AITftCHMENr 2 - PAGE 1 
PROPOSED RISK ASSESSMEm* 
The Fhannalogical and Physiological Consequences of 
Direct In tra intestinal Adninistration of the More Potent Tbxins 
With the raost likely cloning host, ^ ooli , the principal dangers to man of 
cloning toxin genes appear to lie in the intraintestin^d production of toxins 
that may (a) pass through the gut lining and cause damage elsewhere or (b) 
damage the gut directly, or (c) both danage the gut and, as a consequence, 
later pass more easily into the circulation to cause damage elsewhere. The 
extent to which intraintestinal toxins may create a potential danger when 
produced by organisms capable of oolcnizing hcnans is currently lacking and 
is difficult to ascertain, but may be inferred from appropriate animal tests. 
Question 1: Concerning the more potent cytotoxins: how much toxin could 
be produced in the gut without causing death, disfigurement, profound neuro- 
logical changes or severe damage to the intestine itself, and is it therefore 
safe to devise cloning protocols in which 50 mg., for example, of the toxin 
may be produced enter ically. 
Tbxins to use ; Diphtheria toxin (Perhaps repeated with abrin or ricin, but 
the protocol below is mostly for diphtheria toxin). 
Protocol t (a) Cne injection of graded doses (£.£., initially 0.5%-50 mg/kg 
using diphtheria toxin) directly into the guts of, for diphtheria toxin - 
rabbits and/or guinea pigs (not mice), for abriiVricin - mouse and/or rabbit 
and/or guinea pig. Determine the doses Uiat kill. 
1129 ] 
