Document xnpY0qoRQ69gze4D9Ej57xby

1 1 NO. 94-38491 2 JESUS VALENTIN FRIAS : IN THE DISTRICT COURT OF 3 VS. : HARRIS COUNTY, T E X A S 4 SHELL OIL COMPANY, ET AL.: 270TH JUDICIAL DISTRICT 5 6 7 8 9 10 11 12 13 DEPOSITION OF ETHAN A. NATELSON, M.D. 14 SEPTEMBER 25, 1996 15 16 17 18 19 20 21 22 23 Taxable Cost: 24 Charged to Plaintiff Mr. Jeffrey S. Thompson 25 Bar No. 00785101 2 1 INDEX 2 3 THE WITNESS: ETHAN A. NATELSON, M.D. 4 5 EXAMINATION: PAGE 6 By Mr. Thompson 4 7 8 NATELSON EXHIBITS: 9 Exhibit Nos. 1 through 6 3 10 11 12 APPEARANCES: 13 FOR THE PLAINTIFF: 14 Mr. Jeffrey S. Thompson 15 Williams & Bailey Law Firm, L.L.P. 8441 Gulf Freeway, Suite 600 16 Houston, Texas 77017 17 FOR THE DEFENDANT: 18 Mr. Richard Faulk 19 Mr. Kevin. Colbert Gardere Wynne Sewell & Riggs 20 333 Clay Avenue, Suite 800 Houston, Texas 77002 21 -and 22 Mr. Kevin M. Sadler 23 Baker & Botts 1600 San Jacinto Center 24 98 San Jacinto Boulevard Austin, Texas 78701-4039 25 3 1 The oral deposition of ETHAN A. 2 NATELSON, M.D. was taken on SEPTEMBER 25, 3 1996, beginning at 2:00 p.m., in the offices 4 of Gardere Wynne Sewell & Riggs, L.L.P., 333 5 Clay Avenue, Suite 800, Houston, Harris 6 County, Texas, before Johnnie E. Barnhart, a 7 Certified Shorthand Reporter and Notary 8 Public in and for the State of Texas, 9 pursuant to Notice, the Texas Rules of Civil 10 Procedure, and the following stipulation of 11 counsel for the respective parties that: 12 IT WAS STIPULATED AND/OR AGREED 13 that the deposition is to be signed by the 14 witness before any Notary Public or officer 15 authorized to administer oaths. 16 17 ----18 19 (Natelson Exhibit Nos. 1 through 6 20 marked for identification) 21 22 23 24 25 4 1 ETHAN A. NATELSON, M.D., 2 called as a witness and having been first 3 duly sworn, testified as follows: 4 5 EXAMINATION 6 BY MR. THOMPSON: 7 Q Dr. Natelson, could you state your full name 8 for the record, please. 9 A Ethan A. Natelson. 10 Q Dr. Natelson, it's my understanding that 11 you've been asked to give expert testimony in 12 this case. Is that your understanding as 13 well? 14 A Yes. 15 Q On whose behalf have you been asked to give 16 expert testimony? 17 A On behalf of Mr. Faulk, is the attorney who 18 has asked me to render that. 19 Q And do you know who the defendants are in 20 this case on whose behalf you've been asked 21 to render the opinions? 22 A Actually, I'm not sure. 23 Q Do you know the name of the plaintiff in this 24 case? 25 A Yes. 5 1 Q What is the plaintiffs name? 2 A A Mr. Jesus Frias. 3 Q And you understand that Mr. Frias' family has 4 filed a lawsuit against the defendants in 5 this case alleging that Mr. Frias' death was 6 related to his occupational exposure to 7 benzene? 8 A Yes. 9 Q My name is Jeff Thompson. I represent the 10 plaintiffs. We haven't met until just 11 today. 12 Let me show you what I've marked as 13 Exhibit 1. It's a copy of the deposition 14 notice for today. Attached to the notice is 15 a subpoena. Have you had an opportunity to 16 see that subpoena? 17 A No. 18 Q Has Mr. Faulk asked you to bring with you any 19 documents that you created, received, intend 20 to rely upon for purposes of the testimony 21 you intend to give today or at trial? 22 A Yes. 23 Q Have you done that? 24 A Yes. 25 Q What I've done, just to try and save us both 6 1 the time, I've taken a look at what you've 2 brought in. What I'd like to do just very 3 quickly is identify on the record what we've 4 got, and then when we proceed we can refer to 5 it by exhibit number. 6 I've marked as Exhibit 2 a copy of 7 your curriculum vitae, which you've provided 8 dated March 10, 1996. 9 A Yes. 10 Q Is this a current copy of your CV? 11 A Yes. 12 Q I have marked as Exhibit 3, I guess a -- it 13 looks like a billing statement. Why don't 14 you tell me what Exhibit 3 is. 15 A What this is is a billing statement for 16 reviewing the records that I was provided on 17 this particular case. 18 Q All right. And when do you recall originally 19 being retained by Mr. Faulk to review the 20 medical records in this case? 21 A I really don't remember. It may be in some 22 of the correspondence. It was several months 23 ago. 24 Q I've marked as Exhibit 4 -- well, identify 25 for me, if you would, what I've marked as 7 1 Exhibit 4. 2 A This is a proposed letter I drafted after I 3 reviewed these materials. 4 (1 And when you say "these materials," it would 5 be the pile of medical records that we have 6 here today on the table? 7 A Minus Dr. Gardner's deposition. I don't 8 believe I had seen that at the time I wrote 9 this letter. 10 Q Do you recall -- the letter is dated 11 September 3. Did you provide a copy of that 12 letter to Mr. Faulk on September 3? 13 A I discussed it with him on the phone but did 14 not provide a copy of it. 15 Q When did you first provide a copy of the 16 report? 17 A I believe today. 18 Q Explain for me what I've marked as Exhibit 19 3 -- I mean Exhibit 5. 20 A This is a general treatise on benzene that's 21 prepared by the United States Department of 22 Health and Human Services. And it's updated 23 periodically. This is a 1993 edition. 24 Q Exhibit 6? 25 A These are a series of articles concerning 8 1 aplastic anemia from the medical literature. 2 Q Obviously, there's a lot of things that 3 encompass medical literature. Why have you 4 brought with you those specific articles? 5 A Well, these specific articles deal with the 6 etiology of aplastic anemia, the various 7 etiologies of it; the frequency of it. 8 Potential causes of it, treatment of it; and 9 the general characteristics of the various 10 types of aplastic anemia. 11 Q What does etiology mean? 12 A Cause of. 13 Q You mentioned Dr. Gardner's deposition. 14 A Yes. 15 Q There's a copy here. I think you testified 16 that you reviewed the deposition? 17 A Yes. 18 Q Did you take any notes when you reviewed the 19 deposition? 20 A No. 21 Q Also here is the pile of medical records that 22 I believe you testified you reviewed. Are 23 there any other medical records that you've 24 reviewed in this case? 25 A No. 9 1 Q Among the various pages of the medical 2 records are some tabs that are sticking out. 3 Are those tabs something that you added as 4 part of your review? 5 A Yes. 6 Q And what was the purpose of the tabs? 7 A Well, they highlighted certain things that I 8 thought were of particular interest, such as 9 bone marrow reports, lab values, histories, 10 things of that nature. 