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LANDMARKS IN THE HISTORY OF GENETICS

M.Tevfik Dorak, MD, PhD

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Robert Hooke (1635-1703), a mechanic, is believed to give 'cells' their name when he examined a thin slice of cork under microscope, he thought cells looked like the small, rectangular rooms monks lived.

1651 William Harvey suggests that all living things originate from eggs

1694 JR Camerarius does pollination experiments and discovers sex in flowering plants

1735 CV Linnaeus (originally Linne) proposes the taxonomic system including the naming of Homo sapiens.

1761-7 JG Kolreuter finds in experiments on Nicotiana that each parent contributes equally to the characteristics of the offspring.

1798 TR Malthus publishes An Essay on the Principle of Population (foundations of the struggle for existence and the survival of the fittest).

1800 Karl Friedrich Burdach coins the term biology to denote the study of human morphology, physiology and psychology.

1809 JB de Monet Lamarck puts forward his ideas on evolution

1818 WC Wells suggests natural selection in African populations (for their relative resistance to local diseases)

1820 CF Nasse describes the sex-linked transmission of haemophilia

1822-1824 TA Knight, J Goss, and A Seton independently do studies in peas and observe the dominance, recessiveness and segregation in the first filial generation, but did not detect regularities

1828 Karl Ernst von Baer publishes The Embryology of Animals

1830 GB Amici shows that the pollen tube grows down the style and into the ovule of the flower; Charles Lyell publishes his multi-volume Principles of Geology

1831 Robert Brown notes nuclei within cells; Charles Darwin starts his voyage on HMS Beagle (returns in 1836)

1839 MJ Schleiden & T Schwann develop the cell theory [all animals and plants are made up of cells. Growth and reproduction are due to division of cells]

1840 Martin Barry expresses the belief that the spermatozoon enters the egg

1855 Alfred Russell Wallace publishes On the Law Which Has Regulated the Introduction of New Species

1858 Alfred Russell Wallace sends to Darwin a manuscript "On the Tendency of Varieties to Depart Indefinitely from the Original Type"

1859 C Darwin publishes The Origin of Species

Darwin's five theories:

1. The organisms steadily evolve over time (evolution theory)

2. Different kinds of organisms descended from a common ancestor (common

descent theory)

3. Species multiply over time (speciation theory)

4. Evolution takes place through the gradual change of populations

(gradualism theory)

5. The mechanism of evolution is the competition among vast numbers of

unique individuals for limited resources under selective pressures, which

leads to differences in survival and reproduction (natural selection theory).

1864 Ernst Haeckel (Häckel) outlines the essential elements of modern zoological classification

1865 Gregor Johann Mendel presents his principals of heredity [particulate inheritance] to the Brunn Society for Natural History and publishes in the Proceedings of the Brunn Society for Natural History in the following year [CPG p.1] (Brunn is now Brno in Czech Republic)

Mendel's work showed that:

1. Each parent contributes one factor of each trait shown in offspring

2. The two members of each pair of factors segregate from each other during

gamete formation

3. The blending theory of inheritance was not correct

4. Males and females contribute equally to the traits in their offspring

5. Acquired traits are not inherited.

Mendel had referred to the genes as 'particles of inheritance'

1866 EH Haeckel (Häckel) hypothesizes that the nucleus of a cell transmits its hereditary information

1869 Francis Galton publishes Hereditary Genius (study of human pedigrees)

1871 C Darwin publishes Descent of Man (principles of sexual selection)

1875 F Galton demonstrates the usefulness of twin studies for elucidating the relative influence of nature (heredity) and nurture (environment) upon behavioural traits; Oscar Hertwig concludes from a study of the reproduction of the sea urchin that fertilisation consists of the physical union of the two nuclei contributed by the male and female parents

1876 J Horner shows that colour-blindness is an inherited disease

1877 Fleming visualized chromosomes

1882 August Weismann notes the distinction between somatic and germ cells; chromosomes observed by Walther Flemming in the nuclei of dividing salamander cells. He uses the word mitosis

1887 A Weismann postulates the reduction of chromosome number in germ cells

1888 W Waldeyer coins the word chromosome

1889 Johann Miescher isolates DNA from salmon sperm; F Galton publishes Natural Inheritance (biometry)

1892 A Weismann's book Das Keimplasma (The Germ Plasm) emphasizes meiosis as an exact mechanism of chromosome distribution

