not be regulated by an agency of the Government, just simply not by the NIH. For example, she stated, a deletion in a 
pathogen which would be contemplated for release into the environment would certainly fall under the regulatory 
purview of the EPA. 
Dr. Roberts stated he agreed with the proposal as a cautious step forward in relieving unnecessary regulation, in that he 
felt these types of organisms occur naturally and could be made by traditional genetic means other than recombinant 
DNA technology and thereby do not need to be covered by the NIH Guidelines. 
Dr. Sharpies stated that for several reasons she disagreed with the proposal by Dr. Gottesman. She stated she did not 
believe it was possible to make an a priori judgment that a deletion or rearrangement would not result in a negative 
environmental effect She further stated that for any kind of genetic modification it is important to understand how the 
modification will alter the behavior and relationship of the organism in the environment To find out if and how a 
deletion or rearrangement is translated into an environmental change, you have to go and look for the answer. The 
answer does not present itself merely from knowing that all you have done is deleted a tiny bit of DNA from an 
organism's genome; rather, getting the answer requires that some work be done and that some scrutiny be applied. As 
an example, she cited the RAC’s deliberations on the ice-minus bacterium where the removal of a gene for production of 
an ice-nucleating protein led to a shift in the relationship of the bacterium with the ambient environment. Although 
the change in the relationship in this instance is not very likely to result in further negative effects, it cannot be denied 
that a change in the organisms’s role and behavior did occur because of the removal of a single gene. 
Dr. Sharpies also cited other work on the relationship between genes and virulence in Agrobacterium tumefaciens. It 
was found that in grape vines resistance to Agrobacterium infection is the result of a hypersensitivity response by the 
plant to a bacterial gene. When this gene is deleted from the bacterium, the plant no longer resists the infection, and 
this results in tumors in the vines associated with crown gall disease. This genetically determined shift in the host 
range of the bacterium could not have been predicted; it had to be looked for and established by examining the specifics 
of the situation. We know from these examples that single gene deletions, however minor the genetic change they 
entail, can translate into changes in environmental relationships, and you will not find out what those changes are and 
whether they are harmful or not until you look for them. 
Dr. Sharpies said she believed that RAC should continue its oversight of organisms for environmental release as is now 
required regardless of the nature of the genetic change they have undergone to ensure that investigators who propose field 
tests in fact have considered the potential for the genetic change they have made to translate into significant 
environmental differences. 
Dr. Sharpies said the RAC was not burdened by its present workload in oversight of environmental release experiments. 
She pointed out that RAC has not recently received any proposals to conduct field tests and that the "Points to 
Consider" for environmental release has never been used. She stated further her concern that this proposed amendment 
would give a false impression that these organisms do not need review by any group and that the amendment could also 
lead other agencies to adopt a similar attitude. 
Finally, Dr. Sharpies stated she viewed the proposed amendment as an extension of Dr. Gottesman's view of what 
constitutes "recombinant DNA," a view which is based on product rather than process. She stated that she felt this may 
be contrary to the purpose of RAC which exists not to regulate products but to ensure that recombinant DNA research 
is conducted safely. If the research leading to production of particular organisms involves the use of recombinant DNA 
techniques, then Dr. Sharpies believed RAC should have jurisdiction over that research. If field testing of that organism 
is part of the research program, then the RAC's oversight should extend to the field testing. Amending the NIH 
Guidelines in accordance with Dr. Gottesman’s proposal may lead environmental intervenors to initiate further 
litigation. 
Dr. Vidaver said that she agreed with Dr. Gottesman's proposal. She concurred with Dr. Sharpies’ that the purpose of 
the RAC is to review a process. However, she added she does not feel this precludes the RAC from reviewing the 
product Any deletion or rearrangement can have an effect But in the ice-minus and Agrobacterium tumefaciens cases, 
there are already comparable conditions in nature. She did not feel it necessary for the RAC to review deletions or 
rearrangements since perhaps 99 percent of these cases would not be of interest to the RAC, and the probability of such 
organisms having an adverse effect on the environment was minimal. 
Dr. Johnson agreed strongly with Dr. Sharpies that RAC should continue scientific oversight; however, the NIH 
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