A Selected Chronological Bibliography of Biology and
by James Southworth Steen, Ph.D.
to my loving family
This document celebrates those secondary authors and laboratory
technicians without whom most of this great labor of discovery would have
forward any editorial comments to: James S. Steen, Ph.D., Professor Emeritus,
biology is understandable except in the light of genetics.” Francisco José
that much of the work is done because one wants to impose an answer on it. They
have the answer ready, and they [know what they] want the material to tell
them... [Anything else it tells them] they don't really recognize as there, or
they think it's a mistake and throw it out... If you'd only just let the
material tell you." Barbara McClintock (881).
“One of the
more gratifying aspects of scientific work is the knowledge that one’s own
contributions have helped and influenced other scientists and thus furthered
the overall progress of science.” Pedro M. Cuatrecasas (360).
somehow, less interested in the weight and convolutions of Einstein’s brain
than in the near certainty that people of equal talent have lived and died in
cotton fields and sweatshops.” Stephen Jay Gould
(US) for his fundamental studies of the biochemistry of nucleic acids, with
particular regard to recombinant-DNA and Walter Gilbert (US) and Frederick
Sanger (GB) for their contributions concerning the determination of base
sequences in nucleic acids shared the Nobel Prize in Chemistry.
(VE-US), Jean Baptiste Gabriel Joachim Dausset (FR) and George Davies Snell
(US) were awarded the Nobel Prize in Physiology or Medicine for their
discoveries concerning genetically determined structures on the cell surface
that regulate immunological reactions.
Pinto (US), G. Randall Gladstone (US), Yuk Ling Yung (US), Akiva Bar-Nun (IL),
Sherwood Chang (US), and James F. Kasting (US) showed that photochemistry in an
atmosphere containing carbon dioxide or a mixture of carbon monoxide and carbon
dioxide yielded formaldehyde as a major product (83; 872; 1333).
Bauman (NL), Joop Wiegant (NL), Piet Borst (NL), and Piet van Duijn (NL) first
described the direct labeling of a nucleic acid with fluorophores using
fluorescence in situ hybridization (FISH) (99; 100).
Langer (US), Alex A. Waldrop (US), and David C. Ward (US) developed the
'indirect' method (implemented in commonly used FISH kits) that employs
immunogenic or enzymatic detection of tagged nucleic-acid probes following
Burridge (GB-US) and James R. Feramisco (US) discovered the cell adhesion
protein vinculin (236).
Salzmann (US), Ronald W. Ratcliffe (US), F. Aileen Bouffard (US), and Burton G.
Christensen (US) carried out the total synthesis of the antibiotic thienamycin (1448; 1449).
(GB), Peter J. Hudson (GB), and J. Leuan Harris (GB) determined the complete
amino acid sequence of phosphofructokinase
from Bacillus stearothermophilus (919).
Lagarias (US) and Henry Rapoport (US) determined the structure of phytochrome
chromophore attached to an undecapeptide, deduced from NMR spectra (962).
Badger (US), Aaron Kaplan (US), and Joe A Berry (US) developed a technique for
determination of the intracellular inorganic carbon concentration. They
measured it in the unicellular green alga Chlamydomonas
reinhardtii and in the cyanobacterium Anabaena
variabilis, and found that illuminated cells concentrate CO2 by active
uptake of inorganic carbon. Elevation of the CO2 concentration at the
carboxylation site raises the rate of carboxylation and decreases that of
oxygenation. Consequently, algal photosynthesis is not limited by availability of
inorganic carbon (70).
Pollock Klinman (US), Hope Humphries (US), Judith G. Voet (US), and Mary J.
Bossard (US) used isotope effects to isolate the chemical steps involved in the
conversion of dopamine and oxygen to norepinephrine and water (183; 914).
(IL), Jutta Mussig (DE), Bernd Tesche (DE), Siegfried Lorenz (DE), Volker A.
Erdmann (DE), and Heinz Guenter Wittmann (DE) crystallized the large ribosomal
subunits from Bacillus stearothermophilus (1847). Note:
They were the first to crystallize a ribosomal type.
Wing (US), Horace R. Drew (US), Tsunehiro Takano (JP), Chris Broka (US), and
Shoji Tanaka (US) gave hard evidence that the base sequence in DNA can have a
pronounced effect on its structure (1803).
Clarke (US), John Anthony Carbon (US), and Chu-Lai Hsiao (US), using Saccharomyces cerevisiae, were the first
to isolate DNA specific to the centromere region of chromosomes (306-308).
Lechner (DE) and John Anthony Carbon (US) identified a 240-kDa multi-subunit
complex, CBF3, which is a major component of the budding yeast centromere (983).
Bell (US), Raymond L. Pictet (US), William J. Rutter (US), Barbara Cordell
(US), Edmund Tischer (US), Howard Michael Goodman (US), David Owerbach (US),
and Thomas B. Shows (US) determined the nucleotide sequence of the human insulin gene and located it on
chromosome 11 (108; 1272).
Nagata (JP), Hideharu Taira (JP), Alan Hall (GB), Lorraine Johnsrud (CH),
Michel Streuli (US), Josef Ecsödi (CH), Werner Boll (CH), Kari Cantell (FI),
and Charles Weissman (US) cloned double stranded cDNA for interferon
(IF)-producing human leukocytes into Escherichia
coli using the pBR322 vector. This clone produced a polypeptide with strong
biological activity (1198).
