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Federal Register / Vol. 46, No. 233 / Friday. December 4. 1981 / Notices 
5. “Non-MobUtzabJe P/asmkJs ” — 
Plasmid rectors have been created 
which are mobilized and transferred 
from bacterial cell to bacterial cell at a 
markedly reduced frequency than the 
parent strain [12). For example pBR322 
is transferred approximately 100 
thousand times less frequently than its 
colEl parent plasmid under comparable 
mating conditions. Risk assessment 
studies recently carried out at the 
Univiersity of Maryland School of 
Medicine under sponsorship of the 
National Institutes of Health have 
verified in vivo in man decreased 
mobilization of “nonmobilizable" 
plasmid vector pBR325 [10). Seventeen 
volunteers ingested 10'*£. coli HS (a 
smooth normal flora strain) containing 
plasmid pJBJK5 (a non-conjugative, 
mobilizable coUQ variant containing 
tetracycline and chloramphenicol 
resistance genes). This strain heavily 
colonized the intestines of each of the 17 
individuals, all of whom also ingested 
one gram of tetracycline daily. Normal 
flora recombinants containing plasmid 
pJBKS were recovered from 9 to 17 
volunteers. In contrast, when 15 
volunteers ingested E. coli HS 
containing plasmid pBR325 (which also 
encodes for tetracydine resistance), 
although they also became heavily 
colonized while taking tetracyline daily, 
no resident flora recombinants were 
identified containing pBR325. These 
data attest to the decreased 
mobilizability in man of safe vector 
plasmids, even in the presence of 
antibiotic pressure modifying the 
environment in a way that recombinants 
would have enhanced survivability 
RelarencM at Appendix A of Annex B 
(f) Robbins. MB.. McCracken. C.H.. 
Cotschlich. E.C. Ormkov. F.. Orskov. I.. 
Hansen. LA. Escherichia ooli K-1 capsular 
Polysacscharide Associated with Neonatal 
Meningitis. 290:1218-1221. 1974 
[ 2 ) Sarff. LD.. McCracken. C.H.. )r. 
Schiffer. M.S.. Clode. M R. Robbins. |.B.. 
Orskuv I., Orskov. F Epidemiology of 
Eschenchia coh K-1 in Healthy and Diseased 
Newborns Lancet L1099-1104. 1975. 
Smith. H.W., Huggins. MB. Thi- 
Influence of Plasmid-Determined and Other 
Characteristics of Enteropathogenic 
Escherichia coh on their Ability to Proliferate 
in the Alimentary Tract of Piglets. Calves and 
Lambs. ). Med. Microbiol 11:471-492, 1977 
(4) Levine. MM.. Rermels. M.B. Cisneros. 
L. Hughes. T.P.. Nalin. DB.. Young. CJL Lack 
of Person-to-Peraon Transmission of 
Enterotoxigenic Escherichia coh Despite 
Gose Contact. Am. ). Epipdemiol. 111:347- 
355. 1980. 
(5) Black. R.E., Levine. M.M.. et al. 
Unpublished data. 
(fl) Smith. H.W Survival of Orally 
Administered E coh K-1 2 in Alimentary 
Tract of Man Nature 255:500-502. 1975. 
(7) Anderson. E.S. Viability of. and 
Transfer of a Plasmid from. E. coh K-12 in the 
Human Intestine. Nature 255-502-504. 1975. 
( 8 ) Formal. S.B., Homick, R. B. Invasive 
Eschenchia coh. ). Infect. Dis. 137:641-644, 
1978. 
(9) Host-Vector Systems in the Mammalian 
Intestine. Science 209*.391-394. 1980. 
( 10 ) Levine. M.M.. Kaper. )B.. et al 
Unpublished data. 
(77) Petrocbeilou. V., Richmond. M.H. 
Absence of Plasmid or Escherichia coh K-12 
Infection among Laboratory Personnel 
Engaged in R-PIasmid Research. Gene 2: 323- 
327. 1977. 
[ 12 ) Dougan. G., Crosa. ).H.. Falkow. S. 
