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Federal Register / Vol. 49, No. 179 / Thursday, September 13, 1964 / Notices 
misused because the investigators are 
associated with USUHS. The said this is 
"guilt by association." She rejected this 
implication and urged RAC to approve the 
working group recommendations concerning 
Dr. O'Brien's April 4, proposal. 
Mr. Rifkin said: 
“* * * it's rather disingenuous for the 
committee to suggest that I’m only interested 
in diseases that affect the United States of 
America and, therefore, don’t care about 
diseases that affect the world. I think if 
anybody is familiar with my writings of 
books over the years you know that's just not 
true." 
Mr. Rifkin said: 
"* * * the real question here that I think 
that we have to deal with is a question that's 
been raised not just by me; it's been raised in 
several forums. If you get a chance to read, 
for example, the Bulletin of Atomic Scientists, 
which is rather a distinguished journal of 
science, you'll Find there was a long article in 
the November issue by Dr. Sinsheimer of the 
University of California and another historian 
where they raised some problems about 
convertibility and raise some very specific 
suggestions about what might be done by 
various Government agencies to try and 
address this issue, yet it still has not been 
addressed in this committee as of today.” 
Mr. Rifkin added that: 
"In terms of a nuisance factor ‘ ' *. We 
are all American taxpayers. We ar« citizens. 
We come in front of this committee both as 
professionals and lay people to lay out our 
concerns. I have legitimate concerns. You 
might totally disagree with them. You might 
have a totally different perspective. But we 
owe it to each other to discuss these and in 
each case when you have decided and voted 
I have not said another thing on that 
particular area. But I wHl continue to be here 
if I think that the perspectives that I want 
covered are not covered by this committee, 
including this one, and I hope at some point 
you discuss the convertibility of this 
technology for military purposes." 
It has previously been moved and 
seconded that the RAC approve the 
recommendation of the Working Group on 
Toxins that E. coli host-vector systems 
expressing the Shiga toxin gene maybe 
removed from P3 to P2 containment under the 
following conditions: 
a. That the amount of toxin produced by 
the modified host-vector system be no greater 
than that produced by the positive control 
strains 933 E. coli 0157H7 grown and 
measured under optimal conditions: and 
b. The cloning vehicle is to be an EKl 
vector, preferably belonging to the class of 
poorly mobilizable plasmids such as pBR322, 
pBR328, and pBR325. 
By a vote of ^wenty-one in favor, one 
opposed, and one abstention, the RAC 
accepted the motion. 
Dr. Gottesman then moved acceptance of 
the third item of the April 4 request i.e., to 
remove nontoxinogenic fragments of the 
structural gene(s) from P3 to lower physical 
containment at EKl biological containment 
with the stipulation that the modified 
organism will not contain overlapping 
fragments which together would encompass 
the structural genefs). In response to 
concerns expressed earlier in the meeting. Dr. 
Gottesman moved that physical contianment 
be set at P2, higher than the requested Pi 
physical containment level. Dr. Fedoroff 
seconded the motion. By a vote of twenty-one 
in favor, none opposed, and one abstention, 
the RAC accepted the motion. 
Dr. Gottesman felt a motion concerning 
items four and five was not required, but 
moved that RAC indicate that items four and 
Five of Dr. O’Brien's April 4 request do not 
require RAC action. Dr. Holmes seconded the 
motion. By a vote of twenty-one in favor, 
none opposed, and one abstention, the RAC 
approved the motion. 
I-A-5. Decision 
I have reviewed the extensive 
deliberations of the RAC Working 
Group on Toxins and of the full RAC 
concerning the April 4, 1984, requests of 
Drs. Alison O’Brien and Randall 
Holmes. I believe the containment 
conditions recommended by the RAC at 
its June 1, 1984, meeting are adequate to 
contain safely the experiment. I accept 
the RAC recommendations and the 
language of Appendix F-IV-H will be 
modified to indicate this. 
