1818

W. C. Wells

Suggests selection was responsible for African populations that were relatively resistant to local diseases (thus the first to suggest natural selection)

1820

C. F. Nasse

Suggests a sex-linked mode of inheritance for hemophilia

1831

R. Brown

Notes nuclei within cells

1838–39

M. J. Schleiden and T. Schwann

Develop the theory that plants and animals are composed of cells (cell theory)

1858

C. Darwin and A. Wallace

Present abstracts to the Linnean Society of London on the theory of evolution based on natural selection, Darwin publishes On the Origin of Speciesone year later

1866

G. Mendel

Publishes his genetic studies on garden peas, Versuche über Pflanzenhybriden (Experiments on Plant Hybridization)

1871

F. Miescher

Publishes a method for the isolation of a cell nucleus; isolates “nuclein,” which is now known to be a nucleic acid and protein mixture

1875

E. Strasburger

Describes cell division in plants

1876

F. Galton

Uses twin studies to describe the relative influence of heredity and the environment (nature vs. nurture) on behavioral traits

1879

W. Flemming

Demonstrates that nuclear division involves splitting of the chromosome and migration of sister chromatids; later in 1882, he will coin the term mitosis

1899

M. W. Beijerinck

Demonstrates tobacco mosaic disease is the result of a self-reproducing subcellular form of life, the virus

1900

H. de Vries, C. Correns, and E. von Tschermak

Independently perform experiments that parallel Mendel’s studies and arrive at similar results, discover Mendel’s paper, recognize its significance, and stress its importance

1900

K. Landsteiner

Discovers human blood groups

1901

H. de Vries

Uses the term mutation to describe the sudden, spontaneous changes in hereditary material

1902

T. Boveri and W. Sutton

Propose the chromosome theory of inheritance

1905

W. Bateson and R. C. Punnett

Using the sweet pea as an experimental model, report the first example of genes linked to a chromosome (chromosome linkage)

1908

G. H. Hardy and W. Weinberg

Independently formulate the Hardy–Weinberg law of population genetics

1909

A. E. Garrod

With the publication of Inborn Errors of Metabolism, the earliest to discuss biochemical genetics

1909

W. Johannsen

While studying the inheritance of seed size, realizes the distinction between appearance of an organism and its actual genetic composition; coins the terms phenotype, genotype, and gene

1909

H. Nilsson Ehle

Proposes the multiple-factor hypothesis to explain quantitative inheritance

1910

T. H. Morgan

In discovering the white eye mutant in Drosophila, describes sex-linkage in this fly; Drosophila genetics begins

1911

T. H. Morgan

Demonstrates several genes are linked on the X chromosome in Drosophila

1912

T. H. Morgan

Discovers a sex-linked lethal in Drosophila; demonstrates that male Drosophila do not have recombination

1913

A. H. Sturtevant

Experimentally demonstrates the linkage concept in Drosophila and produces the first genetic map

1914

C. B. Bridges

Demonstrates meiotic nondisjunction in Drosophila

1916

H. J. Muller

Discovers interference with recombination in Drosophila

1917

O. Winge

Discusses the importance of polyploidy in the evolution of angiosperms

1917

C. B. Bridges

Finds the first chromosome deficiency in Drosophila

1918

H. Spemann and H. Mangold

Demonstrate embryonic induction

1919

T. H. Morgan

Calls attention to the relationship between the haploid number of chromosomes and the number of linkage groups in Drosophila

1923

J. K. Santos, H. Kihara, T. Ono, and O. Winge

Demonstrate the XX–XY sex determination in certain dioecious plants: Santos for Elodea, Kihara and Ono for Rumex, and Winge for Humulus

1926

S. S. Chetverikov

Begins the genetic analysis of wild populations of Drosophila

1927

B. O. Dodge

Initiates genetic studies on Neurospora

1927

H. J. Muller

Demonstrates that mutations can be induced by x-rays

1928

L. J. Stadler

Demonstrates the dose–frequency curve is linear in artificially induced mutations

