Document ZmYLkEdm5Y1qdX1qDkOY4e0V

1 IN THE SUPERIOR COURT OF THE STATE OF ARIZONA 2 IN AND FOR THE COUNTY OF MARICOPA 3 RAUL ZENDEJAS and ) ARACELI ZENDEJAS, ) 4 Plaintiffs ) ) 5 vs. ) ) NO. CV-2007-005399 6 SHELL OIL COMPANY, SHELL ) CHEMICAL LP, Individually and) 7 as Successor-in-interest to ) SHELL CHEMICAL CORPORATION; ) 8 CONOCOPHILLIPS COMPANY, VON ) VERDE CITRUS PACKING HOUSE, ) 9 INC., an Arizona corporation;) VON VERDE HARVESTING, INC., a) 10 dissolved Arizona ) corporation; and VON VERDE ) 11 CITRUS GROWERS COOPERATIVE, ) INC., a dissolved Arizona ) 12 Corporation, ) Defendants. ) 13 14 ORAL VIDEOTAPED DEPOSITION 15 ETHAN NATELSON, M.D. 16 September 25, 2009 17 18 ORAL VIDEOTAPED DEPOSITION OF ETHAN NATELSON, M.D., 19 produced as a witness at the instance of the Plaintiffs 20 and duly sworn, was taken in the above-styled and 21 numbered cause on September 25, 2009, from 10:20 a.m. to 22 3:48 p.m., before Kelly Hanna, Certified Shorthand 23 Reporter, in and for the State of Texas, reported by 24 computerized stenotype machine at the offices of Haynes 25 and Boone, LLP, One Houston Center, 1221 McKinney 1 1 Street, Suite 2100, Houston, Texas, pursuant to the 2 Texas Rules of Civil Procedure and the provisions stated 3 on the record or attached hereto. 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 2 1 APPEARANCES 2 3 FOR PLAINTIFFS: 4 Mr. Keith E. Patton Shrader & Associates 5 3900 Essex Lane Suite 390 6 Houston, Texas 77027 Telephone: 713.782.0000 7 Fax: 713.571.9605 E-mail: keith@shraderlaw.com 8 FOR DEFENDANTS: 9 Mr. Stan Perry 10 Haynes and Boone, LLP One Houston Center 11 1221 McKinney Street, Suite 2100 Houston, Texas 77010-2007 12 Telephone: 713.547.2039 Fax: 713.236.5455 13 E-mail: stan.petty@haynesboone.com 14 ALSO PRESENT: 15 Kelly Hanna, CSR, RPR, CRR, CMRS, CLR Dory Michael, Videographer 16 Justin Shrader 17 18 19 20 21 22 23 24 25 3 1 INDEX 2 3 ETHAN NATELSON, M.D. PAGE 4 Examination by Mr. Patton .........................7 Signature Page .................................208 5 Court Reporter's Certificate ....................209 6 7 EXHIBITS 8 9 EXHIBIT DESCRIPTION PAGE 10 No. 1 Report by Ethan A. Natelson, 116 M.D., dated 9/1/08 11 No. 2 Curriculum Vitae - Dr. Natelson 187 12 No. 3 13 Notice of Deposition 187 No. 4 List of Charges - Dr. Natelson 187 14 No. 5 15 16 No. 6 Letter dated 12/20/06 (Carrol to Friedman) State Fund, Arizona, Workers' 108 199 Compensation Records 17 No. 7 18 No. 8 List of Testimony Handwritten Notes 188 11 19 No. 9 Benezen and the Dose-Related 129 20 Incidence of Hematologic Neoplasms in China (Hayes, et 21 al.) 22 No. 10 Occupational History and 133 Exposure and the Risk of Adult 23 Leukemia in Shanghai (Adegoke, et al.) 24 25 4 1 EXHIBITS (cont.) 2 EXHIBIT DESCRIPTION PAGE 3 No. 11 A 56-Year Mortality Follow-Up 137 of Texas Petroleum Refinery and 4 Chemical Employees, 1948-2003 (Tsai, et al.) 5 No. 12 Genotoxic Effects in Workers 141 6 Exposed to Low Levels of Benzene from Gasoline (Nilsson, 7 et al.) 8 No. 13 Leukemia in Relation to 145 Occupational Exposures to 9 Benzene and Other Agents: A Case-Control Study Nested in a 10 Cohort of Gas and Electric Utility Workers (Guenel, et 11 al.) 12 No. 14 Health Effects of Gasoline 148 Exposure. II. Mortality 13 Patterns of Distribution Workers in the United States 14 (Wong, et al.) 15 No. 15 Chemical Exposures in the 148 Synthetic Rubber Industry and 16 Lymphohematopoietic Cancer Mortality (Graff, et al.) 17 No. 16 18 Characteristics and Outcome of Patients with Philadelphia Chromosome Negative, bcr/able 151 19 Negative Chronic Myelogenous Leukemia (Onida, et al.) 20 No. 17 The 152 21 myelodysplastic/myeloproliferat ive neoplasms: 22 myeloproliferative diseases with dysplastic features 23 (Orazi, et al.) 24 25 5 1 EXHIBITS (cont.) 2 EXHIBIT DESCRIPTION PAGE 3 No. 18 Dangerous and Cancer-Causing 160 Properties of Products and 4 Chemicals in the Oil Refining and Petrochemical Industries. 5 Part XXX Causal Relationship between Chronic Myelogenous 6 Leukemia and Benzene-Containing Solvents (Mehlman) 7 No. 19 Risk factors of myelodysplastic 176 8 syndromes: a case-control study (Strom, et al.) 9 No. 20 API Toxicological Review 179 10 Benzene September 1948 11 No. 21 Environmental Principles 180 12 No. 22 American Petroleum Institute 192 Health and Environmental 13 Sciences Department Exposure Assessment and Control Task 14 Force dated 11/4/91 Meeting Minutes 15 No. 23 Myelodysplastic Syndromes 194 16 (Deeg, et al.) 17 No. 24 Risk of Cancer as a Result of 195 Community Exposure to Gasoline 18 Vapors (Patel, et al.) 19 No. 25 Beyond Chronic Myelogenous 204 Leukemia (Cortes, et al.) 20 No. 26 Occupational History and 204 21 Exposure and the Risk of Adult Leukemia in Shanghai (Adegoke, 22 et al.) 23 No. 27 Miscellaneous Studies 204 24 25 6 1 (Exhibit Nos. 1-9 marked) 2 THE VIDEOGRAPHER: Now beginning this 3 deposition. The date is September 25th, 2009. 4 Approximate time is 10:20. We're now on the video 5 record. 6 ETHAN NATELSON, M.D., 7 having been first duly sworn, testified as follows: 8 EXAMINATION 9 Q. (BY MR. PATTON) Please introduce yourself for 10 the record. 11 A. My name is Ethan Natelson. 12 Q. Dr. Natelson, do you understand my name is 13 Keith Patton, and I represent Raul Zendejas in a case 14 pending in Phoenix, Arizona? Do you understand that? 15 A. Yes. 16 Q. And do you understand that even though we're in 17 a conference room today in Houston your testimony is 18 just as if it were in front of a judge and a jury? 19 Do you understand that? 20 A. Yes. 21 Q. You've given depositions before, correct? 22 A. Yes. 23 Q. And you have had the opportunity to meet with 24 Shell's lawyer before we started today, correct? 25 A. Correct. 7 1 Q. And what kind of doctor are you? 2 A. I'm a hematologist. 3 Q. And did Shell hire you to give you -- or to 4 give opinions in this case? 5 A. Yes. 6 Q. And what did they ask you -- what did they want 7 from you as an expert in terms of your opinions? 8 A. Well, I believe I was contacted in 2007 by 9 Mr. Perry and he said something to the effect that it 10 was a patient with an unusual diagnosis and he wanted me 11 to review the case and comment about the allegations. 12 Q. And was there any certain conclusion that you 13 were supposed to reach, as opposed to just commenting on 14 the -- on the disease or the allegations? 15 A. No, I wasn't told what to conclude. 16 Q. Okay. You have formed opinions in this case; 17 and you put them in a report; is that right? 18 A. Yes. 19 Q. Okay. We're going to go through that in some 20 more detail here this morning. But what year did you 21 start practicing medicine? 22 A. Well, I finished my internship in 1966. So, 23 theoretically, I became a real doctor in -- in 1966. 24 And that's when I was seeing patients as part of a 25 residency program. 8 1 I then went into the service in around 2 1970 for two years; and when I came back from the 3 service, I would say I was in full-time practice. That 4 would be around, let's say, 1970, '71, somewhere in 5 there. 6 Q. You've been practicing medicine over 40 years? 7 A. Yes. 8 Q. And do you currently practice here in the 9 Houston area? 10 A. Yes. 11 Q. Where at in the Houston area? 12 A. The Methodist Hospital. 13 Q. Okay. And that's here in the Texas Gulf Coast, 14 correct? 15 A. In the Texas Medical Center, yes. 16 Q. Okay. Have you ever diagnosed anyone with 17 myeloid leukemia? 18 A. Yes. 19 Q. Okay. Have you ever treated anyone with 20 myeloid leukemia? 21 A. Yes. 22 Q. Have you ever diagnosed anyone with atypical 23 CML or MDS or AML? 24 A. Yes. 25 Q. Do you regular -- regularly see patients who 9 1 have those forms of leukemia? 2 A. Yes. 3 Q. Okay. Sir, you're familiar with benzene, 4 correct? 5 A. Yes. 6 Q. And is benzene capable of causing any diseases? 7 MR. PERRY: Object to form. 8 A. Yes. 9 Q. (BY MR. PATTON) And what diseases does it 10 cause? What body parts does it affect? 11 A. Well, from the hematologic standpoint, benzene 12 is known to cause aplastic anemia, which is bone marrow 13 failure. It may cause certain forms of myelodysplasia, 14 which are various forms of marrow damage where the bone 15 marrow isn't necessarily aplastic; and it may cause 16 acute myeloid leukemia. 17 Q. Benzene's target organ, so to speak, is the 18 bone marrow. Is that a fair statement? 19 A. Yes. 20 Q. I mean, if benzene is going to make someone 21 sick, it's going to hit their fingernails or their nose 22 or their eyes. It's going to hit their bone marrow, 23 right? 24 A. Well, acute large exposures might have other 25 effects; but in terms of the chronic, long-term effects, 10 1 it would be hematologic. 2 Q. Okay. And is -- is acute -- or I'm sorry -3 atypical CML, is that a myelogenous disease? 4 A. It is a disease of the myeloid cells, yes. 5 Q. Okay. Is myelodysplastic syndrome, or MDS, is 6 that a disease of the myeloid cells? 7 A. Yes. 8 Q. AMS, is that a disease of the myeloid cells? 9 A. Yes. 10 Q. CML, is that a disease of the myeloid cells? 11 A. Yes. 12 Q. Okay. Doctor, I'm going to hand you what we've 13 marked as Exhibit 8; and what I would like to do is make 14 a chart of the -- of the myeloid leukemias, if we -- if 15 we could. If you could write "Myeloid Leukemias" at the 16 top. 17 A. (Witness complies.) 18 Q. And, again, those are diseases where the 19 myeloid cells are affected, correct? 20 A. Yes. 21 Q. It's a leukemia or a leukemia-type condition. 22 Fair statement? 23 A. Yes. 24 Q. Okay. Is AML a myeloid leukemia? 25 A. Yes. 11 1 Q. Okay. Can we write that on there? 2 A. (Witness complies.) 3 Q. MDS, is that also a myeloid disease or a 4 myeloid leukemia? 5 A. It isn't a leukemia. It's a -- it's a myeloid 6 illness. 7 Q. Okay. Can we write "MDS" on there and put 8 "myeloid illness" next to it? 9 A. Okay. 10 Q. I just want to have this chart as we -- we go 11 through some of the studies and talk about this later. 12 And then there is atypical CML. Is that a 13 myeloid leukemia or a myeloid illness? 14 A. It's a myeloid illness, yes. 15 Q. Okay. Let's put that on the list, too. 16 A. Okay. 17 Q. CML, is that a myeloid illness? 18 A. Yes. 19 Q. Okay. Let's put that kind of next to atypical 20 CML, if you've got a little room over there. 21 A. (Witness complies.) 22 Q. Okay. There are subtypes of some of these 23 diseases, these four disease groups that you've put on 24 the chart, correct? 25 A. Yes. 12 1 Q. MDS, myeloid -- myelodysplastic syndrome, that 2 has a number of subtypes, right? 3 A. Yes. 4 Q. Okay. Can you tell us what those subtypes are 5 and write down their abbreviations under the MDS list? 6 A. Well, that list has changed. In other words, 7 MDS, the original proposal was put forth around 1982; 8 and prior to that time, we called MDS preleukemic states 9 as a general category. 10 In -- in 1982, Dr. Bennett, I believe, 11 proposed the original classification, which was used for 12 a number of years; and in that original -- I'll just put 13 "original classification," he put in that classification 14 what we call refractory -- primary refractory anemia. 15 Q. RA or PRA? 16 A. Yes. 17 Q. Okay. What else? 18 A. We put in refractory anemia with ringed 19 sideroblasts, RARS. 20 Q. Okay. And that's -- again, that's just a 21 different presentation of MDS, correct? A different 22 subtype? 23 A. It's a different subtype -- well, it's a 24 different disease than the first one; and what 25 Dr. Bennett did was put these diseases together in a 13 1 classification because they had certain similarities. 2 Q. And the purpose, Doctor, if I'm correct from 3 what I've learned in this case, with our expert, 4 Dr. Gore, the purpose of subdividing MDS is for 5 treatment purposes, isn't it? 6 MR. PERRY: Object to form. 7 Q. (BY MR. PATTON) Or is it? 8 A. No, I wouldn't say that that's so. People -9 some people are what are called lumpers. Some people 10 are splitters. People have a passion for 11 classification. And there are certain usefulnesses to a 12 classification. One might be from an epidemiologic 13 standpoint. One might be from an outcome standpoint. 14 One might be from a therapy standpoint, a causation 15 standpoint. There really would be many reasons why one 16 would like to classify an illness. 17 Q. Okay. 18 A. But I would say treatment would be only maybe 19 one small aspect of that. 20 Q. Before we finish your list, are you a lumper; 21 or are you a splitter? 22 A. I -- I like to be specific as to what the -- as 23 specific as one can be in terms of disease causation. 24 Q. Okay. 25 A. So, in other words, instead of saying 14 1 hepatitis, I'd like to know if it's hepatitis B or C or 2 what it is. I -- I'd like the disease to be as specific 3 as possible. 4 Q. So, you're a splitter; so it helps in your 5 analysis of causation; is that right? 6 A. Yes, it helps -- I think it helps in the 7 analysis of causation. It certainly helps in the 8 analysis of results of treatment and epidemiology. 9 Q. Okay. And as well as outcome and therapy -10 therapy meaning therapy/treatment, those are some of the 11 reasons that you, as a -- as a hematologist, like to 12 split? 13 A. Yes. 14 Q. Okay. Let's keep going with our list. 15 A. Okay. We had primary refractory anemia. We 16 had refractory anemia with ringed sideroblasts. We had 17 chronic myelomonocytic leukemia, or CMML. 18 Q. There's two Ms in that type of MDS, right? 19 CMML -20 A. Yes. 21 Q. -- as compared to CML? 22 A. Yes. 23 Q. Okay. 24 A. Right. 25 And we had refractory anemia with excess 15 1 blasts, and then we had refractory anemia with excess 2 blasts in transformation. 3 Q. Transforming to what? 4 A. AML. 5 Q. Okay. So, that's to say that someone could 6 have a form of MDS, that it would go ahead and kind of 7 move them from one column to the chart to another. They 8 might go from MDS to AML, correct? 9 A. Well, yes. All of these illnesses in this 10 category can move within the classification; and they 11 can move out of the classification, if they become acute 12 myeloid leukemia. 13 Q. It's kind of an evolving disease. It's not 14 like swine flu where you say, okay, you have swine flu. 15 That's it. Someone could have a form of leukemia and, 16 then it moves into another form depending on how the 17 disease progresses. Fair statement? 18 A. Yes. 19 Q. Okay. Are we done with the list yet? 20 A. That was the primary list. I'm thinking if 21 I've left anything out. I think those were the original 22 designations. 23 Q. Okay. 24 A. And then it became modified. It's been 25 modified several times. And CMML, which is really a 16 1 myeloproliferative disease, was taken out of this. CMML 2 had been a long-standing stand-alone illness for many, 3 many years before it was put into this category; and 4 then it was taken out of the category as a separate 5 free-standing disease. 6 Q. But is it still a myeloid disease? 7 A. It is a myeloid disease, yes. 8 Q. Okay. 9 A. But it was taken out of the category of 10 myelodysplasia. 11 Q. So, you want to call it MPD; is that right? 12 A. It's a form of myeloproliferative disease, yes. 13 Q. Okay. Should we make a note on the chart of 14 that? 15 A. Okay. You can call it myeloproliferative 16 disease. Okay. 17 Q. I don't want to cut off your explanations. So, 18 you can continue. 19 A. No, no, no, that's -- that's fine. In other 20 words, most hematologists always felt that it should not 21 have been in this classification because it is a 22 myeloproliferative disease; and eventually those pleas 23 were heard and it was paroled from this classification. 24 Then what's happened is that the splitters 25 came along. 17 1 Q. Including you. 2 A. No, well, I'm -- I'm a casual observer. 3 Q. Okay. 4 A. But sort of splitters within the 5 classification, you might say; and they took -- primary 6 refractory anemia stayed there. Then they took RARS and 7 tried to divide it into a number of categories. 8 So-called pure RARS and -- let's just say pure -- RARS 9 with multilineage dysplasia, meaning that the morphology 10 was very aberrant in one set by the other. 11 Q. "Aberrant," that's a new word to me. 12 A. Meaning that it was further away from normal. 13 In other words, in classic RARS, there are certain 14 particular abnormalities; and they're primarily in the 15 red cell precursors in the bone marrow. You see some 16 where the white cell precursors are abnormal and the 17 platelet precursors are abnormal, and that's referred to 18 as multilineage dysplasia, three different lines being 19 affected. And some people felt there was importance to 20 segregate those -- those lines, that is to say, because 21 it seemed that the people with pure RARS had a better 22 prognosis than those with the multilineage dysplasia. 23 Now, it could be that simply you're 24 looking at the two ends of a bell-shaped curve and that 25 there really is one illness, but nevertheless, they were 18 1 separated out into these two categories where they stand 2 now. 3 And I might go back, by the way, I just 4 remembered, that in the original classification, there 5 was sort of a myelodysplasia unclassified, a U; and that 6 is, it didn't fit into any of these categories. 7 Q. Okay. 8 A. That's still in the newer ones, myelodysplasia 9 U. 10 Then what happened was -- is that the 11 refractory anemia with excess blasts and transformation 12 disappeared because it was decided that really that was 13 acute leukemia and it was -- it already was acute 14 leukemia. And what had happened was we used to have a 15 rule that you had to have 30 percent blasts, 16 myeloblasts, to make a diagnosis of AML. Then that 17 number went down to 20 percent. Well, when that went 18 down to 20 percent, a lot of these refractory anemias 19 with excess blasts and transformation fit into the AML 20 category. 21 Q. So, each of the diseases on Exhibit 8, the 22 chart you're making for us, those are all -- they all 23 have the potential to progress to AML, correct? 24 A. Yes. All diseases in the myelodysplasia 25 category have the potential to progress to AML at 19 1 different incidence rates. 2 Q. But then if you have someone with RAEB in 3 transformation with -- that has the little t next to 4 it -5 A. Yes. 6 Q. -- that's to say, you already know that that's 7 going to become AML? 8 A. Yes. Now, before, it was considered that 9 wasn't quite AML but now it's considered it is AML. 10 Q. Okay. 11 A. Okay? And -- and actually, we've even gone 12 further than that, because in certain forms of AML, you 13 don't even have to have 20 percent blasts anymore to 14 make that diagnosis. In other words, today, if you see 15 a person with a particular chromosome aberration, such 16 as inversion 16, or 15 to 17, translocation that causes 17 promyelocytic leukemia, even though you may have, let's 18 say, 5 percent blasts, by definition, that becomes an 19 acute leukemia, an acute myeloid leukemia, without the 20 20 percent blast number. So, there's been a continued 21 evolution of what we actually call acute leukemia. 22 In any event, getting back to your table 23 here, we -- what's further happened is now, going back 24 to this RARS category, there's been a further subset 25 taken out of this one because some of these patients 20 1 with RARS have very high platelet counts. That's been 2 known for many years. And in recent years it's been 3 shown that that particular group often has an unusual 4 chromosome aberration called the JAK2. 5 Q. And a chromosome -- a chromosome aberration is 6 where there's a notable or marked problem with a 7 specific chromosome? 8 A. Well, it may be a duplication of a particular 9 area on the chromosome, a very tiny defect. It may be 10 loss of part of a chromosome. It may be loss of a whole 11 chromosome. It may be an extra chromosome. There are 12 many kinds of aberrations that can occur. It could be a 13 translocation where a piece of one chromosome moves to a 14 different one in exchange for that chromosome's piece, a 15 so-called reciprocal translocation. 16 In any event, so, now -- now you could say 17 the RARS category has been split out into pure, 18 multilineage dysplasia and -- and those that have this 19 JAK2 aberration so that -- that one category might 20 become three. 21 We still have refractory anemia with 22 excess blasts; and that's been divided into two 23 categories, sort of a 1 and 2, depending on how many 24 blasts you have. 25 And then there is a -- another category of 21 1 just myelodysplasia with multilineage dysplasia, meaning 2 that all three cell lines are -- are affected and that's 3 the general -- I think I've covered most of the ones on 4 the current transformation. These are very fluid, and 5 every so often they are modified a bit. 6 Q. Okay. That -- that bottom half of the page, is 7 there a year where those became the new criteria or the 8 new names, so to speak? 9 A. I can't tell you the exact year. For example, 10 the removal of the RARS because of the JAK2, that's 11 actually proposed. It's been proposed for about two 12 years. I don't know if it currently has been accepted. 13 These are sort of -- it's peculiar how these changes 14 come about. They're often done by the World Health 15 Organization, who are primarily pathologists; and -- and 16 those of us that are clinicians look at this, and it's 17 only been in recent years that the WHO now has a few 18 clinicians on their board. 19 But most of these designations are 20 pathologic designations. In other words, the 21 pathologists looking at the bone marrow and thinking 22 that they can make separations. And what happens is 23 that as many people have commented and as pointed out in 24 some of the articles that I have there, you can give 25 many of these slides to different pathologists; and they 22 1 might be put into different slots. There's a lot of -2 a lot of interpreter variation when you're talking about 3 pure morphology. 4 Q. So, there's interpreter variation among 5 splitters -6 A. That's correct. 7 Q. -- in the hematology and the pathology 8 communities? 9 A. That's correct. You might look, for example, I 10 saw one report where, just in terms of this refractory 11 anemia with ringed sideroblasts, one large institution, 12 virtually all of their patients were in the RARS 13 category. A second institution, virtually all of their 14 patients were in the multilineage dysplasia category 15 when they had ringed sideroblasts. And they really 16 ought to be the same. These are both large studies. 17 So, it looked like the pathologists at one 18 institution were more likely to use the term 19 "multilineage dysplasia" than those at the former 20 institution. 21 And, again, there's a lot of, I think, 22 interpreter variation in these issues. 23 Q. Fair enough. I didn't mean to cut you off. 24 A. No, no, I -- as I say, that's -- that's where 25 we are today. In other words, it's a -- it's a category 23 1 that -- that is -- continues in evolution. 2 Q. Fair enough. AML -3 A. Yes. 4 Q. -- can we subdivide AML? 5 A. Yes. AML formerly has been subdivided into 6 what we call the FAB classification. 7 Q. Is that the M1 to -- through M6? 8 A. Yeah, or M7. And the -- that was purely based 9 on, let's say, morphology, the so-called 10 French-American-British classification. That actually 11 has become pass. It is still used and some textbooks 12 still use it but the World Health Organization has 13 dropped it. 14 Q. So, that's to say that you don't call AMLs by 15 an M1 or an M4 subtype anymore? 16 A. Some people do. Some people don't. As I say, 17 that's, again, a state in transmission -- in -- in 18 change. For example, if I saw a person with what's 19 called M3 promyelocytic leukemia, some people would call 20 it M3. Some people would call it promyelocytic 21 leukemia. The World Health Organization would call it 22 15 to 17 translocation leukemia because you have to have 23 that translocation to get into the game. 24 Q. Got you. 25 A. And, so, what the World Health Organization has 24 1 been trying to do in recent years is to pigeonhole these 2 myeloid disorders into categories that have a very 3 specific molecular or -- or biochemical marker that -4 that, let's say, proves their existence, as opposed to 5 others that don't have that. 6 Q. So, can we make -- to subdivide AML in sort of 7 a simple way to teach us, can we -- can we -- is it 8 still fair to write down those M1 through M6? 9 A. Yes, you can. In other words, there's actually 10 M0 -11 Q. Okay. 12 A. -- meaning very poor differentiation; M1; M2. 13 M3 is the promyelocytic. M4 is -- is, I believe, 14 myelomonocytic. And M5 is pure monocytic. M6 is 15 erythroleukemia. M7, I believe, is megakaryocytic 16 leukemia. They're sort of morphologic variations of 17 AML. 18 Q. So, within each one of those -- let's take M2, 19 for example. Not all M2 patients are the same, correct? 20 Some of them might have other sort of individual things 21 about their disease that make them particular -22 A. Yes. The classification is simply how close do 23 these blasts look compared to the normal cell? In other 24 words, are they -- normal myeloid cells have granules in 25 them. Are these cells devoid of granules? Are there a 25 1 few granules? Are there aberrant granules? For 2 example, in M4 AML, some have very aberrant-looking red 3 or eosinophilic granules. Sometimes that's associated 4 with a particular chromosome defect called inversion 16, 5 sometimes not. 6 And, so, by looking at the morphology, 7 which doesn't necessarily correlate directly with 8 chromosome aberrations except, for example, in M3, you 9 come to a conclusion which category it goes into. 10 Q. But you could even subdivide a little more if 11 you really wanted? 12 A. Yes. And that's what's happening now, is by 13 eliminating these categories of M numbers, you're trying 14 to separate them by some particular molecular marker. 15 Q. Fair enough. 16 With the atypical CML, can we subdivide 17 that anymore? 18 A. No. Atypical CML originally was simply called 19 Philadelphia chromosome negative CML. And then when we 20 came up -- and there were -- if we looked at all CMLs, 21 there were a certain number that fit into that camp 22 where they couldn't be morphologically distinguished 23 from CML with the Philadelphia chromosome. They were 24 just Philadelphia chromosome negative CML. 25 Then things got a little further 26 1 subdivided, because we found that some of those people 2 that were Philadelphia chromosome negative, they had a 3 protein in their blood called the Bcr protein that's 4 produced by the Philadelphia chromosome. And even 5 though you couldn't see the chromosome, it was there 6 because it was making this marker. So, then, in order 7 to become Philadelphia chromosome negative, you also had 8 to be negative for the Bcr locus. 9 And then people came up -- the World 10 Health Organization, their being purists, they wanted 11 CML to be only used for people with the Philadelphia 12 chromosome; and anything else, we've got to find 13 someplace to stick it. We don't -- we don't want it 14 called CML. 15 The M.D. Anderson group said, "Okay, we'll 16 call it atypical CML." And that seems to -- it's still 17 smoldering, but that seems to be an accepted designation 18 now, that atypical CML is a disease that morphologically 19 is indistinguishable from classic CML except it doesn't 20 have the Philadelphia chromosome. 21 Q. So, do we subdivide the CML anymore? 22 A. Well, CML -23 Q. Regular CML, not atypical. 24 A. Regular CML -- no, it's -- it's the disease 25 characterized by the -- by either the Philadelphia 27 1 chromosome or the positive Bcr product and that's the 2 disease that has been, you might say, a miracle, because 3 when I first went into practice, 100 percent of these 4 people would die and then a number were saved by bone 5 marrow transplants and today 90 percent take a pill a 6 day and do fine. 7 Q. Is it -- I'm sorry. 8 A. No, I was going to say -9 Q. Isn't that what happened to Raul Zendejas? He 10 had atypical CML. Back in the day, he would have died. 11 Here he was given a bone marrow transplant. He 12 survived. 13 A. That's correct. 14 Q. Okay. I think we've covered the chart, do you? 15 A. Yes, in general, that's right, yes. 16 Q. Okay. You've brought up some things that I 17 want to talk about in a little more detail and then 18 we'll kind of move on to a new topic. 19 You mentioned cell lines. There -- there 20 are three cell lines within the bone marrow. It's my 21 understanding the bone marrow's function, it's sort of 22 like a -- it's a factory for white cells, red cells and 23 platelets; is that right? 24 A. In general, yes. There are also lymphoid cells 25 in the bone marrow. And plasma cells. There are a 28 1 variety of lymphoid cells. 2 Q. The bone marrow produces red blood cells. 3 Those carry oxygen to our body; is that right? 4 A. Yes. 5 Q. And you need the oxygen in your body for 6 energy, right? 