Dr. Donald S. Fredrickson 
September 23, 1978 
Page 4 
of genetic exchange as used in the Current Guidelines for Recombinant 
DNA Research were employed, then one list of exchangers would include 
any and all gram-negative microorganisms (see Appendix B to this letter). 
If, on the other hand, the criterion of genetic exchange by natural 
physiological processes is restricted to a demonstration of stable in- 
heritance and expression of chromosomal ly transferred and integrated 
genetic material, which was alluded to as the definition being employed 
during discussions of this issue at the August, 1978 RAC Committee Meet- 
ing, then inclusion of all the organisms listed in Appendix A is un- 
justified (see Appendix B to this letter). 
In establishing criteria and delineating the evidence necessary to list 
an organism or group of organisms in Appendix A, I think it realistic 
that relatedness be based on demonstration of genetic exchange and/or 
by demonstration of % 30-40% DNA sequence homology as revealed by DNA 
reassociation kinetics under stringent conditions. The necessity for 
demonstration of exchange by conjugation, transduction, or transforma- 
tion is often a haphazard circumstance influenced by luck in the choice 
of strains, phages and/or growth conditions. It thus seems logical that 
use of current knowledge and techniques of molecular genetics to obtain 
information on relatedness should be permitted. 
The basic idea for the exclusion stated in Section I-E-4 was due to the 
fact that recombinants formed in the laboratory by recombinant DNA 
technology between organisms that exchange DNA naturally would not be 
novel. The issue of safety was secondary. However, the safety issue 
has apparently been used to exclude some but not all organisms listed 
in Appendix D of the Proposed Environmental Impact Statement (p. 33158) 
from the list of organisms in Appendix A of the Proposed Revised Guide- 
lines (p. 33089). In addition, the safety issue has been used inconsist- 
ently since those species of Bordetel la , Pasteurella , Yersinia , Neisseria , 
etc. that are animal pathogens and which have been demonstrated to ex- 
change plasmids, at least, with £. col i are excluded whereas all species 
of Pseudomonas and Erwinia , many of which are plant pathogens and many 
of which have not been demonstrated to exchange genetic information with 
£. col i , are included in Appendix A. I realize that NIH has greatest 
familiarity and responsibility for the public health of humans, but I 
should reiterate what I have often said that the human species is de- 
pendent upon plants, not the other way around. Thus while I am not 
totally opposed to the issue of safety being used to omit certain or- 
ganisms from lists to be included in Appendix A, I do believe that the 
basis for such decisions should be stated and appropriate consideration 
to the safety of all important higher organisms should be given. 
b. The next problem concerns the taxonomic relatedness and evidence for 
genetic exchange among the organisms listed in Appendix A (p. 33089). 
Since I am not an expert on bacterial taxonomy, I have relied on Bergey's 
Manual of Determinative Bacteriology (8th edition) and the guanine-cyto- 
[A-311] 
