Paul Berg

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

Connections Recombinant DNA

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.

Paul Berg (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

Berger was a psychologist who developed the first electroencephalogram (EEG) for recording brain wave patterns.1873-05-21T00:00:00+0000A Swedish chemist, Svedberg invented the ultracentrifuge which he used to research colloids and proteins.1884-08-30T00:00:00+0000Together with Forrest Kendall and Elvin Kabat, Heidelberg was instrumental in determining antibodies to be proteins. 1888-04-29T00:00:00+0000Reuben Ottenberg carries out the first successful blood transfusion using blood typing and cross-matching based on the use of antisera. 1907-01-01T00:00:00+0000Bergstrom shared the 1982 Nobel Prize for Medicine for 'discoveries concerning prostaglandins and related biologically active substances.'1916-01-10T00:00:00+0000Kornberg shared the 1959 Nobel Prize for Medicine for the discovery of the 'mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid.'1918-03-03T00:00:00+0000Lederberg was a major pioneer of bacterial genetics. She discovered the lambda phage and invented the replica plating technique. 1922-12-18T00:00:00+0000Lederberg shared the 1958 Nobel Prize for Medicine for 'discoveries concerning genetic recombination and the organization of the genetic material of bacteria.'1925-05-23T00:00:00+0000Berg helped pioneer recombinant DNA and set up the Asimolar Conference which established guidelines for experiments using the technology.1926-06-30T00:00:00+0000Nirenberg shared the 1968 Nobel Prize for Medicine for interpreting the genetic code and its function of protein synthesis.1927-04-10T00:00:00+0000The American biomedical scientists Michael Heidelberger, Forrest Kendall and Elvin Kabat demonstrate antibodies to be proteins.1935-01-01T00:00:00+0000Swedish chemists Theodor Svedberg and Arne Tiselius and the American biomedical scientist Elvin Kabat start using new biochemical techniques, notably ultracentrifugation and electrophoresis, to investigate the structure of antibodies.1939-01-01T00:00:00+0000Berger was a German psychologist who developed the first electroencephalogram (EEG) for recording brain wave patterns.1941-06-01T00:00:00+0000Kornberg won the 2006 Nobel Prize for working out the protein pathway that a cell's genetic information takes when transferred to a new cell. 1947-04-24T00:00:00+0000A pioneer of antibody engineering, Neuberger developed some of the first techniques for the generation of chimeric and humanised antibodies. He also helped create the first transgenic mice for the production of human monoclonal antibodies. His work paved the way for the generation of safer and more effective monoclonal antibody drugs. 1953-11-02T00:00:00+0000The enzyme was discovered in Escherichia Coli. Its isolation paved the way to understanding how DNA is replicated, repaired and transcribed and the development of recombinant DNA. A collective group of scientists made the discovery: Arthur Kornberg, Maurice Bessman, Ernie Simms, I R Lehman.1955-12-01T00:00:00+0000Arthur Kornberg, American biochemist, discovers DNA polymerase, an enzyme that replicates DNA 1956-01-01T00:00:00+0000Achieved by Arthur Kornberg, the experiment was published in the Journal of Biological Chemsitry in May 1958.1957-10-01T00:00:00+0000The American molecular geneticist Joshua Lederberg and the Austrian-Australian biologist Gustav Nossal publish results from experiments confirming one cell is responsible for the production of just one type of antibody. This confirms the clonal selection theory. 1958-01-01T00:00:00+0000Marshall Nirenberg, American biochemist, and Heinrich Matthaei, German biochemist, discover the coding mechanism for DNA.1961-05-01T00:00:00+00001968-01-01T00:00:00+0000The American geneticist Leonard Herzenberg creates the flueorcence-activated cell sorter, or FACS, an invaluable tool for studying cell structure and function. Coupled later with monoclonal antibodies the FACS is today a vital not only for basic research but medical diagnosis. 