7 A. Yes. 8 Q. And then the white cells, those help fight 9 immunity, correct? 10 A. Well -11 Q. Or they help immunity functions? 12 A. Yeah, in two -- two different ways. The 13 so-called myeloid white cells, the granulocytes, 14 neutrophils, monocytes, they directly phagocytize and 15 kill bacteria. So, they're primarily antibacterial and 16 antifungal to a certain degree; whereas, the lymphoid 17 cells are more immune mediated, making your antibodies 18 to viral diseases, other diseases of that nature. 19 Q. And then our platelets, those help our blood 20 clot if we have a scrape or a cut or even something 21 internally; is that right? 22 A. Yes. The platelets come from the parent cell 23 in the marrow, which is called a megakaryocyte. 24 Q. Generally speaking, is it fair to say that a 25 myeloid leukemia or a myeloid disease causes or involves 29 1 some type of -- of screw-up with the process of one of 2 those -- one or more cell lines. Is that a fair 3 statement? 4 A. Yes. 5 Q. That's to say there's some damage in the bone 6 marrow that is manifesting itself by either moving your 7 white counts higher or lower or your red counts higher 8 or lower or messing up your platelet numbers. Is that a 9 fair description? 10 A. Yes. It interferes with the -- with the 11 mechanics of cell production, AML does. 12 Q. All the -- all of the myeloid -13 A. All of these myeloid diseases do, yes. 14 Q. Okay. If benzene -- before we made your 15 chart -- if benzene is going to hurt someone, it's going 16 to hurt their myeloid cells. It's going to hurt their 17 bone marrow, correct? 18 MR. PERRY: Object to form. 19 A. Well, it's going to hurt -- it can hurt all of 20 the cells, including the lymphoid cells, because in 21 aplastic anemia, the lymphocytes often disappear first. 22 And, so, it's not just the myeloid cells. It's lymphoid 23 cells that may be damaged by benzene, in the case of 24 aplastic anemia. 25 Q. (BY MR. PATTON) For -- I want to kind of move 30 1 to a new topic here. You practice here in the Texas 2 Gulf Coast; is that correct? 3 A. Yes. 4 Q. Is -- how long have you been practicing here? 5 A. Well, except for two years in San Antonio when 6 I was in the service, I've been here since I came here 7 to go to medical school in 1962. Long time. 8 Q. Over 35 years? 9 A. Yeah, more than that, actually, but a long 10 time. 11 Q. Okay. Do you -- have you been treating 12 patients with myeloid leukemias or myeloid diseases 13 throughout that time here in the Texas Gulf Coast? 14 A. Yes, since I was actually an intern seeing 15 patients; and I at that time saw a number of patients 16 with myeloid leukemias. So, since 1966 and including 17 the years I was in the service because I was assigned to 18 the referral hospital for hematology in the Air Force. 19 So, I exclusively saw hematology cases during those two 20 years I was in the Air Force. So, I've been seeing 21 various forms of leukemias and myeloid, lymphoid 22 diseases since 1966. 23 Q. Would you agree with me that there is a really, 24 really large concentration of oil refineries and 25 petrochemical facilities here in the Texas Gulf Coast? 31 1 A. Yes. 2 Q. And would you agree with me that the primary 3 function of some of those refineries is to make 4 gasoline? 5 A. I assume that's correct. I don't know what 6 percentage or how that works. I'm not a refinery 7 person, but I -- I can't disagree with that. 8 Q. You just know in your general life experience 9 that they're making a lot of gasoline here in the 10 Houston area? 11 MR. PERRY: Object to form. 12 A. I'm sure that that's so, but I couldn't 13 quantitate that in any way. 14 Q. (BY MR. PATTON) Sure. Sure. If we go to 15 Phoenix, they're not really making a lot of gasoline 16 there? 17 MR. PERRY: Object to form. 18 A. I don't know that for a fact, but that would 19 seem reasonable. 20 Q. (BY MR. PATTON) Do you have any appreciation of 21 how much gasoline is produced at the refineries here in 22 the Texas Gulf Coast area? 23 A. No. 24 Q. Okay. Do you know if benzene is a component of 25 gasoline? 32 1 A. Well, there is -- there is benzene in gasolines 2 and -- and fuels, yes. 3 Q. Do you -- do you have any understanding of what 4 the generally accepted causes of myeloid leukemias, all 5 those diseases on your chart there, what are the -- the 6 possible causes of myeloid leukemias? 7 MR. PERRY: Object to form. 8 A. Well, the largest category, of course, of 9 myeloid leukemias -- and you have to subdivide them into 10 type. Let's take AML, for example. The vast majority 11 of AML is what we call de novo disease. And we don't 12 know the causation. And it may even be endogenous from 13 normal cell subdivisions, that somehow because they're 14 so enormous in -- in their attempt to maintain normal 15 blood counts, that mistakes may happen. 16 So, some people would say de novo leukemia 17 or primary leukemia or endogenous leukemia, that would 18 account for, perhaps, 85 to 90 percent of the leukemias 19 that we see, acute myeloid leukemias. 20 Then there are a number of other known 21 causes -22 Q. (BY MR. PATTON) Let me stop you real quick and 23 talk about some of these -24 A. Yes. 25 Q. -- before we move to the other ones. 33 1 De novo, that's to say, we just don't know 2 the cause, right? 3 MR. PERRY: Object to form. 4 A. No, not necessarily. That is true, that we 5 don't know the cause; but it describes a leukemia that 6 has certain particular characteristics. For example, 7 favored chromosome abnormalities; certain clinical 8 course; depending on the chromosome aberration; certain 9 age designations, again, depending on the certain 10 chromosome aberrations; certain racial differences. For 11 example, promyelocytic leukemia, M3, is more common in 12 Hispanics than it is in Caucasians. There would be a 13 variety of things that would go into making a diagnosis 14 of de novo leukemia but -- but it is true. We don't 15 have a identifiable external cause for that illness. 16 Q. (BY MR. PATTON) Some patients come in. They 17 get diagnosed with a certain form of leukemia, and for 18 one reason or another you can't isolate the cause. You 19 call it de novo. Is that fair? 20 A. That's -- that's part of the issue, yes. 21 Q. And what's the -- what was it about M3 in 22 Hispanics? 23 A. Well, it's been noticed -- Dr. Tallman, 24 actually who lectured at Methodist just last week, is 25 one of the people who noticed this, that when you look 34 1 at -- at communities with large Hispanic populations, 2 they have a much higher incidence of promyelocytic 3 leukemia. 4 Q. AML M3? 5 A. AML M3. 6 Q. Does Raul Zendejas have AML M3? 7 A. No. 8 Q. Okay. What -- and then endogenous, that's to 9 say your -- your body just kind of makes the change? 10 For instance, my hair might go from dark to gray; and 11 that's just a body change. Is that what endogenous is? 12 A. No. What endogenous means is that we have a 13 massive amount of white cells in the body. And these 14 white cells don't live very long. And we replace all of 15 these millions of cells at least three times every day. 16 And in order to do that, what has to happen is the 17 chromosomes have to fracture, double and reassemble; and 18 accidents can happen. And we have tremendous reparative 19 mechanisms, but if an accident happens and a 20 translocation may occur or a damage that can't be 21 repaired and for whatever reason that damaged chromosome 22 is favored in terms of its reproduction, we may end up 23 with a leukemia and it's -- it's an endogenous event. 24 There wasn't -- there wasn't a medicine. There wasn't a 25 physical external problem that caused it. It was 35 1 something that happened because of the necessity for 2 this massive reproduction of cells that the bone marrow 3 needs to engage in. 4 Q. All right. We have de novo. We have 5 endogenous, and what are the other recognized causes of 6 myeloid leukemias? 7 A. Okay. Well, we have certain, let's say, 8 congenital illnesses. 9 MR. PERRY: Object to form. 10 Just a second. 11 Are you talking about AML or myeloid 12 leukemia? 13 A. AML. I'm still with AML. We have certain 14 congenital illnesses, for example, Down syndrome, 15 trisomy 21, is associated with a high incidence of both 16 acute myeloid and lymphoid leukemia. 17 Q. (BY MR. PATTON) Did Raul Zendejas have any of 18 those? 19 A. No. 20 Q. Okay. And, Doctor, I want to make it clear. I 21 want to talk about generally accepted causes of the 22 whole family of myeloid leukemias. 23 A. Well, but you have to talk about -- if you want 24 to do that, that's fine; but you have to talk about them 25 individually because they are different. 36 1 Q. Fair enough. What else -- what other causes do 2 we have? 3 A. In the case of acute leukemia, it's interesting 4 that an illness, hereditary illness called pernicious 5 anemia is associated with an increased incidence of AML; 6 and the reason for that is that when you get vitamin B12 7 deficiency, it interferes with chromosome duplication 8 and you can get chromosome aberrations simply from that 9 vitamin deficiency. And all the studies that have 10 looked at long-term consequences of people with 11 pernicious anemia find a higher incidence of both 12 stomach cancer and AML in that group. So, that would be 13 another risk factor. 14 Q. Did Raul Zendejas have pernicious anemia? 15 A. No. 16 Q. Okay. What are the other causes? 17 A. What are the other causes? Of course, benzene 18 is a known cause of -- of -- or potential cause of AML, 19 benzene exposure at very high levels. The other 20 incidences are -- are chemotherapy drugs. 21 Q. Hold on a second. Did Raul Zendejas have 22 occupational exposure to benzene? 23 A. Well, he worked with gasoline; and I can't 24 comment as to what concentrations of benzene he has. I 25 don't believe he worked with pure benzene. He worked 37 1 with gasoline which might have 1 to 2 percent benzene in 2 it. So, indirectly, yes, he's working with benzene. 3 Q. You agree with me that Raul Zendejas was 4 occupationally exposed to benzene? 5 MR. PERRY: Object to form. 6 A. He was occupationally exposed to gasoline, of 7 which benzene is a component. 8 Q. (BY MR. PATTON) Okay. If someone comes to 9 you -- are you an internal medicine doctor as well? 10 A. Yes. 11 Q. I mean, you can teach -- teach -- you can treat 12 patients with colds, fevers, other diseases, correct? 13 A. Yes. 14 Q. Okay. If someone comes in and has, let's say 15 diabetes, can that be caused by sugar problems; or how 16 is that? 17 A. Well, diabetes, that's an illness broken into 18 generally two camps, so-called type 1 and type 2 19 diabetes, type 2 being -- having a genetic 20 predisposition typically. Type 1 is more of an acute 21 illness that may be viral induced, often happens at an 22 early age and is a more aggressive illness. 23 Q. But it has something to do with sugar, right? 24 A. Well, when you get diabetes, you can't handle 25 sugar very well because you're lacking insulin or -- 38 1 Q. Can you handle -- I'm sorry. I didn't mean to 2 cut you off. 3 A. Or you have resistance to insulin. The insulin 4 doesn't work very well. 5 Q. Can you handle Twinkies, if you're a diabetic? 6 A. Well, you can if you're taking your insulin 7 properly. If you're taking insulin injections. In 8 other words, the objective is to try to control your 9 blood sugar, because we know that if the blood sugar is 10 constantly very high, that predisposes to vascular 11 defect, vision defect, kidney defects and so on. 12 Q. Twinkies have sugar in them, correct? 13 A. Yes. 14 Q. So, if you're a diabetic, you want to be 15 mindful of Twinkies just as you want to be mindful of 16 putting pure sugar in your coffee, correct? 17 A. Well, you have to -- you have to be -- have a 18 balance between the amount of sugar in your intake and 19 the amount of insulin that you have in the body. 20 Q. As a doctor, you recognize and respect the role 21 of sugar in foods, as compared to pure sugar, as that 22 might affect diabetes, right? 23 MR. PERRY: Object to form. 24 A. I'm not sure I understand that question. 25 Q. (BY MR. PATTON) I'll move on. 39 1 Okay. You said benzene, known or 2 potential cause of myeloid leukemias, correct? 3 A. Yes. 4 Q. And then what other causes -5 MR. PERRY: You said AML or myeloid? 6 THE WITNESS: AML. 7 A. The -8 Q. (BY MR. PATTON) Before we move on, do you not 9 believe -- you do not believe that benzene causes MDS; 10 is that correct? 11 A. No, I do believe benzene can cause certain 12 forms of MDS. 13 Q. Okay. Well, we just talked about -- your 14 lawyer chimed in and said do you just mean AML and I 15 want to be clear on this. 16 A. No, we were talking about AML. I thought I was 17 talking just about AML causation. 18 Q. I want to talk about the myeloid leukemias. 19 A. I understand. But I would like to do that one 20 at a time. 21 Q. Okay. 22 A. In other words, because as I said earlier, 23 there are different causations in these illnesses; and 24 AML is one illness and -- and other things, like CML, 25 they're entirely different illnesses. 40 1 Q. Is benzene capable of causing AML? 2 A. Yes. 3 Q. Can benzene cause MDS? 4 A. Certain forms of MDS, yes. 5 Q. Can benzene cause CML? 6 A. No. 7 Q. Can benzene cause atypical CML? 8 A. No. 9 Q. Okay. We'll go through those in a little more 10 detail. 11 You -- you were mentioning the next cause, 12 chemotherapy drugs? 13 A. Yes. Of what we call secondary leukemias 14 today, and secondary means not endogenous. There is an 15 external event that caused the AML. Many of these, 16 perhaps, oh, 7 to 8 percent of those are caused by prior 17 chemotherapy treatment. For example, we might have a 18 lady with breast cancer and the chemotherapy is 19 successful in treating the breast cancer but causes the 20 development of AML several years later. Or we treat 21 someone for Hodgkin's disease and later on acute 22 leukemia develops. So that chemotherapy and radiation 23 therapy are both known causes of AML. 24 Q. I'll add radiation right under chemo drugs. Is 25 that fair? 41 1 A. Yes. 2 Q. Okay. So, chemo drugs and radiation, those can 3 affect the myeloid cells, correct? 4 A. Yes. 5 Q. Can benzene affect the myeloid cells? 6 A. Yes. 7 Q. CML and atypical CML, those are myeloid 8 diseases, correct? 9 A. Yes. 10 Q. And your testimony here, just as if it were in 11 front of a judge and a jury, is that benzene, yes, it 12 affects the myeloid cells; but it's not going to affect 13 it in such a way to cause those two diseases. Is that 14 your testimony? 15 A. That's correct. 16 Q. Okay. And did we talk about all the causative 17 factors? 18 A. I think that we didn't talk about other 19 underlying bone marrow diseases. For example, people 20 who have myelodysplasia for whatever reason in most 21 cases myelodysplasia is also a de novo disease but 22 various forms of myelodysplasia may terminate in AML. 23 And, so, an underlying myelodysplasia may -- is a 24 causative factor in AML or can be. 25 Q. And you have -- that myelodysplasia, that would 42 1 essentially fit in on that chart of myeloid diseases, 2 correct? 3 A. Yes, myelodysplasia would be a myeloid disease. 4 Q. Okay. And then that can become AML? 5 A. Yes. 6 Q. Okay. 7 A. And then myeloproliferative diseases, those are 8 illnesses like CML or polycythemia vera, myelofibrosis, 9 primary thrombocytosis, chronic myelomonocytic leukemia, 10 all of the myeloproliferative diseases may also 11 terminate in AML at differing incidence rates. 12 Q. Did Raul Zendejas have any exposure to 13 chemotherapy drugs or radiation? 14 A. Not that I'm aware of. 15 Q. And he had some bone marrow disease forms that 16 ultimately became AML; is that accurate? 17 A. Well, he developed what most people would call 18 a blast crisis. That is, he developed very immature 19 cells in the peripheral blood. And in people with CML 20 or atypical CML, when they go into what we call blast 21 crisis, they make large numbers of very immature cells 22 which can be myeloid or they can be lymphoid. They're 23 usually myeloid, perhaps 80 percent are myeloid. Maybe 24 20 percent of the time they're lymphoid. And we call 25 that blast crisis. And it simulates acute myeloid 43 1 leukemia. And if you wanted to call it acute myeloid 2 leukemia, I wouldn't put up a fuss; but most 3 hematologists would simply refer to it as a blast 4 crisis. 5 Q. Depending on how much of a splitter or a lumper 6 they are. Is that fair? 7 A. Yes. You may be seeing myeloblasts or 8 lymphoblasts, which are the characteristics of acute 9 lymphoblastic leukemia or acute myeloblastic leukemia; 10 but the implications of a blast crisis in CML are much 11 different than the implications of acute myeloid 12 leukemia as we know it. 13 Q. If Dr. Carroll -- you understand Dr. Carroll 14 was Raul's main treating doctor. Do you understand 15 that? 16 A. Yes. 17 Q. He gave him two bone marrow transplants; is 18 that right? 19 A. Yes. 20 Q. We took Dr. Carroll's deposition. We looked at 21 his records. You looked at both the depo and the 22 records, right? 23 A. Yes. 24 Q. He says that Raul has AML, correct? 25 A. I don't remember that -- that particular 44 1 statement. I don't dispute it. I just don't remember 2 that. 3 Q. All right. Have we called -- have we talked 4 about all the causes of myeloid leukemias? 5 A. I think we've covered most of them. Let's see. 6 We talked about congenital issues, acquired issues with 7 chemotherapy and underlying diseases, endogenous 8 formation of AML. I think those would be the most -9 most predominant causes. 10 Q. Is smoking a factor in causing myeloid 11 diseases? 12 A. Yes. Smoking is actually -- I had forgotten 13 that. Smoking -- to add that -- smoking is thought to 14 cause acute -- potentially cause acute myeloid leukemia 15 and certain forms of myelodysplasia. 16 Q. Did Raul smoke cigarettes? 17 A. Yes. 18 Q. Okay. I want to talk a little bit more about 19 these -- this de novo category of possible causative 20 factors of myeloid leukemias. Did you say it's 80 or 21 90 percent of all myeloid diseases are considered de 22 novo? 23 A. I said that of acute myeloid leukemia and 24 myelodysplasia about 85 to 90 percent of those diseases 25 are considered de novo diseases. 45 1 Q. Isn't part of the reason they're de novo is 2 because no one asked, no one conducted the more in-depth 3 examination to try to figure out other possible causes? 4 A. No, I don't think that's so. 5 Q. If someone comes in to your clinic and you 6 diagnose them with a form of myeloid leukemia and you 7 take a patient history, do you do that sometimes with 8 your patients? 9 A. Yes. 10 Q. You talk about social history, whether they 11 smoked, what kind of work they did? 12 A. Yes. 13 Q. You asked them about hereditary factors, family 14 history of cancer, things like that? 15 A. Yes. 16 Q. If they come in and they -- they don't tell you 17 that they had previous chemo drugs and previous 18 radiation treatment, would you call it a de novo 19 leukemia? 20 A. Well, if I don't have that information, then -21 then that's a missing important part of history. And if 22 a person had heavy chemotherapy and came in with acute 23 leukemia, it's more likely to be, depending on the time 24 sequence, the drugs he got and so on, it's very likely 25 to be a secondary AML. 46 1 Q. Not a de novo AML? 2 A. Not a de novo. 3 Q. So, he comes in; he raises his hand and he 4 waves it around and he says hey, Doc, hey, Doc, I had 5 chemo drugs and I had a lot of radiation, you would 6 automatically -- well, not automatically, but you would 7 draw the conclusion, as a -- as a doctor, you would say, 8 well, probably a cause of your disease. You're no 9 longer in the de novo category? 10 A. Yes. I would say this, that in no particular 11 case of acute myeloid leukemia can we be certain about 12 causation. In other words, there's no way to look at 13 that slide or that patient and say, aha, this was caused 14 by this and that was caused by that. All we can say is 15 what is probable. 16 And, so, I would say if somebody came in 17 with a past history within, let's say, the last 10, 18 15 years of getting high-dose chemotherapy and they came 19 in with acute myeloid leukemia, I'd say it was highly 20 probable that the chemotherapy was -- was -- leukemia 21 was a consequence of the chemotherapy. 22 Q. But if he just doesn't mention his chemotherapy 23 history, you're not going to say more probable than not 24 that it's chemo drugs. You're going to say, oh, you're 25 de novo, right? 47 1 A. That's correct. 2 Q. So, you would agree with me, Doctor, that part 3 of the reason some 85 percent, give or take, of 4 leukemias or myeloid leukemias are de novo is because 5 nobody asked, right? 6 MR. PERRY: Object to form. 7 A. No. Because, you see, you can find plenty of 8 literature to show where people did ask. For example, 9 one of the types of acute myeloid leukemia is called M6, 10 or erythroleukemia; and that's one that benzene can 11 cause. And there's one -- the larger study in the world 12 done on those cases, and I think they had, like, 13 about -- let's just say 70 cases of erythroleukemia, and 14 they sat down with these patients and took very detailed 15 histories and they came up with the fact that 66 of 16 them, I believe, were -- something in that order -- were 17 de novo. They had no history of any sort of exposure. 18 Some had prior history of myelodysplasia; or they took 19 immunosuppressive drugs for transplants; they had some 20 other drug background that might be causative, and they 21 found one person out of that group who gave them a 22 history of heavy exposure to solvents. So, perhaps that 23 one person had his illness from solvent exposure, 24 perhaps he didn't. But there -- there -- we have enough 25 studies like that. So, we know that the bulk of 48 1 leukemia is without any obvious external causation. 2 Q. (BY MR. PATTON) If somebody comes in and you 3 take your social history and their work history, 4 occupational history and they tell you, hey, you know, 5 my mom had pernicious anemia, family history of cancer 6 and I've been smoking. Would you acknowledge those as 7 positive causative factors in their myeloid leukemia? 8 MR. PERRY: Object to form. 9 A. Well, in acute myeloid leukemia, for obscure 10 reasons to this point, if your mother had breast cancer, 11 you are at higher risk of AML than the general 12 population. And certainly if you smoke, you're at 13 higher risk of AML than the general population. 14 Q. (BY MR. PATTON) So, if you know those things, 15 you can acknowledge them as possible causative factors, 16 right? 17 A. Well, associations. In other words, we -18 again, it's, in an individual case, very difficult to 19 give cause and effect. We can just say statistically a 20 son of a woman with breast cancer has a higher incidence 21 of AML. Statistically a smoker has a higher incidence 22 of AML if they're a heavy smoker. Why that's the case, 23 we don't know. 24 Q. I'm not really asking if there's -- if someone 25 might have a higher incidence. What I'm really asking 49 1 is: If somebody walks into your clinic, you diagnose 2 them with a form of leukemia; you take a social history; 3 they tell you, hey, I've had some chemo drugs; or, hey, 4 I've had radiation; or, hey, I've been smoking, before 5 you start digging deeper into the literature, do you 6 acknowledge and respect those -- those issues as 7 possible causative factors of their leukemia? 8 A. Yes. 9 Q. Okay. But you don't necessarily go as far to 10 do a full investigation to take them out of the de novo 11 category; or do you? 12 A. Well, I think our therapy in acute leukemia is 13 based today in part -- and actually in the main -- on 14 chromosome analysis in the patients -15 Q. And, Doctor, I don't mean to cut you off; but 16 I'm not asking about chromosomal analysis. 17 A. I understand. But you're saying -- your 18 question has to do with whether I might base my 19 treatment on the history of whether it's de novo or 20 secondary. 21 Q. I'm not talking about treatment. 22 A. Okay. 23 Q. I'm talking about -24 A. You'll have to repeat that question, then. 25 Q. Okay. Let's -- that's fair. Let's do that. 50 1 Someone walks into your clinic, okay? 2 A. All right. 3 Q. You diagnose them with a given form of myeloid 4 leukemia, any one on your chart there, okay? 5 A. Okay. 6 Q. And they tell you -- you take a social history, 7 and they say, Doc, I've had a bunch of chemotherapy 8 and/or I've had a bunch of radiation for prior cancer 9 treatment. Do you, as a doctor, recognize those -10 those earlier exposures to chemo drugs or radiation as 11 possible causative factors of their disease? 12 MR. PERRY: Object to form. 13 A. Yes. I think I've already said that. 14 Q. (BY MR. PATTON) Okay. Somebody comes in to 15 you -- and you work here in Houston, and there's a lot 16 of gasoline being made around us. Someone walks in and 17 says, Doc, I've been working at that refinery for 18 30 years. We've been making gasoline. Would you 19 acknowledge benzene as a possible cause of their myeloid 20 leukemia? 21 MR. PERRY: Object to form. Vague. 22 Doesn't specify a type of myeloid leukemia. 23 Q. (BY MR. PATTON) And, Doctor -24 A. Well -25 Q. -- I'm asking generally. Okay. They come in 51 1 and you figure out, hey, this guy has got some type of 2 myeloid leukemia. The pathology is out there right now. 3 It's going to come back and tell you what specific type. 4 Is that kind of how it works? I mean, you don't first 5 see the patient? 6 A. Well, usually you first see the patient or, in 7 my particular case -- let me give you a specific example 8 of how it works. This week a doctor had a patient who 9 was deaf and he wants to put in a cochlear implant in 10 his ears to have him hear better. And the man is 72 11 years old and has never been a sick a day in his life. 12 But like many surgeons do, they get preoperative 13 laboratory work; and lo and behold, his white blood 14 count is 50,000. The normal is 5 to 10,000. So, 50,000 15 is high. And they're lymphoid cells, at least the lab 16 says that. So, he cancels the surgery; and he refers 17 the patient to me. 18 Q. Let me stop you right there real quick. That 19 patient comes in and he has a problem with his white 20 cells and he has a problem with his lymphoid cells, 21 right? 22 A. Yes. 23 Q. And you can tell that off his standard blood 24 work, right? 25 A. I can tell the general category of illness off 52 1 the standard blood work, yes. 2 Q. Okay. What is that general category of 3 illness? Is it a myeloid disorder, a myeloid disease? 4 A. It -- well, it could be if the lab technician 5 is mistaken, because many times what are myeloid cells 6 are mistaken for lymphoid, especially immature cells, 7 and vice-versa. So, at least if -- if the lab were 8 accurate, I would say he would have a 9 lymphoproliferative disease. 10 Q. Does that fit on our chart? 11 A. No. We're not -- only in the case of a blast 12 crisis, which can be lymphoid; but we're talking 13 myeloproliferative diseases. But you're talking how it 14 works when you see a patient with leukemia or you're 15 referred, and I'm saying that's a typical example. 16 Someone comes in with a high white count. They come to 17 the hematologist for an evaluation of what is the cause, 18 what's the classification, what's the type of illness 19 and what kind of therapy would be appropriate. 20 Q. Is part of your job as a hematologist here in 21 the Houston area to determine cause of your patients' 22 diseases? 23 A. Well, that's part of what we do. In other 24 words, a -- a -- even though a hematologist is not a 25 trained epidemiologist, we always take a history from a 53 1 patient; and you might say we have a good understanding 2 of what's likely and what's not likely from our long 3 experience. 4 For example, if I see a patient with hairy 5 cell leukemia, I know that about 80 percent of them are 6 going to be male because I've been seeing hairy cell 7 leukemia for 40 years and 80 percent are male. I don't 8 need an epidemiologist to tell me that because that's an 9 observation made over time. 10 Q. Somebody could give you something of a quiz, 11 give you the pathology that says hairy cell leukemia. 12 You don't even need to look at the top to see male or 13 woman. You're saying, hey, probably a male here? 14 A. It's probably going to be man. And if it's a 15 woman, I'm going to look twice at those slides to be 16 sure that this is not a mistake because that particular 17 illness is a man's disease. 18 Q. If someone came -- I'm sorry. 19 A. No. I was going to say, and if somebody 20 referred me an 18-year-old person and said they had 21 multiple myeloma, I'm going to say, tilt, that's an 22 older person's disease. I'm going to look carefully and 23 see could there be some other etiology. 