33126 
NOTICES 
coll K-12 in the Human Intestine. Nature 
255:502-504. 
(12) Homick. R B. (1977). Unpublished 
experiments reported at the Falmouth 
Workshop on Risk Assessment. See Appen- 
dix Hi. op. clt. ref 6. 
(13) Curtiss in. R. (April 12. 1977). Letter 
to Donald Fredrickson. Available from the 
NIH Office of Recombinant DNA Activities. 
(14) Oorbach. S. L. (July 14. 1977). Letter 
to Donald Fredrickson (Including list of par- 
ticipants at Falmouth Workshop on Risk 
Assessment. June 20-21. 1977). See Appen- 
dix M. op. clt. ref. 8. 
(15) Falkowr. S. (December 7. 1978). Letter 
to Donald Fredrickson. 
(18) Anderson. J. D.. W A. Gillespie, and 
M H. Richmond (1974). Chemotherapy and 
Antibiotic Resistance Transfer Between En- 
terobacteria in the Human Gastrointestinal 
Tract. J Med. Microbiol. 6. 461-473. 
(17) Freler. Rolf (1977). Real and Imag- 
ined Dangers of Recombinant DNA Technol- 
ogy- The Need for Expert Evaluation. To be 
published by the University of Michigan 
Press In a monograph. 77ie Recombinant 
DNA Debate. 
(18) Lewln. B R.. and F. M. Stewart 
(1977). Probability of Establishing Chimeric 
Plasmids in Natural Populations af Bacte- 
ria. Science 196' 218. 
(19) Murray. K.. personal communication: 
W. Szybalskl. personal communication. 
(20) Thomas. M.. J. R. Cameron, and R. 
W. Davis (1974). ItlaMe Molecular Hybrids 
of Bacteriophage Lambda and Eukaryotic 
DNA Proc. Nat. Acad. Set USA 71 4579- 
4583 
(21) Murray. N E.. and K Murray (1974). 
Manipulation of Restriction Targets in 
Phage Lambda to Form Receptor Chromo- 
somes for DNA Fragments. Nature 25J:476- 
481 
(22) Rambach. A. and P. Ttollais (1974) 
Bacteriophage Lambda Having EcoRl En- 
donuclease Sites Only in the Non-essential 
Region of the Genome Proc. Nat. Acad. Scl. 
USA 7! 3927-3930 
(23) Manly. K. R . E. R. Signer, and C. M 
Radding (1989). Nonessential Functions af 
Bacteriophage Lambda. Virology J7.177. 
(24) Gottesman. M. E . and R. A. Weis berg 
(1971). Prophage Insertion and Excision. In 
The Bacteriophage Lambda (A. D. Hershey. 
ed ). Cold Spring Harbor Laboratory, pp. 
113-138. 
(25) Shlmada. K.. R. A. Wetsberg. and M. 
E. Gottesman (1972). Prophage Lambda at 
Unusual Chromosomal Locations: I. Loca- 
tion af the Secondary Attachment Sites and 
the Properties of the Lysogens. J. Mol. Biol. 
6*483-503 
(26) Gargarosa. E. J. (June 20-21. 1977). 
Unpublished experiments, reported at Fal- 
mouth Workshop on Risk Assessment. 8ee 
Appendix M.. op. clt.. ref. 6. 
(27) Appendix Af. op. clt.. ref. 6. 
(28) Appendix H.. op. clt. ref 6. 
(29) Petrochetlou. V.. and M H. Richmond 
(1977) Absence of Plasmid or E. Coll K-12 
Infection Among Laboratory Personnel En- 
gaged in R-Plasmid Research. Gene *323- 
327. 
IV. Roles and Responsibilities 
Analysis of Current Guidelines 
The Guidelines contain a large sec- 
tion. Part IV. defining the roles and 
responsibilities of individuals and In- 
stitutions in assuring compliance with 
required containment levels. The pro- 
cedures described are primarily direct- 
ed at grantees of the National Insti- 
tutes of Health. Similar procedures 
are in force for work within NIH labo- 
ratories and for work sponsored by 
NIH under contracts. 
The principal Investigator is re- 
quired to assess any potential bioha- 
zards. to institute appropriate safe- 
guards and procedures, to minimize ef- 
fects of possible accidents by planning, 
to train and Inform all personnel, and 
to report any accident or any serious 
or extended illness of a worker. All of 
these must be carried out on a con- 
tinuing basis. Thus, the primary re- 
sponsibility for conducting experi- 
ments according to the Guidelines is 
In the investigator's hands. 
