Tobacco Documents Online

1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 1S 19 20 21 UNITED STATES DISTRICT COURT EASTERN DISTRICT OF TEXAS TEXARKANA DIVISION THE STATE OF•TEXAS, . Plaintiff, . vs. . Civil Action No. 5-96CV91 THE AMERICAN TOBACCO, . et al., Defendants. Baltimore, Maryland September 12, 1997 Videotaped deposition of RICHARD E. KOURI, Ph.D., A Witness, called for oral examination by counsel for the State of Texas, taken at the Harbor Court Hotel, 550 Light Street, Caucus Room, before Shari L. Nelson, Notary Public, beginning at 9:50 o'clock a.m. Reported By: Shari L. Nelson, RMR-CRR Riggleman, Turk & Nelson (410) 539-6398 RIGGLEDLAN, TURK & NELSON CTR H~# 04~~85

2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A P P E A P. A N C E S SUSAN NIAL, ESQ., cn behalf of the State of Texas. LARRY W. THORPE, ESQ., on behalf of the State of Texas. CRAIG T. EDWARDS, ESQ., on behalf of the Barnes Plaintiffs in Penrsylvania. LOUIS GOTTLIEB, ESQ., on behalf of New York. STEPHEN J. McCONNELL, ESQ., on behalf of Philip Morris. ROBERT J. KIRSF?ENBERG, ESQ., on behalf of Lorrilard Tobacco Company. DAVID B. ALDEN, ESQ., on behalf of R. J. Reynolds Tobacco Co:apany. BRUCE G. MERRITT, ESQ., and ALAN H. SCHEINER, ESQ., on behalf of CTR. Also Present: Lisa Bauer, Videographer. Judy Scolnik, Ness-Motley. RIGGLEMAN, TURK & NELSON ~..~. ``R l~N 0~' ~..-~.~86

3 1 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 C 0 N T E Pi T S Witness Page RICHARD E. KOURI, Ph.D. Examination By Ms. NiGl. ...... 9 Examination By Mr. Merritt ..... 72 E X F? I B I T S Number Descriotion 1 Curriculum Vitae . . . . . . . . . . 2 Consultancy Aareement. . . . . . . . 3 Check with attached letter to Richard Kouri, Ph.D., from Karen M. Markert dated July 22, 1997. .... 16 4 Subpoena . . . . . . . . . . . . . . 16 5 Subpoena . . . . . . . . . . . . . . 16 6 Affidavit . . . . . . . . . . . . . . is 7 Stages in Carcinoaenesis ...... 25 8 Contract 30 . . . . . . . . . . . . . 25 9 A Frank Statement to Cigarette Smoke rs . . . . . . . . . . . . . . . 3 0 10 Chronic Exposure of Mice to Cigarette Smoke. . . . . . . . . . . 39 11 Distribution list. . . . . . . . . . 46 RIGGLENLkN, TURK & NELSON CT R I I N 0 4313 Bf"

4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Exhibits (Continued) Number Description Marked 12 Memorandum to Robert F. Gertenbach from Leonard S. Zahn dated October 1, 1984 . . . . . . . . . . . . . . . 47 13 Article . . . . . . . . . . . . . . . 59 14 Memo to CTR File from R. B. Seligman dated October 25, 1978 . . . . . . . 65 15 Application for Research Grant . . . 100 16 Letter to William U. Gardner from Richard E. Kouri, Ph.D., dated May 24, 1978 . . . . . . . . . . . . 101 17 ADplication for Research Grant . . . 104 18 Memo to Dr. W. U. Gardner from Hans Meier dated March 10, 1978 ..... 117 19 Final Report . . . . . . . . . . . . 181 20 Agenda-Executive Committee and Contract Committee Meeting . . . . . 186 21 Proposed Studies from CTR 0030- Smoke Inhalation Carcinogenis Studies in Mice . . . . . . . . . . . 193 22 Progress Report for CTR-0030 - Smoke Inhalation Studies in Mice ..... 198 23 Letter to William U. Gardner from Richard E. Kouri and Carol J. Henry. 198 24 Progress Report for CTR-0030 - Smoke Inhalation Studies in Mice ..... 206 RIGGLEMAN, TURK & NELSON C/"R! I C 7 0 43 1r+` b3 8

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 5 25 Official Abstract Form . . . . . . . 213 26 Letter to Sheldon C. Sorr.mers from Carol J. Henry dated December 22, 1981 . . . . . . . . . . . . . . . . 249 27 Letter to Tom Hoyt from Joh-n Parker dated December 6, 1983 . . . . . . . 249 28 Letter to Sheldon C. Sor,..;;ers from Carol J. Henry, Ph.D., dated July 31, 1985 , , , , , , , , , , , , , , 257 29 Letter to Elizabeth K. Weisburger from Carol J. Henry, Ph.D., and Richard E. Kouri, Ph.D., dated August 16, 1985. . . . . . , , , , , 62 0 RIGGLEMAN, TURK & NELSON i..r' TR T al ) 47 04,3389

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 6 P R O C E E D I N G S MS. BAUER: This video deposition is being taken in accordance with Texas Rules on September 12, 1997, at 9:49 a.m. at 550 Light Street in Baltimore, Maryland. The Court Reporter is S:ari Nelson with Riggleman, Turk & Nelson. My name is Lisa Bauer with Riggleman, Turk & Nelson. The equipment being used is a Panasonic camcorder. The caption of the case is the State of Texas versus The American Tobacco, et al, in the U. S. District Court, Eastern District of Texas, Case No. 5-96CV91. Will the attorneys please identify themselves and who they represe nt MS. . NIAL: Susan Nial from Ness-Motley for the State of Texas. MR. THORPE: Larry Thorpe, Reaud, Morgan & Quinn for the State of Texas MR. . EDWARDS: Craig Edw ards, Mellon, Webster & Mel1on, State of Pennsylvania, Barnes. MR. GOTTLIEB: Lou Gott lieb, Goodkind, Labaton, Rudoff & Sucharow, i n the New York class action cases. RIGGLEMAN, TURK & NELSON ~. ~5~' ~~#~ 0~ ~~1~90

7 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 MR. McCONNELL: Stephen McConnell of Dechert, Price & Rhoads representing Philip Morris in the case of Barnes in the Eastern District of Pennsylvania. I would like a stipulation on the record that we're following the Texas Rule and there's a stipulation that for purposes of the Barnes case, that all objections including those as to form are reserved for purposes of trial. Particularly I would like that stipulation on the record for Mr. Edwards. MR. KIRSHENBERG: Robert Kirshenberg from Greenberg & Trauric in New York on behalf of Lorillard Tobacco Company in the New York class actions and I would join in the request with my co-counsel here with respect to the stipulation. MR. ALDEN: David Alden from Jones, Day, Reavis & Pogue on r:half of Reynolds. MR. SCHEINER: Alan Scheiner from Debevoise & Plimpton on behalf of Council for Tobacco Research--U.S.A., Inc. MR. MERRITT: Bruce Merritt, Debevoise & Plimpton, on behalf of Council for Tobacco Research. RIGGLENLkN, TURK & NELSON Cf R f f f~f 043391

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 8 MS. BAUER: The witness today is Doctor Richard Kouri and will now be sworn in . MR. MERRITT: Before we swear the witness, can we just reiterate the stipulation . MS. NIAL: I was going to say, maybe Craig, you want to stipulate for your clients and Mr. Gottlieb for your clients? I think you need to do that verbally. MR. EDWARDS: We just stipulate that all procedural and other objections will be maintained. MR. GOTTLIEB: I'll make the same stipulation for the New York Plaintiffs that all objections will be reserved including objections as to form. MR. MERRITT: Let me add for the record that it's my understanding that under the Texas Rule, all objections whether of substance or form are reserved in the Texas case as well. So as I understand it, we are operating under the same rule here for all the cases that this has been Noticed or cross-Noticed in, and that all objections =or form, objections in the nature of leading question, motions to strike for lack of responsiveness, these are all reserved? MS. NIAL: That is my understanding. RIGGLEhVuN, TURK & NELSON ~w" 7 I T I I I I 04,339212

9 10 11 12 13 14 15 16 17 18 19 20 21 MR. THORPE: That's correct, and the only objection that can be made is as to privilege. MR. MERRITT: That is so stipulated? MR. THOF.?E: So stipulated. MR. EDWF:DS: So stipulated. MR. GOTTLIEB: So stipulated. MS. NIAL: Good morning, Doctor Kouri, I think you need to be sworn in. Would you swear the witness, please. Thereupon --- RICNAR.D E. KOURI, Ph.D. A Witness, called for oral examination by counsel for the State of Texas, having been first duly sworn by the Notary Public, was examined and testified as follows: EYAMIN=.TION BY MS. NIAL Q Doctor Kouri, before we begin the questioning this morning, I would like to go over a few ground rules for you so that we're all on the same page when we go through the deposition. First of all, even though this is informal, informal setting in a hotel room, this is exactly the same as it would be if you were in a courtroom. This deposition can RIGGLE~ULN, TURK & NELSON c,.r Tf`'~', Hf ''f 04339,3

10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 be used in evidence in a courtroom. Second of all, all your answers need to be verbal so that the Court Reporter can take it down. That's, even though we're videotaping this deposition, your answers need to be verbal. A Okay. Q If you don't understanc a question, please ask fcr it to be repeated, or if you can't hear it. If you answer a question, I will assume, as will the other questioners, that you have heard and understood the auestion. A I agree. Q As to breaks, any time you need a break, please ask and they'll be given liberally. Ne understand your situaticn. The only thing I would ask is that it would not be during a pending question but if you need a break, just let me know. A Okay. Q We will try to give Doctor Kouri fairly regular breaks because of his leg. Okay. Doctor Kouri, I wonder if you could tell Ls a little bit about your education, please. A I'm a graduate of Ohio State University RIGGLEMAN, TURK & NELSON Ci yR f f N S.A ""f' 3394'

11 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 undergraduate. My Ph.D. is in ra-liation biology from the University of Tennessee working a: the Oak Ridge National Laboratory, and I did a postdoctcral fellowship at the Roche Institute for Molecular Biology in , Nutley, New Jersey, and in the area of biochemical genetics. Q Do you belong to any L--ofessional associations? A Quite a few. Q Can you name a few of :~hem for us, please? A Human Genome Organization, American Association for Cancer Research, the American As-so-ciation for the Advancement of Science, probably five others. Q Okay. Doctor, I'd like to show you a document which I believe is your current CV and I would like you to identify it for the record. I wcn-der if you could look throuah it, sir, and then tell me whether or not it is your current CV. A Yes, the first two paces is a summary version of the CV and then the bibliography and the biographical sketches is actually the latter half of t'r:is. Yeah, this is mine. Q It is current as of today, Doctor Kouri? A It is current. RIGGLEMAN, TURK & NELSON ~T R 1 --1 t, 1 0 4 -3 3 19 5 k

12 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 MS. NIAL: I am going to make this the first exhibit to the deposition. (Document was marked Kouri Deposition Exhibit No. 1). Q (By Ms. Nial) Doctor Kouri, who first contacted you with regard to CTR's involvement in tobacco litigation? A Mr. Alan Scheiner. Q And is Mr. Alan Scheiner employed by the law firm of Debevoise & Plimpton? Q Yes. Who does he represent? A CTR. Q And how did that first contact occur? A He called me and asked if I would help organize some of the files related to the numbers of-contracts that Microbiological Associates performed under the auspices of CTR from mostly the 1970s. Q Did you meet with Mr. Scheiner? A Yes. Q How many times did you meet with Mr. Scheiner? A Once. RIGGLEMAN, TURK & NELSON ~.r f~f"~r I f f~ 5'~' .~ .,~ ~ C°'.,f

13 10 11 12 13 14 15 16 17 18 19 20 21 Q I wonder, Doctor, if I could show you a document. A Yes. Q Do you recognize that document? A Yes. Q It's a consultancy contract, is it, sir? A Yes. Q F-nd what is the date on that consultancy contract? A February 21st, 1997. Q P_rd have you signed that consultancy contract, sir? A Yes. Q With whom was that consultG~cy arrangement? A tiv_th Debevoise & Plimpton. MS. NIAL: I wonder if we could make that an exhibit. (Document was marked Kouri Deposition Exhibit No. 2). Q (~y Ms. Nial) Now, Doctor, after you met with or while you were meeting with Mr. Scheiner, did you in fact organize documents for Mr. Scheiner? A Yes. Q And what documents did you organize for RIGGLEMAN, TURK & NELSON C T R M N 0 43 '3 9 -1 -"

14 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 1S 19 20 21 Mr. Scheiner? A Mostly the, the proposed studies and the progress reports related to the various contracts and work that was going on by Microbiological Associates for CTR. Q Did Mr. Scheiner leave any documents with you? A No. Q Did Mr. Scheiner provide to you a copy of your 1986 article? A Yes. I didn't have one. Q Did you bill Mr. Scheiner for your time? A Originally yes, I billed for, as per the consulting agreement and then had second thoughts about not setting up this sort of relationship with any sort of money changing hands and so I asked Mr. Scheiner not to pay me and in fact he did not. Q Did Mr. Scheiner after your meeting ask for you to testify for CTR in the tobacco litigation? A No. Q Now, Doctor Kouri, you've met with me and some of my colleagues, have you not? A Yes. RIGGLEINLM, TURK & NELSON CTR I~IN 04~~3 ~a

15 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q And we've met several times; is that correct? A Yes. Q Have we given you any money? A No. Q Have you signed a consultancy agreement with us? A No. Q Doctor, are you here pursuant to a subpoena? A Yes. Q You're I-=re pursuant to a subpoena from the Arch case -- A Yes. Q -- now called the Barnes case that you received from Thomas Mellon; is that correct? A Yes. Q Is this a copy of that subpoena? A Yes. MIR. NIAL: We are going to make that an exhibit and Bruce, here is one for you. Q (By Ms. Nial) You are also here pursuant to two subpoenas issued irn the Texas matter; is that correct? A Yes, I think so. RIGGLEbJM, TURK & NELSON i ~. TR I IN ~".0 4 123 3 9.' R.-W

16 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q One from Mr. Scheir.er at Debevoise & Plimpton? A Yes. Q And one from Grant Kaiser who is plaintiff's counsel in that case; is that correct? A Yes. MS. NIAL: We're going to make those two exhibits. (Documents were marked Kcuri Denosition Exhibit Nos. 3 through 5). Q (By Ms. Nial) Pursuant to the Debevoise & Plimpton subpoena, you were asked to provide certain documents to Debevoise & Plimpton, were you not? A Yes. Q Doctor, I ask you to look at this group of documents. (Witness reviewing documents). A Yes. Q Are those the documents that you have in your files that are responsive to the Debevoise & Plimpton subpoena? A Yes, that's everything I could find. RIGGLEMAN, TURK & NELSON (Ar Tf `+'. f f f "f 04' 400

17 1 2 3 c 5 6 7 8 9 10 11 12 13 14 15 16 17 ls 19 20 21 Q Q Including the deposition of Carol Henry? Correct. We are going to give those to Mr. Merritt. A I should say parenthetically that the deposition from Carol Henry does have some errors in it. The book, there is a copy of actually the book that we're all going to describe later in there and every other page is missing in that deposition. It just must have been Xeroxed improperly. Q Now, Doctor, when you said Doctor Murray, Doctor Henry's deposition had errors in it, you mean the exhibits were in error? A The exhibits, yes, I'm sorry. Q That's okay. MS. NIAL: Just as an aside, Bruce, we have contacted the Court Reporter to determine whether or not the exhibit itself is correct. MR. NIERRITT : Okay. Can we go off the record. (Discussion off the record). Q (By Ms. Nial) Now, Doctor, all of your publications are listed on your current CV; is that correct? RIGGLEDLuli, TURK & NELSON I tr TR { f f`Y 0"'f' ti3 40 1

18 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A Yes. Q You have not provided copies of those publications to Debevoise & Plimpton? A No. Q And Doctor, I would like to show you a copy of another document. And this is a copy of an affidavit signed by you, is it, sir? A Yes. MS. NIAL: If we can attach that as the next exhibit. (Document was marked Kouri Der)osition Exhibit No. 6) Q (By Ms. Nial) Doctor Kouri, did you draft this affidavit? A Yes. Q And you had it notarized -- A Yes. Q -- and forwarded to my office? A Yes. Q And it was initially drafted for the Florida case; do you recall? RIGGLEMAN,'TURK & NELSON L. r f R Hf 'l 0'"`i" 3402

19 10 11 12 13 14 15 16 17 18 19 20 21 A Actually I guess, I think so. Q Now, Doctor, are you familiar with the firm of Microbiological Associates? A Yes. Q And what does Microbiological Associates do? A They're a contract research organization in : Bethesda, Maryland, that performs a variety of contract responsibilities for funding agencies for both govern-ent and nongovernment sponsors. Q Is that what they do currently, sir? A They've expanded that to include much more work for private industry. Q Doctor, did you work at Microbiological Associates? A I did. Q When did you begin working at Microbiolocical Associates? A I think 1971. Q And how long did you work at Microbiological Associates? A Thirteen years. Q What was your position during the time that you RIGGLEMAN, TURK & NELSON 6..r 7.F'""l' 7 ) i 'f 04... 403

20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 were at Microbiological? A I began as Project Director for a variety of contracts and eventuated as Director of Research for the past, for the ten years, that's the post I held at Microbiological Associates. Q You're not currently workinc for Microbiological Associates? A No, I left in 1994. Q Why did you decide to go to Microbiological Associates? A They had some interest in areas that were consistent with my interests, specifically in the areas of carcinogen metabolism. We had some interesting information from my postdoc, the Roche Institute, and I could continue that work at Microbiological Associates. Q Do you know whether or not CTR, the Council for Tobacco Research, had any contracts with Microbiological Associates? A Yes. Q Did they have more than one contract? A Oh, yes. RIGGLEMAN, TURK & NELSON V I /`! 7 II 4I 043404

21 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q What was your role in these contracts? A I originally was a co-pr:ncipal investigator of those contracts with Doctor, with-, actually with Doctor Carrie Whitmire originally and eventually a co-principal investigator with Doctor Carol Henry, a series cf projects, and some of them that I was the principal investiaGtor alone. Q Now, what type of wor'rk did you do with Doctor Henry? A Doctor Henry's was mostly in the area of the smoke inhalation program in which it was setting up a set of model systems to see if we could understa::d or at least study some of the potential biological effects of whole cigarette smoke. Q Did you have a contact w_th CTR while you were doing the work with Doctor Henry? A Yes. Q Who was that,'sir? A Mostly Doctor John Kreisher. Q Now, sir, you had a contract with Microbiological Associates -- excuse me, you had a contract with CTR through Microbiological Associates. Do you know the difference between a CTR contract and a CTR grant? RIGGLEMAN, TURK & NELSON CTI T I I I~, 0434055

22 1 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A In general it was explained to me and that came out later, we are probably going to get into it, but in general a grant was a gift that was a sum, a sum of money given to a grantee to perform a particular set of technological studies with really very little strings attached and that, usually the money was given up front and a final report was given at the end. A contract in theory was a set of responsibilities set out by the contractor, in this case CTR, to be performed by the contractee, and if we did in fact perform those to their satisfaction, we earned a fee for that set of responsibilities. Q Did the control that was exercised by CTR over contract research differ from that exercised over grant research?. A Yes, yes. Q Did ye:: ever have a CTR grant, Doctor Kouri? A Yes, one. Q When did you receive that grant? A I think it was in '81. Q Under what conditions did you receive that grant? RIGGLEMAN, TURK & NELSON (... TR { f N 04,3406

23 A As a grant, just what I said before. Q Now, you said the type of research that you did 10 11 12 13 14 15 16 17 18 19 20 21 with Carol Henry was to expose mice to cigarette smoke; is that correct? A Yes. Q I wonder if you could tell me whether or not the research you did with Doctor Henr7 involved only one experiment. A Oh, no, it was a series of experiments, all designed in, with trying to understand the potential biological effects of whole cigarette smoke. Q Now, the inhalation project that you were workin:g on with Doctor Henry, was that a;,ar'L of a larger program? A Yes. What we tried to do is we tried to understand -- for example, stages of carcinogenesis is something we put together, and we were trying to understand if cancer was going to be one of the endpoints that we would study, then we would try to break it down into a workable set of steps and stages so that we perhaps could understand how cigarette smoke could potentially affect each one of those stages. RIGGLEMAN, TURK & NELSON Cf R Vf N 04"34"07"

9 24 l1J 1 2 3 4 5 6 7 8 P,: 9 10 11 12 13 14 15 16 17 18 19 20 21 Q Doctor, I wonder if I could show you a document. And if you could identify that document for the record, please sir. A This is an example of a -- my job actually was mostly to be a strG:;egist, to try to understand where we were going, where we were now and where we were going to be in perhaps a couple years, and this was an attempt to put a pathway together from which to follow along the lines in these kinds of studies, not necessarily for CTR but for any agency that would have bee-- interested in this sort of activity. And these are the poter=ial steps we thought in ch-emically-induced cancer. Q And who developed the chart that we're looking at, sir? A Actuallv I developed most of it in help with Doctor Kreisher, and then eventually we asked Doctor Henry to get, put her imprimatur and changes and concerns in and then eventually all three of us were involved in the final construction of it. Q Sir, did this chart form the basis of your work at Microbiological tha-- was done for CTR? RIGGLEMAN, TURK & NELSON I C * TR H N 0 4~"~4 0 8

25 1 A Yeah, often, yes. Q Were there components, for example, in your 2 3 a 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 research that covered chemical transformation, carcinogenesis and mutacenesis? A A Q Yes. Were those important csnponents of your research? Yes. Doctor, I would like to show you a document we are going to make an exhibit. (Doc~:ments were marked Kouri Deposition Exhibit Nos. 7 and 8). A Yes. Q (By Ms. Nial) Now, Doctor, I wonder if you could look at the top of that document and identify it,-if you will, for the record. A This seems to be an internal document from the Council for Tobacco Research that just states that two of the contracts that we had currently going on in Microbiological Associates, Contract 14 and 22, were combined into one large contract, Contract 30, and this was the, most of the smoke RIGGLEMAN, TURK & NELSON CTR I I N 0 ~-~3 4 0 9

26 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 inhalation studies. Q Now, the next paragraph where it talks about a special committee, I wonder if you could tell, read into the record what that paragraph states. The Contract Review Committee would be Doctor Feldman, Gardner, Jacobson, Lynch, Meier, Sommers, and CTR staff that met on December 21st and 22nd to review progress. Q Okay. I was actually talking about this paragraph right here where it says a Special Committee on Contracts was appointed. A A Special Committee on Contracts was appointed by Doctor Sommers and after a two-day session the decision was made to delete much of the research on chemical transformation, carcinogenesis, mutagenesis and emphasize the smoke inhalation studies and studies related to the effects of smoke exposure on mice. Q Sir, did you note that at that time, in approximately 1978 when this document was issued, that that part of your research was terminated? A Yes. Q Do you remember who informed you of the RIGGLENIAN, TURK & NELSON 1 C T/ ! /MIN 04"'34Nb 4../'

27 I 1 2 3 4 5 6 7 8 9 10 11 16 17 18 19 20 21 termination? Not exactly. It was being filtered throuc:, both verbally and I think finally formally it was via Tim Finnegan. Q Who is Mr. Finnegan? A He was a counsel for, with Ed Jacobs Z"or the Council for Tobacco Research. Q He was a lawyer? A He was a law•ver. Q Had you met Finnegan before? A Oh, yes. Q And how abou-- Mr. Jacobs? A Yes. Q Did you attend scientific advisory board meetings for the CTR? A A few. Q And were Mr. jacobs or Mr. Finnegan at t'r_c-se meetings? A Usually. Q Did the termination of the components of y--ur research which dealt with chemical transformation, carcinogenesis and mutaaenesis have an impact on your RIGGLE1,LAN, TURK & NELSON Ci R f f f'f 04,3411

28 1 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 research? A Well, yes. It move: the timbre of the research from a, kind of a basic research sort of activity in which we were trying to understand basic mechanism to more finish up the smoke inhalation studies. of let' s Q Okay. Did there cc*.= a time, Doctor Kouri, whe:n you were working on your inhalaticn work that the entire inhalation research project was terminated? A Yes. I Q How were you notified c= that termination? A Again, it was a series of conversations that went I on between ourselves and CTR stG=_, and it had begun really all the way back in 1978 when Doctor Kreisher was rel_eved of his responsibilities at CTR. It was fairly obvious a:t that time at least one of our champions for that sort of ac-ivitv was no longer there and it was likely that our ability to carry on that work long term was likely in jeopardy, and it didn't surprise any of us that in fact it was phased cut. The actual steps involved in that phasing out, I really can't remember but it involved both conversations with Docter Gardner, Doctor LiSanti, and Mr. Finnegan. RIGGLENLz1N, TURK & NELSON Cf ARf f N 04,3''"'!` 12-

29 10 11 12 13 1 15 16 17 18 19 20 21 Q Do you have any understanding of why your research was terminated? A Actually Mr. Finnegan was fairly straight=orward in his statements about that, and it got to the same co*:-rersation or points that we made earlier and that is the difference between a grant and a contract, that there were some legal responsibilities that micht be involved in a contrac_ setting that would have been different than from a grant sett_ng, and therefore it would have been, it's not politically responsible from the CTR point of view to continue carrying on t:__s sort of research from a contract point of view because it could have been, the connotation still could be that the work was in fact coming from CTR to us as a contractor to contrGc=ee. We asked well, let's change it to a grant, then, and the decision was at that time that it just didn't seem to be cons_=tent with what the current ki"ds of administration that was going on at CTR. Q I am wondering if you are familiar with a document that's called a Frank Statement to Cigarette Smokers. I would like to show you a copy of that document and I will m;rk it as an exhibit. RIGGLEhLkN, TURK & NELSON {..r TR { f N 04..1 ~ 413

30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A No, I have never seen this before. Q I wonder if you could take a moment, sir, and read it. Can you read it, sir? A Do you want me to read it out loud? Q No, no, read it to yourself, sir. (Docu-:ent was marked Kouri De:csition Exhibit No. 9). (Witness reviewirc document). A Yes. Q (By Ms. Nial) I wonder if you note, sir, the statement, we accept an interest in . people's health as a basic responsibility paramount to every other consideration business. Do you see that, sir? A Yes. Q Do you believe that the actions of CTR were consistent with this Frank Stateme nt? in our A No. Q Okay. Sir, when you were told that your work on the inhalation project was completed or terminated, were you asked to submit a final report? RIGGLEhJAN, TURK & NELSON Cf R f f l f 04,3414

31 10 11 12 13 14 15 16 17 18 19 20 21 A Yes. Q And who besides yourself was involved in the drafting of that final report, sir? A Doctor Henry, Doctor Gardner, and Mr. Finnegan. Q Did Mr., did Doctor Gardner participate in the actual research? A No. Q And Mr. Finnegan you told me is a lawyer representing CTR; is that correct? A Yes.' Q Did either Doctor Gardner or Mr. Finnegan cive ycu i I any guidelines regarding the drafting of the final re_ort? A Yes. Q What were those guidelines, sir? A They would like to minimize the amount of :..ords that went into the final report. It was really to be a compendium of data, figures, tables, with a minimum a-:ount of context in which to at least review and introduce those tables and figures and it was to be, have very limited to no discussion. Q Was this limited or no discussion guideline typical RIGGLEr]AN, TURK & NELSON CTR NN 04:3415.i

32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 when writing up a scientific report? A Quite the opposite. Q Have you written up scientific reports before, Doctor Kouri? A Yes, yes. Q What is typical when you write up a scientific report? A Well, usually it's incumbent upon the person who carried out the work to try to put it in a context in which it was carried out, either, either context from the point of view of how this particular set of results compared to, sav other species or other conditions or in a historical sense what else has been going on, how does it fit in with what else is bei r.g done in the literature at that particular time. It's much in the same way that any publication is written. Q And the final report that you put together under the direction of Mr. Finnegan and Doctor Gardner did not contain any context; is that correct? A Correct. Q Why do you think Mr. Finnegan -- strike that. why do you -- what was your understanding of why RIGGLEMAN, TURK & NELSON CTR MN 04"34IG

33 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Mr. Finnegan did not want any discussion? A Ple thought it was just to be a one document summary of a lot of complex studies that were carried out f or about a three- to five-year period before that. So that it was, just tried to be a compendium of results -- well, results, too, and tables and figures so that anybody could actually look at those tables and figures and come to scme sort of conclusion. Q Was the report, the final r-e.port a collection of raw data? A Yes. Q Pnd -- A There was some analyses asscciated with those raw data. They were put in the context at least that you could read them. I mean, they weren't a compendium of just raw data. Q Did you intend the final re:ort that you and Doctor Henry drafted to be published and distributed to the public? A No. Q In your opinion, was it appropriate to distribute that report to the public? A No. RIGGLEMAN, TURK & NELSON C T R I - I N 0 423 4 1 f7

