49596 
NOTICES 
DEPARTMENT OF HEALTH, 
EDUCATION, AND WELFARE 
National Institutes of Health 
RECOMBINANT DNA RESEARCH 
Proposed Revised Guidelines 
On June 23, 1976, the Director, Na- 
tional Institutes of Health (NIH), with 
the concurrence of the Secretary of 
Health, Education, and Welfare and the 
Assistant Secretary for Health, issued 
guidelines that govern the conduct of 
NIH -supported research involving re- 
combinant DNA molecules. These guide- 
lines appeared in the Federal Register, 
July 7, 1976 (41 FR 27902 et seq.). The 
purpose of this notice is to report devel- 
opments since that publication and to 
invite public comment on the following 
draft proposing revised guidelines. 
In recombinant DNA experiments, 
"genes” — deoxyribonucleic acid (DNA) 
molecules — from living organisms can 
be transferred to single cells from com- 
pletely unrelated organisms. These ex- 
periments depend on the ability to join 
genetic material from different sources 
and to propagate the resulting elements 
in single bacterial and animal cells. 
The new recombinant DNA technique 
has resulted in a profound and qualita- 
tive change in the field of gentics. Devel- 
opments in genetic research, particularly 
in the last 4 years, open avenues to sci- 
ence that were previously inaccessible. 
Hypotheses and ideas that were not test- 
able can now be rigorously investigated. 
Understanding of basic biological phe- 
nomena has already been enhanced, and 
the promise of recombinant DNA re- 
search for better understanding and im- 
proved treatment of human disease is 
great. Further experimental data will be 
required to delimit the benefits that may 
be derived through this techniques. 
There is also a possible risk that micro- 
organisms with foreign genes could cause 
disease or adversely affect the environ- 
ment if they should escape from the labo- 
ratory and infect human beings, animals, 
or plants. Many recombinant DNA ex- 
periments have been conducted through- 
out the world during the past 5 years and 
are continuing. To date, no known haz- 
ardous organism has been produced in 
this work. Thus, the risk of converting 
harmless organisms to harmful ones by 
recombinant DNA experiments remains 
hypothetical. Further work will eventu- 
ally determine the limits of these hypo- 
thetical risks. 
Approximately 3 years ago, because of 
the perceived potential hazards, scien- 
tists conducting recombinant DNA re- 
search called for a moratorium on cer- 
tain experiments pending an assessment 
of risk and the development of appropri- 
ate guidelines. These scientists requested 
NIH to create an advisory committee to 
develop such guidelines. 
In December 1975 the NIH Recombi- 
nant DNA Molecule Program Advisory 
Committee Cor simply Recombinant Ad- 
visory Committee) proposed guidelines 
to the Director of NIH. The guidelines 
were reviewed at a public hearing before 
the Advisory Committee to the Director, 
NIH, in Februray 1976. After a review of 
all public comments, NIH Guidelines 
were rleeased on June 23, 1976, accom- 
panied by a Director’s Decision address- 
ing the issues raised at the public hear- 
ing and in subsequent correspondence. 
The Guidelines set strict conditions for 
the conduct of NIH -supported research 
in this area. They prohibit certain types 
of experiments and require special safety 
conditions for other types. The provisions 
are designed to afford protection with a 
wide margin of safety to workers, the 
public, and the environment. On July 7, 
1976, the NIH Guidelines were published 
in the Federal Register, and on Septem- 
ber 9, 1976, a Draft Environmental lip- 
pact Statement on the Guidelines was 
similarly presented for public comment 
(41 FR 38425 etseq.). 
A Federal Interagency Committee on 
Recombinant DNA Research recom- 
mended in March 1977 that legislation 
be passed to extend the standards of the 
NTH Guidelines to all recombinant DNA 
activities in the public and private sec- 
tors. On the basis of the recommenda- 
tions, Health, Education, and Welfare 
Secretary Joseph A. Califano, Jr., had 
legislation developed, and an Adminis- 
tration bill was introduced in Congress. 
Congressional hearings were held and 
seperate bills are now being considered 
by the House of Representatives and the 
Senate to convert the Guidelines to 
standards for regulatory purposes. It 
should be noted that certain types of ex- 
periments now covered in the Guidelines 
would no longer be subject to regulation 
in the bills. 
