UNIVERSITY OF WASHINGTON 
SEATTLE, WASHINGTON 98195 
December 27. 1977 
Dr. Donald S. Fredrickson 
Director 
National Institutes of Health 
Bethesda, Maryland 20014 
Dear Dr. Fredrickson* 
Thank you for giving me the opportunity to participate in the 
special meeting of the Advisory Committee to the Director, 
NIH, on December 15-16. I was impressed by the clear and 
forceful presentation of dissenting views, made possible 
by the diverse interests represented by the participating 
witnesses. The revised Guidelines appear to steer a cautious 
middle course which is advisable, given our present knowledge. 
From my testimony you will note that the experiments of 
direct concern to my research group, cloning of the Agrobacterium 
Ti plasmid in E. coli . have been placed in a curious situation 
by the proposed revised Guidelines. They could be considered 
candidates for the list of experiments excluded from the Guide- 
lines. (I have criticized the vagueness of the criteria stated 
for defining what is non-novel recombinant DNA.) On the other 
hand, such experiments, if judged to involve novel recombinant 
DNA, must be performed under P3EK2 containment. This is a 
higher level of containment than is presently required* P2EK2. 
Neither alternative seems appropriate. Because we do not yet 
understand the mechanism by which part of the Ti plasmid is 
incorporated into eukaryotic (plant) cells, we do not know 
how to judge the safety of Ti plasmid fragments. I believe 
it is therefore premature to place our cloning experiments 
outside the Guidelines at this time. The evidence available 
thus far indicates that the Ti plasmid does not function in 
E. coli . I have submitted a statement from Jeff Schell which 
summarizes the evidence that E. coli containing the whole Ti 
plasmid does not incite plant tumors. Nevertheless, in the 
spirit of "erring on the side of caution," I recommend keeping 
these experiments under the Guidelines. 
On the other hand, elevating the level of containment to P3EK2 
seems most unreasonable! a containment level of P2EK2 would be 
acceptable, and P2EK1 would be preferable. I would recommend 
lowering the level of containment slightly (to P2EK1) on the 
basis of our experience with the clones containing Ti plasmid 
fragments. These strains fail to incite plant tumors, although 
they contain all or most of the portion of the Ti plasmid which 
[Appendix A — 148] 