24 Q. If someone comes in and you see the chart and 25 you see -- and you see that, hey, this person has a form 54 1 of myeloid disease, just like one of those on the 2 chart -- you know it's one of those. And you see at the 3 top there worked at a refinery for 30 years making 4 gasoline, are you going to draw the conclusion, hey, 5 benzene probably a factor in this disease? 6 MR. PERRY: Object to form. 7 A. Not necessarily. In other words, I'm aware of 8 the general epidemiologic literature and I have a number 9 of papers in there and I know that for many, many years 10 it's been very difficult to demonstrate an excess of 11 myeloid leukemias in refinery workers over what's in the 12 general population. So, just because they work in a 13 refinery doesn't mean that that's the cause of their 14 illness. 15 Q. (BY MR. PATTON) Well, just because someone had 16 chemotherapy drugs doesn't really mean that's the cause 17 of their illness, does it? 18 A. That's true. In other words, it's a -- it's a 19 consideration -- but I would -- let's say if I found out 20 that somebody had a total of about 20,000 milligrams of 21 Cytoxan as part of their chemotherapy, that would be a 22 much more of a red flag to me than if a guy said, you 23 know, I work -- I've worked at the refinery down the 24 street for 20 years. 25 Q. What if it says he worked with a lot of 55 1 benzene? 2 A. Well, I'd say that's -- if that's so, that -3 that would be significant, if he was working with pure 4 benzene. 5 Q. Have you -- and people refer you -- doctors 6 refer you patients all the time, right? 7 A. Yes. 8 Q. Have you ever made -- do you have any type of 9 survey form that you give them that says, hey, "yes" or 10 "no," chemotherapy drugs, did you smoke, prior 11 radiation, family history, do you have any type of 12 survey that you perform of your patients? 13 A. No. 14 Q. Thirty-five years in the Gulf Coast area, have 15 you ever used such a survey to determine how many of 16 your patients have worked in refineries? 17 A. No. 18 Q. Have you ever done any type of survey to see 19 how many of your patients have worked with solvents? 20 A. No. These are -- I ask all these questions, 21 but I don't -- and I record them in my history and 22 physical, for example, if they smoke and how long and so 23 on, but I haven't gone back to try to do statistics 24 on -- on my patients to see if I have an unusual number 25 of refinery workers with acute myeloid leukemia because 56 1 I know that I haven't. In other words, I don't see a 2 patient and he says, I'm just another guy from the Jones 3 refinery down the street; and I say, oh, yeah, here for 4 AML again. It doesn't work like that. I see people 5 from all walks of life. 6 Q. I understand that, Doctor. 7 A. And that particular occupation doesn't stand 8 out in my years of practice. 9 Q. My question is a little different. And I'll 10 ask a new question. Do you -- have you ever -- do you 11 sit in on meetings with others -- isn't there a Gulf 12 Coast Hematology Association or something like that? 13 A. Yes. 14 Q. Do you sit on separate boards or separate 15 groups within the hospitals that you treat patients at? 16 A. Yes. 17 Q. Have you ever chimed in in one of those 18 meetings and said, hey, you know, benzene can cause 19 these myeloid leukemias. We have people, some of our 20 patients who are working, making gasoline, they're 21 working at refineries. Maybe we should do a study. 22 Have you ever done that? 23 MR. PERRY: Object to form. 24 A. I've never made -- I don't recall ever making a 25 suggestion that we should do a benzene study among our 57 1 patients. 2 Q. (BY MR. PATTON) Okay. Have you ever -- has 3 anyone at those meetings ever suggested that you do 4 that? 5 A. Not that I'm aware of. 6 Q. Would you agree with me that in an area like 7 Houston where there's such a large concentration of 8 refineries, if you and your colleagues here in the Texas 9 Gulf Coast area did that sort of investigation, you 10 might have an improved understanding of benzene as a 11 causative factor in myeloid leukemias? 12 MR. PERRY: Object to form. 13 A. Well, I would have to say that that's been done 14 to a certain extent. In fact, I can remember in the -15 probably the early '80s, there was a lady from 16 M.D. Anderson who came and collected all my cases of 17 acute myeloid leukemia, including their slides, and she 18 was looking to see where they lived in the Gulf Coast, 19 what type of leukemia they had, and I don't know if that 20 data ever got published or not. But that kind of work 21 has been done. 22 Q. (BY MR. PATTON) But did you note -- do you 23 routinely note on your patients' charts whether or not 24 they've been exposed to benzene? 25 A. If they say that, yes. 58 1 Q. Do you ask it specifically? 2 A. Yes. I ask them if they've had any solvent 3 exposure, do they have any unusual habits? Do they 4 paint? Do they do welding work? Do they have any -5 any exposure to unusual pesticides that they spray on a 6 regular basis, yes, we ask those questions. 7 Q. Do you teach other students? 8 A. Yes, we teach students. 9 Q. Okay. So, that's to say, when you do your 10 rounds in the hallway, you might have a group of medical 11 students with you sometimes? 12 A. Yes. Typically on a -- in fact, I just rounded 13 about three months or so ago. We have various levels of 14 residents, internal medicine residents, first, second 15 and third-year residents and a few medical students, in 16 this case, from Weill Cornell Medical School in -- in 17 New York. Yes. We discuss cases. 18 Q. Do you ask them questions? Do you do, like, a 19 Socratic method, a lot of questions and answers to try 20 to quiz them while you're doing that? 21 A. Yes. Some doctors are meaner than others. I 22 would say I'm less mean. In other words, I don't say 23 give me the five causes of this -24 Q. Sure. 25 A. -- kind of thing. And, so, yes, we do ask them 59 1 questions. 2 Q. Does any of that conversation with your 3 residents ever involve the cause of their myeloid 4 leukemia -- a patient's myeloid leukemia? 5 A. I'm sure it would. On this particular 6 rotation, we didn't have any acute myeloid leukemias; 7 but that -- I'm sure -- that would come up, in other 8 words. Whatever the illness is, causation, whether it's 9 hepatitis or congestive heart failure or acute leukemia, 10 any of those illnesses, we would discuss causation, as 11 well as therapy. 12 Q. So, you might have a patient with myeloid 13 leukemia and -- and in the question-and-answer session 14 with the resident, might a conversation start about his 15 exposure to work as a refinery worker or chemical 16 exposure? 17 A. Well, it would -- it would come out in the 18 discussion. In other words, if I saw somebody with 19 acute leukemia, I would ask the intern, what's this 20 person's background, what's his occupation, the same 21 kind of questions I ask the patient if I saw them 22 without an intern or a medical student. 23 Q. Have you ever told a patient that your form of 24 myeloid leukemia was more probable than not caused by 25 benzene exposure? 60 1 A. Yes. 2 Q. Have you ever told a patient that it was more 3 probable or not caused by, say, radiation or chemo 4 drugs? 5 A. Yes. 6 Q. How is it that you drew the conclusion that 7 your given patient, the one that you pointed out, his 8 disease was caused by benzene exposure? How did you 9 reach that conclusion? 10 A. Well, this was a man who had erythro leukemia, 11 which is a form of leukemia that's known to be 12 potentially caused by benzene or other chemicals. 13 Q. I don't see it on the chart. Where is that 14 one? 15 A. That's M6. I'm sorry. 16 Q. Okay. 17 A. And he worked at, I believe, a Cities Service 18 plant in Louisiana and repeatedly he had been in the 19 workplace, found to have a very low white blood cell 20 count, taken away from the workplace and his blood 21 counts recovered. He'd be put back in, and they'd go 22 down again. So, it looked like whatever he was working 23 with was whacking his blood count. And I asked him what 24 he worked with. And he told me that he worked with 25 cycohexene or benzene. He worked with phosphorus 61 1 compounds. He worked with nickel compounds. I've 2 forgotten all he -- he told me with, but he worked with 3 a lot of potential toxins, benzene being one of them. 4 And, so, I said to him, I think it's highly likely 5 because we know you've had enough exposure to acutely 6 damage your marrow, I think that one or more of those 7 chemicals is a consequence of your leukemia. 8 Q. And importantly, you could look at his blood 9 tests that were being conducted at his workplace and you 10 could see that trend of white cell movement, so to 11 speak? 12 A. Well, I could ask him. In other words, he 13 volunteered that information. I -- I did have some 14 records of that, too, but -- but some of this was his 15 recollection of what had happened to him. 16 Q. Can benzene cause white cells to go up? 17 A. I would hate to say never, but traditionally we 18 think of chemicals as causing leucopenia, or low white 19 counts. 20 Q. Benzene can cause white cells to go down? 21 A. Yes. 22 Q. Can benzene cause red cells to go up? 23 A. Not that I'm aware of. 24 Q. Can benzene cause red cells to go down? 25 A. Yes. 62 1 Q. What about platelets? 2 A. Yes, benzene can cause platelets to go down. 3 MR. PERRY: Let's take a restroom 4 five-minute break whenever you get to a point. 5 MR. PATTON: Okay. I'm almost to that 6 point. 7 Q. (BY MR. PATTON) Can benzene cause red cells to 8 go up? I'm sorry. 9 A. I think you -10 Q. Platelets. 11 A. No. 12 MR. PATTON: All right, Doctor. Let's 13 take a break. Off the record. 14 THE VIDEOGRAPHER: Now going off the video 15 record. The approximate time is 11:23. 16 (Recess taken from 11:23 to 11:35.) 17 THE VIDEOGRAPHER: Now back on the video 18 record. Approximate time is 11:35. 19 Q. (BY MR. PATTON) Dr. Natelson, can you estimate 20 for us approximately how many patients you've treated 21 with myeloid leukemias? 22 A. That would be -- be difficult. In other words, 23 for example, right -- currently, following about, I'd 24 say five or six people with chronic myeloid leukemia on 25 various forms of therapy. Over the years I've seen many 63 1 more than that. I've transplanted two people myself 2 with CML. 3 With acute leukemia -4 Q. I'm talking about all of them, the whole family 5 of diseases. 6 A. The whole family of diseases? 7 Q. On Exhibit 8 there. 8 A. Oh, I -- I would have to say that if you're 9 including myelodysplasia, myeloproliferative diseases, 10 CML, AML -11 Q. The whole -- the whole Exhibit 8. 12 A. -- the whole -- it's certainly well in excess 13 of 200. It could be much more than that because in -14 I've been involved in teaching for many, many years. 15 And, so, I follow some of my own patients and see 16 everybody else's, too. And, so, it's been a very large 17 number. These are not common illnesses, but for 18 hematologists, they're frequently seen. 19 Q. Well, especially over 35 years, right? 20 A. Yes, I've seen many, many such patients. 21 Q. Okay. A thousand or more, would you estimate? 22 A. I really couldn't put a number on it. Let's 23 put it this way. I've done at least 7,000 bone marrows 24 in my career and all of those were on somebody and -25 and a lot of them didn't have acute myeloid leukemia or 64 1 one of these neoplasms but a number of them did. And, 2 so, it's just many. I couldn't put a number on it. 3 Q. You said bone marrows. Is that when you do a 4 bone marrow aspiration, a biopsy? You get that -5 A. Yes. 6 Q. -- that big needle and you put it in 7 somebody's -8 A. Oh, it's not that big. As I tell my patients, 9 it doesn't hurt at all. Of course, I'm talking about 10 me. But, no, actually bone marrows, if they're done 11 properly, are not very painful. And -- and as I say, 12 I've done 7,000 in my career. 13 Q. Raul hates them. 14 A. Does he? 15 Q. And maybe he just needs to have someone else 16 doing them. 17 A. I don't know. I mean, I must say that it takes 18 me about five minutes to do one; and it's been a rarity 19 that a patient has any sort of complaint afterwards. 20 Q. Okay. So, of the hundreds, can we say hundreds 21 of patients -22 A. Yes. 23 Q. -- who you've seen with myeloid leukemias? 24 A. Yes. 25 Q. Of the hundreds you've seen, how many have you 65 1 concluded and told that patient, hey, benzene is a 2 factor in your disease or probably a factor? 3 A. I recall that particular patient. 4 Q. Recall one? 5 A. It's an unusual patient. I've certainly seen 6 others that I've told that to, but I -- as we sit here, 7 I can't remember; but I'm -- I'm certain that I have. 8 But that one stands in my mind because we did a number 9 of unusual studies on his case and I have photographs of 10 his bone marrow and a lot of information about him. 11 Q. Is there a certain amount of benzene exposure 12 that you would like to see before you give an opinion 13 that benzene is a -- a causative -- plays a causative 14 role in someone's myeloid leukemia? 15 A. Well, we usually look for cumulative exposure, 16 whether it's chemotherapy or benzene, because that seems 17 to be more closely related to disease. 18 Q. Is there a cumulative threshold, a line, so to 19 speak, above which you conclude, hey, benzene is a 20 causative factor? 21 A. Well, in many cases -- in the case of 22 chemotherapy, we -23 Q. I'm asking about benzene. 24 A. I understand. But I -- I have to preface that. 25 In the chemotherapy, we have very accurate estimates, 66 1 because we know Mr. Brown sat down at high noon and he 2 got so much injected into his vein. There's no argument 3 about what he got. 4 In the case of benzene, we have estimates, 5 which are often guesstimates. And, so, when someone 6 says they have 40 part per million exposure, it might be 7 20 or it might be 80. And, so, we just know it's high. 8 And, so, my -- my philosophy about that is it needs to 9 be a lot of exposure. If one wanted to put a number on 10 it, it would need to be a cumulative dose of greater 11 than 40 part-per-million years because we know that the 12 studies below that don't suggest an increase in AML. 13 Q. It is your opinion that a patient must have 14 above 40 part-per-million years before you can conclude 15 that benzene was a causative factor. Is that your 16 testimony? 17 A. Yes, that would be my testimony. 18 Q. Okay. And then you mentioned chemo drugs. 19 What -- instead of a part per million year, or a PMM, 20 how do you measure those chemo drugs? 21 A. In milligrams. 22 Q. Okay. Does the patient have to tell you, hey, 23 Doc, I had X amount of milligrams of these chemo drugs 24 before you can draw that conclusion? 25 A. Well, you can calculate that. In other words, 67 1 chemotherapy is often very standardized, whether it's 2 breast cancer or Hodgkin's disease; and when you give a 3 person a course of chemotherapy, there's a pretty fixed 4 number of milligrams per kilogram body weight. And, so, 5 you can have a pretty close idea. If someone said I had 6 six courses of chemotherapy, I can tell you to the 7 milligram pretty much what they had. 8 Q. And you can go to the chart and you can add up 9 exactly how many milligrams they had? 10 A. That's correct. 11 Q. Okay. And then you can draw the conclusion 12 pretty quickly because, as you said, he's sitting there 13 at high noon, taking the chemo drugs? 14 A. Yeah. 15 Q. You can say, hey, this chemo definitely caused 16 it because you don't have to estimate anything, right? 17 A. Well, I still can't say the chemotherapy 18 definitely caused it. I can just say that he's had 19 enough milligrams of whatever the particular drug is 20 because it varies a lot in terms of the number of 21 milligrams necessary to predispose to AML. But I can 22 say that this person has had enough exposure to put them 23 into the arena where it's highly likely that the -- that 24 that chemotherapy was the -- that the AML was a 25 consequence of that chemotherapy. 68 1 Q. Well, how about these patients who've come to 2 you with what you have told them, hey, benzene is a 3 causative role in your leukemia? Have they been able to 4 give you the dose of PPMs of benzene that they received? 5 A. No. But they've been able to tell me what they 6 did, how they worked with benzene, what were they 7 working with. 8 Q. Okay. And did they tell you -- how -- how 9 would they describe it? 10 A. Well, they might say, I used pure benzene to 11 wash off parts of my tools. Or they might say, I was 12 engaged in manufacturing products where benzene was a 13 raw product that went into the manufacturing. 14 Q. Products like gasoline, right? 15 MR. PERRY: Object to form. 16 A. It depends on what they did. If they were just 17 transporting it, the gasoline was already concocted. In 18 other words, what -- what they -- what they did in the 19 process, what were they engaged in making. 20 Q. (BY MR. PATTON) But do they give you a dose? 21 Do they give you a dose comparable to when you look at 22 someone's chart with chemo drugs? 23 A. No, they would not. 24 Q. Okay. And then do you require them to go back 25 and hire an industrial hygienist and take wind 69 1 measurements and other calculations before -- and then 2 come back with a piece of paper, hey, Doc, I got X 3 amount of PPM-years. Do you require that of your 4 patients before you give them that opinion? 5 A. No. 6 MR. PERRY: Object to form. 7 Q. (BY MR. PATTON) You can draw conclusions based 8 on your understanding of the -- sort of the nature and 9 duration of someone's exposure to benzene or 10 benzene-containing chemicals. You can draw upon that 11 information and reach conclusions that, hey, benzene 12 might be a causative factor? 13 MR. PERRY: Object to form. 14 A. Well, not so much their -- as I said, in the 15 case that I thought clearly that chemicals caused it, I 16 had evidence of blood count damage; and I might have 17 that, because in many industries patients get routine 18 physical examinations. 19 Q. (BY MR. PATTON) Would you agree with me that 20 routine physical examinations and routine blood counts 21 are helpful for physicians like yourself to determine 22 whether benzene was a possible role in someone's 23 leukemia? 24 A. Yes, I would say that's true. 25 Q. Would you agree with me that regular blood 70 1 counts are helpful in protecting workers who have had a 2 little bit of bone marrow damage such that you can 3 protect those workers by getting them away from the 4 benzene? Is that fair? 5 A. One can argue with that. That's reasonable. 6 Q. For instance, if this guy who you mentioned 7 from Louisiana came in and you started seeing his counts 8 in his blood tests, you could scratch your head and say, 9 hey, don't go back to that job, right? 10 A. Yes. 11 Q. Okay. You would agree with me that regular 12 blood counts are helpful in protecting workers from the 13 harmful effects of benzene exposure? 14 MR. PERRY: Object to form. 15 A. That would be -- yes, that would be one form of 16 protection, yes. 17 Q. (BY MR. PATTON) Okay. What about urine? Can 18 you detect benzene in the urine? 19 A. Well, you can detect metabolites; but they 20 don't last very long. And, so, I wouldn't say that 21 that's a very accurate way of knowing whether somebody 22 had a cumulative exposure that was of consequence. 23 Q. Okay. You believe that the cumulative exposure 24 to be of consequence must be above 40; is that right? 25 A. Yes, meaning that when -- when someone tells me 71 1 the cumulative exposure was 40, it could really be 80; 2 or it could even be higher than that. In other words, 3 I'm looking for a very high, cumulative exposure. 4 Q. Well, in this case we have evidence that Raul's 5 cumulative exposure was around 25. 6 MR. PERRY: Object to form. 7 Q. (BY MR. PATTON) It could have been 50, correct? 8 MR. PERRY: It could have been zero. 9 Object to form. 10 A. I don't know. I can't -- I can't comment about 11 what his exposure was. I'm not an industrial hygienist 12 or a -- or a person who models those types of exposures. 13 Q. (BY MR. PATTON) For each of your patients who 14 you concluded benzene played a causative role, did you 15 have part-per-million-year cumulative dose information 16 at your fingertips? 17 A. No. 18 Q. You did a qualitative assessment where you 19 assessed the quality of the information, what was known 20 about their exposure; and you used that type of 21 assessment to draw your conclusion? 22 A. In part, yes, qualitative and whatever blood 23 count material they provide me. 24 Q. Not just for the one guy but for the others who 25 you've given that opinion, right? 72 1 A. Yes. And actually, you know, when we talked 2 about that, it's come to my mind that I have seen other 3 people who have had the same phenomenon of working in an 4 industry and having reduced blood counts; and I have 5 advised them to stay out of that arena. 6 Q. Because you recognize that benzene can cause 7 myeloid leukemias? 8 MR. PERRY: Object to form. Not specific. 9 A. Well, I recognize that, yes, that is certainly 10 true, benzene can cause certain types of leukemia, AML 11 and certain forms of myelodysplasia. 12 Q. (BY MR. PATTON) Is there a safe level of 13 exposure to benzene? 14 A. Well, obviously, the -- we have benzene in 15 bananas and no people -- nobody would think eating a 16 banana gives a person acute leukemia. So, all we can 17 say is safe from what? And if you're talking safe from 18 acute myeloid leukemia, I think the literature suggests 19 that levels below 40 part per million year cumulative 20 dose would not be suggestive of causation of AML. 21 Q. Do people experience damage to their bone 22 marrow before it reaches full-blown AML? 23 A. Well, certainly people can have myelodysplasia 24 and then that can eventuate in AML. 25 Q. Have you ever had a patient come in and you've 73 1 recognized that benzene was a possible causative factor 2 in their disease, did you ever tell them to go home and 3 don't eat bananas? 4 A. I didn't tell them to go home and not eat 5 bananas. 6 Q. Well, you said -- benzene is in bananas. 7 A. It is. There is benzene in many foods, bananas 8 being one of them that happens to be high in benzene; 9 but we're talking trivial doses, very tiny doses. 10 That's why I say, you know, the dose to me to cause AML 11 needs to be extraordinarily high. 12 Q. Well, you're talking about a cumulative period, 13 where you want to see 40 -14 A. That's correct. 15 Q. -- forty PPM. 16 A. Yeah. 17 Q. What about, like, on a daily period? What do 18 you consider to be a safe level of exposure to 19 benzene -20 A. Well -21 Q. -- when someone is at work with chemicals? 22 MR. PERRY: Object to form. 23 A. Well, there are limits that have been set by 24 government agencies of, you know, 1 part per million 25 daily exposure. And that's reasonable, but I -- as I 74 1 say, that's not my field to determine the measurements 2 of those in a particular person's occupation. 3 Q. (BY MR. PATTON) Well, but -- but it is sort of 4 within your field because you're saying you need to see 5 a 40-part-per-million-year cumulative dose. And I'm 6 asking you on a more short-term basis, okay, on a daily 7 basis. I'm not asking you what government thinks. I'm 8 not asking you what a PEL or a TLB is. I'm asking what 9 you think, as Dr. Natelson, as an expert for Shell, is a 10 safe level of daily exposure to benzene? 11 MR. PERRY: Just one second. He's 12 answered the question. He told you it's not his area. 13 You may not like the answer, but he answered the 14 question. He can answer it again, but you've already 15 asked it and he's already answered it. 16 Q. (BY MR. PATTON) Let me try to ask it again in a 17 different way. 18 Doctor, do you have any opinion on what a 19 safe exposure level to benzene is on a daily basis for 20 someone working with chemicals? 21 MR. PERRY: Same objection. 22 A. No. 23 Q. (BY MR. PATTON) You don't have an opinion on 24 that? 25 A. No. I have an opinion on the cumulative dose 75 1 that related to AML, but individual daily doses, I know 2 what the requirements are, but if a person is over that 3 requirement for 24 hours, I -- I can't comment about 4 that. I don't know that that would be of -- of 5 importance. 6 Q. If someone is being exposed to benzene in their 7 daily work, would it appear in the daily -- or would it 8 appear in regular blood tests? 9 MR. PERRY: Object to form. 10 A. Probably not unless it was a very high number. 11 Q. (BY MR. PATTON) Well, what number would it have 12 to be on a daily basis for it to appear in regular blood 13 tests? 14 A. I would have to look that up. I think that 15 information is known. I believe that when you get 16 something like an acute 20- to 40-part-per-million 17 exposure, you can get a reduction -- significant 18 reduction in the white count, but I'm sure that 19 information is out there, but I don't have it at my 20 fingertips. 21 Q. Have you -- I'm going -- I'm going to give you 22 a number -- new topic here, okay? The number is 50, 23 okay? Would you estimate that you have told more than 24 50 or less than 50 patients that benzene was a factor in 25 their leukemia? Any type of leukemia. 76 1 A. Less than 50. 2 Q. Less than 50. Would you estimate -- how 3 many -- well, first of all, you've testified as an 4 expert in cases involving benzene exposure, right? 5 A. Yes. 6 Q. You have always testified on the side of 7 industry, including Shell, correct? 8 A. Yes. 9 Q. Same number, 50, can you estimate if you have 10 given the opinion more than 50 times or less than 50 11 times that benzene was not a cause of someone's 12 leukemia? 13 A. Well, it would be less than 50 because many of 14 these cases don't have anything to do with -- with acute 15 leukemia, chronic or acute. They have to do with 16 illnesses, like myeloma or lymphoma, other illnesses of 17 which benzene is not causative. 18 Q. Well, let me -- let me approach this in a 19 different way, then. We're setting the number at 50. 20 How many patients with any form of disease, okay, 21 myeloid, non-Hodgkin's lymphoma, what have you, above 50 22 or below 50, how many patients of yours have you told 23 they had a benzene-related disease? 24 A. Below 50. 25 Q. Below 50. 77 1 Have you testified more than 50 times that 2 someone's disease was not caused by benzene? 3 A. I'd have to count that up. I don't know. 4 It's -- it's possible. We have that list of cases. 5 Now, many of them are malpractice cases and other 6 things. They may not all be benzene cases. 7 Q. Okay. We'll go through your chart in a little 8 while. 9 Is it your opinion in this case, Doctor, 10 that Raul Zendejas' leukemia is not related to benzene 11 exposure? 12 A. It is my opinion that his original illness, 13 which is atypical CML or Philadelphia chromosome 14 negative CML, I do not believe that illness can be 15 caused by benzene exposure. 16 Q. Did he have CMML as well? 17 A. CMML? No. That's a separate illness. 18 Q. Did he have AML? 19 A. He had -- he -- he developed a -- blasts in his 20 blood. And, so, he had blasts as a consequence of his 21 underlying atypical CML. That's often referred to as a 22 blast crisis. 23 Q. Did he have AML? 24 A. I wouldn't call it AML. 25 Q. Would you recognize that some other 78 1 practitioners might call it AML? 2 MR. PERRY: Object to form. 3 A. Yes. 4 Q. (BY MR. PATTON) Is it your opinion that benzene 5 was not a causative factor in Raul's blast crisis or 6 AML? 7 A. Correct. It was not a causative factor because 8 that's the natural history of this illness. 9 Q. Now, what do you mean "the natural history"? 10 A. The natural history of people with CML or 11 atypical CML is, depending on the treatment, is to 12 develop a blast crisis over a variable period of time. 13 Q. They can develop AML? 14 A. If you like. They can develop lymphoid blast, 15 too. They can develop an acute illness characterized by 16 an outpouring of immature cells from the bone marrow 17 that we commonly refer to as a blast crisis, either 18 myeloid or lymphoid; and as I've said repeatedly, some 19 might call that an AML syndrome, some might not because 20 its behavior is different than an AML syndrome. 21 Q. Someone can come in as a patient and be 22 diagnosed with any one of those forms of myeloid disease 23 on your chart in front of you, correct? 24 A. Yes. 25 Q. Okay. And someone could possibly then move to 79 1 AML or move to blast crisis, correct? 2 A. Yes. They could move to AML from forms of 3 myelodysplasia, forms of atypical CML or other 4 myeloproliferative diseases. 5 Q. Is it your opinion that unless they come into 6 that chart with AML, there's just no way benzene was a 7 factor? 8 MR. PERRY: Object to form. 9 A. Well, I think I've said, if they come in with 10 myelodysplasia, that can be a benzene-related illness, 11 certain forms of myelodysplasia; and they can eventuate 12 in AML. 13 Q. (BY MR. PATTON) What about myeloproliferative 14 disease, MPD, can that become AML? 15 A. M -- yes, it can become AML. And 16 myeloproliferative diseases have not been related to 17 benzene exposure. 