Attachment IV - Page 11 
makes it inevitable that "suggestions to applicants" will become 
strict review criteria as decisions grow harder. With the normative 
emphasis given to this point by its explicit characterization as a set 
of review criteria, applicants may find it harder to avoid addressing 
this point than some of the more technical considerations that precede 
it. 
The problem with interpreting point C's questions as mandatory, 
however, is that it is not clear what they are asking the applicants 
to discuss. For example, point C-l has presumably already been 
answered in the proposal, under I-B-2-c-l-d and c-2 (p.2943). In 
what sense does it pose a "general," "social" issue "beyond the 
purview of local IRB's? If the point of this question is simply to 
reassure people that it will be addressed in the review, it might be 
made more effectively in other ways. 
Similarly, what is question C-2 asking? Every human gene therapy 
trial being currently considered is both "an extension of existing 
methods of health care" and "a distinct departure from present 
treatments of disease." It depends on how narrowly one construes 
"extension" and "departure." Moreover, are the applicants to respond 
to this question in terms of the existing methods of care for the 
particular disease they plan to treat, or are they to draw analogies 
from health care in general, as the wording here suggests? If the 
point is to have the applicants think about how their procedure fits 
into the traditions and under the norms of current health care 
practices, it might be more effective to ask explicitly for analogies - 
-i.e., to have applicants detail the similarities and differences they 
see between traditional modes of therapy and their own. 
Again, with C-3, are applicants to answer this in terms of their 
particular project, or, as it says here, for somatic cell gene therapy 
in general? If it is the latter, what bearing should such an essay 
have on the review of their particular proposal, other than as 
evidence of their ability to think and write well about human nature 
and the social consequences of science? Each of the three questions 
under C-3 are important ones for the scientific community to be 
thinking about, and the RAC Working Group can play a vital role in 
catalyzing that thought. But this approach, packaging them all 
together at the end of the guidelines in a single vague question to 
applicants, and leaving unclear the significance of their response to 
the review of their proposal, seems certain only to be frustrating for 
scientists. 
If the point is to encourage researchers to think about these 
questions as an integral part of planning their own work, and not as 
extraneous social kibbitzing, then why not work them into the 
guidelines where they are each especially relevant? For example, 
concern that some somatic cell trials will increase the pressure to 
attempt germ-line therapies is a corrollary of questions I-A-4 
[p.2942] about the relative advantages and disadvantages of proposed 
alternative therapies. Similarly, questions about the distinction 
between "curing disease" and "enhancing traits" could be considered 
when discussing the candidacy of the disease selected for treatment, 
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