Document zdkKgqxgM1NKadmVo0BaK5eK0

1 CAUSE NO. 199-02538-04 2 DUANE DRAPER, ET AL., ) IN THE DISTRICT COURT OF ) 3 PLAINTIFFS, ) ) 4 VS. ) COLLIN COUNTY, TEXAS ) 5 PPG INDUSTRIES, INC., ) ET AL, ) 6) DEFENDANTS. ) 199TH JUDICIAL DISTRICT 7 8 ORAL DEPOSITION OF 9 10 ETHAN A. NATELSON, M.D. 11 DECEMBER 10, 2007 12 13 VOLUME 1 14 15 ORAL DEPOSITION OF ETHAN A. NATELSON, M.D., 16 produced as a witness at the instance of the 17 Plaintiff(s), and duly sworn, was taken in the 18 above-styled and numbered cause on the 10th day of 19 December, 2007, from 1:37 p.m. to 4:35 p.m., via 20 telephone, before Kimberly J. Carter, CSR in and for the 21 State of Texas, reported by machine shorthand method at 22 the offices of Schirrmeister Diaz-Arrastia Brem, LLP, 23 700 Milam, 10th Floor, Houston, Texas 77002, pursuant to 24 the Texas Rules of Civil Procedure and the provisions 25 stated on the record or attached hereto. 1 1 APPEARANCES 2 FOR THE PLAINTIFF: 3 Mr. Andrew J. DuPont (via telephone) LOCKS LAW FIRM 4 The Curtis Center 601 Walnut Street, Suite 720 East 5 Philadelphia, Pennsylvania 19106 (215) 893-0100 6 adupont@lockslawpa.com 7 FOR THE DEFENDANT E.I. DUPONT DE NEMOURS AND COMPANY: 8 Mr. Andrew C. Schirrmeister, III SCHIRRMEISTER DIAZ-ARRASTIA BREM, LLP 9 700 Milam, 10th Floor Houston, Texas 77002 10 (713) 221-2500 acs@sdablaw.com 11 12 FOR THE DEFENDANT PPG INDUSTRIES, INC. AND THE SHERWIN WILLIAMS COMPANY: 13 Mr. Christopher Stofko (via telephone) DICKIE, MCCAMEY & CHILCOTE, P.C. 14 Two PPG Place, Suite 400 Pittsburgh, Pennsylvania 15222-5404 15 (412) 281-7272 CStofko@dmclaw.com 16 17 FOR THE DEFENDANT ILLINOIS TOOL WORKS, INC.: Mr. Bryan D. Pollard 18 WILSON, ELSER, MOSKOWITZ, EDELMAN & DICKER, LLP 5000 Renaissance Tower 19 1201 Elm Street Dallas, Texas 75270-2161 20 (214) 698-8000 bryan.pollard@wilsonelser.com 21 22 FOR THE DEFENDANT BASF: Mr. Joseph C. Orlet 23 HUSCH & EPPENBERGER, LLC 190 Carndelet Plaza, Suite 600 24 St. Louis, Missouri 63105-3441 (314) 480-1500 25 joseph.orlet@husch.com 2 1 INDEX ORAL DEPOSITION OF ETHAN A. NATELSON, M.D. 2 DECEMBER 10, 2007 3 PAGE 4 Appearances .................................. 2 5 ETHAN A. NATELSON, M.D. Examination-Mr. DuPont........................ 5 6 Reporter's Certificate........................ 90 7 8 EXHIBIT INDEX 9 EXHIBIT DESCRIPTION MARKED 10 A Invoices of Ethan A. Natelson, M.D. 28 11 B Deposition transcripts of Duane 29 Draper 12 C Letter to Andrew J. DuPont from 29 13 Dr. Edward Agura dated January 30, 2007 14 D Draft report of Bradford Russell 15 31 E Article entitled "Cell lineage 16 specific involvement in acute 36 promyelocytic leukaemia (APL) using 17 a combination of May-Grunwald-Giemsa staining and fluorescence in situ 18 hybridization techniques for the detection of the translocation 19 t(15;17)(q22;q12)" 20 F Article entitled "Clonality analysis 36 of hematopoietic cell lineages in 21 acute myeloid leukemia and translo- cation (8:21): Only myeloid cells are 22 part of the malignant clone" 23 G Article entitled "Clonality analysis 36 of cell lineages in acute myeloid 24 Leukemia with inversion 16" 25 3 1 EXHIBIT INDEX (CONT'D) 2 EXHIBIT DESCRIPTION MARKED 3 H Article entitled "Lymphomas in 36 rheumatoid arthritis patients treated 4 with methotrexate: a 3-year prospective Study in France" 5 I Article entitled "Fluorescent in situ 36 6 hybridization (FISH) in bone marrow and peripheral blood of leukemia 7 patients: Implications for occupational surveillance" 8 J Article entitled "Secondary acute 36 9 myeloid leukemia with inv(16): report of two cases following paclitaxel- 10 containing chemotherapy and review of the role of intensified ara-C 11 therapy" 12 K Four abstracts printed from 36 www.pubmed.gov 13 L Copies of various email messages 87 14 and cover letter to Dr. Natelson dated April 12, 2007 15 M CD-ROM of medical records of Duane 89 16 Draper dated 12/14/05 17 N Curriculum Vitae of Ethan Allen 89 Natelson, M.D. 18 O "Testimony Given by Dr. Ethan A. 89 19 Natelson" 20 P CD-ROM containing documents from 89 the files of Ethan Natelson, M.D. 21 22 23 24 25 4 1 ETHAN A. NATELSON, M.D., 2 having been first duly sworn, testified as follows: 3 EXAMINATION 4 BY MR. DUPONT: 5 Q. Good afternoon, Dr. Natelson. 6 A. Good afternoon. 7 Q. My name is Andrew DuPont. As you know, I'm an 8 attorney for the plaintiffs in this case. And we're 9 doing your deposition here today by telephone, which can 10 sometimes be a little awkward, but if at any point 11 you're not hearing me clearly or I'm not hearing you 12 clearly, we'll kind of both have to speak up. Is that 13 okay? 14 A. That's fine. I can hear you very clearly, so 15 it's a good connection. 16 Q. Excellent. I'm hearing you well as well. 17 So you've given your deposition before, so 18 I assume you are familiar with the kind of ground rules 19 that we like to lay? 20 A. Yes. 21 Q. I'll go over them anyhow just to make sure we 22 are on the same page. 23 If at any point I ask you a question that 24 you do not understand, please feel free to let me know, 25 and I will repeat or rephrase the question to the point 5 1 that you do understand it. Is that okay? 2 A. Yes. 3 Q. Excellent. Particularly, when we're doing 4 this deposition by telephone, if you have a response to 5 give, it needs to be verbal. A nonverbal response, such 6 as a nod or a shake of the head, can't be taken down by 7 the court reporter and certainly can't be seen by me. 8 Similarly, an "uh-huh" or a "huh-uh" is difficult for 9 the court reporter to take down in a manner that we can 10 easily go back and see on the record, so if you can use 11 a "yes" or a "no," if that would be appropriate, I would 12 appreciate that as well. 13 If you do respond to a question, I will 14 assume that you responded based on the way the question 15 was phrased and that you understood the question, and 16 the record will reflect that. Do we have an 17 understanding on that? 18 A. Yes. 19 Q. Great. Thank you. 20 Doctor, could you give us your full name, 21 please? 22 A. Ethan A. Natelson. 23 Q. Dr. Natelson, you are a hematologist 24 oncologist? 25 A. A hematologist. I have done some oncology, 6 1 but my certification is in hematology. 2 Q. And where are you currently practicing? 3 A. At the Methodist Hospital in Houston, Texas. 4 Q. What positions do you hold at that hospital? 5 A. Well, I'm the Director of the Transitional 6 Internship Program or now the Transitional Residency 7 Program at Methodist Hospital, and I'm a member of the 8 Directors of the Internal Medicine Residency at the 9 Methodist Hospital. And I have an appointment through 10 Cornell Medical School, which has an arrangement with 11 Methodist Hospital, as an associate professor of 12 medicine. 13 Q. You're currently involved in your practice in 14 treating individuals with AML? 15 A. Yes. 16 Q. And in the context of your practice when you 17 diagnose a patient, you use something called a 18 differential diagnosis? 19 A. Yes. 20 Q. What factors do you consider in your 21 differential diagnosis when determining the etiology of 22 an acute myelogenous leukemia? 23 A. Well, I look at the history of the patient: 24 what the family history might be, what the occupation of 25 the person might be, whether there's been any exposure 7 1 to radiation or other chemicals, whether there's 2 underlying genetic defects or associated disorders, the 3 type of acute leukemia that it is, whether there's been 4 a preexisting myelodysplastic phase to the leukemia or 5 whether it has suddenly occurred, what types of 6 chromosome abnormalities are involved in the leukemia or 7 if there are any abnormalities in the chromosomes. 8 Those would be the predominant things I 9 look at. Also history of smoking. I think I mentioned 10 the family history. If there is an allegation of 11 chemical exposure, the question is when was that 12 exposure relative to the onset of the leukemia and what 13 type of exposure it was and what levels of exposure. 14 Q. When you're looking at the family history, 15 you're looking for a family history of leukemia? 16 A. Well, in most instances there is no family 17 history of leukemia in a person with acute myeloid 18 leukemia. There might be with chronic lymphocytic 19 leukemia, which frequently has a familial basis. In 20 AML, it only occasionally does. 21 There are other associations. There are 22 certain congenital chromosome abnormalities that favor 23 the diagnosis of AML, such as Down syndrome. There are 24 certain acquired abnormalities, such as pernicious 25 anemia, which is a type of anemia that can cause 8 1 chromosome abnormalities. Those are some of the things 2 we might look for. 3 Q. With respect to occupations, which occupations 4 are you looking for when you want to know if a person's 5 occupational history could be causative or a causative 6 factor in their development of AML? 7 A. Well, we know that certain forms of radiation 8 can cause acute myeloid leukemia, so we're interested to 9 know if this person was associated in any occupation 10 where he might have had radiation exposure. If we're 11 looking in terms of other occupations, and with respect 12 to the allegations in this case, whether a person might 13 have had exposure to some type of industrial chemical, 14 such as benzene, that might be a factor in the leukemia. 15 Q. So benzene exposure is one occupational 16 history factor you're looking at in your differential 17 diagnosis, correct? 18 A. Yes. 19 Q. And would you agree with me that mechanics are 20 one profession or job type that is known to have a 21 history or an expectancy of benzene exposure? 22 A. Well, to a certain degree because certain 23 solvents may have trace amounts of benzene in them. 24 Q. And you would agree with me that painters are 25 a job title that are expected or known to have an 9 1 exposure to benzene? 2 MR. SCHIRRMEISTER: Object to the form. 3 A. I suppose it's the type of paints they're 4 using, but in solvents, oil-based paints, there would be 5 the potential for trace amounts of benzene in certain of 6 the solvents. 7 Q. (By Mr. DuPont) Similarly, auto body 8 repairmen working with solvents would be another job 9 title or category which you would want to consider in 10 the occupational history of someone that's presented to 11 you with AML? 12 A. Yes. 13 Q. And that is because that is another occupation 14 that is known to have benzene exposures? 15 MR. STOFKO: Objection to form. This is 16 Chris Stofko. 17 MR. SCHIRRMEISTER: Object to the form. 18 MR. STOFKO: Andrew, can we have an 19 agreement, any objection by one defense counsel is good 20 for everyone? 21 MR. DUPONT: That's fine, Chris. 22 MR. STOFKO: Thanks. I appreciate it. 23 That way, I won't interrupt as much. 24 Q. (By Mr. DuPont) Doctor, do you recall the 25 question? 10 1 A. Perhaps you could repeat it. 2 Q. Sure. 3 And automobile body repairmen are 4 similarly a job title or category which are known to 5 have exposures to benzene? 6 A. Well, they might. 7 MR. SCHIRRMEISTER: Object to the form. 8 A. I mean, a body repairman might be anything 9 from someone who takes a bumper off and puts a new one 10 on or pounds out a dent. But if they're working with 11 solvents, they might have a potential for benzene 12 exposure. 13 Q. (By Mr. DuPont) When a patient presents to 14 you with a newly diagnosed AML and you're conducting 15 your differential diagnosis, do you ask that patient for 16 specific job types, or do you ask them for just a broad 17 characterization of the work they do and what they work 18 with? 19 A. I typically ask them what types of occupations 20 they've been involved in, do they have any unusual 21 hobbies or work with any particular chemicals, what sort 22 of drug exposures they might have had in the past, 23 things of that nature. 24 Q. And what hobbies are you looking at? 25 A. Again, hobbies that someone might have 11 1 exposure to heavy metals, such as arsenic, or benzene, 2 for example, in the form of solvents or glues, things of 3 that nature. 4 Q. Would you agree with me that family history 5 can be ruled out as a causative factor in a differential 6 diagnosis for Mr. Duane Draper? 7 A. We have no family history of acute leukemia in 8 his particular instance. 9 Q. Okay. So would the answer to that be yes, 10 you'd agree with me that family history can be ruled out 11 as a causative -12 A. Well, we have no evidence for that. We have 13 no evidence for that. 14 Q. I'm sorry, Doctor. One instruction I didn't 15 give you is that it's difficult for the court reporter 16 to do her job if we are speaking over each other. And 17 it's also more difficult when we're on the phone and you 18 can't see me kind of physically stopping my question, 19 and I can't see you stopping your response. So if we 20 can try not to talk over each other, I would appreciate 21 that. 22 But my question to you is: There is 23 nothing with respect to Mr. Draper's family history 24 which would indicate that that is a causative factor in 25 your differential diagnosis; is that correct? 