11 Q All right. I'll give you a chance to explain 12 those in a second. 13 Is there anything else, other than 14 the things that you've brought here today 15 that we've just identified on the record, 16 that you have reviewed in preparation for 17 your testimony today? 18 A Well, I have a large file on aplastic anemia, 19 and I looked through it and selected certain 20 references that I thought were appropriate; 21 but I may well have looked at other papers, 22 also. 23 Q But in terms of specific -- in the case of 24 Exhibit 6, specific articles that you intend 25 to point to, rely upon, quote to the jury in 10 1 this case, you have brought with you those 2 articles. 3 A Primarily, but I can't anticipate what 4 questions you might ask me; so you might ask 5 me something that I would respond to that 6 these articles don't give a frame of 7 reference, which I could subsequently 8 provide. But based on my thinking about this 9 case, these articles are satisfactory to 10 explain my opinions. 11 (a All right. Let me just ask you and maybe we 12 can cut to the chase a little bit: Would you 13 agree with me that Jesus Valentin Frias died 14 of aplastic anemia? 15 A Of complications of aplastic anemia, yes. 16 (a So you agree with that. 17 Do you have any quarrel with the 18 diagnosis of aplastic anemia in this case? 19 A No. 20 Q So with respect -- and one of the things, in 21 fairness -- let me back up. 22 Have you had an opportunity to 23 review any pathology or slides in this case? 24 A Yes. 25 Q So you have reviewed the slides? 11 1 A Yes, I have reviewed the slides. 2 Q But if I understand your previous answer, 3 with respect to the pathologic diagnosis or 4 whether or not Mr. Frias, in fact, had 5 aplastic anemia, you don't have any 6 disagreement with the doctors at MD Anderson, 7 correct? 8 A That's correct. 9 Q Dr. Quraishi? 10 A Dr. Quraishi was one of the doctors who 11 originally saw him at Pasadena Bayshore? 12 Q Correct. 13 MR. FAULK Let me lodge an 14 objection, because I want to make sure that 15 we're not being misleading here. If you're 16 talking about the disease category aplastic 17 anemia, I think the question is fine. But 18 there are different diagnoses of different 19 categories of aplastic anemia and different 20 etiologies of it 21 MR. THOMPSON: That's fine. I am 22 not talking about etiology. I'm trying to 23 get the issues focused here. 24 Q (By Mr. Thompson) You are not going to 25 testify nor do you intend to testify at trial 12 1 that Mr. Frias did not have the disease and 2 die of complications from the disease 3 aplastic anemia. 4 A He did have aplastic anemia and died from 5 complications thereof. 6 Q Would you agree with me that his aplastic 7 anemia was caused by his occupational 8 exposure to benzene? 9 A I think it is highly unlikely. 10 Q What do you think caused his aplastic anemia? 11 A I don't know. 12 Q If I understand your opinion, you don't 13 believe it was caused by occupational 14 exposure to benzene. 15 A Yes. 16 Q But you don't know what caused it. 17 A I would place it in the category of 18 idiopathic aplastic anemia. Idiopathic 19 acquired aplastic anemia, in which there are 20 several possible causes; but we don't know 21 which one it was. 22 Q And idiopathic, if I understand, I guess, 23 medical terminology correctly, is a term used 24 to describe a disease when you just don't 25 know what caused it. 13 1 A Frequently that's true. It means of itself. 2 Q Do you have any opinions about what else 3 might have caused Mr. Frias' aplastic anemia? 4 MR. FAULK: You're asking him to 5 speculate? 6 Q (By Mr. Thompson) No. I'm asking if you 7 have any opinions based on a reasonable 8 medical probability about what agents other 9 than benzene might have caused Mr. Frias' 10 aplastic anemia. 11 A Well, certain viral diseases might have 12 caused his aplastic anemia. 13 (1 What types of viral diseases? 14 A Hepatitis viruses occasionally cause aplastic 15 anemia. 16 Q Which virus? 17 A Well, frequently it's C and also the new 18 virus G. He was tested for C. He was not 19 tested for G. 20 Q Do you see anything in the medical records to 21 indicate that there was any clinical 22 indication that Mr. Frias had hepatitis of 23 any subcategory? 24 A Yes. He had elevated transaminase values on 25 a number of occasions before he came to the 14 1 hospital with aplastic anemia. 2 Q Is that lab finding diagnostic of hepatitis? 3 A No. 4 Q Is it consistent with any other possible 5 explanations? 6 A Well, it's consistent with liver injury, but 7 there could be many, many things that could 8 cause liver injury. 9 Q And, in fact, would you agree with me that 10 prolonged exposure to toxins like benzene 11 could cause liver injury? 12 A Well, I think you would have to qualify the 13 degree of exposure and the levels of 14 exposure. Generally, people who would have 15 liver disease from benzene would be 16 critically ill. That would not be an early 17 finding of benzene toxicity. 18 Q But assuming -- and I will get to levels of 19 exposure. Will you agree with me that liver 20 function could be a clinical manifestation, a 21 liver function problem, that would be 22 reflected in the lab reports that you've just 23 described? 24 A Well, chemicals can cause abnormalities in 25 liver function. 15 1 Q Correct. 2 A We certainly accept that. 3 Q And the tests that you just described would 4 indicate some abnormalities in liver 5 function. 6 A Yes. All it indicates there are 7 abnormalities in liver function. It doesn't 8 indicate the cause. 9 Q Okay. Is there any other indication that you 10 have seen in the medical records you've 11 reviewed that Mr. Frias had any form of 12 hepatitis? 13 A Other than the elevated transaminase? 14 Q Yes. 15 A No. 16 Q Any indication from the records you reviewed 17 that any other physician thought or expressed 18 the opinion that he might have hepatitis? 19 A No. 20 Q What other possible causes, in your opinion, 21 could be expressed for Mr. Frias' aplastic 22 anemia? 23 A Well, in the area of viruses, there's another 24 virus called parvo virus that we see as a 25 cause of marrow aplasia; primarily today in 16 1 patients with AIDS. Also, occasionally in 2 patients with sickle cell disease and other 3 hematologic problems. 4 Q Any indication that Mr. Frias had AIDS? 5 A No. 6 Q Any indication that Mr. Frias had sickle cell 7 anemia? 