5 
3. Another concern relates to the specified containment levels 
for "other cold-blooded animals and lower eukaryotes" on p. 26 
of the guidelines. Of special concern is the frequency with 
which insects, for example, are known to carry agents pathogenic 
to man. The great uncertainty surrounding the use of DNA from 
these sources requires a conservative approach until information 
allows more flexibility. I believe that some protection can be 
obtained by requiring that a donor in this category or its 
DNA be proved free of any pathogen for its containment levels 
to be reduced. The section on "Other cold-blooded animals and 
lower eukaryotes" would thus have two categories. The first 
would be for those eukaryotes proved to be free of any pathogen 
which that species is known to be capable of carrying. Contain- 
ment levels for this group would remain at P2 + EK1. The second 
category would be for all other sources and the containment 
levels would remain at P3 + EK2. How does the committee view 
this suggested classification? Further, in light of imminent 
availability of an EK2 host-vector system, how would the committee 
view raising the containment level for the first category to 
P2 + EK2? 
With respect to the stated concerns for the use of insects, how 
would the committee view a stipulation in the guidelines that 
only insects grown for several generations under laboratory 
conditions be considered a source of insect DNA? 
4. The last line of footnote 3 on p. 27 refers to asking CDC to prepare 
a complete list of Class 2 agents subdivided into low and 
moderate pathogenicity. In view of Dr. Sencer's March 3 reply 
to Dr. Stetten (copies of which were forwarded to you by 
Dr. Stetten' s office on March 9) in which no subdivision was 
made, should the last sentence of this footnote be deleted? 
5. There has been considerable expression of concern that prokaryotes 
which do not exchange genetic information with E_. coli may, when 
they become the host of recombinant DNA, represent a particularly 
potent hazard for altering host characteristics as a result of 
any translation. The guidelines, as they appear on p. 28, do 
not appear to reflect this stated concern. How would the 
committee respond to our requiring that the minimum containment 
for these experiments at present be P2 + EK2 rather than P2 + EK1? 
This recommendation is made in view of the apparent imminence of 
useful EK2 systems and with the understanding that when proof is 
obtained that recombinant genes are not expressed and do not 
change the character of the host, then the committee may recommend 
relaxation of this containment requirement in the future. 
[ 412 ] 
