Federal Register / Vol. 44, No. 179 / Thursday, September 13, 1979 / Notices 
53411 
While these suggestions are relevant 
to risk assessment studies they fall 
within the broad area of research 
supported through the regular grants 
program and should be incorporated 
into applications for such support. When 
specific research activities are requested 
by NIH for support through the grant or 
contract mechanism, the solicitations 
will be widely publicized in the NIH 
Guide for Grants and Contracts and in 
the Commerce Business Daily. 
Correspondents will then have the 
opportunity to make application if their 
interests lie within the area of 
solicitation. 
One submission was received that 
addressed issues outside the Proposed 
Plan. This correspondent expressed an 
interest in pursuing research on some 
specific societal implications of 
recombinant DNA research. This 
general area was also supported in a 
less specific manner by one of the 
commenters cited in paragraph (3) 
above. This correspondent is urged to 
seek funding through the regular grants 
channels of the several agencies 
supporting research on Recombinant 
DNA Molecules. 
II. The Recombinant DNA Advisory 
Committee considered the Proposed 
Plan at its Meeting on May 21. 1979. Dr. 
Richard M. Krause. Director NIAID 
presented a summary of the program 
and responded to questions. 
Members of the public were provided 
an opportunity to address the committee 
and present their views about the 
proposed program. Comments were 
approximately equally divided between 
suggested areas to be added and 
criticisms of the interpretation of the 
polyoma risk assessment experiments 
cited in the Proposed Plan as 
background information. Suggested 
additions were to monitor nosocomial 
infections, monitor transfer from 
laboratory to wild type strains, and 
expand research on the role of plasmids 
and phages in the etiology of diseases. 
Members of the Risk Assessment Sub- 
Committee of the RAC commented on 
the Proposed Plan and other committee 
members were provided opportunity to 
comment and ask questions. The 
Scientific Aspects and Implementation 
sections were received without 
significant criticism and the RAC did not 
recommend changes in regard to other 
issues which were raised by the public. 
The final Plan will permit close 
cooperation between the Program 
constituents and the RAC. As a first step 
the NIAID will work with the Risk 
Assessment Sub-Committee in 
developing areas that require risk 
assessment projects. NIAID will develop 
a plan for the orderly implementation of 
those projects of greatest importance. 
B. Final Plan for a Program To Assess 
the Risks of Recombinant DNA 
Research 
I. Introduction 
With the issuance in December 1978 
of revised guidelines for the conduct of 
recombinant DNA research, the 
Secretary DHEW requested that the 
National Institutes of Health (NIH) 
prepare an NIH Risk Assessment Plan, 
which after review by the Recombinant 
DNA Advisory Committee (RAC) and 
publication in the Federal Register for 
comment, would be made final and 
updated annually. The present 
document is the response to that 
request. 
The major concerns about 
recombinant DNA experimentation have 
included the possible converson of non- 
pathogenic microorganisms to 
pathogenic agents, as well as the 
establishment of organisms containing 
recombinant DNA molecules in the 
ecosystem. Since the hypothetical risks 
and technical basis of recombinant DNA 
research are primarily microbiological in 
nature, the responsibility for 
coordination and implementation of the 
plan was assigned by the Director. NIH 
to the Director. National Institute of 
Allergy and Infectious Diseases 
(NIAID). 
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 
diseases, 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 the 
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. 
II. Background and Present Program 
The revision of the guidelines for 
recombinant DNA research was 
developed primarily through the 
analysis of data generated from basic 
microbiological research, such as was 
done at the Falmouth and Ascot Risk 
Assessment Workshops. An example of 
such free-ranging research efforts which 
have generated data relevant to 
recombinant DNA experimentation was 
the discovery of the intervening 
sequences that interrupt genes in 
eukaryotic DNA. This finding virtually 
assures that shotgun cloning of 
eukaryotic chromosomal DNA into 
prokaryotes will not result in the 
production of biologically active 
proteins. 
Special experiments have been and 
will continue to be specifically designed 
to assess the potential risks associated 
with recombinant DNA experiments. For 
example, within the Intramural Program 
of NIAID two experiments were 
undertaken to assess potential risks of 
this new technology. The first was an 
evaluation of the infectivity of polyoma 
DNA when the entire viral genome was 
cloned in phage and plasmid vectors of 
Escherichia coli K-12. A second 
experiment was a study of the 
pathogenicity and stability of shotgun 
clones of E. coli K-12 containing yeast 
[Saccharomyces] DNA. 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. In the second experimental 
model there was no evidence that the 
inserted DNA produced any special 
hazard. 
Specific risk assessment experiments 
have also been undertaken using the 
NIH contract mechanism. Contracts 
have been used to (1) assess the 
potential for generating aerosols in 
laboratories where recombinant DNA 
research is conducted and (2) to 
examine the EK2 systems for their 
ability to survive and their capacity to 
transfer heterologous cloned segments 
to secondary hosts under conditions 
simulating natural environments. 
An important additional source of 
information is specific DNA risk 
assessment experiments that have been 
undertaken in foreign countries. 
Scientists supported by the European 
Molecular Biology Organization (EMBO) 
have also examined the infectivity of 
recombinant polyoma plasmid and 
phage DNA in tissue culture. The results 
of these studies agree with those of 
biological in vivo assays carried out by 
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