Document DBxKkK0Onk7wk4820mqB0JeO

1 IN THE UNITED STATES DISTRICT COURT FOR THE EASTERN DISTRICT OF TEXAS 2 MARSHALL DIVISION 3 4 CHARLES WILSON and ) LAURA WILSON ) 5 Plaintiffs, ) ) 6 VS. ) Case No. 2:06:CV-286 ) 7 RYCOLINE PRODUCTS, ) INC.; et al., ) 8 Defendants. ) 9 10 11 ****************************************************** 12 ORAL DEPOSITION OF 13 DR. ETHAN NATELSON 14 SEPTEMBER 17, 2007 15 ****************************************************** 16 ORAL DEPOSITION of DR. ETHAN NATELSON, produced as 17 a witness at the instance of the Plaintiffs, and duly sworn, was taken in the above-styled and numbered cause 18 on SEPTEMBER 17, 2007, from 2:16 p.m. to 5:07 p.m., before Denyce M. Sanders, CSR, RPR, in and for the 19 State of Texas, recorded by machine shorthand, at the offices of THOMPSON & KNIGHT, 333 Clay Street, Suite 20 3300, Houston, Texas, pursuant to the Federal Rules of Civil Procedure and the provisions stated on the record 21 or attached hereto; that the deposition shall be read and signed before any notary public. 22 23 24 25 1 1 APPEARANCES 2 FOR THE PLAINTIFFS: 3 SCHMIDT & CLARK 4 2911 Turtle Creek Boulevard, Suite 1400 Dallas, Texas 75219 5 Mr. Keith Patton 6 FOR THE DEFENDANT ASHLAND, INC.: 7 THOMPSON & KNIGHT 8 333 Clay Street, Suite 3300 Houston, Texas 77002 9 Mr. Kevin Parks 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 2 1 EXAMINATION INDEX 2 3 WITNESS: DR. ETHAN NATELSON 4 EXAMINATION 5 BY MR. PATTON BY MR. PARKS 6 7 FURTHER EXAMINATION 8 BY MR. PATTON 9 SIGNATURE REQUESTED 10 11 REPORTER'S CERTIFICATION 12 13 EXHIBIT INDEX 14 15 NATELSON EXHIBIT NO. 1 16 NATELSON EXHIBIT NO. 2 17 NATELSON EXHIBIT NO. 3 18 NATELSON EXHIBIT NO. 4 19 NATELSON EXHIBIT NO. 5 20 NATELSON EXHIBIT NO. 6 21 NATELSON EXHIBIT NO. 7 22 NATELSON EXHIBIT NO. 8 23 NATELSON EXHIBIT NO. 9 24 NATELSON EXHIBIT NO. 10 25 NATELSON EXHIBIT NO. 11 PAGE 6 103 108 111 113 PAGE 57 58 59 60 60 61 62 63 63 64 3 1 NATELSON EXHIBIT NO. 12 2 NATELSON EXHIBIT NO. 13 3 NATELSON EXHIBIT NO. 14 4 NATELSON EXHIBIT NO. 15 5 NATELSON EXHIBIT NO. 16 6 NATELSON EXHIBIT NO. 17 7 NATELSON EXHIBIT NO. 18 8 NATELSON EXHIBIT NO. 19 9 NATELSON EXHIBIT NO. 20 10 NATELSON EXHIBIT NO. 21 11 NATELSON EXHIBIT NO. 22 12 NATELSON EXHIBIT NO. 23 13 NATELSON EXHIBIT NO. 24 14 NATELSON EXHIBIT NO. 25 15 NATELSON EXHIBIT NO. 26 16 NATELSON EXHIBIT NO. 27 17 NATELSON EXHIBIT NO. 28 18 NATELSON EXHIBIT NO. 29 19 NATELSON EXHIBIT NO. 30 20 NATELSON EXHIBIT NO. 31 21 NATELSON EXHIBIT NO. 32 22 NATELSON EXHIBIT NO. 33 23 NATELSON EXHIBIT NO. 34 24 NATELSON EXHIBIT NO. 35 25 NATELSON EXHIBIT NO. 36 4 65 65 65 66 66 67 67 67 68 68 69 69 69 69 69 69 73 74 74 74 76 77 80 80 81 1 NATELSON EXHIBIT NO. 37 2 NATELSON EXHIBIT NO. 38 3 NATELSON EXHIBIT NO. 39 4 NATELSON EXHIBIT NO. 40 5 NATELSON EXHIBIT NO. 41 6 NATELSON EXHIBIT NO. 42 7 NATELSON EXHIBIT NO. 43 8 NATELSON EXHIBIT NO. 44 9 NATELSON EXHIBIT NO. 45 10 NATELSON EXHIBIT NO. 46 11 NATELSON EXHIBIT NO. 47 12 NATELSON EXHIBIT NO. 48 13 NATELSON EXHIBIT NO. 49 14 NATELSON EXHIBIT NO. 50 15 16 17 18 19 20 21 22 23 24 25 5 93 93 93 94 94 95 95 95 1 DR. ETHAN NATELSON, 2 having been first duly sworn, testified as follows: 3 EXAMINATION 4 BY MR. PATTON: 5 Q. Please introduce yourself for the record. 6 A. My name is Ethan A. Natelson. 7 Q. You are a doctor, correct? 8 A. Correct. 9 Q. Tell us what kind of doctor you are. 10 MR. PARKS: Before we get into that, 11 we'll agree that the deposition is pursuant to the 12 Federal Rules and the witness will read and sign the 13 transcript? 14 MR. PATTON: Agreed. 15 Q. (BY MR. PATTON) Please introduce yourself. 16 A. I'm -- as I said, my name is Ethan A. 17 Natelson. I'm a hematologist. 18 Q. And how long have you been a hematologist? 19 A. I did a fellowship in 1969; and since that 20 time, I've more exclusively seen hematology-type 21 patients. 22 Q. As we sit here today, do you have a clinical 23 practice where you see hematology patients on a daily 24 and weekly basis? 25 A. Yes. 6 1 Q. And where is your practice at? 2 A. At the Methodist Hospital. The address is 3 6550 Fannin Street. 4 Q. You are a hired expert in this case, correct? 5 A. Yes. 6 Q. Hired by Ashland, correct? 7 A. Indirectly. Hired by Ricky Raven, but Ashland 8 is the company of record. 9 Q. Okay. How much are you being paid for your 10 time on the case? 11 A. I normally charge $250 an hour to review 12 records and $400 an hour for deposition testimony. 13 Q. And as we sit here today, we marked some 14 exhibits before we started; and Exhibit 50 appears to 15 be your invoicing and billing records, correct? 16 A. Yes. 17 Q. How much time did you spend on this case prior 18 to writing your report? 19 A. I can't tell you that exactly. It's not noted 20 on here, but the total hours are about 15 hours that 21 are listed here; and probably between 10 and 15 hours, 22 I would say, when the report was actually written. 23 Q. Before September 8, appears you've had ten 24 hours total in the case? 25 A. Yes. 7 1 Q. And since September 8, you've spent about five 2 hours before coming here for your deposition? 3 A. Yes. 4 Q. And that includes four hours to prepare for 5 your deposition? 6 A. Yes. 7 Q. Have you been asked to testify at trial in 8 this case? 9 A. I don't recall that. But that's, essentially, 10 a given. In other words, if I agree to be involved in 11 a case, I typically agree to testify at trial. 12 Q. Do you know when this case is set for trial? 13 A. No. 14 Q. You have served as an expert witness in 15 benzene cases before, correct? 16 A. Yes. 17 Q. Have you ever testified in any cases involving 18 MDS or myelodysplastic syndrome? 19 A. I have to look at the list to be certain about 20 that. 21 Q. Okay. We can go over that a little bit later. 22 Before we go on to it more later, have you ever 23 testified on behalf of a plaintiff in a chemical 24 exposure case? 25 A. No. 8 1 Q. Have you ever given the opinion in any 2 litigation that benzene caused a person's given 3 disease, whatever that disease may be? 4 A. No. 5 Q. Is it your opinion in this case that Charles 6 Wilson's MDS is not related to any benzene exposure? 7 A. He has a form -- he has an illness that can be 8 classified as a form of MDS. I don't believe that 9 particular illness can be caused by benzene. 10 Q. Just so I have your opinions clear. It's your 11 opinion in this case, that Charles Wilson's MDS/RARS is 12 not related to any exposure to benzene? 13 A. Yes. That's correct. 14 Q. Stated another way, you will testify at trial 15 in this case that benzene exposure played absolutely 16 zero causative factor in Charles Wilson's MDS or RARS, 17 correct? 18 A. There's no "or." He has one illness, which is 19 RARS; and I don't believe that benzene is related to 20 that illness. 21 Q. Okay. My question is a little more specific. 22 Do you believe that benzene in any way caused or 23 contribute or played any causative factor in Charles 24 Wilson's RARS? 25 A. No. 9 1 Q. Do you, as a clinical physician, ever use a 2 differential diagnosis as a tool for analyzing 3 causation? 4 A. Yes. 5 Q. What is a differential diagnosis? 6 A. Well, we look at the evidence from the case 7 and that could be historical information from the 8 patient, physical findings, laboratory studies, and we 9 try to find a best fit. In other words, illnesses 10 might cause the constellation of findings that we see 11 and then we try to prove that by a particular test or 12 study. 13 Q. Did you, in examining and preparing your 14 opinions in this case, do any sort of differential 15 diagnosis analysis? 16 A. Well, in a sense, someone has an illness like 17 RARS, what you're looking for, are there any, let's 18 say, factors that might give you ringed sideroblasts in 19 the bone marrow, for example, that might suggest that 20 diagnosis is due to an alternate cause than what we 21 consider idiopathic. 22 Q. Okay. And did you do that in this case? 23 A. Yes. 24 Q. And what are the possible causes of RARS? 25 A. Well, one can see large numbers of ringed 10 1 sideroblasts in people who have lead poisoning. And 2 it's -- the bone marrow is not exactly similar. It's 3 similar in the respect that there can be large numbers 4 of ringed sideroblasts, but lead poisoning is more of 5 what we call a hemolytic anemia. And -- but 6 superficially it might be confused with RARS. 7 Q. Do you think lead poisoning caused Charles 8 Wilson's RARS? 9 A. No. 10 Q. Do you have any studies you can point us to 11 that say lead poisoning causes RARS? 12 A. Not that I bring today. As I said, lead 13 poisoning causes ringed sideroblasts in the bone 14 marrow. That's a well-known phenomenon. 15 Q. Benzene causes different forms of MDS; isn't 16 that also a well-known phenomenon? 17 A. Benzene can cause certain forms of MDS, yes. 18 Q. Which forms of MDS can benzene cause? 19 A. Well, the literature tells us that the -- the 20 myelodysplasia that one can see from benzene is very 21 similar to the myelodysplasia that one sees from 22 chemotherapy drugs and, that is, in most instances, 23 it's what we call a hypoplastic form of MDS, meaning 24 that the cellularity of the bone marrow is reduced. 25 And in all forms of MDS, as time goes by, the 11 1 bone marrow can slowly convert to an acute leukemia 2 picture; and so under the MDS classification, if one 3 uses that classification, there are sort of weigh 4 stations on the way; and the normal bone marrow might 5 have, let's say, 1 or 2 percent blast cells. If the 6 bone marrow starts to go bad and develops at least 5 7 percent blast cells, it's sometimes referred to as 8 refractory anemia with excess blasts under the type 1. 9 Under the current modification of that system, 10 if the blast count comes up to close to 19 percent, 11 it's RAEB type 2. If it gets to 20 percent blasts, we 12 call it acute leukemia. So the -- I would say that 13 looking at it purely on a morphologic basis, benzene 14 could form a hypoplastic type of myelodysplasia. It 15 can form a refractory anemia with excess blasts, RAEB 16 situation, and that could progress to an acute 17 leukemia. 18 Q. So you would agree with me that benzene can 19 cause RAEB? 20 A. Yes. 21 Q. Benzene can cause RAEB in transformation? 22 A. Well, that term isn't used anymore, but it -23 I would say yes, in general terms, although that term 24 is now obsolete. 25 Q. You believe benzene does not cause refractory 12 1 anemia, that subtype of MDS, correct? 2 A. Oh, primary refractory anemia, I -- I don't 3 know the answer to that. I would think it might. 4 Q. But benzene does not cause RARS, correct? 5 A. It does not cause RARS. 6 Q. If a patient has RARS, could their disease 7 turn into RAEB? 8 A. Yes. 9 Q. Okay. So as they have RARS, your opinion 10 would be, there's no way benzene could cause that RARS, 11 correct? 12 A. If the illness began as RARS, that is not a 13 benzene-caused illness; and you get into a difference 14 in the way hematologists and sometimes epidemiologists 15 look at things. To me, RARS is a disease continuum. 16 And in some people, it will pass through stages where 17 it -- there's a blast accumulation stage, there might 18 be, let's say, a honeymoon stage, in which the bone 19 marrow shows no increase in blasts. It might pass 20 through a blast stage, it might pass into an 21 erythroleukemia stage. It's still the same illness. 22 It's one illness. I guess the best example would be 23 someone with hepatitis C, may have acute hepatitis, 24 then they may get a chronic hepatitis and then they may 25 get cirrhosis. It's still hepatitis C. It's the same 13 1 illness. You're just looking at different phases of 2 the same process. 3 Q. RARS is one form of the MDS process, correct? 4 A. RARS can be classified as a type of MDS. 5 Q. Is itself a form of the -- of the MDS process? 6 MR. PARKS: Objection. Form. 7 A. Process. That would be -- it is a disease 8 that can be classified as myelodysplasia. 9 Q. (BY MR. PATTON) Okay. Two patients walk into 10 your office -- you have a clinical practice, right? 11 A. Yes. 12 Q. And you have treatment rooms, correct? 13 A. Yes. 14 Q. Okay. And sometimes you'll have one patient 15 in one room and one patient in another room and you'll 16 go back and forth or see one before the other, right? 17 A. Yes. 18 Q. Okay. Let's say we have a patient in room 1, 19 okay, and the patient in room 1 comes to you and just 20 came in, just diagnosed him, he has RARS. Okay? You 21 would tell that patient -- or you could tell that 22 patient, if the topic came up, that patient number 1, 23 benzene played no causal role in RARS because benzene 24 doesn't cause RARS; you can tell that person that, 25 right? 14 1 A. Correct. 2 Q. Okay. Less go to over to room 2, okay? 3 Patient in room 2 has RAEB. Okay? 4 A. Yes. 5 Q. You can tell the patient in room 2, hey, you 6 have RAEB, which is caused by benzene exposure, 7 correct -- possibly caused by benzene exposure? 8 A. Possibly. You know, I have to qualify that 9 because let's assume I looked at the bone marrow under 10 the microscope, all right? And in that bone marrow, I 11 saw 15 percent ringed sideroblasts but I also saw 5 12 percent blast forms. That diagnosis, by the MDS 13 classification, would be RAEB; but I wouldn't know the 14 real diagnosis is RARS. 15 Q. So, wait a minute. How is it somebody could 16 have RARS or RAEB and you don't know? 17 A. It's because of the fact that that's one of 18 the -- one of the bad features of the MDS designation 19 is that it's purely based on morphology, not on the 20 clinical history of the patient. In other words, when 21 a person gets refractory anemia with ringed 22 sideroblasts, generally speaking, the bone marrow 23 avidly holds on to those ringed sideroblasts, even as 24 it passes on into RAEB classification; and sometimes 25 even if it passes into erythroleukemia. But we see the 15 1 fingerprints, the ringed sideroblasts at each stage. 2 So if I looked at a bone marrow that had 5 3 percent blast cells and was MDS-type bone marrow, 4 technically, that's classified as RAEB. But I would 5 know that it's different than an RAEB that I saw with 6 no ringed sideroblasts in the bone marrow because I see 7 the fingerprint. 8 Q. Somebody could come in your office, the 9 patient in room 2 with RAEB and he could have RAEB with 10 no ringed sideroblasts, correct? 11 A. Correct. 12 Q. And you could look at his bone marrow and you 13 could say, all right, there's no way patient number 2 14 here ever had ringed sideroblasts and there's no way 15 he's ever going to have ringed sideroblasts; is that a 16 fair statement? 17 A. That's correct. 18 Q. Okay. So someone with RAEB would never 19 develop -- he would -- patient number 2, with RAEB, 20 could never come back into your office six months later 21 and all of a sudden show some ringed sideroblasts; is 22 that your testimony? 23 A. Could not show 15 percent or greater of ringed 24 sideroblasts. 25 Q. What's the significance of 15 percent or 16 1 greater? 2 A. Because it's a large number. 