A Selected Chronological Bibliography of Biology and Medicine
Part 5B
1957 —
1963
Compiled
by James Southworth Steen, Ph.D.
Delta
State University
Dedicated
to my loving family
This document celebrates those secondary authors and laboratory
technicians without whom most of this great labor of discovery would have
proved impossible.
Please
forward any editorial comments to: James S. Steen, Ph.D., Professor Emeritus,
jsteen08@bellsouth.net
1957
“Humility
and perspective are necessary ingredients of scientific craftsmanship; here
they concur in stressing the far reaches of our ignorance.” Joshua Lederberg (889).
“Discovery
consists of seeing what everybody has seen and thinking what nobody has
thought.” Albert Szent-Györgyi (1504).
"It is necessary to postulate
genes that have opposite effects on fitness at different ages, or, more
accurately, in different somatic environments." George Christopher
Williams (US) (1661). See, Staub 2016. Note:
This theory is now widely accepted in aging research and elsewhere, and it is
called antagonistic pleiotropy theory.
Alexander
Robertus Todd (GB) was awarded the Nobel Prize in Chemistry for his work on
nucleotides and nucleotide co-enzymes.
Daniel Bovet
(CH-FR-IT) was awarded the Nobel Prize in Physiology or Medicine for his
discoveries relating to synthetic compounds that inhibit the action of certain
body substances, and especially their action on the vascular system and the
skeletal muscles.
E. Margaret
Burbidge (US), Geoffrey R. Burbidge (US), William A. Fowler (US), and Fred
Hoyle (US) suggested that the heavy elements originated in the furnaces of
supernovas (191).
Matthew
Stanley Meselson (US), Franklin William Stahl (US), and Jerome R. Vinograd (US)
invented density gradient centrifugation. This technique separates large
molecules based on their different buoyancys in solution (1047).
Marvin Lee
Minsky (US) patented the principle of confocal imaging (1053).
Jordi Folch
(ES-US), Marjorie Berman Lees (US), and Gerald H. Sloane-Stanley (US) devised a
simple method for the isolation and purification of total lipides from animal
tissues (456).
Marvin M.
Nachlas (US), Kwan-Chung Tsou (US), Eustace De Souza (US), Chao-Shing Cheng
(US), and Arnold M. Selingman (US) introduced the use of
2,2'-di(-p-nitrophenyl) -5,5'-diphenyl-3,3'-(3,3'-dimethoxy-4,4'-diphenylene)-di(tetrazolium
chloride) (Nitro BT, or NBT) as the ideal substrate for the cytochemical
demonstration of DPN and TPN diaphorase systems, as well as the succinic
dehydrogenase system. The ‘NBT’ method has since become the most popular method
for the demonstration of dehydrogenases in histochemistry (1111).
Alfred H.
Free (US), Chauncey O. Rupe (US), and Ingrid Metzler (US) formulated two simple
colorimetric tests for protein in urine; one is a tablet test, consisting of a
salicylate buffer and bromphenol blue, and the other is a strip test,
consisting of a paper strip impregnated with a citrate buffer and tetrabromphenol
blue. The basic principle in both tests is that of "protein error of
indicators." Experiments with approximately 5000 urines, taken from both
hospital patients and normal subjects, revealed that these tests are simple,
rapid, accurate, sensitive, specific, and capable of being used with turbid
urines (480). See, George Oliver and
Fritz Feigl, 1883
Leonard T.
Skeggs, Jr. (US) described the first completely automatic method for
colorimetric analysis. It employed a new analytical technique that was
performed in a continuously flowing stream. The determination of urea nitrogen
in whole blood was described as one application of a generally applicable
method (1431).
Gerald O. Aspinall
(GB-CA) and Robin J. Ferrier (GB-NZ) developed a convenient micro-method is
described for following the oxidation of carbohydrates by periodate. The
spectrophotometric procedure is based on changes in the ultraviolet light
absorption of periodate at its maximum at 223 nm, and corrections are made for
absorption by iodate formed (66).
Russell L.
Steere (US) invented freeze-fracture specimen preparation for electron
microscopy (1471).
Hans Moor
(CH), Kurt Mühlethaler (CH), Heinz Waldner (CH), and Albert Frey-Wyssling (CH)
perfected the freeze fracture technique (1090; 1091).
Jordi Folch
(ES-US) Marjorie B. Lees (US), and Gerald H. Sloane-Stanley (US) developed a
simple method to do a total lipid extraction from animal tissues. This method
quickly became the standard for lipid extraction
(456).
Milton W. Hamolsk (US), Myron Stein (US), and A. Stone Freedberg (US)
presented a new in vitro method, based on the ‘uptake’ of I-131
T-3 by red blood cells from whole blood. The simple test accurately
differentiates hyper-, hypo-, and euthyroidism, is unaffected by iodine
exposure, avoids administration of radioactivity to patients, and indicates
several epiphenomena of wide biologic and clinical interest. Their studies were
based on a) the fact that thyroxin (T-4) and triiodothyronine (T-3) molecules
are both hydrophilic and lipophilic, and b) the notion that their hormonal
action might therefore involve alignment at, and alteration of, the aqueous
plasma-lipid membrane interface (612).
Emile Van
Handel (US) and Don B. Zilversmit (US) presented a microprocedure for the
direct determination of triglyceride concentrations in biologic specimens. The
method depends on the quantitative removal of phosphatides from the sample and
the subsequent determination of esterified glycerol (1590).
Donald E.
Wolf (US), Carl H. Hoffman (US), Paul E. Aldrich (US), Helen R. Skeggs (US),
Lemuel D. Wright (US), and Karl August Folkers (US) determined the structure of
beta, delta-dihydroxy-beta-methylvaleric acid (the acetate-replacing factor for
Lactobacillus acidophilus) which was
christened mevalonic acid. In subsequent studies, mevalonic acid was shown to
be a key intermediate in the synthesis of isoprenoid compounds arising from
acetate, including cholesterol, ubiquinones, menoquinones, dolichol, and other
isoprene derivatives (1670).
Arthur J. Kornberg (US) reported that all four of the
deoxynucleotide triphosphates must be present for DNA synthesis to take place (832).
Julian E.
Philip (US), Jay R. Schenck (US), and Martha P. Hargie (US) isolated the
antibiotic ristocetin from Nocardia lurida (1216).
Gordon C.
Mills (US) determined that glutathione
peroxidase is an erythrocyte enzyme, which protects hemoglobin from
oxidative breakdown in the intact erythrocyte (1052).
Alfred H.
Free (US), Ernest C. Adams (US), Mary Lou Kercher (US), Helen M. Free (US), and
Marion H. Cook (US) developed a simple, specific, sensitive, and
speedy test for glucose in urine. Data are presented to show that the test has
a high accuracy with both positive and negative specimens (479).
Tomio
Takeuchi (JP), Tokuro Hikiji (JP), Kazuo Nitta (JP), Seiro Yamazaki (JP), Sadao
Abe (JP), Hisaro Takayama (JP), and Hamao Umezawa (JP) isolated the antibiotic kanamycin from Streptomyces kanamyceticus (1516).
Shuko
Kinoshita (JP), Katsunobu Tanaka (JP), Shigezo Udaka (JP), Sadao Akita (JP),
and Masakazu Shimono (JP) discovered that bacteria can be used to produce
monosodium glutamate and amino acids (811; 812). This led
to a new industry; the microbial production of amino acids for human and animal
consumption.
Theodore W. Rall (US), Earl Wilbur Sutherland, Jr. (US), and
Jacques Berthet (BE) reported the isolation of a small, heat stable molecule,
with a UV light absorption spectrum reminiscent of that of ATP. Careful
chemical analysis revealed that this substance is a cyclic derivative of ATP,
i.e., cyclic AMP (1255).
Earl Wilbur
Sutherland, Jr. (US), Theodore W. Rall (US), and Tara Menon (US) discovered adenyl cyclase, the enzyme that converts
ATP into 3’, 5’-cyclic AMP (1501).
David Lipkin
(US), William H. Cook (US), and Roy Markham (US) determined the structure and
molecular weight of adenosine-3', 5'-phosphate (cyclic AMP) (927).
Gary
Felsenfeld (US), David R. Davies (US), and Alexander Rich (US) discovered that
RNA molecules can form triple helices (433).
Seymour
Kaufman (US) partially purified two enzymes that participate in the conversion
of phenylalanine to tyrosine. He discovered that the reaction also requires the
presence of triphosphopyridine nucleotide (TPNH; now known as NADPH) and oxygen
(790).
Seymour
Kaufman (US) determined
that a co-factor different from any other known vitamin or coenzyme was
necessary for the above reactions. Preliminary studies suggested that the
cofactor interacted directly with TPNH (791).
Seymour
Kaufman (US) found that the cofactor is a double bond tautomer of the inactive
7,8-dihydropteridine (792). The new cofactor was eventually
identified as a tetrahydropteridine.
Michael Sela
(IL), Frederick H. White, Jr. (US), Christian Boehmer Anfinsen, Jr. (US), and
Edgar Haber (US) helped explain the connection between the amino
acid sequence and the biologically active conformation in proteins (33; 597; 1392).
Harry Beevers (GB-US), Hans Leo Kornberg (GB-US), David T. Canvin
(US), Ann Oaks (US), R. William Breidenbach (US), and Bernt P. Gerhardt (DE)
discovered the glyoxylate cycle in seedlings of plants that store fat in their
seed and utilize this fat as a source of energy and for the production of
glucose during early seedling growth. These studies demonstrated that the
glyoxylate cycle of fat-storing seeds is in a specific metabolic/cytoplasmic
compartment, the glyoxysome (108; 166; 227; 520; 836; 837; 1164).
Hans Leo Kornberg (GB-US) and Jack R. Sadler (US) were
able to show that the provision of energy from glycolate could occur via a
dicarboxylic acid cycle, in which an isoform of malate synthetase catalyzed the condensation of glyoxylate and
acetyl coenzyme A as the first step in a sequence of reactions that led from
malate via oxaloacetate and pyruvate to the loss of two carbons as CO2
and to the reformation of the acetyl coenzyme A acceptor (842).
Hans
Leo Kornberg (GB-US) and Tony Gotto (US) described the ancillary route, which
operates to replenish the intermediates of the tricarboxylic acid (TCA) and dicarboxylic
acid cycles, as they are withdrawn during biosyntheses (839).
Hans
Leo Kornberg (GB-US) and J. Gareth Morris (GB) uncovered another novel route
for growth on glycolate. In this pathway (apparently unique to Micrococcus denitrificans), the
utilization of glyoxylate proceeds by a sequence involving an initial
condensation of this C2
compound with glycine to form erythro-beta-hydroxyaspartate, which undergoes
transamination with a second molecule of glyoxylate to reform glycine and to
yield oxaloacetate (840; 841).
Hans Leo Kornberg (GB-US) presented the concept of anaplerotic pathways as those various
pathways, which serve to maintain
the central metabolic routes during the growth of microorganisms
on C2 compounds.
The term anaplerotic was suggested by Abraham Wasserstein (GB) to mean
"filling up again" (835).
Anthony H.C. Huang (US) and Harry Beevers (GB-US) noted that the glyoxysome turned
out
to be the first of a new class of plant organelles called microbodies (709).
Leonard S. Lerman (US), Leonard J. Tolmach (US), and Maurice S.
Fox (US) succeeded in labeling transforming DNA
with 32P and demonstrated that the radioactivity was incorporated
into a genetically transformed strain of Pneumococcus (Streptococcus).
These results provided quantitative information on the stoichiometry of the
transformation event, showing that incorporation of the tracer into recipient
cells was concomitant with genetic modification (463; 904; 905).
Hans Adolf
Krebs (DE-GB) and Hans Leo Kornberg (GB-US) proposed that a single enzyme in a
biochemical pathway might act as a pacemaker that controls the supply of
substrate for subsequent reactions (849).
Aaron Novick
(US) and Milton Weiner (US) concluded that the induced synthesis of beta-galactosidase at low concentrations
of inducer bears close resemblance to the phenomenon of mutation (in the sense
of a chromosomal change). In the case of mutation, a cell is either mutant or
wild type; in the case of enzyme induction a bacterium is either fully induced
and makes beta-galactosidase at maximum rate or is uninduced and makes no beta-galactosidase (1149).
Alfred Day
Hershey (US), Elizabeth Burgi (US), Joseph D. Mandell (US), and Jun-ichi
Tomizawa (US) concluded that the chromosome of bacteriophage is a naked DNA
molecule (664).
Hugh John
Forster Cairns (GB-US-GB) calculated the mass of T2 bacteriophage DNA to be 110
X 106 daltons (208).
Joseph A.
Cifonelli (US) and Albert Dorfman (US) established that the group A
streptococci contain the uridine nucleotide sugars, UDP-N-acetylglucosamine and
UDP-glucuronic acid, requisite for the synthesis of hyaluronic acid (272).
Alvin
Markovitz (US) and Albert Dorfman (US) concluded that the enzyme responsible
for glycosyl transfer among group A streptococci is localized on the protoplast
membrane (1002). This is
one of the first observations relating a macromolecular synthesis—glycosyl
transfer—to membrane-associated enzymes.
Robert L.
Perlman (US), Alvin Telser (US), Albert Dorfman (US), and Howard C. Robinson
(US) developed cell-free preparations of embryonic chick cartilage that
synthesized chondroitin sulfate using glycosyl transfer from
UDP-N-acetylgalactosamine and UDP-glucuronic acid to small acceptor
oligosaccharides. They also characterized a xylosylserine linkage within these proteoglycans (1213; 1306; 1527).
Robert
Emerson (US), Ruth V. Chalmers (US), and Carl N. Cederstrand (US) discovered
the enhancement effect, which occurs during photosynthetic oxygen evolution
when two beams of light, with different wavelengths, are given simultaneously.
The yield of oxygen is greater than the sum of the yields with each beam alone. Chlorella pyrenoidosa was their
experimental organism (408). After the
same effect was found in red algae, diatoms, and a cyanobacterium there evolved
the concept of two pigment systems and two light reactions within the
photosynthetic mechanism.
Harland Goff
Wood (US), Per Schambye (DK), Max Kleiber (CH-US), Georges J. Peeters (BE),
Patrick M.L. Siu (US), Seymour Joffe (US), R. Gillespie (US), Roger G. Hansen
(US), and Harry Hardenbrook (US) found that in cows lactose is synthesized when
free glucose reacts with UDP-galactose (1358; 1674-1676).
Karl Sune
Detlof Bergström (SE), Jan Sjövall (SE), Ragnar Ryhage (SE), and Bengt Ingemar
Samuelsson (SE) obtained crystals of two prostaglandins, alprostadil (PGE1) and
PGF1a. They worked out the structures of the first family of prostaglandins all
of which contain the C-20 carbon framework of prostanoic acid (119-123).
Irving I.
Geschwind (US), Choh Hao Li (CN-US), and Livio Barnafi (CL) isolated,
characterized and determined the amino-acid sequence of a
melanocyte-stimulating hormone from bovine pituitary glands (530).
Klaus
Hofmann (CH-US), Miriam E. Wollner (US), Haruaki Yajima (JP), Gertrude Spühler
(US), Thomas A. Thompson (US), and Eleanore T. Schwartz (US) synthesized a
physiologically active blocked tridecapeptide amide possessing the amino acid
sequence of alpha-melanocyte-stimulating hormone (MSH) (688).
John Clark
Sheehan (US) and Kenneth R. Henery-Logan (US) synthesized Penicillin V (1401; 1402). This was
the first penicillin produced synthetically.
Jens
Christian Skou (DK), Carsten Hilberg (DK), and Peter L. Jorgensen (DK)
discovered the sodium, potassium-stimulated adenosine
triphosphatase (Na+, K+-ATPase). This enzyme breaks down ATP and uses the liberated energy
to transport sodium and potassium ions across cellular membranes, maintaining a
proper balance inside the cell. Skou was the first to identify an enzyme that
controls the movement of ions across the cellular membrane (758; 1434-1437).
Mahlon Bush
Hoagland (US), Paul Charles Zamecnik (US), Mary Louise Stephenson (US), Jesse
Friend Scott (US), Liselotte I. Hecht (US), Paul Berg (US), E. James Ofengand
(US), Richard S. Schweet (US), Freeman P. Bovard (US), Esther Allen (US), and
Edward Glassman (US) performed experiments suggesting that each sRNA (tRNA) is
specific for only one amino acid (117; 682; 683; 1382).
George
Yerganian (US) described the morphologic components of nine isolated human
pachytene bivalents. Each bivalent is characterized by a distinct and
recognizable form assumed after being released from the nuclear membrane. In
the absence of chromosomal lampbrushing, large chromatic knobs, diffuse
segments of chromatin, and in some cases, attached nucleoli, make up the
general features for identifying these particular bivalents (1706).
Charles
Heidelberger (US), Nabendu
K. Chaudhuri (US), Peter B. Danneberg (US), Dorothy Mooren (US), Lois Griesbach (US), Robert
Duschinsky (US), Robert J. Schnitzer (US), Edward Pleven (US), James I. Scheiner (US), and Willi E. Oberhänsli (CH)
synthesized 5-flurouracil (FU) and 5-fluoro-2’-deoxyuridine (FUdR) as antimetabolites
to treat tumors (380; 381; 645).
Seymour
Stanley Cohen (US), Joel G. Flaks (US), Hazel D. Barner (US), Marilyn R. Loeb,
and Janet Lichtenstein (US) showed that the antitumor agent 5-fluorouracil and
its deoxyribosyl derivative are converted to the deoxyribonucleotide in E. coli and provoke thymine deficiency
and ‘thymineless death.’ Fluorodeoxyuridylate, isolated from the bacteria or
synthesized enzymatically in vitro,
is an irreversible inhibitor of the thymidylate
synthetase isolated from phage-infected bacteria (287).
Edmund Klein
(US) developed a protocol for the application of a highly effective topical
anticancer agent, 5-fluorouracil (5-FU), to superficial basal cell carcinoma (815).
Arthur St.
George Joseph McCarthy Huggett (GB) and D.A. Nixon (GB) described a method for
determination of glucose levels in blood and urine using a fungal oxidase preparation (721). This
method has found widespread use in clinical medicine.
Hugo Wilhelm
Knipping (DE), Wilhelm Bolt (DE), Helmut Venrath (DE), Helmut Valentin (DE), Hans
Ludes (DE), and Paul Endler (DE) used xenon-133 to measure lung ventilation (826-828).
George W. Bartelmez
(US) showed that there is continuity between prepregnant and pregnant states
from the standpoint of circulation, this is most apparent in the persistence of
an intrinsic contractile potential in the spiral arteries. This is manifested
during the menstrual cycle by isolated contractions at the myoendometrial
junction which produce ischemia leading to foci of endometrial necrosis and
slough (95).
Chester B.
Martin, Jr. (US), Harry S. McCaughey, Jr. (US), Irwin H. Kaiser (US), Martin W.
Donner (US), and Elizabeth Mapelsden Ramsey (US) found that during pregnancy
the intermittency of flow through individual spiral arteries into the
intervillous space is sufficent to maintain the myometrium (1010).
André Michel
Lwoff (FR) articulated
major differences between viruses and bacteria, based on molecular structure
and physiology. The virus contained either RNA or DNA enclosed in a coat of
protein, and it possessed few if any enzymes except those concerned with
attachment to and penetration into the host cell. The virus was not a cell and
did not reproduce by division like a cell. Its replication occurred only within
a susceptible cell, which always contains both DNA and RNA and an array of
different proteins endowed with enzymatic functions mainly concerned with the
generation of ATP and the synthesis of varied organic constituents of the cell
from chemical compounds in the environment. “Viruses should be treated as
viruses” (952).
John E.
Vogel (US), Alexis Shelokov (US), and Lotta Chi (US) developed the
hemagglutination-adsorption (hemadsorption) technique for detecting myxoviruses (1405; 1599).
Harold
F. Deutsch (US), Jane I. Morton (US) reported that when gamma globulins with molecular weights of about
1,000,000 are treated with mercaptans at neutral pH they are readily converted
into subunits of about one-fifth the size of the parent molecules. Removal of
the mercaptan leads to some reformation of the original protein and this
reaggregation is blocked by alkylating agents. This demonstrated that the
macromolecular type of antibody molecule contains subunits linked by disulfide
bonds (347).
Jordi Casals
(ES-US) grew the yellow fever virus in suckling mice (239).
Norman R. Underdahl (US), Oliver D. Grace (US),
and Alvin B. Hoerlein (US) cultivated a cytopathogenic agent in tissue culture from a case of bovine
mucosal disease (1581). Note: This virus would
later be called bovine virus diarrhea virus (BVDV).
Elvis R.
Doll (US), John T. Bryans (US), William H. McCollum (US), and M.E. Ward Crowe
(US) isolated a filterable agent causing arteritis of horses and abortion by
mares (355). Note: This agent would
become known as equine arteritis virus (EAV).
Telford H.
Work (US), F.R. Roderiguez (US), and Pravin N. Bhatt (IN-US) discovered the Kyasanur
Forest disease virus (1685). Note: This is a
tick-born viral hemorrhagic fever
J. H. Seddon
(NZ), in 1957, submitted a report to the Research Committee of the New Zealand
Council, College of General Practitioners, describing eight cases, in children,
of a new clinical illness that has come to be known as hand-foot-and-mouth disease. His report was not published until
1961 (23; 375; 1391). Hand, foot, and mouth disease (HFMD),
first reported in New Zealand in 1957 is caused by Coxsackievirus A16 (CVA16)
and human enterovirus 71 (HEV71) and occasionally by Coxsackievirus A4-A7, A9,
A10, B1-B3, and B5.
Huang
Zhi-Shang (RU), Anatonina Konstantinova Shubladze (RU), C.S. Huang (RU), Karl
Edward Schneweis (DE), and Gordon Plummer (US) serologically differentiated
herpes simplex virus type 1 (labial) from herpes simplex type 2 (genital) (1223; 1369; 1413; 1711).
Gueh-Djen
Hsiung (CN-US) and Joseph Louis Melnick (US) led the way in using selective
cell cultures and the recognition of distinctive enterovirus plaque morphology
to identify viral pathogens (707). Note: This was a crucial
step in developing rapid methods for differential identification of viruses .
James
Herbert Taylor (US), Philip Sargent Woods (US), and Walter L. Hughes (US) were
the first to apply 3H-labelled thymidine to the study of biological
phenomena. Their work in Vicia (the
broad bean) confirmed the semiconservative mode of DNA replication in
eukaryotes (Eucarya) (1525).
Victor P. Bond
(US), Theodore M. Fliedner (US), Eugene P. Cronkite (US), Joseph R. Rubini
(US), George Brecher (US), and P.K. Schork (US) showed that in vitro incubation with tritiated thymidine of blood from normal individuals and
patients with infection and infectious mononucleosis, demonstrated the presence
of small numbers of labeled large mononuclear cells of different morphological
types indicating that the cells are capable of DNA synthesis and division (155).
Francois
Jacob (FR), Clarence R. Fuerst (US), and Élie L. Wollman (FR) discovered that
viral proteins of the T-even bacteriophages appear to be synthesized either as early or late. Early proteins are
associated with phage multiplication and
late proteins constitute the phage coat (735).
Joel G.
Flaks (US), Seymour Stanley Cohen (US), Arthur J. Kornberg (US), Steven B. Zimmerman
(US), Sylvy R. Kornberg (US), and John Josse (US) subsequently showed that, at
the outset of intracellular phage growth, the T-even phage DNA induces
formation of an ensemble of early
enzymes whose presence is required before replication of the phage DNA can
begin. This ensemble, which is wholly foreign to the uninfected Escherichia coli, includes enzymes that
catalyze the synthesis and glucosylation of 5-hydroxymethylcytosine, the
synthesis of thymine by a new metabolic pathway, and the polymerization of the
phage DNA from its nucleoside triphosphate building blocks. Synthesis of these early enzymes ceases near the end of the
eclipse phase (451; 452; 834).
Carl A.
Scheel (US), Stanley D. Beck (US), and John T. Medler (US) were the first to
develop an artificial diet for a phytophagous piercing-sucking insect (1361).
Stanley D.
Beck (US) and Edward E. Smissman (US) were the first to perform a systematic
study of the chemical basis of plant resistance to insects (103; 104).
Stanley D.
Beck (US) and John F. Stauffer (US) isolated three compounds (A, B, and C) from
first-generation European corn borer resistant corn varieties. These factors
were shown to be deleterious to European corn-borer larvae
(Pyrausta nubilalis (Hbn.) (105).
David W.H.
Barnes (GB) and John Freeman Loutit (GB) made the first attempt to treat
leukemia in mice by bone marrow transplantation after lethal total body
irradiation (TBI) (86).
Edward
Donnall Thomas (US), Harry L. Lochte, Jr. (US), Wan Ching Lu (US), Joseph W.
Ferrebee (US), Joe H. Cannon (US), and Otto D. Sahler (US) made the first
attempts to treat leukemia in humans using high dose chemotherapy or total body
irradiation or a combination of both followed by bone marrow transplantation (1553; 1554).
Theodore W.
Rall (US), Earl Wilbur Sutherland, Jr. (US), and Jacques Berthet (US)
established the concept of transmembrane signaling and the receptor-regulated
production of intracellular second messengers (1254; 1255).
Beatrice
Mintz (US) and Elizabeth Buckley Shull Russell (US) provided the first proof of
the extra-gonadal origin of germ cells in the mammalian embryo (1054).
Joshua
Lederberg (US) and Thomas Foxen Anderson (US) demonstrated that following
bacterial conjugation the female
generates a mixed clone, including recombinants, among the offspring (29; 888).
Salvador
Edward Luria (IT-US), Jeanne W. Burrous (US), Louis S. Baron (US), Warren F.
Carey (US), and Walter M. Spilman (US) demonstrated bacterial conjugation
across species boundaries, Escherichia
coli K-12 to Shigella and Escherichia coli to Salmonella typhimurium (87; 951).
Fu-Chuan
Chao (US) described the microsome/ribosome of yeast as composed of two unequal
pieces, which will separate from one another unless a trace of magnesium is
present (260).
Frederick G.
Germuth, Jr. (US) and George Edward McKinnon (US) demonstrated that purified
soluble antigen-antibody complexes can, by themselves, induce systemic
anaphylaxis and that these soluble complexes form in moderate antigen excess,
diffuse throughout the interstitial fluids, and can react with complement (528).
Edward C.
Franklin (US), Halsted R. Holman (US), Hans J. Muller-Eberhard (US), and Henry
G. Kunkel (US) found an unusual protein component of high molecular weight
(22S) in the serum of certain patients with rheumatoid arthritis (473). Note: This was the first
recognition that rheumatoid arthritis sera contain autoantibodies
specific for determinants on native IgG molecules.
James
Learmonth Gowans (GB), Roy G. Shorter (US), Jesse L. Bollman (US), Newton B.
Everett (US), Ruth W. Caffrey (US), William O. Rieke (US), and E. Julie Knight
(GB) confirmed that the turnover of lymphocytes is more apparent than real,
since the same lymphocytes continuously recycle from blood to lymph; but they
recycle by way of the lymph nodes (423; 572-574; 1412).
Helge Sigurd
Sjövall (SE) had earlier proposed this but thought the lymphocytes recycled
mainly through the tissue spaces of the body generally (1430).
James
Learmonth Gowans (GB), Douglas D. McGregor (GB), Diana M. Cowen (GB), and
Charles Edmund Ford (GB) showed the involvement of lymphocytes in immune
tolerance (576).
Douglas D.
McGregor (GB) and James Learmonth Gowans (GB) made the link between lymphocytes
and antibody formation (1032).
Newton B.
Everett (US), Ruth W. Caffrey (US), and William O. Rieke (US) found that one
population of small lymphocyte lives less than two weeks (423).
Stephen H. Robinson
(US), George Brecher (US), Ira S. Lourie (US), and James E. Haley (US)
determined that another population of small lymphocyte lives at least 10 months (1307).
John S.
Colter (US), Harris H. Bird (US), Arden W. Moyer (US), Raymond A. Brown (US),
Hattie E. Alexander (US), Gebhard Koch (US), Isabel Morgan Mountain (US), and
Olga Van Damme (US) discovered that poliovirus genomic RNA is infectious and
functions as messenger RNA (15; 291).
Robert Paul
Hanson (US) and Carl A. Brandly (US) worked out the epizootiology of vesicular
stomatitis virus (614).
James P.
Duguid (GB) and Robert Reid Gillies (GB) discovered that Shigella flexneri adheres to epithelial surfaces using fimbriae (pili) (376).
Daniel
Israel Arnon (PL-US), Frederick Robert Whatley (GB), and Mary Belle Allen (US)
determined that triphosphopyridine nucleotide (TPN or NADP) acts as a catalyst
in photosynthetic phosphorylation (61).
Daniel
Israel Arnon (PL-US), Frederick Robert Whatley (GB), Mary Belle Allen (US),
Manuel Losada (ES), Achim V. Trebst (DE), Shoitsu Ogata (JP), Harry Y.
Tsujimoto (US), David O. Hall (US), and Alan A. Horton (US) confirmed that the
light and dark phases of photosynthesis could be separated temporally. First,
they illuminated chloroplasts in the absence of carbon dioxide, which resulted
in trapping some of the light energy in a chemical form. They then disrupted
the chloroplasts and removed the grana,
in which the light trapping reaction takes place, and added radioactive carbon
dioxide to the remaining stroma. They
found that the carbon dioxide is converted in the dark into radioactive hexoses
at the expense of the chemical energy generated in the preceding light period.
These experiments also showed that chloroplasts are capable of the entire
photosynthetic process leading to hexose formation; i.e., they are complete
photosynthetic units, just as the mitochondria are complete respiratory units.
Arnon’s
group theorized that light energy drives electrons off chlorophyll and into a redox series where oxidized NADP
ultimately accepts them. While passing through the redox series energy is made available to drive the synthesis of
ATP. If the electrons return to chlorophyll the process represents cyclic photophosphorylation. If
photophosphorylation is cyclical, then reduced coenzyme (PNH2) must be
generated by a dark reaction of some sort. Some sources of reducing power are
sufficiently energetic (e.g., hydrogen) to donate their electrons directly to
coenzyme thereby reducing it. Other sources of reducing power such as
thiosulfate and succinate do not possess the reducing capacity to convert
oxidized coenzyme to reduced coenzyme, therefore additional energy is required.
Arnon’s group proposed (incorrectly) that electrons donated by thiosulfate,
succinate, or other sources are transferred via cytochromes to chlorophyll and
then raised at the expense of light energy to a reducing potential sufficient
to produce reduced coenzyme. If the electrons do not pass to coenzyme they may
be picked up by external acceptors such as nitrogen, or protons generating
ammonia and hydrogen (52-54; 57; 58; 62). Note-Current evidence indicates that organisms
using cyclic photophosphorylation generate reducing power by using ATP to
reverse electron flow through a redox series to produce NADPred. Some electron
sources, such as hydrogen, possess sufficient reducing potential to donate electrons
directly to NADPox.
In higher
plants low energy electrons are split from water and passed to chlorophyll
where they are energized at the expense of light. From the chlorophyll they
pass through a redox series, to
chlorophyll again, then through another redox
series eventually to be accepted by NADPox. to form NADPred. While passing
through the redox series the
electrons drive the synthesis of ATP.
Anton Lang
(RU-US) and Amos E. Richmond (IL) discovered that cytokinin delays senescence
of detached Xanthium (cocklebur)
leaves (873). This
indicated that cytokinins are likely produced in the root then transported to
the shoot where they prevent processes associated with senescence, e.g.,
breakdown of protein and chlorophyll.
Folke Karl
Skoog (SE-US) and Carlos O. Miller (US) put forth the concept of hormonal
control of organ formation in plants. They showed that the differentiation of
roots and shoots in tobacco (Nicotiana
tabacum) pith tissue cultures is a function of the auxin/cytokinin ratio,
and that organ differentiation can be regulated by changing the relative
concentrations of the two substances in the medium; high concentrations of auxin promote rooting, whereas high
levels of cytokinin support shoot
formation. At equal concentrations of auxin
and cytokinin the tissue tends to
grow in an unorganized fashion. This concept of hormonal regulation of
organogenesis in plants is now applicable to most plant species (1433).
Kenneth
David Roeder (GB-US) and Asher E. Treat (US) established that the tympanal
organs of noctuid moths are specifically tuned to the ultrasonic signals used
by bats (1311).
Edwin J.
Furshpan (GB-US) and Davis D. Potter (GB-US) examined the mechanism of nerve
impulse transmission at the giant motor synapses of the crayfish, by inserting
one or two microelectrodes into both pre- and post-synaptic axons. These fibers
could be readily recognized by their distinctive physiological characteristics.
The distance of the pre- fiber electrodes from the synapse was usually 10-20%
of the characteristic length of that fiber. At least one of the post-fiber
electrodes was usually in the immediate region of the junction.
From the
results they hypothesized that electrotonic current readily flows across the
junction, but the ‘synaptic membrane’ is a rectifier allowing positive current
to cross only in the direction from pre-to post-fiber.
This
evidence supported the idea that neurons were communicating through sparks --
electrical synapses. Thus, crayfish provided the first conclusive evidence for
the existence of a different way that neurons could communicate (496; 497).
Karl Patterson
Schmidt (US) was one of the most important herpetologists in the 20th century.
Though he made only a few important discoveries by himself, he named more than
200 species and was a leading expert on coral snakes (330). Note: Schmidt died in
1957 after being bitten by a juvenile boomslang snake (Dispholidus typus).
He wrongly believed that it could not produce a fatal dose.
Edgar Gustav
Franz Sauer (DE) and Eleanore M. Sauer (DE) used a planetarium to subject
Old-World warblers to various synthetic night skies of star settings. They
found these birds capable of stellar navigation (1353; 1354).
Klaus
Schwarz (US) and Calvin M. Foltz (US) were the first to recognize that selenium
(Se) is important to normal human metabolism (1380).
Joseph S.
Wall (US), Robert Steele (US), Richard C. de Bodo (US), Norman Altszuler (US),
Ralph A. DeFronzo (US), Jordan D. Tobin (US), and Reubin Andres (US) made it
possible for the first time to measure, accurately and outside of steady-state
conditions, 1) the rate of hepatic glucose production and glucose
utilization using a radio-tracer infusion method, and 2) insulin
sensitivity and the effect of insulin by the glucose clamp method (342; 1613).
Vernon
Benjamin Mountcastle (US) discovered and characterized the columnar
organization of the cerebral cortex (1104).
Sam L.
Clark, Jr. (US) first spotted autophagy in differentiating kidney cells as they
redirected their metabolic energies (273). Autophagy is the destructive process in
which a double membrane envelops cytoplasm and organelles before targeting them
to lysosomes for destruction.
Thomas
P. Ashford (US) and Keith R. Porter (US) suggested that the lysosomes represent
portions of the cytoplasm (mitochondria included) set aside for hydrolysis with
the general purpose of providing the protoplast with breakdown products for use
in a reoriented physiology. The lysosomal membrane shields the rest of the cell
from the general spread of the degradative process (64). At this time, they did not know
whether microbodies were supplying hydrolytic enzymes to the lysosome.
Pierre Baudhuin (BE), Russell L. Deter (US), and
Christian Rene de Duve (GB-BE-US) discovered that autophagy is a process for
the bulk degradation of proteins, in which cytoplasmic components of the cell
are enclosed by double-membrane structures known as autophagosomes for delivery
to lysosomes or vacuoles for degradation (99; 345; 346). The
term autophagy was introduced in the 1960s.
Anton
Jervell (NO) and Fred Lange-Nielsen (NO) reported on a case of hereditary,
functional syncopal arrhythmia in combination with profound congenital deafness
in a family with six children. Four of the children were deaf and suffered from
episodes of loss of consciousness and exhibited a long QT interval on the
electrocardiograph (751). This is
called the Jervell and Lange-Nielsen
syndrome.
Ciro Romano
(IT), Gianluca Gemme (IT), R. Pongiglione (IT), and Owen Conor Ward (IE)
described an inherited functional syncopal heart disorder with prolonged QT
interval (long QT syndrome type 2) (1313; 1622). This is
called the Romano-Ward syndrome.
Ole Z.
Dalgaard (DK) clarified that adult polycystic kidney disease ADPKD was
familial and transmitted in a dominant manner (317).
Stephen T.
Reeders (GB), Martijn H. Breuning (NL), Kay Elizabeth Davies (GB), Robert D.
Nicholls (GB), Andrew Paul Jarman (GB), Douglas R. Higgs (GB), Peter L. Pearson
(NL), David J. Weatherall (GB) gave the original description of the genetic
linkage of ADPKD to chromosome 16 (1272).
Henri Jean
Pascal Gastaut (FR), Micheline Vigouroux (FR), Carlo Trevisan (US), Henri Régis
(FR), Frederic Andrews Gibbs (US), Erna Leonhardt Gibbs (DE-US), and William G.
Lennox (US) were among the first to describe myoclonic and akinetic seizures in
children with a petit mal type of EEG (Lennox–Gastaut syndrome) (507; 537).
William
Beecher Scoville (US) and Brenda Milner (CA), in 1954, preformed a
"bilateral medial temporal lobe resection combined with orbital
undercutting." This work revealed that humans with hippocampal lesions are
severely impaired in their ability to acquire new long-term memories of people,
places, and events (1384).
Roland Kuhn (CH) observed that imipramine, a tricyclic compound,
could relieve depression in patients (856).
Jacques
Glowinski (FR) and Julius Axelrod (US) found that tricyclic antidepressant
drugs block the uptake of 3H labelled-norepinephrine in brain
neurons (547).
Susan G. Amara
(US) and Michael J. Kuhar (US) reported that cocaine, amphetamines, and
antidepressants also block the uptake of dopamine (prolactin-inhibiting
hormone) and serotonin (24). Prozac
(fluoxetine), a specific serotonin uptake inhibitor is the best-known
antidepressant, which works in this manner.
Lionel
Gordon Whitby (GB), Georg Hertting (AT), and Julius Axelrod (US) found that
cocaine blocks the uptake of norepinephrine in sympathetic nerves. This allows
greater amounts of the neurotransmitter to remain in the synaptic cleft after
cocaine and act on the post-synaptic receptors more intensely and for longer
periods of time (1656).
Julius
Axelrod (US) found that amphetamine blocks the uptake as well as the release of
3H-labelled-norepinephrine in the brain (74).
Heinz
Berendes (DE-US), Robert A. Bridges (US), and Robert Alan Good (US) described a fatal syndrome
in children consisting of chronic suppurative lymphadenitis,
hepatosplenomegaly, pulmonary infiltrations, and eczematoid dermatitis about the
eyes, nose, and mouth (116).
William
Benjamin Schwartz (US), Warren Bennett (US), Sidney Curelop (US), and Frederic
Crosby Bartter (US) described a syndrome of renal sodium loss and hyponatremia
probably resulting from inappropriate secretion of antidiuretic hormone (ADH or
vasopressin) (1379).
Stanley
Reitman (US) and Sam Frankel (US) devised a colorimetric method to detect acute myocardial infarction that is
sufficiently simple to be used in any laboratory (1278). Note: It is called the Reitman-Frankel procedure or test.
Orvan W.
Hess (US) and Edward Hon (US), in 1957, became the first in the world to continuously
monitor electrical cardiac signals from a fetus. They were using a fetal
heart monitor invented by Hess (666).
Michael
Ellis DeBakey (US), E. Stanley Crawford (US), Denton A. Cooley (US), and George
C. Morris, Jr. (US) performed the first successful resection with graft
replacement of a fusiform aneurysm of the entire aortic arch in humans (339).
George W. Comstock
(US) found that Afro-Americans have higher blood pressures at all ages and in
both sexes than do Caucasians (294).
The Asian flu started in southwest China in
February 1957, possibly having originated in 1956 in Vladivostok. Globally it
affected 10-35% of the population but overall mortality was much lower than in
the 1918 epidemic, about 0.25%. The flu spread to Hong Kong and Singapore in
April 1957, Japan in May, elsewhere in Pacific in June, the middle east and
Africa in July, Europe in August-October, and the U.S. in October of 1957 (830).
Burke A.
Cunha (US) reports that this pandemic of influenza A was the first to be
studied using modern scientific techniques (315). Note: Viruses carrying
the H1N1, H2N2 and H3N2 antigen combinations were responsible for the Spanish
flu of 1918, the Asian flu in 1957 and Hong Kong flu in 1968, respectively (1642).
Leslie
Foulds (GB) proposed that the development of cancer is a multistep process (461).
Ernest
Beutler (US) developed the 'Glutathione stability test', the first reliable
means for in vitro detection of
primaquine-sensitivity. It quickly led to the discovery that the defect was
sex-linked and that its basis was a deficiency in the enzyme
glucose-6-phosphate dehydrogenase. This work stimulated awareness that the
metabolism of red blood cells might be important in the origin of hemolytic
disease (134). Note: At this time primaquine was a newly introduced antimalarial
drug. It occasionally induced hemolytic anemia.
Harry P.
Loomer (US), John C. Saunders (US), and Nathan S. Kline (US) reported the
beneficial effects of iproniazid, a monoamine oxidase inhibitor, in the
treatment of severe depression (825; 935). Note: Iproniazid was withdrawn from the market because of its
hepatotoxicity.
Noam Chomsky
(US), in his book Syntactis Structures,
argued that human language, the most blatantly cultural of all our behaviors,
owes as much to instinct as it does to culture (267).
George
Evelyn Hutchinson (US) developed the formal notion of the ecological niche as a
geometric hypervolume with both biotic and abiotic dimensions, a concept that
led to a revolution in niche theory (727; 728)}.
Donald E.
Broadbent (GB) was the first person to bring together the work on information
processing with the problem of attention. He developed a mechanical model,
which successfully illustrated his hypothesis that the human perceptual system
has a limited capacity, that in consequence a selective operation is performed
upon all inputs to the system, and that this operation takes the form of
selecting all inputs having some characteristic in common. Broadbent suggested
that "our mind can be conceived as a radio receiving many channels at
once." The brain separates incoming sound into channels based on physical
characteristics (such as location) (175).
Theodosius Grigorievich Dobzhansky
(RU-US), and Olga Pavlovsky (RU-US) concluded from their experiments with Drosophila pseudoobscura that it may be
reasonably inferred that evolutionary changes involving interactions of natural
selection and random drift of the kind observed in their experiments are not
infrequent in nature (353).
Larry Sandler (US) and Edward
Novitski (US) described meiotic drive as an evolutionary force (1345).
James F.
Crow (US) coined the phrase ultra-selfish
genes to describe genes which spread despite, or rather because of the
damage they cause to their host (314). Note: Meiotic drive chromosomes, B-chromosomes, and Medea genes all exhibit ultra-selfish
behaviour. See, Sandler, 1927.
John
Burdon Sanderson Haldane (GB) writes that it is difficult for breeders to
simultaneously select all the desired qualities, partly because the required
genes may not be found together in the stock. Especially in slowly breeding
animals such as cattle, one cannot cull even half the females, even though only
one in a hundred of them combine the various qualities desired. The problem for
the cattle breeder is that keeping only the specimens with the desired
qualities will lower the reproductive capability too much to keep a useful
breeding stock. Haldane states that this same problem arises with respect to
natural selection. Characters that are positively correlated at one time may be
negatively correlated later, so simultaneous optimization of more than one
character is a problem also in nature (601).
George
Christopher Williams (US) concludes that any factor that decreases the rate of
decline in reproductive probability intensifies selection against senescence.
Any factor that increases the rate of this decline causes a relaxed selection
against senescence and a greater advantage in increasing youthful vigor at the
price of vigor later on. These considerations explain much of what is known of
phylogenetic variation in rates of senescence (1661).
J. Roger
Bray (US) and John Thomas Curtis (US) developed the method of polar ordination
(now known as Bray-Curtis ordination) with its inherent distance measure, the
Bray-Curtis dissimilarity (165).
John Thomas
Curtis (US) wrote The Vegetation of
Wisconsin: An Ordination of Plant Communities. This definitive survey
established the geographical limits, species compositions, and as much as
possible of the environmental relations of the communities composing the
vegetation of Wisconsin (316).
Roger Mason
(GB) Tina Negus (GB), in 1957, along with other school children discovered in
Charnwood Forest, England the Precambrian fossil remains of what may very well
be the oldest known multicellular animal (later named Charnia). Trevor D. Ford (GB) reported this discovery (460). The position of the clade for this
organism in the tree of life remains uncertain.
Jonathan
B. Antcliffe (GB) and Martin D. Brasier (GB) note that Charnia is both
temporally and geographically the most widespread Ediacaran fossil (35).
Guy
M. Narbonne (CA) and James G. Gehling (AU) report that the greatest abundance
of Charnia fossils, which are also the oldest reliably dated Ediacaran fossils,
are found along the southeast coast of Newfoundland (1113).
Ralph Stefan Solecki (US) and coworkers, from 1951-1960, examined
the Shanidar cave in North Central Iraq for fossil remains. Nine partial Homo sapiens neanderthalensis; Homo neanderthalensis skeletons were
removed (1442; 1443). The
specimens have been dated between 23-52 K B.C.E.
Thomas Dale
Stewart (US), discovered Shanidar I at Shanidar cave in Iraq. This Neanderthal
male, 30-45 years of age, had an underdeveloped right shoulder blade, collar
bone, and upper right arm bone. He believes that Shanidar I was crippled, with
a useless right arm, which had been amputated in life just above the elbow (1486).
This is surely one of the earliest known examples of surgery.
1958
“A gifted man
cannot handle bacteria or equations without taking fire from what he does and
having his emotions engaged.” Jacob Bronowski (178).
"Protein
synthesis is a central problem for the whole of biology, and… it is in all
probability closely related to gene action." Francis Harry Compton Crick (308).
Frederick
Sanger (GB) was awarded the Nobel Prize in Chemistry for his work on the
structure of proteins, especially that of insulin.
George Wells
Beadle (US) and Edward Lawrie Tatum (US) for their discovery that genes act by
regulating definite chemical events and Joshua Lederberg (US) for his
discoveries concerning genetic recombination and the organization of the
genetic material of bacteria shared the Nobel Prize in physiology and medicine.
Egon Stahl
(DE) described production and use of thin layers of standard silica gel G for
chromatography. Substances are made visible with the help of aggressive spray
reagents and by heating on these ‘open columns,’ and consequently, adsorption
chromatographic separations and detection of numerous chemical substance
mixtures in the microgram range are possible (1460).
