35 



without effects on the cardiovascular system. We understand that 

 now. 



First of all, let me ask you this. Has such an analogue ever been 

 discovered, to your knowledge? 



Mr. DeNoble. We did discover a lead series of analogues which 

 had met the criteria of reduced cardiovascular effect and main- 

 tained the brain effects. So, yes, we were able to identify at least 

 two analogues that would meet that criteria. 



Mr. Greenwood. So what are the practical implications of that 

 and what uses have been made, if any, to your knowledge, of these 

 analogues? 



Mr. DeNoble. I don't think any use has been made of it. In fact, 

 it was basically put on the shelf. There was not, to my knowledge, 

 any activity around these analogues. 



Mr. Greenwood. Are these analogues found in nature or are 

 they synthetic? 



Mr. DeNoble. They are synthetic. They are organically syn- 

 thesized. 



Mr. Greenwood. Was the goal to somehow remove the nicotine 

 from tobacco and substitute this synthetic analogue? 



Mr. DeNoble. That was exactly the goal, to remove nicotine 

 from the tobacco and have the analogue be a substitute so that you 

 would produce a safer cigarette. 



Mr. Greenwood. Is the idea for the analogue that you were 

 searching for and that you say has been found, to have the same 

 habit-forming qualities of nicotine without the health risks? 



Mr. DeNoble. That's a very difficult question to answer, when 

 you talk about habit forming. If you are asking me, would it main- 

 tain self-administration, would it act as a reinforcing agent, would 

 it maintain the brain receptor qualities, the answer to that is, yes, 

 that is correct. 



Mr. Greenwood. Do you have any information as to why, if that 

 synthetic analogue has been discovered, it hasn't been utilized in 

 the production of tobacco products? 



Mr. DeNoble. No, I don't. But I would also mention that the 

 analogue that I'm talking about, or the series of analogues, meets 

 the criteria. But before you could actually use that, you would have 

 to go through a whole series of other testing, and that was never 

 done. 



Mr. Greenwood. Would it have to be approved by the FDA? 



Mr. DeNoble. I guess that would depend upon how you put it 

 in tobacco. You could, theoretically, genetically engineer plants to 

 grow it, if it's a simple molecule. But that's far beyond my exper- 

 tise. 



Mr. Greenwood. Were you asked to devise the format of this re- 

 search, or were you directed by superiors at Philip Morris as to 

 how your research was to be conducted? 



Mr. DeNoble. No. The goals of the laboratory were pretty 

 straightforward. It was an analogue program. We put together the 

 screening procedures. With the exception of the drug discrimination 

 procedure which was there, we determined the direction of the lab 

 in collaboration with management. I met with my manager weekly 

 to discuss research directions and data. So it was really a collabo- 



