Paul Berg, a Nobel Prize-winning biochemist who ushered in the era of genetic engineering in 1971 by successfully combining DNA from two different organisms, died on Wednesday at his home on the Stanford University campus in California. He was 96.
His death was announced by the Stanford School of Medicine.
After his breakthrough with DNA, Dr. Berg led a momentous convocation of scientists to establish safeguards against the misuse of genetic research.
In 1971, he was already a well-known researcher at Stanford University when he oversaw the artificial introduction of DNA from one virus into another, creating the first recombinant DNA, or rDNA. The achievement was the first link in the chain of advances that has led to the genetic engineering of new therapeutic treatments for diseases and of vaccines, like the messenger RNA versions used to counter the virus that causes Covid-19.
Dr. Berg’s work earned him the 1980 Nobel Prize in Chemistry, which he shared with Walter Gilbert and Frederick Sanger, who were cited for their work on genetic sequencing. In remarks at a Nobel banquet, Dr. Berg said that through his research he had “experienced the indescribable exhilaration, the ultimate high, that accompanies discovery, the breaking of new ground, the entering into areas where man had not been before.”
Often described as the blueprint for every cell, DNA, or deoxyribonucleic acid, is the spiral-staircase-shaped strand of molecules that carry the code by which cells duplicate themselves. Dr. Berg showed that the blueprint could be altered and cells made to produce new offspring that could ultimately do — or not do — very different things from the original cells.
As David A. Jackson, a postdoctoral fellow who was one of Dr. Berg’s trainees, later recalled to Dr. Berg’s biographer, Errol C. Friedberg: “One morning Paul and I got together and he suggested that we attempt to put new genes into SV40 DNA and use the recombinant molecules to introduce foreign DNA into animal cells.”
The researchers used the DNA part of a virus (a circular DNA), which can be propagated in the E. coli bacteria, and incorporated it into a simian virus (a circular SV40 DNA genome). Each of the circular DNAs was converted into linear DNAs with an enzyme. Using an existing technique, these linear DNAs were modified so that the modified ends attracted each other. Mixed together, the two DNAs recombined and created a loop of rDNA, which contained the genes from the two different organisms.
Dr. Berg and his team began preparing for the next step: introducing the rDNA into E. coli and animal cells. But as word about his work spread among researchers, Dr. Berg was challenged to guarantee that this newly created DNA — which, after all, consisted partly of material from a virus that lived in one of the world’s most common bacteria, E. coli — could not escape the laboratory and cause incalculable harm.
Dr. Berg recognized that such an absolute certainty was not then possible, and he halted further experiments, although other researchers quickly moved forward.
Dr. Berg used the break in his experiments to focus on the larger ethical and public health issues raised by the manipulation of genes, including human genes. As a public figure who had testified before Congress in favor of federal funding for basic scientific research, and who had a wide range of contacts among biochemists, he was well positioned to help organize a conference at Asilomar, Calif., in February 1975.
About 150 leading DNA researchers from the United States and 12 other countries — including James Watson, a co-discoverer of the double-helix structure of DNA — discussed and then subscribed to rules to govern their own work. The conference was historic: Never before had scientists gathered to write regulations for their own research.
The eventual recommendations were deemed voluntary and drew a few dissents, including from Dr. Watson, but they were adopted by government regulators. In 2017, the event was the template for another Asilomar convention on a technology many consider equally fraught: artificial intelligence.
Dr. Berg’s early concerns were highlighted four decades after his experiment when a Chinese scientist claimed in 2018 that he had created the world’s first genetically edited babies. Dr. Berg joined 17 other leading microbiologists in condemning the work and calling for a five-year moratorium on the clinical use of technologies for the editing of heritable genes.
Paul Berg was born June 30, 1926, in Brooklyn, a son of Harry and Sarah (Brodsky) Bergsaltz, immigrants from Russia. His father was a furrier.
Paul attended Abraham Lincoln High School, in Coney Island, where he developed his interest in science.
After serving as an ensign in the Navy during World War II, Dr. Berg graduated from Pennsylvania State University in 1948. He received a doctorate in biochemistry from Western Reserve University (now Case Western Reserve University) in Cleveland in 1952, then did postdoctoral work at the Institute of Cytophysiology in Copenhagen and at Washington University in St. Louis. He joined the university faculty in 1955.
Dr. Berg, an expert in enzymes, was recruited to Washington University in 1953 by another future Nobel laureate, Arthur Kornberg (also a Lincoln High School alumnus). In 1959, Dr. Kornberg, who that year received the Nobel Prize in Physiology or Medicine, moved to Stanford University to set up a new biochemistry department and brought along his Washington University team, including Dr. Berg.
As he became increasingly well known for his basic research, some of it funded by the American Cancer Society, Dr. Berg often received letters from the parents of children with cancer, and despite a crowded schedule, he would respond with personal replies of encouragement.
Along with the 1980 Nobel, Dr. Berg was also a recipient of the Eli Lilly Award in Biological Chemistry in 1959, the Albert Lasker Basic Medical Research Award in 1980 and the National Medal of Science in 1983. He was the author, with the molecular biologist Maxine Singer (another organizer of the Asilomar Conference), of “Genes and Genome” (1991); “Dealing With Genes: The Language of Heredity” (1992); and “George Beadle: An Uncommon Farmer” (2003).
He married Mildred Levy in 1947. She died in 2021. He is survived by a brother, Jack, and a son, John.
In later years Dr. Berg would hark back to his student days at Abraham Lincoln High School in Brooklyn in tracing his path to a life in science. He credited in particular the keeper of the school science department’s supply room, a woman named Sophie Wolfe.
“Her love of young people and interest in science led her to start an after school program of science clubs,” Dr. Berg wrote in an autobiographical sketch for the Nobel committee. “Rather than answering questions we asked, she encouraged us to seek solutions for ourselves, which most often turned into mini research projects. Sometimes that involved experiments in the small lab she kept, but sometimes it meant going to the library to find the answers.
“The satisfaction derived from solving a problem with an experiment was a very heady experience, almost addicting,” he continued. “Looking back, I realize that nurturing curiosity and the instinct to seek solutions are perhaps the most important contributions education can make. With time, many of the facts I learned were forgotten, but I never lost the excitement of discovery.”