130 



We've always heard about nicotine as an addicting substance, but 

 now we're learning nicotine is a problem that affects the heart as 

 well. Could you give us the name of the compound that might have 

 been a successful analogue? 



Mr. DeNoble. I'm not a chemist, but I can give you — it was 

 called two-prime methalnicotine. 



Mr. Waxman. Thank you very much. Mr. Kreidler, did you want 

 to pursue further questions? 



Mr. Kreidler. I think my time has expired. Thank you very 

 much, Mr. Chairman. 



Mr. Waxman. Dr. DeNoble, did you look for other substances in 

 tobacco or tobacco smoke that have effects on the brain? 



Mr. DeNoble. Yes, we did. In late 1981, early 1982, we raised 

 the question of whether or not there could be other things in ciga- 

 rette smoke that may have biological activity. 



Mr. Waxman. And what did you look at? 



Mr. DeNoble. What we did was we did basically a computer 

 search of the components that are identified in cigarette smoke. 

 And we looked through the list and we found — a compound that 

 stuck out in our mind was acetaldehyde. This is a compound that 

 has a reasonably high concentration in cigarette smoke; it's a high- 

 ly volatile compound. 



And it was really kind of serendipitous because the work — ^you 

 really wouldn't think this is anything hot, but I had just come off 

 of doing post-doc where I recognized that acetaldehyde is a major 

 metabolite of alcohol. And there were some theories in the 1970's 

 that this metabolite would react in the brain with other chemicals 

 to form other chemicals, and that may be the basis for alcohol ad- 

 diction. 



Well, that theory did not hold up. But what struck me was — and 

 it didn't hold up because your liver is making acetaldehyde, and by 

 the time it gets to the brain, it is all chewed up anyways — ^but here 

 you have a situation where aldehyde is going right into the lung. 



And there are only three ways to get things into the brain quick- 

 ly. One is you put it in the brain, the second fastest way is you 

 put it in the lung, and the third fastest way is you put it in the 

 heart. So it struck us that this compound was getting in the brain, 

 maybe it's doing something that has reinforcing effects. 



Mr. Waxman. And I want to show you a chart, which I'd like to 

 have entered into the record, without objection, as Exhibit 22. It's 

 made from a slide of your acetaldehyde work. 



[Exhibit 22 follows:] 