8 A No. 9 Q So is there any indication in the records 10 that you reviewed that Mr. Frias was 11 suffering from any kind of effect from the 12 parvo virus? 13 A Well, he was not tested for it. So we don't 14 know that he might or might not have it. 15 People who have that are often entirely 16 asymptomatic. The virus doesn't necessarily 17 cause them to feel ill, aside from making the 18 blood count go up. 19 Q Do you have any evidence that you can point 20 to in the medical records that indicates that 21 Mr. Frias had the parvo virus? 22 A No. 23 Q What other possible causes? 24 A Well, the --about 75 or 77 percent of all 25 aplastic anemia is generally classified as 17 1 idiopathic, meaning that there likely is a 2 cause but we don't know what that cause might 3 be. 4 Q What is it that convinces you that it was not 5 caused by benzene exposure? 6 A Well, I think first you have to look at the 7 incidence of that illness. In other words, 8 you're asking us to make a diagnosis of 9 benzene-induced aplastic anemia. Now, 10 Dr. Gardner has been a hematologist for many, 11 many years. I would guess longer than 40 12 years. 13 And in his deposition, he indicates 14 that while he's seen many cases of aplastic 15 anemia, he doesn't have -- he hasn't taken 16 care of a case of benzene-induced aplastic 17 anemia in all of those years. 18 Q Let me interject. Have you? 19 A No. And I've been a hematologist about 27 20 years, almost 30 years. 21 Q All right. 22 A So that in about 70 years of combined 23 experience, we haven't seen such an entity. 24 So first, that tells me that either the two 25 of us, who are working in an area, the Gulf 18 1 Coast area, in which there are a lot of 2 petrochemical industries, and probably many 3 people who have the potential to be exposed 4 to benzene, we haven't seen this particular 5 diagnosis. 6 And that suggests that either the 7 diagnosis is exquisitely rare or we have very 8 unusual practices, that somehow we're not 9 getting to see these patients. 10 Q Okay. Well, let me ask you: What is your 11 understanding of what the expected, you know, 12 from an epidemiologic standpoint, incidence 13 of aplastic anemia is in a general population? 14 A Well, in the United States it's thought to be 15 about two to five cases per million 16 population. So in a city like Houston, a 17 couple of million people, you would see 18 several cases a year, anyway. 19 Q How many patients have you treated, estimate, 20 in your 25 years of practice? 21 A Oh, I would say probably in the range of 20 22 that I've personally treated. I may have 23 seen others that others have treated; but 24 personally taking care of patients, I would 25 say about 20. 19 1 Q How many total patients can you estimate that 2 you've treated in your 25 years of practice? 3 A With all hematologic problems? 4 Q Yes. 5 A Oh, I couldn't even put a number on that. 6 Q A million? 7 A Certainly not millions. I've probably done 8 bone marrows on about seven or eight thousand 9 people with various kinds of blood problems 10 over the years; thousands anyway. Certainly 11 thousands I've done marrows on. And others 12 that I've seen that I haven't done bone 13 marrows on. So a large number of patients. 14 But getting back to your original 15 question as to why I don't think this was 16 benzene induced, I think the first situation 17 is that you look at the incidence of the 18 disease; and based on Dr. Gardner's and my 19 own experience, it suggests that it's very, 20 very rare. 21 And then I've looked at papers from 22 this decade describing patients with aplastic 23 anemia. And as I indicated in my report, 24 benzene was not cited as a cause in any of 25 more than 700 patients. 20 1 So that my conclusion is that this 2 is a very, very rare circumstance. So if I'm 3 going to make that diagnosis, I'd like it to 4 meet certain criteria. There are certain 5 things I would like to see before I would 6 come to that unusual diagnosis. 7 Q What are they? 8 A Well, not necessarily in order of importance, 9 but there are certain things that I would 10 like to see. For example, epidemiologic 11 data. If, for example, I was shown that many 12 of this person's co-workers developed 13 aplastic anemia or that people working in his 14 particular area had a very high incidence of 15 aplastic anemia, many times the incidence in 16 the general population, that would suggest 17 that there's some kind of an agent or agents 18 that he's exposed to that might cause that. 19 But none of this information 20 suggests to me that he has cohorts in the 21 area with a lot of aplastic anemia. So 22 epidemiologically, there's nothing that 23 suggests to me about the locale that he's 24 working that would predispose to aplastic 25 anemia. 21 1 (a Okay. But let me interrupt you for a 2 second. You do know that there was pure 3 benzene being shipped across the barges at 4 the refinery. You know that? 5 A Yes. I accept the fact that this man had the 6 potential to be exposed to benzene. But I'm 7 suggesting that I don't see this area that 8 he's working in as a hotbed of aplastic 9 anemia in terms of epidemiologic data. 10 (a Do you know of any specific studies that were 11 conducted at the Houston refinery docks with 12 regard to, you know, prospective, cohort 13 studies, retrospective cohort -- any kind of 14 epidemiologic study conducted by the 15 defendants in this case at the Houston docks? 16 A No. 17 Q Are you aware of any studies that were 18 conducted by any petrochemical company 19 specifically at a dock operation that 20 involved the shipment of benzene and 21 benzene-containing products? 22 A Well, some years ago I looked at some 23 statistics from the Amoco plant in the 24 Galveston area, I believe, and they had data 25 on illnesses that their employees had, 22 1 frequencies and so on. 2 And as I recall, there were no 3 unusual incidences of either acute leukemia 4 or aplastic anemia. So -- but that's the 5 closest thing I could think of that has to do 6 with what you're asking. 7 Q Okay. 8 A But in any event, getting back to my 9 question, I don't -- nothing in what I've 10 been shown, it may exist, but from what I've 11 seen, I don't see any data that suggests that 12 the incidence was unusually high of aplastic 13 anemia where this person worked. 14 Q Have you seen any information provided to you 15 by the defendants that indicate that there 16 were a number of people who worked out at the 17 docks that died or left the facility 18 suffering from malignancies? 