15 percent is 3 the general number that the World Health authority has 4 put that minimum criteria to make a diagnosis of RARS. 5 Actually, when you see RARS bone marrows, sometimes 6 they'll be 30 percent ringed sideroblasts, sometimes 7 virtually every cell looks like a ringed sideroblast. 8 But the official criteria, just like we talked 9 about 5 percent blast cells to make you RAEB, you need 10 to have 15 percent ringed sideroblasts to make you an 11 RARS. 12 Q. Is it possible for a patient to present with 13 RAEB and then come back later and have RARS? 14 A. No. 15 Q. Impossible? 16 A. Well, I've never seen or read of such an 17 event. 18 Q. Can someone start with RARS and develop into 19 RAEB? 20 A. Yes. 21 Q. Once somebody starts with RARS, the patient in 22 room 1, who you would say no way benzene played a 23 possible causative factor, once they transformed into 24 RAEB, would you then tell that person, hey, I know you 25 used to have RARS, no benzene relationship there, 17 1 however, now you have RAEB which could be caused by 2 benzene; could you tell that patient that? 3 A. No. 4 Q. Why not? 5 A. Because I know that they had RARS and I know 6 that they're just going through the natural history of 7 the illness. 8 Q. And the natural history of the illness is to 9 do what? 10 A. The natural history of the illness, in most 11 people with RARS, the first manifestation is severe 12 anemia. And as time goes by, in certain of the 13 patients, you get into a proliferative stage where you 14 start growing bad looking white cells, not just bad 15 looking red cells, and you may start to accumulate 16 blast cells; and then you may further deteriorate your 17 marrow function and accumulate large numbers of blasts 18 and be classified as acute leukemia. Those three 19 stages of RARS have been recognized for 50 years. 20 Q. Before we started your deposition, you and I 21 marked Exhibits 1 through 42 and those are all the 22 references you cited in support of your opinions in 23 your report, correct? 24 A. Yes. 25 Q. Where is the piece of authority in there that 18 1 says RARS can turn into RAEB and because it keeps the 2 ringed sideroblast fingerprint, there's no way it's 3 related to benzene. Which study are we relying on in 4 support of that contention? 5 A. There are some articles that say that it's a 6 continuum illness. But I don't know of any article 7 that says, that this continuum illness, as it passes 8 through these stages, is -- is -- has anything to do 9 with benzene. In other words, that's not typically 10 addressed. 11 Q. Benzene as a causative factor of the subtypes 12 of MDS is not typically addressed in the scientific 13 literature, correct? 14 MR. PARKS: Objection. Form. 15 A. Yes, it is. 16 Q. (BY MR. PATTON) You're talking about Strom 17 2005? 18 A. No. In other words, for example, Linet's 19 article talks about what -- what -- what myelodysplasia 20 from benzene might look like. Let's find what she says 21 here. 22 In Linet's article, which is entitled, 23 "Clinical Features of Hematopoietic Malignancies and 24 Related Disorders among Benzene-exposed Workers in 25 China, she says, "Overall, findings for benzene-exposed 19 1 workers with myelodysplastic syndromes, included bone 2 marrow hypocellularity and marked dyserythropoietic 3 features such as multinuclearity, megaloblastoid 4 changes, impaired hemoglobinization, abnormal nuclear 5 shape, and dimorphic morphology of red cells." 6 She, as others have said, that the usual 7 finding in benzene-related marrows with myelodysplasia, 8 as it is for chemotherapy-related myelodysplasia, is 9 hypoplasia reduced cellularity. And no one has shown 10 ringed sideroblasts in benzene-poisoned bone marrow. 11 Q. What you just said was from page 1355 of the 12 Linet study, correct? 13 A. Yes. 14 Q. And it starts off -- the portion you were 15 reading from, the portion you highlighted, correct? 16 A. Yes. 17 Q. And it starts off in the left-hand column, 18 "Myelodysplastic syndromes, evident among seven 19 patients based on review of histopathologic tissue or 20 reports, included refractory anemia, refractory anemia 21 with excess blasts, and chronic myelomonocytic 22 leukemia, with subclassification not possible in three 23 cases. 24 "Overall, findings for benzene-exposed workers 25 with MDS included" -- and then you went through that 20 1 with the big words that the court reporter enjoyed. 2 So this revealed -- this Linet study revealed 3 that benzene-exposed workers did have refractory 4 anemia, correct? 5 A. Well, this is -- when you have 74,000 people, 6 and you find one case of something, to demonstrate that 7 that's epidemiologic related, you can't get very far. 8 In other words, the incidences of CMML, for example, is 9 such, that if you took 74 members of the -- 74,000 10 people of the general population, you'd find at least 11 one case. 12 So the fact that she saw a case there, doesn't 13 prove it was related to benzene or not, it just shows 14 what she saw; and what she saw was no case that had 15 ringed sideroblasts. 16 Q. Okay. So she saw one that had, for instance, 17 refractory anemia or RAEB, that doesn't really mean 18 anything because it's 1 in 74,000, right? 19 A. That's correct. The numbers aren't there to 20 tell you anything. 21 Q. But the fact she found zero with RARS, that 22 doesn't mean anything either, does it? 23 A. It doesn't support the proposition that RARS 24 can be caused by benzene. 25 Q. Does this -- does this paper support the 21 1 proposition that benzene causes any bone marrow 2 disease? 3 A. Yes. Because she says that the typical 4 benzene-induced disease is reduced cellularity in 5 marrow. It damages the bone marrow. And the purpose 6 of their report was to indicate that they had a high 7 number of -- they believe they had an increased 8 incidence of AML. 9 Q. So this study confirms what we all know and 10 that's that benzene damages the bone marrow, correct? 11 A. Yes. 12 Q. And your testimony is the Linet study here 13 tells us that benzene damages the bone marrow by virtue 14 of reducing cellularity, correct? 15 A. Yes. 16 Q. And RARS, what's happening with the cells 17 there? Are they being reduced or increased? 18 A. Usually they're either normal to increased. 19 Q. Is it your opinion that when benzene damages 20 the bone marrow, the only way it damages it is to 21 reduce cellularity? 22 A. No. Benzene -- we -- it causes dyspoiesis, in 23 other words, difficulty of maturation, it can cause 24 chromosome abnormalities in the myeloid cells. So it 25 produces a number of types of changes in the bone 22 1 marrow. 2 Q. Okay. Let's talk about the types of changes 3 that benzene causes the bone marrow. Okay? 4 If benzene were to attack and injure the bone 5 marrow -- you agree with me benzene does attack and 6 injure the bone marrow, correct? 7 A. In high enough dose, yes. 8 Q. Okay. If we can talk about dose later. But 9 as far as benzene generally being a damaging agent, so 10 to speak, or an attacker on the bone marrow, if benzene 11 were to attack bone marrow, tell us the ways in which 12 it would attack it. You already said it would decrease 13 cellularity, right? 14 A. Yes. 15 Q. And what does that mean? 16 A. Well, benzene used to be used as a 17 chemotherapy agent for people with chronic leukemias. 18 When they had a very high white cell count, you would 19 put some benzene in a capsule. They would swallow it 20 and the white count would go down because it would 21 reduce bone marrow function. 22 Q. So at some time in the past, doctors would 23 actually treat increased cellularity by giving people a 24 little bit of benzene in a pill and that would 25 automatically knock down the cells? 23 1 A. It would be about a gram of benzene to two 2 grams, so it is a fair amount, but it could reduce the 3 cellularity, yes. 4 Q. Okay. So benzene decreases cellularity, 5 meaning less production of cells? 6 A. Less production of cells. 7 Q. And does that go for red cells and white 8 cells? 9 A. Yes. 10 Q. Bone marrow attacking the -- I'm sorry, 11 benzene attacking the bone marrow. What other ways can 12 it do it? 13 A. Well, the bone marrows in people with benzene 14 toxicity frequently have been cited as having increased 15 numbers of eosinophils. 16 Q. What are those? 17 A. They're a type of reddish granulated white 18 cell that we sometimes associate with allergic 19 reactions. It's a nonspecific finding. But several 20 reports suggest that an increase in eosinophils is seen 21 in the bone marrows of benzene-related people. 22 Q. So benzene can increase certain types of red 23 cells? 24 A. White cells. 25 Q. White cells? 24 1 A. Yeah. Eosinophils are white cells. 2 Q. Okay. So what else can benzene do to the bone 3 marrow? 4 A. Well, is -- benzene is a mutagenic agent. 5 Q. What does that mean? 6 A. Meaning that it can damage chromosomes. 7 Q. Okay. And chromosomes, that's DNA, right? 8 A. That is DNA. 9 Q. So benzene is known to damage chromosomes? 10 A. Yes. 11 Q. And chromosomes are part of our cells, right? 12 A. Yes. 13 Q. Okay. What else can benzene do to the bone 14 marrow? 15 A. Well, if the chromosome damage is substantial 16 enough, it may result in ultimately acute leukemia. 17 Q. And what is acute leukemia? 18 A. Well, acute leukemia is an unrestrained growth 19 of abnormal white cells. 20 Q. And what effect does that have on the body? 21 A. Well, the leukemic cells typically fill up the 22 bone marrow and they're essentially blanks. They don't 23 have any beneficial function; but by filling up the 24 bone marrow, they prevent the bone marrow from making 25 good cells which fight infection, fight bleeding and 25 1 carry oxygen. So a person with a bone marrow full of 2 blast cells or leukemic cells essentially has a 3 nonfunctional bone marrow. 4 Q. Okay. What else does benzene do to the bone 5 marrow? 6 A. Well, it can produce in high doses what's 7 called aplastic anemia, where the bone marrow stops 8 working for a long period of time or possibly an 9 indefinite period of time. 10 Q. Meaning the blood cell machine or factory in 11 the bone marrow absolutely shuts down? 12 A. Yes. 13 Q. Okay. What else can benzene do to the bone 14 marrow? 15 A. Well, it can produce morphologic 16 abnormalities, in other words, by interfering with cell 17 division, you can get abnormal looking cells under the 18 microscope. 19 Q. Interferes with the way cells divide and 20 reproduce? 21 A. Yes. 22 Q. Okay. What else can benzene do to the bone 23 marrow? 24 A. Those are the things that come to mind. 25 Q. Okay. If someone has RARS, what is going on 26 1 with their cells or their chromosomes? 2 A. Well, the typical patient with RARS, has what 3 we call ineffective erythropoiesis. In other words, 4 they're making plenty of cells in the bone marrow, but 5 the cells aren't maturing properly; and so what gets 6 out of the bone marrow to circulate is less than the 7 production that you would see it would suggest. 8 In other words, if I -- just to give a typical 9 example, if I give a normal person a small amount of 10 radioactive iron and I inject that into the blood, 11 within about 30 minutes it disappears and it goes into 12 the bone marrow. 13 Now, over the course of the next week, that 14 radioactive label appears in the circulating blood 15 inside newly-formed red cells, at about 90 percent of 16 it plus comes back out in labeled red cells. If I do 17 the same experiment with someone with sideroblastic 18 anemia, oftentimes about 10 percent of the label comes 19 back out. In other words, the cells are made and break 20 down and remade and break down, but my label -- but 21 they don't come out in the sense of well-formed blood 22 cells. So we call that ineffective erythropoiesis. 23 Q. When we're talking about MDS generally, that 24 classification of diseases, what are the cells or the 25 chromosomes doing or not doing in a patient with MDS? 27 1 A. Well, if you look at MDS in general -- on some 2 of the papers I cite give the numbers -- but there are 3 varying frequencies of chromosome abnormalities, 4 depending on the type, the subgroup of MDS. RARS 5 happens to have the lowest frequency of chromosome 6 abnormalities of any of these syndromes. They can 7 certainly have chromosome abnormalities and a number of 8 have been described, but most people with RARS have 9 normal chromosomes. 10 Q. Okay. What's happening to the cells of a 11 person with MDS? 12 A. Well, in a general sense, the cells are being 13 prevented from maturing properly and undergoing their 14 normal growth potential. 15 Q. If someone has refractory anemia, which is a 16 form of MDS, you would agree with me that their cells 17 are being prevented from maturing properly and/or not 18 growing to their potential, correct? 19 A. That's correct. 20 Q. Same with someone with RARS? 21 A. Similar, yes. 22 Q. Okay. And how is it different for RARS? 23 A. Because of the fact that we see large numbers 24 of ringed sideroblasts in the cells suggesting that 25 there's some primary defect in iron incorporation, that 28 1 iron is piling up in the red cell precursor and not 2 being manufactured into hemoglobin. 3 Q. So someone with RARS, just as someone with RA, 4 the RARS patient is showing you cells which are 5 prevented from maturing properly, they're not growing 6 to their potential, plus they have this little extra 7 signature that deals with iron, correct? 8 A. Yes. 9 Q. Okay. And then what about someone with RAEB? 10 Are their cells prevented from maturing properly and/or 11 not growing to potential? 12 A. Yes. But in RAEB, you're now developing a 13 measurable increase in the population of what we call 14 blast cells or blanks, as I referred to them before, 15 very immature cells that are not functioning. 16 Q. So when you look at RAEB under the microscope, 17 it shows you a little bit different signature than RARS 18 as far as what the cells are doing? 19 A. It's a different signature, yes. 20 Q. Okay. And then someone with RAEB-T or 21 RAEB-transformation to AML, what's the difference 22 there? 23 A. Simply it's a difference in more blast cells. 24 Q. And then CMML, that's a form of MDS, too, 25 right? 29 1 A. No. CMML is another disease like RARS that's 2 been known about for many, many years. In 1982 it was 3 put into the MDS category. It's since been taken out. 4 Most hematologists never thought it belonged there. 5 It's a myeloproliferative disease. There's tremendous 6 overproduction inside the bone marrow. 7 Q. Overproduction of cells in the bone marrow is 8 what characterizes CMML, correct? 9 A. Yes. Overproduction of particularly normal 10 looking granulocytes, and in a particular, monocytes, 11 another type of white blood cell. 12 Q. One with refractory anemia would be showing 13 you decreased cellularity; true? 14 A. No. People with refractory anemia could have 15 reduced cellularity or normal cellularity or even 16 occasionally slightly increased cellularity. 17 Q. Someone with RARS, their cells would be 18 showing you decreased cellularity? 