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Federal Register / Vol. 50. No. 160 / Monday, August 19, 1985 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Recombinant DNA Advisory 
Committee; Meeting 
Pursuant to Pub. L. 92-463, notice is 
hereby given of a meeting of the 
Recombinant DNA Advisory Committee 
at the National Institutes of Health, 
Building 31C, Conference Room 6, 9000 
Rockville Pike, Bethesda, Maryland 
20205, on September 23, 1985, from 9:00 
a.m. to adjournment at approximately 
5:00 p.m. This meeting will be open to 
the public to discuss: 
Points to Consider in the Design and 
Submission of Human Somatic-Cell 
Gene Therapy Protocols; 
Containment for cloning of toxin genes; 
Exchange list for gram positive bacteria; 
Amendment of Guidelines; and 
Other matters to be considered by the 
Committee. 
Attendance by the public will be 
limited to space available. Members of 
the public wishing to speak at the 
'meeting may be given such opportunity 
at the discretion of the chair. 
Dr. William J. Gartland, Jr., Executive 
Secretary, Recombinant DNA Advisory 
Committee, National Institutes of 
Health, Building 31, Room 3B10, 
telephone (301) 496-8051, will provide 
materials to be discussed at the meeting, 
rosters of committee members, and 
substantive program information. A 
summary of the meeting will be 
available at a later date. 
Dated: August 13, 1985. 
Thomas E. Malone 
Deputy Director, NIH. 
(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 
programs. Such 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 aoove about whether individual 
programs listed in the Catalog of Federal 
Domestic Assistance are affected.) 
(FR Doc. 85-19719 Filed 8-16-85; 8:45 am) 
BILLING COOE 4140-01-M 
Recombinant DNA Research; 
Proposed Actions Under Guidelines 
AGENCY: National Institutes of Health, 
PHS, DHHS. 
action: Notice of Proposed Actions 
under NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
SUMMARY: This notice sets forth 
proposed actions to be taken under the 
NIH Guidelines for Research Involving 
Recombinant DNA Molecules. 
Interested parties are invited tb submit 
comments concerning these proposals. 
After consideration of these proposals 
and comments by the NIH Recombinant 
DNA Advisory Committee (RAC) at its 
meeting on September 23, 1985, the 
Director of the National Institutes of 
Health will issue decisions on these 
proposals in accord with the Guidelines. 
DATE: Comments must be received by 
September 18, 1985. 
ADDRESS: Written comments and 
recommendations should be submitted 
to the Director, Office of Recombinant 
DNA Activities, Building 31, Room 3B10, 
National Institutes of Health, Bethesda, 
Maryland 20205. All comments received 
in timely response to this notice will be 
considered and will be available for 
public inspection in the above office on 
weekdays between the hours of 8:30 
a.m. and 5:00 p.m. Comments received 
by close of business September 16, 1985, 
will be reproduced and distributed to 
the RAC for consideration at its 
September 23, 1985, meeting. 
FOR FURTHER INFORMATION CONTACT: 
Background documentation and 
additional information can be obtained 
from Drs. Stanley Barban and Elizabeth 
Milewski, Office of Recombinant DNA 
Activities, National Institutes of Health, 
Bethesda, Maryland 20205, (301) 496- 
6051.. 
SUPPLEMENTARY INFORMATION: The 
National Institutes of Health will 
consider the following actions under the 
Guidelines for Research Involving 
Recombinant DNA Molecules. 
I. Request for Permission To Clone 
Shiga-like Toxin From the Families 
Enterobacteriaceae and Vibrionaceae in 
E. coli K-12 
Dr. Alison O'Brien of the Uniformed 
Services University of the Health 
Sciences had previously (49 FR 36052) 
received permission from the National 
Institutes of Health to clone the 
structural gene of the Shiga-like toxin 
(SLT) of Escherichia coli in E. coli K-12. 
The specific language concerning the 
permission reads as follow^ in the 
current version of the NIH Guidelines 
(49 FR 46279): 
Appendix F-IV-H. The intact structural 
gene(s) of the Shiga-like toxin from £. coli 
mtfy be cloned fn E. coli K-12 under BL3 + 
EK1 containment conditions. 
E. coli host-vector systems expressing the 
Shiga-like toxin gene may be moved from BU 
to BL2 containment conditions provided that: 
(1) The amount of toxin produced by the 
modified host-vector systems is no greater 
than that produced by the positive control 
strain 933 £. coli 0157H7, grown and 
measured under optimal conditions; and (2j 
the cloning vehicle is to be an EKl vector 
preferably belonging to the class of poorly 
mobilizable plasmids such as pBR322, 
pBR328, and pBR325. 
Nontoxinogenic fragments of the Shiga-like 
toxin structural gene(s) may be moved from 
BL3 + EKl to BL2 + EKl containment 
conditions or such nontoxic fragments may 
be directly cloned in E. coli K-12 under BL2 
-I- EKl conditions provided that the E. coli 
host-vector systems containing the fragments 
do not contain overlapping fragments which 
■together would encompass the Shiga-like 
toxin structural gene(s). 
Dr. O’Brien is now requesting 
permission to clone SLT structural 
genes, defined either by nucleotide 
sequence homology with SLT gene 
probes from E. coli or by antigenic 
cross-reactivity of their gene products 
with purified E. coli SLT, from bacterial 
species classified in the families 
Enterobacteriaceae or Vibrionaceae 
into E. coli K-12 under conditions 
similar to those specified in the previous 
permission. Dr. O'Brien wishes to 
broaden the scope of study of SLT toxin 
for the following reasons: (1) To 
investigate the potential role of SLT in 
the pathogenicity of a variety of 
bacteria; (2) to compare the SLT genes 
from various pathogenic bacteria; and 
(3) to facilitate the development of an 
experimental Vibrio cholerae vaccine 
strain deleted for SLT genes. 
Dr. O'Brien has supplied information 
supporting this request to ORDA. 
II. Request To Clone a Hybrid Toxin 
Gene in E. Coli K-12 
Dr. John Murphy of the University 
Hospital of Boston University Medical 
Center requests permission to construct 
a hybrid molecule in which the gene 
coding for interleukin-2 (IL2) is joined to 
a segment of the gene encoding 
diphtheria toxin. The diphtheria toxin 
segment encodes the A subunit and 
portions of the B subunit. The hybrid 
gene would be cloned in E. cob K-12 
host-vector systems. 
[324] 