34 10 11 12 13 14 15 16 17 18 19 20 21 Q If you had been informed by CTR or Mr. Finnegan that the final report was going to be distributed to the public, would you :ave insisted on including a discussion or context of the research? A Oh, absolutely. Q Why is _t important to include in a scientific report the context of the research? A It's a, just a way to view the data in the context of which, what was going on at the time and what we knew at the time. Just, :cY an example, if you were talking about cigarette smoke, I mean you would like to say does this compare to how muc: cigarette that a human might get or how much, how much smoke that, say one of the other studies, say hamsters or rabbits or any other species that might have been carried out before:and, how do they compare. So that one could get an idea cfE what dose that you might have bee:n using compared to say doses anybody else might have used so you get I a'context in which to view the data. Q Does the failure to include a context have an impact on how the data might be interpreted by persons who are reading the raw data? R;GGLEMAN, TURK & NELSON L-~' TR H/4i 0T "3- ) ,14 6

35 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A I think that's f airly obvious. Q Now, Doctor Kouri, are you familiar with what's been called in this litigation the 1984 Blue Book? A Yes. MS. NIAL: Now, I believe, Mr. Merritt -- I wonder if we could at least share your Blue Book. I don't have my copy of it. THE WITNESS: I have mine. MS. NIAL: You have yours? THE WITNESS: (Nodding head Gffirmatively). MS. NIAL: Oh, the witness has his. (Discussion off the record). Q (By Ms. Nial) Now, Doctor, I have in my hand a copy of the 1964 Blue Book which is your copy; is that correct? A Correct. Q If you don't mind, we're not going to attach the Blue Book as an exhibit to this deposition. MR. MERRITT: That's fine. MS. NIAL: I think everybody has a copy of it, at least once. RIGGLEMAN, TURK & NELSON C,TR MN 043419

36 Q (By Ms. Nial) Doctor, were you contacted before 10 11 12 13 1 15 16 17 18 19 20 21 the Blue Book was actually published in 1984? A No. Q When did you become aware of its publication? A When it appeared on my desk. Q When was that? A The actual -- I tried to remember that. ~t's probably late in '84, '85, at least, you know, or maybe even a little later than that w:en it appeared. Q And have you reviewed the Blue Book rece--:1y? A Yes. Q And what does the Blue Book contain? A Pretty much t:e content of the f inal repc=t.. Q Is it exactly in the way that you and Doc-or Henry organized it? A No. Q And what are the differences, if you can recall, sir? A The onlv thinc I could see is that the introduction objective section was moved after the summary instead of before the summary, one, and two, the preface to the book was RIGGLETL~,N, TURK & NELSON rr.wr TI Tr I I• • 4.M• 4,3I2v/'

37 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 something put together by Doctor Sommers and obviously was not a part of the final report. Q Did the change in organization from the way you and Doctor Henry organized it to the new way that appears in the Blue Book have ar:y impact on how the information in the Blue Book would be interpreted? A It mic:t. I think the biggest issue is that it probably shouldn't have been moved as opposed to what impact it had. It just wasn't a verbatim construction from what we had sent. Q O:cay. =-nd it was represented to be a verbatim presentation? A Yes. In fact, I didn't know it until I looked at it. In fact, I didn't know it until Doctor Henry told me about it actually in her deposition is when I realized it. I had never loeked at the book carefully enough to have noted that. She in fac;1 did. Q Did you give your permission for any change in the final report? A No. We didn't even know it was done. Q And this Blue Book is the final report that you put RIGGLEMAN, TURK & NELSON C TR- E~N 0 43 422 1

38 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 together with the changes you've noted without any interpretations included by you or Doctor Henry? A Correct, correct. Q Does your name appear in the Blue Book? A Yes, Doctor Henry and myself are listed as the co-principal investigators of the contract. Q Did you give permission for your name to appear in this Blue Book? A No. Q Are there any authors identified in the text? A No, other than our own. But you were not identified as authors? A Not really. Q Do you think that having your name on this Blue Book as a project director might have been misleadirz to persons looking at the book? A Yes. Q Doctor, I'd like to show you an excerpt frcm the Blue Book which is identified as Foreword. A Yes. MS. NIAL: I will make an exhibit of that RIGGLEDLkN, TURK & NELSON C.r f ~f`~ f ~f ~ 04N3422

39 1 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 section of the Blue Book. (Document was marked Kouri Deposition Exhibit No. 10). (Witness reviewing document). A Yes. MS. NIAL: It looks like it has bee:n inappropriately staplec, gentlemen, and I do apologize for that. Q (By Ms. Nial) Now, Doctor Kouri, this is one of the additions to the Blue Book that you indicated that had been -- I'm sorry, additions to your final report tha-- had been made for the publication as the Blue Book; is that correct? A Yes. Q And who is identified as the'author of this Foreword? A Sheldon C. Sommers, M. D. Q Did Doctor Sommers participate in any of t::e research at Microbiological? A No. Q I wonder if you could take a moment to look at the RIGGLEDLkN, TURK & NELSON i.a' TR kl) ) 043423

40 1 2 3 4 5 6 7 8 9 10 11 12 17 18 19 20 21 Foreword. A Yes. Q Have you reviewed this Foreword before? A Yes. Q Do you agree with the F oreword? A No. Q I wonder, sir, if we could go through the Foreword and if you could tell me what parts of it you do not Ggree with. A The second sentence, for example, says the experiments represented a determined effort to develoc a suitable animal model involving chronic cigarette smoke exposure of inbred mouse strains known to develop various histopathologic types of lung carcinoma after intratracheal administration of pure chemical carcinogens. That's a factual state::~ent but in the context of chronic exposure of mice to cigarette smoke, I, my opinion would be that that suggestion is now that the animal rodel expresses identical histopathological phenotypes as those phenotypes associated with cigarette smoking in humans. I think that's what the connotation is in that sentence, and I RIGGLEMAN, TURK & NELSON (..r f R Mf 'i 04342,'""{"

41 l 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 think most people who read it w~uld take that to mean. And in fact, the types of tumors that we did get in mice, althoug'rh of the major types found in cigarette, in cigarette smoke associated cancers in humans, they are not identical. Thei= location is different and even the types of tumors are different. And we note that because it's a rodent and not a human and because of physiological differences, a variety of" conditions, they are not identilcGl. And so making that statement is a bit misleading. Q Okay. Next state<<enft that you find misleading, sir? A The results, in the nexc, the results observed included these, none of the smoke exposed animals developed pulmonary squamous cell carcinoma. Now, again, that follows exactly what I just sa_; before, the connotation would have been, then, that these mice do get scuamous cell carcinomas of the type that humans get in response or at least associated in a epidemiological fashio~ with cigarette smoke. The kind of tumors that humans get in respcnse to cigarette, associated with cigarette smoke are mainly RIGGLEMAN, TURK & NELSON ~T~~ t~N 0 4 ~'4 f~1.5?

42 10 11 12 13 14 15 16 17 18 19 20 21 bronchogenic squamous cell carcinomas, very often bronchogenic or at least central adenocarcinomas and some peripheral adenocarcinomas as well as oat cell carcinomas. In mice we find no oat cell carcinomas because the cells aren't there and in fact we find no bronchogenic squamous cell carcinomas in mice even with high doses of chemical carcinogens that induce lung cancer in general. So that we don't find the kinds of bronchogenic squamous cell carcinomas in mice even with chemical carcinogens, even known chemical carcinogens, exact kind. So it's not surprising that we didn't find squamous cell carcinomas the way it's written here. As a matter of fact, it would have also been correct if he had said we also didn't find oat cell carcinomas which is in fact we didn't find oat cell carcinomas. And the reason we didn't find oat cell carcinoma is that there isn't an oat cell in a mouse. The reason we didn't find bronchogenic sauamous cell carcinomas in a mouse is that the mouse doesn't seem to get it. So that is irrelevant, that statement, that we didn't have squamous cell carcinomas. Q Okay. I wonder if we could follow on, then, to the RIGGLEMAN, TURK & NELSON HN 043"'f 26-1~"'..a

43 10 11 12 13 14 15 16 17 18 19 20 21 next statement that you believe is misleading. A Mice pretreated with a pure carcinogen did not have significantly increased lung cancers after prolonged smoke exposure and overall numbers of pulmonary neoplasms identified were not statistically significantly different in smoke exposed compared to sham or shelf. S'r.elf should be out of it immediately because that's really a separate animal and different control. Eetween smoke and sham, wha:: the overall numbers that were fcund, if you added every of all the tumors that were found were in fact not different but that's really comparing a:_les and oranges, that's a whole set of a variety of tumors l;sted with a whole set of a variety of tumors. tce could break down those two populations into a set that is apples and apples. For ex-ample, we could take a set of individuals, animals that were taken off test randomly in the smoke exposed group and taken off randomly in the sham treated anim:ls and compare those, those individual sets of animals distinctly as a particular subset. In that particular case, the overall incidence of cancer amona those two groups, between those two groups is in RIGGLEMAN, TURK & NELSON i C 11% fR l f N 04,3`""'i' .~~ i"

44 10 11 12 13 14 15 16 17 18 19 20 21 fact statistically significant at .04, and was stated in the results as such. As we stated here, we had a tendency to mitigate against that statistical significance because any month-by-month cha.r.ge never reached any higher than .07. So we were right on the cusp. In some instances if we did the analysis it would have been statistically significant; in other instances it would not. But in fact the way it's stated here overall incidence is in fact incorrect. If you take a subset, the overall incidence in fact is statistically significar_t. Q Now, Doctor Kouri, if Doctor Sommers had asked you to review this Foreword before it was included in the book, would you have informed him of the inaccuracies of his Foreword? A I would assume I would have. Q But he did not send this Foreword to you for your review before publishing it? A Correct. Q I wanted to ask you about this first sentence in the Foreword, it says the material that follows is the complete and unedited final report of contract research RIGGLEhLAN, TURK & NELSON CTI 7 ! lH 0I+ 1w^ I OWlJ 8

45 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 performed from 1975 to 1983 by Microbiological Associates, Bethesda, M. D., et cetera. Is it correct to say that this is the complete and unedited final report? A Well, obviously it was edited. Q Okay. Doctor, were you aware when you received your copy of the 1985 Blue Book that ir- was widely distributed to members of Congress, to members o-LE Congress? A No. Q Have you since found out that that was correct? A Actually I don't, I have ne-:er seen a distribution list, but verbally I have been lr-orm`w that it went to a lot of people. Q Doctor Kouri, I would like tLo show you what I represent to you is a distribution lis:t for the 1984 Blue Book. A That represents about nine thousand? Q It may be nine thousand. A Is that the five thousand plus the four thousand or something? I don't know exactly how this adds up but yes, that's a fairly -- what's the Pluto Club? Q I do not know. RIGGLEMAN, TURK & NELSON E.~ ~°R ~~~~ 0~'.~42 ' 9

46 A Oh, I'm sorry, I didn't know that, I don't know i 1 10 11 12 13 1 15 16 17 18 19 20 21 what it is either. (Document was marked Kouri Deposition Exhibit No. 11). Q (By Ms. Nial) Doctor, was it appropriate to distribute the 1984 Blue Book to members of Congress without including the internretations that you and Doctor Henry would have of the information? A I think it was inappropriate to send that document to that many people without at least allowing us to have looked at it, okayed that, since our names were associated with it. Q And I would assume, then, Doctor, that you do not approve of this use of the final report? A I'm not even sure what the use-was, to be honest with you. I just krow that they should have asked us first, I think it would have been appropriate. Q At the time of the distribution of the 1984 book, did you see any press releases relating to the publication of this document? A No. RIGGLEM.:kN, TURK & NELSON ~ T R t- -IIN 043430"'

47 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 I wonder if I could show you an exhibit, sir. MS. NIAL:: Can we go off the record for a minute? MS. BAUER: Off the record at 10:38. (Discussion off the record). MS. BAUER: Back on the record at 10:41. MS. NIAL: Doctor Kour_, I would like to show you a document which we are going to make the next exhibit. (Document was marked Kouri Deposition Exhibit No. 12). (Witness reviewina doc::ment). Q (By Ms. Nial) Doctor Kouri, if you would take a second to review that document. A Read the entire thing? Q Yeah. (Witness reviewing docu:aent). A Yes. Q Are vou done? A Yes. Q Now, Doctor, I wonder if you could look first at the first page -- RIGGLEMAN, RIGGLEMAN, TURK & NELSON i.1 TR { f N 043431

48 A Yes. 10 11 12 13 1 15 16 17 18 19 20 21 Q -- which is a memo from Leonard Zahn to Robert F. Gertenbach; is that correct? A Yes. Q Do you know who Leonard Zahn was or is? A Yes. Q Who was he? A He was a per-con who worked for a public relations firm that the Council worked with. Q Okay. F-nd Robert F. Gertenbach, who was Mr. Gertenbach? A At that time he was the new director of CTR, President I think was his title. Q Do you know •..zether Mr. Gertenbach was a scientist? A Actually I dcn' t think so but I don' t k nc:~7 that. Q Okay. In this memo to Mr. Gertenbach, M=. Zahn says the following, -- tell me if I am reading this correctly -- I hope Charlie will look closely at my explanations and translations to make sure I have not oversimplified or cmitted anything that is significant. There are some apparent discrepancies in the MAI summary that he may RIGGLEZNL:~N, TURK & NELSON ~T~~ ~~I~~ 04~~d'f*-;'

49 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 be able to clarify for me. You'll note I have included several negative findings which, in terms of the major thrust of the study, probably are not important. However, they are included to show we are not trying to conceal adverse results. Pinat's your reaction to that statement by Mr. Zahn? A Well, I, I don't think he was in the position to actually even come to any conclusion relative to positive or negative. I don't think he was a technical person. It would have been smarter to have somebody that actually did the studies tell him this, what was important, what wasn't important. Q They didn't ask you about drafting a press release? A No, this is the first time I have even seen this. Q I am reading the press release. Do you think the press release cr at least, excuse me, the draft press release that is attached to this memo fairly represents the results? A Oh, :'io. Q If you could just tell me briefly how you think it is not representative. A Oh, God, this would take too long to go through the whole thing. Much in the same way I started off with the RIGGLEMAN, TURK & NELSON vw.r TR I II I W' 7*.w.+' l 1..+"3

50 1 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 first conversation is largely effective here but the idea of a massive inhalation study in which more than ten thousand mice were exposed is not really -- it's a bit misleading in that the connotation here is that we in fact did the be-all, to end-all study for smoke inhalation and this in fact was the study when that wasn't the case. This was to be a set of studies, in fact this was the first of a series of s-oke inhalation studies that were to be scheduled to try to understand in some regards the potential biological e=fects of whole cigarette smoke. Pie only smoked one strain, we"only smoked one sex, and we only smoked, exposed to one particular kind of cigarette. What we tried to do is shake down -- just _= huge amount of infrastructure was required to carry out a study of that magnitude to include how to generate enough smoke, how to distribute it properly to the animals, to keep those animals happy, alive, and we ran into, you know, the typical sorts of problems when one is handling this number of animals. What's true is the amount of work it takes. That just gives you an indication of how difficult it is to try to do these kind of studies. That fact, that, those words there, when I RIGGLEhL~~1, TURK & NELSON ~ ~mR MN 043 ~ ~4

51 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 originally wrote them were, were to try to connote to the reader ~ow difficult it is to do t:ese studies. It was not to say that this was a huge study in which we have, finally can ask the cuestion of biological effe-cts from whole cigarette smoke and in fact have answered t1r~at auestion. That was never meant to be, nor -- it was just G- idea to try to connote to the reader how, how difficult it is to carry out these studies even under the very limited studies and endpoints we could compare =or this particular study. So the inference here to me is all bassackwards, and we %•:ould never start off that .:ay and massively da da da da da da, because in fact this was t-o be a set of studies c= which the remaining ones never got to be done. Q And the remaining ones d_dn't happen because CTR terminated its support of them? A Correct. Q That's all I have on that document, sir. MS. NIAL: Let's take a break. MS. BAUER: Off the record at 10:49. (Discussion off the record). MS. BAUER: Back on the record at 11:06. RIGGLEMAN, TURK & NELSON {~r ~~ i~s i i i i 0 "" T' .~ 4, ~ %5. 1

52 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q (By Ms. Nial) Doctor Kouri, we are going to begin questioning again, you're still under oath. A Yes. Q Now, Doctor Kouri, before we took our break, we were talkir_c about the press releases and the distribution of the 1984 bock. Do you recall that, sir? A `_' e s . Q As to the distribution of the 1984 book to lay people, I'd like to ask you, sir, would a lay person be able to interpret the content of the 1984 book in your opinion? A 1,•,ould a lay person in your opinion be more likely simply to re-=d Doctor Sommers' summary or Foreword rather t"-an attempting to review the raw data? A Probably. It's tough for me to tell. Q Would it be your opinion, si-r, that someone woul:d need a scie::tific background to interpret the data containe: in the Blue Book? A Absolutely. Q ~L-d even someone with a scientific background, would that person be better served if he was provided with z-he RIGGLEMAN, TURK & NELSON i..x f mR i f H 043436

53 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 interpretations and context that could be provided by the primary researchers? A Absolutely. Not everything was in the report. Q And not everything was in the report, sir, because Mr. Finnegan told you to limit the kinds of information you provided? A No, not necessarily. It was more, for example, context, the fact that what kind of, what kind of tumors do mice get, you know. We, we just annotated them. We didn't put them in any context of the kind of tur:.ors these get compared to h-a--lsters, compared to humans, compared to anything. There was no way to view whether this was just a set of studies viewed of and by itself around that small microcosm in which they were done. Therefore if you weren't aware of some of the other things that were to be associated with it, for example, how much cigarette smoke might be deposited in humans, you couldn't take these data and, and , transpose them under a human situation, to the human without having more information at your hand than was presented in this book. Q And you had that information, sir? RIGGLEMAN, TURK & NELSON situation C " TR M N 0 4 -3 4`3 7"

54 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A We wanted to. Q P-nd why -- and when you say you wanted to have that information, what stopped you from having it? A Mr. Finnegan asked us not to put it in. Q Now, sir, if representatives of the tobacco industry cited the M_crobiological results as supporting their proposition that cigarette smoking does not cause lung cancer, would you agree with that representation? A Excuse me, say it again. Q Okay. If certain representatives of the tobacco industry stated that the results of the Microbiological inhalation project supported the statement that cigarette smoking does not cause lung cancer, would you agree with that representation? A No. Q And what would your opinion be of the results that were found in the Microbiological inhalation -- A Oh, I think they were stated categorically in the paper. Unlike the final report that's here, we actually published a peer review document, publication a year and a half, two years later, in which the data then were compiled RIGGLEMAN, TURK & NELSON CT R k I N 0 43 43 8

55 10 11 12 13 14 15 16 17 18 19 20 21 and then put in a limited context I might add, anyway, but a least a context in which you could look at all the data, and we concluded that cigarette smoke under these sets of and I think that's Q Doctor Kouri, you did not reach the usual ninety- conditions is a weak chemical carcinogen, the correct conclusion from these data. five percent confidence level in the Microbiological is that correct? results; A Depends on how you want to say that. In the way that Doctor Sommers mentioned in the Foreword, if I looked at the overall incidence of cancer in a particular subset, those animals that were taken off test randomly we would have reached statistical significance, that is less than .05. But as we said, which Doctor Sommers failed to state in here, that we felt that even that .04 was mitigated by the fact that at no time did we reach .05 level of significance, actually reached .07 in a month-by-month analysis, and we felt that was a little bit, it's a little more conservative of a statistical analysis but it gave us a feeling. So what I would say we were right on the cusp of statistical significance all the way along the study. Of RIGGLEMAN, TURK & NELSON E~ T R M N 0 4 123 4 13 9

56 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 course that wasn't the primary purpose necessarily for this study either so -- it was to shake down equipment and shake down the whole facility. So the fact that we even got that close was kind of surprising to us as a matter of facz. Q Are mice particularly sensitive to nicotine? A Very much so. Q Did that sensitivity to nicotine have any _mpact on the results of your study? A Likely, although that's supposition. From what i can remember at the time, putting myself twenty years ago, mice constantly fought the cigarette smoke when it cG-e down the tubes for their inhalation. They never really Geapted themselves very well, and we lost animals, a great de-=l of animals through a variety of accidents, machine malfunctions, and the fact that they didn't like nicotine and were very sensitive to nicotine and often died within an hour o= smoke exposure. And so to limit that, we originally were c;ing to expose animals to an entire cigarette's worth of smoke, that is roughly ten puffs, and we had to limit it with the 2R1 cigarette to five puffs, roughly a third of the cigarette to a RIGGLEhLM, TURK & NELSON C~'~/ ~ I-1~~~ 04,3440

57 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 half of the cigarette, only because we just couldn't give any more, we were killing the animals. And so we knew we needed to move away from high nicotine cigarettes if we were really going to be able to do a bona fide bioassay with that particular material. Q Did you have plans to do that kind of lower nicotine inhalation study? A We already had preliminary data with the 3A1 and the 2A1 cigarette which are low alkaloid cigarettes, and those we could come up with a regimen in which toxicity was cut virtually in half to less and still got significant deposition of smoke into the pulmonary tissue. Q Was the research that you had planned for --he complete inhalation study ever completed? A No, but I wouldn't, i would actually say t~at there was never such thing as a complete study. I always v_eweu it I think, at least at the time when we discussed this, these were evolving studies and we were going to learn eve rv time we did it, and we'd doubt if we ever did the perfect inh-mlaticn study but they would get better and better as we learned mcre and more on just the operational details and the manaaement we RIGGLEMAN, TURK & NELSON C TR ~~~~~°~~ 04 ~~~~~ ~,

58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 needed to put into running a program of this size. Q In your opinion, was the termination of the inhalation study at the time CTR chose to terminate it good science? A No, I certainly didn't thi.r.:c so but that was their, they were t:e contractor and it was their decision. Good science I t^:ink would dictate, I thoucht it would dictate that we follow through with some of the interesting sorts of observations that we found at the beginning and to see if we could continue it on. I always thought it was a much better decision to make decisions from knowledge, not ignorance, and not having that information in front o' you was, just unabled you to make an informed decision. Q Doctor Kouri, did you ever have the opportunity to publish some of the results from your inhalation studies done at Microbiological? A Surelv. Q And when did you do that, sir? A we published them pretty much all the way along. Smoke deposition, smoke uptake, impact of cigarette smoke -- well, smoke facilities themselves in general. There was quite RIGGLEMAN, TURK & NELSON Cf R f f f'`f 0''"i' ,,.."'~ 4'"x" 2

59 1 2 3 a_ 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 a few publications. I don't remember the actual nurrLber but I would guess that we averaged as a group a publication every month to six weeks for that whole period of time in which we were doing Council work. So there is probably forty papers. Q Now, on the results of the Microbiological research that were contained in the final report, did you publish on that material? A Yes. Q And I wonder, sir, if I could give you a document. A Yeah, this is the paper. MS. NIP-1: I am going to make that t:e next exhibit. (Document was marked Kc~ri Deposition Exhibit No. 13). Q (By Ms. Nial) Now, Doctor, is Exhibit 13 the article that you publis:eci on those results? A Yes. Q When did that article actually get publis:ed? A It was in the July issue, 1986, of the Jcurnal of National Cancer Institute. Q Did you and C:rol Henry publish this article RIGGLE~!kN, TURK & NELSON C f f`s. N# ' f 0"'l' ..~ 44,.~

60 1 2 3 g 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 together? A Yes. Q Did anyone besides you and Doctor Henry review the article? A Doctor Gardner a::d Mr. Finnegan. Q And did Mr. Finnegan offer any editing advice? A Yes. Q And what editing advice did he offer you? A He asked us to limi t our discussion to the exneriments at hand here without putting much, either historical context or, I don't know, other human context to these studies, and we did. Q And why didn't he want you to give any human context of the studies? A Tough for me to tell. I could surmise that it was just an attempt to simplify this particular study to the data at hand rather than expanding it any. Q Left to your own decisions regarding the publication of this article, would you have limited your comment regarding weak carcinogen to mouse lung? A Would I have altered the -- RIGGLENLM, TURK & NELSON CTR MN 043*7444

61 10 11 12 13 14 15 16 17 18 19 20 21 Q Would you have -- if you could refer to the first sentence of the discussion. The first sentence of the discussion, the results of this study suggest that 2::1 cigarette smoke has weak carcir:ccenic activity in mouse tissue. A Right. Q Would you have limited your opinion or your interpretation of the results to being mouse lung tissue? weak carcinogenic lung in A If, if Mr. Finnegan were not there? Q Yes. A No, that's the correct conclusion. Q Okay. A And Mr. Finnegan agreed with that conclusion. Q Okay. Do you have any opinion about the _moact of the widespread distribution of the Blue Book on the _-:oor:.a:!ce of vour article in 1986? A Actually no because I actually didn't know it had a widespread opinion. So I didn't think it had any impact at the time. In fact, I didn't know it until a month aco that it might have had any impact. RIGGLEM., TURK & NELSON ~~"~' ~N 042344!3

62 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q Doctor Kouri, you've reviewed Doctor Henry's deposition; is that correct? A Yes, I've looked at it. Q There was one particular issue in Doctor Henry's deposition regarding some leases. Do you recall that discussion? A Yes. Q And do you recall that that discussion indicated that CTR wanted to terminate the Microbiological inhalation studies because of the issue of the possible termination of a lease? A Yes, that was the connotation in Doctor Henry's. Q Do you recall the issue relating to the lease? A Yes. Actually I was probably more close to it than Doctor Henry was because I was the Director of Research and in that regard I was her boss. Q tvas the lease on the Microb_ological building the reason that the inhalation project was terminated? A In my opinion no. Q Doctor Kouri, who was Doctor Kreisher? A He was our contact at Council for Tobacco Research T RIGGLEMAN, TURK & NELSON iJ I I\ MI I 04,3446

63 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 related to these projects. Q And approximately how long did you work with Doctor Kreisher; do you recall? A From, it must have been '70 to '78. Q And what happened in 1978? A He was terminated. Q Did he just leave because he had other business elsewhere? A No, at t1re time it was explained to us that he was just, he was relieved of his responsibilities at the Council because of, just, kind of an inability to get along. Q And did you ever experience any inability to get along with Doctor K_eisher? A No. Q Were you aware of any of these problems prior to his termination? A No. Q You earlier described in your testimony, please correct me if I'm wrong, Doctor Kreisher as a champion of your work at Microbiological. What did you mean? A Well, to get any of these, this project done of RIGGLEhRN, TURK & NELSON CTR VIIN 04,344 7.X

64 1 2 3 a_ 5 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 this size, it requires a lot of effort by usually a few people and a champion is what anybody needs to get the project done, and Doctor Kreisher was a champion in terms of he thought this was the kinds of things that ought to be done. And I got enthusiastic in a lot of regards because of his enthusiasm, and we seemed to be making prccress in that area so I felt pretty comfortable with this tea,:~ approach that would be workable. Q Was there anyone else at CTR that you felt was competent to deal with the work going on at Microbiological besides Doctor Kreisher? A The only person who really had some technical expertise on staff was Doctor Gardner. Q Did he ever get involved in your work? A Not on the day -- not to the level that Doctor Kreisher did but he was helpful. Because he was a pathologist, he would, he very often was helpful in some of our interpretation. He carried on more conversations with our pathology team than he did with our, our, say the operating team. Q Now, Doctor Gardner didn't write the Foreword in X RIGGLENLUv, TURK & NELSON CTR HN 04,3448

65 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 the 1984 Blue Book, did he? A No. Q Doctor Sommers wrote that Foreword? A Right. Q Was Doctor Sommers qualified to interpret that data? A Again, my opinion is : o-- actually I don' t know of Doctor Sommers' background in the smoke area. He is an b?. D. but I thought he really had more o= a surgical background as opposed to -- although I might be wrong there. I actually don't know Doctor Sommers' backcroLnd. He came in a little late on the scene. Fle was not there for this whole set of processes that were going on in terms of these studies. I actually don't know when he appeared actually on the scene, and I was kind of surprised when I saw that his name was the one associated with it. It would have been -- Doctor Gardner's is the one I would have expected to see if anybody. Q I would like to show you a document, sir. This will be the next exhibit. (Document was marked Kouri Deposition Exhibit No. 14). RIGGLEMAN, TURK & NELSON CTR MN 04*%344-9

66 1 2 3 a_ 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 (Witness reviewing document). A Yes. Q (By Ms. Nial) When you were meeting with Mr. Scheiner, did he show you this document? A No. Q Now, this document is an October 25th memo from a Mr. Seligman to the CTR file; is that correct? A Yes. Q It's on Philip Morris stationery; is that correct? A Yes. Q I wonder i f you could look first of all in the first paragrap:!. Does it indicate that Doctor Kreisher's employment wit1n CTR had been terminated? A Yes. Q is that about the time that you think Doctor Kreisher had left? A I think. It sounds right. Q I wonder if you could go to the last paragraph which says at a recent meeting, the controversial contract work conducted by Microbiological Associates was terminated at the end of the vear, probably June 1979. t RIGGLEMAN, TURK & NELSON CTR I-IN 04~34ZSO

67 10 11 12 13 14 15 16 17 18 19 20 21 Were you aware that your work at Microbiological was controversial? A No. Q Was this the first time you've heard the word controversial applied to your work at Microbiological? A Yes. Q Do you have any opinion as to why it might have been controversial? A No, not really. Q Okay. Do you know anything about this gra:t for thirty-eight thousar_d dollars that -- A I think, although I might be wrong, I think it was the amount of money that was required by Carol and myself to pull together all of the final tables that were part cf this project and put together this paper. Q Okay. A Or it miczt have been to actually put this together as well. Maybe it was bcth as a matter of fact. Q So you think it might have been money for both putting together the final report -- A The final repcrt and the associated publications. RIGGLErVaN, TURK & NELSON E..r IO~~'~~ {~ f~4~_"i'#4!~z ~.