1894 William Bateson's Materials for the Study of Variation emphasizes the importance of discontinuous variations; Karl Pearson publishes his first contribution to the mathematical theory of evolution (he develops the Chi-squared test in 1900)

1896 EB Wilson publishes The Cell in Development and Heredity

1899 The First International Congress of Genetics held in London

1900 The Dutch botanist Hugo de Vries and two others discover Mendel's principles; W Bateson publishes its translation to English in the following year

1901 Hugo de Vries adopts the term mutation

1902 WS Sutton and T Boveri (studying sea urchins) independently propose the chromosome theory of heredity [full set of chromosomes are needed for normal development; individual chromosomes carry different hereditary determinants; independent assortment of gene pairs occurs during meiosis] [CPG p.27]

1905 W Bateson gives the name genetics (means 'to generate' in Greek) to this branch of science, and introduces the words allele (allelomorph), heterozygous (impure line) and homozygous (pure line); W Bateson & RC Punnett work out the principles of multigenic interaction (linkage) and heredity [CPG p.42]

1908 GH Hardy and W Weinberg independently formulate the Hardy-Weinberg principle of population genetics [CPG p.60]

1909 AE Garrod publishes Inborn Errors of Metabolism [biochemical genetics of albinism, cystinuria, pentosuria and alkaptonuria]; W Johannsen uses the words phenotype, genotype and gene for the first time in his studies with beans CPG p.20]; CC Little produces the first inbred strain of mice (DBA)

1910 Thomas Hunt Morgan discovers the white-eye and its sex-linkage in Drosophila (the beginning of Drosophila genetics) [CPG p.63] [receives the Nobel prize in 1933]; J Herrick describes sickle cell anaemia

1911 TH Morgan shows the first example of chromosomal linkage in the X chromosome of Drosophila [Nobel prize 1933]; EB Wilson shows that the gene for colour-blindness is on the X chromosome (first gene identified on a chromosome); Davenport founds the first US genetic clinic

1912 TH Morgan shows that genetic recombination does not take place in males in Drosophila and also discovers the first sex-linked lethal gene [Nobel prize 1933]

1917 S Wright works out the biochemical basis of coat colour inheritance in animals [CPG p.78]

1919 A Hungarian engineer, Karl Ereky, coins the term biotechnology (to mean production of beer, cheese, bread etc with the help of living organisms)

1925 CB Bridges proposes the balanced chromosome determination of sex theory [relationship between the autosomes and sex chromosomes] [CPG p.117]

1927 HJ Muller demonstrates that X-rays are mutagenic in Drosophila [CPG p.149] [receives the Nobel prize in 1946]

1928 F Griffith discovers type-transformation in pneuomococci

1941 George Wells Beadle & Edward Lawrie Tatum proposes the one gene - one enzyme (polypeptide) concept [CPG p.166] [Tatum receives the Nobel prize in 1958]

1944 Oswald Theodore Avery et al describe the DNA as the hereditary material [Pneumococcus transformation experiments] [CPG p.173]

1946 J Lederberg & EL Tatum demonstrate genetic recombination (conjugation) in bacteria [CPG p.192] [they receive the Nobel prize in 1958]

1949 L Pauling shows that a defect in the structure of hemoglobin causes sickle cell anemia

1950 E Chargaff et al demonstrate for DNA that the numbers of adenine and thymine groups are always equal, so are the numbers of guanine and cytosine groups; B McClintock discovers the transposable elements in maize [CPG p.199] [she receives the Nobel prize in 1983]

Early 1950s Rosalind Franklin and Maurice HF Wilkins at King's College, London show by X-ray crystallography that DNA exists as two strands wound together in a spiral or helical shape

1952 Frederick Sanger et al work out the amino acid sequence of insulin [Sanger receives his first Nobel prize in 1958]; AD Hershey & M Chase demonstrate that the genetic material of bacteriophage T2 is DNA and the DNA enters the host but not the protein [AD Hershey receives the Nobel prize in 1969]; ND Zinder & J Lederberg discover phage-mediated transduction in Salmonella [CPG p.221] [Lederberg receives the Nobel prize in 1958]

