Genetics: Timeline of key events

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The feat was achieved by Henry Harris and John Watkins. The two cells, one derived from a mouse and the other from a human, were fused together using a parainfluenza virus that had been inactivated using ultraviolet light. The resulting hybrid cell contained both human and mouse chromosomes. By fusing cells from different species Harris and Watkins aimed to get a plenitude of stable genetic markers, which were in short supply in animal cells. Their technique was published in H. Harris, JF Watkins, G Campbell, EP Evans, CE Ford, 'Mitosis in hybrid cells derived from mouse and man', Nature, 207 (7 Aug 1965), 606–08. 1965-08-07T00:00:00+0000Muller was an American geneticist. He demonstrated that X-rays could change the genetic make-up of fruit-flies and that the mutations could be passed on to subsequent generations. Published in 1927 this work attracted widespread attention. It marked the first time the genetics of a species was intentionally altered. Muller's work opened up new understanding of how mutations are caused and heralded a revolution in genetics research. He was awarded he 1946 Nobel Prize for 'the discovery of the production of mutations by means of X-ray irradiation'.1967-04-15T00:00:00+0000The technique was developed by Mary Weiss and Howard Green. Their method involved fusing a mouse cell that was unable to make the enzyme thymidine kinase with a human cell that could make the enzyme. They then let the cells multiply in a nutrient solution that was deadly to any cells that lacked the enzyme. This killed off all the cells except one clump of identical cells (clone) that produced the enzyme. These cells they found contained the same identical clone. Weiss and Green's technique provided a crucial step towards human gene mapping. Their work was published in 'Human-mouse hybrid cell lines containing partial complements of human chromosomes and functioning human genes', PNAS USA 58/3 (1967): 1104-11. 1967-09-01T00:00:00+0000W. Arber, S.Linn, 'DNA modification and restriction', Annual Review Biochemistry, 38 (1969), 467-500.1969-07-01T00:00:00+0000The method uses (quinacrine mustard) which causes chromosomes to show light and dark lateral bands along their length. This makes it possible to accurately identify all 22 autosomes and X and Y chromosomes. With this method scientists can observe slight abnormalities and extra chromosomes such as those implicated in Down's syndrome. The staining technique was devised by Torbjourn Casperson, Lore Zech and other colleagues at the Karolinska Institute in Sweden. It was published in T Caspersson, L Zech, C Johansson, EJ Modest, 'Identification of human chromosomes by DNA-binding fluorescent agents', Chromosoma, 30/2 (1970), 213-27, DOI:10.1007/BF00282002 1970-06-01T00:00:00+0000Reverse transcriptase is a restriction enzyme that cuts DNA molecules at specific sites. The enzyme was simultaneously discovered independently by Howard Temin and David Baltimore. Temin made the discovery while working on Rous sacoma virions and Baltimore was working on the poliovirus and vesicular stomatis virus. The discovery laid the foundations for the the disciplines of retrovirology and cancer biology and ability to produce recombinant DNA. The findings were published in D Baltimore, 'RNA-dependent DNA polymerase in virions of RNA tumour viruses' Nature, 226 (1970), 1209–11 and HM Temin, S Mizutani, 'RNA-dependent DNA polymerase in virions of Rous sarcoma virus', Nature, 226 (1970), 1211–13. 1970-07-27T00:00:00+0000The observation was made by Hugh McDevitt and colleagues using two methods of genetic mapping to determine the immune response in immunised mice. The work suggested predictable, inherited susceptibility to some diseases. It was published in HO McDevitt, BD Deak, D Shreffler, J Klein, JH Stimpfling, GD Snell, 'Genetic control of the immune response', Journal of Experimental Medicine, 135 (1972), 1259-78. 1972-02-07T00:00:00+0000The first person who proposed the workshop was Frank Ruddle who convened the first meeting. He was inspired to set up the workshop by the rapid development in mapping by somatic-cell hybridisation. The workshop was sponsored by the National Science Foundation and March of Dimes. It was held at Yale University, New Haven. Papers from the conference were published in Cytogenet Cell Genetics, 13 (1974), 1-216. 1973-06-10T00:00:00+0000A.D. Riggs, 'X inactivation, differentiation, and DNA methylation', Cytogenet Cell Genet, 14 (1975), 9–25; R. Sager, R. Kitchin, 'Selective silencing of eukaryotic DNA', Science, 189/4201 (1975), 426-33. 1975-01-01T00:00:00+0000R. Holliday, J.E. Pugh, 'DNA modification mechanisms and gene activity during development', Science, 187 (1975), 226–32.1975-01-01T00:00:00+0000Tatum was an American biochemist who shared the 1958 Nobel Prize for Medicine for discovering how genes regulate biochemical events in cells. This was based on some experiments he carried out with colleagues at Stanford University in 1941 which involved crossing normal strains of the pink bread mould, Neurospora crassa, with another strain of the mould they had exposed to X-rays to induce genetic mutations. The offspring were found to inherit the mutation which manifested itself as metabolic defect. This led them to conclude that there was a direct link between genes and enzymatic reactions.1975-11-05T00:00:00+0000The suggestion was put forward by J Michael Bishop and Harold Varmus based on their research on the SRC gene of the Rous sarcoma virus, which they found to be nearly identical to a sequence in the normal cellular DNA of several different bird species. The findings were published in D Stehelin, HE Varmus, JM Bishop, PK Vogt, 'DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA', Nature, 260/5547 (1976), 170-3.1976-03-11T00:00:00+0000Monod was a French biochemist who, together with Francois Jacob, worked out the genetic control of enzyme and virus synthesis based on their experiments with Escherichia coli in the early 1960s. They proposed that a messenger molecule in cells carries codes from the DNA in the cell nucleus to the site of protein synthesis in the cell's cytoplasm. This molecule was later called messenger RNA. Based on his work Monrod was awarded a Nobel Prize for Medicine in 1965. 