68 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 It was to wrap it up. MR. McCOr~'NELL: Susan, are you done with this exhibit? MS. NIAL: Yes. MR. McCOl,'NELIL: I note the designation : on the side of the exhibit that says dissemination is prohibited by Court Order. I think at this point I am going to ask that the part of the deposition transcript that pertains to this pace be marked as confidential and subject to whatever sealing order is appropriate in the Barnes case. MS. NIAL: ^his document has gone thrcugh the being produced procedure in the State of Florida and is longer under a protective order of any kind. no MR. McCO"N-EL•L : I don' t know i f that' s the case in the Barnes case. I MR. SCHEINER: Florida is not an active case. This is not being taken in Florida. MS. NIAL: T- understand that, but it's out in the public domain, this document. I object to this deposition being sealed. MR. McCOh~EL•L: I understand that, but we t RIGGLEhLAIN, TURK & NELSON CTR i f H f.A`Y' 3452

69 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 reserve our rights -- I just don't want to waive any right we have in the Barnes case to have this part of the transcript sealed. MS. NIAL: Okay. I' ll just let you k::ow -- MR. THOP.?E: That's going to have to he worked out with the Court in Texas before any sealing is done. MR. McCO`~"NELL: I understand. MS. NIAL: I will just let you know fcr the purposes of your own record that this document was used in the Carol Henry deposition and that deposition is not s`G_ed. Q (By Ms. Nial) Doctor Kouri, after Doctor K_eisher left CTR, did your relat_onship with CTR change? A Yes. Q How did _t ch-=-:ge, sir? A Well, obz-ious_v the style is much different between John and mostly the rela:.ionship we had was then with Bill Gardner, Doctor Gardner, and Mr. Finnegan himself often was involved. So the whole way of doing business was pretty much, from my way of taking it, it was obvious that we were slowing down the basic technical sorts of approaches that we were doing and we were moving towards just completing and finishing RIGGLEDikN, TURK & NELSON CTR I-IN 043453

70 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 whatever activity that was going on at the time. Q As a scientist, are you used to having lavrfers working alongside you when you're doing work? A First time in my life and the only time.in my life. Q Did you travel to New York at all to inform the CTR SF3 of your work? A It wasn't necessarily SAB I should say, it was CTR staff itself. What we tried to do is -- in fact, because Doctor Kreisher wasn't there to ie an effective spokesperson that we thought for our own, for this large contract, Doctor Henry and myself decided that it would just be smarter that we got up there virtually every ~:.cnth because it's a=ot of money, it was a big project, that it would be just smart on our parts to keep everybody that we thought, you know, informed as well as we could in terms of the progress of t:_= project. Q Did the kinds of research that you do change a•_'te= Doctor Kreisher, that you did change after Doctor Kre_sher left? A Yeah, we, all the basic research in terms of mutagenesis, carcinogenesis, the in vitro assay, RIGGLEMAN, TURK & NELSON tr fR 11N 0434,54

71 f-- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 transformation, cigarette smoke condensate related stuff, some of the biochemistry, those were studies that actually were asked to be terminated and they were and so by definition a lot of our work -- in fact, a lot of the work that I specifically was involved in oricinally and historically was no longer really very important cr less important anyway, and we focused pretty much on the, on the smoke inhalation study itself. Q -Now, Doctor Kouri, you, as we said, you've reviewed Doctor Henry's deposition and in that deposition there was some indication by Mr. Merritt that there was some conflict of interest existing between you and Doctor Kreisher. Do you recall that exchange? A Ye s . Q t~;hat was your reactio-: to that exchange when you read it? A I was surprised. Q Was there any conflict of interest existing betwee* you and Doctor Kreisher? A I don't think so. Q Have you ever been accused of that kind of activity RIGGLEMAN, TURK & NELSON t.~ `ig' ~J-~ 043 ~'~5

7 2 1 in your job before? 2 A No. 3 MS. NIAL: If you could give me a minute , I 4 might be able to wrap this up. 5 MR. MERRITT: Okay. 6 MS. BAUER: Off the record at 11:31. 7 (Thereupon, a short recess was taken). 8 MS. BAUER: Back on the record at 11:42. 9 MS. NIAL: Except for reserving my right to 10 redirect, I have no further questions for Doctor Kouri. 11 MR. MERRITT: Let's go off the record. 12 MS. BAUER: Off the record at 11:42. 13 (Discussion off th d) e recor . 14 MS. BAUER: Back on the record at 11:43. EXAMINATION B 15 Y MR. MERRITT 16 Q Doctor Kouri, my name is Bruce Merritt and I' m here 17 representing the Council for Tobacco Research. We have n't met 18 prior to today but you have spoken on a prior occasion with my 19 associate Alan Scheiner? 20 A Correct. 21 Q And you responded to some questions from Ms. Nial RIGGLEhL11N, TURK & NELSON i_r f R f f N 04.,r3 `7 ~1~ ~'~.~

73 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 on your direct exam:nation relating to those communications? A Correct. Q Did Mr. Scheir:er in the course of that meeting with you ask you to do anythir_g that you felt was improper? A Oh, no. Q Or uneth_cai? A No. Q He came and asked you if you would assist him in going through the f:_es relating to the MAI contracts -- A Correct. Q -- and t=--rir_c to parse out what had happened? A Correct. Q And as I understand it, you were busy at the time? A I was. Q And you were willing to meet with him but you required that he pay your customary consulting fee? A I did. Q And that was the fee of a thousand dollars a day I believe? A Correct. Q And as I understand it, you subsequently decided RIGGLEhLM, TURK & NELSON CT F Z t-11 N 0 o 4, 3 -1 ' E;-:- I - i`

74 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 that you didn't want to accept the fee? A Right. Q You didn't understand that there was anything, any strings attached to that money whatsoever? A Absolutely. Q Now, you have met several times with the Ness- Motley firm; is that correct? A Yes. Q And that was in preparation for this deposition? A Once in preparation for this deposition last Monday. Q And you also have had contact with them in connection with preparing an affidavit for the use in one of their lawsuits against CTR? A Right, one other time. Q You understand when I say CTR, I mean the Council for Tobacco Research? A Correct. Q And when I say MAI, I'm referring to Microbiological Associates? A Fine. RIGGLEhL3N, TURK & NELSON C" T I R- 1-IN 0 43 -4 95 8

75 10 11 12 13 14 15 16 17 18 19 20 21 Q You haven't required t:aem to pay you any kind of consulting fee for your time sper:: with them? A No. Q When they asked you to provide them with an affidavit to assist them in the lawsuit, you provided suc: an affidavit? A I did. Q And that was the ciocu-.ent that was marked this morning? A Correct. Q Your -- let me start by asking you, when d-_d ycu first become associated with NL~I? A I think in 1970. Q How long had that bee-- af.ter you got out of graduate school? A Roughly two years. Q Where had you worked in the meanwhile? A I postdoc'd at the Roche Institute for Molecular Biology in Nutley, New Jersey. Q After that you went directly to MAI? A Correct. RIGGLEMAN, TURK & NELSON ~ C' T R I - - 4 U 0 43 4 53

76 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q MAI is a private laboratory; is that correct? A Correct. Q it's not like a laboratory that might be operated at Harvard or Yale? A Correct. Q It's a profit-making organization? A Correct. Q And at some point during the time that you were at MAI, it was in fact acquired by some other company, by the Whittaker Corporation; is that correct? A Yes. Q And so unlike the work that other, that universities or research labs that are nonprofit might have done for CTR, the work that MAI did for CTR was profit making? A Correct. Q And at some point in time, it became a fairly significant portion of MAI's total revenues; isn't that correct? A Correct. Q In excess of ten percent or so at some point? A Probably about that level. RIGGLEMAN, TURK & NELSON ~TR I-IN 043460

77 10 11 12 13 14 15 16 17 18 19 20 21 Q Okay. Was your -- you were the project manager or one of the project directors for the CTR work that MAI was doing; is that correct? A Correct. Q And was your compensation pegged in any way to the amount of work that was done or the profits made by MAI on CTR's work? A No. Q But certainly your position and your stature within the organization was affected by the fact that you were the project director of one of their largest, if not their largest customer? A I don't know if you say my stature was enhanced related to that. I was the Director o' Research or was named the Director of Research I think separate from any relationships with CTR, and that was the job I really held most of the time with Microbiological Associates. Q But CTR was a valuable customer so to speak -- A Certainly, certainly. Q -- of MAI, and MAI's profitability was certainly enhanced by CTR's work being there? RIGGLEMAN, TURK & NELSON CTR I-I I 4I 0413461

78 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A Certainly. Q And it was certainly not enhanced by having the CTR work go away? A Certainly. Q Pnd in terms of your career as a research scientist at MAI and Carol I:er_ry's career as a research scientist at MAI, that wasn't helped by the fact that the CTR work eventually went away? A Yes. Q Yes, it was not helpful? A Yes, it was not helpful. Q Okay. Ar:ci that was a disappointment to you, wasn't it, at the time? A Yes. Q I mean, it would have been, you could have imagined at the time that the work that MAI was doing for CTR might continue for a number of years -- A Correct. Q -- in the future, might be profitable for hMI, might be, might enhance your reputation and stature as a research scientist in the research community? RIGGLEhPaN, TURK & NELSON ~ T F Z N N 0 43 -1 - ,~2-

79 10 11 12 13 14 15 16 17 18 19 20 21 A Certainly. I I Q It's a fair statement, is it not, that at the ti*:e I CTR made the decision to stop co:=inuing the work with MAI, that you expressed some bitter disagreement to Doctor Gardner and Doctor LiSanti, that you felt that it was a bad decision and you disagreed with it and yo~.:were very disappointed; isn't that a fair statement? A I guess I would agree with everything but bitter. Q Well, bitter in the s_-_se that you were ur.:._Gpny? A Well, I think as you say, we're all business pecp_e and technical people in our heart, that was our job. When Jcu see about fifty percent of your responsibilities get taken away in terms of level, yeah, you're d_sappointed, you wis:: it wouldn't have happened. But I also on the other hand was a business person enough to realize thGt things don't co crn forever and we moved on. Q In fact, an organization like CTR has a lot of promising research opportunities made available to it? A Of course. Q And isn't it a fact th:.t an organization like CT:c is always having to deal with deciding where to put a limited RIGGLEMAN, TURK & NELSON L.r f R f f N 0""f' 3` f' 6,,,..~1~

80 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 amount of money among an infinite number of opportunities? A Absolutely. Q And at the time CTR was doing the work with MAI, they were also funding literally hundreds of other grantees -- A Correct. Q -- who were submitting in many cases exciting and cutting-edge type research proposals to CTR and CTR had to choose among them? A Absolutely. Q And the decisions at CTR were over, on these grant applications were overseen by a Scientific Advisory Board? A Yes. Q And these were scientists who were not employees of CTR; is that right? A Yes, that's my recollection. Q A number of these scientists were people that you knew; isn't that right? ' A Yes. Q And they were scientists of substantial stature in the scientific community? A Yes. RIGGLEMAN, TURK & NELSON Cf R i 1 N 043,464

81 10 11 12 13 14 15 16 17 18 19 20 21 Q Were they people of high integrity? A I would think so. Q I mean, for example, Doctor Gardner, Doctor Gardner had been a very prominent professor of anatomy at Yale -- A Right. Q -- before his affiliation with CTR? A Yes. Q In fact, had been the head of the International Cancer, International Congress against Cancer, you know the i organization I'm refe=ring to? A Yes. Q And was k-:own nationally and internationally as a cancer researcher of high integrity? A I agree. Q The other, there were several SAB members that were in fact people that you had suggested as possible SAB members to CTR; isn't that correct? A Oh, I don't know if I ever suggested anybody. There was -- sometimes I'd ask would this person help but I'm not sure I ever up-front suggested anybody. Q Was there anybody on the -- for example, were you RIGGLEMAN, TURK & NELSON CTR HN 0434-GOE-1;

82 1 2 3 a_ 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 familiar with a scientist by the name of Hans Meier? A Yes. Q Was Hans Meier a man of, of significant stature in the scientific community? A I think so. Q Was he a man of high personal and scienti.f.3 c ethics as far as you knew? A I think so. Q Was there anyboody on the Scientific Advisory Board that you felt was not, that didn't fall within that description of being substantial stature and high integrity as far as you knew? A No. Q Henry Lynch, were you familiar with him? A Yes. Q Was he also a scientist whose -- A . Yes. Q -- reputation was, was both national and international? A Correct. Q And a man of high integrity? RIGGLE~Lk-N, TURK & NELSON i..r f A R f fN 0'"'f' 3'°"f' GG

83 10 11 12 13 14 15 16 17 18 19 20 21 A (Nodding head affirma=ively). Q What about the staff? You've mentioned your champion John Kreisher. There was another researcher there named Vince LiSanti? A Correct. Q Did you•believe that Vince LiSanti was a gcod scientist? A Actually I don't mean it this way, Vince wasn't really a scientist. I mean, he, ':^e was, I think his strengt.h was more in management and auctir__s;.ration at a technical level, but he, he, I think he'd admit as well, his background was in dentistry and he wasn't a toxicologist or a carcinogenesis expert, and in that regard he helped us out in some of our, let's say our tissue culture related stu== because he was more familiar with those sorts of activities but had limited background in toxicology or inhalatio.n~, the smoke studies itself. Q But in terms of his ability to administer and manage research such as CTR was conducting under contract with MAI, he had a lot of experience, he had done that for years even before joining CTR? RIGGLEMAN, TURK & NELSON CTM HN 043 ~'r "

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 I 84 A Correct. But I thought the question was in terms of technically and I think he had very minimal technical impact on the project but did help us out from an administration and managerial point of view. That was I think his strengt:? . Q Okay. WGs he a man that ycu think had high integrity? A Sure. Q -were any of the people that we have talked about, the SAB mem:,ers, the staff people, Doczor Gardner, people that would compromise their scientific intecrity or ethics because the tobacco companies asked them to do that? A No, there was nobody there that -- in fact, I was surprised to see the Foreword. Q when you, when you were fir-st approached by Alan Scheiner sc-e months ago and asked if you would assist him in going through the MAI files, you didn't feel that this kind of a contact with somebody representing CTR was any sort of an improper thing, did you? A Ko. Q You didn't expect that he would ask you to do RIGGLEMAN, TURK & NELSON CTR ! ) ) ) 043468

85 10 anything improper? A Absolutely not. , Q Have you ever done anything that you believe to be unethical or a violation of your scientific integrity because CTR asked you to do it? A No. Q So your disagreements with Doctor Sommers' Foreword, your disagreement, your criticism of tiie i.nvclvement of CTR's lawyer in aspects of MAI's writing up of its results 11 12 13 14 15 16 17 18 19 20 21 and the like, none of that rises to the level where they were asking you to do or making you do thincs that you as a scientist felt were unethical? A Correct. Q And you never did anything that you as a scientist felt was unethical as a result of them forcing you or coercing you? A Correct. Q And you wouldn't have done that, would you? A I would not have. Q There -- ultimately when a scientist does research, accumulates data, writes it up and makes it available, either RIGGLEMAN, TURK & NELSON i..x f# R 1f f"f 0 43 4 Go 9

86 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 to the person who hired him to do it or to the world at large, he does it on his own individual scientific responsibility? A Correct. Q And he has to make sure that he's not falsifying data, misinterpreting data, suppressing data, stating things that are, that are misleading or fraudulent, and if he it's his responsibility as well, isn't -Lt? A I'm not sure -- Q Let me withdraw the question. dces, A That was a long one. I wasn't sure exactly what you meant. Q I don't want to, you know, tire you with one question. A I wasn't sure what that one meant. Q A scientist who does research, who writes reports or publishes articles in a journal does it on his own scientific responsibility? A Yes. Q Ultimately every scientific journal article, for example, bears a scientist's name -- A Yes. RIGGLEMAN, TURK & NELSON t..r f R Hi'i 043470

87 10 11 12 13 14 15 16 17 18 19 20 21 Q -- or the names of several scientists? A Co-rrect. Q And they put their name on there as their seal that, that they're accepting responsibility for the integrity of the process and the results? A Correct. Q And CTP,::ever asked you to do anything that violated that; isn't that correct? A Right. Q The work that MAI did with CTR sl,anned a num:oer of years; isn't that r_ght? A Yes. Q You starzed working for CTR either at or shortly after you joined rL?T in 1974? A No, I jcined I think in 1970. Q 1970? A (Nodding head affirmatively). Q When did you start actually doing work with CTR? A 1970. Q So you started in 1970 and the work continued right up until 1981 when, when the last of the inhalation studies RIGGLEMAN, TURK & NELSON Cf R f f f-'i 0"'i' ,..." `.~" .f".f.

i 88 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 terminated? A Yes. Q So that was eleven years that you worked fcr CTR? A Sounds right. Q The work that MAI did for CTR was multifaceted; there were a lot of projects in addition to the smoke inhalation studies? A Correct. Q There was work in mutagenesis? A Yes. Q On carcinogenesis? A Yes. Q Work on transformation? A Yes. Q There was work that was done with, with ma-::-a1 cells or bacteria in little Petri dishes where they were exposed to various substances? A Yes, yes. Q That was kind of the mutagenesis and the carcinogenesis studies? A Yes. RIGGLEhL1w, TURK & NELSON wJ" I p I ~ ! l  ~ ~/./~' 4"MW''- r/+t .4W

89 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q And during that period of eleven years, that work was written up by you on a number of occasions and published in peer review journals? A Yes. Q right? And CTR encouraged you to do that; isn't that A Yes. Q In fact, I think overall there were some sixty peer review journal articles that came out of the MAI/CTR relationship? A I didn't know the number but that sounds ccrrect. Q In addition to the articles there were, there were posters and abstracts that were submitted to internationGl, - A Probably the same number. Q -- international conferences? A Yes. Q In some cases CTR paid to have you or poctc= Henry or Doctor Whitmire attend those conferences? A Correct. Q CTR, CTR's work in that area I think, wouldn't it be fair to say, substantially moved the ball in, in science -- RIGGLEhLAN, TURK & NELSON {..r TR FIN 0M/ 347`3

90 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A Absolutely. Q -- during that decade? A Absolutely. Q This was high quality woYti: A Absolutely. Q in some cases it was cutting-edge work? A F.bsolutely. In most cases it was cutting-edge work. Q Now, when you described jo'.-.-n Kreisher as your champion, he was the guy at CTR 4i: owas sort of in charge of or supposed to look after the MAI study; -- A Yes. Q -- isn't that right? A Yes. Q So when, when you would want to do some additional work or want to propose a modification or an extension of some research that you were doing, you would go to John Kreisher and Kreisher would, would be part of the process of getting the SAB to, to agree, if that's what they were going to do, to do that research; isn't that right? A Yeah, I think so. RIGGLEMAN, TURK & NELSON CTR HN 0434-14

91 10 11 12 13 14 15 16 17 18 19 20 21 Q Have you ever worked in another organization that has done, that has hired a contracting lab such as triAI to do research? A I'm sorry? Q HGve ycu ever, have you ever worked for another organization that, that has been like CTR was in the seventies, that is, that was hiring a research lab to do research for them? A ye=. Q A:d have you ever acted in the capacity of sort of a contract o==icer? A No, I haven't myself. You mean me to give out the contract? Q YeS, yes. A No. Q but have you observed that those organizations invariably have s:;-:ebody who is responsible for each contract? A Correct. Q And that person -- A That's vour contract officer. Q Yeah. And one of the duties of a contract officer RIGGLEMAN, TURK & NELSON t_r f R f f f°f 043"°'I' 7ED

92 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 is to be knowledgeable about what the contractor is doing? A Correct. Q To understand how it fits into the overall program? A Correct. Q And also to l::ok out for the funding agency to make sure they're getting barg for their buck? A Correct. Q He's supnosed to be essentially more of a.^n advocate for his employer than fc= the contracting lab; isn't that true? A Yes. Q And there were times, were there not, when, when Kreisher, Mr. Kreisher cculd have been criticized by somnone at MAI who felt that mav'--e the MAI study wasn't the i::ghest priority for CTR for bei-g too much of an advocate fcr bLk.T.? A I don't think so but I don't know what ycu mear. by that. I mean -- Q Let me try to approach it a different way. When there was an issue as to whether or not MAI should be doing certain additional research at CTR, you could usually count on Mr. Kreisher to be an ad-:ocate for MAI's point of vie:.• because RIGGLE~'-~~T, TURK & NELSON t..r TR i f N 04,3476

93 10 11 12 13 1 15 16 17 18 19 20 21 was required a specific attention, you know, for a study, whatever it is, it was all based on science. I mean, if it was based o: good science and the propcsed studies or the prepc-=ed alteration or the proposed project made sense both technically, financially, and whatever i.t is -- John rronably killed as many projects as he in fact accepted. He ce:tainly you and he had a fair amount of agreement as to what MAI doing? A No, no, I wouldn't -- I would say that if we wasn't an advocate just to rubber stamp any good thoucht t'_at I might have had or I thought I had at that time. HE would look as any project director does and that is he evaluates it based on the data that he has at the time, and of.ten we brought in other people from CTR to help us evaluate some of those studies as well. Vince LiSanti, for example, is one of the ones. So I don't think he was the only person involved and, and they are all based on a typical review cycle or review approach that I think that anyone would have cdcne. ir, fact, a lot of the project directors at NCI with whom I worked would have done the same exact thing. RIGGLEDMN, TURK & NELSON CTR I-IN 04347'•. t

94 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q If there's an infinite amount of money, then all, all good science proposals can be funded; isn't that right? A True. Q But there rarely is infinite amount of money? A Rarely. Q Certainly it's fair, is it noi:, to say that Kreisher was very much in smpat:^.y with the prioriti es that MAI wanted to accomplish? I mean, you collaborated together on that carcinogenesis chart that :ras discussed this morni*:c? A Umh-humh. Q You had, you shared a:_sion as to the sorts of research that you thought would be most helpful in unraveli-ng the mystery of what causes cancer, and Mr. Kreisher was, was similarly-minded in many respects 1-,,o yourr approach to those problems; isn't that a fair statement? A Yes, sympathetic might not be the right word, it's more our objectives and our view c= the problem was fairly similar. Q And in addition, you h-ad a certain personal rapport with Mr. Kreisher; isn't that fair to say? A Only technical. RIGGLEMWN, TURK & NELSON C TR V I N 0 43 4 'fF" G

95 10 11 12 13 14 15 16 17 18 19 20 21 Q Well, but after he left CTR and after you ].eft MAI, you were later business partners together; isn't thaYt right? A That's ten years later, but, but that had -- yes, but again, if the question -- repeat the auestion again. Q You were --- after you left N.AI s::r.:: after he left , ' CTR, some years later you went int:, busines.: w_,1_;.r~ i Kreisher? Kreisher. s. ~ A Ye Q Okay. You had more, you have mo_c: oy a relationship with him than you do with, with, you know, many i of the people that you've had to deal with ir., your career? ~ A At the time at which we were carrying cut these studies, I had no more responsibility or relationship with ~ Doctor Kreisher than I had with any other projec;t director or ~ contract officer. ~ Q So the fact that you became a business partner of his in later years was due to , A Was secondary. I mean, that happened ten years later. Q Okay. Isn't it a fact, though, that when he left CTR, that your relationship with Doctor Gardner was not as RIGGLEMAN, TURK & NELSON C" T R M N 0 4 3" 4 79,

96 1 2 3 4 J 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 supportive in your view as, as Doctor Kreisher's relationship had been? A No, I thought Doctor Gardner was every bit as I enthusiastic, a champion for the projects as Doctor Kreisher wo:s. I Q So you feel that Doctor Gardner was open-minded in terms of what you were doing at MAI? A I did. Q And if Doctor Gardner had concluded in 1980 that CTR's money would be better spent elsewhere than on continuing work with MAI, you would have no reason to believe that that wasn't an honest opinion by a scientist of integrity? A You're right. Q And that's a matter in which different scientists could have a different opinion; isn't that correct? A Correct. Q There's always the problem of limited resources -- A Absolutely. Q -- and different places in which you can spend it? A Yep. Q And you never felt that Doctor Gardner had become RIGGLE10,N, TURK & NELSON Er f m R i t N S..a'Y' 3464.A

97 10 11 12 la 15 16 17 18 19 20 21 an industry shield or had given up his integrity in order to do the will of the tobacco companies? A I have no information that would suggest that. Q Now, when Doctor Kreisher left CTR, I think you testif ied this morni na that you, that at that poi nt w:icxi in the middle of, or in the Spring of 1978, was t::ar you =e'_t t:nac: the amount of work, you felt that MAI's activity or rL=-:I's research began to wind down? A Correct. Q Isn't it a fact, Doctor Kouri, that CTR 101A., the lifetime smoke inh-alation study, hadn't even started GS cf thel . ~ time when Doctor Kreisher left? A It just started. Q And that that was in fact, in terms of mo:!cy s.?zr.t,l the biggest thing that CTR did with MAI? A Correct. Q And that was a study that went on for several years after Doctor Kreisher's departure? A Correct. Q Now, you -- could I ask you to look at Exhibit 14, -- RIGGLErL3N, TURK & NELSON CTR I-IN 0434' 81

98 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A Yes. Q -- which was marke: this morning. You testified that -- now, this is a memo, an internal Philip Morris memo in October of 1978, and Ms. Nial asked you this morning about the last paragraprh of thi s memo which makes reference to the fact that a controversial ~ contract was terminated at the end of the year but a grant to ~ the two principal investigatcYs was approved in the amount of , I thirty-eight thousand. ~ ~ A Yes. Q You testified that you t'r_ought this grant was for the writing up of the, of the inhalation study? A I think so. Q But the inhalatiorn study at that point hadn't even begun; isn't that correct? A I actually don't remember what the -- do you know what the thirty-eight thousand was for, then? Q But I'm not the witness. The question is -- A I don't remember, sorry. Q Isn't it a fact that it couldn't have possibly been for the writing up of the Blue Book or the JNCI article or the RIGGLEhLaN, TURK & NELSON t~I N 1_!' 4,-3 4 82

99 10 11 12 13 14 15 16 17 18 19 20 21 inhalation final report because none of that has happened for years? You didn't start working on the final report until 1981, isn't that right, -- A Correct. Q -- three years later? ~ A Correct. Q Is it a fair statement that your memory on years is not, not -- A That's fine, that's fine. Q Okay. In fact, the grant tzar's at question rier.°_ was CTR Grant 1271 which was a grant to you and Doctor Henry to do mutagenesis and carcinogenesis a d transformation studies with Doctor Benedict; isn't that right? I A I actually -- obvious].y I d_dn' t remember that. Q Eut did you, remember that the contract that Ms. Nial asked you about this morning was in fact simply converted to a grant because CTR felt it was more appropriate f or funding by way of a grant and that it continued for another three years? A Obviously I didn't remember that. I still don't remember it. RIGGLEMAN, TURK & NELSON C T R if'-it N 0 4 .-3 4 °'...~° 3

100 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q Okay. Let me have marked as the next exhibit, let me see if I can refresh your memory, Exhibit 15, which is an Application for Research Grant to CTR dated September 11, 1978. (Document was marked Kouri Deposit ion t':o,:-5), (Witness reviewing documFnt). A Oh, all right, yes. Q (By Mr. Merritt) You remember this as a grant application that you submitted in September of 1978? A Sure, I was in error,.this is -- obviously the thirty-eight thousandd relates to this. I didn't know what it was. Q That was part of the mutagenesis and the transformation and t'r.e carcinogenesis studies that you had previously done under Contract 14? A No, this was a new approach that we felt merited a look from a grant point of view as opposed to a contract point of view because this was in fact a fairly high-risk set of objectives.and experiments that we. proposed here, and there were concerns whether they would actually ever work or not. RIGGLEMAN, TURK & NELSON I i..r f i~ f~ f"~ ti. +~ ""f ..J~ "" F" 8'"i

101 1 This had never been done, this alkaline DNA elution assay had never been done in vivo, that is in animals, in tissue, and we thought it represented an interesting corollary or additional a_Proach to the projects that were going on and because it was represented, it had relatively hiah risk so 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 associated with it, we felt it fit more within a grant point of view than a cortract point of view because we actually didn't know _= this would or would not work at all. So we broke it up. Buz isn't it a fact that in May of 1978, Doctor Gardner asked you to take a look at your proposed studies under Cor_tracz 14 w:ich were mutagenesis, carcinogenesis and transformation studies, and to try and reformulate them as grant studies and t1rat the SAB would consider them; isn't it the fact that that _s how this thing came about? A Aczually I don't recollect that. Q L•e-- me -- A In fact I doubt it. MR. MERRITT: Let me have this marked. (Document was marked Kouri Deposition Exhibit No. 16). RIGGLEMAN, TURK & NELSON ~TR HN 043-485

