NOTICES 
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argue that prokaryotes such as bacteria 
in the intestines of man do exchange 
DNA with this eukaryotic host and that 
the failure of the altered prokaryotes to 
be detected attests to a sharply limited 
capacity of such recombinants to survive. 
Thus nature, this argument runs, has al- 
ready tested the probabilities of harmful 
recombination and any survivors of such 
are already in the ecosystem. The fact is 
that we do not know which of the above- 
stated propositions is corrected. 
The intemtaional scientific commu- 
nity, as exemplified by tire Asilomar con- 
ference and the deliberations attendant 
upon preparation of the present guide- 
lines, has indicated a desire to proceed 
with research in a conservative manner. 
And most of the considerable public 
commentary on the subject, while urging 
caution, has also favored proceeding. 
Three European groups have independ- 
ently arrived at the opinion that recom- 
binant DNA research should proceed 
with caution. These are the Working 
Party on Experimental Manipulation of 
the Genetic Composition of Micro- 
Organisms, whose “Ashby Report” was 
presented to Parliament in the United 
Kingdom by the Secretary of State for 
Education and Science in January 1975; 
the Advisory Committee on Medical Re- 
search of the World Health Organiza- 
tion, which issued a press release in July 
1975; and the European Molecular Bi- 
ology Organization Standing Committee 
on Recombinant DNA, meeting in Feb- 
ruary 1976. 
There is no means for a flat proscrip- 
tion of such research throughout the 
world community of science. There is 
also no need to attempt it. It is likely 
that the evaluation engendered in the 
preparation and application of these 
guidelines will lead to beneficial review 
of some of the containment practices in 
other work that is not technically de- 
fined as recombinant DNA research. 
Recombinant DNA research with 
which these guidelines are concerned in- 
volves microorganisms such as bacteria 
or viruses or cells of higher organisms 
growing in tissue culture. It is extremely 
important for the public to be aware that 
this research is not directed to altering 
of genes in humans although some of 
the techniques developed in this re- 
search may have relevance if this is at- 
tempted in the future. 
NIH recognizes its responsibility to 
conduct and support research designed 
to determine the extent to which certain 
potentially harmful effects from recom- 
binant DNA molecules may occur. 
Among these are experiments, to be con- 
ducted under maximum containment, 
that explore the capability of foreign 
genes to alter the character of host or 
vector, rendering it harmful, as through 
the production of toxic products. 
Given the general desire that no rare 
and unexpected event arising from this 
research shall cause irreversible dam- 
age, it Is obvious that merely to estab- 
lish conservative rules of conduct for 
one group of scientists is not enough. 
The precautions must be uniformly and 
unanimously observed. Second, there 
must be full and timely exchange of ex- 
periences so that guidelines can be al- 
tered on the basis of new knowledge. The 
guidelines must also be implemented in 
a manner that protects all concerned — 
the scientific workers most likely to en- 
counter unexpected hazards and all 
forms of life within our biosphere. The 
responsibility of the scientists involved 
is as inescapable and extreme as is their 
opportunity to beneficially enrich our 
understanding. 
B. Implementation considerations 
within the NIH 
All the commentators had suggestions 
concerning the structure and function of 
decision making as it relates to the prin- 
cipal investigator, the local biohazards 
committee, the peer review group, and 
the NIH Recombinant Advisory Com- 
mittee. These comments and my re- 
sponse on the section of the guidelines 
relating to roles and responsibilities of 
investigators, their institutions, and the 
National Institutes of Health are pre- 
sented below. 
Of considerable concern to all com- 
mentators was the process by which NIH 
would proceed to implement the guide- 
lines. The scientific community generally 
urged that there be no Federal regula- 
tions, while some of the public commen- 
tators recommended the regulatory 
process. 