18 Q. Is it your opinion that benzene played zero 19 role in Raul's myeloid leukemia? 20 A. It is my opinion that benzene exposure played a 21 zero role. 22 Q. I mean, if we're on a scale here, you're pretty 23 far on the end. You're saying zero. It didn't have 24 1 percent factor. It had nothing to do with his 25 leukemia? 80 1 A. I don't believe it had anything to do with his 2 leukemia. 3 Q. Do you agree with me that Raul was exposed to 4 leukemia? 5 A. You misspoke. 6 MR. PERRY: Object to form. 7 Q. (BY MR. PATTON) I'm sorry. Was exposed to 8 benzene. 9 MR. PERRY: Object to form. 10 A. He was exposed to gasoline, which has benzene 11 as a component. 12 Q. (BY MR. PATTON) Is it your opinion in this case 13 that Raul's exposure levels to benzene, whatever they 14 were, were not enough to cause his myeloid leukemia? 15 MR. PERRY: Object to form. 16 A. That would be true. I don't know what his 17 levels would be, but I do not believe that they caused 18 him to have his blast crisis. 19 Q. (BY MR. PATTON) Do you believe -- do you have 20 any opinions as to what may have caused Raul's disease? 21 A. The cause of atypical -- the cause of atypical 22 CML and its natural progression toward an AML-like 23 syndrome is unknown. 24 Q. Do all diseases -- do all myeloid diseases 25 which end up AML, don't they go through some other phase 81 1 of one of the other diseases on your chart there? 2 MR. PERRY: Object to form. 3 A. No. In many cases acute myeloid leukemia, one 4 week you don't have it, the next week you do. 5 Q. (BY MR. PATTON) But aren't there cell changes 6 going on that if you catch a snapshot of those cells 7 before they've gotten to the point of AML diagnostic 8 criteria, you would catch them at different levels, 9 correct? 10 A. Well, as I said -- and we know a lot of this 11 from people who have relapsed. They've had AML and then 12 they go in remission and then relapse. It's remarkable 13 how rapidly AML can take over a normal bone marrow. And 14 that's why I say, a person can have a perfectly normal 15 bone marrow and blood count one week, and two or three 16 weeks later they can have florid AML with 80 percent 17 blasts in their bone marrow. 18 Q. What are the -- what are the blood counts that 19 a normally healthy individual should have? 20 A. Well, the normal total leucocyte count, or 21 white count, is said to be around 5 or 10,000. 22 Q. Okay. White count, 5 to 10,000? 23 A. And that's somewhat racial because black 24 individuals have white counts on average 1500 cells less 25 than -- than white people. So, I commonly would see a 82 1 black person with a 3500 white count. That would be 2 normal for them. 3 Q. What about red? 4 A. The red count -- the -- normal for a man would 5 be hemoglobin of, let's say, 14 or so; and that in part 6 depends on where you live. If you lived in Denver where 7 the oxygen level is low, the normal hemoglobin might be 8 16. In Houston, it's about 14. 9 Q. What about platelets? 10 A. The normal platelet count is generally given as 11 150 to about 250,000. 12 Q. Okay. Now, if someone has AML, what white 13 counts -- what -- what range of white count would you 14 see or expect to see? 15 A. Well, it depends on the phase of the illness. 16 For example, what happens in AML is you suddenly catch 17 the disease and the bone marrow starts to fill up with 18 blast cells; but blast cells have difficulty in escaping 19 the bone marrow. So, the first manifestation is a low 20 white blood cell count. 21 Q. What numbers? 22 A. You might get a white cell count of 1900. 23 Q. Okay. Now, let me ask you this: Do the white 24 cells just go from, say, 5,000 to 1900? That's to say 25 the, was it, 3100 white cells just automatically 83 1 disappear; or do they move down to a lower level where 2 they end up at 1900? 3 A. Well, they -- they move down, depending how 4 fast the leukemic process is ongoing in the bone marrow. 5 As I said, you're -- in the case of the white blood 6 cells, you're replacing them normally three times a day. 7 So, if you suddenly fill up your bone marrow with blast 8 cells, your white count falls pretty dramatically very 9 fast. And then once the bone marrow fills up with those 10 blast cells and they do come spilling out, then suddenly 11 the white cell count rises and can go well over a 12 hundred thousand. 13 Q. There is a transformation, there are 14 manifestations going on in the cells before the disease 15 reaches full-blown AML, correct? 16 A. Well, that's obviously so. In other words, 17 something happened to favor reproduction of a clone of 18 cells that are leukemic. And in many cases we don't 19 have a clue as to what that -- what happened. 20 Q. Benzene can be the thing that makes that 21 happen, though, correct? 22 MR. PERRY: Object to form. 23 A. Well, benzene is a -- is a known potential 24 cause of AML. So, benzene exposure at certain levels 25 can cause damage to cells that may eventuate in AML. 84 1 Q. (BY MR. PATTON) I thought you said benzene can 2 cause MDS as well, right? 3 A. Yes, it can. 4 Q. Okay. 5 A. It can cause MDS, too. 6 Q. And is it your opinion, Doctor, that someone 7 cannot catch a bone marrow disease in between normal and 8 AML, such that we can't tell whether or not someone is 9 progressing towards AML? 10 MR. PERRY: Object to form. 11 A. Oh, I think I understand your question a little 12 better when you said it that way. 13 Q. (BY MR. PATTON) And let me -- let me try to ask 14 it a little bit differently, okay? If you take a 15 snapshot of a normally healthy individual today and you 16 say, okay, this person is healthy. And then you go six 17 months from now; you take a snapshot of them; you say, 18 boom, they have AML, okay? In between that process, 19 they are progressing through these other myeloid 20 diseases, correct? 21 MR. PERRY: Object to form. 22 A. No. In certain circumstances, yes. I'll 23 try -- I can clarify that. In the case of what we call 24 de novo AML, very characteristically we see no changes 25 in the blood count until, bingo, we have AML. If we 85 1 have an illness that's chemical related -2 Q. (BY MR. PATTON) Like benzene related? 3 A. Like benzene related or chemotherapy related, 4 about two-thirds of the time we go through a phase of 5 myelodysplasia, where the -6 Q. Did Raul go through a phase of myelodysplasia? 7 A. No. He's never had myelodysplasia. 8 Q. Okay. 9 A. We see a period of myelodysplasia, which is 10 usually characterized by an advancing anemia, would be 11 the most common phenomenon, sometimes associated with a 12 low white count and low platelet count; and we may see 13 that get worse and worse over time until leukemia 14 eventuates. 15 Q. Did Raul have a myeloproliferative disorder -16 A. Yes. 17 Q. -- MPD? He did have MPD? 18 A. Yes. 19 Q. Does MPD naturally progress to AML? 20 A. It can. 21 Q. It can progress to AML. 22 Does benzene cause MPD? 23 A. No. 24 Q. Benzene causes AML, though, yes? 25 A. It may. 86 1 Q. Okay. What do you believe to be the disease 2 that Raul had? Where does he fit in on the chart? 3 A. He has a myeloproliferative disease, or these 4 days it's been changed to myeloproliferative neoplasm, 5 MPN. So, you can call it MPD or MPN. And his 6 particular form of MPD or MPN is Philadelphia chromosome 7 negative CML or atypical CML. 8 Q. And then he also had blast crisis AML? 9 A. He also developed a blast crisis as part of the 10 natural history of that illness. 11 Q. Is MPD on your chart? MPD is a myeloid 12 leukemia or a myeloid disease, right? 13 A. Myeloproliferative disease would be -- would 14 be -- or myeloproliferative neoplasm -- would be a 15 myeloid disease, yes. 16 Q. Is blast crisis on your chart? Would that be a 17 myeloid disease? 18 A. It could be, if it's a myeloid blast crisis; or 19 it could be a lymphoid blast crisis. 20 Q. What did Raul have? 21 A. He had a myeloid, I believe. 22 Q. Is that a myeloid disease? 23 A. Yes, it involves myeloblasts. 24 Q. Can we write -- is it fair to write "blast 25 crisis" over by the AMLs, or where would you put them? 87 1 A. Well, I wouldn't put it -- call it as an AML 2 because the biologic characteristics of a blast crisis 3 are very different than AML. I would call it blast 4 crisis. 5 Q. Okay. Let's put it on there. 6 A. Let's put it over here. 7 Q. Your natural tendency seem to be to put it over 8 there by AML, as compared to the -9 A. Well, because it's characterized by a lot of 10 blasts, as AML is. 11 Q. Fair enough. 12 A. So, it has similarities with AML. 13 Q. AML is a potential -- is potentially a deadly 14 cancer, correct? 15 A. Yes. 16 Q. Atypical CML, potentially a deadly cancer, 17 right? 18 A. Yes. 19 Q. What are the treatment options for someone with 20 myeloid leukemia? Bone marrow transplant, that's one of 21 them? 22 A. Well, with acute myeloid leukemia, we -- we 23 know off the bat a little bit about the situation based 24 on the chromosome analysis. In other words, we know 25 that if they have either no chromosome abnormalities, 88 1 which about 40 to 50 percent of cases don't have that, 2 or if they have particular chromosome abnormalities that 3 are very unusual -- have unusual susceptibility to 4 chemotherapy, we might cure them with chemotherapy 5 alone. So, our first line might be chemotherapy in an 6 AML. 7 Q. Was Raul Zendejas treated with chemotherapy? 8 A. Of a form. He was treated with Hydroxyurea, 9 which is an oral medicine that we don't much use for 10 acute myeloid leukemia. 11 Q. Do you have an opinion on whether or not that 12 Hydroxyurea caused his AML or his blast crisis? 13 A. No. There is some evidence, limited evidence 14 that long-term use of Hydroxyurea predispose to AML in a 15 patient with myeloproliferative disease; but he just had 16 short-term use of that drug. I don't think it had 17 anything to do with his blast crisis. 18 Q. Raul received a bone marrow transplant, 19 correct? 20 A. Yes. 21 Q. Is that common or typical for folks who have 22 his disease progress? 23 A. Well, that's an interesting question. It's 24 common in people with AMLs. I would think that's 25 probably the most -- the usual circumstance where 89 1 someones tries to transplant a person. 2 In CML-like illnesses, transplantation 3 used to be the standard curative care; but with the 4 advent of the modern drugs, that's done much less 5 frequently. 6 Atypical CML, however, if a person is -7 is young enough, a marrow transplant would be the best 8 form of therapy. 9 Q. Same thing for AML, marrow transplant would be 10 the best form? 11 A. Yes, in many cases AML is the best form to -12 to try to get a cure. And even with a marrow 13 transplant, cures are not as frequent as you might 14 think; but -- but they are useful. 15 Q. In Raul's case, he underwent a bone marrow 16 transplant and then went into remission and underwent a 17 second bone marrow transplant; is that right? 18 A. Yes. 19 Q. Do you have any opinions, Doctor, as to what 20 his chance of survival was before the first bone marrow 21 transplant, after the first one, and then after the 22 second? Do you have any opinion on those? 23 A. Well, only in general terms. In other words, 24 we would think atypical CML is -- without a marrow 25 transplant, you would have to say that it's an 90 1 ultimately fatal illness. It's not always ultimately 2 fatal by conversion to blast crisis, but it's ultimately 3 fatal. You may die of bleeding from a low platelet 4 count or other reasons. So, he had a fatal illness 5 without the transplant. 6 Q. And he was treated like AML, correct? 7 A. In terms of a transplant, a transplant is a 8 transplant. The preparative regimens would be similar 9 regardless of what you're transplanting him for. 10 So, he was -- he was given a transplant, 11 and I believe his preparative regimen was about the same 12 as the type I used in the 1980s. It was a standard 13 preparative regimen for a transplant. And -- and what 14 you expect to see is a person to get a take of the 15 transplant, hopefully not to get too much graft-vs.-host 16 disease and go into remission. 17 Q. Did you see where Raul had graft-vs.-host 18 disease? 19 A. Yes, he did have some graft-vs.-host disease. 20 And that's actually considered a good thing because the 21 graft-vs.-host disease suppresses the leukemic cells or 22 the malignant cells; but you just don't want too much of 23 a good thing. And then he had a second transplant. And 24 in general, if you were taking people and transplanting 25 them for, let's say, CML, typical or atypical, you might 91 1 get people into remission perhaps 70, 80 percent of the 2 time; but over time those patients will relapse, even in 3 typical CML. And, so, if you look at the people over 4 many years who have had transplants with -- with CML, 5 let's say, and you look, let's say, ten years out, I 6 believe the latest figures I've seen are about 7 60 percent of them are still alive. 8 Q. Have you ever given a patient two bone marrow 9 transplants? 10 A. I personally have not, but some of my patients 11 have had -- that I've referred elsewhere for 12 transplants. 13 Q. Is it uncommon to give two bone marrow 14 transplants? 15 A. I would say -- I can't tell you the frequency. 16 I'm not a transplanter full time. But I would say it's 17 obviously less common to give two than to give one. 18 And -- and patients have had three transplants. But 19 what happens is you run out of gas somewhere along the 20 line. You can't get away with doing this kind of 21 treatment over and over to people. 22 Q. Raul comes in; and he's diagnosed with atypical 23 CML, correct? 24 A. Yes. 25 Q. If not for the first transplant, would he have 92 1 probably died? 2 A. Yes. 3 Q. And what would he have died of? 4 A. Well, what most people with acute leukemia die 5 from, because they have very low platelet counts, 6 they're susceptible to bleeding and to infection. So, 7 it wouldn't be the leukemic cells, per se, infiltrating 8 an organ and causing liver failure or something like 9 that or heart failure. It would be because lack of 10 normal white cells predisposed to a major infection and 11 the person died or lack of platelets predisposed to 12 bleeding and they bled in their head and died. 13 Q. My point is this, Doctor -- we're going to go 14 through some of these studies in a little while, okay? 15 A. Yes. 16 Q. If Raul had not received the first bone marrow 17 transplant, would he have died of AML? 18 A. Well, what the articles say is there's about a 19 30 percent incidence of AML-like-disease blast crisis in 20 people with atypical CML. So, you would say he would 21 have a 30 percent chance of dying with AML at a -- and a 22 70 percent chance of dying from the disease with some 23 other manifestation of it. 24 Q. It could become a form of MDS? 25 A. I don't think it would become a form of MDS; 93 1 but he would have died from cytopenia, most likely. 2 Q. If Raul were to die after the bone marrow 3 transplant, the first one, would he have died of AML? 4 A. He could have died of graft-vs.-host disease. 5 Q. What about after the second bone marrow 6 transplant, would he have died of AML? 7 MR. PERRY: Object to form. 8 Q. (BY MR. PATTON) Could he have died of AML? 9 A. Yeah, he certainly could have, yes. 10 Q. Okay. So, in some of these studies, Raul might 11 be called an AML, right? 12 MR. PERRY: Object to form. 13 A. Some people might call him an AML, yes. 14 Q. (BY MR. PATTON) Okay. As far as your -- your 15 opinion that it takes a 40-part-per-million-year 16 cumulative dose to cause benzene -- or to cause a 17 benzene-induced leukemia -- that is your opinion, 18 correct? 19 A. Yes. 20 Q. Okay. Who would agree with you and who would 21 disagree with you on that opinion? 22 MR. PERRY: Object to form. 23 A. I don't know. I've referenced some articles, 24 for example, one study by -- well, I've referenced, I 25 think in this case, a study by Bloemen; and they had 94 1 people working with benzene-specific reactions and their 2 people had a mean exposure of 39 point, let's say, 9 3 part per million years and they didn't have a 4 statistically significant increase in AML. So, in that 5 particular study, I guess they would agree with me, that 6 you would have to have higher than that. 7 Q. (BY MR. PATTON) Are there people out there who 8 disagree with you as to that threshold? 9 A. I'm sure there are. 10 Q. And are there people out there who believe 11 there is no safe level of exposure to benzene? 12 A. I think there likely are, although I think 13 that's kind of an irrational statement. 14 Q. Individual susceptibility may vary when we talk 15 about someone's chances of getting a myeloid leukemia 16 from benzene exposure. True statement? 17 A. That would be speculation. 18 Q. Would you agree with me that some people are 19 just more susceptible to feel or receive the harmful 20 effects of benzene than others are? 21 MR. PERRY: Object to form. 22 A. There's no evidence for that. Some -- I think 23 one article by Richardson suggests that there's a 24 difference in susceptibility based on age. I think 25 that's very soft data. I think that if you look at our 95 1 chemotherapy data, you don't see that. In other words, 2 if you look at the number of milligrams of Cytoxan it 3 takes to catch AML after breast cancer, it's related to 4 the number of milligrams, not the -- not the age of the 5 patient or anything else about the patient. 6 Q. (BY MR. PATTON) So, if we see in certain 7 studies, certain government literature, even certain 8 documents from Shell, where it says "No safe level of 9 exposure to benzene," individual -- "individual 10 susceptibility may vary," you disagree with those 11 statements, correct? 12 A. Well, I say, if you take the position that 13 there's no safe level, that would mean we can't eat 14 bananas anymore. So, that's why I say it's an 15 irrational comment. 16 In terms of the fact that there is 17 different individual susceptibility, that may be so. I 18 don't disagree that that's so. I would just say there's 19 no evidence for that, proven evidence. 20 Q. Would you agree with me that there are studies 21 out there that deal with the myeloid leukemias in 22 general and they do find a statistically significant 23 connection between myeloid leukemias and benzene 24 exposure at cumulative doses below 40 part per million 25 years? 96 1 MR. PERRY: Object to form. 2 Q. (BY MR. PATTON) Do you agree with that? 3 MR. PERRY: Object to form. 4 A. There may be such studies out there. Some 5 would have -- not be statistically significant. And 6 there are some studies out there that find no acute 7 leukemia with higher than 40-part-per-million-year 8 exposures. 9 Q. (BY MR. PATTON) There are studies out there 10 that support the position that -- that less than 40 part 11 per million years can cause leukemia, right? 12 MR. PERRY: Object to form. 13 A. That's probably true. 14 Q. (BY MR. PATTON) Okay. When you reached your 15 conclusion, your opinion, that it takes 16 40-part-per-million-year cumulative dose, how did you -17 how did you rationalize, dealing with those studies out 18 there that show a number less than that, when you formed 19 your opinion? 20 A. Well, because my opinion is based on the 21 overall findings in the literature; and I think that 22 there are enough studies out there suggestive that you 23 only see statistical significance with higher than -24 than 40 part per million years and I think that that is 25 the position taken. I think one of the papers I 97 1 reference is -- is a government agency position. They 2 use that same number. I think that you have to look at 3 all of the evidence and the numbers of patients in the 4 studies, how well the studies were done -5 Q. What if -6 A. -- and so on. 7 MR. PERRY: Wait, wait. Let him finish. 8 Q. (BY MR. PATTON) I'm sorry. I didn't mean to 9 cut you off, Doctor. 10 A. No, go ahead. 11 Q. What if a study is not statistically 12 significant? Is it meaningless? Should we just throw 13 it away? Or how do we deal with that in -- or how do 14 you deal with that in forming your opinions for 15 something like this case? 16 A. Well, what you're looking for in epidemiologic 17 studies, because there is always all sorts of bias in 18 epidemiologic studies, you're looking for a -19 repetitive findings. In other words, in the case of 20 cigarette smoking and AML, there are repetitive 21 findings. Some of them don't show a great excess of AML 22 with cigarette smoking; but when you look at the bulk of 23 the studies, there's general agreement that, whereas, 24 you don't see the incidence of -- like you do with lung 25 cancer from smoking, but you do see ultimately a 98 1 statistically significant increase in AML from cigarette 2 smoking. 3 Q. Those studies -- that's a good topic that you 4 bring up, smoking. Those studies that deal with myeloid 5 leukemias and smoking, do they talk about how much 6 someone needs to smoke before it's a causative factor? 7 A. Well, in the Surgeon General's report, he says 8 a 20-pack-year history predisposes to a doubling of the 9 risk. 10 Q. Twenty pack years, doubling of the risk of -11 A. AML. 12 Q. -- of AML. 13 Is that your opinion? 14 A. Well, I -- I would say that what the literature 15 suggests is that if you're a smoker, the studies -- I 16 think Dr. Estey of M.D. Anderson in a Lancet review said 17 the studies have varied from about a 1.7 to about a 2.3 18 risk increase with -- with smoking and generally that 19 would be someone who has had about a 20-pack-year 20 history. 21 Q. Does the body of literature that deals with 22 smoking and its connection to AML, does it factor in the 23 brand of cigarette? 24 A. Not that I've seen. 25 Q. Does it factor in what year the cigarette is 99 1 from? Like the '70s, as compared to the '90s? 2 A. I would have no idea. 3 Q. Do they factor in whether they're lights or 4 menthols? 5 A. I would have no idea. 6 Q. Do the studies on smoking deal with whether or 7 not they're 100s or regulars? 8 A. I would have no idea. 9 Q. Do they deal with whether they're filtered 10 cigarettes or nonfiltered cigarettes? 11 A. I would have no idea. 12 Q. Do the smoking studies include cigars? 13 A. I don't -- no, I think it's primarily cigarette 14 related. 15 Q. Okay. Do they deal with the manner of smoking, 16 for instance, how many puffs someone takes? 17 A. No. 18 Q. Do those studies factor in how long someone 19 holds in the smoke? 20 A. No. 21 Q. Have you ever seen people who smoke, but they 22 don't really inhale? They just take it in and blow it 23 out. Have you ever seen that? 24 A. Yes. 25 Q. Do the studies take into account that? 100 1 A. No. 2 Q. Do the studies factor in whether or not someone 3 blows the smoke out their nose? 4 A. Not that I've seen. 5 Q. Do the studies deal with whether or not someone 6 smokes inside compared to outside? 7 A. No. 8 Q. Do they deal if someone is smoking in their 9 car? 10 A. No. 11 Q. Do they talk about if the person's coworkers or 12 family smoke? 13 A. No. 14 Q. Does it talk about the dermal contact or the 15 factor of the cigarette smoke making its way into the 16 body of -- of someone from just holding the cigarette? 17 Do the studies factor that in? 18 MR. PERRY: Object to form. 19 A. I don't know that the smoke would get into the 20 body dermally. Chemicals might. But not that I've 21 seen. 22 Q. (BY MR. PATTON) So, the studies that deal with 23 smoking, they just conclude, hey, if someone is smoking 24 X amount of packs per year or even if they're just a 25 smoker, they reach that conclusion without going into 101 1 the details that I've just mentioned. Is that fair? 2 MR. PERRY: Object to form. 3 A. I think that would be fair, yes. 4 Q. (BY MR. PATTON) Okay. Do all of the studies 5 that support a relationship between benzene exposure and 6 a given form of myeloid leukemia, do they reach the 7 conclusion of a causal relationship without going into 8 details, like temperature, like duration, like benzene 9 concentration, like part-per-million-year dose? Do all 10 the studies that support the connection between benzene 11 and leukemia, do they all go into those little nuances; 12 or do some of them reach the conclusion in a more 13 general sense? 14 MR. PERRY: Object to form. 15 A. I think some of them would have -- be in a more 16 general sense because the measurements are not always 17 there and only in some of the studies are there good 18 estimates of what the benzene concentration would be. 19 Q. (BY MR. PATTON) Doctor, you would agree with me 20 that there are studies that support the conclusion that 21 benzene causes AML and those studies -- some of those 22 studies don't necessarily even evaluate 23 part-per-million-year cumulative dose, correct? 24 MR. PERRY: Object to form. 25 A. That's probably true. 102 1 Q. (BY MR. PATTON) There are certain forms of 2 studies that just examine a population, "yes" or "no," 3 whether or not they were occupationally exposed to 4 benzene; and then they can draw the conclusion on the 5 strength of association, correct? 6 A. Well, as I say, I'm not an epidemiologist and 7 I -- I would like to see that the -- generally, it's 8 thought the dose makes the poison and you would like to 9 see if you are trying to attribute a -- a -- an illness 10 to a particular chemical, that they got that chemical 11 and how much they got of it. 12 Q. But how -- have you ever concluded that 13 someone's smoking was a factor in their AML? 14 A. As I said, with AML, we can't prove causation. 15 We can only say it was a risk factor. 16 Q. Okay. So, you can call -- you can call smoking 17 a risk factor in a given patient's AML sometimes, 18 correct? 19 A. If they've been a heavy smoker, yes. 20 Q. Okay. And what makes them a heavy smoker? 21 A. I would say a 20 part -- 20-pack-year history. 22 Q. You wouldn't consider any of those 15 things I 23 went through, on type of cigarettes, whether they 24 inhale. You'd just call it a pack-year history, right? 25 A. That's correct. 103 1 Q. But for benzene, it's a little different. They 2 can't come in and say, hey, I worked around benzene or I 3 worked around gasoline which contains benzene. You're 4 got to see a part-per-million-year dose to reach your 5 conclusion, correct? 6 MR. PERRY: Object to form. Misstates his 7 testimony. 8 A. I have to see a part-per-million dose or 9 evidence, for example, that workers in a particular 10 refinery or a particular setting have higher incidences 11 of AML than -- than a control and it's a properly done 12 study; but in general, I'd like to see a dose level, 13 because we associate cumulative dose of chemicals with 14 AML causation. 15 Q. (BY MR. PATTON) Did you perform any type of 16 cumulative-dose calculation for Raul's exposure to 17 benzene? 18 A. No. 19 Q. Have you seen any cumulative-dose information 20 about Raul's exposure to benzene? 21 A. No. 22 Q. Have you seen any reports from any experts 23 about how much benzene Raul was exposed to? 24 A. No. 25 Q. Have you seen any information from Shell about 104 1 how much benzene workers who are like Raul, who do his 2 type of job or did his type of job, how much benzene 3 they're exposed to? 4 A. No. 5 Q. Have you seen any data from Shell about how 6 much exposure to benzene someone experiences when 7 loading -- top loading gasoline without vapor recovery? 8 A. No. 9 Q. Have you seen any information from Shell as to 10 the efforts that Shell has undertaken to investigate the 11 relationship between top loading gasoline without vapor 12 recovery and the contraction of myeloid leukemias? 13 A. No. 14 Q. Have you seen any data from Shell showing any 15 type of surveys they've conducted on gasoline 16 distribution workers to determine the incidence of 17 myeloid leukemias among that class of workers? 18 A. No. 19 Q. Have you ever -- have you seen any data in this 20 case from Shell about how much benzene was in the 21 gasoline that Raul worked with? 22 A. No. 23 Q. Have you seen any data in this case showing 24 where Shell recommended that gasoline distribution 25 terminals performed blood tests on their workers? 105 1 A. No. 2 Q. Did you look at any of Raul's tissue or blood 3 samples? 4 A. No. 5 Q. Is there any other information you would want 6 to see in this case before -- well, I guess you've 7 already given the conclusion that benzene played zero 8 role in Raul's leukemia; is that right? 9 A. That is my impression because I think the 10 literature tells us that his diagnosis -- and that 11 diagnosis seems unchallenged in the medical records -12 his diagnosis of atypical CML is not a benzene-related 13 illness. 14 Q. Do you have any opinions on what caused Raul's 15 disease or his disease process? 