STANFORD UNIVERSITY MEDICAL CENTER 
STANFORD, CALIFORNIA 94305 
DEPARTMENT OF BIOCHEMISTRY 
PAUL BERG 
Jack, Lulu and Sam Willson 
Professor of Biochemistry 
April 6, 1976 
Dr. Donald S. Fredrickson 
Director 
National Institutes of Health 
Bethesda, Maryland 20014 
Dear Don, 
I realize that you have labored long and hard to understand the 
issues and arguments that comprise the Recombinant DNA controversy. 
They are indeed complex and contentious, all the more so because of 
the paucity of data relevant to resolving them. But you have raised 
some interesting and important questions for the committee to consider. 
As I write this, I know that you have already met with the NIH Committee 
and received their comments; but for what they are worth to you, here 
are my views on some of the questions you posed: 
A. Methods of Containment 
a) I am puzzled by the difficulty several commentators had with 
the concept of physical containment, particularly because it can be de- 
fined more precisely than any of the forms of containment that have been 
discussed. In fact, it is the only tried, tested and accepted means avail- 
able for containing dangerous pathogens; physical containment has been 
relied on for studies with hoof and mouth disease, Herpes B virus and 
the potential pathogens that might have been brought back from the lunar 
surface. I have learned that the British equivalent of the NIH Recombi- 
nant DNA Committee has opted to rely entirely on physical containment 
because experience with it has been so extensive and successful. Admit- 
tedly it is subject to human error but that only means that training and 
vigilance in the use of that containment facility must not be neglected. In 
any case I believe that Barkley's expanded explanation of physical contain- 
ment should alleviate those concerns. 
b) I agree with your suggestion that experiments to be carried 
out in P4 facilities merit special attention by individuals who understand 
the uses and limitations of such facilities. I can imagine such a panel of 
experts periodically visiting and examining the special facilities but what 
of the instance of a University's or Institute's own P4 facility? Who would 
supervise and monitor these once they have been certified as P4 labora- 
tories ? 
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