Federal Register / Vol. 46. No. 210 / Friday. October 30, 1981 / Notices 
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current sections dealing with the use of 
vertebrate viral vectors. 
By a vote of eleven in favor, none 
opposed, with five abstentions, the RAC 
recommended approval of Dr. Miller's 
proposal. 
I accept this recommendation and the 
necessary changes and additions to the 
Guidelines have been made. 
C. Amendment of Section I-D-6 and 
Appendix C of the Guidelines 
Dr. Irvii^ Johnson of Eli Lilly and 
Company m a letter dated July 20, 1981, 
requested that Section I-D^ of the 
Guidelines, which prohibits certain 
large-scale recombinant DNA 
experiments, be amended to read as 
follows (new text in italics): 
“I-D-6. Large-scale requirements [e.g., 
more than 10 liters of culture) with 
organisms conatining recombinant 
DNAs other than those listed in 
Appendix C, Paragraphs 2, 3, and 4 of 
the Guidelines, unless the recombinant 
DNAs are rigorously characterized and 
the absence of harmful sequences 
established (3). (See Section IV-E-l-b- 
(3)-{d).]" 
Modifications of Appendix C would 
be necessitated by adoption of the 
proposal, and Dr. Johnson proposed 
mo^ication to specify that these large- 
scale experiments would require IBC 
review and approval. 
Dr. Johnson said that the RAC has 
already accepted the principle that no 
increased risk results from increased 
volume and that special RAC review of 
large-scale experiments involving host- 
vector systems currently exempted by 
Appendix C is not necessary. He 
submitted that large-scale fermentation 
expertise is found primarily in the local 
IBC and that responsibility for 
protection of workers and the 
environment should rest with the local 
me. 
The proposal was published for public 
comment in the August 4. 1981, Federal 
Register (46 FR 39771). No comments 
were received on the proposal prior to 
the RAC meeting. 
Dr. Johnson's request was discussed 
at the September 10-11, 1981, RAC 
meeting. At the meeting. Dr. Susan 
Wright submitted a letter opposing Dr. 
Johnson's proposal and submitted a 
report entitled “Hazards Involved in the 
Industrial Use of Micro-Organisms" 
prepared for the Commission of the 
European Communities. 
One RAC reviewer discussed Dr. 
Wright's letter point by point and 
summarized major points in the EEC 
report. He stated that he believes the 
EEC report supports Dr. Johnson's 
proposal more than Dr. Wright's 
position. The RAC reviewers concluded 
that the potential environmental 
problems associated with the use of 
well-characterized organisms in large- 
scale recombinant DNA production 
processes appear to be similar to those 
associated with non-recombinant DNA 
large-scale fermentations which 
industry has been performing with an 
excellent safety record. It was pointed 
out that economic considerations 
necessitate strong quality control 
procedures. 
RAC concluded that Dr. Johnson's 
proposed modification would benefit the 
public by facilitating the industrial 
development and production of useful 
products. Thus, by a vote of eleven in 
favor, two opposed, with one abstention, 
RAC recommended the proposal. 
I accept this recommendation. 
Section I-D-6 is amended to read as 
follows: 
“I-D-6. Large-scale experiments [e.g., 
more than 10 liters of culture] with 
organisms containing recombinant 
DNAs other than those listed in 
Appendix C, Sections 2, 3, and 4 of the 
Guidelines, unless the recombinant 
DNAs are rigorously characterized and 
the absence of harmful sequences 
established. (3). [See Section IV-E-l-b- 
(3)-(d)]'' 
The text in Appendix C dealing with 
large-scale experiments (Sections 2, 3, 
and 4) will be replaced with the 
following: 
“Large-scale experiments (e.g., more 
than 10 liters of culture) require prior 
IBC review and approval." 
D. Cloning of Subgenomic Segments of 
Rift Valley Fever Virus 
In a letter dated July 7, 1981, Dr. 
Charles Muscoplat of^olecular 
Genetics, Inc., Minnetonka. Minnesota, 
requested permission to clone 
subgenomic segments of the Rift Valley 
Fever Virus for the development of a 
vaccine. A notice concerning this 
request appeared in the Federal Register 
of August 4, 1981, (46 FR 39771). No 
comments were received on the 
proposal. 
'Hie RAC discussed this proposal at 
its September 10-11, 1981 meeting. It 
was noted that Rift Valley Fever Vims, 
a member of the Bunyaviridae family of 
vimses, is classified as a restricted 
agent by the Department of Agriculture 
since it produces a contagious disease 
both of cattle and sheep, and can be 
transmitted to man. It periodically 
causes disease epidemics especially in 
North Ahica, Asia, and other parts of 
the world. Transmission is by insects. 
Molecular Genetics, Inc., in a joint 
project with the U.S. Army Medical 
Research Institute of Infectious 
Diseases, proposes to clone a purified 
subgenomic segment. Since the vims 
consists of a negative, segmented single 
stranded RNA, cloning of the segment 
encoding the antigenic component poses 
no risk of infectivity. Further, it was 
noted that Molecular Genetics would be 
cloning the M segments of the RNA in 
an E. coli K-12 host-vector system only 
after rigorous safety testing for 
infectivity was performed by the Army 
Medical Research Institute. The RAC 
voted to approve the requested 
experiments to be performed at PI 
physical containment with the 
restriction that the work be performed in 
a laboratory where no other 
bunyavimses are used. In addition, it 
was stipulated that the “snap back” 
procedure be employed for generating 
the DNA. This assures that a complete 
viral genome could not be formed. The 
vote was sixteen in favor, none 
opposed, with two abstentions. 
I accept this recommendation, and 
text has been added to Appendix E of 
the Guidelines indicating this action. 
E. Proposed Exemption for 
Streptococcus Pyogenes and 
Streptococcus Sanguis 
A request submitted by Dr. Joseph 
Ferretti of the University of Oklahoma 
Health Sciences Center that 
Streptococcus pyogenes and 
Streptococcus sanguis be considered as 
natural exchangers of DNA under the 
exemption category of Section I-E-4 and 
Appendix A of the Guidelines was 
considered by the RAC at its September 
10-11, 1981 meeting. This proposal was 
published for comment in the Federal 
Register of August 4, 1981 (46 FR 39771). 
No comments were received on the 
proposal. 
The evidence presented by the 
investigator demonstrating exchange of 
genetic information in both directions by 
natural physiological processes was 
considel^d by the RAC. On the basis of 
the experimental evidence, the RAC 
recommended by a vote of fourteen in 
favor, none opposed, with no 
abstentions that the request be 
approved. 
I accept this recommendation and 
Streptococcus pyogenes has been added 
to sublist F of Appendix A. 
F. Request To Include Streptococcus 
Lactis in a Sublist of Appendix A and to 
Permit Transfer of a Recombinant 
Plasmid From S. Faecalis to S. Lactis 
Dr. Larry McKay of the University of 
Minnesota submitted a request for 
permission to allow the one way 
transfer of Streptococcus lactis DNA 
into 5. sanguis, and that these strains be 
included in the exemption category of 
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