12 1 A. That is correct. 2 Q. And there is nothing in Mr. Draper's medical 3 or social history that would indicate to you that 4 radiation is a causal factor in the differential 5 diagnosis for his AML? 6 A. Yes. That is correct. 7 Q. Similarly, there's nothing in his occupational 8 history that would indicate to you that radiation is a 9 causal factor that must be considered in his particular 10 differential diagnosis for AML? 11 A. No. We have no evidence of radiation 12 exposure. 13 Q. You mentioned genetics as being another factor 14 that you would look at? 15 A. Yes. 16 Q. What, specifically, are you looking at with 17 respect to genetics? 18 A. Well, there are some articles that suggest 19 that children of women with breast cancer, for example, 20 have a higher risk of acute myeloid leukemia. We know 21 that the genetics that have to do with Down syndrome, 22 for example, predispose to acute leukemia. Certainly, 23 we have no evidence he had Down syndrome. Those would 24 be the things I would be looking at. 25 Q. And we also have no evidence that Mr. Draper's 13 1 mother had breast cancer? 2 A. No. 3 Q. So we can, similarly, rule out genetics as a 4 causative factor in his AML? 5 A. Well, I don't know that one can ever rule that 6 out. We don't know what causes most patients with AML, 7 and so all we can say is he has no family history of it. 8 Q. There's no evidence in this case to suggest 9 that Mr. Draper's genetics or genetic history is a 10 causative factor in his development of AML? 11 A. That is correct. 12 Q. You mentioned that the type of AML would be a 13 factor to consider in your differential diagnosis? 14 A. Yes. 15 Q. What do you mean by that? What types are you 16 considering? 17 A. Well, predominantly the chromosome array that 18 we see in the acute leukemia. 19 Q. Are there any chromosome arrays which you can 20 definitively say are not associated with exposure to 21 benzene? 22 A. Well, we don't have many patients with 23 benzene-induced leukemia that have been carefully 24 studied by chromosome analysis. The literature suggests 25 that there is a frequency of abnormalities in the 5th 14 1 and 7th chromosome similar to what we see at 2 chemotherapy. There, presumably, are other 3 abnormalities that are possible from benzene exposure. 4 But I cannot say with certainty what all of the 5 abnormalities that might occur from benzene are. 6 Q. Likewise, you can't say what chromosome 7 abnormalities are not related to benzene exposure? 8 A. Not with certainty. We, of course, can look 9 at the medical literature to see if they're present or 10 have been described. If they haven't been described, it 11 means that's unusual, but it might not mean they 12 couldn't occur. 13 Q. Is there any medical literature that you have 14 seen that you can cite for me today that would indicate 15 that the type of chromosome damage Mr. Draper has is not 16 related to benzene exposure? 17 MR. SCHIRRMEISTER: Object to form. 18 A. Well, Martyn Smith and Zang published an 19 article in which they reviewed the world's literature on 20 chromosome abnormalities and benzene or possibly induced 21 by benzene, and the only mention of inversion 16 in the 22 entire article is a sentence that says it occurs in de 23 novo AML. 24 MR. DUPONT: Respectfully, I move to 25 strike because I don't think that answers my question. 15 1 Q. (By Mr. DuPont) My question is: Can you cite 2 for me a specific study that affirmatively says the type 3 of chromosome damage that Mr. Draper suffers from is not 4 caused by benzene exposure? 5 MR. SCHIRRMEISTER: Object to the form. 6 A. No. 7 Q. (By Mr. DuPont) You mentioned AML arising 8 and then myelodysplastic phase or preceding MDS. What 9 types of MDS would you consider arising prior to 10 diagnosis of AML as being a causative factor in 11 development of AML being related to benzene exposure? 12 A. Well, the classical type of MDS that we see 13 preceding benzene exposure would be what's referred to 14 as a hypoplastic type of MDS where the bone marrow has 15 undergone some suppression and has abnormalities in cell 16 development. That would be the type that's been seen 17 after benzene poisoning and would be the most -- the 18 most suggestive of a benzene effect. Certain 19 myelodysplastic syndromes, such as sideroblastic 20 anemias, for example, have never been described from 21 benzene exposure. 22 There are other syndromes. The 23 classification of myelodysplasia is very cumbersome, 24 complex, and has undergone many revisions since it was 25 proposed around 1982. And an illness called chronic 16 1 myelomonocytic leukemia was originally grouped as a 2 myelodysplastic syndrome. It now is not. It also has 3 not been related to benzene exposure. 4 Q. Smoking was another factor you mentioned. 5 What is the shortest smoking history in terms of pack 6 per year or pack year history which you would relate to 7 being a causative factor in the development of AML? 8 A. Well, I don't know the answer to that in terms 9 of what would be the shortest. The attorney general's 10 report tells us that a 20-pack-year history doubles the 11 risk, so I would accept a 20-pack-year history as 12 potentially conducive to AML. It could be less, but I 13 don't know that. 14 Q. In terms of what the literature establishes, 15 though, it's your position that you have to have at 16 least a 20-pack-year history for a doubling of the risk 17 of AML associated with cigarette smoking? 18 A. I think that would be true, yes. 19 Q. And anything less than 20 packs per year 20 smoking history or a 20-pack-year smoking history, you 21 would not consider a causative factor in development of 22 AML? 23 MR. SCHIRRMEISTER: Object to the form. 24 A. I couldn't be certain about that. In other 25 words, I use that reference point because that is a 17 1 reference point that has been pointed out in the 2 literature. It could be less, but I don't have any 3 evidence of that. 4 Q. (By Mr. DuPont) You cannot say affirmatively 5 that any history of smoking less than 20 pack years is 6 causative in a diagnosis of AML? 7 MR. SCHIRRMEISTER: Object to the form. 8 A. That is correct. 9 Q. (By Mr. DuPont) What level of smoking history 10 must one have to reach a tripling of the risk for AML? 11 A. I don't know that, and I don't know if -- if 12 that is known with accuracy. 13 Q. Doctor, you've testified before that you need 14 to see a tripling of the risk in order to make an 15 association between exposure to a toxin and development 16 of AML? 17 A. I don't think that's correct. I'm not sure 18 which deposition you're referring to, but what I, 19 typically, have said is that -- in the past is that what 20 you're looking for is consistency, and an association of 21 less than tripling might be indicative of an association 22 if you have consistency among the number of studies. If 23 you only had a single study to go by, then I would say 24 that you need, certainly, more than a doubling of the 25 risk. 18 1 Q. What are all the studies that you consider 2 with respect to smoking being causative of AML? 3 MR. SCHIRRMEISTER: Object to the form. 4 A. As we sit here, I can't tell you all of the 5 studies. One of the articles I referenced was a review 6 of that by a prominent hematologist in 2007, and he has 7 lots of references there. I referenced a few others in 8 my report. I'm sure there are many papers that attest 9 to that. 10 Q. (By Mr. DuPont) If a -- strike that. 11 If a patient came to you with newly 12 diagnosed AML and there was no chromosome abnormalities 13 found, would you say to that patient that their AML 14 could not have been caused by benzene exposure? 15 A. No. 16 Q. If a patient came to you with a newly 17 diagnosed AML and their chromosome damage presented as 18 an inversion of the 16th chromosome, would you say to 19 that patient that their AML could not have been caused 20 by exposure to benzene? 21 MR. SCHIRRMEISTER: Form. 22 A. I would have no basis for saying that it could 23 be. In other words, there's no precedent for that in 24 the literature, so I would say, as I normally say in any 25 case of leukemia, we cannot, with certainty, say the 19 1 etiology. But it would be highly unlikely to be due to 2 benzene. 3 Q. (By Mr. DuPont) I just want to get an answer 4 to my question. 5 If a patient came to you with a newly 6 diagnosed AML and an inversion 16 were found that's the 7 chromosome damage, would you say to that patient that 8 their AML was not caused by benzene exposure? 9 MR. SCHIRRMEISTER: Object to the form. 10 A. As I've just said, I cannot say with certainty 11 what causes AML, so I cannot say with certainty what 12 doesn't cause AML. 13 Q. (By Mr. DuPont) But nonetheless, you couldn't 14 tell that person that the presence of an inversion 16 15 meant that their AML was not caused by benzene exposure, 16 could you? 17 MR. SCHIRRMEISTER: Object to the form. 18 A. That is correct. 19 Q. (By Mr. DuPont) You'll agree with me that 20 benzene is a confirmed human carcinogen? 21 A. Yes. 22 Q. And when did benzene first become a confirmed 23 human carcinogen? 24 A. I don't know the date of that confirmation. 25 Q. You'd agree with me that the routes of 20 1 exposure to benzene include inhalation? 2 A. Yes. 3 Q. They include dermal absorption? 4 A. Yes. 5 Q. And they include ingestion? 6 A. Yes. 7 Q. If you were considering the manner in which an 8 individual was exposed to a solvent containing benzene, 9 would you eliminate dermal exposure from your analysis 10 knowing that benzene can be dermally absorbed through 11 the skin of a worker? 12 MR. SCHIRRMEISTER: Object to form. 13 A. No. 14 Q. (By Mr. DuPont) To do so would be eliminating 15 one-third of the risk of the routes to exposure, 16 correct? 17 MR. SCHIRRMEISTER: Object to the form. 18 A. Of those three that you mentioned, yes. 19 Q. (By Mr. DuPont) And to do so would be to 20 underestimate the individual's exposure. Wouldn't that 21 be correct? 22 MR. SCHIRRMEISTER: Object to the form. 23 A. It would be correct, keeping in mind that I'm 24 not a toxicologist, so I can't comment about the various 25 percentage of exposure that one gets from these various 21 1 routes of exposure. 2 Q. (By Mr. DuPont) Doctor, what is latency? 3 A. Latency, with respect to leukemia, is when 4 you -- it's the period of time between when you have 5 reached a dose of the chemical that is leukemogenic and 6 the time that you actually develop the leukemia. 7 Q. You predicted my next question, which is: At 8 what point in time for an individual who's 9 occupationally exposed to benzene do you begin the 10 latency clock running? In other words, at what point in 11 time in that individual's work history do you start 12 calculating the latency period? 13 A. Well, again, it would be when they've had a 14 dose, a cumulative dose, that is considered sufficient 15 to cause AML. 16 Q. Doctor, do you have Mr. Draper's medical 17 records with you? 18 A. Yes. 19 Q. Can you tell me when is the most recent 20 medical records that you've received for Mr. Draper? 21 What are the dates of those records? 22 A. If you'll hang on a second, let me see if I 23 can find it. 24 Q. Please take your time. 25 A. I believe they would be from this disk I have 22 1 here labeled 12/14/05. 2 Q. So would it be true that the most recent 3 records you received are from 12/14/05; otherwise, 4 December 14, 2005? 5 A. Let me just see what I said in my letter if I 6 commented about that. Well, no. Somewhere in here I 7 have a blood count from August the 7th, 2007 -- I 8 mentioned that in my letter -- that showed his blood 9 count to be normal. So in this pile of records 10 somewhere are at least blood counts from 2007. 11 Q. Have you reviewed the medical records up 12 through December 14, 2005? 13 A. Yes. 14 Q. Would you agree with me that the treatment 15 provided to Mr. Draper as evidenced by those medical 16 records is reasonable and necessary for the treatment of 17 his AML? 18 A. Yes. 19 Q. Have you received bills relating to his 20 medical treatment? 21 A. Actually, I don't see any of that in this 22 material I have here. They may be on this disk, but I 23 didn't print them out. 24 Q. Do you recall reviewing medical bills relating 25 to Mr. Draper's medical treatment? 