1928

F. Griffith

Discovers transformation in pneumococci

1929

C. D. Darlington

Suggests that chiasmata function to hold homologues together during metaphase I of meiosis

1930–32

R. A. Fisher, J. B. S. Haldane, and S. Wright

Develop the mathematical foundations for population genetics

1931

C. Stern

Provides the cytological proof of crossing over in Drosophila

1931

H. B. Creighton and B. McClintock

Independently of C. Stern, provide the cytological proof of crossing over in maize

1932

M. Knoll and E. Ruska

Make the prototype of the electron microscope

1933

T. S. Painter

Begins cytogenetic studies of Drosophila salivary gland chromosomes

1934

A. Følling

Discovers phenylketonuria, the first hereditary metabolic disorder associated with mental retardation

1934

H. Bauer

Suggests that the giant chromosomes found in the salivary gland cells of fly larvae are polytene

1935

J. B. S. Haldane

Calculates the spontaneous mutation frequency of a human gene

1935

C. B. Bridges

Publishes the first salivary gland chromosome maps for Drosophila

1937

Th. Dobzhansky

Publishes Genetics and the Origin of Species, a landmark in the study of evolutionary genetics

1939

E. L. Ellis and M. Delbrück

Invent the “one-step growth” method of experimenting with bacterial phages

1939

E. Knapp and H. Schreiber

Demonstrate the correspondence between the effectiveness of ultraviolet light in inducing mutation and the absorption spectrum of nucleic acid

1940

E. B. Ford

Defines genetic polymorphism

1941

G. W. Beadle and E. L. Tatum

Introduce the one gene–one enzyme hypothesis

1944

O. T. Avery, C. M. MacLeod, and M. McCarty

In describing the pneumococcus transforming principle, suggest that DNA and not protein is the hereditary material

1948

H. K. Mitchell and J. Lein

Demonstrate that in certain mutant strains of Neurospora tryptophan synthetase is missing: the first evidence for the one gene–one enzyme theory

1948

P. A. Gorer, S. Lyman, and G. D. Snell

Discover H2, the first major histocompatibility locus found in mice

1948

G. D. Snell

Formulates the laws of transplantation acceptance and rejection; introduces the term histocompatibility gene

1949

A. D. Hershey and R. Rotman

Demonstrate genetic recombination in bacteriophage

1950

B. McClintock

Proposes transposable elements in maize

1950

E. Chargaff

Demonstrates that the numbers of adenine and thymine groups are always equal and the numbers of cytosine and guanine groups are likewise equal in DNA

1951

Y. Chiba

Demonstrates the presence of DNA in chloroplasts

1952

W. Beermann

Suggests that the puffing patterns of polytene chromosomes reflect differential gene activities

1952

A. D. Hershey and M. Chase

Demonstrate that DNA is the genetic material in phages

1953

J. D. Watson and F. H. C. Crick

Propose the double-helix model for DNA

1953

A. Howard and S. R. Pelc

Demonstrate the cell cycle (G₁, S, and G₂ periods preceding mitosis)

1955

S. Benzer

Coins the terms cistron, recon, and muton while working out the fine structure map of the rII region of phage T₄

1956

H. B. D. Kettlewell

Studies industrial melanism in the pepper moth: the first well-documented change in gene frequency by natural selection

1956

F. Jacob and E. L. Wollman

Experimentally interrupt mating in E. coli and demonstrate DNA is inserted from the donor bacterium into the recipient

1956

J. H. Tjio and A. Levan

Demonstrate the diploid number of humans is 46

1956

M. J. Moses and D. Fawcett

Independently observe synaptonemal complexes

1957

V. M. Ingram

Demonstrates that sickle-cell and normal hemoglobin differ by one amino acid

1958

F. Jacob and E. L. Wollman

Demonstrate that the DNA of E. coli is circular and suggest that different linkage groups in Hfr strains result from different insertion points of a factor that ruptures the circular DNA

1958

F. H. C. Crick

Predicts the discovery of tRNA in suggesting that during protein formation the amino acid is carried to the template by an adapter molecule of nucleotides