Lawrence K.
Coachman (US), Edvard A. Hemmingsen (NO-US), and Per Fredrik Thorkelsson
Scholander (SE-NO-US) first proposed that clues about past
atmospheric air composition could be obtained from gas bubbles trapped in
glacier ice centuries or millennia ago (284).
John L.
Riggs (US), Robert J. Seiwald (US), Joseph H. Burkhalter (US), Cora M. Downs
(US), and Theodore G. Metcalf (US) were the first to develop isothiocyanate
compounds as fluorescent labeling agents for immune serum (1290).
Åke Bertler
(SE), Arvid Carlsson (SE), and Evald Rosengren (SE) described the first
chemical method for the analysis of adrenaline and noradrenaline that proved
sufficiently sensitive and specific for permitting accurate quantitative
analyses of extracts of animal tissues in general (127).
Morris John
Karnovsky (ZA-US) and Richard C. Graham, Jr. (US) extended the horseradish peroxidase (HRP) tracer
method of Werner Straus (US) to both the light and electron microscopic level,
by introducing diaminobenzidine (DAB) as an electron donor. HRP oxidizes DAB in
the presence of H2O2 and converts it to an insoluble primer, which causes the
reduction of added osmium tetroxide. The reduced osmium forms an insoluble
electron opaque precipitate, localized to the site of the HRP (782; 1492).
Richard
C. Graham, Jr. (US), Ulla Lundholm (US), and Morris John Karnovsky (US)
reported the cytochemical
staining of peroxidase activity (577).
Ludwig A.
Sternberger (US), Paul H. Hardy, Jr. (US), John J. Cuculis (US), and Howard G.
Meyer (US) developed the cytochemical staining of peroxidase activity into an
immunochemical technique (1480).
Paul A.J.
Janseen (BE), Corn. Van de Westeringh (BE), Anton H.M. Jageneau (BE), Paul J.A.
Demoen (BE), Bert K.F. Hermans (BE), Georges H.P. Van Daele (BE), Karel H.L.
Schellekens (BE), Cyriel A.M. Van der Eycken (BE), and Carlos J.E. Niemegeers
(BE) reported
on the synthesis of haloperidol and its screening in mice (746).
Paul Divry
(BE), Jean Bobon (BE), Jackie Collard (BE), André Pinchard (BE) and Emile Nols (BE)
performed the clinical trials of haloperidol, which became a
treatment for schizophrenia (351).
Vernon
Martin Ingram (DE-GB-US) developed the peptide fingerprinting technique (732).
Herbert E. Carter (US), Donald B. Smith (GB), and D.N. Jones (US), using egg
yolk, were the first to isolate an ether phospholipid (238).
Geigy
Chemical Company introduced the herbicide atrazine, a symmetrical triazine,
which is useful in corn (Zea mays),
orchards, pineapple (Ananas comosus),
sorghum (Sorghum cereale), and sugar
cane (Saccharum officinarum). ref
Amchem
Chemical Company introduced the herbicide chloramben, a benzoic acid
derivative, useful in soybeans (Glycine
max), corn (Zea mays), and
peanuts (Arachis hypogaea). ref
Robert A.
Goldwasser (US), Robert E. Kissling (US), Theodore R. Carski (US), and Thomas
S. Hosty (US) developed rabies immunofluorescence diagnostics (556; 557).
Setsuo
Takeuchi (JP), Kosei Hirayama (JP), Kazaburo Ueda (JP), Heiichi Sakai (JP), and
Hiroshi Yonehara (JP) discovered the antibiotic blasticidin S as an isolate from Streptomyces griseochromogenes (1515).
Tomomasa
Misato (JP), Itaru Ishii (JP), Masaru Asakawa (JP), Yoichiro Okimoto (JP),
Kazuo Fukunaga (JP), and Kensuke Hashimoto (JP) discovered that the antibiotic blasticidin S can be used to
successfully treat rice blast (1055-1058).
Robert Laing
Noble (CA), Charles Thomas Beer (CA) and James H. Cutts (CA) discovered the
effects of extracts of the Madagascar periwinkle (Vinca rosea) on the body’s blood-forming system then isolated and
purified the active substance, vinblastine,
from the leaves (1145). This work
is considered a milestone in the history of cancer drug development. Vinblastine, which blocks the
polymerization of tubulin monomers to form microtubules, is used to treat many
cancers, particularly Hodgkin’s disease, testicular cancer, and breast cancer.
Marion E.
Hodes (US), Robert J. Rohn (US), and William H. Bond (US) reported the effect
of vincaleukoblastine, isolated from Vinca rosea, in human beings…. Complete
hematologic remission was achieved in acute lymphocytic and monocytic leukemia.
In those situations where hematologic remission was not achieved, tumor cell
infiltrates have decreased in size (684; 685).
Anthony San
Pietro (US) and Helga M. Lang (US) discovered ferredoxin and its role in
photosynthesis (1344).
Anthony San
Pietro (US) and Helga M. Lang (US) discovered that the reduction of NADP+
and the evolution of oxygen by illuminated spinach-chloroplast suspensions can
be greatly accelerated by addition of a soluble protein isolated from spinach.
They showed this factor to be an enzyme that promotes the transfer of electrons
to NADP+. Highly purified versions were found to contain iron and
sulfur in a labile form (1344).
Leonard Earl
Mortenson (US), Raymond C. Valentine (US), and James E. Carnahan (US) isolated
a protein from extracts of Clostridium
pasteurianum, which they showed to be essential for nitrogen fixation by
serving as the electron carrier to nitrogenase.
The purified factor was found to have a molecular weight of 6,000 and to
contain seven atoms of iron and seven atoms of acid-labile sulfur. No heme was
present. They called this protein ferrodoxin; it was the first of many
iron-sulfur proteins to be isolated from natural sources (1099; 1100). Various
ferredoxins were quickly recognized as important redox catalysts in
photosynthesis and other metabolic processes.
Kunio Tagawa
(JP), Daniel Israel Arnon (PL-US), Masateru Shin (JP), Harry Y. Tsujimoto (US),
Reinhard Bachofen (CH), and Bob B. Buchanan (US) showed that a red iron-sulfur
protein (ferrodoxin) is a universal part of the photosynthetic apparatus. They
found that ferrodoxin, reduced by light, provides the electrons for generating
the NADPH required for carbon assimilation. They also found that the reduction
of NADP is light independent. This observation suggested that an iron-sulfur
protein resembling bacterial ferrodoxin is one of the components carrying
electrons from photosystem 1 to NADP+
(55; 56; 59; 60; 1511).
Joel
Mandelstam (GB) showed that the breakdown as well as the synthesis of proteins
occurs in intact bacteria (991).
Shigetoshi
Wakaki (JP), Hakudai Marumo (JP), Keitaro Tomioka (JP), G. Shimizu (JP), E.
Kato (JP), Hideo Kamada (JP), Shiro Kudo (JP), and Yasuo Fujimoto (JP) isolated
the antibiotic mitomycin C from Streptomyces caespitosus (1607; 1608).
Shugo Shiba (JP), Asaharu Terawaki (JP), Takeo
Taguchi (JP), and Junya Kawamata (JP) showed that mitomycin C acts by specific damage to DNA (1409).
Henry A.
Lardy (US), Diane Johnson (US) and William C. McMurray (US) tested antibiotics
toxic to animals. They were found to have specific inhibitory effects on
mitochondrial metabolism —some as inhibitors of respiratory enzymes, others as
inhibitors of phosphorylation (oligomycin), some as uncouplers or inhibitors of
respiration specific for certain substrates. Subsequent work in many
laboratories confirmed the prediction that ‘toxic antibiotics might prove to be
generally useful tools for investigating metabolic systems’ (877).
Herbert
Tabor (US), Sanford M. Rosenthal (US), and Celia White Tabor (US) synthesized
doubly labeled [15N, 14C] putrescine and showed that it is incorporated into
spermine and spermidine in Escherichia
coli and Aspergillus nidulans.
Both 15N and 14C were incorporated to the same extent, indicating that
putrescine was incorporated as a unit. They also showed that the biosynthesis
of spermidine in E. coli requires
putrescine, L-methionine, ATP, and Mg2+ and that S-adenosylmethionine was an
intermediate in the reaction (1510). Eventually, the Tabors
determined that S-adenosylmethionine
synthase, S-adenosylmethionine
decarboxylase, and putrescine
aminotransferase were involved in the reaction.
John Cowdery
Kendrew (GB), Gerhard Bodo (GB), Howard Marvin Dantzis (GB), Robert Guy Parrish
(GB), Harold Winfield Wyckoff (GB), Richard Earl Dickerson (GB), Bror Erik
Strandberg (SE), Robert George Hart (GB), David R. Davies (US), David Chilton
Phillips (GB), and Violet Catherine Sinclair Shore (GB) were the first to
report the entire three dimensional tertiary structural for a protein, sperm
whale myoglobin. This model provided the first direct evidence for the
occurrence of the alpha helix in a globular protein (797-799). Note: myoglobin's function is to store
oxygen (originally supplied by hemoglobin) in the tissues. This is particularly
important to diving animals, such as whales, seals, and penguins, thus the
choice of sperm whale tissue as a source.
Kau van
Asperen (NL) discovered that resistance to organophosphate insecticide is due
to a phosphatase-type hydrolysis
resulting from the gene-controlled conversion of an aliesterase for which the organophosphate compounds are inhibitors,
to an A-esterase for which these
organophosphates are substrates (1585; 1586).
Frederic
Middlebrook Richards (US) was the first to demonstrate that a protein, RNase-S, can spontaneously undergo
reversible denaturation, including disulfide bond rupture and reformation (1286).
Frederic
Middlebrook Richards (US) and Paul J. Vithayathil (IN) purified and
characterized RNase S, separated it
into S-peptide and S-protein, showed that almost all enzymatic activity is
recovered when the two components are recombined, and also reported that the
only observed change in covalent structure during the conversion of RNase A to RNase S is the hydrolysis of the peptide bond between residues 20
and 21 (1287). The demonstration that two separate, inactive fragments of the
enzyme RNase A can be reconstituted
to form an active enzyme provided the first experimental evidence that the
ability of a protein to form a three-dimensional structure is an intrinsic
property of its amino acid sequence.
Harold
W. Wyckoff (US), Demetrius Tsernoglou (US), Albert W. Hanson (CA), James R.
Knox (US), Byungkook Lee (US), and Frederic Middlebrook Richards (US)
determined the complete three-dimensional structure of RNase S to 2 Å. This structure tied with three others for the third
protein structure ever solved to atomic resolution. They also showed that RNase S is enzymatically active in
crystal form, putting to rest the widely held view at that time that protein
crystal structures were irrelevant to the conformation and behavior of enzymes
in solution (1697).
Ruth Hubbard
(US) and Allen Kropf (US) showed that the only action of light in vision is to
isomerize the chromophore of a visual pigment from the 11-cis to the all-trans
configuration (712; 855).
Daniel
Edward Koshland, Jr. (US), Stephen C. Mockrin (US), and Larry D. Byers (US)
described their concept of an induced fit
between the enzyme and its substrate. It holds that for many enzymes
flexibility is a prerequisite for activity. This represented a significant
advance over Hermann Emil Fischer’s lock-and-key theory (843; 1082).
Israel
Robert Lehman (US), Maurice J. Bessman (US), Ernest S. Simms (US), Julius Adler
(US) and Arthur J. Kornberg (US) synthesized small polynucleotides in a
cell-free environment (9; 133; 893).
Feodor Felix
Konrad Lynen (DE), Ulf Henning (DE), Clark Bublitz (US), Bo Sörbo (SE) and
Luistraud Kröplin-Rueff (DE) discovered the chemical mechanism producing
acetoacetic acid in the liver of a person exhibiting ketosis because of diabetes mellitus and/or starvation. The
mechanism is a metabolic cycle they called the HMG-CoA
(hydroxymethylglutaryl-CoA) cycle (957).
Otto H. Wieland
(DE), Ludwig Weiss (DE), and I. Eger-Neufeldt (DE) successfully explained how
this represented a deficiency in the citric acid cycle’s ability to handle
excess acetyl-CoA (1658).
Jack Leonard
Strominger (US), and Eiji Ito (US) determined that the first phase of the
synthesis of bacterial cell wall material occurs in the soluble cytoplasmic
fraction and leads to the production of UDP-acetylmuramyl-pentapeptide (733; 1496; 1497). The
antibiotics D-cycloserine and O-carbamyl-D-serine inhibit this phase.
Julius Axelrod (US), Robert Tomchick (US), and Marie-Jeanne
LaRoche (US) discovered that catecholamines are metabolized by deamination, O-methylation, glycol formation,
oxidation, and conjugation to glucuronides and sulfates. In the process they
discovered catechol-O-methyltransferase (75; 76).
William E.M.
Lands (US) discovered phospholipid retailoring or the “Lands” pathway. His work
suggested,
“the diglyceride unit of the phospholipids is metabolically different in some
respect from that of the triglycerides" (872). This initial finding led to a series
of papers describing the selective placement of acyl chains by phospholipid acyltransferases.
Paul Talalay (US), H. Guy Williams-Ashman (US), and Barbara
Hurlock (US) demonstrated that
oxidoreductions of steroid hormones by hydroxysteroid
dehydrogenases (HSDs) could promote reversible
transfer of hydride groups between NAD (H) and NADP (H) (1518; 1519).
Matthew
Stanley Meselson (US), and Franklin William Stahl (US) in an elegant experiment
using density gradient centrifugation and heavy nitrogen proved that the DNA of
Escherichia coli is replicated in a
semiconservative manner (1046).
Francis
Harry Compton Crick (GB) proposed the sequence
hypothesis, which states that DNA base sequence and protein sequence are
collinear. Genetic information must therefore be arrayed in a strictly linear
fashion along the length of a DNA molecule. Crick also proposed the central dogma which holds that genetic
information stored in DNA flows through RNA to proteins. RNA is the
intermediate translator of the genetic code (308; 309). Horace
Freeland Judson says the 1958 paper by Crick “permanently altered the logic of
biology” (761).
Francis
Harry Compton Crick (GB) and James Dewey Watson (US) had, as early as 1953,
from knowledge, intuition, and luck brilliantly deduced that the genetic code
would need to specify only twenty different amino acids. They correctly
specified which twenty (308).
Israel
Robert Lehman (US), Steven B. Zimmerman (US), Julius Adler (US), Maurice J.
Bessman (US), Ernest S. Simms (US), and Arthur J. Kornberg (US) demonstrated
that newly synthesized DNA is made of a single stranded DNA template with the
base content of the template determining the composition of the product (894). This work
was the first laboratory confirmation of the Watson and Crick hypothesis that
DNA serves as a template during its replication.
Gunther
Siegmund Stent (US) reasoned that it would be logical for RNA base sequence
information to be transferred to DNA base sequence information (1474).
Francis
Harry Compton Crick (GB) proposed that amino acids had to first be attached to
some form of adapter molecules before they could chemically bind to an RNA
template (308).
Arthur Beck
Pardee (US), Francois Jacob (FR), and Jacques Lucien Monod (FR) reported the
results of what became known as the PaJaMo
experiment. In Escherichia coli, they
manipulated genes of what was later called the lactose operon, and concluded that the cytoplasm contained a
substance, which carried amino acid sequence information between DNA and the
ribosomes, i.e., a messenger. The experiment also strongly suggested that cells
produce repressors, which turn genes off unless there is an inducer substance
to block the repressor, i.e., negative control (736; 1201; 1202). The 1959
article by Jacob and Monod introduced the word operator as the target of the repressor.
Georges
Cohen (FR) shortly thereafter demonstrated that in the case of tryptophan
synthesis there is an inactive form of repressor, which will not suppress the
pathway unless it interacts with the end product of the pathway (tryptophan),
thereby being converted to the active form, which shuts down the genes of the
pathway (286).
Liselotte I.
Hecht (US), Mary Louise Stephenson (US), Paul Charles Zamecnik (US), Hans Georg
Zachau (DE), George Acs (US), and Fritz Albert Lipmann (DE-US) discovered that
all sRNA (tRNA) molecules have the same three terminal bases, CCA, on the free
3’ end, which binds to the amino acid. Consequently, all amino acids are
transported while attached to the adenosine moiety (643; 644; 1709).
Nathaniel B.
Kurnick (US), Barbara W. Massey (US), and Georgianna Sandeen (US) suggested
that the nuclear damage observed after large doses of radiation might be
mediated through an enzyme system rather than by direct effect on the
chromosomal desoxyribonucleic acid, as was generally thought. Specifically,
they suggested that radiation might inactivate an inhibitor of the enzyme desoxyribonuclease (DNase) thus
permitting autolysis to occur (862).
John R.
McLean (US), George L. Cohn (US), Ira K. Brandt (US), Melvin V. Simpson (US),
Donald B. Roodyn (GB), Patricia J.M. Reis (AU), and Thomas Spence Work (GB)
presented evidence that mitochondria are capable of independent protein
synthesis (1035; 1315).
Guido Pontecorvo
(IT-GB) observed that the rule that genes controlling metabolically sequential
enzymes constitute genetic clusters does not apply, in general, to organisms
other than bacteria (1227).
Richard
Brooke Roberts (US) proposed that the name ribosome
(ribonucleoprotein particles of the microsomal fraction) be used in place of
what had heretofore been called microsomes (1305).
Alfred
Tissières (CH), James Dewey Watson (US), David Schlessinger (US), and Barbara
R. Hollingsworth (US) carried out the first physical characterization of
ribosomes when they isolated four kinds of ribonucleoprotein particles from Escherichia coli cells. They were
observed to have sedimentation coefficients of 30S, 50S, 70S, and 100S (1563; 1564).
John
Spizizen (US) demonstrated DNA mediated genetic transformation in Bacillus subtilis. As this organism
could grow in simple minimal media, it was possible to utilize a variety of
auxotrophic markers (1454). This made it possible to investigate the genetic controls of
biosynthetic pathways as was being done in Escherichia
coli using other gene transfer systems found to be highly transformable.
Refinements to achieve optimal conditions for transformation were later introduced.
Jakob
Reinert (DE), Frederick C. Steward (US), Marion O. Mapes (US), Joan Smith (US)
and Kathryn Mears (US) accomplished the formation of pro-embryonic tissue in
callus clumps and cell suspensions of plant tissue (1275; 1276; 1483; 1484).
Peter C.
Nowell (US), David A. Hungerford (US), and Carter D. Brooks (US) discovered
that phytohemagglutinin (PHA) is mitogenic for peripheral lymphocytes of the
blood. In this same work they were the first to see Giemsa banding of
chromosomes (1156). This
banding is now called G banding of
chromosomes.
Gerald
Maurice Edelman (US), Henry George Kunkel (US), and Edward C. Franklin (US) provided evidence
for interaction of the rheumatoid factor with antigen-antibody complexes and
aggregated gamma globulin. This interaction appears to occur in the circulation
of patients with rheumatoid arthritis.
The question of
whether the rheumatoid factor represents an antibody to gamma globulin was
discussed (387). Note:
This is identification of the first autoantibody and first recognition of
autoimmune disease.
Nathan
Kaliss (GB) discovered a special form of immunological unresponsiveness—immune
enhancement—defined by the depression of cell-mediated immunity by circulating
antibody (768).
Emanuel
Riklis (IL) and Juda Hirsch Quastel (GB-CA) showed that the process of active
transport of sugars (glucose, galactose, and fructose) by the isolated
surviving guinea pig intestine is markedly affected by the cation
concentrations present in the salt solutions bathing the intestine (1291).
Moselio
Schaechter (US), Ole Maaløe (DK), and Niels Ole Kjeldgaard (DK) discovered that
bacteria can grow in a continuum of physiological states determined by the
growth rate (1356). This is a
seminal paper in bacterial growth physiology.
Jacques C.
Senez (FR) and Francis Pichinoty (FR) discovered a group of bacteria, which are
nutritionally halfway between autotrophs and heterotrophs when characterized
metabolically. Desulfovibrio is a
typical organism in this group. This organism can oxidize hydrogen with sulfate
forming water and sulfide. The energy released can be coupled to the
assimilation of organic materials (1398).
Marvin P.
Bryant (US), Milton J. Allison (US), and Raymond N. Doetsch (US) were the first
to show that many rumen bacteria, other heterotrophic bacteria, and most
methanogenic anaerobic bacteria have a very limited ability to utilize organic
nitrogen sources such as amino acids or peptides. Instead, they utilize ammonia
as their essential and major nitrogen source and utilize carbon dioxide and
various volatile fatty acids, such as acetate, as a source of carbon (186).
Gustav
Joseph Victor Nossal (AU) and Joshua Lederberg (US) discovered that a single
lymphocyte can produce only one specific type of antibody (1148). Note: This
became known as the "one cell-one antibody" rule.
Martin C.
Raff (CA-GB), Marc Feldmann (GB), and Stefanello de Petris (GB) offered an
elegant proof of this by showing that incubation of lymphocytes with antigen
can aggregate (cap) all the surface immunoglobulin on antigen-binding cells;
this indicated that the only immunoglobulin on the surface of these cells is antibody
of a single specificity (1252).
Peter Brian
Medawar (GB) coined the phrase
immunologically competent cell to define a cell that is fully qualified to
undertake an immunological response (1039).
John D.
Marshall, Jr. (US), Warren C. Eveland (US), and Chauncey W. Smith (US) compared
three methods for preparing fluorescein conjugated globulins by using two
derivatives of fluorescein amine, and recommended fluorescein isothiocyanate
for fluorescent antibody staining (1009).
Robert E.
Kissling (US) grew the rabies virus in non-nervous tissue culture (hamster
kidney) (814).
Howard
Martin Temin (US) and Harry Rubin (US) developed he first quantitative assay
for viral transformation. In the mid 1950s Rous sarcoma virus, an avian
retrovirus was found to induce morphological changes and extend the life of
chick embryo fibroblast cells in culture. Transformation was detected as foci
of dense morphologically altered cells in monolayers of chick embryo
fibroblasts. It depends on the loss of contact inhibition following
transformation (1543). Note: This
work led to the genetic era of cancer investigation.
Harry Rubin
(US) found that the addition of newly transformed cells to a confluent,
contact-inhibited culture of chicken fibroblasts would result in the
morphologic normalization of the Rous sarcoma virus transformed cells and
inhibition of their proliferation. Transformed focus formation of RSV-infected
cells was suppressed by substituting fetal bovine serum (FBS) for calf serum
(CS) in the medium, or raising the concentration of the latter, but suppression
was effective only when the infected cells were surrounded by normal cells (1331; 1332).
Michael
George Parke Stoker (GB), Moira Sheare (GB), and Charles O’Neill (GB) reported
that mammalian fibroblasts transformed by polyoma virus were also inhibited by
contact with a quiescent layer of mouse fibroblasts. Thus, the transformed
cells seem to obey the regulation state present in the normal culture (1488).
Emilio Weiss
(US), Harry R. Dressler (US), William F. Myers (US), Charles L. Wisseman, Jr.
(US), Anna D. Waddell (US), and David J. Silverman (US) determined that Rickettsia prowazekii microorganisms are
truly bacteria and not life forms halfway between bacteria and viruses, and
rickettsial membranes are not leaky. Relative to Escherichia coli, Rickettsia
are about half the size, have a genome one-third as large, and grow twenty
times slower (1110; 1648; 1649; 1666; 1667).
P.R. Fry
(NZ), Raymond G. Grogan (US), Frank W. Zink (US), William Boright Hewitt (US),
and Kenneth A. Kimble (US) discovered that the soil fungus Olpidium brassicae serves as a host and vector of the lettuce big-vein
virus (494; 583).
A
4,850-year-old Great Basin bristlecone pine (Pinus aristata var. longaeva) tree growing
high in the White Mountains of Inyo County in eastern California was for many
years thought to be the world's oldest known living non-clonal organism, until
it was superseded in 2012 by the discovery of another bristlecone pine in the
same area with an age of 5,068 years (germination in 3050 BC) (1; 4). This age, now in excess of
5,068 years, is yet to be confirmed.
Masasuke Okamoto (JP) and Ernest Robert Sears (US) discovered
that chromosome pairing in wheat is genetically controlled. Consequently, the
chromosomes of many other species, not ordinarily able to pair and recombine
with those of wheat, could be induced to do so by removing chromosome 5B from
commercially grown hybrids (1176; 1389).
Ralph Riley (GB) and Victor Chapman (GB) described the genetic
systems by which pairing of wheat chromosomes at meiosis is limited to those
which are fully homologous, and by which pairing between distantly related
chromosomes is precluded. This basic knowledge allowed them to pair and
recombine chromosomes in a way that is normally illegitimate (1293-1295).
Theodore
Thomas Puck (US), Steven J. Cieciura (US), and Arthur Robinson (US) established
that diploid human cells can be maintained in
vitro for a maximum of one year (50 to 60 passages) before they degenerate
and progress to aneuploid (1244-1246). This
allowed persons with genetic defects to provide stocks with known markers, the
underlying biochemistry of which can be studied in vitro.
Yoshio Okada
(JP) and Jun Tadokoro (JP) showed that high concentrations of the HVJ (Sendai)
virus (alive or dead) cause Ehrlich ascites cells to rapidly fuse (1172-1175).
Erwin
Bünning (DE) proposed that the environment forms a plant’s natural internal
rhythm into 24-hour cycles, each consisting of a 12-hour light-loving or photophile
phase, in which light promotes flowering, followed by a 12-hour dark-loving or
scotophile phase, in which light inhibits flowering (189).
William
Boright Hewitt (US), Dewey J. Raski (US), and Austin C. Goheen (US) discovered
that the ectoparasitic nematode, Xiphinema
index, serves as a vector for soil-borne fanleaf virus of grapevines (669).
Preben
Christian Alexander von Magnus (DK),
Else Krag Andersen (DK), Knud Birkum Petersen (DK), and Aksel Birch-Andersen
(DK) first
identified monkeypox virus in 1958 as a pathogen of crab-eating macaque monkeys
(Macaca fascicularis) being used as laboratory animals (1605).
Ivan Danilovich Ladnyj (RU), Peter Ziegler (), and A. Kima () were the first to
identify monkeypox in man. This
occurred in the Basankusu district, Equateur Region, Zaire, in 1970, 2 years
after the last case of smallpox had occurred in the area (864).
Trevor
Walworth Goodwin (GB) and Hartmut K. Lichtenthaler (DE) showed that the
different leaf colors in autumn deciduous trees arise from the preferential
degradation of chlorophylls over carotenoids and the synthesis of red-colored
pigments like anthocyanins (566; 915).
Edward
Himelblau (US) Richard M. Amasino (US) found that senescence has adaptive value
among plants because of the associated remobilization of nutrients, especially
nitrogen, and, to a lesser extent, phosphorus, sulfur, and other elements (674).
Gottfried
Samuel Fraenkel (DE-US) discovered the reason for secondary plant compounds,
“as only…to repel and attract insects” (468-470).
Miriam
Rothschild (GB), Joseph von Euw (PL-CH), Lev Fishelson (IL), John A. Parsons
(GB), and Tadeus Reichstein (PL-CH) offered the first proof
of the sequestration and storage by brightly colored, aposematic, insect
herbivores of toxic
secondary plant substances and toxic, self-secretions (1320; 1603; 1604).
Leonard
Muscatine (US) provided direct evidence for the transfer of materials from
symbiotic algae to the tissues of a coelenterate (1109).
Robert
K. Trench (US), Richard W. Greene (US), and Barbara G. Bystrom (US) confirmed
the above by showing the assimilation of photosynthetic products of
zooxanthellae by two marine coelenterates (1572; 1573). Note:
This symbiosis promotes the growth and survival of reef corals in nutrient-poor
tropical waters; indeed, coral reefs could not exist without this symbiosis.
Robert K.
Trench (US), Merriley E. Trench (US) and Leonard Muscatine (US) showed that
symbiotic chloroplasts provide photosynthetic products that contribute to mucus
synthesis in two marine slugs (1574).
H.H. West (US), D.A. Graves (US), M.A. Gibson
(US), and J.S. Bleakney (US) observed that the ascoglossan sea slug Elysia
chlorotica feeds on the intertidal alga Vaucheria litorea. It
punctures the algal cell wall with its radula, then holds the algal strand
firmly in its mouth and sucks out the contents as from a straw (578; 1653).
Huimin Cai
(CN), Qiye Li (CN), Xiaodong Fang (CN), Ji Li (CN), Nicholas E. Curtis (US), Andreas
Altenburger (DK), Tomoko Shibata (JP), Mingji Feng (CN), Taro Maeda (JP), Julie
A. Schwartz (US), Shuji Shigenobu (JP), Nina Lundholm (DK), Tomoaki Nishiyama
(JP), Huanming Yang (CN), Mitsuyasu Hasebe (JP), Shuaicheng Li (CN), Sidney K.
Pierce (US), and Jian Wang (CN) confirmed that one of several algal genes
needed to repair damage to chloroplasts, and keep them functioning, is present
on the slug chromosome (205).
Anna Petherick (GB) reported that
Ryan Kerney of Dalhousie University in Halifax, Nova Scotia, Canada, while looking
at a clutch of emerald-green balls—embryos of the spotted salamander (Ambystoma
maculatum) noticed that their bright green colour comes from within the embryos
themselves, as well as from the jelly capsule that encases them.This
viridescence
is caused by the single-celled alga Oophila amblystomatis. Kerney
reported that these algae are, in fact, commonly located inside cells all over
the spotted salamander's body. Moreover, there are signs that intracellular
algae may be directly providing the products of photosynthesis
Richard Bainbridge (GB) showed that the major
factor controlling swimming speed of fish was modulation of tail-beat
frequency, with a small effect of amplitude at lower speeds, results that have
been confirmed for many additional species by other researchers using several
different methods. For much of the swimming range, speed proves to be a linear
function of tail-beat frequency, and the distance travelled per beat, or stride
length, is essentially constant. Bainbridge further showed that size effects of
tail-beat frequency and amplitude could be expressed in a common form by
normalizing speed with body length, describing speed in body-lengths s–1, or L
s–1. Remarkably, most of the variation in tail-beat patterns with speed, for
all three species (dace Leuciscus
leuciscus, goldfish Carassius auratus,
and trout Salmo irideus=Oncorhynchus mykiss) could be expressed
in a single equation, sometimes called Bainbridge's Equation: U/L= 0.25[L
(3F-4)], where U=swimming speed (cm s–1), L=total length (cm), and F=tail beat
frequency (Hz). Expressing speed in body-lengths s–1 is still used in most
studies on swimming to collapse size-related data (78).
Robert
Helmer MacArthur (CA-US) made the first definitive study of community resource
partitioning. He studied five species of warblers (MacArthur’s warblers) that
breed in boreal forests of North America. He and Eric R. Pianka (US) concluded
that feeding in different places and in different manners allowed these species
to coexist in the same community (966; 968; 969).
Knut
Schmidt-Nielsen (DK-US) and Ragnär Fange (SE) found that marine turtles possess
a salt-secreting gland to eliminate
excess salt, which collects in their tissues (1368).
Knut
Schmidt-Nielsen (DK-US) discovered that marine birds eliminate the salts taken
in with food and water by a gland in the head, which can be called the salt-excreting gland or simply the salt gland (1366).
Denis
Parsons Burkitt (GB) postulated that a mosquito-transmitted infectious agent
causes a lymphoma common among African children. This lymphoma became known as Burkitt’s lymphoma (197).
Herbert F.
Oettgen (DE-US) Denis Parsons Burkitt (GB) and Joseph H. Burchenal (US) used
methotrexate to treat malignant lymphoma involving the jaw in African children (1166).
Michael Anthony
Epstein (GB), Bert Geoffrey Achong (TT-GB), and Yvonne M. Barr (GB) cultured
human lymphocytes from Burkitt’s lymphoma
and in the process demonstrated the presence of a Herpes virus (418). These human herpes virus 4
particles (HHV-4) have since
been called Epstein-Barr virus. Note:
This was the first time a virus was shown to cause cancer in humans.
Michael
Anthony Epstein (GB) and Yvonne M. Barr (GB) were the first to grow human
lymphocytes in continuous culture (419).
Victor
Anomah Ngu (CM), John L. Ziegler (US), Avrum Z. Bluming (US), Richard H.
Morrow, Jr. (US), Leroy Fass (US), Sebastian K. Kyalwazi (US), and Paul P.
Carbone (US) made outstanding contributions toward increasing the cure rate of Burkitt's tumor by chemotherapy (1132; 1133; 1712-1714).
Joseph H.
Burchenal (US) promoted the use of Burkitt's
tumor as a model for understanding leukemia (192-194).
George Klein
(SE), Gary R. Pearson (US), Gertrude Henle (US), Werner Henle (US), Volker
Diehl (US), and James C. Niederman (US) reported that infectious mononucleosis is not only caused by a herpetovirus but
is also caused by an agent that cannot be distinguished from the Epstein-Barr virus (652; 816). See, Nil Feodorovich Filatov, 1887.
James C.
Niederman (US), Robert W. McCollum (US), Gertrude Henle (US), and Werner Henle
(US) found that tested sera from 50 randomly selected college freshmen revealed
Epstein-Barr virus antibodies in 12, two of whom had positive histories
of infectious mononucleosis. Of 38 without demonstrable antibodies none
had had IM, but the illness developed in three in the next two years. These and
other observations strongly indicate that Epstein-Barr virus, or a
closely related one, is the etiologic agent of infectious mononucleosis (1134).
George
T. O’Connor (US) noted that current evidence suggested that the etiology of African Burkitts Lymphoma was related to
Epstein Barr virus infection in a
host whose immunologic state had been severely affected by constant and severe
malarial infections (1163). Note: Epstein Barr virus infection is later
shown to cause several other cancers, including nasopharyngeal carcinoma,
Hodgkin lymphoma, and some gastric (stomach) cancers.
Min Chueh
Chang (CN-US) and Thorsteinn Thorsteinsson (US) found that rabbit sperm are not
affected by being placed in Ringer’s solution from 0.5X to 2X in concentration.
Furthermore, at isotonicity these sperm can tolerate a pH range from 5.57 to
10.94 (254).
William
Barry Wood, Jr. (US) and M. Kenton King (US) discovered the leucocytic origin
of endogenous pyrogen in acute inflammatory exudates and investigated its role
in the inflammatory process (1678-1681).
William F.
Jarrett (GB), Frank W. Jennings (GB), W. Ian McIntyre (GB), William Mulligan
(GB), Beatrice A.C. Thomas (GB) and George MacDonald Urquhart (GB) developed an
irradiation-attenuated vaccine against lungworm (Dictyocaulus viviparus) of sheep and cattle (747; 748). Its
commercial name is Dictol.
Börje
Larsson (SE), Lars Leksell (SE), Bror Rexed (SE), Patrick Sourander (SE),
William George Parker Mair (SE), and Bengt Andersson (SE) developed the concept
of radiosurgery. They first employed proton beams coming from several
directions into a small area in the brain, in experiments in animals and in the
first treatments of human patients (878).
Lars Leksell
(SE) later developed a special apparatus known as the Gamma Knife. It is a stereotactic device, which contains multiple
radioactive cobalt sources and is dedicated solely to radiosurgery (897). Gamma Knife
surgery is recognized worldwide as the preferred treatment for brain tumors,
arteriovenous malformations and brain dysfunctions like trigeminal neuralgia.
Basil Isaac
Hirschowitz (ZA-US), Larry E. Curtiss (US), C. Wilbur Peters (US), and H.
Marvin Pollard (US) applied fiber optics in the development and construction of
a completely flexible optical instrument, which allowed direct visualization of
the cavity of the duodenum, the esophagus, and stomach (680).
Ian Donald
(GB), John MacVicar (GB), and Tom Graham Brown (GB) produced what is considered
the most important paper on obstetrical and gynecological sonography ever
written. The paper deals with 100 patients. It contained B-mode sonograms of
the gravid uterus, ovarian cysts, fibroids and ascites and various normal and
pathological conditions. Other papers are included which emphasize the use of
this technique to guide the amniocentesis needle, exclude twins, and avoid the
anterior placenta (356-359).
Maurice
Ralph Hilleman (US), Frederick J. Flatley (US), Sally A. Anderson (US), Mary L.
Luecking (US), and Doris J. Levinson (US) introduced a vaccine to the Asian
influenza (673).
Alfred
Gottschalk (DE-AU) found that as the influenza virus attaches to red cells or
cells of the upper respiratory tract it cuts N-acetyl neuraminic acid, or
sialic acid on the surface of the host cell. When the progeny viruses are
escaping from the infected cell they must cut off this anchoring molecule to
make their getaway. The viral protein that dues the cutting is called neuraminidase
(568; 569).
Richard T.
Huang (DE), Rudolf Rott (DE), K. Wahn (DE), Hans Dieter Klenk (DE), and Takafumi
Kohama (DE) worked out the function of the neuraminidase in membrane
fusion induced by myxoviruses. It was found that the presence of neuraminidase
is essential for fusion between the liposomes and cells (711).
Karl Erik
Aström (SE-US), Elliott Lee Mancall (US), and Edward Peirson Richardson, Jr.
(US) were the first to describe progressive multifocal leukoencephalopathy
(PML) (67). This is a disease of the white
matter of the brain, caused by a virus infection that targets cells that make
myelin--the material that insulates nerve cells (neurons). Polyomavirus JC
(often called JC virus) is carried by most people and is harmless except among
those with lowered immune defenses. The disease is rare and occurs in patients
undergoing chronic corticosteroid or immunosuppressive therapy.
Billie L.
Padgett (US), Gabriel M. ZuRhein (US), Duard L. Walker (US), Robert J. Eckroade
(US), and Bert H. Dessel (US) isolated the polyomavirus JC responsible for progressive multifocal leukoencephalopathy
(PML) (1195).
Herman
Moritz Kalckar (DK-US) proposed that fallout following atmospheric tests of
nuclear weapons could be measured by analysis of the content of strontium-90 in
the milk teeth of young children (767).
Endre
Kelemen (HU), István Cserhati (HU), and Belá Tanos (HU) coined the term thrombopoietin when they described the
humoral substance responsible for the rebound thrombocytosis that follows
states of thrombocytopenia (795).
Thrombopoietin (TPO) stimulates the development of megakaryocyte precursors of
platelets, leading to an increase in the number of circulating platelets in a
manner that is analogous to the erythropoietin (EPO) stimulation of erythroid
precursors.
Bertha A.
Bouroncle (US), Bruce K. Wiseman (US), and Charles A. Doan (US) gave a detailed
description of twenty-six cases of leukemic
reticuloendotheliosis (hairy cell leukemia) which identified it as an
independent hematologic and pathologic entity (160).
Rudolf Rabl
(DE) discovered the first example of gender dimorphism in the human brain,
conferring to women greater thalamic connectivity in the region massa intermedia (1250).
Alice M.
Stewart (GB), Josefine Webb (GB), and David Hewitt (GB) carried out an
epidemiological study to see if there was a relationship between X rays during
pregnancy and leukemia in children (1485). This paper
is significant because it prompted two important discoveries—that all childhood
cancers have fetal origins and that cancers of the immune system can affect
reactions to other diseases before they are themselves recognizable clinically.å
Elizabeth
Stern (CA-US), Alan B. Forsythe (US), Lee Youkeles (US), and J. Dixon Wilifrid
(US) identified 250 stages of a cervical cell's progression from normal to
cancerous, making early cancer detection and treatment possible (1477; 1479).
Elizabeth
Stern (CA-US), Virginia A. Clark (US), and Carl F. Coffeit (US) discovered a
link between oral contraceptives and cervical cancer (1478).
Ernest W.
Walton (GB) provided the definitive description of Wegener’s granulomatosis (1618).
Theodore
Brown Rasmussen (CA), Jerzy Olszewski (PL-CA), and Donald Lloyd-Smith (CA)
described the features of a chronic neurological syndrome characterized by
brain dysfunction, encephalitis, and intractable epilepsy, i.e., Rasmussen’s encephalitis (1267).
Scott W.
Rogers (US), P. Ian Andrews (US), Lorise C. Gahring (US), Teri Whisenand (US),
Keith Cauley (US), Barbara Crain (US), Thomas E. Hughes (US), Stephen F.
Heinemann (US), and James O. McNamara (US) suggested that autoantibodies to
glutamate receptor GluR3 might be the cause of Rasmussen's encephalitis (1312).
Carl Axel
Gemzell (SE), Egon Diczfalusy (SE), and Karl Gunnar Tillinger (SE) used
extracts of human pituitary gonadotropins (hPG), containing both
follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to successfully
induce ovulation in humans (517).
Joshua
Harold Burn (GB) and Michael John Rand (GB) established that reserpine depletes
the stores of norepinephrine in arterial walls. They used reserpine-treated
animals to demonstrate that some sympathomimetic amines (e.g. tyramine and
other noncatechol phenylethylamine derivatives) only act when the tissue
catecholamine stores are intact, and therefore presumably owe their own actions
to the release of catecholamines (198).
Robert H.
Silber (US), Robert D. Busch (US), and Raymond Oslapas (US) introduced a
simplified fluorometric procedure for estimating the quantity of corticosterone
or hydrocortisone. It has practical applications for the estimation of these
steroids in samples that are small in volume or low in concentration, or in
studies that are designed primarily to demonstrate increases or decreases in
adrenocortical hormones in plasma or adrenals without requiring absolute
specificity (1416).
Joaquin
Barraquer (ES) and Joaquin Rutllan (ES) discovered that alpha-chymotrypsin can
be used to enzymatically dissolve the zonules of the eye for removal of a lens
with cataract (90; 91).
Manucher
Javid (US) introduced osmotic diuretics for reduction of intracranial pressure (749).
Malcolm
Andrew Ferguson-Smith (GB) and Ian B. Munro (GB) reported a case of
Klinefelter’s syndrome whose nuclear sex is female, but who shows clearly in a
routine unilateral testicular biopsy active, but scanty, spermatogenesis with
the production of mature spermatozoa (437).
Charles E.
Ford (GB), Patricia A. Jacobs (GB), and Lazlo G. Lajtha (GB) introduced
chromosome analysis using fresh bone marrow (458).
Paul S.
Moorehead (US), Peter C. Nowell (US), William J. Mellman (US), D.M.A. Battips
(US), and David A. Hungerford (US) developed a method for chromosome
preparations of leukocytes cultured from human peripheral blood. The key
ingredient was phytohaemagglutinin, added to remove red cells from plasma,
which coincidently caused lymphocyte transformation (1094). This
method largely replaced the bone marrow method.
G.K.
Chrustschoff (RU) and E.A. Berlin (RU) had much earlier observed that autolysis
of red cells induces cell division in lymphocytes (269).
John H.
Laragh (US), Henry O. Heinemann (US), and Felix E. Demartini (US) reported on
the effect of chlorothiazide on electrolyte transport in man; its use in the
treatment of edema of congestive heart failure, nephrosis, and cirrhosis (876).
James H.
Austin (US) described cases of probable chronic inflammatory demyelinating
polyneuropathy by recognizing a fluctuating motor-predominant neuropathy
that produced severe weakness that would either improve spontaneously or in
response to corticosteroids. He noted that some of the cases presented with
weakness without muscle atrophy and hypothesized that focal areas of segmental
demyelination rather than axonal degeneration were likely the pathological
cause because of the lack of atrophy (70).
Peter James
Dyck (US), Alfred C. Lais (US), Michiya Ohta (US), James A. Bastron (US), Haruo
Okazaki (US), and Robert V. Groover (US) studied 57 patients and subsequently introduced
the name chronic inflammatory polyradiculoneuropathy (to which the term demyelinating
was subsequently added) and thus defined CIDP as a separate disease entity (383).
Anne McLaren;
Anne Laura Dorinthea McLaren (GB) and John Dennis Biggers (GB) successfully grew mouse embryos in vitro. The embryos were then transferred into the
wombs of female mice, where they developed into a healthy litter (1033). Note: This experiment was a
vital proof of principle. It showed that it was possible to mix sperm and eggs
outside the mother’s body and create a healthy embryo, which could then grow to
term in the womb of a recipient mother. Louise Joy Brown (GB) the world’s first
test tube baby (in vitro
fertilization) was born in Oldham, Northern England, on July 25, 1978. Patrick
Christopher Steptoe (GB) and Robert G. Edwards (GB) performed the operation (1476).
Aubrey
Leatham (GB) provided a new classification for heart murmur analysis. Prior to
this work, systolic murmurs were seldom differentiated by their configuration
or timing. Leatham's new classification of mid-systolic ejection murmurs versus
pansystolic regurgitant murmurs, based on his graphic analysis, changed the way
clinicians approached the bedside diagnosis of valvular disease and contributed
to decision making for cardiac surgery (886).
Charles
Theodore Dotter (US) and Louis H. Frische (US) developed a new method to
reliably and safely visualize the coronary vessels. The method employed a soft,
double-lumen balloon catheter. Prior to this time, there had been no reliable
way to visualize the coronary vessels (362).
Hannibal
Hamlin (US), William H. Sweet (US), and William M. Lougheed (US) performed one
of the first successful carotid bifurcation reconstructions (608).
G. Rainey
Williams, Jr. (US) and Frank C. Spencer (US) used hypothermia to treat patients
who sustained neurological damage following cardiac arrest (1662).
Oscar Creech, Jr. (US), Edward T. Krementz (US), Robert F. Ryan
(US), and James N. Winblad (US) developed a technique of regional perfusion
found to be useful with cases of malignant
melanoma, soft tissue sarcomas in
the limbs, and some pelvic cancers (306).
Emil Frei,
3rd. (US), James F. Holland (US), Marvin A. Schneiderman (US), Donald Pinkel
(US), George Selkirk (US), Emil J. Freireich (US), Richard T. Silver (US), G.
Lennard Gold (US), William Regelson (US), demonstrated that combination
chemotherapy with the drugs 6-mercaptopurine and methotrexate can induce
partial and complete remissions and prolong survival in children and adults
with acute leukemia (484-488).
Donald Heath (GB) and Jesse E. Edwards
(US) recognized six grades of progressive histological changes which occur in
the small pulmonary blood vessels in association with the chronic pulmonary
hypertension complicating many congenital cardiac septal defects (640).
Konrad
Zacharias Lorenz (AT) defined ethology
as, “the application of orthodox biological methods to the problems of
behavior” and credited Charles Robert Darwin with being its scientific father.
His comparative studies showed that man and simpler animals have many
behavioral patterns in common (936; 937).