19 A I haven't seen any data of that nature. 20 Q Would malignancies -- would cancer in general 21 and specifically leukemia be relevant to the 22 inquiry that you're talking about? 23 A It would be relevant to acute leukemia but 24 not so much other cancers. We know that 25 probably -- it's a remarkable fact, but 23 1 probably about a third of the cancers we see 2 are related to cigarette smoking. 3 But in the case of chemicals, we're 4 specifically talking typically about things 5 like aplastic anemia, or more commonly acute 6 myeloblastic leukemia. So we talked a little 7 bit about the epidemiologic data or lack 8 thereof. So that would be one thing I would 9 be looking for. 10 Then I would be looking for the 11 fact that there was some laboratory evidence 12 that this person had been exposed to high 13 levels of benzene. Now, such laboratory 14 evidence might be a low white blood cell 15 count at times during his occupation. 16 It might be a very elevated urinary 17 phenol level; something to suggest that he 18 had gotten a blast of benzene. And there are 19 numerous blood counts that I saw ranging over 20 a number of years and all of them were 21 normal. 22 Q How many do you recall seeing over a 20-year 23 period? 24 A Perhaps ten. I don't remember the exact 25 number. But I think in my letter I commented 24 1 over the years that I saw blood counts 2 listed. I don't remember the numbers, but 3 there were probably at least ten. And they 4 all had perfectly normal white cell counts 5 and so on. So there's nothing unusual about 6 his blood counts. 7 Q What about the red blood counts? Did you 8 notice anything unusual about the red blood 9 counts? 10 A Not that would relate to benzene exposure. 11 Q All right. 12 A There were a couple urinary phenol levels 13 that were reported, which were normal. So 14 let's say laboratory-wise, I did not see 15 anything that would suggest to me that he had 16 changes in his blood counts or chemistries 17 count with respect to benzene. 18 Q Did you notice any abnormal urinary phenol 19 counts? 20 A No. 21 Q All right. 22 A I might say there was a urinary phenol level 23 that was thought to be abnormal, but it's not 24 when you look at the data. 25 But in any event, the -- getting 25 1 back to the things I would be looking for. 2 We talked about epidemiology. We talked 3 about the chemistry. Let's say toxicologic 4 data. We know that people who get white 5 counts from benzene typically have prolonged 6 exposures of about 75 to 100 parts per 7 million of benzene. 8 (a When you say "prolonged exposure," you mean 9 repeated exposures at that level? 10 A Yeah, repeated exposures at that level over 11 days, weeks, months. And I didn't see 12 anything that suggested to me that he had 13 levels measured in the ambient air that he 14 was exposed to that were high. That data may 15 exist, but I don't believe it's in any of 16 this material that I was provided. 17 Q If I could show you data that shows that in 18 his work space that he worked at on the 19 docks, I guess 18 years -- I almost said 20 20 -- but 18 years, that there were area 21 monitoring results that range from, you know, 22 one part per million to hundreds of parts per 23 million, would that be relevant to your 24 diagnosis? 25 MR. FAULK: I'm going to object to 26 1 the question because area monitoring results 2 are misleading. They're not relevant to the 3 calculation of personal exposure, and I think 4 you know that. 5 MR. THOMPSON: Okay. Well, let me 6 ask the doctor. 7 MR. FAULK: No. I think 8 MR. THOMPSON: Let me ask the 9 question in fairness. 10 (a (By Mr. Thompson) Do you believe that it 11 would be relevant to deciding whether or not 12 there was, in fact, exposure to examine area 13 monitoring data that related to the 14 workplace, the very work environment that a 15 man worked at for 18 years? 16 MR. FAULK: I'm going to object 17 because the question assumes that Mr. Frias 18 was in the area undergoing those exposures in 19 that particular environment at all times, and 20 that the question doesn't quantify the 21 duration of exposure. 22 Ca (By Mr. Thompson) Do you understand my 23 question, Doctor? 24 A I understand your question, and I'm going to 25 answer it this way: I've worked in 27 1 laboratories for many, many years, and I know 2 that you can have two people working within a 3 few feet from each other in the same 4 laboratory and one is getting tremendous 5 exposures to something and the other one is 6 getting nothing. 7 And depending on where you measured 8 your levels in the air, you might find low 9 levels or high levels or intermediate 10 levels. And unless you can put the person's 11 head under the hood where all the chemicals 12 are, you can't make much out of that data. 13 Q Okay. Well, let me ask you this: If there 14 was monitoring data, personnel monitoring 15 data now, something attached to human beings, 16 that showed that tasks that Mr. Frias 17 performed during his 18 years at the docks 18 involved exposures as high has 750 parts per 19 million, would that be relevant to your 20 differential diagnosis? 21 MR. FAULK: I'm going to object as 22 the question assumes that no protective gear 23 was worn. It's an incomplete hypothetical. 24 It is misleading as stated. 25 Q (By Mr. Thompson) Do you understand my 28 1 question, Doctor? 2 A I understand your question. And as I 3 understand it, you're suggesting that there 4 may be data that he personally was breathing 5 in many hundred parts per million for some 6 extended period of time: 7 Q Yes. 8 A Okay. If I saw such data, I would be 9 interested in that data. As I say, what 10 you're looking for in the case of 11 benzene-induced aplastic anemia is that the 12 exposure dented the bone marrow or the blood 13 counts. And we don't have any evidence that 14 it did in the blood counts and chemistries 15 that we have. 16 So I think that data is 17 interesting. But in looking at it in terms 18 of the meaning of it, we don't see that he 19 had the exposure that we would like to see to 20 cause aplastic anemia. Because to do that, 21 we would expect to see low white counts or 22 other cytopenias from time to time. 23 Q But when you refer to the data, what data did 24 you review that relates to exposure? 25 A I reviewed what was ever in this pile. And 29 1 if you have some particular sheet that you 2 want to go over, we can look at it. 3 Q But the pile I think you're referring to is 4 the medical records, correct? 