102 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 ls 19 20 21 Q (By Mr. Merritt) Let me hand you, Doctor Kouri, a letter that you wrote on May 24, 1978, to Doctor Gardner which contains a revised, a progress report on, on Contract 22 and some other materials. Do you recognize the letter on the first page of that? A I recognize my handwriting. I didn't, I don't remember the letter. Q This is a letter that you wrote? You don't have any question about that? A No, I co::' t. Q And you see t::-- item that you've listed as -- well, read the first paracrap:~ if you would. A Just a little note -- Q You don't need to read it out loud, you carn just read it to yourself. A I'm sorrv. (Witness reviewing document). A Yes. Q Does th:t refresh your recollection as to how it was that this grant application came to be submitted to CTR? A Okay. RIGGLEINLAN, TURK & NELSON CTR Hf "f ;..A'"'f' 3486

103 ` 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q I mean, isn't it a fact, Doctor Kouri, that this application which has been marked as Exhibit 15, that this wasl done as a result of the desire to convert certain of the mutagenesis and carcinogenesis and transformation studies to a grant form and that it was CTR's request to you to do so which you complied with? A No, I think it was in our mind to do this, obviously from your letter of May 24th, '78, that -- Q Excuse me, Doctor Kouri, that's your letter. A From the letter here, that we were to do that but in fact we didn't do that. This particular approach here was not a mutagenesis transformation experiment at all, it represented a separate and distinct approach for evaluating the potential damage that cigarette smoke might cause. It was not an extensiori of any ongoing work in Contract 14 or 22 or whatever this -- it says 14, 25 and 28 in particular letter. We in fact didn't do that. this 20 or Q And that's because you didn't submit an application for that? A Correct, correct. Q Now, Doctor Benedict did submit a grant application RIGGLEMAN, TURK & NELSON V I R l / I I ..I• I 348•/

104 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 for a continuation of some of the work under Contract 14; isn't that correct? A I think so. Q Did he continue doing some of that work? A I don't know. Do you have the contract to refresh my memory? MS. BAUER: Mr. Merritt, I need to change the videotape. This ends Tape No. 1 of the deposition of Doctor Kouri. The time is 12:16. (Discussion off the record). (Document was marked Kouri Deposition Exhibit No. 17). MS. BAUER: This is Tape No. 2 of the deposition of Doctor Kouri, the time is 12:19. Q (By Mr. b:erritt) I've handed you Exhibit 17, and this is an application submitted by Doctor William Benedict of the U.S.C. School of Medicine to CTR for a grant in, in February of 1975? A Umh-humh, yes. Q This grant was a study in transformation and mutagenesis; isn't that correct? RIGGLEhAN, TURK & NELSON i..+ TR f f N 0434,88

105 1 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A Correct. Q And this research continued to be funded by CTR up until 1981; isn't that correct? A I don't know when it actually ended. Q And this was work that was being done somewhat in collaboration between Doctor Benedict and MAI? A Yes. Q So when the memo that was marked as Exhibit 14 recites that, that certain research that was not smoking related was terminated, much of.that research continued under grant to Doctor Benedict as well as to MAI; isn't that right? A Not to Q Well, it didn't continue as to MAI because you didn't choose to su:mit -- you defined what grant application you submitted to CTR? A Correct. I Q And you determined that the research studies, the carcinogenesis studies that are included in that grant application that's there in front of you was the research that you wanted to do; is that right? A This is the work that Bill wanted to do. RIGGLEbL1N, TURK & NELSON C~~"~~' ~~~ ~~.~489

106 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q But I'm referring you now back to your application, Exhibit 15. A- Yes. I'm sorry, say that again, then. Q You determined what kind of carcinogenesis study you would want to be supported by a grant? A Right. Q You never submitted a grant application to CTR to study a carcinogenesis study other than this that wa-s refused; isn't that right? A Correct. Q CTR said that as to further carcinogenesis studies, they wanted you as a grantee to decide what it was yc~ wanted to do and submit it to CTR as a grant application; isn't that riaht? A Except for carcinogenesis 'studies, yes. = think you mean the transformation or mutagenesis or any ots:er alternative assays, yes. Q The transformation and the mutagenesis was being done by Doctor Benedict; is that correct? A No, no, this was, like you said, Doctor Benedict was doing certain aspects of transformation mutagenes_s and we RIGGLEhLkN, TURK & NELSON Cf y f": i fN 0""f` 3'"T' SWICd

107 1 2 3 a_ 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 were doing other aspects with other model systems. Those model systems and those experiments were in fact terminated '79. Doctor Benedict's approach using 10 T 1/2 cells as I think he was using were continued under a separate erant application. Q Well, when you say they were terminated, t:e contract under which they were being supported expired'; that right? A That's right. in 4sn't Q And you had the cption to submit as did Dccz-or Benedict a grant application for further support as a grant of those studies if you felt that that would be where ycu wanted to put your priorities? A Correct. Q And instead you submitted a grant application for a different carcinogenesis study? A That's correct. Q And CTR funded that study? A Correct. Q And Doctor Gardner never told you that you wouldn't be allowed to submit a grant application to do some other sort RIGGLEDP,N, TURK & NELSON tY.r f R i f f"i 0`"i' 3491

108 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 of carcinogenesis -- A Oh, absolutely -- correct, he did not. Q Scientific decisions are filled with discretion, are they not? A They are. Q Discretion on what kind of proposed study a researcher wants to do and wants to rile an application for? A (Nodding head affirmatively). Q Correct? A Correct. Q And discretion on the part of the granting agency in terms of picking among those choices as to which ones they want to support? A Correct. Q And in terms of those decisions, do you believe that Doctor Gardner or the SAB acted without integrity in making the decisions that they made in terms of what they would support? A Say that again. Q Well, do you think that CTR supporting the particular grant applications that were submitted to them by RIGGLEMAN, TURK & NELSON CTR 1 Ml~I •.I' I ,'w~' I w..^ /krr

109 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 you and by Doctor Benedict and not supporting other types of carcinogenesis research that wasn't submitted to them, that that was an unreasonable decision on their part? A No. Q It's a reasonable decision to fund -- A Whatever they want to ~und. Q Yeah, based on what _s submitted to them; isn't that correct? A Correct. Q And Doctor Gardner ne-rer told you that you :Gc to somehow compromise your scientif_c integrity in terms of how you defined what you submitted? A Correct. MR. MERRITT: Th=s is a good time for --s to take a break. How long do you want to -- MS. NIAL: An hour? MS. BAUER: Off th.e record at 12:24. (Thereupon, at 12:26 p.m., a luncheon recess was taken). AFTERNOON SESSION (1:54 p.m.) MS. BAUER: Back on the record at 1:54. RIGGLEMAN, TURK & NELSON 4./ T1 "'6 ) ) N 0l 3l ..+f ~r..,,l~

110 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q (By Mr. Merritt) Doctor Kouri, what year did you leave MAI? A Oh, I think it was -- you would have to look it up. Q Perhaps it would help refresh your recollection iff you would look at your resume, Exhibit 1. A 1S83. Q That was about a year after the CTR contract ended; is that correct? A Yes. Q And where did you go to work at that point? A I went to International Biotechnologies. Q And what was your position there? A Director of Research. Q And how long did you stay there? A Let's see, for three years. Q Was that the, the organization that Mr. Kreisher was involved with? , A Yes. Q So -- that was in 1983? A '8:. Q So when you testified this morning that it was ten RIGGLEMAN, TURK & NELSON tr f~ ff's. 11N (3''"f' 34c.-3"'f`

111 1 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 years between when you left, when Mr. Kreisher or Doctor Kreisher left CTR and w~,-,n you became his partner in this venture, it was really five years? A It was really five years. Q That's -- in =act, you went into this partnership with him immediately on leaving MAI? A Yes. Q And that was within a year of when the end of the CTR work occurred? A Yes. Q Since NLAT, have you ever worked as an actual research scientist? A No. Q You don't wor{ as a research scientist today? A No. Q Your career aS a research scientist per se pretty much ended with the CTR study? A Yeah. Q Doctor Kreisher was a man, was he not, that sometimes had difficulty dealing with people? Wasn't that true in your experience? RIGGLEIN!AN, TURK & NELSON C`TR IaIN 0`4~4910.5i

112 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A No, I guess -- I saw him not having much problem dealing with people. Q Wasn't he occasionally arrogant sometimes in dealing with, especially with older scientists? A No. Q Don't you recall him making critical commer.ts about some of the older members of the SAB? A I'm trying to think. No, I guess I don't recollect any specific instance of a de:-ogatory comment against -- anybody specifically? I mean, what are we talking about? Q Well, do you recall telling Alan Scheiner, my associate here, a few months ago that Doctor Kreisher :ad once said scientists over the age of thirty-five just didn't understand what was happening in science? A Certainly, John made those statements all the time. I guess -- but I guess you were specifically stating a'_-out the Scientific Advisory Board people, and no -- he made a statement in general that he felt the most effective time of a scientist's career was below thirty-five. I mean, yeah, I guess I have a similar sort of belief. Q Wasn't that comment made, though, in the context of RIGGLEMAN, TURK & NELSON i.x f R f f f'i 04,349.6

113 10 11 12 13 14 15 16 17 18 19 20 21 older scientists who didn't agree with his views of carcinogenesis and his -- A No, it was a general ccrnment. Q You never heard, you nFver heard any reports of him, of him having trouble with Doctor Gardner because of disagreements over CTR scientific proc=ams? A No. Q The carcinogenesis chart that you mentioned in your testimony this morning, that's not, that chart wasn't any kind of a secret, was it? A No. Q That chart was in fact publ_shed at some point in a textbook, wasn't it? A Correct. Q So the insights and the truth, to the extent it's reflected in that chart, about carcinccenesis was available for the entire scientific community to pursue? A Oh, yes. Q It wasn't up to CTR to be the only agency supporting research -- A Oh, of course. RIGGLEMAN, TURK & NELSON ~~"R ~`~~` 04~~~ ~

114 1 Q And in fact, CTR, because of its limited resources, 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 was in any event only a small player in a fairly large field of scientific study? A Absolutely. Q And scientific proposals or projects that were based on that chart or otherwise dealing with carcinogenesis that had real merit didn't have to go just to CTR, they could go to NIH or one of a number of other agencies? A Correct. Q Now, one of t1ne areas of research that you worked on in the, and MAI worked on in the mid-seventies dealt with aryl hydrocarbon hydroxylase or AHH? A AHH. Q That was something that you looked at both in man and also in mice; isn't that correct? A Yes. Q That was an enzyme that was thought to be involved in the activation of certain carcinogens; isn't that right? A Correct. Q There was a feeling that the level of AHH in an animal might well affect its susceptibility to carcinogenesis; RIGGLEMM, TURK & NELSON Ci m i""a f iN 0'-T" 34.r* V

115 10 11 12 13 1 15 16 17 18 19 20 21 isn't that correct? A Correct. Q At some point there was even some thought that AHh might be used as a marker for human beings, that possibly would indicate which humans were most susceptible or most at risk for certain types of cancer; isn't that correct? A And that's still being done even at this time. Q And that is research that was being done or some of that research was being done by you in particular at MAI; isn't that correct? A Correct. Q Do you recall that at some point CTR indicated to you that they were not interested in investing as much in that research going forward? A In the human? Q Yes. A We had one contract from CTR related, specifically related to the human work that completed and was not continued. Q And it was not continued because you didn't ask to renew it? RIGGLEMAN, TURK & NELSON CTR VIP 04,34R.E.S.4

116 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A Right. Q Do you recall a conference on AHH that was held at the Down State Medical School in Brooklyn? A Yeah, that was mentioned vaguely. I actually don't remember much about the conference but yes, we had one. Q And do you recall that, that CTR asked Hans Meier who was one of the SAB members to attend that conference and to give an evaluation of the state of the research and whether CTR should be continuing to support it? A Actually until you mentioned it, I didn't realize Hans was even there. Q Okay. Let me show you a document -- A Hans was not an expert in carcinogen metabolism. In fact, I went up to his lab at Jackson Lab and set uo the assay for him. Q But he was a scientist of some considerable stature, was he not? A Yes. MR. MERRITT: Let me have marked as the next in line that document, if you could hand that to the Court Reporter. RIGGLEMAN, TURK & NELSON CTIR 11N 043*-E500

117 1 2 3 a_ 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 (Document was marked Kouri Deposition Exhibit No. 18). (Witness reviewing document). A Yes. Q (By Mr. Merritt) I take it you have not seen -- let me back up. The document that's been marked as Exhibit 18 is a March 10, 1978 memo from Hans Meier to Doctor Gardner entitled Conference on Human Carcinogen Metabolism: AHH. A Right. Q I take it you haven't seen this document be=ore? A No, I have never seen it. Q The conference that he is describing in early March of 1978, is that the Dow:. State Medical School conference? A I guess that is it. Q And there were in fact other people from C~R, both the staff and the SAB who were present at that conference; isn't that correct? A I don't remember actually. Q You don't reme;wer. But you were present at the conference? RIGGLEM.:Lv, TURK & NELSON t..r f m R i f f'i 043501

118 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A Yes. Actually only because I asked somebody. I forgot if I were honestly. Q Could you read the, the first paragraph on the first page, just read it out loud, please. A The very first one? Q Yes. A I should like to make a few observations on the human AHH conference before too much time has elapsed. You may or may not wish to consider my evaluations and conclusions when certain of the present grantees are up for renewal or continuation application. Q And then could you skip down to Paragraph No. 1 that's been marked, and read that please? A One, I am disappointed that the situation with respect to AHH in man is considerably more complex than in inbred strains of mice. No doubt, the prerequisite of mitocen stimulation of lymphocytes in culture is the major drawback. Additional factors influencing results are the culture system and the donor histories. These factors have been identified and enumerated. They make assays in field or population studies not only unreliable but almost impossible. RIGGLEMAN, TURK & NELSON ~T ~~ H ~~ 0 43 ~~~~

119 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q Can you skip over to the second page and read Paragraph No. 4. A 4, it is clear now that AFi:? is neither an absolute risk marker for cancer nor a diagnostic marker in cancer as a whole or lung cancer specifically. Although it is no better than other biomarkers applied in screening procedures for cancer, within kindreds it may be a most useful discriminant of relatives at risk. Thus AHH and other biomarkers as discussed are best studied within the context of a clinical program of human cancer genetics. This setting, Lynch, Guirgis, Harris, Rasco, undoubtedly deserves CTR's continued support while most of the others, Kour_, Contrell, Martin, Alfred, Busbee, should be reduced and some, Fisher, Tyrer, perhaps even eliminated. This is most likely the best way for support money to be spent most effectively in the future. Obviously a great deal has been learned and some progress has been made. The likelihood of AHH beir.a a reliable cancer screen outside families or kindreds is small. Q These were obviously Doctor Meier's reaction to the AHH program? A Yeah. RIGGLEMAN, TURK & NELSON t.r TR f 3 N 043~..~'4.A 3

120 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q It was shortly after this, was it not, that the existing research that you were doing at MAI on AHH was expired and was not renewed; do you recall that? A The specific contract, yes. Q time? And you didn't disagree with that, did you, at the A No. Q You didn't make an application to renew it that was turned down? A Right. Q You don't work in the area of AHH today, do you? A No. Q It's an area where there has been work over the past several years and has evolved a lot from where it was in the 1970s? A Right. We were one part of the group that did move this away from most of Hans' criticisms. Doctor Meier's criticisms here were largely, at least answered to the point that we could conclude, we could carry out some reasonable studies and, and be able to make some conclusions even though the assay is fraught with some of the problems that Hans RIGGLEMAN, TURK & NELSON Cf R f f i'f 043504

121 10 11 12 13 1 15 16 17 18 19 20 21 mentioned, Doctor Meier mentions here. Q That was work, though, that was supported by CTR up -- before this time actually? A Just to that time, yes. Q And thereafter you continued to do work with AHH involving mice in connection with the inhalation? A Funded by CTR? Q Yes. A Yes. Q The mice model that was used in the whole s-:oke inhalation studies was a particular strain of mice, it was the BC3F1 mouse; do you recall that? A Umh-humh. Q Why was that particular strain used? A It was, _t had some attributes we thought were useful in its ability to be a model system for smoke associated biological effects. It was AHH inducible meaning that in response to chemical carcinogens or chemical treatment, it did make higher levels of this particular enzyme. Therefore, it had the ability to metabolize. It was sensitive to pure chemical carcinogen induced certain kinds of RIGGLErLkN, TURK & NELSON CTR HN '`.~43~ 0ES

122 10 11 12 13 14 15 16 17 18 19 20 21 lung cancers. It had a half life that was, in terms of, as a model system, useful. It was clean, meaning that we could get adequate numbers of animals that were free of most adventitious agents meaning the viruses or bacteria confound results if we didn't have it. Things like that might that. Q These various mice strains were genetically pure, were they not? A Correct, this was an F1, it was a cross between two strains, two inbreds. Q When you say genetically pure, it means they have been inbred so completely that all of the mice essentially have the same genetic code? A Correct, there are large sets of identical twins. Q So when you expose two of these mice to different environmental factors and they have different, and different things happen to them, you know it's not because of the genetics because genetically they are identical? A Correct. Q That isn't a situation that's always achievable with other types of animals? A Correct. RIGGLEMAN, TURK & NELSON CfjR Hf"i 043506

123 10 11 12 13 14 15 16 17 18 19 20 21 Q You don't have inbred strains to that degree of purity of say dogs or even of hamsters; isn't that true? A Little bit in hamsters, sorry to say, but dogs is probably a good analogy but yeah, they are not as inbred as we can do with mice. Q Hamsters were not a good model for lung cancer because it was known at that time that hamsters couldn't get lung cancer from smoking; isn't that right? A No, I don't think it was known that they couldn't, it was just the experiments so far that had been done with some hamsters indicated that, that the lesion that seemed to develop in response to cigarette smoke was more in the larynx, the upper pulmonary tree as opposed to the lung proper. Q But it's a fact, is it not, Doctor Kouri, that nobody then or now has ever produced lung cancer from smoke in hamsters? A I don't know that to be the case. Q Did you view hamsters as a better animal model than mice for these studies? A No. Q CTR didn't dictate that these had to be mice RIGGLEMAN, TURK & NELSON CT~'~ IIN 04~~ 50t'`

124 10 11 12 13 1 15 16 17 18 19 20 21 studies, did it? YTasn't this a decision, a scientific decision that MAI participated in? A Sure, and CTR. Q And concurred in? A And concurred in. Oh, absolutely, absolutely, I didn't know what you meant. Of course. I think it was the best model. Q They aiso'had the advantage, mice, didn't they, that they live a shorter period of time than most other experimental animals? A Yes. Q They live less than, for example, than rats? A Yes. Q And there are also more strains of genetically pure~ mice than there are rats? A Correct. Q And they live significantly less than hamsters? A Correct. Q Of course obviously much, much, much less than dogs or other -- A Correct. RIGGLEMAN, TURK & NELSON C T R 11 N C) 473 =5 -0 8

125 1 2 3 q 5 6 7 8 9 10 il 12 13 14 15 16 17 ls 19 20 21 Q And they are also, in terms of cost, attractive animals, you can, -- A Good point. Q -- you can, you can handle and house and buy and maintain mice a lot cheaper than other animals? A Correct. Q Wasn't it kind, wasn't it understood pretty much from the beginning of the inhalation study that in order to get statistically significant results, it was going to be necessary to use thousan:s of animals? A Correct. Q There wasn't a situation where by smoking fifty or a hundred mice, there was going to be any hope of seeing any sort of results? A Correct. Q Females were also used in the two studies that are included there in the B1::e Book. There was an advantage, wasn't there, to using females as opposed to males? A Yes. Q Females are e:sier to cage, aren't they? A Correct. RIGGLED±M, TURK & NELSON •..wr TR I I N 041wM' {n.1 01w1"

126 10 11 12 13 14 15 16 17 18 19 20 21 Q They don't fight? A Correct. Q They are better behaved? A In general. Q But one of the things that had been done in the preliminary studies by MAI was to test whether females and males had the same deposit of particulate matter in their lungs, received the same amount of, had the same carboxyhemoglobin levels in their blood? These are all tests of their ability to absorb the s;~oke; is that correct? A Correct. Q There really wasn't any difference between the males and the females? A Correct. Q Other than gender, they were genetically the same strain? A Correct. Q If they were in the same -- A Correct. Q Males or females? A (Nodding head affirmatively). RIGGLEMAN, TURK & NELSON C ~`R I~l! ~ 0439,10

127 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q The, the machine that was used to expose these animals to smoke was the product of a number of years of development; isn't that correct? A Yes. Q It was called the SEM, S-E-M, 2? A Correct. Q who had underwritten t:-- cost of developing that machine? A CTR. Q And it was actually produced, though, by a company in Brooklyn, wasn't it? A Correct. Q Products Instruments? A (Nodding head affirmatively). Q They actually sold it to the public; isn't that right? A Yes. , Q So what CTR was doing was developing a machine that would be available to other researchers if they wished to use it to perform inhalation studies? A Correct. RIGGLEMAN, TURK & NELSON C" TR I I N 0 43 =5 I I

128 10 11 12 13 14 15 16 17 18 19 20 21 Q That development took five, six years, didn't it? A Yes, I think. I wasn't involved in that. Q The idea of -- what made that machine special as opposed to some things that had been used earlier was that it forced the mice to inhale the smoke through their nose? A I wouldn't say it quite that way, I would go the other way. Mice are obligate nose-breathers, they can't breathe any other way. What it did do was this was a nose- only exposure system as opposed to an aerosol chamber meaning that you didn't blow smoke into an area and have them breathe it and walk around within it but rather we wanted to confine the smoke to just the snout, to the nose proper so that they, they, if they were going to breathe at all, which they do, they would take in the smoke as it went past their nose. Q It was really a much closer analogy or analogous situation to human smoking? I A Yes, thar-'s what we were trying to do. Q That's what CTR wanted? A Certainlv. Q Was any, was any -- the mice didn't like to smoke; isn't that true? RIGGLEMAN, TURK & NELSON V I A/ F / I N 04S.M.r' 5n/. 2

129 10 11 12 13 14 15 16 17 18 19 20 21 A Right, they did not. Q Were any studies done to find out whether in fact they were inhaling the smoke into their lungs? A Yes. Q What kir_d of studies were done for that purpose? A We radiclabeled the smoke itself, for example, meaning -- in fact, we had to design all pieces of equipment that could take a c_garette, an actua]. cigarette and we got one of the components, the normal components of cigarette smoke which is called dotriacontane and radiolabeled that particular molecule, that is made a radioactive version of it,l and then contrived a needle that would be able to go right down the bore of the middle of a cigarette and then rotate and distribute this material along the length of the cigarette as it, as it was pulled: out. So what you ended up with is a radiolabeled cigarette, of a no=--mal component of cigarette smoke being labeled and this was a marker of the particulate phase, the dotriacontane, and therefore we could follow its impingement and its amount of activity that goes to a particular area as an indication of where the cigarette smoke itself went. RIGGLEMAN, TURK & NELSON CTR I-IN 043513

I 130 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q So because it was radioactive, you could actually trace the flow of the particulate matter into the lung of the mouse? A Right. After we exposed the animals to the radiolabeled smoke, we cculd take out various tissues at various times after smoke exposure and study where that material went, where the smoke particulates went early on, and in some regards where at least that molecule went subsequently, which we found actually it didn't Most of it went to the lung which we would like go very far. to see 1.t go, and at the snout and very little anywhere else. So sz-:enty or eighty percent of the total particulate matter that was, that a mouse picked up at all in fact went into the respira-lory tree, the lung. Q When you say particulate matter, that's another way of saying tar, what people in common parlance refer to as cigarette tar? A Correct. Q It's the part of it that's not purely a aas? A Correct. Q So you could expose mice to this with the RIGGLEM.~~1, TURK & NELSON C T R H N 0 43 15: 14

131 1 radioactive label and then kill -Lhe mouse, look at their organs and find out where the sr:;oke had been because would actually be radioactive traces of it where the had, had infiltrated? there 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 smoke A Right. And dotriaco-:=ane was a fairly inert molecule metabolically meaning t:at it didn't seem to be a substrate for a variety of enzymes so where it stood it stayed. Whereas we also looked at some other molecules t1re same way. We monitored for nicotine levels in the mice but did it by either taking urine sa-:ples or blood samples post exposure to measure blood nicoti:~e levels to make sure that it was going where we thought it was going or cotinine actually, it's one of the metabolites of nicotine, and f ound it, as well as carboxyhemoglobin which you just mentioned before which is a monitor, then, for gas phase constituents, and we could measure carboxyhemoglobin levels as a measure for carbon monoxide levels in the cigarette smoke. So we had markers for the gas phase, the particulate phase and a couple different molecules within the particulate phase. So we were very comfortable that the mice RIGGLEMAN, TURK & NELSON CTR IIN 04351STS

132 10 11 ' 12 13 1 15 16 17 18 19 20 21 were in fact breathing and depositing smoke, smoke materials where we hoped that they were going and that respiratory tree. Q is in the And in fact, the depositing of the smoke in, both the gas and the particulate matter in the lung was, was in the parts of the lung that are most similar to human smokers, in the bronchi and the bronchioli and not so much in the alveolar spaces; isn't that right? A No, no, actually I'd have to go back and look at the numbers right now, but it was fairly generally distributed in the mouse. Q Wasn't it a fact, though, that there was relatively little penetration in the alveolar spaces? A Penetration? Q Of the particulate matter of the TPM. A It went to the peripheral spots of the lung and stayed there. , Q And that was like it is with a human smoker? A Yes. Q There was no -- the results of your studies showed that the depositing of the flow of the smoke into the mouse's RIGGLEMAN, TURK & NELSON C* TR I V, 1 0 43 Ei I G

133 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 lung was in much the same way as it is with a human smoker? A Yes. Q The resulting carboxyhemoglobin levels in the mouse's blood were in fact even higher than with a human? A Correct. Q They were like twenty percent; isn't that right? A Correct, higher. Q And in a human smoker is really six or seven percent? A Right. You have a headache at that level. Q These were all fairly state-of-the-art type tests; isn't that right? A Absolutely. Q The development and the resources that went into the development of this model did in fact represent a determined effort tc try and use the sophisticated methods that were available to science at that time to simulate as closely as possible a smoking situation for a mouse that would really be somewhat analogous and as closely analogous as it could be made to a human smoker; isn't that right? A Yes. And I should say it was Doctor Kreisher that RIGGLEDLAN, TURK & NELSON CTR I-IN 0435 17

134 10 11 12 13 14 15 16 17 18 19 20 21 actually did most of the work on the smoking machines. He and really Q And this was something that CTR was eager to be successful in; isn't that right? A Absolutely. the people at Processing Instruments were the ones that came up with the basic idea of how to make that work. Q They wanted to have a model that, an animal model that would get -- A Correct. Q -- lung cancer from smoking like a human wc•ald ge= lung cancer from smoking if, if that were the case, i= that could be achieved? A We never -- I hate to say from what I reme.;ber_, we never said it that way. We were very careful to say biological effects of whole cigarette smoke. Cancer per se as an endpoint was just represented as one of a set of e~;.poir_ts we would like to be able to auantitate as a result of exposure to cigarette smoke. But we were, from my way of thinking, we always looked at it in a bigger picture to try to see what are the spectrum of responses that might be associated with exposure to cigarette smokle, cancer being one of them. RIGGLEhLM, TURK & NELSON Cf r R f fN S.A "'Y` 3518

135 1 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q But lung cancer was clearly the most important of all of the various diseases that might be implicated, wasn't it? A What we wanted to do was to make sure that cigarette smoke itself was going, as you just said, going to the, going to the lung, being deposited within the lung and in a way that's at least analogous to the situation in humans. So we didn't want to compare ones that were completely ridiculous. For example, in inhalation chambers, you found a significant amount of cigarette smoke _n the GI tract, in the gut. Why? Ezcause animals have a tendency to preen each other, and if you put it in, if you put the animals in an inhalation chamber, they would run through and they would land on their backs and they would lick it off of each other and you would get a lot of smoke, you would get a lot of the materials in the GI tract as opposed to the pulmonary tissue. That to our way of thinking was a wholly inadequate model. So we made attempts to make sure that it in fact went to the lung and that's what we were doing. So that was a factor not necessarily with cancer RIGGLEMAN, TURK & NELSON i..r TK HN 0"f' 35.i. 9

136 1 per se in mind but rather smoke inhalation per se in mind. Q But wasn't it a fact that the single disease that 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 CTR was most interested in gaining some understanding on of, as a result of these studies was lung cancer? They were, they were interested in a variety of diseases but the one that was clearly on the top of the list was lung cancer? A Yeah. Q Isn't it a fact that all of your interim progress reports, the first item, the first paragraph under the histopathology reports would always deal with lung cancer? A Yes. Q That, that was because of the statistical association in humans. Obviously the disease from, going way back, that people have associated statistically with human cigarette usage is lung cancer? Exactl%-. It was an endpoint that we felt we could try to see if we could reproduce, you know, in a model system with the hopes being, then, eventually we would find surrogate markers, shorter-term markers that could substitute for some of the biological activity of whole smoke and that was the approach. So that we wouldn't have to do these repeat RIGGLEhLZ1N, TURK & NELSON E:~b~°R 11~`~ 04-~~~0