Carl B.
Huffaker (US) performed predator/prey experiments, which suggested that in a
sufficiently natural environment (of reasonable size for meaningful
interaction), continuity is possible without stipulation of prey immigration or
specific prey refuges (720).
Robert
Ashley Couper (NZ) presented fossil evidence for the earliest undisputed
angiosperm pollen. It is from the Barremian stage (late early Cretaceous), c.120
mya (303).
Roland E.
Beschel (AT) developed the method of using lichen growth to date rocks and
other objects covered by lichens (lichenometry) (130-132). Note:
This method is most accurate within 100 to 9,000 years ago.
1959
“Pythagoras
discovered the simple numerical relations of what we call musical intervals…It
has been suggested that the three intervals of the tuned string were compared
with the three ways of life. While this must remain speculation, it is
certainly true that the tuned string henceforth plays a central part in Greek
philosophical thought. The notion of harmony, in the sense of balance, the
adjustment and combination of opposites like high and low, through proper
tuning, the conception of the mean or middle path in ethics, and the doctrine
of the four temperaments all of these go back in the end to Pythagoras’
discovery…It is very likely that the discoveries in music led to the notion
that all things are numbers. Thus, to understand the world around us, we must
find the number in things.” Bertrand Russell (1335).
"When
playing around in the ocean, dolphins are pleasing to the eye no end, but let
it only add to your thrill that these rascals are a graveyard to our wits. For
is not finding out infinitely more exciting than knowing the answer?" Per
Fredrik Thorkelsson Scholander (1370).
Severo Ochoa
(ES-US-ES) and Arthur J. Kornberg (US) were awarded the Nobel Prize in
Physiology or Medicine for their discovery of the mechanisms in the biological
synthesis of ribonucleic acid and deoxyribonucleic acid.
E. Graham
Bligh (CA) and William J. Dyer (CA) developed a rapid method of total lipid
extraction and purification from biological materials (149).
Rudolf Thalacker
(DE) and Martin Behrens (DE) devised a non-aqueous method for isolation of
chloroplasts (1548).
Clifford Ralph
Stocking (US) and Susan A. Larson (US) first demonstrated the significance of
shuttle transfer across chloroplast membranes in energy metabolism (1487).
Hans W.
Heldt (DE), Ulrich Heber (DE), Gotthard Heinrich Krause (DE), and Kurt A.
Santarius (US) identified specific translocators in the chloroplast envelope
and published on their role in transport (641; 642; 648).
David A.
Walker (GB) wrote an excellent review of the movement of certain key
substances, etc. across the chloroplast envelope (1612).
Leonard
Warren (US) developed a colorimetric assay for the measurement of sialic acids
in which the products of periodate oxidation are coupled with thiobarbituric
acid to form a red chromophore. Since only free sialic acids are measured the
reaction could be used for the detection and measurement of neuraminidase
(sialidase) which hydrolytically releases sialic acids from their bound form (1625).
Stanford
Moore (US), Darrel H. Spackman (US), and William H. Stein (US) described a
procedure for the chromatographic fractionation of mixtures of amino acids by
elution analysis on columns of Dowex-50, a sulfonated polystyrene resin.
Compared to starch the resin columns possess higher resolving power, are more
convenient to operate, are faster, and the separation is not adversely affected
by the presence of inorganic salts in the material chromatographed (1093).
Arnold
Martin Katz (US), William J. Dreyer (US), and Christian Boehmer Anfinsen, Jr.
(US) described a modified method for the separation of peptides on filter paper
that utilizes chromatography followed by high voltage electrophoresis cooled by
a non-explosive organic solvent (786).
Albrecht K.
Kleinschmidt (DE), H. Rüter (DE), Wilhelmine Hellmann (DE), Rudolf K. Zahn
(DE), Annesuse Docter (DE), E. Zimmermann (DE), H. Rübner (DE), A.M. Al Ajwady
(DE) Dimitri Lang (DE) and Diether Jacherts (DE) developed a method, which
allowed the visualization of DNA molecules as smooth, flexible filaments (819; 820).
Hazel D.
Barner (US) and Seymour Cohen (US) presented evidence that phage infection also
stimulates the formation of a new form of thymidylate
synthase, even though this enzyme was already known to exist in uninfected
bacteria. This work suggested that the virus needed not only novel enzymes to
produce the unique base but also needed to augment the activities of
pre-existing enzymes to promote the big metabolic shift toward DNA synthesis (85).
Adolf
Friedrich Johann Butenandt (DE), Roland Beckmann (DE), Dankwart Stamm (DE), and
Erich Hecker (DE) identified and determined the structure of the sex attractant
(bombykol) of the silkworm, Bombyx mori, as (E,
Z)-10,12-hexadecadien-1-ol. This was the first insect pheromone to be identified (203; 204).
Jakob
Schreiber (CH), Willy Leimgruber (US), Mario Pesaro (CH), Peter Schudel (CH),
Terry L. Threlfall (GB) and Albert Eschenmoser (CH) carried out the total
synthesis of colchicine (1374; 1375).
Grant R.
Bartlett (US) developed a method for assaying phosphorus using column
chromatography (96).
Louis
Frederick Fieser (US) and Mary Fieser (US) coined the term steroid to denote any structure like cholesterol (493).
Jon Bremer
(NO) and David M. Greenberg (US), using in
vivo labeled methionine, discovered that phosphatidylethanolamine may
generate phosphatidylcholine via three successive methylation steps (168).
Sydney
Brenner (ZA-GB) and Robert W. Horne (GB) developed the negative staining technique,
invented four years previously by Hall, into a generally useful technique for
visualizing viruses, bacteria, and protein filaments (171).
Joan Oró
(US) Aubrey P. Kimball (US), Richard Reed Fritz (US), and Fenil Master (US)
synthesized amino acids from formaldehyde and hydroxylamine under primitive
Earth conditions (1192).
David F.
Elliott (GB), Eric William Horton (GB), and Geoffrey P. Lewis (GB)
isolated, purified, and determined the amino-acid composition of bradykinin (402-405). They later
determined that it is a nonapeptide (401).
Rodney
Robert Porter (GB), Gerald Maurice Edelman (US), and Miroslav Dave Poulik
(CZ-CA-US) discovered that antibody molecules are composed of four protein
molecules called chains. Each antibody molecule possesses two identical heavy
chains and two identical light chains (389; 1230).
Alfred
Nisonoff (US), Marvin H. Winkler (US), and David Pressman (US) demonstrated
that the antibody molecule has two combining sites with the same specificity
for an antigenic determinant (1143).
Alfred
Nisonoff (US), Franklyn C. Wissler (US), and L.N. Lipman (US) determined the
properties of the major component of a peptic digest of rabbit antibody as the
F(ab’)2 fragment of the antibody molecule, which is the single bivalent
fragment that is produced after pepsin cleavage(1144). Note: Later, it was
found that this F(ab')2 fragment is responsible for antigen interaction and agglutination
and precipitation reactions.
An-Chuang
Wang (US), Stephen K. Wilson (US), John E. Hopper (US), Hugh H. Fudenberg (US),
and Alfred Nisonoff (US) provided evidence for control of synthesis of the
variable regions of the heavy chains of immunoglobulins gamma and
immunoglobulin macroglobulin M by the same gene (1619).
Klaus
Eichmann (US), Amar S. Tung (US), and Alfred Nisonoff (US) discovered the
linkage and rearrangement of genes encoding mouse immunoglobulin heavy chains (394).
Alfred
Nisonoff (US), J.A. Laskin (US), Alfred Gray (US), Norman R. Klinman (US), and
Paul G. Gottlieb (US) discovered how segregation at a locus determining an
immunoglobulin genetic marker for the light chain variable region affects
inheritance of expression of an idiotype (1142).
Mortimer M.
Elkind (US), Harriet Sutton (US) and Willie B. Moses (US) showed that following
exposure of eukaryotic cells to radiation the surviving cells rapidly repaired
the damage caused by radiation, and by the time they had divided once after
initial exposure they had already eliminated its sublethal or recessive lethal damage (398-400). Note: This finding confirmed the
presence of DNA repair mechanisms, later shown to be defective in some cancers.
Lloyd John
Old (US), Donald A. Clarke (US), and Baruj Benacerraf (VE-US) introduced
Bacille Calmette-Guérin (BCG), the tuberculosis vaccine, as a way to stimulate
nonspecific resistance to tumor growth (1180). Note: Today, BCG is
widely used as a first-line treatment for superficial bladder cancer.
Baruj Benacerraf (VE-US) and Philip G.H. Gell
(GB) found that immunization with conjugates (protein carriers linked to a hapten)
is followed by the appearance of delayed hypersensitivity to the protein
“carrier” in the absence of detectable antibodies against it, although
antibodies are produced at that time against the haptenic group itself. Delayed
hypersensitivity to the haptenic group has not been detected at any time;
blocking it with specific antibody does not lead to the appearance of delayed
hypersensitivity, but merely suppresses antibody formation against that group (112).
Bernard B.
Levine (US), Antonio Ojeda (US), and Baruj Benacerraf (VE-US) developed the
concept of Ir (immune response) genes. Individuals with this gene would be able
to recognize certain carriers and thereby synthesize antibodies or manifest
delayed-type hypersensitivity to the target hapten (909).
Ira Green
(US), William E. Paul (US), and Baruj Benacerraf (US) found that
hapten-poly-L-lysine conjugates behaved as complete antigens in genetic
responder and as haptens in nonresponder guinea pigs (582).
Sidney
Walter Fox (US), Kaoru Harada (JP), Kenneth R. Woods (US), Charles Ray Windsor
(US), and Allen Vegotsky (US) showed how amino acids can be heated under Earth
conditions to form proteinoids or "thermal proteins," which when
placed in water self-organize into microspheres or protocells, possible
precursors of the contemporary living cell (464-467).
Siro Senoh
(US), John Daly (US), Julius Axelrod (US), and Bernhard Witkop (US) discovered catechol-O-methyltransferase (CMOT) and
determined that it can catalyze the methylation of a wide variety of natural
catechols. They proposed a metabolic pathway for the metabolism of
noradrenaline and adrenaline (1399).
Antonio
Lima-de-Faria (SE) showed that heterochromatin replicated later than
euchromatin (923).
O. Arunlakshana (US) and Heinz Otto
Schild (GB) demonstrated that
drugs and drug antagonists compete for receptors according to the law of mass
action (63).
William H.
Prusoff (US) reported on 5-iodo-2’-deoxyuridine (IDU), one of the first
compounds tested and shown to be active against DNA viruses (1243). It was
soon shown to be effective against Herpes
simplex virus in a rabbit eye model.
Feodor Felix
Konrad Lynen (DE), Joachim Knappe (DE), Ekkehard Lorch (DE), Gerd Jütting (DE),
Erika Ringelmann (DE), and Jean-Paul Lachance () discovered that biotin is a
coenzyme acting along with enzymes such as carboxylase
in the transfer of activated carbon
dioxide (956; 958; 959).
Howard
Rasmussen (US), Lyman Creighton Craig (US) and Gerty
Hochster (US)
isolated and characterized the main hormone produced by the parathyroid glands,
parathyroid hormone (PTH) (1265; 1266).
Frank Ralph
Batchelor (GB), Frank Peter Doyle (GB), John Herbert Charles Nayler (GB), and
George Newbolt Rolinson (GB) discovered 6-aminopenicillanic acid (6-APA), the
penicillin nucleus. It provided the ideal starting point for the preparation of
new penicillins because different side chains could be attached to the nucleus,
through the free amino group, by chemical means (98).
Federico
Maria Arcamone (IT), Cesare Bertazzoli (IT), Mario Ghione (IT), and Tullio
Scotti (IT) isolated the antibiotics melanosporin
and elaiophylin from Streptomyces melanosporus (46).
Federico
Maria Arcamone (IT), Cesare Bertazzoli (IT), Mario Ghione (IT), and Tullio
Scotti (IT) isolated the antibiotic gabbromycin
or aminosidine sulfate from Streptomyces crestomyceticus (47; 48).
Theodore H.
Haskell (US), James C. French (US), and Quentin R. Bartz (US) isolated the
antibiotic paromomycin from Streptomyces rimosus (625).
Christine O.
Dawson (GB) and James C. Gentles (GB) discovered
the teleomorphs (perfect or sexual state) of Trichophyton (Keratinomyces)
ajelloi (331).
Alvin
Markovitz (US), Joseph A. Cifonelli (US), and Albert Dorfman (US) synthesized
hyaluronic acid in a cell-free preparation of streptococci (1001). This was
the first cell-free synthesis of a heterologous polysaccharide.
Jerker Olof
Porath (SE) and Per Flodin (SE) introduced gel filtration using cross-linked
dextran gels. This produced a so-called molecular sieving (1228; 1229).
Samuel Raymond (US) and Lewis S. Weintraub (US) introduced the
polyacrylamide gel electrophoresis (PAGE) technique. It is superior to starch
gels for separating proteins by electrophoresis (1270).
Baruch Joel
Davis (US) and Leonard Ornstein (US) described the use of polyacrylamide gel
for disc electrophoresis (1187; 1188).
Stauffer
Chemical Company introduced the herbicide EPTC, a thiocarbamate, for use in
crops such as alfalfa (Medicago
sativa), certain beans, potatoes (Solanum tuberosum), and sweet potatoes (Ipomea batatas). ref
An Italian
company, Lepetit, isolated and tested the antibiotic rifampicin (rifampin, rifamycin, or rifaldazine). It was isolated from Streptomyces mediterranei (Amycolatopsis
mediterrani) found in a wooded area of Northern Italy. The antibiotic was
named for a movie, Rififi, being
filmed in the area at the time (562). Rifamycin blocks initiation of RNA
chains by binding to RNA polymerase
(prevents RNA synthesis) in prokaryotes only.
Peter
Karlson (DE) and Adolf Friedrich Johann Butenandt (DE) proposed the name pheromone
to designate substances secreted by an animal to the outside and causing a
specific reaction in a receiving individual of the same species. This term is
synthesized from the Greek pherein
(to carry) and horman (to excite) (779). See, Fabre, 1879; Bethe, 1932; Butenandt,
1961; Corpéchot, 1985; and Cutler,1986.
Samuel B.
Weiss (US) and Leonard Gladstone (US) were the first to describe the
RNA-synthetic activity of a RNA
polymerase. They used rat liver as experimental material (1650).
Audrey Stevens (US), using E.
coli, almost simultaneously discovered
RNA polymerase (1481).
Ru-Chih C.
Huang (US), Nirmala Maheshwari (IN), and James Frederick Bonner (US) discovered
the synthesis of RNA from DNA in peas (158; 710).
Jerard
Hurwitz (US), John J. Furth (US), Monika Anders (US), Priscilla J. Ortiz (US),
and J. Thomas August (US) presented their studies with
the E. coli RNA polymerase, which
provided an enzymatic mechanism by which DNA supported
RNA synthesis (726).
Bention
Nisman (FR), Hiroshi Fukuhara (FR), Tadanori Kameyama (JP), G. David Novelli
(US), Alfred Tissieres (US), David Schlessinger (US), and Francoise Gros (FR)
observed that DNAase inhibits in vitro incorporation of amino acids
into proteins thus suggesting that protein synthesis depends on DNA templates (769; 1141; 1562).
Francois
Jacob (FR) and Jacques Lucien Monod (FR) isolated and genetically analyzed many
mutants in the lactose utilization pathway. Their studies of these mutants led
to the conclusion that induction and repression are under the control of
specific proteins, which are coded for by regulatory genes. They proposed that regulator genes are closely associated
with the structural genes coding for specific enzyme proteins but are distinct
from them. They visualized regulator substance interacting with a genetic
element, an operator, which
controlled expression of the structural genes (736; 739). The term operon was coined in the 1960 paper.
Milislav L.
Demerec (Yugoslavian -US) and
Philip E. Hartman (US) noted that in bacteria the genes controlling enzymes of
the same biochemical pathway tend to remain clustered because they are all
controlled by the same operator gene (343).
Alice L.
Tuttle (US) and Howard Gest (US) discovered that the photosynthetic apparatus
of the photosynthetic bacteria is associated with the cytoplasmic membrane
and/or membranous extensions into the cytoplasm (1578).
Micheline M.
Mathews (US) and William R. Sistrom (US) determined that the function of
carotenoid pigments in non-photosynthetic bacteria is to diminish the harmful
effects of light radiation (1019).
P. Gaastra
(NL) performed experiments designed to analyse the photosynthetic activity of
crop plants. The following features are successively discussed: technical
requirements and details of the experimental set-up, the influence of light
intensity, carbon dioxide concentration, and leaf temperature on photosynthesis
of cucumber, tomato, spinach, turnip, and sugar beet, the effect of light
intensity and carbon dioxide concentration on the stomatal diffusion
resistance, and the stomatal control of photosynthesis (500; 501).
R. Clinton
Fuller (US) and Martin Gibbs (US) found that purple bacteria contain the
Calvin-Benson cycle of carbon fixation (495).
Choh Hao Li
(CN-US) and Phil G. Squire (US) purified and determined the properties of
interstitial cell-stimulating hormone from sheep pituitary glands (912).
Clement L.
Markert (US) and Freddy Møller (US) proposed the term isozyme or isoenzyme to
denote different enzymes which share functional specificity, but which vary
slightly reflecting their tissue of origin, their ontogeny, or their species of
origin (1000).
Louis
Barkhouse Flexner (US), Josefa B. Flexner (ES-US), Richard B. Roberts (US), and
Gabriel L. de la Haba (US) independently discovered isoenzymes (455).
Jennie Ciak
(US) and Fred E. Hahn (US) showed that the antibiotic D-cycloserine, an analog
of D-alanine, inhibits cell wall synthesis (271).
Jack Leonard
Strominger (US) and Robert H. Threnn (US) reported that the antibiotic novobiocin inhibits cell wall synthesis (1498).
Shimon Gatt
(US), Ray Wu (US) and Efraim Racker (PL-AT-US) showed that glycolysis is
dependent on the continuous regeneration of ADP and inorganic phosphate by an ATPase. This was the first indication
that an ATPase is in the family of
glycolytic enzymes (509; 510; 1691; 1692).
Joshua
Lederberg (US) theorized that lymphocytes pass through an obligatory
paralyzable state early in their ontogeny during which an encounter with an
antigen will silence or kill them. If they pass this point without antigenic
stimulation they become inducible, i.e., capable of being activated (890).
Ernst Freese
(US) hypothesized about the molecular basis of mutations caused by base
analogues, such as bromouracil and nitrous acid. He proposed two distinct
classes of base substitutions in DNA. The first was a simple copying error
whereby one purine was switched to another (A for G or the reverse) or one pyrimidine
for another (T for C or the reverse). Such errors he called transitions. Base analogues and nitrous
acid caused transitions. Transitions revert to the wild type
easily.
Most
spontaneous mutations and those induced by dye such as proflavine rarely reverted
to the wild type. He suggested that in these a purine was replaced by one of
two pyrimidines or a pyrimidine by one of the two purines. He called this type
of substitution a transversion (481-483).
Benjamin D.
Hall (US), Paul Mead Doty (US), Uriel Z. Littauer (IL), Heini Eisenberg (IL),
Serge N. Timasheff (US), Raymond A. Brown (US), John S. Colter (US), and
Maurice C. Davies (US) reported that ribosomal RNA from higher organisms
sedimented as two distinct components, 18S and 28S (603; 928; 1559).
Joseph-Felix
Heremans (BE), M.T. Heremans (BE), and Hermann Edward Schultze (BE) described
IgA and laid one of the foundations for our understanding of intestinal
immunity (656).
Stewart S.
Sell (US) and William O. Weigle (US) found that sensitization by injection of
immune precipitates in adjuvant induces not only delayed hypersensitivity but
also the steps leading to immune antigen elimination—i.e., the
production of circulating antibody. It appears that during the course of
immunization the delayed hypersensitive state develops first, then gives way to
the Arthus type of sensitivity as antibody production is manifest (1393).
Kenneth
McQuillen (US), Richard Brooke Roberts (US), and Roy John Britten (US) proved
that in Escherichia coli protein
synthesis occurs on ribosomes (1037).
Tracy Morton
Sonneborn (US) established that the “kappa” particles of Paramecium aurelia represent the first known case of cytoplasmic
inheritance in animals. He hypothesized that intracellular symbiotes and cell
organelles have become inextricably combined during evolution (1446).
Lemuel
Ruscoe Cleveland (US) and Albert Victor Grimstone (GB) described Mixotricha paradoxa, a protozoan symbiotic to Darwin’s termite (Mastotermes darwiniensis), as a very unusual protozoan that is a
composite of a eukaryotic protozoan with three independent prokaryotic
symbionts: spirochetes, bacteria associated with the spirochetes, and
endosymbiotic bacteria (279).
Lynn
Margulis (US) proposed that the eukaryotic cell is an evolutionary chimera, put
together from at least three quite different, previously prokaryotic, lineages (999; 1341).
Tom
Cavalier-Smith (US) coined the collective term Archezoa to include
amitochondrial protists (the diplomonads, mastigamoebae and retortamonads) and
microsporidians. He explained the origin of mitochondria and chloroplasts
within eukaryotic cells by proposing what became known as the endosymbiotic or endosymbiont theory (245; 246). See
Mereschkowsky, 1905.
Gordon
Alastair Maclachlan (CA) and Helen K. Porter (CA) discovered that higher plants
can also continue to produce ATP by photophosphorylation in the absence of CO2 for assimilation (975).
Richard L.
Wood (US) discovered septate junctions. They are found in invertebrate tissues
where they participate in adhesion, sealing, and communication (1677).
Harry Eagle
(US) introduced his minimum essential
medium (MEM) for the cultivation of eukaryotic cells. Except for a small
amount of dialyzed serum this medium is defined and can support cell
multiplication (385).
S. Jon Singer
(US) used antibodies coupled to ferritin to detect cellular molecules in the
electron microscope (1425).
Takashi
Hayashi (JP) found that application of gamma-aminobutyric acid (GABA) strongly
suppressed electrical activity in the mammalian nervous system (636).
Edward A.
Kravitz (US), Stephen William Kuffler (US), David D. Potter (US), and Masanori
Otsuka (JP) proved that γ-aminobutyric acid, or GABA, is the inhibitory
neurotransmitter at the lobster neuromuscular junction (847; 1194).
David W.
Krogmann (US), André Tridon Jagendorf (US), and Mordhay Avron (IL) presented
evidence for the coupling of ATP synthesis to electron transport in illuminated
chloroplasts (854).
Peter Dennis
Mitchell (GB) and Jennifer Moyle (GB) proposed that energy-yielding and
energy-requiring reactions of oxidative phosphorylation are linked by a
high-energy state, rather than by a compound. They theorized that an
electrochemical gradient of protons across the mitochondrial inner membrane
serves as the means of coupling the energy flow from electron transport to the
formation of ATP. The membrane is an integral part of the coupling mechanism
and must be intact in the form of a continuous closed vesicle for oxidative
phosphorylation to take place. They postulated that it is the function of the
electron carriers of the respiratory chain to serve as an active-transport
system or pump to transport protons
from the mitochondrial matrix across the inner membrane, thus generating a
gradient of protons across the membrane, which they postulated to be
impermeable to protons. The electrochemical gradient thus generated is then
postulated to drive the synthesis of ATP by causing dehydration of ADP and Pi. They
determined that mitochondria translocate approximately two protons across the
mitochondrial membrane for each ATP generated by oxidative phosphorylation and
demonstrated that in mitochondria ATP can be artificially generated by making
the medium outside the inner mitochondrial membrane moderately acidic vis-à-vis
the mitochondrial matrix. They were the first to realize that the buildup of
protons in the thylakoid sac of chloroplasts might serve as a source of energy
to drive phosphorylation of ADP to ATP and predicted that the thylakoid
membrane should be asymmetrical (1034; 1059-1079; 1105; 1106). The four
parts of the chemiosmotic coupling theory are stated in the 1966 article
Roger Yate
Stanier (CA), Michael Doudoroff (RU-US), Riyo Kunisawa (US), and Rebecca
Contopoulou (US) found that when photosynthetic bacteria oxidize organic
substrates they use only a small portion of the reducing power gained to reduce
carbon dioxide. Most of these substrates were found to be assimilated directly
as poly-beta-hydroxybutyric acid (PHB) or as polysaccharide (1461).
Michael
Doudoroff (RU-US) and Roger Yates Stanier (CA) used Pseudomonas saccharophilia and Rhodospirillum
rubrum to show that excess substrate carbon accumulates within the cell as
poly-beta-hydroxybutyric acid (PHB). When the external substrate is removed,
the stored PHB is degraded intracellularly. PHB is therefore an important
carbon and energy reserve for these bacteria (364).
Albert Bruce
Sabin (PL-US) grew the reovirus in monkey kidney tissue culture
and coined the name reovirus to reflect the fact that viruses of this group had
been isolated from the respiratory and enteric tracts and were orphan viruses
without known associated disease (reo) (1339).
Philippe
Vigier (FR) and Alice Golde (FR) showed that chick embryo cells infected with
Rous sarcoma virus continued to grow in culture and produce more virus. The
infected cells underwent a change in morphology and exhibited rapid, disordered
growth characteristic of cancer cells (1598).
Bolivian
Health Officials first isolated the Machupo virus from 1959-1962. It is a New
World arenavirus from the Arenaviridae family (151). Machupo virus is the etiological agent of viral hemorrhagic fever (Bolivian
hemorrhagic fever, South American hemorrhagic fever, arenavirus, black typhus,
Ordog Fever).
Armando S.Parodi
(AR), Héctor R. Rugiero (AR), Daniel J. Greenway (AR), Norma E. Mettler (AR), A.
Martinez (AR), Martha C. Boxaca (AR), and J.M. De La Barrera (AR) isolated
Junin virus, the causative agent of Argentine haemorrhagic fever, which
has been known since 1943 (1203).
Lynne Kilham
(US) and Louis J. Olivier (US) isolated a latent virus from rats using tissue
culture (807). Note: This is a
parvovirus known as Kilham rat virus.
Frank
Macfarlane Burnet (AU) and George Keble Hirst (US) suggested that the genome of
the influenza virus might be segmented because of its unexpectedly high
frequency of recombination (199; 681).
Peter H. Duesberg
(US), Marcel W. Pons (US), and George Keble Hirst (US) found that the influenza
virus appeared to consist of about six segments (374; 1226).
Peter Palese
(US), Jerome L. Schulman (US), Duncan McGeoch (GB), Peter Fellner (GB), and Clive
Newton (GB) showed that influenza A viruses (IAVs) and type B viruses (IBVs)
contain 8, negative-sense, single-stranded viral RNA (vRNA) gene segments,
which encode transcripts for 10 essential viral proteins (1031; 1198).
Robert G.
Webster (US), William J. Bean (US), Owen T. Gorman (), Thomas M. Chambers (US),
and Yoshihiro Kawaoka (US) report that two partly overlapping reservoirs of
influenza A viruses exist in migrating waterfowl and shorebirds throughout the
world. These species harbor influenza viruses of all the known HA and NA
subtypes (1641).
Steven J. Gamblin (GB) and John J.
Skehel (GB) reported that the classification of influenza A viruses (IAVs) into
subtypes is based on the genetic and antigenic properties of the surface
antigens hemagglutinin antigen (HA) and neuraminidase antigen (NA), which
mediate viral entry and release, respectively (505).
Björn A.
Afzelius (SE-US) used 40% osmium tetroxide to
treat preparations for the electron microscope and found that in the 9+2
pattern of the axoneme he could spot arms
that reached from one outer doublet toward another. He suggested
that the beating movements of eukaryotic flagella are produced by active
microtubular sliding powered by arms extended from the microtubular doublets
toward one another (10).
Ian R. Gibbons (US) correlated the
presence of the crossing arms with the ATPase activity
of the cilia (533).
Ian R. Gibbons (US) and Arthur J. Rowe (GB) subsequently named
these connecting arms dynein (dynein,
force protein) (536).
Ian R.
Gibbons (US) and Barbara H. Gibbons (US) discovered an ATPase activity in eukaryotic flagella (532; 534).
Ian R.
Gibbons (US) stated that dynein arms are ATPases
responsible for generating the sliding movements between microtubules that
undergo ciliary and flagellar motility with the microtubules being arranged in
9 doublets surrounding two central tubules, the so-called 9+2 arrangement (535).
Dynein was the first microtubule force-producing protein motor to be described
and has since been shown to be involved in intracellular trafficking as well as
locomotion, including translocation of membrane-bounded vesicles in neurons,
Golgi vesicles, kinetochores, and mitotic spindle astral microtubules.
Ian R.
Gibbons (US), Peter Satir (US), Linda A. Amos (US), Aaron Klug (US), Carol
Allen (US), Gary Guy Borisy (US), Bruce R. Telzer (US), Montrose J. Moses (US),
Joel L. Rosenbaum (US), Roy R. Gould (US), Lawrence G. Bergen (US), Ryoko
Kuriyama (US), Steven R. Heidemann (US), J. Richard McIntosh (US), Ursula
Euteneuer (US), J. Richard McIntosh (US), Leah T. Haimo (US), Timothy J.
Mitchison (US), Marc W. Kirschner (US), Conly L. Reider (US), and Stephen P.
Alexander (US) built on one another’s work to discover that dynein
cross-bridges linked microtubules (MTs) together and that MT polymers have polarity (534); microtubules slide past each
other to give cilia their movement (1351); that polarity is reflected by
both the orientation of asymmetric subunits (26) and the different rates at which
the MT “plus” and “minus” ends add subunits (18); several in vitro studies revealed that MTs can be initiated from both
kinetochores and centrosomes (570; 1529) and also that both kinetochore
and centrosome MTs polymerize with their plus ends distal to the organizing
center (118); predicted that in late
anaphase, when chromatin moved to the poles, only minus ends of the centrosome
MTs should be left at the midplate (646); observed that in anaphase
cells, 90–95% of the MTs in a half-spindle were oriented with their plus ends
toward the middle (421); found that in late anaphase,
when chromatin moved to the poles, only minus ends of the centrosome MTs should
be left at the midplate and showed that the majority of MTs in a meiotic
half-spindle are oriented with their plus ends distal to the poles (1528). The idea that half-spindles
contain parallel MTs was sealed. Later good evidence was presented that
kinetochores do indeed capture and stabilize the dynamically unstable MTs growing
from the asters (1081), a process that was documented in vivo (1274).
Annemarie
Weber (DE-US), Ruth Herz (DE), Ingrid Reiss (DE), Wilhelm Hasselbach (DE),
Madoka Makinose (JP), Shinpei Yamada (JP), Taibo Yamamoto (JP), and Yiji
Tonomura (JP), showed that the sarcoplasmic reticulum is a vesicular membrane
possessing a calcium ion, magnesium ion dependent ATPase system capable of reducing external calcium to micromolar
concentrations and that, following the addition of permeate anions such as
oxalate or phosphate, calcium ion precipitates can be detected within the
sarcoplasmic reticulum vesicles. These observations clearly showed that calcium
ion is being transported by the vesicular sarcoplasmic reticulum. Simultaneous
measurements of ATP concentrations revealed that the hydrolysis of one mole of
ATP results in the uptake of two moles of calcium ion. This intercellular
calcium ion pump is the first known example of a cellular energy-driven counter
transport mechanism. ATPase activity
and the state of contraction of natural actomyosin
and myofibrils are unique functions of free calcium ion concentration (626-628; 1630-1638; 1640; 1699).
Richard H.
Kessler (US), Klaus Hierholzer (US), Ruth S. Gurd (US), Robert Franklin Pitts
(US), Lawrence P. Sullivan (US), Walter S. Wilde (US), Richard L. Marvin (US),
John R. Jaenike (US), and Robert William Berliner (US) demonstrated that potassium
accumulates in the more distal parts of the nephron, leaving little question
that this is the site of potassium secretion (744; 803; 1500).
Wilfrid Rall
(US) created a theoretical framework for modeling electrical current flows in
dendritic trees (1256; 1257).
Wilfrid Rall
(US), Robert E. Burke (US), Tom G. Smith (US), Phil G. Nelson (US), Karl Frank
(US), and John Rinzel (US) analyzed theoretically how synaptic potentials (and
currents) spread in the dendritic tree, and how they are expected to influence
the voltage response at the neuron's soma and axon attached to it. They showed
that, in contrast to the accepted notion at the time, distal excitatory
synapses do contribute to the depolarizing charge that reaches the cell body
and that, due to filtering of high frequencies by the distributed capacitance
along the dendritic membrane, the time course of the somatic excitatory
postsynaptic potential (EPSP) changes as a function of input location. The more
distal the synapse is, the slower the EPSP rises and the broader it is at the
soma (1258; 1259; 1299).
Wilfrid Rall
(US) and Gordon M. Shepherd (US) predicted that mitral and granule cells
interact with each other via dendro-dendritic synapses. They also raised the
possibility that dendrites may be decorated by nonlinear (excitable) ion
channels (1260). This model has been tested many
times and is fundamental for current concepts of processing in several neural
systems, including the olfactory bulb, the retina, the olivary nucleus, etc. It
is now widely known that most synaptic inputs are made on dendrites and that it
is there where important plastic changes (which probably underlie learning and
memory processes in the brain) take place.
Lewis Thomas
(US) and Frank MacFarlane Burnet (AU) proposed the immunosurveillance theory, which holds that eliminating
precancerous cells is one of the primary duties of patrolling lymphocytes (200; 1555; 1556). See, Paul Ehrlich, 1909.
Susumu Ohno
(JP-US), William D. Kaplan (US), Riojun Kinosita (JP-US), and Sajiro Makino
(JP) discovered that the chromatin body in cells of female mammals is a
condensed heterochromatic X chromosome (1170; 1171). This
suggested that the condensed X chromosome is inactive.
Mary Frances
Lyon (GB) postulated that in nearly every cell of a woman’s body one or the
other of her two X chromosomes is inactive. The tissues of the adult female are
thus a mosaic in which about half of the cells contain an active paternal X and
half contain an active maternal X. This phenomenon termed dosage compensation by X-inactivation is also called Lyonization (963-965).
Ronald G. Davidson (US), Harold M. Nitowsky (US), and Barton
Childs (US) confirmed, by using gel electrophoresis, that some females had two
forms of the enzyme glucose-6-phosphate
dehydrogenase (G6PD), encoded by alleles on the two X chromosomes. However,
when individual cells were cloned and tested, each clone now only expressed one
form or the other, not both. Therefore, females clearly expressed only one G6PD gene in each cell, and the other
appeared to be silenced (329).
Carolyn J.
Brown (US), Andrea Ballabio (US), James L. Rupert (US), Ronald G. Lafreniere
(US), Markus Grompe (US), Rossana Tonlorenzi (US), and Huntington F. Willard
(US) discovered that the Xist gene is
only expressed from the inactive human X chromosome, so it presumably acts in cis on the chromosome that produces the Xist RNA (179).
Neil
Brockdorff (GB), Alan Ashworth (GB), Graham F. Kay (AU), Penny J. Cooper (GB),
Sandy Smith (GB), Veronica M. McCabe (GB), Dominic P. Norris (GB), Graeme D.
Penny (GB), Dipika Patel (GB), Sohaila Rastan (AU), Sally Swift (GB), and
Steven A. Sheardown (GB) found the same for Xist
in the mouse, and went on to identify the 15 kb untranslated nuclear transcript
that is conserved in sequence and structure between mice and humans. The
targeted knockout of Xist in XX mouse
embryonic stem (ES) cells showed conclusively that the gene is essential for
X-inactivation (176; 177; 793; 1211).
In eutherian
mammals, X-inactivation is random, but in marsupials, imprinting ensures that
the paternal X is preferentially inactivated. The same also happens in
extra-embryonic tissues of eutherian mammals, and probably in pre-implantation
mouse embryos too. A chromosome-counting mechanism seems to allow inactivation
of all but one X chromosome during development.
Jeannie T.
Lee (US) studied transgenic embryonic stem (ES) cells and embryos harboring
deletions of sequences in the antisense strand of the DNA. She found that Xist is regulated by its 40 kb antisense
partner, Tsix, which codes for
another cis-acting untranslated RNA. It now seems that both the imprinting and
counting mechanisms control Xist
through Tsix, thereby ensuring that
only one X chromosome will remain active in the cells (891).
Sydney
Brenner (ZA-GB), George Streisinger (HU-US), Robert W. Horne (GB), Sewell P.
Champe (US), Leslie Barnett (GB), Seymour Benzer (US), and M.W. Rees (GB)
studied the structure of the T2 bacteriophage and found that the tail consists
of a sheath surrounding a core at the base of which are attached tail fibers.
The sheath appears to be built of helically arranged subunits, which form a
hollow cylinder. The sheath can contract in length. The core of the tail is
hollow with a 25-angstrom opening. The sheath is composed of about 200 repeated
subunits each of approximately 50,000 molecular weight. The head covering is
composed of many repeated subunits each with a molecular weight of 80,000. The
tail fibers appear to have a subunit with a molecular weight not less than
100,000. The head, sheath, and tail fibers are all composed of proteins, which
have different primary structures (173).
Robert Louis
Sinsheimer (US) and Walter Charles Cornelius Fiers (BE)) were able to show that
phi-X174, a bacteriophage of Escherichia
coli, is a small tailless polyhedron only 250 Å in diameter, and hence of a
volume about 1/40 that of the T-even phage head. It contains a single DNA
molecule made up of 5000 nucleotides. But most importantly Sinsheimer discovered
that the DNA is single stranded and circular. The single stranded viral DNA
uses one of the host’s enzymes to convert itself into a double stranded replicative form (438; 1427).
Renato
Dulbecco (IT-US), Gustave Freeman (US), and Marguerite Vogt (DE-US) described
the morphological features of cells infected by polyoma virus in vitro. They noted that the virus can
induce a cancer-like state in some cell lines (non-permissive) even though it
does not replicate, while in other cell lines it can replicate causing no
cancer-like condition (permissive) (377; 1600-1602).
John J.
Holland (US), Leroy C. McLaren (US), and Jerome T. Syverton (US) found that the
restriction of poliovirus to primates and the insusceptibility of non-primates
to this infection are due to the presence of specific poliovirus receptors on
the host cells. They also observed that poliovirus RNA alone is infectious over
a much broader host range (692; 693).
Anne Gemmell (GB) and Hugh John Forster Cairns (GB-US-GB) were the
first to demonstrate gene linkage in an animal virus (516).
Irwin
Tessman (US) demonstrated that some naturally occurring viral genomes are
composed of single stranded DNA (1547).
Samuel L.
Katz (US), John Franklin Enders (US), Sidney Kilbrick (US), Milan V.
Milovanovic (CS), and Ann Hollowqy (US) produced a live attenuated measles
(rubeola) vaccine (411; 787; 788). Note: In the decade before 1963 when a
vaccine became available, nearly all children got measles by the time they were
15 years of age. It is estimated 3 to 4 million people in the United States
were infected each year. Also, each year an estimated 400 to 500 people died,
48,000 were hospitalized, and 4,000 suffered encephalitis (swelling of the
brain) from measles.
Carl Lamanna
(US) reported that Clostridium botulinum
produces the most poisonous toxins known (865).
Nirmal Kumar
Dutta (IN), Madhusudan V. Panse (IN-US), D.R. Kulkarni (IN), and Sambhu Nath De
(IN) implicated a toxin in the etiology of cholera (337; 382).
Norman
Strauss (US) and Edelmira D. Hendee (US) demonstrated that diphtheria toxin
completely blocks amino acid incorporation by cultured human cells. It was
found that the toxin inhibits polypeptide chain elongation (1493).
Zanvil
Alexander Cohn (US), F. Marilyn Bozeman (US), Janis M. Campbell (US), James W.
Humphries (US), and Thomas K. Sawyer (US) concluded that the penetration of
host cells by Rickettsia tsutsugamuchi
requires the active participation of both the bacterium and its host cell (288).
Richard L.
Riley (US), Cretyl C. Mills (US), Walenty Nyka (US), N. Weinstock (US), Patrick
B. Storey (US), Louise U. Sultan (US), Mary Catesby Riley (US), and William F.
Wells (US) proved that even small numbers of tubercle bacilli can account for
the spread of human tuberculosis by aerosol and that patients with the highest
counts of tubercle bacilli in their sputa are the most infectious ones (1296; 1297).
Hisakichi
Matsubayashi (JP), Tamotsu Kioke (JP), Ittaku Mikata (JP), Hiroshi Takei (JP),
Setsuo Hagiwara (JP) reported the first authenticated record of a
microsporidian infection in humans—an Encephalitozoon
sp. in a boy with convulsions (1020).
The microsporidia constitute a phylum (Microspora) of spore-forming
unicellular parasites. They were once thought to be protists but are now known
to be fungi. Microsporidian infections of humans sometimes cause a disease
called microsporidiosis. At least 14
microsporidian species, spread across eight genera, have been recognized as
human pathogens. These include Trachipleistophora
hominis. The rise in microsporidiosis is associated with the arrival and
spread of HIV; microsporidiasis is
primarily found in patients with AIDS or are otherwise immuno-compromised (like
organ transplant patients). However, at least three species of Nosema and
one of Brachiola have been documented in immuno-competent patients.
Microsporidia are considered casual, accidental or opportunistic agents in
humans. The transmission of microsporidia is still unclear, but the most common
way is thought to involve inhaling, ingesting or otherwise contracting spores
(for example ocular or sexually transmitted).
Harry Eagle
(US) announced two generalizations about the requirements of mammalian cell
lines propagated in vitro. With few
exceptions both normal and malignant cells have the same nutritional
requirements and differentiation disappears quickly (384). Read article to verify
Waclaw
Szybalski (PL-US), M. Joan Smith (US), Elizabeth H. Szybalski (US), R. Wallace
Brockman (US), and Giorgio Ragni (IT) were the first to mount a systematic
search for mutants among cell lines propagated in vitro (1505-1508).
David A. Hungerford (US), Andrew J. Donnelly (US), Peter C. Nowell (US)
and Sidney Beck (US) described a human individual of outwardly male appearance,
clinically diagnosed a ‘true hermaphrodite.’ This intersex was found to have an
XX sex chromosome complement. The first full description appears here of their
adaptation to cytogenetic use of a method for culturing human leukocytes (723).
Harold B.
Hewitt (GB) and Charles W. Wilson (GB) were the first to obtain survival curves
for mammalian cells irradiated in vivo (667; 668).
Howard Green
(US), R.A. Fleischer (US), Paul Barrow (US), and Burton Goldberg (US) supplied
the first clear evidence that serum complement
produces functional holes in cell membranes rather than membrane ruptures (581).
Anthony G.
Searle (GB) reported a dominant mutant on chromosome 1 of mice, Dominant hemimelia (Dh) which causes
the animals to be congenitally asplenic (1386).
Henry
Quastler (US) and Frederick G. Sherman (US) analyzed data obtained from
autoradiographs of mouse intestinal epithelial cells labeled with tritiated
thymidine. This led to a description of the kinetics of cell proliferation. The
precise localization of the exposed emulsion allows cells synthesizing DNA to
be identified, estimates to be made of the average time cells remain in the
various compartments, the number of cells per compartment, and the number of
cells per unit time in transit from one compartment to another. Additionally,
it was found that for the transition from a proliferative to a 'functional'
cell to occur, the cell must not only be in a certain neighborhood, but it must
also be in a certain phase of its generative cycle (1248).
Georges Schaltenbrand (DE) and Percival Bailey (US) produced a
stereotactic atlas of the human brain that became an instant classic because of
the caliber and accuracy of the photographs of the brain (1357).
Brian F.
Hoffman (US), Paul F. Cranefield (US), Jackson H. Stuckey (US), Norman S. Amer
(US), Richard R. Cappelletti (US), and Rodolfo T. Domingo (US) made the first
recordings of electrical activity of the atrioventricular bundle in humans (686; 1499). Dr. Hoffman and his colleagues
identified the cellular electrophysiologic basis for the actions of digitalis,
catecholamine, and antiarrhythmic drugs.
David Hunter
Hubel (CA-US) and Torsten Niels Wiesel (SE-US) made recordings from single
cells in the striate cortex of lightly anaesthetized cats. The retinas were
stimulated separately or simultaneously with light spots of various sizes and
shapes. Effective driving of a unit required a stimulus specific in form, size,
position and orientation, based on the arrangement of excitatory and inhibitory
regions within receptive fields. Restricted retinal areas that on illumination
influenced the firing of single cortical units were called receptive fields (714).
Robert H.
Wurtz (US) described the technique of recording the activity of single neurons
in the visual system of the conscious monkey, and this study replicated Hubel
and Wiesel's finding in the anesthetized monkey of cells with motion
selectivity and orientation selectivity. The second paper showed that this
system could be used to answer a cognitive question: could neurons in the
striate cortex distinguish, as do normal humans, between the motion across the
retina of stimulus moving in the world and the motion across the retina induced
by the eye's moving across a stimulus stable in the world. The answer was no (1695; 1696).
David Hunter
Hubel (CA-US) and Torsten Niels Wiesel (SE-US) provided the first clue to how
the brain circuits represent the shape of a given object, by demonstrating that
neurons in the primary visual cortex are selectively tuned to respond to the
edges oriented in various angles (716; 718).
David Hunter
Hubel (CA-US) and Torsten Niels Wiesel (SE-US) concluded that the long narrow
stripes of alternating left-eye and right- eye input to layer IV are an
anatomical counterpart of the
physiologically observed ocular dominance columns. Because of this segregation of inputs,
cells of layer IV are almost invariably influenced by one eye only. A cell
above or below layer IV will be dominated by the eye supplying the nearest IVth
layer stripe, but will generally, though not always, receive a subsidiary input
from the
other eye, presumably by diagonal connections from the nearest
stripes supplied by that eye (717).
David Hunter
Hubel (CA-US), Torsten Niels Wiesel (SE-US), and Simon LeVay (US) identified in
neonatal animals a critical period
during which deprivation of visual stimulation may induce permanent blindness.
The length and timing of critical periods
differ among species, which suggests that throughout the brain each functional
unit has a unique program of development. This type of blindness is associated
with changes in the functional architecture in layer IVc of the brain’s striate
cortex (713; 719).
David Hunter
Hubel (CA-US) and Margaret S. Livingstone (US) showed that some neurons in the
brain’s primary visual cortex respond selectively to color but not shape (930).
Ashton
Graybiel (US), Robert H. Holmes (US), Dietrich E. Beischer (US), Gerald E.
