Keep the Doctors and Entrepreneurs Separate in Gene Tests
There’s been a lot of concern lately about the safety of experiments involving gene therapy. Shocked by the death of a young man who took part in a gene-transfer experiment at the University of Pennsylvania last year, Congress held hearings in which one expert after another urged stricter oversight of such testing. A few weeks ago, Health and Human Services Secretary Donna Shalala proposed tough new standards, with fines of $1 million for institutions, and $250,000 for individuals, that don’t adequately protect participants in gene-therapy research. In the wake of the bad publicity, scientists report they’re having trouble recruiting volunteers for gene-therapy research trials.
It’s no wonder people have become skeptical of gene-therapy work. Researchers’ credibility has been seriously eroded. But the source of the erosion was not government, the media or the experimental nature of gene therapy. The problems confronting this new technology are no different from those facing conventional medical research: money, and its corrupting influence on drug-related research.
It wasn’t always so. Medical researchers once considered themselves above the profit motive. In 1954, for example, Jonas Salk, who developed the polio vaccine, was asked who would control the patent. “There is no patent,” he replied incredulously. “Could you patent the sun?”
Several developments have since created a world in which Salk’s view seems quaint. The first was the Bayh-Dole Act of 1980, which accelerates the transfer of scientific discoveries from universities to the marketplace. The act allows universities to claim patents on technologies they invented using federal funding and urges them to cooperate with private industry to commercialize the developments. The act is a boon to scientists, universities and industry. Scientists no longer have to choose between academic prestige and industrial money. Universities can retain their professors and attract new money as well. Industry gains access to some of the country’s brightest minds.
Meanwhile, another development made medical research increasingly commercial: the modern pharmaceutical boom. Since World War II, the drug industry has been expanding, and by the 1980s and ‘90s, the basic research that had been going on for decades yielded lucrative applications. The industry has entered an explosive growth phase, producing many new drugs and profits to go with them.
That, in turn, gave rise to yet another new enterprise: the big business of testing new drugs on people. Before entering the marketplace, all new drugs undergo clinical trials to ensure safety and efficacy. To conduct these trials, drug companies pay medical centers, doctors and private companies to recruit volunteers willing to take an experimental drug. This branch of the industry has become a cash cow worth an estimated $3.3 billion a year.
All these factors created today’s big-money climate in which a company might spend hundreds of millions of dollars to bring out a new drug. There’s nothing wrong with using private capital to develop and test drugs. But questions arise when formerly independent researchers become too entangled in the business aspects of their careers.
The medical community knows several cases in which companies have influenced the design of a trial, pressured investigators for certain results or suppressed findings that criticized their product. Yet, despite the notoriety of these cases, the entanglements continue. Earlier this month, the New England Journal of Medicine, the world’s most prestigious medical publication, printed a study in which the authors praised a certain antidepressant. The journal has strict financial-disclosure rules requiring all authors to list their links to the drug industry. The authors of this study have so many drug-industry ties that the journal had to list them on its Web page, because there was no room to print them.
In that same issue, outgoing editor Marcia Angell lamented the “Faustian bargain” universities have struck with industry that forces them to cater to commercial concerns. Ironically, the journal is replacing her with a doctor who’s had significant financial involvement with at least 21 pharmaceutical companies. The new editor, Jeffrey Drazen, has since agreed to divest his holdings.
If we’re concerned about the influence of money in medical studies, we should seriously worry about its role in genetic research. This technology, based on inserting new DNA into patients’ cells, is a high-risk, high-payoff venture in which a company’s stock price can skyrocket or crash depending on the result of a single trial, or even the rumor of a result. It attracts competitive, hard-driving individuals, quick to patent their discoveries and set up their own companies. It promises billions to those who can successfully bring a new drug to market.
Such an environment can also set the stage for sloppiness and abuse, especially when researchers test their own drugs. Investigators who looked into the death of 18-year-old Jesse Gelsinger at the University of Pennsylvania not only found a pattern of slipshod procedures in informing and protecting patients; they also learned that both the researcher, James M. Wilson, and the university had a large financial interest in the therapy he was testing.
The government has since halted genetic-therapy experiments at several medical centers, including Duke University, St. Elizabeth’s Medical Center in Boston and St. Jude Children’s Research Hospital in Tennessee because of alleged inadequate patient protection. At St. Elizabeth’s, it alleged that the researcher had not only failed to report certain side effects, but also had a significant investment in the therapy he was testing.
All that has led Shalala to propose new standards for patient protection and require researchers to fully disclose their financial dealings. More needs to be done.
Currently, patients who take part in clinical trials must sign a document giving their “informed consent” to the procedure. It’s important not to simply inform patients, but truly educate them. Patients need to understand what a longshot genetic-therapy treatments represent. Of the 400 genetic-transfer therapies tested on people since 1989, only 10% have even made it past basic toxicity testing. Not one has become a licensed medicine.
A firewall between researchers who test drugs and the money that sponsors them must also be built. Disclosure is not enough. The only solution would be to forbid doctors from having any financial stake in the therapies they’re testing, or at least strictly limit them. Harvard Medical School recently took such a position when it refused to relax its strict financial guideline on human-subjects research. Unfortunately, few other medical centers have done the same.
This isn’t the first time that rules have had to be enacted to protect human volunteers. No one can forget the infamous Tuskeegee syphilis study or the human radiation experiments at the Department of Defense. Each incident taught us to enact stricter protective measures for patients.
This latest episode, while not as grievous, teaches new lessons about the need to separate business from medicine. Making that separation may seem contrary to innovation and the U.S. style of science. But it cannot be avoided. Only then will patients who take part in clinical testing know that they’ve placed themselves in the hands of a doctor, not in those of an entrepreneur. *
