Paul Berg

Born 30th June, 1926 (Brooklyn, New York, United States)

Berg was the first to demonstrate the possibility of making recombinant DNA and helped pioneer guidelines to limit the potential harm posed by genetic engineering.

Connections Recombinant DNA

Photo credit: National Library of Medicine

Family Berg is the son of Russian Jewish immigrants who migrated to the United States from a small village near Minsk. Neither of his parents, Harry Berg and Sarah (nee Brodsky), had any formal schooling. His father was a clothing manufacturer. The eldest of three boys, Berg grew up in Sea Gate, a private gated community based on the far west end of Coney Island at the southwestern most tip of Brooklyn, New York. Sea Gate provided an ideal setting for growing up and Berg remembers the great freedom he and his friends had to explore. Berg was active in the local football club, and it was through this that he made many close friends. Early on in his childhood Berg developed a strong interest in science. This was in part awakened by his readings of the lives of medical scientists recounted in 'Arrowsmith' by Sinclair Lewis and 'Microbe Hunters' by Paul DeKruif. His interest in the area was reinforced by Sophie Wolfe, the person who supervised his school's science supply room and ran the after-school science club to encourage students to conduct their own experiments. In 1947 Berg married Mildred Levy whom he had met through a summer job during high school. A year later their son, John Alexander, was born.

Education Berg skipped a grade in elementary school and from the age of 14 to 17 he attended Abraham Lincoln High School, a public high school in Brooklyn. Following this, in 1943, he enrolled to study chemical engineering at New York City College, but decided not take up the place so that could instead join in the war effort. To this end he enlisted as a flyer for the navy. Too young to immediately join the navy, Berg then applied to do biochemistry at Penn State University which he started at the same time as doing some preliminary flight training for the navy. His studies were interrupted after a year when he was called up. This saw him initially serving on a submarine chaser that escorted shipping convoys in the Atlantic Ocean and the Caribbean Sea and then, following the Japanese surrender, helping to return naval ships in the Pacific to the United States. Berg returned to Penn State University in 1946 and completed his undergraduate degree within two years. In 1948 Berg went to Western Reserve University where he completed a doctorate under the supervision of Harland Wood in the department of biochemistry in 1952. During his doctoral research he was able to demonstrate how vitamin B-12 and folic acid enables animals to synthesise the amino acid methionine (previously assumed to be available only through diet).

Career In 1952 Berg took up a postdoctoral position with Hermann Kalckar at the Institute of Cytophysiology in Copenhagen, Denmark. During this time he and Wolfgang Joklik, another postdoctoral fellow, discovered a new enzyme that created nucleoside triphospates for nucleic acid assembly. The following year started work as a post-doctoral researcher in the laboratory of Arthur Kornberg at Washington University, St Louis, Missouri, where he remained for 6 years. It was here that he discovered another unknown class of biological compounds - acyl adenylates. In 1959 Berg moved with Kornberg to help set up a new department in biochemistry at Stanford University's Medical Center. This was to be the setting where he began to shift his focus away from classical biochemistry towards molecular biology and towards experimenting with mammalian cells. His particular interest was learning how genes act and proteins are made. In 1967 Berg took a sabbatical year in the laboratory of Renato Dulbecco experimenting with Polyoma, a murine virus, and SV40, a monkey virus, in mammalian cell culture. On his return to Stanford, Berg set about seeing whether mammalian viruses could pick up genes and transfer them to new cells in the same way that bacterial cells could. This he did with the help of David Jackson and Robert Symons. The original plan was to use the SV40 virus to transfer new genes into mammalian cells, but this proved impractical because it could only transport a limited amount of DNA and often altered the DNA it carried. Based on this Berg and his team set about genetically engineering a virus instead by splicing two DNA molecules, one from a tumour virus and one from a plasmid carrying genes from Escherichia coli bacteria. Within a short time they had achieved their goal, producing the first recombined DNA molecule. In addition to his laboratory work, Berg helped set up, with Arthur Kornberg, of DYAX, a biotechnology research institute, in 1980 and the Beckman Center for Molecular and Genetic Medicine at Stanford in 1985. The aim of the Beckman Center was to encourage multidisciplinary work and connect molecular biology researchers more closely with clinical researchers. Berg was its first director, serving from 1985 to 2000.