16 A. No. I don't -17 Q. You have no opinions on what caused it? 18 A. I don't know what caused it. And that is the 19 position of the medical literature. 20 Q. Dr. Michael Carroll treated Raul Zendejas. Did 21 you see that? 22 A. Yes. 23 Q. He's the one who gave him two bone marrow 24 transplants? 25 A. Yes. 106 1 Q. And I've even seen his efforts described as 2 heroic. Do you agree that it is heroic for someone to 3 go ahead and take the risk of giving Raul two bone 4 marrow transplants? 5 MR. PERRY: Object to form. 6 A. I would agree with that. In other words, 7 that's a -- it's a major undertaking to do a bone marrow 8 transplant. And certainly to do it twice, there is 9 added risks, yes. 10 Q. (BY MR. PATTON) I mean, if you were to meet 11 Dr. Carroll, you might shake his hand and say, hey, good 12 job. You really worked hard to save this patient? 13 A. Yes. 14 Q. Okay. Is there anything about Raul's treatment 15 provided by Dr. Carroll that you disagree with? 16 A. No. 17 Q. Okay. You can't go through the medical records 18 and say, hey, these doctors should have done something a 19 little different? 20 A. No. 21 Q. Okay. I've met Dr. Carroll. I think he's -22 he's a little younger than you. I don't think he's been 23 practicing for 35 years. 24 A. These days, a lot of people are a little 25 younger than I am. 107 1 Q. Okay. Is there any type of advice or 2 suggestion that you might give Dr. Carroll about his 3 treatment of -- of Raul? 4 A. No. I'm sure that the concerns now are late 5 development of graft-vs.-host disease, of course, late 6 relapse of leukemia; and someone like himself who is 7 working daily in a marrow transplant program would have 8 more knowledge than I would about that field. 9 Q. Raul is -- Raul is still at risk of -- of 10 relapsing and coming down with another version of 11 myeloid leukemia, right? 12 A. Yes. 13 Q. How long is he at risk? 14 A. Well, he's -- I would say he's at risk -- in 15 terms of catching another form of acute leukemia, 16 probably about 12 years after the last transplant, but 17 people continue to die off following transplants over a 18 long period of time. 19 Q. Speaking of -- of Dr. Carroll, I'll show you 20 what's been marked as Exhibit 5, and that is some of the 21 medical records -- and we might come back to those -22 but on the top there is a letter from Dr. Carroll, 23 correct? 24 A. Yes. 25 Q. Have you seen that letter before? 108 1 A. Yes. 2 Q. You saw Dr. Carroll's deposition or you read 3 it? 4 A. Yes. 5 Q. What does Dr. Carroll believe to be the cause 6 of Raul's disease? 7 A. He says "I believe there is a reasonable and 8 probable likelihood of a causal relationship between his 9 occupational exposure to refined hydrocarbons and the 10 development of his life-threatening myeloid leukemia." 11 Q. Do you agree or disagree with Dr. Carroll? 12 A. I would disagree with him because there's no 13 literature to support this statement. 14 Q. Did you review the deposition of Dr. Gore taken 15 in this case? 16 A. Yes. 17 Q. Dr. Gore is the expert that the plaintiffs 18 hired to give opinions in this case. Is there anything 19 that you disagree with in Dr. Gore's opinions? 20 MR. PERRY: Object to form. 21 A. Well, I -- I -- I would have to comment that he 22 alleges that I'm misrepresenting what the M.D. Anderson 23 article says about atypical CML, and I would suggest he 24 needs to reread that paper because what I said is 25 exactly what they said. 109 1 Q. (BY MR. PATTON) He called some of your opinions 2 gobbledygook, didn't he? 3 A. Yes, he did. 4 Q. And you disagree with that, correct? 5 A. I think -- I had -- I think my letter was very 6 nicely written and very well supported by the articles 7 that I submitted with it. 8 Q. But doesn't your letter or your report, doesn't 9 it just keep splitting and splitting and splitting this 10 disease such that any analysis and causation would be 11 meaningless? 12 A. No. It's just the opposite. I keep focusing 13 on the disease, the disease, the disease. He has one 14 disease, which is atypical chronic myeloid leukemia; and 15 he lived out the natural history of that illness. And 16 that illness is extremely well described in the medical 17 literature, especially in this very large article by -18 by the -- Dr. Kantarjian and the other people at 19 M.D. Anderson, and there is no known causation of that 20 literature -- of that illness. 21 Q. Some of the literature that we have in front of 22 us and some of the literature that Dr. Gore relies on 23 and that Dr. Infante relies on, they talk about myeloid 24 leukemias in general. They talk about ANLL, meaning 25 acute nonlymphocytic leukemia. Is that correct? 110 1 A. That's correct. That's a term that's not much 2 used in the United States anymore. The British people 3 like to use that term. 4 Q. I mean, some of the studies you have with 5 you -- and I know I've said this a couple of times -6 A. Yeah. 7 Q. -- but we're going to go through them. But 8 some of these deal with myeloid leukemias generally. 9 They don't lump it in or they don't split it down to the 10 different distinctions that you've made in this case, 11 correct? 12 A. It depends what you're referring to. In other 13 words, when I talk about atypical CML, the references 14 that I have there are specific to that illness. 15 Q. Are they specific to causation of atypical CML? 16 A. Well, I think they are because at least one of 17 them, for example, deals with all of the illnesses that 18 the WHO puts into this wastebasket category of theirs, 19 this myeloproliferative/myelodysplastic category; and 20 the statement is made that those diseases are of unknown 21 cause. 22 The World Health Organization has two 23 chapters that I have in here and one of them is a 24 chapter on myelodysplasia and they're not bashful about 25 saying that benzene is a potential cause at high doses 111 1 of that illness; but when you read their chapter on 2 atypical CML, there is no etiology proposed. 3 Q. But some of the other studies, they deal with 4 myeloid leukemias generally, correct? 5 A. It depends on what I'm referencing. In other 6 words, if -- if I'm making a statement that has to do 7 with acute myeloid leukemia, I would reference that. 8 But the -- the -- we've long gone away from trying to 9 talk about leukemia as a general category of illness. 10 Even within a specific type of leukemia, like acute 11 myeloid leukemia, we're getting into a narrower and 12 narrower focus so that we can better understand those 13 illnesses. There -- there are probably differing 14 etiologies among the differing types of acute myeloid 15 leukemia. 16 Q. As far as these studies go, have you ever asked 17 Shell to conduct any research on the incidence of 18 atypical CML from exposure to benzene? 19 A. No. 20 Q. Have you ever asked your colleagues to perform 21 that type of research? 22 A. No. 23 Q. Are you familiar with any specific studies that 24 look into atypical CML and benzene exposure? 25 A. No -- well, no. 112 1 Q. That's to say, the studies by and large, they 2 don't -- they don't stratify or split out atypical CML. 3 They -- they just don't do that, do they, when 4 determining benzene causation? 5 MR. PERRY: Object to form. 6 A. Well, but if you look, for example, at 7 Dr. Axsoy's studies, he doesn't split them out. He just 8 says there isn't any CML, not -- not any kind. In other 9 words, he's -- he's got the study, one of the larger 10 studies; and he's a very good investigator, was trained 11 actually in part in the United States. He reviewed all 12 the slides; and he comments in his article, that in the 13 28 or so thousand, 29,000 people he studied who had a 14 high incidence of AML, he saw a deficit of CML. So, 15 that would be a deficit of anything that looked like 16 CML, whether it was Philadelphia chromosome-positive or 17 negative. 18 Q. (BY MR. PATTON) Have you seen the studies 19 supporting a relationship between benzene exposure and 20 CML? 21 A. You'll have to show me what studies those would 22 be. 23 Q. Okay. 24 A. The three major studies, the Ply film study, 25 didn't show an incidence of CML. I think your expert 113 1 referenced the Chinese studies, and in the -- in one of 2 the articles that he referenced, they found only an 3 increased incidence of AML. 4 Q. We talked about taking a lunch break, and I 5 think we're going to do that. So, I just want to finish 6 up a couple of quick topics. 7 You said my experts. Plaintiffs' experts 8 in this case, Dr. Infante and Dr. Gore, you have looked 9 at their depositions, correct? 10 A. Yes. 11 Q. And you read their depos, right? 12 A. Yes. 13 Q. And are you familiar with the studies they cite 14 in support of their opinions? 15 A. Yes, in the case of Dr. Gore's, we cite the 16 same studies in some instances. 17 Q. Okay. And then Dr. Infante, you're familiar 18 with the studies that he cites, correct? 19 A. Well, I've seen his opinions before, and I have 20 looked at some of his references. 21 Q. Okay. Are there any -- are there any of the 22 references by Dr. Gore or Dr. Infante studies that you 23 think just have no bearing on the relationship between 24 benzene and myeloid leukemia, such that they should just 25 be thrown in the garbage or shredded and not even 114 1 considered? 2 MR. PERRY: Object to form. 3 A. Well, I think a reference is a reference; and I 4 think that there may be useful information in some. For 5 example, I've forgotten which one it is, but Dr. Gore 6 references a -- papers on people exposed to gasoline, 7 and I think one of the tables breaks it down to people 8 with less than 15 years -- or more than 15 years' 9 exposure, and neither group had an increased incidence 10 of AML. 11 Q. (BY MR. PATTON) There's useful information in a 12 lot of these studies, correct? 13 A. Yes. 14 Q. My question, again, though, is a little more 15 specific. Are there any of these studies that Dr. Gore 16 or Dr. Infante relied on that you think are just 17 unreliable studies that shouldn't even be considered in 18 the analysis? 19 MR. PERRY: Object to form. 20 A. Well, I think that one needs to try to focus on 21 the particular illness in question, which is atypical 22 CML; and I think the bulk of the references from those 23 gentlemen don't focus on that illness. 24 MR. PATTON: All right. Let's take a 25 break, and we'll talk some more this afternoon. 115 1 Off the record. 2 THE VIDEOGRAPHER: Now going off the video 3 record. The approximate time is 12:33. 4 (Recess taken from 12:33 to 1:22.) 5 THE VIDEOGRAPHER: Now back on the video 6 record. Approximate time is 1:22. 7 Q. (BY MR. PATTON) Dr. Natelson, I'm going to hand 8 you what we've marked as Exhibit 1 to your deposition; 9 and that is your report, correct? 10 A. Yes. 11 Q. And starting around -- starting right there 12 near the middle of the page, can you read that first 13 sentence "It is important"? Read that for us aloud. 14 A. "It is important to note that Mr. Zendejas 15 never received a diagnosis of myelodysplasia (MDS), as 16 currently defined by the WHO or any other modern-day 17 classification system of hematopoietic disorders." 18 Q. I can stop you right there. Is it your opinion 19 that he did not have any form of MDS? 20 A. He has no form of MDS. 21 Q. Okay. Even if we went back in time and 22 classified his disease, like, in the '70s or '80s? 23 A. No. Atypical CML has never been classified 24 as -- as MDS; and, of course, MDS, 1982, was when it -25 people began to use that classification, and not at that 116 1 time or prior was -- was atypical CML classified as MDS. 2 Q. When did the term "atypical CML" first come 3 about in the community? 4 A. I would say in the early 2000s. 5 Q. So, pre-2000, the term "atypical CML" wasn't 6 used in the hematologic community. Fair statement? 7 A. Well, the illness was there. In other words, 8 it was simply called Philadelphia chromosome-negative 9 CML; and some may have called it atypical, but I think 10 that the term "atypical" is -- is -- is a little bit 11 more of a recent phenomenon. 12 Q. Okay. So, if we look at epidemiological 13 literature, which we're about to start on here pretty 14 quick, we are not going to find the term "atypical CML" 15 used in pre-2000 studies. They might mention 16 Philadelphia negative CML, correct? 17 A. Yes. 18 Q. Okay. So, again, we go through the year -19 studies before 2000, we're just not going to see 20 atypical CML? 21 A. I don't think so. I mean, I -- I hate to be 22 held to that because some author may have used that 23 term, but typically we -- we termed it Philadelphia 24 chromosome-negative CML. 25 Q. Okay. Is it possible that Mr. Zendejas' 117 1 disease would have been called some form of myeloid 2 dysplastic syndrome rather than atypical CML back before 3 2000 or even before the '82 -- 1982 MDS classifications? 4 A. No, not in my opinion. It might have been 5 called atypical or myeloproliferative disease; but it 6 would not have been called myelodysplasia. 7 Q. Okay. Turning to Page 5 of your report, going 8 near the bottom there, you indicate that "the MDS 9 classification system is fluid, primarily descriptive, 10 and a single" classification -- I'm sorry -- a single 11 illness may move within the classification during the -12 the course of the disease, correct? 13 A. Yes. 14 Q. So, in the epidemiological literature, when 15 they evaluate benzene as a causative agent of myeloid 16 leukemias, do they review the course of treatment that 17 each such patient or each such subject went through; or 18 do they just take a snapshot and call the disease what 19 it is at the time? 20 A. I think -- I'm not sure exactly what you're 21 asking with that question. 22 Q. I'm saying that if we have studies, okay? And 23 we're going to go through them. And a lot of them deal 24 with, let's say, MDS, okay? So, they might have a 25 person in the study who is an MDS today; but it's 118 1 possible that that person a few years down the road or 2 even a few months down the road could very well be an 3 AML, correct? 4 A. He's an MDS today but could have been an AML 5 yesterday? I would say no. 6 Q. No, let me -- let me start over. That's not -7 I meant the reverse of that. Let me ask a clearer 8 question. 9 If someone in a mortality study, for 10 example, or another epidemiological study is deemed in 11 that study to be a person with MDS, okay, it is possible 12 that a couple months or a couple years after the time, 13 that snapshot in time, that person might have progressed 14 to AML, correct? 15 A. Yes. 16 Q. Okay. Same question for CML. There are 17 studies that deal with patients with CML in these piles, 18 correct? 19 A. Yes. 20 Q. Is it likely that some patients with CML will 21 transform to AML? 22 A. Yes. 23 Q. So, some of these people in the studies who 24 were CMLs could have ultimately ended up as AMLs. Fair 25 statement? 119 1 A. Well, yes; but you see, in CML, with time, the 2 white cell count gets higher and higher; and the spleen 3 gets larger and larger. And, so, to see somebody, let's 4 say, who has had CML for a number of years and then goes 5 into blast crisis and all that while the illness was 6 undetectable and then when you saw their blast crisis 7 they didn't have a big spleen, that would be -- it's 8 potentially possible, but very unlikely. 9 Q. You agree with me, though, that some patients 10 with CML ultimately progress to AML, correct? 11 A. Oh, yes. 12 Q. I believe Dr. Gore gave the opinion that Raul 13 does not have MPD. Is that correct? In your review of 14 Dr. Gore's opinions in this case? 15 A. I don't remember why he would say -- if he said 16 that or why he would say that. He obviously does have 17 myeloproliferative disease, and that's what his doctors 18 said he had. 19 Q. Going through your report a little bit more, 20 you make mention that -- on Page 6, last paragraph near 21 the middle, you say there is no evidence that gasoline 22 and diesel fuels are carcinogenic. You see that? 23 A. Yes. 24 Q. If someone came to you and let's say they 25 exhibited a medical history with blood counts similar to 120 1 what you described from that gentleman in Louisiana. 2 A. Yes. 3 Q. Okay. And they were a gasoline worker. And 4 they had evidence in the form of regular blood tests 5 showing changes consistent with agenotoxic effect, if 6 you will, okay? And then they told you that their 7 exposure was to gasoline. Would you tell them, no, no 8 way the gasoline is causing it or no way the benzene is 9 causing it because benzene and gasoline -- I'm sorry -10 because gasoline is not carcinogenic? 11 MR. PERRY: Object to form. 12 A. Well, you're asking me sort of two different 13 questions. One is about dropping a blood count, and the 14 other one is -- is carcinogenic. In other words, just 15 getting a low white count is not a cancer. And if I saw 16 someone who had a low white count and was working, let's 17 say, in a -- in a gasoline, I'd want to know what were 18 the circumstances? Was he sick? Did he have the flu 19 when that white count was low? Was he taking a drug 20 that might have influenced the white count? Does he 21 have underlying cirrhosis and an enlarged spleen to 22 account for the low white count? Is he an alcoholic? 23 There would be many reasons a person could have low 24 counts and not have it to be chemical related. So, you 25 would work up the patient and find out why they've had 121 1 the low white count. 2 Q. (BY MR. PATTON) Would you agree with me that 3 somebody could show lower white counts from being 4 exposed to benzene via gasoline? 5 A. I can't agree or disagree. In other words, I 6 don't know that. I would say that -- my understanding 7 is that no agency in the United States -- government 8 agency -- considers gasoline to be a known carcinogen. 9 Q. Alcohol causes damage to the liver, correct? 10 A. Yes, it can. 11 Q. If someone is an alcoholic, they can have 12 damage to the liver as a result, correct? 13 A. Yes. 14 Q. Okay. Has anyone ever designated Jack Daniels, 15 for example, as something that is known to cause damage 16 to the liver or any given liquor? 17 MR. PERRY: Object to form. 18 A. I don't know that. It's possible, but I don't 19 know that answer. 20 Q. (BY MR. PATTON) I mean, have you ever read any 21 studies that connect the relationship between drinking 22 alcohol and suffering damage to the liver? I mean, 23 there's literature out there on that, correct? 24 A. Oh, there's a ton of literature on alcohol 25 ingestion and liver damage, yes. 122 1 Q. Does it deal with specific brands of liquor? 2 A. Not that I'm aware of. 3 Q. Does it deal with specific percentages proof or 4 volume of -- of alcohol in the liquor? 5 A. Some articles may. I -- I can't -- I'm not a 6 liver specialist, and I don't know that, but generally 7 speaking, no. It's the alcohol itself. 8 Q. Do you consider Jack Daniels to be a known 9 cause of liver damage? 10 A. Well, it -- it is alcohol, and it has alcohol 11 in it. And, so, it's a form of liquor; and heavy intake 12 of liquor can cause cirrhosis. 13 Q. Okay. Whether or not some government agency 14 calls gasoline a carcinogen, would you agree with me 15 that benzene, because it's a component in gasoline, the 16 gasoline is, therefore, capable of causing damage to the 17 bone marrow? Do you agree or disagree with that? 18 MR. PERRY: Object to form. 19 A. I -- it's hard to disagree with that. All I 20 can say is that the evidence doesn't suggest benzene 21 causes cancer -- gasoline causes cancer, but I -- it 22 does contain some benzene, as well as other compounds, 23 and it might be possible to get low white counts from 24 gasoline exposure. 25 Q. (BY MR. PATTON) Have you seen studies that show 123 1 that sugar can cause obesity? Is it generally accepted 2 in the scientific community that sugar can cause -3 A. Well, heavy intake of carbohydrates, yes, can 4 cause obesity. 5 Q. Have you seen studies that deal specifically 6 with Twinkies or mashed potatoes or spaghetti? 7 A. No, but I wouldn't be searching out those 8 studies in my usual practice. 9 Q. Would you expect those studies to deal with 10 each and every type of food in drawing the conclusion of 11 what that food's effect or that group of foods' effect 12 might be on -- on a person's body? 13 A. I'm not specifically a nutritionist and -- and, 14 so, I don't know that literature that well. 15 Q. Must a person be exposed to 100 percent pure 16 benzene to suffer -- or to -- for benzene to be a 17 possible cause of their myeloid disease? 18 MR. PERRY: Object to form. 19 A. The answer would be no. 20 Q. (BY MR. PATTON) Okay. So, you respect, Doctor, 21 that even chemicals that contain small amounts of 22 benzene, couple percentage or so of benzene, the benzene 23 in those other chemicals, like gasoline, is still 24 capable of causing adverse effects on someone's bone 25 marrow. True statement? 124 1 MR. PERRY: Object to form. 2 A. Again, it depends on cumulative dose and 3 probably depends on the way the metabolism may be 4 influenced by the associated substances. 5 Q. (BY MR. PATTON) You bring up an interesting 6 point. Metabolism may be influenced by certain 7 substances, right? 8 A. Yes. 9 Q. All human beings -- we all have different 10 metabolism, don't we? I mean, some people metabolize 11 food faster. You see some, you know, skinny people who 12 eat a lot of food. Other people have different 13 metabolism, right? 14 A. Yes, as a general statement, that's true. 15 Q. Okay. We mentioned earlier that you -- is it 16 that you do not believe that individual susceptibility 17 varies when talking about benzene and myeloid diseases? 18 A. No. I said that there is no documented 19 evidence for that. I didn't say it's not possible; but 20 I said that if you look at our chemotherapy data, let's 21 say a model for chemicals causing leukemia, what you 22 find is, in looking at large numbers of patients, is 23 that there is a threshold with each particular 24 chemotherapy agent; and once you get beyond that 25 threshold, we start to see a striking rise in the number 125 1 of AML cases. Well, if there was individual 2 susceptibility, we'd see cases of AML all along the 3 line. We wouldn't have to wait until we got to a 4 particular cumulative dose; but we don't see that with 5 chemotherapy. It seems to be a cumulative dose that 6 sets off the illness. Now, of course, you may have more 7 cases when you get well beyond that cumulative dose. 8 Q. You would agree with me, though, that my body 9 is probably different than your body in its reaction or 10 ability to overcome certain challenges, right? 11 MR. PERRY: Object to form. 12 A. Yes. 13 Q. (BY MR. PATTON) We're just going to have 14 natural differences among you and I as human beings, 15 right? 16 A. Certainly. 17 Q. Okay. Somebody could come in here with the 18 flu. You might catch it; I might not, right? 19 A. Yes. 20 Q. Okay. You might be exposed to -- you might 21 smoke a lot of cigarettes. I might smoke a lot of 22 cigarettes. One of us may or may not get lung cancer, 23 right? 24 A. Correct. 25 Q. When we're talking about benzene affecting 126 1 someone's bone marrow, it affects the DNA, does it not? 2 A. Well, benzene is considered a radio magnetic 3 drug, in that it damages DNA; but the exact mechanism of 4 that damage, I don't know is known -- I don't know is 5 accurately known. 6 Q. Nevertheless, when we talk about our body's 7 repair mechanism, you're going to agree with me that -8 do you agree with me that some individuals are going to 9 have a stronger repair mechanism or an increased ability 10 to go ahead and fight off the challenges that benzene 11 might present to the body than others? 12 MR. PERRY: Object to form. 13 A. I can't say that that's certainly true. I 14 mean, I have no evidence that it is true. I don't 15 dispute it might be true, but I don't believe that's 16 proven. 17 Q. (BY MR. PATTON) So, is that why you believe 18 that it's got to take 40-part-per-million-year 19 cumulative dose before any person's leukemia might be 20 caused by benzene? 21 MR. PERRY: Object to form. 22 A. No, it's because I think there are many studies 23 out there that suggest that it is high-dose benzene that 24 causes -- has the potential to cause AML. And there may 25 be subtle differences, but like chemotherapy, it's a 127 1 cumulative dose; and the cumulative dose is high. 2 Q. (BY MR. PATTON) But some people who receive the 3 chemotherapy do not get AML. Others who do receive it 4 do get AML, right? 5 A. Oh, yes, that is true. 6 Q. Okay. So, individual -- individual 7 susceptibility is varying among that type of chemo as a 8 cause, right? 9 A. Yes, that would be so. 10 Q. I guess I'm just not understanding from you how 11 it is benzene is different. How -- how individual 12 susceptibility does not vary among benzene-exposed 13 workers. Can you explain that? 14 A. Well, let me see if I can explain it by giving 15 you an example. If I anticoagulate you with a drug 16 called Coumadin or Warfarin, that's a commonly-used 17 anticoagulant. In the general population, for a man, it 18 takes 7-and-a-half milligrams a day to anticoagulate 19 you. Okay? Now, some people take 10 milligrams a day. 20 Some people take 15 milligrams a day. Some people only 21 take 2-and-a-half milligrams a day to become 22 anticoagulative. So, yes, there's susceptibility. 23 That's one part of the equation. 24 Now, the second part of the equation is, 25 let's suppose I give you that Warfarin in a mixture with 128 1 other drugs. You're perfectly happy and 2 well-anticoagulated on 7-and-a-half milligrams a day. I 3 give you some Phenobarbital with that 7-and-a-half and 4 suddenly the drug interactions makes your blood clotting 5 system normal. You're no longer anticoagulated because 6 you have two drugs together competing for metabolism. 7 By the same token, if I give you Tagamet, which used to 8 be a lot for ulcer disease, suddenly that 7-and-a-half 9 milligrams of Coumadin is way too much and you're too 10 heavily anticoagulated. And that's why if we -- if we 11 said that benzene is the equivalent to Coumadin, it 12 depends how you get it. In other words, are you getting 13 it as a pure drug; or are you getting it in a mixture of 14 compounds that can influence its metabolism, and 15 gasoline is a mixture of many compounds. 16 Q. Doctor, I am going to mark as Exhibit 9, a 17 certain study. You've been reviewing studies on benzene 18 and leukemia for a number of years. Fair statement? 19 A. Yes. 20 Q. Are you familiar with the Hayes study? 21 A. Yes. 22 Q. Okay. I hand you what I've marked as 23 Exhibit 9. Do you see the summary here on this front 24 page? It talks about background. It has it in bold, 25 and it kind of sums up the whole report. Do you see 129 1 that? 2 A. Yes. 3 Q. Do you see in the -- starting at the bottom 4 there where it says "Results," can you read that for us? 5 A. For workers historically exposed to benzene at 6 average levels of less than 10 parts per million, the 7 relative risk for all hematopoietic syndromes combined 8 was 2.2, confidence limits 1.1 to 4.2, and, for the 9 combination of acute nonlymphocytic leukemia and related 10 myelodysplactic syndromes, the RR was 3.2, confidence 11 limits 1 to 10. For individuals who were occupationally 12 exposed to benzene at constant levels of 25 part per 13 million or more, the relative risk for the combination 14 of acute nonlymphocytic leukemia and related 15 myelodysplastic syndromes was 7.1. 16 Q. Let me stop you right there. This is a 1997 17 article from the Journal of the National Cancer 18 Institute, correct? 19 A. Yes. 20 Q. Is that a reputable journal? 21 A. Yes. 22 Q. Is it peer reviewed, meaning other folks read 23 these articles before they're published? 24 A. Yes. 25 Q. Is it a reliable source of information? 130 1 A. Well, as any journal is, yes. 2 Q. Is it something that you subscribe to? 3 A. No. 4 Q. Is it something that you choose not to 5 subscribe to because you just don't like it? 6 A. No. Actually, I frequently look at it because 7 some of my associates subscribe to it. 8 Q. This is a study that was conducted in China; is 9 that right? 10 A. Yes. 11 Q. Okay. This study, if -- if we analyze what you 12 just read, it says for workers exposed to less than 10 13 ppm, they still had a doubling of the risk; and it was 14 statistically significant, right? 15 MR. PERRY: And, again, you're talking 16 about the summary, not the actual article itself. 17 MR. PATTON: Correct, sir. 18 A. Yes, the summary, yes. 19 Q. (BY MR. PATTON) Okay. Is this a valid study? 20 Is this study statistically significant? 21 A. As they say it, there are considerable argument 22 about what the accurate measurements of benzene were, 23 however. 24 Q. Okay. So, there's -- there's criticisms or 25 challenges that one might make to this study. You can 131 1 poke some holes in it, so to speak? 