capoten).
Brew Atkinson (GB), J. Ian S. Robertson (GB), Martin J. Kendall (US), Steven R.
Smith (US), M.H. Thompson (US), Alessandra Sturani (IT), Carla Chiarini (IT),
Ezio Degli Esposti (IT), Antonio Santoro (IT), Alessandro Zuccalŕ, Pietro
Zucchelli (IT), and Larry Neil Gever (US) reported on Captopril, the first ACE
inhibitor used clinically in the treatment of hypertension and cardiac failure (52; 604; 922; 1605). Note: There are now ten ACE
inhibitors available in the United States for the treatment of hypertension, congestive heart failure, and diabetic
kidney disease: captopril, enalapril, fosinopril, lisinopril, benazepril,
moexipril, perindopril, quinapril, ramipril and trandolapril.
Seymour M. Glick (US-IL), Jesse Roth (US), Rosalyn
Sussman Yalow (US), and Solomon Aaron Berson (US) determined that plasma
radioimmunoassayable human growth hormone (HGH) levels fluctuate widely and
rapidly in response to stimuli that have in common a shortage of carbohydrate
energy substrate, and to stress. Glucose lowers plasma HGH in normals but not
in acromegalics. The HGH response to insulin hypoglycemia distinguishes normals
from hypopituitary subjects (621).
Allan Kliman (US) and Mark E. Lesses (US)
introduced plasmapheresis as a means of collecting plasma for fractionation (945).
Grey Walter (GB-US) discovered a very slow change in electrical potential at
and around the vertex of the head, measured with respect to indifferent
reference points such as the ear lobes. Walter named this event the contingent
negative variation (CNV) because it was seen only after a warning signal had
been given to a human subject, who would then plan a possible movement in
anticipation of a second signal. German researchers discovered a comparable
slow potential in a similar behavioral context, calling it the bereitsschaftpotential (readiness
potential). These electrical potentials permit the observer to predict that a
subject will make a response within the next half to one second, before the
subject is aware of an intention to act. Some psychologists regard this
cerebral phenomenon as evidence that intentional actions are initiated before
awareness of such actions emerges, and that consciousness is involved in
judging the values of actions rather than in the execution of them (1747).
Holmes Dingle (US), George F. Badger (US), and William S. Jordan, Jr. (US)
wrote, Illness in the Home: A Study of
25,000 Illnesses in a Group of Cleveland Families. Among its findings were:
1) three uncultivatable filterable agents are responsible for atypical pneumonia (now know to be
caused by Mycoplasma pneumoniae),
influenza-like illness (now known to be caused by several different
adenoviruses), and the common cold
(now known to be caused by a number of rhinoviruses), 2) many children are
infected by certain types of adenovirus early in life, often without symptoms,
3) adenovirus types responsible for acute
respiratory disease in military recruits are not important causes of
illness in civilians, 4) antihistamine is ineffective for the treatment of
colds, 5) and there are two kinds of non-bacterial gastroenteritis (433).
J. Selikoff (US), Jacob Churg (US), and E. Cuyler Hammond (US) reported on the
mortality experience of a cohort of 632 asbestos insulation workers in the New
York area, during their working years of 1943-1962. They found significant
increases in deaths from lung cancer, mesothelioma, gastrointestinal cancer,
and asbestosis (1494).
T. Doyle (US), Thomas R. Dawber (US),William B. Kannel (US), Sandra H. Kinch
(US), and Harold A. Kahn (US) reported the relationship of smoking habit to
total mortality and to the incidence of new manifestations of coronary heart
disease (CHD) from an examination in 2,282 middle-aged men under medical
surveillance for ten years in Framingham, Mass, and 1,838 middle-aged men
followed for eight years in Albany, NY. It was found that in men who report
habitual consumption of 20 or more cigarettes per day the risk of myocardial
infarction was about three times greater than in nonsmokers, former cigarette
smokers, or pipe and cigar smokers (452).