Mobilization of the Escherichia coh Plasmid 
ColEl (colicin El) and ColEl Vectors Used m 
Recombinant DNA Experiments. ]. Infect. Dis. 
137:676-680. 1971 
Annex C — Minority Reports of Working 
Group on Revision of Recombinant DNA 
Guidelines 
Further Recommendotions 
We the undersigned agree with the 
general thrust of the recommendations 
of the Working Group on Recombinant 
DNA Guidelines. In particular, we 
support the recommendation that those 
experiments, for which containment 
guidelines are retained, are to conform 
to good laboratory practice as described 
in the CDC and AJPHIS Quarantine rules. 
The recommendation that abolishes the 
category of prohibited experiments is 
Boientifically sound in the light of 
current knowledge. The content of the 
suggested containment guidelines 
follows from the overall conclusion that 
research with recombinant DNA 
imposes no more risk than any other 
biological research. The background 
paper amply documents this point. 
Therefore, we find no reason to retain 
the Administrative Guidelines (Section 
IV). The spirit of the Baltimore-Campbell 
resolution and. as titled, its major 
purpose, was to convert the NIH 
Regulations into Guidelines. Retaining 
pages of bureaucratic regulations for 
what is now perceived to require only 
limited oversight is a waste of time and 
effort, will not add to safety in any way 
and will be disdaiiled as bureaucratic 
capriciousness. 
Edward A. Adelberg. Kenneth 1. Bems. 
Herman W Lewis. Sue A. Tolin. 
Norton D. Zinder. 
Given the recommendations for the 
containment guidelines and what would 
be proper for the administrative 
guidelines, we the undersigned conclude 
that special guidelines for recombinant 
DNA are totally unnecessary Therefore, 
we further recommend that as of June 
23, 1962 the NIH Guidelines cease to 
exist. 
The arguments for their retention are 
primarily social and political; they do 
not have a scientific base (see 
Background Paper). It seems right, al 
this time, to disavow such arguments 
and base our conclusions solely on the 
scientific issues. RAC should 
recommend the abolition of the 
Guidelines. In doing so. it should 
prepare a strong statement of its 
rationale to be published in Science and 
Nature as well as the Federal Register. 
This statement should also contain as 
recommendation the containment 
guidelines for recombinant DNA 
experiments developed by the Working 
Group. Prepared as the culmination of 
years of consideration and analysis, 
such a statement would serve to inform 
both the scientific community and the 
public of the safety of research with 
recombinant DMA. 
Edward A. Adelberg. Norton D. Zinder. 
Annex D — Draft Minutes of Relevant 
Portion of September 10-11, 1981 RAC 
Meeting 
Drs. David Baltimore and Allan 
Campbell, RAC members, had proposed 
a major revision of the Guidelines 
(Baltimore-Campbell proposal) which 
was considered by the RAC at its April 
1981 meeting. At the April 1981 meeting, 
a Working Group on Revision of the 
Guidelines was established to review 
the Baltimore-Campbell proposal as well 
as other approaches which might lead to 
a major revision of the Guidelines. The 
Working Group met on June 1, 1981, and 
on July 9. 1981. The Working Group 
prepared a proposal for revising the 
Guidelines, a summary of its actions, 
and a document entitled "Evaluation of 
the Risks Associated with Recombinant 
DNA Research.” Two minority reports 
were prepared by several members of 
the Working Group. The Working Group 
report and the minority reports were 
distributed to RAC members prior to the 
September 1981 meeting. 
Mr. Thornton asked Dr Gottesman to 
introduce the Working Group’s report. 
Dr. Gottesman reviewed the highlights 
of the report. She noted that the revision 
of the Guidelines promulgated on July 1, 
1981, already exempts many 
experiments in three major host-vector 
systems. The Baltimore-Campbell 
proposal would convert mandatory 
Guidelines to a voluntary code of good 
practice and would set as containment 
levels those appropnate for the 
organism being used. The Working 
Group considered various approaches; 
the majority supported a proposal which 
adopts the containment provisions of 
the Baltimore-Campbell proposal but 
retains the mandatory aspect of the 
Guidelines. The proposal has not yet 
been published as a proposed major 
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