2 A. Well, criticism such that the United States 3 Government agencies don't accept this study as -- as 4 accurate. 5 Q. Why not? 6 A. Because of numerous aspects about this study, 7 not just the benzene levels. For example, this study 8 comments about lymphomas, okay? And if you look here 9 at -- it says "Estimates of benzene exposure were 10 derived from work histories. Existing pathologic 11 material and supporting medical records were reviewed to 12 establish diagnoses of disease." I'll say that again. 13 Existing pathological material and supporting medical 14 records were reviewed to establish diagnosis of disease. 15 So, someone reading this would think that 16 all of the cases they reported would have either slides 17 or path -- pathologic material or medical charts. 18 Actually, that's not so. 19 In the case of their lymphoma data, for 20 example, they originally had 17 cases. They were able 21 to get slides on four; and one turned out not to have 22 lymphoma; so that case was dropped out. So, many of 23 their cases, there was no slide review, in the case of 24 lymphoma. 25 Q. Do you think this is a good study, or is it a 132 1 bad study? 2 A. It is a bad study. I mean, it has certain 3 value because it's very large; but the study was very 4 inaccurate. And in the case of lymphoma, for example, 5 they have three cases in there that they have no slides, 6 no pathology report, no medical records and the 7 diagnosis is entirely hearsay; but you wouldn't know 8 that from reading this article. 9 Q. Okay. So, there's a whole world of information 10 beyond this article out there? 11 A. Yes, because this -- this benzene study has 12 been written up many, many times by these various 13 combinations of authors. There's a lot more available 14 information in the literature than what you might find 15 in this piece of paper. 16 Q. Okay. Are you familiar with the Adegoke study? 17 A. Let me see. I think I may have seen that. 18 I -- I think -19 (Exhibit No. 10 marked) 20 Q. (BY MR. PATTON) I marked as -- marked it as 21 Exhibit 10. 22 MR. PERRY: Okay. 23 A. Yes. I have seen this study. 24 Q. (BY MR. PATTON) Okay. Before we talk about it, 25 are you aware of any widespread criticisms or challenges 133 1 to the quality of this study? 2 A. I don't know much about the background of this 3 study. 4 Q. Okay. You see near the top where it says 5 "Results"? 6 A. Yes. 7 Q. It says "Significant increase in leukemia risk 8 was observed in chemical manufacturing industry 9 workers." Odds ratio 3.1, meaning three times as 10 likely, right? 11 A. Correct. 12 Q. And then it shows that 95 percent confidence 13 interval; and for that to be statistically significant, 14 that lower number needs to be 1 or above, right? 15 A. Correct. 16 Q. And this is statistically significant, correct? 17 A. Yes. 18 Q. Do you see, reading on there, where it talks 19 about the dose-response relationship of leukemia risk? 20 MR. PERRY: Is this on the front page in 21 the summary again? 22 MR. PATTON: Yes, sir. 23 A. Yes. 24 Q. (BY MR. PATTON) Okay. Do you have any reason 25 to disagree with the conclusions in this study? 134 1 A. Well, it doesn't identify at least in this 2 abstract what kind of leukemia we're talking about. It 3 just says "leukemia." And we know that there are many 4 forms of leukemia that are unrelated; and in the modern 5 era, you have to be cell-type specific. 6 Q. If you turn to a few -- a few pages to 487, it 7 looks like it deals with total leukemia, ALL, CLL, AML 8 and CML, correct? 9 A. Yes, I see that. 10 Q. And you said that for a study to be valid in 11 the modern era, it needs to deal with cell type? 12 A. It needs to be cell-type specific. In other 13 words, CML as distinguished from AML as distinguished 14 from ALL as distinguished from -- from -15 Q. Is this study cell-type specific? 16 A. They do give different numbers here. 17 Q. Okay. And this is -18 A. That's the distribution of the cases. 19 Q. And this is August 2003, right? 20 A. Yes. They're giving us the distribution of the 21 cases, but -22 Q. Do you see on that right-hand column on 487 23 where it talks about "the odds ratios"? 24 A. Yes. 25 Q. Would you agree with me that this study 135 1 supports a relationship -- a statistically significant 2 relationship between benzene and these forms of 3 leukemia? 4 MR. PERRY: Are you talking about Page 487 5 or Table -6 MR. PATTON: 487. 7 MR. PERRY: -- 1 or Table 3? 8 MR. PATTON: Page 487. 9 A. It says "The ever exposed category had a 10 significantly increased risk for CML and a 11 non-significant increase for ALL and AML." 12 Q. (BY MR. PATTON) And then going to the left-hand 13 column, it shows a risk for leukemia that was increased 14 significantly -- significantly among those who worked in 15 the chemical manufacturing industry. It is 16 statistically significant and shows a three times 17 increase in the risk, correct? 18 MR. PERRY: Object to form. 19 A. Again, they talk about leukemia as a general 20 category. 21 Q. (BY MR. PATTON) And you just don't believe 22 that's fair? 23 A. Well, it has to be broken down to the type. 24 Q. Why does it have to be broken down to the type? 25 A. Because acute -- because myeloid leukemias and 136 1 lymphoid leukemias are -- they're different cells. It's 2 like comparing kidney cancer to lung cancer. I mean, 3 they're different cell lines. 4 Q. But within the -- within the myeloid leukemias, 5 is it your testimony here, that for a study to be 6 meaningful, it has to be split among the 16 or so 7 differentiations you have on Exhibit 8? 8 A. Oh, you're talking in terms of AML? 9 Q. I'm talking in terms of myeloid leukemias. 10 A. I would say that it would be inappropriate to 11 lump myelodysplasia, acute myeloid leukemia and chronic 12 myeloid leukemia in the same ball of wax. 13 Q. Okay. 14 A. They're different illnesses. 15 Q. What was the word you used? How would it be? 16 A. I said it would be inappropriate. 17 Q. Inappropriate. Okay. 18 One of the studies that you brought with 19 you today, and it looks like you've marked it -20 penciled in -- as Exhibit 30 -- Reference 30 to your 21 report, and I will mark it as Exhibit 11. 22 (Exhibit No. 11 marked) 23 Q. (BY MR. PATTON) And this appears to be a 2007 24 mortality study of Texas Petroleum Refinery and Chemical 25 Employees, 1948 to 2003; is that right? 137 1 MR. PERRY: Who is the lead author on 2 that? 3 THE WITNESS: It's T-S-A-I. 4 Q. (BY MR. PATTON) Tsai. 5 MR. PERRY: Okay. 6 A. Tsai. 7 Q. (BY MR. PATTON) Okay. 8 A. And it's actually my Reference 30. 9 Q. Okay. It's your reference. That's something 10 you're relying on in your opinions to say that benzene 11 played no role in Raul's leukemia, right? 12 A. Actually, no. In other words, this -- this is 13 a general piece of information. In other words, my 14 letter covers more than just atypical CML. This -15 this -- I don't remember what the sentence was that I 16 referenced this in, but I think it had to do with the 17 fact that increased incidences of -- of leukemias have 18 not been seen commonly in the -- in the petrochemical 19 industry for many years. 20 Q. That is exactly what you cite it for. 21 Doctor, on the front page, it says who 22 paid for that study; is that right? In the lower 23 left-hand corner there? 24 A. It -- well, it says -- no, it doesn't say it in 25 those terms; but it says "From Shell Health Services, 138 1 Shell Oil Company, Houston, Texas." 2 Q. Do you think Shell paid for that study, or do 3 you think somebody else did? 4 A. I have no idea who paid for this study. 5 Q. Well, why is Shell's name on it? Do you know? 6 A. I don't know. It may be that the person who 7 did the study worked for Shell. 8 Q. And you believe that that study supports the -9 what does that study stand for? 10 A. Well, looking at the "Observed" and "Expected," 11 they had AMLs. They had observed 11, expected 12.16. 12 And then putting it as a category of acute 13 nonlymphocytic, they had observed 12, expected 12.41. 14 Q. Okay. What is "acute nonlymphocytic"? 15 A. Well, it's -- it's basically the same as AML. 16 It's just that there are some cases that you're -- are 17 harder to tell that it's -- it's AML or if it's an 18 undifferentiated leukemia -19 Q. Well, what about -20 A. -- and you can't categorize it very well. 21 Q. I didn't mean to interrupt you. What about on 22 your Exhibit 8? Are those all ANLLs, those diseases? 23 A. Those are AMLs we're talking about. 24 Q. Not in Exhibit 8, sir. The chart we made? 25 A. Well, I've got a column of AMLs. 139 1 Q. And you've got a column of MDSs? 2 A. MDSs, yes. 3 Q. And you've got CML, atypical CML? 4 A. Yeah. 5 Q. Okay. 6 A. And myeloproliferative neoplasms. 7 Q. Are those all ANLLs, everything on that chart 8 on your left hand? 9 A. No. That term would only -- no. That term 10 isn't on this. That's simply the AMLs plus a couple of 11 cases that you're hard pressed to tell whether they're 12 AML or ALL. They're undifferentiated leukemia. 13 Q. Is MDS a form of ANLL? 14 A. No. 15 Q. No? 16 A. No. 17 Q. Isn't MDS a myeloid leukemia? 18 A. No. MDS is a -- you might say is a preleukemia 19 syndrome, potentially preleukemic. If you have MDS, you 20 don't have AML. If you had AML, you'd have AML. 21 Q. Well, doesn't the exhibit -- the Shell study 22 that you have there, doesn't that lump all ANLLs 23 together? 24 A. No, no, no. 25 Q. And it lumps all AMLs together, right? 140 1 A. It's got AMLs; and it's got CML as a separate 2 category, three observed and 4.5 expected. It's got 3 lymphoblastic, or ALL, 3 observed; 1.8 expected. And 4 chronic lymphocytic leukemia, 9 observed; 7.8 expected. 5 So, it breaks them down as to types of leukemia. 6 Q. But it lumps all the AMLs together, doesn't it? 7 A. It lumps all the AMLs together, yes. 8 Q. It doesn't differentiate between the M1 to M6, 9 right? 10 A. That's correct. 11 Q. Well, isn't -- isn't it inappropriate to lump 12 them all together? Isn't that what you said ten minutes 13 ago? 14 A. Well, not at the time -- no. Even today 15 they're typically lumped together. Ideally, they would 16 be separated. That's the gold standard these days. But 17 this paper is written some years ago. 18 Q. I'm going to show you what I'll mark as 19 Exhibit 12, and this is an article by Nilsson, in 1996, 20 "Genotoxic Effects in Workers Exposed to Low Levels of 21 Benzene from Gasoline." 22 (Exhibit No. 12 marked) 23 Q. (BY MR. PATTON) Have you ever seen this study 24 before? 25 A. I don't think so. 141 1 Q. If you look in -- in the -- on the top in the 2 summary of this study, it says "Multiple linear analysis 3 adjusting for smoking habits showed a significant 4 association between the exposure level of benzene during 5 the shift and the increase of 80HdG," which is a large 6 word that I won't say or attempt to say for the court 7 reporter's sake -- "in the urine over the shift among 8 exposed workers." 9 And I'll represent to you, Doctor, that 10 this study looks at the amount of benzene or its 11 metabolites detected in urine while workers were exposed 12 to benzene from gasoline. Does that seem accurate to 13 you based on what you -14 A. I have no reason to dispute that. 15 Q. Okay. Is it your opinion that benzene and its 16 metabolites can be detected in urine while people are 17 working with benzene? 18 A. Yes. 19 MR. PERRY: Object to form. 20 Q. (BY MR. PATTON) Okay. So, you would agree with 21 me that urine tests are a possible useful tool in 22 determining the level of benzene with which someone 23 might be exposed to during a given day? 24 A. Yes. It has to do with the timing of the test. 25 In other words, if you took the test while they're in 142 1 the process of working, it would be more accurate than 2 if you took it the next day. 3 Q. Okay. So, if all of us, instead of working in 4 this conference room today, we go work at a refinery 5 where they're making gasoline and where they're using 6 benzene, okay, people could come in, take a urine test 7 from us and they could determine the amount of benzene 8 or its metabolites in our body at that given moment, 9 correct? 10 MR. PERRY: Object to form. 11 A. I don't know if you could accurately determine 12 the concentration of benzene by the metabolites. That's 13 beyond my expertise, but you could detect likely that 14 there was some exposure to benzene. 15 Q. (BY MR. PATTON) Do you see in the lower 16 right-hand corner, that sentence -- or paragraph 17 beginning "A common"? It says "A common occupational 18 source of exposure to benzene is handling of gasoline." 19 A. Yes. 20 Q. Do you agree with that? 21 A. Yes. 22 Q. Do you have any reason to disagree with that? 23 A. I have no reason to disagree with that. 24 Q. Turn to Page 319 of this study. 25 MR. PERRY: Is this Exhibit 11? 143 1 MR. PATTON: Yes. 2 MR. PERRY: Okay. 3 MR. PATTON: Might be 12. 4 MR. PERRY: Exhibit 12? 5 Q. (BY MR. PATTON) What -- what exhibit did I put 6 on there? 7 A. Twelve. 8 Q. Twelve. 9 MR. PERRY: Twelve. Okay. 10 Q. (BY MR. PATTON) Doctor, see on Page 319 under 11 "Exposure"? 12 A. Yes. 13 Q. Okay. Can you read that for us? 14 A. 319 under "Exposure." Oh. The concentration 15 of benzene, 8 hour time-weighted average, in the 16 breathing zone of the exposed workers was 0.13 part per 17 million, mean value 003 to 0.6, during the shift. The 18 mean exposure to benzene among controls was .002 part 19 per million. 20 Q. So, these are men who are working with 21 gasoline; and the amount of benzene in the air is .13, 22 right? 23 A. Yes. 24 Q. But benzene levels can still be detected in 25 their urine even at that low level, correct? 144 1 A. Yes. 2 Q. Do you have any reason to disagree with that? 3 A. No. 4 Q. Okay. If someone was being exposed to, let's 5 say, ten times as much benzene from gasoline or from any 6 other operations, would you agree with me that the more 7 benzene they're exposed to, the more detectable it would 8 be in the urine? 9 MR. PERRY: Object to form. 10 A. That would likely be true. 11 Q. (BY MR. PATTON) Okay. If you -- if you 12 increase the amount of exposure, you'll increase the 13 amount of benzene output. Fair statement? 14 MR. PERRY: Object to form. 15 A. Well, yes. 16 Q. (BY MR. PATTON) Are you familiar with the 17 Gunel study? 18 A. No. 19 MR. PATTON: I'll mark this as Exhibit 13. 20 (Exhibit No. 13 marked) 21 Q. (BY MR. PATTON) This is a 2002 study by Guenel. 22 Have you ever seen this study before? 23 A. No. 24 Q. Have you read that front page? 25 A. I read the front page, yes. 145 1 Q. It shows the risk of leukemia increasing at 3.6 2 times what is expected for those workers exposed to 3 benzene above 16.8 ppm years. 4 Did you see that? 5 A. Yes. 6 Q. And it also shows that there was an indication 7 of a dose-response relation, odds ratio 1.2 -- that 8 means 1.2 times more likely -- and that is statistically 9 significant -- per 10 part-per-million years increase in 10 exposure. 11 Do you see that? 12 A. Yes. 13 Q. Okay. And it shows that "The link with benzene 14 was more pronounced for acute leukemia than for chronic 15 leukemia, but no association with a particular cell type 16 was apparent." 17 This study, would you agree with me, 18 supports the -- the theory that even lower doses than 40 19 ppm-year cumulative dose have been shown in the 20 literature in statistically significant numbers to 21 increase the risk of myeloid leukemia. Do you agree 22 with that? 23 MR. PERRY: Object to form. 24 A. Just a minute. I'm looking at their acute 25 myeloid leukemia here and it says -- I'm looking at 146 1 their Table IV. And under acute myeloid leukemia, it 2 says the confidence limits at greater than 5.5 are .7 to 3 8.5. So, that would be not statistically significant. 4 And the same would be true for chronic myeloid leukemia. 5 Q. (BY MR. PATTON) But do you see in Table IV 6 where it says "All acute leukemia," greater than 16.8 7 PPM years? 8 A. Yes, but they don't tell you what kind of 9 leukemias they're talking about. It just says "All 10 acute leukemias." So, they've lumped -- they have a 11 very low number of cases, six cases. So, it's a small 12 study; and they don't tell you what kind of leukemia 13 they got. 14 Q. Are you critical of this study because it 15 doesn't show what type of leukemia? 16 A. Well, that particular category. In other 17 words, all I see is when we get down to acute myeloid 18 leukemia, I don't see anything statistically 19 significant, at least in that Table VI. I see all acute 20 leukemias; and when you've got tiny numbers like that, 21 sticking in one case of ALL or two might totally change 22 the statistics. 23 Q. Well, isn't that the same thing that happens 24 with some of the studies that you're relying upon? 25 A. I don't think so. I think I try to use 147 1 cell-type-specific studies. 2 Q. Okay. Exhibit 14, this is a paper by Wong, 3 1993. This looks like it's been copied and restapled 4 more than once. You're familiar with this, right? 5 (Exhibit No. 14 marked) 6 A. Yes. 7 Q. (BY MR. PATTON) Does that split it down by 8 subtype, or does it lump them altogether? 9 A. It says, for the two cohorts combined, standard 10 mortality rate for acute myeloid leukemia was 1117.1. 11 So, that looks like it's specific for AML. 12 Q. Don't other parts of the conclusions, though, 13 lump them together? 14 A. Well, he has another table in here that puts 15 all lymphato -- hematopoietic cancer together, which 16 today would be, I think, inappropriate because you're 17 putting apples and orange -- apples and oranges 18 together; but when you're speaking of acute myeloid 19 leukemia, that's very specific. 20 (Exhibit No. 15 marked) 21 Q. (BY MR. PATTON) Well, you have another study 22 here, Doctor, from Graff? 23 A. Yes. 24 Q. This looks like Reference 34? 25 A. Right. 148 1 Q. I just put the sticker over the year. So, I 2 don't know what year it is. 3 MR. PERRY: 2005. 4 Q. (BY MR. PATTON) This lumps together 5 lymphohematopoietic cancer, right? 6 A. Yes. 7 Q. Doesn't that include both lymphoid -- or 8 lymphatic cancers and myeloid leukemias like we have on 9 Exhibit 8? 10 A. It does; but in the text, he breaks it out by 11 cell type. 12 Q. Does he break it out by -- well, first of all, 13 are MDSs included with AMLs in this -- in this study? 14 A. No. 15 Q. They are AML only, correct? 16 A. Well, there's -- I think there's more than AML 17 in the study, but -- but MDS, I don't believe, is part 18 of that study. 19 Q. Did this study by Graff go through and 20 determine which of these folks in the study with AML 21 actually went through atypical CML or went through an 22 MDS phase? 23 A. No. 24 Q. Can you point me to any study that you're 25 relying upon in your opinions that benzene played zero 149 1 role in Raul's leukemia, can you point me to any studies 2 that track the disease progression that a given subject 3 went through before he was called an AML? 4 A. Well, the M.D. Anderson articles do that. 5 Q. Okay. Any others? 6 A. Well, that -- that comes to mind. I would have 7 to look to see what I referenced under that; but, in 8 other words, the -- in the M.D. Anderson study, they 9 show the natural history of the illness because they 10 classify all their people and then they follow them 11 until death. 12 Q. Doctor, what I have given you is the stack of 13 all the other studies you're relying upon supporting 14 your opinion that benzene played no role in Raul's 15 leukemia. Is that the complete stack there? 16 A. That -- yeah, whatever all I brought with me, 17 yes. 18 Q. And what else we've marked as exhibits? 19 A. And what else you've marked as exhibits. 20 Q. And my question for you, Doctor, is: Please 21 pull out each and every study in that stack that tracks 22 the disease progression that a given AML subject went 23 through before he was called an AML in the study. 24 MR. PERRY: Object to form. 25 A. Well, in the -- in the M.D. Anderson study, 150 1 they discuss -- I believe it's -- well, let me see if I 2 can find it in here. They tracked 189 patients and they 3 were carefully studied and at the time of diagnosis all 4 they had was Philadelphia chromosome negative CML. And 5 then they studied these people to see how many developed 6 AML; and I believe they found, let's see, blast 7 transformation -- blast transformation of disease 8 preceded death in 8 of 26 patients for whom the cause of 9 death was known, 31 percent. It also says patients were 10 documented with a myeloid phenotype. The median time 11 from referral to blast crisis from the date of referral 12 was 11.5 months. 13 So that in this large group of patients, 14 probably one of the largest, if not the largest 15 reported, all of these people didn't have acute leukemia 16 when they were seen and they followed them and they 17 developed blast crisis, many of them, and died. 18 Q. Doctor, my original question was a little bit 19 different. It was about benzene as a cause. Does that 20 study in your hand deal with benzene as a cause? 21 A. I see. No, it does not deal with benzene as a 22 cause. 23 (Exhibit No. 16 marked) 24 Q. (BY MR. PATTON) Okay. And I'll mark that, in 25 fairness, as Exhibit 16. And my question, sir, was: 151 1 Can you point us to any studies in your stack, anything 2 that you're relying on in this case in giving your 3 opinion that benzene played no role in Raul's leukemia? 4 A. Yes. 5 Q. Can you point us to any other studies that talk 6 about the relationship between benzene and AML or any 7 other form of leukemia where they tracked the patient's 8 disease progression? 9 A. Well, this is a discussion, this article, my 10 Reference 3; and it discusses the whole category of 11 myelodysplastic/myeloproliferative neoplasms and points 12 out these are all myeloproliferative diseases. And it 13 says the etiology of this category of illness is not 14 known. And when it says that it means it's not known it 15 was caused by Twinkies or gasoline or benzene. The 16 etiology is unknown. And, so, that's a pretty 17 straightforward statement. 18 (Exhibit No. 17 marked) 19 Q. (BY MR. PATTON) Did they perform a study, in 20 this Exhibit 17 by Orazi, did they perform a study to 21 examine the relationship between benzene and any of 22 these diseases? 23 A. No. This is a review of the literature by 24 these gentlemen and a review of this particular disease 25 classification. 152 1 Q. Just to go back through my original question, 2 sir, is this a study that talks about benzene as a cause 3 of leukemia which tracks a patient's disease progression 4 before it becomes AML? 5 MR. PERRY: Object to form. 6 A. It doesn't do that. 7 Q. (BY MR. PATTON) Okay. So, that's -- you're 0 8 for 2 now. Are there any other studies in your stack 9 there which -- which talk about the relationship between 10 benzene and leukemia and track a patient's disease 11 course? 12 MR. PERRY: That's a different question 13 than you initially started asking him. 14 THE WITNESS: Yeah. 15 MR. PERRY: So, just -- you've changed the 16 question during this course, so now you're asking a 17 completely different question. Because early on you 18 weren't including the issue about benzene and the 19 progression of something to AML. 20 Q. (BY MR. PATTON) Let me make it clear, sir. 21 What I want to know is -- and here's the point I'm 22 trying to make and the question I'm trying to get 23 answered. I understand that there's a relationship 24 between benzene and AML. You acknowledge that, correct? 25 A. I acknowledge that, yes. 153 1 Q. Okay. Now, my question is: Is before some of 2 these subjects in the study who are -- are recognized as 3 a benzene-induced AML, before they become AML, do any of 4 these studies track their disease progression, whether 5 it was MDS or atypical CML? 6 MR. PERRY: Object to form. 7 A. I'm still not exactly understanding your 8 question. In other words, if I take people who have 9 a -- I think what you're saying is, if I take people who 10 have atypical CML, can I go back in time and see when 11 they had normal blood counts and what they were exposed 12 to? Well, of course not. In other words, they come in 13 with a particular illness and you make that diagnosis 14 and you don't find any evidence of AML and then you 15 follow them until they're dead. 16 Q. (BY MR. PATTON) Sir, that's not my question at 17 all. 18 A. I'm not understanding your question, then. 19 Q. And I want to get on the same page with you 20 here, okay? Some of these charts that we've reviewed in 21 some of these studies, they deal with patients who have 22 AML, right? 23 A. Yes. 24 Q. Okay. And they talk about benzene as being a 25 cause of someone's AML, correct? 154 1 A. Yes. 2 MR. PERRY: Objection. They don't talk 3 about there being a cause. They're looking at odds 4 ratio. They don't make a statement about being a cause 5 of any specific AML. That's not true. That's not what 6 the studies say. 7 Q. (BY MR. PATTON) Doctor, would you agree with me 8 that some of the studies that you've relied upon today 9 examine the relationship between benzene and AML? Fair 10 statement? 11 A. I think so, yes. 12 Q. Okay. Would you agree with me that some of 13 those studies take a look at how much people were 14 exposed to benzene and how many people got AML, as 15 compared to the general population? Isn't that sort of 16 what these studies are doing? 17 A. Some of them, yes. 18 Q. Okay. And some of these studies, when they 19 compare the numbers, they might show a -- a statistical 20 significance that there are more AMLs among 21 benzene-exposed workers than normally expected in the 22 general population, correct? 23 A. Yes. 24 Q. Okay. So, that's the point of some of these 25 studies, to examine the relationship between benzene and 155 1 leukemia by looking at benzene-exposed workers in 2 comparison to the general population. Fair statement? 3 A. Yes. 4 Q. Okay. In each such study which goes through 5 what we just talked about here in the last 90 seconds, 6 okay, for those patients who are -- who are designated 7 as AML, okay, my question for you is: You acknowledge 8 that sometimes people might have MDS and it progresses 9 to AML. True statement? 10 A. Yes. 11 Q. Sometimes people have atypical CML which 12 progresses to AML. Fair statement? 13 A. Yes. 14 Q. Okay. My question, sir, is: Of any of the 15 AMLs examined in these studies, do the authors of those 16 studies show what disease progression the person went 17 through before they had AML? For instance, does it show 18 that, you know, AML No. 6 actually had another disease 19 before it? 20 A. I don't know that that's true of any of these 21 studies; but I would point out that most people, if they 22 had a patient with CML, for example, and they went into 23 blast crisis, they wouldn't put that into a study as an 24 AML. They would put it in as a CML. 25 Q. Do the criteria of each of these studies tell 156 1 us why they're calling someone a -- an AML as compared 2 to a CML, or would you agree with me that some of the 3 AMLs in some of these studies are probably blast crisis 4 AMLs? 5 MR. PERRY: Object to form. 6 A. I think it's very unlikely that more than an 7 extraordinarily rare case would be a blast crisis of AML 8 in these studies. 9 Q. (BY MR. PATTON) And what's the basis for that 10 opinion? 11 A. Because of the fact that when a blast crisis 12 occurs, it's a very recognizable illness, especially if 13 it's in the setting of a CML; and it would simply be 14 classified as blast crisis of CML on the death 15 certificate. It wouldn't be AML. I think that what 16 you're suggesting can rarely happen, that a person -17 because I've seen this before -- a person comes in and 18 they have a positive Philadelphia chromosome and AML and 19 you're left to wonder, well, did they really used to 20 have CML and now they've got AML? Or does this happen 21 to be a case of AML with a Philadelphia chromosome? And 22 actually, many times it is AML with a Philadelphia 23 chromosome. They didn't have the chronic leukemia. We 24 see that very commonly in acute lymphoblastic leukemia, 25 where a large number of people have a Philadelphia 157 1 chromosome, that's a causative factor in ALL; but it's 2 not a case of CML. They happen to have the Philadelphia 3 chromosome. 4 So, I think what you're suggesting would 5 be highly unlikely to make up any more than a tiny 6 percentage of these cases. 7 MR. PATTON: Objection, nonresponsive. 8 Q. (BY MR. PATTON) Sir, do you have any studies 9 which examine the relationship between benzene and blast 10 crisis CML? 11 A. No. 12 Q. Do you have any studies which -- which examine 13 the relationship between atypical CML and benzene 14 exposure? 15 A. No. 16 Q. Do you have any studies that examine the 17 relationship between CMML and benzene exposure? 18 A. Not that I have here today, but that is -19 there are such studies out there. 