1953 On the basis of Chargaff's chemical data (1950; numbers of A and T, and C and G are the same in DNA), and Wilkins and Franklin's already available X-ray diffraction data, James D Watson & Francis HC Crick describe the DNA's double helix structure by inference [CPG p.241] [they share the Nobel prize in 1962]

1956 JH Tijo & A Levan show that the diploid chromosome number for humans is 46 (Hereditas 1956;42:1-6); S. Ochoa's laboratory discovers RNA polymerase and A Kornberg's group DNA polymerase and synthesize nucleic acids in vitro [they receive the Nobel prize in 1959]

1957 VM Ingram reports the amino acid sequence of HbS; H Frankel-Conrat, A Gierer and G Schramm independently demonstrate that the genetic information of tobacco mosaic virus is stored in RNA [CPG p.264]

1958 MS Meselson & FW Stahl demonstrate that DNA replication is semiconservative (in E.coli)

1959 J Lejeune et al show that Down's syndrome is a chromosomal abnormality [trisomy of a small telocentric chromosome] as the first identification of the genetic basis of a disease; PA Jacobs & JA Strong identify the chromosomal basis of Klinefelter's syndrome as XXY

1960 Riis & Fuchs performs the first prenatal sex determination; Moorhead performs the first chromosome analysis

1961 MF Lyon and LB Russell independently show that one of the X chromosomes is inactivated in females; SB Weiss & T Nakamoto isolate RNA polymerase; MW Nirenberg starts experiments to unveil the genetic code [gets the Nobel prize in 1968 together with Khorana]; F Jacob & J Monod publish Genetic Regulatory Mechanisms in the Synthesis of Proteins in which they propose the operon model for regulating gene expression in bacteria [they receive the Nobel prize in 1965]. Robert Guthrie in New York performs first genetic screening of newborns (for phenylketonuria).

1962 Werner Arber notices that E.coli extracts restrict viral replication with some enzymatic activity, hence the name restriction endonucleases. He later shared the 1978 Nobel prize with Smith and Nathan.

1964 DJL Luck & E Reich isolate mitochondrial DNA from Neurospora; WD Hamilton proposes the genetical theory of social behaviour; F Lilly et al shows the genetic basis of susceptibility to leukemia in mice (first documented MHC - disease association)

1965 S Brenner et al discovers the stop codons; RW Holley works out the first complete nucleotide sequence of a tRNA (yeast alanine tRNA) [receives the Nobel prize in 1968 together with Nirenberg and Khorana]

1966 B Weiss & CC Richardson discover DNA ligase; VA McKusick publishes Mendelian Inheritance in Man which is available online.

1967 CB Jacobson & RH Barter use amniocentesis for prenatal diagnosis of a genetic disorder; MC Weiss & H Green works out the autosomal chromosomal assignment of a human gene for the first time [thymidine kinase gene]; HG Khorana et al establishes the genetic code [receives the Nobel prize in 1968 together with MW Nirenberg]; amniocentesis and chromosome analysis are developed

1968 RT Okazaki et al report the discontinuous synthesis of the lagging DNA strand; M Kimura proposes the Neutral Gene Theory of Molecular Evolution; RP Donahue et al assigns the Duffy blood group locus to chromosome 1; S Wright publishes the first volume of Evolution and the Genetics of Populations

1969 HA Lubs finds a fragile site on the X chromosome and its clinical correlation (mental retardation in males); M Delbruck, SE Luria and AD Hershey receive the Nobel Prize for their contributions to viral genetics

1970 M Mandel & A Higa develop a method for transformation of bacteria [CaCl₂ method]; D Baltimore & HM Temin isolate reverse transcriptase from two oncogenic RNA viruses; R Sager & Z Ramanis publish the first genetic map of non-mendelian genes (chloroplast genes of Chlamydomonas); T Casperson et al do the first chromosome banding. Hamilton Smith and Daniel Nathans successfully used HindIII to manipulated DNA sequences reproducibly (and received the 1978 Nobel Prize along with Arber (see 1962).

1971 ML O'Riordan et al shows all 22 pairs of human autosomal chromosomes by quinacrine dying and identifies the Philadelphia chromosome as an aberrant chromosome 22; AG Knudson suggests that the retinoblastoma locus acts as a dominant anti-oncogene.

