NOTICES 
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I 
i Include scientists who represent disei- 
; piines actively engaged in recombinant 
DNA research. In my view, it is most im- 
portant that this committee have the 
I necessary expertise to assure that the 
■ guidelines are of -the highest scientific 
j quality. The committee has provided this 
1 expertise in the past, and it must con- 
tinue to do so. The committee shall also 
include members from other scientific 
disciplines. 
It should be noted that the present 
! committee recommended on its own ini- 
! tiative that a nonscientist be appointed. 
1 Emmette S. Redford, Ph.D., LL.D., Ash- 
bel Smith Professor of Government and 
Public Affairs at the Lyndon B. Johnson 
School of Public Affairs, University of 
Texas at Austin, serves in that capacity. 
! An ethicist has also been nominated for 
appointment. 
The Advisory Committee to the Direc- 
tor, NIH, shall serve to provide the 
I broader public policy perspectives. This 
committee, at its meeting on February 
I 9-10, 1976, reviewed the proposed guide- 
lines with the participation of public wit- 
nesses, and shall continue to provide such 
review for future activities of the Recom- 
binant Advisory Committee. 
In response to suggestions, the respon- 
sibilities of the Recombinant Advisory 
Committee have been expanded. In ad- 
j dition to reviewing the guidelines for 
possible modification as scientific evi- 
j dence warrants, the committee will 
certify EK2 and EK3 systems. In re- 
I -sponse to requests by the investigator, 
local committee, or study section, the 
committee will also provide evaluation 
and review in order to advise on levels 
of required containment, on lowering 
of requirements when cloned recom- 
binants are to be used, and on questions 
concerning potential biohazard and ade- 
quacy of containment provisions. 
Commentators also asked that the 
committee review ongoing research 
initiated prior to the implementation of 
the guidelines. Now that the guidelines 
are being released, NIH-funded investi- 
gators in this field will be asked to give 
assurance, within a given period, that 
they will comply. Any investigators who 
constructed clones under the Asilomar 
guidelines will be asked to petition NIH 
for special consideration of their case, 
if the new guidelines require higher con- 
tainment than did the Asilomar guide- 
lines. Here the advice of the Recombi- 
nant Advisory Committee will be sought. 
There were also suggestions that the 
committee certify chemical purification 
of recombinant DNA, but as I indicated 
earlier, these procedures are too well 
known to require NIH monitoring. 
5. In light of comments received, NIH 
will provide review, through appropriate 
NIH offices, of data from institutional 
biohazards committees (including acci- 
dent reports) and will ensure dissemina- 
tion of these findings as appropriate. Dr. 
William Gartland will head the newly 
created NTH Office of Recombinant DNA 
Activities for these purposes. In addi- 
tion, NIH will provide for rapid dissemi- 
nation of Information through its 
Nucleic Acid Recombinant Scientific 
Memoranda 'NARSM), distributed by 
the National Institute for Allergy and 
Infectious Diseases. NIH will also pro- 
vide an appropriate- mechanism for ap- 
proving and certifying clones before 
containment conditions can be lowered. 
With these extended modifications, the 
section of the guidelines dealing with 
roles and responsibilities now sets forth 
a more fully developed review structure 
involving the principal investigator, 
local biohazards committees, and the 
Recombinant Advisory Committee, as 
well as peer review committees. Guide- 
lines now provide extensive opportunity 
for advice, from the local to the national 
level. Several levels of review and scru- 
tiny are provided, ensuring the highest 
standards for scientific merit and con- 
. ditions for safety. 
The Recombinant Advisory Committee 
in conjunction with the Director’s Ad- 
visory Committee shall continue to serve 
as an ongoing forum for examining 
progress in the technology and safety of 
recombinant DNA research. Their re- 
sponsibility, and that of the NTH Di- 
rector, is to ensure that the guidelines, 
through modification when called for, 
reflect the soundest scientific and safety 
evidence as it accrues in this area. Their 
task, in a sense, is just beginning. 
Donald S. Fredrickson, 
Director , 
National Institute of Health: 
guidelines for research involving 
RECOMBINANT DNA MOLECULES 
June (076 
I. Introduction. 
II. Containment: 
A. Standard practices and training 
B. Physical containment levels: Pi level 
(Minimal): P2 Level (Low): P3 Level (Mod- 
erate): P4 Level (High). 