23 1 A. I'm sure I did not. 2 Q. Did you report the -- review the report of 3 Ginny Stegent, an expert on behalf of the plaintiffs in 4 this case? 5 A. If it's in my materials here, I have. I don't 6 recall it, as we are speaking. 7 Q. Doctor, I have several invoices in my copy of 8 your file, one dated October 10, 2007, and another dated 9 May 23rd, 2007. Do you have those in front of you? 10 A. Let's see. Yes. I have my invoices. 11 Q. And how many invoices do you have in front of 12 you? 13 A. Four. 14 Q. Four of them. 15 What are the dates on those invoices? 16 A. Let's see. December 26, '05; April 23rd, '07; 17 October 10, '07; November 6, '07. These may be 18 rebilling some of these, but those are the dates on the 19 invoices. But the actual charges are four. 20 Q. What are the charges reflected on the 21 December 26th, 2005, invoice? 22 A. $937.50. 23 Q. And what do those charges relate to? 24 A. Review of some records. 25 Q. Medical records? 24 1 A. Yes. 2 Q. Any other records? 3 A. No. 4 Q. The April 23, 2007, invoice, what are those 5 charges for, and how much are those charges? 6 A. Those are $625. They're records of 7 Mr. Draper's deposition testimony, some medical records, 8 some non-medical records, some expert reports of Arthur 9 Frank, Burton Davidson, Edward Agura, Martyn Smith, Mark 10 Nicas. 11 Q. I'm actually looking at a May 23, 2007, 12 invoice for the same balance, which appears to be -13 involves similar materials, and it says a second 14 invoice? 15 A. It could be that that's just a rebilling. 16 Q. Okay. I understand. 17 A. And, by the way, while we're talking and you 18 had asked me about medical records, I have a letter from 19 the treating physician on January 30th, 2007, on 20 Mr. Draper. 21 Q. Okay. How does that letter describe 22 Mr. Draper's course of treatment? 23 A. I'm not sure what, specifically, you're 24 asking. 25 Q. Well, does he describe it as a complicated 25 1 course of treatment? Was he responding well to 2 treatment? 3 A. Well, the letter isn't long. I can go through 4 it. He indicates he had his leukemia discovered in the 5 fall of 2002. He had initial treatment that was not 6 complicated for acute leukemia, and he promptly went 7 into remission. And then he remained in remission for a 8 time, but in January of 2004, he relapsed. And he 9 received additional treatment, which did not get him 10 into remission but then additional treatment 11 subsequently that did get him in remission. 12 And then because he was having trouble 13 staying in remission, he had an allogeneic marrow 14 transplant, which he indicates was well tolerated, and 15 that he's been in complete remission since that time. 16 Q. And you would agree with me that "complete 17 remission" does not mean that an individual is cured 18 from the leukemia? 19 A. That is correct. 20 Q. There is an October 10, 2007, invoice. How 21 much is that for? 22 A. $1,625.00. 23 Q. And then November 6, 2007, deposition 24 transcripts? 25 A. Yes. That's -- 26 1 Q. What's that for? 2 A. $750. 3 Q. And you're currently billing at $400 per hour 4 for deposition and trial testimony? 5 A. Yes. 6 Q. And $250 an hour for all other testimony? 7 A. Yes. 8 Q. Excuse me. All other services? 9 A. Yes. 10 Q. You mentioned in conjunction, I believe, with 11 your April 23rd, 2007, invoice that included review of 12 the deposition transcript from Mr. Draper. Is that the 13 March 21, 2006, deposition transcript? 14 A. Well, let me look and see what I have here. 15 That's March 21, 2006. 16 Q. Is that the only transcript of Mr. Draper's 17 deposition that you have reviewed? 18 A. Yes. 19 Q. What services were provided by you in 20 conjunction with the November 6, 2007, invoice? In 21 other words, what were you billing for that? 22 A. That had to do with an office conference with 23 Mr. Schirrmeister, review of the report of Mr. Russell 24 and of Mr. Keller. 25 Q. Was that the first time that you had the 27 1 opportunity to review either Mr. Russell or Mr. Keller's 2 report in this case during that conference that's 3 reflected in your November 6, 2007, invoice? 4 A. I don't know. I don't remember when they 5 came, but, obviously, they came before this bill was 6 sent. 7 Q. Did you review either Mr. Russell or 8 Mr. Keller's reports prior to preparing your own report 9 in this case? 10 A. I don't know the answer to that without some 11 detailed study of these records. The date of the report 12 is October the 10th, and so if I had something prior to 13 October the 10th, I would have looked at it before I 14 wrote that report. 15 MR. DUPONT: Before I get too far afield, 16 let's mark the invoices as Exhibit A. 17 (Exhibit A marked.) 18 Q. (By Mr. DuPont) Doctor, let me ask you: Did 19 you make any notations on Mr. Draper's deposition 20 transcript? 21 A. No. 22 Q. Okay. 23 MR. DUPONT: Let's mark the transcript as 24 Exhibit B, and the -- I think it's January 30, 2006, or 25 2007 letter of Dr. Edward Agura as C. 28 1 (Exhibits B and C marked.) 2 MR. SCHIRRMEISTER: What do you want to 3 mark as B? 4 MR. DUPONT: Mr. Draper's deposition 5 transcript. 6 Q. (By Mr. DuPont) Doctor, have you made any 7 notes concerning this case? 8 A. No. 9 Q. Prior to your final report which you issued, 10 did you have any drafts of your report? 11 A. I probably did, but the way this operates is 12 that I might get the medical records first, before any 13 reports or other information, depositions and so on, so 14 what I normally do is I type out a summary of what the 15 case is, the medical facts of the case. And then as 16 the -- all of the materials are assembled, then I modify 17 that and add other features and add references and 18 finish the report. 19 Q. Do you have your initial summary or any of the 20 subsequent drafts of your summary that you made prior to 21 executing your final report? 22 A. No. I normally don't keep any hard copies, 23 and I revise the letter on my computer so all that ends 24 up being there is the final report. 25 Q. Prior to executing your final report, did you 29 1 show a draft of your report to any of the attorneys for 2 the defendants in this case? 3 A. No. 4 Q. Prior to executing your final report, did you 5 show a draft of your report to any of the other experts 6 that have issued reports on behalf of the defendants in 7 this case? 8 A. No. 9 Q. Did you review the expert reports of any of 10 the other, I'll call, either doctors or toxicologists 11 testifying or providing reports on behalf of the 12 defendants in this case? 13 A. I reviewed what reports I have here, which are 14 mentioned in those bills. Let's see. I reviewed a 15 report written to Mr. Schirrmeister from Brad Russell. 16 Q. When did you receive Mr. Russell's report? 17 A. The draft -- the letter is entitled 18 "October 8, 2007," and I received it, according to this 19 e-mail I have, 10/10/07. 20 Q. And who is that e-mail from? 21 A. Let's see. It's from Andrew Schirrmeister to 22 me, carbon copy to Mr. Stofko. 23 Q. And you understand that that is a draft of 24 Mr. Russell's report? 25 A. No. I don't know that. I just have the 30 1 report. Oh. It does -- excuse me. I'm sorry. It does 2 say -- on the e-mail, it says "draft report." 3 MR. DUPONT: Let's go ahead and mark that 4 report, along with the e-mail, as Exhibit D, if you 5 don't mind. 6 (Exhibit D marked.) 7 Q. (By Mr. DuPont) Did you see the drafts of any 8 of the other expert reports for -- that were submitted 9 on behalf of the defendants? In other words, did you 10 see drafts of any of those reports before the final copy 11 was executed? 12 A. No. 13 Q. Did you speak with any of the other doctors or 14 toxicologists that issued reports on behalf of the 15 defendants prior to issuing your report? 16 A. No. 17 Q. Were you asked by any of the attorneys for the 18 defendants in this case to address specific issues in 19 your report or cite any specific literature in support 20 of your report? 21 A. No. 22 Q. Were you provided with any literary references 23 from any of the attorneys on behalf of the defendants in 24 this case? 25 A. No. 31 1 Q. Were you provided with any notes or 2 memorandums that provided kind of a template or an 3 outline of what your report should look like from any of 4 the attorneys for the defendants in this case? 5 A. No. 6 Q. Doctor, I have a document in front of me 7 that's entitled, "Dr. Ethan Natelson's File Inventory, 8 December 3, 2007," with the caption "Duane Draper versus 9 PPG Industries, Inc., et al." on top. Do you have that 10 as -- is that part of your file? 11 A. Not that I know of. I'm not sure what that is 12 that you're referring to. 13 Q. Okay. And I'm not suggesting that it is. I'm 14 just trying to -- I'm trying to think of an easy way to 15 do this. 16 Okay. Let's do this. Do you have your 17 December -- excuse me -- your October 10, 2007, report 18 in front of you? 19 A. Yes. 20 Q. The back of your report, there's a number of 21 literary references? 22 A. Yes. 23 Q. And those are the references that you relied 24 upon in drawing the opinions and conclusions in your 25 report? 32 1 A. Yes. 2 Q. Part of your opinions concern -- and I'm going 3 to butcher this, and then we'll abbreviate it -4 "Topoisomerase II Inhibitors and Their Effect on 5 Chromosome Damage in the Lymphocytes and Myeloid Cells." 6 Generally, that's accurate? That's a topic that you 7 discuss? 8 A. Yes. 9 Q. And one of the conclusions you reach is 10 that -- we'll call it topo II -- topo II inhibitors, the 11 chromosome damage that they cause in lymphocytes is not 12 relevant to chromosome damage in myeloid cells. Is that 13 accurate? 14 A. Let me just see what I wrote there. What I 15 said is that most chemotherapeutic agents cause 16 chromosomal abnormalities in the lymphocytes of patients 17 receiving these drugs whether the drugs are known 18 leukemogens or not. Such abnormalities are not 19 sustained and are rapidly repaired and then return to 20 normal. 21 And I go on to mention that one of the 22 drugs we used for many, many years in chemotherapy is 23 methotrexate, which produces striking abnormalities in 24 chromosomes and lymphocytes, both in the test tube and 25 in people, and yet is not known as a leukemogen. 33 1 And so that and many other articles call 2 into question the notion that simply demonstrating 3 abnormalities in a lymphocyte has much to do with acute 4 myeloid leukemia in an entirely different cell line. 5 And, specifically, with reference to inversion 16, I 6 also provided Mr. Schirrmeister with papers that show 7 that the -- given patients who have inversion 16 8 leukemia, their lymphocytes don't bear that particular 9 abnormality. 10 Q. Okay. Why don't we start with that last 11 portion of what you just said. Can you point to me on 12 your literary references at the end of your October 10 13 report those papers you rely upon with respect to your 14 analysis of the lymphocytes and inversion 16? 15 A. Well, let's go back to that paragraph. Well, 16 let's see. It started out with references 48, 49, 50 17 through 51, and then subsequent to this report I gave 18 some additional references to Mr. Schirrmeister 19 concerning inversion 16 and a few of the other balance 20 translocations which demonstrate that they don't carry 21 chromosome abnormalities in the lymphocytes. And you 22 probably should have copies of those articles because 23 they were to be added to my file. 24 MR. SCHIRRMEISTER: Those are the ones 25 that we read into the record before the deposition 34 1 began, so I'm not sure if the court reporter took those 2 down. 3 MR. DUPONT: Okay. They're attached to a 4 note that says: "Dear Mr. Schirrmeister, These three 5 articles are not listed in my report" -6 THE WITNESS: That's correct. 7 MR. SCHIRRMEISTER: You want me to mark 8 those? 9 MR. DUPONT: Can we take that note, along 10 with the reports that that note applies to, and mark 11 them as the next exhibit? 12 MR. SCHIRRMEISTER: I'm not sure if we 13 have a copy of the note. 14 THE WITNESS: Yeah. I don't have the 15 note. 16 MR. SCHIRRMEISTER: Is it the -- do you 17 have the note in front of you, Andrew? 18 MR. DUPONT: I do. 19 MR. SCHIRRMEISTER: Does it say "Mariette, 20 McDevitt and Seymour"? 21 THE WITNESS: No. The one he's talking 22 about are these three. These are the three that I gave 23 you. Those are ones I just brought today. 24 MR. SCHIRRMEISTER: Oh. Okay. 25 THE WITNESS: These are ones that I 35 1 previously gave you, and that's the ones he's talking 2 about, I believe, in that e-mail. 3 MR. SCHIRRMEISTER: And then we have an 4 additional three today that were brought to the 5 deposition. So we have six in all. 6 MR. DUPONT: And the note that starts: 7 "These three articles are not listed in my report, but I 8 would add them to the references that I would cite in 9 the Draper case," is that there with those initial three 10 reports? 