60082 
NOTICES 
Attend) x B 
The Secretary or Health. 
Education. and Welt are. 
Washington. D.C. 20201. 
December 15. 1978. 
MEMORANDUM TO: Assistant Secretary 
for Health. Director. National Institutes. 
National Institutes of Health. 
SUBJECT Assessing the Risk of Recombin- 
ant DNA Research. 
With the issuance today of revised Guide- 
lines for recombinant DNA research, the re- 
sponsibility of the National Institutes of 
Health to conduct and support experiments 
designed to determine the risks of recombin- 
ant DNA research becomes even more Im- 
portant than It has been In the past. The re- 
vised Guidelines now require a finding by 
the Director of NIH that each proposed 
action under the Guidelines “presents no 
significant risk to health or the environ- 
ment." It Is critical that these Judgments, to 
the maximum extent possible, be based on 
the firm foundation of documented re- 
search that Is subject to peer review. 
Experience and knowledge gained from 
the broad range of recombinant DNA re- 
search already underway will provide much 
Information for assessing risks. But In many 
areas special research and careful attention 
will be needed. To discharge our responatbll- 
Ity to assess risk before certain research Is 
conducted on a wide-spread basis. NIH 
should formulate a plan for carrying out a 
balanced program of more such risk-assess- 
ment experiments either at NIH directly or 
under NIH-supported grants or contracts. In 
my view, the more risk assessment experi- 
ments NIH carries out. the better we will be 
able to Judge whether the Guidelines— and 
actions taken under them— afford appropri- 
ate protection for health and the environ- 
ment. 
Your overall plan to conduct risk assess- 
ment experiments should be published far 
public comment and presented for review to 
the Recombinant DNA Advisory Committee 
annually. The first such plan should be 
ready for publication and submission to the 
Advisory Committee by March 30. 1979. 
Joseph A. Califano. Jr. 
Notice or Release or Revised NIH 
Guidelines roR Recombinant DNA 
Research 
Today, the Director. National Insti- 
tutes of Health, with the approval of 
the Assistant Secretary for Health and 
the Secretary of Health. Education, 
and Welfare, is authorizing the release 
of revised NIH Guidelines for Re- 
search Involving Recombinant DNA 
Molecules. The Guidelines and a Deci- 
sion of the NIH Director to issue the 
revised guidelines are published below. 
Dated: December 15. 1978. 
Donald S. Fredrickson. 
Director, 
National Institutes of Health. 
Decision or the Director. National 
Institutes or Health. To Issue Re- 
vised Guidelines por Recombinant 
DNA Resera ch 
December 1978. 
Contents 
I. Scope of the Guidelines. 
General Applicability. 
Prohibitions and Exemptions — General 
comments. 
Prohibitions — Specific Comments. 
Exemptions — Specific Comments. 
II. Containment. 
Physical Containment. 
Shipment. 
Biological Containment. 
Flexibility in Choosing Physical and Bio- 
logical Containment Levels. 
III. Containment Guidelines for Covered 
Experiments. 
General Considerations. 
Risk Assessment. 
Specific Concerns. 
IV. Roles and Responsibilities. 
Of the Institution ( General >. 
Of the Institution (Special). 
Of NIH (General). 
Of NIH (Specific). 
V. Footnotes and References. 
Appendix A (Director's Decision concern- 
ing Appendix A of the Guidelines). 
Appendix B (Director's Decision concern- 
ing Appendix B of the Guidelines^ 
Appendices 
L Environmental Impact Assessment. 
II. Federal Interagency Advisory Commit- 
tee (list of members). 
III. Exchange of letters between Senators 
and Secretary CaJifano. 
I. Scope op the Guidelines 
A number of commentators at the 
September 15 hearing and correspon- 
dents addressed issues concerning the 
scope of the Guidelines. Views were 
expressed for an against exempting 
experiments from the Guidelines even 
though some argued that the risk was 
minimal or nonexistent. Specific issues 
that were raised are discussed below. 
GENERAL APPLICABILITY 
Several commentators spoke to the 
scope of the applicability of the 
Guidelines. Some questioned the right 
of NIH to apply the Guidelines to in- 
vestigations not supported by NIH at 
an institution that receives some NIH 
funding for recombinant DNA re- 
search. Others, however, urged that 
the scope be broadened to include all 
institutions receiving NIH or. Indeed. 
DHEW funding for whatever purpose. 
I addressed these concerns in my De- 
cision accompanying the proposed re- 
vision published in the Federal Regis- 
ter on July 28. 1978. I noted that par- 
tial adherence to the Guidelines 
within an institution would defeat the 
purpcwe of extending maximal protec- 
tion to the community. Thus, it would 
be inconsistent for NIH to provide 
funds for recombinant DNA activities 
to an institution that did not meet the 
standards of the Guidelines in all of 
its recombinant DNA research, regard- 
less of the source of funding. This 
principle is sound and NIH has the au- 
thority to apply it. 
Some commentators took exception 
to the statement in the section on 
General Applicability that once cer- 
tain research is approved at the local 
level, it may proceed. Several corre- 
spondents pointed out that the lan- 
guage conveys the sense that all re- 
combinant DNA research can proceed 
solely on the basis of local approval. 
This is not the case and this section 
does not. in fact, deal appropriately 
with the matter. Accordingly, the 
topic has been deleted from the Appli- 
cability section and dealt with exten- 
sively in part IV of the Guidelines and 
in the Administrative Practices Sup- 
plement. 
Another commentator urged that 
the requirements of the Guidelines be 
extended to NIH-supported research 
In foreign countries. The proposed re- 
vised Guidelines (PRG) state that the 
Guidelines are applicable, but if the 
host country has rules for the conduct 
of recombinant DNA projects, then a 
certificate of compliance with those 
rules may be submitted to NIH in lieu 
of compliance with the NIH Guide- 
lines. so long as the safety practices of 
the two are reasonably consistent. Of 
course, in countries with no guidelines, 
the NIH Guidelines must apply to 
NIH-supported research. 
prohibitions and exemptions — 
GENERAL COMMENTS 
There were a large number of com- 
ments on prohibitions, exceptions to 
prohibitions, and exemptions from the 
Guidelines. There was some confusion 
on the difference between exceptions 
and exemptions. Experiments except- 
ed from the prohibitions are assigned 
appropriate containment levels and 
thus must be conducted In compliance 
with the Guidelines. For experiments 
under the exemptions (and not affect- 
ed by prohibitions;, the Guidelines do 
not apply at all. 
Several of the commentators spoke 
to one or more of the criteria used for 
exempting experiments from the 
Guidelines. Some said that the crite- 
rion for granting exemptions should 
be safety and not whether DNA ex- 
change occurs In nature. This issue is 
discussed in the Environmental 
Impact Assessment accompanying the 
revised Guidelines in the Federal Reg- 
ister of July 28. 1978. 
It was noted there that, according to 
some commentators, safety rather 
than “novelty” should be the criterion 
for exclusion. That is. any recombin- 
ant molecule that poses a potential 
threat to the public health or the en- 
vironment should be covered by the 
Guidelines regardless of whether the 
molecule is a novel one. An opposing 
view, expressed by other commenta- 
tors, was that a proper criterion 
should be whether the potential 
hazard of the recombinant molecule 
would differ significantly from the 
biohazard posed by a molecule already 
found in nature or from a biohazard 
that can be successfully handled by 
conventional methods. It proved Im- 
possible to reconcile these differences 
of opinion In the definition itself, and 
FEDCRAL REGISTER. VOC 43. N O. 247 — FRIDAY. DECEMBER 73. 1978 
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