Champlin (US), George P. Pedigo (US), W. Carroll Hixon (US), Thomas R.A. Davis
(US), Norman L. Barr (US), Wallace G. Kistler (US), Jorma I. Niven (US), Edward
Wilbarger (US), Donald E. Stullken (US), William S. Augerson (US), Robert Clark
(US), and James H. Berrian (US) gave an account of experiments in which two
monkeys were recovered unharmed after ballistic space flight (579).
Crawford
Stanley Holling (CA) distinguished two levels of predation: (1) the behavioral
acts performed by an individual predator searching for and consuming prey; and
(2) the population processes of mortality and fecundity influencing the growth
of predator and prey populations. He quantified both the behavioral and
population components in terms of the number of individual prey killed as a
function of prey density (698).
William
Henry Hildemann (US), William D. Linscott (US), M.J. Morlino (), James
Learmonth Gowans (GB), Douglas D. McGregor (US), and Paul Ichiro Terasaki (US)
discovered that in both mammals and birds normal peripheral blood contains
immunologically competent cells in its leukocyte moiety and from among them it
is the small lymphocyte which initiates the graft
versus host reaction (575; 671; 1544).
Eugene
Raymond Hall (US) and Keith R. Kelson (US) issued their big systematic Mammals
of North America with keys for identification, descriptions, measurements,
and 500 distributional maps (605).
Charles
Edmund Ford (GB), Ken W. Jones (GB), Paul Emanuel Polani (GB), J. Carlos de
Almeida (GB), Joseph H. Briggs (GB), Patricia Ann Jacobs (GB), John A. Strong
(GB), William L. Russell (US), Liane Brauch Russell (AT-US), Josephine S. Gower
(US), and Bruce M. Cattanach (US) deduced the existence of male determinants on
the Y chromosome in both mice and humans (244; 459; 743; 1337).
Kendall
Brooks Corbin (US) introduced artane, or benzhexol, for treatment of Parkinson
disease (297).
Robert Schwartz
(US) and William Dameshek (US) prevented rabbits from producing antibody
against human serum albumin by treating them for two weeks with the
antimetabolite, 6-mercaptopurine. This "drug-induced tolerance"
remained after drug treatment was stopped, even though the animals could react
normally against another protein antigen, bovine gamma globulin. Thus, the
tolerance seemed to be specific for an antigen introduced at the time of drug
administration (1377).
William R.
Meeker, Jr. (US), Richard M. Condie (US), Daniel Weiner (US), Richard L. Varco
(US), Robert Alan Good (US), Robert Schwartz (US), and William Dameshek (US)
demonstrated a 6-mercaptopurine dose-related prolongation of rabbit skin
allograft survival rate (1041; 1378).
Roy Y. Calne
(GB), Charles F. Zukoski (US), Hyung M. Lee (GB), and David M. Hume (US)
obtained very similar results with canine renal homografts (216; 1719).
Gertrude
Belle Elion (US). Sandra W. Callahan (US), George Herbert Hitchings (US), and
R. Wayne Rundles (US) synthesized azatioprine, an analog of 6-mercaptopurine,
to use in chemotherapy (397).
Roy Y. Calne
(GB) carried out extensive preclinical studies in dogs on the efficacy of using
6-mercaptopurine and its analogue azathioprine as immunosuppressive agents in
transplantation surgery. He successfully delayed kidney rejection in dogs from
the usual ten days to forty-four days (217).
Roger Michael Hardisty (GB) and Joel Margolis (PL-AU) suggested
activation of plasma thromboplastin
antecedent (PTA) by activated Hageman factor
(617).
Oscar Davis Ratnoff (US), Earl Warren Davie (US), and David L.
Mallett (US) provided clear evidence for
the activation of plasma thromboplastin antecedent (PTA) by activated Hageman
factor (1269).
Jean-Pierre Soulier (FR), Odette Prou-Wartelle (FR), and Doris
Menache (FR) suggested that activated plasma
thromboplastin antecedent (PTA) activates
Christmas factor (1449).
Oscar Davis Ratnoff (US) and Earl Warren Davie (US) proved the
activation of Christmas factor
by activated plasma
thromboplastin antecedent (PTA) (1268).
Hilda
Margaret Bruce (GB) found that if she housed newly mated pregnant females with
male mice that were not the father of the carried embryo the rate of
miscarriages increased, these females subsequently returning to estrus and
mating with the new male. No increased rate of miscarriages occurred when
pregnant mice were paired with juvenile or castrated mice (183; 184). This is referred to as the Bruce effect.
Andrzej
Krzysztof Tarkowski (PL) showed that a single blastomere isolated from a 2-cell
stage mouse embryo is fully able to develop and the result is a healthy and
fertile mouse
Oliver Murray Wrong (GB) and Howard E.F. Davies (GB) described the
urinary response to an acid load, taken as a single oral dose of ammonium
chloride. Study of normal subjects and patients with different forms of kidney
disease distinguished the factors influencing urinary acidification and
ammonium excretion (1687).
Charles S.
Lieber (US), Leonora M. DeCarli (US) and Rudi Schmid (US) documented two new
fundamental concepts: (1) Ethanol exerts direct effects on the liver which
might play a role in the development of liver disease. (2) Some of these
effects on the liver could be traced to the metabolism of ethanol (918; 920).
Charles S.
Lieber (US), Don P. Jones (US), and Leonora M. Carli (US) established in vivo: with the development of a new alcohol
feeding technique as part of a nutritionally adequate, totally liquid diet,
rats were shown to develop a fatty liver—the first stage of alcoholic liver
disease—in the absence of dietary deficiencies. This was later confirmed in man
(919).
Charles S.
Lieber (US), Leonora M. DeCarli (US), and Emanuel Rubin (US) noted, the final
and irreversible stage of liver disease, namely cirrhosis, was produced in the
baboon despite adequate diets (917).
Charles S.
Lieber (US) showed the link between ethanol effects and its metabolism, led to
the demonstration that alcoholic hyperuricemia, ketosis, hypoglycemia, and
various other metabolic complications can be ultimately attributed to such a
mechanism. Extension of this concept prompted studies concerning the
hepatotoxicity of acetaldehyde. Further investigation of the metabolism of
ethanol resulted in the discovery of an alternate pathway in the microsomes
associated with activation and inactivation of drugs, hepatotoxic agents,
carcinogens, and endogenous steroids (916).
Alan J.
Johnson (US) and W. Ross McCarty (US) were the first to report that
artificially induced thrombi in human volunteers could be lysed by infusion of
purified streptokinase (SK)
preparation (752).
Inga Marie Nilsson (SE) and Bertil Olow (SE) administered various doses
of streptokinase (SK), SK plus
plasminogen, and SK plus E-amino caproic acid (EACA) in a series of 67 surgical
patients. SK produced a high fibrinolytic activity but had a significant effect
on the coagulation factors. It proved possible to counteract the coagulation
defect by SK combined with EACA without affecting the lysis of the clot (1135; 1184).
Henri-Géry Hers (BE) first identified hepatic
phosphorylase deficiency (Hers disease) when he saw three patients
presenting with hepatomegaly and glycogen storage in the liver (658).
Paul E.
Teschan (US), Thomas F. O’Brien (US), and Charles R. Baxter (US) introduced
“prophylactic daily dialysis” for the treatment of acute renal failure. Blood
cloting was very common (1546).
Wayne
Quinton (US), David Dillard (US), Belding Hibbard Scribner (US), Rachit Buri
(US), John E.Z. Caner (US), Robert M. Hegstrom (US), and James M. Burnell (US)
developed dialysis arterioveneous cannulas using teflon tubing. For the first
time, blood flow could be keep open for days allowing continuous dialysis (1249; 1385). Note: Improvements to the technique came
rapidly and by 1962 the world’s first freestanding dialysis center was opened
in Seattle, Washington.
S.T. Boen
(NL), Adyr Soares Mulinari (BR), David H. Dillard (US) and Belding Hibbard
Scribner (US) published on Boen’s concept for peritoneal dialysis (150).
M. Henry
Cass (GB) and Russell C. Brock (GB) described the standard current practice of
combining the multiple pulmonary venous and venacaval anastomoses into two
large atrial anastomoses during the replacement of the heart in dogs. No dogs
survived this operation (243).
Richard R.
Lower (US) and Norman E. Shumway (US) independently developed the same
procedure but preserved allografts with immersion hypothermia. The dogs
survived (940).
Norman E.
Schumway (US), Richard R. Lower (US), Raymond C. Stofer (US), Edward J. Hurley
(US), and Eugene Dong, Jr. (US) begin a long series of experiments in animal
heart transplantation (940-943; 1414).
Richard R.
Lower (US), Raymond C. Stofer (US), and Norman E. Shumway (US) conceptualized
and refined the atrial cuff technique of orthotopic heart transplantation in
dogs. This innovation enabled the transplanted heart to adequately support the
circulation and allowed the recipient dogs to survive and exercise normally for
up to three weeks (943). Tissue
rejection was a serious problem at this time.
Richard R.
Lower (US), Raymond C. Stofer (US), Edward J. Hurley (US), and Norman E.
Shumway (US) completed technically successful canine heart-lung transplantation
in nonimmunosuppressed dogs with 5-day survival (942). With long
survival the same operation was done under cyclosporine two decades later,
first in monkeys then in man.
Richard R.
Lower (US), Raymond C. Stofer (US), Edward J. Hurley (US), Eugene Dong, Jr.
(US), Roy B. Cohn (US), and Norman E. Shumway (US) discovered that dog hearts
intended as allografts can be preserved for 7 hours by immersion at 2°to 4C° (939; 941).
Bruce A.
Reitz (US), John L. Pennock (US), and Norman E. Shumway (US) reported
successful heart-lung transplantation in humans (1279).
Basil M.
Wright (GB) and Colin B. McKerrow (GB) introduced the peak flow meter to
measure maximum forced expiratory flow rate (1686). This is
especially helpful in diagnosis of pneumoconiosis, i.e., lung damage due to
inhalation of minute particles.
Henry L. Price (US), Harry W. Linde (US), Richard E. Jones (US), Gerald
W. Black (US), and Mary L.
Price (US), following the development of a sensitive, highly specific method for
detecting catecholamines determined, for the first time, whether certain
general anesthetics caused sympathetic nervous excitation in man. They found
that diethyl ether and cyclopropane did so, thus explaining the great safety of
these anesthetic agents, since their directly depressant actions on myocardium
are partially antagonized by sympathetic stimulation (1240).
Norman
Orentreich (US) performed autograft hair transplant surgery to remedy hair loss
(alopecias) (1185).
Francis
Daniels Moore (US), Louis L. Smith (US), Thomas K. Burnap (US), Frederick D.
Dallenbach (DE), Gustave J. Dammin (US), Ulrich F. Gruber (CH), William C.
Shoemaker (US), Richard W. Steenburg (US), Margaret R. Ball (US), and John S.
Belko (US) developed the surgical technique for orthotopic canine liver
transplantation (1092).
Thomas Earl
Starzl (US), Carl G. Groth (US), Lawrence Larry Brettschneider (US), Israel
Penn (US), Vincent A. Fulginiti (US), John B. Moon (US), Herve Blanchard (US),
Alfred J. Martin, Jr. (US), Ernest K. Cotton (US), and Kendrick Arthur Porter
(US) gave the first report of prolonged survival rates of children after
orthotopic liver transplantation (1464; 1465).
Orrie A.
Couch, Jr. (US) reported the first successful surgical treatment of ventricular
tachycardia, when he resected a ventricular aneurysm in a male patient with
anterior wall/apex aneurysm (302).
Colonel R.
Montgomery (GB), Robin D. Powell (US), George J. Brewer (US), Alf S. Alving
(US), Joseph S. Lunn (US), G. Robert Coatney (US), Don Edgar Eyles (US), C.C.
Hoo (MY), McWilson Warren (US), Arthur Anamthara Sandosham (MY), Martin D.
Young (US), Peter G. Contacos (US), Joseph E. Stitcher (US), Jack W. Millar
(US), Edith D. Box (US), Quellin T. Box (US), and David Payne (CH) reported chloroquine resistance in Plasmodium falciparum and Plasmodium vivax, the 2 parasite species
responsible for most human malaria cases. Foci of resistant P. falciparum were detected in Malaya,
Colombia, the Cambodia-Thailand border, and Porto Velho, Brazil during the late
1950s (161; 295; 424; 1088; 1089; 1208; 1235; 1346; 1708).
Victor Bruce Darlington Skerman (AU) composed keys for the
identification of bacteria and wrote A
Guide to the Identification of the Genera of Bacteria (1432).
Bengt E.
Gustafsson (SE) found that germ-free
rats fed a diet without vitamin K rapidly become hemorrhagic and required their
diet to be supplemented with vitamin B to survive. Germ-free rats require a
higher intake of exogenous sources of vitamins K, B12 and B6 compared to their
conventional counterparts. Microbial communities are in direct and continuous
contact with their host from birth, contributing to host nutrition and
metabolism through vitamin production (594).
Denise Kelly (GB), Timothy King (GB), Rustam Aminov (GB), Silvia C.
Resta (US), Dan R. Littman (US), and Eric G. Pamer (US) showed that gut
bacteria play a pivotal role in immune modulation and development of the
nervous system and are the main source of vitamin K, and to a lesser extent the
vitamin B complex (796; 929; 1280).
Meyer Friedman (US) and Ray H. Rosenman (US) used three groups of men,
selected solely according to the behavior pattern which they habitually
manifested in their work, were compared with respect to their serum cholesterol
levels, clotting times, presence of clinical coronary disease, and presence of
arcus senilis. A group (A) of 83 men were chosen as manifesting an intense,
sustained drive for achievement and as being continually involved in
competition and deadlines, both at work and in their avocations. In this group
the serum cholesterol level, the frequency of arcus
senilis, and the incidence of coronary
artery disease were much higher than in a group (B)
of 83 men who manifested the opposite sort of behavior pattern and a group (C)
of 46 unemployed blind men selected as manifesting a chronic state of
insecurity and anxiety. Clinical coronary artery disease was seven times more
frequent in group A than in group B or group C. Analysis of factors other than
the overt behavior pattern described indicated that this pattern per se was
largely responsible for the striking differences found (491).
Morton H. Maxwell (US), Robert E. Rockney (US), Charles R. Kleeman (US),
and Mary R. Twiss (US), reported that complications of earlier methods of
peritoneal dialysis are eliminated by a new technique of intermittent dialysis
utilizing commercially prepared electrolyte solutions, special catheters, and a
"closed system" of infusion and drainage. This was mechanically successful
in 76 instances. Conditions treated satisfactorily included acute renal
failure, barbiturate poisoning, intractable edema, hepatic coma, hypercalcemia,
and chronic uremia. Although less efficient than the artificial kidney on an
hourly basis, peritoneal lavage is easier to use over extended periods of time (1027).
Eugene F. Poutasse (US) developed renal arteriography. He
discovered that in many patients with renal hypertension the condition can be
corrected by removing the obstruction, grafting a new vessel, or removing the
part of the kidney supplied by the diseased artery (1234).
Seymour Solomon Kety (US) used adoption as a means of separating
environmental and genetic factors in the transmission of schizophrenia among
family members. He concluded that about 50% of schizophrenia is of genetic
origin, and the mode of inheritance polygenic (804).
Maxwell
Finland (US), Wilfred F. Jones, Jr. (US), and Mildred W. Barnes (US)
highlighted that the introduction and widespread use of chemotherapeutic and
antibiotic agents has resulted in profound changes in the number and character
of infections that are being encountered. Emphasis has been placed most
recently on the number and seriousness of staphylococcic infections,
particularly those occurring within hospitals. This has been brought strikingly
into our consciousness because of the large number of outbreaks in nurseries
and maternity wards and by the high incidence of infections in originally clean
surgical wounds and as complications of debilitating diseases, events which
have resulted in considerable morbidity and appreciable mortality within
hospitals. There is also some evidence of extension of these infections into
the communities. The problem has been recognized as being world-wide and
extending to all areas where antibiotics have been extensively used (439).
Samuel Noah
Kramer (US) reported that Sumerian cuneiform tablets list various drugs to be
used in the treatment of common ailments, c. 5,500 BCE (846).
Mary Douglas
Nicol Leakey (GB-KE) found a hominid skull belonging to the ultra-robust Australopithecus boisei: Paranthropus boisei: Zinjanthropus boisei at Olduvai Gorge, Tanzania (881). Australopithecus boisei: Paranthropus boisei: Zinjanthropus boisei existed between
2.1 and 1.1 million years ago. It is like robustus,
but the face and cheek teeth are even more massive, some molars being up to 2
cm across. The brain size is very similar to robustus, about 530 cc. A few experts consider boisei and robustus to be
variants of the same species.
The journal Biochemical and
Biophysical Research Communications was founded.
1960
"By
their diseases ye shall know them - the endocrines." James H. Means (1038).
"Gamble
did more than anyone to bring the various ideas of the behavior of body water
and electrolytes into a coherent picture. He was responsible for many of the
fundamental concepts. His way of looking at extracellular fluids was his great
contribution and provides the basis for modern fluid therapy." Daniel C.
Darrow (US) commenting on the work of James L. Gamble (US) (326).
Willard
Frank Libby (US) was awarded the Nobel Prize in Chemistry for his method to use
carbon-14 for age determination in archaeology, geology, geophysics, and other
branches of science.
Frank
Macfarlane Burnet (AU) and Peter Brian Medawar (GB) were awarded the Nobel
Prize in Physiology or Medicine for discovery of acquired immunological
tolerance.
Theodore H.
Maiman (US) built the first practical laser, a device that produces
monochromatic coherent light, or light in which the rays are all of the same
wavelength and phase (981). His invention relied on theoretical
work by Charles Hard Townes (US) and Arthur Leonard Schawlow (US) (1360). The term laser (Light Amplification by Stimulated
Emission of Radiation) was coined for the device.
Irving
Friedman (US) and Robert L. Smith (US) described obsidian hydration as a new
method for dating obsidian artifacts (490). The
relative and occasionally absolute dates ascribed to obsidian artifacts are
possible because obsidian "sorbs" moisture from the atmosphere. This
method is most accurate for objects between 500 and 200,000 years old.
Alan B.
Cameron (US), and Raymond J. Thabet (US) introduced the sigmoidoscope as part of
routine cancer clinic examinations. This permitted early identification of
colorectal cancer as well as precancerous polyps, leading to increased survival
rates (218).
Iris
Lansdrop-Vogelaar (NL), Marjolein van Ballegooijen (NL), Deborah Schrag (NL),
Rob Boer (NL), Sidney J. Winawer (NL), J. Dik F. Habbema (NL), and Ann G.
Zauber (NL) noted
that today, it is estimated that screening, by sigmoidoscopy, colonoscopy,
barium enema, or fecal occult blood testing, may result in a 20% decrease in
colorectal cancer mortality (874).
George A.
Bray (US) offered a modification of the naphthalene-dioxane system for counting
radioactive compounds in aqueous solutions using a liquid scintillation counter
that has a relatively high efficiency for both carbon-14 and tritium. The
modification of the naphthalene-dioxane procedure has been used to count
glycolytic intermediates on paper chromatograms. It has also been used to
determine radioactive glucose incorporation into glycogen by counting the acid
hydrolyzate of the isolated glycogen (164).
John Oró
(US), E. Stephen-Sherwood (US), and Aubrey P. Kimball (US) synthesized adenine,
thymine, amino acids, and other biochemical compounds from HCN in a primitive
Earth environment (1189; 1191; 1475).
Emil Palecek
(CZ) discovered the electroactivity of nucleic acids (1196).
Karl A. Piez
(US) and Louise Morris (US) modified the Sparkman, Moore, and Stein procedure
for amino acid analysis by using a continuous salt and pH gradient for elution
and separation on a single column of all the amino acids in protein
hydrolysates, including hydroxyproline and hydroxylysine (1218).
W. Gordon Whaley (US), Hilton H. Mollenhauer (US), and James H. Leech
(US) gave the
first demonstration of a substantial number of organelles in the plant cell and
thus a closer equation of the plant cell and the animal cell. They depicted
plant systems in which progressive stages of differentiation could be followed (1654).
David M.
Neville, Jr. (US) described a procedure for isolating cell membranes from rat
liver homogenates (1129).
Leslie G.
Paleg (AU) established the basis of a new understanding of the relationship
between the cereal embryo and endosperm. It gave the first indication of a
hormonal effect on enzyme activity in plants, and suggested a very sensitive,
short, and reliable hormonal bioassay (1197).
David L.
Trout (US), E. Harvey Estes, Jr. (US), and Samuel J. Friedberg (US) identified
substances that interfere with Dole’s titrimetric method for measuring plasma
free fatty acids and added a step to remove them from the fatty acid extract (1576).
Jules Hirsch
(US) described a simple method for the analysis of the fatty acid composition
of stored fat in man. The composition is a close reflection of mean dietary fat
composition over years, and changes slowly in relation to dietary changes (675).
Beginning in
the 1960's the National Aeronautics and Space Administration (NASA) has
directly or indirectly provided numerous contributions to medicine. Examples
are digital imaging breast biopsy system, breast cancer detection using solar
cells, laser angioplasty, ultrasound skin damage assessment, human tissue
stimulator, cool suit, programmable pacemaker, ocular screening, automated
urinalysis, medical gas analyzer, voice-controlled wheelchair, arteriosclerosis
detection, ultrasound scanners, automatic insulin
pump, portable x-ray device, invisible braces, dental arch wire, palate surgery
technology, clean room apparel, implantable heart aid, magnetic resonance
imaging (MRI), bone analyzer, and cataract surgery tools.
Joseph D. Mandell (US) and Alfred Day Hershey (US) developed a
fractionating column which could separate closely similar nucleic acids, e.g.
those derived from T2 and T4 bacteriophages of E. coli; deoxyribonucleic acid broken by hydrodynamic shear from
its starting material (990).
Mary Ellen
Jones (US) and Leonard Spector (US) established that carbon dioxide or
bicarbonate is the source for the initial activation step leading to carbamyl
phosphate formation by carbamyl-phosphate
synthetase in animal tissues. They showed that oxygen was added to the
orthophosphate residue of carbamyl phosphate via equilibration of water with
bicarbonate (757).
Maria A.
Rongine DeFekete (AR), Luis Federico Leloir (AR), and Carlos Eugenio Cardini
(AR) discovered the role of sugar nucleotides in the synthesis of starch (341).
Robert Burns
Woodward (US), William A. Ayer (US), John M. Beaton (US), Friedrich Bickelhaupt
(NL), Raymond Bonnet (GB), Paul Buchschacher (US), Gerhard L. Closs (DE-US),
Hans Dutler (CH), John Hannah (US), Fred P. Hauck (US), Sho Ito (JP), Albert
Langemann (US), Eugene LeGoff (US), Willy Leimgruber (US), Walter Lwowski
(DE-US), Jürgen Sauer (DE), Zdenek Valenta (CZ) and Heinrich Volz (DE) reported
the total in vitro synthesis of
chlorophyll a. In the process the authors discovered the remarkable
susceptibility of chlorophyll to electrophilic attack (1684).
Martin
Strell (DE), Anton Kalojanoff (DE), and Hugo Koller (DE) independently carried
out the total synthesis of chlorophyll a (1495).
Sakae Katoh (JP) discovered plastocyanin, a small copper
containing protein which functions as an electron transfer agent between
cytochrome f of the cytochrome b6f complex of photosystem 2 and P700+
from photosystem 1 (784).
He and Atusi
Takamiya (JP) worked on the photo-reduction (Hill reaction)
of this substance and its effect on the photo-reduction of other known Hill
reagents (785).
Peter M. Colman (AU), Hans C. Freeman (AU), J. Mitchell Guss (AU),
Mitsuo Murata (), Valerie A. Norris (AU), John A.M. Ramshaw (AU), Madhugiri
P. Venkatappa (IN) used x-ray crystal analysis at 2.7 angstrom resolution to
determine the 3-dimensional structure of oxidized [Cu (II)] plastocyanin from
poplar leaves (290).
Earl B.
Herr, Jr. (US), Michael E. Haney, Jr. (US), Gail E. Pittenger (US), and Calvin E.
Higgins (US) isolated the antibiotic capreomycin
from Streptomyces capreolus (657).
Maynard E.
Pullman (US), Harvey S. Penefsky (US), Anima Datta (IN), and Efraim Racker
(PL-AT-US) were the first to identify an enzyme of oxidative phosphorylation,
the Factor 1 or F1 portion of the ATP synthase unit from mitochondria (1210; 1247).
Helmut
Beinert (DE-US) and Richard H. Sands (US) used paramagnetic resonance
spectrometry (EPR) to discover the class of cellular electron carriers called
iron-sulfur centers (110). These
centers are involved in the transfer of reducing equivalents from the flavin to
ubiquinone.
Maxine Frank
Singer (US), Russell J. Hilmoe (US), and Leon A. Heppel (US) showed that short
oligonucleotides could serve as primers for polynucleotide phosphorylase
(PNPase). Specifically, they found that oligoribonucleotides with an
unesterified, terminal, C-3' hydroxyl group served as primers for the
polymerization of adenosine 5'- diphosphate, uridine 5'-diphosphate, and
thymine ribonucleoside pyrophosphate catalyzed by polynucleotide phosphorylase. The oligonucleotides were starting
points for chain proliferation but were not incorporated into the finished
polymer (1423).
Maxine Frank
Singer (US), Russell J. Hilmoe (US), and Leon A. Heppel (US) discuss the
polymerization of guanosine diphosphate by PNPase.
They showed that GDP, when present alone, is not polymerized by enzyme
fractions from Agrobacterium agile or
Escherichia coli. However,
polymerization of GDP did take place in the presence of oligonucleotide primers
with an unsubstituted hydroxyl group at carbon 3' of the terminal nucleoside
residue. Unlike polymerization reactions with adenosine 5'-diphosphate, uridine
5' diphosphate, and thymine ribonucleoside pyrophosphate, the primers were
incorporated into the polymer (1424).
George R.
Stark (US), William Howard Stein (US), and Stanford Moore (US) discovered that
cyanate, formed from urea, can carbamylate the amino groups of proteins (1462).
Kimiko
Sato-Asano (JP) and Fujio Egami (JP) discovered takadiastase ribonuclease T1, an enzyme that cleaves RNA chains at
guanylic acid (G-) residues (1352).
Torkel
Weis-Fogh (DK-GB) describes resilin. He explains its roles in the thorax of
flying insects: as elastic tendons in dragonflies and as elastic wing hinges in
locusts. He also shows that these structures could be strained for weeks
without plastic deformation and, by simple tests, that the elasticity was
rubber-like. This contrasted with commercial rubbers, which are polymeric
unsaturated hydrocarbons: resilin is a cuticular protein that, typically, is
deposited after ecdysis. Weis-Fogh notes the ability of resilin structures to
snap back after deformation but shows that their rubbery nature is affected by
their hydration and pH. He describes a simple test to identify resilin: with
very dilute solutions of methylene Blue or toluidine Blue, the protein stains a
deep sapphire blue (1646).
John Bishop
(US), John Leahy (US), Richard S. Schweet (US), and Howard M. Dintzes (US)
demonstrated that proteins grow by stepwise addition of individual amino acids
beginning at the amino terminal end and growing toward the carboxyl end (140; 350).
Esther A.
Allen (US), Edward Glassman (US), Eugene Cordes (US) and Richard S. Schweet
(US) were the first to refer to soluble
RNA (sRNA) as transfer RNA (tRNA) (19).
Alexander
Rich (US) showed that RNA and DNA can accommodate one another to form a hybrid
helix containing one strand of poly dT and one strand of poly rA. This was the
first experimental demonstration of a hybrid helix (1284). This immediately
provided experimental support for a model of how DNA could “make” RNA.
John J.
Furth (US), Jerard Hurwitz (US), and Monika Goldmann (US) demonstrated that the
formation of a DNA-RNA hybrid is critical to the transfer of information from
DNA to RNA (499).
Charles
Yanofsky (US) and Patricia St. Lawrence (US) suggested that certain mutations
might lead to the formation of either altered tRNA or altered AA-tRNA synthetases which could modify
the translation process (1703).
Francis
Harry Compton Crick (GB), Sydney Brenner (ZA-GB), and Francois Jacob (FR) were
at Cambridge University on Good Friday brainstorming about how the genetic code
might work when they conceived the notion of the messenger—a molecule, which
delivered the gene’s instructions to the location where proteins are, assembled (761).
Britton
Chance (US) and Gunnar Hollungar (US) found experimental evidence that the
reduction of mitochondrial NAD can be accomplished by oxidation-reduction
couples having potentials several hundred millivolts higher than that of the
NAD couple. These results indicated that the respiratory chain could utilize
energy conserved at some sites to drive energy-requiring reactions at others (252).
Akira
Tsugita (US), Duane Tolbert Gish (US), Janis D. Young (US), Heinz Ludwig
Fraenkel-Conrat (DE-US), C. Arthur Knight (US), and Wendell Meredith Stanley
(US) worked out the entire 158 amino acid sequences of the capsomere protein
subunits in tobacco mosaic virus (1577).
Cedric
Inglis Davern (US) and Matthew Stanley Meselson (US) discovered that the
ribosomal RNA of bacteria is extremely stable (327).
Charles G.
Kurland (SE) showed that the 18S RNA molecule is part of the 40S ribosomal
subunit while the 28S RNA is part of the 60S ribosomal subunit (861).
Julius
Marmur (US), Paul Mead Doty (US), Dorothy Lane (US), Carl L. Schildkraut (US),
Joseph Eigner (US), and Robert Rownd (US) discovered that double stranded DNA
can be converted to single-stranded units by heat treatment. Such treatment is
a type of denaturation and is called melting.
They showed that the complementary single strands of DNA recombine to form
native double helices when they are kept for several hours at sub-denaturing
conditions (approximately 65° C). This is called annealing or renaturation.
The degree and efficiency of annealing
is believed to be related to base sequence homology and therefore a reflection
of phylogeny (363; 1004; 1006-1008; 1364).
Arthur J.
Kornberg (US), Samuel Bernard Weiss (US), Charles Clifton Richardson (US),
Baldomero M. Olivera (US), Israel Robert Lehman (US), Steven B. Zimmerman (US),
John W. Little (US), Carol K. Oshinsky (US), and Martin Frank Gellert (US) made
major contributions to discovering those proteins associated with DNA
replication (833; 1183; 1652; 1715).
Richard H. Epstein (CH), Antoinette
Bolle (CH), Charles M. Steinberg (US), Eduard Kellenberger (US), Robert S.
Edgar (US), Millard Susman (US), Getta Harmr Denhardt (US), and Ilga Lielausis
(US) determined that at least seven viral gene products are required for the T4
bacteriophage to replicate its DNA (420). These results strongly suggested
that the replication of DNA requires not one but a group of enzymes.
Masayasu
Nomura (JP-US), Benjamin D. Hall (US), and Solomon Spiegelman (US) found that
viral RNA produced immediately following infection of Escherichia coli by T2 bacteriophage is not soluble viral RNA nor
is it ribosomal viral RNA. It appears to associate itself with the 30S
ribosomal particles (1146).
Ulrich
Clever (DE) and Peter Karlson (DE) discovered that the molting hormone, ecdysone, induces puffs in the giant
salivary chromosomes of Chironomus tentans (282).
Peter
Karlson (DE) proposed that hormones, such as ecdysone, control gene activity by stimulating transcription and
translation (778).
Peter
Karlson (DE), Hans Hoffmeister (DE), Walter Hoppe (DE), and Robert Huber (DE)
were the first to identify ecdysone,
a molting hormone found in arthropods. They extracted it from 1,000 pounds of
silkworm pupae (780).
Wolfgang
Haupt (DE) presented evidence that the photoreversible pigment (phytochrome) is
associated with the cell membrane in Mougeotia,
a green alga (632; 633).
Mohammad
Iqbal Hussain Aleem (PK-US) and Alvin Nason (US), while studying Nitrobacter, gave the first conclusive
evidence that oxidative phosphorylation occurs in chemolithotrophic bacteria (14).
Robert
Emerson (US) and Eugene I. Rabinowitch (US) demonstrated the importance of
auxiliary pigments to the efficiency of photosynthesis (409).
Richard H.
Hageman (US) and Donna Flesher (US) found that both light and substrate,
nitrate, are required for the formation (induction) of nitrate reductase in leaves of young maize seedlings. Light was
also required for maintenance of nitrate
reductase in seedlings well supplied with endogenous nitrate. Correlations
between activity and changes in protein content indicated that the in vitro activities reflected in situ activities (599).
Richard H.
Hageman (US), Christopher F. Cresswell (ZA), and Eric J. Hewitt (GB) demonstrated
the enzymatic conversion of nitrate to ammonia in the presence of the
non-physiological electron donor reduced benzyl vologen in higher plants (598). Note: This work stimulated a search for the endogenous reductant
which was characterized as ferredoxin providing support for the close
association of photosynthesis and nitrite assimilation. It was recognized
that nitrate availability influenced the tissue levels of nitrate reductase and it was suspected that the enzyme was
substrate induced.
Leonard
Beevers (US) and Richard H. Hageman (US) provided a review of nitrate
metabolism in higher plants. In addition to reviewing the properties of enzymes
involved in nitrate and nitrite assimilation, the review discussed the factors
regulating activity and level of the enzymes and the physiological consequences
of an altered nitrate metabolism (109).
Hans Joachim
Müller-Eberhard (DE-US-DE) and Ulf R. Nilsson (SE) isolated the beta
1C-globulin (C3c) component of complement (1107).
Benjamin H.
Sweet (US) and Maurice Ralph Hilleman (US) discovered simian virus 40 (SV40) as
a vacuolating agent in African green
monkey cell cultures (1503).
John D.
Smith (US), Gustave Freeman (US), Marguerite Vogt (US), and Renato Dulbecco
(IT-US) demonstrated that simian virus 40 (SV40), and polyoma virus are both
DNA viruses in which the DNA occurs in a cyclic, or circular, shape as well as
a linear form; both forms giving rise to new virus and to cancer when they
enter receptive cells, but the ring form is more active (378; 1440).
Vernon Riley (US) K.E.K. Rowson (GB), Myer H.
Salaman (GB), and D.H. Adams (GB) found that lactate dehydrogenase-elevating
virus (LDV), a.k.a. Riley's virus, when coupled with a transplantable tumors of
many types caused a five- to ten-fold increase in plasma lactate
dehydrogenase (LDH) activity within 3 days of transplantation and before
the tumors were clinically obvious. To produce this dramatic increase in plasma
enzyme level it was not necessary to transplant cells; cell-free plasma from
tumor-bearing mice was equally effective. The raised enzyme level could be
serially transmitted from mouse to mouse and proved to be caused by a virus
which replicated rapidly in mouse macrophages (1298; 1327; 1328).
David Arthur
John Tyrrell (GB), Griselda Hitchcock (KE-GB), M.L."Will" Bynoe (BR),
Helio Gelli Pereira (BR), and Christopher Howard Andrewes (GB) grew the
rhinovirus (common cold) in primary
human fetal and monkey kidney tissue culture (1579).
Christopher
Howard Andrewes (GB) named them rhinoviruses (31).
Michael
George Rossmann (US), Edward Arnold (US), John W. Erickson (US), Elizabeth A.
Frankenberger (US), James P. Griffith (US), Hans-Jürgen Hecht (DE), John E.
Johnson (US), Greg Kamer (US), Ming Luo (US), Anne G. Mosser (US), Roland R.
Rueckert (US), Barbara Sherry (US), and Gerrit Vriend (NL) worked out the three
dimensional structures of human rhinovirus (HRV) by x-ray crystallography (1319).
Donald E.
Staunton (US), Vincent J. Merluzzi (US), Robert Rothlein (US), Richard Barton
(US), Steven D. Marlin (US), and Timothy Alan Springer (US) discovered that
I-CAM-1 is the major surface receptor for the rhinoviruses (CAM=cell adhesion
molecules) (1470).
Steven D.
Marlin (US), Donald E. Staunton (US), Timothy Alan Springer (US), Christian
Stratowa (AT), Wolfgang Sommergruber (AT), and Vincent J. Merluzzi (US)
solubilized the I-CAM-1 receptor and found that it would block the normal
rhinovirus receptor site. This could have promise as a prophylactic for the common cold (1003).
Walter
Plowright (GB), R.D. Ferris (GB), and Gordon R. Scott (GB) discovered the
bovine malignant catarrhal fever virus (1222).
Daniel S.
Rowe (US), Richard H. Michaels (US), Robert Merritt Chanock (US), Hyun Wha Kim
(US), Andrew J. Vargosko (US), Ann Deleva (US), Karl M. Johnson (US), Christine
Cumming (US), Robert H. Parrott (US), Horace C. Turner (US), Robert Joseph
Huebner (US), Albert Zaven Kapikian (US), Joseph A. Bell (US), and Francis M.
Mastrota (US) first described viral pneumonia caused by respiratory syncytial
virus (RSV) in older adults (259; 775; 1204; 1321). RSV was
not appreciated as a significant pathogen until outbreaks of infection in
nursing homes were reported in the 1980s.
William H.
Barker (US) and John P. Mullooly (US) noted that influenza vaccination of
elderly persons led to a reduction in pneumonia and influenza hospitalizations
and deaths (82).
Marvin R.
Lamborg (US) and Paul Charles Zamecnik (US) developed the first bacterial
cell-free system, which proved to be reliable for metabolic experiments (867).
Alfred
Tissières (CH), David Schlessinger (US), and Francoise Gros (FR) improved this
system and reached the conclusion that in Escherichia
coli the active ribosomes are 70S
units, which contain a functional component. The 30S or 50S units are not
active (1562).
Francois
Jacob (FR), David Perrin (FR), Carmen Sanchez (FR), and Jacques Lucien Monod
(FR) worked with the Lac segment of Escherichia coli and defined the operon as the genetic unit of co-ordinate expression, i.e., composed of a
combination of structural and regulator genes used to control the production of
enzymes necessary for the utilization of lactose
(739).
Monica Riley
(US), and Arthur Beck Pardee (US), Francois Jacob (FR), and Jacques Lucien
Monod (FR) performed an experiment with Escherichia
coli which indicated that for a protein to be produced a gene must
continually express itself through the production of an intermediate molecule
which is not ribosomal RNA (1292).
Alain
Bussard (FR), Shiro Naono (FR), Francoise Gros (FR), and Jacques Lucien Monod
(FR) performed an experiment where Escherichia
coli was grown in the presence of a base analog of uracil
(beta-fluorouracil). The results implicated an RNA molecule as an intermediate
between DNA and protein synthesis (202).
Martynas
Ycas (US) and Walter S. Vincent (US) found a transient RNA in yeast cells with
base ratios matching those of the yeast’s DNA (1705).
Francois
Jacob (FR), Jacques Lucien Monod (FR), Sydney Brenner (ZA-GB), Matthew Stanley
Meselson (US), Francois Gros (FR), Howard H. Hiatt (US), Walter Gilbert (US),
Charles G. Kurland (SE), Robert W. Risebrough (US), and James Dewey Watson (US)
reported their classic experiments proving the existence of messenger RNA (172; 584; 737; 738).
“The
molecular structure of proteins is determined by specific elements, the structural genes. These act by forming a
cytoplasmic transcript of themselves,
the structural messenger, which in turn synthesizes the protein. The synthesis
of the messenger by the structural gene is a sequential replicative process,
which can be initiated only at certain points on the DNA strand, and the
cytoplasmic transcription of several, linked, structural genes may depend upon
a single initiating point or operator.
The genes whose activity is thus coordinated form an operon.
The operator
tends to combine (by possessing a base sequence) specifically with a certain
(RNA) [now known to be proteinaceous] fraction possessing the proper
(complementary) sequence. This combination blocks the initiation of cytoplasmic
transcription and therefore the formation of the messenger by the structural
genes in the whole operon. The specific repressor
(RNA?), acting with a given operator, is synthesized by a regulator gene.
The
repressor in certain systems (inducible enzyme systems) tends to combine
specifically with certain specific small molecules. The combined repressor has
no affinity for the operator, and the combination therefore results in activation of the operon.
In other
systems (repressible enzyme systems) the repressor by itself is inactive (i.e.,
it has no affinity for the operator) and is activated only by combining with
certain specific small molecules. The combination therefore leads to inhibition
of the operon.
The
structural messenger is an unstable molecule, which is destroyed in the process
of information transfer. The rate of messenger synthesis, therefore, in turn
controls the rate of protein synthesis…
The property
attributed to the structural messenger of being an unstable intermediate is one
of the most specific and novel implications of this scheme…This leads to a new
concept of the mechanism of information transfer, where the protein
synthesizing centers, (ribosomes) play the role of non-specific constituents
which can synthesize different proteins, according to specific instructions
which they receive from the genes through M-RNA”
(737).
Charles C.
Shepard (US) was the first to grow Mycobacterium
leprae in an experimental animal. He injected the microorganism into the
footpads of mice (1407).
Robert Day
Allen (US), John W. Cooledge (US) and Prudence J. Hall (US) showed that the cytoplasm
of amoeba retains the ability to move by cytoplasmic streaming when extracted
from cells (21).
Peter C.
Nowell (US) found that the mucoprotein plant extract, phytohemagglutinin (PHA)
is a specific initiator of mitotic activity: in its presence, cell division
occurs; on its absence, no mitosis appears. The data suggested that the
mitogenic action of PHA does not involve mitosis per se but rather the stage preceding mitosis—the alteration of
circulating monocytes and large lymphocytes to a state wherein they are capable
of division (1151).
Peter C.
Nowell (US) found that the glucocorticoid prednisolone 21-phosphate has almost
precisely the opposite effect in its role as an inhibitor of mitosis in
leukocytes (1152).
Daniel B.
Fisher (US) and Gerald C. Mueller (US) were the first to report the
relationship between inositol lipids and cell proliferation (lymphocytes
stimulated with phytohemagglutinin) (446).
Robert Lee
Hill (GB) and Fay Bendall (GB) used herbicide inhibitors to block steps in the
electron transport system of photosynthesis. These techniques revealed what
they called the Z pathway. The first
leg of the Z is the flow of electrons
from water through photosystem 2. The electrons then flow through a series of
carriers that connect photosystems 2 and 1; this series forms the diagonal of
the Z. As they pass through this
series, electrons lose energy; some of the released energy is used to pump
protons across the membrane housing the carriers. The electrons then pass
through photosystem 1 and are transferred to a short transport chain leading to
the final acceptor of the chloroplast system, NADP+ (672).
Mordhay
Avron (IL) presented a detailed study for optimizing the conditions for
preparation of chloroplasts from leaves of higher plants and of the reaction
conditions for measuring photophosphorylation. Under the conditions specified,
the world record rate (which still holds) of light-induced ATP formation,
approaching 2500 μ moles X mg chl-1 X hr-1, was
attained. A simple assay system for following the incorporation of radioactive
inorganic phosphate into ATP is described and is used to evaluate several
mechanistic aspects of the process (71).
James M.
Shewan (GB), Geoffrey Hobbs (GB), and William Hodgkiss (GB) defined the methods
and determinative criteria appropriate to the identification of psychrophilic
bacteria. Broad groups are outlined based on a small number of preliminary
tests. The further differentiation of motile gram-negative organisms of the
genera Pseudomonas, Aeromonas, and Vibrio is described (1408).
Hoechst
Chemical Company introduced the herbicide linuron,
a substituted urea, useful in soybeans (Glycine
max), corn (Zea mays), sorghum (Sorghum cereale), wheat (Triticum spp.), and potatoes (Solanum tuberosum). ref
Samuel
McDonald McCann (US), Samuel Taleisnik (AR), and H.M. Friedman (US) obtained
crude aqueous extracts from hypothalamic tissues, which stimulated the
secretion of luteinizing hormone. A polypeptide seemed to be the likely
candidate as stimulant. The active substance was named LH-releasing factor
(LRF) (1030).
Peter J.
Nowell (US) discovered that given the proper chemical stimulus lymphocytes will
proliferate (1441).
J. Herbert
Taylor (US) showed that in the Chinese hamster chromosomes do not replicate in
synchrony but rather there is an orderly temporal sequence in the replication
of individual chromosomes. The pattern is maintained from one generation to the
next (1522).
André
Govaerts (BE) found that lymphocytes from the thoracic duct of dogs that had
been given a kidney graft are cytotoxic for kidney epithelial cells of the
donor dog but not for those from non-donor dogs (571).
Stephen V.
Boyden (GB-AU) and Ernst Sorkin (CH) were the first to describe cytophilic
antibodies in terms of their intermediary role between effector cell and
antigen. They were detected as specific antibodies, which would passively
sensitize macrophages for subsequent attachment of radiolabeled or cellular
antigens (162; 163).
Edward C.
Cocking (GB) developed the enzymatic isolation and culture of protoplasts. The
method involves removing the cell wall with purified preparations of cellulase and pectinase, while regulating protoplast expansion with an external
osmoticum. The cultured protoplasts regenerate new cell walls, form cell colonies,
and ultimately form plantlets (285).
David L.
Dewey (GB) was the first to demonstrate that anoxia (reduced oxygen) makes
cells more resistant to radiation (348).
Georges
Barski (FR), Serge Sorieul (FR), Francine Cornefert (FR), and Boris Ephrussi
(RU-FR) made the first observations indicating that the somatic cells of
animals can hybridize in vitro. It
was Serge Sorieul (FR) who did the cytogenetic monitoring and made the
discovery (93; 94; 416).
Boris
Ephrussi (RU-FR) and Serge Sorieul (FR) observed that following the in vitro hybridization of different cell
types there is a slow progressive reduction in chromosome number (416).
Henry Harris
(GB) induced hybridization of cells on a large scale, with cells of widely
different species as well as cells of widely differing types in the same
species (621).
Kenneth
David Roeder (GB-US), Lillian S. Tozian (US), Nancy Milburn (US), and Elizabeth
A. Weiant (US) determined conclusively that coordinated patterns of motor
spikes destined for the phallic apparatus of mantids and cockroaches are
generated endogenously in the last abdominal ganglion and are suppressed most
of the time by descending signals from the brain
(1051; 1310).
Robert J. Fitzgerald (US) and Paul H. Keyes (US) found that dental caries
was induced in ‘caries-inactive’ albino hamsters by oral inoculation of pure
cultures of a Streptococcus isolated
from a caries lesion of a caries active hamster. A streptomycin-resistant
mutant of this organism was used to demonstrate its presence in caries lesions
and to trace the transmission of the labeled’ organisms between
animals (450).