Many who opposed changing tire pro- 
posed guidelines into Federal regulations 
expressed concern for flexibility and ad- 
ministrative efficiency, which could best 
be achieved, in their view, through vol- 
untary compliance. Other commenta- 
tors, however, believed it imperative to 
proceed toward regulation. In their view, 
the guidelines could be implemented for 
purposes of NIH funding and would gov- 
ern the conduct of experiments until 
regulations wefe in effect. Another com- 
mentator who thought regulation would 
be harmful rather than helpful sug- 
gested that if there were to be regula- 
tions. they should be along lines similar 
to those that govern the sale, distribu- 
tion, use, and disposal of radioisotopes. 
The question of how best to proceed 
now that the guidelines have been re- 
leased deserves careful attention. I share 
the concern of those who feel that the 
guidelines must remain flexible. It is es- 
pecially important that there be oppor- 
tunity to change them quickly, based on 
new information relating to scientific 
evidence, potential risks, or safety as- 
pects of the research program. 
The suggestions for regulation need 
further attention at this time. The 
process for regulation not only involves 
the Director of NIH. but also the Assist- 
ant Secretary for Health and the Secre- 
tary of Health, Education, and Welfare. 
These guidelines are being promulgated 
now in order to afford additional protec- 
tion to all concerned. Consideration of 
their conversion to regulations can pro- 
ceed with continuing review of their con- 
tent and present and future implica- 
tions. Meanwhile, the NIH shall continue 
to provide the opportunity for public 
comment and participation at least 
equivalent to that provided if steps 
towards regulations were to proceed im- 
mediately. The guidelines will be pub- 
lished in the Federal Register forthwith 
to allow for further public comment. 
C. Implementation considerations beyond 
the purview of NIH 
Special concern has been expressed by 
many commentators regarding the ap- 
plication of the guidelines to research 
outside NIH by investigators other than 
its grantees or contractors. It has been 
urged that the guidelines be made ap- 
plicable to recombinant DNA research 
conducted or supported by other agen- 
cies in HEW and by NSF, ERDA, DoD, 
and other governmental departments. 
Most commentators believe that these or 
similar guidelines should also govern 
research in the private sector, including 
industry, voluntary organizations, and 
foundations. Many feel that experiments 
conducted in colleges, universities, and 
even in high schools require some form 
of monitoring. And finally, all agree that 
in view of the potential hazards of re- 
combinant DNA research to the bio- 
sphere. some form of international 
understanding on guidelines for the re- 
search is essential. 
The committee, in the proposed guide- 
lines. has suggested as one mqans of con- 
trol that a description of the physical 
and biological containment procedures 
practiced in a research project be in- 
cluded in the publication of research re- 
sults. In the scientfic community this 
can be a powerful force for conformity, 
and we will undertake to present the rec- 
ommendation to all appropriate jour- 
nals. We are also prepared to take steps 
to disseminate the guidelines widely, and 
to arrange for a continual flow of in- 
formation outward concerning the ac- 
tivities of the Recombinant Advisory 
Committee and the Advisory Committee 
to the Director, NIH, in the evolution of 
the guidelines and their implementation. 
In response to these suggestions, I 
have already held a meeting with rele- 
vant HEW agencies and with represent- 
atives from other departments of the 
Federal Government. The purpose of the 
meeting was to exchange information on 
recombinant DNA research and to dis- 
cuss the NIH guidelines. It served as an 
important beginning to address a com- 
mon concern of these public institutions. 
A number of the representatives indi- 
cated that various departments might 
very well adopt the guidelines for re- 
search conducted both in-house and sup- 
ported outside. Following up. I have be- 
gun preliminary discussions with the As- 
sistant Secretary for Health and the 
Secretary of HEW. to determine possible 
methods to ensure adoption of the guide- 
lines by all Federal agencies. Encouraged 
by these efforts, we held a meeting on 
June 2 with representatives of industry 
to provide them with full information 
about the guidelines and to help deter- 
mine the present and future interests of 
industrial laboratories in this type of re- 
search. The meeting provided one of the 
first opportunities for industry repre- 
sentatives to convene for a discussion of 
this research area, and an industry com- 
FEDERAL REGISTER, VOL. 41, NO. 131 — WEDNESDAY, JULY 7, 1976 
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