Achievements Berg is best known his development of techniques to splice and join DNA molecules which laid the foundation for the emergence of recombinant DNA technology which paved the way to the rise of the modern biotechnology industry. Berg is also held up as a role model for questioning the ethical implications of genetic engineering. He was pivotal to the organisation of the Asilomar Conference on Recombinant DNA in 1975, which gathered together a group of about 140 professionals to debate the potential hazards of the technology and draw up guidelines to regulate its use. In 1980 he was awarded, along with Walter Gilbert and Fred Sanger, the Nobel Prize in Chemistry. This was given in recognition for his 'fundamental studies of the biochemistry of nucleic acids, with particular reference to recombinant DNA.' The same year he was also awarded the Albert Lasker Award for Basic Medical research. In addition he received wards from amongst others the American Chemical Society's Eli Lilly Prize in biochemistry (1959); the V. D. Mattia Award of the Roche Institute of Molecular Biology (1972); and the National Medal of Science (1983).

Paul Berg: timeline of key events

Date Event People Places
May 21, 1873Hans Berger was born in Coburg, GermanyBergerCoburg, Germany
August 30, 1884Theodor H E Svedberg was born in Flerang, SwedenSvedbergUppsala University
April 29, 1888Michael Heidelberger was born in New York City, USAHeidelbergerNew York City
1907First successful blood transfusionOttenbergMount Sinai Hospital
January 10, 1916Sune K Bergstrom was born in Stockholm, SwedenBergstromKarolinska Institute
March 3, 1918Arthur Kornberg was born in Brooklyn NY, USAKornbergStanford University
December 18, 1922Esther Lederberg was born in Bronx, New York, USALederbergWisconsin University
May 23, 1925Joshua Lederberg was born in Montclair, NJ, USALederbergUniversity of Wisconsin
June 30, 1926Paul Berg was born in New York NY, USABergStanford University
April 10, 1927Marshall W Nirenberg was born in New York NY, USANirenbergNational Institutes of Health
1935 - 1936Antibodies shown to be proteinsHeidelberger, Kendall, KabatColumbia University
1939Antibodies start to be investigated using quantitative immunochemistrySvedberg, Tiselius, KabatUniversity of Uppsala
June 1, 1941Hans Berger diedBerger
April 24, 1947Roger D Kornberg, winner of the Nobel Prize for Chemistry in 2006 born in St. Louis MO, USAKornbergStanford University
November 2, 1953Michael Neuberger was born in London, United KingdomNeubergerLondon
December 1955First discovery of the enzyme DNA polymeraseKornberg, Bessman, Simms, LehmanWashington University in St. Louis
1956DNA polymerase discovered to replicate DNAKornberg Washington University in St. Louis
October 1957First synthesis of DNA in a test tubeKornbergWashington University in St. Louis
1958The cell is confirmed responsible for antibody productionLederberg, NossalUniversity of Wisconsin, Walter and Eliza Hall Institute
May 1961Coding mechanism for DNA discoveredNirenberg, MatthaeiNational Institute for Health
1968Paul Berg started experiments to generate recombinant DNA moleculesBergStanford University
1970Fluorescence activated cell sorter createdHerzenbergStanford University
1971First plasmid bacterial cloning vector constructedBerg, Mertz, JacksonStanford University
June 1971First time potential biohazards of recombinant DNA raisedMertz, Berg, PollackStanford University
October 1972First paper published on generating recombinant DNABerg, Jackson, SymonsStanford University
November 1972First easy-to-use technique published for constucting recombinant DNA. J. Mertz, R. Davis, Proceedings of the National Academy of Science, USA 69/11, pp. 2270-74.Berg, MertzStanford University Medical School
November 1, 1972Nature editorial voiced concern about generating recombinant DNABerg, Jackson, SymonsStanford University
July 1974First concerns about potential biohazards of recombinant DNA publishedBerg, Baltimore, Boyer, Cohen
1975Temporary moratorium on genetic engineeringBerg
1977Monoclonal antibodies developed for automatic fluorescence-activated cell sorter Milstein, Herzenberg, OiLaboratory of Molecular Biology, Stanford University Medical School, University of Toronto
June 1982Steven Rosenberg and colleagues first describe lymphokine-activated killer cellsGrimm, Mazumder, Zhang, RosenbergNational Cancer Institute
January 6, 1983Widespread loss of DNA methylation found on cytosine-guanine (CpG) islands in tumour samplesFeinberg, VogelsteinJohns Hopkins University