J. Drenick (US), Marion E. Swendseid (US), William H. Blahd (US), and Stewart
G. Tuttle (US) selected eleven obese, ambulatory patients that were then starved
for periods of 12 to 117 days. Only water and vitamins were consumed. Weight
losses averaged 0.91 pounds (0.41 kg) daily. Hunger was virtually absent.
Complications which developed during starvation were severe orthostatic
hypotension in three cases; severe normocytic, normochromic anemia in one case;
and gouty arthritis in two cases. With refeeding all ill effects were promptly
reversed. Serum electrolytes, lipids, proteins, and amino acids remained
unchanged during starvation. Serum uric acid increased; blood glucose levels
fell in some cases. Considerable amounts of body protein and potassium were
lost. Prolonged starvation is not advised for obese patients with a history of
ischemic cardiovascular or cerebral disease, with history of gout, or with
hepatic diseahypole (453).
L. Dubois (US) and Denny L. Tuffanelli (US) reported that diagnosis of systemic
lupus erythematosus (SLE) was confirmed by the presence of lupus
erythematosus cells in 75.7% of the patients, findings of skin biopsies in 6.0%
and of renal biopsies in 1.2%, and by the clinical picture alone in 17.1%.
Negroes comprised 34% of the subjects. Spontaneous remissions occurred in 35%
of the patients. Proven familial SLE occurred in 2%. Myalgia was present in
48.2%. No history of cutaneous involvement at any time was found in 28%.
Classic skin lesions of chronic discoid lupus at the onset of their illness
were present in 10.8%. Urinary abnormalities were noted in only 46.1%. Uremia
caused 34% of the 135 deaths and progressive central nervous system involvement
caused 18.4%. The prognosis has markedly improved. The mean duration is now
94.8 months for the entire series versus 38.5 months in an untreated control
Lesch (US), William Leo Nyhan (US), and William J. Oliver (US) described two
young male patients (brothers) presenting with excessive uric acid and blood in
the urine, spasticity, choreoathetosis, mental retardation, and compulsive
aggressive behavior that led them to bite away their lips and tongue and to
bite away the ends of their fingers (1016; 1251). This metabolic disease was later named The Lesch-Nyhan Syndrome.
Catel (DE) and Johann-Anton Schmidt (DE) were probably the first to describe
this syndrome (271).
Edwin Seegmiller (US), Arthur I. Grayzel (US), Leonard Laster (US), and Lois
Liddle (US) found that an increased rate of purine biosynthesis de novo contributes to the hyperuricemia
in most gouty patients (1490).
Edwin Seegmiller (US), R. Rodney Howell (US), and Stephen E. Malawista (US)
reported that microcrystals of uric acid interact with all of the major
synovial cell types, including neutrophils, fibroblasts, and
monocytes/macrophages to produce a variety of inflammatory mediators (1491).
Jarvis Edwin Seegmiller (US), Frederick M.
Rosenbloom (US), and William N. Kelley (US) discovered that the rare genetic
disease, Lesch–Nyhan syndrome, was due to a profound deficiency of
an enzyme known as hypoxanthine guanine phosphoribosyltransferase
(HGPRT). Deficiency that causes high levels of uric acid in the blood
and leads to the development of gouty arthritis and the formation of
uric acid stones in the urinary tract, i.e, Kelley-Seegmiller syndrome (1492).
N. Kelley (US), Frederick M. Rosenbloom (US), and Jarvis Edwin Seegmiller (US)
found that a partial loss of hypoxanthine
guanine phosphoribosyltransferase (HGPRTase)
activity is associated with excessive purine synthesis in some patients with
H. Beutner (US) and Robert E. Jordan (US) demonstrated the skin antibodies in
sera of pemphigus vulgaris and bullous pemphigoid patients by indirect immunofluorescent
H. Beutner (US), Walter F. Lever (US), Ernest Witebsky (US), Robert Jordon
(US), and Burton Chertock (US) found antibodies to an intercellular substance
of stratified squamous epithelium using indirect immunofluorescent (IF)
staining in the sera of eight out of 16 patients with pemphigus vulgaris.
