97 
per se, but also what is the likelihood that it could become more patho- 
genic as a result of some gene which you introduced into it? 
MR. HUTT: So you can never know what all the objective criteria are. 
DR. SINSHEIMER: If you knew enough about it to say, "Well, you have 
really got to put three separate genes in it, and that would be the only 
way you could make it pathogenic," then that would be a more definitive 
statement. Do you agree? 
DR. FREDRICKSON: Dr. Allan Campbell of the RAC. 
DR. CAMPBELL: Could I just ask Bob Sinsheimer for a clarification here, 
because I don't quite understand what you are saying. What is there that 
you could do with any other organism that hasn't already been done with E. 
col i K-12 in this respect? 
DR. SINSHEIMER: I am not asking that any more be done with K-12, Allan. 
Secondly, this will hark back to some suggestions that were made a year and a 
half ago. One might go back to the idea of trying to find some organisms 
which you knew only were adapted to a very restrictive environment, you know, 
and at one point you were talking about possibly using the rmoph i les , where 
you have a whole host of genes and so forth which you know produce products 
which are adapted only to high temperatures. Do you follow what I am getting 
at? 
DR. CAMPBELL: Well, I don't quite follow it logically, and this isn't 
the time for an extensive discussion, but I don't see quite logically how 
you can know whether it is easier to change those characteristics by adding 
a few genes than it is to change the properties of K-12 by adding a few 
genes . 
DR. SINSHEIMER: Well, just a priori, an organism which has been adapted 
over many, many generations to life only in a temperature above 60 degrees, I 
would imagine, would require more changes to make it grow, say at 37, than an 
organism which at one time certainly was adapted to grow in the human intes- 
tine, K-12, but has lost a number of things presumably in the laboratory, but 
we don't know how many things. That is what I am saying. 
DR. FREDRICKSON: Dr. Hornick. 
DR. HORNICK: My name is Dr. Hornick, and I am in infectious disease. 
We have been feeding organisms for a number of years to try to develop 
oral vaccines, and we have taken K-12 and mixed it with some virulent 
Sh igel la . Dr. Formal has made these strains, and then we fed them, 
with the idea of trying to make a better oral vaccine. So when you put 
genes in for Shigel la — and Sh igel la , in order to cause disease, has to 
penetrate and has to multiply in the epithelial cell — If it doesn't 
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