Recombinant DNA Advisory Committee - 12/1*2/94 
subcommittee to address these issues. 
Mr. Capron stated that development of stem cell technology and gene transduction of spermatogonia point to 
a future for gene therapy. One additional legal and ethical consideration of in utero gene therapy is the 
involvement of the body of the mother. Birth is recognized as a single event in the achievement of a legal 
personhood. Fetal intervention cannot be imposed if there is a parental objection. Mr. Capron considered 
that the question of abortion as an entrance criterion is relevant in 3 ways: (1) If the disease is serious 
enough, the usual ethical and legal prohibitions against late term abortion are overcome by agreement between 
the doctor and the parents. (2) The relevance of abortion is to avoid harm to a born person. Abortion is a 
relevant criterion for Phase I or even Phase II trials. If there is any harm known, it should not be passed onto 
a born person. (3) Another way in which abortion is relevant is in providing a justification for this form of 
treatment For autosomal recessive disease such as a -thalassemia, it is possible to offer parents in vitro 
fertilization and pretesting of the embryos with the implantation only of the unaffected one. For those people 
who absolutely object to the destruction of any embryonic life form, in utero gene therapy offers an alter nati ve 
treatment 
Mr. Capron favored the idea of creating a subcommittee, and its purview should be extended to questions of in 
utero gene therapy that might lead to germ line alterations. Such questions arise from Dr. Ralph Brinsteris 
work on sperm germ cells. The subcommittee is not only to speculate about the science itself but to ask the 
structure through which the issues can be analyzed from an ethical viewpoint. The deliberations would be 
carried out through a series of meetings with involvement of experts in the field. Mr. Capron said this 
moment is very important for him in observing the RAC reaching this point as he prepares to leave a decade 
of service to the RAC. 
Dr. Chase commended Drs. Noguchi and Patterson on formulating the in utero gene therapy issues in such a 
way that the public can have some input The research in this subject should not be confined to people who 
are already in the middle of a pregnancy, but it should be extended to individuals who are about to begin 
families. Dr. Chase suggested inviting individuals from the Ethical, Legal and Social Implications Program of 
the NIH National Center for Human Genome Research to the RAC for discussion since there is a potential 
for developing a research plan on this topic There are medical, legal, and ethical issues regarding eligibility 
criteria for abortion. The issue of the right of the fetus versus the right of the mother deserves attention in a 
public discussion. 
In agreement with Mr. Capron’s statement that the present discussion leads to issues of germ line alteration, 
Dr. Par km an dted the work of Dr. Zanjani and his colleagues who have injected into the peritoneal cavities of 
immuno- in competent fetal sheep a retroviral vector bearing the neo % gene marker. The fetal sheep treated 
with the vector were born with the vector sequences in multiple organs. These vector sequences were then 
transmitted to the subsequent generation, apparently through the germ line. Similar unintended alteration of 
the germ line could occur by attempting to treat CF in the fetal lung. Dr. Par km an said the RAC should 
focus its attention on addressing the germ line issue in terms of the categories of how germ line alteration 
might occur, which are acceptable, and which are not acceptable. 
Regarding the informed consent from the affected parents. Dr. Par km an said most of the families with serious 
genetic diseases have prior knowledge of their condition, and it would not be a traumatic decision to be made 
in a short order during pregnancy as suggested by Dr. Zallen. 
Ms. Meyers noted that fetal therapy appears to be more pertinent to some neurological diseases since it 
prevents the irreversible brain damages in the early stage of the disease. Dr. Parkman pointed out that only a 
subset of neurological disorders will benefit from the fetal therapy. If the defect is primarily within the 
neurons, such as the Tay-Sachs disease, fetal therapy will not offer any additional advantage. 
Mr. Capron said the RAC should start to discuss the issues of fetal or germ line therapy and should be 
prepared before it receives its first protocol. Dr. Chase agreed that such a preparation is needed for the RAC, 
and he suggested the subcommittee to include germ line issues in its purview. Dr. Parkman favored a focus on 
the more important germ line issues. Dr. Glorioso agreed that the fetal gene therapy should be considered 
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Recombinant DNA Research, Volume 20 
