Federal Register / Vol. 44, No. 232 / Friday, November 30. 1979 / Notices 
69241 
without inserted recombinant DNA 
concluded that "the insertion of foreign 
DNA into a plasmid had little effect on 
its mobilizahility.” 
A recent study (1979) included in the 
"Background Documents on E. coli K- 
12/Pl Recommendation" is the paper 
“Survival of E. coli Host-Vector Systems 
in the Mammalian Intestinal Tract" by 
Drs. Stuart B. Levy, Bonnie Marshall, 
Andrew Onderdonk, and Debra Rowse- 
Eagle, which concludes, "These results 
demonstrated an absence of detectable 
transfer of pBR322 during transit in the 
intestinal tract of the human volunteers, 
despite survival of the laboratory K-12 
strain of almost a week at reasonably 
high titers.’' 
The Rowe-Martin polyoma 
experiments (copies of the published 
scientific papers are included in the 
"Background Documents on £. coli K- 
12/Pl Recommendation”) provide 
valuable data on the question of the 
likelihood of an animal virus 
recombinant DNA insert being 
transferred out of an E. coli K-12 host 
cell used in its propagation into a 
eukaryotic cell. 
What is the Probability of Recombinant 
DNA Experimentation Leading to 
Autoimmune Disease? 
Included in the "Background 
Documents on E. coli K-12/P1 
Recommendation" are copies of a letter 
sent by Dr. Wallace Rowe to leading 
immunologists and their replies. 
Appended to the Rowe letter were (1) a 
paper by Dr. Jonathan King (Journal of 
Infectious Diseases 137, 663, 1978) which 
says, "Several kinds of pathologies 
might result from infection by chimeric 
E. coli strains displaying foreign 
proteins. One model is an autoimmune 
condition associated with exposure to 
antigens cross-reacting with human 
antigens" and (2) a letter from Dr. Jon 
Beckwith which says "Several 
laboratories * * * have used 
recombinant DNA techniques to 
construct strains which produce hybrid 
proteins between the peptide hormones 
insulin and/or somatostatin and 
bacterial proteins * * * [There is] a real 
possibility that these modified peptide 
hormones could break tolerance/induce 
an autoimmune response in humans to 
their own hormones if they reached the 
appropriate sites in the body. This, in 
turn, could clearly have severe effects 
on the health of the affected 
individuals.” 
Dr. Rowe asked in his letter for an 
"objective evaluation of the evidence for 
or against the possibility of such disease 
mechanisms occuring." The responses 
received are included in the 
"Background documents on E. coli K- 
12/Pl Recommendation.” The 
respondents were Drs. Baruj Benacerraf, 
Norman Talal, Frank Dixon, Philip 
Paterson, William Paul, and Richard 
Asofsky. In summary, they concluded 
that the probability of recombinant DNA 
experimentation leading to autoimmune 
disease was remote, — "grossly 
exaggerated and based upon the 
orrurrence of hypothetical events" — 
[One must distinguish] "between 
autorecognition (which is physiologic 
and necessary for proper immunologic 
communication), autoimmunity, and 
autoimmune disease.” — “I see the 
eukaryotic proteins secreated by E. coli 
bearing foreign DNA sequences as no 
more likely to induce autoreactive 
immune responses than the negative 
antigenic constituents of this 
prokaryotic vector cell itself.” — 
Ad Hoc working Group on Risk 
Assessment 
An Ad Hoc working Group on Risk 
Assessment convened by the National 
Institute of Allergy and Infectious 
diseases met on August 30, 1979. They 
discussed the N1H Plan For A Program 
to Assess the Risks of Recombinant 
DNA Research which was published in 
the Federal Register on September 13 [44 
FR 53410). Specific areas of concern 
involving E. coli K-12 were discussed in 
detail; old evidence as well as evidence 
accumulated in the preceding months 
were reviewed. The Working Group 
expressed their "solid support for the 
proposed exemption of K-12 based 
cloning from the Guidelines providing 
that Pi laboratory practices were 
employed." This was reported to the 
RAC at their September meeting, and is 
contained in the "Background 
documents on E. coli K-12/P1 
Recommendation." 
Lack of Demonstrated Hazard To Date 
The Environmental Impact 
Assessment of July 1978 stated, "No 
evidence has come to light that any of 
the thousands of individual recombinant 
DNA clones constructed over the last 5 
years have yielded a product harmful to 
man or the environment. On the other 
hand, many examples of useful 
knowledge obtained through such 
techniques continue to accumulate 
rapidly." The negative aspect of this 
statement remains unchanged as of this 
date. The useful new knowledge 
obtained through the use of the 
technology has continued to accrue. 
Ill— C. Letters Received Subsequent to 
the September 6-7 RAC Meeting: The 
"E. coli K-12/P1 Recommendation” 
made by the RAC on September 6 was 
reported in the press. Subsequently, I 
received 26 letters concerning this 
recommendation. These letters are part 
of the book, "Background Documents on 
E. coli K-12/P1 recommendation,” 
available from ORDA. The major points 
made in the letters, and my response to 
them, are as follows: 
Only 10 of 25 Members of the RA C 
Voted in Favor of the ‘E. coli K-12/P1 
Recommendation " 
A number of commentators objected 
to the fact that only 15 RAC members 
voted on this issue, out of a total of 25 
authorized members on the RAC. Since 
only 10 of these 15 voted in favor of the 
motion, they constituted less than a 
simple majority of authorized RAC 
members. 
Although the RAC is authorized to 
have 25 members, at the September 6-7 
meeting only 24 members were actually 
appointed. Three members missed the 
entire meeting. Ten attended only part 
of the meeting. Only eleven attended the 
entire meeting. Of these, one is the 
chairman, Dr. Setlow, who only votes in 
case of a tie. 
HEW regulations (45 CFR 11.5) 
implementing the Federal Advisory 
Committee Act, applicable to all HEW 
advisory committees, state. "Unless 
otherwise established in the charter of 
the committee, a quorum shall consist of 
a majority of the committee’s authorized 
membership." The charter of the RAC is 
silent on the matter of a quorum. The 
authorized RAC membership is 25; 
therefore, 13 RAC members constitute a 
quorum. 
At the May 21-23, 1979, RAC meeting, 
a Working Group on Procedures was 
established. The Working Group 
reported at the September 6-7 RAC 
meeting. (A discussion of this item was 
originally scheduled as one of the first 
agenda items, but was moved to later in 
the meeting because the arrival of Dr. 
Ahmed, a member of the Working 
Group, was delayed.) The Working 
Group report had been sent to RAC 
members in advance of the September 
6-7 meeting. It contained a number of 
recommendations on six issues: 
speaking time for members of the public; 
outside consultants; conflict of interest; 
working groups and subcommittees; 
presentation of agenda materials to the 
RAC; and quorum and voting 
procedures. Each of the 
recommendations was voted on at the 
September 6-7 meeting. Dr. Ahmed 
presented, a minority view of the 
Working Group that "For major actions 
under the Guidelines, a quorum should 
consist of two-thirds of the committee 
membership (17 members)." After 
discussion of this proposal by the RAC, 
a substitute motion — that there be no 
change from current procedures for 
[ 227 ] 