137 0 analyses of a three-year study armed with four or five thousand animals to try to compare such things as male versus female or one cigarette versus another cigarette. Q But one of the purposes of doing this whole thing, of investing all of this money and all of this time was to try and in fact develop a positive animal model, that is an animal model where you can in fact induce cancer such as it is found in humans in an experimental animal? A One of the aporoaches and one of the major approaches was in fact that case, that's true. Q And this kind of money spent would be largely ,1 12 13 14 1 16 17 ls 19 20 21 wasted if you couldn't do that? If in fact you couldn't develop a positive animal model, your efforts wouldn't be, really would be wasted; isn't that true? A The only thing I can say is you never prove a negative. So the fact that one didn' t f ind it under a given set of conditions doesn't mean that it didn't occur or it can't occur. So I would say that we would like to see it. A negative we could never prove. Q But a negative -- A Only a positive would ever -- RIGGLErLM, TURK & NELSON CTI 1 I MI I / W' 41w~' 4~w~' 2 1

138 Q I'm sorry, I didn't mean to interrupt you. A 10 11 12 13 1 15 16 17 18 19 20 21 positive would have value because then you you would be able to then go on and would have a model, understand what sorts of things were contributing to the disease? A Correct. Q You might conceivably be able to use an animal model as a means of developing s;,me kind of a safer cigarette -- A Correct. Q -- by changing components? A Absolutely. Q There would be a lot of value to a successf-ul animal model, isn't that correct, -- A Correct. Q -- whereas there wouldn't be much value to a failure, to failing and not being able to develop an animal model? A It's the latter -- I don't know how to answer thaz I don't know how you value -- you can't prove a negative. So I can't say at one time anything was a failure. One, if one does their studies and you think you're doing the right set RIGGLEMAN, TURK & NELSON C" T R N N 0 4 3 5-', 2-:~

139 1 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 conditions in which you're expecting a biological effect to occur and you don't see it under those conditions, it's not necessarily logical to say it's the assay that's wrong. It might have been you didn't do some step in the actual providing that material to the animal under a different conditions. set of So there is a variety of reasons, and we all know that as a scientist, you can never prove a negative, you can only prove a positive. So I don't know how to answer your auestion in terms of failure o= a model. The model was not a failure, it had already prove^"d to be a workable model- much before we actually did the or started off on the large study we did do. Q Well, the point I was making -- you're you cannot prove, it's hard to prove a negative in science, but the real value of this, of investing the kind of money that CTR invested in this, in the background studies, the preliminary work, developing the machine, sorting out the particular mouse, making sure that the smoke gets into the lung, all of that sophisticated cutting-edge science, that was all done with the hope and the desire that the result would be RIGGLEMAN, TURK & NELSON CTR ~~~~ ~~~~~~~

140 10 11 12 13 14 15 16 17 18 19 20 21 an animal that in fact would be a positive animal that you could induce disease in from the cigarette, that you could, you could create lung cancer like it occurs in human beings; that was the end objective of this study, wasn't it? A It was one of the objectives. Q It was the most importa::t one, wasn' t it? A Yeah. Q And CTR didn't have an interest back when they started this project in spending all of its money to develop an animal model that in fact wouldn't get disease or wouldn't be usable for -- A Oh, I don't think so. Q They sincerely wanted in fact to be able to create -- A I think so. Q - - lung cancer in these mice in a way that would be like the lunG cancer that you see in human smokers, that was / where they were going and that's what they wanted; isn't that correct? A All the information I got from my contacts at CTR, which was mostly John Kreisher at this time, would be RIGGLEMAN, TURK & NELSON CTI! 1 1 1 I 0 4 3 •mrn* 2I

141 1 2 3 4 5 6 7 8 9 10 11 12 13 14 . 15 16 17 18 19 20 21 consistent with what you just said. Q And nobody, you know, Doctor Gardner, you know, did he have any different opinion? A No. Q He was also sincerely interested in trying to develop a positive animal model? A Yes. Q As far as you knew, the members of the SAB were as well? A Yes. Q This was in fact a big part of CTR's annual budget that was tied up in this? A lie recognized that. Q And implicit in that is there was a lot of research that they might otherwise have wanted to support in the f orm of grants that wasn't getting support? A Right. I think what some of the -- for example, some of the things that was done was to utilize this contract in some regard as a focal point for generating a set of animals that had been smoke exposed under a standard set of conditions so that tissues, molecules, materials could be RIGGLEMAN, TURK & NELSON C T R N N 0 4 '352 IS

142 1 provided to a variety of other grantees so that they could in 2 fact be able to study what they, their own particular model 3 systems, whatever they're trying to study, in a condition in 4 which at least we know that the animals are being exposed 5 under a standard set of conditions and we wouldn't have ten 6 different smoke inhalation chambers running around the United 7 States trying to provide exposed animals to labs but rather 8 standardize that in sort of a way. 9 We also served in a typical contraci: fashion, then, 10 to provide mice to a variety of other CTR grantees to that 11 effect when they needed it. 12 Q Such as Doctor Benedict? 13 A Such as Doctor Benedict. 14 Q But those were essentially ancillary studies, were 15 they not? 16 A Those were studies that were initiated bv the 17 grantees themselves. 18 Q The main enchilada in the smoking of mice was the 19 whole smoke inhalation study, isn't that correct, and that's 20 what most of your final report dealt with, that's what most o 21 your proposals and your progress reports dealt with, that was RIGGLE,\L:kN, TURK & NELSON i. x f F R N f`f 0 43 ~'~ .2-1 ['°.~

143 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 the key central focus of CTR's interests; isn't that right? A You say it slightly differently than I would. It was the major study and the r.:ajor amount of money that we were spending on and therefore it represented certainly a large focus of the activity. Going orn up front, this study was to be one of a series of studies, but in fact it was the only cne that was finished. So by definition because it took cn so much of our resources to get that particular study do::e, it obviously served as a focus for a heck of a lot of our progress report's, proposed s=--dies and everything else because probably ninety-five percent of our resources were used to generate that study. Q And that reflected, did it not, the focus Gnd. the direction of the interest of the SAB? A Yeah. Q They thought that this development of a positive animal model was extremely i?-)ortant and that that was probably the single most impc=tant thing that MAI was doing for them; isn't that a fair statement, as far as you know? A I guess as far as I know. Q After the animals were smoked for whatever period RIGGLEi%LPtv, TURK & NELSON CTR I wl / I 043527

144 10 11 12 13 14 15 16 17 18 19 20 21 of time it was - and there were actually two long-term inhalation studies, CTR 100 and CTR 101A; isn't that right? A Right. Q One was a long term, appro-r.imately a half a lifetime, and the second one was a full lifetime study. After those animals had been smoked for the requisite period of time, they were then examined, thFy were then killed and examined histopathologically; isn't :-hatt correct? A Correct. Q Scientists always manage to make -- A Make big words. Q -- yeah, to make big words. How was it determined how many of these animals were to be examined? I i A It was a guess. Q The purpose was to -- let me, let me back up. ~ In the lifetime study, isn't it a fact that after the first year, all of the animals were examined on death except ones that were, where they had already started to decay or somethina like that? RIGGLEMAN, TURK & NELSON C"TR MN 0423E-52~~

145 1 2 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A Correct, correct. Q In the first year, only a representative sampling? A Correct. Q Pnd why was that? A It was just -- doing histopathology is a fairly expensive endeavor and so what we did in the first year is we took a reasonable cross section we thought at the time, that is asked some statisticians and said X number of animals died, we don't expect to see a relatively high level of lesions in this area, what number do you think we could use in order to sample that population in order to aet a reasonable estimate of what histopathological changes micht have occurred within that? And they concluded, I don't know what the actual number was, ten or twelve percent of that total number ought to give us a reasonable picture of all the lesions that occurred in that population of animals up to say a three or four percent population level, and we did that and found everybody was normal. In other words, we didn't find any pathological changes in the first year of animals, so we felt it was not worth the added cost to go back and, and RIGGLEMAN, TURK & NELSON C TR M N 0 43 52- E-3

146 10 11 12 13 14 15 16 17 18 19 20 21 histopathologically evaluate every one of those first animals. They just hadn't been on test long enough to expect to find some of the biological effects we might attribute to cigarette smoke. Q That was in fact because prior studies that you had done -- A That's right. Q -- had shown in the first year nothing, nothing oi significance happened? A Good point, good point. Q And after that first year, virtually all of the mice were examined? A Exactly. Q Both smoked and nonsmoked? A Correct. Q And all of their respiratory organs were examined; isn't that correct? A Correct. Q Including the larynx? A Including. Q So I take it that people who would criticize the RIGGLEMAN, TURK & NELSON CTR IwIN 043530

147 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 MAI study as being bad science because it used mice as opposed to other animals, you would disagree with that? A Oh, absolutely. Q Strongly? A Strongly. Q And people who assert there was some methcdology flaw in the program because it didn't examine histopathologically all of the mice in the first year, you would disagree with that? A I would disagree. Q And people who ccntend that the larynx sho•--ld have been examined because it wasn't, you would disagree with that because they're wrong? A It was. Q It was examined? A I think there's a good example right there of people who read this report here and because it didn': have the context in which everything was done and all those little entities were not mentioned, they came to the wrong conclusion. Q But in fact it does mention in the report, doesn't RIGGLEKAN, TURK & NELSON i..M TR f ~ H 0"'i' 3" =53.i.

1 148 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 it, -- A Oh, it might, but again, it's so big in terms of tables and figures and a compendium that those sorts of details cet lost unless you really look at it with a fine-toothed comb. Q And isn't it -- but in terms of the methodology of how many animals were used, how many animals were chosen for examination, the tissues that were examined -- and the- weren't just examined by eye, they were examined microscopically; isn't that right? A Absolutely. Q You feel that that was state of the art for the time and that that was -- A Yes, absolutely. Q -- and it was your best effort as a scientist to develop a methodology that would -- A If we had to do it over again, we probably wouldn't do it any differently, even in hindsight twenty years later. Q Now, you talked a little bit in the morning about the difference between a grant and a contract as a means of research. These inhalation studies were done under a contract RIGGLEMAN, TURK & NELSON ~~°~' V I N 0 4 3" z 93 2-

149 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 with CTR? A Correct. Q And in fact, it was, eventually came to be known as Contract 30? A Correct. Q Some of the earlier <.Jr; that MAI did was done under different contract num:.ers, there was a 14 and a 22? A Yes. Q There were a number cf them, weren't there? A Yes. Q Contract research is customarily different than grant research, not just at CTR but everywhere; isn't that right? A Correct. Q When-an agency has research done by contracz, it's essentially hiring a researcher to do a particular project? A Correct. Q And that researcher has a legal obligation to do the project that he's been hired to do? A Correct. Q It's like hiring a contractor to put the reof on RIGGLEMAN, TURK & NELSON WT I ! I I N 0 41..,' E; ' 33

150 10 11 12 13 14 15 16 17 18 19 20 21 your house? A Correct. Q He may want to put a tile roof on but if you hire him to put a shake roof on, that's what he's supposed to do? A Correct. Q Now, in this case MAI was part of the process by which the protocols and the project was defined? A Correct. Q It wasn't like CTR just came to MAI and said do this? A Correct. Q But MkI had an obligation to do the project that everybody haod agreed would be done under the contract; isn't that right? A Riaht. Q Whereas as a grant, it's simply almost like a gift, money is given to a researcher and he can do what he says he's going to do or not, there are very few strings attached; is that correct? A Correct. Q There's nothing illegitimate or improper about RIGGLEMAN, TURK & NELSON CTR MN 043-534

151 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 doing contract research? A Oh, no. It's probably the most common way to get the work done. Q The NIH does it? A It does. Q Research that requires a large outlay of capital, you know, a lot of equipment, a lot of extra personnel, that I i requires work over an extended period of time, that's almost I always done by contract, isn't it? I I A Yes. I i Q Because it isn't very well-suited for waiting for I i an applicant to come and submit a grant application? A Correct. Q Now, isn't it also a fairly universal provision in contract research that the results of the contract research actually belong to the agency that hired the lab to do it? A Correct. Q And typically contract research contracts, whether they're with the government or private agencies, typically require that before the researcher can publish, he must submit a draft of a publication for review by the contracting agency; RIGGLEMAN, TURK & NELSON C' 7°~ t1f N 0 43 53E5

152 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 isn't that right? A Right. Q So CTR, if it required MAI to submit manuscripts for its review, was simply acting in the mainstream of science? A Yep. Q And NIH and NCI and Damon Runyon and the American Cancer Society, they all do the same; isn't that richt? A Most often, yes. Actually some of those don't give off contracts, that's the only reason why it's a little different. Q But isn't it -- A The government does. Q Doesn't American Cancer Society? A I don't think they give off contracts. They might I but -- Q You don' t know? A I don't know. Q isn't it also the case that research results from contract research are often attributed by the outside world to the agency that has hired the lab to do it? RIGGLE1%LZ2T, TURK & NELSON •r..r TI ! ! I I I 04353G

153 A Yes. Q So that if, for example, there are results of 10 11 12 13 14 15 16 17 18 19 20 21 research that the agency doesn't necessarily agree with, it's in sort of a quandary, isn't it, because if it allows those results to be released, the world will assume that this is the result of its efforts and those results will be attributed to it even though it doesn't agree with it? A I think so, yes, I didn't know what you -- that was a little convoluted but -- Q Let me give you an example. The NIF-: occGsionally sponsors research by way of contract? A Right. Q Doesn'tt the NTH take the view that if it doesn't agree with the research results, that it takes a hard look as to whether those results can be released because the world will view them as the results of NIH research even th.ough the NIH itself didn't do the research? A I don' t know what, I don' t know what you mean by a hard look. Let's say I've never been in a situation where anybody from NIH for the sake of an argument either acreed or didn't agree to a particular study and in any way didn't allow RIGGLEb±AN, TURK & NELSON C T 1 ! M N 0 43 E537

154 10 11 12 13 1 15 16 17 18 19 20 21 us to do certain things or didn't allow us to publish a certain thing with those preconceptions in mind. I've never been associated with that. I don't know of an instance in which a funding agency like NIH in fact inhibited somebody from not presenting some particular data because for some reason they felt that it was disagreeing with some preconception that they had. I don't know of any -- nothing has ever happened to me personally to that effect and I don't even know of one. Q But they would have the right? A No. Q Wouldn't they have a right under the contract? A I doubt it. We did pretty much -- this was full public disclosure of most of the stuff we were doing. Q Do not most contracts in a research setting provide that the agency funding it is the o:%-ner of the research results? A Yes. Q And that it has the right to control when, -- A No. Q -- at a minimum when but possibly also if the RIGGLEMAN, TURK & NELSON CTR. V/ I I 0I 3We^ 34.a'

155 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 research results are released? A No, no, I've never had, I've never signed a contract with NIH with that provision in mind. Q How many contracts have you had with NIH? A Twenty. Q If someone who was working at the NIH overseeing contracts said that that was in fact a standard provision an^ that it was frequently exercised, would you disagree with them? A Yeah. Q Based on your experience? A Eased on my experience. Q Okay. Have you ever worked for NIH? A No. Q They have produced hundreds or thousands of contracts, have they not? A I would assume. Q Have you ever been in a situation where the NIH disagreed with the results of a contract research? A No. Q So you've never been in a situation where, where RIGGLEMAN, TURK & NELSON CTR 11N 0143E539.

156 10 11 12 13 1 15 16 17 18 19 20 21 there was a real disagreement? A Most of the studies, the data spoke for themselves. There couldn't be a disagreement, almost by definition. Q Okay. But it is true, is it not, that the owner of the results is in fact the contracting agency? A Yes. Q And it's true in your experience that there is a provision requiring that before those results are published, that the manuscript has to be presented to the NIH or to the contracting agency for their review? A Correct. Q That's pretty standard? A That's pretty standard. Q And it is a different situation in terms of the relationship betwee;n the results and the contracting agency than it would be if it were a simple grant? Correct. , Q With a grant, the researcher publishes his results and no one is going to attribute those results to the agency that provided the money? A Correct. RIGGLEM.11N, TURK & NELSON CT~`. HN 0432=540

157 10 11 12 13 14 15 16 17 18 19 20 21 Q Whereas if the person is operating under a contract, someone might well say those results are the work of that agency that put up the money? A You know, I think there is -- I mean, that was in fact the conversation that Mr. Finnegan had with us to say that that event does occur. In reality I have never been in a situation where that in fact occurred, that there was something that happened -- say for NIH. is a little different animal. Again, the government No, I t~~ink it might be the case if you were doing a contract for a private company, I think that sort of restriction is fai=-ly common when doing it for a company, but I when you did it for a funding agency such as, usually CTR I and/or NIH which represented more of a funding agent, that was their job to give out and distribute contracts and grants.' In those cases I never really have seen any restrictions either in what you can do with those. It was more, it was more being polite to give the paper, for example, the manuscript to the funding agency before you published it rather than kind of like you had to. I've never, even with CTR, did I ever have RIGGLEMAN, TURK & NELSON CTR HN 043=541

158 10 11 12 13 14 15 16 17 18 19 20 21 something rejected, in other words, don't publish this because I don't like it. It never happened. It's never happened in over, I guess I have a hundred and ten or so, whatever publications, I've never been refused the publication of a paper because they didn't agree. Q Well, the provision in a contract that re~:ires a researcher before he publishes to submit a manuscript to the, to the contracting agency, there's nothing improper w_th that? A Absolutely not. Q That doesn't necessarily imply that he's gc_ng to be unable to publish his results? A Absolutely. Most often -- I've never had Gn instance where it was. Q That includes CTR? A That includes CTR. Q In fact, it simply gives the supporting agency the opportunity to make suggestions of an editing nature wich may in fact be helpful? A Absolutely. Q Researchers -- A Good point. RIGGLEbAN, TURK & NELSON CTR- tMIN 043" ~~-~

159 1 2 3 4 5 6 7 8 9 10 11 16 17 18 19 20 21 Q Researchers often benefit -- A Absolutely. When more people look at a paper and with different viewpoints and different eye, very often it becomes a better publication as a result of that and that's pretty standard. Q And ultimately when the researcher puts his name on the final product and submits it for publication, he is essentially saying that whatever suggestions he has accepted or rejected -- A Correct. Q -- are ones tnat he agrees with? A We agree. Q And the fact that somebody says you're overstating your results and suggests a different approach, it still is up to the scientific responsibility of the researcher to decide whether to agree to that or not? A Correct. Q Nobody at CTR ever put you in a position where they told you you had to make changes that offended your sense of scientific integrity; isn't that correct? A Yes. RIGGLErLkN, TURK & NELSON CTR f f N 043w~a,.~ 4,2~

160 Q In fact, CTR consistently throughout this relationship with MAI and even for years after that encouraged you and Doctor Henry and Doctor Whitmire and the other researchers involved to publish your results? A Correct. There was never any instruction that you should 10 11 12 13 1 15 16 17 18 19 20 21 take results and bury them or suppress them or hide them from the world? A Nope. Q And in fact, the final report that you produced relating to this inhalation study contains those results for the world to see and any scientist who wants to know what you did to those mice and what happened to the mice, tl:e information is there for them to see; isn't that correcc? A It's correct the way you stated it. However, we did, when we wrote the final report, it was certainly r.ot with the idea in mind that the world was going to see this final report. I mean, it was, it was very difficult -- I mean, all it is is a compendium of tables and figures. So it was always going to be very difficult -- I never expected to see this in the hands of whatever number, nine thousand people. It wasn't RIGGLEMAN, TURK & NELSON t.r TR Hf 'I 0"'f` 32==44

161 10 11 12 13 14 15 16 17 18 19 20 21 written with that audience in mind. It was written for a certain small people that were involved integrally in this study to such an extent that they would be able to interpret in some fashion what these data might mean because we didn't have enough time and were asked not to put much embellishment into this particular document. So this wasn't for human consumption. Now, on the other hand, this was, the 1986 paper, -- Q T-e JNCI? A -- the JNCI paper was for general distribution and was written with those thoughts in mind. So we had, we could put a certain amount of context. We still were asked to ;:eep the context to the mice and specifically there and as said before, it didn't offend my -- it offended my sensibilities a little bit but not my, my integrity. you've I never, there was nothing I didn't do or couldn't do that was wrong. It's just that I would have liked to have been able to explain in a little more detail so as to give even a lay person to understand what the heck was going on in a different sort of context, and I was a little disheartened that we didn't get a chance to put it in that context. RIGGLEMAN, TURK & NELSON CTR HN 04354=5

162 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q But in terms of what you put in the final report of the inhalation studies, you didn't, you didn't not disclose any data in there or you didn't put anything in there that constituted a violation of your integrity as a scientist? A Absolutely not. Q And there was nothing that CTR could have done or did do to try and get you to compromise your A Absolutely not. Q They had paid umpteern million -- integrity? A They never asked, I might add. There was never an intonation by anybody, Mr. Finnegan, Doctor Gardner, Doctor Kreisher, that was never even a comment by anybody that anything would have ever been changed or altered or asked not to do it. These were the data, this was the data that came out and this is what we stuck with. Q Your conclusion in JNCI that cigarette smoke was weakly carcinogenic in the mouse's lung, they never asked you to take that out? A No. Q And you wouldn't have taken it out if they had asked? RIGGLEMAN, TURK & NELSON CTR HN 043546

163 10 11 12 13 14 15 16 17 18 19 20 21 A That's right, we wouldn't have published the paper if they asked and we would have had a fight right then. Q In fact, not only did they not ask you to take it out, they encouraged you to publish it and paid you and Doctor Henry for your time spent in writing that article -- A Correct. Q -- even though they in fact didn't agree with the results? A No, sorry to say, they agreed exactly with the results. Q With the weakly carcinogenic? A Yes, they signed off on it, Doctor Gardner and Mr. Finnegan were there all the way through. This was only done with their assent. It was never done in contradistinction to those, to their opinion. Q Didn't they ask you to put in the JNCI article that these were not necessariiy, the results were not necessarily concurred in by CTR? A Right. Q And that's because they weren't necessarily sure that they were concurring in those results? RIGGLE~LM, TURK & NELSON C T R t-1 N 0 4 3 '1; -4' 7~'

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 164 I A That was never stated, I'm sorry to say, that comment, the first time that's ever been mentioned is you just mentioned it. Q Wasn't that in a letter that was sent to you that you and, and Doctor Henry had that you could, that you would publish the article and you would s:ate very explicitly that the conclusions that you reached and Doctor Henry reached in the article were not necessarily the opinions of CTR -- A Correct. Q -- isn't that right? A Correct. Q Isn't that in fact in the published JNCI article -- A Correct. Q -- there in front of -- A Correct. Q -- you? A The connotation was -- Q Let me just have an answer to that question. Isn't that right? A Absolutely, yes. But the connotation was in your question that I took it to mean the time before that that RIGGLEMAN, TURK & NELSON CTR MN ~°.~4354' 8

165 10 11 12 13 14 15 16 17 18 19 20 21 meant that there was in fact disagreement with this particular paper and that's where I said no, there's never been a statement to date -- all they cared about is to make the statement that this, these were opinions from us, not them. They never said to us and to amf:,cdy, I've never heard it before ever stated that they disagreed with those conclusions. In fact, you're the first p4rso:: who has ever told me that. Q Well, I didn't tell you that. My question to you is, they made it clear, though, that these were your conclusions? A Correct. Q These were not CTR conclusions? A Right. Q They made it clear to you -- A We were the ones that did the study. Q You could publish your conclusions without hindrance by CTR? A Correct. Q All they asked was that you indicate that they were your conclusions and not CTR's conclusions? A Correct. RIGGLEMAN, TURK & NELSON E:~ ~`" ~~' C~ ~~ 04°.~ 549.

166 10 11 12 13 14 15 16 17 18 19 20 21 Q That's because it was contract research and not grant research? A Sure. Q And there is a possibility that because it's contract research, people might think that CTR endorses it or supports it when they might not; isn't that right? A Right, but actually that statement now appears in a variety of journals right now so it wasn't that -- it was surprising perhaps that it occurred that early and that was the only time CTR ever asked us to put that statement in one of our publications, that is true, but nobody ever hinted to us or even said it or intimated to us that they disagreed with those conclusions that are in there. Nobody ever said that. I mean, we went through the whole thing obviously letter by letter and page by page and word by word and Mr. Finnegan and Doctor Gardner never said that they disagreed with those conclusions. Q Did they -- in other words, they said you had a free hand to write whatever conclusions you came to; isn't that right? A I had a free -- we all agreed that these were the RIGGLEMAN, TURK & NELSON CTR HN 043550

167 10 11 12 13 14 15 16 17 18 19 20 21 conclusions. We -- all four of us sat down and we all went through this thing, we were all concluding this, the paper, the conclusions that are in the paper. We had a free hand. am not sure what you mean. Q Who was it that sat down and, and agreed? A Doctor Gardner, Mr. Finnegan, Doctor Henry and myself. Q This was when you were writing which article? A T~e 1986 paper, the JNCI article. Q This was in 1985? A I take it. Q You were then in New Haven at the time? A Yes, I guess that's right. Q Did this meeting take place in New Haven? A Which meeting? Q This meeting you are talking about where the four of you sat down and agreed on -- A Oh, no, this was all done -- actually it must have been done earlier than that because I don't remember -- this was all finished before I ever went to New Haven, this paper. Q The JNCI article? RIGGLEMAN, TURK & NELSON C-14Z HN 04:35r5I

168 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A Yeah. Q Would it surprise you that in fact the article was not agreed to be paid for until 1985? A Not agreed to be paid for? Q Isn't it a fact that the article was not written, your time which was billed for the writing of this article was not incurred until 1985? Is it your testimony that that's not right? A I actuall-y don't -- I don't remember. I didn't realize -- I don't remember the dates. Q Do you have a clear vision of sitting down with Doctor Gardner and, and Tim Finnegan and talking about the conclusions of this? A Yes. Q And that was in connection with the JNCI artic le? A Yes, and it took place in Bethesda, Maryland. Q You clearly remember that? A I think, ves, I think it's Bethesda, Maryland. It wasn't in New Haven if that's what you mean. Q Isn't it a fact, Doctor Kouri, that Doctor Gardner was dead when you first started writing the JNCI article, that RIGGLErLAN, TURK & NELSON I C T R H N 0 43 5- E. 1" -

169 10 11 12 13 14 15 16 17 18 19 20 21 he wasn't at any meeting with you discussing any things, you're just making that up; isn't that true? A Pardon? Q Isn't that true, that you don't have any recollection of sitting down and discussing the.J'NCI article with Doctor Gardner because he was dead before you started ~ writing the JNCI article? i A No. I Q You have a clear recollection of him being there? A I have a clear recollection of him being there. I ~ Q Okay. The time you spent writing the JNCI article , was time that you billed CTR for; isn't that right? A Yes. Could I ask a question? When did Doctor Gardner die? I don't remerlber. Q If you have a clear recollection of him being alive in 1985, then it w:s obviously after that. A I didn't say that, I didn't say '85, I said I had a clear recollection of him being there at the meeting in which these were discussed. That's what I answered. Q You have a clear recollection of him being there RIGGLEMAN, TURK & NELSON CTR HN 043,553

170 .10 11 12 13 1 15 16 17 18 19 20 21 when the conclusion weakly carcinogenic in your draft J-1ICI article was being discussed? A Now we're talking about one specific event. Let's say the discussion of the paper, the contents of the paper was discussed by Doctor, with Doctor Gardner, with Mr. Finnegan, with Carol Henry at offices in Eethesda, Maryland. Now, I don't remember what the date was. Obviously if Doctor Gardner passed away in 1985, it had to be pre-1;35. That's all I said. I'm sorry if I couldn't remember precisely what date. Obviously I could not have met with Doctor Gardner if he were dead. Q The issue is do you remember when it was you started writing the JNCI article? A Probably similar to when we were analyzing the data for this. This would have been 1984. Q Well, that document, the JNCI article was not written for over a year after the submission of the fi:al report; isn't that correct? A I think that's the case. Q So the final report was submitted in Februa?-y of 1984? RIGGLENLkN, TURK & NELSON CTR HN 043554.