1970-01-01T00:00:00+0000This was done in Dale Kaiser's laboratory by Douglas Berg together with Janet Mertz and David Jackson1971-01-01T00:00:00+0000Robert Pollack contacted Paul Berg to raise concerns about the potential biohazards of experiments his doctoral research plans to do involving the introduction of genes from the oncovirus SV40 in the human gut bacteria, E-Coli. Following this Berg self-imposed a moratorium on experiments in his laboratory involving the cloning of SV40 in E-Coli. 1971-06-01T00:00:00+0000D A Jackson, R H Symons, P Berg, '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', PNAS USA, 69/10 (1972), 2904-09.1972-10-01T00:00:00+0000Janet Mertz and Ronald Davis publish an easy-to-use technique for constructing recombinant DNA. 1972-11-01T00:00:00+0000This was prompted by the publication of the recombinant DNA experpiments published by Berg, Jackson and Symons1972-11-01T00:00:00+0000Berg, P, Baltimore, D, Boyer, J W, Cohen, S N, et al, 'Biohazards of Recombinant DNA,' Science, 185 (1974): 3034.1974-07-05T00:00:00+0000Asilomar Conference in California declares moratorium on genetic engineering research in order to have time to estimate the biohazard risks of recombinant DNA research and develop guidelines.1975-01-01T00:00:00+0000American geneticist and biochemist, Leonard Herzenberg and Argentinian biochemist, Cesar Milstein, devise monoclonal antibodies for use on an automatic fluorescence-activated cell sorter, FACS. This improves the reliability of the FACS allowing the instrument to go on to become a major tool not only for cell sorting and cellular biology but the diagnosis of disease. The work is done in collaboration with the American geneticist and immunologist Leonore Herzenberg and Vernon Oi, then a graduate student in genetics at Stanford University. 1977-01-01T00:00:00+0000EA Grimm, A Mazumder, HZ Zhang, SA Rosenberg, 'Lymphokine-activated killer cell phenomenon', Journal Experimental Medicine, 155 (1982), 1823-41.1982-06-01T00:00:00+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+0000SA Rosenberg, 'Adoptive immunotherapy of cancer: accomplishments and prospects', Cancer Treat Rep, 68/1 ( (1984): 233–55.1984-01-01T00:00:00+0000Two teams of scientists publish methods for the generation of chimeric monoclonal antibodies, that is antibodies possessing genes that are half-human and half mouse. Each team had developed their techniques separate from each other. The first team was lead by Michael Neuberger together with Terence Rabbitts and other colleagues at the Laboratory of Molecular Biology, Cambridge. The second team consisted of Sherie Morrison and colleagues at Stanford University together with Gabrielle Boulianne and others at the University of Toronto. 1984-12-01T00:00:00+0000SA Rosenberg et al, 'Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer', New England Journal of Medicine, 313 (1985), 1485-92.1985-12-05T00:00:00+0000Greg Winter together with other colleagues from the Laboratory Molecular Biology demonstrate the feasibility of building a new more human-like monoclonal antibody by grafting on to the humab antibody portions of a variable region from a mouse antibody. This reduced the mouse component of the monoclonal antibody to just 5%, making the monoclonal antibody safer and more effective for use in humans. The technique was published in PT Jones, PH Dear, J Foote, MS Neuberger, G Winter, 'Replacing the complementarity-determining regions in a mouse antibody with those from a mouse', Nature, 321 (29 May 1986), 522-5.1986-05-01T00:00:00+0000MT Lotze, AE Chang, CA Seipp, C Simpson, JT Vetto, AS Rosenberg, 'High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer', JAMA, 256 (1986), 3117-24. 1986-12-12T00:00:00+0000SA Rosenberg et al, 'A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone', New England Journal of Medicine, 9/316 (1987), 889-97. 1987-04-09T00:00:00+0000This patent is filed on the basis of work reported in M Brüggeman, HM Caskey, C Teale, H Waldmann, Williams, Surani, and MS Neuberger, A repertoire of monoclonal antibodies with human heavy chains from transgenic mice, Proc Natl Acad Sci USA, 86 (Sept 1989), 6709-13. 1988-01-01T00:00:00+0000Jasin, M, Berg, P, 'Homologous integration in mammalian cells without target gene selection', Genes Development, 2/11 (1988): 1353-63.1988-11-01T00:00:00+0000SA Rosenberg et al, 'Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report', New England Journal of Medicine, 319 (1988), 1676-80.1988-12-22T00:00:00+0000Study conducted by French Anderson in collaboration with Steven Rosenberg in 52 year old cancer patient as preliminary experiment to test gene therapy in children with severe combined immunodeficiency disorder. 1989-05-01T00:00:00+0000Together with Forrest Kendall and Elvin Kabat, Heidelberg was instrumental in determining antibodies to be proteins. 1991-06-25T00:00:00+0000Three groups of scientists separately report the successful generation of different strains of transgenic mice for the generation of human monoclonal antibodies. Two of the teams are based in biotechnology companies: GenPharm (led by Nils Lonsberg), Cell Gensys (led by Larry Green) , and the other involved a collaboration (led by Marian Bruggemann and Michael Neuberger) between scientists at the Laboratory of Molecular Biology, Braham Institute and the University of Cologne.1994-01-01T00:00:00+0000P.W. Laird, L. Jackson-Grusby, A. Fazeli, S. L. Dickinson, W. E. Jung, E. Li, R.A. Weinberg, R. Jaenisch, 'Suppression of intestinal neoplasia by DNA hypomethylation', Cell, 81 (1995),197-205, April 21, 1995,1995-04-21T00:00:00+0000Research conducted by KA Smale et al at Queen's University (Canada), Y. Li et al at University College London, T Imaizumi et al at Yale Univbersity School of Medicine, Guntinas-Lichius et al at the University of Cologne, H H Nash et al the Uniformed Services University of the Health Sciences, M J Ruitenberg et al at the Netherlands Institute for Brain Research.1996-01-01T00:00:00+0000Bergstrom shared the 1982 Nobel Prize for Medicine for 'discoveries concerning prostaglandins and related biologically active substances.'2004-08-15T00:00:00+0000Study conducted by team led by Shelley Berger published in Molecular Cell.2005-02-17T00:00:00+0000Lederberg was a major pioneer of bacterial genetics. She discovered the lambda phage and invented the replica plating technique. 2006-11-11T00:00:00+0000Research conducted by collaboration between Wistar Institute and Vienna Biocenter, published in 'Nature'.2006-11-15T00:00:00+0000Kornberg shared the 1959 Nobel Prize for Medicine for the discovery of the 'mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid.'2007-10-26T00:00:00+0000Lederberg shared the 1958 Nobel Prize for Medicine for 'discoveries concerning genetic recombination and the organization of the genetic material of bacteria.'2008-02-02T00:00:00+0000Nirenberg shared the 1968 Nobel Prize for Medicine for interpreting the genetic code and its function of protein synthesis.2010-01-15T00:00:00+0000A pioneer of antibody engineering, Neuberger developed some of the first techniques for the generation of chimeric and humanised antibodies. He also helped create the first transgenic mice for the production of human monoclonal antibodies. His work paved the way for the generation of safer and more effective monoclonal antibody drugs. 2013-10-26T00:00:00+0000The drug, a monoclonal antibody, was approved by the FDA for the treatment of patients with melanoma. 2014-12-22T00:00:00+0000B Zetsche, J Gootenberg, O Abudayyeh, I Slaymaker, et al, 'Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System', Cell (2015): 1-13.2015-09-25T00:00:00+0000UK scientists show how the TALENs gene editing tool can be used to switch on the immune system to stop cancer. L. Menger, et al, 'TALEN-Mediated Inactivation of PD-1 in Tumor-Reactive Lymphocytes Promotes Intratumoral T-cell Persistence and Rejection of Established Tumors', Cancer Research, 2016, doi: 10.1158/0008-5472.CAN-15-3352. 2016-04-15T00:00:00+0000LD Landegger et al, 'A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear', Nature Biotechnology, 6 Feb 2017, doi:10.1038/nbt.37812017-02-06T00:00:00+0000J. S. Gootenberg, O.O. Abudayyeh, J. W. Lee, et al, 'Nucleic acid detection with CRISPR-Cas13a/C2c2', Science, 13 April 2017, eaam9321, DOI: 10.1126/science.aam9321 2017-04-13T00:00:00+0000
Date Event People Places
21 May 1873Hans Berger was born in Coburg, GermanyBergerCoburg, Germany
30 Aug 1884Theodor H E Svedberg was born in Flerang, SwedenSvedbergUppsala University
29 Apr 1888Michael Heidelberger was born in New York City, USAHeidelbergerNew York City
1907First successful blood transfusionOttenbergMount Sinai Hospital
10 Jan 1916Sune K Bergstrom was born in Stockholm, SwedenBergstromKarolinska Institute
3 Mar 1918Arthur Kornberg was born in Brooklyn NY, USAKornbergStanford University
18 Dec 1922Esther Lederberg was born in Bronx, New York, USALederbergWisconsin University
23 May 1925Joshua Lederberg was born in Montclair, NJ, USALederbergUniversity of Wisconsin
30 Jun 1926Paul Berg was born in New York NY, USABergStanford University
10 Apr 1927Marshall W Nirenberg was born in New York NY, USANirenbergNational Institutes of Health
1935 - 1935Antibodies shown to be proteinsHeidelberger, Kendall, KabatColumbia University
1939Antibodies start to be investigated using quantitative immunochemistrySvedberg, Tiselius, KabatUniversity of Uppsala
1 Jun 1941Hans Berger diedBerger 
24 Apr 1947Roger D Kornberg, winner of the Nobel Prize for Chemistry in 2006 born in St. Louis MO, USAKornbergStanford University
2 Nov 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
1 Nov 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
6 Jan 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
9 Apr 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
22 Dec 19889 out of 15 melanoma patients successfully treated with autologous tumor-infiltrating lymphocytes cultured with the cytokine IL-2RosenbergNational Cancer Institute
May 1989First human test demonstrated safety of retroviral vector for gene therapy and potential of laboratory produced tumor killing cells for cancer immunotherapyAnderson, RosenbergNational Institutes of Health
25 Jun 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
21 Apr 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 - 1996Experiments 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
15 Aug 2004Sune K Bergstrom diedBergstromKarolinska Institute
February 2005Enzyme Ubp10 demonstrated to protect the genome from potential destabilising molecular eventsBerger, EmreWistar Institute
11 Nov 2006Esther Lederberg diedLederbergWisconsin University
15 Nov 2006New enzyme identified as suppressor of p53 protein, a key molecule for controlling cancer in humansBergerWistar Institute, Vienna Biocenter
26 Oct 2007Arthur Kornberg diedKornbergStanford University
2 Feb 2008Joshua Lederberg diedLederbergUniversity of Wisconsin
15 Jan 2010Marshall W Nirenberg diedNirenbergNational Institutes of Health
26 Oct 2013Michael Neuberger died in CambridgeNeuberger 
22 Dec 2014First immune checkpoint inhibitor drug targeting PD-1 (nivolumab, Opdivo®) approved in US Honko, Freeman, LonbergMedarex, Bristol-Myers Squibb, Ono Pharmaceutical
25 Sep 2015New protein, Cpf1, found which could simplify genome editing. Zhang, Zetsche, Gootenberg, Abudayyeh, SlaymakerBroad Institute, Massachusetts Institute of Technology
15 Apr 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
6 Feb 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
13 Apr 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

