Ethical Issues in Gene Therapy 
The subjects in the first gene therapy trials will likely be infants 
or children in danger of increasing morbidity or death as a result of 
their inherited disease and its predictable symptoms. In Lesch-Nyhan 
syndrome, in the absence of allopurinol therapy, most patients have 
died before 5 years of age. A few survivors, with this form of therapy, 
have lived to 20 or more years (Bergsma, 1982, p. 645). Candidates 
for Lesch-Nyhan gene therapy will likely be children. In ADA and 
PNP deficiency, the subjects will likely be infants, since the gross 
impairment of the T-cell functions in these children renders them at 
significant risk of death from infection in the first year of life (Emery 
and Rimoin, 1983, pp. 1294—1295). Current regulations governing 
research review require the review body to determine that: 
Where some or all of the subjects are likely to be vulnerable to coercion or 
undue influence, such as persons with acute or severe physical or mental illness 
. . . appropriate additional safeguards have been included in the study to protect 
the rights and welfare of these subjects (Protection of Human Subjects, 1983, 
45 CFR 46.111(b)). 
Arc additional protections needed for these likely subjects? Some 
reasons suggest that the 1RB may at least consider this possibility. 
First, the threat of the disease to the child may foster a tendency 
to reason that higher risks are worth taking, even for benefits that are 
unclear or unknown. The danger of the child’s life situation itself 
may be used as a justification for risk-taking in research. This form 
of reasoning was long ago criticized by Beecher (1970, p. 85) who 
pointed to “reports wherein the term hopelessly incurable seems 
to be used to justify dangerous experimentation”. Decisionmakers 
should guard against this form of reasoning both in research review 
and the process of consent itself, even if the degree of risk does not 
approach the level of ‘dangerous’. Desperation about the child’s con- 
dition is not a sound premise for experimental gene therapy. Children 
in imminent danger of death should not be selected as subjects for 
the first trials. 
Analogous moral experience has accumulated in Phase I cancer 
trials with adults and children (Lipsett, 1982, p. 941;Capron, 1983, 
p. 882; Ackerman and Strong, 1983, p. 883). Even though therapeutic 
intent is present, veracity compels that the purpose of a Phase I trial 
be explained to patients and parents as primarily scientific in nature. 
However, the most compelling reason to begin for Phase I cancer 
trials is the potential for human benefit, based on in vitro and animal 
studies. This motivation must not be omitted from the presentation 
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