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Federal Register / Vol. 45. No. 182 / Wednesday. September 17, 1980 / Notices 
... 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
I ' 
National Institutes of Health 
Program To Assess the Risks of 
Recombinant DNA Research: 
Proposed First Annual Update 
AGENCY: National Institutes of Health. 
ACTION: Notice of proposed first annual 
j update of a program to assess the risks 
I of recombinant DNA research. 
SUMMARY: On September 13, 1979 the 
initial plan was published in the Federal 
Register. This notice sets forth a 
proposed first annual update of the 
program to assess the risks of 
recombinant DNA research. Interested 
parties are invited to submit comments 
concerning the plan. After consideration 
of those comments and comments by the 
NIH Recombinant DNA Advisory 
Committee, the Director of the National 
Institutes of Health will publish the final 
update in the Federal Register. 
DATE: Comments must be received by 
December 16, 1980. 
ADDRESS: Written comments and 
recommendations should be submitted 
to the Chief, Office of Specialized 
Research and Facilities, NIAID, Building 
31, Room 7 A04, 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 p.m. 
FOR FURTHER INFORMATION CONTACT: 
Additional information may be obtained 
from Dr. John Nutter, Chief, Office of 
Specialized Research and Facilities. 
NIAID. National Institutes of Health, 
Bethesda, Maryland 20205 (301-496- 
5643). 
SUPPLEMENTARY INFORMATION: 
L Introduction 
With the issuance in December 1978 
of revised guidelines for the conduct of 
.recombinant DNA research, the 
Secretary DHEW requested that the 
National Institutes of Health (NIH) 
prepare an NIH Risk Assessment Plan 
which after review by the Recombinant 
DNA Advisory Committee (RAC) and 
publication in the Federal Register for 
comment, would be made final and 
updated annually. The present 
document is the initial response to the 
request for an annual update. 
II. Scientific Aspects 
We stated in the Final Plan and it is 
still our conviction that: 
“The vast majority of information relevant 
to recombinant DNA risk analysis has 
already come from research not primarily 
designed to provide information on risk. This 
will undoubtedly continue to be the case. 
This information will be obtained chiefly 
from publications in the scientific literature, 
from persons with special scientific 
knowledge, and from ongoing basic 
biomedical research. Risk assessment 
analysis will require continuing review of 
data developed in the fields of microbiology, 
infectious diseases, and related biological 
research. 
Some essential information has been, and 
will continue to be. derived from projects 
specifically designed to assess various 
aspects of potential risks associated with 
recombinant DNA experimentation. Such 
experiments will be supported by the 
Intramural and the Extramural programs of 
NIH. Many experiments may also be 
conducted in the private sector or may be 
funded by other agencies or governments. 
The essential goal of a successful risk 
assessment plan will be the development of 
means to collect, collate, coordinate, 
evaluate, and disseminate data obtained from 
all sources." 
The Scientific Aspects of the Plan 
noted that a number of events must 
occur before a laboratory 
microorganism becomes a possible risk 
to people or higher organisms outside 
the immediate laboratory environment. 
A major aspect of the risk assessment 
plan was to acquire and analyze 
information and data relevant to those 
elements for the three general categories 
of host-vector systems in use; 
prokaryotic, lower eukaryotic and 
higher eukaryotic systems. Initial 
emphasis was on the prokaryotic E. coli 
K-12 systems because those were, and 
remain, the systems predominately used 
by investigators and because needed 
areas of investigation had already been 
identified. Seven areas were identified 
as requiring particular consideration 
and progress has been made in 
collecting and/or analyzing data for all 
of them. Before considering these it is 
Worth saying that, despite intensive 
study by the RAC Subcommittee on Risk 
Assessment and NIH staff, several 
conferences and workshops to consider 
specific issues and several experiments, 
no risks of recombinant DNA research 
have been identified that are not 
inherent in the microbiological* and 
biochemical methodology used in such 
research. A synoptic report of progress 
follows and all data, reports, and other 
documents referred to are available on 
request. 
Prokaryotic Host- Vector Systems 
1. Survival in the environment and the 
potential for selective advantage of 
organisms carrying recombinant DNA 
should they survive was cited as a 
matter of concern. NIAID had four 
contractors working on various aspects 
of this issue; the contracts were 
originally awarded to provide 
independent testing in the process 
whereby EK2 systems could possibly be 
elevated to EK3 status. The tests were 
performed in situations simulating 
accidential spills in the laboratory, in a 
model sewage treatment system, in mice 
and cultures simulating the mouse 
gastrointestinal system, and finally in 
germfree mice and humans. The status 
of the work of all four contractors, at the 
time the Plan was initially published, 
can be found in the Recombinant DNA 
Technical Bulletin, Vol. 2 No. 2, July 
1979. The expiration date of all contracts 
has now been reached and Final Reports 
are or soon will be available. 
a. The work of the contractor testing 
in “accidental spill situations” was 
completed shortly after publication of 
the Plan and was in two areas: (1) to 
determine whether selected strains of E. 
coli, used as hosts to propagate 
recombinant-DNA molecules, and some 
phage and phasmid vectors would 
survive or retain their capacity to infect 
or transform host cells after exposure to 
the environments expected to occur in 
the event of spill or aerosolization, (2) to 
Inventory and simulate common 
procedures used in recombinant DNA 
laboratory studies so that aerosol output 
potential of the procedures could be 
accessed. 
Considerable effort was expended on 
quantitative descriptions of the 
biological characteristics of hosts and 
vectors of concern in current rDNA 
studies and the physical disperson 
aspects have been examined with 
particular attention to procedures 
unique to such laboratory work. 
The data on biological survival 
characteristics are applicable to 
evaluation of potential dosage to 
workers or to the environments both 
from accidents creating massive release 
and from the continuing releases 
incidental to the laboratory procedures. 
Evaluation of the effect of survival of 
the agents in the course of routine work 
should assist in prudent and cost- 
effective application of physical and 
biological containment. Further, it can 
lend emphasis to the areas in which 
training in "good practice” can be most 
productive. 
b. The Survival of EKl and EK2 
Systems in Sewage Treatment Plant 
Models. 
In an early series of studies utilizing 
bench scale models of wastewater 
treatment facilities, E. coli DP50supF, E. 
coli Chi 1776 and phage Charon 4A 
concentrations were shown to be 
reduced by at least two orders of 
magnitude by a conventional treatment 
chain (including primary settling 
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