5 A Yes. 6 Q And have you reviewed any industrial hygiene 7 monitoring data in this case? 8 A I've reviewed only what's in this pile. Some 9 of it has to do with his work history. There 10 are some urinary phenol measurements in 11 there. I don't recall if there are any air 12 measurements of benzene. 13 MR. FAULK: Just to be clear, there 14 are records in the pile that are company 15 records. They're not just medical records 16 from hospitals and physicians. 17 Q (By Mr. Thompson) But do you recall, Doctor, 18 specifically whether you have reviewed any 19 monitoring data, whether it be personnel 20 monitoring data or area monitoring data, that 21 deal with levels of benzene in the ambient 22 air at the docks? 23 A I can't recall specifically that from this 24 pile. 25 Q You were talking under Part 2, and I think 30 1 Part 3 as well, as things you would look for 2 as evidence of exposure. Do you recall that? 3 A Yes. 4 Q And you talked specifically about lab testing. 5 A Right. 6 Q Wouldn't the monitoring data that was done by 7 the refinery for the job classification that 8 Mr. Frias worked in be relevant to your No. 2 9 in how you would determine the cause of his 10 aplastic anemia? 11 A Well, I think it would be relevant if it was 12 clear that this person was breathing in or 13 getting through his skin or some other way 14 those kinds of levels. In other words, if 15 you could demonstrate to me that someone was 16 sitting and breathing for an eight-hour day 17 300 to 500 parts per million benzene, I would 18 think that's significant, yes. 19 Q What about 10 parts per million? 20 A No, I wouldn't think that was significant. 21 Q Eight hours a day every day? 22 A Not to cause aplastic anemia. 23 Q And it's your opinion that there needs to be 24 some peaks of exposure? 25 A No. I think you're -- yes and no. Both 31 1 peaks and long durations of exposure. 2 Q So if I understand what you're saying, that 3 you -- I mean, you would agree with me that 4 aplastic anemia is a disease that has been 5 and can be associated with chronic exposure 6 to benzene? 7 A At high levels, yes. 8 Q And what do you define as high levels? 9 A Typically levels in the 300 range. 10 Q And it's your opinion that Mr. Frias would 11 have had to have been exposed to levels at 12 300 parts per million continuously for 18 13 years for you to connect -14 A No, not for 18 years. 15 Q Okay. How long? 16 A Possibly a few years. Possibly three or four 17 or five years might do it at those kinds of 18 levels. 19 Q How does peak exposures at a hundred, say, to 20 300 parts per million, if that's the range 21 we're talking about, the 300, I think, is a 22 number you used, right? 23 A Yes. 24 Q How does that relate to the development of 25 the disease if it is superimposed upon 32 1 continual low-level exposure? 2 MR. FAULK: I'm going to object to 3 the question because it doesn't define the 4 duration of the exposures. 5 Q (By Mr. Thompson) Do you understand my 6 question, Doctor? 7 A Yes, in general. 8 All I think we can say is that the 9 most people who've written about aplastic 10 anemia from benzene indicate that in general 11 the illness is dose related. And the more 12 dose you have over the longest period of time 13 means the more material you were supposed to, 14 and that puts you at a higher and higher risk 15 of getting aplastic anemia. 16 Q And when you talk about dose over a period of 17 years, that could be a cumulative number, 18 correct? 19 A Yes. 20 Q So the cumulative number could be arrived at 21 either by a long period of low to moderate 22 exposure or a shorter period, I think as you 23 described it, of high exposure. 24 MR. FAULK: I'm going to object to 25 the use of the term "cumulative," because it 33 1 assumes that everything is building up 2 without metaplasis. I think it's misleading 3 in that point. 4 A Well, I think that what you're looking for, 5 and, again, to specifically answer your 6 question, I'm not sure that I can, but I 7 think what you're asking is the relationship 8 between high levels and duration. 9 And what I'm suggesting is that the 10 higher the level and the longer you're 11 exposed to that level, the more benzene 12 you're exposed to. And the more benzene 13 you're exposed to the more likely you are to 14 get some complication from it. 15 (a (By Mr. Thompson) Do you -- in your opinion, 16 is there a threshold in a cumulative number 17 in parts per million years that somebody 18 needs to reach before it would be your 19 opinion that you could link aplastic anemia 20 to established benzene exposure? 21 A I don't know that number. 22 Q Do you have a range? 23 A Well, as I said, generally the people with 24 aplastic anemia have been described as having 25 rather enormous exposures. Exposures of 300 34 1 to 500 parts per million for very long 2 periods of time. Years. So what their 3 cumulative dose would be, I don't know. It 4 would be very high. 5 to I interrupted you when you had gotten to No. 3, 6 which is toxicologic data. 7 A Okay. Next would be the characteristics of 8 the aplastic anemia. Now, all aplastic 9 anemia is not exactly alike. The end result 10 may be alike, in other words, the bone marrow 11 that has very little cellularity. But the 12 aplastic anemia that's been described with 13 benzene is a little different than what we 14 call idiopathic aplastic anemia. 15 Q How? 16 A It's different because of the fact that in 17 idiopathic aplastic anemia the bone marrow is 18 empty, as it is with this case. In the 19 aplastic anemia from benzene, typically the 20 bone marrow is not empty. It may be, but 21 that's not the characteristic finding. 22 The bone marrow is what we call 23 dysplastic. It may have reduced numbers of 24 cells, but the cells that are present are 25 very sick looking. And we refer this as a 35 1 myelodysplasia or a dysplastic syndrome. 2 And some people, for example one of 3 these articles I have here, refers to it, I 4 think, as a proliferative aplasia, meaning 5 that there is bone marrow growing and 6 proliferating, but it's proliferating in a 7 sick fashion. 8 And actual aplasia from benzene is 9 an unusual finding. It is not the 10 characteristic marrow finding. That's noted, 11 in particular, in this article from one of 12 the textbook. 