33060 
NOTICES 
Many of the commentators agreed 
that both the original guidelines and 
the PRG-RAC were overly stringent 
with regard to virus experiments. In 
commenting on the PRG-RAC. the 
PM BO Standing Committee on Re- 
combinant DNA Research wrote: 
The EM 30 Committee believes that the 
containment categorization of experiments 
with animal virus DNA's which is proposed 
by the N1H Advisory Committee is too indis- 
criminate and excessively stringent consid- 
ering the proposed classification of experi- 
ments with other classes of DKA and the 
longstanding, accepted safety precautions 
for handling Intact virus particles and viral 
nucleic acids ’ ’ V The EMBO Committee 
proposes that it would be more reasonable 
either to consider experiments with viral 
DNA on a case by-case basts or to produce a 
detailed set of recommended ca’egorles for 
experiments with specific viral DNA's. The 
EMBO Committee hopes in the near future 
to establish an ad hoc international group 
of virologists to draw up such proposals. 
In response to this suggestion (l.e., 
for an international group of virol- 
ogists to consider this Issue), a Joint 
U-S.-EMBO Workshop To Assess 
Risks for Recombinant DNA Experi- 
ments Involving the Genomes of 
Animal. Plant, and Insect Viruses was 
held In Ascot. England, on January 26- 
28. 1978. The workshop was attended 
by 27 distinguished scientists from the 
United States, the United Kingdom. 
West Germany. Finland. France. 
Sweden, and Switzerland. The report 
of the ••Ascot" Workshop was pub- 
lished in the Federal Register on 
March 31. 1978. and appears as appen- 
dix E to the accompanying Environ- 
mental Impact Assessment. The work- 
shop concluded: 
The probability that K-12 organisms car- 
rying viral DNA inserts could repiesent a 
significant hazard to the community was so 
small as to be of no practical consequence 
* • * viral genomes or fragments thereof, 
cloned in E. coll K-12 using approved plas- 
mid or phage vectors. po>e no more risk 
than work with the infectious virus or Its 
nucleic acid and In most. If not all cases, 
dearly present less risk. In fact, the work- 
shop participants agreed that cloning of 
vlraJ DNA in E colt K 12 may provide a 
unique opportunity to study with greatly re- 
duced risks the biology of extremely patho- 
genic and virulent viruses. 
On April 6-7. 1978 (as announced on 
March 17 in the Federal Recister). a 
working group sponsored by the RAC. 
composed of distinguished American 
microbiologists, met to review the 
report of the "Ascot" Workshop. The 
report of this working group appears 
as appendix F to the accompanying 
Environmental Impact Assessment. 
The working group unanimously en- 
dorsed the "Ascot” report with certain 
minor amendments. Their report, in- 
cluded recommended new language to 
be inserted in the PRG-NIH in place 
of the sections dealing with viruses in 
the PRG-RAC. This report was pre- 
sented to the RAC at its April 27-28. 
1978, meeting, and was unanimously 
endorsed by the RAC with certain 
minor amendments. I have accepted 
these recommendations of the RAC. 
with certain additional minor amend- 
ments. and these now constitute the 
sections dealing with viruses in part 
III of the PRG-NIH. 
Recombinant DNA Experiments In- 
volving DNA from Plants and 
Plant Pathogens 
One of the comments made at the 
December 1977 meeting of the Adviso- 
ry Committee to the Director. NIH 
was that "the NIH guidelines do not 
adequately deal with the use of recom- 
binant DNA in plants * * * ’ Other 
commentators have expressed similar 
sentiments, ami the suggestion has 
been made that "a subcommittee be 
formed to deal with plants and plant 
pathogens and make specific recom- 
mendations for revision of the guide- 
lines.” In response, a Workshop on 
Risk Assessment of Agricultural Path- 
ogens. composed of distinguished 
American plant pathologists, was held 
on March 20-21. 1978 (as announced 
on March 6 In the Federal Register). 