Emtage (GB), William C.A. Tacon (GB), Graham H. Catlin (GB), Brian Jenkins
(GB), Alan G. Porter (GB), and Norman H. Carey (GB) demonstrated the
feasibility of producing controlled amounts of influenza antigenic determinants
by genetic engineering (471).
(US), John W. Stewart (US), and Ann Marie Schweingruber (US), working with Saccharomyces cerevisiae, established
that there is no absolute requirement for a particular sequence 5′ to the
initiation codon, consistent with their previous suggestion that translation
starts at the AUG codon closest to the 5′ end of the mRNA (1534).
Adams, Jr. (US) and George F. Kalf (US) determined that DNA polymerase of mitochondria can act in the forward direction as
a 5' to 3' polymerase and has a
3' to 5' exonuclease proofreading
Matsui (JP), Jacqueline Segall (CA), P. Anthony Weil (US), and Robert Gayle
Roeder (US) developed cell-free systems, which they used in the identification
of complex sets of proteins called accessory factors that are essential for
each individual RNA polymerase (e.g., TFIIA, TFIIB, TFIIE, TFIIF and TFIIH for
Pol II, and TFIIIB and TFIIIC for Pol III) to "read" specific target
genes (1097; 1508).
Orgel (GB) and Francis Harry Compton Crick (GB) coined the phrase “selfish DNA”
when referring to DNA sequences which encode a tendency to accumulate within
the genome (1261). Note: This is not to be confused with “selfish genes” which is a
directional increase in the proportion of individuals bearing the gene at a
particular locus. “Selfish DNA” is characterized by an increase in the mean
copy number of the element within the genome.
Guarente (US), Thomas M. Roberts (US), and Mark Steven Ptashne (US) described
methods allowing for the efficient expression in Escherichia coli of cloned eukaryotic genes (664).
Low (US) and Donald B. Zilversmit (US) demonstrated that alkaline phosphatase is attached to membranes of Staphylococcus aureus by a strong
interaction with phosphatidylinositol (1048). Note:
This discovery of anchor molecules had an impact on several areas of cell
Chakrabarty (US) filed for a U.S. patent on strains of the bacteria —Pseudomona aeruginosa and Pseudomonas putidas —which had been
genetically engineered to degrade crude oil. The patent was awarded to General
Electric in 1980 by the U.S. Supreme Court and issued in 1981 (269).
Rimm (US), Debra Horness (US), Jacky Kucera (US), and Frederick R. Blattner
(US) reported the construction of three new lambda-phage-cloning vectors, Charons (Ch) 27, 28, and 30. Ch27
and Ch30 are suitable for cloning small and large DNA fragments, respectively,
cut with BamHI, BglII, BclI, MboI, Sau3A, EcoRI, HindIII, SalI, and XhoI (1402).
Büchel (CH), Bruno Gronenborn (FR), and Benno Müller-Hill (DE) determined the
nucleotide sequence of the lacY gene coding
for lactose permease (M protein) in Escherichia coli and predicted that the
enzyme would consist of 417 residues with a molecular weight of 46,504 (228).
Harrison Hartwell (US) defined seven genes that function in two cell types of Saccharomyces cerevisiae (MATa and alpha) to control the differentiation of cell type and one gene, STE2, that functions exclusively in MATa cells to mediate responsiveness to
polypeptide hormone (717).
Wyman (US) and Ray White (US) discovered a locus in the human genome, not
associated with any specific gene, which is a site of restriction fragment
length polymorphism (RFLP). The polymorphism was found by hybridizing a
16-kilobase-pair segment of single-copy human DNA, selected from the human
genome library cloned in phage lambda CH4A, to a Southern transfer of total
human DNA digested with EcoRI. DNAs from a number of individuals from
within Mormon pedigrees, as well as random individuals have been examined. The
locus is highly variable, with at least eight alleles present, homozygotes
accounting for less than 25% of the individuals examined. The polymorphism
appears to be the result of DNA rearrangements rather than base-pair
substitutions or modifications. Examination of the DNA from seven members of a
family revealed fragment lengths that are consistent with their inheritance as
Mendelian alleles through three generations (1824).
Jeffreys (GB), Polly Weller (GB), Victoria Wilson (GB), Alain Blanchetot (US),
and Swee Lay Thein (GB) found two core
DNA sequences common to the repeated sequences described by Arlene R. Wyman
(US) and Ray White (US) in 1980. They developed complements to these core
sequences to probe for the core sequences in partially digested and
electrophoresed human DNA. The banding patterns, which appear upon
electrophoresis and probing, are inherited in a Mendelian fashion. One half of
the bands in a child’s DNA fingerprint are inherited from the mother and
one half from the father (833; 1781). Note:
The highly repetitious DNAs with the same core sequence are referred to as minisatellites.
Jeffreys (GB), Victoria Wilson (GB), Swee Lay Thein (GB), John F.Y. Brookfield
(GB), Robert Semeonoff (GB), Peter Gill (GB), David J. Werrett (GB) Päivi
Helminen (FI), Christian Ehnholm (FI), Marja-Liisa Lokki (FI), and Leena
Peltonen (FI) described methodology for doing DNA fingerprinting. It was Jeffreys who coined the term DNA fingerprinting and the first to use
DNA polymorphisms in paternity, immigration, and murder cases (594; 737; 831; 832). See, Colin Pitchfork, 1988. Note: DNA fingerprinting is now
called DNA profiling.
Schäfer (DE), Hans Zischler (DE), Uli Birsner (DE), Andrea Becker (DE), and
Jörg Thomas Epplen (DE) described the classical DNA fingerprinting method using
radio-labeled DNA probes containing minisatellite or oligonucleotide sequences
which are hybridized to DNA that has been digested with a restriction enzyme,
separated by agarose electrophoresis, and immobilized on a membrane by Southern
blotting or - in the case of the oligonucleotide probes - immobilized directly
in the dried gel. The radio-labeled probe hybridizes to a set of minisatellites
or oligonucleotide stretches in genomic DNA contained in restriction fragments
whose size differ because of variation in the numbers of repeat units. After
washing away excess probe the exposure to X-ray film (autoradiography) allows
these variable fragments to be visualized, and their profiles compared between
Zilla Wong (GB),
Victoria Wilson (GB), Ilaben Patel (GB), Sue Povey (GB), and Alec John Jeffreys
(GB) devised single-locus profiling
to overcome some of the limitations in the classic method. Here a single
hypervariable locus is detected by a specific single-locus probe (SLP) using
high stringency hybridization. Typically, four SLPs were used in a reprobing
approach, yielding eight alleles of four independent loci per individual (1814). Note: This method requires only 10 ng of genomic DNA and has been
validated through extensive experiments and forensic casework, and for many
years provided a robust and valuable system for individual identification.
Alan L. Edwards (US),
Andrew B. Civitello (US), Andrew B. Hammond (US), and C. Thomas Caskey (US)
developed DNA profiling methods based on the polymerase chain reaction
(PCR) exhibiting improved sensitivity, speed, and genotyping precision (464). These quickly
supplanted the classic methodology. Note: Microsatellites —in the forensic
community usually referred to short tandem repeats (STRs) —were found to be
ideally suited for forensic applications. STR typing is more sensitive than
single-locus RFLP methods, less prone to allelic dropout than VNTR (variable
number of tandem repeat) systems, and more discriminating than other PCR-based
typing methods, such as HLA-DQA1.
Michael D. Coble (US) and John M.
Butler (US) developed validated standard protocols using miniSTRs that are used
in laboratories worldwide (240; 319).
(DE), Petra Otremba (DE), Carmen Krüger (DE), Sybille Bergner-Greiner (DE),
Petra Anders (DE), Bärbel Henske (DE), Mechthild Prinz (DE), and Lutz Roewer
(DE) produced positive results by incorporating miniSTR markers into commercial
kits thus improving the application of these markers for all kinds of DNA
evidence. Reproducible results could be obtained from as little as three
nucleated cells and extracted even from severely compromised material (1199). Note: The probability that two individuals will have identical
markers at each of 13 different STR loci (a number commonly used) within their
DNA is less than one in a billion.
Ballantyne (AU), Victoria Keerl (DE), Andreas Wollstein (NL), Ying Choi (NL),
Sofia B. Zuniga (NL), Arwin Ralf (NL), Mark Vermeulen (NL), Peter de Knijff
(NL), and Manfred Kayser (NL) provided a new future for forensic Y-chromosome
analysis: rapidly mutating Y-STRs for differentiating male relatives and
paternal lineages. Currently forensic Y chromosome typing has gained wide
acceptance with the introduction of highly sensitive panels of up to 27 STRs
including rapidly mutating markers (77).
Krouse (US), Menasche N. Nass (US), Jeanne M. Nerbonne (US), Joel Nargeot (FR),
Henry A. Lester (US), Nigel J.M. Birdsall (GB), Jane Stockton (US), Norbert H.
Wassermann (US), and Bernard F. Erlanger (US) compared the activation of cell
membrane ion channels via nicotinic and muscarinic acetylcholine receptors
(AChRs). They found the muscarinic response to be about a thousand times slower
than the nicotinic response (941; 1205).
Kinsella (US) and Peter S. Aronson (US) concluded that isolated renal
microvillus membranes contain a tightly coupled Na+-H+ exchanger that may play
an important role in proximal tubular acidification (899).
Edward Heuser (US) and Mark W. Kirschener (US) used rapid freeze drying of
cellular cytoskeletons, along with coating the dried sample in platinum to make
a high-contrast replica, the result was a highly detailed, three-dimensional
electron micrographic (EM) view of the cytoskeletal filaments. This study also
showed that the major components of the cytoskeleton — microtubules, actin
filaments, and intermediate filaments — could each be identified based solely
on their ultrastructural appearance (746).
method proved useful in “seeing” all manner of cellular phenomena, including,
notably, clathrin-coated pit formation (745),
the budding of COPI-coated vesicles from golgi (1775),
and the dynein arm power stroke (611).
M. Svitkina (US), Alexander B. Verkhovsky (CH), and Gary G. Borisy (US)
improved the quick-freeze, deep-etch EM technique by adding immunogold
labeling. The study identified plectin as a cross-linking molecule between
intermediate filaments and both microtubules and actin filaments in the
Ford Doolittle (CA) and Carmen Spienza (CA) conjecture that natural selection
operating within genomes will inevitably result in the appearance of DNAs with
no phenotypic expression; whose only function is survival within genomes.
Prokaryotic transposable elements and eukaryotic middle-repetitive sequences
can be seen as such DNAs and thus no phenotypic or evolutionary function need
be assigned to them (423).
As Matt Ridley puts it, “Genes do behave as if they have selfish goals, not
consciously, but retrospectively: genes that behave in this way thrive and
genes that don’t don’t (1399).
Eiklid (NO), Sjur Olsnes (NO), and Alexander Pihl (NO) reported on the
mechanism by which the plant toxins abrin from the Indian Licorice seed, ricin
from the Castor Bean, and modeccin from Wild Granadilla (Adenia digitate) enter cells. Cells possess different populations
of binding sites with differences in ability to facilitate the uptake of the
toxins. Abrin may bind to cells specifically bearing the mannose receptor on
their cell surface, since this receptor is found in a particularly high density
on cells of the reticulohistiocytic system, the system that is affected in
particular by the toxicity of abrin. Ricin is known to bind to the mannose receptor
on specific cells i.e., macrophages or non-parenchymal liver cells. Modeccin binds
to surface receptors containing terminal galactose residues (466; 1255). Note: Upon
entering the cell, all three of these toxins inhibit protein synthesis by inactivating the 60S ribosomal
K. Draper (US), Melvin I. Simon (US), Kristen Sandvig (NO), and Sjur Olsnes
(NO) discovered how the toxic portion of the diphtheria toxin enters the cell
cytoplasm by translocation across the cell membrane (435; 1457).
Tse (US), Karla Kirkegaard (US), and James Chuo Wang (CN-US) found that the
covalent bond formed between topoisomerase
I and DNA in E. coli and Micrococcus luteus is most likely a
phosphotyrosine linkage. They also determined the topoisomerase cleavage sites
in a number of single-stranded DNA restriction fragments. They found that there
was no nucleotide specificity on either the 3-prime or the 5-prime side of the site
of cleavage. The protein-DNA linkage formed upon cleavage of double-stranded
DNA by M. luteus DNA gyrase is
accompanied by the covalent linking of subunit A, but not subunit B of gyrase,
to the 5-prime side of the DNA via a phosphotyrosine bond (1695).
Klaus-Joachim Blobel (DE-US) expanded the signal hypothesis to say that
topogenic sequences within discrete segments of targeted proteins are decoded
by specific receptors, either during (cotranslational) or shortly after
(post-translational) their biosynthesis. The specificity of such signal
sequence-receptor interactions targets the proteins to the correct
intracellular membranes where they are fed into translocons that move them
across the hydrophobic core of the lipid bilayer. Similarly, it has been
proposed that another class of topogenic sequences — termed stop-transfer
sequences — interacts with the translocon to arrest further transport and
thereby achieve an asymmetric transmembrane orientation of integral membrane
F. Castellucci (US), Eric Richard Kandel (US), James H. Schwartz (US), Floyd D.
Wilson (US), Angus C. Nairn (US), Paul Greengard (US), Leonard K. Kaczmarek (US),
Keith R. Jennings (US), Felix Strumwasser (US), and Ulrich Walter (DE) formulated
the hypothesis that a neurotransmitter in the nervous system functions in an
analogous manner to that of a hormone by activating adenylyl cyclase to elevate cAMP levels. The cyclic nucleotide then
activates protein kinse activity, which catalyzes the phosphorylation of a
substrate protein. The phosphorylated substrate, by means of one or more
additional reactions, elicits the physiological response characteristic of the
neurotransmitter in question. Collaborative studies subsequently performed by
Greengard’s team provided evidence for a causal relationship between protein
phosphorylation and the physiological response in neurons and neurosecretory
cells. The impact of this work was profound, since it provided insight into the
biological processes that regulate synaptic transmission and therefore
presented a more detailed understanding of neuronal function (260; 853).
De Camilli (IT-US), Richard Cameron (US), Paul Greengard (US), Susan M. Harris (US),
and Wieland B. Huttner (US) demonstrated that the magnitude of neurotransmitter
release was governed by the phosphorylation state of certain proteins localized
to the presynaptic nerve endings. Included among these proteins were the synapsins,
so named because they were detected in synaptic vesicles localized to nerve
endings (391; 392).
Note: Eric Richard Kandel (US), Paul Greengard (US), and colleagues
showed conclusively that the magnitude of neurotransmitter release in response
to a nerve impulse was regulated by phosphorylation/dephosphorylation
reactions. As a consequence, a basic foundation was laid for elucidating the
biological processes associated with synaptic transmission.
J. Novick (US), Charles Field (US), and Randy Wayne Schekmann (US) found that
electron microscopy of Saccharomyces
cerevisiae secretory mutant cells reveals, with one exception, the
temperature-dependent accumulation of membrane-enclosed secretory organelles.
They suggested that these structures represent intermediates in a pathway in
which secretion and plasma membrane assembly are colinear (1233).
Salminen (FI) and Peter J. Novick (US) found that their analysis of SEC 4 in Saccharomyces cerevisiae predicts a
protein product of 23.5 kd molecular weight that shares 32% homology with ras
proteins and is essential for growth. They proposed that the SEC 4 product is a
GTP-binding protein that plays an essential role in controlling a late stage of
the secretory pathway (1447).
R.B. Pelham (GB), Kevin G. Hardwick (GB), and Michael J. Lewis (GB) reported
that luminal endoplasmic reticulum (ER) proteins carry a signal at their C
terminus that prevents their secretion; in S.
cerevisiae this signal is the tetrapeptide HDEL. Indirect evidence suggests
that HDEL is recognized by a receptor that retrieves ER proteins from the
secretory pathway and returns them to the ER (1318; 1319).
J. Lewis (GB), Deborah J. Sweet (GB), and Hugh R.B. Pelham (GB) showed that
presumptive endoplasmic reticulum (ER) proteins from the budding yeast Kluyveromyces lactis can terminate
either with HDEL or, in the case of BiP, with DDEL. They concluded that ERD2
encodes the receptor that sorts luminal ER proteins (1013).
