BOSTON - Three years into one of history's largest trials of a new AIDS treatment, Steve Lagakos realized that it wasn't working and ordered a halt. Lagakos' verdict disappointed tens of thousands who suffer from the deadly disease, more than 2,500 patients who had volunteered for the study and the Harvard scientist himself, who has dedicated his career to the fight against the illness.
When Lagakos delivered the news to the trial sponsors at a Chicago hotel, Immune Response Corp. executives seemed to take it in stride. But as the months passed, they first suggested, then insisted, that Lagakos and his collaborator, Dr. James O. Kahn of the University of California, San Francisco, report that its therapeutic vaccine had some effect.
Lagakos and Kahn refused and published their unflinching findings last November. That might have been the end of it. But the company took the extraordinary step of filing an arbitration claim seeking up to $10 million, alleging that the scientists had defamed its product.
"Just put yourself in my position," says Dennis J. Carlo, president and chief executive of the biotech company. "I spent over $30 million. I would think I have certain rights."
The company's actions may have been unusual, but efforts by industry to manipulate, delay or suppress the findings of university-based research are not, scientists say. That's because the difference between favorable and unfavorable results in a drug study can be measured in the billions of dollars. Many academic researchers, unlike Kahn and Lagakos, keep quiet to avoid angering corporate sponsors, according to Drummond Rennie, a medical journal editor who has studied the issue.
As pharmaceutical and biotech companies pour money into universities, there is growing concern over their clout on campuses. Marcia Angell, the former editor of the New England Journal of Medicine, says industry influence has so distorted medical literature that she calls this the "misinformation age" of medical research.
Increasingly, scientists working with companies are blocked from providing information to other researchers. In some corporate-sponsored studies, journal editors say, key data are omitted. A cancer researcher at the National Institutes of Health said a medical company would let him use a biological substance only if he kept the results of his work secret for a decade. As companies fund more medical research, scientists say, those sorts of demands are more common.
Some worry that corporate money will skew the research agenda, inspiring academic scientists to conduct research that promises quick results or profits, rather than pursue work that could save lives but make less money.
"The mission of academic medicine should not be confused with the mission of investor-owned businesses," says Angell.
One pharmaceutical company nearly abandoned a new cancer drug in the mid-1990s that an oncologist at Oregon Health Sciences University helped develop. Novartis, a leading drug manufacturer, thought the drug, Gleevec, might work only against rare cancers, making it unprofitable. Novartis pursued the drug - hailed as a breakthrough when it won FDA approval last month - only after cancer patients mounted a campaign.
Industry-sponsored research has helped spur the discovery of exciting new drugs. But some scientists worry that corporate money will subvert the centuries-old traditions of science, the free exchange of information that has allowed researchers to build on others' successes and learn from others' failures. This isn't just a philosophical question, some dry academic debate. For the public, medical research can be a matter of life and death.
"To me, as a doctor who takes care of patients every day, it boils down to a pretty simple issue: If you don't share information, then you potentially delay the time to find effective treatments for patients," says Dr. Steven Rosenberg, chief of surgery at the National Cancer Institute. "If you delay effective treatments, then people die."
Increasingly, drug companies try to enlist the help of the researchers who conduct drug studies and write about them in journals. Drugmakers regularly sponsor all-expense-paid educational conferences at luxurious resorts and posh hotels, where academics give talks. A 1998 survey in the Journal of the American Medical Association found that 43 percent of scientists at major universities had accepted gifts, including lab equipment and trips to meetings, from industry. Many recipients said donors expected something in return, including previewing articles for publication or patent ownership of any products.
Many researchers also collect consulting fees. The chief of psychiatry at Brown University's medical school, for example, received more than $500,000 in fees from drug companies in 1998, much of it from the makers of antidepressants he praised in journals. And so many prominent academic researchers serve as paid industry consultants that the Food and Drug Administration, needing their expertise, allows them to sit on drug approval advisory committees. Sometimes, half the panelists have a financial stake in the outcome, through ties to the drug manufacturer or a competitor.
Researchers generally say their alliances with industry help in the hunt for important treatments and don't threaten their independence. Companies, they say, want to buy their expertise, not their integrity.
But based on his experience, Dr. William B. Applegate, now chairman of the department of internal medicine at Wake Forest University School of Medicine, is not convinced.