19 A. No. There are usually increased numbers -20 normally -- well, overall cellularity of the bone 21 marrow is usually to normal -- normal to moderately 22 increased; and the increase is typically in red blood 23 cell precursors that contain the ringed sideroblasts. 24 Q. Benzene causes refractory anemia, correct -25 can cause? 30 1 A. I think so, yes. 2 Q. Can cause RAEB, right? 3 A. Yes. 4 Q. Can cause CMML? 5 A. There's no evidence for that. 6 Q. Okay. But that's not a myelodysplastic 7 syndrome? 8 A. No. It's a myeloproliferative disease. 9 Q. Okay. And benzene does cause RAEB? 10 A. Yes. It does cause RAEB. 11 Q. Benzene causes AML? 12 A. Yes. 13 Q. Someone with RARS could develop into AML? 14 A. Yes. 15 Q. If Mr. Wilson, his disease of RARS developed 16 into AML, would your opinion be no way it could be 17 caused by benzene exposure because it had the RS 18 signature on it, therefore his AML could in no way be 19 caused by benzene exposure, would that be your opinion? 20 A. My opinion would be that this is part of the 21 natural history of the illness. 22 Q. What if someone came into your office and went 23 into the exam room and you looked at -- you visited 24 with the patient, you looked at all their data, you 25 looked at all their labs and they had AML. Could you 31 1 tell from looking at their AML whether they went 2 through a ringed sideroblasts phase of refractory 3 anemia? 4 A. Usually not. 5 Q. Okay. So someone -- let's say Mr. Wilson, for 6 example -- no. Let's not use Mr. Wilson. Let's say 7 patient number 3. Okay? 8 Patient number 3 comes into your office, 9 presents with AML, and you look at the data and you 10 can't tell whether or not he went through an RARS phase 11 before he got to AML; true? 12 A. Well, when you say that, in other words, RARS 13 is going to cause certain things. In other words, if 14 we know and have blood counts from six months ago or a 15 year ago that were perfectly normal, we would know he 16 didn't have RARS. Now he's got acute leukemia. So 17 part of that would be the history and the records we 18 have. 19 Q. What if a patient came into your office, never 20 saw a doctor before in his life, okay, no prior blood 21 test, no -- no nothing, okay, and he had AML. Is it 22 possible that his body went through an MDS phase before 23 becoming AML? 24 A. Yes. 25 Q. Is it possible that his body went through an 32 1 MDS phase such that for one reason or another, he 2 didn't get treated for it and all of a sudden here he 3 is with AML; possible? 4 A. Yes. 5 Q. What about someone who has RARS, untreated, 6 doesn't go to the doctor, no lab work, shows up with 7 AML. Is it possible that that AML patient that you saw 8 could have RARS before they got to AML, correct? 9 A. Yes. 10 Q. And so in that instance, if someone has AML 11 and you don't know what they had before, you can't 12 exclude benzene as a cause, right? 13 A. Well, in anybody with AML, we can't say with 14 certainty of what the cause was. We can only talk 15 about in probabilities. And so when I see a case of 16 AML, I can't say with 100 percent certainty what the 17 cause is. I can only talk in what is likely and what 18 is not likely. 19 Q. And what is possible? 20 A. And what is possible. 21 Q. So if someone comes in with RARS, you can say 22 with confidence that you believe that there's no way 23 benzene played any causative role in RARS, correct? 24 A. Correct. 25 Q. Someone could come into your office and their 33 1 RARS developed naturally into AML, and you would tell 2 them, your AML is possibly related to benzene exposure; 3 true? 4 MR. PARKS: Objection. Form. 5 A. Well, it would depend on their history. In 6 other words, if they had a -- a heavy benzene exposure 7 history and they have AML, that's always a 8 consideration depending on a number of features. 9 Q. (BY MR. PATTON) How many people in your career 10 have you diagnosed with MDS? Approximately. 11 A. Well, it's a fairly common illness. I could 12 say easily 100 or 150. 13 Q. 100 to 150 patients with MDS who you 14 diagnosed, right? 15 A. Yes. 16 Q. Can you estimate of that number approximately 17 how many had RARS? 18 A. Well, I think my figures would be not much 19 different than that's in the literature. I'd say 20 probably 15 to 18 percent. 21 Q. Okay. My question is a little more specific, 22 though. How many did you diagnose with RARS? 23 A. Well, I thought I answered that. Let's assume 24 I saw 100 people with RARS. Probably 15 to 18 of 25 them -- 100 people with MDS, 15 or 18 of them would 34 1 have RARS. That's the usual percentage. It's not a 2 common form of myelodysplasia but it's not rare either. 3 Q. Every MDS patient you've seen, have you told 4 them, hey, you have MDS and you have a certain subtype 5 of MDS? 6 A. Typically, yes, if I can. In other words, MDS 7 frequently is unclassifiable. The -- the illness 8 doesn't neatly fit into one category or another. 9 Q. Someone could come into your office and into a 10 treatment room -- we'll call them patient number 4 -11 and patient number 4, you can say you have a 12 myelodysplastic syndrome. And they would say, well, 13 what is a myelodysplastic syndrome and what would you 14 tell them? 15 A. I'd say it's a disordered blood cell 16 production in the bone marrow. 17 Q. You have a disorder -- patient number 4, you 18 have a disordered blood cell production? 19 A. I would tell them they have a sick bone marrow 20 or disorder of bone marrow function. That might 21 venture into acute leukemia. 22 Q. Someone with MDS has a sick bone marrow, 23 right? 24 A. Yes. 25 Q. Could you tell patient number 4 which subtype 35 1 he has? 2 A. Patient number 4 is someone who just came off 3 the street with AML? 4 Q. With MDS. 5 A. Oh, with MDS. Well, it would depend on the 6 characteristics of the bone marrow. 7 Q. You could look at his bone marrow and for sure 8 class him as RA, RARS, RAEB or RAEB-T, right? 9 A. Or none of those. Just like the article from 10 the Chinese of benzene study. They said some were 11 unclassifiable. 12 Q. What makes a MDS unclassifiable? 13 A. Well, generally we -- where we have sometimes 14 trouble classifying them is when a bone marrow has very 15 reduced cellularity but the cells are maturing, that's 16 to say they look normal, there just aren't enough of 17 them; and sometimes is very difficult to separate MDS 18 from what we call aplastic anemia. It depends on a 19 number of features and we look for other things that 20 might suggest MDS, such as a chromosomal normality or 21 responds to a particular form of treatment. 22 And -- but hypoplastic -- severe hypoplastic 23 MDS is very difficult to separate out from aplastic 24 anemia. 25 Q. What's hypoplastic mean again? 36 1 A. Very reduced cells. In other words, it's not 2 unusual to see a myelodysplasia bone marrow that only 3 has, let's say, 20 percent of normal cellularity. An 4 aplastic anemia bone marrow may have 5 percent of 5 normal cellularity. 6 Q. What percentage of normal cellularity did 7 Charles Wilson have? 8 A. I've never seen his slides. I've asked 9 Mr. Raven to get me his slides, but we could look at 10 his bone marrow report and see what they said. 11 MR. PATTON: Let's take a break. Off the 12 record. 13 (Break.) 14 Q. (BY MR. PATTON) Dr. Natelson, which of the 42 15 references to your report says, in effect, benzene does 16 not cause or cannot cause RARS? 17 A. Well, the paper I wrote says that. 18 Q. Okay. Where is your paper at? 19 A. It's in here. It's in here. Okay. 20 Q. You wrote this paper in 2007? 21 A. I don't remember when I wrote it. Probably 22 could be early 2007 or late 2006. This journal has had 23 it for a long while. They -- they accepted it, but 24 then I never got the galley proofs and finally they 25 said it's going to go into a particular issue. 37 1 Q. And this is Exhibit 14, your paper? 2 A. Yes. 3 Q. You testified in litigation on a couple of 4 occasions before drafting this paper, that benzene did 5 not cause a given person's RARS, right? 6 A. Yes. 7 Q. You say here on page 2, "A critical review of 8 the refractory sideroblastic disorders strongly 9 suggests that benzene exposure is not a potential cause 10 of this distinct and still-evolving subset of MDS." 11 A. Yes. 12 Q. You said that, right? 13 A. Yes. 14 Q. RARS is a type of -- I'm sorry. RARS is a 15 type of refractory sideroblastic disorder, right? 16 A. Yes. 17 Q. Are there additional subtypes of -- let me ask 18 my question more clearly. 19 Are there -- how many different types of 20 refractory sideroblastic disorders are there? 21 A. Well, I suppose it depends on who you ask; but 22 generally there are three types now that people like to 23 talk about. The first type is what has undergone 24 several different names. Currently it's RARS. And 25 what that refers to is a bone marrow that has the 38 1 ringed sideroblasts in there, but very little 2 dyspoiesis or abnormal cells outside the red cell line. 3 Some people call this pure sideroblastic anemia or 4 RARS. 5 And in recent years, the -- the World Health 6 authority has separated this form of RARS from patients 7 with RARS who have funny looking white cells or 8 platelets, and that's referred to as RARS with -- I 9 have to look at my paper -- with -- morphologic 10 abnormality. They have a euphemism for what it is. 11 But it's a type of RARS where there are morphologic 12 abnormalities in multilineage cells; in other words, 13 it's not just the red cell precursors. 14 Personally, I think what they're doing is 15 describing two different ends of a bell-shaped curve. 16 But some people set great store by this. 17 Q. And what's the third type? 18 A. The third type -- it's been known for many, 19 many years that some patients with RARS have an 20 extremely cellular bone marrow with some degree of 21 myelofibrosis in it and very large numbers of 22 platelets. 23 Q. So what do they call this one? 24 A. RARS-T for thrombocythemia. And that 25 particular one is of interest because a newly-described 39 1 molecular marker, may be called the JAK-2 marker may be 2 positive in that form, and the JAK-2 marker is possible 3 in many patients with myeloproliferative diseases. In 4 other words, 95 percent of people with polycythemia 5 vera have a possible JAK-2 study, and it's become a 6 standard way of confirming that diagnosis. 7 That was the illness in the Mielke case you 8 mentioned. In -- in this situation, this is sort of a 9 crossover. There are people with RARS who have the 10 JAK-2 abnormality, and so they're put into a category 11 of RARS-T. So those would be the three distinctions. 12 Q. Okay. Does RAEB have further distinctions? 13 A. No. 14 Q. Does -15 A. Excuse me. I take that back. The original 16 RAEB did not. The current modern one has a type 1 and 17 a type 2 based on the presence of -- the frequency of 18 blast cells. In other words, with -- with small 19 increase in blast cells is RAEB 1; with a larger 20 increase, it's RAEB 2. 21 Q. Does AML have subtypes? 22 A. Yes. 23 Q. How many different subtypes of AML are there? 24 A. Well, generally seven types of subtypes you 25 have under the -- what's called the FAB or 40 1 French-American-British classification. 2 Q. What are the seven subtypes of AML under the 3 FAB? 4 A. Well, the -- the distinctions are -- some of 5 them are quite distinct. The M-3 is the -- what we 6 call promyelocytic leukemia. And the M-7 is the -- I 7 believe erythroleukemia, and then some people say M-8 8 for megakaryocytic leukemia. And the remainder are 9 various forms of AML with little differentiation in 10 the -- in the blast cells or sort of a monocytic 11 designation, I believe, M-5 is a pure monocytic 12 leukemia and M-0 are leukemias that are very primitive 13 looking and so on. 14 So the distinctive ones, really, are 15 promyelocytic leukemia, which actually may not have 16 much increase in blasts and, of course, erythroleukemia 17 and megakaryocytic leukemia. 18 Q. And there's an M-4 type of AML, right? 19 A. M-4, myelomonocytic leukemia, and it's 20 interesting because today, the -- this FAB distinction 21 is less and less of importance and we're looking more 22 at chromosome abnormalities; and treatment is 23 predicated a little differently than it used to be. 24 Q. Is there an M-1 or a M-2 type? 25 A. M-0, M-1, M-2, they're all AMLs with a small 41 1 amount of differentiation. M-0 has virtually none, M-1 2 a little more and M-2 a little more and so on. 3 Q. Let's take an example of M-4 AML. 4 A. Yeah. 5 Q. Are there further subtypes of AML M-4? 6 A. No. 7 Q. Are there further subtypes of M-3? 8 A. Yes. In promyelocytic leukemia, sometimes one 9 form is large granular-type and the other is sort of 10 normal granular type. 11 Q. So there's two subtypes of M-3 AML? 12 A. Yeah. 13 Q. How about M-7 AML? 14 A. Erythroleukemia, no. Usually erythroleukemia 15 is a erythroleukemia. 16 Q. What about M-8? Are there any subtypes with 17 M-8? 18 A. Well, it depends on who you look at. Some 19 people with -- have a very peculiar form of leukemia 20 that's called acute myelofibrosis and some people 21 believe that's an M-8 leukemia and some believe it's 22 not. It's an unusual leukemia where the bone marrow 23 very quickly fills up with fibrous tissue and blasts 24 and runs a very acute course. It clearly is an acute 25 leukemia, but it's distinct from many of the other 42 1 forms of acute leukemia. 2 Q. So there are a couple of subtypes within M-8? 3 A. Yes, I think so. 4 Q. What about M-5? Are there subtypes within 5 that? 6 A. Pure monocytic leukemia, no. That's generally 7 the same. I mean, there -- there are, of course, 8 different chromosome arrays in their leukemias, but 9 that doesn't change the FAB classification. 10 Q. But if we wanted to stratify and look at each 11 possible smaller layer, we could look at, for example, 12 in M-8 -- we could look at an AML, M-3, subtype 1 with 13 certain chromosomal features; and we could further -14 A. You could, although in M-3, there's a 15 particular translocation that's very common, the 1517 16 translocation that's characteristic of both morphologic 17 types. So they're not -- that particular illness isn't 18 segregated by chromosomes, but it is by morphology. 19 Q. What about M-0 leukemia? Any subtypes in 20 that? 21 A. No. 22 Q. M-4? 23 A. No. 24 Q. There are no subtypes of M-4? 25 A. Well, all leukemias may have a different 43 1 chromosome array; and in leukemia, the feature that is 2 most prominent about determining prognosis is the 3 chromosome array. And so certain chromosomes are 4 considered good. Like inversion 16, for example, or 5 the 8 to 21 translocation or promyelocytic leukemia, 6 those are all -- the treatment is highly effective; 7 whereas, leukemias that have loss of the seventh or 8 part or all of the seventh chromosome are less 9 favorable. 10 Q. What about M-1 or M-2? Are there any subtypes 11 within those? 