171 10 A Yes. Q So the JNCI article was not written until the middle part of 1985 and was not published until 1986? A I don't, I don't remember the numbers. I do remember, I think you'll see even there that verbatim there are statements, paragraphs, taken right out of this report that's found its way into the paper, the 1986 paper. So this was a continuation, a continuing process going from here to the paper. Q But nowhere, nowhere in the final report is your 11 12 13 14 15 16 17 18 19 20 21 conclusion about cigarette smoke being weakly carcinogenic in the mouse's lung? That was your principal conclusion, was •it not, in the JNCI article? A Yes. Q That nowhere appears in the final report; isn't. that ricI-t? A Actually I don't know, I don't remember it that way. Q So -- A I haven't read it to that level. Q So you don't know today whether that -- RIGGLEMAN, TURK & NELSON W I W I! I I I ! 04,3v...!' {p~ 5

172 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A That statement is not here? I don't know if it's not here. I actually don't know. Q I thought you had testified this morning that you were not allowed to express that conclusion in the final report? A No, no. Q You in =act were allowed to express your conclusions in the final report? done. Sure. We probably didn't have all the analysis I can't even, I can't tell you that. Q So whatever Tim Finnegan told you about the final report, it was not that you had to keep out your final, your conclusion -- A Right, right. Q -- you were free to include the conclusion? A Sure. Q You were free to include the conclusion in the JNCI article? A True. Q That's a conclusion that was not forced on you by CTR? RIGGLEMAN, TURK & NELSON CTR I-IN 04"356G

173 10 11 12 13 1 15 16 17 18 19 20 21 A The weakly carcinogenic? Q Yes. A Was not forced? Q Well, you weren't forced to arrive at any particular conclus_on, that was a conclusion that you arrived at on your own acccrding to your analysis of the data; isn't that right? A And -- well, -- I'm not sure which way -- say that again, I'm sorry. Q Well, the conclusion that you reached was your own conclusion, it was::'t imposed on you by Doctor Gardner --- A Oh, yeah. Q -- or by Tim Finnegan? A No, it wasn't imposed, it was agreed by all of us that that was the conclusion. MS. NIAL: Would this be an appropriate point to take a break? MR. MERRITT: Yeah. MS. BAUER: Off the record at 3:00 p.m. (Thereupon, a recess was taken). MS. BAUER: Back on the record at 3:19. RIGGLEMAN, TURK & NELSON C,'-`TR HN ~'~43=535"i

174 10 11 12 13 1 15 16 17 18 19 20 21 Q (By Mr. Merritt) Doctor Kouri, you testified this morning that when you looked at the Blue Book the first time and saw the Foreword by Doctor Sommers, that it struck you as odd that it was Doctor Sommers and not Doctor Gardner; do you recall that? A Yes. Q Isn't it a fact that Doctor Gardner was in fact dead and therefore unable to write a Foreword or anything else at that point? A That's certainly true. I forgot. Q Is it a fair statement to say that your recollection in terms of specific dates, in some cases even years is not -- A Sure. Q -- as precise -- A Umh-humh. Q -- as it once was? A Yes. Q This was a long time ago? A This was a long time ago. Q And there are things that, that you may not be RIGGLEMr1N, TURK & NELSON CTR- I aI N U 4 ~'~.~5 8

175 perceiving in terms of its exact chronological order; isn't •that correct? A Correct. Q Now, I would like to focus again on the, on the two) 10 11 12 13 1 15 16 17 18 19 20 21 inhalation studies that comprise the major part of the Blue Book and the final report that you prepared. The first one was a study called CTR100 which involved 2A1 cigarettes, these were high tar, low nicotine cigarettes? A Correct. Q The mice %aere exposed for approximately twel ve to fifteen months? A I think that's right, eighty-eight weeks, is that what it was? Someth_ng like that. Q You would have to do the math on it. A Actually I don't remember it myself. I thought that's what I looked at last night to be honest with ycu. Q It was approximately half to two-thirds of a lifetime, -- A That sounds right. Q -- of a mouse lifetime? A That's right. RIGGLEIMAN, TURK & NELSON V I0I 1 I I 1 l 043559

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 I 176 Q Mice live about two and a half years, this strain of mice lived about two and a half years. In addition to the eiposure which involved havinc a group that were exposed to smoke, a group that were called sham exposed, they were put in the machines but not actually exposed and then a third group which : was the shelf control, - A Correct. Q -- in addition to thos~ three groups, there were also three groups which were treated with a chemical carcinogen, in this particular case methyl.cholanthrene; isn't that correct? A Correct. Q And the purpose of that particular study was what as opposed to just the simple smokir:g experiment? A It was an attempt at that time to see if we could somehow hasten or progress or alter the kinds of tumors that might be induced by a known chemical carcinogen by followup treatment with cigarette smoke, exposure to whole cigarette smoke. Q Were these essentially promotion tests? A Well, at that time it was thought to be promotion, RIGGLEMAN, TURK & NELSON v./ I R I I I I 4/• /, 1.M M.+' SrmP '..I'

177 10 11 12 13 1 15 16 17 18 19 20 21 I should say in retrospect now because hindsight is a hundred percent now, methylcholanthrene ob-liously is what they call a whole chemical carcinogen, it has initiating and promoting I activity itself. So it probably wasn't a great idea to have used that compound in an initiation promotion assay. Q At that time and I guess is still true today, a lot of people believe that cancer is at least a two-step p=ocess? A At least. Q Something initiates the mutation in the cell and in the cell's DNA which makes a tur,.or possible k.ut doesn't c-re-ate the tumor and then something else promotes it and causes it to grow to become a tumor? A Correct. Q That's a layman's overgeneralization. A That's fine. Q But it's a two-step process of initiation a:.d then promotion? A There are probably multiple steps in betwee:: there and subsequent to promotion as well. Q And wasn't part of the thinking behind this methylcholanthrene portion of CTR100 that this would test RIGGLEMAN, TURK & NELSON v.r~ T I 4 1 11 • 043 •rw~' Ld .i

178 1 whether mice who had had cancer essentially initiated through 2 the chemical carcinogen, whether exposure to smoke would 3 promote it, -- 4 A Correct. 5 Q -- would provide that second step? 6 A Correct. 7 Q Fnd that same format was used in the second 8 inhalation study, 101A, was it not also, only a different 9 carcinogen was used? 10 A Right. 11 Q Pnd in 101A, it was benzo(a)pyrene? 12 A Correct. 13 Q And lOlA was different from 100 in the sense that a 14 different cigarette was used; isn't that right? 15 A Yes. ' 16 Q 2R1? 17 A Right. , 18 Q In the second, the lifetime study? 19 A Correct. 20 Q And that 2R1 is a high tar, high nicotine? 21 A Correct. RIGGLEMAN, TURK & NELSON t.x f m~"~e i~ i'f S~ "'f' .~ v"~ C°'~D 2

179 10 11 12 13 14 15 16 17 18 19 20 21 Q Whereas in the earlier one it had been high tar, low nicotine? A Correct. Q In lOlA the animals were exposed for essentially their entire lifetime? A Correct. Q And according to your original proposal, the idea was to try and give them, although obviously there's let me withdraw that. some According to your original proposal, the plan was to try to expose them in a way that would be comparable to a. human smoker smoking three to four packs a day; isn't that correct? That was sort of the target analogy that was being sought? A That might be the case. Actually I don't remember the numbers so -- Q There was an attempt to try and translate -- , A To a sianificant amount of tar. Q Yeah, to translate the experience of a moderate smoker, human-wise, to a, to a mouse in terms of the exposure the mouse would have? RIGGLEMAN, TURK & NELSON CTR HN 04,3=563

180 10 11 12 13 14 15 16 17 18 19 20 21 A If I may -- Q Let me have an answer if I could to that question. Is that yes or no and then you can answer. A I can't -- ask the auestion one more time, then. Q The goal was to try and develop a mouse exposure that would be comparable, as comparable as you. coulcd muke it to a moderate human smoker? A Yes. Q And that obviously had some difficulties and pitfalls because you are not dealing with a human smoker, you are dealing with a mouse? A Correct, and that's actually what I wanted to say. We found it very difficult to figure out how to conclud-e-, how to measure that. Did you want to do it on per surface area on a lung because the human has a huge surface area as op:osed to the mouse, it's quite, it's quite different, or do you want to do it per lung or per wet weight. There was a variety of ways to try to compare that. We could come up with numbers that, know I can remember this, that changed from only a couple cigarettes' worth of tar per mouse was actually impinged as opposed to all the way up to, you know, two and three racks RIGGLEMAN, TURK & NELSON C;`TR I~IN 043*564

181 10 11 12 13 14 15 3.6 17 18 19 20 21 per day depending on the denominator that we used, per gram what weight of tissue or per unit surface area or per just total lung volume itself, total lung. So it was not clear how vie should come to that conclusion. We wanted to do more work or try to do some more analysis on that ended up doing it. and we just ne:*er Q But the reason you're going through all theSe calculations and all of these exercises -- A To try to make them as coraparable as we cou=d. Q Let me ask you, if you could -- MR. MERRITT: Off the record for a se.^_„nd.. MS. RAUF;R: Off the record at 3:26. (Discussion off the record). MR. P-IERRITT : Can you mark this as the next exhibit. (Document was marked Kour_. Deposition Exhibit No. MS. BAUER: Back on the record at 3:27. Q (By Mr. Merritt) I've just handed you a document entitled -- it has on the front to Microbiological Associates, and the first page is a February 28, 1984 letter from Carol RIGGLErLz1N, TURK & NELSON ~°~`R MN 0~~~~~~

182 Henry and Richard Kouri to Vincent LiSanti at CTR. Do you recognize this document? A Yes -- actually, I don't have the letter to Vince LiSanti, though. MR. MERRITT: Let:'s go off the record for a 10 11 12 13 14 15 16 17 18 19 20 21 second. MS. BAUER: Off the record at 3:28. (Discussion off the record). MS. BAUER : Back o.^n the record at 3: 2 9. Q (By Mr. Merritt) Do you recogni7P Exhibit 19 as the final report that was prepared for CTR Cont:ract 30? A Yes. Q This was a report that was written by you and Doctor Henry; is that correct? A Correct. Q And it represents the findings and a description of the methodology of the inhalation studies that were done, all , of the inhalation studies that were done under Contract 30 bv MAI? A Correct. Q Okay. Let me ask if you would look at Page 42. RIGGLEMAN, TURK & NELSON i..x TR { f N 0`"'f' 3SGL:.7

183 10 11 12 13 14 15 16 17 18 19 20 21 A Yes. Q This is the beginning of a section that deals with the first of the two inhalation'studies that we have been talking about, CTR100? A Yes. Q And this shows, does it not, that the study startecid in June of 1977? A Yes. Q And that study ran to completion? A To completion, yes. Q I mean both of these studies, both CTR100 and lOiA ran to completion; is that correct? A To their scheduled completion, yes. Q Now, the results of these, of the CTR100 were essentially negative in the sense that none of the animals that were exposed to the test cigarette that was being used that study developed any lung cancer; isn't that correct? / in A Correct. Q And with regard to the mice that were treated with methylcholanthrene, the mice that were smoked actually had less cancer, less lung cancer than the ones that, that were RIGGLEMAN, TURK & NELSON C T R I - I N 0 43 56 '1"

184 10 11 12 13 14 15 16 17 18 19 20 21 not smoked; isn't that correct? A I think that's true. I don't remember the actual numbers myself. Yes. Q So at least in terms of this one study which was not a lifetime study but was a long-term study, the results were negative in terms of the ability to create through smoke inhalation lung cancer in animals; isn't that correct? A Right, it was not -- however, I should say that that was not an endpoint to the study, that is cancer in the smoke exposed animals. We knew if we exposed animals for eighty-eight weeks, the probability of generating cancer we thought was going to be fairly small for a compound with a weak, with a potentially as weak carcinogenic effects as whole cigarette smoke. Q One of the purposes of the study -- A Just, just to check to see if we could find some. We didn't really expect to see much in that period of time. Q But on the 101A which was the subsequent study, -- A Correct. Q -- the full lifetime study, it was your expectation that you would be able to produce lung cancer in the animals? RIGGLErLAN, TURK & NELSON CTR HN 043~~GG

185 A We were trying, we were trying. Q Now, let me ask you to turn to, let me ask you to turn to Page 101. A Yes. 10 11 12 13 1 15 16 17 18 19 20 21 Q This is the portion of the book that, that describes the results of CTR101A; isn't that correct? A Correct. Q That was a study that was started in September of 1978 and concluded in approximately the middle of 1981? A I think that's right. Q Okay. Now, it was during sort of midterm of this particular study that CTR decided not to do any further inhalation studies; isn't that correct? A I think thar.'s right. Q And in fact, it was, there was a meeting in June of 1980 at the, of the subcommittee which was sometimes called the Executive Committee of the SAB that oversaw 4-AI projects at which the discussion was raised as to whether or not this, these studies should be continued; isn't that correct? A Is that the document we were talking about before? What document are you referring to? I don't specifically -- RIGGLEMIUN, TURK & NELSON U-67"R HI-A 0435GS4

186 Q Well, I will, I will see if I can refresh your 10 11 12 13 14 15 16 17 18 19 20 21 memory on that. (Document was marked Kouri Deposition Exhibit No. 20). Q (By Mr. Merritt) T- am showing you a document that' s been marked as Exhibit 20 which is entitled Ex.ecutiv=_ Committee and Contract Committee P!eeting, Friday, June 20, 1980, at 9:00 a.m., and consists of agenda and report. A Okay. Q Does that refresh your recollection that there was a meeting -- A Yeah, umh-humh. Q -- in June of 1980 at which the purpose was to decide whether or not CTR inhalation work with MAI should continue beyond 101A? A Correct. Q And you and Doctor Henry both came and made a presentation to the membzrs of the SAB that were present there? A Yep. Q And that was Doctor Bing, Doctor Feldman, Doctor RIGGLEhLi1N, TURK & NELSON CTR I`IN 043-1571"U"

187 Gardner, Doctor Jacobson, Doctor Meier -- A (Nodding head affirmatively). 10 11 12 13 14 15 16 17 18 19 20 21 Q -- and Doctor Sommers who would normally have been there was not present at that meeting? A Correct. Q You recollect that meeting? A Yeah. Q It's also true, is it not, that there were no lawyers present at that meeting? A I don't remember that. I don't think there was. I think actually it would have been here if there were. Q But there was -- Doctor LiSanti and Doctor Gardner were also there? A Yes. Q Do you recall that at that meeting one of t~_e issues that was perplexing the SAB was the fact that the continued, the third inhalation study that was going to, that you and Doctor Henry wanted to perform was going to require an additional four and a half million dollars of CTR funds; do you recall that dollar amount being your estimate? A That sounds right. RIGGLEMAN, TURK & NELSON 4.l I r I ! 11N 0I35•/ 1

188 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q Okay. And it was going to require a three-year commitment on the part of CTR? A Correct. Q And you recall, do you not, that in the months prior to this meeting, there had been some concern expressed by CTR over the fact that MAI was coing to either have to renew its lease and require CTR to commit to a full three years or it was going to have to move animal:- to a different laboratory because its current lea:e was ending? A A Umh-humh. Do you recall that? Umh-humh. Q You recall that there were some people at CTR that were somewhat upset about that because they didn't learn about it until February of 'that year? A Right. Actually so did I, I was upset as well. Q Because you hadn't learned about it? A I hadn't heard it either. Q In fact, the CTR had, a good portion of what CTR had invested in these studies over the year had been spent in fitting out about eight thousand scn:are feet of MAI RIGGLEMAN, TURK & NELSON C T R V-4114 0 4 -3 Si~r "2

189 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 laboratory? A Correct. Q Do you recall also that there was concern expressed at this meeting about the possibility that a third inhalation study would only produce a necativ:• result, in other words would not succeed in producing what some people on the SAB felt was the intended hope which was humanlike lung cancer? A I don't remember that. That could very wel'L have been a concern. Q Okay. Wasn't, wasn't _r- in fact the case that a lot of people at CTR wanted an ar._ mal model that would produce not just lung cancer but squamous cell carcinoma? A It never was stated that way. Q Well, isn't it -- squa«:ous cell carcinoma was as o` this time the form of lung cancer that was most commonly associated with smoking in humans; isn't that right? A Bronchogenic squamous cell carcinoma. Q But squamous cell carcinoma? A The only reason I make a difference here is that the mouse doesn't get the same kind of squamous cell carcinoma that a human gets, that it's purported that humans get in RIGGLEMAN, TURK & NELSON CTR MN 043573

190 1 2 3 a_ 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 exposure to cigarette smoke. So squamous cell carcinoma was just a type of tumor that represented, that certain of the cell types in a mouse, you know, could become carcinogenic. I don't think it was anything unique that it had to be cigarette smoke that caused that effect or not cigarette smoke. We knew we weren't going to get bronchogenic sauamous ce11l carcinoma anyway because that mouse didn't get it. Q But the mouse did get squamous cell carcinoma? A Right, but it got it in the wrong spot from a human point of view. Q But it got squamous cell carcinoma? A Riaht, it just happened to get it in the wrong spot. That means the physiology is different enough to not to get, that it's not really comparable, but we had to live with that. Q Now, as of the time that this meeting took place in June of 1980, the ongoing lOlA which was then about a year and a half into it had not in fact produced any lung cancers that were associated with smoking; isn't that correct? A And we didn't expect any. Q Well, whether it was expected or not, the tumors RIGGLEMAN, TURK & NELSON CTR MN 04~~574

191 10 11 12 13 1 15 16 17 18 19 20 21 that were being produced by the study at that point, and there were some, were not tumors that.you regarded as associated with smoking? A No. Q So the results -- A No, I meant I dor.' t think I agree witl-i that comment. Q Okay. A At June of 1980 from my recollection, that's about the same distance that the original study with the 3A1 or the 2A1, the low alkaloid cigarette went. Right? So we already knew that up to this time that smoke alone was likely not going to cause a biological effect of and by itself. I think you will even see in the agenda here that the experiments that are being updated are Experiment 100, female mice 3MCA 2A1 and 100 female mice benzo(a)pyrene 2R1. In other words, we had data on the carcinogen induced tumors but we didn't have any data on the smoke alone. In fact, we didn't expect to have any. So this decision not to continue was done before we knew we did or did not have a biological effect on cigarette RIGGLEMAN, TURK & NELSON CI I 9 I /N 04 3 {pt" / 5

i 192 1 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 smoke exposure in these animals. Q So it's your testimony that the decision could not have been affected by a concern one way or the other about the results? A Correct, we didn't know, we didn't have them yet. Q And the decision was nort to stop lOlA but to sim}:ly not do the next one in line which was 1, would have been called 101B? A Something like that, yes. Q So it certainly was not the SAB's concern about what the results of 101?1 were that motivated them -- A Right. Q -- because they were going to allow lOlA to continue to completion; isn't that right? A As a result of this meeting I would say yes. Q And in fact it did, CTR did, even though CTR decided not to do a third study, not to do 101B, it allowed lOlA to continue to completion sometime the following year? A Right. Q And at that particular time the results were known but the results were not known when the SAB made its decision RIGGLEMAN, TURK & NELSON CTR HN 04~~57`6

193 10 11 12 13 14 15 16 17 18 19 20 21 in June of 1980? A Correct. (Document was marked Kouri Deposition Exhibit No. 21). Q (By Mr. Merri:t) Doctor Kouri, before you look at that, I don't want to hG-ie you read that cover to cover right I now. Let me go back to a question 1 asked you a few minutes ago. Isn't it a fact that in your original proposal for 101A, you were assuming that t::ere would be approximately a two percent squamous cell carcinoma incidence in the smoke exposed mice versus a zero incidence in the nonexposed mice and that that was the assumption upon which you made certain projections? A You know that sounds right, I actually didn't remember that until you -lust said•it but I recollect that that's generally what we had hoped. Q That was important because at least to some people at CTR, the fact of squamous cell carcinoma was important because that, although in a different location, is the type of carcinoma that human smokers get? A Human smokers get alveologenic adenocarcinomas to RIGGLEIN!AN, TURK & NELSON CTR MN '`.~4~~.~"'°~ 7~."

194 1 almost the same extent, just slightly smaller than 2 bronchogenic squamous cell carcinomas. 3 The two kinds of tumors that we're describing here 4 are sauamous cell carcinomas and adenocarcinomas. The two 5 most prevalent tumors in humans, when exposed to cigare=te ; ~moke, are in fact squamous cell carcinoma and adenocarcino-:a, 7 and the third one is called oat cell carcinoma. Mice do no-_ 8 get oat cell carcinoma because they do not seem to have the 9 equivalent of an oat cell. They get, they can get squa:nous 101 cell carcinoma and they can get adenocarcinoma but theV do??' t 11 get it in the same location that humans get it in most often. 12 So there are two smoke associated tumors in humans, 13 adenocarcinoma and squamous cell carcinoma. It is true that 14 there are slightly more squamous cell carcinomas in hu--=ns 15 than there are adenocarcinoma, but in general there micht be, 16 say forty percent are squamous cell and twenty-five percent is 17 adenocarcinoma or something like that. I mean, I could be 18 wrong by a little bit but you could look it up. You'll see 19 it. 20 Q But Doctor Kouri, going back to when this happened 21 in the late 1970s, isn't it a fact that a lot of people didn't RIGGLEMAN, TURK & NELSON (.+ f R W'f 0""f'3"578

195 10 11 12 13 14 15 16 17 18 19 20 21 believe that adenocarcinomas were associated with smoking in the 1970s as opposed to what you may have heard or read since that time? A It would, it was about that time in which that -- now we' r_ e talking about within a c;,up].e of years. Let' s say at that time, early eighties was _.. fuct the realization th.Gt a variety of tumors were associc.ted, lung tumors were associated with exposure to smoke. Now, we can go back in literature and look it up, and I would, I would bet that about '80, perhaps even earlier there were articles in the literature that showed correlations between whole cigarette smoke and incidence of adenocarcinoma. Q But isn't it a fact that it wasn't until into t;:e eighties, several years into the eighties that the Surgeon General for the first time identif_ed adenocarcinoma as something that was associated with smoking whereas sa_uamous cell had been thought to be associated with smoking for decades; isn't that right? A I can't answer that. I don't know. Q And in fact, when you made your projections for this study, you were assuming that you would get a two percent RIGGLEMAN, TURK & NELSON G T R M N 0 4 - 3" 5557 9

196 10 11 12 13 14 15 16 17 18 19 20 21 difference in squamous cell carcinoma between the smoked and the nonsmoked mice? A Fine. I didn't remember the numbers but okay. Q Isn't it a fact that there were scientists on the SAB for whom sauamous cell carcinoma was really the target type of carcinoma for an animal model? A I don't know that. Q Let me -- isn't it a fact that in your reports that you were giving to CTR, your interim reports during 1980 and 1981, the only carcinomas that you were seeing in the mice, in the smoked mice or in the sham exposed or control mice were adenocarcinoma? A Correct. Q And that these are tumors that in fact are expressed spontaneously by mice even if you do nothing to them? A Correct. Q And in fact, approximately five percent of the mice that were just sitting on the shelf in the lab and that weren't having anything done to them were getting adenocarcinoma? RIGGLEMAN, TURK & NELSON CTR HN 0435-80

197 A Correct. Q These are called spontaneous tumors because they -- A They had no etiology. Q Nothing has to be done to the mouse for them to 10 11 12 13 14 15 16 17 18 19 20 21 have it, they get them essentially genetically; isn't that ~ ~ right? ` i A Correct. ~ i ! Q Isn't it a fact that you consistently referred to ( these tumors throughout the period off time in which you reporting on the results of 101A as nor_ associated with smoking? A Pardon r;;e? were Q Isn't it a fact that you consistently, durir.g the course of lOlA when the mice were beginning to get adenocarcinomas, described them in your own reports as tumors that were not associated with smoking? A I guess I would have to see that. Q Well, -- A No, I don't remember ever stating that. I mean, I don't remember making that statement. If I did, I wouldn't have known why we did that. We didn't know what was RIGGLEMAN, TURK & NELSON i.r f f"s. HN 0'."i° 3:...~ 8-31

198 10 11 12 13 14 15 16 17 18 19 20 21 associated with smoking and not associated with smoking. Certainly when it came on earlier, that would have been even if I had done it, I would think it would have been premature to say that this was or was not associated with smoking. Q But in fact, isn't it true that neither you nor Doctor Henry nor anybody at C"!'F, thought that adenocarc:_nor.iGs were smoke associated or smoke related? A Absolutely not. Q So you wouldn't have ever described them as not smoking related in your reports; is that right? A I -- if I did, I don't think I should have : ecause I don't know that. In fact, I don't even know that now. MR. MERRITT: Next exhibit, please. (Documents were marked Kouri Deposition Exhibit Nos. 22 and 23). (Witness reviewing documents). A Yes. Q (By Mr. Merritt) Let me ask you if you would, Doctor, to look first at Exhibit 23 which is a May 9, 1980 RIGGLEMAN, TURK & NELSON VF TR I 1 I I 04,3582

199 10 11 12 13 14 15 16 17 18 19 20 21 letter report to Doctor Gardner signed by Richard Kouri and Carol Henry. Do you recognize this as a report that you prepared to the SAB or I beg your pardon, a report that you prepared to CTR on or about May 5, 1980? A It looks to be, yes. Q This was in fact jus_ a few weeks before t'r:e Jur.e 1980 meeting of the Executive Co-mmittee that we were talking about a few minutes ago? A I guess that' s richt. Q This was in fact the most recent status repcrt ore the progress of 101A as of' the t:.r,e the SAB made its decision; is that correct? A I'm sorry? Q This would have been the most recent report on the status of lOlA as of the time -- A No, we presented it then at that meeting, t::e mc-st recent. Q Prior to the, prior to the meeting. A Oh, yes, this would have been the one in frcnt of it. Q Now, as of the time that this report was prepared, RIGGLEMAN, TURK & NELSON Cf+R i f f"f 0435A83

200 10 11 12 13 14 15 16 17 18 19 20 21 if you would look on Page 3, you were seeing in the mice some adenocarcinomas, isn't that correct, at least one at that point? A Where are we? Q On Paragraph 4, do ycu see that? A Yes. Q Yet you reported, did you not, in Paragraph 3 above that the only smoke associated lesions observed are low levels of PAMA and congestion; -- A Umh-humh. Q -- isn't that correct? A Right. Q PAMA being pigmented alveolar macrophage accumulation? A Right. Q And that's not a form of cancer, right? A Correct. , Q That's -- nor is lung, nor is congestion a form of cancer? A Correct. Q In fact, you went on to say that there were no RIGGLEMAN, TURK & NELSON CT R 111 H (D 4 -3 r-58 4

201 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 malignant lung lesions had been observed in either the smoke or sham animals at that point. A Okay. Q But the fact was that there was adenocarcinomas at that point which you did not regard as a smoke associated lesion; isn't that right? A I guess what we're talking about here is a matter of semantics. .Therz was one tumor found, and I'm sure that wasn't statistically significant from zero. Q You found one tumor and that was -- A I don't even know where it was. Q But it was an adenocarcinoma, right? A It was an adenocarcinoma, at least that's what it says here. I don't know what the data are so it's tough to say what that refers-to. Again, this is taken out of a context of having described these data at length previously and then this was a summary of those data and I don't have the data in front of me so I don't know what that refers to. In fact, that could have been on the shelf control for all I know, right? Q Well, it's your report, not mine. RIGGLEINLAN, TURK & NELSON CTR VIN 043..,~ 8....lr

202 ! 10 11 12 13 14 15 16 17 18 19 20 21 A Well, I can't tell from this. Q Let me ask you now to look at Exhibit 22, this is a few weeks later. A Yes. MR. SCHEINER: Let's go off the record for a minute. MS. BAUER: Off the record at 3:54. (Thereupon, a short recess was taken). MS. BAUER: Back on the record, 3:56. Q (By Mr. Merritt) Let me refer you to Exhib_z 22 which is a progress report for CTR-30 for the period September 1, '79 through August 31, 1980, which has been marked as Exhibit 22. Do you recognize that as the status report for the inhalation studies that were prepared, that was prepared in, in or around August or September of 1980? A Yes. Q This is several weeks after the document you just testified about? A Right. Q As of this particular time, if you look at Page 40, the mice that had been exposed to smoke had a total of six or RIGGLEM.3N, TURK & NELSON i,.r f~~'~.f i~ f~ f"~ '"f' 3~~ Lv.f 6

203 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 had a total of three adenocarcinomas, isn't that correct, at that time? A Yes. Q And if you look back on, at Page 3 in the text you find there were in fact a total of six lung carcinomas that were observed in both the smoke and sham exposed animals? A Correct. Q You can also -- and these were adenocarcinc~::as or ones that are described irn your terminology as AAC; isn't that right? A Correct. Q That stands for alveolar adenocarcinoma? A Correct. Q Now, in fact, as of that time, even thouah t:ere were six lung carcinomas, six adenocarcinomas among bc=^ the smoked and the sham mice, you nonetheless said, quote, the only smoke associated lesion observed to date has been the accumulation of pigmented alveolar macrophages or P.PLML?; isn't that right? A That's right. Q So as of the time you wrote this report in RIGGLErLAv, TURK & NELSON CTR HN 043587`

204 1 2 3 a 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 September of 1980, you did not regard those adenocarcinomas as smoke related? A No, that's not what it says. It says the only smoke-related lesion observed was PP1'4As, I agree with that. What we found is there was the same number of alveologenic adenocarcinomas in the sham as there were in the treated so therefore they were not smoke related. That does not say that alveologenic adenocarcinomas are not smoke-related, it just happens to state that those two were not significantly different from a statistical point of view and therefore they weren't a smoke-associated lesion. Q So -- A Up to that time. That's all it says. So you were doing a statistical analysis and comparison on these things as you went along in, in -- A I don't think you had to when you see 2, 2 and 3 for the noncompressing nodule, this is the ANCN, the compressing nodule, ACN, and the AC are all these AACs. You can see -- we had a tendency to lump these together. We didn't know it at the time but later we proved that those particular kind of lesions could progress to overt RIGGLEMAN, TURK & NELSON (rx f R Hf "f 0432515138

205 10 11 12 13 14 15 16 17 18 19 20 21 alveologenic adenocarcinoma and you could see the 2, 2 and 3 was obviously not a difference between 2, 2 and 3. So I don't think it took much of statistics to figure out that those were not statistically significant and therefore they were not a smoke-associated lesion. Q Well, except -- A At that time. Q -- you don't say anywhere in this paragraph that your conclusion that they're not smoke associated is based on their relative comparison. In fact, you don't even mertion in this paragraph -- A That's true. Q -- the numbers for the smoke and the sham? A That's true. Q You simply say that there have been six lun_r, carcinomas which you know to be adenocarcinomas but you don't consider them at that time to be smoke associated? A Correct. Q I take it there was also at this point in time no squamous cell carcinomas; isn't that right? A Correct, although it would have been here. Well, RIGGLEMAN, TURK & NELSON r.~ f f"~ i f f'~ ;. "~' 3589

206 10 11 12 13 1 15 16 17 18 19 20 21 yes. We did not find it. Q Let me now -- mark this. (Document was marked Kouri Deposition Exhibit No. 24). Q (By Mr. Merritt) Moving ahead several months, I am now handing you Exhibit 24 which is a progress report for Contract 30 prepared by Carol Henry and a number of other doctors, including yourself, dated March 15, 1981. A Correct. Q And I wculd like to direct your attention to Paragraph, to Page 1 of this document. A Umh-humh. Q You reccgnize this as a progress report that you submitted to CTR in about March of '81? A It souncs right. Q Now, once again, you recite, do you not, in the second sentence of the bottom paragraph on Page 1 that the only smoke-associa-Led lesion observed to date has been the accumulation of pic:lented alveolar macrophage or PAMA? A Correct. Q You alse note at that point that eight alveolar RIGGLEhL11N, TURK & NELSON CTR N0•3-b.. ~".