I-B. Proposed Amendment of 
Procedures for Scale-Up of Organisms 
Listed in Appendix C 
In May 1983, Dr. Irving S. Johnson of 
Eli Lilly and Company proposed that 
procedures be modified for experiments 
involving more than 10 liters of culture 
of "exempt" organisms listed in 
Appendix C of the NIH Guidelines for 
Research Involving Recombinant DNA 
Molecules. In September 1983, Dr. Max 
Marsh of Lilly Research Laboratories 
offered an alternate modification of 
Appendix C and requested it be referred 
to the RAC Large-Scale Review Working 
Group. The proposals were reviewed by 
the RAC at its September 19, 1983, 
meeting and referred to the Large-Scale 
Review Working Group. The RAC 
Large-Scale Review Working Group met 
on February 7, 1984. After evaluating 
data and discussing the issues (the 
Minutes of the meeting are available 
from ORDA), the Large-Scale Review 
Working Group proposed the following 
modifications to the Guidelines: 
1. In Appendix K-II-D of Appendix K- 
U, Pl-LS Level, the work "minimize" 
would be substituted for the word 
“prevent." Appendix K-II-D would read 
as follows: 
Appendix K-II-D. Exhaust gases removed 
from a closed system or other primary 
containment shall be treated by filters which 
have efficiencies equivalent to HEPA filters 
or by other equivalent procedures (e.g.. 
incineration) to minimize the release of _ 
viable organisms containing recombinant 
DNA molecules to the environment. 
2. The second paragraph of Appendix 
C-IL Experiments Involving E. coli K-12 
Host-Vector Systems; Appendix C— III. 
Experiments Involving Saccharomyces 
cerevisiae Host-Vector Systems; and 
Appendix C-IV, Experiments Involving 
Bacillus subtil is Host- Vector Systems; 
would be modified to read as follows: 
For these exempt laboratory experiments, 
Pi physical containment conditions are 
recommended. 
3. A paragraph would be added 
following the second paragraph of 
Appendix C— II, Appendix C— III, and 
Appendix C-IV. The paragraph would 
read as follows: 
For large-scale fermentation-experiments 
Pl-LS physical containment conditions are 
recommended. However, following review by 
the IBC of appropriate data for a particular 
host-vector system, some latitude in the 
application of Pl-LS requirements as outlined 
in Appendix K-II-A through K-II-F is 
permitted. 
4. A reference to Appendix C would 
be added to the fourth sentence of 
Appendix K-I, Selection of Physical 
Containment Levels. The sentence 
would read as follows: 
The Pl-LS level of physical containment is 
required for large-scale research or 
production of viable organisms containing 
recombinant DNA molecules which require 
Pi containment at the laboratory scale (see 
Appendix C). 
As a possible substitute, NIH staff 
proposed the following alternate 
modification of Appendix K-l, Selection 
of Physical Containment Levels. The 
following sentence would be added 
following the fourth sentence of 
Appendix K-l, Selection of Physical 
Containment Levels: 
(The Pl-LS level of physical containment is 
recommended for large-scale research or 
production of viable organisms for which Pi 
is recommended at the laboratory scale such 
as those described in Appendix C). 
An announcement of these 
recommendations of the Large-Scale 
Review Working Group and the 
substitute proposed by NIH staff 
appeared in the April 24, 1984, Federal 
Register (49 FR 17672). During the thirty 
day comment period three comments 
were received. These comments were 
from Mr. C. Searle Wadley and Dr. John 
H. Keene of Abbott Laboratories. Dr. 
Judith A. Hautala of Genex Corporation, 
and Dr. J. Allan Waitz of Schering 
Corporation. 
Mr. C. Searle Wadley and Dr. John H. 
Keene of Abbott Laboratories, North 
Chicago,. Illinois wrote: 
The risk assessments have been done with 
the exempt organisms for which the proposed 
amendments apply. There is no evidence we 
are aware of to indicate that there is any 
Increased risk to personnel or public health 
[529] 
