human cloning

contributed to weakening an already questionable experiment. When the initial guidelines were extended into the clinical realm, before the Human Gene Therapy Working Group began to grapple with the specific issues in gene therapy 1983, the guidelines were poorly suited for clinical experiments. Second, the bureaucratic decision to exempt the experiment from review was perverse because it removed scrutiny while weakening the likelihood of clinical benefit, which was already extremely low. Third, and most on point when contemplating rules governing human cloning, the Cline case revealed the pathologies of multiple parallel reviews.

Dr. Cline’s experiments were either safe and likely to work or not, and the most important considerations were those that an IRB should review, not whether recombinant DNA was involved or not. Yet the local UCLA IRB encountered serious difficulty in reviewing the protocol, in part because it was an experiment with national, even worldwide implications, but review was local. When RAC shifted to reviewing human gene therapy, it in effect became a national IRB for such experiments. This was highly beneficial for the science and for the protection of the human subjects involved, for several reasons. Human gene therapy has always been “hot,” and those who do it are local stars because they attract money, prestige, and publicity. It can be difficult for local IRBs to contend with the local star, but when review moves to the national level, NIH can bring in the nation’s best minds without worrying as much about local impact. The procedures generally get more thorough technical review at a higher level of expertise. The RAC process is open and visible because unlike FDA review it is public. And it is credible and accountable because the deliberations are covered by the media, especially when major decisions are made or when controversies come to light. It is good for the science because the right information is gathered to comply with the “points to consider” document, which was itself drafted and revised following an open process.

These positive aspects of gene therapy review highlight the consequences of not having an EAB to perform the same functions for other kinds of research. Gene therapy demonstrates that a national IRB can function, despite the fact that RAC was technically operating under recombinant DNA guidelines rather than human subject regulations. Yet this came to be only because the trivial and marginally relevant fact that recombinant DNA was involved in gene therapy. That fact enabled a national committee to construct a document that addresses the same points IRBs should be concerned about.

If NIH had clicked its heels twice, it could have had a review process for difficult research issues all along. The successful national review model grew out of recombinant DNA, but if history were logical, it should have grown out of the human subjects’protections. In the past decade, NIH has careened from crisis to crisis about embryo and fetal research, research involving the cognitively and emotionally impaired, and fetal tissue research. FDA has been excoriated over its handling of RU486, use of placebos in drug trials for schizophrenia, and insufficient regard for AIDS patients and cancer patients to get access to clinical trials. Yet the nation has in its handling of gene therapy a credible model for a transparent and accountable system of national review. The lesson for NIH is the need for the ability to convene national-level IRBs to review particularly vexing research areas. The lesson for FDA is to make its rulemaking and deliberations more open.

H-23