APPENDIX C: CHRONOLOGY
G. W. Beadle and B. Ephrussi and A. Kuhn and A. Butenandt work out the biochemical genetics of eye-pigment synthesis in Drosophila and Ephestia re- spectively. W. M. Stanley succeeds in isolating and crystallizing the tobacco mosaic virus. He mistakenly believes it is pure protein. C. B. Bridges publishes the salivary gland chromosome maps for Drosophila melanogaster. H. Spemann receives a Nobel Prize for his studies on embryonic induction. J. Schultz notes the relation of the mosaic expression of a gene in Drosophila to its position relative to heterochromatin.
N. V. Timofeyeff-Ressovsky and M. Delbru¨ck make estimates of gene volumes from target theory calculations. T. Caspersson uses cytospectrophotometric methods to investigate the quanti- tative chemical composition of cells. J. J. Bittner shows that mammary carcinomas in mice can be caused by a virus- like factor transmitted through the mother’s milk.
A. H. Sturtevant and T. Dobzhansky publish the first account of the use of inversions in constructing a chromosomal phylogenetic tree. C. Stern discovers somatic crossing over in Drosophila. R. Scott-Moncrieff reviews the inheritance of plant pigments. The major part of this work was done by a group of English geneticists at the John Innes Horti- cultural Institute, and these early workers established that gene substitutions resulted in chemical changes in certain flavanoid and carotenoid pigments. T. Dobzhansky publishes Genetics and the Origin of Species, a milestone in evo- lutionary genetics.
A. F. Blakeslee and A. G. Avery report that colchicine induces polyploidy. T. M. Sonneborn discovers mating types in Paramecium. F. C. Bawden and N. W. Pirie show that the tobacco mosaic virus, although being made mostly of protein, also contains a small amount (about 5%) of RNA.
P. A. Gorer discovers the first histocompatibility antigens in the laboratory mouse.
H. A. Krebs discovers the citric acid cycle. H. Karstrom points out that the synthesis of certain bacterial enzymes is stimu- lated when the substrates these enzymes attack are added to the medium. He coins the term “adaptive enzymes” for these and differentiates them from the “constitutive enzymes” that are always formed irrespective of the composition of the medium.
P. L’He´ritier and G. Teissier demonstrate frequency-dependent selection of mutants in laboratory populations of Drosophila melanogaster. E. Chatton stresses the fundamental differences between the group of organ- isms comprising the bacteria and blue-green algae, which he named prokaryotes, and all other living organisms, which he called eukaryotes.
H. J. Muller defines a telomere as a functional gene that seals the chromosome at each end. He points out that a chromosome cannot persist indefinitely with- out having its ends sealed by these specialized chromomeres.
B. McClintock shows that a maize chromosome which lacks a telomere will fuse with any nearby chromosome which also lacks a telomere. The dicentric chromosome that results will generate a bridge at the next mitosis, and a break- age-fusion-bridge cycle will follow. Therefore telomeres play a capping func- tion vital to the stability of each chromosome. T. M. Sonneborn discovers the killer factor of Paramecium.
M. M. Rhoades describes the mutator gene Dt in maize. H. Slizynska makes a cytological analysis of several overlapping Notch deficien- cies in the salivary gland X chromosomes of Drosophila melanogaster and deter- mines the band locations of the w and N genes. E. L. Ellis and M. Delbru¨ck perform studies on coliphage growth that mark the beginning of modern phage work. They devise the “one-step growth” experi- ment, which demonstrates that after the phage adsorbs onto the bacterium, it replicates within the bacterium during the “latent period,” and finally the prog- eny are released in a “burst.” G. A. Kausche, E. Pfankuch, and H. Ruska publish the first electron micro- scope photographs of a virus (tobacco mosaic).
A. A. Prokofyeva-Belgovskaya discovers the heterochromatization phenom- enon. P. Levine and R. E. Stetson discover maternal immunization by a fetus carrying a new blood group antigen inherited from the father. This antigen is subse- quently identified with the human Rh blood group system as the cause of erythroblastosis fetalis. A. W. K. Tiselius and E. A. Kabat demonstrate that antibodies belong to the gamma class of serum globulins.
E. Knapp and three colleagues demonstrate that the effectiveness of ultraviolet light in inducing mutations in Sphaerocarpus donnelli corresponds to the absorp- tion spectrum of nucleic acid. G. W. Beadle proposes that corn is a domesticated form of teosinte and sug- gests that mutations in as few as five genes can account for the morphological transformation of teosinte into corn. G. Domagk receives the Nobel Prize for his discovery of Prontosil.
This and other sulfa drugs revolutionize the treatment of infectious diseases. W. Earle establishes the strain L permanent cell line from a C3H mouse. H. W. Florey, E. Chain, and five colleagues successfully extract and purify pen- icillin. They show in experiments with mice that it is by far the most powerful chemotherapeutic agent then known against bacterial infections. G. W. Beadle and E. L.
Tatum publish their classic study on the biochemical genetics of Neurospora and promulgate the one gene-one enzyme theory. J. Brachet and T. Caspersson independently reach the conclusion that RNA is localized in the nucleoli and cytoplasm and that a cell’s content of RNA is directly linked with its protein synthesizing capacity. C. Auerbach and J. M. Robson use Muller’s C1B technique to prove that mus- tard gas induces mutations in Drosophila. Because of secrecy imposed during World War II on research with poison gas, the results, which opened the field of chemical mutagenesis, were not published until 1946.
A. J. P. Martin and R. L. M. Synge develop the technique of partition chroma- tography and use it to determine the amino acids in protein hydrolyzates. A. H. Coons, H. J. Creech, and R. N. Jones develop immunofluorescence tech- niques to demonstrate the presence of antibody-reactive sites on specific cells. K. Mather coins the term polygenes and describes polygenic traits in various organisms.
R. Schoenheimer publishes The Dynamic State of Body Constituents and de- scribes the use of isotopically tagged compounds in metabolic studies. He intro- duces the concepts of “metabolic pools” and the “turnover” of the organic com- pounds in cells. S. E. Luria and T. F. Anderson publish the first electron micrographs of bacte- rial viruses. T2 has a polyhedral body and a tail! G. D. Snell sets out to develop highly inbred strains of mice to study the genes responsible for graft rejection. A. Claude isolates and names the microsome fraction and shows that it contains the majority of the RNA of cells.
J. Hammerling makes grafts between species of giant algae belonging to the genus Acetabularia. He shows that the basal nucleus of each cell controls the morphological development of the cytoplasm at the apex of the stalk centime- ters away. S. E. Luria and M. Delbru¨ck initiate the field of bacterial genetics when they demonstrate unambiguously that bacteria undergo spontaneous mutation. O. T. Avery, C. M. MacLeod, and M.
McCarty purify and chemically charac- terize the pneumococcus transforming principle. It is 99.9% DNA, and they later show that deoxyribonuclease inactivates it. They conclude that genetic information is carried by DNA molecules. T. Dobzhansky describes the phylogeny of the gene arrangements in the third chromosome of Drosophila pseudoobscura and D. persimilis. E. L. Tatum, D. Bonner, and G. W. Beadle use mutant strains of Neurospora crassa to work out the intermediate steps in the synthesis of tryptophan. R. R. Humphrey demonstrates that the female is the heterogametic sex in uro- deles. M. J. D. White publishes Animal Cytology and Evolution, the first monograph to review progress in the study of the evolutionary cytogenetics of animals. S. E.
Luria demonstrates that mutations occur in bacterial viruses. E. B. Lewis describes the stable position effect phenomenon in Drosophila. R. D. Owen reports that in cattle dizygotic twins are born with, and often retain throughout life, a stable mixture of each other’s red blood cells. This chimerism, which results from vascular anastomoses within the chorions of the fetuses, provides the first example of immune tolerance. A. Fleming, E. B. Chain, and H. W. Florey receive the Nobel Prize for the discovery, purification, and chemical characterization of penicillin. A. Claude introduces cell fractionation techniques based upon differential cen- trifugation and works out methods for characterizing the fractions biochemi- cally.
Genetic recombination in bacteriophage is demonstrated by M. Delbru¨ck and W. T. Bailey and by A. D. Hershey. J. Lederberg and E. L. Tatum demonstrate genetic recombination in bacteria. Mutations are chemically induced in Drosophila by J. A. Rapoport using form- aldehyde. J. Oudin develops the gel-diffusion, antigen-antibody precipitation test that bears his name.
