The full story of 36-year-old Jolee Mohr’s recent death in a gene therapy clinical trial for rheumatoid arthritis is still unfolding. The study, sponsored by Seattle-based Targeted Genetics, remains on hold. A team of 20 doctors and scientists at the University of Chicago Medical Center has combed through autopsy samples. The FDA has yet to announce the direct cause of death, and the Recombinant DNA Advisory Committee (RAC) will discuss the case at its September 17 meeting.

There’s a lot we don’t yet know. But there’s a fair amount we do know, and much of it is troubling. Gene therapy’s high public profile has led journalists to investigate information released by Mohr’s family that raises questions about the study’s design, inclusion criteria, and conduct. Some are specific to the Targeted Genetics study while others are broader. Even if no one had died, a number of these issues would still be quite relevant given gene therapy’s record to date: inconclusive at best, and certainly disappointing given the high hopes repeated over two decades.

One key concern is whether people whose conditions aren’t life-threatening – such as those with rheumatoid arthritis – should participate in risky experimental procedures like gene transfer. Mohr, for example, held down a full-time job and cared for her five-year-old daughter. According to her husband, she went boating the weekend before she was injected with the gene transfer product, suggesting that she continued to enjoy an active lifestyle. It bears asking: was the risk here worth the potential benefit? Questions have also been raised about the commercial influences embedded in the relationships between Targeted Genetics, Mohr’s personal physician (whose arthritis clinic received payments for recruiting subjects), and the for-profit institutional review board that Targeted Genetics hired to review its protocol.

Mohr’s death has been repeatedly acknowledged as a tragedy, but the status quo in gene therapy research is also receiving a striking defense. Some gene therapy insiders have tried to diminish its significance by characterizing it as an unfortunate aspect of medical progress. One of the earliest such comments was published here in Bioethics Forum eight days after Mohr’s death by UCSD medical professor and past president of the American Society of Gene Therapy, Theodore Friedmann.

Friedmann is noticeably troubled by the media coverage of Mohr’s death, which at that point consisted of Rick Weiss’ Washington Post articles. He takes offense at “some [who] have called this the ‘latest setback’ to the field of gene therapy.” Not only does he question this characterization’s fairness, he suggests that it “reflect[s] some observers’ continued inability to distinguish between the inevitable setbacks and failures in any field of clinical biomedical research and the worthiness of the field itself.” He furthermore notes that “things will inevitably go wrong even in the best designed and most carefully carried out studies.”

But Friedmann’s pragmatism loses its force when one considers his own acknowledgment that “Very few relevant facts have yet become available.” On what basis is it possible to imply that Mohr’s death was the result of an “inevitable” failure, or that the Targeted Genetics study was well designed or carefully carried out? The blanket assertion that things inevitably go wrong in clinical trials speaks little to whether the outcome in this particular trial was inevitable.

In fact, Friedmann had reason to know that experts in the field had previously expressed doubts about the study’s design. That’s because he chaired the 2003 meeting at which the RAC discussed Targeted Genetics’ protocol for the arthritis study and raised numerous concerns. To be sure, Weiss reports in his July 28 article that Friedmann “said he does not recall the meeting.” Having been reminded by Weiss, perhaps Friedmann should have reviewed that meeting’s minutes – which are available online – to refresh his memory on the committee’s now prescient concerns before suggesting that Mohr’s death was an unfortunate inevitability.

Friedmann also asserts that “the setbacks in clinical gene therapy trials have been few – two patient deaths and a handful of other serious occurrences proved to be a direct result of gene transfer procedures.” However, this issue is not as clear-cut as he suggests. We simply don’t know how many deaths or serious problems gene transfer experiments have produced since most of the records have never been made public. After Jesse Gelsinger’s gene transfer death in 1999, reporters Rick Weiss and Deborah Nelson filed FOIA requests and received 691 reports of serious adverse events – including some deaths – that had previously not been filed, despite the RAC regulations. Since most of these have never been investigated to determine which were a “direct result” of gene transfer, we cannot yet say that the research has hand only a “few” setbacks.

Friedmann is not alone in arguing that Mohr’s death has no serious implications for gene therapy. Northwestern University professor of medicine Eric M. Ruderman argued in the Chronicle of Higher Education that many of the concerns raised about the situation were “overblown.” Ruderman addresses two issues in particular: the fact that Mohr's personal physician recruited her after his clinic received payment for these services (presumably without disclosing this relationship to patients) and that Mohr signed the consent form immediately rather than taking it home for closer consideration.

Ruderman acknowledges that these were perhaps not best practices: “You don't want a patient pushed into something,” he said. But he takes issue with characterizing these as “rules.” In fact, Ruderman told the Chronicle of Higher Education that both of these practices are routine at Northwestern, where he serves on an institutional review board.

Both of these matters go to the heart of what “informed consent” means. When deciding whether to participate in a clinical trial, many people could be swayed by knowledge that their personal physician has a financial interest in their participation, or by being asked to consider the consent form in a few minutes rather than over several days. While some have expressed concerns about whether Targeted Genetics’ consent form adequately conveys the level of risk entailed or the lack of medical benefits expected, one key issue has not yet been discussed: At the very end of the 15-page document, the reader is advised to direct “any questions concerning your rights as a study subject” to the Western Institutional Review Board, describing WIRB as “a group of people who perform independent review of research.”

This one-liner could easily give false reassurance to potential research subjects. WIRB is not independent in any ordinary sense of the word; clients like Targeted Genetics pay it to review research protocols. That is about as dependent as relationships get; WIRB’s business – its existence – depends on keeping clients happy. Moreover, quaintly describing WIRB as a “group of people” is a bit like calling Wal-Mart a “group of retail sellers”; both are the largest commercial operations of their kind in the United States. Bioethics has largely focused its conversations regarding informed consent on process and procedures. But the ethical breaches that can easily come out of such business arrangements need to be brought into more consent discussions.

Given all this, protesting that no “rules” were broken casts doubt on many researchers’ claims – in a variety of existing and emerging fields – that voluntary guidelines rather than enforceable regulations provide adequate protections to patients and research subjects. It is surprising that some have seemed more interested in defending the status quo and discrediting those who raise questions than in learning lessons that might prevent future problems and improve research subjects’ overall safety.

Marcy Darnovsky is associate executive director at the Center for Genetics and Society. Osagie K. Obasogie directs CGS’ project on Bioethics, Law, and Society. Both write for the blog Biopolitical Times.