Brooklyn and a stockroom teacher
Paul Berg was born in Brooklyn, New York, on June 30, 1926, the eldest of three children of Harry Berg, a clothing manufacturer, and Sarah (Brodsky) Berg, a homemaker. Both parents were Jewish immigrants from Russia. He grew up in Sea Gate, a small gated community at the southern tip of Brooklyn, and by junior high school had decided to be a scientist after reading Sinclair Lewis’s Arrowsmith and Paul de Kruif’s Microbe Hunters.
At Abraham Lincoln High School, which would later also produce the Nobel laureates Arthur Kornberg, Jerome Karle and David Julius, his greatest influence was not a classroom teacher but Sophie Wolfe, who ran the science stockroom and started after-school science clubs. Rather than answer students’ questions, she encouraged them to find the answers themselves through small experiments or trips to the library. Looking back, Berg said that nurturing curiosity and the instinct to seek solutions were perhaps the most important things education can give, and that although he forgot many facts, he never lost the excitement of discovery.
Navy, Penn State and the chemistry of life
Berg graduated from high school in January 1943, a year after Pearl Harbor. He briefly studied chemical engineering at the City College of New York, then enlisted in the Navy hoping to fly. While waiting for flight training he began studying biochemistry at Pennsylvania State University; when the Navy cut pilot training he served instead on submarine chasers until the end of the war. He returned to Penn State and earned his degree in biochemistry in 1948. The year before, he had married Mildred Levy, whom he had met through a summer job in high school; their marriage lasted until her death in 2021, and they had one son, John.
He did his doctorate at Western Reserve University in Cleveland under Harland Wood, using newly available radioactive tracers to follow chemicals through living cells. He was among the first to show, in the test tube, how folic acid and vitamin B12 help the body make the amino acid methionine. He then trained with Herman Kalckar in Copenhagen, where he co-discovered a new enzyme, and with Arthur Kornberg at Washington University in St. Louis, where he discovered how cells activate fatty acids and amino acids before using them, work that helped explain the first steps of protein synthesis.
Building Stanford biochemistry
In 1959 Kornberg moved most of his department from St. Louis to the new Stanford University School of Medicine in Palo Alto, and Berg came with him. The group built a famously collaborative department, sharing space and equipment, and Berg chaired it from 1969 to 1974. He was an inspiring teacher who twice won the medical school’s Kaiser award for excellence in teaching; in 1971 his students even filmed an interpretive dance of protein synthesis based on his lectures, with Berg narrating.
By the mid-1960s his interests had shifted from bacteria to the cells of mammals. He spent a sabbatical year with Renato Dulbecco at the Salk Institute, learning to grow animal cells and to work with tumour viruses such as SV40, a monkey virus that can carry its small circle of DNA into cells. Back at Stanford he had an idea: if SV40 naturally carried its own genes into mammalian cells, perhaps it could be made to carry other genes too.
The first recombinant DNA
To test the idea, Berg and his colleagues needed a way to join two unrelated pieces of DNA. In 1971 and 1972, working with David Jackson and Robert Symons, they cut open the circular DNA of SV40 and a circle of DNA from the bacterial virus lambda carrying genes from the bacterium E. coli, including genes for digesting the sugar galactose. Using enzymes, they gave the cut ends matching sticky tails, mixed the pieces, and sealed them into new hybrid circles containing DNA from both sources. Their paper, published in the Proceedings of the National Academy of Sciences in 1972, described the first man-made recombinant DNA molecule.
It was the founding act of genetic engineering. Within a year Stanley Cohen and Herbert Boyer had developed a simpler way to splice and copy genes in bacteria, and the new technology spread rapidly. Recombinant DNA made it possible to isolate a single human gene, study it, and put it to work. The first fruit for patients was human insulin made by bacteria, approved in the United States in 1982, replacing insulin extracted from the pancreases of pigs and cattle. Today the same technology produces growth hormone, clotting factors for haemophilia, vaccines against hepatitis B, and the antibody drugs used against cancer and autoimmune disease, and it underpins genetic testing and has transformed agriculture.
