Competing Attractions Of Private Research Prove Alluring To Top Academic Scientists

Moves to companies by a small group of HHMI investigators shows the growing appeal of commercial- sector biological research jobs. Howard Hughes Medical Institute investigators are acknowledged to be among the most creative and accomplished basic researchers working in academic laboratories today. Yet even these top scientists sometimes feel the urge for a different set of challenges. Some long for the chance to develop useful new drugs and therapeutics based on their ideas or to run a larger, more broadly influential research enterprise outside the cloister of the university_options not available under the terms of their investigator status. Perhaps the clearest evidence of this can be found in a small, but growing band of researchers who have voluntarily given up the unusually generous support and intellectual freedom HHMI offers to pursue such alternative careers in industrial laboratories. The fact that some have been willing to move into industrial research, however, is indicative of the increasingly competitive attractions of private-sector science, according to current and former HHMI investigators and other researchers. "I didn't have to give up the exploratory type of research that is really a part of my soul," says Joan S. Brugge, a former professor of microbiology at the University of Pennsylvania and HHMI investigator who became scientific director for Ariad Pharmaceuticals Inc., Cambridge, Mass., in May 1992. "But at the same time, I'd be in an environment where I'd be able to directly apply my experience to do something meaningful." Overall, the number of HHMI scientists who have jumped to private labs in the past few years is not large_perhaps a half-dozen. In addition to Brugge, others who have recently chosen to leave HHMI for private science include: Steven McKnight, research director since April 1992 of the privately held biotechnology company Tularik Inc., South San Francisco, Calif.; Michael Bevilacqua, vice president for inflammation and medicinal chemistry for Amgen Inc. in Thousand Oaks, Calif., as of October 1993; and C. Thomas Caskey, who joined Whitehouse Station, N.J.-based Merck and Co. Inc. at the end of 1994 to direct its research laboratories at West Point, Pa. "All these people have been terribly successful," observes Phillip A. Sharp, chairman of the biology department at Massachusetts Institute of Technology and winner of the 1993 Nobel Prize for physiology or medicine. Sharp, who is chairman of the scientific advisory board and a member of the board of directors for Biogen Inc. in Cambridge, Mass., is also a former member of the HHMI medical advisory board. "They've made major research advances, taught students, lectured around the world_and then they've come to a stage in their careers where they have to make a decision. Do I try to do it again? Is that what the next 15 years holds? Or do I take this opportunity to make the transition into a new environment with a new set of problems and challenges?" "These are very personal decisions," says Purnell W. Choppin, president of HHMI. "These were all people who were doing extremely well scientifically but thought that it was time, in their lives, to do something a bit different. Some people want new mountains to climb. It's just a feeling that some people develop, that, at a certain time, they can make an even greater contribution in a slightly different area and have a different kind of challenge personally." HHMI began its research support program in the mid-1950s and currently supports about 275 investigators located at more than 60 host institutions with salaries, staff, laboratory space, and resources for equipment. The largest private philanthropy in the United States, with total assets of more than $8 billion, HHMI spent $262 million on biomedical research in 1994. When HHMI employs an investigator, it provides support for the person and the laboratory_rather than for a given project_in three-, five-, and seven-year blocks; and it judges the results retrospectively, on the basis of the intellectual destinations reached, rather than on the goals originally charted. In return for its support, however, HHMI demands of its investigators a high degree of academic purity in the pursuit of science. Investigators may not consult for companies in which they own "a significant equity position" more than 5 percent of a company's stock_and they are required to spend at least 75 percent of their time on their research. Because of their proven scientific talents, HHMI investigators are often targeted by both fledgling biotechnology and established pharmaceutical companies hoping to fill top research positions. Most decline, preferring their HHMI- supported research freedom. But many investigators do engage in paid scientific consulting, within HHMI guidelines, for many of the same reasons that a few have left the institute. "The idea that you might direct research that would lead to something that directly influences the health of people_that's a pretty powerful thing," affirms HHMI investigator Robert J. Lefkowitz, a professor of medicine and biochemistry at Duke University Medical Center. Lefkowitz sits on the scientific advisory boards of Ge-nentech Inc., South San Francisco, and Ariad Pharmaceuticals_where Joan Brugge is scientific director_but has chosen to limit his industrial involvement to consulting. "It's a chance to interact with some very