Gene Therapy's Tragedy: A Lesson for Stem Cell Research?
Many observers have cited the hype and subsequent failed promises of medical gene transfer as a cautionary tale for the "next big thing" in biomedicine, such as stem cell research. In this week's Science (and in a related interview in Nature), a gene transfer researcher makes a similar argument. And given the details of James Wilson's career, which he did not fully disclose, his advice should carry particular weight.
In the 1990s, gene transfer
(a.k.a. gene therapy) was touted as a likely, imminent cure for a wide
range of genetically-related medical conditions. Wilson was a prominent
scientist at the University of Pennsylvania, described in a press
release as the "Michael Jordan of gene therapy."
By 2000, hundreds of gene transfer clinical trials were underway, but
the lack of progress relative to the claims was becoming apparent. The
death of an 18-year-old, Jesse Gelsinger, in a clinical trial led by
Wilson "initiated a chain of events that seriously derailed the field."
Now, he concludes:
It would be unfortunate if the field of hESC [human embryonic stem cell] research missed this lesson from history and took a similar trajectory. Yet many of the social and economic forces that drove gene therapy's burst of clinical activity also exist today in the stem cell arena. Without passing judgment on the scientific merits of any individual clinical study or plan, I am concerned that expectations for the timeline and scope of clinical utility of hESCs have outpaced the field's actual state of development and threaten to undermine its success.
The hyperaccelerated translation to the clinic that occurred in the field of gene therapy in the 1990s was driven by multiple factors, including: (i) a straightforward, if ultimately simplistic, theoretical model indicating that the approach "ought to" work; (ii) a large population of patients with disabling or lethal diseases and their affiliated foundations harboring fervent hopes that this novel therapy could help them; (iii) unbridled enthusiasm of some scientists in the field, fueled by uncritical media coverage; and (iv) commercial development by the biotechnology industry during an era in which value and liquidity could be achieved almost entirely on promise, irrespective of actual results....
Many of the factors that fueled gene therapy's premature expansion are major drivers of the hESC and iPS [induced pluripotent stem cell] research agenda today. A large and vocal population of patients suffering from a wide variety of ailments is pressing for stem cell-based therapies. Disease-specific stem cell research groups are more politically sophisticated than ever, in some cases employing congressional lobbyists. Unrealistic expectations have been fueled by relentless media coverage, driven in part by a factor not present in the gene therapy roll-out: a debate over the ethics of research on human embryos and embryo cells, which has served as a "news hook" that brings media attention to even the most incremental of advances.
Wilson is concerned about a similar "rush to the clinic" with hESC trials, particularly including the field's first, long promised (1, 2, 3, 4) by Geron and recently approved by federal regulators.
Wilson's advice for stem cell research comes on the heels of the publication of a 6000-word explanation, which he calls
an "apology" for something that he says was ultimately "my
responsibility." Wilson published the essay in an obscure scientific
journal as part of a 2005 settlement with the US Department of Justice.
However, Wilson leaves out a few key details. At the time of the
clinical trial in which Gelsinger died, Wilson failed to disclose -
even to Gelsinger's father, after his son's death - that he held a 30% share of Genovo,
the company which would benefit from a successful outcome of the trial.
He was subsequently barred from working on human subjects, an endeavor
to which he seems to have returned and a field from which he still stands to profit. When Genovo was later sold to Targeted Genetics, Wilson pocketed $13.5 million.
In turn, Targeted Genetics conducted a clinical trial in which a woman
died in 2007. The informed consent process, approved by a private institutional review board (IRB), was criticized as inadequate (1, 2, 3), although the National Institutes of Health's Recombinant DNA Advisory Committee did not find the company to be at fault. "IRBs for hire" have recently come under increased scrutiny. And Targeted Genetics, whose current 25-cent stock price is about one percent of its peak value, is likely to close shop.
Update (May 18): The account by Gelsinger's father [PDF] provides an interesting contrast to that of Wilson. This exchange soon after Jesse's death, is striking:
My first question to him while sitting on my back porch was, "What is you financial position in this?" His response was that he was an unpaid consultant to the biotech company, Genovo, behind the research effort. Being naïve, I accepted his word and continued my support for him and his work.
Previously on Biopolitical Times: