Federal Register / Vol. 46, No. 149 / Tuesday, August 4, 1981 / Notices 
39771 
4. Request for Permission to Clone 
Subgenomic Segments of Rift Valley 
Fever Virus. 
Molecular Genetics, Inc., of 
Minnetonka, Minnesota in collaboration 
with the U.S. Army Medical Research 
Institute of Infectious Diseases, Fort 
Detrick, Md„ has requested permission 
to clone, under PI conditions, segments 
of Rift Valley Fever Virus encoding for 
antigenic determinants. 
5. Request to Clone Saccharomyces 
Cerevisiae DNA in Salmonella 
Typhimurium. 
Drs. Christopher Marvel and Edward 
Penhoet of the University of California, 
Berkeley, have requested permission to 
clone Saccharomyces cerevisiae DNA 
in Salmonella typhimurium using a 
nonmobilizable plasmid (YEpl3). 
6. Proposal To Amend Section III-B- 
3. 
Dr. Michael J. Ross, of Genentech, 
Inc., has requested the RAC to evaluate 
a proposal to amend Section III-B-3 of 
the Guidelines. Section III-B-3 currently 
specifies that the Director, NIH may set 
containment levels after a case-by-case 
review of certain experiments involving 
non-HVl host-vector systems. The 
cloning of higher eukaryotic DNA into 
non-certified host-vector systems is 
cited as an example. Dr. Ross proposes 
a provision which would permit cloning 
of DNA from anymonpathogenic species 
into nonpathogenic lower eukaryotes at 
the P3 level of containment; cloning of 
DNA from any nonpathogenic species 
into nonpathogenic prokaryotes would 
be allowed at the P2 level of 
containment. Data supporting the 
contention that the donor and recipient 
are nonpathogenic would be submitted 
to the local IBC. 
7. Proposed Amendment of Section /- 
D-6. 
Dr. Irving Johnson of Eli Lilly and 
Company has requested that Section I- 
D-6 be amended to read as follows (new 
text in italics): 
“I-D-6. Large-Scle experiments [e.g., 
more than 10 liters of culture] with 
organisms containing 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].] 
It is noted that certain other 
modifications of the Guidelines will be 
necessary in order to make them 
co'nsistent with the adoption of the 
amendment. For instance, the text 
dealing with large-scale experiments in 
Sections 2, 3, and 4 in Appendix C 
would be replaced with the following 
revised text: 
“Large-scale experiments (e.g., more 
than 10 liters of culture) require prior 
IBC review and approval.” 
8. Request to include streptococcus 
Pyogenes on Sublist F of Appendix A 
Dr. Joseph Ferretti of the University of 
Okahoma Health Sciences Center, 
Oklahoma City, Oklahoma, has 
requested that Streptococcus pyogenes 
and streptococcus sanguis be 
considered as natural exchangers of 
DNA under the exemption category of 
Section I-E-4 and included in Sublist F 
of Appendix A. He has submitted 
information concerning the evidence for 
exchange of genetic information 
between these organisms. 
9. Proposed Amendment of III-C-2a 
and Addition of a New Section III-C-7- 
c. 
Dr. Lois Miller of the University of 
Idaho, Moscow, Idaho, has proposed the 
following revision of Section III-C-2-a 
regarding experiments involving 
invertebrate viral vectors: 
“III-C-2. Invertebrate Host-Vector 
Systems. 
III-C-2-a. Invertebrate Viral Vectors. 
Experiments involving invertebrate 
virus vectors can be done as follows: 
III-C-2-a-(l). Recombinant DNA 
molecules containing no more than two- 
thirds of the genome of any invertebrate 
virus [all viruses from a single Family 
(36) being considered identical (50)] may 
be propagated and maintained in cells in 
tissue culture using Pi containment. For 
each experiments, it must be shown that 
the cells lack helper virus for the 
specific Families of defective viruses 
being used. The DNA may contain 
fragments of the genomes of viruses 
from more than one Family but each 
fragment must be less than two-thirds of 
a genome. 
III-C-2-a-(2). Recombinants with less 
than two-thirds of the genome of any 
invertebrate virus may be rescued with 
helper virus using P2 containment unless 
it is classified by the CDC as a class 3 
agent (1) in which case P3 containment 
is required. 
III-^-2-a-(3). Experiments involving 
the use of other whole or defective virus 
genomes to propagate DNA sequences 
from prokaryotic or eukaryotic 
organisms (and viruses), or as vectors to 
transform nonpermissive cells, will be 
evaluated by NIH on a case-by-case 
basis [45] and will be conducted under 
the prescribed physical and biological 
containment conditions. (See Section 
IV-E-l-b-(3)-(c).) 
NIH will also review on a case-by- 
case basis [45] all experiments involving 
the use of virus vectors in animals and 
will prescribe the physical and 
biological containment conditions 
appropriate for such studies. (See 
Section IV-E-l-b-(3)-(c).)" 
Dr. Miller also proposes that a new 
Section, III-C-7-c, be added to the 
Guidelines, as follows: 
“III-C-7-c. Transfer to Invertebrates. 
DNA from any nonprohibited source 
[Section I-D], except for greater than 
one quarter of a eukaryotic viral 
genome, which has been cloned and 
propagated in E. coli K-12, may be 
transferred with the E. coli vector used 
for cloning to any eukaryotic cells in 
culture or to any invertebrate organism 
and propagated under conditions of 
physical containment comparable to Pi 
and appropriate to the organism under 
study (2A). Transfers to any other host 
will be considered by the RAC on a 
case-by-case basis (45)." 
10. Containment Conditions for 
Cloning and Expression of DNA Coding 
for Diphtheria Toxin. 
In the revised Guidelines issued on 
July 1, 1981, Dr. John Murphy of Harvard 
University was given permission to 
clone in E 'coli K-12, under P4 
containment conditions, restriction 
fragments of Corynephage Beta carrying 
the structural gene for diphtheria toxin. 
Dr. Murphy requests that he be 
permitted to carry out the experiments 
within NIH high-contaimnent facilities 
with the selection of laboratory 
practices and containment equipment to 
be specified by the local biosafety 
committee (IBC). 
11. Development of New Host-Vector 
System based on Corynebacterium 
Glutamicurh. 
Dr. Daniel Liberman of Massachusetts 
Institute of Technology, Cambridge, 
Massachusetts, has requested 
assignment of appropriate containment 
conditions for development of a new 
host-vector system based on the gram 
positive bacterium Corynebacterium 
glutamicum as host with three possible 
types of vectors, including hybrid 
plasmids. 
Richard M. Krause, 
Director, National Institute of Allergy and 
Infectious Diseases. 
July 28, 1981. 
OMB's “Mandatory Information 
Requirements for Federal Assistance Program 
Announcements" (45 FR 39592) requires a 
statement concerning the official government 
programs contained in the Catalog of Federal 
Domestic Assistance. Normally NIH lists in 
its announcements the number and title of 
affected individual programs for the guidance 
of the public. Because the guidance in this 
notice covers not only virtually every NIH 
program but also essentially every federal 
research program in which DNA recombinant 
molecule techniques could be used, it has 
been determined to be not cost effective or in 
the public interest to attempt to list these 
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