The autoantibody nature of these antibodies could be demonstrated by testing
the patient's skin with the patient's own serum (134).
E. Jordon (US), Ernest H. Beutner (US), Ernest Witebsky (US), George Blumental
(US), William L. Hale (US), and Walter F. Lever (US) observed that indirect
immunofluorescent (IF) staining in 14 of 16 patients with active lesions of bullous
pemphigoid the sera contained antibodies specific for the basement zone
beneath stratified squamous epithelium while the sera from six patients in
remission contained no demonstrable antibodies. The sera of 18 patients with dermatitis
herpetiformis and 94 patients with various bullous and nonbullous
dermatoses yielded negative reactions to the basement zone by indirect IF staining.
In four of five skin biopsy specimens from patients with bullous pemphigoid
direct IF staining indicated that γ-globulin had been bound in vivo
to the basement zone (865).
H. Beutner (US), Robert E. Jordan (US) and Tadeusz P. Chorzelski (PL) found in pemphigus
that these antibodies react with a surface protein on epithelial cells, and in bullous pemphigoid they fix to the
basement membrane, as seen by indirect immunofluorescence (IF) tests of sera on
normal epithelia. Direct IF tests of patients’ biopsies show that these
antibodies react in vivo with normal
skin and oral mucosa (133).
Ernest Pillsbury Walker (US), et al.,
completed a two- volume Mammals of the
World. It is a great reference work in which each genus is illustrated, and
its characteristics and habits tersely stated (1737).
Earl Starzl (US), David T. Rowlands, Jr. (US), Charlie H. Kirkpatrick (US),
W.E.C. Wilson (US), David Rifkind (US), and William R. Waddell (US) discovered
that splanchnic venous blood of dogs contains hepatotrophic factor(s), the most
important of which was later proved to be insulin;
the finding dictated methods of liver allograft revascularization (1580).
Earl Starzl (US) established rules to prevent ABO-incompatibility in renal
transplantation surgery (1578).
Austrian (US) and Jerome Gold (US) reported on examined cases of pneumococcal
bacteremia treated at the Boston City Hospital in Massachusetts, between 1929
and 1935. Clinical manifestations; biology of infections caused by several
pneumococcal types; results of diagnostic examinations; disease overview;
treatment regimen; mortality in untreated and treated infections (56).
Austrian (US), Robert M. Douglas (US), Gerald Schiffman (US), A. Maureen
Coetzee (ZA), Hendrik J. Koornhof (ZA), Stanley Hayden-Smith (ZA), and Robert
D.W. Reid (ZA) developed a pneumococcal vaccine, during the process of which
they established that of 83 known types of pneumococci, 14 types were
responsible for 80% of the pneumococcal infections in man, and that the outer
coatings or capsules of these 14 types should be included in an effective
vaccine (54; 55). Austrian also played a major role in the
successful clinical trials, which resulted in the vaccine's licensure.
J. Luessenhop (US) and Alfredo C. Velasquez (US) introduced endovascular
surgery for arteriovenous malformations (AVMs) and aneurysms (1066).
Earle Skipper (US), Frank M. Schabel, Jr. (US), William S. Wilcox (US), L.
Bruce Mellett (US), John A. Montgomery (US), Lee J. Wilkoff (US), Harris H.
Lloyd (US), and R. Wallace Brockman (US) proposed a model for tumor growth
which was formulated and popularized by investigators at the Southern Research
Institute. Called the log-kill model, it was the original, and is still the preeminent,
model of tumor growth and therapeutic regression. They determined that a given
dosage of a chemotherapy drug killed a relatively consistent fraction of cells
in a malignant-cell population, as opposed to an absolute number. All that was
needed was for a single leukemic cell to survive, and the doubling would start
anew, and the disease would return with a vengeance. One survivor: That was all
the curability of cancer in several animal tumor model systems, and first
introduced the concepts of total cell kill. Their experimental work
elucidated the logic of chemotherapy as an adjunct to surgery and has
delineated the idea of prompt eradication of all evidence of disease (1534-1538).