1972 DE Kohne et al studies the evolution of primates by DNA:DNA hybridisation; In P Berg's laboratory, the first recombinant DNA is produced in vitro [P Berg receives the Nobel prize in 1980]

1974 RD Kornberg describes the chromatin structure (nucleosomes); RW Hedges & AE Jacob discover the bacterial plasmid as an ampicillin-resistant gene (transposon)

1975 EM Southern describes the Southern transfer method; F Sanger & AR Coulson develop the DNA sequencing method; R Dulbecco, H Temin, and D Baltimore receive Nobel prizes for their studies on oncogenic viruses

1976 WY Kan et al perform the first DNA diagnosis (prenatally) in alpha-thalassaemia by RFLP analysis; JM Bishop & HE Varmus demonstrate the protooncogene to oncogene relationship [they receive the Nobel prize in 1989]

1977 JC Alwine et al describe the Northern blotting method; RJ Roberts and PA Sharp separately describe split genes in adenovirus; J Collins & B Holm develop cosmid cloning technique; K Itakura et al chemically synthesize a gene for human somatostatin and express it in E Coli, thus produce the first human protein in vitro; W Gilbert induces bacteria to synthesize insulin and interferon; Sanger et al publish the complete sequence of phage FX174 (5387 nucleotides) [Sanger & Gilbert receive the Nobel prize in 1980, second for Sanger]

1978 W Gilbert coins the terms intron and exons; T Maniatis et al develop the genomic library screening technique. Boyer & Swanson cofound the first biotechnology company, Genentech. The first test-tube baby is born in the UK

1979 Edwards & Steptoe achieve in vitro fertilisation; DV Goeddel et al produce human growth hormone using recombinant DNA technology

1980 JW Gordon et al produce the first transgenic mouse; Dr Chakrabarty is awarded the first patent for a genetically engineered (unicellular) organism; GD Snell, J Dausset, and B Benacerraf receive the Nobel prize for their studies on the MHC

1981 Identification of the first cancer causing gene; DNA analysis is developed for diagnosis of sickle cell trait

1982 Sanger et al publish the complete sequence of phage lambda (48,502 nucleotides). The first transgenic mouse is created (carrying a rat growth hormone gene)

1983 Gene for Huntington's disease is located to chromosome 4

1984 Alec Jeffreys develops genetic fingerprinting. The first American test-tube baby is born

1985 Cystic fibrosis gene is located to chromosome 7

1986 RK Saiki, KB Mullis and five colleagues describe the polymerase chain reaction [Mullis receives the Nobel prize in 1993]; muscular dystrophy gene is identified

1987 R Sinsheimer proposes the human genome project; the US Patent Office rules that multicellular organisms produced by genetic engineering may be patented

1989 LC Tsui, F Collins and co-workers clone the cystic fibrosis gene; TR Cech & S Altman receive the Nobel Prize for establishing the existence of catalytic RNAs

1990 WF Anderson in the USA reports the first gene successful therapy in humans (in ADA deficiency causing SCID); the California Hereditary Disorders Act comes into force; human genome project begins

1993 Huntington's disease gene is identified; gene therapy for SCID and cystic fibrosis begins in the UK

1994 The FlavrSavr tomato is approved by the FDA as the first GM food to go on the market (now discontinued)

1997 Complete Saccharomycetes cerevisiae genome is sequenced; complete E.coli genome is sequenced [Science 277;1453-74]

1998 Caenorhabditis elegans becomes the first animal whose genome is totally sequenced [Science 282:2012-8]

1999 A human MHC (HLA-DR52) haplotype is totally sequenced (October). Human chromosome 22 becomes the first one to be sequenced completely (November)

2003 Complete sequence of human Y-chromosome is published [Nature 423:825-38]

Compiled from:

Classic Papers in Genetics. JA Peters (Ed). Englewood Cliffs: Prentice-Hall, Inc. 1959 [CPG]

Genetics in Context [timeline]: http://www.esp.org (scroll down and choose Chronology)

AH Sturtevant's A History of Genetics: Chronology Appendix

King RC & Stansfield WD. A Dictionary of Genetics. New York: Oxford University Press

A Student’s Guide to Biotechnology: Words and Terms. Greenwood Press, 2002

Dynamic Timeline from Human Genome Project Website

Nobel Prizes in Genetics by Britannica

M.Tevfik Dorak, MD, PhD

Last updated on 28 November 2005

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