Over the course of a nearly two-hour conversation about his life and career, as a breeze flutters through the trees on the Stanford University campus outside, those words linger like an unspoken Zen koan. Berg ’48 Agr, ’95h Sci, who turned 93 last June, is as intellectually spry as ever, able to break down complex ideas into simple concepts in the Brooklyn accent that lingers from his childhood. He’s spent the past six decades at Stanford, where he’s established himself as one of the most accomplished biochemists in the world; he also happens to be the only Penn State alumnus with a Nobel Prize on his résumé. In 1980, his work on recombinant DNA—essentially genetic material formed in a lab—earned him the Nobel Prize in Chemistry. (Officially, Berg was granted half the prize, while Walter Gilbert and Frederick Sanger shared the other half.) By then, he was already a towering presence in his field, and one of the most prominent voices guiding the future of genetic engineering.

And while it’s hard to argue that a Nobel Prize isn’t the defining moment of a scientist’s career, Berg’s legacy actually extends far beyond his work in the laboratory. As deeply as he was involved in spurring a future marked by an increased understanding of the building blocks of the human genome, he was also one of the first to acknowledge the potential hazards of what was then a burgeoning new frontier. In the 1970s, as anxiety over the future of genetic engineering grew—as science fiction brought us visions of genetically engineered superviruses and designer babies infused with desirable genetic traits—Berg helped lead a movement to regulate these ideas before they got out of hand. It became his job, almost by proxy, to aid his fellow scientists in helping to subsume their egos and acknowledge their limits.

By pausing his own research in the face of such questions, Berg helped spur discussion of the larger existential concerns about the manipulation of DNA: How much is too much? And as genetic research continues to probe new frontiers that are both thrilling and daunting—including the well-publicized story of a Chinese scientist who used advanced technology to alter the genetic codes of two human embryos—Berg still feels that obligation to monitor the pace of progress.

Of he and like-minded peers, Berg says, “What we did was about establishing trust between scientists and the public. We were saying to the public, ‘We’ve done things. It’s incredibly important. But let’s go slow.’ We weren’t sure at the time, but in retrospect, everybody thinks it was an extremely ethical and courageous thing to do.”

To get a sense of how far the science surrounding the human genome has come over the course of Berg’s lifetime, all you have to do is flash back to the 1940s, when Berg, the 16-year-old son of a furrier, graduated from Abraham Lincoln High School in Brooklyn’s Coney Island neighborhood. He didn’t really want to study chemistry in college; he also wasn’t sure he wanted to study biology. That’s when a friend told him about this college in central Pennsylvania that offered a degree in a relatively new field known as biochemistry.

It was the first Berg had heard of that discipline, and it was the first time Berg thought about attending Penn State. He’d already decided to join the Navy after the bombing of Pearl Harbor, and enlisted when he was 17, after only a couple of months on the University Park campus in 1943. He returned to Penn State after serving on a submarine during the war, and finished his degree in 1948 while his wife, Millie, worked as a nurse. By then, Berg realized that Penn State’s program was mostly targeted toward students seeking a career in the agriculture and food industries. Wanting to delve deeper into academic research, he wound up at Case Western Reserve University in Cleveland, and then at Washington University in St. Louis, where he worked for renowned biochemist Arthur Kornberg.

It was in St. Louis that Berg had his first major breakthrough. He decided to delve into research done by a pair of Nobel-winning biochemists, and in so doing, wound up disproving their proposed model and discovering an important new reaction related to the synthesis of an enzyme involved in human metabolism. That work set Berg on the path to becoming a star in his field, and eventually earned him, at the age of 40, an appointment to the prestigious National Academy of Sciences. That he had the confidence to challenge the assertions of established researchers also served as a display of the kind of inherent self-assuredness that has defined Berg since childhood.

Even now, Berg admits that he’s prouder of the work he did in St. Louis than the work he did that later won him the Nobel, in part because the work on recombinant DNA felt as if it would inevitably be solved by someone—and because the Nobel-winning lab work was largely performed by graduate and postdoctoral students studying under Berg. But in St. Louis, Berg says, “I did all the experiments myself. And when it was possible to show that these two guys had screwed up, and that I had solved the problem and discovered something totally new—to me, that was the most exciting reward.”

Berg eventually altered the focus of his studies, turning toward a burgeoning field of research on DNA that had been spurred, among other things, by James Watson and Francis Crick’s high-profile discovery of the double-helix shape of DNA in the 1950s. When Kornberg left St. Louis for Stanford to start a biochemistry program in 1959, Berg went with him, and began researching the possibility of “joining” genes from different organisms in order to create entirely new strands of DNA that could be studied in the lab. In order to do this, Berg turned to SV40, a virus found in monkeys that was easily manipulated; eventually, he found he could combine SV40 with a portion of DNA from a bacterial virus by creating “sticky ends” that allowed them to adhere to each other—in the process creating the first “chimeric,” or mixed-species, recombinant DNA.

