UNIVERSITY OF WASHINGTON 
SEATTLE, WASHINGTON 98195 
School of Medicine 
Department of Microbiology and Immunology, SC-42 
April 4, 1978 
Dr. Donald S. Fredrickson, Director 
National Institutes of Health 
Bethesda, Maryland 20014 
Dear Dr. Fredrickson: 
I would like to propose for consideration of the Recombinant Advisory Com- 
mittee the fallowing addition to the list of prohibited experiments (section 
IIIA.ii of the revised Guidelines): 
"Formation of recombinant DNAs containing genes for the biosynthesis 
of potent toxins (e.g. botulinum or diphtheria toxins, psilocybin , venoms 
from insects, snakes, etc.)." 
The justification for inclusion of psilocybin in the list of potent toxins 
that would be hazardous products of cloned DNA is as follows: Psilocybin is a 
simple fungal metabolite whose effects on animals are potent. It is formed 
from tryptamine, a normal metabolite of higher organisms, by one or two simple 
enzymatic steps (S. Agurell and J. L. G. Nilsson (1968), Biosynthesis of 
Psilocybin II: Incorporation of Labeled Tryptamine Derivatives. Acta Chem, 
Scand. 22, 1210.). Thus the cloning of DNA from Psilocybe spp. or Panaeolus 
spp . in E. col i could create a strain that synthesizes this drug. Escape of 
such a recombinant DNA could be disastrous. 
If this cloning experiment is not included in the list of prohibited experiments, 
I would suggest that it be specifically mentioned under section IIIB.e.l as 
a P3EK2 experiment, and the language be changed to include toxins other than 
polypeptide toxins. 
It is advisable to include specific mention of this issue in the guidelines 
because the potential hazard is not immediately obvious, and the substance 
psilocybin, while not a "potent polypeptide toxin," nevertheless poses just 
as serious a problem because of its simple mode of biosynthesis. 
Thank you for considering this point. 
Sincerely yours, 
Mary-Dell Chilton 
Research Associate Professor 
[Appendix A — 272] 
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