23 
Dr. F^edoroff said the transfer of this recombinant ENA into Anabaena or 
Nostoc is currently permitted, under P3 containment conditions, by Section 
111-6-2 of the Guidelines. Dr. Wblk requested a lowering of containment 
to PI. Er. Pedoroff said the request was internally inconsistent in that 
Dr. WoDc states that no cyanobacteria are known or suspected pathogens; 
however, the si^sporting documentation indicates that these organisms do 
produce toxins. She moved that RAC e^jprove the request ccxitingent upon 
ORDA receiving doci^ntation that the strains Dr. Wolk uses will not be 
toxin producers. 
Drs. Bems, MoGarrity and McKinney felt it inaj^opriate to approve an 
inoonnplete, inconsistent prc^xosal. Dr. Fedoroff withdrew her original 
notion, emd then moved disa^^oval of the proposal with the request that 
the principal investigator submit a clearer and internally ocxisistent 
proposal. By a vote of nineteen in favor, ncxie apposed, and no abstentions, 
the RAC adopted the motion. 
XVIII. GUIDELINES FOR REOOMBINANr ENA EXPERIMEMS WITH GENES CODING FOR TOXINS 
Dr. Maas initiated the discussion of the proposed guidelines for recombinant 
ENA experiments with genes coding for toxins (tabs 996 , 997, 1015/An;iI). 
Dr. Maas stated that an ^ hoc working group had been constituted several 
months ago to attempt to evaluate Secticm I-D-2 of the Guidelines vhich 
deals with potent toxins. Ihe working group was composed of Drs. Werner 
Maas and Alan Bemheimer of New York Ehiversity, Dr. John Collier of Yale 
University, Dr. Susan Gottesman of the NIH, Dr. Michael Gill of Tufts 
thiiversity. Dr. wyrcxi Levine of the Uhiversity of Maryland, and Dr. James 
Mason of the Utah State Department of Health. He said that the grxxp 
evaluated toxins as pharmacological agents per se without consideration of 
other characteristics of the organism that produces the toxin. 
Dr. Novick, citing recent research showing that a toxin produced by a 
Bacillus is functicxicdly e;^ressed in E. coli host-vector systens, said 
that the document is timely. 
Dr. Levine pointed out that important vaccine development is dependent on 
recombinant ENA manipulaticxis. He said the proposal under consideraticxi 
will advance work in this area by clarifying the status of toxins under 
the Guidelines. He then deferred to Dr. Gill, an ad hoc consultant, who 
had been instrumental in constructing the propxosal on toxins. 
Dr. Gill called the committee's attention to tab 1015/VIII in the Federal 
Register . The proposal would modify Section I-D-2 of the Prchibitions 
and would add a new Appendix G to the Guidelines. Containment conditions 
are assigned for cloning toxins in ^ coli K-12 . A principal investigator 
wishing to use other host-vector systems would have to COTitact ORDA v^ich 
will consult with the ad hoc working group on toxins. Toxins were divided 
into four grotps on the~basis of potency. Cloning of ENA coding for toxins 
with an LD 50 of less than 100 nanograms per kilogram body weight is prohi- 
bited; cloning of genes oodir^ for toxins with an LD 50 of 100 nanograms 
[112] 