intellectually stimulating colleagues from around the country and to share an enterprise." Lefkowitz notes that private-sector research_whether as a consultant or a full-time employee_can be financially rewarding, especially for scientists used to academic pay scales. According to a survey conducted by the American Association of University Professors in Washington, D.C., the average salary for a full professor at a research university in the academic year 1993-94 was $68,700. Coopers and Lybrand, an accounting and consulting firm in Boston, reports that, in 1994, the compensation for research and development officers at biotech companies ranged from just over $100,000 in smaller companies to more than $260,000 at the larger ones; pharmaceutical research directors were comparably compensated, according to a recent survey by the American Association of Pharmaceutical Scientists in Alexandria, Va. It should be recognized, however, that these are average salary figures, and HHMI investigators are not average academic scientists, in either achievement or compensation. Before his move to Merck, Caskey's position as an HHMI investigator and a professor of molecular genetics, biochemistry, medicine, and cell biology at Baylor College of Medicine carried a salary and benefits package approaching $300,000, placing him among the most highly compensated researchers in HHMI and academia. To date, Lefkowitz has resisted leaving HHMI and academia, despite "numerous opportunities that have been waved in my face," he says. "The one thing that one has in academia that one doesn't have in the pharmaceutical industry is total freedom to do whatever kind of research you want to do and have the money for. You don't have to kowtow to the research programs being directed by those above you." Brugge, too, notes this difference between the two environments, the need to submit one's personal aims, scientifically, to those of the company's drug-discovery goals. "At Ariad right now, everything we do has to be focused on what we need to know, as opposed to what would be nice to know. In academics, one really positive aspect is that you can explore and follow your interests to a great extent. You lose a bit of your individuality in a company." On the other hand, with its overtly practical drives, industrial research can sometimes stimulate science to take more productive directions, according to Brugge and several HHMI investigators involved in consulting. "It's a totally different game," says David H. Beach, a senior scientist at Cold Spring Harbor Laboratory in New York and an HHMI investigator who chairs the scientific advisory board of Mitotix Inc., a biotechnology startup in Cambridge, Mass. "In essence, it adds a whole new dimension to one's thinking about biological results. Previously, you'd get a result and you'd say, 'Which journal can I get it into?' When you're thinking about drug discovery, it's a totally different perspective. What you're always asking with any result is 'Is this applicable in any context that I can think of?'" Steven McKnight, formerly an HHMI investigator at the Carnegie Institution in Washington, D.C., says he holds both institutions in the highest regard, but saw new opportunities for himself in private-sector science. "What attracted me to Tularik, first and foremost," McKnight recalls, "was the challenge, the risk of building a new company that would provide new jobs to skilled scientists in the general field of molecular biology. Secondarily, yet of near equal importance, was my desire to help catalyze the application of discoveries, made largely in the academic sector, regarding gene regression." HHMI investigator Robert Tjian, a professor of molecular and cell biology at the University of California, Berkeley, is a friend of_and sometime scientific collaborator with_McKnight. Tjian is also a consultant to Tularik and was involved with the company from its inception. Like Lefkowitz and Beach, he has chosen to limit his commercial involvement and maintain his HHMI academic status. "In principle, I can see myself working in either environment," Tjian says. "But because of the particular nature of my research, it doesn't make a whole lot of sense for it to be done in a nonacademic setting. I'm working on basic mechanisms of transcription. You can see a line to clinical studies, but it's a pretty long distance between the two." Although his and McKnight's work involved similar scientific concerns, Tjian observes, their research diverged at a certain point: "He could pursue his questions as well, if not better, in an industry setting." According to Phillip Sharp, the movement of top researchers from HHMI and the academic sector into industrial science is one proof of a qualitative change that has been under way in biology for about 15 years. "There is more opportunity now to do interesting science in the private-sector biology labs than there has ever been before. That sort of relationship existed between the private sector [and academia] in physics 40 years ago. And chemistry has had that relationship throughout the last 60 years and still does. Biology has now, over the last 10 years or so, developed that interrelationship." The shift, Sharp says, demonstrates a "coming of relevance" for molecular biology. Additional reporting for this story was provided by Karen Young Kreeger.

Competing Attractions Of Private Research Prove Alluring To Top Academic Scientists

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