V. Schu (US), Kaoru Takegawa (JP), Michael J. Fry (US), Jeffrey H. Stack (US),
Michael D. Waterfield (US), and Scott D. Emr (US) discovered that VPS34 of Saccharomyces cerevisiae encodes a
110-kD protein with two regions of 33% sequence identity to a comparable
carboxy-terminal domain of the bovine PI-3 kinase. Functional and genetic
analyses demonstrated the catalytic identity of the yeast protein and the role
of this enzyme reaction in the sorting of vacuolar proteins in vivo (1500).
M. Ross (US) and Alfred Goodman Gilman (US) described the hormone-regulated
adenylate cyclase system, which represents the origin of our understanding of
the role of G proteins within the cell (1418).
Van Schaftingen (BE), Louis Hue (BE), and Henri-Géry Hers (BE) reported the
discovery of fructose 2,6-bisphosphate, a novel and potent allosteric
stimulator of liver
6-phosphofructo-1-kinase. Their demonstration that the concentration of
fructose 2,6-bisphosphate was greatly increased in hepatocytes incubated in the
presence of glucose, and its disappearance on incubation with glucagon,
provided an elegant switching mechanism between the two opposing pathways of
glycolysis and gluconeogenesis (1725-1727).
Van Schaftingen (BE), Louis Hue (BE), Mark H. Rider (GB), Simon J. Pilkis (US),
Thomas H. Claus (US), Irwin J. Kurland (US), and Alex J. Lange (US) found that
fructose 2,6-bisphosphate not only stimulates 6-phosphofructokinase-1 but also inhibits fructose 1,6-bisphosphatase-1. Fructose 2,6-bisphosphate was thus a
key regulatory signaling molecule of glycolytic/gluconeogenic flux that
provided a switching mechanism between the two opposing pathways of hepatic
carbohydrate metabolism (795; 1331; 1724).
Hue (BE) and Guy G. Rousseau (BE) were the first to show that fructose
2,6-bisphosphate concentrations were elevated in several transformed cell lines
and that growth factors and oncogenes increased fructose 2,6-bisphosphate
synthesis by induction of a 6-phosphofructokinase-2/fructose
1,6-bisphosphatase-2 isoenzyme that displayed no detectable bisphosphatase
Note: Diphosphate and bisphosphate
D. Rhein (US) and Robert H. Cagan (US) found that fish possess olfactory cilia
with binding sites for amino acids that the fish smell, providing evidence for
the existence of receptors for odorants (1384).
B. Buck (US), Richard Axel (US), Nina S. Levy (US), Heather A. Bakalyar (US),
Randall R. Reed (US), Marc Parmentier (BE), Frédéric Libert (BE), Stéphane
Schurmans (BE), Serge Schiffman (BE), Anne Lefort (BE), Dominique Eggerickx
(BE), Catherine Ledent (BE), Catherine Mollereau (BE), Catherine Gérard (BE),
Jason Perret (BE), Anton Grootegoed (BE), Gilbert Vassart (BE), Nissim Ben-Arie
(IL), Doron Lancet (IL), Clare Taylor (GB), Miriam Khen (IL), Naoml Walker
(IL), David H. Ledbetter (US), Romeo Carrozzo (US), Katen Patel (GB), Denise
Sheer (GB), Hans Lehrach (GB), and Michael A. North (GB) determined that the
initial step in olfactory discrimination requires the interaction of odorous
ligands with a family of seven-transmembrane-domain receptors on olfactory
sensory neurons. The repertoire of mammalian olfactory receptors is extremely
large and consists of about 1000 different genes (110; 229; 1011; 1291).
Chess (US), Michael M. Dowling (US), Linda B. Buck (US), Richard Axel (US),
John Ngai (US), Kerry J. Ressler (US), and Susan L. Sullivan (US) obtained in situ hybridization results suggesting
that each olfactory neuron expresses only one or a small number of receptor
genes, such that individual olfactory neurons are functionally distinct (286; 1213; 1381).
D. Mills (GB), Ronald A. Laskey (GB), Phillippa Black (GB), and Edward M.
DeRobertis (US) presented evidence of selective entry of nucleoplasmin (a
protein) through the nuclear envelope (1154).
Jean Smith (US) showed that the mouse blastocyst, rather than being a symmetrical
sphere, is slightly distorted and has recognizable axes. What's more, these
axes appeared to match up with those of the fetus, suggesting that the former
sets up the latter (1570; 1571).
Lavenham Gardner (GB), M.R. Meredith (GB), and D.G. Altman (GB) verified Smith's
Szmuness (PL-US), Cladd E. Stevens (US), Edward J. Harley (US), Edith A. Zang
(US), William R. Oleszko (US), Daniel C. William (US), Richard Sadovsky (US),
John M. Morrison (US), and Aaron Kellner (US), between 1973 and 1980, designed
and executed what has been described as the finest clinical field trial in the history
of medicine, one that tested a vaccine for hepatitis B. The controlled,
randomized, double‐blind trial in 1,083 homosexual men from New York confirmed that a
highly purified, formalin‐inactivated vaccine against hepatitis B prepared from HBsAg
positive plasma, is safe immunogenic, and highly efficacious (1635).
