Tobacco Documents Online

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 27 Pennsylvania? A. Stanley -- Q. A. Reimann. Reimann, oh , yes. He was mostly -- he was a Council researcher and mostly an administrator. He founded the Institute in Philadelphia. I met him a few times. He had a good reputation, not so much as an inspiring scientist, but as an organizer of new approaches, and I respected him. Q. What about William Rienhoff from Maryland, a profess or of surgery at Johns Hopkins? A I don't know . . Q. What about Sheldon Sommers? A. Sheldon Sommers, he's a pathologist who was at Boston University and then became a pathologist of the Council for Tobacco Research. Sheldon I respected w hen he was at B.U., and I knew him as a teacher a nd a researcher in some ways; bu t when he began wor ki ng wi th the Council , he became totally subjectiv e, an d it wa s he who wanted us t o change the terminology of the lesions we found i n hamsters and I had very littl e respect for him. Q. What about Edwin Wilson from Harvard? A. Oh, he was an old statistician, and he was DORIS 0. WONG ASSOCIATES ~ "('R 11N 041 SISK

1 1 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 28 highly regarded in his profession. And he had an obsessive feeling that statistics could be interpreted in a favorable way for the tobacco industry. And so I respected him because he was imposing, but I thought he was very wrong, and what sh uld I ? o say Q. But•although you disagreed with him, you had a lot of respect for him as a scientist? A. Oh, yes, his background was superb. Q. Obviously we talked a lot about people who were involved with the Council or on the SCientific Advisory Board of the Council when you worked with them. Would it be fair to say that, among the people yo u knew that were on the Scientific Advisory Board of CTR, you respected them as scientists? MS. SCHNEIDER: Objection to the form. A. I wouldn't generalize. Some of them I did and some of them I didn't. Q. What type of work did you do with your CTR r t f di ? g an un ng A. Well , we started out doing skin painting, and in the '60s we published a paper with our results showing that the tars from cigarettes --that was stand ard cigarettes -- and pipe tobacco and DORIS 0. WONG ASSOCIATES CTR t-IN 041STREE-5

i 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 29 cigars were equally carcinogenic when applied to the skin of mice. And that took a long time and took a lot of our time and effort and money. And at the same time we tried to evaluate the susceptibility of various species of animals to smoke; and we developed with the participation of the inventor -- what was his name -- Richard Walton a smoking machine which could puff smoke very much as a smoker would do, and where you could insert animals into tubes and they would inhale this cigarette smoke. And we found very soon that mice and rats were very susceptible to the toxic effects and died, and hamsters, on the contrary, liked to smoke. They were sort of tranquilized and were sitting there inhaling the smoke. And so we decided to go into a study of.the hamster for inhalation toxicity of cigarette smoke, and that's how we started out. And because Dr: Little had these various inbred strains of hamsters, we were able to show that some were very susceptible to the effects of smoke in terms of how it changed the anatomy of the epithelium in the respiratory tract, and some were much less susceptible. So finally that lead us in the late '60s DORIS O. WONG'ASSOCIATES E:x TR I-IN 0411913~'.:~

i 30 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 and early 170s to set up a big experiment where we exposed dozens of hamsters -- maybe there were hundreds really, I would have to check the exact figure -- and exposed them five days a week twice a day for a number of inhalations for many months. And at the end of 18 months, between 12 and 18 months, half of the hamsters of the susceptible strain -- to be exact it was 42 percent -- had cancer or precancerous lesions in their upper respiratory tract and some changes, not cancerous changes, in their lungs that showed that the tobacco smoke also had reached the lungs. And in the non-susceptible strain, there was very little change in the respiratory epithelium, and cancer was only found in 4 percent of these animals; in other words, ten times more rarely. Now, that irritated, obviously, the Council for Tobacco Research, and this is when they switched to a system of grant -- not grant support but the contract. And when you receive a letter explaining the meaning of the contract, it was an absolute secure system for them to control whatever you could publish. But my interpretation was that applied only to the end of the study and not to the body of DORIS O. WONG ASSOCIATES CTR t`~~ti~ 04 1 ~'~°~~`f~"

31 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 the study -- MR. KLUGMAN: I object to that testimony and move to strike. It's not responsive. Q. What I want to focus now on is your grant research first, and then I want to go to the contract. The grant research you did for CTR, you thought that was all scientifically significant work, didn't you? A. Yes. Q. And you believed it was relevant to smoking and health, didn't you? A. It was the only thing that existed in animal tests that had any significance on what might be the case in humans. Q. Was it your practice throughout your scientific career to acknowledge funding support in your articles? A. Oh, yes. Q. To the best of your knowledge, were your funding acknowledgements in your articles always correct? A. Oh, yes. Q. And you were free to publish your CTR grant-funded research even when the results might be DORIS 0. WONG ASSOCIATES E.,. TR VIN #~~41S49'

