Dr. Fredrickson 
- 4 - 
11/14/77 
than that required for handling the most hazardous compo- 
nents", 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 to P3) requires an increase 
of two steps in biological containment (EK1 to EK3). This re- 
quirement again puts the experiments in the realm of the un- 
obtainable, since no EK3 Vectors are yet available (or even in the 
testing state). 
The special concern for this category apparently relates to a 
situation in which DNA of an animal tumor virus is presented to 
a cell (presumably via E. coli K1 2 infection of the gut) in a 
form for which it has no natural resistance. Since it already 
seems clear that the E. coli K1 2 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 conserva- 
tism in this versus other types of viral research seems to have 
disappeared. Data from preliminary experiments of Martin and 
Rowe using the model system of polyoma virus and its highly 
susceptible mouse host, showed that naked polyoma virus DNA 
could indeed cause viral infection of mice and the highest in- 
fectivity was observed after subcutaneous injection. Impressive 
as this fact seems, this infectivity is still only 5 x 10“^ of the 
specific infectivity of the virus in its native form. One inter- 
pretation of these data is that preparing naked DNA is quite an 
effective method of attenuating this virus. Thus, research with 
DNA, or recombinant DNA including these viral genes, seems 
to provide an important safety advantage- -at least in this particu- 
lar virus- sensitive host system. It seems probable that such 
research would provide an even greater safety advantage when 
dealing with this and other viruses in a virus-insensitive host 
system (i. e. the hypothetical situation in which an investigator 
somehow becomes infected with an E. coli K12 containing viral 
genes). Further, the viruses in this category are not human 
pathogens, and they represent animal model systems which are 
of great biomedical importance. The current practical morator- 
ium on recombinant DNA research with these systems does not 
seem to be a sound balance of benefit versus risk® 
[Appendix A — 65] 