Issac Harary
(US) and Barbara Farley (US) discovered that rat heart cells,
separated by trypsin treatment, and
grown attached to glass in a liquid medium, exhibit periodic contractions like
a whole beating heart. The rate of beating, which is up to 150 beats per
minute, is affected by cardiac drugs and by metabolic substrates and inhibitors (615).
Arthur L.
Hall (US) and Richard J. Martin (US) reported the results when a naval
aviator-flight surgeon wore a Mark III Mod II Navy full pressure suit (3.5 psi)
in an altitude chamber for 76 h at altitude equivalents up to 170,000 ft. More
than 72 h were spent above 30,000 ft. and 47 h above 80,000 ft. Fluid balance,
caloric intake, O2 consumption, and leak rates were measured. The suit was well
tolerated, with the biggest problem being the effects of the low-humidity O2 on
the oro-nasal pharynx (602).
Jan Gosta
Waldenström (SE) presented his concept of monoclonal versus polyclonal
gammopathies. He described patients with a narrow band of
hypergammaglobulinemia as having monoclonal protein. Although many of these patients
had multiple myeloma, others had no evidence of malignancy and were described
as having essential
hypergammaglobulinemia or benign
monoclonal gammopathy (1610). Most
physicians now use the term monoclonal
gammopathy of undetermined significance (MGUS) because some of these
patients will eventually develop multiple myeloma, macroglobulinemia, or a
related disorder.
David G.
Harnden (GB) accomplished the culture of fibroblastic cells from tiny pieces of
skin that could be taken from patients or volunteers. He used these cells for
studying the chromosomes of patients with a variety of developmental
abnormalities (620).
John Hilton
Edwards (GB), David G. Harnden (GB), A. Hugh Cameron (GB), V. Mary Crosse (GB),
and Otto H. Wolff (GB) were the first to describe the trisomy-18 syndrome in man (392). The
affected infants exhibit: mental retardation, a peculiar skull with a small
mandible and prominent occiput, low-set and malformed ears, a receding chin and
stubby fingers, tightly flexed, with the index commonly overlapping the medius.
The feet are of rocker-bottom type. Ventricular septal defect is often present.
Klaus Patau
(DE), David W. Smith (US), Eeva Therman (FI), Stanley L. Inhorn (US), and Hans
P. Wagner (CH) were the first to confirm the human trisomy-13 syndrome by cytogenetic analysis (1207; 1439). The infants are mentally
retarded and have multiple abnormalities. Such eye defects as colobomata or
anophthalmia are common and there are neurological features such as fits and
hypotonia. Cleft palate and harelip are often present. Sometimes capillary
hemangiomata are present. Congenital heart disease is characteristic. The
constellation of findings in this condition was described as far back as the
1600's.
Malcolm
Andrew Ferguson-Smith (GB), Alan W. Johnston (GB), and Stanley D. Handmaker
(GB) reported two patients with primary
amentia and micro-orchidism associated with an XXXY sex-chromosome constitution
(436).
Peter C.
Nowell (US) and David A. Hungerford (US) discovered that a marker chromosome,
the Philadelphia chromosome (Ph+), is consistently associated with chronic myelogenous leukemia (CML).
They speculated that it was caused by a translocation (1154; 1155). Note: this was the first chromosomal
abnormality associated with cancer using cytogenetics. See, Janet Davison Rowley, 1977.
Janet
Davison Rowley (US) using chromosome banding techniques found that the
Philadelphia chromosome is a reciprocal translocation between chromosome 22 and
another chromosome, usually chromosome 9, rather than a deletion of chromosome
22 as had previously been thought (1324). This was the first time that a
specific human disease was linked to a chromosomal rearrangement.
Janet Davison Rowley (US) reported another translocation between
chromosomes 8 and 21 in acute
myeloblastic leukemia cells (1325).
Peter C.
Nowell (US) encouraged the use of chromosome studies to diagnose various
cancers (1153).
Janet
Davison Rowley (US), Harvey M. Golomb (US), and Charlotte Dougherty (US)
reported that a 15/17 translocation is a consistent chromosomal change
associated with acute promyelocytic
leukemia in man (1326).
Annelies de
Klein (NL), Ad Geurts van Kessel (NL), Gerard Grosveld (NL), Claus R. Bartram
(NL), Anne Hagemeijer (NL), Dirk Bootsma (NL), Nigel K. Spurr (NL), Nora
Heisterkamp (NL), John Groffen (NL), and John R. Stephenson (NL) showed that
when the Philadelphia chromosome is formed (a reciprocal translocation between
chromosomes 22 and 9) in cells resulting in human chronic myeloid leukemia that an oncogene on chromosome 9 is
translocated to chromosome 22 near the immunoglobulin locus (336).
Riccardo
Dalla-Favera (US), Marco Bregni (US), Jan Erikson (US), David Patterson (US),
Robert Charles Gallo (US), and Carlo M. Croce (US) discovered that the (8;14)
translocation characteristic of Burkitt’s
lymphoma involves the transposition of the cellular homologue of the myc viral oncogene, normally located on
chromosome 8, to the immunoglobulin locus on chromosome 14 (318). This was
the first indication that translocations can lead to in-frame fusion and the
formation of chimeric genes that encode a fusion mRNA and protein.
Nora C.
Heisterkamp (US), Kees Stam (US), John Groffen (US), Annelies de Klein (US),
and Gerard Grosveld (US) figured out that the Philadelphia chromosome
translocation resulted in the fusion of two genes that created a new gene known
as BCR-ABL (647).
Tracy Gross
Lugo (US), Ann Marie Pendergast (US), Alfred J. Muller (US), and Owen N. Witte
(US) discovered that this fusion gene causes the body to produce an abnormally
active form of an enzyme called a tyrosine
kinase that stimulates uncontrolled cell growth in white blood cells (950). Chronic myelogenous leukemia (CML) is not the result of a series of
gene mutations, but rather is caused by one translocation resulting in a
singular mutatiion, the BCR-ABL fusion gene.
Brian J. Druker (US),
Shu Tamura (US), Elisabeth Buchdunger (CH), Sayuri Ohno (US), Gerald M. Segal
(US), Shane Fanning (US), Jürg Zimmermann (CH) and Nicholas B. Lydon (GB) proved that Bcr-Abl protein tyrosine kinase could be
targeted in leukemia cells, a crucial finding that led to the development of
Gleevec (369). Note: The BCR-ABL oncogene is present in 95% of patients with
chronic myelogenous leukemia.
Michael J. Mauro (US), Michael E. O’Dwyer (US)
and Brian J. Druker (US) developed imatinib (ST1571 or Gleevac) to target the
abnormal protein produced by this genetic translocation (1025; 1026).
Brian
J. Druker (US), Moshe Talpaz (US), Debra J. Resta (US), Bin Peng (US),
Elisabeth Buchdunger (DE-CH), John M. Ford (US), Nicholas B. Lydon (GB), Hagop
Kantarjian (LB-US), Sayuri Ohno-Jones (US), and Charles L. Sawyers (US)
established the efficacy and safety of imatinib (Gleevec), a specific inhibitor
of the Bcr-Abl protein tyrosine kinase, in
treatment of chronic myeloid leukemia (368).
A. Thomas
Look (US), Tim Veldman (US), Christina Vignon (US), Evelin Schrock (US), Janet
Davison Rowley (US), and Thomas Ried (US) found that most translocations in acute leukemia and in sarcomas lead to
in-frame fusion genes that along with their protein products represent unique
tumor markers of considerable diagnostic importance (934; 1594).
Aaron Bunsen
Lerner (US), James D. Case (US), Seithikurippu R. Pandi -Perumal (IN), Nava
Zisapel (IL), Venkataramanujan Srinivasan (IN), and Daniel P. Cardinali (AR)
provided research that led to the incidental discovery of the sleep-promoting
effects of melatonin (907; 1200).
Richard
Wurtman (US), Amnon Brzezinski (IL), Mark G. Vangel (US), Gillian Norrie (GB),
Abraham Ben-Shushan (IL), Ian Ford (GB), and Irina Zhdanova (US) reported that melatonin
treatment significantly reduced sleep onset latency, increased sleep efficiency
and increased sleep duration (187; 1694).
Venkatramanujam
Srinivasan (IN), Daniel P. Cardinali (AR), Uddanapalli S. Srinivasan (IN),
Charanjit Kaur (IN), Gregory M. Brown (CA), D. Warren Spence (CA), Rüdiger
Hardeland (DE), Seithikurippu R. Pandi-Perumal (IN) Seithikurippu R.
Pandi-Perumal (IN) , Ahmed S. BaHammam (IN), Vijay K. Bharti (IN),
and Burkhard Poeggeler (DE) showed that melatonin exhibits protective
effects against certain neurodegenerative disorders such as Alzheimer's
disease and Parkinson's disease (1199; 1457; 1458).
Annemarieke de
Jonghe (NL), Joke C. Korevaar (NL), Barbara C. van Munster (NL), Sophia E. de
Rooij (NL), Tracy A. Bedrosian (US), and Randy J. Nelson (US) reported that melatonin
relieves the symptoms of Sundowning syndrome (107; 335).
Ze-Ping Hu
(CN), Xiao-Ling Fang (CN), Nan Fang (CN), Xiao-Bian Wang (CN), Hai-Yan Qian
(CN), Zhong Cao (CN), Yuan Cheng (CN), Bang-Ning Wang (CN), Yuan Wang (CN),
Flavia Radogna (IT), Marc Diederich (IT), Lina Ghibelli (IT), Luigi Fabrizio
Rodella (IT), Gaia Favero (IT), Eleonora Foglio (IT), Claudia Rossini (IT),
Stefania Castrezzati (IT), Claudio Lonati (IT), Rita Rezzani (IT), Petra H.
Wirtz (CH), Maria Spillmann (CH), Carmen Bärtschi (CH), Ulrike Ehlert (CH), and
Roland von Känel (CH) credited melatonin with anti-inflammatory,
antioxidant, anticoagulopathic as well as endothelial-protective properties (708; 1251; 1309; 1665). See,
McCord, 1917.
John Rock
(US), Celso-Ramon Garcia (US), Gregory Goodwin Pincus (US), Min Chuch Chang
(US), and Carl Djerassi (US) contributed to the discovery of a method of so
altering a female’s physiology by means of synthetic hormones as to keep her
infertile without altering her capacity for sexual enjoyment. This is a
situation, which takes place naturally during pregnancy, and the synthetic
hormone duplicates that condition. They helped produce the first oral
contraceptive pill after being persuaded to do so by Margaret Sanger, a leader
in the American birth-control movement, and Katherine Dexter McCormick, an heir
to the International Harvester fortune. Pincus received a grant from the
Planned Parenthood Federation in 1951. Pincus and Chiang began to look for a
progestin or a synthetic progestin that could be used as a birth control agent.
After much experimentation with more than 200 substances, the two derived the
steroid compounds from the roots of the wild Mexican yam. The steroids were
found to be successful in inhibiting ovulation in laboratory animals and
appeared to be harmless. Pincus started conducting field tests for the steroids
in pill form with hundreds of women in Brookline, Massachusetts; Puerto Rico;
and Haiti in 1955. They proved to be effective. The only side effects were
brief feelings of nausea (1308). The United
States Food and Drug Administration (FDA) authorized the marketing of these
steroids for limited use in 1957. Three years later the FDA licensed Enovid, a
birth-control pill produced by G.D. Searle Company.
Arhur J.
Buller (GB), John Carew Eccles (AU-GB-AU), and Rosamund M. Eccles (AU)
demonstrated the reversal of contractile characteristics in fast- and
slow-twitch muscles after cross-innervation in the cat (188).
John O.
Holloszy (US) demonstrated adaptation of the energy metabolism system in rat
skeletal muscle to chronic exercise training (700).
Philip D.
Gollnick (US), Robert B. Armstrong (US), Carl W. Saubert, IV (US), Karin Piehl
(US), Bengt Saltin (SE), Walter L. Sembrowich (US), and Raymond E. Shepherd
(US) addressed the question of whether a stimulus such as exercise training
could produce not only metabolic adaptations, but also transform fiber types in
human skeletal muscle. In the 1972 paper they reported that skeletal muscle
from trained endurance athletes is predominantly slow-twitch fibers with a
relatively high oxidative capacity. The 1973 paper concluded that chronic
exercise training does not significantly alter the distribution of fast- and
slow-twitch fibers in human skeletal muscle (558; 559). It is now
generally recognized that skeletal muscle fibers do not exist in three discrete
forms at the subcellular level, but rather in a continuum based on the
multitude of combinations of myosin
heavy and light chain isoforms, polymorphic expression of protein isoforms,
metabolic potential, and calcium ion handling characteristics. Moreover, all
these cellular characteristics exhibit some degree of plasticity in response to
exercise training.
Leif Wide
(SE) and Carl A. Gemzell (US) described an immunological method for the assay
of chorionic gonadotrophin (HCG) in human urine. The method is useful as a
simple and rapid pregnancy test and can be applied for quantitative
determinations of HCG in urine (1657).
Lawson
Wilkins (US) found that masculinization of the female fetus frequently resulted
from administration of progestins to mothers in treating habitual or threatened
abortion. In 25 cases the mothers were given estrogens with the progestins in
order that the estrogen might offset the virilizing effect of the progestin,
but the evidence showed that the estrogens did not prevent fetal
masculinization (1659).
Harold
Theodore Hammel (US), James Daniel Hardy (US), Madeline M. Fusco (US), and
Bjørn Hellstrøm (NO) found that moderate local cooling of the hypothalamus
elicits vasoconstriction and shivering without thermal drives from the
periphery and in the presence of possible inhibitory drives due to elevated
skin and visceral temperature (609; 649).
Harold
Theodore Hammel (US), Don C. Jackson (US), Jan A.J. Stolwijk (NL-US), James
Daniel Hardy (US), and Sigmund B. Strømme (NO) found that
for the dog and rhesus monkey, 1) a
resting animal shivers in
a cold environment with the same or higher hypothalamic temperature
as the same animal in a neutral environment; 2) a resting animal pants
in a hot environment with the same or lower hypothalamic
temperature as the same animal in a neutral environment; 3) the
hypothalamus is nonetheless strongly responsive to an increase
or decrease of 1 C; 4)
the rate of heat loss increases at the onset
of sleep while the hypothalamic temperature is falling;
5)
the hypothalamic temperature is 1–2 C lower during sleep
even though thermoregulatory responses are the same as when
awake; 6) the rate of
heat loss decreases upon awakening while the
hypothalamic temperature is rising (610).
William L.
Nastuk (US), Otto J. Plescia (US), Kermit E. Osserman (US), and John A. Simpson
(GB) proposed that myasthenia gravis
is an autoimmune disorder involving an immunologic response to a protein in the
neuromuscular junction (1118; 1420).
Ockert
Stephanus Heyns (ZA), W.A.B. Roberts (ZA), and H.G. Smulian (ZA) introduced
abdominal decompression as a method of pain relief in labor. He applied
negative pressure via a shell (Heyns bag) that could be controlled by the patient
(670).
George
Milton Shy (US) and Glenn A. Drager (US) described a progressive neurological
disorder accompanied by postural hypotension, rigidity and tremor (Shy–Drager
syndrome) (1415).
Jacques
Genest (CA), Wojciech Nowaczynski (CA), Erich Koiw (CA), Tamás Sandor (HU),
Pierre Biron (CA), John Henry Laragh (US), Marielene Angers (US), William G.
Kelly (US), and Seymour Lieberman (US) showed that angiotensin II infused
intravenously caused increased aldosterone production (518; 875). Note:
This established a connection between kidney function and hormone production by
the adrenal gland.
Georges
Klein (SE), Hans Olof Sjögren (SE), Eva Klein (SE), Karl E. Hellström (SE),
Lloyd J. Old (US), Edward A. Boyse (US), Donald A. Clarke (US), Elizabeth A.
Carswell (US), Amiela Globerson (IL), and Michael Feldman (IL) were the first
to prove the existence of specific antigenic differences in animal tumors (546; 817; 1179).
Charles S. Kennedy (US), Elmer B. Miller (US), Donald C. McLean
(US), Marvin S. Perlis (US), Raymond M. Dion (US) and Victor S. Horvitz (US) were the
first to put into practice an operation referred to as a hemicorporectomy. The
procedure involves removal of the bony pelvis, both lower limbs, the external
genitalia, the bladder, rectum and anus. The operation was completed in a
single stage in a 74-year-old man with locally invasive rectal cancer. The
patient died of pulmonary edema 10 days post-operatively (800).
J. Bradley
Aust (US) and Karel B. Absolon (US) performed the first successful
hemicorporectomy (at the level between the lowest lumbar vertebra and the
sacrum) on a 29-year-old paraplegic with malignancy arising in a decubitus
ulcer
in 1961. The procedure was performed in two stages and the patient
survived for 19 years, before finally succumbing to pulmonary edema (68).
John J. Shea, Jr. (US), Harold G. Tabb (US), and David F. Austin
(US) performed the first transcanal, under-surface tympanoplasties using
connective tissue from veins (69; 1400; 1509).
Albert Wollenberger (DE), Otto Ristau (DE), and Georg Schoffa (DE)
described how tissue and organs can be frozen in situ in a fraction of a second by being compressed to a thin
layer between two aluminum blocks that are precooled in liquid nitrogen and for
convenient handling form part of a clamp (1672).
Thomas Earl
Starzl (US) and Harry A. Kaupp, Jr. (US) performed transplantation in dogs of
multiple abdominal viscera, including liver and intestine, nearly identical to
human procedures done three decades later (1466).
Cyrus E. Rubin (US), Lloyd Brandborg (US), Patricia C. Phelps (US), and
Hawley C. Taylor, Jr. (US) upon examination of patients from infancy to old age
with celiac disease or idiopathic sprue found abnormalities of villous
architecture in duodenojejunal biopsies from all. Such abnormalities were not
seen in normals or in patients with a wide variety of other types of
malabsorption. Heal mucosal morphology was normal in two celiac sprue patients
with abnormal duodenojejunal mucosa (1330).
Nathan Oram
Kaplan (US), Margaret M. Ciotti (US), Milton W. Hamolsky (US), Robert E. Beiber
(US), and Don Dennis (US) were among the first to recognize the potential of
using isoenzyme analysis in clinical diagnosis and for this reason developed
methods for detecting lactic acid
dehydrogenase isoenzymes in human serum (344; 611; 776). Tissue breakdown
releases LDH, and therefore LDH can be measured as a surrogate for tissue
breakdown, e.g. hemolysis. Other disorders indicated by elevated LDH include
cancer, meningitis, encephalitis, acute pancreatitis, and HIV. It can also be
used as a marker of myocardial infarction. Following a myocardial infarction,
levels of LDH peak at 3–4 days and remain elevated for up to 10 days.
David A.
Price Evans (US), Keith A. Manley (US), and Victor Almon McKusick (US)
investigated the large person to person variations in the metabolism of
isoniazid, which was in general use to treat tuberculosis. They concluded that
the variation is due to a genetic polymorphism (422).
Sidney
Farber (US), Giulio D'Angio (US), Audrey Evans (US), and Anna Mitus (US), at
what is now Dana-Farber Cancer Institute, achieved the first remissions in
Wilms tumor of the kidney, a common form of childhood cancer. By prescribing
the antibiotic actinomycin D in addition to surgery and radiation therapy, they
boosted cure rates from 40 to 85 percents (426).
Myron
Prinzmetal (US), Ali Ekmekci (US), Rexford Kennamer (US), Jan K. Kwoczynski
(US), Herbert Shubin (US), and Hideo Toyoshima (US) observed a variant form of angina
pectoris in 23 patients. Electrocardiograms, recorded during this type of
anginal pain, showed an elevation of the S-T segment which disappeared when the
pain stopped. The electrocardiogram may, therefore, show findings opposite to
those of ordinary angina pectoris. Sufficient diagnostic features are
pointed out to allow for clinical diagnosis of typical cases (1242).
Henry A.
Schroeder (US) examined
the relation between mortality from cardiovascular disease and treated
municipal water supplies. In all cases correlations were negative, i.e., softer water was
associated with higher death rates. Some factor either present in hard water or
missing or entering in soft water appears to affect death rates from
degenerative cardiovascular disease (1376).
John
Christopher Wagner (AU), Chris A. Sleggs (AU), and Paul Marchand (AU), wrote a
seminal paper in establishing mesothelioma
as a disease arising from exposure to asbestos. Primary malignant tumors of the pleura are uncommon. Thirty-three cases
of diffuse pleural mesothelioma were described; all but one has a probable
exposure to crocidolite asbestos (Cape blue) (1606).
James C.
McNulty (AU) reported the first diagnosed case of malignant mesothelioma. It was in an Australian asbestos worker (1036).
Min C. Li
(US), Willet F. Whitmore Jr. (US), Robert Golbey (US), and Harry Grabstald (US)
reported striking improvement obtained when some cases of patients with
advanced metastatic testicular cancer were treated using a combined drug
therapy (913).
Francis F.
Foldes (US), Robert Molloy (US), Pearl G. McNall (US), and Ludwig R. Koukal
(US) performed a clinical comparison of toxicity of intravenously given local
anesthetic agents in man (457).
Nikolaas Tinbergen (NL) explained that during predation the cognitive
process appears to consist of a transitory increase in a predator's ability to
detect cryptic prey when items of a similar appearance are encountered in rapid
succession, a phenomenon termed "hunting by searching image". Because
of the shift in detectability, visual predators tend to search for only a
limited number of prey types at any moment in time, focusing on the most common
prey available and effectively overlooking the others (1560).
Nelson
Hairston (US), Frederick E. Smith (US) and Lawrence B. Slobodkin (US) are
generally credited with originating the concept of a trophic cascade, although
they did not use the term. Hairston, Smith and Slobodkin argued that predators
reduce the abundance of herbivores, allowing plants to flourish. Often referred
to as the green world hypothesis (600).
Robert
Helmer MacArthur (US) presented three mechanistic niche apportionment models
for species. He believed that ecological niches within a resource pool could be
broken up like a stick, with each piece of the stick representing niches
occupied in the community (967).
Elwyn LaVerne
Simons (US), from 1960-1968, conducted the most extensive excavations ever
undertaken on the Oligocine formation of the Fayum in Egypt, contributing
enormously to our knowledge of the early development of the higher primates (1419).
Petros
Kokkoros (GR) and Antonis Kanellis (GR) reported on the fossil remains of a Homo erectus; Homo erectus petraloniensis from near Petralona in eastern Greece (831). It is
dated at 350,000-400,000 BP
The journal Analytical Biochemistry was first
published.
c. 1961
Beecham
Labs: Ampicillin
1961
“We report
genetic experiments which…suggest that the genetic code is of the following general
type: (a) A group of three bases…codes one amino-acid. (b) The code is not of
the overlapping type… (c) The sequence of the bases is read from a fixed
starting point…. If the starting point is displaced by one base, then the
reading into triplets is displaced and thus becomes incorrect.” Francis Harry
Compton Crick, C. Leslie Barnett, Sydney Brenner, and Richard J. Watts-Tobin (310). This is the
monumental paper explaining
that the genetic code is triplet in nature.
Researchers
at Ames Diagnostics created the first blood sugar monitor. This monitor was
called Ames Reflectance Meter. ref
“[The]
system of regulation [of the rate of protein synthesis] appears to operate
directly at the level of synthesis by the gene of a short-lived intermediary,
or messenger, which becomes
associated with the ribosomes where protein synthesis takes place.” François
Jacob and Jacques Lucien Monod (737).
Francois Jacob
(FR) and Jacques Lucien Monod (FR) comment, “the discovery of units of
coordinated genetic activity and of regulator genes which control the activity
of structural genes, via cytoplasmic repressors, able in turn to interact
electively with exogenous or endogenous chemical agents, appears to offer
precisely the type of elements needed to build the complex and precise chemical
networks of information transfer upon which the development and physiological
functioning of organisms must rest.” François Jacob and Jacques Lucien Monod (737).
Melvin
Calvin (US) was awarded the Nobel Prize in Chemistry for his research on carbon
dioxide assimilation in plants.
Georg von
Békésy (HU-US) was awarded the Nobel Prize in Physiology or Medicine for his
discoveries of the physical mechanism of stimulation within the cochlea.
Lawrence
Hugh Aller (US) stated that nucleosynthesis within stellar interiors generates
carbon, nitrogen, oxygen, phosphorus, and other biogenic elements (22).
William
Henry Oldendorf (US) described the results of experiments in X-ray scanning an
object from many angles along its perimeter. These experiments showed that
cross-sectional images might be obtained from the detection and recording of
slight density variations in the composition of structures within the head. He
used a collimated beam and arranged the source and a sensitive crystal
detector, so that they spun at opposite poles around the object to be
visualized. This data could then be assembled into coherent images of the
object under scan (1181). Note: This work directly anticipated and demonstrated the
feasibility of computerized axial tomography. A device, the CT scanner, using
similar principles, was introduced in April 1972 by EMI, Ltd.
Allan MacLeod Cormack (ZA-US) developed mathematical theory and
built machines to achieve two-dimensional x-ray image reconstruction, i.e.,
axial tomagraphy (298; 299).
Godfrey
Newbold Hounsfield (GB) devised a system whereby the brain can be scanned from
its perimeter by a collimated beam. The transmitted beam is measured, and its
variations recorded at frequent intervals by a sensitive crystal detector, as
the beam and the detector scan across the brain from many different directions.
Very small differences in the tissue absorption of a collimate beam are
measured and recorded, and these data are subsequently reconstructed by a computer
giving a cross-sectional image of the anatomy of the brain in detail, i.e.
computerized axial tomography (CAT scan) (704). See, Vallebona, 1930.
Sydney M.
Friedman (CA) and Miyoshi Nakashima (CA) demonstrated that a cannula-type
metal-connected electrode is a practical device for the measurement of sodium
in single aliquots of biological materials such as blood or urine. They
presented evidence suggesting significant sodium binding in plasma (492).
Helmut K.
Mangold (DE-US) described the technique of thin- layer chromatography (TLC) and
its applicability in the lipid field, stressing the simplicity, sensitivity,
capacity, versatility, and efficiency of the method (992).
Joan Oró
(ES) found that concentrated solutions of ammonium cyanide in water can produce
the nucleotide adenine, a discovery that contributed to theories on the origin
of life. He also described a mechanism for the synthesis of adenine from
hydrogen cyanide under possible primitive Earth conditions (1189; 1190).
Walter B. Dandliker (US) and George A. Feigen
(US) used polarized fluorescence to give the first description of a true
homogeneous assay in which the antigen-antibody event was measured directly in
real time (319).
Morris John
Karnovsky (US) presented a simple method for staining with lead at high pH in
electronmicroscopy (781).
John H.
Venable (US) and Richard A. Coggeshall (US) developed a simplified lead citrate
stain for use in electron microscopy (1595).
David
Aminoff (US) developed the thiobarbituric acid assay to follow the chemical and
enzymatic release of sialic acid from many biologically important compounds.
This assay is extremely sensitive, specific, and reproducible (25).
Robert G.
Martin (US) and Bruce Nathan Ames (US) studied enzymes using sedimentation
rates in sucrose (1013).
George L.
Ellman (US), K. Diane Courtney (US), Valentino Andres (US), and Robert M.
Featherstone (US), developed a spectrophotometric method for determining
acetylcholinesterase activity of tissue extracts, homogenates, cell
suspensions, etc. The activity is measured by following the increase of yellow
color produced when the thio anion produced by the enzymatic hydrolysis of the
substrate (acetylthiocholine) reacts with dithiobisnitrobenzoate. The method
was used to study the activity of human erythrocytes and homogenates of rat
brain, kidney, lungs, liver, and muscle tissue (406).
Harry P.C.
Hogenkamp (US), Horace Albert Barker (US), and Jeffrey N. Ladd (US) determined
that the entity used as an enzymatic cofactor in living systems, including
mammals, is not vitamin B12, but what is now called coenzyme B12. This coenzyme
possesses an adenosyl residue and lacks the cyanide ion of vitamin B12 (690; 691).
P. Galen
Lenhert (US) and Dorothy Mary Crowfoot-Hodgkin (GB) used x-ray analysis to
reveal the structure of coenzyme B12 along with the surprise that it contains a
cobalt-carbon bond, the first true organometallic system (as distinct from a
single cyanide ligand) to be discovered in living systems (900).
Choh Hao Li
(CN-US), Johannes Meienhofer (US), Eugen Schnabel (DE), David Chung (US),
Tung-Bin Lo (US) and Janakiraman
Ramachandran (US) synthesized a biologically active nonadecapeptide corresponding
to the first nineteen amino-acid residues of adrenocorticotropins (ACTH). In
addition to adrenal-stimulating activity the nonadecapeptide also has
melanocyte-stimulating activity, as does the complete ACTH hormone with 39
residues (911).
Klaus Hofmann
(CH-US), Haruaki Yajima (JP), Noboru Yanaihara (JP), Teh-Yung Liu (US), and
Saul Lande (US) synthesized a tricosapeptide possessing essentially the full
biological activity of natural ACTH (689).
Allen B.
Edmundson (US) and Christophe Henri Werner Hirs (GB-US) reported the entire 153
amino acid primary structure of sperm whale myoglobin (390).
William
Howard Stein (US), Arthur M. Crestfield (US), and Stanford Moore (US) began an
investigation that led to the understanding of the connection between chemical
structure and catalytic activity of the active center in the bovine pancreatic ribonuclease A
molecule (307; 1472).
Eraldo Antonini
(IT), Jeffries Wyman (US), Romano Zito (IT), Alessandro Rossi-Fanelli (IT), and
Antonio Caputo (IT) used carboxypeptidase
A to digest the C-terminal tyrosine and histidine from the human hemoglobin
beta chain and carboxypeptidase B to
remove the C-terminal lysine, tyrosine, and arginine on the human hemoglobin
alpha chain. The resulting protein appeared intact but had an increased oxygen
affinity, lowered cooperativity, and dramatically reduced Bohr effect (37).
Romano Zito
(IT), Eraldo Antonini (IT), and Jeffries Wyman (US) used carboxypeptidases A and B,
to show that the rate of digestion is different for the oxy- and deoxy-forms of
the hemoglobin molecule, indicating a differential accessibility of the
C-terminal residues to these enzymes (1716).
Georg
Hertting (AT), Julius Axelrod (US), Irwin J. Kopin (US), and Lionel Gordon
Whitby (GB) found that sympathetic nerve endings take up and retain circulating
norepinephrine when it is released into the bloodstream. They also found that
norepinephrine released from sympathetic nerve endings has one of three fates:
1) uptake by the nerve ending, 2) uptake by effector cells, and 3) entering the
bloodstream (665).
David E.
Wolfe (US), Lincoln T. Potter (US), Keith C. Richardson (US), and Julius
Axelrod (US) found that norepinephrine is stored within granulated (microsomal)
vesicles of non-myelinated axons in the sympathetic system (1671).
Beth J. Hoffman
(US), Eva Mezey (US), Michael J. Brownstein (US), Mary C. Ritz (US), Richard J.
Lamb (US), Steven R. Goldberg (US), and Michael J. Kuhar (US) found that the
monoamine neurotransmitters serotonin and dopamine (prolactin-inhibiting
hormone) are also inactivated by uptake into nerves (687; 1303).
Leslie
Iversen (GB) reported that the amino acid neurotransmitters gamma-aminobutyric
acid (GABA), glycine, proline, and L-glutamate are taken up by neurons and thus
inactivated (734).
Maarten E.A.
Reith (US) reported that the neurotransmitter uptake sites are
sodium/chloride-dependent transporters (1277).
Boris
Magasanik (AT-US) coined the phrase catabolic
repression to describe a phenomenon discovered in bacteria and given the
name glucose effect (979; 980). See, Dienert, 1900.
Ellis
Englesberg (US), Joseph Irr (US), Joseph Power (US), and Nancy Lee (US)
accumulated evidence in Escherichia coli for
a mode of gene regulation called positive control. They deduced the existence
of an activator protein required for the expression of the genes determining
arabinose metabolism in Escherichia coli
(412; 413).
Richard S.
Makman (US) and Earl Wilbur Sutherland, Jr. (US) found that the level of cyclic
AMP (cAMP) increases strongly in glucose starved E. coli cells (987).
Benoit de
Crombrugghe (US), Robert L. Perlman (US), Harold Elliot Varmus (US), and Ira
Harry Pastan (US) found that cyclic AMP overcomes the glucose repression of the
synthesis of several inducible enzymes including beta-galactosidase,
galactokinase, glycerokinase, and thymidine
phosphorylase. From these results, Pastan concluded, “Since glucose lowers
the intracellular concentration of cyclic AMP in E. coli, we propose that the intracellular level of cyclic AMP
regulates the rate of synthesis of many inducible enzymes in E. coli and other microorganisms and
that glucose lowers the rate of synthesis of these enzymes by decreasing the
intracellular level of cyclic AMP” (334).
Ira Harry
Pastan (US), Robert L. Perlman (US), Agnes Ullmann (FR), and Jacques Lucien
Monod (FR) discovered that cyclic AMP in Escherichia
coli can overcome glucose’s catabolic repression of the lactose operon (1206).
Geoffrey
Zubay (US), Daniele Schwartz (US), Jonathan Roger Beckwith (US),
Michael Emmer
(US), Benoit de Crombrugghe (US), Ira Pastan (US), and Robert Perlman (US) characterized
an activator of the lac operon.
(Expression of the lac operon is
inhibited in the presence of glucose and its catabolites, and increased levels
of cyclic AMP (cAMP) had shortly before been shown to reverse the inhibitory
effect of glucose and its catabolites.) They proposed that cAMP binds to a
protein factor, the catabolite gene-activator protein (CAP), causing it to bind
to a DNA site in the lac promoter
thus stimulating the initiation of transcription. Using the first cell-free
system for transcription and translation, they showed directly that CAP plus
cAMP stimulated the expression of the lac
operon. They isolated and characterized the same factor based on assays of cAMP
binding activity and named it cAMP receptor (CR) protein (later revised to CRP) (410; 1717).
Ira Harry
Pastan (US), Robert L. Perlman (US), Harold Elliot Varmus (US), Max E.
Gottesman (US), Wayne B. Anderson (US), Beatrice Chen (US), and Benoit de
Crombrugghe (US) found that cyclic
AMP has a major role in controlling gene expression in E. coli
and subsequently showed it did this by producing an allosteric
change in a specific cyclic AMP-receptor protein (CRP). This
change increased the affinity of CRP for DNA sequences in the
promoter of many genes. Therefore, transcription
was initiated, and gene activity increased (333; 1206; 1593).
This was the first example
of positive control of gene expression.
Wayne B.
Anderson (US), Arthur B. Schneider (US), Michael Emmer (US), Robert L. Perlman
(US), and Ira Harry Pastan (US) described the purification and properties of
cyclic AMP receptor protein (CRP) (30).
Charles D.
Salmon (FR), D. Salmon (FR), Geneviève Liberge (FR), Robert G. Andre (FR), Patricia
Tippett (GB), and Ruth Sanger (GB) discovered a new erythrocytic blood group
antigen present in 80 per cent of subjects of the white race. It is called
Auberger's (1343).
Hoffmann-LaRoche
Laboratories (CH) introduced the drug valium. ref
Hans Leo
Kornberg (GB-US) and Antonio M. Gotto, Jr. (US) discovered the glycerate
pathway by which phosphoenolpyruvate is formed from glyoxylate. This pathway
allows an organism to grow when its sole organic carbon source is glycine,
glycollate, or oxalate (838).
Feodor Felix
Konrad Lynen (DE), Dieter Oesterhelt (DE), Eckhart Schweizer (DE), and Klaus
Willecke (DE) discovered fatty acid
synthetase, the enzyme system which catalyzes the synthesis of saturated
long-chain fatty acids from malonyl-CoA (954-956; 961; 962).
Howard
Marvin Dintzis (US), and Mike A. Naughton (US) showed that polypeptide chains
grow by stepwise addition of single amino acids, starting with the
amino-terminal amino acid and finishing with the carboxyl-terminal amino acid (350; 1121).
Emanuel
Margoliash (IL), Emil L. Smith (US), Gunther Kreil (AT), and Hans Tuppy (AT)
determined the primary structure of horse heart cytochrome c (998).
David Elson
(IL), Francis Galibert (FR), Christopher J. Larsen (FR), Jean Claude Lelong
(FR), Michel Boiron (FR), Roland Rosset (FR), and Roger Monier (FR) discovered
the 5S ribosomal RNA (5S rRNA) (407; 504; 1318).
Jacques J.
Pene (FR), Ernest J. Knight, Jr. (US) and James Edwin Darnell, Jr. (US) discovered
the 5.8S ribosomal RNA (5.8S rRNA) (1209).
Ying Ying Chang
(US), Eugene Patrick Kennedy (US), Julian Kanfer (US) and Alvin R. Tarlov (US)
worked out most of the steps in the metabolic pathway for phospholipid
synthesis (255; 770; 771; 801; 802; 1521). This
became known as the Kennedy pathway.
Daniel
Nathans (US) and Fritz Albert Lipmann (DE-US) developed a bacterial cell-free
system that supported protein synthesis. They found that during protein
synthesis amino acids are transferred from aminoacyl-sRNA to polypeptide on
ribosomes of E. coli (1119).
Richard
Schweet (US), Hildegarde Lamfrom (DE-US), Esther Allen (US), Ellen R. Glowacki
(US), and Paul M. Knopf (US) developed one of the first in-vitro
translation systems, using rabbit reticulocyte lysate to study protein
synthesis (a process called translation) in a cell-free context. This allowed
them to make a number of contributions to the field. By mixing components of
different animal cells, and showing that sheep ribosomes (protein-making
complexes) could make rabbit hemoglobin and vice versa, they provided some of
the first direct experimental evidence for the existence of messenger RNA and
its role in determining what protein ribosomes make (868-871; 1381).
Jacques
Lucien Monod (FR), Jeffries Wyman (FR), Jean-Pierre Changeux (FR), Arthur Beck
Pardee (US), John C. Gerhart (US), and Harold Edwin Umbarger (US) presented
evidence that enzymes involved in feedback controls have two separate sites,
one for the substrate and another for the feedback molecule (256; 521; 522; 1086; 1580). Monod was
to name this phenomenon allostery,
from the Greek allo, other, and stere, solid. The enzymes are said to be
allosteric (1085; 1087).
Robert
Kellogg Crane (US), David Miller (US), and Ivan Bihler (US) presented for the
first time their discovery of the sodium-glucose cotransport as the
mechanism for intestinal glucose absorption (304; 305). Note: Their discovery of
cotransport led directly to the development of oral rehydration
therapy; a treatment that counterbalances the loss of water and
electrolytes caused by cholera via a glucose containing salt solution that
accelerates water and electrolyte absorption. This is possible because cholera
does not interfere with sodium-glucose cotransport (223; 595).
Robert
William Holley (US), Bhupendra P. Doctor (US), Jean
Apgar (US), Susan H. Merrill (US), Paul L. Zubkoff (US), James T. Madison (US),
John Robert Penswick (US), George A. Everett (US), Mark Marquisee (US), Ada
Zamir (US), Merton R. Bernfield (US), Marshall Warren Nirenberg (US), Jacques
R. Fresco (US), Bruce Michael Alberts (US), Paul Mead Doty (US), Hans Georg
Zachau (DE), Dieter Dütting (DE), Horst Feldmann (US), Huei-Kuen Kung (US),
Uttam L. RajBhandary (US), Simon H. Chang (US), Alexander Stuart (US), Robert
D. Faulkner (US), Ronald M. Hoskinson (US), Har Gobind Khorana (IN-US),
Alexander Aleksandrovich Bayev (RU), T.V. Vekstern (RU), Andrei Darievich Mirzabekov
(RU), L. Li (RU), Vladimir D. Axelrod (RU), Antomina I. Krutilina (RU), I.
Fodor (RU), L.Ya Kazarinova (RU), Howard Michael Goodman (US), John Norman
Abelson (US), Arthur Landy (GB), Sydney Brenner (ZA-GB), J.D. Smith (GB), Shyam
K. Dube (US), Kjeld Adrian Marcker (DK), Brian F.C. Clark (GB-DK), Suzanne Cory
(GB), Shosuke Takemura (JP), Takaharu Mizutani (JP), Masazumi Miyazaki (JP),
Matthys Staehelin (CH), Harald Rogg (CH), Bruce C. Baguley (CH), Theodore
Ginsberg (CH), Walter Wehrli (CH), Jeanne A. Nelson (US), and Susan Clark
Ristow (US) purified then worked out the primary nucleotide sequences for the
yeast and some bacterial tRNA molecules then postulated that they have a
cloverleaf like structure with unpaired bases in some regions and paired bases
in others (39-41; 101; 126; 354; 370; 489; 563; 694-696; 977; 978; 1125; 1212; 1253; 1459; 1514; 1710).
Benjamin D.
Hall (US) and Solomon Spiegelman (US) showed that single stranded T2 phage DNA
can form a hybrid with RNA from T2 infected
Escherichia coli, thus, for the first time demonstrating the potential of
DNA-RNA hybridization experiments (604).
Agnar P.
Nygaard (US) and Benjamin D. Hall (US) reported a technique for detecting
RNA-DNA hybrids by their retention on nitrocellulose membrane filters (1158).
David
Gillespie (US) and Solomon Spiegelman (US) perfected this procedure for
detecting RNA/DNA hybrids by annealing sheared, single-stranded RNA with high
molecular weight DNA immobilized on nitrocellulose membrane filters. This
technique was useful in determining the degree of homology or complementarity
between a fragment of RNA and a fragment of DNA (540).
Murray G.
Williams (GB), Allan F. Howatson (CA) and June Dalziel Almeida (CA) performed a
morphological characterization of papillomavirus
of the human common wart (verruca
vulgaris) using
the electron microscope (1663). This virus is also known as human papova virus.
John Josse
(US), Armin Dale Kaiser (US), and Arthur J. Kornberg (US) were the first to
produce good experimental evidence that the two backbones of DNA run in
opposite directions (antiparallel) (759).
Francis
Harry Compton Crick (GB) and James Dewey Watson (US) had suggested this antiparallel structure (311; 1626-1628).
Samuel
Bernard Weiss (US) and Tokumasa Nakamoto (US) reported that the antiparallel
arrangement occurs between the messenger RNA and its complimentary DNA template
during transcription (1651).
Francis
Harry Compton Crick (GB), C. Leslie Barnett (GB), Sydney Brenner (ZA-GB), and
Richard J. Watts-Tobin (GB) proposed that “A group of three bases (or, less
likely, a multiple of three bases codes one amino-acid. The code is not of the
overlapping type… The sequence of bases is read from a fixed starting point.
This determines how the long sequences of bases are correctly read off as
triplets. There are no special commas
to show how to select the right triplets. If the starting point is displaced by
one base, then the reading into triplets is displaced, and thus becomes
incorrect. The code is probably degenerate;
that is, in general, one amino-acid can be coded by one of several triplets of
bases” (310).
Sydney
Brenner (ZA-GB), C. Leslie Barnett (GB), Francis Harry Compton Crick (GB), and
Alice Orgel (GB) predicted that adding or subtracting a base pair from DNA was
“likely to cause not the substitution of just one amino acid for another, but a
much more substantial alteration, such as…a considerable alteration of the
amino acid sequence, or the production of no protein at all” (170).
Marshall
Warren Nirenberg (US), and Johann Heinrich Matthaei (DE) used synthetic mRNA
polynucleotides such as poly U (UUUUUUU…) and poly A (AAAAAAA…) to see how they
influenced the polypeptides synthesized. They found that poly U yielded
polyphenylalanine, poly A yielded polylysine, poly C yielded polyproline. They
further demonstrated that it was single-stranded versions of these
polynucleotides and not double- or triple-stranded versions, which were active
as templates for protein synthesis (1022; 1138).
Peter
Lengyel (US), Joseph F. Speyer (US), and Severo Ochoa (ES-US-ES) also made
synthetic polynucleotides and carried out very similar experiments (899).
Francois
Jacob (FR) and Jacques Lucien Monod (FR) postulated that in Escherichia coli a specific repressor
molecule exists that binds near the beginning of the ß-galactosidase gene at a specific site called the operator and
that, by binding to the operator site on the DNA, sterically prevents RNA polymerase from commencing synthesis
of ß-gal mRNA; and that lactose acts as an inducer which, by binding to the
repressor, prevents the repressor from binding to the operator. In the presence
of lactose, the repressor is inactivated and the mRNA is made. Upon removal of
the lactose, the repressor regains its ability to bind to the operator DNA and
switch off the lactose gene (738).
Francois Jacob (FR), Raquel Sussman
(FR), and Jacques Lucien Monod (FR) provided evidence that the lambda CI repressor is a protein (740).
Konrad Beyreuther (DE), Klaus Adler
(DE), Norbert Geisler (DE), and Alex Klemm (DE) determined the amino acid
sequence of the Lac repressor in E. coli
(136). Note: Philip J. Farabaugh (US) and Konrad Beyreuther (DE) corrected
the primary structure (135; 425).
David VanNorman Goeddel (US),
Daniel G. Yansura (US), and Marvin H. Caruthers (US) reached the conclusion
that Lac repressor binds to two major grooves on one side of the DNA (549; 550).
Francois
Jacob (FR) and Élie L. Wollman (FR) were able to estimate the efficiency of the
integration process in bacteria. They found that once a donor gene has been
transferred from Hfr cell to F minus cell, its chance of being integrated into
a recombinant genome is about 0.5 (741).
Francois
Jacob (FR) and Élie L. Wollman (FR) found it possible to relate genetic linkage
inferred from recombinant analysis to the temporal distances established based
on transfer kinetics. They found that the two loci lac and pur are
separated, on the one hand, by a crossover probability of 22% and, on the other
hand, by one minute of transfer time. Hence 22% linkage is equivalent to one
minute of transfer. Since transfer of the entire chromosome requires about 100
minutes, and since the Escherichia coli
genome is represented by a circular DNA molecule of 4000 kb pairs, we can
calculate that the probability of crossover per nucleotide base pair is (22% x
100)/(1 x 4 x 106) = 0.0006% (741).
Leonard S.
