A3TACW1ENT II - PAS: 1 
FIRST CRAFT PlCSarr TO RAC CN JANUARY 9, 1981 
Cloning of Ttscins 
I. P r e ant i le 
lt)«reas it is unliJoely that newel pathogens of clinical significance 
for nan night be created by the cloning of genes for toxic proteins 
into new host bacteria that colonise hunans or that may pass genetic 
information to organims capable of colonizing hunans, it is neverthe- 
less prudent to restrict the cloning of genes for potent toxins. 
The theoretical dangers stem from the habits of. the new bacterial host 
and the toxicity of the toxin per se rather than knoMi attributes of 
the organism that contributes the toxin gene(s), its ecology, virulence, 
amount of toxin it may synthesize in humans or elset4)ere, and the possi- 
bility that it exchanges genetic information with certain ether organians 
in nature. Likewise, the toxins role, or otherwise, in pathogenicity of 
the donor organiam is not necessarily of relevance. 
The extent to which toxins are a danger is usually difficult to ascertain 
for hunans. The specification thus attempts to define a level of activity 
below «4iich proteins might be considered safe and specifies minimal accep>- 
table safety tests on animals t^ich might predict hunan safety levels. 
Because there are wide OlO^ fold) differences in susceptibilities of 
animals to toxins, human safety may be inferred with reasonable assurance 
only if an agent is shown to non-potent to another primate or to several 
lower mammals. The specification is worded so that non-potenney (potency) 
for lower animals would be over-ridden by evidence of potency (non-potency) 
to primates or hunans. 
CRAFT 1/7/81 
157J 
