Historic posts are reprinted verbatim from their original source.

Source: Lisa M. Krieger, San Jose Mecury News, Febrary 17, 2000

PACIFIC GROVE — The genetic-research pioneers who 25 years ago warned of public-health and environmental catastrophes if their science went awry are debating a new threat: rampant commercialization and carelessness.

A quarter-century after they first gathered at the rustic Asilomar retreat, these now-graying scientists have returned for a three-day conference. And they are warning that pressures on researchers to compete and on biotech firms to earn profits, while withholding information about their failures, are undermining a tradition of scientific integrity established at the original Asilomar Conference of 1975.

“The major thing we achieved (in 1975) was . . . public trust,” said Paul Berg, who convened the original conference and is now director of the Beckman Center for Molecular and Genetic Medicine at Stanford University’s School of Medicine.

“This led to public acceptance of the belief that science was in reasonably responsible hands.”

“In retrospect, very few . . . foresaw the pervasive, complex, robust and rich ramifications of recombinant DNA technology. Nor could most have predicted the pace at which fundamental understanding of biology has deepened,” Berg said.

Dr. Donald S. Fredrickson, the former director of the National Institutes of Health, put it more harshly. “Morality has been soiled. Entrepreneurs are repressing any information that suggests an unfavorable outcome as `proprietary’ — and keep it secret,” Fredrickson said. “We need a re-awakening — a moral re-evaluation.”

Although the three-day symposium will not result in a formal statement about current issues, it has triggered heated debate about a world of biology that has profoundly changed in 25 years. Biotech has grown from a field dominated by academic researchers to one driven by companies with millions of dollars at stake. The industry has developed a wide array of life-saving therapies. But there is growing tension between the tradition of openness and the demand for greater privacy by commercial biotech companies, according to the 50 participants from throughout the United States and several other countries.

This tension boiled to the surface in September when Jesse Gelsinger, 18, died of complications of gene therapy at University of Pennsylvania. The incident increased public concern about whether scientists could be trusted.
Experimental therapy

Gelsinger had been undergoing experimental gene therapy developed at the Institute for Human Gene Therapy at the University of Pennsylvania. The institute was directed by James M. Wilson and was financed partially by a biotech company that Wilson founded — an arrangement that has drawn the interest of government investigators. The university has admitted mistakes and administrative lapses but denies liability for the death.

Since the incident, medical centers have reported to the NIH 691 cases of serious adverse effects in gene therapy experiments, the agency disclosed last week. Many of these reports, required by law, were delayed weeks, even months.
A review by Rep. Henry Waxman, D-Los Angeles, found that 652 of the 691 cases were reported late; fewer than 6 percent were filed on time. Moreover, at least some of the previously unreported deaths remained unexplained, raising the possibility that Gelsinger was not the first to be killed by gene therapy complications.

The prestigious Pennsylvania gene research program has since been charged with “numerous serious deficiencies.” That disciplinary action follows similar transgressions, although no deaths, at Duke University, the Los Angeles Veterans Administration Hospital, the University of Illinois at Chicago, the University of Alabama-Birmingham, the University of Colorado Health Sciences Center and Virginia Commonwealth University.

Genetic research is going through a significant transition, said the scientists at Asilomar, where they once met to ponder the risks of a gene-splicing technique that has now become routine.

In 1974 — long before the ethical quagmire of human cloning, embryo research and other technologies now on the horizon — they were so jittery about the impact of their science that they called for a self-imposed moratorium on some research.
The Asilomar agreement, brokered by leading molecular geneticists such as NIH’s Maxine Singer and Stanford’s Berg, marked the first time that any major branch of science had voluntary suspended its work.

In the early years, almost all research was federally funded, with expectations of open disclosure of results and research plans. The scientists held the moral reins, creating a tough advisory committee to oversee research.

“In recent years, there has been a shift away from the culture of civic mindedness to greater individualism,” said Parris Burd, director of regulatory affairs for the Redwood City-based biotech firm Maxygen. “We need to educate our young scientists of their civic responsibilities and obligation to participate (in the public review process).”

Now debate rages over whether scientists should be required to report biotech research failures to the NIH, which can disclose them to the public, in addition to the Food and Drug Administration, which keeps such information confidential.

Regulatory changes

The Biotechnology Industry Organization is seeking regulatory changes that could decrease public reporting of adverse events the organization considers proprietary.

But consumer advocates such as Dr. Peter Lurie of Public Citizen’s Health Research Group in Washington, D.C., say “one cannot conduct quality or ethical research in an environment in which other scientists’ experiences are hidden. Denying information can be hazardous; this may be the real lesson of the Gelsinger episode.”

“We did not foresee the emergence of venture capital . .. . and researchers who invest in and oversell the promise (of their research) and keep adverse effects quiet . . . and who advance their careers with little time spent on long-term thinking,” said Singer, then a research biochemist at the NIH and now president of the Carnegie Institute in Washington, D.C.

“While this creates exciting and constructive competition,” Singer said, “some scientists have compromised their behavior.”