On April 11, 1957, the Secretary, 
DHEW, adopted as official policy for 
DHEW the “NIH Guidelines for Re- 
search Involving Recombinant DNA 
Molecules” (42 FR 40485). The NIH 
Guidelines, as released in 1976, have gov- 
erned all NIH supported or conducted 
recombinant DNA research. From dis- 
cussions relating to the release of the 
NIH Guidleines, it is recognized that 
there is need for a continual updating in 
light of new knowledge. In 1977 the Re- 
combinant Advisory Committee, which 
had proposed the original guidelines, 
began the process of revising the current 
NIH Guidelines on the basis of informa- 
tion accumulated on the effectiveness of 
physical and biological containment and 
on the biology of the hosts and vectors 
utilized in recombinant DNA research. A 
Subcommittee to the full Committee held 
open meetings in March and April to 
consider comments received since the 
NIH Guidelines were released. On the 
basis of these deliberations, revisions 
were proposed and were considered by 
the full Committee at public meetings in 
May and June. On September 1, 1977, the 
proposed revised Guidelines were re- 
ferred to the Director, NIH, for final 
decision. 
The proposed revised Guidelines will 
be published in September for comment 
in the “NIH Recombinant DNA Tech- 
nical Bulletin.” The Bulletin is a new 
NIH publication that will attempt 
to link investigators involved in recombi- 
nant DNA research both in the United 
States and abroad with the advisory 
groups and organizations active in this 
area. 
To provide further opportunity for 
public comment and consideration, the 
proposed revised Guidelines are offered 
below. All comments received will be 
considered by the Director, NIH, and by 
the Advisory Committee to the Director, 
NIH, at its December meeting. On the 
basis of the comments received and re- 
view by the Advisory Committee, the Di- 
rector will subsequently issue final 
Guidelines accompanied by a decision 
document explaining the modifications. 
Please address any comments on these 
draft policies and procedures to the Di- 
rector, National Institutes of Health, 
9000 Rockville Pike, Bethesda, Md. 20014. 
All comments should be received by No- 
vember 15, 1977. Additional copies of this 
notice are available from : 
Director, Office of Recombinant DNA Activi- 
ties, Building 31, Room 4A52, National In- 
stitutes of Health, 9000 Rockville Pike, 
Bethesda, Md. 20014. 
Dated: September 16, 1977. 
Donald S. Fredrickson, 
Director, 
National Institutes of Health. 
Table op Contents 
I. Introduction. 
II. Containment. 
a. Standard practices and training. 
b. Physical containment levels. 
c. Shipment. 
d. Biological containment. 
III. Experimental guidelines. 
a. Experiments that are not to be per- 
formed. 
b. Containment guidelines for permissible 
experiments. 
IV. Roles and responsibilities. 
a. Principal Investigator. 
b. Institution. 
c. NIH Initial review groups (study sec- 
tions) . 
d. NTH Recombinant DNA Molecule Pro- 
gram Advisory Committee. 
e. NIH. 
V. Footnotes. 
VI. References. 
appendices 
A. Packaging and shipping of recombinant 
DNA materials. 
B. Classification of microorganisms on the 
basis of hazard. 
I. Introduction 
The purposes of these Guidelines Is to 
establish procedures for handling organisms 
and viruses containing recombinant DNA 
molecules. Recombinant DNA molecules are 
defined as molecules consisting of segments 
of DNA from different genomes which have 
been Joined end-to-end outside living cells 
and have the capacity to Infect some host 
cell and be maintained therein. These 
Guidelines, however, pertain only to "novel 
recombinant DNAs,” here defined as mole- 
cules that consist of segments of any 
DNA from different species that are not 
known to exchange chromosomal DNA by 
natural physiological processes. The Director 
of NIH with the advice of the Recombinant 
DNA Molecule Program Advisory Committee 
shall prepare the list of those combinations 
of DNAs (viral, extrachromosomal or chromo- 
somal) which are not considered novel for 
this purpose and are. therefore, not covered 
by these Guidelines. In general, recombinant 
FEDERAL REGISTER, VOL. 42, NO. 187 — TUESDAY, SEPTEMBER 27, 1977 
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