THE UPJOHN COMPANY 
KALAMAZOO. MICHIGAN 49001. USA 
TELEPHONE (616) 323 4000 
September 21, 1988 
Director 
Office of Recombinant DNA Activities 
12441 Parklawn Drive 
Suite 58 
Rockville, MD 20852 
Dear Sir: 
I wish to respond to the proposed actions under the Guidelines for Recombinant 
DNA Research as published in the Federal Register .53, 34246-47, 2 September 
1988. 
In particular I wish to lend my support to Dr. Anne Vidaver's proposed 
amendment of Section I-B. Transposition is a natural physiological recom- 
bination event. Although the transposition phenomenon may involve a coin- 
tegrate intermediate of the recombinant and nonrecombinant replicons, the 
resolution of the intermediate is precise and does not normally result in 
the exchange of sequences outside the transposon. The use of a recombinant 
vector to deliver a transposon to a host should not render as recombinant 
subsequent cultures which have lost the recombinant plasmid and which have 
the nonrecombinant transposon inserted into the chromosome or a nonrecombinant 
resident plasmid. 
Within the scope of Dr. Vidaver's proposal, I would like to pose the following 
question. Does the proposal extend to genetic events mediated by site 
specific or homologous recombination in which a recombinant transposon is 
exchanged for a nonrecombinant (wild type) transposon? If not I would 
propose that the following paragraph be added to Dr. Vidaver's proposed 
amendment : 
Likewise strains resulting from the deletion of a recombinant 
transposon or exchange of a recombinant transposon for a wild 
type transposon via site specific or homologous recombination 
are not considered to be recombinant and are not covered by 
these Guidelines. 
Thank you for your attention. 
Sincerely yours, 
Recombinant DNA Research, Volume 13 
Jack J. Manis, Ph.D. 
Associate Director 
Bioprocess R&D 
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