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Federal Register / Vol. 44, No. 179 / Thursday, September 13, 1979 / Notices 
the Intramural scientists of NIH already 
described. 
III. Recombinant DNA Risk Assessment 
Plan: Scientific Aspects 
There are threee major types of host- 
vector systems presently being used for 
recombinant DNA research, and the risk 
assessment program will naturally be 
focused on these. They are (1) 
prokaryotic host-vector systems, 
primarily, E. coli and Bacillus subtilis; 
(2) lower eukaryotes, namely, 
Saccharomyces cerevisiae and 
Neurospora crassa; and (3) eukaryotic 
viruses in cultured cells of higher 
eukaryotes. 
A number of events must occur before 
a laboratory microorganism becomes a 
possible risk to people or higher 
organisms outside the immediate 
laboratory environment. The assessment 
of risk involves a determination of the 
probability for the occurrence of these 
various events. The particular data that 
are most susceptible to analysis, or most 
likely to provide a definitive answer 
concerning risk, will differ for the 
various host-vector systems. Data 
elements will include the probabilities 
of: 
(1) Dispersal of the organism 
containing recombinant DNA into the 
environment. 
(2) Survival of the organism in the 
environment or transfer of the 
recombinant molecule into another 
organism. 
(3) Acquisition of a selective 
advantage by the recombinant- 
containing organism so that it can 
populate a significant ecological niche. 
(4) Change in the natural biology of 
the recombinant-containing organism so 
that it becomes a danger to some higher 
organism, as, for example, by its 
conversion into a pathogen or into a 
vehicle for transferring foreign DNA into 
cells of the higher organism. 
A major aspect of the risk assessment 
plan will consist of acquiring and 
analyzing information and data relevant 
on these elements for the various host- 
vector systems. 
The following compilation of research 
activities in neither final nor inclusive. 
Furthermore, those mentioned here will 
require more than a single year to 
complete. While the present interest 
emphasizes E. coli host-vector systems 
in animals, in the near future the focus 
may shift to other host-vector 
combinations and their impact on the 
ecosystem. 
Prokaryotic Host- Vector Systems 
With regard to acquisition of new 
experimental data, the initial emphasis 
will be on the E. coli K-12 systems, 
since these are the major systems being 
used and areas where such data are 
needed have already been identified. 
The following areas will be given 
particular consideration. 
(1) The survival in the environment 
and potential selective advantage of 
organisms carrying recombinant DNA. 
(2) Further evaluation of the 
transmission of vectors from E. coli K- 
12 to other bacteria in the 
gastrointestinal tract of animals and 
human beings. 
(3) Testing E. coli K-12 host-vector 
systems carrying recombinant DNA for 
virulence or increased ability to colonize 
the gastrointestinal tract of mice. 
{4) Animal studies of hormone- 
producing strains of E. coli generated by 
recombinant DNA technology. 
(5) Further evaluation of the biological 
activity of polyoma virus cloned in E. 
coli host-vector systems. 
(6) The biological activity of E. coli K- 
12 clones carrying DNA copies of RNA 
tumor viruses. 
(7) The possible occurrence of 
autoantibodies or autoreactive cells due 
to the production of eukaryotic 
polypeptides by bacteria that colonize 
higher organisms. 
Lower Eukaryotes 
Areas where new experimental data 
would be desirable include (1) 
determining the competitive advantage 
for survival of S. cerevisiae in relevant 
natural environments and (2) 
determining the ability of several types 
of eukaryotic viruses to replicate in S. 
cerevisiae and N. crassa when 
introduced via a recombinant molecule. 
Higher Eukaryotes 
The major concern that centers on the 
use of animal virus vectors to clone 
foreign DNA segments in cells of higher 
eukaryotes involves the unlikely 
possibility of (1) creating novel 
nondefective viruses as a result of the 
insertion of a new DNA fragment or (2) 
altering the host range of the viral 
vector. The risks associated with these 
problems will be evaluated continuously 
through the review of the general viral 
literature. Only a limited number of 
experiments are currently being 
conducted with these systems and it is 
highly improbable that the events 
enumerated above would occur. Specific 
risk assessment experiments are not 
being planned at present for these 
systems. 
IV. Implementation of Plan 
In order to implement the plan, NIAID 
will: 
(1) Recruit and appoint an eminent 
scientist as a Special Assistant to the 
Director for Risk Assessment to provide 
leadership and coordination of all 
activities concerned with the evaluation 
of risks of research and research 
products related to recombinant DNA 
and other genetic research involving 
potentially infectious or toxic organisms. 
In this role, this scientist will be 
responsible for representing the plan to 
the Recombinant DNA Advisory 
Committee (RAC), the scientific 
community, international organizations, 
and the public; will advise on the 
collection and assessment of data and 
edit and coordinate reports on progress; 
and will chair workshops and 
conferences as necessary to address 
special problems of risk assessment. 
This individual will also review ongoing 
research for data pertinent to risk 
assessment by such means as analysis 
of data from research which is published 
or presented at meetings, by direct 
contacts with scientists, and through 
review of Memoranda of Understanding 
and Agreement (MU As) filed with the 
Office of Recombinant DNA Activities 
(ORDA). Liaison will be maintained 
with those who have related 
responsibilities in other countries and 
international scientific organizations. 
The Institute will recruit and appoint 
such ancillary staff as are needed by the 
Special Assistant. 
(2) Develop and issue such requests 
for applications or proposals as are 
necessary to ensure the conduct of risk 
assessment research required to answer 
specific questions or to fill gaps in data 
being accumulated from other research. 
It is anticipated that these specific needs 
will be identified by the activities of the 
Special Assistant for Risk Assessment, 
the RAC, and scientists addressing the 
issues in workshops and conferences. 
(3) Prepare and send periodic reports 
to the RAC identifying questions, 
problems, and evaluations of scientific 
information pertinent to their various 
advisory functions. 
(4) Respond to inquiries from 
scientists, the public, DHEW, or other 
government agencies regarding 
available data on risk assessment and 
evaluation of those data. 
In order to carry out these 
responsibilities, the NIAID will enlist 
the services of the following existing 
NIH offices, committees, and people to 
provide information, to advise and 
evaluate, and to review, as appropriate, 
reports for completeness and accuracy. 
(1) Recombinant DNA Advisory 
Committee (RAC) 
A Risk Assessment Subcommittee has 
recently been established in the RAC to 
provide the NIH with broad technical 
and public policy advice concerning risk 
assessment. This subcommittee will 
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