Former Director's Memoir
By Rich McManus
Photos by Ernie Branson
On the Front Page...
Among the privileges of being an esteemed ex-director of NIH are that you can deliver a lecture in Lipsett Amphitheater wearing a comfortable pair of sneakers, and that, a quarter century after the fact, you can let the world in on your savvy political machinations including hard-sell tactics that verged on the questionable that enabled science to tread in new directions despite Frankensteinian fears in the public imagination at the time.
No, we're not talking about human embryonic stem cell research here, though Dr. Donald S. Fredrickson's talk on Dec. 11 was quite consciously a lesson in introducing to the public scientific advances that laymen initially found almost unpalatable. Rather, he was describing the advent of recombinant DNA research, which grew out of discoveries on the West Coast in the early 1970's, before Fredrickson became director of NIH in 1975. His recollections, given as a History of Genetics Lecture, form the basis of his new book, The Recombinant DNA Controversy: A Memoir, available in the FAES book store.
"It's not to be forgotten that we're 3 months into a war," he began, "but we're also in the midst of a revolution and we have been for the past 30 years and it's the most important one in the history of medicine and biology. I was in the first phase of it," he recalled of his 6 years as NIH director, "and it was the most enjoyable period of my life, I think."
Relying on memory and on anecdotes from the book, Fredrickson, 77, traced the labyrinthine 5-year journey from when he first learned about restriction enzymes and molecular biology's ability to cut and paste segments of DNA, to eventual creation of HHS guidelines governing recombinant DNA research, and establishment of a recombinant DNA advisory committee (RAC) that exists to this day. Though the means to these ends was somewhat tortuous, Fredrickson argues that science's success in being able to use this new tool, in the face of initial public alarm, was due to two things: keeping the public, via Congress, fully informed, and maintaining, intact, what he called a sort of "Jeffersonian social contract" between intellectual leadership and society at large whereby mutual respect and openness, not harsh regulation, rule the day.
The talk was a kind of primer for new NIH directors: here's what to do when history throws you a curve you didn't see coming. Fredrickson, a heart disease expert with a sort of unselfconscious patrician air (he could not bring himself to use the word "protests" to describe much-publicized anti-recombinant DNA research uproars in Ann Arbor, Paris and Cambridge, Mass.; he called them "manifestations"), had no idea what recombinant DNA research was all about when he took office on July 1, 1975.
Two years earlier, at a Gordon conference on nucleic acids, Dr. Herbert Boyer, in whose laboratory the first restriction enzyme capable of cleaving DNA EcoR1 had been discovered, had informed molecular biologists that the technique had evolved to the point that "we can put any pieces of DNA together that we want," Fredrickson recounted. Realizing immediately that the public would fear creation of new and dangerous chimeras, scientists including then NCI biologist Dr. Maxine Singer urged that a letter be drafted to the National Academy of Sciences, and published in Science, that would alert the world to the new recombinant science, and propose rules for its application.
"A group formed to decide what it all meant, and (Stanford biologist) Paul Berg was named chair," Fredrickson said. The group agreed on four immediate goals: institute a world moratorium on the research, to allay public fears of the creation of new genes; consider what might happen if novel genes were set loose; ask the NIH director, then Dr. Robert Stone, to appoint a committee to draft guidelines and perform risk assessment; and hold an international meeting very soon with all the leaders in the field to discuss guidelines.
Back at NIH, Stone quickly formed a 15-person study section the first RAC, all of whom were biological scientists save one layman. The big international meeting was held at Asilomar, Calif., a favorite retreat destination for Stanford's science faculty, to which Berg belonged; interestingly, Fredrickson would not visit Asilomar for another 25 years. At this meeting, scientists from many nations and scientific specialties hammered out concerns about containment and crafted a framework for guidelines, only to be deflated late in the meeting with news, from lawyers, about liability issues. "A fear arose that the government would take it all over," Fredrickson said. Indeed, the NIH representative to the meeting, Bill Gartland, was told by the vice chairman (Dr. David Baltimore) at the meeting's end, "Tomorrow, it will all be yours."
"Little did I know what was coming," said Fredrickson, who succeeded Stone. The new director relied on advice from eminent NIAID virologist Dr. Wallace Rowe to get up to speed on the new science of recombinant DNA. From what he learned from Rowe and other prominent intramural scientists, Fredrickson set three goals: the public must have a say and be kept informed on the guidelines; the guidelines must be just that, not regulations holding the force of law; and NIH should be the venue for establishing the guidelines, as well as the principal source of funding of the new science.
Fredrickson quickly hired what he dubbed "my kitchen RAC" lawyer and physician Dr. Joseph Perpich, who "knew the choreography of Capitol Hill" from having worked on Sen. Ted Kennedy's staff, and Dr. Bernard Talbot, then an NIAID scientist and now a medical officer at NCRR, who was asked to go out and recruit intramural specialists who could advise Fredrickson.
The details of how Fredrickson's management team shepherded a livable version of the recombinant DNA research guidelines through NIH's parent agency HHS, its leader Joe Califano, while at the same time recruiting support from Congress through some key personal contacts form much of the book.
In one episode, Fredrickson writes about a session at the Navy hospital bedside of an important congressional leader who happened to be a diabetes patient and amputee to whom Fredrickson suggested, within earshot of several influential congressmen, that the new research could lead to production of human insulin; conceded the author, "I guess I was unscrupulous." Other chapters chronicle how Fredrickson's team avoided the pitfalls of regulation, dealt with court cases (Mack v. Califano, Friends of the Earth, et. al.), witnessed public approbation (one "manifestation" near Harvard included the banner "Stop DNA Research There are already more forms of life in Harvard Square than the world can stand") and negotiated that all-time wonk albatross, the Environmental Impact Statement.
Fredrickson says he is "quite sure" that NIH's strong effort to keep the public informed saved recombinant DNA research, but he allows that the agency's methods didn't keep everyone happy. He doesn't seem to care, as long as NIH came out respectably.
"The guidelines are still alive after 25 years," he declared, and so is the RAC, despite one of Fredrickson's successors' efforts to kill it. "In all, it was a good reflection on NIH, and certainly brought great credit to the scientists who participated."
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