Nobel Prizes are awarded to H. J. Muller for his contributions to radiation genetics; to J. B. Sumner for crystallizing enzymes; and to W. M. Stanley for his studies on the purification and chemical characterization of viruses. A. M. Mourant suggests that earliest European populations were Rh− and that modern-day Basques have the highest Rh− frequencies known because through isolation they have maintained the genetic characteristics of their paleolithic ancestors. David Lack publishes Darwin’s Finches. In this monograph he describes how the finches of the Galapagos archipelago are transformed by evolution from competing to non-competing species by “fine-tuning” their habitat preferences and beak morphologies for different foods. A. Boivin, R. Vendrely, and C.
Vendrely analyze the DNA of nuclear suspen- sions of several beef tissues. They observe that the amount of DNA per somatic nucleus is the same and twice the amount in sperm nuclei. They predict that the amount of DNA per cell is constant and distinct for each species. H. E. Shortt and P. C. C. Garnham discover the stage in the life cycle of the malaria parasite specific to hepatocytes in primates. H. K. Mitchell and J. Lein show that tryptophan synthetase is missing in certain mutant strains of Neurospora. This finding constitutes the first direct evidence for the one gene-one enzyme theory. P. A.
Gorer, S. Lyman, and G. D. Snell discover the major histocompatibility locus in the mouse. It resides on chromosome 17 and is named H2. O. Ouchterlony develops the double-diffusion antigen-antibody precipitation test that bears his name. H. J. Muller coins the term dosage compensation. J. Lederberg and N. Zinder, and, independently, B. D. Davis develop the peni- cillin selection technique for isolating biochemically deficient bacterial mu- tants. J. Clausen, D. D. Keck, and W. M. Hiesey describe the genetic structure of ecotypes among species of herbaceous plants along an altitudinal transect in the Sierra Nevada mountains of California. G. D. Snell introduces the term histocompatibility gene and formulates the laws of transplantation acceptance and rejection. B. Ephrussi, H. Hottinger, and A. M. Chimenes discover petite cytoplasmic mutations in yeast. A. D.
Hershey and R. Rotman generate a genetic map for T2 bacteriophage that contains three linkage groups. In subsequent studies these linkage groups are found to merge into a linear molecule that has cyclically permuted se- quences.
D. M. C. Hodgkin and three colleagues use x-ray crystallography to determine the structure of the penicillin molecule at atomic resolution. A. Kelner discovers photoreactivation of potential UV damage by visible light in Saccharomyces. J. V. Neel provides genetic evidence that the sickle-cell disease is inherited as a simple Mendelian autosomal recessive. L. Pauling and three colleagues show that the HS gene produces an abnormal hemoglobin. M. L. Barr and E. G. Bertram demonstrate that the sex chromatin is morpho- logically different in the neurons of male and female cats. B. McClintock discovers the Ac, Ds system of transposable elements in maize. W. Hennig publishes Grundzuge einer Theorie der phylogenetischen Systematik.
It sets forth the criteria by which genealogic relationships between groups of organisms can be uncovered. An extensively revised English translation titled Phylogenetic Systematics will be published in 1966. This serves as an introduc- tion to cladistics for scientists in English. H. Swift uses Feulgen microspectrophotometry to determine the DNA con- tents of individual nuclei for a variety of tissues from mice, frogs, and insects. In accordance with the 1948 prediction of Boivin, Vendrely, and Vendrely, the DNA contents fall into classes that are integer multiples of a haploid value, defined as C. E.
Chargaff lays the foundations for nucleic acid structural studies by his analyt- ical work. He demonstrates for DNA that the numbers of adenine and thymine groups are always equal, and so are the numbers of guanine and cytosine groups. These findings later suggest to Watson that DNA consists of two poly- nucleotide strands joined by hydrogen bonding between A and T and between G and C. The finding that the DNAs from yeast and from the tubercle bacillus are relatively rich in AT and GC, respectively, disproved the tetranucleotide hypothesis. A. Lwoff and A.
Gutman study a lysogenic strain of Bacillus megatherium and demonstrate that each bacterium harbors a noninfectious form of a virus that gives the host the capacity to generate new phage without the intervention of exogenous bacteriophages. They propose the term prophage for this noninfec- tious phase. Together with L. Siminovitch and N. Kjeldgaard, Lwoff shows that prophage can be induced by ultraviolet light to produce infective virus. H. Latta and J. F. Hartmann introduce glass knives for ultramicrotomy. E. M.
