The Honorable Joseph A. Califano 
October' 13, 1978 
Page 4 
some degree of Federal regulation will be necessary for the foreseeable 
future. I refer, for example, to the certification and monitoring of the use 
of host-vector systems. NIH anticipates applications for a variety of orga- 
nisms other than E. col i K- 1 2 and concedes that knowledge of their character- 
istics is inferior to the information acquired over many years about E. coli . 
It may be necessary to devise entirely new criteria in order to evaluate the 
safety of these new systems. Yet Dr. Fredrickson assures us that "the same 
considerations of safety and risk associated with the use of E. coli K-12 will 
also apply to any new host-vector system to be certified in the future." 
Subject to unusual case-by-case exceptions, moreover, the proposed guidelines 
retain the existing prohibitions on certain presumably hazardous categories 
of experiments, the release into the environment of organisms containing 
recombinant DNA, and the production of certain large cultures. In spite of 
suggestions that the burden of proof has shifted to those who would restrict 
the research, the revised guidelines are on the whole consistent with the 
present policy of imposing safeguards unless there is strong evidence that 
the activities pose no significant risk. As the Subcommittee's report points 
out, such evidence will be acquired gradually, over the course of several 
years. 
In these circumstances, it is no less anomalous now than it was a year to two 
ago to restrict one class of researchers but not another, merely on the 
basis of their location and source of funds. Furthermore, voluntary adherence 
to the guidelines' prescriptions will become increasingly problematic as the 
research proliferates, more positive results are achieved, and the line between 
research and development is crossed. Far from obviating the need for any 
regulation, the progress that is being made in recombinant DNA research 
underscores the importance of universal standards uniformly applied. 
The adoption of new NIH guidelines representing a more informed assessment of 
risks should facilitate action on legislation. My impression is that overall 
the proposed revisions represent a considerable advance in comprehensiveness 
and specificity over the present guidelines and that they will permit further 
progress in recombinant DNA research under appropriate safeguards. I commend 
Dr. Fredrickson, his colleagues and advisers for their efforts. 
On the other hand, the proposed guidelines retain or create some ambiguities 
and weaknesses, particularly with respect to administrative procedures, that 
should be corrected. Fearful of "the heavy tax of formalism," Dr. Fredrickson 
has endeavored to retain as much discretion as possible in administering these 
regulations. Flexibility is important in a rapidly changing field of research, 
but the revisions reflect too little regard for accountability and predict- 
ability. I believe that the changes recommended in the attachment will 
further reduce public controversy and uncertainty among scientists and research 
institutions as well as promote compliance with the guidelines or with formal 
regulations if Congress acts next year. 
[A-417] 