11 MR. SCHIRRMEISTER: I don't have the note. 12 MR. DUPONT: Okay. 13 MR. SCHIRRMEISTER: I'll just list the 14 studies, and then there was an additional three as well. 15 MR. DUPONT: Okay. We'll mark those two 16 sets of three as two separate exhibits. 17 (Exhibits E - J marked.) 18 MR. SCHIRRMEISTER: Okay. We're up to J. 19 And then there are also four abstracts, which I'll mark 20 as just one. 21 MR. DUPONT: Okay. 22 (Exhibit K marked.) 23 Q. (By Mr. DuPont) Doctor, do you consider 24 yourself to be an expert in the mechanisms of 25 benzene-induced leukemia? 36 1 A. No. 2 Q. Do you consider yourself to be an expert in 3 the manner in which chemotherapeutic topo II inhibitors 4 cause leukemia? 5 A. No. 6 Q. Do you actively research in the area of the 7 manner in which chemotherapeutic topo II inhibitors 8 cause leukemia? 9 A. No. 10 Q. Have you ever researched that in terms of 11 active laboratory research? 12 A. Not topoisomerase II. I have been engaged in 13 projects with topoisomerase I, which is a similar type 14 enzyme. 15 Q. Who would you consider to be the lead 16 researchers in the area of the manner in which 17 topoisomerase II inhibitors cause leukemia? 18 A. I don't know. 19 Q. Who would you consider to be the lead experts 20 in that area? 21 A. I don't know the answer to that. I know 22 Richard Irons has studied that, Dr. Eastman has studied 23 that, several have published papers in that area. 24 Q. Would you agree with me that Dr. Martyn Smith 25 is an expert in the area of the manner in which 37 1 topoisomerase II inhibitors cause AML? 2 MR. SCHIRRMEISTER: Object to the form. 3 A. Well, much of Martyn Smith's work has been 4 done in lymphocytes, and as I've said, lymphocytes are 5 not the cell in question here. They're myeloid cells. 6 So the relevance of much of his work in lymphocytes I 7 have difficulty relating to acute myeloid leukemia. He 8 has written many papers, he has various theories and 9 hypotheses that he mentions in his papers, but much of 10 this is based on lymphocyte work, which I think can be 11 very deceptive. 12 MR. DUPONT: Move to strike because I 13 don't think that answers my question. 14 Q. (By Mr. DuPont) My question, sir, is whether 15 you consider Martyn Smith to be an expert in the manner 16 in which topo II inhibitors cause leukemia. 17 MR. SCHIRRMEISTER: Object to the form. 18 A. I don't know. 19 Q. (By Mr. DuPont) Do you consider Dr. Smith to 20 be an expert in the manner in which benzene metabolites 21 cause leukemia? 22 MR. SCHIRRMEISTER: Object to the form. 23 A. I don't know the answer to that either. 24 Q. (By Mr. DuPont) Doctor, what are the 25 different types of topo II inhibitors? 38 1 A. Well, there are many drugs that inhibit an 2 enzyme. And enzyme inhibitors can be, for example, as 3 the one we've studied in topoisomerase I, a drug that 4 blocks the active site of an enzyme. Those would be 5 drugs like camptothecin, which is the ones I'm familiar 6 with. There are other drugs that can directly damage 7 certain enzymes. There are drugs that can act as 8 competitive inhibitors of enzymes. At the end of the 9 day, the bottom line is they inhibit the natural 10 function of topoisomerase system, which is to help in 11 reproduction of DNA. 12 Q. You understand there to be a group of topo II 13 inhibitors that are referred to as catalytic inhibitors? 14 A. Yes. 15 Q. And a group of topo II inhibitors that are 16 referred to as topoisomerase II poisons? 17 A. Yes. That's the term that Dr. Martyn Smith 18 used in his deposition. 19 Q. Can you tell me which of the studies that 20 you've cited to or relied upon relate to topo II 21 catalytic inhibitors? 22 A. Well, the studies that I cite have to do with 23 the hematology of topoisomerase inhibitors; in other 24 words, the consequences. And, for example, in clinical 25 medicine it's very difficult to assess the effect of a 39 1 single topoisomerase inhibitor on a patient because of 2 the fact that when they're used in chemotherapy, they're 3 often multiple ones are used at the same time. 4 So that in general when you look at 5 hematology literature on the consequences of 6 topoisomerase II inhibitors, their results are often 7 painted with a broad brush. For example, I have one 8 article that I've referenced in my report that's an 9 international -10 Q. Doctor, what I'm asking is: Which reports 11 address specifically topo II catalytic inhibitors versus 12 the topo II poison? 13 MR. SCHIRRMEISTER: The witness was 14 answering the question. 15 A. Well, I'm trying to answer the question. 16 Dr. Martyn Smith identified etoposide, for example, as a 17 topoisomerase II poison, and he alleged that that does 18 not cause inversion 16 in his deposition. 19 Now, what I'm looking at here is an 20 article that's an international workshop on inversion 16 21 by experts in this field. And what the experts in this 22 field show is they look at large numbers of people who 23 have inversion 16 and also another translocation called 24 15;17. And what they show in their tables is the most 25 common drug associated with inversion 16 is etoposide. 40 1 That's the drug that Martyn Smith says doesn't cause 2 inversion 16. 3 And, in fact, in the text of that article, 4 it says: "In the inversion 16 subgroup, doxorubicin," 5 which is adriamycin, "and etoposide were the most 6 frequently administered topoisomerase II inhibitors." 7 Talking in the inversion 16 group, excuse me, 8 "Doxorubicin and etoposide were the most frequently 9 administered topoisomerase II inhibitors, whereas 10 doxorubicin and mitoxantrone were the most frequently 11 administered T-II inhibitors in the translocation 12 (15;17) group. The difference in frequency of 13 administration of etoposide between the two subgroups 14 approaches statistical significance." 15 So, in other words, what these authors are 16 saying, in contrast to what Martyn Smith says, is that 17 etoposide looks to be prominent in the cause of topo -18 of inversion 16, and mitoxantrone, another type of 19 inhibitor, prominent in the cause of 15;17 20 translocation. 21 MR. DUPONT: Move to strike. 22 Q. (By Mr. DuPont) My question is: Which 23 references that you cited to in your report or which 24 you've brought with you to your deposition today deals 25 specifically with topo II catalytic inhibitors versus 41 1 topo II poisons? 2 MR. SCHIRRMEISTER: Object to the form. 3 A. None of the references do. 4 Q. (By Mr. DuPont) Okay. The etoposide is a 5 topo II poison as opposed to a catalytic inhibitor? 6 A. That's what Dr. Martyn Smith says. 7 Q. Well, do you disagree that etop- -- excuse 8 me -- that etoposide is a topo II poison? 9 A. It causes inhibition of the enzyme, which is 10 the key issue. How it does that, I'm not an expert on. 11 Q. So your interpretation is that if 12 topoisomerase II causes inhibition of an enzyme, it must 13 be a catalytic inhibitor as opposed to a poison? 14 A. No. I'm saying that there are many mechanisms 15 to inhibit an enzyme, and I'm not an expert on all the 16 various mechanisms to inhibit topoisomerase II. There 17 are several. But I am familiar with the medical 18 literature on the consequences of inhibiting the 19 activity of topoisomerase II, and I've just read you 20 quotes from an article dealing in that subject. 21 Q. Prior to your executing the October 10, 2007, 22 report, and prior to your deposition today, you have not 23 been able to identify for me any literature that you've 24 considered directly as it relates to topo II catalytic 25 inhibitions? 42 1 A. I would have no reason to search out such 2 literature. 3 MR. SCHIRRMEISTER: Object to the form. 4 MR. DUPONT: Counsel, why don't we take a 5 brief break? We've been going about an hour. 6 MR. SCHIRRMEISTER: Okay. 7 (Recess from 2:47 p.m. to 3:00 p.m.) 8 Q. (By Mr. DuPont) Dr. Natelson, before the 9 break, we discussed the McDevitt article to some extent? 10 A. We mentioned it, yes. 11 Q. Okay. And that's the 2007 publication? 12 A. Yes. 13 Q. The purpose of that article was to perform a 14 pilot study to validate the use of FISH technique to 15 examine chromosomal abnormalities in peripheral blood 16 cells? 17 A. In patients with acute leukemia, yes. 18 Q. All right. And that study found, in fact, 19 that it was a -- using FISH to analyze chromosomal 20 aberrations in peripheral blood cells was, in fact, a 21 valid method? 22 A. With certain chromosome abnormalities. In 23 other words, they primarily studied people with 24 trisomiate, which causes many things other than acute 25 myeloid leukemia and can be found in lymphoid cells and 43 1 also chromosome 5 and 7 abnormalities. They didn't 2 study inversion 16, for example. 3 Q. Okay. Well, they studied breaks in 4 chromosomes at 11q, didn't they? 5 A. I think deletions at 11. I don't have it in 6 front of me. But yes. Something that had to do with 7 the chromosome 11. 8 Q. And what that study did was actually validate 9 the use of looking at chromosome aberrations down in the 10 peripheral cells as a method for comparing aberrations 11 found in the myeloid cells. Would that be correct? 12 A. Well, it was a method for looking at these 13 changes in people who actually have acute leukemia in 14 place. In other words, not a method for predicting 15 leukemia. These are people who already have leukemia. 16 And the real question that Martyn Smith's 17 work deals with is, can one look at people who are 18 exposed, find abnormalities in the lymphocytes and 19 suggest that that might have a relationship to acute 20 myeloid leukemia. In other words, could that be 21 predictive of risk. And as I showed you with some of 22 these articles, we already know that it's not because 23 there are many drugs out there that cause these kinds of 24 abnormalities in lymphocytes, but they don't cause acute 25 myeloid leukemia. 44 1 MR. DUPONT: All right. Move to strike. 2 Q. (By Mr. DuPont) And I'd just like to get an 3 answer to the question that I asked, and that is: This 4 study actually demonstrated, meaning McDevitt -5 actually demonstrated that the same types of chromosome 6 aberrations that you see in myeloid cells caused by 7 secondary sources are the same type that you see in 8 peripheral blood cells caused by secondary leukemia -9 secondary sources; is that correct? 10 MR. SCHIRRMEISTER: Object to form. 11 A. I think I said that, that in patients with 12 acute leukemia in place, one can find commonalities of 13 chromosomes in the lymphocytes in certain of the 14 patients in that study with certain chromosome 15 abnormalities. 16 Q. (By Mr. DuPont) And the commonality is 17 between the lymphocytes and the myeloid cells, correct? 18 A. Yes. 19 Q. But it's your position that that commonality 20 only exists with respect to certain types of chromosome 21 damage? 22 A. Well, I don't know that, but at this point, 23 we're discussing a case with inversion 16. And as we've 24 shown, that study has been looked at in people with 25 inversion 16, and those abnormalities are not seen. 45 1 Q. And, Doctor, your position, though, is that 2 McDevitt looked at specifically inversion 16 and ruled 3 inversion 16 out as a type of chromosome damage that's 4 consistent in myeloid cells and lymphocytes? 5 A. Well, I don't know why he chose the subjects 6 that he did, but, specifically, he used FISH looking at 7 people who had certain particular chromosome 8 abnormalities. 9 Q. But his study doesn't stand for the 10 proposition that inversion 16 is not a chromosome damage 11 that's seen both in the lymphocytes and the myeloid 12 cells? 13 A. No. He did not mention inversion 16 in the 14 article. 15 Q. Doctor, in coming to your opinions in this 16 case, did you consider the differences in the incidences 17 of inversion 16 caused by topo II poisons versus topo II 18 catalytic inhibitors, or did you group them all 19 together? 20 A. I grouped them all together because that's the 21 way the hematologic literature approaches this issue. 22 Q. And what is the basis for your saying that? 23 What is the basis for you saying that it's valid to 24 group all of the topo II inhibitors together as opposed 25 to looking at individual groups of topo II inhibitors? 