The Uniuersify of Michigan 
Medical School 
Ann Arbor, Michigan 48109 
Department of Microbiologv and Immunology 
6643 Medical ScierKe Building II 
Telephorte (313) 763-3531 
January 26, 1982. 
Dr. William J. Gartland, Jr. 
Director, Office of Recombinant DNA Activities 
Building 31 1 Room 4A52 
National Institutes of Health 
Bethesda, Maryland 20205 
Dear Dr. Gartland: 
This letter is to comment on the two proposals for revision of the NIH 
Guidelines for Research Involving Recombinant DNA Molecules, referenced and 
summarized in your letter of December 18, 1981. 
I have worked extensively, partly supported by a NIH contract, on 
problems of transfer of recombinant DNA molecules in coli -plasmld 
host-vector systems (partly summarized in ref. 1) and have discussed the 
potential hazards of such systems to the general population (2,3) • Much the 
same reasoning I used there can also be applied to most other host-vector 
systems. For these reasons I concluded then - and would like to reaffirm 
now - that the early serious fears expressed by some concerning the hazards of 
experimentation with recombinant DNA were contradicted by the then known facts 
and concepts of microbial ecology and pathogenicity. They were therefore 
inappropriate from the outset as a basis for restricting this research. As is 
now well known, additional research, including my own, has consistently 
confirmed this viewpoint. I therefore can support the general Intent of the 
current proposals to remove the bureaucratic burden of mandatory guidelines 
from all those research projects which must now submit to it simply because 
they happen to employ this technique. 
I feel compelled to point out, however, that the above reasoning and 
research concerning the safety of recombinant DNA technology was based on the 
assumption that the hosts employed were of a kind which were unlikely to 
colonize man or the environment and that the vectors could not reasonably be 
expected to transfer to indigenous host microorganisms or host cells. As 
implied by Dr. Susan Gottesman's proposal, these statements certainly define 
the boundaries within which we can make informed Judgements of safety. Beyond 
that, I know of no argument to allay the fears of those who may consider it 
dangerous to introduce genes that promote pathogenicity (especially those 
coding for toxins) into microorganisms which can colonize man or his 
environment or to introduce genes that may enhance pathogenicity (e.g. by 
specifying adhesins or metabolic traits such as iron chelation) into known 
(6971 
