CALIFORNIA INSTITUTE OF 
TECHNOLOGY 
PASADENA. CALIFORNIA 9112B 
DIVISION OF SIOLOOY ISO 29 
September 6, 1978 
Donald S. Frederickson 
Director 
National. Institutes of Health 
Bethesda, MD 200lU 
Dear Dr. Frederickson : 
I would like to comment on the proposed revised guidelines for 
recombinant DNA research published in the Federal Register on July 28, 
1978. As a researcher conducting experiments which involve recombinant DNA 
procedures I view the proposed revisions as a significant improvement over 
the present guidelines. The shift of decision-making responsibilities to 
local Biohazard Committees and the reduction in containment requirements 
for several classes of experiments will enchance the effective use of recombinant 
DNA techniques in basic research without posing a threat to public safety. 
It is my opinion that the relaxation of containment reauirenents are Justified 
by the state of our understanding of the potential biohazards of recombinant 
DNA experiments. No hazards have been demonstrated, and the possibility 
of converting E. coll K12 to an uncontrollable pathogen appears exceedingly 
unlikely. 
The research in my laboratory will be affected directly by the proposed 
revisions of the guidelines. First, because of the requirement that all 
changes in protocol have to be approved by the NIH office of recombinant 
DNA activities, we have often been subjected to unnecessary delays. For 
example, in the past it has taken as long as 1-2 months to gain approval 
to use a certified EK2 host-vector system which was not listed on our 
original memorandum of tinder standing and agreement. The provision 
requiring approval of minor changes in protocol at the national level 
inhibits the development of new experimental strategies within the context 
of existing guidelines, impedes progress and, in my opinion, does not 
serve the welfare of the public. By shifting more responsibility to 
local committees, long delays in implementing non-substantive modifica- 
tions of protocols or direction could be avoided. Second, the lowering 
of containment requirements for shotgun experiments with adult primate 
DNA from PU + EK2 to P2 + EK2 will make it possible for many laboratories 
to approach the question of the molecular basis of genetic disorders in 
man. For example, my laboratory and others have been studying the structure 
and chromosomal organization of human globin genes. Using recombinant 
DNA procedures we have isolated large segments of embryonic human genomic DNA 
which carry both of the 6 and 6 globin genes in a linked complex. 
One of the objectives of this research is to compare the sequences within 
and surrounding these genes in normal individuals to those in 
patients suffering from genetic disorders in hemoglobin expression 
(thalassaemias) . In order to accomplish this it is necessary to work 
with adult DNA samples. Under the present guidelines cloning adult 
human DNA can be performed only under PU + EK2 containment , and as I 
[A-83] 