46 1 A. Well, that's what these articles say. In 2 other words, we have a situation where we very rarely 3 use a single topoisomerase inhibitor on a single 4 patient. They're often multiples. And so it's very, 5 very difficult to separate in clinical medicine which 6 particular topoisomerase inhibitor did what. 7 But you look at frequency, he says. This 8 article I quoted mentioned -- from Anderson, and it 9 looked in this particular article that etoposide had the 10 most frequent association with inversion 16. But the 11 article pointed out, as many other articles do, that 12 many drugs cause inversion 16. They don't have to be 13 topoisomerase inhibitors. 14 Q. Which, if we're going to look for specific 15 references that you relied upon for the position of 16 looking at topoisomerase inhibitors generally as opposed 17 to individual groups of topoisomerase inhibitors, those 18 would be citations 48 through 51 plus the six studies 19 that you brought today? 20 A. Well, those would be some of them. Of course, 21 I wasn't specifically trying to focus on that point, but 22 these articles do address that. 23 Q. Can you cite for me any other articles that 24 address that? 25 A. Well, let's just see. I don't see any other 47 1 articles that I brought today that specifically get into 2 that subject, aside from the Anderson article. 3 Actually, there are two Anderson articles. Let me see 4 if I really cited the both of them. 5 For example, the article I cited in my 6 report is entitled -- it's by Anderson, called "Balanced 7 Chromosome Abnormalities." And this is another article 8 by Anderson from 1998. And in this particular one, for 9 example, they noted, as I think Martyn Smith said, 10 "Translocations to 11;23 predominated following therapy 11 with epipodoxophyllins, whereas patients with 12 translocations such as inversion 16 most often had 13 received anthracyclines." That's the adriamycin type. 14 "In a multivaried analysis taking age into 15 consideration, however, these drug-specific associations 16 were no longer significant. Younger age and not a 17 specific type of DNA topoisomerase inhibitor seems to 18 predispose specifically to the development of TMDS and 19 TAML with translocations." 20 And so that this article would say, 21 essentially, the same thing that the other Anderson 22 article, which is a few years later in the larger 23 workshop, is that it's very difficult to separate 24 clinically the actions of these topoisomerase inhibitors 25 in humans because of the fact they're often used in 48 1 combination. They're not typically used as single 2 drugs. And that's what these people say. 3 Q. And your review was limited to the clinical 4 aspect because you're not a researcher on benzene's 5 effects on the chromosomes, are you? 6 MR. SCHIRRMEISTER: Object to the form. 7 A. No. In other words, I consider myself a 8 clinical hematologist. I'm quite familiar with the 9 literature, as a hematologist uses it, on chromosomes 10 and acute leukemia. I'm not a biochemist. But I'd 11 leave it at that. 12 Q. (By Mr. DuPont) Do you have anything more 13 recent than the two Anderson studies in support of your 14 position that it is appropriate to look at topoisomerase 15 II inhibitors as a group as opposed to specific types of 16 topoisomerase II inhibitors in evaluating their ability 17 to cause an inversion at chromosome 16? 18 A. No. 19 Q. What literature have you looked at that 20 examines topoisomerase II that those types of 21 inhibitors -- their effects on the myeloid cells with 22 respect to chromosome damage? 23 A. You're talking about the use of those 24 inhibitors in tissue culture, for example, or something 25 like that? 49 1 Q. In tissue culture or any other methodology of 2 studying the issue. 3 A. I haven't look at that specifically. 4 Q. Have you researched any articles that relate 5 to looking at topoisomerase II inhibitors causing 6 chromosome damage in progenitor cells? 7 A. Well, which progenitor cells? Are you talking 8 about bone marrow myeloid cells? 9 Q. Stem cells, any other progenitor cells. 10 A. Well, I think one of the papers I referenced 11 had to do with Dr. Iron's work looking at certain 12 topoisomerase II inhibitors in bone marrow myeloid 13 cells, which would be stem cells. 14 Q. And which paper was that? 15 A. This 47, the Stillman paper. 16 Q. Do you have an opinion, as we sit here today, 17 as to whether or not topo II catalytic inhibitors cause 18 inversion 16? 19 A. I would have to say that the literature 20 suggests that it does, can. 21 Q. All right. And that opinion would apply to 22 both inversion 16 found in lymphocytes as well as 23 myeloid cells? 24 A. I would have no idea what would happen in 25 lymphocytes. I don't know that -- I don't have any 50 1 articles that have to do with trying to get inversion 16 2 out of a lymphocyte. 3 Q. What do you consider the longest latency 4 period to be for an AML arising as a result of exposure 5 to a topo II catalytic inhibitor? 6 A. Well, in general, the leukemias that are 7 caused by topoisomerase inhibitors are thought to be 8 primarily short latency, let's say less than five years, 9 as opposed to the broad category of therapy-induced 10 leukemias, which, generally, is given around 2 to 10 or 11 2 to 12 years. 12 Q. And I want to be clear as to topoisomerase II 13 catalytic inhibitors. Do you know what the latency 14 period, the longest latency period found in the 15 literature is for that? 16 A. I can't tell you that it's broken out. As we 17 said, the literature, the hematologic literature, simply 18 uses the term "AML from topoisomerase II inhibitors" 19 without specifying their biochemical mechanism of 20 action. 21 Q. I want to jump back a little bit. When we 22 were talking about the latency period for occupational 23 benzene exposures, you told me that you would start the 24 latency period running from the time in which the 25 cumulative dose reached an amount sufficient to cause 51 1 AML; is that correct? 2 A. Yes. 3 Q. What do you consider a cumulative dose 4 sufficient to cause AML to be? 5 A. Well, if you look at the various studies that 6 the -- that we rely on, the Pliofilm study, and 7 according to Dr. Wong's analysis, that's about 200 part 8 per million cumulative exposure to catch leukemia in 9 that particular group. In another one I reference 10 that's a somewhat similar but newer study, about the 11 same number of people, they only found statistically 12 significant incidence at around 200 part per million 13 year exposure. I reference another one where they 14 didn't find an increase at 40 part per million year 15 exposure. 16 So I don't know with certainty what that 17 total dose might be, but it's very high, and certainly 18 more than 40 parts per million and probably more than 19 100 part per million cumulative dose exposure. 20 Q. Do you have an understanding of what OSHA's 21 permissible exposure limit is for benzene? 22 A. In very general terms, you know, 1 part per 23 million, I believe. 24 Q. And OSHA applies permissible exposure limit 25 based on an eight-hour workday, correct? 52 1 A. Yes. 2 Q. And a 40-year work life? 3 A. Yes. 4 Q. So if you and OSHA -- strike that. 5 If you take the cumulative dose for a 6 40-year work life of a part-per-million-per-day 7 exposure, that gives you a 40-part-per-million-year 8 dose, does it not? 9 A. Yes. 10 Q. And OSHA, in setting the permissible exposure 11 limits, were required to consider the effects of the 12 economy on reducing the permissible benzene exposure 13 levels; is that correct? 14 MR. SCHIRRMEISTER: Object to the form. 15 A. I would not be an expert on what OSHA uses as 16 their reasoning. 17 Q. (By Mr. DuPont) Okay. Nonetheless, OSHA 18 believes that you will see a doubling of the risk of AML 19 at 40 part per million years with cumulative exposure? 20 MR. SCHIRRMEISTER: Object to the form. 21 A. I don't know that. 22 Q. (By Mr. DuPont) Assuming that that's what 23 OSHA believes, your threshold would be, what, five times 24 that level? 25 MR. SCHIRRMEISTER: Object to the form. 53 1 MR. STOFKO: Object to the form. Chris 2 Stofko. 3 A. Well, as I've cited, the literature suggests 4 it's considerably higher than that. 5 Q. (By Mr. DuPont) Okay. So the federal 6 government has it wrong? 7 MR. SCHIRRMEISTER: Object to the form. 8 A. No. The federal government wants to be 9 protective, and so they would want to set a limit less 10 than what might cause large amounts of leukemia. 11 Q. (By Mr. DuPont) Do you know what the federal 12 government found the risk of AML to be at 40 parts per 13 million years of exposure? 14 A. No. 15 Q. You mentioned that there was three 16 epidemiological studies that you rely upon. The first 17 was authored by Otto Wong. The second one also dealt 18 with 200 part per million years exposure. Who was that 19 authored by? 20 A. Costantini. That's No. 28. 21 Q. And the third study that you claim does not 22 find a doubling of the risk at 40 parts per million 23 years of exposure, which study is that? 24 MR. SCHIRRMEISTER: Object to the form. 25 A. No. 23, the Bloeman study, B-L-O-E-M-A-N. 54 1 Q. (By Mr. DuPont) As a clinician, do you have 2 to find a doubling of the risk association in order to 3 accept in the treatment of a patient that there is a 4 causal relationship between an agent and a result? 5 MR. SCHIRRMEISTER: Object to the form. 6 A. Not if there's -- well, I would like to see 7 more than two if you had a single article, but what 8 you're looking for, as I think I said before, is 9 consistency. If you had a number of studies that all 10 found a doubling of the risk, that would make it very 11 likely to be true. If you simply found one study that 12 found a tripling of the risk and it wasn't confirmed 13 with other studies, that wouldn't prove much to me. 14 Q. (By Mr. DuPont) Doctor, you're familiar with 15 the Chinese studies authored by Hayes, et al.? 16 A. Yes. 17 Q. And they find a cumulative dose of 40 part per 18 million years? 19 A. Well, that's what they allege. 20 Q. I'm sorry? 21 A. That's what they allege, yes. 22 Q. And you're familiar with the Deborah Glass 23 Health Watch study? 24 A. Yes. 25 Q. And they find a cumulative dose of 8 part per 55 1 million years with a more than doubling the risk for 2 leukemia? 3 A. There is no doubling of the risk in that study 4 because the most recent version of that shows that the 5 incidence of leukemia in that cohort is identical with 6 the national average for leukemia. 7 Q. My question is that the 2003 Deborah Glass 8 Health Watch study shows a cumulative dose of 8 part per 9 million years benzene causing more than a doubling of 10 the risk for leukemia. Isn't that correct? 11 MR. SCHIRRMEISTER: Object to the form. 12 A. That's what she alleges, yes. 13 Q. (By Mr. DuPont) All right. You would agree 14 with me that based on those studies, there's been a 15 downward trend in the cumulative dose of benzene leading 16 to a doubling of the risk of AML? 17 MR. SCHIRRMEISTER: Object to the form. 18 MR. STOFKO: Object to the form. Chris 19 Stofko. 20 A. I wouldn't agree with that because, as I said, 21 the only thing the Glass study demonstrates is that when 22 you don't have a control group that has the same -23 particularly in a small study, when you don't have a 24 control group that has similar incidence to the general 25 population, you can come to outlandish conclusions. And 56 1 in that study, they had about eight cases of leukemia in 2 about 18,000 people. In the Pliofilm study, with only a 3 tenth as many people -- about 1,800 people -- they had 4 seven cases of leukemia. 5 So just looking at that study, you would 6 guess that it wasn't a hotbed of AML, and in the later 7 analysis by Gunn, it shows that the incidence of 8 leukemia was identical to the -- to the population at 9 large. 10 Q. (By Mr. DuPont) What do you rely upon for 11 ascertaining the amount of benzene exposure Mr. Draper 12 had? 13 A. Well, I am not a benzene modeler, and I don't 14 know what exposure he had, so I have to rely on the 15 various experts that model it based on what compounds he 16 used, how frequently he used them, what level of benzene 17 was in those compounds, whether it was ventilated, not 18 ventilated. There's considerable guesswork there, but 19 that's what those types of experts do. And so I 20 certainly, on my own, couldn't come up with an accurate 21 estimate of what exposure he had. 22 Q. Have you reviewed the transcript from 23 Dr. Smith's testimony in this case from his deposition? 24 A. Yes. 25 Q. And what are your comments on that? First of 57 1 all, did you take any notes on that transcript? 2 A. No. 3 Q. What are your comments on his testimony? 