2 
Dr. Friedman called the Working Group on Gram Positive Bacteria to order at 
9:00 a.m. on Decenber 2, 1985. He said the purpose of the meeting was to 
evaluate a proposal (Attachment II) submitted by Drs. Richard Novick and 
Joan Polak of the Public Health Research Institute of the City of New York, 
Inc. , New York, New York, to establish a comprehensive listing of gram-positive 
Eubacteriales under Section III-D-4 of the National Institutes of Health (NIH) 
Guidelines for Research Involving Recombinant DNA Molecules. 
Section III-D-4 states that certain recombinant ENA molecules axe exerrpt from 
the NIH Guidelines. These exempt molecules "consist entirely of ENA segments 
from different species that exchange DNA by known physiological processes, 
though one or more of the segments may be a synthetic equivalent." Organisms 
have been exempted under Section III-D-4 based on data documenting exchange 
of ENA between the organisms. Appendix A of the NIH Guidelines lists these 
exerrpt organisms. 
Dr. Fnedman called the attention of the working group to the philosophical 
basis used to construct Appendix A (Attachment III). In evaluating a 
pair of organisms for inclusion on a list of Appendix A, an estimate is made 
of the probability that the combination of genes might have occurred naturally. 
If the combination is not a "novel" one, there should be no special hazard in 
creating such an organism by recombinant DNA technology; and the combination of 
organisms can then be exempted from the NIH Guidelines. The natural transfer 
of genes between bacteria occurs by transduction, trams format ion, or conjugation. 
In 1978, in constructing Appendix A, four categories of mechanisms of conjugal 
genetic exchange were considered: (1) Organisms which exchange chromosomal 
genetic information which is stably integrated into the host chromosome. 
This most stringent criterion for exchange requires significant homology between 
the combining segments. (2) Organisms which exchange chromosomal information 
that is not necessarily integrated into the chromosome of the recipient. This 
sort of exchange cam occur in the absence of extensive ENA homology between 
the organisms and requires only that the plasmid and its chromosomal genes be 
maintained in the recipient organism. (3) Organisms which show evidence of a 
plausible mechanism for exchange. In this cause, the plasmid itself has been 
shewn to move from organism to organism. It has been shown to pick up chromo- 
somal genes but the transfer of these chromosomal genes in interspecies matings 
has not necessarily been demonstrated. (4) Organisms vhich cam receive or 
donate broad host range plasmids. The assumption is that chromosomal genes 
may be picked up by these plasmids and transfer of chromosomal genes to other 
species will occur. 
In 1978, the NIH Director decided the data supporting criteria 3 and 4 were 
not compelling enough to be used as a basis for exempting organisms from the 
NIH Guidelines. 
Dr. Friedman said genetic material may be exchanged in one direction or in 
both directions, and organisms can be placed in a list in Appendix A on the 
basis of one-way exchange of genetic information. 
[ 533 ] 