Hertz (US), Griff T. Ross (US), Mortimer B. Lipsett (US), Charles B. Hammond
(US), William D. Odell (US), Delbert M. Bergenstal (US), Edward B. Price (US),
Theodore F. Hilbish (US) and Min Chiu Li (US) made outstanding contributions to
the successful chemotherapeutic treatment of human gestational choriocarcinoma,
a solid tumor (694; 744; 745; 1028-1030).
F. Lucey (US), Emerson Hibbard (US), Richard E. Behrman (US), F. Ofelia
Esquivel de Gallardo (US), William Frederick Windle (US), and Maria D. Faro
(US) discovered a consistent and precise pattern of brain damage following
asphyxiation and resuscitation of the infant at birth. They found that this
suffocation is a frequent cause of mental retardation, and cerebral palsy. They
were also the first to correlate this pathology with the clinical symptoms of
cerebral palsy, and the first to associate it with the condition known as kernicterus, in which specific centers
of brain are colored yellow (520; 1064; 1811).
Theodore Dotter (US) and Melvin P. Judkins (US) were the first to use the
catheter for intentional percutaneous transluminal angioplasty. It was used to
benefit a patient with a painful left foot. The foot had a nonhealing ulcer and
gangrenous toes (449). Charles Theodore Dotter (US) is generally
credited with developing a new medical specialty, interventional radiology.
Grüntzig (CH) and Heinrich Hopff (CH) developed a balloon catheter capable of
dilating peripheral arteries (667).
Vernon Ingram (DE-GB-US) introduced the use of the laser for eye surgery (820).
B. Hill (US), David T. Rowlands, Jr. (US), and David Rifkind (US) reported that
pulmonary infections were present terminally in 26 of 32 patients dying one to
two hundred and seven days after receiving an organ transplant. The responsible
organisms included many unusual agents not commonly producing clinical disease.
Candida, Aspergillus, Nocardia,
Pneumocystis and Cytomegalovirus
were identified in 28 cases, and various bacteria, notably Pseudomonas, in 17 cases. Multiple infections were common (755).
Andrew L. Bassett (US), Robert J. Pawluk (US), Robert O. Becker (US), and
Arthur A. Pilla (US) reported that electromagnetic fields promote bone fracture
repair (96; 97).
R. Hamilton (US) and Michael S. Gazzaniga (US) reported evidence of laterality
(hemispheric preference) in discrimination of visual tasks (color and
brightness) in non-human primates (692).
H. Denenberg (US) following his work with hemispheric laterality in rats
presented his theory that the brain possesses innate functional asymmetry (415).
Jane van Lawick-Goodall (GB), Frans B. M. de Waal (NL-US), and Geza Teleki (US)
studied the social behavior of free-living chimpanzees. They showed that many
human practices and potentials, from politics and child rearing to violence and
even morality, have parallels in the lives of our closest animal relatives.
Between 1960 and 1997 Valerie Jane Goodall observed chimpanzees doing the
following: eating as omnivores; tool making; planning; using man-made objects;
suffering from polio and AIDS; expressing awe- (chimps spontaneously danced at
the sight of a waterfall); participating in warfare between groups;
cannibalism; establishing coalitions; transferring a female to a different
group; adolescent female, adopted
baby, after its mother died of pneumonia; males leading females away from the
community and establishing short-term monogamous relationships. This is
believed to be, so the males can ensure that the offspring are theirs;
transferring technology (chimps from one community modeled the tool making behavior of chimps in another community);
giving birth to twins; chewing the plant Aspilia, a medicinal plant believed to
relieve stomach pains or reduce internal parasites (400; 627-629; 1647).
William Donald Hamilton (GB) proposed a
theoretically robust explanation of altruism, kin selection, and inclusive
fitness based on genetics. If the success of genes shared with relatives is included
in total fitness, then even sterile individuals can have fitness if their
relatives are very successful. Helping behavior of sterile social insects could
assure their fitness in this way. Hamilton offered the simple inequality that
the ratio of cost and benefit incurred by helping must be less than the degree
of relatedness (C/B<r) (693). These
ideas have since been extended to social behaviors of many species—vertebrate
as well as invertebrate.