12 A. Well, they would have different chromosomes; 13 and, again, the prognostic subdivision is, these days, 14 more in order of what the chromosome analysis is. 15 Q. Benzene causes -- or can cause AML, correct? 16 A. Yes. 17 Q. You've never testified in litigation that 18 benzene caused a certain plaintiff's AML? 19 A. That's correct. 20 Q. And opining in AML cases, that benzene was not 21 a cause of the worker's AML, did you ever give that 22 opinion based on the type of subtype or the type of 23 chromosomal array that was present for that given 24 worker? 25 A. I may have, yes. 44 1 Q. So that's to say that in opining in AML cases 2 that benzene did not cause this worker's AML, you might 3 have opined in that regard based on -- based on the 4 amount of exposure, right? 5 A. Only in part. A typical example might be an 6 acute leukemia with inversion 16. And that's never 7 been described from benzene exposure at any dose level. 8 And so that doesn't mean that it can't cause that, it 9 just means that it's not very likely. And as I said, I 10 can only talk in probabilities. So faced with someone 11 with, let's say, an inversion 16 leukemia and we know 12 that 80 or 90 percent of them are de novo, not caused 13 by any benzene exposure and we know it's never been 14 described with benzene exposure, obviously more 15 commonly than not, it's going to be not benzene 16 exposure. And then, of course, you add in what is the 17 exposure and that has some pertinence, too. 18 Q. What kind of AML does benzene cause? 19 A. Well, the AML that benzene causes is really no 20 different than AML that can be caused by modern day 21 chemotherapy. It's -- it's a kind of a leukemia that 22 typically has chromosomal abnormalities. Most of them 23 involving the fifth and the seventh chromosome. There 24 could be others. 25 It's a person who has very high exposures to 45 1 benzene, very high cumulative part-per-million 2 exposure. And it's a form of acute myeloid leukemia, 3 as opposed to acute lymphoblastic or chronic leukemia. 4 So it's an acute myeloid leukemia in the setting of a 5 very high benzene exposure that -- that might be 6 characterized by a 5 or a 7 chromosome abnormality. 7 Q. What if a patient has a 5 or a 7 chromosomal 8 abnormality and an inversion 16 and exposures, let's 9 say they have 400 ppm years of cumulative exposure, 10 would you give the opinion that benzene was a possible 11 cause of that person's AML? 12 A. It depends on the sequence, for example. You 13 see, chromosome abnormalities beget other 14 abnormalities. So what you commonly see is someone may 15 come in with a single chromosome abnormality; and as 16 they're treated with chemicals and go into remission 17 and relapse, they start to accumulate more and more 18 abnormalities. 19 Well, that's simply -- those abnormalities are 20 sort of not the primary event. They're secondary 21 phenomenon. The key phenomenon is what is the original 22 abnormality. So if someone presented with an inversion 23 16, regardless of what happened down the line in their 24 chromosome array, that's not likely to be benzene 25 induced. 46 1 Q. You've never testified that benzene caused a 2 given person's AML, correct? 3 A. Yes. 4 Q. Okay. Would you ever testify on behalf of a 5 plaintiff in a benzene exposure case? 6 A. Would I? I've never been asked to. 7 Q. If I wanted you to testify on behalf of a 8 plaintiff that I represent, what type of AML and what 9 type of chromosome abnormalities and what type of 10 exposure would I need to be able to present to you for 11 you to support causation? 12 MR. PARKS: Objection. Form. 13 A. It would have to be an AML. It would have to 14 be a person who had a very high benzene exposure. 15 Q. (BY MR. PATTON) How high? 16 A. Probably at least 100 part per million, 17 preferably 200 part per million. Very high exposure. 18 It would have to be an exposure that bore certain time 19 frame relevance to the leukemia. In other words, if 20 you showed me someone that 30 years ago had an exposure 21 and today has leukemia, I would say that doesn't fit 22 because benzene is a disease of short latency as is our 23 modern day chemotherapy. 24 So I would be looking at the latency involved, 25 the chromosome array, the benzene exposure, and when 47 1 you got all done with all of that, I could only say 2 it's possible this was due to benzene because in any 3 given case, there is no side in the leukemia that 4 proves one etiology over the other. 5 Q. Before we started talking about AML subtypes, 6 we were talking about your paper, Exhibit 14. 7 A. Yes. 8 Q. Besides your paper, Exhibit 14, what other 9 citations or authority do you have that say effectively 10 benzene does not cause RARS specifically? 11 A. Well, there are many such papers. I list them 12 in my paper and many of them are here. You can start 13 back with Wintrobe, whose textbooks we have here. 14 Dr. Wintrobe had a large personal series and an 15 interest in RARS; and he concluded, by carefully 16 questioning his patients, that benzene was not 17 associated with RARS. 18 Q. And is that in your exhibits? 19 A. That's in these first two articles dealing 20 with his situation. Then we talked about the fact that 21 in the Chinese, a benzene study of Hayes, there were a 22 large numbers of people, they had their bone marrow 23 slides reviewed. None of them had RARS. 24 In the work by Aksoy, Aksoy was a Turkish 25 hematologist, but he trained in the United States. And 48 1 he looked at people in the '70s; and at that time, iron 2 stains on the bone marrow and sideroblastic anemia was 3 well-known; and he carefully analyzed all the people he 4 saw with benzene exposure. There was no RARS. 5 In the Pliofilm study -- it's primarily on 6 death certificates, we don't have the original 7 slides -- there was no description of anybody with 8 RARS. So those are three studies where no one 9 identified anybody with RARS. 10 Then we have Dr. Irons' study in which he 11 looked at heavily exposed benzene people. Found bone 12 marrow abnormalities, specifically looked for RARS and 13 it wasn't there. And then we have the article by Ruiz, 14 who also had about 33 cases of people with heavy 15 benzene exposure that had sick bone marrows. He 16 specifically looked for RARS and said there were no 17 ringed sideroblasts. So all of these studies are 18 people exposed to high levels of benzene with 19 documented abnormalities in their marrow but no ringed 20 sideroblasts. 21 Then we have indirect evidence -22 Q. Let me stop you real quick. Hayes, Aksoy, the 23 Pliofilm study, Irons and Ruiz -24 A. Yeah. 25 Q. -- all looked at chromosome abnormalities? 49 1 A. No. They looked at morphology. They looked 2 to see if there were any ringed sideroblasts 3 identified, and they didn't find any. I believe Irons 4 did look at chromosomes and but -- and some -- some 5 patients in the Chinese study had chromosomes but not 6 many. 7 Then there are sort of indirect articles. For 8 example, one of those articles in here is a person took 9 84 people with RARS and he carefully questioned them as 10 to whether or not they had any benzene exposure. And 11 only one person did and that person also was radiated. 12 And so, essentially, benzene didn't look to be a 13 prominent factor in that group of 84 people with RARS. 14 Then we have the Strom article, and he (sic) did much 15 the same, questionnaire studies of people with RARS 16 compared with other forms of MDS. 17 And in that study, she concluded that -- that 18 there was no relationship with benzene exposure among 19 the group with sideroblastic anemia or CMML. And so 20 all of those studies -- when you come right down to it, 21 there isn't a single article in the world's literature, 22 not a case report, not an epidemiologic study, that 23 says RARS can be caused by benzene. 24 Q. You believe that benzene causes RAEB, right? 25 A. It may. 50 1 Q. Is there a single epidemiological study or 2 even an isolated case report in the world's medical 3 literature that shows RAEB may be related to or a 4 consequence of benzene exposure? 5 A. I believe in the Strom article they felt that 6 there was a relationship in their RAEB patients. 7 Q. What about unspecified types of MDS? Isn't 8 there support in the literature that benzene causes MDS 9 when MDS is not viewed in terms of subtypes? 10 MR. PARKS: Objection. Form. 11 A. Well, we -- there -- there isn't really epi -12 if you -- if benzene has to stand on its own feet, 13 there is no epidemiologic proof that benzene causes 14 myelodysplasia. We only assume that it does by analogy 15 to the fact that our chemotherapy drugs can cause 16 myelodysplasia, certain forms of it. So we have some 17 basis to think that benzene can. 18 So by analogy, we think benzene can because 19 our chemotherapy drugs, the modern day drugs can. When 20 we look at our modern chemotherapy drugs, they don't 21 cause RARS. So the plausibility disappears with 22 respect to RARS. 23 Q. (BY MR. PATTON) Based on the absence of -24 A. RARS from modern chemotherapy drugs. 25 Q. You said in your report that -- in bold that 51 1 you're unaware of any epi studies or even an isolated 2 case report. What about the cases you testified 3 involving RARS; those cases were before the Strom 4 study, correct? 5 A. Yes. 6 Q. Okay. And did you opine in those cases that 7 benzene was in no way any causative factor of the 8 person's RARS? 9 A. That's correct. 10 Q. Would you consider those prior cases that you 11 testified in -- certainly they're -- obviously they're 12 not case reports but aren't those incidences where a 13 person was exposed to benzene and it could have been a 14 causative factor? 15 A. Well, their alleged exposures, which have not 16 been subjected to peer review in a journal, where the 17 reviewers had a chance to look at the data to see if 18 they were realistic; and so the bottom line is, they're 19 not published. 20 Q. And if someone were to submit that type of 21 case report in a journal, would you act as a critic of 22 it and say, well, there's no way benzene causes RARS? 23 A. It depends on the case. For example, I don't 24 recall all of those cases, but if it's a person that 25 had nonmeasurable alleged benzene exposure 30 years ago 52 1 and now when he's 70, he has RARS, I wouldn't accept 2 that as a relationship. 3 Q. You call Charles Wilson's RARS -- you also 4 call it by the name AISA. What is that? 5 A. Well, over the years, people have used 6 different titles for this illness and sideroachrestic 7 anemia is an early one. Sideroachrestic means "iron 8 loving." Then people used to call it "acquired 9 sideroblastic anemia," meaning you didn't have it and 10 now you do. Then people used the term "idiopathic 11 acquired sideroblastic anemia," meaning we don't know 12 the cause. And then people have used the term "pure 13 sideroblastic anemia" and people have used the term 14 "RARS," or refractory anemia with ringed sideroblasts. 15 So this is an illness that is many, many names over 16 years; but to a hematologist, we -- we know what it is. 17 Q. What is a hematologic illness? 18 A. I would say it's a blood related illness. 19 Q. Which would include a bone marrow related 20 illness? 21 A. Which could include a bone marrow illness, 22 yes. 23 Q. How many different types of hematologic 24 illnesses are there? 25 A. Almost an infinite number. I, you know, 53 1 through my career, I've seen many, many different kinds 2 of hematologic illnesses. 3 Q. Thousands? Hundreds? 4 A. I've certainly seen probably in the -- I've 5 done, for example, I would say, somewhere between 5 and 6 7,000 bone marrows in my career. 7 Q. And they're all different? 8 A. Well, they're not all different, but the 9 they're all people with hematologic disorders. 10 Q. How many different types of hematologic 11 disorders are there? 12 A. I -- I've never stopped to count them. In 13 other words, there are three basic cell lines -- the 14 red cell line, the platelet line and the white cell 15 line. And each one of those cell lines has a myriad of 16 disorders that can be associated with it. And so there 17 would be a lot. 18 Q. Would you agree with the statement that 19 benzene generally is a possible cause of hematologic 20 illnesses? 21 A. Yes. 22 Q. How many different types of myelodysplastic 23 syndromes are there? 24 A. It depends on who's classification you look 25 at, and it keeps changing. And the original 54 1 classification was fairly simple, but it -- every few 2 years it's changed; and there are some proposed new 3 changes. 4 We look at the unclassified type, as we talked 5 about; two different -- or three different types of 6 sideroblastic anemias, two different types of 7 refractory anemia with excess blasts. Those are some 8 of the types. 9 Q. Are you familiar with, generally, the world's 10 literature on benzene as a cause or possible cause of 11 hematologic illnesses? 12 A. In general terms, yes. 13 Q. Could you estimate in general terms how many 14 different articles have been written on benzene as a 15 cause of hematologic illnesses? 16 A. I -- I couldn't hazard a guess. 17 Q. Over 10,000? 18 A. I doubt that. 19 Q. Over a thousand? 20 A. I don't know. 21 Q. How many articles are you aware of that 22 examine RARS in the context of what causes RARS 23 specifically? 24 A. Well, all of these articles that I cited 25 are -- are -- involved in some form or fashion like 55 1 that. 2 Q. Okay. Let's go through the articles that you 3 cite. 4 A. Yes. And let's start with first one. The 5 Kushner, 1971 article, yes. 6 Q. What does that have to do with your opinions? 7 A. Well, Dr. Wintrobe and his associates looked 8 at 17 of their own patients and they reviewed the 9 world's literature at that time on this illness; and 10 they concluded the pathogenesis of RARS remains 11 unknown. And he specifically talks in the article 12 about benzene, and they couldn't relate any of their -13 the illness in any of their patients to that. So -14 Q. What page does he talk about benzene? 15 A. It's either this or the other article, but I 16 may have highlighted it. Let's see. He says, there -17 in his discussion, he says, lack of evidence for an 18 associated inflammatory or neoplastic disease, 19 nutritional deficiency or a well-defined exposure to 20 drug or toxins, which produced this. So I would put 21 benzene under the toxins in that particular article. 22 And then later, last, he talks about no 23 particular pattern of exposure -- talking about 24 toxin -- emerges from the histories of the patients 25 reviewed. 56 1 Q. The 17 patients? 2 A. No. He's also reviewed all of the other ones 3 in the literature to that point. 61 patients in total. 4 And -- so he couldn't find any evidence of benzene as a 5 cause in his or other patients at that time. And this 6 is in 1971. 7 Q. We also cited or marked as an exhibit later 8 on, Wintrobe's textbooks, correct? 9 A. Yes. 10 Q. Can we pull those out for a second. 11 A. Sure. 12 Q. Does Wintrobe's 10th edition talk about what 13 causes RARS? 14 A. They have a section in etiology on there and I 15 Xeroxed it and also in the 11th edition. They're 16 written by the same person. 