I 32 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 considered adverse to the tobacco industry, right? A. Absolutely. Q. And all grantees, to your knowledge, were free to publish their research? A. As far as I knew then, yes. Q. I want to talk about your skin painting work for a moment. Essentially you concluded that skin painting tests were not very helpful in evaluating the potential carcinogenicity of smoking to humans? A. Well, there is a principle here. If in toxicology you want to develop a test that is meaningful, it should involve the same system as is affected in humans. And this just didn't exist. And the skin painting, which was used by Wynder in 1953 to show that there is a relationship between cancer induction in the epidermis and smoke, tars, that was the only method that was available. Much later Auerbach found that he could induce cancer or he felt he was inducing cancer in the respiratory tract of dogs; but there the limitation was that the spontaneous incidence of cancer in this nature in the dog was quite high, and dogs are difficult to study. It's not as easy as a small animal like a DORIS 0. WONG ASSOCIATES i..x +f a P-c. f-f f"f 04.f 13S39

I 33 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 rat, a mouse or a hamster. So Dr. Little was really the inspiration for us to go after other animals, and accidentally Dr. Whitney came with her inbred hamsters. Q. Now, on your skin painting work, you actually concluded that tar was really the wrong substance applied to the wrong animal, didn't you? A. To the wrong place. Q. Yes. And the conditions of the skin painting experiments were very artificial when compared to human smoking, weren't they? A. Yes. Q. You actually reached a number of significant conclusions about skin painting, didn't you? For example, you concluded at times the condensate could actually inhibit tumor activity in certain animals, didn't you? A. I don't remember that. Q. You don't remember that. I may pull that out later. I think I read that in one of your articles. You also conclude that an artifact in the collection or storage process that was not in the original smoke was responsible for tumors in some DORIS 0. WONG ASSOCIATES ~ ~ rf"ti mtw'i Oei..2oti..d o

I 34 1 2 3 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 experiments, didn't you? A. I think we mentioned that. Q. What do you mean when you say an artifact in the collection or storage process? What does that mean? A. I don't remember what happened, but it must be a reference to a specific change, maybe failure of a refrigerator or that kind of thing, or failure of the machine to smoke the cigarette at the pace that it should be smoked, that kind of thing. Q. Now, when you take smoke and change it into tar and store it, that's very different from the smoke, fresh whole smoke that humans inhale, isn't it? A. Oh, absolutely. Q. And to take that further, to make sure I'm clear, fresh, whole smoke is different than sidestream smoke of a cigarette too, isn't it? A. ETS? MS. SCHNEIDER: Objection to the form. I don't know about that. And do you know whether it differs from MS. SCHNEIDER: Objection to the form. A. From what? DORIS 0. WONG•ASSOCIATES ca/ u R! l l ) 042001

35 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Q. Environmental tobacco smoke. A. I don't know anything about that. Q. Is it correct to state that the dose to which an animal is exposed is a very important factor in determining whether smoke can cause tumors? A. Yes. Q. Dose is really a critical factor, isn't it? A. I would think so. Q. As a matter of fact, didn't you claim that one reason your hamsters didn't get lung cancer was because a large enough dose didn't get into their lungs; it stopped at the larynx? A. Well, that is a logical conclusion. Q. To get cellular changes, you really have to have a significant exposure dose, don't you? MS. SCHNEIDER: Objection to the form. A. Right. Q. Based on your work, did you determine how many cigarettes per day an animal would have to be exposed to to get cellular changes? A. I don't think we did that kind of quantitation. Q. Wouldn't three or four cigarettes a day be DORIS 0. WONG ASSOCIATES L.r T~`'~'. f S f'i 042-00e~"}

36 1 2 3 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 too low to get changes? A. I don't think -- we didn't determine a minimal dose. We get the maximal exposure. Q. So when you were exposing your hamsters, you basically gave them all the smoke that they could tolerate without dying, didn't you? A. Yes, without showing any weight loss or any other changes. Some of these hamsters have a spontaneous heart disease, and that could increase theoretically if you expose them to smoke. And we tried to keep that from happening. Q. Just so I'm clear, the doses of smoke your hamsters were exposed to are much higher than a human smoker would receive; isn't that. correct? MS. SCHNEIDER: Objection to the form. A. I don't think you can really say. As I just pointed out, we haven't got the exact dose; can only say the number of cigarettes per day per hamster. we Q. You don't believe that epidemiology alone without a confirmation in an animal model can establish a causal relationship between any substance -- A. Say that again. DORIS 0. WONG ASSOCIATES L..r Nf R j If 'f 0'420S.a ,~'~