GNN - Genome News Network  
  Home | About | Topics
   
Introduction | Overview
2004 Rat
2002 Mouse
2001 30,000 Genes
2000 The Human Genome
1999 Fruit Fly
1998 Worm
1996 An Extremophile
1996 Yeast
1995 Haemophilus
1991 Venter
1986 Human Genome
1986 Hood
1983 Mullis
1978 Botstein
1977 Gilbert & Sanger
1973 Boyer & Cohen
1972 Berg
1970 Smith
1970 Temin & Baltimore
1969 Beckwith
1967 Weiss & Green
1961 Jacob & Monod
1961 Nirenberg
1960 mRNA
1957 Crick
1956 Kornberg
1953 Crick & Watson
1950 Chargaff
1944 Avery
1943 Delbruck & Luria
1941 Beadle & Tatum
1934 Bernal
1927 Muller
1913 Sturtevant
1910 Morgan
1909 Johannsen
1908 Garrod
1904 Bateson
1902 Boveri & Sutton
1900 Rediscover Mendel
1888 Boveri
1882 Flemming
1876 Galton
1869 Miescher
1866 Mendel
1859 Darwin


 Printer Friendly
Genetics and Genomics Timeline
1972
Paul Berg (1926-) creates first recombinant DNA molecules

Paul Berg assembled the first DNA molecules that combined genes from different organisms. Results of his experiments, published in 1972, represented crucial steps in the subsequent development of recombinant genetic engineering. By stepwise methods such as he devised, individual genes could be isolated and inserted into mammalian cells or into such rapidly growing organisms as bacteria. The genes themselves could then be studied, and their protein products expressed and even manufactured in quantity.


Paul Berg
The prospect of recombinant DNA emerged from a series of advances in biochemistry—most especially, from discoveries of new enzymes. Particularly important were the restriction enzymes that act as "scissors" to cut molecules of DNA at specific points. Similarly, ligases are enzymes that forge covalent bonds. The discovery of DNA ligase provided a kind of chemical soldering that could restore DNA after a foreign gene was spliced into it. These and other enzymes, captured from nature, could be used as tools in genetic engineering.

In creating hybrid DNA molecules, Berg employed the much-studied SV40 monkey virus and a bacterial virus known as the l (or lambda) bacteriophage. The SV40 virus has few genes, lacks a protein coat, and is is convenient to work with. The l bacteriophage normally invades a type of E. coli, where it replicates according to the nutritional environment. The DNA of both viruses takes the form of closed loops. Berg's original idea was to open the SV40 DNA, and splice into it genes snipped out of the bacteriophage. The virus could then replicate in cells, as in nature, and the products of the bacteriophage genes could also be expressed.

In Berg's cut-and-splice method he created, in the DNA of both viruses, what came to be known as "sticky ends." Restriction enzymes were first used to open the circular units of DNA of phage and virus. In separate operations, types of terminal transferase (another enzyme) were used to add complementary DNA bases (adenine and thymine) to the ends of the molecules. When both kinds of DNA were incubated together, the ends would anneal naturally. Addition of DNA ligase would seal the plasmid. In succeeding with a series of enzymatic reactions, Berg wrote that his methods "are general and offer an approach for covalently joining any two DNA molecules together."

Potential dangers of recombinant genetic engineering emerged even before Berg published his landmark paper. Although the SV40 virus was thought to be innocuous in humans, the prospect of an altered form of the virus spreading through such a common bacterial agent as E. coli caused Berg to defer part of his research program. He did not insert the recombinant virus into bacterial cells as he originally planned. (With bacterial and animal genes, Herbert Boyer and Stanley Cohen took this step shortly.) A professor at Stanford University, in 1974 Berg published a widely discussed letter on the potential dangers of recombinant DNA research. Subsequently, a moratorium on research in 1975 provided time for regulations to be devised and put into effect in 1976.

In 1980 Paul Berg shared the Nobel Prize in Chemistry with Walter Gilbert and Frederick Sanger, for "his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinant DNA."

Paul Berg winner of the
1980 Albert Lasker Award for Basic Medical Research

Jackson, D.A. et al. Biochemical method for inserting new genetic information into DNA of simian virus 40: Circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proc Nat Acad Sci USA 69, 2904-2909 (October 1972).

Back to GNN Home Page