COVINGTON u BURLING 
Donald S. Fredrickson, M.D. 
February 20, 1976 
Page Four 
comments. The remaining portions of the guidelines appear 
justified, with the qualification that the rationale for those 
portions should, as I have discussed in this letter, be spelled 
out in much greater detail. 
My specific comments and recommendations with respect 
to the proposed guidelines are as follows: 
1. From all that I heard at the meeting, as well as 
my own background in the field of government regulation, I am 
satisfied that the concept of "physical containment" is both too 
imprecise and too subject to the vagaries of human fallibility 
that it does not offer sufficient protection against harm except 
for those experiments for which the risk is so extraordinarily 
low that it is virtually non-existent. For any experiment in 
which there is a significant risk to the public, therefore, 
development of "biological containment" safeguards is absolutely 
essential. If you wish to have specific documentation for the 
fallibility of physical containment, I would suggest that you 
review the Food and Drug Administration experience with compliance 
by the regulated industry with good manufacturing practices, 
compliance by investigators with requirements such as those 
for obtaining informed consent, and compliance by all types of 
those laboratories with acceptable animal testing procedures. 
Accordingly, NIH should place a very high priority on 
exploring the precise level of risk involved in the various 
experiments on recombinant DNA molecules that have been or may be 
undertaken, and in developing and confirming biological contain- 
ment both for E. Coli (EK-2 and EK-3) and for other organisms to 
be used as hosts and vectors. Serious consideration must be 
given to the possibility of prohibiting use of EK-1 and other 
organisms which do not reach an acceptable biological containment 
level after an interim period of time, as suggested by the Boston 
group; and if you believe that this is not necessary in order to 
protect the public you should clearly state the basis for your 
decision. 
2. Prior to the meeting, it appeared that the Boston 
group was making a major argument that E. Coli simply should not 
be used at all as the host organism. The argument made in their 
prior submissions was based on the concern that, since E. Coli is 
a normal resident of man, it simply is not a safe host for this 
experimentation. At the meeting, on the other hand, the repre- 
sentatives of the Boston group appeared to me to recede from this 
position, and to accept the argument that development of EK-2 
and EK-3 organisms would provide for sufficient public protection. 
[477] 
