Germline Gene Therapy: Yes or No?
Authors: Inder M. Verma
Journal: Molecular Therapy (2001)

Most gene therapy practitioners go to great lengths during their talks to emphasize that only somatic cell gene therapy is being contemplated at present. Thus, delivery of therapeutic genes is strictly for the benefit of the recipient and not to be passed on to succeeding generations. In fact, clinical protocols using viral or non-viral vectors have to rigorously establish that no inadvertent germline transfer will occur. I was therefore neither surprised nor concerned when Francis Collins, in his keynote address at the 4th Annual ASGT Meeting in Seattle last month, urged the scientific community to declare a moratorium on germline gene therapy. But the word “moratorium” did not sit well with me, and when I raised this with other attendees at the meeting, I found that I was not alone. There are two principle reasons for proposing a moratorium: safety and ethics. But what if procedures can be designed to precisely correct the defect in the egg (for example, change Δ508F, a mutation in the majority of cystic fibrosis patients, back to wild type)? Although no precise technology now exists, one can imagine the use of ribozymes, RNA-DNA hybrids, etc., followed by in vitro fertilization and successful pregnancy. The child will be born healthy, disease-free, and, presumably, able to have unaffected offspring. I am quite sure that most scientists would not shy away from germline gene therapy if such precise and safe technology were available. The larger issue—and the dilemma—is ethical: Will this technology open the floodgates to “designer babies”? Usual examples include height advantage, improved physical features, and as-yet-undefined intelligence traits. There is, of course, the question of “tinkering with nature,” which many find morally objectionable. I have also heard arguments that such gene correction may interfere with evolution, although without any coherent and credible explanation as to how. I believe that declaring a moratorium on germline gene therapy in perpetuity does not make sense. However, if the safety and efficacy of the procedure is not fully established in experimental model systems, then germline gene therapy should not be allowed. Among the cherished goals of scientists is not only the exploration of nature, but also providing relief from disease and suffering. I have little doubt that some scientists at this moment are trying to devise technologies for precise gene correction and it is only a matter of time before such procedures will be used for germline gene correction. We are better off by setting standards for acceptable safety rather than legislating the complete prevention of such technology. In fairness to Francis Collins, he did not advocate that germline gene therapy should never be contemplated. I believe what he meant was that scientists should be proactive to declare a moratorium on certain genetic manipulations that may arouse suspicion, fear, and uncertainty in the general public. Perhaps it is more honest and fruitful if the scientists took a stand that germline gene therapy should not be contemplated at present because there are no available reliable and safe procedures. Ultimately society will have to be involved in setting the ethical and moral guidelines. I am glad that these issues are being discussed publicly, which does remove the veil of secrecy so often associated with sinister scientific plots. Molecular Therapy encourages you to share your views on this important societal issue with us and our other readers.