Herbert Leroy Needleman (US) provided the first clear evidence
that lead, even at very low levels, could adversely affect a child's IQ (1208). See, quote from Benjamin
Fujiwara (JP), Shoichi Chida (JP), Yoshitane Watabe (JP), Haruo Maeta (JP),
Tomoaki Morita (JP), and Tadaaki Abe (JP) reported that among 10 infants
treated for respiratory distress syndrome with artificial surfactant in this
landmark trial, significant improvements in blood pressure, acid-base status,
arterial oxygenation, and radiologic findings were observed. Infants also
required significantly less oxygen therapy and ventilator pressure following
surfactant administration (557).
Barth (DE), Edwin Sylvester Brokken, Jr. (US), Lyndia S. Blair (US), and
William C. Campbell (US) discovered the antiparasitic nature of Ivermectin (92; 164). Note:
It is derived from avermectin, a macrocylclic lactone, which is naturally
produced in soil by Streptomyces
avermitilis. Ivermectin proved to be remarkably effective in humans,
leading to a hope that a cure for river blindness (caused by the
human parasite Onchocerca volvulus) was
Brooks (US), Victor J. Sank (US), Giovanni Di Chiro (IT-US), Walter S. Friauf
(US), and Stephen B. Leighton (US) designed a high resolution positron emission
tomograph: the Neuro-PET (212).
Schiepers (US) and Carl K. Hoh (US) described positron emission tomography as a
diagnostic tool in oncology (1481).
Rohren (US), Timothy G. Turkington (US) and R. Edward Coleman (US) described
the clinical applications of positron emission tomography (PET) in oncology (1416). Note: Positron emission tomography (PET) uses an injected dye to
view tissues that are highly metabolically active. PET can identify tumors that
are fast growing and active. It is more sensitive at detecting small tumors and
metastatic tumors than CT or MRI and so may aid in early diagnosis.
Rizk (EG) provided a detailed anatomical and histological description of the
ventral abdominal walls of 116 specimens (41 human and 75 from nine mammalian
families) of various ages and both sexes (1405).
David E.R. Sutherland (US), Frederick C. Goetz (US), and John S.
(US) performed the world's first living-donor (segmental) pancreas
F. House (US) and Aziz Belal, Jr. (EG) pioneered the early diagnosis and
translabyrinthine removal of schwannomas (784).
Manabu Kuriyama (JP), Ming C.
Wang (US), Lawrence D. Papsidero (US), Carl S. Killian (US), Takashi Shimano
(US), Luis Valenzuela (US), Tsuneo Nishiura (JP), Gerald P. Murphy (US), and T.
Ming Chu (US) associated levels of prostate specific antigen (PSA) with risk
for prostate cancer leading to the first routine protein biomarker test used in
cancer screening and prevention (952).
Brown (US), Robert S. Langer (US), Michael V. Sefton (US), Halimena M. Creque
(US), Moses Judah Folkman (US), Kam W. Leong (US), and Brigitta C. Brott (US)
pioneered the field of controlled drug release delivery systems (slow release
oral systems, transdermal patches, injectable microspheres, and slow release
implants). These delivery systems involve macromolecules that have been
incorporated into solid polymers from which they are released at controlled
rates (218; 354; 1004; 1507). Note: This development has
revolutionized medical therapy, permitted new therapies for patients, and by
reducing the dose administered, has avoided complications and reduced costs.
Examples of current drug applications include nitroglycerin, nicotine, cancer
chemotheraputics, hormones and vaccines. In subsequent work, they determined
the mechanism of release of drugs from polymers and then identified the factors
that could be used to control the rate of release.
Shepard (GB), Richard J.W. Rees (GB), Celia Lowe (GB), Philip Draper (GB),
Morton Harboe (NO), Harvindar Kaur Gill (NO-MY), Abu Salim Mustafa (NO), Juraj
Ivanyi (GB), and Tore Godal (NO) played important roles in the production of a
vaccine for leprosy. It was licensed to the Wellcome drug company in England (433; 434; 593; 1533).
Bloom (US) directed clinical efficacy trials of this vaccine for leprosy under
the auspices of the World Health Organization (172).
Victor Bruce Darlington Skerman (AU), Vicki F. McGowan (AU), and Peter Henry
Andrews Sneath (GB) edited the Approved
List of Bacterial Names. This publication had a major impact on
bacteriology throughout the world and marked the culmination of an ambition to
reform the nomenclature of the bacteria (1557).
United States of America the Commission on Uniform State Laws proposed the
Uniform Determination of Death Act. It stated that an individual, who has
sustained either irreversible cessation of circulatory and respiratory
functions, or irreversible cessation of all the functions of the entire brain,
including the brain stem, is dead. A determination of death must be made in
accordance with accepted medical standards. The National Conference of
Commissioners on Uniform State Laws approved it in 1981, in cooperation with
the American Medical Association, the American Bar Association, and the
President's Commission for the Study of Ethical Problems in Medicine and
Biomedical and Behavioral Research.
Bob B. Buchanan (US) discovered that thioredoxin, a small protein
earlier found in bacteria by others, functions in regulating photosynthesis. In
fulfilling this function, thioredoxin, in effect, acts as an "eye,"
allowing chloroplasts, the site of photosynthesis, to distinguish light from
dark. The chloroplast thioredoxin system functions by breaking critical
intrachain disulfide bonds on key enzymes thereby altering their activity in
the light. In this way, the plant is able to maximize the energy obtained from
the sun (227).
Farnham (US), Terry Platt (US), Howard B. Gamper (US), John E. Hearst (US),
Peter H. von Hippel (US), David G. Bear (US), William D. Morgan (US), James A.
