Federal Re^ster / Vol. 45, No. 231 / Friday, November 28, 1980 / Notices 
7938! 
pathogenic prokaryotes (see Section IH- 
B-3).” 
3. Proposed Application Procedures 
for Minor Modifications of Previously 
Approved Large-Scale Recombinant 
DNA Experiments. 
A Working Croup of the Recombinant 
DNA Advisory Committee (RAC) has 
requested that the following language 
outlining proposed procedures for minor 
modirications of previously approved 
large-scale recombinant DNA 
experiments be published In the Federal 
Register for public comment: 
"Procedures have been developed for 
considering applications to grow more 
than ten liters of an organism containing 
recombinant DNA. These procedures 
Include consideration of the request by a 
working group of the NIH Recombinant 
DNA Advisory Committee, submission 
of the request to the full RAC after 
consideration by the working group, and 
subsequent submission to the Director, 
NIH for flnal review. This procedure 
has taken a minimum of two months. 
Therefore, the following procedures are 
proposed to expedite consideration of 
requests to grow more than ten liters of 
recombinant DNA-contalning organisms 
whan these proposals represent minor 
modifications of previously approved 
experiments. Modifications Include 
deletion of sequences from the 
recombinant DNA, changes In 
promoters, addition of short segments 
not affecting the nature of the expressed 
products, and minor changes In the 
properties of the host. Changes are 
considered minor If they do not affect 
either the containment properties of the 
vector or the host, or the natiire of 
products made, or add new products. 
Therefore, the procedures for dealing 
with minor modifications have the 
objective of determining that the change 
Is indeed minor. To determine whether a 
change is minor, two levels of review 
will take place: (1) By ORDA. which will 
decide upon receipt of a request to 
process It as a new request or as a 
minor modification, and in the latter 
case (2) by a working group of at least 
two members of RAC" 
The Working Croup has proposed that 
the following language be added to the 
"Application Procedures for Large-Scale 
Rerambinant DNA Experiments": 
'‘8. Proposals that the submitter 
coiuiders to represent minor 
piodlflcations of already approved 
experiments will be handled by an 
expedited procedure. A request must be 
submitted to ORDA. This request should 
Include the changes made, the way in 
which these changes were made (e.g.. 
mutagenesis, recloning), and the nature 
and results of any tests done to 
determine that no major change has 
occurred (e.g., restriction enzyme 
analysis, tests for produced products, 
tests of vector mobilization). 
"ORDA will determine whether the 
submission represents a minor 
modification of an approved experiment 
If so, the request will be submitted 
promptly to a working group of at least 
two RAC members. If possible, these 
members should have been present at 
the RAC discussion of approval of the 
original experiment If any member of 
the working group does not agree that 
the request represents a minor 
modification, 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 contaiiunent 
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 submlssionr* 
4. Request to Clone Saccharomyces 
Cerevisiae DNA in Tetrahymena. 
Dr. Eduardo Orias of the University of 
California, Santa Barbara, requests 
(Mrmission to clone Saccharomyces 
cerevisiae DNA in Tetrahymena 
thermophila using S cerevisiae! E coli 
hybrid plasmids. 
5. Proposal to Amend Item 4 of 
Appendix E 
Dr. Qarence Kado of the University of 
California. Davis, has proposed that the 
fourth entry in appendix E be modified 
to read as follows: 
*X3onad datlrsd fragment from any non- 
prohlblted source may be transferred Into 
Afroboclenum lumefociens cootalning a T1 
plasmid (or derive tes tbereoO. using a 
noncontugative £ coli plasmid vector 
coupled to a fragment of the Tl plasmid and/ 
or the orgln of replication of an 
Agrobocterium plasmid, under containment 
conditions that would be required for the 
desired DNA In HVl systems (i.e.. that 
spedfled in the subsections of Section (ID-A]. 
Transfer Into plant parts or cells in cultiue 
would be permitted at the same containment 
leveL" 
8. Request for Lowering of 
Containment Under Entry Four of 
Appendix E. 
Dr. Mary-Dall Chilton of Washington 
University in St. Louis requests a 
redaction in physical containment for 
the manipulation in Agrobacterium 
tumefaciens of (1) the Saccharomyces 
cerevisiae alcohol dehydrogenase 1 
gene cloned In pBR322, and (2) the gene 
coding for the maize (Zea mays) seed 
storage protein zein, cloned in Charon 
4A. TTie cloned DNA and the vectors 
will be introduced into tobacco plants. 
Appendix E, entry four, currently sets 
containment for such experiments at P3. 
Dr. Chilton requests approval for these 
experiments under P2 physical 
containment. Her justification is 
outlined in a letter to ORDA. 
7. Request for HVl Certification of a 
Schisosaccharomyces Pombe Host- 
Vector System and Inclusion in Section 
III-O. 
Dr. Benjamin D. Hall of the University 
of Washington requests that the fission 
yeast, Schizosaccharomyces pombe, 
together with yeast-£. coU hybrid 
recombinant plasmids be certified as an 
HVl host-vector system. Dr. Hall in 
addition requests that this system be 
Included under Section IIl-O. He has 
provided ORDA with supporting 
dociimentation. 
Dated: November 20, 1060. 
Donald 8. Fredrickson, 
Director. National Institutes af Health. 
Note.— OMB’t "Manadatory Information 
Requirements for Federal Assistance Program 
Announcements" (45 FR 30502) requires a 
statament 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 
progrem 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 ettempt to list these 
programs. Suxdi a list would likely require 
several additional pages. In addition. NIH 
could not be certain that every federal 
program would be included as many federal 
agencies, as well as private organizations, 
both national and international, have elected 
to follow the NIH Guidelines. In lieu of the 
individual program listing. NIH invites 
readers to direct questions to the Information 
address ebove eboul whether individual 
programs listed In the Catalog of Federal 
Domestic Assistance are affected. 
NIH programs are not covered by OMB 
CIrctilar A-65 because they fit the description 
of "programs not considered appropriate" in 
Section 8-{b)ri4) and (5) of that Circular. 
(TS Doc so-roisniod ii-as-sot s«s onl 
BWJJNQ COOC 4110-OS-M 
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