Donald S. Fredrickson, M.D. 
11/9/77 Page 2. 
The modification I suggest would remove any ambiguity and would 
eliminate the apparent contradiction with the statement contained later 
in the paragraph 1 of the "Introduction" section of the Guidelines. 
(2) Other host vector systems. Many of the practical benefits of 
recombinant DNA will depend on the ability to manipulate genes within 
organisms that produce medically and biologically important products such as 
antibiotics. The development of cloning systems in such species is, in my 
opinion, of great value. Yet, in revising the guidelines, the authors of 
the section on "Other host vector systems" seem to have given little 
consideration to the importance of being able to manipulate the genes 
of such species per se , and have instead dealt with other host vector 
systems simply as possible alternatives to E_. coli for the cloning of 
genes of higher organisms. 
The revised guidelines state that cloning in host vector systems 
other than _E . coli must use strains that have "low potential for survival 
in their natural environment," regardless of the lack of pathogenicity of 
the species or the nature of the natural environment of that species. 
This appears to be a direct transfer with little additional thought of 
considerations pertaining to the use of _E. coli K12 for recombinant DNA 
experiments. I think it is important to. recall that the ^'low survival" 
attributes of _E. coli K12 were initially put forth as a response to those 
who had concerns about using a bacterial strain that they believed might 
inhabit the human intestine. At that time, critics proposed that only 
bacterial species unassociated ecologically with humans or with domestic 
animals should be used. Subsequently, data has been presented to 
indicate that E_. coli K12 has little, if any ability to colonize the human 
gastrointestinal tract. Somehow, in the course of events, the argument 
that it is safe to use _E. coli K12 as a host because it does not coloniz- 
the human intestine, has been distorted. The statement is now being made 
that JE. coli K12 should be the only approved host, and that other bacterial 
species — no matter how non-patbogenic and remote from human ecology — 
must not be used unless it is specifically demonstrated that the recipients 
have a low potential for survival in their natural environment (whatever 
that environment may be). 
I believe that this new requirement will seriously impede and perhaps 
entirely cripple work aimed at using a variety of non-pathogenic bacteria 
as hosts in experiments aimed at improving the quality or quantity of 
biological products made by those bacteria. For example, an experiment 
involving the introduction of genes by recombinant DNA methods from 
Streptomyces coelicolor to Streptomyces lividans , in order to design a 
more effective antibiotic , could simply not be done in the wild type 
antibiotic-producing strain at any level of containment whatsoever. 
[Appendix A — 313] 