207 10 11 12 13 14 15 16 17 18 19 20 21 adenocarcinomas have been observed in the smoke group compared to only two in the sham exposed group. A Correct. Q So at this point the smoke animals had four times as many as the sham exposed? A Right. Q Which is more than the final total that you, is a higher percentage difference than the final describe in your s1CI article? A Right. total as you Q And yet you still did not describe those adenocarcinomas as smoke related? A They were not statistically significant differences, those numbers, so therefore they were not smoke associated. Q Even though they are adenocarcinomas and there is a clear difference between the smoke and the nonsmoke group. A Right. Q Isn't it a fact that you didn't regard them as smoke associated because adenocarcinomas were not generally regarded as smoke associated in 1978 and '79 -- RIGGLEMAN, TURK & NELSON CTR I~1N 0435'.31

208 1 2 3 4 5 6 7 8 9 10 11 12 17 18 19 20 21 I A No. Q -- and 1980? A No, at least I think we stated exactly this way because we didn't know what was smoke associated and what was not and rather than a preconception, we would not state that they were different or smoke associated unless they pYoved statistical significance. We were trying to -- these are very difficult studies here. These are snapshots of a very complex s:udy done for a long time and we didn't even know exactly rcw we were going to be able to analyze the data because -- again, you're going to -- this study is, was a very complex s-udy, it was designed in mind to shake dowrr the equipment for a lifetime study. An ancillary objective with this experiment was in fact to see if we could keep enough animals lor_c'enough that they could possibly express some disease phenotypes that might be associated with lung cancer, with smoke expos--,re a~d especially in the lung itself. So we didn't know what to expect actually, and so up front I think it would have been -- I mean, even if we had said it right now, it would have been premature to call RIGGLEMAN, TURK & NELSON CTR I'IN 0 4 ~~C -4 20-

209 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 things -- the only reason why it was smoke associated, the PAMAs, is the only PAitiIAs virtuall j we ever found were on smoke exposed animals and it was pretty obvious that the smoke was going where we wanted it to go so it is indicating that it was there. But in terms of the actual tumors -- as a matter o= fact, in retrospect, I probably -- iL says fibrosarcomas, don't know what the data are here, I guess maybe it but there miaht have been already more fibrosarcomas in the smoke associated group than the sham. Again, we didn't call that at this time smoke associated, we didn't know, but in retrospect when we actually analyzed the data, you know, virtuallv two years after this, those fibrosarcomas were highly significantly associated with smoke exposure. We don't kncx why necessarily but they are. But we didn't have .preconceptions, we didn't try to make conclusions before we had all the data in front of us. At least I tried not :.o. Q Isn't it a fact that the reason you didn't regard adenocarcinomas as smoke associated at this point in time was that the animals sitting on the shelf that hadn't been exposed to any smoke at all were getting them at the rate of almost four percent which was three times the rate that the smoked RIGGLEMAN, TURK & NELSON CTR HN 043593

210 10 11 12 13 14 15 16 17 18 19 20 21 animals were? A No, no, I'll repeat, your beginning statement there is incorrect. We didn't have a preconception of what was smoke associated and what was not. So I didn't care necessarily what it was, and the sham, the shelf animals we knew was an inappropriate control for any experiment here because they were virtually a different species by that ti,;,e because they were already growing at almost twice the rate as the, both the sham and the shelf. So that they were fed, you know, chow ad libitum, whatever they wanted, and so therefore they were pretty fat and happy and we knew that those animals were going to be a very difficult group to try to compare at all but we felt we had to keep that particular group of animals as a control anyway because somebody was going to ask us why didn't we just keep some on the side. We knew that wasn't an effective comparison and never assumed we were going to compare the sham and the smoke groups to the shelf, at least not from a smoke point of view. The correct control was sham, and that was it, not shelf. Q But you did have a shelf group? A Of course. RIGGLEMAN, TURK & NELSON CTR HN 0435`94

211 10 11 12 13 14 15 lo' 17 18 19 20 21 And the shelf group was in fact mice that had not been exposed to smoke? A Correct. Q They were sitting in cages on a shelf somewhere in the laboratory? A Correct. Q And they cot adenocarcinoma at the rate that mice genetically get it s:or.taneously; isn't that A Correct. right? . Q That rate almost from the beginning of this study was always higher than the rate that you saw either in the smoked or in the shar-.; isn't that correct? A I don't kTow that. I don't think I ever did the analysis. Q It certai-lv was the case as of March of i9S1 when you submitted this reoort; isn't that right? A Well, you said it might have been for that. Q Isn't that right there in front of you, 3.8 percent? A Right, I've said before we''ve never made a comparison between shelf and sham and smoke because it's an RIGGLENILkN, TURK & NELSON CTR HN 0435-9.5

212 10 11 12 13 14 15 16 17 18 19 20 21 improper comparison. Q Isn't that what you're doing, aren't you in fact comparing them right here in Exhibit 24, you say 8, parentheses, 1.4 percent, alveolar adenocarcinomas have been observed in the smoke exposed group compared to 2, parentheses, .5 percent, and 6, parentheses, 3.8 perce:::, for the sham exposed and the shelf control groups respectively. A Right. Q Aren't you in fact comparing them? Aren't you fact comparing them? A Yes. Q And isn't it -- in fact, the comparison sho;:S that the shelf control group are in _act getting substantially mcre of these adenocarcinomas, these spontaneous group -- A I can't conclude that. Q before -- You need to let me answer, finish the question A I'm sorry. Q Isn't it a fact in this very sentence where vou compare them, the shelf group are getting them at the rate of almost four percent and the smoked are getting them at only a RIGGLEMAN, TURK & NELSON CTR MH 043596

213 10 11 12 13 1 15 16 17 18 19 20 21 little more than one percent; isn't that a fact as you have written in your own words in this document? A Correct. Q Okay. MS. EAUER: This ends Tape No. 2 of the deposition of Doctor Kouri. The time is 4:08 p.m. (Thereupon, a short recess was taken) (Document was marked Kouri Depositicn Exhibit No. 25) . MS. BAUER : T:r i s i s Tape No. 3 of the deposition of Doctor Kouri. The time is 4:23. Q (By Mr. Merritt) Doctor Kouri, I've put in =ror.t of you Exhibit 25 which is a one-page document with 13th International Cancer Congress at the top, Official Abstract Form. Do you recall going to a meeting of the InternationG_ Cancer Congress in September of 1982 in Seattle, Washir_aton? A Q A Q No, I didn't go. Doctor Henry went? Right. And this is a meeting that is periodically held for scientists in, in the international medical and biomedical RIGGLEM.AIN, TURK & NELSON CTR ~N 043,--59- ~

214 10 11 12 13 14 15 16 17 18 19 20 21 research community who are involved with cancer research; is that correct? A Correct. Q And the document in front of you is an abstract that was to be displayed at this meeting as a poster that was prepared by you and Doctor Henry; isn't that correct? A Yes, I think Doctor Henry did it. ~ Q But you certainly agreed, she certainly consulted ~i t with you before -- I A She must have shown it to me, yes. Q This would in fact have been the first public statement of tre results of the 101A inhalation studies; isn't that correct? A Umh-humh. Q This was in fact a statement that was being made to the scientific community and in particular the scientific community involved with cancer research? , A Umh-humh. Q And this was done after, in fact significantly after the completion of 101A; isn't that correct? A What's the date of this? RIGGLEMAN, TURK & NELSON C T R M N #~.0 43 '5- .9. 13

215 10 10 11 12 13 14 15 16 17 18 19 20 21 Q Do you know? A Do I know? No, I don't know. I was asking. I guess it was supposed to have been there before December ist, '81. Okay. Q This was after the completion of the exposure of the mice in 101A? A A Just about that time, isn't it? Well, wasn't the -- . Actual ly 7 co_^.' t remember the numbers right -ncw. Q Wasn't the final report originally sc:^eduled for delivery in December of 1981? A Ri ght, but I thin'.{ we had animals st.i l1 on test ar:d we certainly didn't complete all the pathology by then or all the analysis. Q You had enouch information* that you were willing to go to the scientific ce-:-runity and tell them things which you assumed you had some basis for telling them, right? A Right, these are preliminary data. Q It doesn't say anywhere preliminary, does it? A That's what abstracts are. Q But it doesn't say anywhere preliminary? RIGSLE,Nt:kN, TURK & NELSON C ~"~* ~~N ~~~~ "~~ C.39

216 A That's what abstracts are. 10 11 12 13 14 15 16 17 18 19 20 21 Q Okay. But my question to you is does it say anywhere that this is preliminary? A That's what abstracts are. Q Okay. We can do this for a long time but I'm entitled to an answer to my question. Does t1his c'.ocumeat that's been put in front of you, Exhibit 25, say anywh~=e these results are preliminary? Does the word prelim:.nG:y appear anywhere in this document? t Za l.. A No. i Q This was admitted -- I am not trying to make yo Iu say that this is a peer reviewed article. A Right, that's what I meant. I Q This is a poster, it is an abstract? A It is a preliminary observe, it's a prelimi--ary exnosition of the data as it existed at that time. Q And it's not a statement that one'makes wit:out any sort of basis; isn't that correct? You just don't tell the scientific community, whether it's in a poster or anything else, something that you don't think you have some basis for saying? RIGGLEMAN, TURK & NELSON •.rwr I R ! wI I I 043600

217 10 11 12 13 1 15 16 17 18 19 20 21 A Sure. It's a snapshot of the data at that time. Q Pnd at this point, according to this thing, over fifteen hundred mice were evaluated? A Yes. Q Isn't that what it sals: A Yes. Q That's substantially a?1 of the mice that were evaluated in the study; isn't that correct? A I guess. I actually don' t know. I don' t have the numbers in front of me. I can't ccmoare that but that sounds right. Q Wasn't it a fact that this particular abstract .tias submitted, was something that you and Carol Henry and CTR people were aware of and discussed the appropriate ti:ning and isn't it a fact that this was not done until in fact th.e exposure and the examination of the mice was completed? A I think the examination of the mice histopathologically was done, obvicusly not all of the analysis for statistical significance, all of the data had not been analyzed in '81. Q Okay. But it had been analyzed enough that you RIGGLEMAN, TURK & NELSON C.a f R f fN 04-~,:'~ ~'~ S,.A ,f,

218. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 were comfortable going to the International Cancer Congress and presenting the information that you present in this document; isn't that right? A Correct. Q One of the things that you say in this document was that, the only smoke-induced lesion was an accumulatiorn of: pigmented alveolar macrophages which again is our friend PA.NLA; isn't that right? A Correct. Q That's w.nat you say.there. You go on to say the incidence of spontaneous lung cancer, parenthesis, alveolar adenocarcinomas, end of parenthesis, was approximately five percent. A Right. i.e., Q So even as of the date that this was done and presumably even as of the date that this poster was displayed to the scientific community in 1982, you did not regard , adenocarcinomas as smoke related? A As statistically associated with smoke exposure, that's right. The}• are not, they weren't, at least I didn't think they were at that time. RIGGLEMAN, TURK & NELSON C/ / 1 / l / I `wI' / ,3•ru1 0i4w L

219 Q And even as of the time that this was done, you 10 11 12 13 14 15 16 17 18 19 20 21 felt in a one-paragraph abstract that it was important enough to tell the scientific community that the incidence of spontaneous lung cancer, the adenocarcinomas that the mice get just by virtue of being mice, was five percent, and you further go on to say that exposure of smoke failed to alter this tumor incidence? A Correct. Q Those are your words? A Correct. Q You furtrer go on to say that although exposure to smoke in this model resulted in significant changes in short term endpoints, no carcinogenic effects were noted, those are your words; isn't t~at correct?. A Right. w:at I'm saying all the way along here, these abstracts are snapshots of the data as we interpret and analyze up to that time. I think the thing -- instead of focusing on a set of interim reports that were incomplete both in terms of their analysis, their review and their conversations -- I mean, I mean the final -- like you say, an abstract in fact is a snapshot of what was going on. The RIGGLEbLAN, TURK & NELSON G T Fe I'LIN o 4:~G 0 3

220 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 final report in terms of what hit the literature is peer reviewed and we cari argue about what we need to argue about I think in terms of this is the final report that went into the JNCI. I mean, these other thincs are taken out of context and which we didn't have all the, it seems like we did not 1have all the data. We haven't cFrta:nly analyzed aJ.7l tre d=-.--a to date. We were in the process o: analyzing the data at that time, one point. The second point is I am not sure right now, one sends these abstracts in, you know, fairly early on and you make them nonspecific as best you can and I don't have any real idea what data was actually presented at the meet=ng. Often one presents the data and says I'm going to present s:,me data and you present what you actually have at the time as opposed to what you literally sa_d here because you didn't have that at that time. That's the whole idea. This _s what it looked like at whatever this date might have been in '81 and when we finally went to the meeting, some other data might have been presented. I actually don't even remember wi:at was presented. In fact, I didn't go, Carol went to this meeting. But I will say that when you finally look at all RIGGLEMAN, TURK & NELSON CTR 1 / IN 04,3604

221 10 11 12 13 14 15 16 17 18 19 20 21 the data, analyze the data, this is what comes out of it, of which we all agreed, CTR and ourselves, that these are the good summary of the best est_mates of what we could come up with when analyzing these studies, riot these interim reports which are difficult to interpret in view of the fac;: t:at they were just looked at as snaps:ots c= that experImc.zt st...:; as it was unfolding. We did not know how to analyze all ':zese ' data until we got it all out. and we could sit back for -nayh,e f I I six months and try to understand v:::at it might be toll_ng us. It's a big study, and it was dor.e -- and we tried to do a variety of methods, that we ;aere continually trying t;: a:^av::e~ this data. I think it's a little bit unfair to take a^ic like this and hold my feet to the fire that this is in fact what we meant. This is in fact what we meant. Q Well, and that was in fact what was publis'~ed? A That's the only thing that counts. Q And CTR didn't prevent you from publishing that? A Exactly. This here is just what it is, it was an interim piece of information and it says alveologenic adenocarcinomas were not smoke associated which is in =act at that time the data would seemingly suggest that that w:s the RIGGLEMAN, TURK & NELSON Cf R f f f`f 04364.d 5

222 case, they were not smoke associated. When we actually got in there and did the analysis and compared apples and apples and oranges to oranges, we could find conditions in which there was a statistical significantly difference between adeno, the incidence of adenocarcinomas in the smoke versus the sham and that's what we said. Now, that doesn't mean that this was, that this - 10 11 12 13 14 15 16 17 18 19 20 21 all that meant is that this was the information we had at the time and this was the information that f_nally came same data when we finally sat down and out of the analyzed it. I think -- I don't even know, maybe we actually presented this data, these data, that is the data that made up the JNCI paper, at the actual meeting but I don't know. I actually don't remember. That was fifteen years ago. But I know what abstracts are and abstracts in general are not peer reviewed publications, they're, you know, as best we can get an ability to take a snapshot and tell some people what data looked like right now, currently. Q Okay. Do you have any reason to believe let me withdraw that. RIGGLEMAN, TURK & NELSON that - CTR I7N 04ti..p 1,~ C)iAnA

223 I'm not trying to hold your feet to the fire on 10 11 12 13 14 15 16 17 18 19 20 21 this. Did you read Carol Henry's deposition? A I read it. Q Do you disagree with her testimony that at the timel that this happened, that a lot of peoplp ic'.t that adenocarcinomas were not smoke associated? i ~ A No, I didn't remember that but okay. ; i Q Isn't it a fact that there were scientists, i including peotile like Doctor Sommers, who didn't believe that adenocarcinemas were, or didn't believe that the scientific record was t-ere to establish that they were smoke related? A I don't remember that but that might be the case. Q And so isn't it in fact a fair statement or let me phrase it di:ffferently. Are you saying that it would be unreasonable or improper or unethical for Doctor Sommers to have stated, taken the position that squamous cell carcinomas were the only associated lung cancers as of the time that this was happening, meaning in the early eighties? A No, I don't think we knew that. Squamous cell RIGGLEMAN, TURK & NELSON smoke CTR W-1 04~60'?"

224 10 11 12 13 14 15 16 17 18 19 20 21 carcinoma was definitely not the only smoke-related lesion in humans in the early eighties. There were a variety of cancers that were associated with cigarette smoking in humans. I Q Do you think -- so it's your testimony that it would be unreasonable for a scientist looking at the five percent rate of spontaneous expression of these adenocarcinomas to say that they're not smoke associated for that reason? A Right, I would say it's improper to come to that conclusion. Q Because you disagree with it? A I just said it's improper to come to that conclusion because you didn't hac,e -- these are the data that we ought to be arguing about, not those, because these are the data that we eventually all agreed made sense regardless of what went on before, what we thought before, we didn't think alveologenic adenocarcinomas were or were not associated with cigarette smoke up until that time. I mean, I think it's unfair to worry about what happened before when we actually sat down, did the analysis and in the cold light of day do those sorts of comparisons and we all sat in the room and RIGGLEMAN, TURK & NELSON CTR I-IN 04,3608

225 concluded that they were in fact -- Q But that document that you're waving, the JNCI article, was not written until 1985. The issue is whether somebody prior to that time might have taken the view reasonably and legitimate].y that the failure to find any squamous cell carcinoma was a significG,at findin;r, evel thougrh there were adenocarcinomas noted: A All I want to say,'I wa:: answering your quest_on 10 11 12 13 1 15 16 17 18 19 20 21 when you said ciidn' t you think Doctcr Sommers had i:h.e right to write down so-~.,amous cell carcinoma wa s sn,cke associated in that passage o` this book, that's in '84. My answer was no, don't think he had the right to answer that question bec=use we didn't know that for a fact it was or was not the only smoke-associated lesion and in fact the data in here unequivocally showed that there was another tumor that was in fact associated with smoke lesions and it eventually was in that data. These data and these data are identical. Doctor Sommers chose to read the data and make a statement about there is no smoke-associated cancers in here when in fact that is an improper conclusion. RIGGLEMAN, TURK & NELSON CI I! I I I 7 04,3609

226 1 2 3 g 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Q He didn't, he didn't say that there was no smoke, he said there was no squamous cell carcinoma. A And he said that the incidence of cancer, the total incidence of cancer in the smoke and the sham were not different. Q Were not significantly different, isn't thut what he said? A That's richt, and that's -- Q Isn't tha: a fact? A That is r_ot a fact. Q In fact, at the .05 confidence level, there was no difference between the s<<,oking and the sham exposed mice; isn't that correct? A No, that is not. Q Okay. A-_c: where do you -- let me withdraw that. A Let's reau the paper. The paper in 1986, which comes out of this paper here, I just happen to know where it is, it says the final incidence of seven lung cancers all alveologenic adenocarcinoma -- the final incidence of seven lung cancers all AAC in four hundred seventy-four smoke exposed mice comparz~3 to zero lung cancers in two hundred RIGGLEMAIN, TURK & NELSON CTR MN 043610

227 seventy-two sham exposed mice was significantly different. That's .04. Q Where is that? A That' s what it was. 10 11 12 13 1 15 16 17 ls 19 20 21 MS. NIP?•. What page he is 1.ooking for. THE Tr'iIT:'JESS. I'm sorry, _t e ra,J= -- r:y page II doesn't have, it's Page 9 of the fax. MS. NIAL: The fax you sent Q (By Mr. Merrit'L) Are you rea~:ing fy-om a chart or are you reading from -- A I'm reading from the text. Under discussion. The numbers are .04 coming from here but I can't remember where ~itt is here. Q Tell me, in fGct -- well, -- I want to follow-up on your prior statement. Tell me, Doctor Kouri, where is it in this JNCI article do you cite a finding at .04 percent confidence level? A The .04 is somehow not in this text, it says significant but it's in the Blue Book. Does it say .04? MS. NIAL: Yes. THE WITNESS: Where is it? RIGGLENILkN, TURK & NELSON iwI' I I 7 I I I I 04,3611

228 1 MS. NIAL: It's on Page 209 in the first 2 column where it begins with Table 4 presents the results and 3 it's down about four lines or so, three lines from the bottcm, 41 again on Page 209. Chronic cigarettes -- 5 THE WITNESS: There it is, .04, there ir- is. ~ f i 6 So I should have read that part f_Ysi-,. ~ 7 A Now, this is an indication example that it wouldn'tj ~ 8 have been a bad comment. However, Doctor Sommers ar.t:uG±ly j 9 writes in his Foreword, and if he wouldn't have stated it t::i Is 10 way, I probably would have cautioned him against it had I seen~ 11 it first, it says the overall nurri:ers of pulmonary neoplasms 12 defined were not statistically sicnificant, when in facz if 13 you looked at the overall number, overall numbers in the smc::e 141 and sham group for.those animals that were taken off random=y, 15 it is in fact statistically signifficant. But we in our own 16 way to try to be conservative miticated that conclusiorr by the 17 month-by-month cumulative probability however never reached 18 the level of significance less than .05. In fact, it was .07 19 at any given month. 20 But the total cumulative frequency which is in fact 21 the overall numbers that was written here by Doctor Sommers -- RIGGLEMAN, TURK & NELSON

229 he just got himself in trouble by making that statement. if we would have reread that slightly differently, we would have been correct, but the way it's written here, it's in fact incorrect. Q 10 11 12 13 1 15 16 17 18 19 20 21 Well, it's not incorrect because this particular passage that you're referring to only referr~ to one su::::et of the total population; isn't that right? A That's right. Q And as to the differences on the entire oc;:•--lation of all the mice, it was not statistically signif:~cant a- .05? A That is an unfair comparison. You cannot compare sets of individuals, some were taken off test randorr;' :-, :,om~-: were allowed to die of their tumors. It's a weil-ki:ow: iact that one has to analyze the data based on the method by which they were removed from tests. So you cannot compare ta~ complete -- it would be the same example -- well, I wi_1 aive you -- the examples are immaterial right now. Let's just say you really cannot compare overall incidences in two dif"ferent ones. The latency might be different. There are a loz of different reasons why two things could be statisticall-,• significantly different and yet, you know, the overall lI RIGGLEhLM, TURK & NELSON I 4.M f!R { f f 7 0 4 ,,.~- 66 .01.w:1`

230 10 11 12 13 14 15 16 17 18 19 20 21 incidence is identical. In fact, i~-- obfuscates the issue, it doesn't clarify. Q Now, the fact is that th:s particular passage that you have relegated in the JNCI article to the sixth page is::'t referred to anywhere in the abstrwc= up front -- in fact, w::ati I you say up front is that the differezce between the =;moke an:.=~ i I sham exposed groups was not statistically significant at P-05 i but only the data suggested that the tumors occurred with a ~' ! shortened latency in the smoke exposed group at P-1U; isn't I I that correct? A Yes. Q You didn't make any reference to this particular ' subset of the population; isn't tha-L right? A Right. Q W:at's even more significant, though, is that Doctor Sommers didn't have this JNCI article in front of hir when he wrote the preface to the Blue Book? A He had all the same data that we had. Q He had your final report; isn't that correct? A Right. Q You have the final report there in front of you. RIGGLEMAN, TURK & NELSON CTR MN 043614

231 10 11 12 13 14 15 16 17 18 19 20 21 A Pnd it says exactly the same thing. Q Well, let's see if it does. On Page -- let me ask you if you will look at the report itself. This is the document as you prepared it, isn't that correct, Exhibit 19? A 'r;-c: zt. . Where should we look' Q Lookk cn Page 4. A 4. Yes. Q Page 4:is in fact your summary of the data an,a in fact starting on Page 3 is your su,:.-nary of the data of 101A; isn't that correct? A Yes, that's what I think it _s. Q W~en you went through the hundreds of pures that go into this book and pulled out what you thought the significant findings were to be included in the summiiary up front, .t::2I.s is what you put i*_,: the summary, right, on Page 4? A Ri ght, okay. Q In Page 4 the first time you talk about cancer is at the bottom paragraph of Page 4 and what do you note? You note that all lung cancers observed in the 3, in the BC3F1/Cum mice were alveolar adenocarcinomas, AAC; you thought that was an important finding, didn't you? RIGGLEMAN, TURK & NELSON CTR HN 043615

232 A Correct. Q That's in fact the very first thing you say about 10 11 12 13 1 15 16 17 18 19 20 21 cancer in this study, right? Q Yes. The seccr.d thing you say is no squamous cell carcinomas or other pulmonary carcinomas were observed in ch.e smoke, sham or, shelf control group. That was the -- you also thought that that was an important finding, did you not.? A This is -- right, right. Q You go on to say that a total of nineteen adenocarcinomas were observed out. of a total of nine hundred and seventy-eight animals at risk in the smoke exposed group while seven adenocarcinomas were observed out of the six hundred and.fifty-o~.e sham exposed animals at risk. You then co on to say data analysis in four different ways indic:ted that no differences were observed between the smoke or sham exposed groups at a .05 confidence , level. Those were your words, right? A Correct. Q Those are in fact the first four sentences, the first four items of information that you would want a reader RIGGLEMAN, TURK & NELSON C ~~ ~".4.~b I b

233 10 11 12 13 14 15 16 17 18 19 20 21 to see in terms of summary of what this study was all about? A Correct. Q And what you say is they're all adenocarcinomas, there were no squamous cell carcinomas, and there was no statistically significant difference between the smoke and the sham exposed analyzed four different ways; isn't that co.Tre::+:.? A That's what it says. ~ Q Now, you don't inciaion in t:hi s parti cular suiT:,,:ary I anywhere a 0.04 con=idence level, do you? A We didn't analyze it that way up to that date. Q But this was the report that Doctor Sommers had when he wrote his Foreword; isn't that correct? A Isn't that the same thing we were always taiki.ng about? This thing was never meant for wide di ssemir_atic::. It was meant for an ability to analyze these data as in-depth as anybody could. We hadn't analyzed all the data to date, neither should have anybody else. But they wanted it this way, we gave it to them this way. I'm sorry to say, this is al pitfall that happens when one is not allowed to, to really look at all of the data and do the analysis that we eventually did to get rid of the data, to get the paper. RIGGLEMAN, TURK & NELSON W I R I i I I I q .~.I/' ~~ "11/r•' 3617

234 1 2 3 a_ 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 The point here is the paper, not this. This, this data are the exact same data that gave rise to this paper. This is the peer reviewed publication in which the analyses were done. They finally came to that conclusio:n ar:d those were the conclusions for the data. They're here, too. The fact that we didn't analyze it all. the ways that perhG_ s we had up to that time was immaterial. I mean, these are the, those are the conclusions. We're looking at al)_ the same data. Q And the conclusion that you're relying on today didn't, you didn't bother to mention, although you say it's very significant today, even in your JNCI article, you don't bother to mention it until six pages into the article; isn.'t that right? What you say in the, in the abstract on the first page is the same thing you've said here in the final report which is that there was no statistically significant difference between the two groups; isn't that right? Look at it. Isn't that right? Look at it. A Wait, wait. Q My question is, am I not right? A Yes, yes. Can I address your issue? What I am RIGGLEM.ZUv, TURK & NELSON FR 043- 6113

235 10 11 12 13 1 15 16 17 18 19 20 21 trying to address here -- wait a minute, we're a little bit miscommunicating in one regard. What I'm trying to say all the way along, we have exact same data right? What I in both places. All said, and i've told you, I've tried to say this before, the .04 overall incidence that was sta~;i=ticGlly significant, we in our o-.rn minds argued and mitigate.^ that being a, something I wanted to hang my Gc c;inwt I I I ~ 4 ~ aq i.o hat on, be -- in other words, I didn't think I needed to write that said, you know, .04 and make a big issue o-f that, reason why I didn't think it was a a big i s sue is that w:.en wv analyzed it month by month, we only got .07. rLna I wrote it in here, and it states ir : here we somewhat m,iticate the fact that it was .04 by t'r:e fact we never reached statistical signif icance at any monthly i nterval , all right? So what I was trying to say right c=f the bat here is that we're right on the cusp of stati=tic-a1 significance when we did these analyses. Now, we almost got it, regardless of how we did it, and that's the same data that are here. - Okay. What I'm only arguing about and the only thing I have argued about all the way along was the comment that Doctor Sommers made by summarizing these data, and the only RIGGLEINLM, TURK & NELSON Cf R f f f'1 04,..`'~ 6.h 9

236 10 11 12 13 14 15 16 17 18 19 20 21 mistake he made was when he said o7erall incidence. Now, I would not have had a problem with that, the only trouble is the overall incidence, the way he mentioned it, seven out of the four seventy-two and zero out of two seventy-two is in fact statistically significant. T^e monthly by monthly weren't:, and we had increased 1Gte::cy but the only way you would have picked those up -- we didn't have all the dGta here. All I was trying to say here is not the data - we're kind of going a little besideways here. The only mistake I think that was made, and I wrote it in my affidav: is that I think it would have served everybody's best interests if Carol and I would have been able to look at this book before never got a my argument done and the what I said. exactly what I it went out, especially with the Foreword, and we chance. And I, the only thing I've ever said i= along here is that I think that was, a mistake was way it's written it's misleading. That's in fact And I think the reason it's misleading is I'm saying right now. I wouldn't have allowed him to say it the way he said case. it in here if that were the RIGGLEMAN, TURK & NELSON t..+ f R f f N 04,36220

237 10 11 12 13 14 15 16 17 18 19 20 21 Q But the fact is that you're accusing him of intending to mislead people -- A No, no. Q -- for stating nothing other than what you yourself - state in the very first paragraph A Exactly. Q -- of the summary of yo--,r own report that you've written? A Those are the prob?.ems associated with taki.nc a paper that hadn't already been Gna:yzed completely, as a compendium, all it is is a compendium of tables. You will i have to admit, I don' t think anY :^ody has ever seen a boo}: th size have so few written words; there must be twenty pages of written words and a hundred and fi=ty tables and a hundred and fifty figures. I mean, that's all it is is a compendium of data and there was very little analysis that was done which is what they asked for. Nobody expec;.ed this to go into the literature and in fact, Charlie understood what he needed to do is to try to put something in context and he decided to do it that way. And I wish he wouldn't have done it that way because in fact he was a little misleading the way he wrote it RIGGLEMAN, TURK & NELSON CTR f fN 0'"x'3621

238 1 in. 2 Q I understand that you wished he hadn't done it, I 3 understand that you are irritated that he did it without 4 consulting with you, but the fact of the matter is that the 5 findings that he reports in that Foreword are almost listed 6 verbatim out of your own summary in the re?c:rt. Now, maybe 7 you could have set him straight if he had as::.--:d you -- 8 A Right. 9 Q -- but he didn't ask you. 10 A That's cor=ect. 11 Q Anci - - 12 A That's the only issue I have. 13 Q Are you testifying that because, that this could 141 not simply have been an honest error on his part to have 151 simply taken your summary -- 16 A I think it was an honest error. 17 Q You think it was an honest -- you don't have any 18 evidence that he intended to somehow distort your findings? 19 A Absolutelv, I think it was an honest error. 20 Q Because what he said is literally true? 21 A It was an honest error for us. We hadn't analyzed RIGGLEMAN, TURK & NELSON t..x f F f`s. HN 0` f' 362r''',...