Lerman (US), Vittorio Luzzati (FR), and F. Masson (US) demonstrated that
acridines bind to DNA by inserting between adjacent stacked base pairs—a
process Lerman called “intercalation”—which results in the partial unwinding of
the DNA double helix and an increase in viscosity (901-903). Note: Intercalation is relevant to the
action mechanisms of certain antibiotics, antiparasitics (including
antimalarials), anticancer agents, and carcinogens and mutagens.
Eric
Terzaghi (US), Yoshimi Okada (US), Joyce Emerich (US), Masayori Inouye (US),
Akira Tsugita (US), and George Streisinger (Hungarian-US) produced biochemical
evidence that acridines lead to additions or deletions within DNA (1545).
Charles R.
Spotts (US) and Roger Yate Stanier (CA) proposed that the expression of
streptomycin-sensitivity, resistance and dependence, are concerned with a
single intracellular site, specifically the ribosome. Subsequent studies
confirmed their proposal (1455; 1456).
Morris Goodman (US), John Barnabas (US), Genji Maysuda (JP), G.
Wiliam Moore (US), Didier Casane (FR), Stephanie Boissinot (US), Benny H.J. Chang
(US), Lawrence C. Shimmin (US), and Wen-Hsiung Li (CN-US) found that computer
programs applied to data from phylogenetic trees and protein polymorphism can
be used to find the rate of molecular evolution of different species. It can be
shown that this is slower for higher primates than for other mammals (242; 564; 565). See,
Sarich, 1967 and Margoliash, 1963
Wen-Hsiung Li (CN-US) and Masako Tanimura (US) suggested that the
variation in rate among mammals is primarily due to differences in generation
time, rather than changes in DNA repair mechanisms. They also proposed a method
for estimating the divergence times between species when the rate constancy assumption
is violated (914).
Jean-Pierre
Waller (FR), J. Ieuan Harris (GB), and Pierre-Francois Spahr (CH) performed
experiments suggesting that ribosomes of Escherichia
coli contain at least 20 different types of proteins; most of which carry a
net negative charge (1450; 1616).
Peter E.
Reynolds (GB) reported that vancomycin
inhibits incorporation of cell-wall amino acids into cell-wall material
(peptidoglycan) of bacteria (1283).
Joseph
Polkinghorne Martin (AU), Ernest Victor Abbott (AU), and Cecil Graham Hughes
(AU) were the first to report chlorotic
streak of sugar cane (Saccharum
officinarum) as a disease (1011).
Göran Möller
(SE) used the fluorescent antibody technique to demonstrate mouse
isoantigens at the cellular level (1083).
Hans G.
Schlegel (DE) and Norbert Pfennig (DE) showed that Thiorhodaceae are much
easier to isolate if a mud extract is added to the medium and that many
Thiorhodaceae require vitamin B12 as a growth factor (1365).
Zoltán
Klement (HU), Lászió Lovrekovich (HU) and Gyula L. Farkas (HU) were the first
to report the defensive hypersensitive reaction (HR) of plants to a bacterial
pathogen. In the HR the plant responds to the pathogen by generating a
hypersensitive necrosis, which prevents the spread of the pathogen (821-823).
Heather J. Shelley (GB), John M. Bassett (GB), and Robert
David George Milner (GB) described the changes in tissue glycogen concentration
which occur during fetal life and the first few days after birth. Large amounts
accumulate in the liver and skeletal muscles of many species as a store for use
after birth. The high concentration in the heart enables the fetus to survive
for long periods without oxygen (1403).
Robert Boyle (GB) had remarked on the ability of fetal and
newborn animals to survive for long periods without oxygen, an ability which
was lost with increasing maturity, however, the mechanism was obscure (1403; 1404).
Ronald Finn
(GB), Cyril Astley Clarke (GB), William Thomas Atkin Donohoe (GB), Dermot
Lehane (GB), Richard Bonar McConnell (GB), Philip Macdonald Sheppard (GB),
William Kulke (GB), John C. Woodrow (GB), Julius R. Krevans (US), and Catherine
M. Durkin (GB) revealed how the unborn child is protected from the immune
system of the mother then documented the sequence of events leading to Rh disease in the child. In 1959, they
began the first prospective study of the relation between ABO blood type and Rh
antigen incompatibilities. By monitoring the blood of Rh-negative mothers
during pregnancy and after delivery, they established that fetal erythrocytes
enter the mother's blood stream usually at delivery and that, when the fetus
and the mother are ABO-incompatible, the mother's immune system destroys the
cells before she can become sensitized to Rh antigen.
Finn
postulated that if an Rh-negative mother were given anti-Rh antibody soon
enough, any fetal erythrocytes in her circulation would be inactivated before
her immune system could become sensitized to the Rh antigen. At a scientific
meeting in 1960, he became the first Rh investigator to suggest this. Using crude
semen from sensitized Rh-negative donors, he showed that sensitization could be
prevented in Rh-negative male volunteers. Experiments with pure anti-Rh
antibody, given by American investigators who were independently pursuing
similar research, confirmed these findings. In 1964, Finn and Clarke proved
their point in a carefully-designed clinical trial, among high-risk Rh-negative
women (274-276; 440-445; 1682).
Vincent J.
Freda (US), John G. Gorman (US), William Pollack (US), John G. Robertson (US),
Elmer R. Jennings (US), and John F. Sullivan (US) also demonstrated that
anti-Rh antibody given at the time of delivery, will block sensitization and
prevent Rh disease in the woman's
next Rh-positive child (474-477).
Manfred
Martin Mayer (DE-US) proposed the one-hit
theory of immune hemolysis. He postulated that a single membrane lesion is
sufficient to cause lysis of an erythrocyte and that a single complement
molecule at least at some stage of reaction suffices for production of this
lesion (1028).
Fred A. Rommel
(US) and Manfred Martin Mayer (DE-US) qualified the theory slightly (1314).
Annemarie
Weber (DE-US) and Sandra Winicur (DE) showed that contraction and relaxation of
muscles is dependent upon the concentration of free calcium ion (1639).
Francois
Henri Duckert (CH), Ernst G. Jung (CH) and David H. Shmerling (CH) discovered
blood coagulation Factor XIII, also called fibrin stabilizing factor (FSF), Laki-Lorand factor (LLF), or fibrinase (373).
Jacques
Roskam (BE), Jean Hugues (BE), and Yves Bounameaux (BE) showed that the
collagen component of connective tissue leads to platelet adhesion and
aggregation culminating in viscus
metamorphosis (1317).
Erich E.
Windhager (US) and Gerhard Hans Giebisch (AT-US) found that active transport of
sodium occurs in the proximal convolution of the renal tubule (1664).
Marilyn Gist
Farquhar (US), Steven L. Wissig (US), and George Emil Palade (RO-US) observed
that in both the normal and the nephrotic glomerulus the basement membrane
functions as the main filtration barrier; however, in nephrosis, the basement
membrane is defective and allows leakage of increased quantities of ferritin
and presumably plasma proteins. The basement membrane defect appears to be fine
and widespread, occurring at or near the molecular level of organization of the
filter. The accumulation of unfiltered ferritin in axial regions together with
the demonstration of its subsequent phagocytosis by the "deep"
endothelial cells suggest that the latter may function in the removal of
filtration residues. Finally, the findings indicate that in the nephrotic, as
in the normal animal, the epithelium acts as a monitor that recovers, at least
in part, the protein which leaks through the filter, and that in nephrosis, the
recovering activities of the epithelium are greatly enhanced because of the
increased permeability of the basement membrane (427; 431).
Howard E.
Morgan (US), Margaret J. Henderson (US), David M. Regen (US), Robert L. Post
(US), Tomi Kim Sawyer (US), and Charles Rawlinson Park (US) studied the
regulation of glucose uptake in muscle by insulin and other hormones. They
showed that the limiting step for glucose uptake is the transport of the sugar
across the cell membrane and that this is accelerated by insulin and anoxia.
Diabetes was shown to decrease this transport and reduce its sensitivity to
insulin. Hypophysectomy reduced basal glucose transport but made it more
sensitive to insulin, whereas growth hormone treatment in vivo had the opposite effect. Diabetes was also shown to
decrease glucose phosphorylation, which was relieved by hypophysectomy or
adrenalectomy and restored by treatment with growth hormone or cortisol (650; 651; 1096; 1097; 1232).
Guido Majno
(RO-US), George Emil Palade (RO-US), and Gutta Ingeborg Schoefl (US) found that
endogenous chemical inflammatory mediators, of which histamine is the
prototype, increase the permeability of blood vessels by causing gaps to appear
between endothelial cells. The leaking vessels always belonged to the venous
side of the circulation. The heaviest deposits were found in venules 20 to 30
microns in diameter (984; 985).
Guido Majno
(RO-US-CH), Stephen M. Shea (US), and Monika Leventhal (US) used morphologic
and statistical evidence to suggest that endothelial cells contract under the
influence of inflammatory mediators, and that this contraction causes the
formation of intercellular gaps (986).
Francois
Jacob (FR) and Élie L. Wollman (FR) proposed that the chromosome of the Escherichia coli F+ bacterium
is circular. They envisaged that the mutation
from F+ to Hfr represents the spontaneous breakage of the circular chromosome and the assignment of an origin
O to one of the two chromosome ends
created by that breakage. This now
rectilinear Hfr chromosome was then supposed to be capable of being transferred
to the F- cell, beginning with the O locus, a process that the circular F+ (and presumably,
also circular F-) chromosome was imagined to be incapable of
performing.
The F
plasmid carried by an F+ bacterium can be inserted into the
host-cell chromosome in either clockwise or counterclockwise orientation at
many different sites, to generate a diversity of Hfr strains with different
points of origin and either direction of transfer. Second, the aberrant
excision of the plasmid from the chromosome of an Hfr bacterium can give rise
to a variety of different F´ plasmids, with individual plasmids carrying
different amounts of host-cell chromosome contiguous to the inserted fertility
factor (741).
Irwin
Rubenstein (US), Charles A. Thomas, Jr. (US), and Alfred Day Hershey (US)
determined the molecular weight of T2 bacteriophage DNA to be 130 million by
using radiographic determination of the phosphorus content (1329).
Matthew
Stanley Meselson (US) and Jean-Jacques Weigle (CH-US) provided the first
conclusive proof that bacteriophage recombinants do contain part of the DNA of
the parental genomes that entered the cross, and hence that genetic exchange
occurs because of breakage and reunion rather than copy choice (1048).
Seymour
Benzer (US) used deletion mutants for establishing the detailed map of the rII region in a way that made it
unnecessary to cross every mutant of the collection to every other mutant. He
divides the rII region of the T4
phage genome into segments, each segment being defined by the length of the map
covered by one deletion but not by another. It was then a simple task to make a
preliminary placement of each rII
mutant to be mapped into its appropriate segment, by establishing the deletions
with which the mutant does and does not produce wild-type recombinants in
crosses. He proceeded to assign each of the rII
mutants to one of 47 segments of the rII
region (113). Note:
This is the origin of the cis-trans test.
Marvin
Fishman (US) found that RNA extracted from macrophages exposed to T2 phages in vitro could when incubated, in vitro; with normal, nonimmune rat
lymph node cells stimulate them to make anti-T2 antibodies (447).
In 1961, a
cholera pandemic originated in Indonesia. It ravaged populations across Asia
and the Middle East, eventually reaching Africa by 1971. By 1973, the pandemic
had spread to Italy. There were also small outbreaks of the same strain — El
Tor — in Japan and the South Pacific late in the same decade (639).
Tim Loeb
(US) and Norton David Zinder (US) discovered the RNA bacteriophage f-2 (931).
Heinz Stolp
(DE) and Mortimer P. Starr (US) described and named Bdellovibrio bacteriovorus which Stolp and Hartmut Petzold (DE) had
isolated in 1962 (Bdello (=leech).
They determined it to be an ectoparasite, which invades and lyses gram-negative
bacteria (1489; 1490).
Jeffrey C.
Burnham (US), Tadayo Hishimoto (US), and Samuel F. Conti (US) provided electron
microscopic observations on the penetration of Bdellovibrio bacteriovorus into gram-negative hosts (201).
Louis
Stanley Diamond (US) prepared axenic cultures of Entamoeba histolytica (349).
L. Jonathan
Tolmach (US), Thomas Terasima (US), Warren K. Sinclair (US), and Richard A.
Morton (US) noted that a cell’s sensitivity to radiation fluctuates during the
mitotic cell cycle (1421; 1422; 1568).
Malcolm
Andrew Ferguson-Smith (GB) and Stanley D. Handmaker (US) presented evidence
that five pairs of chromosomes in man are satellited (435).
Malcolm
Andrew Ferguson-Smith (GB), Marie E. Ferguson-Smith (GB), Patricia M. Ellis
(GB), and Marion Dickson (GB) confirmed that the chromosomes showing secondary
constrictions most frequently in this human somatic material are chromosomes
13, 14, 15, 21 and 22. In these five pairs, a secondary constriction in the
short arm separates a terminal mass, the satellite, from the rest of the
chromosome arm. Secondary constrictions were also observed at specific sites in
other chromosomes, although less frequently. In chromosomes 1, 6, 9 and 17 the
constriction peculiar to each appeared in over 20% of the available chromosomes
of the respective chromosome pair (434).
Leonard
Hayflick (US) and Paul S. Moorhead (US) discovered
that human cells (fibroblasts) derived from embryonic tissues can only divide a
finite number of times in culture. They noted that cultures stopped dividing after an average of
fifty cumulative population doublings (CPDs) (637; 638). This
phenomenon is known as Hayflick's limit,
Phase III phenomenon, or replicative senescence (RS).
Ian A.
Macpherson (GB) and Michael George Parke Stoker (GB) devised the baby hamster
kidney (BHK) cell line. Baby Hamster Kidney fibroblasts (BHK cells) are an
adherent cell line used in molecular biology to study transfections and viral
infections (976).
Alexander
Mauro (US) discovered what he called "satellite cells" associated
with striated muscle fiber. He suggested that they might be pertinent to the
vexing problem of skeletal muscle regeneration.
James Edgar
Till (CA) and Ernest Armstrong McCulloch (CA) discovered the clonal nature
of hematopoietic stem cells (HSCs) (1558).
Werner
Rosenau (US) and Henry D. Moon (US) demonstrated that lymphocytes from one
inbred-mouse strain, previously sensitized to cells from another strain with a
background of different histocompatibility, would destroy the latter type of
cells in tissue culture.
The lymphocytes aggregated about
the (homologous, allogeneic) target-cells, resulting in marked, progressive
cytopathogenic changes, with extensive lysis of the targets. These events
occurred without the demonstrable involvement of serum complement or antibody
and permitted the direct study of cytolytic cellular immune reactions (1316).
Roy L. Swank
(US) observed that the microviscosity of stored blood is significantly greater
than that of fresh blood leading to the discovery and filtration theory of
microaggregates (1444; 1502).
James W.
Apple (US) and Stanley D. Beck (US) published a landmark paper on voltinism in the European corn borer in
which they tested the hypothesis that the adaptation of the borer to local
conditions involves changes in the frequencies of genetic factors controlling
its photoperiodic responses (42).
Susumu Ohno
(JP-US) found that the chicken (Gallus
domesticus) genome consists of approximately 39 chromosome pairs, including
the sex chromosomes Z and W (1169).
James Edgar
Till (CA) and Ernest Armstrong McCulloch (CA) demonstrated in mice that bone
marrow from genetically identical animals contains stem cells, which can
restore their immune system following its destruction by irradiation. They
observed that irradiated animals given graded doses of bone marrow cells
intravenously at doses insufficient to prevent death had bumps on their spleens. Andy J. Becker (CA), Ernest Armstrong
McCulloch (CA), and James Edgar Till (CA) concluded that each bump is a colony of myeloerythroid cells
derived from a single bone marrow precursor cell. These are called colony-forming units for the spleen
(CFUs) (106; 553; 1558).
Louis
Siminovitch (CA), Ernest Armstrong McCulloch (CA), and James Edgar Till (CA)
provided convincing evidence that splenic colonies truly represented the
proliferation of primitive hematopoietic stem cells (1417; 1418).
Alan M. Wu
(CA), James Edgar Till (CA), Louis Siminovitch (CA), and Ernest Armstrong
McCulloch (CA) reported that B and T cells develop from multipotent
hematopoietic stem cells through restrictions during lineage progression (1688).
Andrzej
Krzysztof Tarkowski (PL) reported the birth of the first chimaeric mice
produced experimentally by injecting blastomeres from one embryo into a
genetically different embryo (1520).
Ananda S.
Prasad (US), James A. Halsted (US) and Manucher Nadimi (IR)
reported a syndrome of iron deficiency anemia, stunting, hypogonadism, and
hepatosplenomegaly in Iranian farmers. They speculated that zinc deficiency was
the cause of the stunting and delayed development (1236).
Ananda S. Prasad (US), August Miale, Jr. (US), Zoheir Farid (EG),
Harold H. Sandstead (US), Samir Bassilly (EG), William J. Darby (US), and
Arthur R. Schulert (US) confirmed the hypothesis concerning zinc deficiency
mentioned above (1237; 1347).
Edward Peirson Richardson, Jr. (US) provided the original description
of progressive multifocal leukoencephalopathy, a neurological disorder
characterized by destruction of cells that produce myelin, an oily substance
that helps protect nerve cells in the brain and spinal cord, also known as
central nervous system (CNS) white matter. It is caused by a virus called JC
virus (JCV), named after the initials of the patient in whom it was first
discovered, John Cunningham. The virus is widespread, found in up to 85% of the
general adult population. It remains inactive in healthy individuals and causes
disease only when the immune system has been severely weakened (1288).
Note: John Cunningham virus (JCV) constitutes a family of polyoma
viruses, which plays important roles in the progressive multifocal
leukoencephalopathy (PML) and tumorigenesis.
Frank James
Dixon (US), Joseph D. Feldman (US), and Jacinto J. Vazquez (US) found that in
experimental animals making antibody responses too small to cause elimination
of antigen but sufficient to result in the formation of circulating complexes
chronic progressive disease develops. A chronic disease like glomerulonephritis
can be turned on or off by changing the dose of antigen (352). This
behavior of the immune system appears to be the underlying agent of chronic
diseases such as rheumatic fever, rheumatoid arthritis, chronic
glomerulonephritis, lupus erythematosus,
and polyarteritis nodosa. Individuals
who are poor antibody formers would appear to be predisposed to develop these
chronic diseases.
Charles R.
Anderson (US), Leslie Spence (US), Wilbur G. Downs (US), and Thomas H. Aitken
(US) first isolated oropouche virus (a bunyavirus) from a patient with an acute
febrile illness on the island of Trinidad off the coast of Brazil (28).
Fred Brown
(GB), James L. Bittle (US), Richard A. Houghten (US), Hannah Alexander (US), Thomas
M. Shinnick (US), J. Gregory Sutcliffe (US), Richard A. Lerner (US), David J.
Rowlands (GB), C.B. Bolwell (GB), Alan L. Brown (GB), Paul V. Barnett (GB),
Richard O. Campbell (GB), Berwyn E. Clarke (GB), Nigel R. Parry (GB), Elizabeth
J. Ouldridge (GB), Johnny D. Callahan (US), Fernando A. Osorio (US), Jung H.
Sur (US), Ed Kramer (US), Gary W. Long (US), Juan Lubroth (US), Stefanie J.
Ellis (US), Katina S. Shoulars (US), Kristin L. Gaffney (US), Daniel L. Rock
(US), William M. Nelson (US), David Cavanagh (GB), David V. Sangar (GB), Marie
Chow (US), John F.E. Newman (ZA), David J. Filman (US), James M. Hogle (US),
Graham Fox (GB), Nigel R. Parry (GB), Paul V. Barnett (GB), Brian McGinn (GB),
Michael James Francis (GB), Gillian Z. Hastings (GB), John McDermed (GB), Yi-An
Lu (GB), James P. Tam (GB), Peter A. Lowe (GB), Juan Lubroth (US), Marvin J.
Grubman (US), Tom G. Burrage (US), Peter W. Mason (US), Barry Baxt (US), James
Harber (US), Andrew Murdin (US), Eckard Wimmer (US), Richard F. Meyer (US),
Gwen D. Babcock (US), Kathy Toohey (US), Frances E. Nargia (US), J. Mezencio
(BR-US), J. Zamparoa (US), Cecelia Whetstone (US), Marc H.V. Van Regenmortel
(FR), Jean Paul Briand (FR), Sylviane Muller (FR), B. Cartwright (GB), Timothy
R. Doel (GB), Elizabeth Rieder (US), Thomas Bunch (US), Donald N. Black (GB),
Timothy J.R. Harris (GB), Fan Shen (US), Pei De Chen (US), Alan M. Walfield
(US), John Ye (US), James A. House (US), Chang Yi Wang (US), Ravindra Acharya
(GB), Elizabeth Fry (GB), and David Stuart (GB) performed seminal studies on
the chemical structure, replication, diagnosis, and vaccinology of
foot-and-mouth disease viruses (5; 142; 153; 154; 182; 215; 247; 248; 268; 462; 471; 622; 938; 946; 947; 1016; 1050; 1114; 1131; 1289; 1322; 1323; 1349; 1406).
Theodoras
Krawicz (PL) introduced cryosurgery to remove lens from the eye with a tiny
probe that could attach by freezing a small area on the surface of the cataract (848).
Lowell O. Randall (US), George A. Heise (US), William Schallek (US),
Robert E. Bagdon (US), Ralph F. Banziger (US), A. lu. Boris (US), Robert A. Moe
(US), and William B. Abrams (US) first described the pharmacological properties of Valium. It was
qualitatively like Librium but more potent in many pharmacological tests for
taming, muscle relaxant, anticonvulsant, and sedative effects. It was well
tolerated in rats, dogs, monkeys, and man (1261).
Thomas A. Waldmann (US), Jesse L. Steinfeld (US), Thomas F. Dutcher (US),
Jack D. Davidson (US), and Robert S. Gordon, Jr. (US) described a new syndrome
they named intestinal lymphangiectasia
in patients previously diagnosed as having idiopathic
hypoproteinemia. Intestinal
lymphangiectasia is characterized by a generalized disorder of lymphatic
channels including dilated small intestinal lymphatics that leads to excessive
gastrointestinal protein loss and to hypoproteinemia and edema (1611).
Gordon Allen (US), Clemens E. Benda (US), Jan A. Böök (SE), Cedric O.
Carter (GB), Charles E. Ford (GB), E. H. Y. Chu (US), Ernst Hanhart (CH),
George Jervis (US), W. Langdon-Down (GB), Paul Jérome Lejeune (FR), Hideo
Nishimura (JP), J. Oster (DK), Lionel S. Penrose (GB), Paul E. Polani (GB),
Edith L. Potter (US), Curt Stern (US), Raymond Alexander Turpin (FR), Josef
Warkany (US), and Herman Yannet (US) campaigned for human trisomy 21 (mongolism)
to have its name changed to a designition such as "Langdon-Down
anomaly" or "Down's syndrome or anomaly" (20).
Edward H.
Lambert (US), E. Douglas Rooke (US), Lealdes McKendree Eaton (US), and Corrin
H. Hodgson (US) described a disease, which was later called Lambert-Eaton Syndrome (LES). Its
symptoms are very similar to those of myasthenia
gravis but it is caused by defective release of acetylcholine from the
presynaptic membrane (866).
Resistance
to chloroquine by the malarial parasite was reported in South America and Asia. ref
Franz Gabl
(DE) and Helmut Wachter (DE) reported that the three major human immunoglobulins,
IgG, IgA, and IgM occur in whole mixed saliva (502).
J. Richard
Crout (US), John J. Pisano (US), and Albert Sjoerdsma (US) elucidated the
biochemical pathways of catecholamines and developed diagnosis of
pheochromocytoma prior to exploration (313).
Hugh Edward de Wardener (GB), Ivor H. Mills (GB), W.F. Clapham (GB), and
Clive James Hayter (GB) showed that when glomerular filtration rate and the
steroid hormone aldosterone are controlled, the dog kidney is still able to
increase sodium excretion in response to a salt load. Several lines of evidence
argued for a small-molecule signal as a definitive modulator of sodium
excretion by the kidney (338).
Christopher D. Cain (US), Frank C. Schroeder (US), Stewart W. Shankel
(US), Mark Mitchnick (US), Michael Schmertzier (US), Neal S. Bricker (US) reported
the identification and natriuretic activity of two closely related small
molecules isolated from human urine, xanthurenic acid 8-O-beta-d-glucoside and
xanthurenic acid 8-O-sulfate. Both compounds caused substantial and sustained
(1- to 2-h) natriuresis in rats and no or minimal concomitant potassium
excretion. They surmised that these compounds constitute a class of kidney
hormones that also could influence sodium transport in nonkidney tissues given
that these tryptophan metabolites presumably represent evolutionarily old
structures (206).
Kurt Brück (DE) showed that, in the neonate, the actions of the
thermoregulatory control elements are adjusted to the heat loss conditions
which are determined by factors related to body size. It disproved the
widespread concept of a grossly undeveloped thermoregulatory system. It is not
the unresponsiveness but the very sensitive thermoregulatory reactions which
require the observation of special environmental conditions for the well-being
of the neonate (185).
Doreen
Kimura (CA) found that in left-hemisphere dominant patients, speech is comprehended
more accurately in the right ear and music in the left (808).
Ralph Waldo
Gerard (US) was probably the first to suggest that endogenous stress hormones
can “hasten the fixation process” of new memories thus leading to a vivid
experience (519).
David H.
Carr (CA), Murray Llewellyn Barr (CA), and Earl R. Plunkett (CA) described the Carr-Barr-Plunkett syndrome
characterized by four X chromosomes (48 XXXX). The symptoms include mental
deficiency (IQ average 55) and variable abnormalities, including mid-facial
hypoplasia, hypertelorism, micrognathia, epicanthic folds, clinodactyly of the
fifth finger, radioulnar synostosis, narrow shoulder girdle, webbed neck,
amenorrhea, and irregular menstrual cycles. Behavioral disorders may be associated (236).
James Edgar
Till (CA) and Ernest Armstrong McCulloch (CA) described a technique for the
measurement of the number of cells in a bone marrow suspension capable of
continued proliferation. It involves 'the formation of colonies of
proliferating cells' which, in irradiated mice, appear as gross nodules in the
spleen (1558).
Jacob
Gershon-Cohen (US), Mortimer B. Hermel (US), and Simon M. Berger (US) reported
the results of a five-year survey for detection of breast cancer by periodic
x-ray examinations. Their results suggested that routine mammography is useful
for early detection of breast cancer (529).
Albert
William Liley (NZ) found a correlation
between the spectrophotometrically estimated bilirubinoid pigment concentration
in amniotic fluid and the severity of fetal anemia in Rh hemolytic disease. The
paper presents a method by which this correlation could be used with precision
in selecting the optimal time for delivery of each baby (921).
Albert
William Liley (NZ) reported the first successful intrauterine blood
transfusion. It was to save the life of a severely anemic Rh-positive fetus (922).
Byron H.
Waksman (US), Simone Arbouys (US), and Barry G. Arnason (US) demonstrated the
efficacy of using anti-lymphocyte serum to enhance skin allograft survival
rates in rats (1609).
Michael
Francis Addison Woodruff (GB) and N.A. Anderson (GB) showed that thoracic duct
drainage along with anti-lymphocyte serum further enhanced survival rates of
skin allografts in rats (1683).
Anthony P.
Monaco (US), William M. Abbott (US), H. Biemann Othersen (US), Richard Lawrence
Simmons (US), Mary L. Wood (US), Martin H. Flax (US), and Paul Snowden Russell
(US) demonstrated the therapeutic value of anti-lymphocyte serum for improving
canine kidney transplant survival (1084).
Thomas Earl
Starzl (US), Thomas L. Marchioro (US), Kendrick Arthur Porter (US), Yoji
Iwasaki (US), and G. James Cerilli (US) carried out the first clinical trial of
anti-lymphocyte globulin as an adjunct to azathioprine and prednisone for
enhancing human kidney transplant survival (1467). With the
later advent of monoclonal antibodies these anti-lymphocytic sera became much
more specific.
A. Benedicta
Cosimi (US), Robert B. Colvin (US),
Robert C. Burton (US), Robert H. Rubin (US), Gideon Goldstein (US), Patrick C.
Kung (US), W. Peter Hansen (US), Francis L. Delmonico (US), and Paul S. Russell
(US)
introduced monoclonal anti-CD3 antibody to clinically enhance survival of renal
allografts (301).
John C.
Callaghan (CA) and Jose Delos Angeles (US) developed an artificial placenta for
extracorporeal support of newborns with respiratory
distress syndrome (RDS) (214).
Abraham M. Rudolph (US), James E. Drorbaugh (US), Peter A.M. Auld (US),
Arnold J. Rudolph (US), Alexander S. Nadas (US), Clement A. Smith (US), and
John P. Hubbell (US) performed cardiac catheterization studies in newborn
infants which demonstrated that the ductus
arteriosus is usually closed functionally in normal gestationally mature
babies within 15-20 hours. Premature infants with respiratory distress had a
widely patent ductus arteriosus with
a large shunt, predominantly left-to-right, within the first 20 hours after
birth (1333).
Geoffrey M. Berlyne (US) was the first to report of renal ultrasound in
which the focus was mainly on the value of ultrasound in aiding renal biopsy (124).
Harold R.
Novotny (US) and David L. Alvis (US) were the first to demonstrate the
technique of fluorescein angiography in the human eye. This enabled excellent
contrast studies of ocular circulation and the diagnosis of vascular disease (1150).
Frank J.
Ayd, Jr. (US) found among 3,775 patients treated with tranquilizers of the
phenothiazine group, 1,472 developed extrapyramidal reactions; 21.2% had
akathisia, 15.4% parkinsonism, and 2.3% dyskinesia. There was correlation
between the absolute frequency of these reactions and the chemical structure
and milligram potency of the phenothiazine derivative used. Akathisia and
parkinsonism occurred twice as often in women as in men, but dyskinesia
happened twice as often in men. Dyskinesia was most prevalent between ages 5
and 45, akathisia between 12 and 65, and parkinsonism between 15 and 80.
Dyskinesia occurred the earliest, akathisia next, and parkinsonism last in the
course of treatment. These reactions appeared only in neurologically
susceptible patients. A close parallel was found between drug-induced and
naturally occurring extrapyramidal reactions. Drug-induced striopallidal
symptoms can be adequately treated with antiparkinsonian drugs (77).
James R.
Jude (US), William Bennett Kouwenhoven (US) and G. Guy Knickerbocker (US)
performed the first external cardiac massage to restart a heart (760).
John F.
Burke (US) found that there is a definite short period when the developing
staphylococcal dermal or incisional infection may be suppressed by antibiotics.
This effective period beginning the moment bacteria gain access to the tissue
and is over in 3 hours. Systemic antibiotics have no effect on primary
staphylococcal infections if the bacteria creating the infection have been in
the tissue longer than 3 hours before the antibiotics are given. Antibiotics
cause maximum suppression of infection if given before bacteria gain access to
tissue (196).
Desmond G. Julian (GB) presented the first description of the
coronary care unit (CCU) to the British Thoracic Society in July 1961 (764).
Kesava
Mukund Lele (IN) and John Walton (GB) reported that the earliest plant stomata
appeared in Zosterophyllum myretonianum.
These were more like stomata found in modern moss sporophytes. The type found
in vascular plants appeared 4 to 5 million years later (898).
William Homan
Thorpe (GB) "showed that even where a programmatic element in behavior is
unmistakeably large, environmental clues and cues are necessary for its
complete realization. Even so, the programmatic element in behaviour is large
enough and distinct enough to unseat the fundamental axiom of empericism that
nothing enters the mind except by way of the senses." (1040; 1557).
Keller
Breland (US) and Marian Breland (US) after 14 years of continuous conditioning
and observation of thousands of animals, concluded that the behavior of any
species cannot be adequately understood, predicted, or controlled without
knowledge of its instinctive patterns, evolutionary history, and ecological niche
(167).
J. McVicker
Hunt (US) assembled the evidence against the beliefs that intelligence is
essentially fixed, and that development is predetermined by each individual’s
heredity. The evidence supported plasticity in development and suggested that,
once the adaptive interaction between young individuals and their environmental
circumstances are better understood, it should be possible to increase the
average level of intelligence within the population substantially, as then and
now measured, by something like 30 points of IQ (724).
Vero Copner
Wynne-Edwards (GB) expounds a general theory that animals can limit their own
numbers by social mechanisms. In so doing they avoid depleting their food
resources, in the way man has so often done by overexploiting whales, fish, and
game; or by overgrazing with livestock (1698).
Brian W. Logan (AU), Richard Rezak (US), and Robert N.
Ginsburg (US) discovered living cryptozoon and associate stromatolites at Shark
Bay, Western Australia (932; 933).
The Tokyo University Scientific Expedition to Western Asia
(Director: Hisashi Suzuki) discovered fossil remains of Homo sapiens neanderthalensis; Homo
neanderthalensis in a cave in Wadi Amud, north of Tiberias, Israel (1584).
The remains are c. 25K-40K BP
Jonathan
Leakey (KE-GB), Phillip V. Tobias (ZA), and John R. Napier (GB) found several
fossilized bone fragments of a Homo habilis
skull at Olduvai Gorge in Kenya. Leakey’s wife Meave carefully assembled the
fragments to make a nearly complete skull minus the lower jaw. The skull was
named KNMER 1470 for its registration at the Kenya National Museum in East
Rudolf. Potassium argon dating placed it at 2.61 Ma old (882; 885).
Louis
Seymour Bazett Leakey (KE), Phillip V. Tobias (ZA), and John R. Napier (GB)
proposed that KNMER 1470 be designated as a new species, Homo habilis (884).
Valerii P.
Alexeev (RU) described KNMER 1470 as Pithecanthropus
rudolfensis (16). The name
was subsequently changed to Homo
rudolfensis.
Louis
Seymour Bazett Leakey (KE), in 1961, discovered the upper jawbone of Kenyapithecus wickeri; Rangwapithecus wickeri in
14 Ma deposits in Kenya (883).
Brian W. Logan (AU), Richard Rezak (US), and Robert N.
Ginsburg (US) discovered living cryptozoon and associate stromatolites at Shark
Bay, Western Australia (932; 933; 1219; 1220).
Stanley M. Awramik (US), J. William Schopf (US), Malcolm R.
Walter (US), and Bonnie M. Packer (US) found rock bearing 3.5 Ga. microfossils
within early Archean (Gk. archaios=ancient)
stromatolites (73; 1371; 1373). The
microfossils were interpreted to be prokaryotes and to represent the oldest
fossils known (1372).
Publication of the first issue of CDC's Morbidity and
Mortality Weekly Report (then U.S. Communicable Disease Center)
c.
1962
The
methylbenzimidazole carbamates (MBCs) were introduced as systemic plant
fungicides. These include benomyl, carbendazin, thiophanate, and thiophanate-methyl.
See, C.J. Delp, 1987. Benzimidazole
and related fungicides. In Modern Selective Fungicides—properties,
applications, mechanisms of action. H. Lyr, Ed. Longman Group, London. These
fungicides inhibit the formation of normal microtubules.
1962
“A living
system is constantly fighting against, rather than relying upon, thermodynamic
equilibrium. The thermodynamic significance of specific cellular control
systems precisely is that they successfully circumvent thermodynamic
equilibration (until the organism dies, at least…. Still, the arbitrariness,
chemically speaking, of certain allosteric effects appears almost shocking at
first sight, but it is this very arbitrariness which confers upon them a unique
physiological significance, and the biological interpretation of the apparent
paradox is obvious. The specific structure of any enzyme-protein is of course a
pure product of selection, necessarily limited, however, by the structure and
chemical properties of the actual reactants. No selective pressure, however
strong, could build an enzyme able to activate a chemically impossible
reaction. In the construction of an allosteric protein this limitation is
abolished, since the effector does not react or interact directly with the
substrates or products of the reaction but only with the protein itself…. By
using certain proteins not only as catalysts or transporters but as molecular
receivers and transducers of chemical signals, freedom is gained from otherwise
insuperable chemical constraints, allowing selection to develop and
interconnect the immensely complex circuitry of living organisms.” Jacques
Lucien Monod (761).
"Let
us never forget that Nature is the most original of all experimenters and that
it is the patient’s physician who is privileged to learn most directly from her
sometimes cruel, but never meaningless, clinical presentations." William
Bosworth Castle. From his speech accepting the Kober Medal of the Association
of American Physicians, in 1962.
Max
Ferdinand Perutz (AT-GB) and John Cowdery Kendrew (GB) were awarded the Nobel
Prize in Chemistry for their studies of the structures of globular proteins.
Francis
Harry Compton Crick (GB), James Dewey Watson (US) and Maurice Hugh Frederick
Wilkins (GB) were awarded the Nobel Prize in Physiology or Medicine for their
discoveries concerning the molecular structure of nuclear acids and its
significance for information transfer in living material.
Tibor Barka
(US) and Paul J. Anderson (US) analyzed problems inherent in the histochemical
demonstration of acid phosphatase activity and described methods which provide
reliable, accurate localizations (81).
Osamu
Shimomura (JP-US), Frank H. Johnson (US), and Yo Saiga (US) extracted, purified
and noted the properties of aequorin, a bioluminescent protein from the
luminous hydromedusan, Aequorea. Green fluorscent protein (GFP) was also
isolated at this time (1411).
James G. Morin
(US) and J. Woodland Hastings (US) detected an intermolecular energy transfer
between aequorin and GFP in jellyfish (1098).
Osamu
Shimomura (JP-US) characterized the structure of the chromophore of Aequorea
green fluorescent protein (1410).
Douglas C. Prasher
(US), Richard O. McCann (US), and Milton J. Cormier (US) cloned and expressed
the Cdna coding for aequorin, a bioluminescent calcium-binding protein (1239).
Douglas C.
Prasher (US), Virginia K. Eckenrode (US), William W. Ward (US), Franklyn G.
Pendergast (US), and Milton J. Cormier (US) determined the primary structure of
the Aequorea victorea green fluorescent protein (1238).
Chris W. Cody
(US), Douglas C. Prasher (US), William M. Westler (US), Frank G. Pendergast
(US), and William W. Ward (US) determined the chemical structure of the
hexapeptide chromophore of the Aequorea green fluorescent protein .
Martin
Chalfie (US), Yuan Tu (US), Ghia Euskirchen (US), William W. Ward (US), and Douglas
C. Prasher (US) discovered how to use green fluorescent protein as a marker for
gene expression (249).
Mats Ormö
(US), Andrew B. Cubitt (US), Karen Kallio (US), Larry A. Gross (US), Roger
Yonchien Tsien (US), S. James Remington (US), Fan Yang (US), Larry G. Moss (US),
and George N. Phillips, Jr. (US) produced the first crystal structures of
wild-type and enhanced GFP. Tsien designed T203Y mutant based on crystal
structure of S65T GFP. It is yellow fluorescent (1186; 1700).
Mikhail V. Matz
(RU), Arkady F. Fradkov (RU), Yulii A. Labas (RU), Aleksandr P. Savitisky (RU),
Andrey G. Zaraisky (RU), Mikhail L. Markelov (RU), and Sergey A. Lukyanov (RU) cloned
six fluorescent proteins homologous to the green fluorescent protein (GFP) from
Aequorea victoria. Two of these have spectral characteristics
dramatically different from GFP, emitting at yellow and red wavelengths. Many
new fluorescent proteins and chromoproteins were discovered. GFP was found to
tolerate insertion of entire proteins in certain locations and can be
circularly permuted (1024). Note: DsRed, a red
fluorescent protein from coral, was discovered.
Robert E.
Campbell (US), Oded Tour (US), Amy E. Palmer (US), Paul A.. Steinbach (US), Geoffrey
S. Baird (US), David A. Zacharias (US), and Roger Yonchien Tsien (US) produced
a monomeric form of red fluorescent protein (mRFP1) which proved to be much
more useful than DsRed as a genetically encoded fusion tag (222).
Malte C.
Gather (US) and Seok Hyun Yun (KR-US) showed that fluorescent proteins in cells
are a viable gain medium for optical amplification, and report the first
successful realization of biological cell lasers based on green fluorescent
protein (GFP) (508).
Klaus
Scherrer (CH) and James E. Darneil, Jr. (US) described how techniques developed
for extraction of infectious viral nucleic acid were used to extract cell RNA,
resulting in the recognition, for the first time, of high molecular weight
nuclear RNA from mammalian cells. The dominant rapidly labeled peaks, ‘45S’ and
‘35S,’were subsequently found to be ribosomal precursor RNA, and the
polydisperse material was characterized as the so-called ‘heterogeneous nuclear
RNA,’ the hnRNA (1362).
Wendell
Caraway, Jr. (US) deals with a survey and discussion of variables and potential
sources of error in the individual specimen that affect the chemical
specificity of clinical laboratory tests. Special attention is directed to
factors less subject to correction by means of the usual technics of quality
control. These include consideration of chemical specificity, anticoagulants,
stability of specimens, hemolysis, lipemia, control of temperature and pH,
contamination, effect of medications, and normal physiologic variations in
persons (228).
William
Wallace Cleland (US), from his analysis of many enzymatic reactions, described
a general method for predicting initial velocity, dead end, and product
inhibition patterns by inspection of the mechanism (278).
Thomas
Samuel Kuhn (US) argued that science is not a steady, cumulative acquisition of
knowledge but instead a series of peaceful interludes punctuated by
intellectually violent revolutions. He described science in terms of
paradigms—pervasive frameworks of scientific thoughts (857).
Lucien G.
Caro (CH) and Robert P. van Tubergen (CH) described methods used in obtaining
high resolution in autoradiography, with special emphasis on the technique of
electron microscopic autoradiography, together with control experiments
designed to establish the optimum conditions or procedures. These methods give
a good localization of the label, at the subcellular level, and good
reproducibility in relative grain counts (235).
Aaron H.
Anton (US) and David F. Sayre (US) presented a reliable, quantitative, highly
sensitive, adaptable method for the estimation of catechol-amines in diverse
biological material from various vertebrate species. This method involves the
selective adsorption of the catecholamines onto a constant amount of aluminum
oxide, elution with constant volume of perchloric acid (0.05 N), and their
measurement by the formation of a fluorescent trihydroxyindole derivative in
the presence of potassium ferricyanide and alkaline (10 N alkali) ascorbate (36).
Dianne Mattingly (GB) greatly improved and simplified a fluorimetric
method for the estimation of free 11-hydroxycorticoids in human plasma. Their
plasma concentration is a valuable measure of adrenocortical activity, provided
that the normal circadian rhythm is considered (1023).
Arthur S.
Barclay (US), in 1962, collected the bark of the Pacific Yew tree, Taxus brevifoli Nutt. as part of a joint
effort by the United States Department of Agriculture and the National Cancer
Institute to discover new anticancer agents (810). Circa 1963
its extract was found it be anticancerous in an animal study. ref
Scientists
at the Research Triangle Institute (RTI) in North Carolina extracted from the
Pacific Yew an anticancer agent they named taxol.
Mansukh C.
Wani (US), Harold L. Taylor (US), Monroe E. Wall (US), Philip Coggon (US), and
Andrew T. McPhail (US) reported the molecular structure of taxol based on x-ray crystallographic studies (1621). Taxol is an antileukemic and antitumor
agent isolated from Taxus brevifolia Nutt.
Peter B.
Schiff (US), Jane Fant (US), and Susan Band Horwitz (US) discovered
that taxol interferes with cell
division by binding to the protein tubulin, which is a key factor in mitosis.
Unlike some other cancer drugs, which prevent tubulin from assembling into
microtubules, taxol binds to
assembled microtubules and blocks them from disassembling (1363).
Colin C.F.
Blake (GB), Ruth H. Fenn (GB), Roberto J. Poljak (FR), Don F. Koenig (US),
Gareth A. Mair (GB), A.C. Tony North (GB), David Chilton Phillips (GB), V.
Raghu Sarma (GB), and Louise N. Johnson (GB) used x-ray analysis to solve the
structure of lysozyme, the first
enzyme to be so analyzed. They also got the first detailed molecular view of an
enzyme’s active site. The analysis was carried out on crystalline lysozyme from egg white at a resolution
of two angstroms (145-148; 754; 1217). The
Johnson paper is the first in which x-ray crystallographic studies gave direct
information about the active site.
Christian
Boehmer Anfinsen, Jr. (US) demonstrated that the information
required to fold the polypeptide chain of ribonuclease
into the specific three-dimensional form of the active enzyme resides in the
sequence of amino acids (32).
Gustav V.R.
Born (GB) introduced a photometric method with which platelet aggregation and
its inhibition by adenosine diphosphate and related compounds respectively are
investigated quantitatively (159).
James L. German, 3rd (US), using human blood cells, found that
experiments using pulse-labeling with tritiated-thymidine provide information
concerning the location of synthesis of DNA at various times, and the pattern
has been found to be complex. The different chromosomes follow no consistent
pattern such as replication beginning at the centromeres and continuing to the
telomeres. However, during the final 150 to 180 minutes of the S period, one
chromosomal region after another becomes fully replicated although the pattern
at this time also is complex and different in each chromosome.
One striking finding strongly suggested that the pattern of DNA
replication may be of functional significance.
These experiments gave the best confirmation of the single-X
origin of sex chromatin (527).
Hans Ris
(CH-US) and Walter Plaut (US) found DNA in the chloroplast of Chlamydomonas moewusii. They speculated
that this may represent the genetic system of the chloroplast and hypothesized
that the chloroplast represents an evolved endosymbiont (1300).
Edward H.L.
Chun (US), Maurice Vaughn, Jr. (US), Alexander Rich (US) Ruth Sager (GB), M.R.
Ishida (US) and John T.O. Kirk performed the first unambiguous isolations of
DNA from chloroplasts of spinach, beet, Chlamydomonas, and ChlorelIa reported
by Edward H. L. Chun, Maurice H. Vaughan, Jr., and Alexander Rich; from Chlamydomonas
by Ruth Sager (US) and M. R. Ishida (US); and from broad bean by John T. O.
Kirk (GB) (270; 813; 1342).
Daphne J.
Osborne (GB) noted that as leaves age and yellow, changes take place within the
cells which include degradation of proteins and nucleic acids. She discovered
that senescence and loss of integrity of these macromolecules could be arrested
by simply applying the requisite plant hormone to the leaves opening a new and
exciting era in studies of cellular senescence. The incorporation of
radioactive precursors indicated that the hormone-maintained synthesis of
nucleic acids and proteins deferred senescent change and retained cellular
homeostasis (1193).
