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Federal Register / Vol. 46, No. Ill / Wednesday, June 10, 1981 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
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 first 
annual update of the NIH program to 
assess the risks of recombinant DNA 
research. 
EPFECTIVE date: June 10, 1981. 
FOR FURTHER INFORMATION CONTACT: 
Additional information may be obtained 
from Dr. William J. Gartland, Jr., 
Director, Office of Recombinant DNA 
Activities, NIAID, Building 31, Room 
4A52, National Institutes of Health, 
Bethesda, Maryland 20205 (301-496- 
6051J. 
SUPPLEMENTAL INFORMATION: 
I. Decision of the NIH Director to issue 
the Final Plan. 
The proposed first annual update was 
published in the Federal Register, 
Volume 45, No. 182, Wednesday, 
September 17, 1980, pages 61874 to 
61878. A formal closing date for public 
comment of December 16, 1980, was 
established. 
A. Eight correspondents submitted 
comments on the plan. They were 
divided into generic categories as 
follows: 
1. General Opposition to the Risk 
Assessment Program. 
One correspondent objected to the 
fact that the program failed to evaluate 
the risks “created by the regulations of 
recombinant DNA research.” It was 
stated that risk assessment studies 
should be addressed to the risks created 
in the laboratory by the use of chemicals 
employed as disinfectants: by excessive 
use of autoclaves; by use of automatic 
formaldehyde atomizer guns; and other 
various dangers due to crowded 
conditions and inadequate ventilation of 
laboratories. The commentator 
suggested that the name of the program 
should be changed to "Program to 
Assess the Hpyothetical Risks of the 
Recombinant DNA Technique.” Further, 
the author objected to the title of the 
course “Microbiological Principles and 
Techniques for Work With Potentially 
Biohazardous Agents Including 
Recombiant DNA” to be sponsored by 
the NIH. 
In response to the main criticism 
raised, the laboratory practices and 
containment procedures specified in the 
Guidelines are those that have been 
widely used in containing 
microorganisms. 
A second commentator said that there 
is absolutely no evidence, thus far, that 
indicates that recombinant DNA 
research is unusually risky. Further, he 
stated that intended programs to 
evaluate risks will never be able to 
prove that the risk is negative. The 
commentator concluded that “the NIH 
should get out of the recombinant DNA 
businesses rapidly as possible.” 
As I noted in issuing the first final 
plan, I am required to establish that 
actions under the NIH Guidelines for 
Research Involving Recombiant DNA 
Molecules present no significant risks to 
health or the environment. 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 
plan is an attempt to satisfy this 
remaining need and will afford an 
opportunity to assess progress toward 
achieving the scientific objectives. 
2. Criticism of the Program and the 
Risk Assessment Experiments. 
One writer expressed concern that the 
proposed risk assessment plan update 
does not address “non-scientific risks,” 
such as risks of accidents due to 
carelessness or arrogance, risks of 
sabotage, and risks of intentional misuse 
of recombinant DNA technology. An 
objection was also raised to a statement 
in the Plan which asserts that much 
information on recombinant DNA risk 
analysis has come from research not 
primarily designed to assess risks. It is 
the opinion of the writer that it is not 
good scientific practice to base policy 
and conclusions on research that was 
not designed specifically to provide 
information on risk. 
The objective of the risk assessment 
program is to obtain information derived 
from scientific experiments relevant to 
the use of recombinant DNA molecules 
which would also be applicable to cases 
of accidents, carelessness, etc. 
It still remains our conviction as 
stated in the first Final Plan that: 
The vast majority of information relevant 
to recombinant DNA risk analysis has 
already come from research not primarily 
designed to provide information on risk. This 
will undoubtedly continue to be the case. 
This information will be obtained chiefly 
from publications in the scientific literature, 
from persons with special scientific 
knowledge, and from ongoing basic 
biomedical research. Risk assessment 
analysis will require continuing review of 
data developed in the fields of microbiology, 
infectious deseases, and related biological 
research. 
Some essential information has been, 
and will continue to be, derived from 
projects specifically designed to assess 
various aspects of potential risks 
associated with recombinant DNA 
experimentation. Such experiments will 
be supported by the Intramural and 
Extramural programs of NIH. Many 
experiments may also be conducted in 
the private sector or may be funded by 
other agencies or governments. 
The essential goal of a successful risk 
assessment plan will be the development of 
means to collect, collate, coordinate, 
evaluate, and disseminate data obtained from 
all sources. 
Another commentator criticized the 
interpretation of the results of polyoma 
risk assessment experiments. The 
correspondent noted that positive 
results were obtained with regard to 
oncogenicity and infectivity when 
cloned dimeric polyoma DNA was 
carried in intact phage lambda particles. 
The published results and 
interpretations derived from the 
polyoma DNA risk experiments have 
been the subject of wide reviews and 
discussions. The consensus of most 
scientists supports the conclusions of j 
the investigators who conducted the 
polyoma risk assessment experiments 
that neither potentially infectious nor 
tumorigenic recombinant DNA was 
transferred out of the EK2 host into ! 
susceptible mice or hamster cells to I 
produce progeny virions or tumors. | 
Further, propagation of polyoma viral j 
DNA as a component of a recombinant 
DNA molecule in E. coli K-12 reduces 
its biologic activity as an infectious unit 
many orders of magnitude relative to the 
virus. ■ 
3. Support and General Suggestions > 
for the Program. ) 
Three correspondents submitted 
letters supporting the Proposed Plan as 
published, and made some general 
suggestions for improvement. One i 
commentator said that the risk ' 
assessment work has helped to allay 
many initial fears of this area of f 
research. This correspondent also felt ^ 
that it will be difficult to devise 
systematic standards for training all the f 
workers in various areas of recombinant 
DNA research. > 
Another commentator stated that it 
would be prudent to provide risk J! 
assessment experiments to assess ^ 
parameters of possible hazards for some jw 
of the more widely used host organisms ' 
not heretofore assessed. J* 
One commentator stated that it was ’ 
his impression that at the Pasadena f‘ 
Recombinant DNA Risk Assessment '' 
Workshop the question was not one of ^ 
concern about antibody to insulin made 
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