1976-05-31T00:00:00+0000Lysenko was a Russian biologist who rejected the principles of Mendelian genetics and embraced the ideas of Jean-Baptiste Lamark who promoted the idea that an organism could pass on characteristics that it acquired during its lifetime to its offspring. Much of his work was directed towards trying to convert wheat crops to grow in different seasons. Stalin appointed Lysenko director of the Institute of Genetics in 1940, a position he retained until 1965. His rejection of orthodox genetics set Soviet agriculture and biology back by many decades. 1976-11-20T00:00:00+0000The method, known as the oocyte stem, was developed by Janet Mertz together with John Gurdon and Edward M DeRobertis. It was published in EM. De Robertis, JB. Gurdon, GA. Partington, JE Mertz, RA, 'Injected amphibian oocytes: a living test tube for the study of eukaryotic gene transcription?', Biochemistry Society Symposium, 42 (1977),181-91.1977-01-01T00:00:00+0000A German biophysicist, Delbruck helped discover how viruses replicate their genetic structure, showing that bacterial resistance from viruses is due to random mutation and not the result of adaptive changes. This work showed that viruses reproduce in one step and not exponentially as happens in the case of cellular organisms. In 1969 he was awarded the Nobel Prize for Medicine on the back of this work. Blending biochemistry with genetics, Delbruck made substantial contributions to uncovering important aspects of genetics.1981-03-09T00:00:00+0000S.J. Compere, R.D. Palmiter, 'DNA methylation controls the inducibility of the mouse metallothionein-I gene lymphoid cells', Cell, 25 (1981), 233–240. 1981-07-01T00:00:00+00001982-01-01T00:00:00+00001982-01-01T00:00:00+0000A.P. Feinberg, B. Vogelstein, 'Hypomethylation distinguishes genes of some human cancers from their normal counterparts', Nature, 301/5895 (1983), 89-92.1983-01-06T00:00:00+0000
Date Event People Places Sciences
7 Aug 1965Mouse and human cells successfully fusedHarris, Watkins, Campbell, Evans, FordOxford UniversityCell, Genetics
15 Apr 1967Hermann J Muller diedMullerIndiana UniversityGenetics
Sep 1967Chromosome with a specific gene isolated from hybrid cells produced from fused mouse and human cellsWeiss, GreenNew York UniversityDNA, Genetics, Genomics
Jul 1969Discovery of methylase, an enzyme, found to add protective methyl groups to DNAArber, LinnUniversity of GenevaDNA methylation, Epigenetics
Jun 1970First method published for staining human or other mammalian chromosomes Casperson, Zech, Johansson, ModestKarolinska InstituteDNA, Genetics
27 Jul 1970Reverse transcriptase first isolatedBaltimore, Temin, MizutaniMassachusetts Institute of Technology, University of WisconsinGenetics, Virology, Recombinant DNA
7 Feb 1972Immune response genes discoveredMcDevitt, Deak, Shreffler, Klein, Stimpfling, SnellStanford University, University of Michigan, Jackson LaboratoryGenetics, Immunology
10 Jun 1973 - 13 Jun 1973First international workshop on human gene mapping heldRuddle DNA, Genetics, Geonomics
1975DNA methylation suggested as mechanism behind X-chomosome silencing in embryosRiggs, Sager, KitchenCity of Hope National Medical Center, Harvard UniversityDNA methylation, Epigenetics, Embryology
1975DNA methylation proposed as important mechanism for the control of gene expression in higher organismsHoilliday, PughNational Institute for Medical ResearchDNA methylation, Epigenetics
5 Nov 1975Edward L Tatum diedTatumStanford University, Yale UniversityGenetics
11 Mar 1976Proto-oncogenes suggested to be part of the genetic machinery of normal cells and play important function in the developing cellBishop, Varmus, Stehelin, VogtUniversity of California San FranciscoDNA, Genetics, Oncology
31 May 1976Jacques Monod diedMonodPasteur InstituteGenetics
20 Nov 1976Trofim Denisovich Lysenko diedLysenkoLenin All-Union Academy of Agricultural SciencesEvolution, Genetics
1977First method developed for studying gene regulation in a higher organismMertz, Gurdon, De RobertisLaboratory of Molecular BiologyGenetics
9 Mar 1981Max Delbruck diedDelbruckCalifornia Institute of TechnologyGenetics, Virology
Jul 1981First evidence provided to show that DNA methylation involved in silencing X-chromosomeCompere, PalmitterHoward Hughes Medical InstituteDNA methylation, Epigenetics
1982 - 1985Studies reveal azacitidine, a cytoxic agent developed by Upjohn, inhibits DNA methylation  DNA methylation, Epigenetics
1982Azacitidine fails to win FDA approval for treatment of acute myelogenous leukaemia due to lack of controlled studies showing clinical benefit  Epigenetics, Oncology
6 Jan 1983Widespread loss of DNA methylation found on cytosine-guanine (CpG) islands in tumour samplesFeinberg, VogelsteinJohns Hopkins UniversityDNA methylation, Epigenetics