1958

M. Meselson and F. W. Stahl

Demonstrate the semiconservative replication of DNA in E. coli

1959

S. Ochoa

Discovers the first RNA polymerase; with A. Kornberg receives Nobel Prize for work with the in vitro synthesis of nucleic acids

1959

E. Freese

Suggests that mutation can occur by changes in single base-pairs in DNA; uses the terms transition and transversion

1960

P. Doty, J. Marmur, J. Eigner, and C. Schildkraut

Demonstrate that separation and later recombining of complementary strands of DNA are possible

1961

F. Jacob and J. Monod

Propose the operon theory of gene regulation; also suggest the existence of mRNA

1961

S. Brenner, F. Jacob, and M. Meselson

Demonstrate the presence of mRNA with F. Gros, W. Gilbert, H. Hiatt, C. G. Kurland, and J. D. Watson

1961

M. F. Lyon and L. B. Russell

Independently find evidence suggesting deactivation of one of the X chromosomes in female mammals

1961

B. D. Hall and S. Spiegelman

Demonstrate a technique for producing hybrid molecules containing one strand of DNA and one of RNA that leads to the isolation and characterization of mRNAs

1961

F. H. C. Crick, L. Barnett, S. Brenner, and R. J. Watts-Tobin

Demonstrate that the genetic language is a three-letter code

1962

J. B. Gurdon

Demonstrates that the somatic and germinal nuclei are qualitatively alike; his experiment on frogs involved enucleating an egg and replacing the nucleus with an intestinal cell nucleus; normal fertile frogs develop from the modified egg

1963

E. Margoliash

Sequences cytochrome c polypeptides from a variety of organisms and produces the first phylogenetic tree utilizing a specific gene product

1963

L. B. Russell

Demonstrates that a piece of an autosomal chromosome translocated to an X chromosome would be deactivated with the X chromosome

1964

A. S. Sarabhai, A. O. W. Stretton, S. Brenner, and A. Bolle

Demonstrate colinearity of gene and protein product in the virus T₄

1964

C. Yanofsky, B. C. Carlton, J. R. Guest, D. R. Helinski, and U. Henning

Demonstrate the colinearity of gene and protein product (tryptophan synthetase) in the bacterium E. coli

1964

D. D. Brown and J. B. Gurdon

Illustrate the nucleolus is involved in the production of 18S and 28S rRNAs

1965

L. Hayflick

Discovers human diploid cells in tissue culture have about 50 doubling cycles

1965

R. W. Holley

Completely sequences alanine tRNA from yeast

1965

A. J. Clark and A. D. Margulies

Find bacteria mutants that are abnormally sensitive to UV light; this suggests enzyme systems for repairing damaged DNA

1966

H. G. Khorana and M. W. Nirenberg

Working independently complete the genetic code

1966

F. H. C. Crick

Proposes the wobble theory to explain the degeneracy pattern found in the genetic code

1966

M. Waring and R. J. Britten

Demonstrate the presence of repetitious nucleotide sequences (repetitive DNA) in vertebrates

1966

V. A. McKusick

Publishes a catalogue listing about 1,500 genetic disorders of Homo sapiens (Mendelian Inheritance in Man)

1966

R. C. Lewontin and J. L. Hubby

Use electrophoretic techniques to demonstrate heterozygosity of proteins in natural populations

1966

H. Harris

Uses electrophoretic techniques to demonstrate human enzyme polymorphisms

1967

K. Taylor, S. Hredecna, and W. Szybalski

Demonstrate genes on the same chromosome may have different orientations of transcription: one gene may be read 3′–5′ on one strand, another read 3′–5′ on the other strand of the double helix

1968

R. T. Okazaki

Reports that short lengths of DNA are synthesized during replication discontinuously; plieces are later spliced together (Okazaki fragments)

1968

H. O. Smith, K. W. Wilcox, and T. J. Kelley

Isolate the first restriction endonuclease (Hind II)

1968

S. Wright

Publishes the first of four volumes of Evolution and the Genetics of Populations

1968

E. H. Davidson, M. Crippa, and A. E. Mirsky

Demonstrate a long-lived form of mRNA is stored in the egg for use in early embryogenesis

