NOTICES 
[sic] establish a study committee to con- 
sider this problem and to recommend 
specific actions or guidelines, should that 
seem appropriate.” 
In response, NAS formed a committee, 
and its members published another let- 
ter in Science 185, 303, (1974). Entitled 
“Potential Biohazards of Recombinant 
DNA Molecules,” the letter proposed: 
First, and most important, that untU the 
potential hazards of such recombinant DNA 
molecules have been better evaluated or un- 
til adequate methods are developed for pre- 
venting their spread, scientists throughout 
the world join with the members of this com- 
mittee in voluntarUy deferring * * * [cer- 
tain] experiments • • *. 
Second, plans to link fragments of animal 
DNAs to bacterial plasmid DNA or bac- 
teriophage DNA should be carefully 
weighted • • • . 
Third, the Director of the National Insti- 
tutes of Health is requested to give immedi- 
ate consideration to establishing an advisory 
committee charged with (i) overseeing an 
experimental program to evaluate the poten- 
tial biological and ecological hazards of the 
above types of recombinant DNA molecules; 
(II) developing procedures which will mini- 
mize the spread of such molecules within 
human and other populations; and (iii) de- 
vising guidelines to be followed by investiga- 
tors working with potentially hazardous re- 
combinant DNA molecules. 
Fourth, an international meeting of in- 
volved scientists from all over the world 
should be convened early in the coming year 
to review scientific progress in this area and 
to further discuss appropriate ways to deal 
with the potential biohazards of recombi- 
nant DNA molecules. 
On October 7, 1974, the NIH Recombi-' 
nant DNA Molecule Program Advisory 
Committee (hereafter “Recombinant Ad- 
visory Committee”) was established to 
advise the Secretary, HEW, the Assistant 
Secretary for Health, and the Director, 
NIH, “concerning a program for develop- 
ing procedures which will minimize the 
spread of such molecules within human 
and other populations, and for devising 
guidelines to be followed by investigators 
working with potentially hazardous re- 
combinants.” 
The international meeting proposed in 
the Science article (185, 303, 1974) was 
held in February 1975 at the Asilomar 
Conference Center, Pacific Grove, Cal- 
ifornia. It was sponsored by the National 
Academy of Sciences and supported by 
the National Institutes of Health and the 
National Science Foundation. One hun- 
dred and fifty people attended, including 
52 foreign scientists from 15 countries, 
16 representatives of the press, and 4 
attorneys. 
The conference reviewed progress in 
research on recombinant DNA molecules 
and discussed ways to deal with the po- 
tential biohazards of the work. Partici- 
pants felt that experiments on construc- 
tion of recombinant DNA molecules 
should proceed, provided that appropri- 
ate biological and physical containment 
is utilized. The conference made recom- 
mendations for matching levels of con- 
tainment with levels of possible hazard 
for various types of experiments. Certain 
experiments were judged to pose such 
serious potential dangers that the con- 
ference recommended against their being 
conducted at the present time. 
A report on the conference was sub- 
mitted to the Assembly of Life Sciences, 
National Research Council, NAS, and 
approved by its Executive Committee on 
May 20, 1975. A summary statement of 
the report was published in Science 188, 
991 (1975), Nature 225, 442, (1975), and 
the Proceedings of the National Academy 
of Sciences 72, 1981, (1975). The report 
noted that “in many countries steps are 
already being taken by national bodies 
to formulate codes of practice for the 
conduct of experiments with known or 
potential biohazard. Until these are es- 
tablished, we urge individual scientists 
to use the proposals in this document as 
a guide.” 
The NIH Recombinant Advisory Com- 
mittee held its first meeting in San Fran- 
cisco immediately after the Asilomar 
conference. It proposed that NIH use the 
recommendations of the Asilomar con- 
ference as guidelines for research until 
the committee had an opportunity to 
elaborate more specific guidelines, and 
that NIH establish a newsletter for in- 
formal distribution of information. NIH 
accepted these recommendations. 
At the second meeting, held on May 12- 
13, 1975, in Bethesda, Maryland, the 
committee received a report on biohaz- 
ard-containment facilities in the United 
States and reviewed a proposed NIH con- 
tract program for the construction and 
testing of microorganisms that would 
have very limited ability to survive in 
natural environments and would thereby 
limit the potential hazards. A subcom- 
mittee chaired by Dr. David Hogness was 
appointed to draft guidelines for re- 
search involving recombinant DNA mole- 
cules, to be discussed at the next meet- 
ing. 