20 Q. Are there any studies with you today that 21 examine the relationship between myeloproliferative 22 disease -- you said Raul had MPD, right? 23 A. He has MPD, yes. 24 Q. Do you have any studies which examine the 25 relationship between benzene exposure and MPD? 158 1 A. Not to -- not of these studies. 2 Q. So, in giving your opinions here today that 3 benzene played no role in Raul's leukemia, you chose to 4 bring with you no studies examining his specific type of 5 leukemia with benzene exposure. Fair statement? 6 MR. PERRY: Object to form. 7 A. No. That would be false. I've brought studies 8 on the specific illness he has, and these studies 9 indicate that illness is of cause unknown. That means 10 not caused by Coca Cola, not caused by Twinkies, not 11 caused by benzene. Because, for example, in the case of 12 the World Health Organization, if you look at their 13 section under myelodysplasia, you'll see comments about 14 that that illness may be caused by high exposures to 15 benzene. When you look at their section here on 16 atypical -- AML, there is no etiology because none is 17 known; and that would mean that it's not Coca Cola; it's 18 not Twinkies; it's not sugar; it's not benzene. 19 Q. (BY MR. PATTON) And would you -20 A. It is unknown. 21 Q. Would you agree with me, Doctor, that part of 22 the reason why etiology is to some extent unknown for 23 some patients is because doctors like yourself aren't 24 asking the questions enough? 25 MR. PERRY: Object to form. 159 1 A. No. I think that's totally false, because if 2 you look, for example, at Dr. Aksoy's study, he studied 3 a huge number of patients, about 28 or 29,000 people. 4 And he was a hematologist trained in the United States. 5 He looked at all the slides. He classified the 6 patients, and he commented that there were no patients 7 with the phenotype of chronic -- one patient -- with the 8 phenotype of chronic myeloid leukemia among these 9 benzene-exposed subjects. And to me that is significant 10 and suggests that high level benzene exposure does not 11 cause a CML-like illness, whether it's primary CML or 12 atypical CML. 13 Q. Well, let's talk about CML-type illnesses. 14 Are you familiar with a paper by Dr. Myron 15 Mehlman about CML? 16 A. I think I've seen that. 17 MR. PATTON: I will mark as Exhibit 18, 18 Mehlman, 2006. 19 (Exhibit No. 18 marked) 20 Q. (BY MR. PATTON) Have you seen this study 21 before? 22 A. I have seen it recently, yes. 23 Q. Can you read for us on the front page there, in 24 the middle of the paragraph, under "Abstract," where it 25 says "A review"? Can you read that for us? 160 1 A. (Reading) A review of the epidemiologic 2 literature on workers exposed to benzene or 3 benzene-containing solvents and products shows, without 4 question, that this exposure is significantly related to 5 other types of leukemia and lymphoma. 6 Q. Continue. 7 A. "In this article, we review the literature on 8 the relationship between benzene exposure and chronic 9 myelogenous leukemia (CML) and find that benzene and 10 benzene-containing products are significantly related to 11 morbidity and mortality from CML." 12 Q. And if you turn a few pages, you see -- you've 13 read this report before, right? 14 A. Not in detail. 15 Q. If you turn to Page 112, it references a 16 previous study by Yin, which found a significant excess 17 of CML in benzene exposure. Do you have any reason to 18 disagree with that? 19 MR. PERRY: To what Yin said or what 20 Mehlman says Yin says? 21 MR. PATTON: What Mehlman says Yin says. 22 MR. PERRY: Okay. Because there's a 23 difference. 24 A. The Yin article, I think, is in -- in the -- in 25 the background of what your other expert said, and Yin 161 1 says there's only an increase in AML. But I can read 2 you what he says here. He says -- Infante -- looking at 3 data from benzene-exposed workers in China between the 4 year 1972 to '81 previously reported by Yin found a 5 significant excess of CML in benzene-exposed workers. 6 Q. (BY MR. PATTON) If you turn to Page 114, this 7 is in the Annals New York Academy of Sciences. Is that 8 a reputable journal? 9 A. It's a -- it's a journal. Sometimes the 10 articles are not peer reviewed, they're invited, but 11 what is it that you'd like me to -12 Q. Well, is it a reliable source? Is this study 13 reliable? 14 A. Well, I don't -- I haven't read the source, but 15 I've seen good articles and bad in this particular 16 journal. 17 Q. On Page -18 A. But it is a journal. Go ahead. 19 Q. On Page 114, he references that "A number of 20 other studies have shown increased risk of CML from 21 exposure to petroleum products containing benzene." And 22 he goes on to cite and talk about a handful of studies. 23 And then near the end there, he references a study by 24 Linet, which shows a 1.5-fold excess of CML revealed for 25 motor mechanics, who were exposed to gasoline. 162 1 Is it your testimony today, sir, that 2 there is no reliable scientific evidence connecting 3 benzene exposure and CML? 4 A. My opinion, based on the extensive studies by 5 Dr. Lichtman on the subject, who I think I referenced, 6 that there are no consistent information linking CML to 7 benzene exposure and the prevailing opinion in the 8 medical community based on the scientific peer-reviewed 9 literature and what is taught in textbooks and what is 10 taught in medical schools is there is no relationship 11 between CML and benzene exposure. 12 Q. You would agree with me, however, that there 13 are a handful of studies out there, such as the Mehlman 14 article which reviews some of these studies, which does 15 show some support for that theory, correct? 16 A. Well, it depends on what you say. For example, 17 he's reading from what he says here. The Chinese cohort 18 study of Yin reported an imprecise 2.5 excess risk for 19 CML and exposures to benzene, confidence levels 0.7 to 20 16.9. So, most people would say that's a nonsignificant 21 study. It proves nothing. 22 Q. The point I'm trying to make, Dr. Natelson, is 23 that certain patients with AML, they had CML before they 24 had AML, right? 25 A. It's a very rare circumstance; but, yes, that 163 1 is true. 2 Q. Do you agree that all forms of acute 3 myelogenous leukemia first go through a chronic phase, 4 or is that just not the case? 5 A. No. In fact, it's just the opposite. About 6 90 -- 85 to 90 percent of AML is de novo AML, meaning 7 it's of abrupt onset. And there's no prior 8 myelodysplastic or abnormal hematopoietic phase. The 9 remainder are secondary and there may be MDS or 10 myeloproliferative disease or chemotherapy or abnormal 11 blood counts, but the vast majority of leukemia off the 12 street is a sudden onset. 13 Q. But, in fact, the studies dealing with 14 benzene-exposed populations, compared to the general 15 populations, when they deal with AML, they do not 16 necessarily look at the complete disease progression or 17 disease picture of a given patient when drawing the 18 conclusions in their studies. Fair statement? 19 A. Well, you have to look at a particular article. 20 I mean, some articles are based on death certificates. 21 I mean, there are a lot of different types of articles. 22 And I think early on in the deposition I mentioned one 23 about erythroleukemia, in which they looked at some of 24 these things you're talking about. But, again, you have 25 to look to individual studies; and what's out there, my 164 1 charge, as a testifier, is to relate what is the 2 prevailing medical opinion in the scientific medical 3 community, and the prevailing opinion, based on numerous 4 articles, is that the only known cause of chronic 5 myeloid leukemia is radiation exposure. 6 MR. PATTON: Objection, nonresponsive. 7 Q. (BY MR. PATTON) Sir, I did not ask you about 8 the cause of chronic myelogenous leukemia. 9 A. All right. 10 Q. I did not ask you about radiation exposure. 11 A. All right. 12 Q. Here's my question. If you give me an answer, 13 we can take a break. 14 In all the studies that you have with you 15 today, okay, that examine the relationship between AML 16 in the general population, compared to AML in 17 benzene-exposed workers, do any of those studies track a 18 person's disease course, that's to say, showing that he 19 had CML before AML or he had MPD before AML or he had 20 MDS before AML? Can you point us to any studies that 21 make that type of critical analysis of disease 22 progression before they call someone an AML? 23 A. Let me just see. I mean, I can think of one 24 that might say that. Just see if I happen to have that 25 referenced here. 165 1 Well, I have one article on 2 therapy-related leukemia; but it doesn't specifically 3 get at the percentages that you're after. There are 4 such articles out there, but I have not referenced one 5 here. 6 MR. PATTON: Let's take a break. 7 THE VIDEOGRAPHER: Now going off the video 8 record. Approximate time is 2:25. 9 (Recess taken from 2:25 to 2:37.) 10 THE VIDEOGRAPHER: Now back on the video 11 record. Approximate time is 2:37. 12 Q. (BY MR. PATTON) Doctor, we took a short break 13 and I just want to round out some of what we were 14 talking about and then I want to go to a new topic. 15 A. Good. 16 Q. Okay? 17 A. Okay. 18 Q. But just to round it out just so I'm clear. 19 A. All right. 20 Q. When -- when this case goes to trial, I won't 21 have the benefit of -- of having any additional 22 documents or studies that you might rely on in forming 23 your opinions, okay? So, I just want to make sure we 24 have everything in front of you today that we're going 25 to go through that support your opinions, okay? 166 1 A. Yes, that's true. 2 Q. Okay. If -- first of all, have you brought any 3 studies with you that specifically examine benzene as a 4 causative factor of atypical CML? 5 A. No. 6 Q. Okay. And you wouldn't expect to see those 7 studies because they weren't really calling it atypical 8 CML until around 2000, right? 9 A. Well, but I think that -- that it would have 10 been called either CML unclassified or CML Philadelphia 11 chromosome negative. In other words, it would have been 12 lumped in with CML cases. 13 Q. Did you bring with you literature today that 14 shows benzene doesn't cause CML? 15 A. I think the Aksoy study I referenced suggests 16 that. 17 Q. Okay. The Aksoy study supports your conclusion 18 that benzene is not connected with CML? 19 A. Yes. 20 Q. Or not -- benzene doesn't cause CML. 21 Would you agree with me, however, that 22 there are some studies, including those referenced by 23 Mehlman, which do show some association between benzene 24 exposure and CML, whether or not they're statistically 25 significant, whether or not it's accepted in the 167 1 textbooks, but would you agree with me that there are 2 studies supporting a causative relationship? 3 A. Yes. 4 Q. Doctor, have you brought with you any studies 5 that examine benzene as a causative factor when you -6 when you look at someone's disease through the road of 7 MDS, then on to AML; or atypical CML, then on to AML? 8 And what I'm trying to ask in maybe a different way is: 9 When we look at these studies, we're looking at a 10 snapshot of that person's disease in time. Fair 11 statement? 12 A. Yes. 13 Q. If we examine, like, the Strom study, which 14 we're going to talk about in a minute, it deals with 15 certain MDS subtypes. And you agree with me that the 16 epidemiology -- epidemiological literature you've 17 brought with you today and the EPI that deals with 18 benzene and leukemias, any leukemias, those studies take 19 a snapshot of the person's disease. Fair statement? 20 A. Yes. 21 Q. In the case of AML studies, okay, related to 22 benzene exposure, those studies take a snapshot at what 23 is essentially the end of the disease, right? You don't 24 go from AML, then back down to a different disease, on 25 Exhibit 8, do you? 168 1 A. No. Once you have AML, that becomes an 2 end-stage disease. 3 Q. AML is an end-stage disease, right? 4 A. Yes. 5 Q. Okay. So, if you're dealing with a study that 6 examines MDS, it's possible that the MDS individuals in 7 the study could progress to AML, right? 8 A. Yes. 9 Q. But it's not going to go back from AML because 10 it's an end-stage disease? 11 A. Yes. 12 Q. Okay. Would you agree with me that none of the 13 studies supporting your opinion that benzene played no 14 role in Raul's leukemia, you have not brought with you 15 any studies today which track the course of atypical CML 16 through to AML in the context of causation. Fair 17 statement? 18 A. In the context of causation, that would be 19 true. 20 Q. Okay. And if Raul -- well, first of all, the 21 people who perform these studies, they're not all 22 medical doctors, are they? 23 A. Which studies are we talking about? 24 Epidemiologic studies? 25 Q. All the studies we have on the table today. 169 1 A. Well, sometimes they're a mixture of doctors, 2 pathologists, clinicians, epidemiologists and so on. 3 Q. And I think you mentioned earlier that there 4 was a -- one of your colleagues -- or a hematologist at 5 a certain university that might always call a certain 6 disease a certain type, where others might call it a 7 different type, right? 8 A. Yes. 9 Q. What was the example you gave? 10 A. I'm trying to remember what I -- what I said 11 about that. I don't remember saying exactly that. I 12 don't remember what I said, but I -- I think I may have 13 said that some people would call blast crisis -- most 14 people would call blast crisis blast crisis. Some might 15 call it acute leukemia. 16 Q. Okay. So, some people, on death certificates, 17 for the AML patients, in some of these studies, okay, 18 once those people have passed away, there's a death 19 certificate created, right? 20 A. Yes. 21 Q. Okay. And then somebody calls it cause of 22 death; and they could call it blast crisis, or they 23 could call it AML, correct? 24 A. Yes. 25 Q. If Raul were to die, on his death certificate, 170 1 would it be feasible for a medical professional to call 2 it AML, given his current disease stage? 3 MR. PERRY: Object to form. 4 A. It -- it might happen because the person that 5 signs the death certificate oftentimes is not the person 6 that's taking care of the patient. 7 Q. (BY MR. PATTON) Okay. And you would agree with 8 me that when we go through all these studies here on the 9 table and all the studies you're relying on in your 10 opinions in this case, you cannot tell me with any 11 degree of certainty whether some of those AML patients 12 weren't eventually like what Raul may be, someone who 13 went through atypical CML and ended up with AML? 14 A. I can't tell you that with certainty; but I 15 would believe, based on my experience, that that would 16 be a very rare event. 17 Q. Atypical CML by its nature is a very rare 18 event, isn't it? 19 A. Yes. 20 Q. Who would you normally expect to get atypical 21 CML? 22 MR. PERRY: Object to form. 23 Q. (BY MR. PATTON) People of a certain age or 24 people of a certain race? Are there any factors that 25 you see in most atypical CMLs? 171 1 A. Well, there's a wide age range. I think in 2 the -- in the M.D. Anderson study, they have cases as 3 young as -- as 24 and -- and then some probably in the 4 70s and 80s. I think their mean age was in the 60s. 5 It's a little older than the mean age of standard CML. 6 Q. Raul was, like, 28 years old when he was 7 diagnosed? 8 A. Yes. 9 Q. Is that right? Less than half of the age of 10 60? 11 A. Yes, but as I say, they had cases as young as 12 age 24. 13 Q. Doesn't that support the conclusion -- or not 14 the conclusion -- but the possibility that more likely 15 than not, his disease was caused by something, as 16 compared to de novo or endogenous? 17 MR. PERRY: Object to form. 18 A. I -- I think it doesn't tell you that. In 19 other words, we don't know the cause for this illness; 20 and we don't know if it might have been something 21 congenital that didn't show up until he was 24. We 22 don't know if it was caused by an external agent. We 23 don't know if it was endogenous. But we do know that 24 when we study the -- the large number of these patients, 25 as M.D. Anderson studied, there is no known etiologic 172 1 factor. 2 Q. (BY MR. PATTON) You brought it up again. Did 3 M.D. Anderson specifically examine the relationship 4 between benzene exposure and atypical CML? 5 A. Not -- not that they say in that paper. 6 Q. Did they examine the relationship between chemo 7 treatment and atypical CML? 8 A. Not that they say in the paper. 9 Q. Smoking and atypical CML? 10 A. Not that they say in the paper. 11 Q. Radiation and atypical CML? 12 A. Not that they say in the paper. 13 Q. Doctor, I'm showing -- well, I just -- I want 14 to close this out, and then I'll hopefully move on to 15 the new target -- or new topic. 16 So, in forming your opinions today, is it 17 accurate to say that you can't bring me a single study 18 which examines Raul's specific disease type. Instead, 19 in forming your opinions, you have to put together these 20 other multiple pieces of studies, so to speak, in 21 drawing your conclusion of benzene played no role? 22 MR. PERRY: Object to form. Misstates his 23 testimony. 24 A. Well, I think that that's not a correct way to 25 phrase it. For example, in the case of M.D. Anderson, 173 1 if you study any patient they work up for leukemia, 2 there is always a long, dictated history and physical, 3 in which they go into their smoking history, any 4 evidence of any prior myelodysplastic disease, any 5 evidence of this and that, their alcohol history. They 6 have very extensive histories and physicals. There's no 7 reason to think that when they came across an atypical 8 CML patient, they would suddenly not do that and take a 9 different kind of history and physical and omit all of 10 those data. 11 So, I have every reason to believe that 12 all of those patients that they reported were questioned 13 intensively; and if they felt there was an etiologic 14 factor, they would put it in their report. 15 Q. (BY MR. PATTON) Where is this report you're 16 talking about? 17 A. That's probably -- is it this one? No, I don't 18 think so. 19 Q. Is this it? 20 A. That's it, yes. 21 Q. Okay. Let me take a look at it. 22 MR. PERRY: Which reference number is it? 23 MR. PATTON: Exhibit 16, Reference 4. 24 A. Is that the one? Yeah, it must be. 25 Dr. Kantarjian is on it? 174 1 Q. (BY MR. PATTON) Yes. 2 MR. PERRY: So, the lead author is Onida, 3 O-N-I-D-A? 4 THE WITNESS: Yeah. 5 MR. PERRY: It's also Reference 5. 6 Q. (BY MR. PATTON) Doctor, I've just reviewed 7 Exhibit 16, and granted, I did it rather quickly; but 8 there are two words I didn't see appear anywhere in this 9 study. Word one is cause; and word two is benzene. So, 10 I don't see where this study even examines cause. Am I 11 wrong? 12 A. Well, what I'm telling you is -- you're -- what 13 you're suggesting is that when an M.D. Anderson doctor 14 encounters a patient with this illness -15 Q. Dr. Natelson -16 A. -- they change their way of doing a history and 17 physical. 18 Q. Let me stop you right there. I'm not asking 19 you or suggesting anything. I am asking you whether 20 this study, Exhibit 16, regardless of what the 21 M.D. Anderson doctors do or don't do, my question is 22 this: Where in here does it examine cause? 23 A. I think I've -- I've said before, it does not; 24 and does not mention benzene. 25 Q. Okay. Thank you. 175 1 New topic. 2 A. All right. 3 Q. I'm going to mark as Exhibit 19, the Strom 4 study. You're familiar with the Strom, 2005, 5 M.D. Anderson study? 6 A. I have two of her papers. One, I think, more 7 recent than that. Let me see if it's the one I'm 8 thinking of. 9 Q. This one does examine cause? 10 A. Yes, I am familiar with this study. 11 (Exhibit No. 19 marked) 12 Q. (BY MR. PATTON) Can you turn to Page 1915, 13 Table 3? 14 A. 1915, Table 3. 15 MR. PERRY: This is Strom, "Risk factors 16 of myelodysplastic syndromes: a case-control study"? 17 MR. PATTON: Yes, sir. 18 Q. (BY MR. PATTON) And, Dr. Natelson, preliminary, 19 okay? I recognize that you do not consider Raul's 20 disease to be an MDS, right? 21 A. That's correct. 22 Q. Okay. Would you agree with me, though, that 23 Table 3 -- well, MDS is a form of myeloid disease. It 24 is a myeloid leukemia, so to speak, correct? 25 MR. PERRY: Object to form. 176 1 A. It's not a leukemia. It is a myeloid disease. 2 Q. (BY MR. PATTON) It's a bone marrow disease, 3 right? 4 A. It's a bone marrow disease. 5 Q. Okay. This study at Table 3, you see the 6 category "Benzene/solvent/gasoline"? 7 A. We're talking Table 3. I see "Family history," 8 "Smoking," "Alcohol," "Fertilizer/pesticide," 9 "Benzene/solvent/gasoline," yes. 10 Q. Okay. And it shows for the high exposure 11 category, it shows a doubling of the risk; and it is 12 statistically significant for all MDS, correct? 13 A. Let's see. Where am I looking at? All MDS -14 yes -- yes. 15 Q. Okay. Doctor, would you agree with me that 16 this study by the folks at M.D. Anderson supports the 17 conclusion that benzene/solvent/gasoline exposure, at 18 high exposure, they go through in there and they don't 19 really detail what exactly they classify as high, but it 20 recognizes a statistically significant risk between this 21 form of bone marrow disease and gasoline/solvent/benzene 22 exposure, correct? 23 A. Well, I think -- let me just read again the 24 conclusion. I thought -- well, let me just look at this 25 case just a little further. 177 1 This particular study was at a time when 2 chronic myelomonocytic leukemia was included in the MDS 3 category, and I believe that this study demonstrated 4 that CMML and RARS were not associated with benzene or 5 solvent exposure. And if you looked at the table, it 6 says what you said, but I believe that those two 7 diseases did not have that association. 8 Q. That's an interesting point you bring up. 9 Because when you look at the table I cite, Table 3, it 10 lumps the diseases together, right? And then there are 11 other tables where they -- they split it out a little 12 more, correct? 13 A. Yeah, that's correct. 14 Q. Would you agree with me that where the diseases 15 are lumped together, there's a little more statistical 16 power in that analysis? 17 MR. PERRY: Object to form. 18 A. Well, it may be more statistical power; but 19 you're lumping -- you might be lumping apples with 20 oranges. So, you -- you gain by numbers, but you may 21 lose by content. 22 Q. (BY MR. PATTON) But when you split too much -23 and you're a splitter, right? 24 A. Well, I'm -- I'm -- let's say, I'd like to put 25 the right disease in the right -- the right peg in the 178 1 right hole. 2 Q. But when you split too much, you might miss 3 something, correct? 4 MR. PERRY: Object to form. 5 A. Well, if you have like diseases. But as I say, 6 the CMML is a myeloproliferative disease and -- and no 7 longer is in the MDS category, and that's one of the 8 problems you encounter when you constantly change 9 classifications, instead of simply looking at diseases 10 as specific entities. 11 Q. (BY MR. PATTON) But when you look too 12 specifically, you might lose the forest through the 13 trees, so to speak? 14 MR. PERRY: Object to form. 15 A. Well, I think you might have a more accurate 16 study when you look specifically at the particular 17 disease. 18 (Exhibit No. 20 marked) 19 Q. (BY MR. PATTON) Sir, I'm going to show you what 20 I've marked as Exhibit 20; and this is a document from 21 the API. Do you know what the API is? 22 A. American Petroleum Institute or something like 23 that. Yes, American Petroleum Institute. 24 Q. Okay. And I'm going to mark as Exhibit 21, 25 something I found on the Internet that talks about what 179 1 the API is and what it does. 2 First of all, are you a member of the API? 3 A. No. 4 Q. Have you -- I hand you Exhibit 21 there. 5 (Exhibit No. 21 marked) 6 Q. (BY MR. PATTON) Have you relied on studies 7 funded by the API in reaching some of your opinions in 8 this case? 9 A. I have no idea. 10 Q. Okay. If you look at Exhibit 21, sir -- I gave 11 you the wrong copy. 12 A. I'm sorry. 13 Q. If you look at Exhibit 21 -- if you look at 14 Exhibit 21, sir, it talks about what the API does as far 15 as studying chemicals, things of that nature. Do you 16 see that? If you look four bullet points down. 17 MR. PERRY: You're looking at 20 right 18 now. 19 Q. (BY MR. PATTON) Yeah, you're looking at 20 20 right now, sir. 21 MR. PERRY: He's talking about 21. 22 Dr. Natelson, the other one. 23 A. Oh, this. 24 MR. PERRY: That one. That's what he's 25 talking about, 21. 180 1 A. I'm sorry. 2 Q. (BY MR. PATTON) Go down to the fourth bullet 3 point. 4 A. Yes. 5 Q. It talks about "To advise promptly appropriate 6 officials, employees, customers and the public of 7 information on significant industry-related safety, 8 health and environmental hazards, and to recommend 9 protective measures." 10 Do you see that? 11 A. Yes. 12 Q. And then if you go down a few more, you see "To 13 extend knowledge by conducting or supporting research on 14 the safety, health and environmental effectiveness of 15 our raw material, products, processes and waste 16 materials." 17 Do you see that? 18 A. I see that. 19 Q. Okay. What I've showed you marked as 20 Exhibit 20 is an API Toxicological Review of benzene 21 dated 1948. Have you ever seen this document before? 22 A. If I have, I don't recall. 23 Q. Okay. I want to go through -- first of all, 24 this is the API. Again, it's kind of a research 25 conglomerate of industry organizations, so to speak; but 181 1 this is a document they put out some 60 years ago about 2 the dangers of benzene. 3 If you turn to the second page, "Probable 4 Sources of Contact," do you see where I've marked "By 5 far the greatest" amount of benzene -- "amounts of 6 benzene are blended into motor gasolines," do you see 7 that? 8 A. Yes. 9 Q. Okay. Turn to the next page, and do you see 10 where it says "Chronic Effects"? 11 A. Yes. 12 Q. Can you read that for us? 13 A. "Chronic benzene poisoning results from 14 repeated or continuous exposure to relatively low 15 concentrations of benzene vapor." 16 Q. Do you agree or disagree with that statement? 17 A. Well, it certainly can be true. I can't 18 disagree with that. 19 Q. And can you read on, "The level"? 20 A. "The level and degree of exposure necessary to 21 produce poisoning apparently vary widely." 22 Q. Do you agree or disagree with that? 23 A. No, I disagree with that. I think -- this is a 24 1948 article. I would hope that in the last 50 or 25 60 years we've learned a little more than -- than what 182 1 they have here. 2 Q. Is it your testimony, sir, that we've learned 3 that chronic benzene -- the chronic effects of exposure 4 to benzene over time just really aren't that 5 significant? Is that your position? 6 A. No, my -- my position is that they are 7 significant, but it's the cumulative-dose level that one 8 has. So, low levels over a long enough period of time, 9 yes, can be toxic; but what we're really looking at is 10 the cumulative dose and -- and that it takes a 11 considerable dose of benzene to produce these illnesses. 12 Q. Let's go over to the next column on Page -- I 13 think it's Page 3. Do you see where I marked 14 "Practically all"? 15 A. Yes. 16 Q. Can you read that for us? 17 A. "Practically all of the chronic effects of 18 exposure are a result of the influence of benzene or its 19 oxidation products on the blood-forming system. A 20 variety of reactions may be encountered, and there is 21 little correlation between the degree and duration of 22 exposure and the severity or nature of the findings in 23 the blood on microscopic examination. There is no 24 single change in the blood or blood-forming organs which 25 is universally present in benzene poisoning." 183 1 Q. Do you agree or disagree with that statement? 2 A. I would -- I would disagree with that 3 statement. 4 Q. This seems to imply that there is no single 5 change in the blood or the bone marrow which is 6 universally present in benzene poisoning, rather a 7 variety of reactions or responses by someone's body may 8 occur. You don't agree with that? 9 A. No. I think there is evidence, as I cited in 10 my letter, what the bone marrow looks like in chronic 11 benzene poisoning. 12 Q. Let's turn to the next page. You see where 13 I've marked in the right-hand column "Chronic benzene 14 poisoning is extremely refractory to treatment." What 15 does "refractory" mean? 16 A. "Refractory" means it doesn't respond well. 17 Q. How did Raul Zendejas respond to treatment? 18 A. Well, he didn't respond well. 19 Q. Okay. Go on down where it says "Examinations." 20 This talks about a preemployment examination of benzene 21 workers, which should include a detailed history, 22 physical, chest X-ray and a complete blood count. Do 23 you think that's helpful from a safety and health 24 standpoint? 