1968

J. E. Cleaver

Demonstrates that xeroderma pigmentosum in humans is the result of a defective DNA repair mechanism

1969

C. Boon and R. Ruddle

Use somatic hybrid cell line containing human and mouse chromosomes to correlate the loss of human chromosomes with loss of phenotypic characters; this leads to the use of hybrid lines to assign specific loci to particular human chromosomes

1969

H. A. Lubs

Demonstrates a fragile site on the human X chromosome in some mentally retarded males

1970

T. Caspersson, L. Zech, and C. Johansson

Use quinacrine dyes to demonstrate specific fluorescent banding patterns in human chromosomes

1970

R. Sager and Z. Ramanis

Publish a genetic map of eight genes residing on the chloroplast chromosome of Chlamydomonas: the first non-Mendelian genetic map

1971

M. L. O’Riordan, J. A. Robinson, K. E. Buckton, and H. J. Evans

Discover that all 22 pairs of human autosomes are visually identifiable by staining with quinacrine hydrochloride

1972

G. H. Pigott and N. G. Carr

Hybridize DNA from cyanobacteria to the chloroplasts of Euglena gracilis; this genetic homology supports the theory that chloroplasts are descendants of endosymbiotic cyanobacteria

1972

J. Mendlewicz, J. L. Fleiss, and R. R. Fieve

Demonstrate a psychosis (manic-depression) is genetic and a dominant gene located on the short arm of the X chromosome is involved

1972

D. E. Kohne, J. A. Chisson, and B. H. Hoyer

Use DNA–DNA hybridization techniques to study the evolution of primates; conclude that the chimpanzee is closely related to humans

1972

P. Berg

Produces the first recombinant DNA in vitro

1973

H. Boyer and S. Cohen

Use a plasmid to clone DNA; this led to recombinant DNA techniques

1974

A. Tissieres, H. K. Mitchell, and U. M. Tracy

Discover six new proteins are synthesized in Drosophila when given heat shocks

1974

B. Ames

Develops a rapid method for detecting mutagenic compounds

1975

Asilomar meetings

Historic meeting where molecular biologists from all over the world meet to write rules to guide research in recombinant DNA; in the USA, the NIH Recombinant DNA Committee issues guidelines to minimize any potential risks of this research

1975

D. Pribnow

Determines the nucleotide sequences of two bacteriophage promoters; forms a model of promoter function

1975

E. M. Southern

Demonstrates a method for transfer of DNA fragments from an agarose gel to nitrocellulose filters

1975

G. Morata and P. A. Lawrence

Demonstrate a mutant (engrailed) whose normal function defines the boundary between wing compartments as the wing develops in Drosophila;normal cells recognize anterior versus posterior compartments

1976

B. G. Burrell, G. M. Air, and C. A. Hutchison

Report the presence of overlapping genes in the phage ϕX174

1976

Genentech

First genetic engineering company

1977

A. M. Maxam, W. Gilbert, and F. Sanger

Work out methods for nucleotide sequencing of DNA

1977

F. Sanger, et al.

Sequence the DNA genome of bacteriophage ϕX174

1977

W. Gilbert

Synthesizes insulin and interferon in bacteria

1977

P. Sharp, R. Roberts, et al.

Demonstrate introns in eukaryotic genes

1979

J. C. Avise, R. A. Lansman, and R. O. Shade

Using restriction endonucleases and mitochondrial DNA, measure the relationships of organisms in natural populations

1979

B. G. Barrell, A. T. Bankier, and J. Drouin

Discover that the genetic code of human mitochondria has some atypical characteristics

1979

D. V. Goeddel, et al.

Synthesize the human growth hormone gene

1980

U.S. Supreme Court

Rules that patents can be awarded for genetically modified microorganisms

1980

L. Olsson and H. S. Kaplan

Manufacture a pure antibody in a laboratory culture

1981

L. Margulis

Summarizes the evidence for the symbiosis theory for the origin of such organelles as mitochondria and chloroplasts, in Symbiosis in Cell Evolution

1981

J. D. Kemp and T. H. Hall

Transfer a gene from beans to sunflowers via a plasmid of the crown gall bacterium

1981

T. R. Cech, A. J. Zaug, and P. J. Grabowski

Demonstrate self-splicing in rRNA: first evidence of molecules other than proteins acting as biological catalysts

1981

S. Anderson, B. G. Barrell, F. Sanger, et al.

Completely sequence the human mitochondrial genome

1982

Eli Lilly International Co.

