Getting Sober on Stem Cells

Stem cell research might need to be the tortoise to gene therapy’s hare. In the most recent issue of Science, James M. Wilson of the University of Pennsylvania, cautions stem cell research advocates to avoid the hype surrounding much work in the field (sub’s required). Wilson understands first-hand the pitfalls of proceeding too quickly with a novel therapeutic technology, as he was the principal investigator in a gene therapy trial that resulted in the death of 18-year-old Jesse Gelsinger in 1999.

As a safeguard, he recommends the National Institutes of Health establish a body like the Recombinant DNA Advisory Committee, which reviews any gene therapy trails funded by NIH, to conduct pre-clinical review of the basic stem cell research. This echoes the recommendation Michael Peroski and I made in our report, “A Life Sciences Crucible.”

Wilson fears that advocates and the media are overselling stem cells in the same way both groups oversold gene therapy in the 1990s. To avoid a similar fate for new therapies, he recommends thorough basic research, better communication of how that research process works, attention to realistic timeframes and scopes for stem cell therapies, and greater preclinical transparency. But similar to our recommendations, Wilson does not want this new board to add another level of bureaucracy to the Food and Drug Administration’s review. Its goal should be to allay public concerns and allow for transparent discussion of novel trial-related issues.

Boosters promoted novel gene therapies during the late 1980s and 1990s. There were over 400 gene therapy clinical trials worldwide by 2000. However, Wilson notes that in a September 2000 review, the FDA concluded that “the hyperbole has exceeded the results” and “little has worked.” Gene therapy did produce some positive clinical results that help curtail hereditary blindness and immune deficiencies. Nevertheless, there were many adverse events such as treatment-induced cancers and Gelsinger’s death.

Even though gene therapy was not burdened by a polarizing ethical debate like embryonic stem cell research, ethical and scientific warning signs went unheeded. In 1995, then-NIH director Harold Varmus convened a panel which issued a report concluding that there were “only a minority” of clinical studies that had been designed in ways that might yield “useful basic information” on gene transfer vectors and host-vector interactions. The panel recommended that more basic research was necessary to develop an understanding of gene transfer in animals. These warnings turned out to be right, since just about “every major unexpected toxicity encountered in gene therapy clinical trials can be attributed to complex interactions between vector and host that were not predicted by, or understood at the time of, preclinical studies,” as Wilson explains.

He assigns blame not only to the scientists but also to an uncritical news media, overeager patient advocates looking for a panacea, and the economic fervor surrounding the biotech bubble before it burst. But he remains slightly more optimistic about stem cell research, since there have been more papers published on the basic biology of stem cells than there were on gene therapy before the latter field’s first clinical trials. He still cautions, however, that researchers must look carefully at the clinical safety and utility of human embryonic stem cells and induced pluripotent stem cells, since “[q]uestions about engraftment, rejection, and toxicity abound.”

In our report, we note that the FDA, while still having ultimate authority, will nevertheless have a steep learning curve to overcome as stem cells enter clinical trials. Regulators, researchers, patients, and ethicists need a place to consider the adverse events, discuss the risks and benefits of the therapies, and issue general guidelines for FDA as it develops its own long-term protocols for clinical trials involving stem cells. Wilson even recommends that the Recombinant DNA Advisory Committee-like body consider whether the clinical guidelines developed by International Society for Stem Cell Research should be codified as NIH guidelines.

As stem cell research proceeds under the responsible and ethical guidelines outlined by the Obama administration, let us heed Wilson’s words of caution: “It would be unfortunate if the field of stem cell research missed this lesson from history” and “no one is served by bypassing the hard work of basic research and experiments in animal models.”

More on stem cells: Timeline: A Brief History of Stem Cell Research

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