Nobel winner Paul Berg, 96, was pioneer in gene splicing

Paul Berg, a Nobel laureate biochemist whose breakthrough in splicing DNA molecules helped place the foundations for the biotech industry, but who was once so concerned about possible risks from manipulating genes that he asked scientists to allow government oversight, died Feb. 15 at his home on the Stanford University campus in California. He was 96.

Stanford announced the death in a statement. No cause was given.

Berg’s question — as he and other scientists in the 1950s and ’60s learned more about the double-helix structure of DNA — was whether it was possible to transfer, from one organism to another, bits of genetic information. Success would give biologists and medical researchers an entirely new tool kit, once considered only the realm of science fiction stories about cloning.

In 1972, he gave the answer. Berg published a paper in a scientific journal that revealed he had mixed DNA from E. coli bacteria and a virus, SV40, linked to tumors in monkeys and transmissible to humans. An uproar followed.

Medical ethicists questioned whether Berg was toying with the natural order by creating what became known as recombinant DNA. Public health officials and others wondered if swapping DNA could create new plagues or unleash environmental catastrophes. “Is this the answer to Dr. Frankenstein’s dream?” later asked Alfred Vellucci, the mayor of Cambridge, Mass., home of Harvard University and the Massachusetts Institute of Technology.

Berg, too, had worries. He paused his experiments with SV40 and E. coli, uneasy over intersplicing the DNA of a disease-causing virus and a common intestinal bacteria.

A 1974 letter Berg signed with 10 colleagues, published in the journal Science, noted “serious concern that some of these artificial recombinant DNA molecules could prove biologically hazardous.” The letter called for an international meeting of the scientific community to “deal with the potential biohazards of recombinant DNA molecules.”

The gathering took place in a former chapel in Pacific Grove, Calif., in February 1975 with more than 140 scientists from around the world. They agreed to a general set of principles that included limits on the types of genes used and safeguards to keep recombinant DNA confined to laboratories. The guidelines reached at the Asilomar Conference Center were adopted in 1976 by the National Institutes of Health and similar oversight groups in other countries.

Many of the ground rules set by the conference have been revised or dropped as researchers developed greater understanding of genetics. Yet in hindsight, the worst-case thinking of the early years was merited, many researchers say.

“We had to be terribly cautious,” George Rathmann, the former chief executive of the biotech firm Amgen, said in 2005. “You can’t put these things back in a bottle.”

Other participants, however, described Berg and others as overstating the possible risks from the gene-splicing discoveries.

“It was a reflection of the Vietnam era and earlier history,” Waclaw Szybalski, then a professor and geneticist at the University of Wisconsin at Madison, told Science News in 1985. “Physicists were guilty of the atomic bomb, and chemists were guilty of napalm. Biologists were trying very hard to be guilty of something.”

Berg stood by his caution at the time. “I couldn’t say there was zero risk,” he recalled several years after being awarded the Nobel Prize in chemistry in 1980. He shared the prize with two other genetic researchers, Walter Gilbert and Frederick Sanger.

The Nobel Committee noted how Dr. Berg’s pioneering experiment in transplanting DNA molecules “has resulted in the development of a new technology, often called genetic engineering or gene manipulation.”

That also brought major commercial opportunities for what became the biotech industry, ranging from genetically modified crops to hundreds of drugs and therapies. The early products in the 1980s included vaccines for types of hepatitis and insulin. Previously, insulin from animals such as cattle and pigs were used in human treatment.

Recombinant DNA has been used in monoclonal antibodies that can be used as part of COVID treatment, and in the latest coronavirus vaccine, Novavax, which was given emergency approval by the U.S. Food and Drug Administration last year.

In gene therapy, researchers are exploring ways to use CRISPR-based technology — essentially genetic scissors that can insert, repair or edit genes — for conditions caused by genetic mutations such as cystic fibrosis, Duchenne muscular dystrophy and Huntington’s disease.

Berg did not patent his findings, allowing pharmaceutical companies and other researchers to advance his work.

“You did science,” he said, “because you loved it.”

Science club beginnings

Paul Berg was born June 30, 1926, in Brooklyn as one of three sons of a father who worked in clothing manufacturing and a mother who was a homemaker. In high school, his interest in research was first kindled by a woman named Sophie Wolfe, who ran the science club after classes, he recounted.

During World War II, he tried to enlist at 17 to become a Navy aviator but was turned down because of his age. He later did preliminary flight training while studying at Pennsylvania State University. He was called up during the war and served on ships in the Atlantic and Pacific. Berg graduated in 1948 from Penn State, and received his doctorate from Western Reserve University (now Case Western Reserve University) in 1952.

Berg did postdoctoral work in cancer research and was an assistant professor of microbiology at the Washington University School of Medicine from 1955 to 1959, when he accepted a position at Stanford’s medical school.

In the early 1980s he led a campaign that raised more than $50 million to build the Beckman Center for Molecular and Genetic Medicine, which opened in 1989. Berg served as director of the center until 2000.

In 2004, Berg was one of 20 Nobel laureates who signed an open letter asserting that the administration of President George W. Bush was blocking or distorting scientific evidence to support policy decisions. The letter cited omissions of climate change data or decisions to ignore scientific analysis that questioned White House claims over Iraq’s weapons capabilities before the U.S.-led invasion in 2003.

Berg married Mildred Levy in 1947; she died in 2021. Survivors include a son, John.

Berg gave another contribution to molecular biology: the lingo. A recurring joke in research circles refers to the moment of the gene-splicing discovery. Anything before that is “B.C.,” before cloning.