C. Shipment. 
D. Biological containment levels 
HI. Experimental Guidelines: 
A. Experiments that are not to be per- 
formed. 
B. Containment guidelines for permissible 
experiments : 
1. Biological containment criteria using E. 
Coli K-12 host-vectors; EK1 host-vectors; 
EK2 host-vectors; EK3 host-vectors. 
2. Classification of experiments using the 
E. Coli K-12 containment systems: 
(a) Shotgun experiments: 
(i) Eukaryotic DNA recombinants; 
(ii) Prokaryotic DNA recombinants; 
(iii) Characterized clones of DNA recom- 
binants derived from shotgun experiments. 
(b) Purified cellular DNAs other than 
plasmids, bacteriophages, and other viruses. 
(c) Plasmids, bacteriophages, and other 
viruses: 
(i) Animal Viruses; 
(ii) Plant Viruses; 
(iii) Eukaryotic organelle DNAs; 
(lv) Prokaryotic plasmid and phage DNAs. 
3. Experiments with other prokaryotic 
host-vectors. 
4. Experiments with eukaryotic host-vec- 
tors: 
(a) Animal host-vector systems; 
(b) Plant host-vector systems; 
(c) Fungal or similar lower eukaryotic 
host-vector systems. 
IV. Roles and Responsibilities : 
A. Principal investigator; 
B. Institution; 
C. NIH Initial Review Group (Study Sec- 
tions) ; 
D. NIH Recombinant DNA Molecule Pro- 
gram Advisory Committee; 
E. NIH Staff. 
V. Footnotes. 
VI. References. 
VII. Members of the Recombinant DNA 
Molecule Program Advisory Committee. 
Appendices 
A Statement on the use of Bacillus »ub- 
tilis in recombinant molecule technology. 
B. Polyoma and SV40 Virus. 
C. Summary of Workshop on the Design 
and Testing of Safer Prokaryotic Vehicles 
and Bacterial Hosts for Research on Recom- 
binant DNA Molecules. 
D. Supplementary Information on Phys- 
ical Containment (Including Detailed Con- 
tents) . 
I. INTRODUCTION 
The purpose of these guidelines is to 
recommend safeguards for research on 
recombinant DNA molecules to the Na- 
tional Institutes of Health and to other 
institutions that support such research. 
In this context we define recombinant 
DNAs as molecules that consist of dif- 
ferent segments of DNA which have been 
joined together in cell-free systems, and 
which have the capacity to infect and 
replicate in some host cell, either au- 
tonomously or as an integrated part of 
the host’s genome. 
This is the first attempt to provide a 
detailed set of guidelines for use by study 
sections as well as practicing scientists 
for evaluating research on recombinant 
DNA molecules. We cannot hope to an- 
ticipate all possible lines of imaginative 
research that are possible with this pow- 
erful new methodology. .Nevertheless, a 
considerable volume of written and 
verbal contributions from scientists in a 
variety of disciplines has been received. 
In many instances the views presented to 
us were contradictory. At present, the 
hazards may be guessed at, speculated 
about, or voted upon, but they cannot be 
known absolutely in the absence of firm 
experimental data — and, unfortunately, 
the needed data were, more often than 
not, unavailable. Our problem then has 
been to construct guidelines that allow 
the promise of the methodology to be 
realized while advocating the consider- 
able caution that is demanded by what 
we and others view as potential hazards. 
In designing these guidelines we have 
adopted the following principles, which 
are consistent with the general conclu- 
sions that were formulated at the Inter- 
national Conference on Recombinant 
DNA Molecules held at Asilomar Confer- 
ence Center, Pacific Grove, California, in 
February 1975 ( 3 ) : (i) There are cer- 
tain experiments for which the assessed 
potential hazard is so serious that they 
are not to be attempted at the present 
time. <ii) The remainder can be under- 
taken at the present time provided that 
the experiment is justifiable on the basis 
that new knowledge or benefits to hu- 
mankind will accrue that cannot readily 
be obtained by use of conventional meth- 
odology and that appropriate safeguards 
are incorporated into the design and ex- 
ecution of the experiment. In addition to 
an insistence on the practice of good - 
microbiological techniques, these safe- 
guards consist of providing both physical 
FEDERAL REGISTER, VOL. 41, NO. 1 31— WEDNESDAY, JULY 7. 1976 
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