John C. Fletcher 
Department of Health and Human Services, 1985). In the interim 
between final preparation of such protocols and research review, a 
pause is available for reflection. 
At attempt in 1980 to treat two patients with betathalassemia by 
cells containing recombinant DNA was inconclusive. Scientists and 
others also criticized this experiment as premature and ethically un- 
acceptable (Friedmann, 1983, p. 26). Just after this event occurred, 
criteria for experimental gene therapy (Anderson and Fletcher, 1980) 
were set forth for a Fitting scientific prelude to the ethical accept- 
ability of human trials: 
An animal trial should show that: 
(1) New, curative genes can be directed to specific cells and remain there 
long enough to be effective, 
(2) The added genes will express their product in the target cells at a suffi- 
cient and appropriate level, and 
(3) No harm will result to the treated or surrounding cells, to the test animal, 
or its offspring. 
Anderson, in this issue (1985) and elsewhere (Anderson, 1984) 
describes the state of the art of genetic experiments in animals as of 
late 1984. Retroviral vectors for gene therapy, compared with other 
possibilities, are a “reasonably efficient delivery system” (Anderson, 
1984, p. 404). More work is needed to strengthen reliability and 
safety of these vectors. As animal experiments progress in these 
directions, plans have been made to treat patients with Lesch-Nyhan 
syndrome and two disorders that involve deficiencies of the immune 
system, namely, adenosine deaminase deficiency (ADA) and purine 
nucleoside phosphorylase deficiency (PNP) (Rawls, 1984, p. 40). The 
technique will probably involve removal of some of the patient’s 
bone marrow, insertion of normal genes by means of a retroviral 
vector, and reinsertion of the treated cells into the patient. It is 
hoped that these treated cells will be able to produce the missing 
product needed by the patient. 
Proposals for somatic cell therapy have met with two types of 
ethical objections. First, from the premise of protection of human 
research subjects, physicians most knowledgeable in this field have 
stressed that the three criteria above are as yet incompletely met 
(Friedmann, 1983, p. 51). Problems still remain to show that infec- 
tion, malignancies, or sterility do not result in experimental animals 
due to gene therapy. Trials of transplanted, treated bone marrow still 
need to be done in mice and primates. Studies in primates will be 
[336] 
Recombinant DNA Research, Volume 12 