4 A. Well, I guess the overall thing that I noticed 5 that was of interest to me about the testimony was that 6 he believes that cigarette smoking can cause inversion 7 16. Now, I'm not aware of any literature that supports 8 that, but let's assume that's so. He says it's so. 9 He also indicates that most people with 10 AML, perhaps 80 percent, don't have it from industrial 11 benzene exposure. So, therefore, a person with no 12 industrial benzene exposure can catch acute leukemia and 13 inversion 16, and someone who's a smoker, according to 14 Martyn Smith, can catch acute leukemia with inversion 15 16, yet when it comes to his differential diagnosis, 16 those two areas are not considered. In other words, 17 it's like they don't exist. 18 And so what he's telling us is he believes 19 that an extraordinarily rare cause of leukemia, in his 20 mind, is what caused this illness over what he admits 21 are the far more common possibilities. 22 Q. Are you telling me that Dr. Smith hasn't 23 considered cigarette smoking in his differential 24 diagnosis, or are you telling me that he's considered it 25 and found that benzene exposure is a much more 58 1 significant risk than that presented by cigarette 2 smoking? 3 A. Well, he doesn't discuss in that deposition 4 why. In other words, he says he believes -- he simply 5 comments when asked whether smoking can cause inversion 6 16, he said yes. He also commented that most leukemia 7 is de novo without any known exposure to benzene. His 8 conclusion, though, is this man has leukemia from 9 benzene. And he doesn't go into why he eliminates 10 cigarette smoking or what makes Mr. Draper immune to de 11 novo AML. 12 Q. What is the risk of AML from -- strike that. 13 You'd agree with me that there's a much 14 higher population of individuals who smoke cigarettes in 15 this country than there are individuals who are 16 occupationally exposed to benzene? 17 A. Yes. 18 Q. And you would agree with me that the 19 difference in the size of those populations is an order 20 of magnitude, isn't it? 21 A. Yes. 22 Q. And due to the orders of magnitude difference 23 in those exposed to cigarette smoke and those 24 occupationally exposed to benzene, that has a 25 substantial effect on the risk of contracting AML from 59 1 cigarette smoke versus the risk of contracting AML from 2 benzene exposure, doesn't it? 3 MR. SCHIRRMEISTER: Form. 4 A. I think you have to specify the group. In 5 other words, many people can be occupationally exposed 6 to small amounts of benzene, but that's not why they 7 catch leukemia. Many people smoke cigarettes, but 8 that's not why they catch leukemia. They're sort of 9 apples and oranges. But what you can say at the end of 10 the day is that there are many more people catching 11 leukemia from cigarettes than occupational exposure to 12 benzene. 13 Q. (By Mr. DuPont) And that's because there's 14 many, many more people smoking cigarettes than there are 15 occupationally exposed to benzene. Would that be 16 correct? 17 A. Well, that's true. 18 Q. Okay. Besides benzene, can you name any other 19 leukemogens in cigarette smoke? 20 A. Well, there's some radioactivity alleged to be 21 in cigarette smoke. There are many chemicals. But we 22 don't know why cigarette smoking causes leukemia, and I 23 can't name any other known leukemogens besides benzene. 24 Q. Would you agree with me that it's the benzene 25 content of cigarette smoke that is associated with the 60 1 leukemia risk from cigarette smoking? 2 MR. SCHIRRMEISTER: Object to the form. 3 A. No. We know that it's not. There's not 4 enough benzene in cigarette smoking to cause leukemia. 5 And the truth of the matter is, we really don't know 6 that it's a chemical in the cigarettes. It could be an 7 effect that the cigarette smoke has on the lungs cause 8 production of certain compounds in the body. I don't 9 think we even know that it's a specific compound in the 10 cigarettes. All we know is that cigarette smokers have 11 a higher risk of AML. 12 Q. (By Mr. DuPont) Can you point to any studies 13 that establish that radioactive content of cigarette 14 smoke that causes leukemia? 15 A. No. 16 Q. Can you tell me what percentage of the risk of 17 AML, of causing AML, benzene accounts for within 18 cigarette smoke? 19 A. I would say very little because the 20 part-per-million-year accumulations from cigarette 21 smoking, depending on who writes about it, could be as 22 low as a half-a-part-per-million-year accumulation or as 23 high as five or six. But neither one of those numbers, 24 in my mind, is high enough to cause AML. 25 Q. Did you come up with a cumulative dose of 61 1 benzene exposure consumed by Mr. Draper by virtue of his 2 smoking cigarettes? 3 A. Did I? No. 4 Q. In looking at the report of Bradford Russell, 5 were you aware in using that data in your evaluation of 6 whether Mr. Draper's AML was caused by benzene 7 exposure -- were you aware that Mr. Russell did not 8 account for dermal absorption of benzene? 9 A. I don't recall. I did read what was sent to 10 me. I don't remember all of the details. I just 11 remember the final conclusion that he mentioned. 12 Q. Doctor, what is the Environmental Protection 13 Agency's position on whether or not there's a threshold 14 for which benzene does not cause leukemia? 15 MR. SCHIRRMEISTER: Object to the form. 16 A. I couldn't tell you accurately that. 17 Q. (By Mr. DuPont) Do you know what the IARC's 18 position is with respect to a threshold below which 19 benzene cannot cause leukemia? 20 MR. SCHIRRMEISTER: Object to the form. 21 A. No. 22 Q. (By Mr. DuPont) Same question for the 23 National Institute of Occupational Safety and Health. 24 MR. SCHIRRMEISTER: Object to the form. 25 A. No. 62 1 Q. (By Mr. DuPont) Doctor, what is your opinion 2 as to the relative risk from cigarette smoking presented 3 to Mr. Draper's leukemia compared to benzene exposure? 4 And let's start off with your assumption that he had 5 .123 part per million years of benzene exposure. 6 MR. SCHIRRMEISTER: Object to the form. 7 A. Well, I would say that neither -- if that were 8 the case, neither the occupational exposure nor the 9 cigarettes would have enough benzene to cause AML. 10 Q. (By Mr. DuPont) Well, I want to know benzene 11 exposure occupationally versus cigarette smoking. 12 A. Well -13 MR. SCHIRRMEISTER: Object to the form. 14 Q. (By Mr. DuPont) What is the risk between -15 for causing leukemia created by the cigarette smoking as 16 a whole versus the benzene exposure occupationally at 17 the assumption Mr. Russell makes of .123 part per 18 million years? 19 A. Okay. I would say that there is no increased 20 risk at the .125 part per million years. I would say 21 that as a 20-pack-year history person, he's got a double 22 the risk for a cigarette-induced AML, so, therefore, his 23 risk is twice what the risk would be from his 24 occupational exposure. 25 Q. And if we were to change Mr. Draper's 63 1 occupational exposure to 8 part per million years 2 cumulatively, how would that affect your assessment of 3 the risk of his contracting AML from occupational 4 benzene exposure? 5 MR. SCHIRRMEISTER: Object to the form. 6 A. I'd say 8 part per million years would still 7 be too low to be the threshold to catch AML. 8 Q. (By Mr. DuPont) Regardless, unless his 9 exposure is above 200 part per million years, you would 10 testify that his exposure was too low to cause his AML? 11 A. Well, I don't know exactly what it is. As 12 I've said, it could be as low as 100, it could be 13 slightly lower than that, but we know it's higher than 14 40 based on the studies and the literature. And I would 15 say at the levels you're talking about, 8 or .125, those 16 are just not in the ball game. 17 Q. And also for you, 40 part per million years 18 would not be in the ball game as creating a doubling of 19 the risk of causing AML? 20 A. I would say it would be very unlikely. 21 Q. And under no circumstances would you accept 22 that someone with 40 part per million years cumulative 23 exposure to benzene contracted AML from benzene 24 exposure? 25 A. Well, as I've said, I think, repeatedly, I 64 1 cannot tell why any given person with AML has that AML. 2 There are certain things we look at. You -- if you 3 showed me a person, for example, who had a period of 4 myelodysplasia, was a heavy benzene worker, had a minus 5 7 chromosome defect and an estimate was made because it 6 is, in fact, just an estimate of 40, I would say, "Well, 7 that's a consideration because maybe really that 40 was 8 really 80 or 100 or 200." Because all of these 9 estimates are just guesses. 10 But I think when you're dealing with 11 levels as low as 8 or below that, it's just, for me, not 12 a consideration, especially when you're talking about a 13 type of leukemia that's never been described from 14 benzene exposure at any level. 15 MR. DUPONT: Object to the nonresponsive 16 nature to that question. 17 Q. (By Mr. DuPont) Doctor, is it your position 18 that AML M4 has never been described in the literature 19 as arising from benzene exposure? 20 A. Well, M4 leukemia -- I think in the Chinese 21 studies there was M4 mentioned, and inversion 16 can be 22 either an M2 or an M4. I would say that the descriptive 23 nature of the leukemia is probably there from benzene, 24 but the chromosome analysis is not. 25 Q. So you would agree that M4 leukemias are 65 1 related to benzene exposure, correct? 2 MR. SCHIRRMEISTER: Object to the form. 3 A. I think they could be. Yes. 4 Q. (By Mr. DuPont) But you would disagree to the 5 extent that the M4 has an inversion of 16? 6 A. Well, the inversion of 16 needs to be 7 demonstrated. In other words, what these -- the FAB 8 classification that we look at by morphology is 9 oftentimes very iffy, and pathologists don't always 10 agree on how they should be classified. 11 And most people don't pay much attention 12 to that classification anymore, and it's clear that the 13 chromosome analysis is the key issue in determining 14 prognosis and many other things. And, to a certain 15 extent, the M classification is obsolete. But be that 16 as it may, if we're talking about inversion 16 leukemia, 17 I need to see the chromosome analysis. 18 Q. Doctor, when did chromosome analysis -- strike 19 that. 20 You'd agree with me that Mr. Draper's 21 polycystic kidney disease has been caused by his acute 22 myelogenous leukemia and treatment? 23 A. I would say it has absolutely nothing to do 24 with his acute myeloid leukemia and treatment. 25 Q. Would you agree with me that his polycystic 66 1 kidney disease has been exacerbated or worsened from his 2 AML and treatment therefor? 3 A. I don't know that. It would be possible. 4 Q. Well, have you treated patients with 5 polycystic kidney disease before? 6 A. Yes. 7 Q. Have you treated patients with leukemia that 8 have also had polycystic kidney disease? 9 A. I can't remember a single one who's had that 10 combination. Polycystic kidney disease is actually 11 quite common. I've seen many patients with it over the 12 years, but I just simply can't recall seeing one with 13 acute leukemia. 14 Q. Are chemotherapeutic agents used for the 15 treatment of AML toxic to the kidneys? 16 A. They certainly can be, yes. 17 Q. Well, in fact, they are, aren't they? 18 A. Depends on which agent you're talking about. 19 In other words, the platinum type agents are highly 20 toxic to the kidney. Agents like cyclophosphamide or 21 vincristine are not particularly toxic if the patient is 22 well hydrated. Some are intermediate. It depends on 23 which agent you're talking about. 24 Q. Would you agree with me that if a 25 chemotherapeutic agent used for AML was toxic to the 67 1 kidneys, then that chemotherapeutic agent would 2 exacerbate or make worse the polycystic kidney disease 3 condition? 4 A. Well, if chemotherapy damaged the kidneys -5 and I would also point out that when you're giving 6 people chemotherapy, you often need to give them 7 antibiotics if they get infections. And so sometimes if 8 you have a person who has a kidney problem from 9 chemotherapy, it isn't the chemotherapy drug; it's the 10 consequences of the chemotherapy drug in terms of other 11 medications. But it isn't unusual to get kidney damage 12 in people being treated for acute leukemia, but 13 frequently it's not the drug itself. 14 Q. But would it also not be unusual that a 15 chemotherapeutic agent that is toxic to the kidneys 16 would make worse any preexisting kidney disease? 17 A. Well, certainly, if you have preexisting 18 kidney disease and you give any drug, whether it's 19 chemotherapy or antibiotic, and it further damages the 20 kidneys, that worsens the situation with the polycystic 21 kidney disease. 22 Q. Doctor, is it your opinion that methotrexate 23 is not carcinogenic? 24 A. That is the position of the medical 25 literature. 68 1 Q. So the answer is yes, it's your opinion that 2 methotrexate is not carcinogenic? 