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feelings of the Europeans as stated by John Tooze earlier. For the sake of 
brevity I would just like to read from the pertinent section of my letter to 
Dr. Fredrickson where I address retroviruses per se, but my comments, I 
think, could be taken in general to pertain to the Guidelines, the levels 
outlined in the Guidelines for animal viruses. 
In my opinion, there is little use in designing experimental Guidelines 
for "permissible experiments" which cannot be practically met. This is the 
case for the classification of DNA viruses and DNA transcripts of retrovi- 
ruses. Furthermore, the designation of containment for this class of experi- 
ments seems disproportionately conservative on several counts. I go on 
to list them. Viruses in this class belong to the NCI category low-risk. 
In their naturally infectious form, such viruses can be handled at what 
would correspond to a P2 level of containment. If we accept the Guidelines' 
conservative approach of assigning recombinant organisms to a level not 
less than required for handling the most hazardous components, then a rea- 
sonable level for these experiments might be P3 . Instead, they have been 
placed at the unobtainable level of P4 plus EK1 . 
To compound the problem, essentially no flexibility has been provided, 
for in this particular instance a decrease of one step in physical contain- 
ment, P4 to P3, requires an increase of two steps in biological containment, 
EK1 to EK3 . This requirement again puts the experiment in the realm of the 
unobtainable, since no EK3 vectors are yet available or even in the testing 
st age . 
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 vector virus is presented 
to a cell, presumably via E. coli infection of the gut, in a form for which 
it has no natural resistance. Since it already seems clear from what we 
have heard that E^_ coli K-12 carrying a DNA insert cannot become an epidemic 
pathogen, especially if it is in 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 area of research versus other 
types of viral research seems to have disappeared. 
How real is the hazard to the investigator? We already have some data 
from preliminary experiments of Majrtin and Rowe which bear directly on this 
point. Using the model system of polyoma virus in its highly susceptible 
mouse host, they show that naked polyoma virus DNA could indeed cause viral 
infections of mice, and the highest infectivity was observed after subcutane- 
ous injection. Impressive as this fact seems, this infectivity is still 
only five times 10~ 5 of the specific infectivity of the virus in its native 
form. One interpretation 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 particular virus and sensitive host sys- 
tem. It seems probable that such research would provide an even greater 
safety advantage when dealing with this and other viruses in a virus insen- 
sitive host system — that is, the hypothetical situation in which an investi- 
gator somehow becomes infected with an E. coli K-12 containing viral genes. 
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