STANFORD UNIVERSITY MEDICAL CENTER 
DEPARTMENT OF GENETICS 
October 9, 1980 
Dr. Donald Frederickson 
Director 
National Institutes of Health 
Building 1, Room 124 
Bethesda, MD 20205 
i Dear Dr. Frederickson: 
I understand from talking with Dr. William Gartland and others present at 
the last RAC meeting that an amendment to Action 916 offered by Dr. Richard 
Novick at the meeting would require the use of non-conjugative plasmids for 
the cloning of J3. subti 1 is or £. col i- derived DNA in Streptomyces species. 
Since non-conjugative Streptomyces plasmids are not known to exist, and since 
an action approved previously by the Committee permitted cloning of the above 
DNA's in S. coel icolor under P2 conditions without specifying the nature of 
the vector. Dr. Novick 's amendment would have the effect of reversing a 
previous decision by the RAC and increasing the level of containment required 
for experiments that have been permitted under P2 conditions for some time. 
Thus, the amendment is a "major action"; it does not seem appropriate that it 
be made a part of the Guidelines in the absence of a 30-day period providing 
an opportunity for workers in the field and others to offer comments on it. 
It should also be noted that the concept of "conjugati ve" versus 
"non-conjugative" plasmids has been derived from enteric bacteria and may not 
apply to a wide variety of other bacterial species. For example, the 
mechanism for genetic exchange in Streptomyces species is not fully 
understood; it may be a consequence of hyphal fusion that permits transfer of 
plasmid and chromosomal genes. If this is true, it may never be possible to 
isolate a "non-conjugative" plasmid per se to meet the requirements specified 
by Dr. Novick's amendment. 
Since all of the Streptomyces species that exchange genetic information 
with S>. coel icolor are free-living non-pathogenic soil organisms — and since 
the change in the Guidelines originally proposed under Action 916 involved 
genes from only non-pathogenic, well-characterized donor bacteria, I urge your 
approval of the original proposal without the amendment. 
APARTMENT OF GENETICS, STANFORD UNIVERSITY SCHOOL OF MEDICINE, STANFORD, CALIFORNIA 94305 • (415) 497-5052 
Stanrey N. Cohen 
Professor 
SNC:ps 
[ 317 ] 
