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host-vector systems, so that now there are essentially three levels of 
review before an EK2 system or an EK3 system is approved. That is, first 
an expert working group, which reports then to the Recombinant Advisory 
Committee, which finally reports to Dr. Fredrickson. Questions about the 
system can be asked at all levels. That is now written into the proposed 
Guidelines . 
The possibility of rescinding certification for an approved EK2 vector 
if, for instance, some new information is found suggesting that it isn't as 
good as we thought it was. I think that possibility always existed, but it 
was never explicitly stated. Now it is quite explicitly stated. 
For instance, the specification that if an EK2 system is approved, the 
approval does not automatically extend to modifications which the investiga- 
tor may think are minor, but the Committee may not think they are minor. 
Any kind of modification of an approved EK2 system must at least come to our 
Committee for consideration, and we can ask for whatever data we consider 
appropriate to make sure it has been thoroughly tested. 
Finally, provision that, for instance, HV2 and HV3 systems be distrib- 
uted in such a way that NIH has maximum control over what is distributed, 
that strains are not passed from laboratory to laboratory gathering whatever 
mutations they may in between, but that there be central distribution of 
such systems to insure that at least what is sent out from NIH is the cor- 
rect strain, and that it is really in the investigator's responsibility to 
check that it continues to be the correct strain. 
So in conclusion, the major changes in this section are introduction of 
the HV1, HV2, HV3 nomenclature, with the emphasis on the possibility for new 
HV1 systems other than E. coli K-12, and a tightening of the HV3 require- 
ment s . 
I think that is all. 
DR. FREDRICKSON: Thank you, Dr. Gottesman. Won't you remain for just 
a moment to see if we have some questions or comments from the Committee. 
Dr. Ginsberg. 
DR. GINSBERG: I am somewhat confused by the no antibiotic resistance. 
I find that overcaution often raises doubts in people's minds about the 
primary basis upon which you have started. That is, if the host is as 
crippled as you say, and if the vector is non-transmissible , why do you 
care what antibiotic markers are in the vector? 
DR. GOTTESMAN: I think your point is well taken. I think at the mo- 
ment we don't have in vivo data on survival and transmission of any of 
these things. That is, the EK2 certification is based on laboratory simula- 
tions, let us say, of what transmission might be or survival might be. We 
certainly hope they will be borne out in vivo . So this is, in a sense, a 
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