Human Gene Therapy Subcommittee - 11/21-22/91 
mutagenesis that would be relevant to this issue. 
Dr. Mclvor stated that the issue of homologous recombination is quite pertinent if germ 
line transfer will likely be considered in the context of human disease, perhaps recessive 
disease. 
Dr. Mclvor suggested that the issue of inadvertent germ line effect should be segregated 
from the issue of intentional germ line intervention. The issue of inadvertent effects is 
relevant to current protocols, whereas intentional intervention is an issue of the future. 
Dr. Parkman noted that it is critical for the subcommittee to consider the ethical and 
scientific issues resulting from specific attempts to introduce genetic changes into the 
germ lines of patients. Mr. Capron commented that in the Points to Consider , there is 
currently no absolute prohibition against the risk for vertical transmission. Therefore, 
this issue needs to be addressed. The possibility of vertical transmission of a gene to the 
offspring of an individual should be the first agenda item that the HGTS discusses and to 
consider this part of the process of examining the larger issue of intentional germ line 
intervention. 
Dr. McGarrity noted that another critical issue that must be considered by the HGTS is 
that of fetal intervention. It is probable that the issues surrounding fetal genetic 
intervention will emerge prior to germ line intervention. This case would provide a 
model for which to discuss the ethical, legal, and moral issues regarding informed 
consent in germ line intervention and would provide a starting point for discussion. 
From a medical standpoint, there are numerous diseases in which the optimal time to 
intervene will be in utero. Dr. Parkman said that the issue of fetal intervention relates to 
pre-implantation diagnosis. Mr. Capron questioned the relevance of the fetal 
intervention issue because it is unclear that the germ line effect on a fetus would be 
different from that on an eight-week old child. Dr. McGarrity added that although 
scientifically there is no difference in germ line effect, the issue will be perceived 
differently by the public, therefore, it is important to provide a basis for considering the 
moral and ethical issues. However, fetal protocols cannot be considered at this time due 
to the Federal ban on fetal research. 
Dr. Cook-Deegan noted that it is difficult to predict the safety concerns and to regulate 
the technology associated with genetic intervention in an embryo or fetus. Novel 
regulatory issues are raised because the issue of possible teratogenicity exists. Unless 
you obtain complete gene conversion through targeted homologous recombination, there 
is always the possibility of inserting a gene that is capable of producing other changes 
that will pass through the whole developmental cycle. How would the safety issues be 
defined? Dr. Parkman acknowledged that a gene could be inserted into a mature cell 
and produce no deleterious effects. However, the same gene could have a deleterious 
effect if inserted into a cell that has not differentiated. 
Recombinant DNA Research, Volume 15 
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