3 A. Methotrexate does not cause acute leukemia or 4 non-Hodgkin's lymphoma, to be more specific. 5 Q. Well, I want to know, generally: Is it your 6 opinion that methotrexate is not carcinogenic? 7 A. I don't know about other tumors, skin tumors 8 and so on. I can only comment about non-Hodgkin's 9 lymphoma and acute myeloid leukemia. 10 Q. How about lymphoma? Does methotrexate cause 11 lymphoma? 12 A. I noticed that was very interesting that 13 Martyn Smith said that. He implied I wasn't familiar 14 with the literature, epidemiologic literature on that 15 subject, and, in fact, that's why I included one of the 16 articles I did by this Mariette person, because that 17 article gives the answer to what you're asking. 18 MR. DUPONT: Objection as nonresponsive. 19 Q. (By Mr. DuPont) Is it your opinion that 20 methotrexate does not cause lymphoma? 21 A. The literature is very clear that methotrexate 22 does not cause non-Hodgkin's lymphoma. 23 Q. You're saying "non-Hodgkin's lymphoma" and I'm 24 saying "lymphoma." My question is: Is it your 25 position -- is it your opinion that methotrexate does 69 1 not cause lymphoma? 2 A. Well, there's a study -- in fact, the one I 3 referenced from France found an increase in Hodgkin's 4 disease, but Hodgkin's disease is only about a tenth in 5 frequency of non-Hodgkin's lymphoma. And we know that 6 Hodgkin's disease can be caused by viral diseases which 7 are caused by immunosuppression. So I would say that 8 particular study suggested an increase in Hodgkin's 9 lymphoma but not non-Hodgkin's lymphoma. 10 Q. Okay. We're kind of dancing around this and 11 my question is very specific and I just want to get a 12 response to my question. 13 Is it your opinion that methotrexate does 14 not cause lymphoma? 15 A. That is my opinion. Correct. 16 Q. Would you agree with me that benzene is a more 17 potent carcinogen than cigarette smoke? 18 A. It depends on the dose. 19 Q. Well, if we were to take equal doses of 20 benzene and cigarette smoke, would you agree with me 21 that benzene is a more potent carcinogen than cigarette 22 smoke? 23 A. Absolutely not because smokers get enormous 24 amounts of lung cancer, 2,000 times what the general 25 population does. They don't get any -- they might get a 70 1 doubling of the risk of leukemia. And we don't know 2 that that leukemia is due to benzene. 3 Q. Would you agree with me if we were to take 4 equal doses of exposure to benzene and cigarette smoke, 5 that benzene is a more potent leukemogen than cigarette 6 smoke? 7 A. Well, I don't see how you can do that 8 experiment. In other words, if you take someone who's a 9 heavy smoker, let's look at the high side of what 10 benzene they might accumulate. That might be 5 or 6 11 part per million years. Well, 5 or 6 part per million 12 years of somebody who gets it solely from benzene 13 doesn't have AML. 14 Q. Well, you're comparing the benzene content of 15 cigarette smoke to benzene exposure outside the context 16 of cigarette smoke? 17 A. I thought that's what you asked. 18 Q. Okay. Well, perhaps I wasn't clear, for which 19 I apologize. 20 Is it your position that it's the benzene 21 content of cigarette smoke that causes leukemia? 22 A. My position, it is not the benzene content. 23 Q. If we were to look at somebody occupationally 24 exposed to benzene at an equal dose of cigarette smoke 25 in another individual, would you agree with me that 71 1 looking at the cigarette smoke dose as a whole, not just 2 as benzene content, versus the occupational benzene 3 dose, that benzene is a more potent leukemogen than 4 cigarette smoke as a whole? 5 MR. SCHIRRMEISTER: Object to the form. 6 A. I don't know how to answer the question. In 7 other words, I don't exactly know what you're asking. 8 If you're asking me whether somebody who has the same 9 content of benzene, I can figure that one out because 10 we've said that benzene and cigarettes may only be a 11 maximum of 5 or 6 part per million years, and that 12 doesn't cause leukemia. 13 But if you're asking me -- I can't figure 14 it out exactly. I can't make the comparison that you're 15 asking. 16 Q. (By Mr. DuPont) Doctor, are you familiar with 17 any cohort studies that implicate the importance of 18 dermal absorption of benzene in assessing the cause of 19 leukemia amongst those exposed to benzene? 20 A. No. 21 Q. Would you agree with me, Doctor, that it's 22 also important to analyze, in addition to cumulative 23 doses of exposure, intermittent peak exposures that an 24 individual sustains to benzene? 25 A. Well, in general, the literature suggests that 72 1 the cumulative dose is the major -- the major number 2 we're looking for. And, of course, a very high peak 3 dose ultimately gives you more cumulative dose. 4 Q. Okay. But would you agree with me that 5 intermittent peak doses are more important in 6 determining the cause of leukemia from benzene exposure 7 than is just looking at cumulative doses? 8 MR. SCHIRRMEISTER: Object to form. 9 A. No. I don't think the literature would 10 confirm that. 11 Q. (By Mr. DuPont) Do you know what the EPA's 12 position is on that? 13 A. No. 14 MR. DUPONT: Why don't we take another 15 short break? Is that okay with you, Doctor? 16 THE WITNESS: Yes. 17 (Recess from 3:51 p.m. to 4:03 p.m.) 18 Q. (By Mr. DuPont) Doctor, would you agree that 19 hematotoxicity increases the risk of benzene-induced 20 leukemia? 21 A. Hemato- -- I'm not certain what you're asking. 22 You mean if I take somebody who already has an existing 23 damaged marrow and then gave them benzene? 24 Q. Well, what is your understanding of what 25 hematotoxicity is? 73 1 A. Well, hematotoxicity would be if I gave a 2 chemical or a drug and I saw a fall in the blood counts; 3 in other words, a fall in the white blood cell count, 4 the red blood cell count, the platelet count, or reduced 5 cellularity of the bone marrow. In other words, 6 something that damages production of blood would be 7 hematotoxicity. 8 Q. Okay. Would you agree with me that somebody 9 whose blood is hematotoxic has an increased risk for 10 developing benzene-induced leukemia when they're exposed 11 to benzene? 12 A. I think what you're asking me is if I have 13 somebody who's got abnormal blood counts and then I hit 14 them with benzene, are they more likely to catch 15 leukemia than someone who has normal blood counts when I 16 hit them with benzene? 17 Q. Correct. 18 A. I think that's the question you're asking. I 19 would have no idea. 20 Q. Have you reviewed any studies that address 21 that issue? In other words, are there any studies that 22 stand for the proposition that hematotoxicity increases 23 the risk of benzene-induced leukemia? 24 A. Well, maybe in this way. The Aksoy studies, 25 the Turkish shoe worker studies, what Dr. Aksoy noticed 74 1 is that if he had people who got marked depression of 2 their blood counts as a consequence of the benzene 3 exposure, even though the blood counts recovered, 4 several years later, they might come down with leukemia. 5 In other words, what he was showing is 6 that they had enough benzene to actually depress the 7 bone marrow. And I think if you had enough benzene to 8 actually depress the bone marrow, then that suggests 9 there might be a risk of later development of leukemia. 10 Q. What if you had enough benzene to depress the 11 white blood count? 12 A. I don't know -- I don't know the answer to 13 that, and I guess it would depend on how low. You know, 14 if I saw a person -- and I did see one such person 15 several years ago who was a petrochemical worker who 16 repeatedly in the arena would get his white cell count 17 knocked down to very low levels, and then he would 18 recover when he was taken away from the exposure. And 19 he went through that cycle several times. Ultimately, 20 he developed acute leukemia. Whether or not a single 21 depression would do that, I don't know the answer to 22 that. 23 Q. So what you're telling me is yes, you believe 24 decreased white blood cell counts can lead to an 25 increased risk of benzene-induced leukemia if someone is 75 1 exposed to benzene while his counts are decreased. You 2 just don't know how low those counts have to be or how 3 frequent the exposure has to be? 4 MR. SCHIRRMEISTER: Form. 5 A. Well, I can't think of a particular study that 6 takes people with low blood counts already and then 7 exposes them to either benzene or chemotherapy and sees 8 if they get higher rates of leukemia than someone with 9 normal blood counts that they expose to benzene or 10 chemotherapy drugs, for example. I don't know the exact 11 model for what you're describing. All that I can 12 comment is that if someone has enough drug to depress 13 the bone marrow, obviously, they've gotten a very 14 substantial dose of that drug. 15 Q. (By Mr. DuPont) How much benzene exposure is 16 necessary to depress the white blood cell count? 17 A. I don't know that with accuracy. I think -- I 18 really can't say. I have that information, I think, in 19 my files, but I'd probably better not comment on that. 20 I don't recall the exact numbers. 21 Q. Would you agree with me that there's no 22 threshold for the hematologic effects of benzene 23 exposure, particularly on white blood cell counts or 24 lymphocytes? 25 MR. ORLET: Object to the form. 76 1 A. No. I don't understand that question because 2 that would suggest that eating a banana might lower your 3 white count. There's benzene in bananas. I mean, you 4 have to have a substantial dose of benzene to lower the 5 blood count, and a very substantial cumulative dose to 6 catch leukemia. 7 Q. (By Mr. DuPont) How substantial of a dose do 8 you have to have to benzene to lower your white blood 9 cell count? 10 A. I'd have to say -- this is an educated 11 guess -- I think in the range of acutely 50 part per 12 million or something of that nature. I'd have to really 13 look it up from my files. I can't tell you with any 14 bona fide accuracy. 15 Q. Are you familiar with Elizabeth Ward's study 16 on the rubberworker pliofilm cohort that was published 17 in 1995? 18 A. No. I'm generally familiar with that cohort. 19 I don't know that particular study. 20 Q. Doctor, are you familiar with any studies that 21 link topo II catalytic inhibitors to inversion 16 in 22 AML? 23 A. I just commented on -- or previously, on the 24 Anderson study that mentioned several types of 25 topoisomerase II inhibitors that could be linked to 77 1 inversion 16, and these included the mitoxantrone type 2 and the etoposide type and the adriamycin type. 3 Q. And excuse my ignorance, but are any of those, 4 or any other types reported by Anderson, catalytic 5 inhibitor topo II's? 6 A. I don't know the biochemistry of 7 topoisomerase II well enough to tell you that. I know 8 they inhibit the enzyme. 9 Q. If you could turn to the -- I think you said 10 October 8th draft of Mr. Russell's report. Can you tell 11 me what the cumulative dose calculation he makes is in 12 that report? 13 A. Now, which report, my letter or the other 14 report? 15 Q. You testified earlier, and we marked it as one 16 of the first three exhibits, that you received the 17 October 8th draft report from Bradford Russell. 18 A. Let's see if we can find that. 19 MR. SCHIRRMEISTER: Here it is. 20 A. Okay. I'm sorry. I have the report. And 21 what is it, again, that you're asking? 22 Q. (By Mr. DuPont) I'd just like for you, since 23 I'm not there with you, unfortunately, and I can't look 24 at it -- if you can tell me what cumulative dose of 25 benzene he calculates in that draft of his report. 78 1 A. Well, this is -2 MR. SCHIRRMEISTER: Might want to just -3 he can read the last paragraph into the record. 4 MR. DUPONT: Yeah. That would be fine. 5 MR. SCHIRRMEISTER: Just read that. 6 A. Yeah. 7 "If Mr. Draper's estimated daily exposure 8 to trace benzene while working as a painter or painter's 9 helper was .0668 part per million for eight hours per 10 day, 5 days per week and 48-50 weeks per year, then this 11 would be equivalent to .0668 part per million years. 12 Mr. Draper painted with DuPont paints for approximately 13 3.083 years during the period from 1979 to 2003, 14 therefore, his estimated cumulative exposure to trace 15 benzene from painting with DuPont products would have 16 been .0668 part per million years," star, "3.083 years 17 or .021 part per million years." 18 Q. (By Mr. DuPont) From looking at that draft 19 report, can you tell whether or not Dr. Russell is 20 calculating exposure to benzene from solvent use as 21 distinguished from paint exposure? 