extensions of the philosophy of revision of the NIH Guidelines, as has been set out previously to conform with new 
applications and experience in the field. He stated that he had just attended a decennial review conference on cell and 
molecular biology of cell cultures, and that the previous meeting, 10 years ago, had stressed research on monoclonal 
antibodies and growth factors. This year the emphasis was on gene expression and recombinant DNA technology, and 
oncogenes. He mentioned the great advances in research on monoclonal antibodies and growth factors that has taken 
place in the past decade; if recombinant DNA experiences a similar growth in the next decade, the NTH Guidelines will 
have to be very flexible to keep up with these changes. 
Dr. Gottesman stated that she felt Dr. McGarrity had presented the sense of the working group meeting very well but 
that he had left out some things which the working group had spent a lot of time discussing. She stated the working 
group felt the term "deliberate release" unfortunately had a "nasty" conotation, but that in the end no better alternative 
phrase could be agreed upon. 
Dr. Gottesman explained that the issue of the definition of "recombinant DNA" was discussed by the working group in 
the case where pieces of DNA are spliced together in vitro, but no "foreign" sequences are added. The current NIH 
Guidelines still define this as recombinant DNA because the current definition says nothing about where the molecules 
come from; as long as the molecules are "constructed outside living cells by joining natural or synthetic DNA segments 
to DNA molecules that can replicate," then it is recombinant DNA. 
Dr. Gottesman stated that we have not had to face this issue in the past because self-cloning or rearrangements 
involving an organism and the organisms that normally exchange DNA with it have been exempt from overview for 
laboratory experimentation under the NIH Guidelines. But now as we consider human gene therapy or deliberate release 
into the environment, the question is whether it is appropriate to cover in the NIH Guidelines organisms in which 
recombinant DNA has been used in their construction, but which are not recombinant in the sense of having foreign 
DNA in them. The new proposed definition would be one way of pulling this set of organisms out of the NIH 
Guidelines entirely. An alternate way of dealing with this is not to change the definition of recombinant DNA but to 
deal with this set of organisms elsewhere in the NIH Guidelines. 
Dr. Gottesman then brought up the issue of deliberate release by questioning the semantics of the term "release." Does 
this just mean there is no roof? Does it require establishment of the organisms in the environment? Does "deliberate" 
mean that the release had to be planned to constitute "deliberate release"? If "deliberate release" were defined very 
narrowly it could produce an either/or situation whereby if you weren’t covered by the deliberate release definition, you 
could come under Section IH-D of the NIH Guidelines, "Exempt Experiments." 
Dr. Gottesman said she favored setting up additional categories under Section III-A-2 of the NIH Guidelines which 
would be similar to Appendix L of the NIH Guidelines in which approval could be given by a subcommittee of the 
RAC for certain defined types of "deliberate release" experiments without having to have them go through the Federal 
Register notice procedure and come before the full RAC. Further, she stated, that RAC should consider setting up 
working groups to start to write these new Appendices modelled after Appendix L. 
Dr. McGarrity then stated that the Working Group on Release into the Environment has previously drafted a "Points to 
Consider" document for the introduction of microorganisms into the environment, and that this could be a starting point 
for a new Appendix M. 
In response to a question from Dr. Pramer, Dr. Gartland noted that Appendix L has never been used to approve a 
proposal. Dr. Talbot stated that a proposal was submitted under Appendix L, but it was determined that it did not meet 
the criteria in Appendix L. 
Dr. Clowes said that he believed the conclusions of the working group were most valuable. Currently Section I-B of 
the NIH Guidelines states: 
"In the context of these Guidelines recombinant DNA 
molecules are defined as either (1) molecules which 
are constructed outside living cells..." 
Dr. Clowes felt the wording should read: 
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