17 Q. Where in the 10th edition or 11th edition does 18 it talk about what causes RARS? 19 A. Well, it says idiopathic acquired 20 sideroblastic anemia, and it says etiology and 21 pathogenesis. And then this is the -- those pages have 22 to do with etiology, the cause and the pathogenesis. 23 This is the other, same thing in the other chapter. It 24 just says etiology and pathogenesis. 25 Q. Okay. Exhibit 2, that is the Cheng, 1979? 57 1 A. That's also a Wintrobe article. And by this 2 time, it's several years later. Now he's got 29 3 patients he's been studying personally, and he's come 4 to the same conclusion that -- that there's no -- no 5 well-defined exposure to drugs or toxins. 6 Q. Where is that at? 7 A. Under discussion. "By definition, there is no 8 recognized associated inflammatory or knee plastic 9 disease, nutritional deficiency or well-defined 10 exposure to drugs or toxins." 11 Q. Does he explain what he means "by well-defined 12 exposure to drugs or toxins"? 13 A. Well, he does in one of these articles, he 14 talks about that because he mentioned the term 15 "benzol." I'm not sure if it's this review. He 16 doesn't specifically mention what toxins he sought. 17 Q. So Exhibit 2 doesn't specifically examine 18 benzene as a causative factor of RARS; true? 19 A. Well, he examines what he thought might cause 20 it and he talks about toxins and he was certainly well 21 aware of -- of benzene as a toxin to the bone marrow. 22 Q. Okay. What is the value of Exhibit 3, the 23 Cazzola 1988 article? 24 A. And this is continuing on. In other words, 25 these are sequential by years, this is now -- we're up 58 1 to 1988. And the title starts, "Idiopathic refractory 2 sideroblastic anemia is a disorder of unknown 3 etiology." So by -- nothing has changed, when you get 4 up to 1988, that doctors are still taking histories and 5 physicals and looking for causes, and no cause is 6 identified. 7 Q. May I see that? And then Exhibit 4, what is 8 the value of that and your opinions in this case? 9 A. Well, only in this way, these are some of the 10 authors who attempted to divide RARS into a good 11 prognosis and bad prognosis group. And talking, for 12 example, about pure idiopathic acquired sideroblastic 13 anemia as opposed to those that had bad looking cells. 14 And from the description of the marrow, Mr. Wilson fits 15 into the good group. 16 Q. So that talks about prognosis, not about 17 causation? 18 A. Talks about prognosis, not about causation. 19 I -- he talks about the fact that we excluded other 20 causes, looking for alcoholism, lead poisoning, drugs, 21 blah, blah, blah, metabolic disorders. And so, and 22 he -- he does talk about benzene. He says in this 23 technical group, of their 84 patients, he identified 24 one patient who claimed to have had benzene exposure 25 and that person had radiation therapy. 59 1 Q. Okay. And then what Exhibit 5 and its value 2 in your opinion in this case? 3 A. Similar in that -- this is another group that 4 claimed on cytomorphologic grounds, the sideroblastic 5 anemia can be divided into pure sideroblastic anemia, 6 PSA, or RARS, which he thought was a preleukemic state. 7 And so, again, it's suggesting that someone with a -8 with problems like Mr. Wilson, that are only evident in 9 the red cell line, they generally do better than those 10 who have multilineage dysplasia. 11 Q. This Exhibit 5 does not examine causation of 12 RARS; true? 13 A. Correct. 14 Q. Exhibit 6, what is the value of that in your 15 opinion? 16 A. This is a general discussion on sideroblastic 17 anemia, and the -- one of the things that's useful 18 about this is, they talk about the problems with iron 19 overload which often is a major problem in people with 20 this situation. 21 Q. Does it discuss causation? 22 A. I don't know if it does or not. They say at 23 the end, sideroblastic anemia is talking in the general 24 category of sideroblastic anemias, vary in etiology and 25 pathophysiology; but under the -- under the RAS group, 60 1 they don't offer any -- in other words, they -- they 2 talk about the fact that their history looked for 3 possible toxin or drug exposures and blah, blah, blah 4 but they don't -- they don't suggest anything. 5 MR. PATTON: Let's take a short break. 6 Off the record. 7 (Break.) 8 Q. (BY MR. PATTON) Doctor, what is the value of 9 Exhibit 7 as it bears on your opinions in this case? 10 A. Well, this is an article by Dr. Lynch, who 11 used to be my partner many years ago; and I'm, again, 12 reunited with him in the Department of Medicine at 13 Methodist, and I saw many of these patients. And it's 14 a study of sideroblastic anemia of the group that were 15 seen in the Baylor experience. 16 And they had 85 with RARS and they discussed 17 the frequency of survival and conversion to AML and so 18 on in that particular group. 19 Q. Does it discuss causation of RARS? 20 A. No, it does not. Primarily was concerned with 21 incidences and progression of disease and so on. 22 Q. Would you agree with me that most of the 23 literature specific to RARS does not examine causation? 24 MR. PARKS: Objection. Form. 25 A. No, I wouldn't agree with that. Because when 61 1 you see a patient with any hematologic disease or any 2 other disease, causation is part of what you learn in 3 medical school. You try to look for the cause. And 4 you may do that by history taking, looking at the drugs 5 the patient has, the occupational history. So all 6 doctors, to a certain extent, are trained to look for 7 causation. 8 Q. (BY MR. PATTON) What is the value of Exhibit 8 9 in your opinions in this case? 10 A. Well, I think as I mentioned, the bone marrow 11 avidly holds on to ringed sideroblasts, but they do 12 decline with time. And this is a study that looks at 13 the percentage of ringed sideroblasts over time as the 14 disease progressed from RARS to RAEB. 15 Q. So Exhibit 8 examines the incidence of RARS 16 evolving or changing somehow into RAEB and discusses 17 the way the RS signature goes away? 18 A. Well, it changes. It doesn't go away. It's 19 reduced, in other words. But they -- they do discuss 20 that; yes. And, of course, one would expect that to 21 occur. They show that, for example, in 20 percent of 22 patients with RAEB, they still show ringed sideroblasts 23 accounting for greater than equal to 20 percent of the 24 bone marrow. 25 So, in other words, they hang onto those ring 62 1 sideroblastics pretty well. So in many cases of RAEB, 2 you can still see the 15 or 20 percent ringed 3 sideroblasts that I mentioned earlier, even though it 4 is now moved by virtue of the increase in blast forms 5 into an RAEB classification. 6 Q. Although in some cases of RARS transformed 7 into RAEB, the RS signature goes away, right? 8 A. Correct. 9 Q. What's the value of Exhibit 9 in your opinions 10 in this case? 11 A. Well, this was -- is a general discussion on a 12 myelodysplasia and talks about the original category. 13 It talks -- it's really a general article. 14 Q. Does this general article, Exhibit 9, talk 15 about the cause of RARS? 16 A. I don't recall what it says in there, if it 17 has a section on etiology. 18 Q. Okay. Exhibit 10, what is the value of that 19 in your opinion? 20 A. Another general discussion on the etiology and 21 epidemiology of MDS. And this particular article, the 22 author says the precise mechanisms responsible for the 23 initiation of MDS are currently unknown. 24 Q. What does that author mean by "precise 25 mechanism"? 63 1 A. Well, how -- how illness is -- is caused. 2 Q. Does it acknowledge benzene as a possible 3 causative factor? 4 A. It talks about radiation, chemotherapy agents, 5 cigarette smoking. He mentions benzene in the form of 6 cigarette smoking; occupational and environmental 7 carcinogens. "An increased or possible odds ratio was 8 found for MDS patients exposed to radiation, 9 halogenated organics and metals." Elevated odds ratio 10 were found for copper, arc welding fumes and hydrogen 11 peroxide, with borderline agents for -- for degreasing 12 agents. And it talks about fertilizers as well as 13 petrol and diesel derivatives. 14 Q. Okay. 15 A. It says, "In addition, it is clear that an 16 association between exposure to an agent and the 17 development of MDS is a long way from establishing 18 cause and effect." 19 Q. What is the value of Exhibit 11 in your 20 opinions in this case? 21 A. Well, it points out that the natural history 22 of these diseases ranges from a chronic course that may 23 span years to a rapid course toward leukemic 24 progression; and specifically, "Unfortunately, the 25 nomenclature and classification systems used to 64 1 describe these conditions are cumbersome and 2 contentious." And I would certainly endorse that 3 statement. 4 Q. And does that discuss causation, Exhibit 11? 5 A. No. This is just a classification. 6 Q. What is the value of Exhibit 12 in your 7 opinions in this case? 8 A. That's the next one we're up to? 9 Q. Yes. 10 A. In this case, it would point out what I've 11 said, is that MDS may develop after exposure to toxins, 12 such as benzene, chemotherapy drugs or high doses of 13 radiation, although its etiology is unknown in more 14 than 80 percent of patients. And he talks, in this 15 case, about the prior terminology for this illness. 16 Q. Okay. What about Exhibit 13? 17 A. Again, it does talk -- this is a 18 classification of MDS -- and they talk about causation, 19 unless associated with prior chemotherapy, radiation or 20 toxic exposure eludes discovery. Indicating that in 21 most of those patients we don't know the cause. 22 Q. And then Exhibit 14, this is your article, 23 correct? 24 A. Yes. 25 MR. PATTON: Can I get a copy of Exhibit 65 1 14 before we leave today? 2 MR. PARKS: Yeah. Remind me. 3 Q. (BY MR. PATTON) Exhibit 14 speaks for itself? 4 A. Speaks for itself, yes. 5 Q. Exhibit 15, what is the value of that in your 6 opinions? 7 A. This one points out, as we've talked about, 8 "The myelodysplastic syndromes represent a 9 heterogeneous group of disorders with different biology 10 and prognosis," that they're different diseases. And 11 in specific, this patient is being treated with 12 erythropoietin to try to stimulate red cell production. 13 And this article discusses how effective that might be, 14 as well as other remedies to try to improve the blood 15 counts. 16 Q. Exhibit 15 is mostly about treatment -17 A. Yes. 18 Q. -- differences amongst the different types of 19 MDS? 20 A. Yes. 21 Q. Exhibit 16? 22 A. This is an article looking that -- looking at 23 chromosomes and other things in these -- in these 24 patients. And it points out, "From clinical 25 cytomorphologic, cytogenetic and molecular aspects, the 66 1 myelodysplastic syndromes are heterogenous diseases." 2 Q. Meaning different? 3 A. Yeah. There are many different diseases 4 classified under this rubric. 5 Q. Exhibit 17 and 18 say pretty much the same 6 thing? 7 A. That's correct. 8 Q. And do 16, 17 or 18 look at causation? 9 A. No. They mention incidents -- well, they -10 they do comment. It says that some were therapy 11 related, can be caused after exposure to alkylating 12 agents, radiation or both. But that they're mostly 13 idiopathic and it also a -- one of the more current WHO 14 classification schemes. 15 Q. What about Exhibit 19? What's the value of 16 that in your opinions in this case? 17 A. Well, I think we discussed this. This is sort 18 of a blue ribbon panel looking at Gulf War exposures to 19 pesticides and solvents; and this group which was 20 composed of many different epidemiologists, pointed out 21 when you're looking specifically at etiology via 22 epidemiologic studies, that there's inadequate evidence 23 to determine whether an association exists between 24 chronic exposure to benzene and myelodysplastic 25 syndromes. 67 1 Q. May I see that? Exhibit 20, what is the value 2 of that paper in your opinion? 3 A. Well, in Dr. Haas' deposition he was asked 4 questions and it got confusing because he was talking 5 about two different classification systems as if they 6 were the same one. 7 And we talked about there's a classification 8 system for MDS, which is strictly morphology based. 9 Then there's a scoring system for -- involving 10 prognosis; and in his -- in his discussion he was 11 talking about low risk, intermediate risk and high risk 12 as though that's a classification. It is, but it's 13 different than the other classification that we used of 14 the separate diseases. 15 And he also indicated that -- that people who 16 have low risk disease, where he put Mr. Wilson in, 17 might have an average survival of ten years, I think is 18 what he said. And that's not borne out by these 19 articles. In this particular one -- there are two of 20 these articles -- it says median survival was 21 respectively 6.5 years in the low risk group. 22 Q. And that's Exhibits 20 and 21? 23 A. Yes. The next one has to do with what we 24 mentioned, RARS-T, "Ringed sideroblasts with 25 thrombocytosis." 68 1 Q. Mr. Wilson doesn't have that, correct? 2 A. He does not have that. 3 Q. That's Exhibit 22? 4 A. Yes. 5 Q. Exhibit 23? 6 A. Same with 23. Same with 24. 7 Q. And what about 25? 8 A. 25 is the way this is treated because, in his 9 particular situation, he's occasionally got some blood 10 transfusions; but Dr. Haas has been watching his iron 11 levels and they're not particularly elevated; and if 12 they get elevated, we have mechanisms of getting rid of 13 the iron. And so he's following him from that 14 standpoint. And this discusses that. 15 Q. And 26 is the Linet article? 16 A. Yes. 17 Q. And this looked at the 74,000 or so workers 18 and did not find a case of RARS, correct? 19 A. Correct. 20 Q. Any other value to Exhibit 26 in your opinions 21 in this case? 22 A. No. As we discussed, she comments on what the 23 usual finding is in a MDS marrow from people with 24 benzene exposure. 25 Q. Exhibit 27, what is the value of Dr. Wong's 69 1 study? 2 A. Dr. Wong's study is really sort of a critique 3 of the Hayes article and comments about what he thinks 4 are -- are dose response observations; and in this -5 in this study and his opinion that the exposures in the 6 Chinese benzene studies were not much different than 7 what they were in the Pliofilm study. 8 Q. Does he examine RARS specifically? 9 A. No. 10 Q. Does he look at MDS? 11 A. I don't believe so, no. 12 Q. So what is the value in that? Cumulative 13 dose? 14 A. Yeah. This is an article and so is the 15 following on what -- on risks of AML after cumulated 16 doses. 17 Q. Do you have any opinions as to what cumulative 18 dose of benzene Mr. Wilson experienced? 19 A. Well, your expert, I think, said he had 18.1 20 part per million levels; and in one of these recent 21 depositions, the counter from the defense side was he 22 had around 5 part per million, I think, something like 23 that. That was the differential. 