22 A. Well, he says: "With the summary data 23 presented, it is possible to estimate Mr. Draper's 24 8-hour time-weighted average concentration to trace 25 benzene based on potential exposures during 6 major 79 1 tasks." And -- let me see about that. Well, he lists 2 in here aerosols, gas, diesel, thinners, wash thinner, 3 PrepSol, putty, paints. So he's mentioned a number of 4 items. 5 Q. You previously said that the products 6 Mr. Draper worked with contained trace amounts of 7 benzene. What is your basis -- first of all, what do 8 you mean by "trace amounts"? 9 A. Not pure benzene. In other words, if one -10 if he used a thinner, it might conceivably have small 11 amounts of benzene in it, as you might say a contaminant 12 or a trace material, but it's not pure benzene. 13 Q. What is your understanding of how much benzene 14 is in petroleum-based thinners? 15 A. I don't know how much is, and I'm sure it 16 varies by product. 17 Q. Do you have an understanding of a range of 18 contents of benzene in petroleum-based solvents? 19 A. No. 20 Q. Can you tell me whether it's more or less than 21 .1 percent? 22 A. I would think it would be less than .1 23 percent. 24 Q. And what's your basis for saying that? 25 A. Well, because I don't think it would be much 80 1 higher. In other words, the solvents are made usually 2 by differential distillation, and the amount of benzene 3 that would be in the particular cuts they use for these 4 solvents wouldn't be very much. 5 Q. Would you agree with me that Mr. Draper was 6 being exposed on a daily basis to benzene when working 7 with the defendants' products? 8 MR. SCHIRRMEISTER: Object to the form. 9 MR. ORLET: Object to the form. 10 A. Probably, yes. 11 Q. (By Mr. DuPont) Have you spoken with anyone 12 from DuPont concerning the benzene content of DuPont 13 products? 14 A. No. 15 Q. Have you spoken with any of Mr. Draper's 16 coworkers regard the manner in which DuPont or any other 17 defendants' products were used? 18 A. No. 19 Q. And you haven't treated Mr. Draper? 20 A. That's correct. 21 Q. Doctor, have you ever testified on behalf of a 22 plaintiff in a case where it was alleged that benzene 23 exposure caused an injury? 24 A. No. 25 Q. Have you ever diagnosed a patient and found 81 1 that that patient's AML was caused by benzene exposure? 2 A. Well, as I mentioned, I had one patient who I 3 felt confident his leukemia was caused by chemical 4 exposures, but he had exposures to a number of things 5 besides benzene. But benzene was one of them and 6 certainly could have been the most important chemical. 7 Q. Doctor, you testified in a case concerning 8 Charles Wilson? 9 A. Yes. 10 Q. Have you given any testimony since that 11 deposition? And just to refresh your recollection, that 12 was on September 17, 2007. 13 A. Yes. The only other one I have is on a case 14 called Dorsey McCann. That was on September 26th, '07. 15 Q. Do you recall who represented the plaintiff in 16 that case? 17 A. No. 18 Q. On behalf of which defendant or defendants did 19 you issue an opinion in that case? 20 A. Well, the case was Dorsey McCann versus The 21 Sherwin Williams Company, and there probably were a 22 number of defendants. I can't remember which -- the 23 attorney that originally asked me to see the case, who 24 he was representing. 25 Q. Was it Mr. Stofko that asked you to review the 82 1 case? 2 A. I don't think so, but I don't remember. Could 3 have been. 4 Q. And what was your opinion in the McCann case? 5 MR. SCHIRRMEISTER: I don't think it's 6 appropriate to question the witness about opinion in 7 another case. I'm going to instruct him not to answer. 8 You can get the deposition from the other attorney, if 9 you want it. 10 Q. (By Mr. DuPont) Well, can you tell me what 11 disease was allegedly caused by benzene exposure in the 12 McCann case? 13 A. It was AML. 14 Q. Can you tell me what subtype of AML it was? 15 A. No. I can't remember that in enough detail to 16 comment. 17 Q. And did that individual, Mr. McCann, have any 18 damage to his chromosomes? 19 A. I don't remember whether he did or not. 20 Q. And it was your testimony in that case that 21 the gentleman's benzene exposure did not cause his AML? 22 MR. SCHIRRMEISTER: We're not going to go 23 there. It's a different case. Witness is instructed 24 not to answer. 25 MR. DUPONT: Counsel, I think it's more 83 1 than relevant to his opinions in this case. 2 MR. SCHIRRMEISTER: Well, it may be, but 3 that case is pending, and I'm not going to have the 4 witness testify about another case in which he's not 5 represented by his counsel. 6 Q. (By Mr. DuPont) Doctor, if we were to break 7 the amount of time that you spend professionally on 8 testifying in litigation versus treating patients, how 9 does that breakdown fall in terms of -- is it 50/50? 10 75/25? 11 A. Oh, I would say it's much less than 75/25. I 12 can give you this figure because I was asked something 13 like that a year or two ago, and so I was asked 14 relatively how much income I made from this, which I 15 suppose in some respects would correlate to time spent. 16 And what we calculated is for the ten-year period from 17 1995 to 2005, roughly about 12 percent of my income was 18 from testimony. And so extrapolating, conceivably 19 12 percent of my time was too. 20 Q. When did you first testify in -- first start 21 testifying in litigation? 22 A. Around 1992. 23 Q. Since then, approximately how many cases have 24 you given testimony in? 25 A. Well, keep in mind that many on this list are 84 1 not benzene cases, but the total number of cases I've 2 testified in are 55 since 1992. 3 Q. And in how many of those cases did you provide 4 an opinion on behalf of the plaintiff in the litigation? 5 A. I could count them up. Let's see. Looks like 6 nine cases I testified for the plaintiff. 7 Q. Did any of those cases involve exposure to 8 benzene? 9 A. No. 10 Q. Did any of those cases involve an individual 11 who was injured by exposure to any chemical? 12 A. In some cases it was injured by exposure to 13 drugs, which I guess you could classify as a chemical. 14 Q. All right. And would those have been cases 15 relating -- brought against the manufacturer or maker of 16 the drug, or cases brought against another physician 17 that had administered the drug? 18 A. Usually another physician. 19 Q. So those would have been medical negligence 20 cases? 21 A. Yes. 22 Q. Do you have any criticisms of the opinion 23 issued by Dr. Agura in this case? 24 A. I have to look at it again. 25 THE WITNESS: Do we have that anywhere in 85 1 the material? 2 MR. SCHIRRMEISTER: Andrew, do you mean 3 does he have any criticism of Mr. Draper's care and 4 treatment for his condition? 5 MR. DUPONT: No. I want to refer to -- I 6 believe it's a January 30 -7 THE WITNESS: Oh. 2007 patient letter? 8 Yeah. If I can find that. 9 Q. (By Mr. DuPont) January 30, 2007. 10 A. I can't find it. I don't know where it is. 11 MR. SCHIRRMEISTER: Here it is. 12 A. All right. The letter from Dr. Edward Agura. 13 Q. (By Mr. DuPont) Yes, sir. 14 A. Yes. And what is it you're asking about it? 15 Q. I'm asking if you have any comments on his 16 opinions set forth in his report. 17 A. Well, his opinion is based on the fact that 18 Mr. Draper told him he had exposures to solvents and 19 Dr. Agura says that -- he opines that the occupational 20 exposure contributed to the leukemia. I don't agree 21 with that. 22 Q. Okay. So you would not agree with Dr. Agura 23 that occupational exposure to solvents containing 24 benzene contribute to leukemia? 25 A. No, they can. But in this particular case. 86 1 Q. And you understand that Dr. Agura is 2 Mr. Draper's treating oncologist hematologist? 3 A. Yes. 4 Q. Doctor, have you brought with you all of your 5 correspondence between yourself and any attorney for a 6 defendant in this case? 7 A. Yes. 8 Q. Can we go ahead and mark those as the next 9 exhibit? 10 A. I don't know what that would be, aside from 11 various e-mails here, which I have. Here are three. 12 See if I've got any -13 Q. I'd like to include any e-mail, letter, fax, 14 notes, anything of that nature. 15 MR. SCHIRRMEISTER: What's the next 16 number? 17 THE REPORTER: L. 18 (Exhibit L marked.) 19 MR. DUPONT: Okay. Do we have that? 20 MR. SCHIRRMEISTER: Yep. It's marked. 21 MR. DUPONT: What's left? Do we have the 22 original citations from his report? I just kind of want 23 to sort out what I want to attach as an exhibit and what 24 I don't want to attach. 25 MR. SCHIRRMEISTER: You have all of his 87 1 literature references. You got something -- what was it 2 you asked Dr. Natelson about, index of authorities or 3 something like that? What was the language that you 4 used? 5 MR. DUPONT: You know, it might have been 6 something that your office put together. 7 MR. SCHIRRMEISTER: Yeah. It was. 8 MR. DUPONT: "Dr. Ethan Natelson File 9 Inventory, December 3, 2007"? 10 MR. SCHIRRMEISTER: Right. My office 11 prepared that. 12 MR. DUPONT: Okay. 13 MR. SCHIRRMEISTER: That's a complete set 14 of his file, other than what we've marked today. 15 MR. DUPONT: So is this -- all right. 16 MR. SCHIRRMEISTER: He brought some 17 additional articles. He brought some published -- some 18 abstracts. There's a Russell draft, I think, that we've 19 marked, and some additional e-mail correspondence. I 20 believe that's it. 21 MR. DUPONT: Let me ask you: Do you have 22 a copy of the CD-ROM that you used to forward me his 23 file? 24 MR. SCHIRRMEISTER: Do I have one? 25 MR. DUPONT: Yes. With you there. 88 1 MR. SCHIRRMEISTER: No, I don't. 2 MR. DUPONT: I guess what I'm trying to 3 get at is -- and we can go off the record. 4 (Recess from 4:32 p.m. to 4:35 p.m.) 5 (Exhibits M, N and O marked.) 6 (Exhibit P to be marked.) 7 MR. DUPONT: Back on the record real 8 quick. 9 Q. (By Mr. DuPont) Doctor, have you understood 10 all my questions today? 11 A. Virtually all of them. 12 Q. Okay. And have I treated you fairly? 13 A. Absolutely. 14 Q. Excellent. 15 MR. DUPONT: Well, I appreciate your 16 coming down, and hope we speak with each other again. 17 THE WITNESS: All right. 18 MR. SCHIRRMEISTER: Thank you. 19 (Deposition concluded at 4:35 p.m.) 20 (Signature was waived.) 21 22 23 24 25 89 1 CAUSE NO. 199-02538-04 2 DUANE DRAPER, ET AL., ) IN THE DISTRICT COURT OF ) 3 PLAINTIFFS, ) ) 4 VS. ) COLLIN COUNTY, TEXAS ) 5 PPG INDUSTRIES, INC., ) ET AL, ) 6) DEFENDANTS. ) 199TH JUDICIAL DISTRICT 7 8 REPORTER'S CERTIFICATION 9 DEPOSITION OF ETHAN A. NATELSON, M.D. DECEMBER 10, 2007 10 11 I, Kimberly J. Carter, Certified Shorthand Reporter 12 in and for the State of Texas, hereby certify to the 13 following: 14 That the witness, ETHAN A. NATELSON, M.D., was duly 15 sworn by the officer and that the transcript of the oral 16 deposition is a true record of the testimony given by 17 the witness; 18 That examination and signature of the witness to the 19 deposition transcript was waived by the witness and 20 agreement of the parties at the time of the deposition; 21 That the original deposition was delivered to 22 Mr. Andrew J. DuPont; 23 That the amount of time used by each party at the 24 deposition is as follows: 25 Mr. Andrew J. DuPont 2:30 90 1 Mr. Christopher Stofko 0:00 Mr. Joseph C. Orlet 0:00 2 Mr. Bryan D. Pollard 0:00 3 That $_____ is the deposition officer's charges to 4 the Plaintiff for preparing the original deposition 5 transcript and any copies of exhibits; 6 That pursuant to information given to the deposition 7 officer at the time said testimony was taken, the 8 following includes all parties of record: 9 Mr. Andrew J. DuPont, Attorney for the Plaintiff Mr. Andrew C. Schirrmeister, III, Attorney for 10 the Defendant E.I. DuPont De Nemours and Company 11 Mr. Christopher Stofko, Attorney for the Defendant PPG Industries, Inc., and 12 The Sherwin Williams Company Mr. Bryan D. Pollard, Attorney for the Defendant 13 Illinois Tool Works, Inc. Mr. Jospeh C. Orlet, Attorney for the Defendant 14 BASF 15 That a copy of this certificate was served on all 16 parties shown herein on __________ and filed with the 17 Clerk pursuant to Rule 203.3. 18 I further certify that I am neither counsel for, 19 related to, nor employed by any of the parties or 20 attorneys in the action in which this proceeding was 21 taken, and further that I am not financially or 22 otherwise interested in the outcome of the action. 23 24 25 91 1 Certified to by me this _______ day of ____________, 2 2007. 3 ______________________________________ 4 KIMBERLY J. CARTER, Texas CSR No. 7721 Expiration Date: 12/31/08 5 FAST PACE REPORTING, INC. Firm Registration No. 389 6 2425 West Loop South, Suite 200 Houston, Texas 77027 7 (713) 650-3500 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 92