Stopping to think
Berg did not rush ahead. Colleagues pointed out that his planned next step, putting DNA from SV40, a virus that causes tumours in some animals, into E. coli, a bacterium that lives in the human gut, might create an organism that could escape the laboratory and do harm. No one knew how real the risk was. Berg decided not to do the experiment.
As public fears grew of new plagues and environmental damage, Berg chaired a committee of the National Academy of Sciences, which in 1974 published a letter asking scientists everywhere to pause certain kinds of recombinant DNA experiments voluntarily until the risks could be assessed. It was a rare case of researchers restricting their own work before any government required it. In February 1975 Berg and Maxine Singer of the National Institutes of Health organised and chaired the Asilomar Conference on Recombinant DNA in Pacific Grove, California, attended by about 150 scientists along with lawyers, physicians and journalists. The meeting agreed that containment should match the estimated risk of each experiment, recommended weakened bacteria that could not survive outside the laboratory, and ruled out the most dangerous work. The NIH turned its recommendations into formal guidelines in 1976, and other countries followed. As experience showed the hazards to be smaller than feared, the rules were gradually relaxed. After Asilomar, Berg said, science moved forward gloriously.
Nobel Prize and after
In 1980 Berg received half of the Nobel Prize in Chemistry “for his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinant-DNA”; Walter Gilbert and Frederick Sanger shared the other half for methods of reading DNA sequences. He also received the Lasker Award that year and the National Medal of Science in 1983.
In 1980 he co-founded DNAX, a research institute that used recombinant DNA to study the immune system and became a leading immunology centre. Wanting to bring laboratory science closer to patients, he campaigned for and raised more than $50 million to build Stanford’s Beckman Center for Molecular and Genetic Medicine, which opened in 1989, and directed it until 2000. He helped create the Berg Scholars Program to train physician-scientists and was involved in designing Stanford’s research-focused Discovery Curriculum, launched in 2018. In 2004 he campaigned for California’s Proposition 71, which created a $3 billion state institute to fund stem cell research when federal support was restricted. With Maxine Singer he wrote books explaining genetics to general readers and a biography of the geneticist George Beadle.
Jewish roots
Berg was the son of Jewish immigrants from Russia and grew up in interwar Brooklyn; at Penn State he belonged to a Jewish fraternity. He spoke little in public about religion, and his own accounts of his youth centre on libraries, books and the stockroom teacher who taught him to think for himself.
His career followed a path familiar to many children of Jewish immigrants of his generation: the New York public schools, wartime service, the new opportunities of postwar American science, and a lifelong conviction that knowledge should be shared. He is listed among the Jewish Nobel laureates in chemistry.
Character
Colleagues described Berg as brilliant, demanding and generous. He always declined to patent his discoveries and shared results before publication, unusual in a competitive field. One colleague said he did not suffer fools but was always in service of a higher calling, whether raising money, pushing a scientific idea forward or recruiting talent. His son John remembered that he taught tolerance and encouraged students to pursue even unlikely ideas; he was never looking to be famous, John said, he just did what he loved.
He argued that scientists must take part in public debates about science and that research should be judged on its merits rather than by the politics of the moment. In 2004 he joined other Nobel laureates in criticising the misuse of science in government policy.
Legacy
Paul Berg died at his home on the Stanford campus on February 15, 2023, aged 96. His legacy is double. The technique he pioneered became genetic engineering, which has given the world medicines taken by millions of people, from insulin to cancer antibodies, along with new vaccines, diagnostics and crops. And at the moment of creating it, he showed how scientists can stop, weigh the risks of their own work in public, and agree on rules to make it safe.
Asilomar is still cited whenever a powerful new technology raises fears, from gene editing to artificial intelligence. Berg’s example, that the people who make a discovery share responsibility for its consequences, may prove as lasting as the discovery itself.
Sources & further reading
Paul Berg, Biographical, NobelPrize.org · Nobel laureate Paul Berg dies at 96, Stanford Medicine · The Paul Berg Papers: Biographical Overview, Profiles in Science, National Library of Medicine · Paul Berg, Science History Institute · Paul Berg, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
A life of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.