McSwiggen (US), and Thomas D. Yager (US) established the bubble paradigm to describe the transcription of RNA from DNA (494; 573; 1339; 1746; 1827; 1828).
Jani Nüsslein-Volhard (DE), Eric F. Wieschaus (US), Gerd Jürgens (DE), and
Hildegard Kluding (DE), using Drosophila as their experimental material,
discovered that during embryonic development homeotic genes act hierarchically, parceling up the embryo into
smaller and smaller sections to create ever more detail. They proposed that gap genes help establish large-scale
body patterns, whereas the segment-polarity
and pair-rule genes control
segmentation. The two-segment expression pattern of pair-rule genes, they suggested, could reflect an initial
segmentation into seven double segments that later divide in half — perhaps
avoiding errors that could arise in dividing the relatively few cells of the
blastoderm evenly into 14 segments (852; 1239; 1240).
Fronhöfer (DE), Christiane Jani Nüsslein-Volhard (DE), and Wolfgang Driever
(DE) discovered the first classic morphogen in Drosophila melanogaster, Bicoid (Bcd). Bcd is a maternal effect gene involved in anterior development in
the fruit fly, and it controls the expression of zygotic segmentation genes,
such as hunchback, in the developing
embryo. This 55 KDa protein is localized in a visible gradient (with the
highest concentration at the anterior) within the nuclei of cleaving embryos.
This was the first work to identify a protein gradient in Drosophila
embryos and led the authors to conclude that the protein was indeed a morphogen
which had long-range effects on neighboring cells (437-439; 549).
Berleth (DE-CA), Maya Burri (DE), Gudrun Thoma (DE), Daniel Bopp (CH), Sibyll
Richstein (DE), Gabriella Frigerio (DE), Markus Noll (CH), Wolfgang Driever
(DE), and Christiane Jani Nüsslein-Volhard (DE) determined that the egg of the
fruit fly, Drosophila melanogaster,
is already marked front and rear, top and bottom, before it is fertilized. The
mother in the very process of egg formation deposits at one location strands of
messenger RNA—not a gene, but the gene’s transcript—for a protein called Bicoid. The Bicoid protein is distributed in a broad anterior-posterior
gradient, with peak levels present at the anterior pole (134; 437; 1236-1238). This
gradient controls the differentiation of head structures and is also important
for initiating the segmentation cascade.
(FR), Judith P. Johnson (DE), Colin V. Beechey (GB), Sandra J. Andrews (GB),
Jürgen Peters (GB), and Anthony G. Searle (GB) discovered that in mice the
genes coding for the production of the immunoglobulin heavy chain and serum prealbumin
are located on chromosome 12 (1138).
Jean P. Van
Wauwe (BE), Jan R. De Mey (FR), and Jan G. Goossens (BE) found that OKT3, a
monoclonal anti-human T cell antibody (IgG2), induces DNA synthesis in human
peripheral lymphocyte cultures. OKT3 appeared to be a T lymphocyte mitogen as
only sheep red blood cell rosetting lymphocytes were responsive. As this interaction
can trigger mitogenesis, the cell membrane determinant recognized by OKT3 could
be described as a T cell stimulation receptor (1769).
(DE), Claude Nicolau (FR), and Peter H. Hofschneider (DE) were the first to
introduce a foreign gene into a mammalian cell using electroporation. The gene
was bacterial beta-lactamase (1813).
Sutcliffe (US), Thomas M. Shinnick (US), Nicola Green (US), Fu-Tang Liu (US),
Henry L. Niman (US), and Richard Alan Lerner (US) discovered previously unknown
viral proteins of the Moloney leukemia virus by starting with the viral nucleic
acid sequence, synthesizing a protein from a particular nucleic acid segment,
making rabbit antibodies to this protein, then reacting the antibodies with
Moloney infected cells. The result was the precipitation of two previously
unidentified viral proteins (1005; 1627).
(FI-CH-US), Jürgen Kartenbeck (DE), Kai Simons (FI-DE), and Erik F.B. Fries (SE)
discovered the pathway by which semliki forest virus (SFV) —a
membrane-containing animal virus— enters BHK-21 cells. After attaching to the
cell surface, the majority of viruses were rapidly trapped into coated pits,
internalized by endocytosis in coated vesicles, and sequestered into
intracellular vacuoles and lysosomes. Direct penetration of viruses through the
plasma membrane was never observed (735).
Harris (GB) suggested that genes can be controlled either at the level of
transcription (DNA copying into RNA) in the nucleus or at the level of
translation (protein production) in the cytoplasm after the messenger RNA has
been exported from the nucleus. Harris performed an experiment in which he
showed that once mRNA is formed and exported to the cytoplasm, the control
mechanism for translation is then in the cytoplasm. If an antibiotic blocks
transcription, mammalian cells continue to synthesize specific proteins for
long periods in culture (709).
Botstein (US), Raymond Leslie White (US), Mark H. Skolnick (US), and Ronald W.
Davis (US) suggested that a large number of DNA sequence polymorphisms must
exist in the human population, and that some of these should be detectable as
variants in the length of DNA fragments produced by restriction enzymes
(restriction fragment-length polymorphisms or RFLPs). These RFLPs could be
detected using Southern blotting experiments on human genomic DNA. Importantly,
and unlike classical polymorphic antigenic and enzyme markers, these new loci
could be identified in non-coding regions of the genome as well as within
genes. Linkage relationships among RFLPs could be established using pedigrees,
and genetic linkage to a locus of interest would allow a gene to be mapped and
defined, even if the RFLPs were not in the gene. They estimated that at least
150 highly polymorphic regions at regular intervals in the human genome would
make it feasible to construct a human genetic-linkage map and to localize
disease genes (185).