7 Aug 1965

Mouse and human cells successfully fused

15 Apr 1967

Hermann J Muller died

Sep 1967

Chromosome with a specific gene isolated from hybrid cells produced from fused mouse and human cells

Jul 1969

Discovery of methylase, an enzyme, found to add protective methyl groups to DNA

Jun 1970

First method published for staining human or other mammalian chromosomes

27 Jul 1970

Reverse transcriptase first isolated

7 Feb 1972

Immune response genes discovered

10 Jun 1973 - 13 Jun 1973

First international workshop on human gene mapping held

1975

DNA methylation suggested as mechanism behind X-chomosome silencing in embryos

1975

DNA methylation proposed as important mechanism for the control of gene expression in higher organisms

5 Nov 1975

Edward L Tatum died

11 Mar 1976

Proto-oncogenes suggested to be part of the genetic machinery of normal cells and play important function in the developing cell

31 May 1976

Jacques Monod died

20 Nov 1976

Trofim Denisovich Lysenko died

1977

First method developed for studying gene regulation in a higher organism

9 Mar 1981

Max Delbruck died

Jul 1981

First evidence provided to show that DNA methylation involved in silencing X-chromosome

1982 - 1985

Studies reveal azacitidine, a cytoxic agent developed by Upjohn, inhibits DNA methylation

1982

Azacitidine fails to win FDA approval for treatment of acute myelogenous leukaemia due to lack of controlled studies showing clinical benefit

6 Jan 1983

Widespread loss of DNA methylation found on cytosine-guanine (CpG) islands in tumour samples

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