Dr. Rapp agreed with Dr. Gottesman that the use of recombinant DNA techniques to engineer an organism that exists 
in nature does not make it unique. However, he said the RAC was created to generate public confidence, and he was 
concerned about "whittling away" the types of experiments covered by the NTH Guidelines. 
Dr. Sharpies said that in the meeting of the Working Group on Definitions it became apparent that geneticists were 
using the term "rearrangement" to include duplications. Therefore, if the RAC supported the proposed amendment, this 
would mean it would not review organisms that are used to double, triple, quadruple or possibly increase by 100 times 
the production of a given protein. This would not be limited to moving one gene or changing the position of one gene 
relative to another. 
Dr. Miller of the Food and Drug Administration (FDA) stated he felt the RAC was to be commended for its tradition of 
timely and appropriate modifications to the NIH Guidelines, and that such actions have made RAC a benchmark for 
other groups and for regulation around the world. He cited the example of the evolution of the NIH Guidelines in 
regard to most large-scale uses of recombinant organisms where cloning has been done in B. subtilis, Saccharomyces, 
or E. coli which has streamlined both research and commercial applications of this technology. 
Dr. Miller stated he supported the proposed amendment which continues this tradition. He said just because the RAC 
would exempt something from oversight does not mean that all other Federal agencies would do the same. The FDA, 
he stated, has an extremely extensive and tight net of what is overseen and regulated. The ice-minus Pseudomonas 
syringae which, under this proposal, would be exempt from oversight by RAC has been subjected to very substantial 
regulation outside the NIH. Recombinant DNA manipulated live attenuated vaccines would continue to be treated by 
the FDA the same way as those that are conventionally manipulated. The U.S. Department of Agriculture (USD A) 
will do the same for animal vaccines. He added that his colleagues in the European Commission and in Japan who are 
involved in Governmental regulation were pleased to learn of this conservative but important step forward being 
considered by the RAC. 
Dr. Pramer stated his support for the proposed amendment adding that if the RAC/NIH redefines recombinant DNA 
molecules in the way recommended by the Working Group on Definitions, it will by that action remove from its 
purview the very experiments under discussion in this proposal. 
Dr. Davis said the definition of the recombinant DNA process should be used to delineate classes of unique and 
potentially dangerous products. He agreed with Dr. Gottesman that the RAC's scientific credibility was very important, 
and at present was very high and should remain so. He stated that if RAC did not "continue to exhibit the flexibility to 
whittle away those things that are so obviously harmless, we will lose that credibility." 
Dr. Davis then questioned Dr. Sharpies concerning her example of the Agrobacterium that has become more virulent as 
a result of the deletion of a particular gene. He said that in the medical field, which he knows much better than the 
plant field, virulence and ability to produce epidemics are two different concepts. It is perfectly easy to isolate a variant 
of the diphtheria bacillus that produces several times as much toxin as the ones that are normally encountered, but they 
do not spread in nature. Their overall ability to survive is impaired even though in an animal test they might be 
extremely virulent. He asked if there is any evidence if this Agrobacterium organism that has had a deletion that makes 
it more virulent has also gained an ability to spread. 
Dr. Sharpies replied that the only way to answer that question was to require an investigator to go and do an experiment 
to find out Dr. Davis questioned, "But it is not found in nature?" Dr. Sharpies replied, "That's right." 
Dr. Cohen inquired as to the use of the word "organisms" as opposed to "microorganisms" in the proposed amendment. 
Dr. Gottesman explained that the proposal is general in nature. At the moment, investigators are easily able to make 
deletions in microorganisms, viruses, and plasmids. For rearrangement where the word "organisms" appears, it 
specifically refers only to non-chromosomal or viral sources of DNA and does not cover even microorganism 
chromosomal DNA. 
Mr. Elliott Norse, Director of Public Affairs for the Ecological Society of America, stated that there seems to be some 
disagreement about whether deletions and rearrangements were environmentally significant or not. It was his 
understanding Dr. Davis felt they were trivial and Dr. Gottesman felt they may not be trivial, but this was irrelevant to 
the question at hand. Mr. Norse stated he believes they are not trivial. Quantitative changes in the characteristics of 
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