Lederberg discovers lambda, the first viral episome of E. coli. G. Gey establishes the human HeLa permanent cell line. J. Mohr is the first to demonstrate autosomal linkage in humans (between the genes specifying the Lewis and Lutheran blood groups). C. Stormont, R. D. Owen, and M. R. Irwin describe serological cross-reactions in the multiple allelic B and C blood group systems of cattle. Y. Chiba demonstrates the presence of DNA in chloroplasts using the Feulgen- staining cytochemical technique. N. H. Horowitz and U. Leupold generate large populations of temperature- sensitive mutations to determine what percentage of the genes in E. coli and N. crassa perform functions that are indispensable. The values obtained were 23% and 46%, respectively. C. Petit reports the existence of a minority-genotype advantage in populations of Drosophila melanogaster and points out that this phenomenon can lead to frequency-dependent selection and stable polymorphism. G. G. Simpson publishes a phylogeny of the horse family that shows that the evolutionary tree has multiple side branches.
Earlier paleontologists mistakenly used the evolution of the horse as an example of orthogenesis. L. Pauling and R. B. Corey propose that most proteins form one or both of two secondary structures: the alpha helix and the beta sheet. V. J. Freeman reports that a specific bacteriophage confers upon its host, Cory- nebacterium diphtheriae, the ability to produce the diphtheria toxin. M. H. F. Wilkins and R. Gosling prepare DNA for x-ray crystallographic analy- sis and take the first x-ray photograph that shows a meaningful diffraction pat- tern. R. E. Franklin and R. Gosling discover that, under conditions of high humidity, DNA undergoes a transformation from an A to a B configuration. Franklin sub- sequently proposes that the B form is a helical molecule with the phosphate groups on the inside. F. H. C. Crick concludes from Franklin’s crystallographic data that the DNA chains in the helix are aligned in an antiparallel configuration. D. M. Brown and A. Todd demonstrate that DNA and RNA are 3′-5′ linked polynucleotides. G. E. Palade publishes the first high-resolution electron micrographs of mito- chondria. The organelle has an outer membrane and an inner one, which has shelf-like invaginations. He calls these cristae mitochondriales. R. Dulbecco adapts the techniques of bacterial virology to study animal viruses. He counts plaques made by western equine encephalomyelitis virus on mono- layers of cells obtained from chick embryos. D.
Mazia and K. Dan isolate the sea urchin mitotic apparatus and start work on its biochemical characterization. N. D. Zinder and J. Lederberg describe transduction in Salmonella typhimu- rium. The transducing phage was P22. J. Lederberg discovers and names plasmids. J. Lederberg and E. M. Lederberg invent the replica plating technique. J. T. Patterson and W. S. Stone publish Evolution in the Genus Drosophila, which summarizes an encyclopedic body of information dealing with the chro- mosomal evolution of this most studied genus of flies. A. H. Bradshaw reports that certain populations of grasses living near mine entrances in Great Britain can tolerate high concentrations of heavy metals (copper, lead, zinc). This is evidence for the recent natural selection of tolerant genotypes. W. Beermann observes stage and tissue specificities in the puffing patterns of polytene chromosomes and suggests that these are the phenotypic reflections of differential gene activities.
A. D. Hershey and M. Chase demonstrate that the DNA of phage enters the host, whereas most of the protein remains behind. G. Pontecorvo and J. A. Roper describe the parasexual cycle in Aspergillus nidu- lans. R. Briggs and T. S. King develop a method for taking a nucleus of a living cell from a Rana pipiens blastula and implanting it into an oocyte whose own nu- cleus had been removed.
Many of the oocytes carrying these implanted diploid somatic nuclei underwent cleavage and some eventually developed into tad- poles. However, when nuclei from gastrulae were used, most of the implanted embryos died. This showed that the nuclei of embryonic cells acquire develop- mental restrictions concomitant with cell specialization. A. J. P. Martin and R. L. M. Synge receive the Nobel Prize in chemistry for their invention of chromatographic separation techniques. J. D. Watson and F. H. C. Crick publish the double-helix model of DNA. It proposes that each molecule is composed of two antiparallel, helically inter- twined chains held together by hydrogen bonds between purines and pyrimi- dines. The supporting crystallographic data appear in the same issue of Nature in a second paper by Wilkins, A. R. Stokes, and H. R. Wilson, and a third paper by Franklin and Gosling. They conclude that the B configuration is the one found in living cells. In a subsequent issue of Nature, Watson and Crick pro- pose the semiconservative mechanism for the replication of DNA molecules. C. C.
