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Mr. Wyden. Now, you have indicated that your work showed 

 that rats did develop the tolerance to nicotine. You have indicated 

 that this is one of the warning signals of potential abuse liability 

 or addiction. I'm curious, my understanding is that you submitted 

 this particular manuscript that I cited, to the management of Phil- 

 ip Morris. You were seeking approval to publish the results. 



When you asked them for approval to publish those results — re- 

 sults that to me seem important for the public — were you denied 

 the right to publish them? 



Mr. DeNoble. Yes. Let me just say two things about that work 

 first. We were certainly not the first to demonstrate nicotine toler- 

 ance, that has been shown for a long time. This study identified 

 certain behavioral parameters that contributed to nicotine toler- 

 ance. 



So after conducting this study and asking to get it out, and sub- 

 mitting it, we thought it was a relatively benign study because, al- 

 though tolerance is a characteristic of many drugs of abuse, it is 

 not necessarily a predictor of abuse, but it is a characteristic of 

 many compounds. We thought it was relatively benign. 



The company saw it as very threatening because the word "toler- 

 ance" was appearing at that time in the Diagnostic and Statistical 

 Manual of the American Psychiatric Association as a criterion or 

 an indicator of drug dependence. By using that criterion, they felt 

 this work was too dangerous and one, would not let it go out, and 

 two, did not want further tolerance work to continue. 



Mr. Wyden. So, in effect, what you are saying is because you 

 were showing that these studies were showing a tolerance for nico- 

 tine, this would establish a drug dependence, and this was again 

 defined by a major health group, the American Psychiatric Associa- 

 tion, and this would be damaging to them? 



Mr. Mele. Well, let me clarify. I think Philip Morris' assessment 

 of the work was wrong. I don't think tolerance, again, identifies 

 necessarily dependence-producing agents. It is a characteristic of 

 many of those but it is not a single identifying characteristic. But 

 they misidentified the DSM manual and made their judgment. 



Mr. Wyden. In addition to saying that you couldn't publish the 

 tolerance paper, did the management there take other steps to cur- 

 tail your research into tolerance? 



Mr. Mele. Well, they preferred that tolerance work did not con- 

 tinue. 



Mr. Wyden. So you were 



Mr. Waxman. If the gentlemen would yield. Let's just get names, 

 if we could, for the record. Who are these people you are talking 

 about? 



Mr. Mele. Dr. Jim Charles was the one who came to my ofiice 

 with the manuscript review request and asked me to write an in- 

 ternal document, but that it could not go out because it dem- 

 onstrated tolerance. And in his mind, or somebody's mind, it indi- 

 cated a dependence-producing situation. 



Mr. Wyden. In terms of what happened after they said you 

 couldn't publish the paper, did you communicate to the manage- 

 ment, Mr. Charles specifically, that you wanted to examine wheth- 

 er rats develop tolerance that would cause them to suffer physical 