Market the first drug (human insulin) made by recombinant DNA techniques

1982

E. P. Reddy, R. K. Reynolds, E. Santos, and M. Barbacid

Report the genetic changes in a line of human bladder carcinoma cells that activate an oncogene

1984

W. McGinnis, C. P. Hart, W. J. Gehring, and F. H. Ruddle

Demonstrate that the homeobox of Drosophila is also found in mice, suggesting a developmental function for the homeobox

1985

K. Mullis

Develops the polymerase chain reaction (PCR) for amplifying small amounts of DNA; receives the Nobel Prize in 1993

1985

A. J. Jeffries, V. Wilson, and S. L. Thien

Devise DNA fingerprint techniques

1987

C. Nüsslein-Volhard, H. G. Frohnhüfer, and R. Lehmann

Demonstrate a small group of maternal effect genes determine the polarized pattern of development in Drosophila

1987

E. P. Hoffman, R. H. Brown, and L. M. Kunkel

Isolate the protein (dystrophin) produced by the muscular dystrophy gene

1987

D. C. Page et al.

By cloning a section of the human Y chromosome, discover a factor influencing testis differentiation and thus illuminate the mechanism of sex determination in humans

1987

R. L. Cann, M. Stoneking, and A. C. Wilson

Using mtDNA erect a genealogical tree tracing all human mtDNAs to a common African maternal ancestor

1987

S. Tonegawa

Awarded Nobel Prize for work on the genetic mechanisms that generate antibody diversity

1988

N. Wexler, M. Conneally, and J. Gusella

Associate Huntington disease with human chromosome 4

1988

P. Leder and T. Stewart

Develop a genetically altered animal (oncomice) patented by Harvard University: the first U.S. patent for genetically altered animals

1989

L-C. Tsui, et al.

Identify the cystic fibrosis gene and predict its product’s amino acid sequence

1989

J. M. Bishop and H. E. Varmus

Share Nobel Prize for studies of the cellular origin of retroviral oncogenes

1990

W. F. Anderson et al.

First to treat patients with gene therapy

1993

J. Hall and R. Stillman

Report producing genetically identical embryos from cells fertilized in vitro; although the initial cell was an abnormally fertilized egg, this experiment drew attention to the possibility of cloning humans

1993

R. J. Roberts and P. A. Sharp

Independently discovered split genes and jointly awarded the Nobel Prize

1995

E. B. Lewis, C. Nüsslein-Volhard, and E. F. Wieschaus

Awarded Nobel Prize for their research on genetic control of the embryo’s early development

1996

A. Goffeau et al.

Complete the nucleotide sequencing of yeast, Saccharomyces cerevisiae

1997

F. R. Blattner et al.

Sequence the genome of Escherichia coli

1997

I. Wilmut et al.

Successfully clone a mammal, “Dolly,” from an udder cell of a pregnant female sheep

1998

C. elegans Sequencing Consortium

Reports sequencing the first multicellular eukaryote, a nematode

1999

The Human Genome Project

The first human chromosome, 22, is sequenced, 33.5 million bp

2001

L. H. Hartwell, R. T. Hunt, and P. M. Nurse

Awarded the Nobel Prize for discovering the key regulators of the cell cycle

2002

S. Brenner, H. R. Horvitz, and J. E. Sulston

Share Nobel Prize for their work on the genetic regulation of organ development and on programmed cell death

2003

The Human Genome Project

Announces completion of the Human Genome Project; the sequence of approximately 20,000–25,000 genes comes to a total of about 3 billion bp

2006

A. Z. Fire and C. C. Mello

Share Nobel Prize for their work on RNA interference and gene silencing by double-stranded RNA