Kathryn S.E.
Cheah (GB) and Daphne J. Osborne (GB) found that in dry seeds, fragmentation of nuclear DNA and activation of DNases occur in
vivo during embryo senescence. This loss of DNA integrity could be the
source of chromosomal aberrations and impaired transcription observed when
seeds of low viability germinate (264).
Peter
Reichard (AT-SE), using Escherichia coli,
managed to purify two enzyme fractions, A and B (later called R) that
participated in the formation of deoxycytidine phosphates from CMP. He found
that Fraction A catalyzed the phosphorylation of cytidine 5-phosphate (CMP) to
cytidine 5-diphosphate (CDP) whereas Fraction B (later called R) carried out
the reduction of the cytidine diphosphate to deoxycytidine diphosphate (dCDP).
The reaction catalyzed by Fraction B required ATP, Mg2 ions (1273).
Anders
Ehrenberg (SE) and Peter Reichard (AT-SE) discovered that R2 contains a signal
characteristic of a free radical. The presence of this signal is also linked to
the enzymatic activity of R2, suggesting that ribonucleotide reduction proceeds
by radical chemistry. They also found that it contains two atoms of iron (393).
Jens Harder
(SE), Rolf Eliasson (SE), Elisabet Pontis (SE), Marcus D. Ballinger (US), and
Peter Reichard (AT-SE) showed that the overall reduction of CTP occurred in two
steps. The first step is the activation of the reductase (dA3) by dA1 and RT. During this step AdoMet (S-adenosyl-L-methionine) is reductively
cleaved into methionine and 5-deoxyadenosine. The second step involves the
actual reduction of CTP with dithiothreitol as the hydrogen donor (616).
James Whyte
Black (GB), John S. Stephenson (GB), Anne C. Dornhorst (GB), and Brian F.
Robinson (GB) discovered the first clinically useful beta-blocker, called pronethalol. The doses at which it is
useful are carcinogenic in mice (144; 361).
James Whyte
Black (GB), Albert Frederick Crowther (GB), Robin G. Shanks (GB), Lloyd
Hollingsworth Smith, Jr. (GB), and Anne C. Dornhorst (GB) produced propanolol, a much safer and more
efficient beta blocker (143).
Beta-blockers
are so called because they block the absorption of hormones by beta-receptors
in the nervous system. Blocking these receptors causes the heart to slow down
so it uses less oxygen. It also lowers the blood pressure.
R. Charlier (BE), G. Deltour (BE),
Rene Tondeur (BE), and Fernand Binon (BE) discovered amiodarone (262). This drug is used to treat angina pectoris and cardiac arrhythmias.
Donald J.
Mason (US), Alma Dietz (US), and Clarence DeBoer (US) isolated the antibiotic lincomycin from Streptomyces lincolnensis found in soil near Lincoln, Nebraska (1015).
Wagn O.
Godtfredsen (DK), Sverre Jahnsen (DK), Henning O.B. Lorck (DK), Knud Roholt
(DK), and Leif Tybring (DK) isolated the antibiotic fusidic acid (fucidin)
from Fusidium coccineum (548).
B.B. Gokhale
(IN), Arvind A. Padhye (IN-US), M.V. Joglekar (IN), and R. Anjaneyuln (IN)
isolated the antifungal antibiotic hamycin
from Streptomyces pimprina (551).
Albert L. Chaney (US) and Edward P. Marbach (US) described a
simplified indophenol reaction for the measurement of ammonia in biological
fluids (253).
Kurt M. Dubowski (US) described a single-reagent manual method for
measurement of glucose in biological fluids (372).
Gilbert N.
Ling (CN-US) presented the principles of his new theory and developed the Association-Induction (A-I) Hypothesis.
This theory incorporates the ideas that (a) cell water is structured—by
“structured” it is meant that the water molecules are not free or random but
exhibit an orderly arrangement as in ice crystals—although cellular structured
water is much less solid than ice (b) cell cations are associated mostly with
macromolecules and (c) cation pumps do not exist
(925).
George Yohe
Lesher (US), Ernest J. Froelich (US), Monte D. Gruett (US), John H. Bailey
(US), and R. Pauline Brundage (US) prepared and identified nalidixic acid as an antibacterial agent worthy of clinical
development. It is the prototype of the highly potent class of antibacterial
agents called quinolones (908).
Martin Frank
Gellert (US), Kiyoshi Mizuuchi (US), Mary H. O'Dea (US), Tateo Itoh (JP), and
Jun-Ichi Tomizawa (JP) identified DNA
gyrase of bacteria as the target of nalidixic
acid and oxolinic acid (515).
Hitoshi Koga
(JP), Akira Itoh (JP), Satoshi Murayama (JP), Seigo Suzue (JP), and Tsutomu
Irikura (JP) discovered the fluorinated quinolone norfloxacin, which possesses considerable broad-spectrum
antibacterial activity (829).
Gerald Maurice Edelman (US) and Joseph A. Gally (US) found that
the light chains of myeloma proteins
and Bence Jones proteins are identical (386).
Calvin M.
Kunin (US) discovered an antigen common to all Enterobacteriaceae and
designated it as enterobacterial common antigen (CA or ECA) (858; 859). It has
also been called the Kunin-antigen.
Through the efforts of many its composition was ultimately determined to be an
amino sugar polymer built of N-acetyl-D-glucosamine and
N-acetyl-D-mannosaminuronic acid partially esterified by acetic and palmitic
acids.
Joseph D.
Mann (US), Amos Cahan (US), Allen G. Gelb (US), Nathalie Fisher (US), Jean Hamper
(GB), Patricia Tippett (GB), Ruth Sanger (GB), and Robert Russell Race (GB) discovered
the Xg blood group antigen (993).
Roger Wolcott Sperry (US) provided the direct histological evidence and proposed the chemoaffinity hypothesis for axon
guidance, i.e., growing axons are guided principally by molecular determinants,
rather than mechanical determinants such as cells, extracellular material and
other neurons. The growing axons take a path by responding to specific
guidance molecules that either attract or repel the growth cone (1451).
Ferruccio M.
Ritossa (IT) described a new puffing pattern in salivary gland chromosomes of Drosophila following heat shock (1301). This was
the first description of a heat shock response.
Alfred
Tissières (CH), Herschel K. Mitchell (US) and Ursula M. Tracy (US) were the
first to identify the relevant gene products—the heat shock proteins (1561).
Michael J.
Chamberlin (US), Paul Berg (US), John J. Furth (US), Jerard Hurwitz (US), and
Monika Anders (US) described the purification and characterization of a RNA polymerase from Escherichia coli. This enzyme catalyzes the synthesis of RNA from
the four ribonucleoside triphosphates, and is completely dependent on DNA (250; 498).
Johann
Heinrich Matthaei (US), Oliver W. Jones (US), Robert G. Martin (US), and
Marshall Warren Nirenberg (US) created a cell-free protein synthesizing system
in which they could test the effect of template RNA (mRNA) on amino acid
sequence. They found: (1) that longer polynucleotide chains are more effective
than shorter ones at directing the synthesis of polyphenylalanine from
polyuridylic acid, 2) One molecule of polyuridylic acid may direct the
synthesis of a number of molecules of polyphenylalanine, 3) randomly mixed
polynucleotides as well as homopolynucleotides
can be used to direct cell-free amino acid incorporation, 4) two coding units
corresponding to leucine were found; thus, part of the code was shown to be degenerate, 5) certain nucleotide
sequences in a polynucleotide did not code for any amino acid: therefore, the
presence of nonsense coding units was
suggested, 6) the minimum number of nucleotides per coding unit appeared to be
three, and 7) comparison between the composition of RNA coding units in E. coli and amino acid replacement data
in tobacco mosaic virus suggested that at least a part of the code may be
universal (1021).
Bernard
Weisblum (US), Seymour Benzer (US), and Robert William Holley (US) found that Escherichia coli contains two different
sRNAs (tRNAs) acting as acceptor-carriers for leucine. One reacts with poly UC,
while the other reacts with poly UG. This provides an explanation for the
degeneracy observed in coding experiments with leucine. The experiments also
confirm that the coding specificity is carried by the sRNA (tRNA) (1647).
Dario
Giacomoni (US) and Solomon Spiegelman (US), using RNA-DNA hybridization
techniques, concluded that the genome contains tRNA complementary sequences for
more than twenty amino acids. This evidence they concluded supports the idea
that the code is degenerate. They found that tRNA molecules specific for a
given amino acid did differ in some of their nucleotide sequence if taken from
different species (531).
Sewell P.
Champe (US) and Seymour Benzer (US) found that 5-fluorouracil is incorporated
into messenger RNA in place of uracil, there acting partially like cystine.
This allows 5FU to partially reverse defective phenotypes of certain rII
mutants of phage T4. The results are consistent with the idea that only one strand
of the DNA duplex is copied into useful messenger RNA (251).
Julius
Marmur (US), Carol M. Greenspan (US), Emil Palecek (CZ), Frederick M. Kahan (US),
James Levine (US), and Manley Mandel (US), using Bacillus subtilis and the bacteriophage SP8, also presented
experimental evidence that only one of the two complementary strands of DNA
acts as a template for messenger RNA (1005).
Raymond
Valentine Tomlinson (CA-US), Gordon Malcolm Tener (CA), Robert William Holley
(US), James T. Madison (US), and Ada Zamir (US) developed methodologies by
which they could determine the nucleotide base sequence in small
oligonucleotides (697; 1570; 1571).
Seymour
Benzer (US) and Sewell P. Champe (US), Alan Garen (US), and Obaid Siddiqi (IN)
discovered, using the T4 bacteriophage of Escherichia
coli, that nonsense mutations can
produce codons which behave as nonsense
codons, meaning they do not code for an amino acid (115; 506).
Seymour
Benzer (US), Sewell P. Champe (US), Sydney Brenner (ZA-GB), Anthony O.W.
Stretton (US), Samuel Kaplan (US), Leslie Barnet (GB), Eugene R. Katz (US),
Francis Harry Compton Crick (GB), Martin G. Weigert (US), Erich Lanka (DE), and
Alan Garen (US) provided evidence that there are three nonsense codons, UAA (ochre),
UAG (amber), and UGA which do not
specify an amino acid. Brenner, Stretton, and Kaplan suggested that the
nonsense codons should be more properly considered to be the codons for
polypeptide chain termination (115; 169; 174; 1643; 1644).
Giuseppe Macino (IT), Gloria Coruzzi (US), Francisco G. Nobrega
(US), May Li (US), and Alexander Tzagoloff (US) performed a sequence
analysis of yeast mitochondrial DNA regions coding for structural genes of
cytochrome b, cytochrome oxidase, and the ATPase.
They concluded that the classic UGA terminator regularly occurs as a tryptophan
codon in yeast mitochondrial DNA (970).
Susan G.
Bonitz (US), Roberta Berlani (US), Gloria Coruzzi (US), May Li (US), Giuseppe
Macino (IT), Francisco G. Nobrega (US), Marina P. Nobrega (US), Barbara E.
Thalenfeld (US), and Alexander Tzagoloff (US) established the codon recognition
rules in yeast mitochondria as follows: The four
codons of unmixed families are recognized by single tRNAs that always have a U
in the wobble position of the anticodon. Two different tRNAs read the codons of
the mixed families. Codons terminating in a C or U are recognized by tRNAs with
a G and codons terminating in a G or A are recognized by tRNAs with a U in the
corresponding positions of the anticodons. There are two exceptions to these
rules. In the AUN family for isoleucine and methionine, the isoleucine tRNA has
a G and the methionine tRNA has a C in the wobble position. The tRNA for the arginine
CGN family also has an A in the wobble position of the anticodon. It is of
interest that the CGN codons have not been found in the mitochondrial genes
sequenced to date. The simplified decoding system of yeast mitochondria allows
all the codons to be recognized by only 24 tRNAs
(157).
Dennis
Francis Cain (US) and Robert E. Davies (US) poisoned muscles with 1-fluoro-2,
4-dinitrobenzene (DFNB), thus preventing phosphocreatine from reconverting ADP
to ATP. The amount of ATP lost with each muscle twitch was determined and was
found to account for the energy needed to cause the muscles to shorten.
Finally, ATP had been shown to be the direct source of energy for muscle
contraction (207).
Ellis T.
Bolton (US) and Brian John McCarthy (US) reported a DNA-agar technique for
determining the degree of complementarity between two fragments of DNA (152).
Maurice Hugh
Frederick Wilkins (GB) demonstrated that the B form of DNA was present in all
the organisms he tested, from viruses to mammals
(1660).
Francois
Chapeville (US), Fritz Albert Lipmann (DE-US), Günter von Ehrenstein (US),
Bernard Weisblum (GB), William J. Ray (US), and Seymour Benzer (US) developed a
method to demonstrate directly that only the sRNA (tRNA) molecule, and not its
attached amino acid, found the place on the template (mRNA) calling for that
amino acid (261).
Marshall
Warren Nirenberg (US) and Johann Heinrich Matthaei (DE), and Oliver W. Jones
(US) performed an experiment demonstrating that when poly-uracil directs the
synthesis of poly-phenylalanine a transfer RNA specific to phenylalanine is an
obligate intermediate in the process (1139).
Sydney
Brenner (ZA-GB) invented the term codon
as it applies to an RNA sequence, which specifies a specific amino acid (761).
Cyrus
Levinthal (US), Alexander Keynan (IL), and Akiko Higa (US) used Bacillus subtilis to demonstrate that
messenger RNA is used on average 10-20 times with a half-life of 20 minutes (910).
Daniel
Nathans (US), Gursuran Notani (US), James H. Schwartz (US), and Norton David
Zinder (US) used a cell-free system from E.
coli with bacteriophage f2 RNA to produce viral coat protein identical in
amino acid sequence to that isolated directly from the virus. This was the
first example of purified mRNA directing the synthesis of a specific protein (1120).
Jonathan R.
Warner (US), Alexander Rich (US), Cecil E. Hall (US), and Paul M. Knopf (US)
found that the predominant species of ribosome synthesizing hemoglobin
consisted of a cluster of five ribosomes acting on the same messenger RNA
strand (1623; 1624). These
findings were interpreted to mean that the ribosomal particles begin protein
synthesis by attaching at one end of the messenger RNA strand then move along
it as the polypeptide chain elongates. This represents the discovery of
polyribosomes (polysomes).
Alexander
Rich (US) and Walter Gilbert (US) independently discovered that a single
messenger RNA molecule can be read simultaneously by several ribosomes. These
complexes of mRNA with ribosomes are called polyribosomes (polysomes) (538; 539; 1285).
Lloyd Barr
(US) and Maynard M. Dewey (US) described intercellular connections (gap
junctions) between smooth muscle cells in canine gut tissue (88).
Tracy Morton
Sonneborn (US) and Janine Beisson (US), in studies of the cortex of Paramecium aurelia, showed that the form
and arrangement of the pre-existing structures determine the form and
arrangement of new structures (111; 1447; 1448).
Mary Agnes
Chase (US) and Cornelia D. Niles (US) produced their Index to Grass Species. This is a verified card index, some 80,00
cards, for all (worldwide) published names of grasses (263). The
collection accessions of Chase, mostly grasses, ran to about 12,000 numbers.
Knut
Schmidt-Nielsen (DK-US) reported that desert reptiles maintain their osmotic
regulation by avoiding excessive heat exposure, eating prey with high water
content, and excreting uric acid (1367).
Michael Hollings (GB) was the first to clearly
implicate a virus infection as the cause of die-back
disease of cultivated mushrooms (699).
Aron Arthur
Moscona (US) and Robert E. Hausman (US) proposed that cells recognize each
other using very specific surface molecules (634; 1101).
Youssef
Hatefi (IR-US), Arne G. Haavik (US), L.R. Fowler (US), and David E. Griffiths
(GB) reconstituted a functional electron transport system from fragmented beef
heart mitochondria and identified its components
(630).
Walter
Plowright (GB) developed a rinderpest vaccine which is so effective that it has
almost eradicated the disease (1221).
William C.
Russell (GB) demonstrated plaques in tissue culture caused by Herpes virus type 1 (1336).
James S.
Porterfield (GB), Jordi Casals (ES-US), Charles H. Calisher (US), and Nick
Karabatsos (US) participated in the development of the arbovirus serological
classification scheme (213; 240; 241; 1231).
Julio G.
Barrera-Oro (AR-US), Kendall O. Smith (US), and Joseph Louis Melnick (US)
discussed the quantitation of papova virus particles in human warts (92).
George Bellamy
Mackaness (AU-US) while studying the phagocytosis of Staphylococcus aureus, showed that this bacterium was relatively
resistant to phagocytosis by macrophages, unless a specific immune serum was
provided. The greater efficiency observed with polymorphonuclear phagocytes led
him to suggest that the antibacterial mechanisms of the two cell types were
fundamentally different (971).
George
Bellamy Mackaness (AU-US) discovered that successful infection by Listeria monocytogenes depends upon its
ability to multiply within macrophages and monocytes. He also showed that
inactivation of Listeria monocytogenes
is better achieved in convalescent mice, thanks to the presence of resistant
macrophages, because of immunological activation occurring during the primary
infection (972; 974). Note: This work led him to introduce the
concept of macrophage activation.
Robert J.
North (GB) and George Bellamy Mackaness (AU-US) used electron microscopic
observations of peritoneal macrophages from mice immunized with L. monocytogenes to reveal structural
differences with macrophages from normal mice (1147).
George
Bellamy Mackaness (AU-US) while studying Brucella
abortus or M. tuberculosis
infection, in addition to Listeria, showed that the acquired resistance
was dependent on the immunological reactivity of the host and specific
antibodies against microbial antigens (973).
George
Bellamy Mackaness (AU-US) discovered cellular cooperation. He demonstrated that
the acquired resistance was dependent on the activation of macrophages through
a product resulting from specific interaction between sensitized lymphoid cells
and the microorganism (974).
James Gerald
Hirsch (US) characterized a bactericidal substance isolated from
polymorphonuclear cells he called, “phagocytin”. Phagocytin, identified in
rabbit neutrophils, was bactericidal on gram-negative and -positive bacteria
but was not bacteriolytic. Extracts from human and guinea pig neutrophils were
less efficient, and the activity was absent from mouse and rat cells (676).
James Gerald
Hirsch (US) and Alice B. Church (US) also reported that group A streptococci
exert an antiphagocytic effect through the action of the hyaluronic acid
capsule and M protein. Factors present in human plasma but absent in rabbit
plasma can counteract this antiphagocytic effect (678).
James Gerald
Hirsch (US) and Zanvil Alexander Cohn (US) used microscopic and
“cinemicrophotographic” studies to provide details of the fusion between the
granule membrane and the invaginated cell membrane overlying the ingested
particle with discharge of granule contents directed into the phagocytic
vacuole (677; 679).
Gordon T.
Archer (US) and James Gerald Hirsch (US) identified a similar mechanism within
eosinophils (49).
Zanvil
Alexander Cohn (US), and Edith Wiener (US) discovered that specific phagocyte
granules, the lysosomes, discharge their contents into the phagosome containing
the ingested microorganism, leading to the digestion of the microbes (289).
Ralph van
Furth (NL) and Zanvil Alexander Cohn (US) identified blood monocytes as the
precursors for tissue macrophages and bone marrow as the source of monocytes (1589).
Ralph van
Furth (NL) published an elaborate figure depicting the origin and kinetics of
mononuclear phagocytes and the nature of the involved hematopoietic factors (1588).
Janet V.
Passonneau (US) and Oliver H. Lowry (US) observed that during glycolysis high
levels of inorganic phosphate counteracted the ATP inhibition of 6-phosphofructokinase (1205).
Allan McCulloch
Campbell (US) proposed a model for the attachment of the prophage to the
bacterial chromosome. According to this model, the phage genome is capable at
some stage during its life cycle of circularizing—i.e., its ends become
physically associated with each other. Lysogenization results from a reciprocal
crossover between a specific region of the circularized phage genome and its
homolog in the bacterial chromosome. The result is the prophage is inserted
into the bacterial chromosome. The vegetative phage and the prophage are both
linear structures, derived by cutting the same circle at different points. The
gene order on one is a circular permutation of that on the other (219-221). Note:
Enrico Calef (IT), Giuseppe Licciardello (IT), Alfred Day Hershey (US),
Elizabeth Burgi (US), Laura Ingraham (US), Martin Frank Gellert (US), Ray Wu (CN-US),
and Armin Dale Kaiser (US) made significant contributions which led to the
understanding of lambda prophage insertion (212; 514; 663; 1689).
Werner Arber
(CH) and Daisy Dussoix (CH) found that lambda
bacteriophages carry a host specificity determined by the bacterial strains on
which they were produced. Upon infection of a different bacterial host (1) the
phage DNA may be either accepted or rejected based on this specificity, (2) if
accepted, the phage multiplies, and progeny phage are produced carrying the
same specificity of the original infecting phage. Working with Escherichia coli K-12 Arber discovered
that lambda virus will not grow in
cells infected with P1 virus. His results suggested that P1 is methylated and
thus protected from cellular nucleases (43; 44).
Werner Arber
(CH), Urs Kuhnlein (CA), Stuart M. Linn (US), Matthew Meselson (US) and Robert
Yuan (US), working with extracts of Escherichia
coli strain B, discovered a specific enzyme capable of methylating DNA and
another specific enzyme capable of breaking down unmethylated DNA (43; 45; 926; 1049). These
extracts contained the first known restriction
endonucleases, which represent a cellular defense mechanism, preventing
hydrolysis of the parental DNA by nucleases in the cell. The nucleases protect
against the introduction of foreign DNA.
Robert Louis
Sinsheimer (US), Barbara Starman (US), Carolyn Nagler (US), and Shirley Guthrie
(US) studied the intracellular replication of single stranded DNA from øX174
and found that the circular infectious plus
strand serves as template for the synthesis of a complementary minus strand, yielding the
double-stranded replicative form, or RF. At early stages of infection, RF
replicates semiconservatively to yield daughter RF molecules. At late stages of
infection, when phage-capsid protein molecules are already present, a new,
asymmetric mode of replication sets in. Now only the minus strands of the RF
serve as template for the synthesis of a daughter plus strand, thereby
expelling the old plus strand from the RF molecule. The expelled plus strand is
then encapsulated into a progeny phage capsid (1428; 1429).
Seymour
Benzer’s (US) second, and probably most important use of the rII mutants provided an experimental
definition of the gene. In order to examine whether two different rII mutants belong to the same
functional unit, he adapted to phages the cis-trans
or complementation test, which had
been developed previously with higher organisms for the very purpose of probing
the nature of the functional unit of the gene. Benzer’s complementation test is
based upon the finding that, in a strain K bacterium infected jointly with rII mutant and r+ wild-type phages, both types can grow normally. The
normal rII+ gene of the
wild-type parent is, therefore, able to supply the function necessary for
growth in the strain K bacterium, not only for itself but also for the
defective rII mutant. Or, in genetic
parlance, in mixed infection the r+
wild-type gene is dominant over its rII
mutant allele. Based on this test, Benzer found that rII point mutations fall into two functional groups, A and B; all
mutants belonging to one group complement any member of the other group in the
production of infectious progeny in joint growth in strain K, but do not
complement in this way any members of their own group. It turned out,
furthermore, that the two groups A and B could be assigned definite positions
on the genetic fine structure map of the T4 phage (114). It was
Seymour Benzer (US) who introduced the concept of the cistron: the smallest unit of function of the gene.
John J.
Trentin (US), Yoshiro Yabe (US), and Grant Taylor (US) demonstrated that a
human virus, adenovirus type 12, possesses oncogenic properties upon
intrapulmonary injection into newborn hamsters (1575).
James
Learmonth Gowans (GB), Douglas D. McGregor (US), Diana M. Cowen (GB), and
Charles Edmund Ford (GB) found that the small lymphocyte can mount both
cellular and humoral immune responses to specific antigens (576).
Audrey N.
Roberts (US) and Felix Haurowitz (CZ-US) showed that when a cell takes in
antigen it is deposited in the cytoplasm and not the nucleus (1304).
David W.
Dresser (US) was the first to perform an experiment, which showed that T cells
of the immune system require a minimum of two signals to become activated. They
must be exposed to both antigen and to a molecular signal from the
antigen-presenting cell (367).
Stanislaw
Dubiski (PL), Jan Rapacz (PL), Anna Dubiska (PL), Julian B. Fleishman (GB),
Roger H. Pain (GB), Rodney Robert Porter (GB), and Gerald W. Stemke (CA)
demonstrated that immunoglobulins are composed of two polypeptide chains
encoded by unlinked genes (371; 453; 1473).
Vincenzo
Buonassisi (US), Gordon Hisashi Sato (US), and Arthur I. Cohen (US) developed a
reliable method for producing and maintaining highly differentiated tumor cell
lines in vitro (190).
Ernest
Robert Sears (US) used telocentric chromosomes in wheat to determine the
frequency of crossing over between a genetic locus and the centromere (1387; 1388).
John
Bertrand Gurdon (GB), Tom R. Elsdale (GB), Donald D. Fischberg (GB), Donald D.
Brown (GB), Vreni Uehlinger (GB), Charles D Lane (GB), Hugh R. Woodland (GB), Gerard
Marbaix (GB), Ronald A. Laskey (GB), O. Raymond Reeves (GB), transferred nuclei
from adult cells into eggs and showed that the resulting cells took on
embryonic characteristics. This advance established that cells retain all of
their genes as they specialize and that fully developed cells can be re-set to
an embryonic state — controversial discoveries at the time (180; 181; 586-593).
Kazutoshi
Takahashi (JP), Shinya Yamanaka (JP), Keisuke Okita (JP), Koji Tanabe (JP), Mari Ohnuki
(JP), Merumi Narita (JP), Tomoko Ichisaka (JP), Kiichiro Tomoda (JP), Masato Nakagawa
(JP), Michiyo Koyanagi (JP), Takashi Aoi (JP), Yuji Mochiduki (JP), and Nanako
Takizawa (JP) unlocked a new realm of practical possibilities for nuclear reprogramming
when they made adult cells behave like embryonic cells by adding only a few
factors. This revelation has offered scientists novel ways to harness and study
the powers of embryonic development (38; 1112; 1177; 1178; 1512; 1513).
Robert
Palese Perry (US), Jan-Erik Edström (SE), Joseph Grafton Gall (US), Max Luciano
Birnstiel (CH), Margaret I.H. Chipchase (US), Beal B. Hyde (US), J. Jacob (GB),
Julio L. Sirlin (GB), Donald D. Brown (US), John Bertrand Gurdon (GB), Mikhail
I. Lerman (RU), V.L. Mantieva (RU), Georgii Pavlovich Georgiev (RU), Ferruccio M. Ritossa
(IT), and Solomon Spiegelman (US) established the
nucleolus as the site of ribosomal RNA synthesis
(138; 139; 180; 391; 906; 1214; 1302).
John M.
Thoday (GB) and John B. Gibson (GB) established a population of Drosophila melanogaster from four gravid
females. They applied selection on this population for flies with the highest
and lowest numbers of sternoplural chaetae (hairs). In each generation, eight
flies with high numbers of chaetae were allowed to interbreed and eight flies
with low numbers of chaetae were allowed to interbreed. Periodically they performed
mate choice experiments on the two lines. They found that they had produced a
high degree of positive assortative mating between the two groups. In the
decade or so following this, eighteen labs attempted unsuccessfully to
reproduce these results. This is an example of isolation by disruptive selection (1549).
Basil
Kassanis (GB) discovered satellite virus in some cultures of tobacco necrosis
virus (783). Satellite
RNAs are virus associated RNAs which depend on a helper virus for replication.
They do not share any significant nucleotide sequence identity with the genome
of the virus with which they associate.
Jacobus M.
Kaper (US), Marylou Tousignant (US), Hervé Lot (FR), and Howard E. Waterworth
(US) associated satellite RNA with cucumber mosaic virus (CMV) and showed that
CMV containing this satellite RNA induced a lethal necrosis in the tomato (773; 774).
Beverly Wolf
(US) and Rollin Douglas Hotchkiss (US) discovered that some bacteria become
resistant to sulfonamides by producing a target enzyme (tetrahydropteroic acid)
which has a reduced affinity for the drug (1669).
Thomas W.
Whitaker (US) and Glen Norton Davis (US) authored the leading world text on
cucurbits (1655).
Oliver Evans Nelson, Jr. (US), using the waxy locus (wx) in maize
(Zea mays L.), demonstrated that
genes of higher organisms, like those of lower ones, could mutate at several different
sites (1126; 1127).
Oliver Evans Nelson, Jr. (US) and Howard W. Rines (US) showed that
the product of the waxy gene is a
starch-bound ADP-glucose glucosyl
transferase (1128).
This was one of the earliest identifications of an enzyme underlying a
phenotype in a higher plant. Nelson later extended these observations to show
that transposable elements can produce mutations themselves by inserting
themselves at any of many different positions within the gene.
Frank M.
Hull (US) completed his monograph on robber flies of the world. Robber flies
(Diptera: Asilidae) comprise one of the largest groups of extant flies (722).
E. Donnall
Thomas (US), John A. Collins (US), Emery C. Herman, Jr. (US), Joseph W.
Ferrebee (US), Ronert B. Epstein (US) Jeanl Bryant (US), C. Dean Buckner (US),
Reginald A. Clift (US), Alexander Fefer (US), F. Leonard Johnson (US), Paul
Neiman (US), Robert E. Ramberg (US), and Rainer Storb (US) used bone marrow
transplants to replace blood-cell-generating hematopoetic cells in patients
with leukemia who had radiation therapy. Initially, transplants were from twin
donors and later from donors matched by cell surface antigens. More recently,
culturing stem cells extracted from the patient’s blood before treatment has
been the method (1550-1552).
André Michel
Lwoff (FR), Robert Horne (FR), and Paul Tournier (FR) were the first to
develop a means of virus classification, based on the Linnaean hierarchical
system. This system bases classification on phylum, class, order, family, genus,
and species.
They used size and shape as distinctive criteria (953).
Albert S.
Cosgrove (US) was the first to describe infectious
bursal disease of chickens (300). It has
been called Gumboro disease after the
geographic location of these outbreaks (Gumboro, Delaware).
Y. Cho (US)
and Samuel Allen Edgar (US) identified the causative agent as a picornavirus (265).
Lisbeth M.
Kraft (US) and W. Robert Adams (US) discovered a lethal mouse hepatitis virus,
strain MHV-LIVIM (6; 845).
Toshio
Murashige (US) and Folke Karl Skoog (SE-US) devised an improvised nutrient
medium which enabled substantially greater growth of tobacco tissue cultures—Murashige
and Skoog medium or (MSO or MS0 (MS-zero).
The new
formulation was conspicuously high in all macronutrient salts, also included all
micronutrients, and provided iron in the slowly but more readily available
chelated form. Among organic substances, sucrose was increased from 2 to 3% and
myo- inositol was made a standard addendum. When suplemented with suitable
additions of auxin and cytokinin, the medium enhanced the monthly yield of
tobacco callus from 5 g to 125 g/culture (1108).
Note: This is the most commonly used
medium in plant tissue culture experiments.
Victor Herbert (US) identified the stages of the development of folate
deficiency, events he demonstrated by placing himself on a folate deficiency
diet. Evidence of biochemical deficiency was progressively followed by the
development of classic anemia characteristics: insomnia,
irritability, fatigue, memory impairment and in this case the appearance of
abnormal red cell precursors called megaloblasts in the bone marrow. He nearly died of
heart failure from the potassium depletion induced as a side effect (655).
James van
Gundia Neel (US) proposed that diabetes today may be the result of a “thrifty”
genotype made disadvantageous by environmental changes (1123; 1124).
Carl R.
Morgan (US) and Arnold Lazarow (US) presented a detailed account of a two-step
procedure for radio-immunoassay of insulin. In the first reaction, insulin
forms a soluble complex with its specific antibody obtained from immunized
guinea pigs. In the second reaction, this soluble complex is precipitated by an
antibody to guinea pig serum obtained from immunized rabbits. Using a
radioactive insulin tracer, the amount of radioactivity in the precipitate is
dependent upon the concentration of insulin in the reaction mixture; i.e., with
increasing concentrations of unlabeled insulin, the amount of radioactive
insulin in the precipitate is decreased correspondingly (1095).
John Hans Menkes (US), Milton Alter (US), Gerd K. Steigleder (DE),
David R. Weakley (US), and Joo Ho Sung (US) described an X-linked recessive
disorder characterized by early retardation in growth, peculiar hair, and focal
cerebral and cerebellar degeneration in a family of English-Irish descent
living in New York (1042).
David Miles Danks (AU), Peter E. Campbell
(AU), J. Walker-Smith (AU), Brian J. Stevens (AU), J. Morton Gillespie (AU), J.
Blomfield (AU), Brian Turner (AU), Valerie Mayne (AU), Elizabeth Cartwright
(AU), and Rudge R.W. Townley (AU) announced that Menkes syndrome (congenital hypocuremia)
is a disease of copper transport (322-325).
Julian F. Mercer (US), Janie Livingston (US), Bryan Hall (US),
Jenny A. Paynter (AU), Catherine Begy (US), Settara Chandrasekharappa (US),
Paul J. Lockhart (AU), Andrew Grimes (AU), Mrinal Bhave (AU), David Siemieniak
(US), and Thomas W. Glover (US) succeeded in identifying and
cloning the Menkes gene (1043).
S. Ikuta
(JP) and S. Murakami (JP) discovered the Sid.Cad blood group antigen. A rare
erythrocyte blood group antigen expressed on both
sialoglycoprotein and ganglioside structures (730).
From 1962 to
1965 there was pandemic of rubella in
Europe which later spread to the United States (830).
Marc Armand
Ruffer (GB) demonstrated the presence of
Schistosoma haematobium ova in the kidneys of mummies belonging to the 20th
dynasty (1220-1000 BCE) of Egypt (1334).
J. Jansen,
Jr. (NL) and Hans J. Over (NL) revealed the presence of the parasitic worm Trichuris trichiura (whipworm) in a 2100
to 2500-year-old human refuge mound in Northwest Germany (745).
Michael
Potter (US) and Charlotte Robertson Boyce (US) found that adjuvants containing
mineral oil could cause plasma cell malignancies (plasmacytomas), or
plasmacytomas, in mice (1233).
David J.
Weatherall (GB) and Corrado Baglioni (IT-US) used hemoglobin fingerprinting to
prove that the alpha chains of fetal and adult hemoglobin are derived from the
same genetic loci (1629). Weatherall and Baglioni then
added further evidence that the fetal-to-adult hemoglobin switch involves a
change in the expression of non-alpha chains during development.
Jean
Hamburger (FR), Jean Vaysse (FR), Jean Crosnier (FR), Jean Auvert (FR), Claude
M. Lalanne (FR), and James Hopper, Jr. (US) performed a successful renal
transplantation between two living related but non-twin humans. The recipient
was preconditioned with total body irradiation and post-surgically treated with
steroids (606).
René Küss
(FR), Marcel Legrain (FR), Georges Mathé (FR), Raymond Nedey (FR), and Maurice
Camey (FR) performed a renal tansplantation between two nonrelated humans. The
recipient was preconditioned with total body irradiation and post-surgically
treated with steroid and 6-mercaptopurine. The graft survived for eighteen
months (863).
Sylvester J. Sanfilippo (US) and Robert A. Good (US) were the
first to describe what became known as Sanfilippo
syndrome, a rare inherited dementia transmitted as an autosomal recessive (1348).
Hans Kresse
(AT) and Elizabeth Fondal Neufeld (US) purified Sanfilippo A Corrective Factor
from normal human urine. They found that incubation of stored
mucopolysaccharide with the purified factor resulted in release of inorganic
sulfate, suggesting that the Sanfilippo A Factor is a heparan sulfate sulfatase (851).
Bruce A.
Gordon (CA), Vera Feleki (CA), Cathryne H. Budreau (CA), and Louise Tyler (CA)
demonstrated that in cases of Sanfilippo
Syndrome heparan sulfate polymer is inadequately desulphated because of a
significantly low amount of heparan
sulfate sulfatase. Large amounts of heparan sulfate are excreted in the
urine (567).
Masu
Masayuki (JP) and Masu Kazuko (JP) found that this reaction occurs within the
Golgi apparatus (1014).
Hans Kresse (AT) described Sanfilippo
Syndrome Type A (mucopolysaccharidosis
IIIA) as an autosomal recessive lysosomal storage disease caused by a
deficiency of heparin sulfamidase required for
heparan sulfate degradation (850).
Hans Kresse
(AT) and Kurt von Figura (DE) demonstrated that Sanfilippo Syndrome Type B is the
result of a deficiency of the enzyme known as N-acetyl-alpha-D-glucosaminidase (NAG) required for
heparan sulfate degradation (853).
Udo Klein
(DE), Hans Kresse (AT), Kurt von Figura (DE) determined that Sanfilippo Syndrome Type C
is caused by a deficiency in acetyl-CoA:
a-glucosamine N acetyl transferase required for heparan sulfate degradation (818).
Hans Kresse (AT), Eduard Paschke (AT), Kurt von Figura (DE),
Walter Gilberg (DE), and Walburga Fuchs (DE) proposed that Sanfilippo Disease Type D results from a deficiency of N-acetylglucosamine-6-sulfate
sulfatase required for heparan sulfate degradation (852).
Frederic
Crosby Bartter (US), Pacita Pronove (US), John R. Gill, Jr. (US), and Ross C.
MacCardle (US) described hyperplasia of the juxtaglomerular complex with
hyperaldosteronism and hypokalemic alkalosis coexisting with normal blood
pressure: now called Bartter’s Syndrome (97).
Richard C.
Reba (US), John McAfee (US), and Henry Wagner (US) used measurement of Hg-203
chlormerodrin accumulation by the kidneys for detection of unilateral renal
disease (1271).
Rolf Luft
(SE), Dennis Ikkos (SE), Genaro Palmieri (US), Lars Ernster (SE) and Björn A.
Afzelius (SE), upon examination of a young woman with severe hypermetabolism,
mild weakness, and normal thyroid function, discovered Luft disease, the first mitochondrial disease and the first example
of organellar medicine (949).
Rolf Luft
(SE) introduced the phrase mitochondrial
medicine (948).
Ian J. Holt
(GB), Alexander E. Harding (GB), John A. Morgan-Hughes (GB), Douglas C. Wallace
(US), Gurparkash Singh (US), Marie T. Lott (US), Judy A. Hodge (US), Theodore
G. Schurr (US), Angela Lezza (IT), Louis J. Elsas (US), and Eeva K.
Nikoskelainen (FI) were the first to associate
mutations in mitochondrial DNA with human disease (701; 1614).
John
Brereton Barlow (ZA) and Wendy A. Pocock (ZA) were the first to interpret a
form of congenital heart disease in which one or both leaflets of the mitral
valve protrude into the left atrium during the systolic phase of ventricular
contraction as an expression of a mitral valve prolapse (Barlow’s syndrome) (83; 84). It may be
associated with valve infection, arrhythmias and atypical chest pain.
Inheritance is autosomal dominant.
Spyros D.
Moulopoulos (US), Robert Stephen (US), Stephen R. Topaz (US), Willem Johan
Kolff (NL-US) invented the use of a single chambered intra-aortic balloon,
positioned in the descending thoracic aorta, to accomplish the same
hemodynamics as did arterial counterpulsation (1102; 1103). The
primary goals of intra-aortic balloon treatment are to increase myocardial
oxygen supply and decrease myocardial oxygen demand: secondarily to improve
cardiac output (CO), ejection fraction (EF), increase coronary perfusion
pressure, increase systemic perfusion, decrease heart rate, decrease pulmonary
capillary wedge pressure, and decrease systemic vascular resistance.
Bernard Lown
(US), Raghavan Amarasingham (US), and Jose Neuman (US) developed a new method
for terminating cardiac arrhythmias transthoracically. They used a synchronized
capacitor discharge (944; 945).
Michael
Ellis DeBakey (US), E. Stanley Crawford (US), George C. Morris, Jr. (US), and
Denton A. Cooley (US), to counteract narrowing of an artery caused by an
endarterectomy, performed the first successful patch-graft angioplasty. This
procedure involved patching of the slit in the artery from an endarterectomy
with a Dacron or vein graft. The patch widens the artery so that when it is
closed, the channel of the artery returns to normal size (340).
David H.
Hubel (US) and Torsten N. Wiesel (US) studied the visual cortex in
anaesthetized cats by recording extracellularly from single cells.
Light-adapted eyes were stimulated with spots of white light of various shapes,
stationary or moving. Receptive fields of cells in the visual cortex varied
widely in their organization. They tended to fall into two categories, termed'
simple' and 'complex'. There were several types of simple receptive fields,
differing in the spatial distribution of excitatory and inhibitory ('on' and
'of’) regions. For maximum response the shape, position and orientation of
these stimuli were critical. Receptive fields were termed complex when the
response to light could not be predicted from the arrangements of excitatory
and inhibitory regions. The stimuli that were most effective in activating
cells with simple fields- slits, edges, and dark bars-were also the most
effective for cells with complex fields. Four fifths of all cells were
influenced independently by the two eyes. In a binocularly influenced cell the
two receptive fields had the same organization and axis orientation and were
situated in corresponding parts of the two retinas. It is suggested that
columns containing cells with common receptive- field axis orientations are
functional units, in which cells with simple fields represent an early stage in
organization, possibly receiving their afferents directly from lateral
geniculate cells, and cells with complex fields are of higher order, receiving
projections from several cells with simple fields within the same column (715).
János Hugo
Bruno “Hans” Selye (AT-HU-CA) discovered calciphylaxis, anaphylactoid edema,
new roles of mast cells, new models of experimental cardiovascular diseases,
and the anesthetic properties of steroids that are certainly associated with
the “stress syndrome” (1394-1397).
Michael S.
Gazzangia (US), Joseph E. Bogen (US), and Roger Wolcott Sperry (US) found that
the general picture of collosal functions based on the animal studies tends to
be supported in current early testing of a 48-year-old male war veteran with
recent complete section of the corpus callosum, anterior and hippocampal
commissures (511).
In 1962-1965
a rubella (German
measles or three-day measles) pandemic started in Europe and spread to the United States
Leslie
Alexander Geddes (GB-CA-US), Hebbel E. Hoff (US), David M. Hickman (US), Andrew
G. Moore (US), Carlos Vallobana (US), and Joseph Canzoneri (US) developed the
method of obtaining the electrocardiogram and respiration from chest electrodes
for NASA, which is routinely used in patient monitoring today (512; 513).
Fred J.
Ansfield (US), John M. Schroeder (US), and Anthony R. Curreri (US) found that of
428 patients with measurable lesions treated with 5-fluorouracil (5-FU), 91 met
all their criteria of improvement for an average duration of 9 months before
reactivation of the disease occurred. The lesions found most responsive to the
drug were cancer of the breast, colon or rectum, stomach, cervix, ovary, and
malignant hepatoma. Squamous-cell carcinoma of the head and neck, carcinoma of
the lung, hypernephroma, and malignant melanoma were unresponsive (34).
Ronald A.
Malt (US), in 1962, led a team of surgeons who accomplished the first
successful replantation of a completely severed human limb (989).
Stanley
Schachter (US) and Jerome Singer (US) hypothesized that "an emotional
state may be considered a function of a state of physiological arousal and of a
cognition appropriate to this state of arousal". They were interested in
what happens if you covertly induce a physiological change in a subject, will
they cognitively assign an emotional state to their bodies' heightened arousal
when they have no apparent causal reason for their bodily changes? That people
will assign an emotion to a physiological change based on the available
emotions in the social situation. They found that people will assign an emotion
to a physiological change based on the available emotions in the social
situation, i.e., people search the immediate environment for emotionally
relevant cues to label and interpret unexplained physiological arousal (1355).
Irving
Bieber (US), Harvey J. Dain (US), Paul R. Dince (US), Marvin G. Drellich (US),
Henry G. Grand (US), Ralph H. Gundlach (US), Malvina W. Kremer (US), Alfred H.
Rifkin (US), Cornelia B. Wilbur (US), and Toby B. Bieber (US) demonstrated the
influence of specific types of disordered parent-child relationships in the
genesis of male homosexuality, particularly the salience of defective
father-son inter-relatedness, and it identified a continuity of disturbed relations
with other males in childhood and preadolescence (137).
Rachel
Carson (US) wrote Silent Spring,
which awakened people to the danger to life posed by the indiscriminate use of
pesticides and herbicides (237).
John M. Teal
(US) did a relatively detailed study of the energy flow in a salt-marsh
ecosystem of Georgia (1526).
Martin Fritz
Glaessner (CZ-AU) and Mary Wade (AU) determined fossils in the Ediacara Hills
of South Australia (Ediacaran fauna) to be late Precambrian in age, making them
the oldest-known multicelled organisms (542-545).
Reidar Nydal
(NO) radiocarbon dated a total of six wooly mammoths yielding an average age of
31,400 BP (1157).
Émile
Ennouchi (FR) reported the discovery of fossil remains of archaic Homo sapiens sapiens at Jebel Ighoud
southeast of Safi, Morocco (414; 415). The
fragments have been dated to c. 300K BP
The journal Biochemistry
was founded.
1963
“The one
mark of maturity, especially in a physician, and perhaps it is even rarer in a
scientist, is the capacity to deal with uncertainty.” William Bennett Bean (102).
John Carew
Eccles (AU), Alan Lloyd Hodgkin (GB) and Andrew Fielding Huxley (GB) were
awarded the Nobel Prize in Physiology or Medicine for their discoveries
concerning the ionic mechanisms involved in excitation and inhibition in the
peripheral and central portions of the nerve cell membrane.
Manfred
Eigen (DE), Leo DeMaeyer (DE), Joseph Schoen (DE), Gerhard Schwarz (DE), Georg
Czerlinski (DE), Hartmut Diebler (DE), Walter Kruse (DE), Günter Maass
(DE), and Georg Ilgenfritz (DE) developmented relaxation techniques that made
possible a quantitative study of fast elementary reactions and a dissection of
complex reaction mechanisms, which could be explained in terms of elementary
steps. Application to biological reactions led to the conclusion that enzymes
are optimal catalysts (395; 396).
David
Domingo Sabatini (US), Klaus George Bensch (US), and Russell J. Barrnett (US)
introduced gluteraldehyde (usually followed by osmium tetraoxide) as a fixative
for electron microscopy (1338).
Edward S.
