Page two 
Dr. Donald S. Frederickson 
October 13, 1977 
since many more types of experiments are possible using EK1 vectors. The 
inconsistency I see is the failure to provide a similar flexibility for 
other P2 + EK2 experiments, for example, shotgun experiments with DNA from 
mammals other than primates, or from birds (page 49601). 
'2. There is little use in designating experimental guidelines for "permissible 
experiments" which cannot practically be met. This is the case for the 
classification "DNA viruses and DNA transcripts of retrovirus genomes". 
Furthermore, the designation of containment for this class of experiments 
seems disproportionately conservative on several counts: 
(a) Viruses in this class belong to the NCI category called " low- 
risk" . In their naturally infectious forms, such viruses can be 
handled at what would correspond to a P2 level of containment.' If 
we accept the Guidelines' conservative approach of assigning recom- 
binant organisms to levels "not less than that required for 
handling the most hazardous components", then a reasonable level 
for these experiments might be P3. Instead, they have been placed 
at the unobtainable level of P4 (+EK1) . To compound the problem, 
essentially no flexibility has been provided, for in this particular 
Instance, a decrease of one step in physical containment (P4 ■* P3) 
requires an increase of two steps in biological containment (EK1 -*• EK3). 
This requirement again puts the experiments in the realm of the 
unobtainable, since no EK3 vectors are yet available (or even in the 
testing stage). 
(b) What is the special concern for this category? As far as I can 
tell, it relates to a scenario in which DNA of an animal tumor virus is 
presented to a cell (presumably via E_. coli K12 infection of the gut) 
in a form for which it has no natural resistance. Since it already 
seems clear that the E,. coli K12 carrying a DNA insert cannot become 
an epidemic pathogen (especially if it is an EK2 strain) the only 
potential hazard is to the Investigator and not to the public . Therefore, 
the basis for special concern and conservatism in this versus other 
types of viral research seems to have disappeared. 
(c) How real is the hazard to the investigator? We already have some 
data from preliminary experiments of Martin and Rowe which bear directly 
on this point. Using the model system of polyoma virus and its highly 
susceptible mouse host, they showed that naked polyoma virus DNA could 
continued 
[Appendix A — 10] 
