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Federal Register / Vol. 46. No. 233 / Friday, December 4. 1981 / Notices 
request* for excepboos from iiKlividuals. 
Institution* or corporations regardless of 
whether the applicant is affiliated with or 
supported by NIH. Such exceptions will 
generally be approved for specified levels of 
physical and biological containment.” 
This will be followed by a listing of 
those exceptions which are presently 
authorized and the containment levels 
approved for the excepted experiments. 
(4) Part VI of the NIH Guidelines shall 
be eliminated, with the following 
exceptions; 
(a) Those definitions listed In Part IV- 
C which may be needed clarify 
statements made elsewhere in the 
Guidelines shall be retained. 
(b) Those portions of Part IV-E 
deAning the composition of RAC and 
prescribing rules for RAC procedures 
shall be retained. 
(c) The following statement shall be 
added; 
"Each institution conducting or sponsoring 
racombmant DNA research should take 
responsibility for monitoring its own 
activiUe* in this area. Any unusual event* 
that might be associaled with the use of 
recombinant DNA molecule* should be 
reported to the Director. NIR” 
(5) Section VI of the Guidelines will 
be eliminated, except for those portions 
of section VI-F relevant to the 
protection of proprietary information 
submitted in support of requests for 
exceptions from the prohibitions. 
Explanation and /uaUftcation 
The action has two major effects; 
(A) It revokes the mandatory nature of 
the Guidelines by eliminating those 
I sections specifying regulatory 
procedures and their underlying 
organizational machinery. Tliese 
Guidelines would then resemble the 
CDC Guidelines in setting standards and 
providing guidance rather than in 
regulating the performance of 
experiments. This purpose is 
accomplished by items. 1. 2. 4 and 5 of 
the proposal. 
Item 5 (elimination of most of section 
VI) is included because, with the 
elimination of section IV, compliance 
with the Guidelines will effectively 
become voluntary for all individuals, 
regardless of NIH support. Special 
provision for voluntary compliance by 
individuals and institutions not 
supported by NIH then becomes 
superfluous. 
(B) It reduces the prescribed level of 
physical containment for most 
experiments to Pi. This purpose is 
accomplished by item 3. 
These two changes are justified from 
the following considerations; 
(A) Elimination of Regulatory 
Procedures. Opinions differ as to the 
widsom of the actions and arguments 
which led to the adoption of the NIH 
Guidelines in 1976. However, there is 
fairly general agreement on two points; 
(i) The establishment of Guidelines has 
had some beneficial effects. In 
particular, it has raised the general level 
of awareness among investigators and 
institutions of the importance of 
considering possible hazards that might 
arise during microbiological research. 
(ii) Since 1976. neither experimental 
evidence nor solid theoretical arguments 
have been advanced to support the 
position that recombinant ONA research 
poses any danger to human health or to 
the integrity of the natural environment. 
At this point, we doubt that the 
beneficial side effects of continued 
regulation justify the expenditure of time 
and money required to maintain a 
regulatory apparatus that has been 
developed to protect society from 
hazards that appear to be non-existent. 
(B) Reduction of Recommended 
Containment Levels. In the absence of 
known or suspected hazards, it seems 
unjustified to single out certain classes 
of experiments as requiring elevated 
levels of physical containment The cost, 
in discouraging variety and innovation 
and thereby limiting access to useful 
knowledge, is real, whereas the benefit 
is likely to be zero. The use of Pi 
containment together with the highest 
available level of biological containment 
appropriate to the experimental purpose, 
wdl keep the probability of escape and 
establishment very low without 
interfering with the conduct of most 
research. 
The prohibitions remain in force. 
Although we consider it unlikely that 
experiments in the prohibited categories 
will generate serious hazards, they 
represent the one area of the Guidelines 
which is addressed to risks whose 
nature can be specified, and that are in 
principle assessable. Restructuring of 
some of these categories aimed at 
delineating areas of real concern is 
desirable and is currently underway in 
the case of toxin genes. The results of 
such restructuring would be to define 
additional exceptions from the 
prohibitions, which would then appear 
in Part 111 of the Guidelines as amended 
by this measure. 
Annex B. — Documents Prepared by 
Working Group on Revision of the 
Guidelines 
Summary of Committee Actions. Report 
to R.\C 
At the April 1981 RAC meeting, a 
working group was established to 
consider major revisions of the 
recombinant DNA Guidelines. The 
working group, appointed by RAC 
chairman Ray Thornton, consists of 13 
members. 9 of whom were RAC 
members as of June 1980 (2 have since 
ended their terms). 2 liaison RAC 
members, and 2 other scientists who 
have had long involvement with the 
recombinant DNA issue. The list of 
members is attached. The working group 
is chaired by Susan Gottesman. Two 
meetings were held; one on June 1. 1981. 
at which 8 members were present, and 
one on July 9. 1981. at which 11 members 
were present. Minutes of both meetings 
are available. There was a clear 
consensus by the working group that 
some major restructuring of the 
guidelines was appropriate. There was 
major disagreement about how far such 
a revision should go. The basic issues 
are; (1) Are there qualitatively unique 
dangers associated with Recombinant 
DNA research? and (2) If so. what 
response is necessary for guarding 
against such hazards: is some special 
procedure required? If there are not 
qualitatively unique dangers involved, 
are the remaining risks adequately 
addressed by already existing 
procedures for dealing with research 
dangers? If not. should one use the 
recombinant DNA issue to develop 
appropriate procedures for the more 
general issues? 
After an analysis of the risks (detailed 
in the accompanying document), the 
following general conclusions were 
reached; 
(1) Accidental combinations of genes, 
rising out of “shotgun" cloning 
experiments or experiments where 
expression is not speciAcally 
engineered, are extremely unlikely to 
lead to serious problems, in most 
organisms, the barriers to expression of 
foreign genes, the necessity for new 
enzyme activities to function as an 
integrated part of an existing pathway, 
and the selective disadvantage of 
carrj’ing recombinant DNA. will 
interfere with such organisms 
establishing themselves in the 
environment and thus ultimately with 
their potential to cause harm. Therefore, 
for these experiments, the minimal 
controls associated with good 
laboratory practice should be sufficient. 
Many such experiments have already 
been exempted by the NIH from any 
special procedures. 
(2) A particular subset of experiments 
may pose some possibility of risk. In 
these experiments, the expression of 
foreign functions may have been 
deliberately increased, or normal 
functions will have been engineered to 
operate more efficiently. While there is 
no evidence that this risk is qualitatively 
(271) 
