Il\ I'rcnch Anderson 
primate, including human, DNA are different from those in mouse 
DNA. Therefore, the nature of any viral recombinants would be 
different. Treated bone marrow should be reimplantcd into primates, 
the successful transfer of intact vector DNA into blood-forming cells 
demonstrated, the expression of at least small amounts of gene 
product verified, and the existence of infectious recombinant viruses 
sought. 
Conclusion 
It now appears that effective delivery-expression systems are becom- 
ing available that will allow reasonable attempts at somatic cell gene 
therapy. The first clinical trials will probably be carried out within 
the next year. The initial protocols will be based on treatment of 
bone marrow cells with retroviral vectors carrying a normal gene. 
The safety of the procedures is the remaining major issue. Patients 
severely debilitated by having no normal copies of the gene that 
produces the enzyme HPRT, ADA, or PNP are the most likely first 
candidates for gene therapy. 
It is unrealistic to expect a complete cure from the initial attempts 
at gene therapy. Many patients who suffer from severe genetic dis- 
eases, as well as their families, are eager to participate in early clinical 
trials even if the likelihood is low that the original experiments will 
alleviate symptoms. However, for the protection of the patients 
(particularly since those with the most severe diseases and, therefore, 
the most ethically justifiable first candidates arc children), gene 
therapy trials should not be attempted until there are good animal 
data to suggest that some amelioration of the biochemical defect is 
likely. Then it would be necessary to weigh the potential risks to the 
patient, including the possibility of producing a pathologic virus or 
a malignancy, against the anticipated benefits to be gained from the 
functional gene. This risk to benefit determination, a standard proce- 
dure for all clinical research protocols, would need to be carried out 
for each patient. 
In summary, Institutional Review Boards and the NIH should 
carefully evaluate therapeutic protocols to ensure that the delivery 
system is effective, that sufficient expression can be obtained in 
bone marrow cultures and in laboratory animals to predict probable 
benefit, even if small, for the patient, and that safety protocols have 
demonstrated that the probability is low for the production of either 
a malignant cell or a harmful infectious retrovirus. Once these criteria 
are met, I maintain that it would be unethical to delay human trials. 
Recombinant DNA Research, Volume 12 
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