Bradford Hill (GB) made a landmark presentation of criteria for inferring
causality from observational data dealing with environment and disease (753). Austin Bradford
Ralph Ehrlich (US) and Peter Hamilton Raven (US) defined the process of
coevolution as a reciprocal interaction in which evolution of new chemical
defenses in a plant taxon is followed by evolution of new means of
circumventing those defenses in specialist butterfly herbivores. They concluded
that repeated coevolutionary interactions of this sort have been critical to
the diversification of both butterflies and flowering plants (487).
Henry de Lumley (FR) and Marie-Antoinette de
Lumley (FR), in 1964, discovered the fossil remains of a Homo erectus/Homo sapiens
transitional form in the Verdouble Valley in Southeastern France. The age of
this fossil man (Arago man) is uncertain (c.a 130,000) (396).
Goes in Must Come Out”
great Dr. Starling, in his Law of the Heart
the output was greater, if, right at the start,
cardiac fibers were stretched a bit more,
their force of contraction would be more than before.
the larger the volume in diastole,
greater the output was likely to be.
when the heart reaches a much larger size,
leads to Heart Failure, and often, Demise.
relevant law is not Starling's, alas,
the classical law of Lecompte de Laplace.
patient is dying in Decompensation,
reduce his Blood Volume, or call his Relation.
the right heart keeps pumping more blood than the left,
lung circuit's congested; the systemic -- bereft.
no one is healthy with pulmo-congestion,
law of Doc. Starling's a splendid suggestion.
balance of outputs is made automatic
blood-volume partition becomes steady-static.” Alan Chadburn Burton (CA) (232).
Burns Woodward (US) was awarded the Nobel Prize in Chemistry for his
achievements in organic synthesis.
Jacob (FR), Jacques Lucien Monod (FR), and André Michel Lwoff (FR) shared the
Nobel Prize in Physiology or Medicine for their discoveries concerning genetic
control of enzyme and virus synthesis.
Benjamin Rubin (US) patented the bifurcated needle for delivery of smallpox
Instruments produced the first commercial scanning electron microscope. ref
Burns Woodward (US) accomplished the total synthesis of colchicine (1825).
Chemical Company introduced the herbicide paraquat,
a bipyridyl quaternary ammonium salt, useful in sugar cane (Saccharum officinarum) and fruit trees. ref
Holmes Dingle (US) developed a rapid method for separating and determining DDT
in fat (432).
M. Kligman (US) reported that the unequivocally demonstrated spectrum of
biologic activities of dimethyl sulfoxide includes enhancement of penetration
through plant and animal membranes and preservation of living cells and
tissues during freezing. It is exceptionally nontoxic. The acute median
lethal dose values for mice are, for example, (a) 21,400 mg/kg (oral
administration), and (b) 3,820 mg/ kg (intravenous administration) (944).
Tauri (JP), Giichi Okuno (JP), Yuji Ikura (JP), Takehiko Tanaka (JP), Masami
Suda (JP), and Mitsuo Nishikawa (JP) reported phosphofructokinase deficiency, also known as glycogen storage disease type
VII or Tarui's disease. They found phosphofructokinase activity was
decreased in erythrocytes with patients inheriting the disorder in an autosomal
recessive pattern (1640).
Walton H. Marsh (US), Benjamin Fingerhut
(US), and Henry Miller (US) published modifications of the direct assay
of urea with diacetyl monoxime, applicable to both manual and automated
Ivan Stanley De la Lande (AU) and Michael J.
Rand (AU) described the pharmacology of an isolated, perfused nerve-blood
vessel preparation which responded rapidly and reproducibly to sympathetic
nerve stimulation. As a result, the preparation has come into widespread use
for the study of adrenergic transmission in arteries and of the modification of
transmission by drugs, particularly drugs acting via pre-synaptic receptors (394).