James F. Gusella (US), Nancy S. Wexler (VZ), P. Michael
Conneally (US), Susan L. Naylor (US), Mary Anne Anderson (US), Rudolph E. Tanzi
(US), Paul C. Watkins (US), Kathleen Ottina (US), Margaret R. Wallace (US),
Alan Y. Sakaguchi (US), Anne B. Young (VZ), Ira Shoulson (VZ), Ernesto Bonilla (VZ),
and Joseph B. Martin (US) of The US–Venezuela Huntington's Disease
Collaborative Research Project discovered the approximate location of a
causal gene for Huntington's disease (672; 673).
Grantham (FR) articulated the genome hypothesis as, “The genetic code is used
differently by different kinds of species. Each type of genome has a particular
coding strategy, that is, choices among degenerate bases are consistently
similar for all genes therein. This uniformity in the selection between
degenerate bases within each taxonomic group was discovered by applying new
methods to the study of coding variability. It is now possible to calculate
relative distances between genomes, or genome types, based on use of the codon
catalog by the mRNAs therein” (632).
Poiesz (US), Francis W. Ruscetti (US), Adi F. Gazdar (US), Paul A. Bunn, Jr.
(US), John D. Minna (US), Marvin S. Reitz (US), Vaniambadi S.
Kalyanaraman (US), Samuel Broder (US), Elaine S. Jaffe (US), William Blattner
(US), Flossie Wong-Staal (CN-US), Thomas A. Waldmann (US), Vinvent T. DeVita,
Jr. (US), Robert Charles Gallo (US), Mitsuaki Yoshida (JP), Isao Miyoshi (JP),
Yorio Hinuma (JP), Takashi Uchiyama (JP), Junji Yodoi (JP), Kimitaka Sagawa
(JP), Kiyoshi Takatsuki (JP), and Haruto Uchino (JP) were the first to discover
a virus which causes cancer in humans; a human retrovirus. The virus, named
Human T Lymphocyte Virus-1 (HTLV-1), causes a rare form of adult T cell
leukemia by integrating upstream of a cellular regulatory gene and causing it
to over express itself leading to excess production of T cell growth factor,
which stimulates proliferation of T lymphocytes (206; 1343; 1344; 1706; 1849). Note:
This is the discovery of HTLV-1, the first pathogenic human retrovirus.
Mach (CH), Stephan Carrel (CH), Michel Forni (CH), Jürg Ritschard (CH), Alfred Donath
(CH), Pierre Alberto (CH), Jean-Francois Chatal (CH), Jean-Denis Lumbroso (CH),
Franz Buchegger (CH), Christian Berche (CH), Jean-Yves Douillard (CH), Meenhard
Herlyn (CH), Zenon Steplewski (CH), and Hilary Koprowski (CH) used a
radiolabeled monoclonal antibody (MAb) that had been shown to react
specifically in vitro and ex vivo to human colorectal carcinoma and
inhibit growth of human carcinomas grafted in nude mice. They treated colorectal
carcinoma patients and patients with other types of cancer. Results showed the
potential value and limitations of this particular MAb for tumor detection by
immunoscintigraphy (1057; 1058).
Ruth Arnon (IL), Michael Sela (IL), Monique Parant (IL), Louis Chedid
(FR), Francoise Audibert (FR), and Michel Jolivet (FR) prepared totally
synthetic antigens, and
these led to neutralization of a virus, MS2, as well
as to protection against diphtheria and cholera (48; 58).
Liotta (US), Karl Tryggvason (FI), Spiridione Garbisa (IT), Ian Hart (US), Calvin
M. Foltz (US), and Samir Shafie (US) showed that tumors secrete proteases that
degrade collagen and that cell lines with the highest levels of collagenase had
the highest potential for metastasis (1030). Note: For tumors to metastasize they must pass through the
epithelial and endothelial basement membranes and gain access to the blood
Lance A. Liotta (US), Raya Mandler
(US), Genesio Murano (US), David A. Katz (US), Richard K. Gordon (US), Peter K.
Chiang (US), and Elliott Schiffmann
purified, and partially characterized a cell motility-stimulating factor from
the serum-free conditioned medium of human A2058 melanoma cells. They term this
activity "autocrine motility factor" (AMF) (1029).
Hideomi Watanabe (JP), Kenji
Takehana (JP), Massayo Date (JP), Tetsuya Shinozaki (JP), and Avraham Raz (US) demonstrated that "autocrine
motility factor" (AMF)
is the previously cloned cytokine and enzyme designated as neuroleukin, and
phosphohexose isomerase, which has been independently implicated in cell
motility, and to be a cancer progression marker (1768).
Brechot (FR), Christine Pourcel (FR), Anna Louise (FR), Bernadette Rain (FR),
and Pierre Tiollais (FR) reported that hepatitis B virus (HBV) DNA frequently
integrates into the genome of human primary liver cancer cells (194; 195).
Constance A. Crowley (US), John T.
Curnutte (US), Richard E. Rosin (US), Janine André-Schwartz (US), John I.
Gallin (US), Mark Klempner (US), Ralph Snyderman (US), Frederick S. Southwick
(US), Thomas P. Stossel (US), and Bernard M. Babior (US) discovered an inherited abnormality of neutrophil adhesion. It exhibits X-linked
genetic transmission and it is associated with a missing protein of 110,000