24 Q. What about your opinion, based on that 25 information and from what you know on working on these 70 1 cases, do you have any opinion as to how much benzene 2 he would have been exposed to? 3 A. I wouldn't be able to calculate that. 4 Q. Do you believe that the printing solvents that 5 he used from Ashland would have contained benzene? 6 A. They might have contained small amounts of 7 benzene, yes. 8 Q. What's the basis of your opinion that the 9 Ashland solvent blends may have contained small amounts 10 of benzene? 11 A. Well, various forms of mineral spirits are 12 well known to have trace amounts of benzene in them. 13 And so that's been looked at. I think I referenced two 14 articles that had to do with similar types of solvents; 15 and so, it wouldn't surprise me if there were very 16 small amounts of benzene in the materials he worked 17 with. 18 Q. So is it your opinion in the case that Charles 19 Wilson did work with or around benzene on a daily basis 20 when using the Ashland solvent blends? 21 MR. PARKS: Objection. Form. 22 A. I can't dispute or comment about that. I -23 I'm not an expert on those solvents and -- and couldn't 24 make estimates on how much he worked with -25 Q. (BY MR. PATTON) Did you speak to anyone from 71 1 Ashland in the course of reviewing materials and 2 formulating your opinions in this case? 3 A. No. 4 Q. Did you ask to speak with anyone from Ashland? 5 A. No. 6 Q. Did you see any documents from Ashland that 7 indicated how much benzene was in these products? 8 A. There is a document in there to that effect 9 that I recently received that talks about some of these 10 products. 11 MR. PATTON: Kevin, do you know what 12 documents he's talking about? 13 MR. PARKS: The produced stuff Friday. 14 MR. PATTON: Documents produced this past 15 Friday? 16 MR. PARKS: I'm not sure if that's what 17 he's talking about. 18 THE WITNESS: Yeah. I just received 19 that. 20 MR. PATTON: Is that in the pile I have 21 here today? 22 THE WITNESS: It's here, yeah. 23 MR. PATTON: Can we find that? Let's go 24 off the record. 25 (Break.) 72 1 Q. (BY MR. PATTON) Dr. Natelson, the documents 2 which you referenced to talk about, the benzene content 3 of the Ashland solvent blends, you're referring to the 4 documents marked as Ashland-Wilson 4029 through 4051, 5 correct? 6 A. Yes. 7 Q. These are 2004 or 2005 documents. Actually, 8 one appears to be 2000. Let me ask it this way. 9 None of these seem to date back to the 10 pre-2000 time period, do they? 11 A. I didn't notice that. We can quick -- it's 12 not a long document. We can look through that. This 13 says 2005. 2005. 2005. 2005 again. 2005 again. 14 Q. In any event, Doctor, you have not seen any 15 documents in this case that would tell us the benzene 16 content of the Ashland solvent blends, which Mr. Wilson 17 is alleged to have used, that talk about benzene 18 content between 1978 through 2000, right? 19 A. Correct. 20 Q. Okay. 21 MR. PATTON: Kevin, did you also produce 22 earlier pre-2000 specifications? 23 MR. PARKS: Today. That's in the stuff I 24 gave you today. 25 Q. (BY MR. PATTON) Exhibit 28, what is the value 73 1 of that document and in forming your opinions? 2 A. That's, again, another article by Dr. Wong 3 talking about the cumulative dose of benzene necessary 4 to cause AML. 5 Q. Doesn't talk about MDS, right? 6 A. Correct. 7 Q. And 29 and 30, those are the Aksoy articles? 8 A. These are Aksoy articles discussing the 9 hematologic effects of chronic benzene poisoning. 10 Q. And what are those effects? 11 A. Well, he has lists of all of the things that 12 he saw here, low white count, low platelet count, 13 pancytopenia, what's called a Pelger-Huet anomaly. 14 It's a funny looking white cell. Large platelets, 15 eosinophilia, we mentioned earlier. 16 Then he has results of bone marrow studies and 17 11 people who were using a lot of benzene, and so it 18 demonstrates what he said in his article, that he's 19 commonly seeing these patients. He was doing bone 20 marrows on them and he doesn't describe any RARS. 21 Q. And then what about Exhibit 31? 22 A. That's the same thing. In other words, he -23 he talks about the type of leukemia that he saw in some 24 of those people. 25 Q. You're talking about Exhibit 30, right? 74 1 A. Yeah. 30. Yeah. 31 is Dr. Irons' study; and 2 he says much the same thing that Dr. Linet said, 3 distinguishing features of benzene-induced dysplasia, 4 include marked dyserythropoiesis, meaning a lot of 5 funny looking red blood cells, eosinophilic dysplasia 6 and abnormal granulation of the white cell precursors; 7 and that's the thing that he saw. And he did iron 8 stains in this marrow and did not find any ringed 9 sideroblasts, and he shows pictures of some of these 10 cells. 11 Q. May I see that? 12 A. (Hands over document.) 13 Q. Who funded this study by Irons? 14 A. I don't know. 15 MR. PATTON: Off the record. 16 (Discussion off the record.) 17 MR. PARKS: I just wanted to indicate -18 Keith had asked earlier about whether we had produced 19 documents showing benzene contents for dates earlier 20 than 2000 and indicated those were produced today. 21 Those may have been produced on Friday, September 14th. 22 I'm just not sure. I'd have to go back and look at the 23 production records on that. I just didn't want there 24 to be any confusion on that. Thanks. Sorry about, 25 Keith. 75 1 Q. (BY MR. PATTON) Dr. Natelson, what is the 2 value of Exhibit 32 on your opinions in this case? 3 A. Again, this shows what happens to a bone 4 marrow when you have chronic benzene poisoning; and it 5 shows that the bone marrow cellularity is reduced, 6 there's lots of fat in here. And he specifically 7 states, in none of the patients ringed sideroblasts 8 were observed. And so he did iron stains on all of 9 these people. There were like 33 patients or so. 10 So his description of the bone marrow, Irons' 11 description of the bone marrow, Dr. Linet's description 12 of the bone marrow, they're all quite similar in three 13 different groups of people with benzene exposures. 14 Q. What about -- what would the description be of 15 people with AML in terms of cellularity? 16 A. Well, AML, there's a lot of cellularity in 17 most cases. The -- the bone marrow is often what we 18 call packed, meaning it's 100 percent cellular. 19 Q. So it would look different than what Ruiz and 20 Irons and others observed, right? 21 A. Yes. Yes. 22 Q. So Exhibit 32 isn't the end all, be all to 23 what benzene-affected cells look like; fair statement? 24 MR. PARKS: Objection. Form. 25 A. Well, it is. In other words, it's what they 76 1 look like before one has acute leukemia, you might say. 2 Q. (BY MR. PATTON) Okay. What's the value of 3 Exhibit 33? This is the Strom study, right? 4 A. This is the Strom study. I think I described 5 him earlier as a "he" but it's actually a "she," I 6 believe. 7 In any event, she said that among refractory 8 anemia and ringed sideroblast cases, smoking and 9 agricultural chemical exposure were the only risk 10 factors identified. 11 Q. Strom examined some 105 patients with the 12 combined category of RA and RARS, correct? 13 A. Yes. 14 Q. This is reflected in Table 6? 15 A. Yes. 16 Q. It talks about benzene/solvent/gasoline 17 exposure, right? 18 A. Yes. 19 Q. What is the amount of low/medium 20 benzene/solvent/gasoline exposure that's reflected in 21 the Strom study? How much benzene are we talking about 22 in that category? 23 A. I have no idea. 24 Q. What about high? 25 A. I have no idea. 77 1 Q. What did the questionnaire look like that 2 asked these 105 people whether or not they were exposed 3 and how they were exposed to benzene/solvent/gasoline? 4 A. I don't know that. 5 Q. Is this the primary study upon which you rely 6 in opining that benzene does not cause RARS? 7 A. No. As we've gone through, there are many 8 other studies. This is just one more study. 9 Q. And this is the only recent study to look at 10 benzene as a cause of various forms of MDS by subtype; 11 true? 12 A. Yes. I believe that's correct. 13 Q. And, in fact, the Strom study looked at 37 14 patients at MDS who had RARS from '99 to 2004, correct? 15 A. Yes. They have 37 patients in that group. 16 Q. Did they deal with or did the Strom study 17 address which patients maybe had RARS then transformed 18 into RAEB? 19 A. No. 20 Q. Does it talk about how many of these people 21 had RARS and then transformed into AML? 22 A. No. 23 Q. You would agree with me, Doctor, that it's 24 possible that MD Anderson had a patient from '99 to 25 2004, who had RARS and then later developed into AML 78 1 and, therefore, was not examined in the context of MDS 2 marrow, survived from '99 to 2004 for this study; true? 3 A. No. I would say, no, that's probably not 4 true. Because likely, if they had -- she's looking 5 through the records, I'm assuming, and trying to pull 6 out anybody who ever had a diagnosis of RARS at MD 7 Anderson. I'm guessing that's what she did. And that 8 would give her her 37 people. What later transpired 9 with those 37 people is sort of not what this article 10 is looking at. 11 Q. And you certainly don't know the background of 12 these 37 people, do you? 13 A. No. 14 Q. How would you find that out if you had to? 15 A. If I had to, I guess I could call Dr. Strom up 16 and ask her what, you know, could she make available 17 who these patients were or their case histories and 18 things of that nature. 19 Q. And, again, you don't know what Dr. Strom 20 asked for in context of what the nature and duration or 21 amount of benzene exposure that this category of 37 22 RARS patients experienced; true? 23 A. Correct. 24 Q. And in fact, Table 6, combines the RA and RARS 25 category, right? 79 1 A. Yes. They are unbound in one of the tables 2 that deals with smoking. I don't know if that's the 3 one -- let me look at the situation here. 4 Yes. In this particular table, she's got them 5 separated and it looks as though the group with the 6 least amount of smoking history is the one in the RARS 7 category. Excuse me. The least amount of never 8 smoking, in other words, that the smokers were -- were 9 in this category. 10 Q. Okay. Let's look at Exhibit 34, the Zhang 11 article. 12 A. This is a general article about the nature of 13 chromosomal aberrations detected in people exposed to 14 benzene. 15 Q. Does it talk about MDS? 16 A. It does not specifically talk about MDS. 17 Q. Does it talk about RARS? 18 A. No. 19 Q. And Mr. Wilson had no chromosomal 20 abnormalities, right? 21 A. Correct. 22 Q. Exhibit 35, what is the value of that document 23 for your opinions? 24 A. Well, in this article it talks about 25 chromosome abnormalities and the treatment of MDS. And 80 1 as I said earlier, we -- or I opined that benzene can 2 cause MDS by its comparison with modern day 3 chemotherapy drugs; in other words, that would be the 4 reason to think that it might. And the author says a 5 diagnosis of chromosomal abnormalities are present in 6 40 to 60 percent of patients with primary MDS and 7 greater than 90 percent of people with therapy-related 8 MDS. 9 So, in other words, if I equate benzene and 10 therapy-related MDS, I would expect most all of them 11 would have chromosome disorders, and he doesn't. 12 Q. What is the value of Exhibit 36 on your 13 opinions in this case? 14 A. Pointing out that this is a significant 15 disease, and this author indicates that approximately 16 two-thirds of patients succumb to the disease about 17 three to four years after presentation. He also gives 18 incidence figures and also the classification system. 19 Q. Speaking of the severity of disease and the 20 treatment of MDS, you read Dr. Haas, the treating 21 physician's deposition, correct? 22 A. Yes. 23 Q. Is there anything besides the severity part 24 that we talked about earlier? 25 A. Well, I think the two things in there is he 81 1 thought that CMML was still -2 Q. A subtype. 3 A. -- a subtype of MDS, which it isn't. He 4 talked about those two classification systems which 5 were blurred. We'd have to look specifically -- I 6 don't remember anything else that hit me in the face 7 when I looked at it. 8 Q. Did you see where he talked about the future 9 treatment that Charles Wilson will require for his 10 disease? 11 A. I don't remember what he said about that. 12 But -- but if he survives for a long period of time, he 13 will likely have -- need other treatment. 14 Q. Did you have any -- well, did you look at the 15 testimony by Dr. Haas as to the reasonableness and 16 necessity of the treatment required for Charles 17 Wilson's continuing treatment? 18 A. Well, yes. I don't remember exactly what he 19 said. But in general, what one tries in this illness 20 is to reduce the number of units transfused and yet 21 maintain a stable blood count. So he's giving him 22 Aranesp, which is a form of erythropoietin, to try to 23 improve his blood counts. 24 Q. Now I think he said he's getting Procrit. 25 A. Same thing. It's just a different 82 1 formulation. 2 Q. Procrit and Aranesp are, essentially, the same 3 treatment? 4 A. They're identical. 5 Q. Okay. For all practical purpose, they're 6 identical? 7 A. For all practical purposes. The difference 8 was Procrit came out first, and Aranesp is a 9 long-acting preparation and it was assumed that it 10 would be better because you got a shot and it would 11 stay in your system longer. That's never turned out to 12 be true. The response rate to Aranesp and Procrit are 13 essentially identical. 14 Q. On page 5, I want to turn to your report now. 15 Turning to your report, I want to ask a few questions. 16 On page 5 -17 A. Yes. 18 Q. The portion beginning "In summary." 19 A. Yes. 20 Q. You say that "the cause for RARS/AISA 21 Mr. Wilson remains unknown, as it typically occurs in 22 members of the general population without any history 23 of toxic chemical exposures," correct? 24 A. Yes. 25 Q. You would agree with me that RARS -- strike 83 1 that. 2 You would agree with me that cancers in 3 general occur among the general population without any 4 history of toxic or chemical exposures, correct? 5 A. Certainly. 6 Q. And you would also agree with me that chemical 7 exposure can cause certain types of hematologic 8 disorders, right? 9 A. Yes. 10 Q. You would agree with me that toxic chemical 11 exposures cause some forms of MDS, right? 12 A. Yes. I believe that's true. 13 Q. And you agree with me that toxic exposures, 14 including benzene exposures, can cause AML? 15 A. Yes. 16 Q. Turning to page 2 of your report at the top of 17 the page. Do you believe Mr. Wilson's heart disease or 18 the treatment for his heart disease played any 19 causative role in his MDS? 20 A. No. I wouldn't see any relationship. 21 Q. Do you have any other opinions as to what 22 might have played a causative role in Charles Wilson's 23 MDS? 24 A. I don't know why he has MDS. 25 Q. Just know it wasn't related to benzene, right? 84 1 A. Well, this form, as we've talked about. This 2 form has never been shown related to benzene. 