53056 
Federal Register / Vol. 48, No. 227 / Wednesday, November 23. 1983 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Recombinant DNA Research; Actions 
Under the Guidelines 
agency: National Institutes of Health, 
PUS, HHS. 
action: Notice of Actions under N1H 
Guidelines for Research Involving 
Recombinant DNA Molecules. 
| 
summary: This notice sets forth actions 
taken by the Director, National Institute 
of Allergy and infectious Diseases 
(NIAID), by authority of the Director, 
NIH, under the June 1983 NIH 
Guidelines for Research Involving 
! Recombinant DNA Molecules (48 FR 
24556). 
EFFECTIVE DATE: November 23, 1983. 
FOR FURTHER INFORMATION CONTACT: 
Additional information can be obtained 
from Dr. William J. Gartland, Office of 
Recombinant DNA Activities (ORDA), 
National Institutes of Health, Bethesda. 
Maryland 20205, (301) 496-6051. 
SUPPLEMENTARY INFORMATION: Two 
major actions under the NIH Guidelines 
for Research Involving Recombinant 
| DNA Molecules are being promulgated 
today. These proposed actions were 
published for comment in the Federal 
Register of August 16, 1983 (48 FR 
37198), and reviewed and recommended 
for approval by the Recombinant DNA 
Advisory Committee (RAC) at its 
1 meeting on September 19, 1983. In 
accordance with Section IV-C-l-b of 
the NIH Guidelines, these actions have 
been found to comply with the 
Guidelines and to present no significant 
risk to health or the environment. 
Part I of this announcement provides 
background information on the actions. 
Part II provides a summary of the 
actions and additional announcements 
of the Director, NIAID. 
I. Decisions on Actions Under 
Guidelines 
A. Inclusion of S. Mu tans in Sublist F of 
Appendix A 
Dr. Francis Macrina of the Medical 
College of Virginia of the Virginia 
Commonwealth University requested 
the Streptococcus mutans be included in 
Sublist F of Appendix A of the NIH 
Guidelines for Research Involving 
i Recombinant DNA Molecules. Dr. 
j Macrina argued thati>. mutans should 
I be included in this sublist for the 
following reasons: 
1. A broad host range streptococcal 
plasmid, pAM/3l (conferring 
erythromycin resistance), is 
conjugatively transmissible to S. 
mutans. Strains of S. mutans inheriting 
this plasmid are able to transmit it via 
conjugal transfer. 
2. The report of non-plasmid 
associated conjugal transfer of 
tetracycline resistance from S. mutans to 
other strains of S. mutans and to S. 
faccalis. support the claim of natural 
genetic transfer from S. mutans to other 
streptococci. 
3. A tetracycline resistance 
determinant from a naturally-resistant S. 
mutans clinical isolate shares sequence 
homology to the Tn916 (Tc r ) conjugative 
transposon originating in S. faecalis. 
4. Naturally transformable strains of 
S. mutans are readily transformed with 
plasmid or chromosomal DNA from 
other mutans as well as sanguis strains. 
5. S. mutans is far less virulent than 
two of the current members of Sublist F. 
S. pneumoniae and 5. pyogenes. 
The proposal was published in the 
August 16, 1983 Federal Register (48 FR 
37199). No comments were received. 
The RAC reviewed this proposal at its 
September 19, 1983, meeting. It was 
judged that the data supplied by Dr. 
Macrina showed that S. mutans 
exchanges DNA by known physiological 
processes with the other organisms 
already listed in Sublist F of Appendix 
A of the Guidelines. The RAC 
recommended that S. mutans be 
included in Sublist F of Appendix A by a 
vote of 14 in favor, 0 opposed, and 0 
abstentions. 
I accept this recommendation, and S. 
mutans has been added to Sublist F, 
Appendix A. Sublist E of Appendix A 
will remain as previously published as 
S. lactis is included in Sublist E, but not 
Sublist F. 
B. Modification of Appendix L 
The RAC Working Group on Revision 
of the Guidelines at its January 21, 1983. 
meeting recommended that Guidelines 
for field experimentation involving 
plants modified by recombinant DNA 
techniques be developed for 
consideration at the April 11, 1983, RAC 
meeting. 
The Guidelines in force at that time 
required RAC review and NIH approval 
as well as IBC approval for the 
"deliberate release into the environment 
of any organism containing recombinant 
DNA.” The proposal developed by the 
working group would have changed this 
so that provided experiments met 
certain criteria, growing of plants 
containing recombinant DNA in the field 
would have been able to proceed 
without RAC review and NIH approval. 
IBC approval would have been required 
as would notification to ORDA. 
The RAC considered the proposal at 
its April 11. 1983, meeting and discussed 
it extensively. RAC made several 
modifications in the specific criteria and 
modified the procedural aspects of the 
proposal. The RAC recommended that 
the modified language be incorporated 
into a new appendix (Appendix L) 
which would require review and 
approval of experiments both by the 
Institutional Biosafety Committee (IBC) 
and also by the Plant Working Croup of 
the RAC. 
The exact language of Appendix L 
was subsequently developed by NIH 
Staff based on the recommendations 
made at the RAC meeting. The United 
States Department of Agriculture 
(USDA) Recombinant DNA Committee 
then reviewed the RAC 
recommendation, including the proposed 
wording for Appendix L, and endorsed 
their adoption. 
The Nil I accepted the proposed 
language and incorporated it into the 
Guidelines as Appendix L (48 FR 24548 
and 24580). Subsequently, Dr. Sue Tolin, 
the liaison member of the Department of 
Agriculture to the RAC, in consultation 
with other members of the RAC Plant 
Working Croup, proposed amendments 
to Appendix L— II— C which gives some of 
the criteria allowing review by the RAC 
Plant Working Group without the 
requirement for full RAC review. 
Appendix L— II— C currently reads as 
follows: 
Appendix L-lt-C. The vector consists of 
DNA: (i) From exempt host-vector systems 
(Appendix C): (ii) from plants of the same or 
closely related species: (iii) from 
nonputhogenic prokaryotes or nonpathogenic 
lower eukaryotic plants: (iv) from plant 
pathogens only if sequences aausing disease 
have been deleted; or (v) chimeric vectors 
constructed from sequences defined in (i) to 
(iv) above. The DNA may be introduced by 
any suitable method. 
Dr. Tolin proposed that Appendix L- 
II— C be modified to read as follows: 
Appendix L-II-C. The vector consists of 
DNA: (i) From exempt host-vector systems 
(Appendix C); (ii) from plants of the same or 
closely related species; (iii) from 
nonpathogenic prokaryotes or nonpathogenic 
lower eukaryotic plants; (iv) from plant 
pathogens only if sequences resulting in 
production of disease symptons have been 
deleted; or (v) chimeric vectors constructed 
from sequences defined in (i) to (iv) above. 
The DNA may be introduced by any suitable 
method. If sequences resulting in production 
of disease symptoms are retained for 
purposes of introducing the DNA into the 
plant, greenhouse-grown plants must be 
shown to be free of such sequences before 
such plants, derivatives, or seed from the~ 
can be used in field tests. 
The proposal was published in the 
August 16, 1983, Federal Register (48 FR 
37199) for comment. No comments were 
received. 