25 A. Well, as a hematologist, I think it's good for 184 1 people to get complete blood counts. 2 Q. I agree. 3 And it says anyone with history of 4 previous benzene intoxication or any evidence of 5 abnormality of the blood or blood-clotting mechanism, 6 they should be eliminated from such employment. 7 Do you see that? 8 A. Yes. 9 Q. Okay. Do you agree with that? 10 A. Well, I think if somebody has a -- has certain 11 kinds of anemias or bone marrow hypoplasia, they 12 shouldn't be around potentially myelosuppressive drugs. 13 Q. Okay. Next page. You see where I've marked, 14 individuals exposed to concentrations approaching the 15 safe limits should be examined at monthly intervals at 16 least? 17 Do you see that? 18 A. Which page are you -19 MR. PERRY: Which page is this? 20 Q. (BY MR. PATTON) Second from the last. 21 MR. PERRY: The last being the references? 22 A. Yeah, "Periodic" -- I see. Periodic 23 re-examinations should be carried out regularly, their 24 frequency being determined by the severity of the 25 exposure. Individuals exposed to concentrations 185 1 approaching the accepted "safe" levels should be 2 examined at monthly intervals at least. The examination 3 should include a brief interval history and physical 4 examination, together with a complete blood study, 5 including white and differential counts and estimate of 6 the platelet levels. The ratio of inorganic to total 7 urinary sulfates should be determined in order to detect 8 the presence of excessive absorption and excretion of 9 benzene. 10 Q. (BY MR. PATTON) And it says at the end there, 11 "It would be well to continue periodic blood counts for 12 several months after exposure has ceased." 13 Do you see that? 14 A. Yes. 15 Q. Doctor, you recognize the blood and urine tests 16 are or can be an important part for companies to 17 evaluate the -- the status of benzene exposure to its 18 workers? 19 A. Yes. 20 Q. That's an API document, right? 21 A. Yes. 22 Q. Are you aware that the API opposed increased 23 safety standards for benzene-exposed workers? 24 MR. PERRY: Object to form. 25 A. No. 186 1 Q. (BY MR. PATTON) Are you aware that the API -2 that OSHA implemented a lower threshold standard, 3 meaning increased safety, and the API challenged that 4 increased standard all the way to the Supreme Court? 5 Are you aware of that? 6 MR. PERRY: Object to form. 7 A. No. 8 Q. (BY MR. PATTON) Exhibit 2 is your CV. Is this 9 a complete and accurate current copy of your CV? 10 A. Yes. 11 Q. I marked as Exhibit 3, your deposition notice. 12 In this deposition notice, it basically asks you to 13 bring anything and everything having to do with this 14 case or supporting your opinions. Have you done that 15 today? 16 A. Yes. 17 Q. We're going to mark all the studies near the 18 end, but I just want to make sure. 19 Are there any other studies in the 20 universe of scientific literature which you may rely on 21 in forming your opinions that you did not bring with you 22 today? 23 A. No. 24 Q. Okay. Exhibit 4, this is a list of your 25 charges; is that right? 187 1 A. Yes. 2 Q. You worked 12-and-a-half hours at first and 3 then another 7 hours before -- yesterday; is that right? 4 A. Yes. 5 Q. And you charge how much per hour to testify? 6 A. $250 an hour to review and phone calls, 7 et cetera. $400 an hour to testify. 8 Q. Okay. Exhibit 7, I don't have a copy of, but 9 if you want, I can get a copy, if it will make it easier 10 to go through -- I think we're going to need a copy. 11 MR. PATTON: Let's go off the record. 12 THE VIDEOGRAPHER: Now going off the video 13 record. The approximate time is 3:04. 14 (Recess taken from 3:04 to 3:19.) 15 THE VIDEOGRAPHER: Now back on the video 16 record. Approximate time is 3:17. 17 Q. (BY MR. PATTON) Dr. Natelson, we took a break 18 and I've marked as Exhibit 7 -- actually, before we 19 started your deposition. Exhibit 7 is a list of 20 testimony you've given in cases either by trial or 21 deposition; is that right? 22 A. Yes. 23 Q. This dates back to 2004, correct? 24 A. Yes. 25 Q. What year did you first start testifying in 188 1 benzene exposure cases? 2 A. Probably -- I don't know exactly, but it would 3 be probably in the early to mid-1990s. 4 Q. I counted -- we counted through these together, 5 the cases on this list since 2004 that you've testified 6 in which involved benzene; and it's a little over 30; is 7 that right? 8 A. If -- I wasn't counting while you were -- but 9 that -- that's probably so. 10 Q. Okay. Sir, have you ever testified on behalf 11 of a plaintiff in a benzene exposure case? 12 A. No. 13 Q. Have you always testified on behalf of 14 industry? 15 A. Of the defense, yes. 16 Q. Was it your testimony in each of these cases 17 that benzene was not a substantial factor in the 18 person's disease? 19 A. Yes. 20 Q. Was it your testimony in each of these diseases 21 that benzene was not -- that there was not a 51 percent 22 chance that benzene caused the disease? 23 MR. PERRY: Object to form. 24 A. I don't know that I used that number, but I -25 I testified that I -- that more likely than not benzene 189 1 was not the causative factor. 2 Q. (BY MR. PATTON) Did you testify in any of these 3 30 or so cases that benzene was a causative factor in 4 the disease? 5 A. No. 6 Q. Most of these cases arise down here in the 7 Texas Gulf Coast, correct? 8 A. Most of them, yes. 9 Q. Sir, if someone wanted to hire you to testify 10 for a plaintiff in a benzene exposure case, what 11 criteria would you have to see before giving the opinion 12 that benzene was -- was a substantial factor in the 13 person's disease? 14 A. Well, first, it would have to be a disease that 15 benzene is known to potentially cause. That could be 16 aplastic anemia, certain forms of acute myeloid 17 leukemia, certain forms of myelodysplasia. So, it would 18 have to be the right disease. 19 Then it would be -- have to be a person 20 who had a substantial benzene exposure. 21 Then it would have to be a person in whom 22 there were no complicating factors, potential other 23 causes, such as -- other potential causes other than 24 benzene, for example, smoking or chemotherapy, other 25 potential causes. 190 1 Q. Would you agree with me that someone's given 2 form of myeloid leukemia may have more than one 3 substantial cause? 4 A. I don't know that to be so. I think we like to 5 look for -- in medicine we operate under Ockham's law, 6 that there is one cause for the illness. There may be 7 multiple manifestations, but we like to look for a 8 single causative factor. 9 Q. When you said the exposure to benzene would 10 have to be substantial, what do you mean by that? 11 A. Above 40-part-per-million years, cumulative 12 dose. 13 Q. And who would you expect to give you that 14 assessment of cumulative dose? 15 MR. PERRY: Object to form. 16 A. It could be someone who is involved in those 17 types of measurements. 18 Q. (BY MR. PATTON) You would need to see some type 19 of report from another expert? 20 A. Yes, I couldn't determine that myself, in other 21 words. 22 Q. But as a practitioner, have you determined that 23 benzene was a substantial cause of someone's disease 24 without looking at a cumulative report by an expert? 25 A. Yes, in certain circumstances, yes. 191 1 Q. But to testify, you would want a cumulative 2 report? 3 A. I think I would like to see a cumulative 4 report. And I -- also, I would like to see other 5 factors commonly not mentioned. We know that 6 chemical-induced leukemia, 90 percent of the time, has 7 easily demonstrable chromosome aberrations. So, I'd 8 like to see if they were present and what type of 9 aberrations they were because certain aberrations have 10 never been described with benzene poisoning or 11 benzene-induced leukemia. 12 I also would like to know -- I think I 13 commented about competitive factors or other risk 14 factors. 15 (Exhibit No. 22 marked) 16 Q. (BY MR. PATTON) I am going to mark as 17 Exhibit 22, a document from the API. Have you ever seen 18 this document before? 19 A. No, I don't think so. 20 Q. Sir, I'll represent to you that this is a 21 document that was produced in this case; and it is 22 meeting minutes from 1991 from the API when they were 23 talking about research to conduct in conjunction with 24 their international symposium on the health effects of 25 gasoline. They're studying -- or they're examining what 192 1 kind of studies and research they may want to do with 2 respect to benzene and gasoline. 3 Do you understand that? 4 A. Yes. 5 Q. Have you ever been invited to such a meeting on 6 behalf of the API? 7 A. No. 8 Q. Have you ever been invited to such a meeting on 9 behalf of Shell? 10 A. No. 11 Q. Have you ever been to the Doral Resort and 12 Country Club in Miami, Florida? 13 A. No. 14 Q. Okay. That's where they had this meeting. And 15 just so we're clear, sir, you've never been a part of 16 any such API activities? 17 A. No. 18 Q. If asked to be involved, would you do so? 19 A. Probably not. 20 Q. The next exhibit I am going to mark -- is it 21 because you don't golf or you just don't have the time? 22 A. Well, I only golf once every ten years and it's 23 not the right time for me. And I hate to travel. I 24 hate to fly. And, so, I -- I would probably not go to a 25 meeting like that. 193 1 Q. So, you wouldn't be interested in going to the 2 Doral Resort and Country Club in Miami, Florida -3 A. No. 4 Q. -- to talk about benzene and gasoline research? 5 A. No. 6 Q. I am going to mark as Exhibit 23, a -- some 7 sections from a textbook titled Myelodysplastic 8 Syndromes, and Dr. Gore, plaintiffs' expert in this 9 case, he was an author of some of the sections of this 10 textbook. 11 (Exhibit No. 23 marked) 12 Q. (BY MR. PATTON) Have you ever seen this 13 textbook before? 14 A. No. 15 Q. If you turn to the second page there, Page 17, 16 it talks about "Probable Causative Factors for MDS"; and 17 it's got a little Table 3.1. 18 A. Yes. 19 Q. And it talks about "Potential causative agents 20 in the etiology of MDS," again, a bone marrow disease. 21 A. Uh-huh. 22 Q. And it talks about definite causes, chemo 23 drugs. And you testified earlier that it's easy to call 24 chemo drugs a possible cause of someone's leukemia 25 because you can so quickly observe the dose they were 194 1 given and then the response? 2 A. You can accurately receive the dose, and the 3 follow-up is very good on chemotherapy patients. So, 4 you know the latency period very accurately. 5 Q. Now, for probable causes, which include 6 benzene, it's a little -- it's a little tougher to call 7 the definite cause because you have to make certain 8 estimations, right? 9 A. Yes. 10 Q. Do you think it would be possible to cause -11 to call benzene the definite cause of someone's disease? 12 A. Well, I don't think so because I couldn't do 13 that with anything. We don't have -- there's no marker 14 on any case of AML that says this was caused by this, 15 and that was caused by that. We can only say in all 16 probability whether it was or wasn't. 17 Q. The next exhibit, Doctor, I will mark as 18 Exhibit 24. 19 (Exhibit No. 24 marked) 20 MR. PATTON: I'm almost done. 21 Q. (BY MR. PATTON) This is Exhibit 24. This is a 22 study from -- this is a study regarding the Tranguch 23 Gasoline Spill in Pennsylvania. 24 Have you ever seen this study before? 25 A. No. 195 1 MR. PERRY: Is that the lead author, 2 Patel? 3 MR. PATTON: Yes. 4 Q. (BY MR. PATTON) Have you read the Abstract on 5 the front there? And I'll give you a couple minutes to 6 look through this. 7 A. I see the Abstract. 8 Q. Do you see where it indicates a statistically 9 significant four-fold risk for leukemia from those who 10 lived near this gasoline spill? 11 A. Yes. 12 Q. Do you understand this study deals with 13 gasoline being spilled from underground leaky storage 14 tanks? 15 A. Yes. 16 Q. Okay. Do you understand my client, Raul 17 Zendejas, stood on top of a loading rack with a large 18 hose that unloaded gasoline into tanker trucks and into 19 other -- other vessels, so to speak? 20 MR. PERRY: Object to form. 21 A. Yes. 22 Q. (BY MR. PATTON) Would you agree with me that 23 someone who was top loading gasoline without any vapor 24 recovery measures is going to be exposed to more benzene 25 than someone who lives in an area where there is benzene 196 1 underground? 2 MR. PERRY: Object to form. 3 Q. (BY MR. PATTON) Or do you -- or do you have no 4 opinion? 5 A. I have no opinion on that. 6 Q. Would you agree with me that this study 7 supports the conclusion that benzene via gasoline 8 exposure has in some populations showed an increased 9 risk of leukemia? 10 MR. PERRY: Object to form. Misstates 11 the -12 A. Well, I would have to comment, that there are a 13 very tiny number of cases; and it is -- it is 14 statistically significant. I see what it says, and I 15 would say it's a very small study. 16 Q. (BY MR. PATTON) You have criticisms of this 17 study because of its size? 18 A. Yes. When you only have four cases, you have 19 one case expected and you see four, there are clusters 20 of leukemia that occur without known cause. We had one, 21 I can recall, from a small town in Texas when I was a 22 house officer and everybody went down there at -- there 23 was no reason for it and it didn't reoccur. And we had 24 about five or six cases that all came to Methodist 25 Hospital; and then just as quickly as they started, they 197 1 disappeared. It was just a cluster, and there was no -2 no chemical, no sickness, no nothing anybody could put 3 their fingers on. And these things happen. When you 4 only have four cases, that's not enough to be certain 5 about anything, I don't think. 6 Q. Speaking of epidemiology in general, are you an 7 epidemiologist? 8 A. No. 9 Q. As a health professional, would you agree with 10 me that all the studies you brought with you today, as 11 well as the studies that plaintiffs' experts rely on, 12 all of those are subject to evaluation; they're all 13 subject to praise and subject to criticism. Fair 14 statement? 15 A. Yes. 16 Q. We could go through any of these studies, pull 17 out some strengths, some weaknesses, come up with some 18 arguments on both sides of these studies, correct? 19 A. Yes. 20 Q. But at the end of the day, you do agree with me 21 that benzene is shown consistently throughout the 22 epidemiological literature to support a -- that 23 benzene -- the conclusion that benzene causes leukemia? 24 MR. PERRY: Object to form. 25 A. Benzene may cause acute myeloid leukemia. 198 1 Q. (BY MR. PATTON) Benzene may cause certain forms 2 of MDS on your chart there, Exhibit 8, right? 3 A. Yes. 4 Q. You do not believe benzene causes atypical CML? 5 A. No. 6 Q. Have you reviewed Dr. Infante's opinions in 7 this case? 8 MR. PERRY: He hadn't gotten the 9 deposition yet, and Infante didn't prepare a report. 10 Q. (BY MR. PATTON) Have you reviewed Dr. Gore's 11 deposition? 12 A. Yes. 13 Q. I think I asked you this earlier, and I'm not 14 going to ask you again. 15 To finish up here, Exhibit 6 to your 16 deposition seems to be some State Fund, Arizona, 17 workers' compensation records. What is the 18 significance, if any, of those? 19 A. Nothing to me. This was just material I was 20 sent. 21 Q. Okay. Doctor, what I want to do is go through 22 all the exhibits real quick. 23 No. 1 is your report, correct? 24 A. Yes. 25 Q. Two is your CV? 199 1 A. Yes. 2 Q. Three is your deposition notice? 3 A. Yes. 4 Q. Four are the billing records? 5 A. Yes. 6 Q. No. 5 is certain medical records. You, in 7 fact, have on disk additional medical records, right? 8 A. Correct. 9 Q. Is there any significance in some of the 10 records that you've printed, which are in Exhibit 5, 11 that bear on your opinion or your interpretation of 12 Raul's diagnosis? 13 A. Well, the statement by this physician -- I'm 14 not sure how you pronounce the name -- Fayssoux, who 15 indicates the diagnosis was myeloproliferative disorder 16 and that he had a chronic myeloproliferative disorder. 17 I thought the bone marrow report was kind 18 of interesting. It's -- it's a minor point, but the -19 when we look at myelodysplasia, one of the things we 20 look for are what are called Pelger-Huet cells. And 21 normally a neutrophil, or a granulocyte, has multiple 22 lobes in it; and that's what we mean when we call it a 23 poly. It's got multiple nuclear lobes. 24 A Pelger-Huet cell is a mature 25 granulocyte, but it's like a bow tie. It only has two 200 1 lobes. And what happens to these cells is normally 2 granulocytes mature in the marrow and they come out and 3 circulate. And many years ago it was shown that if you 4 acquired Pelger-Huet cells, that is to say, you found 5 somebody who didn't used to have them and now they had 6 them in the peripheral blood, it was a sign of 7 underlying myelodysplasia, myelodysplastic syndrome, 8 sick bone marrow, acute leukemia. It was not a good 9 thing to have Pelger-Huet cells in the peripheral blood. 10 But it's a peripheral blood phenomenon. In other words, 11 a Pelger-Huet cell, by definition, to be a Pelger-Huet 12 cell, must be seen in the peripheral blood. And what 13 this report says, it says there is a pseudo Pelger-Huet 14 anomaly, mostly in the bone marrow, not on the 15 peripheral blood smear. 16 Well, if it's not in the peripheral blood 17 smear, it's not a Pelger-Huet anomaly. In other words, 18 that's a peripheral blood phenomenon. 19 And, so, some people think they can look 20 at a bone marrow and look at the immature cells and tell 21 whether they're going to -- going to grow up to be a 22 Pelger-Huet cell, but the bottom line is, by convention, 23 that's a peripheral blood finding. 24 So, I think this report is not accurate 25 from that standpoint. It's a minor point -- 201 1 Q. Are those -2 A. -- and doesn't change the diagnosis. 3 Q. Are those abnormal cells generated in the bone 4 marrow? 5 A. They're generated in the bone marrow, but the 6 bottom line is, you see, in order to know that they 7 wouldn't fully develop, they've got to be able to mature 8 and come out and circulate. And when they come out and 9 circulate and they're still not mature, you can know 10 there was some inhibition of the maturation process. 11 While they're still in the bone marrow, they've still 12 got time to mature. 13 So, it's hard to be really accurate by 14 calling Pelger-Huet cells in the bone marrow; and that's 15 why, by convention and by all descriptions and by every 16 comment in textbooks, it's a peripheral blood 17 phenomenon. And, so, I thought the report was 18 interesting when he says I didn't see them in the 19 peripheral blood. I saw them in the bone marrow. 20 That's his tilt. In other words, that's -- they're not 21 a bone marrow phenomenon. 22 Q. Is it a bone -- is it a -- a cell abnormality, 23 though? 24 A. It is a cell abnormality, that's right. 25 Q. Raul did have that cell abnormality? 202 1 A. Well, the pathologist said he had it in the 2 bone marrow. As I say, you could use the term -- I 3 think there is maturation abnormalities in the bone 4 marrow. I think when you use the Pelger-Huet term, 5 you're talking about an observation in the peripheral 6 blood; and he didn't have that observation in the 7 peripheral blood, as the doctor indicates. I just 8 thought it was cute. It doesn't have any influence on 9 the case whatsoever, but I thought it was interesting. 10 That's why I highlighted it. 11 Q. Exhibit 6, the State Fund records. 12 Exhibit 7 is your testimony list? 13 A. Yes. 14 Q. Can you write "Dr. Natelson" at the bottom of 15 Exhibit 8 there with -- you have a pen next to you? 16 MR. PERRY: There's the red marker right 17 there, the one you used. 18 A. Oh, this. Oh, this. 19 MR. PERRY: That's Exhibit 8. 20 A. What would you like me to write? 21 Q. (BY MR. PATTON) Just write your name on it 22 somewhere. 23 A. (Witness complies.) 24 Q. Okay. I'll take that. 25 A. Oh, okay. 203 1 Q. Exhibit 9 through 19 are all studies. 2 Exhibit 20 and 21 are API references. 3 Can I see those? 4 A. These. 5 Q. Twenty-two is the meeting at the Doral Resort 6 and Country Club in Miami, Florida where you weren't 7 invited. I meant that as humor. 8 Twenty-three is the MDS textbook. 9 Twenty-four is the Tranguch study. 10 And 25 is the Cortes and Kantarjian, 11 M.D. Anderson article, "Beyond Chronic Myelogenous 12 Leukemia," correct? 13 A. Yes. 14 Q. That's Exhibit 25. 15 (Exhibit No. 25 marked) 16 Q. (BY MR. PATTON) And 26 -- Exhibit 26 -- I will 17 mark -- is the Adegoke study. I think we talked about 18 this a little earlier. 19 A. We did. 20 Q. And then as a group exhibit -- I will mark the 21 remainder of your studies as Exhibit 27. 22 (Exhibit No. 26 and 27 marked) 23 Q. (BY MR. PATTON) And this includes a Vardiman 24 article; Schnatter, Lewis; Williams and Paustenbach; 25 your article, Dr. Natelson, on benzene-induced AML; the 204 1 U.K. study by Sorahan; Satin, S-A-T-I-N, "A 50-Year 2 Mortality Follow-up of a Large Cohort of Oil Refinery 3 Workers in Texas; Catenacci, C-A-T-E-N-A-C-C-I, 4 "Myelodysplactic syndromes: A comprehensive review"; a 5 letter to the editor from Blood, 2006, about JAK2 6 mutation; therapy induced -- or therapy-related leukemia 7 by Rund; Pedersen-Bjergaard, "Myelodysplactic 8 Syndromes"; an article in The Oncologist by 9 Dr. Lichtman; CML, "Chronic Myeloid Leukemia," by 10 Druker; Lynge, L-Y-N-G-E, "Risk of Cancer and Exposure 11 to Gasoline Vapors"; RARS article; Linet article. 12 MR. PERRY: L-I-N-E-T. 13 Q. (BY MR. PATTON) Vardiman article; Silver; 14 Beran, Dr. Beran, "Prognostic significance of 15 monocytosis in patients with MDS"; Orazi; Ruiz; Tefferi; 16 Morgan; Eastmond; Whysner; Smith; Gulf War and Health; 17 Cole; Schechter, Hematology 1999; Pazdur, Cancer 18 textbook; Pamela Williams and Dennis Paustenbach; Aksoy; 19 Wong; Satin; Wong; Sorahan; Divine; Gun; Bloemen; Wong; 20 ATSDR, 1995, "Toxicological Profile For Gasoline." 21 Sir, is it going to be your testimony in 22 this case that because gasoline is not classified as a 23 carcinogen, that the benzene in gasoline cannot cause 24 myeloid damage? 25 MR. PERRY: Object to form. 205 1 Q. (BY MR. PATTON) I think I asked that before. 2 A. No, it's just -- it's just an observation. 3 Q. Okay. Zhang article; Olney article; the Monash 4 Health Watch 2007 update; ATSDR, "Toxicological Profile 5 for Benzene, August 2007"; Jamall; and Swerdlow. 6 Let's take a short break. 7 Actually, I have one more. The Irons 8 article. 9 I think this is my last question. Did 10 Raul Zendejas have any hypocellular bone marrow and 11 dyserythropoietic changes? 12 A. Well, his bone -- hypocellular means few cells. 13 He had a hypercellular bone marrow, meaning lots of 14 cells. So, he had the opposite. 15 Q. And what's that dyser -16 A. Dyserythropoiesis just means morphologic 17 dysplastic changes. The cells look funny. 18 MR. PATTON: Okay. Let's go off the 19 record real quick. 20 THE VIDEOGRAPHER: Now going off the video 21 record. Approximate time is 3:41. 22 (Recess taken from 3:41 to 3:48.) 23 MR. PATTON: I have no further questions. 24 Doctor, thank you for your time; and we'll 25 attach all the exhibits to the deposition. 206 207 1 (Proceedings concluded at 3:48 p.m.) 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 1 CHANGES AND SIGNATURE 2 WITNESS NAME: Ethan Natelson, M.D. 3 DATE OF DEPOSITION: September 25, 2009 4 PAGE LINE CHANGE REASON 5 ________________________________________________________ 6 ________________________________________________________ 7 ________________________________________________________ 8 ________________________________________________________ 9 ________________________________________________________ 10 ________________________________________________________ 11 ________________________________________________________ 12 ________________________________________________________ 13 ________________________________________________________ 14 ________________________________________________________ 15 ________________________________________________________ 16 ________________________________________________________ 17 ________________________________________________________ 18 ________________________________________________________ 19 ________________________________________________________ 20 ________________________________________________________ 21 ________________________________________________________ 22 ________________________________________________________ 23 ________________________________________________________ 24 ________________________________________________________ 25 ________________________________________________________ 208 1 I, ETHAN NATELSON, M.D., have read the foregoing 2 deposition and hereby affix my signature that same is 3 true and correct, except as noted above. 4 5 ___________________________ ETHAN NATELSON, M.D. 6 7 THE STATE OF _______________) 8 COUNTY OF __________________) 9 10 Before me, ____________________________, on this day 11 personally appeared ETHAN NATELSON, M.D., known to me or 12 proved to me on the oath of _________________ or through 13 __________________________ (description of identity card 14 or other document) to be the person whose name is 15 subscribed to the foregoing instrument and acknowledged 16 to me that he/she executed the same for the purpose and 17 consideration therein expressed. 18 Given under my hand and seal of office on this _____ 19 day of __________________, _______. 20 21 __________________________ NOTARY PUBLIC IN AND FOR 22 THE STATE OF _____________ 23 My Commission Expires: _________ 24 25 209 1 IN THE SUPERIOR COURT OF THE STATE OF ARIZONA 2 IN AND FOR THE COUNTY OF MARICOPA 3 RAUL ZENDEJAS and ) ARACELI ZENDEJAS, ) 4 Plaintiffs ) ) 5 vs. ) ) NO. CV-2007-005399 6 SHELL OIL COMPANY, SHELL ) CHEMICAL LP, Individually and) 7 as Successor-in-interest to ) SHELL CHEMICAL CORPORATION; ) 8 CONOCOPHILLIPS COMPANY, VON ) VERDE CITRUS PACKING HOUSE, ) 9 INC., an Arizona corporation;) VON VERDE HARVESTING, INC., a) 10 dissolved Arizona ) corporation; and VON VERDE ) 11 CITRUS GROWERS COOPERATIVE, ) INC., a dissolved Arizona ) 12 Corporation, ) Defendants. ) 13 14 15 REPORTER'S CERTIFICATE 16 ORAL VIDEOTAPED DEPOSITION OF ETHAN NATELSON, M.D. 17 September 25, 2009 18 19 I, Kelly Hanna, Certified Shorthand Reporter in and 20 for the State of Texas, hereby certify to the following: 21 That the witness, ETHAN NATELSON, M.D., was duly 22 sworn and that the transcript of the deposition is a 23 true record of the testimony given by the witness; 24 That the deposition transcript was duly submitted on 25 __________________ to the witness or to the attorney for 210 1 the witness for examination, signature, and return to me 2 by _______________________. 3 That pursuant to information given to the deposition 4 officer at the time said testimony was taken, the 5 following includes all parties of record and the amount 6 of time used by each party at the time of the 7 deposition: 8 Mr. Keith E. Patton (3h52m) Attorney for Plaintiffs 9 Mr. Stan Perry (0h0m) Attorney for Defendants 10 11 That a copy of this certificate was served on all 12 parties shown herein on ______________________ and filed 13 with the Clerk. 14 I further certify that I am neither counsel for, 15 related to, nor employed by any of the parties in the 16 action in which this proceeding was taken, and further 17 that I am not financially or otherwise interested in the 18 outcome of this action. 19 Further certification requirements pursuant to 20 Rule 203 of the Texas Code of Civil Procedure will be 21 complied with after they have occurred. 22 23 24 25 211 1 Certified to by me on this ______ day of 2 ___________________, ______. 3 4 5 6 7 8 ________________________________ Kelly Hanna, CSR, RPR, CRR, CMRS 9 Texas CSR 1654 Expiration: 12/31/2009 10 Firm No.: 69 2501 Oak Lawn 11 Suite 600 Dallas, Texas 75219 12 888.656.DEPO 13 14 15 16 17 18 19 20 21 22 23 24 25 212 1 FURTHER CERTIFICATION UNDER TRCP RULE 203 2 3 The original deposition was/was not returned to the 4 deposition officer on ______________________. 5 If returned, the attached Changes and Signature 6 page(s) contain(s) any changes and the reasons therefor. 7 If returned, the original deposition was delivered 8 to Mr. Keith E. Patton, Custodial Attorney. 9 $______ is the deposition officer's charges to the 10 Plaintiffs for preparing the original deposition and any 11 copies of exhibits; 12 The deposition was delivered in accordance with Rule 13 203.3, and a copy of this certificate, served on all 14 parties shown herein, was filed with the Clerk. 15 Certified to by me on this ______ day of 16 ______________________, ________. 17 18 19 20 _________________________________ Kelly Hanna, CSR, RPR, CRR, CMRS 21 Texas CSR 1654 Firm No.: 69 22 Expiration: 12/31/2009 2501 Oak Lawn 23 Suite 600 Dallas, Texas 75219 24 888.656.DEPO 25 213