13 So that the bone marrow findings 14 that he has of severe aplasia, while not 15 they certainly don't eliminate benzene as a 16 cause, they are not the classical feature of 17 benzene-induced pancytopenia and aplasia. 18 And in addition to the marrow 19 morphologic findings, because of the fact 20 that benzene is a leukemogenic agent and a 21 myelodysplasia inducing agent, frequently 22 chromosomes in people that have sick bone 23 marrows from benzene poisoning are abnormal. 24 So that classically in idiopathic aplastic 25 anemia the marrow chromosomes are normal. 36 1 In people that have had a period of 2 dysplasia, as you might think from chronic 3 exposure to benzene, frequently their marrow 4 chromosomes are abnormal. And in this case, 5 the chromosomes were normal, so I think that 6 more favors idiopathic aplastic anemia, 7 although it does not exclude completely 8 benzene-induced aplastic anemia. 9 Q And you've said that a couple of times. Have 10 you or have you -- what have you done to 11 exclude benzene as a cause of the aplasia in 12 Mr. Frias' case? 13 A Nothing. 14 MR. FAULK: Other than what he just 15 told you? 16 A Other than what I just told you. Because of 17 the fact that patients who walk in with 18 aplastic anemia very rarely, if ever, have a 19 sign on them that says "I have aplastic 20 anemia from ," and the agent is listed. We 21 always infer the diagnosis based on the 22 history, the physical, the epidemiologic 23 data, the history of drug and chemical 24 exposure, the laboratory findings. 25 We make an inference. We never can 37 1 prove with absolute certainty that the 2 aplastic anemia that we're seeing came from 3 what we think it came from. 4 Q (By Mr. Thompson) And what you've described 5 is, I guess you would agree with me, that the 6 traditional method that the medical doctors 7 employ in diagnosing disease is a 8 differential diagnosis? 9 A Yes. 10 Q And what you do when a patient walks in your 11 door is you take a history, correct? 12 A Yes. 13 Q You do a physical exam? 14 A Yes. 15 Q Oftentimes, based on the history and physical 16 you might have an impression of what you 17 think in your medical opinion might be the 18 possible problem, correct? 19 A Yes. 20 Q And you would then maybe note that as an 21 impression, but note what additional 22 things -- and that impression might create a 23 differential diagnosis, a list of 24 possibilities, correct? 25 A Yes. 38 1 Q And you would then decide whether or not you 2 needed to do testing or something that would 3 help rule out or move the different 4 possibilities up or down your list. 5 A Yes. 6 Q Of that -- of those things that we've just 7 described, the history, the physical, the lab 8 testing or objective testing, is there any 9 one of those three things that you can rely 10 solely upon? 11 A Well, as I've said, there is no one test in 12 any form of aplastic anemia that proves with 13 certainty -- we're talking about acquired 14 aplastic anemia -- there is not any one test 15 that proves with certainty that a specific 16 agent caused the illness in that particular 17 person. 18 Q For that reason, a doctor in your position or 19 doctor in Dr. Gardner's position or 20 Dr. Quraishi's position necessarily must rely 21 to a large degree on the history and 22 physical. 23 A Yes. 24 Q Would you agree with me that the history in 25 the case of aplastic anemia is particularly 39 1 important in trying to determine the 2 etiology? 3 A Yes. 4 Q Can you tell whether or not anybody 5 specifically inquired into Mr. Frias' 6 exposure to benzene on the job? 7 A Well, I believe the history and physical from 8 MD Anderson Hospital comments about the fact 9 that he had possible exposures to benzene. 10 It doesn't detail a work history from him. 11 It comments about his occupation and his 12 potential exposures. 13 Q Is it -- based on your professional opinion 14 and your review of the records, is it your 15 opinion that MD Anderson, the doctors that 16 treated him at MD Anderson, made an attempt 17 to decide whether or not benzene causes 18 aplasia? 19 A Well, I think that they did in the sense that 20 they took the history and physical as you 21 commented and they talked to the patient, 22 they examined him, they interpreted the lab 23 data, and made a judgment as to whether or 24 not they felt a drug or a chemical or a virus 25 or whatever was the cause of his aplastic 40 1 anemia. And their judgment was that it was 2 in the idiopathic category. 3 Q And that's your reading of their reports? 4 A Yes. 5 Q What about Dr. Quraishi? 6 A I don't recall with certainty what he said. 7 I believe that they did an original bone 8 marrow at the admitting hospital and the 9 patient was transfused. I don't recall. 10 We'd have to look at his history and physical 11 to see what he commented on. 12 Q If Dr. Quraishi had concluded that the 13 aplasia that he saw -- because Dr. Quraishi 14 was the referring physician, correct? 15 A Yes. 16 Q If he had concluded after his history and 17 physical and his review of the referral 18 report from MD Anderson that the aplasia was 19 caused by benzene exposure, would that be 20 important to your evaluation in this case? 21 A Not necessarily. 22 Q Why not? 23 A Well, different doctors have different 24 opinions about things. And when I see a 25 patient with cancer, I would like to review 41 1 the slides, I would like to be certain I 2 agree with that diagnosis. The fact that 3 someone else has made a particular diagnosis 4 may or may not be helpful. 5 Q Have you reviewed the testimony of Mr. Frias' 6 co-workers in this case? 7 A As I say, I've looked through what's in that 8 pile; and if that was included in there I 9 probably glanced through it. 10 Q Do you recall reviewing any testimony about 11 the work practices at the docks as it related 12 to specifically to benzene? 13 A I don't recall that. 14 Q Do you remember ever being informed or seeing 15 anything in the documents you reviewed that 16 talked about using benzene to wash down the 17 surface of the dock out at the dock? 18 A I don't recall that specifically. 19 Q Or washing hands and tools and clothes in 20 benzene? 21 A I don't recall that. 22 Q In your practice, you treat, I think you 23 said, a number of people that work in an 24 industrial setting, correct? 25 A Yes. 42 1 Q And you've evaluated, I assume, people with 2 blood disorders to try and determine whether 3 or not benzene was a cause. 