DEPARTMENT OF HEALTH. EDUCATION. AND WELFARE 
PUBLIC HEALTH SERVICE 
NATIONAL INSTITUTES OF HEALTH 
September 13, 1978 
NATIONAL INSTITUTE OF 
ENVIRONMENTAL HEALTH SCIENCES 
P O. BOX 12233 
RESEARCH TRIANGLE PARK. N.C. 27709 
Dr. Donald Fredrickson 
Di rector 
National Institutes of Health 
Bethesda, Maryland 20016 
Dear Dr. Fredrickson: 
I have received a copy of the Proposed Revised Guidelines for Recombinant 
DNA Research (Federal Register 43, 33042-33178). While I am in agreement 
with almost all the RAC proposed revisions and their reasons for them, I 
would like to question the following: 
The proposed containment for shotgun recombinant DNA work on non-primate 
mammals and birds is P2 + EK2, yet for cold-blooded animals, plants and 
many of the RNA and DNA viruses it is P2 + EK2 or P3 + EK1 . Is there a 
sound scientific basis for not also allowing non-primate and bird recombi- 
nant DNA work to be also carried out under P3 + EK1? The restriction to 
the use of only P2 + EK2 is not a trivial point, since many experiments 
using EK2 vectors are extremely difficult, indeed some simply impossible 
(e.g., those involving lysogenic X systems) in an EK2 system. In particu- 
lar, I find it difficult to see why segments of some transforming viruses 
may be cloned under P3 + EK1 conditions, yet DNA from a non-primate mammal 
or bird in which any one sequence is diluted out at least one in 10 5 with 
the other sequences present cannot be carried out under these same conditions. 
I would appreciate it If you could bring to the attention of the Advisory 
Committee this suggestion, i.e., allowing non-primate and bird shotgun DNA 
experiments at P2 + EK2 or P3 + EK1 levels. 
Yours sinrprplv 
Stephen E. Harris, Ph.D. 
Senior Staff Fellow 
Laboratory of Environmental Toxicology 
[A-139] 
