Mistakes Were Made (by Geneticist James Wilson)
Wired recently ran a long story headlined "The Fall and Rise of Gene Therapy." The title is displayed with images of two viruses, captioned:
This virus laid waste to James Wilson's career.
This virus could bring him redemption.
That's just not true. James Wilson laid waste to his own career as a pioneer of human gene therapy. (He did remain a professor at the University of Pennsylvania.) He did not, however, single-handedly destroy the prospects of gene therapy, as the article implies, and we should be properly skeptical as to whether he might single-handedly restore the field.
The first virus pictured was used in an experiment Wilson ran in 1999 that resulted in the death of 18-year-old Jesse Gelsinger, a subject in a gene-therapy clinical trial whose own disease was mild and well under control. His death was a tragedy no matter what the surrounding circumstances.
At first, Gelsinger's father, Paul Gelsinger, supported the scientists. Paul's support continued even after he learned that monkeys had died during the pre-clinical work; he was assured that adjustments had been made. (His personal account is here [pdf].) Then he started learning about the conflicts of interest involving Penn and, in particular, Wilson.
Most damningly, Wilson specifically told Paul Gelsinger that he was an "unpaid consultant" to Genovo, the company that at least partly funded the research and had exclusive rights to license the related patents. That was disingenuous at the very least. Wilson held 30% of Genovo's stock, and eventually cashed in, reportedly to the tune of $13.5 million.
There were more problems concerning conflicts of interest, many of them detailed in this FDA letter, and in other links here. Wilson was indeed punished, and his gene-therapy career did indeed go "into free fall" as the Wired story by Carl Zimmer notes. But it was his own doing.
There are curious omissions in the Wired account. The FDA's investigation of Jesse Gelsinger's death revealed that ten other gene-therapy subjects had previously died, in four different labs, and not been properly reported. Indeed, NIH discovered (paywall) that less than 4% of "serious adverse events" occurring in gene transfer trials were being reported as required.
A couple of years later, two children who had gene therapy in Paris for a fatal auto-immune disease ("boys in a bubble") developed leukemia, apparently when the retrovirus used lodged the new gene in an unfortunate place. That led to a temporary halt to all gene therapy trials.
In 2007, a woman died in a gene therapy trial, but investigators ruled that it was not directly caused by the treatment (see 1, 2). In recent years, however, reports of successful gene transfer treatments suggest that the techniques may eventually prove useful for a limited number of conditions.
Meanwhile, Wilson has been trying to rehabilitate his reputation, which is understandable. He has also been doing what seems to be good science, which is laudable. But we should focus on the systemic failures and the human lapses in judgment, not on a simplistic narrative of tragic failure and redemption through hard work.
You know who really deserves our thanks? Paul Gelsinger. He has worked tirelessly, mostly with Citizens for Responsible Care and Research, in an effort to ensure than no one else suffers as his family did. He quite rightly added his brief comments to the Wired story. In 2008, after Wilson had published an article (paywall) about informed consent (discussed here), Gelsinger summed up his position:
So, my son, doing the right thing, was killed by a system and people rife with conflicts of interest, and real justice has been found to be very lax. It's essentially business as usual. You may think that I am bitter, but I am not. My son gave me the best possible example on how to be. The system showed me what everything is really all about. Hopefully, given enough time they'll fix this, but I'm not holding my breath. Anyone considering joining a clinical trial needs to be aware that they are dealing with a system that is seriously flawed.
Previously on Biopolitical Times: