NOTICES 
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propriate notice and opportunity for 
public comment. 
Prohibitions 
Two changes in this section have 
been initiated to make it more com- 
patible with the new "Definition” and 
"Exemptions” sections. The first was 
to transfer this section from part III 
of the guidelines to part I. This is 
again to emphasize that the exemp- 
tions are not applicable to the six ac- 
tivities listed as being prohibited. The 
second was to drop all references to 
novel recombinant DNA’s and natural 
genetic exchange. My other actions 
were based upon the following com- 
ments: 
• There was general endorsement of 
the provision in this section which 
grants to the Director, NIH, upon the 
recommendation of the RAC, the au- 
thority to waive any of the prohibi- 
tions. The widespread support for this 
authority reflects the realization that 
many important risk-assessments ex- 
periments may not be able to proceed 
otherwise. NIH is now supporting and 
will continue to support experiments 
that will yield knowledge contributing 
to a better understanding of the 
nature of potential risks of recombin- 
ant DNA. This section has been ex- 
pended in the PRG-NIH to indicate 
that if any experiments are excepted 
from the prohibitions, they will "at 
that time be assigned appropriate 
levels of physical and biological con- 
tainment.” 
• It was urged that the advice of 
other Government agencies, such as 
the Environmental Protection Agency 
(EPA) and the Occupational Safety 
and Health Administration (OSHA), 
should be sought when the Director, 
NIH, considers invoking this waiver 
authority. The Federal Interagency 
Committee on Recombinant DNA Re- 
search provides for coordination of 
policies in this area. EPA and OSHA 
are represented on the Committee. 
The advice of relevant research and 
regulatory agencies will continue to be 
sought when appropriate. 
• It was suggested that the RAC as 
presently constituted should not be 
the sole advisory body because societal 
as well as scientific considerations 
mast enter into the waiver decision. As 
explained in greater detail in part IV 
of this document, the membership of 
the RAC will be broadened modestly 
as needed for expertise, but provisions 
for public notice and opportunity to 
comment, and other appropriate ad- 
minstrative practices, can be used to 
ensure adequate public input when 
the issues warrant. 
• It was suggested that an Environ- 
mental Impact Assessment or State- 
ment should accoinpany each waiver. 
My waiver decisions will include a 
careful consideration of the potential 
environmental impact, and certain de- 
cisions may be accompanied by a 
formal assessment or statement. This 
must be determined on a case-by-case 
basis. 
• It was suggested that waiver of 
the prohibition on the large-scale use 
of culture containing recombinant 
DNA’s be issued on the basis of indus- 
try’s experience in dealing with such 
cultures. While such experience will 
surely be weighed in the decisionmak- 
ing, I believe that it should not be the 
sole criterion for granting such a 
waiver. 
• Agricultural scientists noted the 
importance to their research commu- 
nity of being allowed eventually to re- 
lease organisms containing recom- 
binant DNA into the enviromnent. 
When the original guidelines were pre- 
sented to me in draft form in 1976, the 
release of organisms containing recom- 
binant DNA molecules into the envi- 
ronment was to be allowed if a series 
of controlled tests had been done to 
leave no reasonable doubt of safety. At 
that time I rejected this waiver provi- 
sion because of the limited scientific 
evidence available that any of the po- 
tential benefits from such a release 
were near realization. 
The prohibition of deliberate release 
into the environment of recombinant 
DNA-containing organisms can be 
waived if all of the requirements for a 
waiver are met (and if the require- 
ments of the National Environmental 
Policy Act are considered). Given the 
limited experience of NIH in agricul- 
tural research, the U.S. Department of 
Agriculture would be deeply involved 
in this process. I have given written 
notice of this opinion to the appropri- 
ate officials of the USDA. 
• The Standing Advisory Committee 
on Recombinant DNA Research of the 
European Molecular Biology Organi- 
zation (EMBO) has noted that the list 
of pathogenic organisms under prohi- 
bition I-D-l, especially those in class 
5, may not be appropriate for ail Euro- 
pean countries, and that "the decision 
as to which pathogenic orgamisms 
should be classified as too dangerous 
to use must be the responsibility of na- 
tional or regional authorities.” In re- 
sponse to this a footnote could be 
added to the guidelines stating that 
prohibition I-D-l relates only to re- 
search in the United States. I have de- 
cided, however, not to include such a 
footnote, because these guidelines are 
directed to NIH grantees and contrac- 
tors, almost all within this country. In 
other countries, different criteria may 
govern. 
• A final change in the PRG-NIH 
relates to prohibition I-D-l. As dis- 
cussed below in this document in part 
III, considerable changes have been 
made in the section^dealing with the 
use of viral DNA in recombinant DNA 
experiments. The history leading to 
these changes, including the report of 
the “Ascot” workshop (appearing as 
appendix E to the accompanying Envi- 
ronmental Impact Assessment) and 
the report of the working group held 
on April 6-7, 1978 (appearing as ap- 
pendix F to the accomjsanying Envi- 
ronmental Impact Assessment), are 
discussed in detail in part III of this 
document under the heading "Recom- 
binant DNA Experiments Involving 
Viral DNA.” 
One of the Working Group’s recom- 
mendations, arising out of the “Ascot” 
report and endorsed by the RAC at its 
April 27-28, 1978, meeting and en- 
dorsed by me, is that the previous pro- 
hibition on the use in recombinant 
DNA experiments of Vesicular Stoma- 
titis Virus (VSV) and of oncogenic vir- 
uses classified by the National Cancer 
Institute (NCI) as "moderate risk” 
should be lifted; instead, use of these 
viruses should be permitted under con- 
tainment conditions to be specified in 
part III of the guidelines. The reason- 
ing behind this is that recombinant 
DNA experiments with pieces of these 
viruses cloned in E. coli K-12 pose no 
more risk, and actually appear to pose 
clearly less risk, than work with the 
whole infectious virus itself. Since the 
Center for Disease Control (CDC) and 
NCI recommend that work with these 
whole viruses not be prohibited, but 
rather be performed under contain- 
ment conditions similar to P3, there is 
no scientific reason to prohibit recom- 
binant DNA work with these viruses. 
Therefore, prohibition I-D-l in the 
PRG-NIH no longer prohibits the use 
of VSV or oncogenic viruses classified 
by NCI as moderate risk; containment 
conditions for their use are specified 
in part III of the guidelines. 
General Definitions 
In response to commentators’ sug- 
gestions that terms be more precisely 
defined, I have added a new section to 
the PRG-NIH with such definitions. 
Many of these terms are further dis- 
cussed in part IV of PRG-NIH. 
In summary, part I of the PRG-NIH 
has been extensively modified from 
that proposed in the PRG-RAC. In an 
effort to be responsive to the sugges- 
tions of commentators and to make 
the guidelines more comprehensible, 
the definition of recombinant DNA 
molecules has been simplified and 
clarified, the "Prohibitions” section 
has been transferred from part III to 
part I, and new sections have been 
added to part I including "Exemp- 
tions.” part I, now entitled "Scope of 
the Guidelines.” is composed of the 
following sections: 
• Purpose 
• Definition of Recombinant DN7 
Molecules 
FEDERAL REGISTER, VOL 43, NO. 144 — FRIDAY, JULY 28, 1978 
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