MASSACHUSETTS INSTITUTE OF TECHNOLOGY Cambridge. Massachusetts 02139 
Dr. Donald S. Fredrickson 
Director 
Department of Health Education and Welfare 
Public Health Service 
National Institutes of Health 
Bethesda, Maryland 20014 
Dear Dr. Fredrickson, 
I think revisions of the NIH guidelines are long over due. 
I fault you and NIH for being so slow and formal In adopting the 
revisions and hope that after this 105 days of useless waiting, there 
will be no futher delay. The next and final step in this DNA 
recombinant guideline farce Is to do away with federal guidelines 
and the expensive paper work Involved. 
The following comments should be considered in forming 
the final draft of the guidelines. 
1. In Section III-A-2a-(l) DNA Viruses , there should be some 
stated definition as to whether a DNA virus is a transforming or non- 
transforming virus. In particular it would be helpful to relate this 
classification to either class 1-4 of Appendix B or the classification 
of oncogenic viruses. 
2. In Section I I I -C - 1 -£- ( 1 ) , the requirement that defective vectors 
of Ad5 or 2 have deletions of 2 capsid genes is awkward. The best 
defective adenovirus vector system available is one where the transforming 
region of Ad2 or 5 Is deleted (making this an absolutely defective virus and 
a non-pathogen) and the foreign DNA substituted at this site. The 
growth of the defective virus Is complemented by infection of an Ad5 DNA 
transformed cell line; the 293 cell line. I recommend removing the 
term capsid and substituting it with essential genes . 
3. In Section IV-A-l-d- last sentence of paragraph. I do not 
believe NIH has a right to require an Institution to insure that all 
principal investigators. Irrespective of funding, have agreed to carry 
out their responsibilities under the guidelines. 
Center for Cancer Research 
Room E17-529B 
August 11, 1978 
S5 rirorol v vmiro 
Phillip A. Sharp 
Associate Professor 
PAS /ms 
[A- 9 ] 