21 May 1873

Hans Berger was born in Coburg, Germany

30 Aug 1884

Theodor H E Svedberg was born in Flerang, Sweden

29 Apr 1888

Michael Heidelberger was born in New York City, USA

1907

First successful blood transfusion

10 Jan 1916

Sune K Bergstrom was born in Stockholm, Sweden

3 Mar 1918

Arthur Kornberg was born in Brooklyn NY, USA

18 Dec 1922

Esther Lederberg was born in Bronx, New York, USA

23 May 1925

Joshua Lederberg was born in Montclair, NJ, USA

30 Jun 1926

Paul Berg was born in New York NY, USA

10 Apr 1927

Marshall W Nirenberg was born in New York NY, USA

1935 - 1936

Antibodies shown to be proteins

1939

Antibodies start to be investigated using quantitative immunochemistry

1 Jun 1941

Hans Berger died

24 Apr 1947

Roger D Kornberg, winner of the Nobel Prize for Chemistry in 2006 born in St. Louis MO, USA

2 Nov 1953

Michael Neuberger was born in London, United Kingdom

Dec 1955

First discovery of the enzyme DNA polymerase

1956

DNA polymerase discovered to replicate DNA

Oct 1957

First synthesis of DNA in a test tube

1958

The cell is confirmed responsible for antibody production

May 1961

Coding mechanism for DNA discovered

1968

Paul Berg started experiments to generate recombinant DNA molecules

1970

Fluorescence activated cell sorter created

1971

First plasmid bacterial cloning vector constructed

Jun 1971

First time potential biohazards of recombinant DNA raised

Oct 1972

First paper published on generating recombinant DNA

Nov 1972

First 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.

1 Nov 1972

Nature editorial voiced concern about generating recombinant DNA

Jul 1974

First concerns about potential biohazards of recombinant DNA published

1975

Temporary moratorium on genetic engineering

1977

Monoclonal antibodies developed for automatic fluorescence-activated cell sorter

Jun 1982

Steven Rosenberg and colleagues first describe lymphokine-activated killer cells

6 Jan 1983

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

1984

Experiments show that injections with T-cell growth factor interleukin-2 can shrink tumours in humans

1984

First chimeric monoclonal antibodies developed which lays foundation for safer and more effective monoclonal antibody therapeutics

Dec 1985

IL-2 based immunotherapy shown to reduce tumours in patients with melanoma and renal cell cancer

May 1986

First humanised monoclonal antibody created

Dec 1986

Anti-tumour responses observed in 3 out of 10 patients given high-doses of Interleukin-2 (IL-2)

9 Apr 1987

Successful results reported for trial using the cytokine IL-2 and lymphokine-activated killer cells to treat cancer

1988

Patent application filed for a method to create transgenic mice for the production of human antibodies

Nov 1988

Gene 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.

22 Dec 1988

9 out of 15 melanoma patients successfully treated with autologous tumor-infiltrating lymphocytes cultured with the cytokine IL-2

May 1989

First human test demonstrated safety of retroviral vector for gene therapy and potential of laboratory produced tumor killing cells for cancer immunotherapy

25 Jun 1991

Michael Heidelberger died in New York City, USA

1994

First transgenic mice strains reported for producing human monoclonal antibodies

21 Apr 1995

First evidence published to demonstrate reduced DNA methylation contributes to formation of tumours

1996 - 2002

Experiments with rats conducted by different research teams around the world confirm olifactory ensheathing cells help repair spinal cord

15 Aug 2004

Sune K Bergstrom died

Feb 2005

Enzyme Ubp10 demonstrated to protect the genome from potential destabilising molecular events

11 Nov 2006

Esther Lederberg died

15 Nov 2006

New enzyme identified as suppressor of p53 protein, a key molecule for controlling cancer in humans

26 Oct 2007

Arthur Kornberg died

2 Feb 2008

Joshua Lederberg died

15 Jan 2010

Marshall W Nirenberg died

26 Oct 2013

Michael Neuberger died in Cambridge

22 Dec 2014

First immune checkpoint inhibitor drug targeting PD-1 (nivolumab, Opdivo®) approved in US

25 Sep 2015

New protein, Cpf1, found which could simplify genome editing.

15 Apr 2016

Gene editing used to prompt immune cells to combat cancer

6 Feb 2017

Gene therapy shown to restore hearing in deaf mice

13 Apr 2017

CRISPR shown to be sensitive diagnostic tool for detecting single target of DNA or RNA molecule