239 1 2 3 a 5 10 ,1 12 13 14 15 16 17 18 19 20 21 all the data that way. I think it was an honest error for him. Q Even the finding you are focusing on today dealing with the subset of animals that were randomly tayen off which are the ones that died in the course of inhalation, that was not something that was featured in the introduction to the JNCI article? A Correct. Q You noted it but you didn't note it r_cht up frcnt? A Right. we modified that -- exactly as I said before, we recognized it was there. We didn't make a bia issue out of it because we weren't sure -- it's Yig'r.t on the cusp. The conclusion was exactly as we stated here, 2R; whole cigarette smoke in BC3:1 mice is weakly carcinogenic, and I think the data support that. And that's all the conclusion was and I think we all aareed that was the right conclusion. Q But my question to you is, isn't it a=act that somebody reading this article who just read your abstract wouldn't even have focused on the particular finding that you're now talking about today? A Yeah, I agree with you. RIGGLENILM, TURK & NELSON C/ R H~• •, / 1~•~rl' ilpsr ~

240 10 11 12 13 14 15 16 17 18 19 20 21 Q If you just read the abstract which is the introduction -- it's the thing that you put up there because a lot of people don't read the article; isn't that right? A Correct. Q When you write the abstract, you want to put in the things there that you want the readerr to e-.Tet, - A Right. Q -- and he is going to niss & lot of deta; lhut the important stuff you put i n the abstract? A Right. Q That finding that you're talkin:;~ about todaJ, this .04 statistical significance was not in that introducto=y section; isn't that right? A Right. Q And a reader just looking at this and not reading the rest of it could honestly in good faith come to the conclusion that what you were saying is that there was=:'t a statistically significant difference, unless he read through the entire article; isn't that right? A Yes. Q Okay. Because it -- RIGGLENLM, TURK & NELSON (..+ f f"~"i f f ~~ ~ 0"T 36.'s.~..'~. 4

241 1 2 3 4 5 6 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A I agree. Q Okay. So my questiorn to you is, how can you condemn Charlie Sommers for taking conclusions out of your summary in the final report and conclusions that he could also have gotten out of the first parGcraph of the JNCI article? A What the conclusion in tY:Gt paper is that 2R1 whole cigarette smoke is weakly carcinogenic, that's the conclusion, ricrht, that's in that article, that's in the ~, ' J bst:racll-., it s i;l;'; the summary, it's in the conc].usioa, wherever it is, right? That isn't the conclusion in the Foreword to this book, tha~'= my problem, all right? It does not say that 2R1 whole cigarette smoke was weakly carcinogenic to BC3F1 mice. Tn ~ fact, the connotation was that it was not carcinogenic. Q Well, -- A And I'm saying that is _n fact misleading. It might be an honest mistake because he didn't -- because -- and I said the only honest mistake here is the word he used here was overall incidence because he happened to pick a word overall incidence that even I didn't, didn't make into a big issue as evidenced by what you just said, I didn't even put it into the summary of the paper as a big deal. But Charlie, RIGGLEMAN, TURK & NELSON C f f`~. f f f'~ i..~' f,..~ 6 2 ~

242 10 1 12 13 1 15 16 17 18 19 20 21 Doctor Sommers thought it was a big enough deal to write it in and he happened to choose the wrong words because the way he wrote it, he actually is wrong because he happened to pick one in which the overall incidence was in fact statistically significantly different. I mean, the way he ;r•rote it, he would have had to write cigarette smoke was in fact associated with cigarette smoke exposure. I mean, that's the way he -•- because the way he wrote it but I dor.'r oven think that wa~ a right conclusion either the way it was done because of t.hF, fact that, again, the way the animals came off test and a variety of other re-asons that this is a better way to state it. He just chose a set of simplified words in order to try to convey a set of ideas that this, this particular experiment, and as I read this in sum total was largely negative, right? That's what I think this Foreword states, that this experiment was largely negative, when in fact the real conclusion is that it's a weak carcinogen and it's not unlike what we would have expected cigarette smoke to be even in humans because it's a weak carcinogen. Q The weak carcinogen is your conclusion, right? A It was all our conclusions. RIGGLENLM, TURK & NELSON E~~.T R M N 0 4 3 622 6

243 Q That's not the, the data is something objective 10 that's not subject to -- A That's correct. Q And the data was in there? A Right. Q And Charlie in his Foreword was not saying don't read the data, don't turn the pages and see what the data resulted? A Right. Q He is reciting some of the findings are as follows 11 12 13 14 15 16 17 18 19 20 21 and he lists them? A Right. Q And everything that he lists is consistent with whatt you had provided to him? A Everything would have been fine if he didn't say the overall numbers cf pulmonary neoplasms, pulmonary neoplasms -- now, these are alveologenic adenocarcinomas, squamous cell carcinoma, anything he is talking about identified were not statistically significantly different in the smoke exposed mice compared to sham or shelf, and that's not quite right. RIGGLEDIAN, TURK & NELSON CTR ~~ 04,362-r-11

244 Q But in fact it's pretty darn close to what a normal 10 11 12 13 1 15 16 17 18 19 20 21 reader would get out of the very first paragraph of report in which you say -- A No. Q your final -- data analysis in four different ways indicate.d that no differences were obserfed betweern the smoke or sham exposed group. A I agree with you. T: e on:!,~ thing that r.eal;_, counts is not this document here crh,c:ri i: a compil~.ti o=: cf data, but when we actually sat down among all of us, ;-TR included, analyzed the data and came to the conclusicn _t was weakly carcinogenic. Now, T_ ccr.'t know why that -- that comment should have been in here. We hadn't analyzed a~_1 `-he data in that way because we did-:'t have time to analyz3 it ;;o and this thing came out and 1 just flipped out because xe didn't even analyze all the data yet when this thing csme out. I couldn't have come to that conclusion that was written in the Foreword. In fact, I didn't even pay any attention to it until I was asked for this proceedings or I would have never even read it. I wouldn't have compared the actual words to the data here and realized, oh, man, we shouldn't have done it RIGGLEMAN, TURK & NELSON Cf f"ti 1114N 0'" f' ,36.28

245 10 11 12 13 14 15 16 17 18 19 20 21 that way in retrospect. Q or -- In fact, you never con-.plained about that Foreword A Oh, I did, you better believe I did. Q Isn't it a fact that subsequent to that Forewora you and Carol Henry had a number of dealings with CTR, you continued to accept money from C':': to write tr:.,~ JNCI arti c=__., and you thanked them for their e_.courac_rement and their supUor=i I and nowhere in your correspondence with them is there any hinti of any disapproval whatsoever o_ t'r.at Foreword? A I don't know, I can',- argue, I can't remember whether there was something written down, but there certainly was -- as soon as this came out, when I saw it, I called Bo^ Hockett who is the person that I originally got this from and Bob was the one -- Q You think Bob was alive then, too? A I don't know when Bob was. I thought I got this thing originally and it said from Bob Hockett but I could be mistaken. No, I don't know when Bob -- Q You didn't call Bob Hockett, did you? Are you telling me you remember? RIGGLEMAN, TURK & NELSON CTR MN 043-6295

246 10 11 12 13 14 15 16 17 18 19 20 21 A I said I think my thing came in here and what I was trying to get ahold of is Bob Hockett. I can't remember what -- wait a minute, now we are talking about whether he died or not, let's not get into that. All I'm talking about here -- I may be wrong but I thought I had a little card in here that sa_d from, thanks, or +,:Lunks to r:rom Bob but I dor.' t' know when -- I thought that's wha'- :ni~;_: ; aid. I don't: know ` how I just remembered that. Q Isn't it a fact that you have never in :•:iitir.g at I any time up until this litigation was filed complained or fi protested or criticized in any way the publishing of the Blue ! Book? I A No, that's not right. Q Tell me what writing you have produced. A I don't know about writing. You said in wr=ting. I just don't remember whether we ever wrote anything. Q There was a lot of correspondence, wasn't there? A There might have been. I wouldn't be a bit surprised if it were in writing. Q And in fact, didn't you understand that CTR -- let me withdraw that. RIGGLEMAN, TURK & NELSON CTR M) -4 0' 7 w1' \.eY ti..* 0

247 10 11 12 13 14 15 16 17 18 19 20 21 Let me go back just briefly to your conclusion, this conclusion that you contend is statistically significant at .04. You acknowledge that it's not contained in the ~ abstract at the beginning -- A Correct. Q -- of the JNCI art;clE? A ~ ~ Correct. ~ It's towards the back. You also acknowled^e . C + this is an analysis of one subset of the mice ~:hat were studied under the 101A? ~ 1 A Correct. ~! i Q As to the other subset, the ones that were presume_i to have d;ed of their lesions, there was no difference betweer,~ smoking and sham? A Correct. 1 Q A:;d you also acknowledge, do you not, that the fact that the two are inconsistent has a tendency to lessen the impact of your conclusion? A Correct. Q So this is not a strong conclusion? A Correct. RIGGLEMAN, TURK & NELSON CTR MH 0436-31

248 Q This isn't something that strongly points to a 10 11 12 13 1 15 16 17 18 19 20 21 particular conclusion -- A Correct. Q -- about mice carcinogenesis; isn't that right? A That's the reason it was called a weak chemical carcinogen. I agree w? r.'r. you a hundred percar_i:. Q You in fGcL felt necPssary to ciiscl^se in t:_=~ ~~~7CI article that in your opini cn thE, fact that Lhe Lwo trs .: d.~.6 not agree tends to lessen thc _rapact of thF c:c1n; J.us_or. that smoke exposed animals i n the subset popu' ac.ion hi,;:d a significantly higher i nci dence of lung car_ce.r than the sham exposed animal? A That' s exactly right. I' d havce to say that was a comment, as I remember, and don't take -- th:,.,- was, th_s was something we did have some conversations with rlr. Fin^_yGn about because that was an issue and his point was don'-L you think that the fact that it never reached statistical significance in a monthly interval mitigated in some regards against the fact that it was in total but it wasn't in any given month, and I had a tendency to agree with him. I thought that was a proper way to caution the reader, and so I RIGGLEM~v, TURK & NELSON C. r f i`'~". f f f`f 043632

249 did it. MS. NIAL: Bob, is this a good time to take a 10 11 12 13 14 15 16 17 18 19 20 21 break? MR. MERRITT: Yeah, let's take a break. MS. BAiJE.°.: Of f the record at 5: C2 . (Thereuron, a shorc recess was ta}:e::3 . (Documents were marked K3u=i : ::position Exhibit Nos. 2 6 and 27). .MS. BAUER: Back on the record at 5.13. Q (By Mr. Merritt) Doctor Xouri, this morr.i::_c you testified to your opiniorn t'r.at people may have in fact been misled by Doctor So:nrners' preface to the Blue Book. Do you recall that testimony? A Yes. Q Do you in fact know of anyone who was misled by reading that? A No, no. Q Do you know of any smoker or any Congressman or any scientist or anybody whatsoever who read that preface cr that Foreword and as a result was misled? RIGGLEINL~v, TURK & NELSON CI R f IH 043633

250 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A Only Doctor Sommers. Q Going back to the end of 1981, let me ask, let me ask you to look at Exhibit 26. Do you recognize this? This is a letter dated December 22nd, 1981, from Carol Henry to Doctor Sommers and Thomas Hoyt. December 1981 was followina the comnletion of the exposure portion of Contract 10if.; is that correct? A I think that's right. Q And at that time Doctor Eenry in this leC::e_- promises to bring the final report with her to a meetirg ai: CTR that was scheduled for January of 1982; is that correct? A Yes. Q Isn't it a factt that -- and this time frame corresponds with earlier projectio::s that the rEport wculd re written up and submitted to CTR at the end of 1981; isr_'t trat a fact? A I think that's right. Q Now, in fact the final report was not submitted to CTR for over two years; isn't that correct? A Right. Q And isn't it a fact that that was the cause of scme RIGGLEMAN, TURK & NELSON CTR MN 04,3634

251 10 11 12 13 14 15 16 17 18 19 20 21 aggravation and, and perhaps anger is too strong a word but clearly irritation on CTR's part that it was not getting its report; isn't that true? A Yeah, I think that's trae. Q In fact, part of the reason that that was happening was that you and Doctor Henry had been assigned to other projects, isn't that right, that was part of it? A Right. Q She got pregnant at scme point and was unable to work on this? A That might be true, tcc. I actually forgot about that. Q And then at the end o= '82 or the beginning of 'c3, a year or so after this letter was written, you left MAI and were starting a new job that had ti:ne requirements? A Right. Q And so without pointing any fingers, -- A It took a while. Q -- it is in fact the case that CTR waited a long time to get this report? A Correct. RIGGLEMAN, TURK & NELSON E~ 1"' ~'~~~ 0~-~~6. °.~95

252 10 11 12 13 14 15 16 17 18 19 20 21 Q And that people at CTR were aggravated because they had spent a lot of money on these things and they wanted to see something to show for it; isn't that right? A I'm sure. I Q And isn't it also a fact that in addition to the report, it was contemplated early on that there published manuscripts in peer review journals? A Correct. would be Q And that among the things that were happening in '81 and '82 were questions to you and Doctor Henry about when will we see some manuscripts for publications; isn't that right? A Yes. Q There were in fact going to be four manuscripts, there was going to be one describing methodology, one describing the results of the smoke inhalation studies, one describing the results of the, of the promotion using the methylcholanthrene and benzo(a)pyrene, and then a fourth one that was going to be a comparison with human data; isn't that right? A I think that's right. Actually I had forgotten RIGGLEMAN, TURK & NELSON G TR MN 043636

253 about that but now that you said it, I agree with you. Q Let me ask you to look at a document marked Exhibit 27 which is a letter from John Parker of Microbiologica]. Associates to Tom Hoyt dated December 6th, 1983, and this relates to the, to this ongoing negotiation or discus-sion that was going on between CTR and MAI as to A, when do we get our report and B, when do we start seeing these manuscripts? ! A I think that's riaht. ~ Q And this letter is dated December of '83.. ^his is ~ 10 11 12 13 1 15 16 17 18 19 20 21 two years after the project has essentially been ccr,._'.::zed and the second and third and fourth manuscripts anyway anc the final report itself have riot yet been delivered; is that correct? A Yes. Q Now, in this letter or attached to this letter are a series of proposed outlines for these various mariusc=-_pts. A Umh-humh. Q And I'll refer you specifically now to a pace that has at the top Figure 1. Do you see that? A Yes. Q That's in fact an outline of the second manuscript RIGGLEINLM, TURK & NELSON t..r Tf~'. Mf'f 04123637

254 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 of the four; isn't that correct? A Yes. Q And that's in fact roughly an outline of the JNCT article that was subsequently written; isn't that correct? A I think so, yes. Q And so in fact -- let me ask you what I askFc': you before and you were a little uncertain at the time, th~:: JNCI article was actually written after, at least after the date of this letter; isn't that right? A I actually don' t know that to be a fac::. 1 mean, it could easily -- this, this inventory or this intrcduction, methods and results could have literally been, we already had drafts of that paper written. Q It could have been but you don't remember one way or the other? A That's right, I can't remember, but there's nothing in here that says it was done before or after this time. Q Except that in this letter John Parker, who is -- A He is the President of Microbiological Associates. Q John Parker on behalf of MAI is saying we propose this to you as a general sort of outline of the areas that RIGGLEMAN, TURK & NELSON WJ I ! 1 HI • 043ind' 1..r aa

255 10 11 12 13 14 15 16 17 18 19 20 21 would be covered in the various manuscripts? A Correct. Q The one that's identified as Figure 1 is JNCI article and the article as it was finally prepared by you and I Doctor Fenry roughly corresponds to this outline? A Right, a draft might hGve already been written for all I know. That's the reason why it looks like this. Q On the very first page of this letter Doctor Parker says thaL the second and third manuscripts have been scheduled for completion by February 1984. A Right. Q Which was in fact also the, which was in fact tr.e date that the, that the final report was ultimately given *_~:. CTR; isn't that right? A Yes. Q But in fact it wasn't presented to CTR in February of '84, the JNCI manuscript? A That's right. Q And in fact, it wasn't submitted to CTR for over a year and a half later; isn't that true? A Correct. RIGGLEMAN, TURK & NELSON L..M f R f f i'f S..a `T 3L'.,:b 39

256 10 11 12 13 14 15 16 17 18 19 20 21 Q So in February of 1984, CTR has waited at that point over two years for the final report; isn't that right? A Yeah. Q And it's been promised a manuscript but it doesn't have it; isn't that right? A Right. Q And it doesn't know in fact when it's going to get the manuscript; is-r't that right? A Yes. Q I mean, it wasn't until the middle of '85 t`!at Carol Henry proposed to CTR that they pay you and Doctor Henry to invest the time to actually write the article and get it out; isn't that the case? A I don't have that letter in front of me that says -- I don't know what the dates were, but I certainly remember the fact that we were remiss in getting all this done. It was obviously not high in the priority list, most of which because of you said a long time ago, it seemed like a long time ago, when you said that CTR did represent a healthy percentage of the work that was going on at Microbiological Associates and without it, we had to scamper around to, to RIGGLEMAN, TURK & NELSON iWr f R f f f"'f 04,..~ 644.,A

257 10 11 12 13 1 15 16 17 18 19 20 21 fill that gap, and that was our primary priority to do that. Off the record. (Discussion off the record). (Document was marked Kouri Deposition Exhibit No. 28). MS. 3AUER: Back or, the record at 5:26. Q (By Mr. r`.erritt) Let me ask you if you would look at a document that's been marked as Exhibit 28 and which is a July 31, 1985 letter from Carol Henry to Sheldon SomneYs at CTR, and do you recognize this letter? A No, I didn't remember it but I think Carcl told me she was going to send it. Q And it shows a copy was sent to you. You were aware that during this time, meaning July of 1985, there were negotiations over CTR providing funds -- A Yeah. Q -- to enable you and Doctor Henry to take the time to write up the JNCI article? A Umh-humh. Q And CTR in fact agreed to provide thirty-eight thousand dollars for a total of two hundred and eighty hours RIGGLEMAN, TURK & NELSON Cf R f f f`f 0413641

258 of time for yourself and Doctcr Kouri, I beg your pardon and Doctor Henry to write the JNCI article? A Yep. 10 11 12 13 1 15 16 17 18 19 20 21 Q Now, this is well c-rer a year after the final report was submitted to CTR i:: February of 1984? A I agree. Q Arid it's over a year after this particular manuscript was promised to CT.F; isn't that correctc' A (Nodding head affirmatively). Q Now, the scientific community had been made aware in the 1970s that there was a:-- inhalation proj ect that was really unprecedented in size Gnd sophistication that was being done by MAI under sponsorship by CTR? This was not a secret; is that correct? A Right. Q And there were people on the SAB, for example, who were then sitting, who were then employees of the National Cancer Institute who had told people that this study was being done and the scientific community in fact had a legitimate interest in what the outcome of this work was; isn't that right? RIGGLEhLLN, TURK & NELSON c7R l 7) ) ti..A 4....A f d f ).IG.a

259 1 2 3 4 10 11 12 13 14 15 16 17 18 19 20 21 A I, I think that the -- did they have a scientific interest? No, I can't address that issue whether they had an interest or not. Nobody ever asked me outside of CTR, you know, to get that thing done. r:obody was, nobody was, you know, waited with bated breath, t*:at they were waiting for that publication. Q But isn't it a fact t:at CTR did get inquir_es I ( ~ about the status of the study ~.:r.d' that in fact the study had , been concluded years before? ~ A Oh, yes, it took us a while to get it done. we were remiss. Q And CTR had spent. several million dollars dcir.g this? I A Oh, I, I agree with you. I i Q And in February of 19124 when they get your final report, late, when they don't gez a manuscript that has been promised to them in 1984 and don't know when they're going to get it and in fact don't get it for over a year later, was it i unreasonable for them to consider ways in which the results of this study, the data and methodology could be made available to scientists without having to wait until you or Doctor Henry RIGGLEMAN, TURK & NELSON t..r f R f f N 043643

. 260 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 finally get around to writing a manuscript? A Perfectly reasonable request. Q And so I take it you're not saying that there's j anything necessarily nefarious about the fact that CJ':2 was I~ wanting in 1984, when they final].y had the final repor+::, some ~I I way to get this out, -- ; i A It -- Q -- that was not unreasonable of them? A That's not unreasonable. + ~ l Q In fact, the only way they could cat t'r:i s ~ information out was by giving people the final reoort because that's all they had at that point; isn't that correct? A I don't have any argue -- I guess the only time it would have been, it would have seemingly been proper to just give us -- they did make some subtle changes in this final report from us a:.d they put a Foreword on it. It would have, normally it would have been pretty smart just to run it by us first and tell us what they were going to do with it, that that's what they intended to do, but that wasn't done. Q I understand that you are not happy about that. A That's all I've ever said. RIGGLEMAN, TURK & NELSON CTR 1111N 043644

261 10 11 12 13 1 15 16 17 18 19 20 21 Q But the fact of the matter is, -- A They could and they didn't. Q -- putting aside that discourtesy if that's what it was to you -- A That's it. Q -- putting aside -- A I'll go with that. Q -- the possibility that you might have corrected Doctor Sommers in his misunderstanding of your results, the mere fact that they said let's publish this thing so the scientific community can have it, that in itself was not unreasonable or unez-^ical or improper? A No, I'v:r r.ever said that. The simple fact of putting this in the pGper was no problem, that would have been fine. I guess all T would have wanted-to do was look at it then. Because what T said is I would have rewritten or written it slightly differently had I known that's what we were going to do with it up front. I mean, we got the thing out. This is a monstrous undertaking and it was under duress at that time that we were doing, we were remiss at getting this done, I'll be the first to apologize and have to, to the RIGGLEMAN, TURK & NELSON CT R 1"IN 0 43 6 4 5-

262 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 CTR staff when we did it, but that happened. I'm sorr~y. And that, but when we finally got around to doing it, we got it into there, we followed up as best we can, as fast as we can to get the paper out. It wasn't very t_:nely. I wish it were more timely but at the time, I hate to say it just wasn't the highest priority on Carol nor my plate at the time, we were out doing other things and I'm sorry about that. Q And the problem was that CTR as of 1984 didn't know when it would actually get on your plate? A I think that's true. Q Okay. MR. MERRITT: Give me like one second. Can we just huddle quickly without -- MS. NIAL: Let's go off the record. MS. BAUER: 0:f the record at 5:34. (Discussion o-ff the record). MR. MERRITT: Next one. (Document was marked Kouri Deposition Exhibit No. 29). MS. BAUER: Back on the record at 5:36. Q (By Mr. Merritt) Doctor Kouri, I have just handed RIGGLEhLLv, TURK & NELSON

263 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 you a document which is an August 16, 1985 letter from Doctor Henry and yourself to Doctor Elizabeth Weisburger at the Journal of the National Cancer Institute. A Correct. Q This is a letter that you and Doctor Henry sent to, to the JNCI at about that time? A Correct. Q Reading, directing your attention to the second paragraph of this letter, could you read the, the paragraph starting with the third sentence? A A final report? Q Yes. A A final report describing these studies was submitted to CTR. As a result of requests for copies of this rather extensive report, CTR elected to print the final report verbatim in bound book form for general dissemination. The work presented in this manuscript has not been published in any journal. Q Was it in fact your understanding at this time that that was the reason why CTR had elected to have the final report printed? RIGGLEMAN, TURK & NELSON CTR ~~~~ 043647

264 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 A I don't really know. That seemed to be the easiest way to state this when we were going to submit the paper. Obviously the attempt here was to recognize that this volume existed in the public literature and we wanted to make sure that it would not prevent us from publishing the paper. That was the attempt here. Q But the sentence that is contained in this letter that you wrote, was that true, was that a true statement? A I don't know if it was true or not true, it just seemed to be the right thing to say at the time. Q But it was something that at the time you said to -- A ?t seemed to be a nice way to state, you know, what happened, and so we were being polite about everything without, without raising any heckles from anybody. I don't think from this letter, I don't think it makes any sense, I mean makes any connotation whether we liked the publication of , this journal or didn't -- or this book or didn't like it, it was just the simple fact we wanted to make sure it didn't inhibit our ability to publish the original paper. Q You wouldn't have lied to the JNCI in connection RIGGLEMAN, TURK & NELSON CTR HN 043648

265 10 11 12 13 14 15 16 17 18 19 20 21 with submitting your manuscript? A I don't think that would be a lie, that's right. Q This sentence whether you like it or not or whether you are happy about it or not, it reflected your understanding that CTR had elected to print the book because they had received recuests about it; isn't that correct? A Right. Q That's what this sentence says? A Right. MR. MERRITT: I have nothing further. MS. BAUER: Off the record at 5:39. This concludes the deposition of Doctor Kouri. (Thereupon at 5:39 o'clock p.m., the examination of the witness was concluded). RIGGLEMAN, TURK & NELSON ~""~" ~ t..r f A f S` f~~ f'f 043

266 1 2 3 4 5 6 7 8 9 10 11 12 13 14 i. 5 16 17 18 19 20 21 CERTIFICATE OF DEPONENT I hereby certify that I have read and examined the foregoing transcript, and the same is a true and accurate record of the testimony given by me. Richard E. Kouri, Ph.D. CERTIFICATE OF NOTARY PUBLIC/REPORTER STATE OF MARYLAND ) CITY OF BALTIMORE ) I hereby certify that on the 12th day of September 1997, before me, pe=sonally appeared RICHARD E. KOURI, Ph.D., who was first duly sworn by me to tell the truth, the whole truth and nothing but the truth; That the testimony of the said RICB,~RD E. KOURI, Ph.D., was reduced to writing under my direction, and the foregoing is a true record of the testimony given by the said deponent. I further certify that in my presence it was stipulated and agreed by and between counsel for the RIGGLEMAN, TURK & NELSON 4,._ &b

267 \ 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 respective parties that the sealing and filing by the Notary be waived. I further certify that I am not attorney, relative I nor employee of any party hereto, nor otherwise interested in I the event of this cause. In Witness Whereof, I have hereunto set my hand and affixed my Notarial Seal, this 15th day of September, 1997. ';5'UA4' ~. -&~ Shari L. Nelson Notary Public in and for the State of Maryland. My Commission Expires February 1, 1998. RIGGLED!A-N, TURK & NELSON CTR HN 0436=51