Dr. Donald S. Fredrickson 
September 23, 1978 
Page 2 
has been the absence of any noticeable biohazard associated with the construction 
of any recombinant during the past several years. While reassuring, it should be 
noted that biohazards were not looked for and, indeed, all experiments were con- 
ducted under levels of physical and biological containment that we now agree were 
over-restrictive and which would preclude manifestation and/or detection of any 
biohazard should they have arisen. Thus it is scientifically invalid to use the 
experience of five years' research as a justification to argue that biohazards 
do not exist. It will thus be necessary to design and conduct experiments ex- 
pressly for the purpose of determining whether the introduction of foreign DNA 
does or does not result in manifestation of biohazards and such experiments 
have not been done". I should hasten to add that such experiments have commenced 
but have not been fully reported. I would, therefore, prefer that you downgrade 
the importance of the above-cited argument for the safety of recombinant DNA 
research and rely instead on the substantial body of factual information and 
valid experimentation to substantiate the basis for the conclusion that recombi- 
nant DNA research with col i K-12 host-vectors is far safer than any of us had 
originally believed four years ago. 
2. Section I. Scope of the Guidelines (p.33069-33070). The organization and clarity 
of this section has vastly improved over both the previous Guidelines and the draft 
arrived at by the RAC. I do, however, have some specific comments on Sections I-D 
Prohibitions and I-E Exemptions as described in the following four points. 
3. Sections I-D-l and I-D-2 (p. 33070). Since VSV and moderate risk oncogenic 
viruses are or can be construed to be Class 3 agents, there is a paradox which, 
while dealt with in the Decision of the Director to Issue Revised Guidelines 
statement, still persists in the Revised Guidelines as now written. It should be 
stated explicitly in Section V, footnote 2 (p. 33086) that the basis for allowing 
cloning of genetic information from VSV and moderate risk oncogenic viruses is 
the likely difficulty of faithful transcription and/or translation of this genetic 
information in prokaryotic host-vector systems, which would therefore be less 
likely to lead to a biohazardous condition than might cloning genetic information 
from Class 3 prokaryotic or lower eukaryotic organisms. I might add that I hope 
that, in the near future, NIH would thoroughly consider the basis for prohibitions 
I-D-l and I-D-2 in light of the fact that recombinant DNA research with organisms in 
the Class 3 category as well as the deliberate cloning of genes specifying potent 
toxins can provide information not now available on the biochemical and genetic bases 
of pathogenicity of some of these agents and can also provide information that might 
lead to effective means of diagnosis, treatment and/or prevention of diseases caused 
by these agents. Such work is definitely in the national interest and means for its 
conduct and performance should be facilitated. I thus strongly believe that the 
lifting of these two prohibitions should not be decided solely on a case-by-case 
basis but rather should be based on a general consideration of the benefits and 
risks of any and all experiments in either of these two categories. The facts 
that the allowed cloning of genetic information from some Class 3 viral agents 
already constitutes an exception to Section I-D-l and the existence of P4 contain- 
ment and the eventual approval of EK3 host-vector systems whose uses are not stip- 
ulated for any experiments in the Proposed Revised Guidelines should serve to justify 
[A-309] 
