17 
Dr. Gill said many investigators would like to study a mutated Shiga 
toxin gene. He asked if the Shiga-like toxin gene would be available to 
other researchers if it were made in a P4 facility. Dr. Randall Holmes 
said his laboratory would make the strains available as soon as the data 
are published, assuming the strains can be removed from the facility. 
Dr. Be ms called the vote on the motion. By a vote of twelve in favor, 
none opposed, and one abstention, the motion to permit the experiments 
at the P4 containment level was carried. 
Dr. Landy offered a motion to permit the experiments using P3 laboratory 
practices and containment equipment in a P4 facility. Dr. McKinney said 
that when P3 practices are followed in a P4 facility, additional protection 
beyond P3 is provided as the facility has a completely separate ventilation 
system; all liquid waste from the facility goes to a waste treatment 
plant for sterilization prior to discharge, and all materials in the 
facility are doubly sterilized. When work is performed under full P4 
conditions, a Class III glove box is used. 
Dr. Landy called the question on his motion. By a vote of nine in 
favor, one opposed, and one abstention, the question was called. By a 
vote of five in favor, seven opposed, and one abstention, the motion 
was defeated. 
B. Request to Reevaluate Conditions Under Which the Shiga Toxin Gene 
may be Cloned 
Dr. Bems introduced the letter (tab 1085) of Er. K. N. Timmis of 
the Uhiversite de Geneve for discussion. Dr. Timmis requested that 
the NIH reevaluate the conditions inder which the Shiga toxin gene may 
be cloned in Escherichia coli host-vector systems. He argued that 
Shigella dysentenae and E. ooli are closely related organisms and 
that the degree of uncertainty inherent in "shotgun" cloning is related 
to the evolutionary distance between tlie two ENAs being ccmbined . He 
contended that the joining of genetic segments frcm closely related 
species known to excharge genetic information with one another by 
natural processes, involves predictable hazards that do not exceed the 
sum of the hazards exhibited by each of the contributing organisms. 
He felt the overriding principle of the Guidelines should be the 
relatedness of the ENA species being combined, rather than the specific 
toxicity of the toxin molecules. He thought use of the later criteria 
introduces an illogical inconsistency into the Guidelines. 
Dr. Gill said no inconsistency exists in the Guidelines; Section III-A 
takes precedence ever other sections of the Guidelines. He emphasized 
that the fact the organisms exchange genetic information does not imply 
the absence of risk. Er. Gottesman reaffirmed that the Guidelines 
are internally consistent. She recommended that ORDA, in responding 
to Er. Timmis' letter, relate the RAC discussion and RAC's action 
regarding the Shiga-like toxin gene. 
r?3] 