Further, In applying for grants to 
carry out experiments with recombin- 
ant DNA. the investigator must in- 
clude an estimate of the potential bio- 
hazards and a statement of the con- 
tainment procedures to be used. The 
application must Include certification 
of the existence and availability of ap- 
propriate facilities, procedures, and 
training. The Guidelines Indicate that 
institutions In which recombinant 
DNA experiments are carried out must 
establish biohazards committees that 
examine equipment and facilities and 
certify their compliance with the re- 
quirements. Such committees will also 
serve as a source of advice and refer- 
ence on physical containment facili- 
ties. on properties of biological con- 
tainment, and on training of person- 
nel. 
According to the Guidelines, the cer- 
tification and the investigator's assess- 
ment of the hazard and containment 
would be considered by NIH study sec- 
tions during the normal scientific 
review of the application. The Guide- 
lines leave flexible the question of re- 
solving any differences between the in- 
vestigator's evaluation and that of the 
study section. The Guidelines do state, 
however, that if differences cannot be 
resolved, the matter should be re- 
ferred to the Recombinant Advisory 
Committee or the NIH Office of Re- 
combinant DNA Activities. 
Application of the guidelines to work 
not supported by NIH 
Several agencies of the U S. Govern- 
ment other than the National Insti- 
tutes of Health provide support for 
biological and medical research. Some 
of these currently sponsor recombin- 
ant DNA experiments, and others may 
do so in the future. Activities of the 
research agencies represented by the 
Federal Interagency Committee on 
Recombinant DNA Research were re- 
viewed by the Committee in the fall of 
1976. All member research agencies 
adopted the NIH Guidelines and 
standards, including the National Sci- 
ence Foundation, the Department of 
Agriculture, the Energy Research and 
Development Administration, the De- 
partment of Defense, the National 
Aeronautics and Space Administra- 
tion. and the Veterans Administration. 
Several conferences have been held 
at NIH and at other relevant Govern- 
ment agencies with representatives of 
private industry in the United States. 
As best detemined by the Federal 
agencies, recombinant DNA research 
conducted in the private sector com- 
plies with the physical and biological 
standards of the NIH Guidelines. Rel- 
evant industries have agreed to follow 
the Guidelines on a voluntary basis. 
The issue of recombinant DNA re- 
search has been studied by national 
and International bodies in many 
countries. In most cases some form of 
control has been recommended, but 
nowhere has a total ban on the re- 
search been advocated. Canada, the 
Federal Republic of Germany. France, 
the Soviet Union, and the United 
Kingdom have issued guidelines that 
differ in detail but are similar concep- 
tually to the NIH Guidelines. Other 
countries are generally following the 
NIH or U.K. Guidelines, including 
Denmark. Israel, the Netherlands. 
Sweden, and Switzerland. The interna- 
tional Council of Scientific Unions and 
the World Health Organization have 
urged nations to adopt the principles 
embodied in these two sets of guide- 
lines. The U.K. Guidelines have been 
endorsed by the European Science 
Foundation and the European Molecu- 
lar Biology Organization. 
Scientific and governmental activi- 
ties comparable to those in the United 
States have been under way in the 
United Kingdom since January 1975. 
A working party established at that 
time recommended that recombinant 
DNA research In the United Kingdom 
be permitted to continue under appro- 
priate controls. In August 1976 a fol- 
lowup working group chaired by Sir 
Robert Williams issued a report estab- 
lishing guidelines. 
In Canada, in March 1976, a special 
committee of the Canadian Medical 
Research Council recommended guide- 
lines to govern the handling of recom- 
binant DNA molecules in Council-sup- 
ported research. The Council adopted 
these guidelines in February 1977. 
Many other nations have reviewed 
recombinant DNA activities to deter- 
mine what measures were necessary 
for safety. With the urging of regional 
and International bodies, most have 
adopted the NIH or U.K. Guidelines as 
a basic framework for safety practices 
and procedures. 
Alternatives: RAC-Proposed Revisions 
Part IV (Roles and Responsibilities) 
of the PRG-RAC is described below. 
As In the current (1976) Guidelines, 
FEDERAL REGISTER, VOl. 43. NO. 148— FRIDAY, JULY 28. 1978 
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