3 Q. And so it's your opinion that no matter what 4 other forms his disease might take, because he has the 5 RS ringed sideroblast signature, there's no way his 6 future diseases could in any way be related to benzene; 7 true? 8 A. Well, I think with that diagnosis comes the 9 natural history of that diagnosis. And the natural 10 history of that diagnosis is to have progressive 11 hematologic problems, even leukemia, although that's 12 not a big number in his case. 13 And so I -- it wouldn't surprise me if he went 14 on to develop acute leukemia. And I don't see why 15 anybody would need to implicate benzene or anything 16 else, now that he's got RARS. 17 Q. Turning to your CV which is marked -18 A. Yes. 19 Q. -- as Exhibit 48. Turning to your -- the list 20 of your publications. 21 A. Yes. 22 Q. Do any of the publications that you've written 23 discussed benzene, besides Exhibit 14? 24 A. Yes. This article, article 74, deals with 25 benzene. 85 1 Q. What's article 75 about? 2 A. Well, that's the one you looked at. That's 3 the sideroblastic anemia one. 4 Q. Okay. What's the general opinion or 5 conclusion set out in -- in article number 74? 6 A. It's a general discussion of what is known 7 about benzene-induced AML and comments on things such 8 as latency, cumulative part per million years, 9 incidents. It's just a general review of the 10 literature in this subject. 11 Q. Who paid you to write exhibits -- or articles 12 74 and 75? 13 A. Nobody paid me to do that. 14 Q. What is the horticulture stuff in your 15 study -- or your CV? 16 A. Oh, is just a hobby. I'm president of a 17 couple of larger organizations. 18 Q. Marked as Exhibit 49 is a list of your cases. 19 Starting on the front page, item number 1, that was a 20 benzene case, right? 21 A. Yes. 22 Q. And you testified on behalf of the defendant? 23 A. Yes. 24 Q. Did you testify as to what did cause that 25 worker's disease? 86 1 A. No. 2 Q. You just testified that benzene did not cause 3 it, correct? 4 A. Correct. 5 Q. And were you retained by Amoco on that case? 6 A. I don't know. I was retained by 7 Mr. Shoebotham, who works in this law firm. I don't 8 know what the company was. 9 Q. Back in 1992, you were also hired by 10 Mr. Shoebotham? 11 A. Yes. That's the first -- that was probably 12 the first time I ever had anything to do with 13 benzene-related testimony. 14 Q. And then item 4, who hired you in that case? 15 A. You know, I'm not sure about Mims. Smothers 16 was the case that -- that Mr. Shoebotham asked me 17 about. I can't remember who asked me about Mims. But 18 it was definitely Smothers. And this is the one that 19 Jon Shoebotham asked me to look at. 20 Q. And you opined that benzene did not cause that 21 worker's ALL? 22 A. Well, I opined he had ALL. In other words, 23 the allegation was he had AML and, therefore, could 24 have been caused by benzene but, in fact, he had ALL. 25 Q. What about number 5? Who retained you in item 87 1 5? 2 A. It's been too long ago for me to remember. 3 Q. You testified in that case, though, that 4 benzene exposure did not cause the worker's disease, 5 right? 6 A. Yes. I testified that benzene did not produce 7 multiple myeloma. 8 Q. As we sit here today, are you still of the 9 opinion that benzene does not cause or cannot cause 10 anyone's multiple myeloma? 11 A. Yes. That is my opinion. 12 Q. What is multiple myeloma? 13 A. Well, it's a bone marrow disease characterized 14 by overproduction of what are caused plasma cells. And 15 those cells replace the bone marrow that cause 16 tremendous bone destruction, kidney failure and 17 eventually death. 18 Q. Item number 8, Hodgkin's disease and causation 19 with Fulbright & Jaworski. Did that deal with benzene? 20 A. You know, I think it had to do with radiation. 21 I believe this was a man who worked for Schlumberger, 22 and he claimed he was exposed to a radiation machine 23 about 100 yards away from where he worked. 24 Q. Following page -25 A. Yeah. 88 1 Q. -- item 10, Frias case? 2 A. Yes. 3 Q. That involved gasoline, correct? 4 A. That involved gasoline. Well, the allegation 5 was benzene in the gasoline caused aplastic anemia. 6 Q. Is it your opinion that benzene, when a 7 component of gasoline, can never cause a bone marrow 8 disease? 9 A. Well, that -- that is what the literature 10 states. In other words that, there's no evidence that 11 gasoline exposure can cause cancer. 12 Q. So, therefore, even though there's benzene in 13 gasoline, someone exposed to benzene via gasoline can 14 never experience a resultant bone marrow disease, would 15 that be your opinion? 16 A. Certainly the gasolines of today which contain 17 small amounts of benzene. I think in -- in England, 18 the gasolines contained at one time much more benzene 19 than we had. But in the United States, yes, I don't 20 believe gasoline can cause problems. 21 Q. Were you retained or working on behalf of 22 Shell Oil in that company -- or in that case? 23 A. That's what it indicates. 24 Q. Item 13, benzene exposure, again, is the cause 25 of aplastic anemia. It was your opinion that benzene 89 1 did not cause the worker's aplastic anemia? 2 A. Yes. That was an easy one because this was my 3 patient. And I had questioned him in great detail, as 4 had other doctors, and he always denied any benzene 5 exposure. So -- so therefore, it was kind of a 6 no-brainer. 7 Q. What about exhibit -- or item 15? 8 A. This had to do with allegation of benzene 9 causing non-Hodgkin's lymphoma. 10 Q. Do you believe that benzene can cause 11 non-Hodgkin's lymphoma? 12 A. No, I do not believe that it can. 13 Q. Number 17, once again, chemicals did not cause 14 cerebral NHL? 15 A. That's correct. This was -- in one of these 16 cases, I think there were either two -- maybe there 17 were two patients in this; and in one of them, the 18 records clearly showed that the patient had the 19 cerebral lymphoma before he went to work in this 20 company. And I don't recall the details of the other 21 case, but I don't believe that benzene exposure causes 22 non-Hodgkin's lymphoma whether is in the brain or 23 anywhere else. 24 Q. What was the disease in item 18? 25 A. That was acute lymphoblastic leukemia, ALL. 90 1 Q. What were the details of case 19? 2 A. The details of that, this was a ship captain, 3 as I remember. And he had what I thought, by looking 4 at the mirror, was a myeloproliferative disease. Of 5 course, myeloproliferative disease can eventuate into 6 AML, as in our Mielke case. And he did develop AML. 7 But the allegation was that the basic process was 8 exposure to benzene, and I thought the basic process 9 was myeloproliferative disease, which is not benzene 10 related. 11 Q. Item 22? 12 A. I don't remember any of the details, but this 13 was a case of idiopathic sideroblastic anemia. Similar 14 to the one today. And I testified that there was no 15 known chemical causation. I don't remember anything 16 about the latency or anything else about this case. 17 Q. Has your testimony ever been excluded by any 18 court? 19 A. No. 20 Q. What about 23? 21 A. This was an AML case, but I -- I don't 22 remember any of the details about that one. 23 Q. 24, is that RARS -24 A. That's also RARS. 25 Q. And your opinion was, just like in this case, 91 1 benzene cannot cause RARS, right? 2 A. Correct. 3 Q. What kind of exposure did that worker 4 experience? 5 A. I can't remember with any accuracy. 6 Q. 27 and 28 deal with CLL and NHL, right? 7 A. Yes. 8 Q. You believe benzene does not cause CLL or NHL? 9 A. Correct. 10 Q. And case number 30, the Cowey case, what 11 subtype of MDS did that person have? 12 A. It could have been RARS. I don't remember. 13 It was form of myelodysplasia all right. I just can't 14 remember the details of that. 15 Q. What about 31? 16 A. Can't remember details about that one either. 17 Q. So as we sit here today, you're unsure of the 18 subtype -19 A. I'm unsure -20 Q. -- of MDS? 21 A. -- of the subtype of these two cases. 22 Q. Number 34, do you believe benzene can cause 23 APML or APL? 24 A. There isn't really a lot of evidence for that. 25 I think it's possible. 92 1 Q. What about in 35? That person also had RARS, 2 right? 3 A. Yes. 4 Q. What was the nature of exposure in that cause? 5 A. I don't remember the details of that. 6 Q. Do you remember who deposed you in that case? 7 A. No. 8 Q. 36, the Minnehan case? 9 A. The famous Minnehan case. That was an 10 inversion 16 case. 11 Q. And so whenever someone has inversion 16, that 12 means it's not benzene related? 13 A. It's never been reported in the world's 14 literature and so it makes it unlikely. In other 15 words, I can't prove what it didn't. But I would say 16 in all medical probability, it's not likely to happen. 17 Q. 42, what were the various lymphoproliferative 18 disorders? 19 A. There must have been multiple defendants in 20 this case, but they were either CLL or non-Hodgkin's 21 lymphoma. 22 Q. And what about 43, benzene as a cause of AML? 23 A. I don't remember the details of that. 24 Q. 44, again, CLL? 25 A. That was a CLL. 93 1 Q. Again, you don't believe that was caused by 2 benzene? 3 A. Correct. 4 Q. Same with 45? 5 A. Same with 45. 6 Q. Does CLL have subtypes? 7 A. Well, just like there is a risk assessment, 8 low risk, high risk, intermediate risk, CLL has that. 9 We have certain markers that we apply to CLL. One is 10 called CD-38 and the other is ZAP-70. And with those 11 prognostic markers, you can predict what their course 12 is going to be. So I would say, yes, there probably 13 are subcategories of CLL. 14 Q. And in opining against causation in the two 15 CLL cases, 44 and 45, did you rely on that further 16 stratification or that additional subtyping? 17 A. No. I'm not certain that either one of these 18 people had that subtitle. I don't recall that in any 19 event. 20 Q. 46, that was also an NHL and CLL case? 21 A. Well, 46, one of them has Hodgkin's disease 22 and the other one has chronic lymphocytic leukemia; and 23 I don't think either of those illnesses are going to be 24 benzene related. 25 Q. Let me finish this one and we'll take a break. 94 1 A. Yeah. 2 Q. 47 is an AML case? 3 A. Yes. 4 Q. What was the problem with causation in that 5 case? 6 A. Well, that's an 8 to 21 translocation case; 7 and 95 percent of those cases are idiopathic and 5 8 percent are chemical related. So, yes, it's 9 theoretically possible that benzene could cause it, but 10 in all medical probability, it would be pretty weak. 11 And this person had very limited exposure. 12 Q. What about 48? 13 A. 48 -- interesting. I guess that's -- I don't 14 remember the name, but that's a Dallas -- case in 15 Dallas that actually went to trial. And I think -16 could that be taken -- I can't remember if that's 17 page -- is that right? 18 Q. Yes. 19 A. I don't -- too many cases, I don't remember 20 all the details of that. But anyway, I mean, we -21 that case was won by the defendants. 22 Q. 49, I'm familiar with. You testified against 23 causation for Mr. Mielke, right? 24 A. Yes. 25 Q. Number 51, this was your most recent 95 1 deposition? 2 MR. PARKS: I've got the updated list. I 3 gave you a copy of it. It has two more on it. 4 A. Okay. 5 Q. (BY MR. PATTON) What was the problem with 51 6 in terms of benzene as a causative factor? 7 A. Well, it wasn't really clear this man had any 8 benzene exposure at all. He worked as sort of a 9 roustabout on a ship and -- and he mainly lowered -10 lowered cables down on a rigging and pulled them back 11 up; and it was very hard to figure out where in the 12 world he got any benzene. They had no benzene on the 13 boat anyplace. And also, the exposure was -- alleged 14 exposure was extraordinarily remote to his AML. 15 Q. And then 52? 16 A. Yes. 17 Q. What was the problem with causation? Well, 18 first of all, what was that disease? 19 A. Well, he had -- he had RARS that involved into 20 erythroleukemia; but this man had like about an 80-pack 21 year history with smoking and smoking is related to 22 RARS. And his alleged exposure to benzene were 23 extremely remote to the diagnosis. I can't remember 24 how, but they were many years remote. 25 Q. Who deposed you in that case? 96 1 A. I don't remember. 2 Q. And 53, was that a benzene case? 3 A. Yeah. That's a benzene case that has to do 4 with a man who worked in a bagging factory. 5 Q. And you testified on behalf of Ashland in that 6 case? 7 A. Yes. 8 Q. You've testified on behalf of Ashland in the 9 Wilson case, in the Vettrus case, number 53; you also 10 testified in behalf of Ashland in item 49, the Mielke 11 case. 12 Are there other cases that you testified on 13 behalf of Ashland for? 14 A. I wouldn't know because many of these cases, 15 as you well know, they'll have 125 defendants and I 16 don't pay any attention to who those are. I look at 17 the facts of the case. 18 Q. In either event, when you take the 53 cases 19 you've testified in since 1992, 31 of those dealt with 20 benzene and you testified against causation in each of 21 those 31 cases, correct? 22 A. Correct. 23 MR. PARKS: Objection. Form. 24 Q. (BY MR. PATTON) Did you testify in any of 25 those cases that benzene was a possible causative 97 1 factor in the worker's disease? 2 A. I'm sure in all of those cases if I wrote a 3 report, I said what I normally say, is that in no form 4 of leukemia can we be absolutely certain as to the 5 cause, but we're looking at probabilities, which is 6 more probable. And -- so I -- I -- certain I didn't 7 say benzene could not possibly cause this acute 8 leukemia. 9 Q. For the Wilson case, are you looking at 10 benzene as a possible cause in terms of a black and 11 white type of picture or there's just no way benzene 12 causes RARS or is it a little more gray to you, that 13 benzene is a possible cause, however, it's just not 14 strong enough for you to have that opinion? 15 MR. PARKS: Objection. Form. 16 A. I would say it's a black-and-white issue. In 17 other words, there have been enough papers looking at 18 this issue in populations with heavy exposure to 19 benzene to know that it's just simply not -20 Q. (BY MR. PATTON) Did Strom look at populations 21 heavily exposed to benzene? 22 A. I don't know how heavily those patients were 23 exposed. 24 Q. For record, Exhibits 1 through 42, plus 43 25 through 46, are the references from your report, plus a 98 1 couple hematology texts, correct? 2 A. Yes. I think there's one reference we didn't 3 cover that I added, I think, at the very end, the 4 Silver reference. I don't think we discussed that. 5 Q. What's the value of the Silver reference? 6 A. Well, it has to do with a conference on 7 myelodysplasia, myeloproliferative diseases and the 8 importances that -- talking about frequency and 9 causation of these illnesses. And the experts, 10 including Dr. Bennett, who invented this 11 classification, said very few instances of 12 environmental toxins have been identified. 13 MR. PATTON: All right. Let's take a 14 short break. Off the record. 15 (Break.) 