the University of Alabama in Birmingham I university station / BIRMINGHAM, ALABAMA 35294 
the Medical Center / department of microbiology / September 23, 1978 
Dr. Donald S. Fredrickson 
Director 
National Institutes of Health 
Bethesda, Maryland 20014 
Dear Don: 
I have read the Proposed Revised Guidelines for Recombinant DNA Research and 
accessory information as published in the Federal Register on July 28, 1978 
(p. 33042-33178) . Overall I am impressed with the way NIH has considered all 
evidence, opinions and other relevant information in drafting a well organized, 
comprehensive and realistic set of Guidelines to allow the substantial benefits 
now arising from this research to be attained for the benefit of all. In arrang- 
ing my comments on the Proposed Revisions of the Guidelines for Recombinant DNA 
Research, I decided to consider each section of the Guidelines in order of appear- 
ance and to intermix my comments of support for certain sections with those seeking 
clarification of apparent ambiguity as well as those dealing with several minor 
and two more substantial criticisms of the Guidelines as now proposed. These two 
more significant criticisms concern Appendix A which lists microorganisms that 
exchange genetic information and the levels of containment for some experiments 
involving cloning of eukaryotic viral DNA sequences in EK1 host-vector systems 
of Escherichia col i K-12. 
My comments are as follows: 
1. The basis for the conclusion that recombinant DNA research with the E_. col i 
K-12 host-vector systems is much safer than originally believed and the means by 
which this conclusion was reached are presented in a complete and thorough manner 
in the Decision of the Director to Issue Revised Guidelines and in the Proposed 
Environmental Impact Statement. I agree with this conclusion that was initially 
stated in my letter to you of April 22, 1977 and which I have reiterated on 
numerous more recent occasions. However, in view of the substantial data to 
support this conclusion, I was somewhat bothered to read statements such as 
"....no evidence has come to light of a product created by these techniques that 
has been harmful to man or the environment" (p. 33044, Col. 1) with the implica- 
tion that these negative results are indicative of the safety of recombinant DNA 
research. I have criticized the use of this particular argument in behalf of 
the safety issue in a paper presented June 6, 1978 at the Third International 
Symposium on the Genetics of Industrial Microorganisms in Madison, Wisconsin. 
A preprint copy of this paper, which will soon be published in ASM News as well 
as in the Proceedings of the Symposium, is attached as Appendix A to this letter. 
In it I state "The sixth factor [leading to the general belief that recombinant 
research with E. coli K-12 host-vector systems is safer than originally believed] 
AN AFFIRMATIVE ACTION / EQUAL OPPORTUNITY EMPLOYER 
[A-308] 