4 A Yes. 5 Q Have you ever, in your practice, concluded 6 that benzene, in fact, caused any of the 7 blood disorders that you've treated in 8 patients? 9 A Yes. 10 Q What kind of work did those patients do? 11 A Well, I can recall one fellow -- I even, in 12 fact, recall his name, Joel Landers -- who 13 had worked for many years with a variety of 14 chemicals; I believe in a Louisiana plant. 15 And he had had a number of blood counts 16 showing depression of his white count that 17 would later recover over the years. 18 And he was taken away from 19 chemicals, put back in, taken away. And 20 eventually he developed a severe 21 myelodysplastic syndrome which eventuated in 22 acute leukemia. And I felt fairly confident 23 that based on the work records that he had 24 and the exposures that he had that it was 25 probably chemically related. 43 1 Q Do you know what -- specifically what kind of 2 chemicals he worked around in his job? 3 A I believe that benzene was there, but that 4 was not the predominant chemical that he 5 worked with. And I'm just blanking on what 6 it was, but it was not benzene. 7 Q. Was that a product that might have contained 8 benzene? 9 A I just really don't recall. I would have to 10 look back on his records. He worked with a 11 lot of nickel, very high doses of nickel in 12 some kind of chemical bonding operation. And 13 phosphorus at very high levels. I really 14 don't remember all the chemicals he worked 15 with, but it was considerable numbers of 16 chemicals. 17 (1 But of all of those things that you've just 18 named, I don't think any of those have been 19 associated with myelodysplasia. 20 A Well, heavy metals. Arsenic has been 21 associated with acute leukemia; and he was 22 exposed to a lot of heavy metals. And 23 probably arsenic was used in the nickel 24 production that he was involved with. So it 25 could have been arsenic related. He may well 44 1 have worked with benzene, too, but he 2 certainly worked with chemicals. 3 Q Any other that you can recall? 4 A I've seen a couple of people with 5 myelofibrosis, which is another unusual 6 disease that has been thought to be caused by 7 benzene. And I saw one fellow, I recall, who 8 for about 30 years had driven trucks that 9 contained benzene and would commonly lift the 10 lids to sniff to see if it was really in 11 there. 12 And he developed myelofibrosis; and 13 I thought many, many years of exposure at 14 probably high levels. It was high risk that 15 that caused it. We don't know what causes 16 most myelofibrosis, but I thought in that 17 particular case it was suggestive that 18 benzene would be the cause. 19 Q In your example of myelofibrosis -20 A Yes. 21 Q -- rare disease, relatively rare disease, 22 correct? 23 A Well -24 Q I think that's what you said. 25 A Well, it is rare; but it depends on who 45 1 you're talking to. In other words, to a 2 hematologist, it isn't rare. I might see a 3 case a year. But to a general practitioner, 4 they might see a case in their whole lifetime 5 of practice. 6 Q What I mean, and what I'm getting at, is that 7 is a disease not unlike aplastic anemia that 8 in the general population is a rare thing to 9 see. 10 A It's not as rare as aplastic anemia, but it 11 is an infrequently seen disease, yes. 12 Q And I think your other comment about 13 myelofibrosis was that it was a disease for 14 which they commonly don't have an explanation. 15 A That's correct. In most cases we don't have 16 any exposure history to chemicals, and we 17 call it idiopathic. 18 Q In this particular instance, you believe that 19 it was not idiopathic and could be caused by 20 the chemical exposure because of the 21 information you received about the job this 22 man performed. 23 A Yes, in part. 24 Q How many years did he perform the job you've 25 described? 46 1 A It's a fuzzy recollection, but I would guess 2 it was almost 30 years. 3 Q If I understood your description correctly, 4 he drove a tanker truck of some sort and got 5 involved in sampling or looking at the 6 product in his truck. 7 A That's correct. On a regular basis. 8 Q And that would be the kind of job that, based 9 on your basic understanding of, you know, the 10 industry in general, would potentially 11 involve high levels of exposure. 12 A From his description, yes. 13 MR. THOMPSON: Do you need to take 14 a break? 15 MR. FAULK: I've got a couple 16 things I have to do. Can we take about five 17 minutes? 18 MR. THOMPSON: Yes. That's fine. 19 (A recess was taken) 20 Q (By Mr. Thompson) Doctor, we had kind of 21 been, in outline form, going through the 22 steps that you were describing as -- you were 23 describing to me how you had determined that 24 you believe that Mr. Frias' aplasia was not 25 related to benzene exposure. 47 1 A Yes. 2 Q And as we went through, the first point you 3 made was to review available epidemiology. 4 A Yes. 5 Q Right? No. 2 was to look for evidence of 6 exposure, and you specifically referred to 7 the lab testing, correct? 8 A Yes. 9 Q No. 3 was reviewing toxicological data that 10 was available. 11 A Yes. 12 Q And with regard to that, what specifically 13 did you -- I assume you're talking about 14 what's out there in terms of the medical 15 literature and articles. 16 A Yes. 17 Q Studies and things that have been done. 18 A Yes. 19 Q How is that different from the epidemiology, 20 in particular? 21 A Well, epidemiology might give you clues as to 22 an etiology. Perhaps I can give an analogy. 23 You might find, let's say, that a farmer or 24 farmers have a very high incidence of some 25 particular problem. Well, that would be 48 1 found on an epidemiologic basis. Let's say 2 all your farmers in Utah are dying at age 3 50. So there must be something that's 4 killing them. 5 Well, then you have to go and look, 6 Well, was it the pesticides they sprayed? Is 7 it the fact they're exposed to certain 8 viruses that their animals have? Is it the 9 fact that they're exposed to certain soil 10 bacteria? 11 In other words, the epidemiology 12 doesn't prove what the agent was; it simply 13 gives you a general idea of hot spots of 14 disease or areas that you might want to focus 15 down on to try to look at causes. Whereas 16 specific chemical data gets into the fact, 17 Well, okay, now we accept that a particular 18 chemical causes a particular problem. 19 Well, how much of that chemical 20 does it take to cause that problem? So when 21 you're looking at chemical data, it's a 22 little different than epidemiologic data. 23 There is some crossovers. 