Federal Register / Vol. 46, No. 48 / Thursday, March, 12, 1981 / Notices 
16455 
the working group does not agree that 
the request represents a minor 
modirication, the application will then 
be referred to the full RAC at its next 
meeting. If the working group is 
unanimous in concluding that the 
changes do not alter the organism in a 
way that is likely to affect containment 
of the organism or the vector, or the 
nature of the expressed product 
significantly, from that presented 
originally to RAC, recommendation for 
approval will be transmitted to ORDA, 
and, through ORDA, to the submitters. 
Consideration of requests by working 
groups should explicitly address the 
following issues; Is the change likely to 
compromise biological containment 
provided by the host or the vector? Does 
the change add to the biological 
activities associated with the expressed 
products in a way not considered by the 
original submission?” 
During the thirty day comment period, 
no comments were received. 
Prior to publication in the Federal 
Register, the RAC discussed the 
proposal at the September 25-26, 1960 
meeting; the proposed procedures were 
considered to be reasonable. 
The RAC subsequently discussed the 
proposal at the January 8-9, 1981 
meeting and by a vote of seventeen in 
favor, none opposed and one abstention, 
recommended approval of the proposed 
language. 
I accept this recommendation. The 
complete text of the revised procedures 
for review of large-scale experiments 
appears in Part II of this announcement. 
2. Proposed Procedures for Change of 
Locale of Previously Approved Large- 
Scale Recombinant DMA Experiments. 
During the discussion of proposed 
procedures dealing with minor 
modifications of previously approved 
large-scale recombinant DNA 
experiments at the January 8-9, 1981, 
RAC meeting, the question of how to 
process changes of site for large-scale 
production was raised. In this situation, 
recombinant clones, which had been 
approved for scale-up at one site, would 
be moved to another physical facility. A 
second IBC might then be charged with 
oversight responsibilities. 
RAC recommended that a registration 
document, which would indicate 
compliance with the NIH Guidelines and 
its large-scale procedures should be 
filed with ORDA by the IBC of the new 
institution. ORDA could then give 
approval for large-pcale growth of the 
clones at the new site. No RAC review 
would be required. 
I accept this recommendation. 
Accordingly, the following additional 
language will be added to the 
"Application Procedures for Large-Scale 
Recombinant DNA Experiments": 
"7. Should a clone, previously 
approved for scale-up at one physical 
facility, be proposed to be moved to a 
second physical facility, the IBC with 
oversight responsibility at the second 
site shall submit to ORDA a registration 
document and receive ORDA approval, 
prior to initiating scale-up. No RAC 
review would be required. 
The complete text of the revised 
procedures for review of large-scale 
experiments appears in Part II of this 
announcement. 
I-H. Proposals To Clone Genes of Foot 
and Mouth Disease Virus 
The RAC at its December 6-7, 1979, 
meeting had reviewed a four stage 
proposal submitted by Dr. Howard 
Bachrach of the United States 
Department of Agriculture Plum Island 
Animal Disease Center and Dr. Dennis 
Kleid of Genentech, Inc., entitled 
"Cloning and Expression in E. coli of the 
VPS protein of Foot and Mouth Disease 
Virus." In the Federal Register of 
January 17, 1980 (46 FR 3552J, I, as 
Director, NIH, accepted the RAC 
recommendation to allow Stage I to 
proceed. At that time I noted, “Dr. 
Campbell stated that it was ^e sense of 
the RAC that this motion constituted the 
‘major action* and that future 
recommendations of the RAC approving 
further stages of the experiment woidd 
be ‘minor actions.’ ” 
In the Federal Register of July 29, 1980 
(45 FR 50528), I, as Director, NIH, 
accepted a recommendation made by 
the RAC at its June 5-6, 1980, meeting 
that certain clones containing cDNA 
copies of pieces of the Foot and Mouth 
Disease virus, made on Plum Island 
under Stage I of the protocol, be allowed 
to be removed from Plum Island, as they 
"were well characterized, lacked 
infectivity, and represent, in aggregate, 
only 75% of the FMD viral genome.” 
On January 9, 1981, the RAC reviewed 
a request of October 17, 1980, from Dr. 
Kleid to modify Stage IV of the protocol, 
dealing with cloning of various FMD 
types. The RAC by a vote of 20 in favor, 
none opposed, and one abstention, 
recommended that this be accepted with 
the conditions that a working group of 
the RAC, but not the full RAC, would 
examine data on the infectivity of the 
clones produced on Plum Island, before 
they were allowed to leave Plum Island, 
and that such clones be well 
characterized, shown to lack infectivity, 
and shall not contain, individually or 
collectively, more than 75% of the viral 
genome. 
1 accept this recommendation. 
/-/. Containment Levels for 
Recombinant DNA Experiments 
Involving Streptomyces and Other Non- 
Pathogenic Actinomycetes 
Dr. Stanley Cohen of Stanford 
University Medical Center, in a letter 
dated November 18, 1980, submitted the 
following proposal for consideration by 
the RAC: 
“That all members of the non- 
pathogenic Actinomycetes genus 
Streptomyces and the plasmids native to 
this genus be approved as host-vectdr 
systems for the cloning imder PI 
conditions of DNA derived from other 
non-pathogenic prokaryotic organisms 
such as Streptomyces and other non- 
pathogenic Actinomycetes species, 
Escherichia coli K-12, Bacillus subtilis. 
Bacillus lichenformis, Bacillus 
circulans, and other non-pathogenic 
Bacillus species, and for the cloning of 
DNA derived from non-pathogenic 
unicellular eukaryotic micro-organisms 
siich as Saccharomyces cerevisiae and 
Neurospora crassa, " 
The RAC noted that they had 
recommended earlier in the meeting (see 
I- A above) that all experiments 
involving nonpathogenic prokaryotes 
and lower eukaryote's, be allowed at Pi. 
Dr. Cohen's request involves a subset of 
these. The RAC, by a vote of 18 in favor, 
none opposed, and two abstentions, 
recommended that the proposal be 
accepted. 
I accept this recommendiftion, and a 
new entry will be added to Appendix E 
as follows: 
“27. All members of the 
nonpathogenic Actinomycetes genus 
Streptomyces and the plasmids native to 
this genus are approved as host-vector 
systems for the cloning under Pi 
conditions of DNA derived from other 
nonpathogenic prokaryotic organisms 
such as Streptomyces and other 
nonpqthogenic Actinomycetes species, 
Escherichia coli K-12, Bacillus subtilis. 
Bacillus lichenformis, Bacillus 
circulans, and other nonpathogenic 
Bacillus species, and for the cloning of 
DNA derived from nonpathogenic 
unicellular eukaryotic microorganisms 
such as Saccharomyces cerevisiae and 
Neurospora crassa. ” 
II. Summary of Actions Under 
Guidelines — ^Arranged According to 
Position in Guidelines 
II- A. Amendment of Second Paragraph 
of Part III 
The final sentence in the second 
paragraph under Part III is amended to 
read as follows: 
"Prior IBC review is required for all 
other experiments described in the 
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