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Federal Register / Vol. 44, No. 179 / Thursday, September 13, 1979 / Notices 
DEPARTMENT OF HEALTH, 
EDUCATION, AND WELFARE 
'< 
National Institutes of Health 
Recombinant DNA Research; Final 
Plan For a Program To Assess the 
Risks of Recombinant DNA Research 
AGENCY: National Institutes of Health. 
ACTION: Notice of final plan for a 
program to assess the risks of 
recombinant DNA research. 
SUMMARY: This notice sets forth the final 
plan for the first annual NIH program to 
assess the risks of recombinant DNA 
research. 
EFFECTIVE DATE: September 13, 1979. 
FOR FURTHER INFORMATION CONTACT: 
Additional information may be obtained 
from Dr. John Nutter, Chief, Office of 
Specialized Research and Facilities, 
NIAID, National Institutes of Health, 
Bethesda, Maryland 20205 (301-496- 
5643). 
SUPPLEMENTAL INFORMATION: 
A. Decision of the NIH Director to issue 
the Final Plan. 
I. The Proposed Plan was published in 
the Federal Register, Vol. 44, No. 64, 
Monday, April 2, 1979, pages 19302 to 
19304. Following one extension, a formal 
closing date for Public Comment of June 
2, 1979 was established. Thirteen 
correspondents submitted comments on 
the plan and they were divided into four 
generic categories as follows: 
(1) Opposition to the Program. One 
correspondent noted that there is far 
less public and scientific concern today 
regarding DNA technology than there 
has been in prior years. Risk assessment 
studies were characterized as being 
costly and time consuming, diverting 
responsible scientists from research 
activities and being of questionable and 
limited probative value. Additionally he 
noted that there exists no definitive 
evidence of risk associated with any 
research involving recombinant 
organisms or products isolated from 
such organisms. 
I am required to establish that actions 
under the NIH Guidelines for 
Recombinant DNA Research present no 
significant risks to health or the 
environment. Furthermore, to the 
maximum extent possible, these 
judgments should be based on a 
foundation of documented research that 
is subject to peer review. While I concur 
with most scientists that the perception 
of risk from this research is certainly 
less now than earlier, there still remain 
selected areas where data are 
insufficient to determine risk. This final 
plan is an attempt to satisfy this 
remaining need and will afford an 
opportunity to assess progress toward 
achieving the scientific objectives at 
least annually. 
In response to other concerns of this 
correspondent it should be noted that 
the Special Assistant for Risk 
Assessment, NIAID does not have 
authority to make rulings superseding 
the Guidelines, nor will he function in a 
preliminary review role for submissions 
to, the Recombinant DNA Advisory 
Committee (RAC). He/she will, as 
specified in the Plan, provide scientific 
leadership, aid in the interpretation of 
data from diverse sources and be the 
focus for the interaction of the Risk 
Assessment Program with the RAC. 
(2) Criticism of supporting statements. 
Three correspondents criticized the 
interpretation of recent risk assessment 
experiments involving polyoma virus 
(see also RAC section below). The 
controversy seems to be essentially 
centered on the concluding sentence in 
the second paragraph of section II of the 
Proposed Plan; “In each case, there was 
no evidence that the inserted DNA 
produced any special hazard.” It should 
be said that this experiment was 
performed by NIH scientists at the 
request of RAC and was conducted 
under P4 conditions; these 
circumstances limit the number of 
experimental variables that can be 
completed within a reasonable time. 
Accordingly, the protocols were 
reviewed widely by virologists before 
the studies were initiated. 
Since one of the initial concerns 
related to the potential for the delivery 
of recombinant DNA molecules to 
mammalian cells by prokaryotic hosts 
attention was focused on that model. 
We have again reviewed all available 
data in the light of the criticisms 
received. We conclude that in the 
polyoma virus risk assessment 
experiments, potentially infectious or 
tumorigenic recombinant DNA 
molecules were not transferred out of 
EK2 hosts into susceptible mouse or 
hamster cells to produce either progeny 
virions or tumors. We have altered the 
wording in the Final Plan to reflect this 
conclusion. 
(3) Support and General Suggestions 
for the Program. Four correspondents 
submitted letters supporting the 
Proposed Plan as published and made 
general suggestions for improving its 
effectiveness and impact. 
Both the Proposed and Final Plan 
indicate that the Special Assistant for 
Risk Assessment will represent the Plan 
to the RAC. The Special Assistant will 
be a member of NIAID, the Institute 
with programmatic responsibility. RAC 
will, in its advisory capacity, continue to 
have a major impact on the constitution 
of the relevant programs. We envision 
the Special Assistant reporting progress 
to the RAC at its meetings and the 
Committee will review each annual 
updated Plan. 
The importance of considering issues 
and synthesizing information in 
conferences and workshops was noted. 
We recognize the beneficial impact of 
this approach for identifying both 
problems and solutions and the Plan 
affords both the leadership and support 
for such activities. One area for such an 
approach is the question of autoimmune 
responses and this is included in the 
Plan along with other topics under 
Prokaryotic Host-Vector Systems. 
Additional areas may be added as a 
result of RAC advice and, the interaction 
of the Special Assistant with the 
scientific community and interested 
public groups. 
Encouragement to extend the specific 
studies on prokaryotic host-vector 
systems to Bacillus subtilis was 
received. The NIAID will seek the 
advice of RAC, through its Risk 
Assessment Sub-Committee, for 
suggested studies and other aspects of 
this plan. The proper emphasis and level 
of integration of B. subtilis studies with 
those based on E. coli will be a subject 
for discussion with that group. 
One correspondent suggested the 
support of “worst-possible case” 
experiments by the NIH in maximum 
containment laboratories in order to 
reveal the maximum magnitude of the 
hazards. The Plan indicates that the NIH 
has facilities appropriate for the conduct 
of such studies and we anticipate 
continuing to maintain such laboratories 
in a state of readiness. Therefore, if the 
NIH receives requests for facility 
support or advice from RAC to perform 
directly such experiments the capacity 
to do the work will exist. 
(4) Specific suggestions related to 
personal research interests. 
Five individuals submitted statements 
indicating the relationship of their 
research to the various areas indicated 
in the Proposed Plan. Most of these 
comments suggested biological 
approaches or experiments that fall 
within the Plan's areas of scientific 
interest. Areas indicated were: 
ecological studies employing novel 
tracing techniques of the host strains, 
transfer of genetic information between 
unrelated bacteria, new approaches to 
the study of E. coli colonization of 
laboratory animals, and a suggested 
protein of biological importance for 
inclusion in studies of prolonged 
colonization. 
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