1984Experiments show that injections with T-cell growth factor interleukin-2 can shrink tumours in humansRosenbergNational Cancer Institute
1984First chimeric monoclonal antibodies developed which lays foundation for safer and more effective monoclonal antibody therapeuticsNeuberger, Rabbitts, Morrison, Oi, Herzenberg, Boulianne, Schulman, HozumiLaboratory of Molecular Biology, Stanford Univerity Medical School
December 1985IL-2 based immunotherapy shown to reduce tumours in patients with melanoma and renal cell cancerRosenbergNational Cancer Institute
May 1986First humanised monoclonal antibody createdDear, Foote, Jones, Neuberger, WinterLaboratory of Molecular Biology
December 1986Anti-tumour responses observed in 3 out of 10 patients given high-doses of Interleukin-2 (IL-2) Rosenberg, Lotze, Chang, Seipp, Simpson, VettoNational Cancer Institute
April 9, 1987Successful results reported for trial using the cytokine IL-2 and lymphokine-activated killer cells to treat cancerRosenbergNational Cancer Institute
1988Patent application filed for a method to create transgenic mice for the production of human antibodiesBruggeman, Caskey, Neuberger, Surani, Teale, Waldmann, WilliamsLaboratory of Molecular Biology, Babraham Institute, Cambridge University
November 1988Gene targeting technique shown to be efficient in modifying DNA in mammalian cells which can be adapted for other systems. This is the first time genome modification appears possible. Jasin, BergStanford University
December 22, 19889 out of 15 melanoma patients successfully treated with autologous tumor-infiltrating lymphocytes cultured with the cytokine IL-2RosenbergNational Cancer Institute
June 25, 1991Michael Heidelberger died in New York City, USAHeidelberger
1994First transgenic mice strains reported for producing human monoclonal antibodiesBruggemann, Green, Lonsberg, NeubergerCell Genesys, GenPharm, Laboratory of Molecular Biology
April 21, 1995First evidence published to demonstrate reduced DNA methylation contributes to formation of tumoursLaird, Jackson-Grusby, Fazeli, Dickinson, Jung, Li, Weinberg, JaenischMassachusetts Institute of Technology, Massachusetts General Hospital
1996 - 2002Experiments with rats conducted by different research teams around the world confirm olifactory ensheathing cells help repair spinal cordSmale, Li, Imaizumi, Guntinas-Lichius, Nash, RuitenbergQueen's University, University College London, Yale University, University of Cologne, University of the Health Sciences, Netherlands Institute for Brain Research
August 15, 2004Sune K Bergstrom diedBergstromKarolinska Institute
February 2005Enzyme Ubp10 demonstrated to protect the genome from potential destabilising molecular eventsBerger, EmreWistar Institute
November 11, 2006Esther Lederberg diedLederbergWisconsin University
November 15, 2006New enzyme identified as suppressor of p53 protein, a key molecule for controlling cancer in humansBergerWistar Institute, Vienna Biocenter
October 26, 2007Arthur Kornberg diedKornbergStanford University
February 2, 2008Joshua Lederberg diedLederbergUniversity of Wisconsin
January 15, 2010Marshall W Nirenberg diedNirenbergNational Institutes of Health
October 26, 2013Michael Neuberger died in CambridgeNeuberger
September 25, 2015New protein, Cpf1, found which could simplify genome editing. Zhang, Zetsche, Gootenberg, Abudayyeh, SlaymakerBroad Institute, Massachusetts Institute of Technology
April 15, 2016Gene editing used to prompt immune cells to combat cancerQuezada, Johnson, Menger, Sledzinska, Bergerhoff, Vargas, Smith, Poirot, Pule, Hererro, PeggsUniversity College London, Cancer Research UK, Cellectis
February 6, 2017Gene therapy shown to restore hearing in deaf miceLandegger, Pan, Askew, Wassmer, Gluck, Galvin, Taylor, Forge, Sankovic, Holt, VandenbergheEaton Peabody Laboratories, Harvard Medical School, Medical University of Vienna, UCL, Boston's Children's Hospital, Harvard Stem Cell Institute, University of North Carolina, Grousbeck Gene Therapy Center
April 13, 2017CRISPR shown to be sensitive diagnostic tool for detecting single target of DNA or RNA moleculeAbudayyeh, Bhattacharyya, Collins, Daringe, Donghia, Dy, Essletzbichler, Freije, Hung, Joung, Koonin, Lee, Livny, Myhrvold, Regev, Sabeti, Gootenberg, Verdine, ZhangBroad Institute, Massachusetts Institute of Technology, Harvard University, Howard Hughes Medical Institute

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