32 



Mr, Mele. Yes. Under the conditions which we ran the studies, 

 which were very limited, we did not find a physiological depend- 

 ence. 



Mr. Bliley. Isn't it true that while you were employed at Philip 

 Morris, you also did experiments to determine if discontinuing the 

 use of nicotine or acetaldehyde created physiological withdrawal 

 symptoms, and that you told your superiors at Philip Morris that 

 your research showed that discontinuation of nicotine or acetal- 

 dehyde did not cause physiological withdrawal symptoms? 



Mr. Mele. Yes. Again, under the conditions of those experiments, 

 we could not identify any physiological withdrawal. 



Mr. Bliley. And you did all of your experiments, of course with 

 Dr. DeNoble, were with rats? 



Mr. Mele. Correct. 



Mr. Bliley. Isn't it true that some rats in your experiments at 

 Philip Morris like nicotine more than other rats? 



Mr. Mele. Some rats may administer higher doses, or have dif- 

 ferent dose response curves than other rats. That is very typical of 

 any drug effect in any rat or any animal. There are individual dif- 

 ferences. 



Mr. Bliley. Isn't it true that albino rats did not seem to like nic- 

 otine as much as hooded rats? 



Mr. Mele. I didn't work with albino rats at all when I was at 

 Philip Morris. 



Mr. Bliley. Though you didn't work with albino rats, isn't it gen- 

 erally true that albino rats don't seem to like nicotine as much. Dr. 

 DeNoble? 



Mr. Mele. I'm not sure. I can't answer that question. 



Mr. DeNoble. I can't answer that question either. I'm not sure 

 where that data is coming from. 



Mr. Bliley. Well, isn't it true. Dr. DeNoble, that you decided to 

 use hooded rats in your experiments because hooded rats were 

 easier to get to self-administer? 



Mr. DeNoble. No. That's incorrect. There was a paper published 

 in the early 1980's, I believe, around 1980 actually, which dem- 

 onstrated that the albino rat was not a prototypical animal to do 

 drug research because it had altered biochemistry, because it is an 

 albino. 



The hooded rat has an intact, more generalizable biochemistry in 

 the brain, so that a hooded rat's biochemistry is much closer to that 

 of a monkey's, and it's closer to that of a human. So we elected to 

 do all of our studies in hooded rats, whether it be self-administra- 

 tion, tolerance, dependence, because their brain biochemistry rep- 

 resented more what a normal animal is. 



Mr. Bliley. Thank you. Thank you, Dr. DeNoble. Thank you, Mr. 

 Chairman. 



Mr. Waxman. Thank you, Mr. Bliley. Mr. Synar? 



Mr. Synar. Thank you, Mr. Chairman. First of all, believe it or 

 not, I think Mr. Waxman, Mr. Wyden, and I understand why the 

 executives of these seven major tobacco companies came in here a 

 couple of weeks back, and in the face of overwhelming historical 

 medical evidence, denied the addictiveness of nicotine. They have 

 been counseled by their attorneys that an admission on their part 

 would increase their chances of liability. 



