Nobel Prize winner and recombinant DNA pioneer Paul Berg dies

Paul Berg, PhD, an emeritus professor of biochemistry who won the 1980 Nobel Prize in chemistry, died Feb. 15 at his home on the Stanford University campus, surrounded by loved ones. He was 96.

Berg, the Robert W. and Vivian K. Cahill Professor of Cancer Research Emeritus, shared the prize for creating the first recombinant DNA molecule by combining DNA from two different organisms. That work set in motion the field of genetic engineering, which has led to lifesaving drugs and opened new avenues of genetic research.

“I cannot overstate Paul’s brilliance, compassion and enthusiasm for discovery,” said Lloyd Minor, MD, dean of the Stanford School of Medicine. “The joy of discovery motivated Paul throughout his career, and he generously gave his time to instill that joy in countless many. His death is a huge loss for the scientific community, Stanford Medicine and the fortunate among us who called him a colleague and friend.”

Berg authored a 1972 paper in the Proceedings of the National Academy of Sciences in which he revealed that he had inserted DNA from one organism — in this case, the bacterium E. coli — into the DNA of another. As his test case, Berg and his colleagues inserted three genes involved in glucose metabolism into the genome of the animal virus SV40. That accomplishment eventually earned him the Nobel Prize.

The work set off a political and public firestorm. Soon after he first combined DNA from two different organisms, Berg faced public fears that inserting the genes of one organism into the DNA of another would lead to the creation of new plagues, alter how organisms evolve or wreak environmental havoc.

In response to the outcry, Berg led the call for a pre-emptive, voluntary moratorium on genetic engineering research, which gave him time to organize the now famous 1975 Asilomar conference on recombinant DNA. At the conference, the researchers hammered out guidelines that allowed experimentation to proceed under federal oversight. Those guidelines were subsequently promulgated by the National Institutes of Health and adopted by similar bodies in other countries.

Brooklyn beginnings

Berg was born June 30, 1926, in Brooklyn, New York, the son of Jewish Russian immigrants. He earned his bachelor’s degree in biochemistry from Pennsylvania State University in 1948 and his doctorate from Western Reserve University in 1952.

After a two-year postdoctoral fellowship at the American Cancer Society, he moved to the Washington University School of Medicine, where he was a professor from 1955 to 1959.

Berg arrived at the Stanford School of Medicine in 1959, when the school was moving from San Francisco to the Palo Alto campus and establishing itself as a leading research institution. He helped create the new biochemistry department along with another future Nobel laureate, Arthur Kornberg, MD, and five other colleagues from Washington University. The group built a collaborative culture in the fledgling department.

“Paul’s legendary research contributions and leadership changed the trajectory of biomedical research. His boundless curiosity, enthusiasm for science, visionary thinking, and deep interest in and support of trainees set the joyful esprit de corps that has permeated the department for decades. It spurred the impactful science and careers of our thousand trainees and colleagues, including me,” said Mark Krasnow, MD, PhD, the Paul and Mildred Berg Professor of biochemistry.

Berg was committed to sharing research space and scientific findings, his colleagues said. He always declined to patent his findings and shared information in advance of publication, a rarity in an often-secretive field. Berg called himself a purist when it came to science, saying that in his formative years, “You did science because you loved it.”

In a 2005 interview with Medical Center Report, Berg said that although public policy work doesn’t afford “the headiness of a good scientific experiment,” it does bring its own satisfaction. After the Asilomar conference, he said, “science moved forward gloriously.”

Advocate for science

Berg continued to pursue research interests as well as advocate for scientific freedom. He spoke out about government regulations limiting funding for stem cell research, and in 2004 he promoted California Proposition 71, which created the California Institute of Regenerative Medicine. The agency, initiated with $3 billion, is a major funder of stem cell research in California and is a model for funding stem cell research in other states.

“Paul always wanted scientists to be responsible for what they do, and he wanted science to be evaluated on the basis of the success of the science, not the politics of the moment,” said Irv Weissman, MD, the Virginia and D.K. Ludwig Professor in Clinical Investigation in Cancer Research. “Paul was by far the most influential in explaining to people why, if they wanted discoveries for the diseases they have, you need to be able to do the research.”

Berg advocated for scientists to become more engaged in debating the role of science in society. He argued that the freedom to pursue research, unfettered by government restrictions, falls under the first amendment right to free speech. As part of his effort to separate science from politics, Berg was one of 20 Nobel laureates who signed a 2004 open letter accusing the Bush administration of citing bad science to support policy decisions.

Building Stanford Medicine

Berg served as chair of the Department of Biochemistry from 1969 to 1974. In the early 1980s he began a campaign to build the Beckman Center for Molecular and Genetic Medicine. He raised more than $50 million for the building, which opened in 1989, and he served as director of the center until 2000, when he became emeritus.

“Paul didn’t suffer fools,” said Christopher Scott, PhD, research staff emeritus of biomedical ethics who worked under Berg when he was the director of the Beckman center. Scott is now at the Baylor College of Medicine. “He could be a real tough guy, but he was always in service of a higher calling, whether it be fundraising, pushing a scientific idea forward or recruiting some of the best talent the world had to offer to Stanford.”

Berg raised $4 million for the Li Ka Shing Center for Learning and Knowledge, which he said would rejuvenate the campus. The main auditorium on the second floor in the building is named for Berg and his wife, Millie, who died in 2021.

In 1971 Berg’s students filmed an interpretive dance of protein synthesis based on his lectures. He twice won the Henry J. Kaiser Award for Excellence in Teaching at the Stanford School of Medicine.

“There has arguably not been a faculty member in Stanford Medicine’s long history who was more dedicated to developing student researchers,” said PJ Utz, MD, a professor of immunology and rheumatology. “It did not matter to Paul whether medical students generated new knowledge in the basic, translational, clinical, physical or social sciences: Research and advancing medicine are what mattered to Paul.”

Utz helped Berg establish the Berg Scholars Program, which trains physician-scientists through a master’s program in biomedical investigation that complements a medical degree.

Berg was also instrumental in designing the Discovery Curriculum, launched in 2018, which provides students access to new courses and financial incentives to pursue long-term research. He delivered the commencement address that same year, touching on the joy of discovery and students’ role in the future of biomedicine.

Pursuing passions

Berg’s open mind kept him connected to his students, said his son, John Berg. If students came up with ideas that at first sounded unsubstantiated, he would ask them to explore further, helping them gain independence as a scientist. If there was a creative spark, he knew they would succeed.

“He taught me how to be a better person, taught me tolerance and always encouraged me to pursue the things I was passionate about,” said John Berg.

It could be intimidating to have a dad who was invited to the White House or had met the king of Sweden, he said, but his dad was always humble.

“He didn’t think twice about sounding the alarm and getting people to look at what we are doing rather than just plunge ahead for the glory — he was never looking to be famous, he was never looking to win the Nobel Prize; he just did what he did because he loved it,” John Berg said.

Paul Berg had memberships in the National Academy of Science, the American Academy of Arts and Sciences, the Royal Society of London, the American Philosophical Society, and the French Academy of Sciences. He earned the National Medal of Science; the AAAS Scientific Freedom and Responsibility Award; and honorary doctors of science from Washington University in St. Louis, Oregon State University and Pennsylvania State University.

Read more:

An interview with Berg
Berg’s support of Stanford Medicine
How Berg handled an early career mix-up
The protein synthesis dance

Julie Greicius contributed to the story.