12/07/87 
Dr. Walters welcomed the new members of the subcommittee, Drs. Epstein, Erickson, and 
Parkman and the Ad Hoc Consultant, Dr. Mulligan. 
Dr. Walters cited: 
1) the proposed letter - Drs. Gorovitz, Motulsky, Grobstein, Rich will be 
thanked for their service and asked to be ad hoc . 
2) the Howard Temin letter of Dec. 1, read paragraphs 2,3, 4, 5, and 6. 
3) the Australian document, p.14, cited 2.9.2 and bottom page, re. ADA and 
PNP; p.15 cited 2.9.3; p. 16 cited 2.10; p.18 cited 2.12, paragraph 2, re. 
animal experimentation, and paragraph 3. 
4) World Medical Association document, p.2, points 3-7; to keep abreast of 
the ethical discussion worldwide. 
The Anderson Preclinical Data Document 
Dr. Anderson stated that they were not ready to submit a formal protocol today, but would 
discuss the issues. Members of his group were present with data. He stated that he has been 
working with the Food and Drug Administration (FDA) and nothing will be kept confidential. 
Dr. Epstein said that the document required great effort. There were three categories of 
substantive comments: technical efficacy, technical safety, and therapeutic efficacy. First, 
technical efficacy raised three issues: (1) incorporation of genes into target cells, the rate of 
which remains low; (2) expression of the gene, which has been low and transient; and (3) 
likelihood of transformed genes to take hold. 
Second, safety issues received principal consideration. Dr. Epstein believed that it would be 
preferable to avoid the use of helper viruses, though more work was required on this issue. 
Animal studies currently fail to provide sufficient information about helper viruses. Furthermore, 
the relevance of animal models is far from certain; even lower primates may prove to be 
inappropriate models for humans. An additional issue of great importance is the balance 
between technical efficacy and safety. Most reviewers asked for both; one reviewer stated that 
if safe, it might be appropriate to proceed with human subjects, even if it is uncertain that a given 
individual can be helped. 
Third, therapeutic efficacy has not been established. Some reviewers questioned whether 
adenosine deaminase (ADA) deficiency was an appropriate disease to try. Dr. Epstein explained 
the consensus view: the treatment method that employs polyethylene glycol-ADA (PEG-ADA) 
will be examined more closely before other treatments are attempted. He noted that the long- 
term effects of PEG-ADA are unknown, and that PEG-ADA could be used as well as gene 
therapy. 
Finally, Dr. Epstein stated that the structure of the protocol had been criticized. Because it 
contains a tremendous amount of data, the protocol is very difficult to read. He hoped that in 
Recombinant DNA Research, Volume 13 
[93] 
