COVINGTON S. BURLING 
Donald S. Fredrickson, M.D. 
February 20, 1976 
Page Five 
Nonetheless, I believe it would be useful for the preamble fully 
to discuss this issue and to state why development of EK-2 and 
EK-3 organisms will provide adequate public protection even 
though E. Coli is prevalent in man. 
3. I would urge reconsideration of the use of SV-40 
virus with anything less than a physical containment level of 
P-4 at this time. The written materials I have seen contain 
no scientific documentation for the assertion that this cancer 
virus, which clearly can infect man, produces no harmful effects. 
Indeed, although this assertion was made by two individuals at 
the meeting, in discussions during breaks in the meeting a number 
of people hotly disputed that assertion. Some have stated that 
there is clear evidence that the SV-40 contamination of polio 
vaccine did in fact result in harmful effects in children. 
I am not technically competent to judge the merits of 
this issue. On the other hand, any scientist who wishes to 
use in this type of experimentation a virus which is known 
to cause cancer in animals, and which is also known to infect 
humans, clearly must bear a substantial burden of showing that 
there is no possibility whatever of harm to man before it should 
be permitted. Any doubt whatever should be resolved on the side 
of public safety. At the very least, therefore, if you do not 
conclude to ban all experimentation with SV-40 or at least place 
it under P-4 conditions, the preamble to the document must explain 
in detail the reasons for your decision. 
4. The guidelines should be carefully reviewed to deter- 
mine proper use of the terms "shall" and "should". To a lawyer, 
"should" means "you are not required to do this." As Dr. Hogness 
stated at the meeting, the NIH Advisory Committee paid little or 
no attention to this distinction, and it is therefore necessary 
that this aspect of the guidelines be reconsidered in detail. 
5. The guidelines should also be revised to state 
explicitly what will be done with existing cloned material of a 
type that will no longer be permitted. Recommendations with 
respect to this issue were included in the minutes of the NIH 
Advisory Committee's meetings, but were not included in the guide- 
lines themselves. 
6. The procedure for approval of EK-2 and EK-3 materials 
should be stated explicitly in the guidelines. The guidelines 
should also state that no experiments may be conducted with EK-2 
and EK-3 organisms without first obtaining approval of the NIH 
Advisory Committee. These conclusions were apparently also 
included in the minutes but not fully reflected in the guidelines. 
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