10320 Bren Road East 
Minnetonka, Minnesota 55343 
612, 935-7335 
Molecular Genetics Inc 
November 22, 1982 
William J. Gartland, Jr., Ph.D. 
Department of Health & Human Services 
Public Health Service 
National Institutes of Health 
Bethesda, MD 20205 
Dear Doctor Gartland: 
I wish to respond to your request for information on the functioning of our 
IBC and concerns with regard to the revised Guidelines. 
I will respond to the questions you proposed: 
A. What are the problems with the revised Guidelines ? 
Generally, I see two basic problems with the Guidelines. First of all, 
I feel they require too much from the committee as a whole, and I will go 
into more detail regarding this in later questions. 
Secondly, the Guidelines encourage voluntary compliance by commercial 
industries but the RAC may not have been appraised of industries special 
concerns as evidenced by some Guideline requirements . I am especially 
concerned about paragraph III-B-4-a. For example, we wanted to determine 
if a crude bacteria lysate would induce neutralizing antibody against a 
specific virus in rabbits. The bacteria were producing portions of the 
viral coat protein from a fragment of the coat protein gene cloned into 
a plasmid vector and the rabbit is not a host for the virus. One could 
read paragraph III-B-4-a as requiring us to show that whole virus was not 
produced in rabbits. This experiment is questionable for a couple of 
reasons: It is a negative-type experiment -we are required to show that 
same thing does not happen; and the animal is known to not be a host. 
Simply the fact that only two-thirds or less of the virus is present 
should be sufficient evidence to suggest that productive infections would 
not occur, even in a host animal. 
Paragraph III-B-4-a becomes of greater concern when one considers an 
eventual commercial vaccine product since no physical containment whatsoever 
will be maintained. However, standard killed vaccines contain the whole 
viral genome in higher concentrations than a recombinant DNA product would 
without great concern. 
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