Sponsored by the U S. Department of 
Agriculture, the National Science 
Foundation, and the NIH. the report 
of this workshop appears as appendix 
G to the accompanying Environmental 
Impact Assessment. The report was 
presented to the RAC at Its April 27- 
28. 1978. meeting and was unanimous- 
ly endorsed by the RAC with certain 
minor amendments. I have accepted 
these recommendations of the RAC 
with certain additional minor amend- 
ments: these involve changes in the 
PRG-NIH In sections dealing with the 
use of plants and plant pathogens in 
recombinant DNA research. 
Using the 10 criteria previously dis- 
cussed in light of what is known today. 
I believe the revisions in containment 
standards proposed by the PRG-NIH 
are sound. The changes in contain- 
ment standards in the PRG-NIH are 
discussed below In greater detail for 
each of the subsections of part III. 
SPECIFIC CONSIDERATIONS 
Section III— Opening Paragraphs 
As discussed above In part I of this 
document, the section of the guide- 
lines numbered III-A in both the 1976 
guidelines and the PRG-RAC and en- 
titled Experiments Thai Are Not To 
Be Performed" has been moved in the 
PRG-NIH to become section I-D enti- 
tled Prohibitions." This leads to a re- 
numbering of the remaining subsec- 
tions of part III ol the PRG-NIH as 
compared to the PRC-RAC. 
Two new paragraphs have been in- 
serted at the beginning of part III of 
the PRG-NIH. The first reminds the 
reader to consult part I "where listings 
are given of prohibited and exempt ex- 
periments." 
The second Inserted paragraph is a 
"general flexibility clause.” Insertion 
of such a "clause" was recommended 
by the RAC at its April 27-28. 1978. 
meeting. It recognizes that the classifi- 
cation of experiments given in part III 
will necessarily be imperfect, as inves- 
tigators in the future devise new ways 
to conduct recombinant DNA experi- 
ments not currently foreseen and 
therefore not explicitly considered in 
the guidelines. Also, new data may 
become available showing that certain 
particular experiments currently as- 
signed a particular containment level 
are. indeed, clearly more (or less) safe 
than envisioned at this time. There- 
fore. this "clause" states that 
"changes in these levels for specific 
experiments (or the assignment of 
levels to experiments not explicitly 
considered here) may be expressly ap- 
proved by the Director. NIH. on the 
recommendation of the Recombinant 
DNA Advisory Corfimittee (RAC)." 
Section III-A-l-a. Shotgun Experi- 
ments info E. coli K-12 with In- 
serted Eukaryotic DNA 
At a number of places in this subsec- 
tion the principal investigator is al- 
lowed to choose between two combina- 
tions of containment procedures. For 
example, in several Instances one Is 
permitted to use P2 + EK1 or PI + EK2. 
This was endorsed by some commenta- 
tors but questioned by others. This 
concept of flexibility was addressed in 
part II of this document I also wish to 
point out that the concept is not a new- 
one— it was allowed under the original 
guidelines. Based upon events of the 
past 2 years, the RAC merely proposed 
that this principle be extended to cer- 
tain specified additional cases where 
they believe it appropriate. I agree 
with their proposals and have there- 
fore Included in the PRG-NIH ali 
such specific cases of flexibility recom- 
mended in the PRG-RAC. 
On the other hand, in certain other 
specific cases (e.g., DNA from birds) 
the PRG-RAC recommended the con- 
tainment level te P2-*-EK2, without 
the option of P3 + EK1. Certain com- 
mentators urged that in all cases 
where the containment level of 
P2~FK2 is given, the option of 
P3^EK1 be allowed. However, the 
RAC felt that in view of their in- 
creased confidence in the biological 
containment offered by the EK2 
system. P2-EK2 offers more contain- 
ment than P3^EK1, and that 
P2 + EK2 without the option of 
P3 + EK1 should be the containment 
level for certain specified classes of ex- 
periments. I accept the view of the 
RAC and have therefore specified in 
the PRG-NIH the containment levels 
of P2 + EK2 without the option of 
FE0ERAI REGISTER, VOL 43 NO. 14*— ERIDAY, JUIT 28, 1978 
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