29 
diphtheria toxin structural gene. Dr, Mur0iy preposed to use P4 contain- 
ment and to perform the experiments at Fort Detrick, If P3 containment 
were permitted, he would prepose to perform the experiments at Sidney 
Farber Cancer Center in Boston or at Harvard University in Cambridge, 
Massachusetts, ft:, Murphy would perform risk assessment experiments, 
and would study toxin secretion, localization in ^ ooli , and the entry 
of toxin into euJcaryotic cells. 
Dr, Levine spoke of one potential future benefit of the proposed research: 
hormexies that home to specific organs, might be linked to porticMis of the 
diphtheria toxin and the oothination molecules might serve as highly 
specific agents in cancer chemotherpy. Dr, Levine strcxigly supported 
that porticxi of the request dealing with possible risk assessment studies. 
He noted that P3 containment conditions are specified by the general toxin 
class ificaticxi, previously adopted by RAC; and he felt P3 was adequate 
containment. 
Dr, Gottesroan as)ced Dr, Gill to review the data on the potency of diphtheria 
toxin, v*iich had led to its position in J^pendix G in the class allowed 
at P3 + E3Q ocxitainment. Dr, Gill said the LD 50 of diphtheria toxin, in 
the most sensitive small animal (guinea pig), is 160 nanograms per kilogram 
body weight. Hie LD 50 in hunans is estiitated to be equal to or less 
than 100 nanograms per kilogram body weight, Hiis figure was extr^olated 
from an incident in Japan in v^ich children were inadvertently injected 
with diphtheria toxin rather than dipihtheria toxoid. It thus falls close 
to the borderline of 100 nanograms par kilogram body weight, vAiicii would 
separate a toxin the clcxiing of whose gene would be pirohibited from a toxin 
the cloning of v^xjse gene wDuld be allowed at P3 + EKl in Appendix G, 
Dr, Gottesroan said that she would support P4 ccxitainment for the proposed 
expariment. Dr, Levine said he could support P4 cxxitainment, but questioned 
i^ether this might ccxiflict with the acticxi taken earlier in the meeting 
on the general toxin classification. Dr, Talbot said that Dr, Fredrickson 
could resolve any ccxiflict when he promulgates his decisicxi on the recoramen- 
daticxis from this meeting, 
a:, Levine moved acceptance of the proposal at P4 cc«tainment. Dr, Goldstein 
seccxided the motion. Be a vote of fifteen in favor, nexa eppased, and one 
abstention, the RAC adopted the motion. 
Dr. Levine suggested* that if the genes are successfully cloned, an E, coli 
host-vector system containing the plasmid and capable of colonizing a pig 
might be used in an additional risk assessment experiment. Hie pigs 
should be colonized under P4 containment conditicxis. Dr. Murphy exparessed 
interest in pursuing such experiments, but it was pointed out that it may 
not be possible to introduce a pig into the P4 line. 
[118] 