But here is where an ethical quandary first arose. One of Berg’s students went to the East Coast to describe the experiments to some colleagues. The student was met with outrage and concern: There were fears that SV40 could cause cancer, and by combining it with bacteria, worries arose that it could be transmitted out of the lab and into the general population. This was in the early 1970s; in 1969, Michael Crichton had published The Andromeda Strain, a novel about the outbreak of a deadly extraterrestrial virus.

At first, Berg viewed the controversy as utter bunk, an example of the irrational fears of a general public that too often was quick to distrust scientific methods and instead embrace the dystopian visions of science fiction. He initially resisted the calls for restrictions on his research. But then he spent six months speaking to experts—researchers who had been working on tumor viruses—and slowly, his mind began to change. “They more or less would have argued that it’s almost impossible to contain them in a lab,” Berg says. “The charge was, ‘You’re going to spread cancer to the human population.’ I thought it was ridiculous, because we had ways to contain that, but I couldn’t prove to myself that I could say with zero probability that nothing would happen.”

Berg agreed to halt his experiments. It was the first time, he says, that the nation expressed real fears about the consequences of genetic engineering on the human population. And the question Berg and his colleagues had to face was, What could be done about it? How do you encourage the advancement of these monumental leaps in scientific understanding while still enforcing an overarching code of ethics?

The answers would come several years later, at a picturesque conference center called Asilomar in Monterey, Calif., a short walk from the Pacific Ocean. Here, Berg found himself thrust into a role refereeing one of the most consequential scientific gatherings in modern history.

February 1975: After a series of back-and-forths, of carefully worded letters written to scientific journals, and occasionally hyperbolic public discussion about the appropriate path for the future of DNA research, a handful of scientists had recommended a voluntary and temporary moratorium on certain types of experiments until a consensus could be reached. The scientists agreed that a conference should be convened, and Berg was appointed its leader. He chose to hold it at Asilomar, not far from the Stanford campus. Roughly 150 scientists from around the world flew to California and spent several days engaged in a spirited and often contentious debate. One writer would later call it “the Woodstock of molecular biology.”

How much risk was too much? Luminaries like James Watson insisted at Asilomar that the fears were overblown, and that restricting science would only make things worse. Some, Berg recalls, accused others of engaging in precarious research rather than casting a critical eye on themselves. But after several days of discussions, a breakthrough came when legal experts were asked to testify about the consequences of an experiment gone wrong. “They brought up the idea of, ‘What if you’re doing experiments that are identified as potentially dangerous, and something bad happens?’” Berg says. “‘Then Congress would come in and impose. And you guys will be sued.’ So everyone began to feel we had to do something.”

Berg and several others stayed up all night on the last evening of the conference in order to draft a statement. In it, they agreed to lift the moratorium on certain experiments, but suggested strict guidelines on how those experiments should be conducted. Fail to follow those guidelines, and you’d lose the money granted to you by organizations like the National Institutes of Health.

“In short order, these recommendations became the basis for rules adopted around the world,” wrote Alex Capron, one of the legal experts who testified at Asilomar, in a 2015 New York Times op-ed. “‘Asilomar’ came to be shorthand for the social responsibility of science.”

And that, Berg says, is a level of impact he could never have anticipated.

“It’s interesting that Asilomar has now become a paradigm which is almost implanted in the consciousness of research,” he says. “We felt like a bunch of amateurs at the time. We bungled things. But we built some sort of edifice.”

Berg never envisioned, early in his career, that he’d become so enmeshed in the public policy surrounding science itself. But in the years before and after Asilomar, he became a prominent voice, consulting with experts in other fields as they sought ways to confront their own ethical issues without blocking the path to advancement. In the mid-2000s, he advocated strongly against a ban on embryonic stem-cell research. And in early 2019, he signed on to a letter that advocated a global moratorium on genetically engineered humans in the wake of a Chinese scientist’s use of what’s known as CRISPR technology to modify the genes of a pair of twin embryos.

There are, of course, tremendous possibilities inherent to CRISPR technology itself, particularly for curing disease. The problem, Berg says, is that the Chinese scientist took it a step further: By editing genes in the “germline” of those children, those genetic modifications will be passed on to the next generation, rather than be limited to a single person. And that step introduced the kinds of risks that feel, to Berg, as if they’re still far beyond modern science’s understanding. What are the potential cascading effects of altering such genes over the course of generations? What are the unintended impacts? Could it actually introduce new types of disease, or introduce new and frightening complications?

“We don’t really know,” Berg says. “Let’s not be arrogant about this and say, ‘We think that this is a good thing to do.’ Clinical trials and things like that should be part of this. But we should be very cautious about proceeding.”

This is the challenge in creating a code of scientific ethics: If it’s too restrictive, it can impede progress itself. Nearly any technology or scientific advancement in human history carried the potential to be perverted for dark purposes, Berg says, as those two words—TOO MUCH—linger in the background. But often, the benefits of progress outweigh the harm. It’s a matter of balancing research and responsibility.

“And I think,” Berg says, “we’re just going to have to live with that.”

This feature appeared in the March/April 2020 issue of the Penn Stater. Paul Berg died Feb. 14, 2023. He was 96.

Michael Weinreb is the author of four books, including Season of Saturdays: A History of College Football in 14 Games.