Dr. William Gartland 
2 . 
October 26, 1978 
It may be that of the experiments I have described, there is 
a hierarchy of potential dangers. I was drawn to think of this in 
the first place by the use of our strains by Hofnung and colleagues 
to put a hybrid somatostatin cn the cell surface of E_. coli. In this 
case, the modified hormone would be exposed to the "outside world" 
and would be in a position to elicit an immune response. Similarly, 
any strains which secrete individual hormones into the media would 
raise this possibility. Strains producing modified hormones in the 
cytoplasm or periplasm might create less of a problem. 
It is my understanding that this potential problem is not 
covered by the guidelines. I would like for you and the Recombinant 
DNA Advisory Committee to consider this problem and let me know 
whether it is considered that these concerns are valid, and, if so, 
what steps will be taken. For instance, it seems reasonable to me to 
carry out animal tests with these bacterial strains to see whether 
they can induce the breaking of tolerance. Also, I would like to 
know the containment which would be necessary for such experiments. 
I realize that there is a general impression that E. coli K12 
does not persist long enough in the body to cause problems. But my 
own feeling is that not enough experimentation has been done to 
scient if ically substantiate that impression. It seems to me that 
particularly when there is a concrete possibility of health hazard, 
that a more detailed examination of the problem should be carried out. 
Since in one of the cases I have described, strains constructed 
in this laboratory have been used, I personally feel responsible for 
any consequences of the work. I am eager to hear the response of 
yourself and the RAC. I am sending a copy of this letter to Dr. 
Susan Gottesman who worked as a graduate student in this laboratory 
and, I believe, is a member of the Advisory Committee. 
JB/ara 
cc: Susan Gottesman 
Walter Gilbert 
Maurice Hofnung 
Malcolm Casadaban 
Herbert Boyer 
Sincerely, 
Jon Beckwith 
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