11 
Dr. Gottesman said the working group could construct a recormendation on 
one of several methods of exempting experiments fran the NIH Guidelines: (1) 
The working group could attempt to add organisms to Appendix A on the basis of 
plasmid exchange using the broadest definition of exchange. (2) Another approach 
would be to attempt to exempt organisms under Appendix C. Experiments involving 
the cloning of genes in ooli K-12, Saccharcrnyces cerevisiae , asporogenic 
Bacillus subtilis host-vector systems or in tissue culture, are exempt under 
Appendix C of the NIH Guidelines based on the argument that these organisms 
would not present a hazard. A generic statement of this type would probably 
not work, however, for groupings including pathogens. (3) A third approach 
would be to exempt experiments involving the DNA of the broad host-range plasmids 
vhich exchange freely within the gram-positive bactena when propagated and 
maintained in those bacteria. 
Dr. Cohen reiterated that all experiments involving organisms being con- 
sidered by the working group are currently permitted under the NIH Guidelines. 
He questioned whether any advantage would be gained in modifying the NIH Guide- 
lines regarding these organisms. 
Dr. Dean said the major impact would be on large-scale work with gram-positive 
bacteria since large-scale procedures nust be reviewed and approved by the IBC 
prior to initiation of the experiments. Dr. Baltz said a cost factor must 
also be considered when procedures involving these organisms are scaled-up. 
Dr. Dean said it might be useful at this time to recommend the third option of 
exempting experiments involving those plasmid-bome genes known to be exchanged 
among gram-positive bacteria. Procedures for certain types of experiments 
would be simplified, e.g. , research with the Bj_ thur ingiens is plasmid-bome 
crystal protein or with drug resistance genes. An established list of gram- 
positive organisms vhich exchange plasmids might make it easier to exempt 
these organisms as a group as evidence of chranoscmal exchange is generated. 
Dr. Lovett questioned whether a great deal would be gained by creating such an 
exenpt list of broad host-range plasmids when those plasmids are propagated 
and maintained in gram-positive bacteria. B^ thur ingiens is and B^ subtilis 
would be on this list but might also be exempted from the NIH Guidelines on 
the basis of a high level of DNA homology. B^ thur ingiens is is not a hazard 
for humans, and this argument might support exenpting this organism under 
Appendix C. 
Dr. Gottesman said exenpting an organism such as B^ thuringiensis which is an 
insect pathogen would entail consideration of host range. Issues that would 
have to be considered include: what factors control host range and could 
modification of the host range adversely affect beneficial insects? 
Dr. Dean thought investigators encounter problems vhen they scale-up manipu- 
lations. He thought industrial IBCs tend to be very conservative; language 
exenpting extrachrcmosomal DNA from the NIH Guidelines would sinplify matters 
for individuals working with extrachrcmoscmal ENA from gram-positive bacteria. 
[542] 
