27902 
NOTICES 
DEPARTMENT OF HEALTH, 
EDUCATION, AND WELFARE 
National Institutes of Health 
RECOMBINANT DNA RESEARCH 
Guidelines 
On Wednesday, June 23. 1976, the Di- 
rector, National Institutes of Health, 
with the concurrence of the Secretary of 
Health. Education, and Welfare, and the 
Assistant Secretary for Health, issued 
guidelines that will govern the conduct 
of NTH supported research on recombi- 
nant DNA molecules. The NIH is also 
undertaking an environmental impact 
assessment of these guidelines for re- 
combinant DNA research in accordance 
with the National Environmental Policy 
Act of 1969. 
The NIH Guidelines establish carefully 
controlled conditions for the conduct of 
experiments involving the production of 
such molecules and their insertion into 
organisms such as bacteria. These 
Guidelines replace the recommendations 
contained in the 197£> Summary State- 
ment o/ the Asilomar Conference on Re- 
combinant DNA Molecules. The latter 
would have permited research under less 
strict conditions than the NTH Guide- 
lines. 
The chronology leading to the present 
Guidelines is described in detail in the 
NTH Director’s decision document that 
follows. In summary, scientists engaged 
in this research called, in 1974, for a 
moratorium on certain kinds of experi- 
ments until an international meeting 
could be convened to consider the poten- 
tial hazards of recombinant DNA mole- 
cules. They also called upon the NIH to 
establish a committee to provide advice 
on recombinant DNA technology. 
The international meeting was held at 
the Asilomar Conference Center, Pacific 
Grove. California, in February 1975. The 
consensus of this meeting was that cer- 
tain experiments should not be done at 
the present time, but that most of the 
work on construction of recombinant 
DNA molecules should proceed with ap- 
propriate physical and biological bar- 
riers. The Asilomar Conference report 
also made interim assignments of the 
potential risks associated with different 
types of expei*Vments. The NIH then as- 
sumed responsibility for translating the 
broadly based Asilomar recommenda- 
tions into detailed guidelines for re- 
search. 
The decision by the NTH Director on 
these Guidelines was reached after ex- 
tensive scientific and public airing of the 
issues during the sixteen months which 
have elapsed since the Asilomar Confer- 
ence. The issues were discussed at pub- 
lic meetings of the Recombinant DNA 
Molecule Program Advisory Committee 
< Recombinant Advisory Committee; and 
the Advisory Committee to the NTH Di- 
rector. The Recombinant Advisory Com- 
mittee extensively debated three differ- 
ent versions of the Guidelines during 
this period. 
The Advisory Committee to the NIH 
Director, augmented with consultants 
representing law, ethics, consumer af- 
fairs and the environment, was asked to 
advise as to whether the proposed Guide- 
lines balanced responsibilty to protect 
the public with the potential benefits 
through the pursuit of new knowledge. 
The many different points of view ex- 
pressed at this meeting were taken into 
consideration in the decision. 
The NIH recognizes a special obligation 
to disseminate information on these 
guidelines as widely as possible. Accord- 
ingly. the Guidelines will be sent to all 
of the approximately 25,000 NTH grantees 
and contractors. Major professional so- 
cieties which represent scientists work- 
ing in this area will also be asked to en- 
dorse the Guidelines. The Guidelines will 
be sent to medical and scientific jour- 
nals and editors of these journals will 
be asked to request that investigators 
include a description of the physical and 
biological containment procedures used 
in any recombinant research they report 
on. International health and scientific 
organizations will also receive copies of 
the guidelines for their review. 
Filing of an environmental impact 
statement will provide opportunity for 
the sciehtific community. Federal, State 
and local agencies and the general public 
to address the potential benefits and haz- 
ards of this research area. In order for 
there to be further opportunity for pub- 
lic comment and consideration, these 
guidelines are being offered for general 
comment in the Federal Register. It 
must be clearly understood by the reader 
that the material that follows is not 
proposed rulemaking in the technical 
sense, but is a document on which early 
public comment and participation is in- 
vited. 
Please address any comments on these 
draft policies and procedures to the Di- 
rector, National Institutes of Health. 
