Human Gene Therapy 
in any gene transfer procedure, the damaging effect caused by a 
harmful insertion site could be great when it occurs in the egg but 
may be negligible when it occurs in one or a few of a large number 
of bone marrow cells. 
The third objection to microinjection of eggs is limited usefulness. 
Not only is it ethically questionable to experiment on human eggs 
because of the expected losses, but even if ‘success’ were obtained, 
it would be applicable primarily when both patients arc homozygous 
for the defect. When the parents are both carriers of a recessive trait, 
only one fertilized egg out of four would result in an affected child. 
Since a homozygous defect cannot yet be recognized in early em- 
bryos, and since the procedure itself carries such a high risk, it would 
be improper to attempt any manipulation in this situation. Further- 
more, most of the very serious genetic disorders result in infertility 
(or death before reproductive age) in homozygous patients. Conse- 
quently, there would be little use for the procedure even if it were 
feasible. 
Ethics 
Even when the technical capability becomes available to attempt 
germ line gene therapy in humans, there are major medical and ethical 
concerns to consider. The medical issues center primarily around the 
question: will the transmitted gene itself, or any side effects caused 
by its presence, adversely affect the immediate offspring or their 
descendants? Since in this case one must study several generations 
of progeny to obtain answers, it will clearly take longer to gain 
knowledge from animal studies on the long-term safety of germ line 
gene therapy than on somatic cell gene therapy. 
Germ line therapy deserves careful ethical consideration well in 
advance of the time when the technical capability for carrying it out 
arrives. The critical ethical question is: should a treatment which 
produces an inherited change, and could therefore perpetuate in 
future generations any mistake or unanticipated problems resulting 
from the therapy, ever be undertaken? 
What criteria would be needed to justify the use of this unique 
type of therapy? At least three conditions should be met prior to the 
time that germ line gene therapy is attempted in human beings. 
First, there should be considerable previous experience with so- 
matic cell gene therapy that clearly establishes the effectiveness and 
safety of treatment of somatic cells. There is a wide range of biologi- 
cal variability among humans. Even if the first few patients treated 
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Recombinant DNA Research, Volume 12 