The NIH committee, beginning with 
the draft guidelines prepared by the 
Hogness subcommittee, prepared pro- 
posed guidelines for research with recom- 
binant DNA molecules at its third meet- 
ing, held on July 18-19, 1975, in Woods 
Hole, Massachusetts. 
Following this meeting, many letters 
were received which were critical of the 
guidelines. The majority of critics felt 
that they were too lax, others that they 
were too strict. All letters were reviewed 
by the committee, and a new subcommit- 
tee, chaired by Dr. Elizabeth Kutter, was 
appointed to revise the guidelines. 
A fourth committee meeting was held 
on December 4-5, 1975, in La Jolla, Cali- 
fornia. For this meeting a “variorum edi- 
tion” had been prepared, comparing line- 
for-line the Hogness, Woods Hole, and 
Kutter guidelines. The committee re- 
viewed these, voting ltem-by-item for 
their preference among the three varia- 
tions and, in many cases, adding new 
material. The result was the “Proposed 
Guidelines for Research Involving Re- 
combinant DNA Molecules, “which were 
referred to the Director. NIH, for a final 
decision in December 1975. 
As Director of the National Institutes 
of Health, I called a special meeting of 
the Advisory Committee to the Director 
to review these proposed guidelines. The 
27903 
meeting was held at NIH, Bethesda, on 
February 9-10, 1976. The Advisory Com- 
mittee is charged to advise the Director, 
NTH, on matters relating to the broad 
setting — scientific, technological, and 
socioeconomic — in which the continuing 
development of the biomedical sciences, 
education for the health professions, and 
biomedical communications must take 
place, and to advise on their implications 
for NIH policy, program development, 
resource allocation, and administration. 
The members of the committee' are 
knowledgeable in the fields of basic and 
clinical biomedical sciences, the social 
sciences, physical sciences, research, edu- 
cation, and communications. In addition 
to current members of the committee; I 
invited a number of former committee 
members as well as other scientific and 
public representatives to participate in 
the special February session. 
The purpose of the meeting was to seek 
the committee's advice on the guidelines 
proposed by the Recombinant Advisory 
Committee. The Advisory Committee to 
the Director was asked to determine 
whether, in their judgment, the guide- 
lines balanced scientific responsibility to 
the public with scientific freedom to pur- 
sue new knowledge. 
Public responsibility weighs heavily in 
this genetic research area. The scientific 
community must have the public’s con- 
fidence that the goals of this profound- 
ly important research accord respect to 
important ethical, legal, and social values 
of our society. A key element in achieving 
and maintaining this public trust is for 
the scentific community to ensure an 
openness and candor in its proceedings. 
The meetings of the Director’s Advisory 
Committee, the Asilomar group, and the 
Recombinant Advisory Committee have 
reflected the intent of science to be an 
open community in considering the con- 
duct of recombinant DNA experiments. 
At the Director's Advfcory Committee 
meeting, there was ample opportunity for 
comment and an airing of Qie issues, not 
only by the committee members but by 
public witnesses as well. All major points 
of view were broadly represented. 
I have been reviewing the guidelines 
in light of the comments and suggestions 
made by participants at that meeting, as 
well as the written comments received 
afterward. As part of that review I asked 
the Recombinant Advisory Committee to 
consider at their meeting of April 1-2, 
1976, a number of selected issues raised 
by the commentators. I have taken those 
issues and the response of the Recom- 
binant Advisory Committee into account 
in arriving at my decision on the guide- 
lines. An analysis of the issues and the 
basis for my decision follow. 
T. GENERAL POLICY CONSIDERATIONS 
A word of explanation might be inter- 
jected at this point as to the nature of 
the studies in question. Within the past 
decade, enzymes capable of breaking - 
DNA strands at specific sites and of cou- 
pling the broken fragments in new com- 
binations were discovered, thus making 
possible the insertion of foreign genes 
into viruses or certain cell pai tides (plas- 
FEDERAl REGISTER, VOL 41, NO. 131 — WEDNESDAY, JULY 7, 1976 
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