9000 Rockville Pike, Bethesda, Maryland 
20014. All comments should be received 
by November 1, 1976. 
Additional copies of this notice are 
available from the Acting Director, Office 
of Recombinant DNA Activities, National 
Institute of General Medical Sciences, 
National Institutes of Health, 9000 Rock- 
ville Pike, Bethesda, Maryland 20014. 
Donald S. Fredrickson, 
Director, 
NIH National Institutes of Health. 
<toe 25, 1976. 
Decision of the Director, National In- 
stitutes of Health To Release Guide- 
lines for Research on Recombinant 
DNA Molecules 
June 23, 1976. 
Introduction 
l. General Policy Considerations. 
A. Science Policy. 
B. Implementation Within the NTH. 
C. Implementation Bevond the Purview 
of NIH. 
D. Environmental Policy. 
n. Methods of Containment (See Guide- 
lines II ) . 
m. Prohibited Experiments (See Guide- 
lines m. A). 
IV. Permissible Experiments: E. Coli K-12 
Host-Vector Systems (See Guidelines IT I. B, 
1 ). 
V. Classification of Experiments Using the 
E. Coli K-12 Containment Systems (See 
Guidelines HI. B, 2). 
VI. Classification of Experiments Using 
Containment Systems Other than E. Coli K- 
12 (See Guidelines HI. B. 4). 
vii. Boles and Responsibilities (See 
Guidelines IV). 
INTRODUCTION 
Today, with the concurrence of the 
Secretary of Health, Education, and Wel- 
fare and the Assistant Secretary for 
Health, I am releasing guidelines that 
will govern the conduct of NTH -sup- 
ported research on recombinant DNA 
molecules (molecules resulting from the 
recombination in cell-free systems of 
segments of deoxyribonucleic acid, the 
material that determines the hereditary 
characteristics of all known cells) . These 
guidelines establish carefully controlled 
conditions for the conduct of experiments 
involving the insertion of such recom- 
binant genes into organisms, such as bac- 
teria. The chronology leading to the pres- 
ent glidelines and the decision to release 
them are outlined in this introduction. 
In addition to developing these guide- 
lines. NTH has undertaken an environ- 
mental impact assessment of these guide- 
lines for recombinant DNA research in 
accordance with the National Environ- 
mental Policy Act of 1969 (NEPA) . The 
guidelines are being released prior to 
completion of this assessment. They will 
replace the current Asilomar guidelines, 
discussed below, which in many instances 
allow research to proceed under less 
strict conditions. Because the NIH guide- 
lines will afford a greater degree of scru- 
tiny and protection, they are being re- 
leased today, and will be effective while 
the environmental impact assessment is 
under way. 
Recombinant DNA research brings to 
the fore certain problems in assessing 
the potential impact of basic science on 
society as a whole, including the manner 
of providing public participation in those 
asessments. The field of research involved 
is a rapidly moving one, at the leading 
edge of biological science. The experi- 
ments are extremely technical and com- 
plex. Molecular biologists active in this 
research have means of keeping in- 
formed, but even they may fail to keep 
abreast of the newest developments. It 
is not surprising that scientists in other 
fields and the general public have diffi- 
culty in understanding advances in re- 
combinant DNA research. Yet public 
awareness and understanding of this line 
of investigation is vital. 
It was the scientists engaged in recom- 
binant DNA research who called for a 
moratorium on certain kinds of experi- 
ments in order to assess the risks and de- 
vise appropriate guidelines. The capa- 
bility to perform DNA recombinations, 
and the potential hazards, had become 
apparent at the Gordon Research Con- 
ference on Nucleic Acids in July 1973. 
Those in attendance voted to send an 
open letter to Dr. Philip Handler, Presi- 
dent of the National Academy of Sci- 
ences, and to Dr. John R. Hogness, Presi- 
dent of the Institute of Medicine, NAS. 
The letter, appearing in Science 181, 1114, 
(1973), suggested “that the Academies 
FEDERAL REGISTER, VOL 41, NO. 131 — WEDNESDAY, JULY 7, 1976 
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