Reynolds (US) introduced
a method for staining ultrathin sections for electron microscopy with solutions
of lead citrate at high pH. Lead
citrate solutions are stable for long periods of time and do not significantly
contaminate the sections with unwanted precipitate (1282).
Lars
A. Carlson (SE) described the final version of his method for determination of
serum triglycerides with major emphasis on practicality. Water-soluble
interfering substances are removed; the method is specific for triglycerides,
and it can easily be used for tissues (229).
Robert S.
Lees (US), Frederick T. Hatch (US), Donald S. Frederickson (US), Robert I. Levy
(US), Ronald A. Wong (US), Paul G. Banchero (US), Lin C. Jensen (US), Suzanne
S. Pan (US), Gerald A. Adamson (US), and Frank T. Lindgren (US) drew attention
to an important group of diseases that are common and often potentially fatal.
They introduced a new system of classifying blood lipid disorders, which is a
useful and practicable system for the classification, investigation, and
treatment of hyperlipoproteinemic patients. They developed a suite of
relatively simple methods that would enable quantitative or semiquantitative
measurements of lipoprotein patterns from sera of animals and humans when
performed in biophysically unsophisticated laboratories (478; 629; 892; 1673).
Frantz
A. Vandenheuvel (CA) obtained a plausible tri-dimension arrangement of
molecules in the lipid bilayer of myelin. Data on myelin was obtained from
analytical, X-ray, and other studies then integrated by using exact molecular
parameters and force calculations (1592).
Robert Bruce
Merrifield (US) described the development of solid-phase peptide synthesis (1044; 1045).
Robert
Schwyzer (CH) and Paul Sieber (CH) synthesized the 39-residue porcine
adrenocorticotropic hormone by solution-phase segment condensation methods (1383).
Severo Ochoa
(ES-US-ES), Susumu Nishimura (JP), David S. Jones (GB), and Har Gobind Khorana
(IN-US) developed a non-enzymatic in
vitro technique for synthesizing long strands of RNA with known, simple
repeating units. Using these they determined the base sequence for many codons (805; 806; 1140; 1165; 1445).
Du Pont
Chemical Company introduced the herbicide bromacil,
a derivative of uracil, for the control of a wide variety of weeds in citrus
and pineapple crops.
Dow Chemical
Company introduced the herbicide picloram,
a picolinic acid derivative, for the control of most perennial broadleaf and
woody species. ref
Eli Lilly
Chemical Company introduced the herbicide trifluralin,
a dinitroaniline, useful in cotton (Gossypium
spp.) and soybeans (Glycine max). ref
Donald F.
Ashman (US), Richard M. Lipton (US), Meyer M. Melicow (US), Tracy D. Price
(US), Thomas R. Price (US) found cyclic guanylic acid (cyclic GMP) in urine (65; 1241).
Alfred W.
Alberts (US), Peter Goldman (US), Pindaros Roy Vagelos (US), Philip Warren
Majerus (US), and Barbara Talamo (US) discovered the role of the acyl carrier
protein in fatty acid synthesis (12; 13; 554; 555; 982; 983).
Kazuhiko Ohkuma (JP), Frederick T. Addicott (US), Jessye Lorene Lyon (US),
Orrin E. Smith (US), Wilfred E. Thiessen (US), Harry R. Carns (US), J.L.
McMeans (US), O.E. Smith (US), John W. Cornforth (AU-GB), B.V. Milborrow (GB),
G. Ryback (GB), and P.F. Wareing (GB) isolated, determined the structure of,
and named abscisic acid during their
studies of leaf adscission. They first named this plant hormone abscisin II then later changed it to
abscisic acid (7; 8; 1167; 1168).
Andrew C.
Allan (GB), Mark D. Fricker (GB), Jane L. Ward (GB), Michael H. Beale (GB), and
Anthony J. Trewavas (GB) showed that abscisic acid is also involved in plant
response to water stress and to function in the gain and loss of solutes during
changes in stomatal guard cell turgor (17).
Charles J.
Epstein (US), Robert F. Goldberger (US), and Christian Boehmer Anfinsen, Jr.
(US) articulated what they called the thermodynamic
hypothesis to explain the three dimensional structure of a native protein
in its normal physiological milieu (solvent, pH, ionic strength, presence of
other components such as metal ions or prosthetic groups, temperature, etc.) as
the one in which the Gibbs free energy of the whole system is lowest; that is,
that the native conformation is determined by the totality of interatomic
interactions and hence by the amino acid sequence, in a given environment (417).
David Ezra
Green (US) and Sidney Fleischer (US) were the first to emphazize the importance
of lipid-protein interactions within membranes with structure and function of
membranes being largely determined by lipid-protein interactions (580).
Robert F.
Goldberger (US), Charles J. Epstein (US), Christian Boehmer Anfinsen, Jr. (US),
Pál Venetianer (HU), and Ferenc Brunó Straub (HU) discovered that the
endoplasmic reticulum in cells that are actively secreting proteins with
disulfide bridges contains an enzyme system which catalyzes the rapid formation
of the correct native disulfide pairing (552; 1596).
Merton
Franklin Utter (US) and D. Bruce Keech (US) discovered pyruvate carboxylase and noted that this enzyme works in concert
with phosphoenolpyruvate carboxykinase
to convert pyruvate to phosphoenolpyruvate by a sequence, which differs from a
reversal of the glycolytic pathway (794; 1582; 1583).
Shu-Fang
Wang (US), Frank S. Kawahara (US), and Paul Talalay (DE-US) discovered the
mechanism of delta 5-3-ketosteroid
isomerase (KSI), which catalyzes the migration of the double bond from
delta 5 to the delta 4 position of 3-ketosteroids. They found that the
isomerization proceeds without exchanging protons with the medium, suggesting
that there is a direct transfer of a proton from position 4 to 6 on the enzyme
surface. Talalay and his colleagues were able to gain insight into the
mechanism of KSI from absorption and fluorescence spectra of enzyme-steroid
complexes. They concluded that the reaction involves an enolic intermediate (1620). KSI occurs in animal tissues
concerned with steroid hormone biosynthesis such as the adrenal, testis, and
ovary.
Zdenek Hruban (US), Benjamin Spargo (US), Hewson Swift (US), Robert W.
Wissler (US), and Ruth G. Kleinfeld (US) using ultrastructural studies
established an intracellular process consisting of the sequestration of
cytoplasmic components followed by the formation of complex dense bodies, which
correspond to the lysosomes of biochemists. This natural process is enhanced by
cellular injury. The noxious agent codetermines the structure of the bodies (706).
Philip J.
Randle (GB), Peter B. Garland (GB), C. Nick Hales (GB), and Eric A. Newsholme
(GB) performed a series of experiments that were designed to test the
supposition that cardiac and skeletal muscle possess mechanisms that allow them
to shift readily back and forth between carbohydrate and fat as oxidative
energy sources, depending primarily on the availability of free fatty acids
(FFAs). These experiments eventually focused on the biochemical mechanisms that
are involved in the switch from carbohydrate to fat metabolism. The main
features of the model that was developed were that increased fat oxidation in
muscle would inhibit both pyruvate
dehydrogenase (PDH) and phosphofructokinase
by accumulation of acetyl-CoA and citrate, respectively. These roadblocks
placed in the glycolytic pathway would lead to increased glucose 6-phosphate
concentration, inhibiting hexokinase
and resulting in reduced glucose uptake and oxidation. This homeostatic
mechanism became known as the glucose
fatty acid cycle or the Randle cycle (1262-1264).
John Walter Drake (US) published the first spectrum for UV-induced
mutagenesis. His experimental system was the r II
region of bacteriophage T4 (366).
Thomas H.
Plummer, Jr. (US) and Christophe Henri Werner Hirs (US) isolated ribonuclease B in pure form from
pancreatic juice and showed it to be the same as A but with the addition of a
carbohydrate side-chain attached to one asparagine residue (1224; 1225).
Robert E.
Canfield (US), Jacqueline Jollès (FR), Pierre Jollès (FR), Sandra Kammerman
(US), Joan H. Sobel (US), and Francis J. Morgan (US) determined that lysozyme is a single polypeptide chain
of 129 amino acid subunits of 20 different kinds
(224; 225; 755; 756).
Robert G.
Martin (US) discovered that the enzyme responsible for carrying out the first
step in histidine biosynthesis in Salmonella
typhimurium exhibits the phenomenon of feedback inhibition. He presented
evidence that the enzyme’s conformation changes because of binding L-histidine (1012).
John C.
Gerhart (US), Arthur Beck Pardee (US), Howard K. Schachman (US), Jean-Pierre
Changeux (FR), and Merry M. Rubin (US) presented evidence that aspartate transcarbamylase from Escherichia coli mediates indirect,
i.e., allosteric, interactions among substrate and/or inhibitor molecules which
bind at topographically distinct sites on the enzyme surface. This allosteric
binding led to changes in enzyme conformation (257; 258; 523-525).
Feodor Felix
Konrad Lynen (DE), Michio Matsuhashi (JP), Shosaku Numa (JP), and Eckhart
Schweizer (DE) discovered that long-chain acyl-CoA derivatives exhibit a
typical end-product inhibition of lipogenesis at the level where acetyl-CoA carboxylase is active (960).
Solomon
Spiegelman (US) and Miyuki Hayashi
(JP-US) found an enzyme capable of specifically recognizing and replicating
viral RNA. This is the discovery of nucleic acid polymerases (replicases) (1453).
Ichiro
Haruna (JP) and Solomon Spiegelman (US) coined the term template specificity to describe the affinity of these polymerases (623).
Miyuki Hayashi (JP-US), Marie N. Hayashi (JP-US) and Solomon Spiegelman
(US) discovered that only one strand of a DNA’s double helix transmits the
genetic information to the cell’s protein making machinery (635).
Ichiro
Haruna (JP) and Solomon Spiegelman (US) performed the first in vitro synthesis of infectious viral
RNA (Qß) (624).
Marvin J.
Weinstein (US), George M. Luedemann (US), Edwin M. Oden (US), Gerald H. Wagman
(US), Jean-Pierre Rosselet (US), Joseph A. Marquez (US), Carmine T. Coniglio
(US), William Charney (US), Hershel L. Herzog (US), and Jack Black (US)
isolated the antibiotic gentamycin (gentamicin) from Micromonospora purpurea, an actinomycete (1645).
Charles H.
Wallas (US) and Jack Leonard Strominger (US) reported that the antibiotics restocetin A and B inhibit bacterial cell wall synthesis (1615).
Peter J.
Gomatos (US) and Igor Tamm (US) found that reovirus has double-stranded RNA as
its genome (560; 561).
Hiroshi
Yoshikawa (JP) and Noboru Sueoka (JP) determined elative frequencies of various
genetic markers in the DNA of B. subtilis,
strain W23, in exponential and stationary growth phases using a transformation
system. If the chromosome replication has a polarity, the frequency of each
marker in the exponential phase should be a function of its location on the
chromosome. The results indicate that such polarity exists in B. subtilis. Based on the results, a
genetic map has been constructed in which the adenine marker is located near
the point of origin, from which the chromosome starts replicating, and
methionine and isoleucine near the terminus. The results also indicate that
chromosomes in the stationary phase are in completed form (1707).
Michael
Cannon (US), Robert Krug (US), and Walter Gilbert (US), using Escherichia coli, determined that sRNA
(tRNA) has a high affinity for ribosomes (226).
Marshall
Warren Nirenberg (US), Oliver W. Jones, Jr. (US), Philip Leder (US), Brian F.C.
Clark (GB-DK), William S. Sly (US), Sidney Pestka (US), Joseph F. Speyer (US),
Peter Lengyel (US), Carlos Basilio (US), Albert J. Wahba (US), Robert S.
Gardner (US), and Severo Ochoa (ES-US-ES) determined the most likely base
compositions, not order, of approximately 50 codons by analyzing proteins synthesized
using randomly-ordered RNA templates containing different combinations of the
four nitrogenous bases. These results also showed that multiple codons can
correspond to the same amino acid, therefore the code was characterized as
being degenerate (1136; 1137; 1452).
Heinz
Guenter Wittmann (DE), and Brigitte Wittmann-Leibold (DE) used the synthesis of
coat protein in tobacco mosaic virus to provide experimental evidence that codons
are translated in a linear non-overlapping fashion (1668).
Y. Yasumura
(JP) and M. Kawakita (JP) established the 'Vero' lineage cell line in cell
culture. These kidney epithelial cells, extracted from an African green monkey (Chlorocebus
sp.), are continuous and aneuploid. A continuous cell lineage can be replicated
through many cycles of division and not become senescent (1704). Note: This cell line is
important for cancer research in vitro.
Ralph B.
Arlinghaus (US), Gabriel Favelukes (AR), Richard S. Schweet (US), Akira Kaji
(US), and Hideko Kaji (US) discovered that when poly-U mRNA is used Phe-tRNA
attaches to ribosomes prior to the formation of the peptide bond (51; 766).
Violet Daniel (IL) and Uriel Z. Littauer (IL) purified and
characterized tRNA nucleotidyltransferase
from rat liver. The enzyme was found to have an important role
in the proofreading and repair of the universal 3'-CCA end of
tRNA (320; 321).
Jacov Tal (IL), Murray P. Deutscher (IL), and Uriel Z. Littauer
(IL) showed that tRNA
nucleotidyltransferase adds CMP to tRNA... N by
a nonprocessive mechanism (1517).
Elizabeth
Burgi (US), and Alfred Day Hershey (US) worked out a method for determining the
molecular weight of DNA using sedimentation rates in a sucrose solution (195).
Ruth Sager
(US) and Masahiro R. Ishida (JP) were the first to isolate DNA from chloroplasts.
The material was Chlamydomonas (1342).
Mordhay
Avron (IL) discovered the chloroplast-coupling factor, CF1, for
photophosphorylation, later known as ATP
synthase (72).
Frantisek
Franek (CZ), Roald S. Nezlin (CZ), Gerald Maurice Edelman (US), Donald E. Olins
(US), Joseph A. Gally (US), Norton David Zinder (US), Seymour Jonathan Singer
(US), Russell F. Doolittle (US), Edgar Haber (US), Dan Inbar (IL), Jacob
Hochman (IL), and David Givol (IL) determined that both the variable heavy
regions (VH) and the variable light regions (VL) of the antibody molecule
contribute to the antigen-binding function. The effector functions being
carried out by constant regions (388; 472; 596; 731; 1182; 1426).
Hugh Esmor
Huxley (GB) was the first to suggest a likely mode of aggregation of myosin molecules to form cylindrical myosin filaments. He discovered myosin decoration, an important
technique in muscle chemistry. The reaction of microfilaments with heavy meromyosin subfragment (HMMS-1) reveals,
upon microscopic examination, an unmistakable characteristic arrowhead pattern (729).
Jean Hanson
(GB) and Jack Lowy (GB) demonstrated that F-actin
filaments consist of a helical array of G-actin
molecules and proposed that tropomyosin
molecules lie end-to-end along each groove of the F-actin helix (613).
Dorothy Mary
Moyle Needham (GB) and James M. Williams (GB) demonstrated the presence of myosin molecules in vertebrate smooth
muscle cells (1122).
Haim
Ginsberg (US) and Leo Sachs (US-IL) were the first to report the in vitro growth of cells of hemopoietic
origin and documented the generation of mast cells from cultures of thymic
cells (541).
Murray
Llewellyn Barr (CA), Evelyn L. Shaver (CA), and David H. Carr (CA) described
the Barr-Shaver-Carr syndrome. These
patients have 48 chromosomes (XXXY karotype). XXXY syndrome resembles Klinefelter's
syndrome: tall slim build, flat nasal bridge, epichantal folds, mild
prognathism, delayed puberty, testes small or undescended, small penis,
gynaecomastia (excessive breast development in the male), and mental
retardation (89).
George
Joseph Todaro (US) and Howard Green (US) showed that with mouse embryo cells,
transformed cell lines that were capable of indefinite propagation grew out of
the cultures regularly. Compared to untransformed cells the transformed cells
were able to grow from much smaller inocula, reach higher saturation density,
and form multilayers (no contact inhibition). One of their established cell
lines (3T3) is nontransformed and exbibits contact inhibition. They concluded
that, “the malignant properties of many established lines may be the result of
the selective processes usually operating in cell culture and not related to
the process of establishment per se.” (1565).
George
Joseph Todaro (US), Howard Green (US), and Burton D. Goldberg (US) developed an
aneuploid mouse fibroblast line 3T3 that appears very sensitive to contact
inhibition of cell division. Two different oncogenic viruses, SV40 and polyoma,
rapidly transform this line (1566).
Yoheved
Berwald (IL) and Leo Sachs (US-IL) showed that known chemical carcinogens can
transform normal hamster cells in vitro (128; 129).
Ulrich
Clever (DE) and Carole G. Romball (US) gave the first evidence that steroid
hormones can affect gene activity (280; 281; 283).
Charles
Yanofsky (US), Bruce C. Carlton (US), John R. Guest (GB), Donald Raymond
Helinski (US), and Ulf Henning (DE) studied mutations associated with the
synthesis of tryptophan synthetase
alpha subunit in Escherichia coli and
found that the relative position of each amino acid replacement matched the
relative position of its respective mutation along the genetic map (1701; 1702). This was
proof of the sequence hypothesis (colinearity) proposed in
1957 by Francis Harry Compton Crick (GB), which held that DNA sequence and
protein sequence are colinear. Genetic information must therefore be arrayed in
a strictly linear fashion along the length of a DNA molecule. See, Crick, 1958.
Anand S.
Sarabhai (IN), Anthony O.W. Stretton (US) Sydney Brenner (ZA-GB), and
Antoinette Bolle (CH) reached the same conclusion almost simultaneously (1350).
George
Streisinger (HU-US) Robert S. Edgar (US), and Georgetta Harrar Denhardt (US)
proposed that the linear T-even phage DNA molecule is terminally redundant, so
that its sequence of genes can be represented as: abcdef…wxyzabc. When
such a terminally redundant phage DNA molecule replicates in the infected cell,
genetic recombination can proceed within the region of terminal redundancy of
two daughter molecules, giving rise to concatenates of the type: abcdef…wxyzabc
x abcdef…wxyzabc abcdef…wxyzabcdef…wxyzabc.
These
concatenates would then have to be cut into phage-genome-sized pieces before
incorporation into the heads of infective progeny particles. If this cutting
process were to be of such a nature that it started to take its measure of
phage-genome length always at the same genetic site, say at a, then there would arise only one kind
of terminally redundant phage genome—namely, that redundant for the abc sector. Hence terminal-redundancy
heterozygotes could arise only for genes residing in that sector. But if the
cutting process were to start taking its measure of genome length at any
randomly chosen genetic site, then there would arise a collection of phage genomes
whose terminal redundancy would be circularly permutated, such as ghijkl…cdefghi
and mnopqr…ijklmno . It is in this paper that the circular nature of the
T4 genome was proposed (1494).
Alfred Day
Hershey (US) and Elizabeth Burgi (US), and Laura Ingraham (US) demonstrated
that the DNA of the lambda
bacteriophage of Escherichia coli
could exist as a linear molecule or as a circular molecule. The circularity is
possible because each end has a single chain overhang, which is complementary
to a single chain overhang on the other end of the molecule. These overhangs
produce ends, which behave as though they are sticky and are called cohesive
sites (COS) (662; 663).
Ray Wu (US)
Armin Dale Kaiser (US) later determined the structure and base sequence of
these cohesive ends (1690).
Ray Wu (US)
and Ellen Taylor (US) completed sequencing the cohesive ends of lambda phage and showed that they were
only 12 nucleotides long out of the 50,000 nucleotides of the complete molecule (1693).
Hubert Henri
Malherbe (ZA), Robert Harwin (ZA), and M. Ulrich (ZA) were the first to
describe simian rotavirus particles (988).
Ruth F.
Bishop (AU), Geoffrey P. Davidson (AU), Ian H. Holmes (AU), Brian J. Ruck (AU),
Thomas H. Flewett (GB), A.S. Bryden (GB), and Heather A. Davies (GB) gave the
first descriptions of Rotavirus in
association with a human disease—diarrhea in infants and young children (141; 454).
Geoffrey P. Davidson (AU), Ruth F. Bishop (AU), R. Rugely W.
Townley (AU), and Ian H. Holmes (AU) demonstrated Rotavirus, the cause of acute
sporadic enteritis in children, using electron microscopy (328).
Wilbur George Downs (US), Charles R. Anderson (US), Leslie Spence
(US), Thomas H.G. Aitken (US), and Arthur H. Greenhall (US) discovered Tacaribe
virus: the first known western hemisphere arenavirus (365).
Stanley
Hattman (US) and Toshio Fukasawa (US) provided the first clue to explain how
foreign viral DNA is protected from attack by host cell nucleases. T-even
bacteriophage DNA is glucosylated as it is replicated in Escherichia coli strain B host cells rendering it immune to enzyme
degradation (631).
Hugh John
Forster Cairns (GB-US-GB) demonstrated the circular nature of the bacterial chromosome using autoradiography. In the
1963a paper he discovered the replication fork (209-211).
Friedrich
Bonhoeffer (DE) and Alfred Gierer (DE) proved that at most a few replicating
forks of Escherichia coli DNA are
active at any given time (156).
James
Herbert Taylor (US) performed the experiment, which established to the
satisfaction of most scientists that physical breakage and exchange of DNA
molecules occur during eukaryotic recombination. He used the grasshopper, Romalea (1523; 1524).
Margit M.K.
Nass (SE) and Sylvan Nass (SE) reported intramitochondrial fibers with DNA
characteristics (1115; 1117). Some
consider this to be the discovery of mitochondrial DNA (mtDNA). Others consider
the following article by Schatz, et al., to represent the discovery.
Gottfried
Schatz (AT-CH), Ellen Haslbrunner (AT), and Hans Tuppy (AT) presented evidence
that preparations of mitochondria from baker’s yeast contain a significant
quantity of DNA (1359).
Margit M.K. Nass
(SE), Sylvan Nass (SE), and Björn A. Afzelius (SE) presented evidence that
preparations of mitochondria from many other sources contain a significant
quantity of DNA (1116).
David B.
Slautterback (US), Myron C. Ledbetter (US) and Keith R. Porter (US) gave
intracellular "microtubules" their name, fully described them, and
recognized their ubiquity (887; 1438).
Peter K.
Helper (US) and Eldon H. Newcomb (US) presented a study of the relationship of
microtubules to cell plate formation in dividing cells (653).
Eldon H.
Newcomb (US) examined in detail the evidence correlating the orientation of
plant cortical microtubules with that of newly deposited wall microfibrils.
Considerable evidence suggests that cortical microtubules may control the
orientation of cellulose microfibrils as the latter are being deposited in the
cell wall (1130).
Madeleine Sebald (FR) and Michel Véron (FR) established the taxonomic
legitimacy of the genus Campylobacter
(Greek, curved rod) (1390).
Albert A.
Stonehill (US), Stephen Krop (US), and Paul M. Borick (US) introduced
glutaraldehyde as a germicide (1491).
Emanuel
Margoliash (IL), Walter Monroe Fitch (US), Gillian M. Air (AU), Edward Owen
Paul Thompson (AU), Abel Schejter (IL), Barry J. Richardson (AU), Geoffrey B.
Sharman (AU), Thomas H. Jukes (US), Richard Holmquist (US), and Emil L. Smith
(US) presented data on the amino acid sequences of hemoglobin and cytochrome c from many species. This data was
sufficient to permit construction of elaborate family trees (11; 448; 449; 762; 763; 994-997).
Bill
Henriksen Hoyer (US), Brian John McCarthy (US), and Ellis Truesdale Bolton (US)
pointed out that similarities in polynucleotide sequences in DNA from different
species could be used as a measure of phylogenetic proximity. They also
recognized that some such sequences might represent genes that have been
retained with little change throughout vertebrate history. Possibly
representing features held in common such as bilateral symmetry, notochord,
hemoglobin, and others (705).
Emile
Zuckerkandl (US) and Linus Carl Pauling (US) predicted that comparing gene and
protein sequences directly and indirectly would allow phylogeny to be
reconstructed. They pointed out that the sequence of a nucleic acid or protein
is much more evolutionarily informative than is knowledge about whether its
activity is present or absent (usually inferred from the presence of a
corresponding metabolic product). The identification of specific macromolecular
sequences in natural biomass therefore provides a more precise and powerful
characterization of a population than do inventories of lipids or
chromatophores. Sequences allow a quantitative definition of both the genetic
diversity and the organismal relationship within a niche (1718).
Marilyn Gist
Farquhar (US) and George Emil Palade (RO-US), using frogs and toads, discovered
the tight junction, or occluding junction (zonula
occludens) between cells. They deduced that the diffusion of water, ions,
and small, water-soluble molecules is impeded along the intercellular spaces of
the epidermis by zonulae occludentes while it is facilitated from cell
to cell within the epidermis by zonulae and maculae occludentes. (428-430).
Phillippa
Claude (US) and Daniel A. Goodenough (US) determined that the depth (number of
occluding strands) in a tight junction correlates with the leakiness or
tightness of a tight junction (277).
Bruce
R. Stevenson (US), Janet D. Siliciano (US), Mark S. Mooseker (US), and Daniel
A. Goodenough (US) isolated a polypeptide of approximately 225,000 D that is
the first protein known to be specific to tight junctures and potentially a
ubiquitous component of all mammalian tight junctions (1482).
Howard
Martin Temin (US) proposed the provirus
hypothesis to explain how RNA viruses might cause human cancer. According
to the provirus concept, after infection of a cell by an RNA tumor virus, the
cell makes a DNA copy from the viral RNA and incorporates the genetic
information into its own DNA. This gives the cell the capacity to produce
oncogenic viruses and transforms it from a normal cell to a neoplastic one (1530-1532; 1534; 1537; 1538).
Howard
Martin Temin (US), Satoshi Mizutani (US) and David Baltimore (US) discovered
that Rous Sarcoma virus contains reverse
transcriptase, an enzyme capable of synthesizing DNA from RNA (79; 80; 1533; 1535; 1536; 1539; 1541; 1542).
Inder M.
Verma (US), Gary F. Temple (US), Hung Fan (US), and David Baltimore (US)
demonstrated that the reverse
transcriptase could be used in vitro to synthesize cDNA from
mammalian mRNAs (1597).
Daniel L.
Kacian (US), Sol Spiegelman (US), Arthur Bank (US), Masaaki Terada (US),
Salvatore Metafora (US), Lois W. Dow (US), and Paul A. Marks (US) used avian myeloblastosis virus reverse transcriptase
to synthesize DNA complementary to human globin mRNA in vitro (765).
Howard
Martin Temin (US) presented what he called the protovirus hypothesis to explain the origin of RNA tumor viruses.
He suggested that the relationships between avian ribodeoxyviruses and
reticuloendotheliosis viruses are a relic of the origin of these viruses; that
these ribodeoxyviruses are representatives of a part of the avian genome, which
evolved by a process of DNA to RNA to DNA information, transfer and escaped to
become viruses. He speculated that the process is widespread in vertebrates (1540).
Piero
Carninci (JP), Catrine Kvam (IT-NO), Akiko Kitamura (JP), Tomoya Ohsumi (JP),
Yasushi Okazaki (JP), Mitsuteru Itoh (JP), Mamoru Kamiya (JP), Kazuhiro Shibata
(JP), Nobuya Sasaki (JP), Masaki Izawa (JP), Masami Muramatsu (JP), Yoshihide
Hayashizaki (JP), Claudio Schneider (IT), Yoko Nishiyama (JP), Arthur Westover
(JP), Masayoshi Itoh (JP), Sumiharu Nagaoka (JP), Yuko Shibata (JP), Norihito
Hayatsu (JP), Yuichi Sugahara (JP), and Hideaki Konno (JP) improved the
synthesis of full length cDNA molecules by biotin capping of the mRNAs to
ensure that only full-length cDNAs were selected. After first-strand cDNA
synthesis, RNAse I was used to destroy any part of any mRNA that was not bound
to cDNA. This caused the removal of the 5' biotin cap from the mRNAs of all
non-complete cDNAs. Magnetic beads were used to select only the full-length
cDNAs for second-strand synthesis and cloning (232-234).
Ralph
Mitchell (US) and Martin Alexander (US) discovered soil bacteria, which can
lyse fungi (1080).
James Edward
van der Plank (ZA) wrote, Plant Diseases:
Epidemics and Control in which he taught plant pathologists how to
interpret the logistic progress of an epidemic in terms of compound and simple
interest, infection rates and latent periods, and horizontal and vertical
resistance (1587).
George Henry
Hepting (US) wrote Climate and forest
diseases, a paper considered the authoritative treatise on climatology and
plant pathology (654).
Resistance
to the insecticide, carbaryl,
appeared between 1963 and 1966 in the Orchard leafroller in New Zealand, in
cotton leafworm, Spodoptera, in Egypt, and in the tobacco budworm, Heliothis virescens, on American cotton
(Gossypium spp.). refs
Eugene J.
Van Scott (US) and Thomas N. Ekel (US) reported that epidermal hyperplasis is
found to be primarily due to expansion of the germinative cell population, less
so to increased mitotic rates. Expansion of the germinative cell population may
be initiated by proliferation of supporting connective tissue (1591). Note: Psoriasis is a notable example. See, other references under Eugene J. Van Scott.
Henry George
Kunkel (US), Mart Mannik (US), and Ralph C. Williams (US) found that human
antibodies against three different antigens were themselves antigenically
unique in rabbits. Furthermore, the rabbit anti-antibodies were active only
against the antibodies of a particular person. They would not couple with
antibodies against the same immunogen isolated from different people. Thus,
idiotypes were found to be clone-specific (860).
Fred S. Kantor
(US), Antonio Ojeda (US), and Baruj Benacerraf
(VE-US) presented
evidence, which established that conjugation of the immunogenically silent
polylysine molecule with dinitrophenyl groups results in a synthetic antigen
capable of inducing anti-DNP antibodies in guinea pigs (772).
Nils Kaj
Jerne (GB-DK) and Albert A. Nordin (US) developed the hemolytic plaque
technique for demonstrating which cells within a mixture produce antibody (750).
Charles W.
Todd (US), Arnold Feinstein (GB), Thomas J. Kindt (US), Marion E. Koshland
(US), Judith J. Davis (US), and N. Joan Fujita (US) discovered a group a allotype on several different
immunoglobulin isotypes in the rabbit. This finding challenged a basic paradigm
of genetics, the one-gene-one-polypeptide chain theory and suggested multiple
gene control of a single polypeptide chain (432; 809; 844; 1567).
Olga K.
Archer (US), David E.R. Sutherland (US), and Robert Alan Good (US) proposed
that rabbit gut associated lymphoid tissue (GALT) might be the functional
equivalent of the bursa in the chicken (50).
Thomas B.
Tomasi, Jr. (US), Sheldon D. Zigelbaum (US), and William B. Chodirker (US)
showed that immunoglobulin gamma (IgG) is almost absent in lacrimal fluid
(tears), and that virtually all lacrimal immunoglobulin is immunoglobulin alpha
(IgA) (266; 1569).
The Centers
for Disease Control (CDC) reported one of the few smallpox epidemics in Western
nations in recent years not evidencing a predominant spread among hospital
contacts. The outbreak emphasizes the sinister role of mild or vaccine-modified
cases of smallpox in initiating and propagating outbreaks of severe disease (2). Note: Sweden was the first major country to eliminate indigenous
smallpox, a distinction it achieved in 1895 (702).
Georges
Mathé (FR), Jean Louis Amiel (FR), Leon Schwarzenberg (FR), Albert Cattan (FR),
Maurice Schneider (FR) Marco J. de Vries (NL), Maurice Tubiana (FR), Claude M.
Lalanne (FR), Jacques-Louis Binet (FR), Martine Papiernik (FR), Gabriel Seman
(FR), Michio Matsukura (JP), Annabelle M. Mery (FR), V. Schwarzmann (FR), and Albert
Flaisler (FR) accomplished the first prolonged engraftment of human allogeneic
bone marrow. The adult recipient with leukemia
conditioned with total body irradiation died without disease reoccurrence after
20 months, probably from complications of graft-versus-host disease (1017; 1018). Note: Soon after they identified what
was then called secondary disease,
the debilitating and wasting condition that follows transplantation, they
deduced that this must be due to an immune reaction of the cells in the donor
marrow against the cells in the patient.” Mathé and colleagues thus became the
first to define what is now known as graft
versus host disease, and to study it in man.
Ernst Klenk
(DE) and Winfried Kahlke (DE) showed that the Refsum disease in humans is associated with accumulation of
phytanic acid in blood and tissues (824). The
cardinal clinical features of Refsum disease are retinitis pigmentosa,
chronic polyneuropathy, and cerebellar signs.
Jérôme Jean
Louis Marie Lejeune (FR), Jacques Lafourcade (FR), Roland Berger (FR), Jacques
Vialette (FR), Marc Boeswillwald (FR), Philippe Seringe (FR), and Raymond
Alexandre Turpin (FR) characterized and named the Cri du Chat Syndrome ("cry of the cat" in French) as a
genetic disorder caused by the loss or misplacement of genetic material from the
fifth chromosome. They described the syndrome after the sound that many of the
babies and young children make when crying (895).
Robert
Royston Amos Coombs (GB) and Philip George Houthem Gell (GB) proposed a
classification scheme, which defined 4 types of hypersensitivity reactions. The
first 3 are mediated by antibody, the fourth by T cells (296). The Gell
and Coombs classification now contains six categories: Type 1: Immediate
Hypersensitivity; Type 2: Cytotoxic Antibody; Type 3: Immune Complex; Type 4:
Delayed Hypersensitivity; Type 5: Stimulating Antibody; Type 6: Antibody
Dependant Cell Mediated Cytotoxicity (ADCC).
Henri-Géry
Hers (BE), Nicole Lejeune (FR), Denise Thinès-Sempoux (FR), Pierre Baudhuin
(FR), and Helmuth Loeb (BE) discovered that the absence of a lysosomal enzyme, acid maltase, is the cause of a fatal
genetic glycogen storage disorder, glycogenesis
II or Pompe’s disease (100; 659; 896).
Henri Géry
Hers (BE) proposed the concept of inborn lysosomal diseases (660).
Henri-Géry
Hers (BE) and Francois Van Hoof (BE) noted that this concept applies to most
polysaccharidoses, lipidoses, and other storage diseases (661).
Vaughn Critchlow (US), Robert A. Liebelt (US), Mildred Elwers
Bar-Sela (US), W. Mountcastle (US), and Harry S. Lipscomb (US) performed a
rigorous series of experiments directed at resolving
a controversy of whether there were differences in
pituitary-adrenal function
between male and female animals under resting conditions. Their experiments
provided validation that
the pituitary-adrenal axis is sexually dimorphic under
resting (control) conditions and can be modulated both by hormonal
status and by neurological processes inhibited by barbiturates (312).
Thelma B.
Dunn (US) and Arleigh W. Green (US) found that newborn mice receiving estrogen
injections developed tissue pathologies such as cysts, cancers, and lesions.
Results indicate that exposure to naturally occurring hormones early in life
can produce harmful health effects and point to possible early life causes of
cancer in adult human populations (379).
Robert M. Berne (US), Eckehardt Gerlach (DE), B. Deuticke (DE),
and Robert H. Dreisbach (US) proposed that adenosine mediates
local metabolic control of
coronary blood flow. The balance between oxygen
supply and myocardial oxygen consumption is reflected in the
intracellular myocardial oxygen tension (PO2).
If myocardial oxygen
consumption increases (as during exercise), then there
will be a fall in cardiac myocyte PO2
that will lead to the breakdown
of adenine nucleotides (ATP, ADP, AMP) and to the
generation of adenosine that diffuses out of the cardiac cell.
The adenosine crosses the interstitial space to act on adenosine
receptors on coronary arteriolar smooth muscle to cause
vasodilation. The
ensuing increase in coronary blood flow delivers more oxygen
to the myocardium and thus returns myocardial PO2
back toward the normal operating range (125; 526).
Arvid
Carlsson (SE) and Margit Lindqvist (SE) described for the first time a specific
action of major neuroleptic (antipsychotic) drugs upon the metabolic processes
in the brain, and a mode of action was proposed. Chlorpromazine and haloperidol
enhanced the turnover of dopamine (prolactin-inhibiting hormone) and
noradrenaline in the brain (230).
Emanuel
Grunberg (US), Edith H. Titsworth (US), and Michael Bennett (US) reported the
antifungal activity of 5-fluorocytosine (585).
Oleh
Hornykiewicz (AT) reported the clinical effectiveness of L-dopa in patients
with post-encephalitic Parkinsonism,
a current mainline drug for the treatment of Parkinson disease (703).
Oliver W.
Sacks (GB) revealed the clinical effectiveness of L-dopa in patients with post-
encephalitic Parkinsonism (1340).
Nils-Erik
Birger Andén (SE), Arvid Carlsson (SE), Jüri Kerstell (SE), Tor Magnusson (SE),
Rolf Olsson (SE), Björn-Erik Roos (SE), Bertil Steen (SE), Göran Steg (SE),
Alvar Svanborg (SE), Georg Thieme (SE), and Bengt Werdinius (SE) carried out
clinical trials for the treatment of Parkinsonism with L-dopa (27).
Samuel
Lawrence Katz (US), John Franklin Enders (US), Sidney Kibrick (US), Ann
Holloway (US), C. Henry Kempe (US), Francis L. Black (US), Martha L. Lepow
(US), Saul Krugman (US), and Robert J. Haggerty (US) transformed their
Edmonston-B strain of measles (rubeola) virus into a vaccine and, in 1963,
licensed it in the United States (787-789). In 1968,
an improved and even weaker measles (rubeola) vaccine, developed by Maurice
Hilleman and colleagues, began to be distributed. This vaccine, called the
Edmonston-Enders (formerly “Moraten”) strain has been the only measles vaccine
used in the United States since 1968 (503).
John H. Karam (US), Gerold M. Grodsky (US), Peter H. Forsham (US) and
Nancy B. McWilliams (US) showed that obese, non-diabetic subjects had levels of
serum immunoreactive insulin three to four times higher than those of
non-obese, normal subjects after identical rapid intravenous glucose loads.
These findings established the relevance of obesity in interpreting the
excessive insulin responses to glucose in early maturity-onset diabetics (777).
William
Griffith McBride (AU) discovered the link between thalidomide and child deformities (1029).
James W. Lash
(US) and Lauri Saxén (FI) suggested how thalidomide
might cause limb defects in human embryos (879; 880).
John
Lindenbaum (US) and Edgar Leifer (US) found varying degrees of hepatic injury,
usually mild, and with fatty degeneration as the most commonly reported change
noted after prolonged administration of halothane or 2-bromo,
2-chloro-1,1,1-trifluoroethane (Fluothane) to animals (924).
Philip
Jacobs (GB) gave a good clinical description of ankylosing spondylitis (742).
Ralph
Douglas Kenneth Reye (AU), Graeme Morgan (AU), Jim Baral (AU-US), George Magnus
Johnson (US), Theodore D. Scurletis (US), and Norma B. Carroll (US) described
an encephalopathy (Reye’s syndrome)
which is more common in childhood (3; 753; 1281).
Eugene S. Hurwitz
(US), Michael J. Barrett (US), Dennis Bergman (US), Walter J. Gunn (US), Paul Pinsky
(US), Lawrence B. Schonberger (US), Joseph S. Drage (US), Richard A. Kaslow
(US), D. Bruce Burlington (US), Gerald V. Quinnan (US), John R. LaMontagne (US),
William R. Fairweather (US), Delbert Dayton (US), Walter R. Dowdle (US) in
a Public Health Service study confirmed that the syndrome is associated with
aspirin consumption by children with viral diseases such as chicken pox.
Caution when administering salicylates to treat children with viral illnesses,
particularly chickenpox and influenza-like illnesses is prudent (725).
John Richard O’Brien (GB) concluded that aspirin might be
protective in several thrombotic conditions. He was one of the first to call
for a trial of aspirin after a thrombotic event such as a heart attack, and to
show that low doses of the drug were likely to be effective (1159-1162).
Hughes W.
Day (US) reported that the first coronary care unit had reduced patient
mortality by 60%, leading to the rapid proliferation of such units (332).
Thomas Earl
Starzl (US), Thomas L. Marchioro (US), and William R. Waddell (US)
reported
evidence that human kidney allografts performed under azathioprine/prednisone
induced variable donor specific nonreactivity. This represents the first
systematic use of azathioprine and prednisone with long survival of most kidney
allografts (1463; 1469).
Thomas Earl
Starzl (US), Thomas L. Marchioro (US), Kurt N. von Kaulla (US), Gilbert Hermann
(US), Robert S. Brittain (US), and William R. Waddell (US) performed the first
successful orthotopic liver transplantation in humans. Immunosuppression was
used in all three attempts with the best survival time course being 21 days (1468).
James D.
Hardy (US), Sadan Eraslan (TR), Martin L. Dalton, Jr. (US), Fikri Alican (US),
M. Don Turner (US), Watts R. Webb (US), and George R. Walker, Jr. (US)
performed the first successful lung transplant in humans. A
pneumonectomy for carcinoma with pleural
adhesions had to be performed first. The patient died
on the 17th post-operative day (618; 619).
Joseph Louis
Melnick (US) was among the first researchers to demonstrate that the poliovirus
belongs to a group known as enteroviruses and that they only rarely invade the
central nervous system.
In 1955 the
Committee on the ECHO viruses issued its first report in which 13 antigenically
distinct members of the ECHO group were listed (293). Since then the name of the
committee has been changed to indicate that it deals with poliomyelitis,
Coxsackie, and ECHO viruses, which are now regarded as members of a single
family of human enteroviruses (292).
Craig Wallis
(US) and Joseph Louis Melnick (US) led a team that developed thermostabilized
live polio vaccines, making possible the immunization of millions of people in
countries without deep-freeze storage facilities. His team showed that the
poliovirus was transmitted among people chiefly by fecal contamination (1617).
Most of the
human enterovirus serotypes were discovered and described between 1948 and 1963
because of the application of cell culture and suckling mouse inoculation to
investigations of cases of infantile paralysis (paralytic poliomyelitis) and
other central nervous system diseases (Committee on Enteroviruses, 1962; Panel
for Picornaviruses, 1963).
The history
of the enteroviruses is described, and how poliovirus came to be recognized as
the prototype species of the genus, a subdivision of the family Picornaviridae.
Albert Sabin was one of the main contributors. He isolated several enterovirus
types and established them as causative agents of human disease. The
enteroviruses were discovered only after new methods were introduced for
working with viruses. They are now recognized as constituting one of the genera
of the picornavirus family. Pico-rna-virus stands for viruses, which are small
(pico), and have an RNA genome. The enterovirus genus includes the polioviruses,
the coxsackieviruses and the echoviruses of humans, plus a number of
enteroviruses of lower animals (e.g., monkeys, cattle, pigs, mice). Over 100
serotypes are now recognized, the first having been the polioviruses.
Peter L.
Carlton (US) suggested that brain-acetylcholine acts to inhibit nonrewarded
behaviors. This activity thereby provides a kind of ‘guidance system’ by which
irrelevant behaviors are eliminated from the animal’s goal-directed repertoire
of responses (231).
John L.
Hamerton (GB) and Harold P. Klinger (CH) speculated that man might have rapidly
evolved from chimpanzee/gorilla type ancestors (both of which have 48
chromosomes) via chromosomal rearrangements. On examining the chromosomes of
primates generally it is seen that a decrease in the total number of
chromosomes is related to an increase in the number of metacentric at the
expense of acrocentric chromosomes. This could be brought about if two
acrocentric chromosomes broke in the middle (in one case losing the centric
region) and the two long portions joined together to make a single new long
metacentric chromosome (607).
Martin W. Donner
(US), Elizabeth M. Ramsey (US), and George W. Corner, Jr. (US) explained the
mechanism of circulation within the placenta of the rhesus monkey, first
hypothesized upon the basis of anatomical data, then established by
radioangiographic studies (360).
English country names and code elements taken from the
International Organization for Standardization:
DZ = Algerian; US = American; AR = Argentinian; AU = Australian;
AT = Austrian; AT/HU = Austro/Hungarian; BA = Bosnian-Herzegovinian; BE =
Belgian; BR = Brazilian; GB = British; BG = Bulgarian; CM = Cameroonian; CA =
Canadian; TD = Chadian; CL = Chilean; CN = Chinese; CO = Colombian; CR = Costa
Rican; HR = Croatian; CU = Cuban; CY = Cypriot; CZ = Czechoslovakian; DK =
Danish; NL = Dutch; EC = Ecuadorian; EG = Egyptian; EE = Estonian; ET =
Ethiopian; FI = Finnish; FR = French; DE = German; GR = Greek; GT = Guatemalan;
GU = Guamanian; HU = Hungarian; IS = Icelander; IN = Indian; ID = Indonesian;
IR = Iranian; IQ = Iraqi; IL = Israeli; IE = Irish; IT = Italian; JP =
Japanese; KE = Kenyan; KR = South Korean; KW = Kuwaiti ; LV = Latvian; LB =
Lebanese; LT = Lithuanian; LU = Luxembourgian; MK= Macedonian; MG = Malagasy;
MT = Maltese; MY = Malaysian; MX = Mexican; NA = Namibian; NZ = New Zealander;
NG = Nigerian; NO = Norwegian; PK = Pakistani; PA = Panamanian; PE = Peruvian;
PH = Filipino; PL = Polish; PT = Portuguese; PR = Puerto Rican; RO = Romanian;
RU = Russian; SA = Saudi Arabian; SN = Senegalese; CS = Serbian-Montenegrin; SK
= Slovakian; ZA = South African; ES = Spanish; LK = Sri Lankan; SE = Swedish;
CH = Swiss; SY = Syrian; TW = Taiwanese; TH = Thai; TN = Tunisian; TR =
Turkish; UG = Ugandan; UA = Ukrainian; UY = Uruguayan; VE = Venezuelan; ZW =
Zimbabwean
1. 1958. Edmund Schulman: 1908-1958
(Obituary). Tree-Ring Bull. 22:2-6
2. 1963.
Smallpox—Stockholm, Sweden, 1963. MMWR
Morb. Mortal Wkly. Rep. 12:172-236
3. 1980. Reye
Syndrome — Ohio, Michigan. MMWR Morb.
Mortal Wkly. Rep. 29:532-9
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C. LaMarche, Jr., 1937-1988 (Obituary). Tree-Ring
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