33110 
NOTICES 
as needed for expertise, but provision 
(or public notice and opportunity to 
comment, and other appropriate ad- 
ministrative practices, can be used to 
insure adequate public Input when the 
issues warrant. 
• It was suggested that an Environ- 
mental Impact Assessment or State- 
ment should accompany each waiver. 
Waiver decisions will include a careful 
consideration of the potential environ- 
mental impact, and certain decisions 
may be accompanied by a formal as- 
sessment 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 cultures containing recombinant 
DMA s be issued on the basis of indus- 
try's experience in dealing with such 
cultures. While experience will surely 
be weighed In the decision mat mg. It 
whould not be the sole criterion for 
granting such a waiver. 
• Agricultural scientists noted the 
importance to their r esea rch commu- 
nity of being allowed eventually to re- 
lease organisms containing recombin- 
ant DMA into the environment. When 
the original Guidelines were proposed 
to the NIH Director in draft form in 
1976. the release of organisms contain- 
ing recombinant DNA molecules Into 
the environment was to be allowed If a 
series of controlled tests had been 
done to leave no reasonable doubt of 
safety. This waiver provision was re- 
jected at that time because of the lim- 
ited scientific evidence available that 
any of the potential benefits from 
such a release were near realization. 
As now p r oposed, the prohibition of 
deliberate release into the environ- 
ment of recombtnant-DNA-coataining 
organisms can be waived If all the re- 
quirements for a waiver (and those of 
the National ftirtronmental Policy 
Act ) are met. Given the limited experi- 
ence of NTH in agricultural re se arch, 
the VS. Department of Agriculture 
would hare to be deeply Involved in 
this process, and written notice of this 
suggestion has been given to the ap- 
propriate officials at USD A. 
• The Standing Advisory Committee 
on Recombinant DNA Research of the 
European Molecular Biology Organi- 
sation UMBO) has noted that the list 
of pathogenic organisms under prohi- 
bition I-D-l. especially those tn Class 
5. may not be appropriate for all Euro- 
pean countries. The decision as to 
which pathogenic organisms should be 
classified as too dangerous to work 
with must be the responsibility of na- 
tional or regional authorities. EMBO 
has recommended that a footnote be 
added to the Guidelines stating that 
the prohibition of etio logic agenu re- 
lates to research tn the United States. 
Such a footnote, however, is unneces- 
sary because those Guidelines are di- 
rected to NTH grantees and contrac- 
tors. aim ort all within this country. 
• A final change in the PRG-NIH 
relates to prohibition I-D-L As dis- 
cussed in detail In the Decision" ac- 
companying the PRG-NIH. the prohi- 
bition against using in recombinant 
DNA experiments vesicular stomatitis 
virus and oncogenic viruses classified 
by the National Cancer Institute as 
“moderate nsk" has been lifted. 
Proposed Action.' Environmental 
Impact iufirvnl 
Part I of the PRG-NIH as discussed 
in this Assessment rests on the past 2 
years of scientific developments relat- 
ing to the safety of recombinant DNA 
research. The proposed alternatives to 
the current Guidelines reflect that evi- 
dence. 
The suggested definition in the 
PR G- RAC spoke to the conclusion 
that recombinant DNA molecules only 
pose s potential hazard when placed In 
an organism, and that events In the 
laboratory which mimic those tn 
nature pose no special hazard to work- 
ers or the environment. The commit- 
tee also recommended, and there was 
strong public support for. a mecha- 
nism to allow exceptions to the "Pro- 
hibitions." as for the conduct of rtsk- 
assessm«mt r es e a rch. 
The PRG-NIH also Incorporate a 
number of the alternatives to the 1976 
Guidelines suggested by the public 
commentators. A!! of the changes re- 
flected tn the PRG-NIH permit re- 
search to go forward which would not 
have a significant effect on the envi- 
ronment. Indeed, additions hare been 
made to insure that the safety stand- 
ards are extended under certain cir- 
cumstances to meet environmental 
and occupation concerns. 
The scope of the Guidelines contin- 
ues to be limited to recombinant DNA 
research. Other techniques tn genetic 
re s e a rch, such as cell fusion and chro- 
mosomes transfer, may result tn the 
formation of recombinant molecules; 
but Inherent tn these techniques Is a 
range of natural barriers to the forma- 
tion of hazardous organisms, and thus 
the issuance of Federal standards is 
unnecessary. It should also be noted 
that such techniques have been used 
tn the laboratory for decades with no 
harmful effects on either health or 
the environment. 
The definition In the PRG-NIH 
clearly states that the Guidelines are 
Intended to pertain to the construc- 
tion and handling of naked recombin- 
ant DNA molecules as well as organ- 
isms and viruses containing such mole- 
cules. This is to insure that the prohi- 
bitions on the use of naked DNA 
remain in effect. And the definition 
now explicitly Includes synthetic mole- 
cules under the standards of the 
Guidelines, thereby increasing the 
margin of safety. 
In response to the recommendations 
of public commentators, the PRG- 
NIH now require that all recombinant 
DNA research at NTH- funded institu- 
tions comply with the safety standards 
of the Guidelines and be under the 
purview of local institutional bioha- 
zard committees. Again, this will mini- 
mize the environmental impact, if any. 
of this research. 
The list of exemptions, as previously 
explained, provides that certain re- 
combinant DNA research need not be 
subject to the control of the NTH 
Guidelines on the basis of safety to 
the laboratory personnel, to the great- 
er community, and to the environ- 
ment. The proposed exemptions in 
large part are responsive to the great 
number of comments received. The 
Prohibitions" section, in the 1976 
Guidelines under Pan III. has been 
transposed to Part I In the PRG-NIH 
to insure that none of the ' Exemp- 
tions" apply to the "Prohibitions." 
Thus, once again, care has been taken 
to minimize the possibility of environ- 
mental impact. 
Under the first exemption, experi- 
ments with recombinant DNA mole- 
cules that are not tn an organism need 
not be subject to the Guidelines. This 
is based on the safety of these experi- 
ments. The second exemption permits 
certain “self-cloning" experiments to 
be done outside the jura diet ion of the 
Guidelines. Again the basis is occupa- 
tional and environmental safety. The 
third exemption also concerns “self- 
cloning” and permits certain experi- 
ments previously classified as Pi - UK 1 
to be excluded from the Guidelines. 
This was strongly endorsed by several 
public commentators on the basis of 
no hazard. 
The fourth exemption deals with ex- 
periments that mimic exchanges al- 
ready occurring in nature. It allows 
certain of the experiments previously 
classified at PI - UK1 to be excluded 
from the Guidelines, again with the 
strong endorsement of several public 
commentators on the basis of no 
hazard. The final provision allows ex- 
emptions when it is found that experi- 
ments do not present significant nsk 
to health or the environment. This 
standard was expressly recommended 
as the basis for exemption by several 
public commentators, especially from 
environmental groups, and is directly 
responsive to the concerns that there 
be an explicit reference to health or 
the environment for the basis of ex- 
emption. Further, in the exercise of 
this and the previous exemption, sev- 
eral procedural requirements have 
been introduced that will afford sig- 
nificant opportunity for public com- 
ment to insure appropriate attention 
FEOtkAl *KWmt VOL O. MO. 144 — FWDAY, MY 29. 1979 
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