16 Q. (BY MR. PATTON) Dr. Natelson, you reviewed the 17 report and the deposition of Dr. Infante, correct? 18 A. Yes. I don't recall the deposition but I 19 think I read his report but it's been sometime ago I 20 looked at it; but whatever is here, I looked at it. 21 Q. What criticisms, if any, do you have of 22 Dr. Infante's opinions in this case? 23 A. Well, he's testifying as an epidemiologist, 24 and he is not familiar with refractory anemia and 25 ringed sideroblasts from a treatment or diagnosis or 99 1 clinical interaction standpoint. So he's looking at -2 when he looks at numbers, he's looking at it from a 3 totally different aspect than I am. 4 Q. But he looks at it in terms of the body of 5 benzene literature, so to speak, dealing with benzene 6 and MDS rather than dealing very often with benzene and 7 the subtype of RARS; fair statement? 8 A. Well, as I've said, there is no -- there is no 9 epidemiologic evidence in the world's literature that 10 suggests that the RARS can be formed from benzene; but 11 as to critiquing his comments, it would be better for 12 another epidemiologist to do that. In other words, 13 I -- I'm more comfortable talking about what the 14 treating physician says because we're both treating 15 physicians. 16 Q. But isn't there sufficient evidence in the 17 literature that benzene causes MDS when not viewed by 18 subtype? 19 A. Well, not according to this large expert panel 20 of people; but as I've said, I accept that it does by 21 analogy with the chemotherapy literature; but according 22 to many experts in the field, one can't do that if it 23 has to stand on its own. 24 Q. All of the chemotherapy literature related to 25 MDS doesn't necessarily look at chemotherapy as a cause 100 1 of, say, RARS or a cause of RAEB; true? 2 A. Well, I think frequently it does, because 3 chemotherapy literature, you're talking about people 4 who get exquisite follow-up. And all of those people 5 have had bone marrows; and certainly if RARS were -6 were what one saw, one would know that, and we don't 7 see that. I've seen many people with 8 chemotherapy-induced acute leukemia and MDS, and I 9 haven't seen any with refractory anemia and ringed 10 sideroblasts. 11 Q. You have seen people reflected in the 12 literature who have MDS and which was caused or believe 13 to be caused by benzene exposure; fair statement? 14 A. Say that again. 15 Q. You would agree with me that there are 16 instances in the literature where benzene was shown to 17 cause MDS, right? 18 A. Yes. 19 Q. And that points us to the conclusion that 20 benzene caused a given person or a handful of people, 21 however many people, it caused their MDS; fair 22 statement? 23 A. That's a strong possibility, yes. 24 Q. Okay. And there's also at least a possibility 25 that in some of those case instances where it wasn't 101 1 looked at as -- where it wasn't examined by subtype, 2 that the person could have had RARS, which is the type 3 of MDS reflected in the study, and that was caused by 4 benzene? 5 MR. PARKS: Objection. Form. 6 Q. (BY MR. PATTON) It's at least possible? 7 A. I have no idea, in other words, we have a 8 enough cases -- as far as I am concerned, we have 9 enough cases that were studied to suggest that's not 10 going to happen. 11 Q. What about Dr. Aparent? Did you review his 12 report and/or his deposition? 13 A. I -- what -- I'm not certain if I did or 14 didn't. 15 Q. Dr. Aparent was a toxicologist retained on 16 behalf of the plaintiff in this case. Did you review 17 his report or his deposition? 18 A. I may have looked at it. I can't recall any 19 details of that. 20 Q. Besides Exhibits 1 through 42, plus the 21 handful of other pieces of authority as I've been 22 calling them, are there any other -- is there any other 23 peer reviewed literature or any other authority upon 24 which you may rely on in expressing your opinions 25 against causation in the trial of this case? 102 1 MR. PARKS: Objection. Form. 2 A. No. I think in terms of literature, my 3 article and these references are sufficient. 4 Q. (BY MR. PATTON) Are these the same references, 5 generally speaking -- obviously with the exception of 6 Strom because of the year -- are these the same 7 references that you relied on in your earlier MDS/RARS 8 cases? 9 A. Some of these certainly would be, yes. 10 Q. Did you draft the report all by yourself? 11 A. Yes. 12 Q. Did anyone help you in terms of looking for 13 literature or typing? 14 A. No. 15 Q. Are there any other copies of your report? 16 A. No. I mean, have it on my computer at home. 17 That's it. 18 MR. PATTON: Thank you for your time. I 19 know Mr. Parks has a couple questions for you so we'll 20 go from there. 21 E X A M I N A T I O N 22 BY MR. PARKS: 23 Q. Dr. Natelson, I'm Kevin Parks representing 24 Ashland in this case. And I just want to ask you a few 25 questions about some of the testimony you've provided 103 1 to Mr. Patton today. 2 He asked you several questions about the 3 reasonableness and necessity of Mr. Wilson's medical 4 treatment. Do you recall those questions? 5 A. I don't recall in detail what they were. 6 Q. But you recall testifying about that? 7 A. Yes. 8 Q. And when he was asking you about the 9 reasonableness and necessity of Mr. Wilson's future 10 treatment, you were talking -- your answers were in 11 terms of what form of the treatment he would likely 12 need in the future as opposed to the reasonableness and 13 necessity of any expenses for those treatments? 14 A. Right. The expenses are not my field. Many 15 treatments for hematologic diseases are very expensive. 16 Q. And, in fact, you've mentioned to me that the 17 charges reflected in Dr. Haas' medical records appear 18 to be excessive, though you would have to go do some 19 investigation on billing expenses to really opine on 20 that? 21 MR. PATTON: Objection. Form. 22 A. Well, it's a little bit of a game. In other 23 words, when you have a service done at a hospital, 24 there is a very large charge applied. Then the 25 insurance company gives another figure, which is 104 1 usually about a third as much as the -- what they 2 allow; and then there's a lesser figure of what they're 3 going to pay. 4 So when you finally get into what gets paid 5 for a service, it seems to bear very little 6 relationship to the original charge, which is very 7 high; but that's not my field but it just an 8 observation. 9 Q. (BY MR. PATTON) Okay. You also reviewed 10 Dr. Haas' recent testimony in relation to this case, 11 and do you recall where he talked about the Wintrobe 12 text? 13 A. Yes. 14 Q. And Dr. Haas indicated that he relied on the 15 Wintrobe text for his belief that benzene can cause 16 MDS? 17 A. Yes. 18 Q. And, in fact, didn't you -- or have you gone 19 and looked at the Wintrobe text and brought some of 20 those excerpts with you today as far as observations 21 made in that text on causation and RARS? 22 A. Yes. 23 Q. And is there a separate section of that text 24 that deals with causation of RARS? 25 A. Yes. A subset. There's a chapter that has to 105 1 do with sideroblastic anemia; and then within that 2 chapter, RARS is a subheading. 3 Q. And in the Wintrobe text, is benzene 4 identified as a potential cause of RARS? 5 A. No. 6 Q. The article that you've written that is 7 planned for publication, when -- when do you expect 8 that will be published? 9 A. Well, it's listed as November -- in the 10 November edition. 11 Q. And was that article peer reviewed? 12 A. Yes. 13 Q. What was your purpose in writing that article? 14 A. Well, my purpose was this: I don't think this 15 is a question that has been discussed much in the 16 hematologic literature. In other words, there are a 17 number of articles out there that deal with the 18 subject; but I don't think anybody, since the time of 19 Dr. Damashek, has written a general discussion about 20 this situation. 21 Q. And by this general subject, do you mean 22 whether benzene can cause RARS? 23 A. Yes. 24 Q. And what is the conclusion in your article? 25 A. Well, my conclusion is that there's no 106 1 epidemiologic evidence or case report data to suggest 2 that benzene can cause RARS and considerable data that 3 would suggest that it can't. 4 Q. Mr. Patton also asked you questions, for 5 instance, as to whether benzene can cause AML? 6 A. Yes. 7 Q. And you agreed that it could? 8 A. Yes. 9 Q. And then he asked you questions about the fact 10 that RARS can develop into AML as the natural -- in the 11 natural history -- in the course of the disease, if you 12 will? 13 A. Yes. 14 Q. But if you have a patient who has been 15 diagnosed with RARS who then develops AML, wouldn't you 16 rule out benzene as a potential cause because you know 17 that benzene does not cause RARS? 18 A. Both situations. We know that AML is the 19 natural progression of a number of cases of RARS, and 20 we also know that there is no relationship between 21 benzene and RARS. So if a person with RARS develops 22 AML, I would think that's just simply the natural 23 progression of the illness. 24 Q. So even if Mr. Wilson does proceed on to 25 develop AML, your opinion would remain that benzene did 107 1 not cause that? 2 A. That's correct. 3 MR. PARKS: Thank you for your time. 4 I'll pass the witness. 5 FURTHER EXAMINATION 6 BY MR. PATTON: 7 Q. Dr. Natelson, what is the multiple hit theory 8 as it relates to bone marrow diseases? 9 A. Well, the notion is that, for example, someone 10 gets, let's say, damage to a chromosome. It may be 11 minor damage or major damage. And that changes the 12 milieu, for example. It produces a growth factor or a 13 growth factor that has a certain advantage and starts 14 proliferating cells in the bone marrow; and then a 15 second genetic event occurs which takes those 16 proliferating cells and makes them leukemic. 17 And so it takes multiple hits to drive a 18 normal bone marrow to a leukemic bone marrow because of 19 the fact that the bone marrow has tremendous reparative 20 processes. And it's very difficult to -- to sustain 21 damage in the bone marrow because of the fact that even 22 chromosome defects can be repaired. 23 Q. Would you agree with me that some individuals 24 are more susceptible or more likely to take those hits 25 to the bone marrow, so to speak, a little harder than 108 1 others? 2 A. That's theoretically possible, yes. 3 Q. Is it theoretically likely, as far as the 4 concept of susceptibility goes, for people who have 5 different forms of cancer. Some people are more likely 6 to get cancer than others for one reason or another, 7 right? 8 A. That is so. We don't know the reasons for 9 that. But that is true, that in some instances there's 10 genetic predisposition, but -- but those -- the 11 research in that is really in its infancy. 12 Q. But you agree with me that some people have a 13 genetic predisposition to be more susceptible to 14 contracting, say, leukemia or a bone marrow disease 15 from exposure to benzene than other people would be; 16 fair statement? 17 A. Well, certainly. I don't know the answer to 18 that. I would say it's quite -- it's possible. I 19 don't know that for a fact. 20 MR. PATTON: All right. Thank you for 21 your time. 22 MR. PARKS: Reserve the rest of our 23 questions until the time of trial. 24 MR. PATTON: And for the record, can we 25 have the agreement, Kevin, that you will, for cost 109 1 sake, take the exhibits, copy them, return the original 2 to Dr. Natelson, send me a copy within, say, five days; 3 is that fair? 4 MR. PARKS: That's fair. 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 110 1 WITNESS CORRECTIONS AND SIGNATURE 2 Please indicate changes on this sheet of paper, giving the change, page number, line number and reason 3 for the change. Please sign each page of changes. 4 PAGE/LINE CORRECTION REASON FOR CHANGE 5 _______________________________________________ 6 _______________________________________________ 7 _______________________________________________ 8 _______________________________________________ 9 _______________________________________________ 10 _______________________________________________ 11 _______________________________________________ 12 _______________________________________________ 13 _______________________________________________ 14 _______________________________________________ 15 _______________________________________________ 16 _______________________________________________ 17 _______________________________________________ 18 _______________________________________________ 19 _______________________________________________ 20 _______________________________________________ 21 _______________________________________________ 22 _______________________________________________ 23 _______________________________ DR. ETHAN NATELSON 24 25 111 1 SIGNATURE OF WITNESS 2 3 I, DR. ETHAN NATELSON, solemnly swear or affirm 4 under the pains and penalties of perjury that the 5 foregoing pages contain a true and correct transcript 6 of the testimony given by me at the time and place 7 stated with the corrections, if any, and the reasons 8 therefor noted on the foregoing correction page(s), and 9 that I am signing this before a Notary Public. 10 11 _______________________________ 12 DR. ETHAN NATELSON 13 14 STATE OF T E X A S * 15 COUNTY OF ___________ * 16 SUBSCRIBED AND SWORN TO BEFORE ME BY 17 __________________ on this, the _____ day of 18 ________________, 2007. 19 20 21 _______________________________ 22 Notary Public, State of Texas 23 My Commission Expires: _______________________ 24 Job 2-64038 25 112 1 THE STATE OF TEXAS : COUNTY OF HARRIS : 2 I, DENYCE SANDERS, a Certified Shorthand Reporter and Notary Public in and for the State of 3 Texas, do hereby certify that the facts as stated by me in the caption hereto are true; that the above and 4 foregoing answers of the witness, DR. ETHAN NATELSON, to the interrogatories as indicated were made before me 5 by the said witness after being first duly sworn to testify the truth, and same were reduced to typewriting 6 under my direction; that the above and foregoing deposition as set forth in typewriting is a full, true, 7 and correct transcript of the proceedings had at the time of taking of said deposition. 8 I further certify that I am not, in any capacity, a regular employee of the party in whose 9 behalf this deposition is taken, nor in the regular employ of this attorney; and I certify that I am not 10 interested in the cause, nor of kin or counsel to either of the parties. 11 That the amount of time used by each party at 12 the deposition is as follows: 13 Mr. Keith Patton - 02:28:54 Mr. Kevin Parks - 00:05:48 14 15 GIVEN UNDER MY HAND AND SEAL OF OFFICE, on this, the 25th day of September, 2007. 16 17 _____________________________ 18 DENYCE SANDERS, CSR, RPR Notary Public in and for 19 Harris County, T E X A S 20 21 My Commission Expires: 4-6-09 Certification No.: 4038 22 Expiration Date: 12-31-07 U.S. LEGAL Support, Inc. 23 363 N. Sam Houston Parkway, 9th Floor, Houston, Texas 77060; 713.653.7100 24 Firm No. 122 25 113