DEPARTMENT OF MICROBIOLOGY AND MOLECULAR GENETICS 
HARVARD MEDICAL SCHOOL 
25 Shattuck Street 
BOSTON, MASSACHUSETTS 0211S 
January 22, 1981 
Dr. William Gartland, Jr. 
Director 
Office of Recombinant DNA Activities 
NIAID 
National Institutes of Health 
Bethesda, Maryland 20205 
Dear Bill: 
I am writing in ref erence to the two alternative proposals for 
revision of the NIH guidelines for Recombinant DNA research which 
will come before the RAC at its February meeting. 
Despite my sympathy for the rationale behind the Baltimore-Campbel 
proposal I believe it to be premature to do away with all mandatory 
aspects of the guidlines. Unexpected surprises still do arise as was 
seen by (i) the survival for longer than expected periods of time of 
the 'disabled’ coli strains during testing with human subjects; 
(ii) higher than expected survival of 'disabled' coli in sewage 
treatment plant tests; (iii) the converting of coli K-12 into a 
pathogen through the cloning of a hemolysin determinant from the 
wild type strain (Portnoy & Falkow, 1981, Bacteriol . 148 , 877); 
and (iv) the production of infectious polio virions from a cDNA copy 
(Racaniello & Baltimore, 1981, Science 214 , 916). Other similar examples 
could be sited. 
The alternative proposal by Susan Gottesman constructively deals 
with my concerns while still doing away with much of the undesirable 
red tape and delays previously associated with the guidelines . In 
particular, this modified but still mandatory version of the guidelines 
still covers what I believe to be areas of possible hazard: (1) the 
deliberate introduction of recombinant organisms into the environment 
(history records that the deliberate release of new organisms into 
an environment has sometimes been disastrous) . Certainly in this 
area there should at least be the opportunity for public review and 
approval before such studies are carried out; (ii) the deliberate 
introduction of antibiotic resistance genes into organisms in which 
such genes are not normally found; (iii) the cloning of toxin genes 
(those specified in appendix G of the present guidelines) . To this 
list I would also prefer to see something added with respect to 
cloning experiments which might produce a pathogenic virus (see above 
Racaniello & Baltimore article) . 
The Gottesman proposal appears to me to retain both NIH (ORDA) 
and local (IBC) oversight of recombinant DNA research in areas of 
legitimate scientific concern. It allows for efficient and uniform 
decisions to be made based on retention of national standards for 
the setting of containment levels. These aspects of the Gottesman 
proposal combined with the fact that it both lowers containment 
where appropriate and reduces much of the cumbersome paperwork 
make it appear far more desireable than the alternative Baltimore- 
Campbell proposal. 
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