equivocal evidence Chat polyoma-mouse DNA recombinants arise naturally in 
the laboratory and very likely in the wild. Most probably the same is true 
for SV40 and the DNA of its host cells. Both types of recombinants have been 
in virus stocks for years and may already have Infected innumerable people 
and animals. Moreover, such naturally-arising recombinants are presently 
being studied in several laboratories in this country and abroad using routine 
containment. Consequently, I see no justification, other than political con- 
siderations, for restricting the construction of these viral-host DNA recom- 
binants in vitro . Perhaps politics is an overriding factor but Chen we ought 
to be explicit about saying so. 
2) The draft revision of the Guidelines calls for P2-EK2 containment 
for shotgun experiments with mammalian DNA. It is not clear as to whether 
the same recommendation is made for attempts to clone integrated polyoma or 
SV40 DNA sequences from non-primate mammalian DNA in E. coli . I note that 
page III (9g) focuses on cloning integrated retrovirus nucleotide sequences 
from mammalian cell DNA but says nothing about nucleotide sequences of inte- 
grated DNA viruses. Is it Intended that such experiments be done only under 
the containment stated on page III-9 (1) (a), i.e. P4-EK1 or P3-EK3? As I 
read this text it says that shotgun experiments with mouse DNA can be done 
in E. coll using P2-EK2 if one is looking for Che hemoglobin or HGPRT gene 
but if one is seeking a viral sequence from the same pool the it must be 
done in P4 or P3-EK3 (or in effect it is now forbidden). Can it be inferred 
from this that experiments directed to Isolating polyoma or SV40 DNA segments 
is far more dangerous than the possibility of cloning an unknown cryptic viral 
sequence? My own view is that the entire question of what containment is 
appropriate for cloning animal virus DNAs, free and Integrated, in pro- and 
eukaryote vector-host systems needs to be reexamined. I would urge you to con- 
vene an appropriate group of experts to make recommendation on this matter for 
the next cycle of revisions in the Guidelines. 
There is one other aspect of the proposed revisions that I'd like to 
comment upon. On p. IV-9, where the responsibilities of NIH staff are out- 
lined, I read that "no grants or contracts (and presumably fellowships) are 
awarded for recombinant DNA research unless (a)..., (b) have been properly 
reviewed and recommended for approval and (c) Include a properly executed 
M.U.A. ;... I interpret that to mean that awarding, and not the consideration 
of the grant, contract or fellowship application, is contingent upon the 
submission of an M.U.A. At present, before a fellowship proposal can be 
reviewed by an NIH committee there must be an M.U.A. on file. This require- 
ment ha 8 created an additional burden on the investigator and the institutional 
review committees. Very often the investigator already has M.U.Ais and 
approved facilities for the work being proposed. But now a new M.U.A. must 
be sought and authorized, etc. etc., even if tha applicant doesn't get the 
fellowship or doesn't do that project. As I interpret the new version it 
seems much more reasonable and accomplishes tha same purpose: No fellowship 
research can be undertaken without an M.U.A. Perhaps it would ba sufficient 
to have the fellowship application show that the preceptor has facilities 
required for the work but the formal M.U.A. would be needed prior to activa- 
tloa of the fellowship. 
[Appendix A — 13] 
