Dr. Donald S. Fredrickson 
September 22, 1978 
Page 3 
advisory body. In addition, other program directors (USDA, NSF, etc.) 
should be able to authorize exemptions (specifically, under I-E-4) 
based on review by RAC or another scientifically competent review 
panel. Finally, I feel that greater latitude should be given to IBCs 
for assignment of levels of containment to experiments not explicitly 
covered by the guidelines. Under PRG-NIH, such experiments must be 
submitted in an MUA to ORDA, reviewed by RAC (Appendix C, section E-2) 
and then approved by the Director of NIH (IV-B-l-e) . 
While all possible experiments could never be foreseen, PRG-NIH is 
considerably improved over the current guidelines in providing greater 
detail in the classification of experiments. More importantly, however, 
the background information and discussion in the footnotes and accom- 
panying the PRG-NIH in the form of the Decision Document and supporting 
appendices serve to provide a well-reasoned conceptual framework for 
the assignment of containment levels to experiments not specifically 
dealt with in the guidelines. Thus, the guidelines wind up being just 
that - guidelines. On the other hand, it seems that PRG-NIH says, 
"nothing expressly permitted is strictly forbidden. . .until approved," 
rather than reasonable persons (IBCs) following the framework provided 
by PRG-NIH can determine appropriate containment levels for experi- 
ments not expressly covered by the guidelines. These decisions, of 
course, would be subject to review by ORDA and, if necessary, RAC. 
6. There is an additional complication arising from the increased central- 
ization of decision-making authority and the prohibition of everything 
not expressly permitted in the PRG-NIH. There is an apparent paradox 
that obviously nonhazardous experiments which are currently permitted 
will have to stop, pending what will undoubtedly be a long, tedious 
procedure for subsequent approval. For example, cloning of DNA segments 
from one Streptomyces species into another Streptomyces species has 
been approved by both IBCs and NSF as clearly falling within the 
intent of the current guidelines. In the PRG-NIH, exemption I-E-4 
might be cited to permit such manipulations. Unfortunately, Appendix A 
fails to list any Streptomyces species. Further, the prohibition on 
the use of conjugative HV1 vectors will substantially retard the devel- 
opment of plasmids such as SCP2 for cloning vectors. 
The simplest solution to this problem is the institution of HVO as a 
level of biological containment. HVO's could be approved by IBCs for 
use as alternate host-vector systems as long as the host were non- 
pathogenic. Vectors would not necessarily have to provide the level 
of containment required for HV1 (e.g., nontransmissibility of plasmids). 
Finally, analogous to the suggestion in Appendix G (II-D-a) , all 
experiments conducted with HVO systems require a one-step higher 
level of physical containment than the comparable experiment performed 
with an HVl system. 
[A-265] 