Patterson uses a radioactive dating procedure (the uranium-lead clock) to determine the age of the earth (4.6 billion years). K. R. Porter takes electron micrographs of tissue-cultured animal cells. He de- scribes and names the endoplasmic reticulum and identifies it as the source of cytoplasmic basophilia. C. C.
Lindegren discovers gene conversion in Saccharomyces. A. Howard and S. R. Pelc demonstrate by autoradiography that during the cell- division cycle of plants there exists a period following mitosis during which DNA synthesis does not take place (G1), a subsequent period of DNA synthesis during which the DNA content of the interphase nucleus is doubled (S), a second growth period (G2), and then mitosis. W. Hayes discovers polarized behavior in bacterial recombinations. He isolates the Hfr H strain of E. coli and shows that certain genes are readily transferred from Hfr to F− bacteria, whereas others are not. R. E. Billingham, L. Brent, and P. B. Medawar show that immunological toler- ance can be produced experimentally.
Porter-Blum and Sjostrand ultramicrotomes become commercially available. J. B. Finean, F. S. Sjostrand, and E. Steinmann publish the first electron micro- graphs of sectioned chloroplasts. G. D. Snell finds that the major histocompatibility complex of the mouse (H-2) is composed of multiple loci. N. Visconti and M. Delbru¨ck put forth a hypothesis to explain genetic recom- bination in bacteriophages. A. J. Dalton and M. D. Felix provide the first detailed description of the ultra- structure of the Golgi complex.
A. C. Allison provides evidence that individuals heterozygous for the sickle- cell gene are protected against subtertian malaria infection. This is the first case of genetic balanced polymorphism described in a human population. H. Bickel, J. Gerrard, and E. M. Hickmans report that babies with phenylketo- nuria show great improvement in mental development and behavioral perfor- mance after being fed a synthetic diet low in phenylalanine. J. Dausset observes that some patients who had received multiple blood trans- fusions produced antibodies against antigens found on the white blood cells of other individuals but not against those of their own cells. These antibodies de- fined the first HLA antigens and led to the definition of the human histocom- patibility system. E. S.
Barghoorn and S. A. Tyler report finding fossils of filamentous and coc- coid microorganisms in sedimentary rocks over 2 billion years old. This discov- ery demonstrates that life existed in the Proterozoic era. E. Mayr advances the peripatric speciation concept. L. Pauling receives the Nobel Prize in chemistry for his research into the nature of the chemical bond and the structure of complex molecules including pro- teins. M. B. Hoagland obtains cell-free preparations that synthesize protein. F. Sanger and five colleagues are the first to work out the primary structure for a protein.
They show that insulin contains two polypeptide chains held to- gether by disulfide bridges. S. Benzer works out the fine structure of the r II region of phage T4 of E. coli, and coins the terms cistron, recon, and muton. H. Fraenkel-Conrat and R. C. Williams reconstitute “hybrid” tobacco mosaic virus from nucleic acid and protein components arising from different sources. The reconstituted particles are normal in appearance and infectivity. This is the first example of the self-assembly of an active biological structure. O. Smithies uses starch-gel electrophoresis to identify plasma protein polymor- phisms. N. K. Jerne puts forth the natural-selection theory of antibody formation. Ac- cording to this proposal, antibody molecules are already present in the host, having developed during fetal life. An invading foreign antigen selects the anti- body molecule that provides the best fit and binds to it.
The formation of this complex stimulates the further production of the selected antibody. These con- cepts are incorporated into later clonal selection theories. M. Grunberg-Manago and S. Ochoa isolate polynucleotide phosphorylase, the first enzyme involved in the synthesis of a nucleic acid. N. E. Morton develops the lod score method for estimating linkage from pedi- gree data. R. H. Pritchard studies the linear arrangement of a series of allelic adenine- requiring mutants of Aspergillus. He concludes that crossing over can occur between different alleles of the same gene, provided they are characterized by mutations at different subsites. C. de Duve and four colleagues describe intracellular vesicles that contain hy- drolytic enzymes and name them lysosomes.