Federal Register / Vol. 46. No. Ill / Wednesday. June 10. 1981 / Notices 
30773 
by recombinant DNA, but rather to any 
hybrid proteins made between bacterial 
proteins and insulin or other peptide 
hormones. With regard to this comment 
the central issue on this point is whether 
or not autoimmunity could follow 
administration of self proteins in any of 
several forms; hybrid proteins were one 
of the forms briefly discussed. 
Another correspondent wrote that the 
increased responsibility given to the 
local Institutional Biosafety Committees 
will provide for more expeditious 
monitoring of recombinant DNA 
research. The commentator suggested 
that some effort be made to collate 
information eminating from ORDA 
memoranda, the Federal Register, and 
the Recombinant DNA Technical 
Bulletin. It was also suggested that 
thought should be given to preparing a 
tabular listing of a classification of 
microorganisms on the basis of hazard 
and their recommended containment 
levels. While these are not comments 
specifically on the rish-assessment plan, 
I wish to Indicate that ORDA is 
exploring ways to summarize major 
actions of the RAC Also, the Centers for 
Ehsease Control in a joint effort with 
NIH. has published for comment 
"Proposed Biosafety Guidelines for 
Microbiological and Biomedical 
Laboratories.” 
B. The Recombinant DNA Advisory 
Committee considered the Proposed 
First Annual Update of the Risk 
Assessment Plan at its meetings on 
September 25. I960, and January 8. 1961. 
At the latter meeting. Dr. Luther 
Williams, a RAC member, presented a 
summary oi the program, as published in 
the Federal Register on September 17. 
1960. and responded to questions. 
Committee members and the public 
were provided an opportunity to present 
their views, questions, criticisms, or 
suggestions. A RAC member raised a 
point regarding the wording in the 
second paragraph, third column of page 
61876 of the Federal Register of 
September 17. I960, dealing with 
colonization of the intestinal tract H 
was recommended that the word 
"known" should be deleted from the last 
clause of the paragraph. This has been 
done, and the clause now reads as 
follows; „ even though £. coli K-12 
has apparently lost those characterisbcs 
Riat are required for colonization of the 
normal intestinal tract.” A public 
commentator suggested that additional 
references should be added to the risk 
assessment plan. This has been done in 
this document. The RAC did not 
recommend any other sugnificant 
changes in the plan as a result of other 
issues which were raised at the RAC 
meeting. 
IL Final Plan for a Program to Assess 
the Risks of Recombinant DNA 
Research 
A. Introduction. 
With the issuance in December 1978 
of revised guidelines for the conduct of 
recombinant DNA research, the 
SecreUry. DHEW (now DHHS), 
requested that the Nabonal 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 first annual 
update. 
B. Scientific Aspects. 
We stated in the Final Plan and it is 
sbll our convicbon 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 tnformation will be obtained chiefly 
from publications in the scientific literature, 
from persons with special scientific 
knowledge, and froaa ongoing basic 
biomedtcal research. Risk assessment 
analysis will require conttnutaig review of 
data developed in the fields of microbiology. 
Infectious diseases, and related biological 
resea ich. 
Soma 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 supporied by the 
Intramural and tha Extramural programs of 
NIH. Many axperiments 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 Scienbfic Aspects of the Plan 
noted that a number of events must 
occur before ■ 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. coil 
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 coiisideration, 
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 
1. Prokaryotic Host- Vector Systems. 
a. 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 
accidental spills in the laboratory, in a 
model sewage treatment system, bi mice 
and cultures simulating the mouse 
gastrointestinal system, in germfree 
mice, and finally in 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. 
(1) 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. 
coU, used as hosts to propagate 
recombinant DNA molecules, and some 
phage and plasmid 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 
assessed. 
Considerable effort was expended on 
quantitative descriptions of the 
biological characteristics of hosts and 
vectors of concern in current rDNA 
studies, and the physical dispersion 
aspects have been examined with 
particular attention to procedures 
unique to such laboratory work. 
(1351 
