Federal Register / Vol. 45, No. 85 / Wednesday, April 30, 1980 / Notices 
28909 
"The members of the committee shall be 
chosen to provide, collectively, expertise in 
scienctific fields relevant to recombinant 
DNA technology and biological safety — e.f 
microbiology, molecular biology, virology, 
genetics, epidemiology, infectious diseases, 
the biology of enteric organisms, botany, 
plant pathology, ecology, and tissue culture. 
Appropriate representatives of industry shall 
aisQ be chosen to provide expertise in 
fermentation technology, engineering, and 
other aspects of large-scale production. At 
least 20 percent of the members shall be 
persons knowledgeable in an applicable law, 
standards of professional conduct and 
practice, public attitudes, the environment, 
public health, occupational health, or related 
fields. Representatives from Federal agencies 
shall serve as non-voting members. 
Nominations for the RAC may be submitted 
to the NIH Office of Recombinant DNA 
Activities." 
The first and third paragraphs of 
Section IV-E-2 would remain 
unchanged. 
C. Amend Section IV-E-2, 
Recombinant Advisory Committee, to 
add a new section IV-E-2-b, as follows: 
‘TV-E-2-b. A permanent subcommittee of 
the RAC shall be responsible for advising the 
Director of NIH, on the actions, listed in 
Section IV— El— 1— b— (3) — (d) pertaining to large- 
scale applications. Submissions that are in 
compliance with the Guidelines may be 
recommended by the subcommittee to the 
Director of NIH for approval. The 
subcommittee shall also be authorized to 
consider preliminary plans for large-scale 
operations and to recommend approval 
contingent upon completion of the large-scale 
facility according to tiiose plans. The 
subcommittee will be responsible for 
expeditiously processing applications.” 
19. Request for Use of Con/ugadve 
Plasmids and Transducing Phages in an 
Escherichia coli K-12 Host. Dr. A. L 
Bukhari of the Cold Spring Harbor 
Laboratory has requested permission 
from the RAC to employ conjugative 
plasmids or transducing phages in 
recombinant DNA experiments 
involving Escherichia coli DNA when a 
small fragment of heterologous DNA is 
used as a linker. In the specific request, 
Dr. Bukhari requests approval to use a 
fragment of Adi DNA as linker DNA. 
20. Request for Exception to a 
Prohibition to Clone DNA from a Class 
3 CDC Agent. Dr. Sebastiao Baeta 
Henriques of the Instituto de Ciencias 
Biologicas, Belo Horizonte, Brazil, 
requests the RAC to approve an 
exception to a prohibition to clone genes 
from Schistosoma mansoni, a Class 3 
CDC agent, in E. coli K-12. This request 
was considered briefly at the March 6-7, 
1980 RAC meeting. Dr. Henriques was 
requested to provide information as to 
why he is requesting NIH approval for a 
non-NIH project to be conducted in 
Brazil. Dr. Henriques has provided NIH 
with an additional letter of explanation. 
Additional Announcements of the 
Director, NIH 
Section IV-E-l-b-{3)-(d) of the 
Guidelines gives responsibility to the 
Director, NIH, for "authorizing, under 
procedures specified by the RAC, large- 
scale experiments (i.e., involving more 
than 10 liters of culture) for recombinant 
DNAs that are rigorously characterized 
and free of harmful sequences." 
Accordingly, several requests for 
authorization to culture, on a large scale, 
recombinant DNA host-vestor systems 
have been received and reviewed by the 
NIH. 
I. Genentech, Inc. 
On the recommendation of the RAC, 
the following requests from Genentech, 
Inc. have been approved by the Director, 
NIH: 
A. On April 1, 1980, the Director, NIH 
approved a request from Genentech, Inc. 
for the large-scale culture up to 750 liters 
of EKl host-vector systems containing a 
plasmid into which has been ligated a 
combination of chemically synthesized 
DNA and cloned cDNA coding for 
human growth hormone. 
B. On April 9, 1980, the Director, NIH 
approved a request from Genentech, 
Inc., for the large-scale culture up to 750 
liters of EKl host-vector systems 
constructed to produce various chimeric 
fusion proteins containing either 
somatostatin, human insulin A chain, 
human insulin B chain, human 
pro insulin, and thymosin alphaL 
Both requests were approved with the 
understanding that Genetech, Inc., has 
agreed to permit an observer, designated 
by NIH, to visit the facilities if NIH 
should choose to inspect the site, and to 
certain additional stipulations. 
The principal investigators are Drs. 
Michael Ross and Norm S. C. Lin. The 
work is to be done, as stipulated by the 
Genentech, Inc. submission, in a “P2 
laboratory housing fermentors modified 
and tested to totafly contain the 
recombinant organisms until they are 
chemically or physically killed at the 
end of each fermentation * * * at the 
research and development facility at 460 
Point San Bruno Boulevard, South San 
Francisco, California 94080.” 
II. Eli Lilly & Co. 
A. On April 7, 1980, the Director, NIH, 
approved a request from Eli Lilly and 
Company for large scale culture of an 
EKl host-vector system containing a 
plasmid coding for human proinsulin 
covalently joined to E. coli (1- 
galactosidase, at the P2 and Pl-LS 
levels of containment. 
B. On April 7, 1980, the Director, NIH, 
approved a request to amend a previous 
submission of Eli Lilly and Company. In 
the previous submission, which was 
approved on October 5, 1979 by the 
Director, NIH, Eli Lilly and Company 
requested permission to culture on a 
large-scale EKl hoot-vector systems 
separately carrying the chemically 
synthesized insulin A chain and B chain. 
The February 1980 submission requested 
permission to amend this protocol to 
permit culture of the same host-vector 
systems in larger volumes at the Pl-LS 
level of containment. 
C. On April 9, 1980, the Director, NIH 
approved a joint request from Eli Lilly 
and Company and Genentech, Inc., for 
large scale culture of EKl host-vector 
systems producing human proinsulin, 
insulin A chain, and insulin B chain as 
chimeric fusion proteins in RAC- 
approved fermentors of Eli Lilly and 
Company at the P2 and Pl-LS levels of 
containment. . 
These requests were approved with 
the understanding that Lilly Research 
Laboratories have agreed to permit an 
observer, designated by NIH, to visit the 
facilities if NIH should choose to inspect 
the site. 
The principal investigator for these 
projects is Dr. Lawrence E. Day. The 
large scale growth of the organisms is to 
be carried out at plant facilities located 
at 1200 South' Kentucky Avenue, 
Indianapolis, Indiana 46206. 
Dated: April 23, 198a 
Donald S. Fredrickson, 
Director, National Institutes of Health. 
[FK Doc. 80-12986 Filed 4-29-90: 8:45 m] 
BILL! NO CODE 4110-09-91 
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