By Todd Stein
February 3, 2000
Photo: Photodisc

It has been half a year since Jesse Gelsinger, an 18-year-old Arizona man, died in an experiment at the University of Pennsylvania in Philadelphia after receiving a dose of corrective genes encased in a weakened cold virus. Gelsinger’s death, the first directly attributed to genetic therapy, led the Food and Drug Administration on Jan. 21 to temporarily shut down human gene therapy experiments at the university after uncovering “serious deficiencies” in ensuring patient safety.

That action has cast a long shadow over a bright new field that had offered hope to patients and the promise of profits to investors. Yet after months of public testimony and an exhaustive review of the Gelsinger case, federal regulators, the biotech industry, and the medical community are still divided over what—if anything—can be done to make the controversial experimental therapy safer.

At the heart of the debate is the question of government oversight—to whom should researchers report deaths and serious illnesses related to gene therapy experiments, and who should have access to that information? “I think it’s safe to say that there is a great level of uncertainty and uneasiness about current oversight mechanisms being adequate,” said Gladys B. White, PhD, RN, director of the Center for Ethics and Human Rights at the American Nurses Association (ANA).

Proceed with caution

Since Gelsinger’s death, there have been news reports that other patients died during the course of experiments—from their diseases, not the therapy—and that the scientists involved did not report those deaths to the National Institutes of Health (NIH) as required. This has created a growing cloud of suspicion over gene therapy, raising questions about whether other scientists may have withheld information that could have prevented Gelsinger’s death. These concerns led the NIH to hold an advisory committee hearing in December 1999 to consider tougher controls for gene therapy experiments.

Amy P. Patterson, MD, director of the office of biotechnology activities at the NIH, said the agency wants to put a sharper edge on regulations that require gene therapy researchers to report to the health agency any deaths or serious illnesses. “The NIH wants to make it clear that if people are receiving federal funds, they must comply with our guidelines,” Patterson said in a statement. “One potential consequence of not complying is suspension or termination of funding.”

Buried beneath the concern over government supervision is the larger question of whether gene therapy should be allowed at all. Most countries have outlawed the transfer of healthy genes from one organism to another, and public opinion polls show a majority of Americans are skeptical about the procedures. The U.S. biotech industry has poured millions of dollars into private research efforts, hoping to find cures for diseases such as cancer, AIDS, and heart disease. But the research has produced no miracle cures so far, and researchers acknowledge that the fledgling industry could be set back years by another disaster like Gelsinger’s death.

Unlike other therapy

“Gene therapy should be regarded with extreme care and precaution because of the possibility that mutations and perpetual transmission of genetic material might occur,” said Rita Black Monson, DNS, MPH, RN, co-chair of the National Coalition for Health Professional Education in Genetics and chair of the credential committee of the International Society of Nurses in Genetics, a Hanover, N.H., nonprofit organization with more than 300 members.

“It’s very different from other forms of experimental therapy because we don’t understand how mutations may occur, nor do we have the means to control them. We could end up producing entirely new diseases.”

Monson supports gene therapy research—with conditions. She insists that NIH protocols must always be followed, noting that the researchers who tried to cure Gelsinger of ornithine transcarbamoylase deficiency, a rare metabolic disorder, failed to follow at least two key protocols: they used an injection to deliver the genes rather than the required IV drip and neglected to inform participants about the deaths of monkeys in previous tests. Yet Monson doubts that the NIH would have the financial means to enforce its rules.

First, some regulations

While the ANA has not taken a position on gene therapy, White supports a proposal that the NIH’s Recombinant DNA Advisory Committee be granted the authority to approve or deny all gene therapy experiments that use federal funds. And she supports the creation of a government body that would collect data from ongoing gene therapy experiments and disseminate it to other researchers. “It is important for researchers using one method to hear from someone else who may be six months ahead in the research,” White said. “If you just wait for the total result to be reported and charge the NIH with reporting deaths alone, you miss an important benefit of the accumulating data in the course of a trial. It could save lives.”

Other observers question whether the oversight rules can be applied to the widely different methods of gene therapy, some of which affect only one organ, while others can introduce new genetic material into the population at large.

“There’s a huge difference between seeing if you can turn on some genes in the heart to dilate certain blood vessels versus implanting whole new genes from another organism that affect all the genes in the body and can be passed on to the next generation,” said Felissa Lashley, MSN, RN, dean of the Southern Illinois University School of Nursing in Edwardsville, and a practicing geneticist. “Passing on new genetic material to descendants is a very thorny path ethically. I don’t think anyone has the right answer. And the right answer may not be right for everyone.”