P.E. Hartman 11/2U/77 ■ 
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(3) Legislation in (2) should lay out standards for strict, exrert, and 
unannounced monitering both of jxiblic and of private institutions, including 
commercial firms. The legislation should orovide authorization for a bucet 
to include record-keening and monitering activities. The legislation should 
lay out formal penalties, including the option for criminal penalties in cases 
where there Is severe and blatant disregard for law and nubile safety. 
Monitering of numerous samoie laboratories should Include close checks on 
vectors and host strains. Even the experts don't know where one of the most 
widely used DNA vehicles originated (Cohen, 3.". and Chang, A.C.Y. 1977 J. Bact. 
132 :73^-737) , and the literature is replete in microbial genetics with strain 
substitutions, lost genetic markers, etc., etc. And , by many of the better, 
more exnerienced research scientists. 
Monitering of a different kind should be performed right now, namely an 
In-depth investigation of oerhaos two laboratories (including personnel, families, 
environment, etc.) that have been working with recombinant DNA fer some time. 
This Investigation should be carried out by an unbiased and highly exnert 
research team that knows its epidemiology, bactericlgy (including familiarity 
with obligate anaerobes such as bacteroides, the fusiforms, etc.), and modem 
RNA/DNA methodology. For example, does laboratory Pseudomonas carry Xenotus 
5S or ribosomal RNA, or any SVLO genes? It is clear that different DNA segments 
soliced into circular or potentially circular (lambda) DNA molecules have 
various survival values, but right now we have absolutely no idea what has 
already haopened and, thus, little basis for projection (see Richmond and Lederber 
in "Recombinant Molecules" 1977). 
(li) The Director and the Recombinant DNA Molecule Program AdvisoryCommittee should 
proceed with extreme caution in exercising exclusions to "novel recombinant DNA" 
designation. No blanket exclusions (eg. "Enteric bacteria") should be made. In 
fact, no exclusions of particular soecies should *be made. Great heterogeneity 
is to be found even among natural isolates of E. coll (So and Falkow 1977 " 
Recombinant Molecules"). Plasmid transfer is extremely wide among bacterial 
"species", "genera", "families" and even among "families" classified in different 
Parts of "Bergey's Manual" (Sanderson, K.E. 1976 Ann. R^v. Micro. 30 : 327— 3U9 ; 
Jones, D, Sneath, P.H.A. 1970 3act. Rev. 3U :)o.C— 3 1 ) in SDite of minimal effort 
and only moderate technology so far used to detect such transfers. Therefore, 
genetic exchange in Nature cannot be a criterion for exclusion. I think it 
entirely reasonable at this point to classify ALL organisms under the Proposed 
Guidelines and exclude, for example, £. coli K12 DNA In E.coli K12. The 
revised Guidelines have provisions for exclusions in specific instances with 
well-defined DNA molecules that seem to cover basic scientific needs. 
I hope that the Committee and the Director give attention to the above 
four points. In closing, I want to ooint out that the First Amendment is not 
an issue. Publishing IDEAS is a far-cry from actually making recombinant 
molecules. Recombinant DNA technology affords very obvious prosoects for misue 
which, unfortunately, many non-microbiologists do not seem able to visualize 
or, at least, do not want to recognize. I suggest that nationwide promulgation 
of the Guidelines be followed by Executive Order, in follow-up of President 
Nixon's renouncement of development and stockpiling of biological warfare agents 
(Nov. 25, 1969), and, thereafter, international agreements.be made to help assure 
that the new technology will be put to beneficial uses insofar as possible. 
Finally, let me state that man's exoeriments are NOT Nature's exoeriments. 
Construction of a recombinant molecule by a sequence of steos, sometimes six 
steps each with a "probability" of 10*^, and selective growth of the output 
molecule cannot be called "Nature's experiment.. . it's happening all the time".' 
Respectfully yours. 
William p~. G ill Professor in Biology 
[Appendix A — 82] 