24 Q It's more specific and more chemical specific. 25 A Yes. 49 1 (a Whereas epidemiology is population specific. 2 A If you will, yes, sir. 3 (a I guess in an ideal world in this case you 4 would be looking for an epidemiologic study 5 that addresses only, you know, I guess dock 6 workers who worked at the Houston refinery 7 between the years 1976 and 1994. 8 A Well, if you wanted to focus that carefully. 9 But I would simply be looking for something 10 that, let's say, Gulf Coast industry people, 11 for example. You could get either cone down 12 with the microscope or go up on low power, 13 depending on how much you wanted to do. Or 14 people in Texas or people in southern United 15 States. 16 In other words, are there hot spots 17 of aplastic anemia? And then you might focus 18 down and see why are those hot spots there. 19 But I don't know of any evidence that we have 20 that we have hot spots of that in this 21 environment. In fact, Dr. Gardner's and my 22 experience would certainly suggest that we 23 don't. 24 Q Are there any specific epidemiological 25 studies that address aplasias that you have 50 1 reviewed and based, in part, your opinions 2 that you are expressing today? 3 A Well, some of these studies I believe have to 4 do with epidemiology in terms of you asked 5 earlier what's the incidence. That's in a 6 sense an epidemiologic study. How many 7 patients per particular population. Then you 8 look at what was the age, what was the sex, 9 what differences do you see. And certain 10 things do stand out in epidemiologic 11 studies. 12 For example, in aplastic anemia 13 there's some suggestion that, like Hodgkin's 14 disease, there are a younger group of people 15 that catch it and an older group that catch 16 it. And there are also certain sex 17 differences that appear. But I don't know 18 that any of that data was pertinent to this 19 case. 20 Q If I understand your process correctly, 21 you're saying you should look to the 22 available epidemiology. You're not 23 suggesting that you would go out and conduct 24 a study. 25 A No, certainly not. 51 1 Q You look to the available epidemiology and 2 see if it points you in a direction. 3 A That's correct. 4 Q Is it your opinion that the epidemiology out 5 there with respect to industry in general, 6 benzene in general, whatever, however you 7 want to characterize it, does not point in 8 the direction of benzene as a possible cause 9 of aplastic anemia? 10 A Well, the information that's out there 11 suggests that in the past, when industries 12 were unregulated, benzene was a significant 13 cause of aplastic anemia. But that for many 14 years, benzene-induced aplastic anemia is 15 negligible. 16 Q Why is that? If you can draw a correlation 17 between those two facts, I would think that 18 it had something to do with the fact that the 19 industries now are more tightly regulated as 20 to benzene. 21 A That may be so. 22 Q So to the extent that you've got a worker in 23 an environment that for whatever reason is 24 not being closely monitored or regulated, of 25 what value is that data? 52 1 MR. FAULK: I'm going to object 2 that the question is vague and ambiguous. 3 A I'm not exactly sure what you're asking me. 4 Q (By Mr. Thompson) I guess, if I understood 5 your testimony correct, is that the 6 epidemiology that is out there, that you are 7 familiar with, indicates that historically 8 benzene exposure has been associated with 9 aplastic anemia. 10 A Yes. 11 Q But that in more recent epidemiology, that 12 the correlation or, in fact, the incidence of 13 aplasias are going down in an industrial 14 context. 15 A Have gone down, yes. 16 Q Have gone down. And I think that we agree 17 that a possible explanation for that could be 18 the fact that industry, in fact, over the 19 last 20 years has had to reduce the levels of 20 benzene exposure. 21 A Yes, that would be a reasonable assumption. 22 Q But you would agree with me that historically 23 that the studies done during the years when 24 the levels of exposure were, I guess in your 25 words, high, that the studies show a 53 1 relationship between benzene and aplastic 2 anemia? 3 A Yes. 4 Q Then when we get to Step 3, because we're 5 trying to differentiate between the two, the 6 toxicological data would be looking at what's 7 been published, what's out there as to the 8 specific poison benzene and how it affects 9 the body. 10 A Yes. 11 Q The fourth thing I think we talked about I 12 think was really pathology, which is looking 13 at the disease process itself. And I think 14 that you characterized or pointed out the 15 difference between aplasia and dysplasia. 16 A Yes. 17 Q And if I understand your opinion correctly, 18 it's that aplasia is rarer and doesn't -19 hasn't tended to be as associated with 20 benzene? 21 A That's correct. In benzene, while aplasia 22 can certainly occur, it's been primarily 23 dysplasia, which may eventually lead to 24 aplasia. But that aplasia itself is 25 considered to be certainly less common than 54 1 dysplasia. 2 Q. And when you say that the dysplasia may 3 eventually develop into aplasia, what does 4 that mean? 5 A Well, when you see sick bone marrows, for 6 example, in people that we give chemotherapy 7 to, like benzene that may cause a dysplastic 8 syndrome. And as you follow such patients, 9 what you find is that the bone marrow may 10 become aplastic, the cells may disappear from 11 it. 12 The sick cells, the few sick cells 13 that are there, may become air. They may be 14 gone. Or the sick cells may get so sick they 15 convert into a leukemia. So you can see 16 various changes that occur in dysplastic 17 marrow. They can go different directions. 18 (a Based on your review of the medical records 19 in this case, it's your opinion that 20 Mr. Frias' disease process never passed 21 through a dysplastic state? 22 A Correct. Because it appeared that his 23 illness occurred quite suddenly. One day he 24 noticed red spots on his feet and the next 25 day he noticed bleeding from a tooth, and 55 1 then he came into the hospital and was found 2 not to have any blood. So his disease 3 appeared to occur very abruptly. 4 Q No clinical indication in your review of the 5 medical records that there might have been 6 something wrong with him prior to? 7 A Not that I saw. 8 Q But at any rate, it's not your testimony that 9 because -- assuming that he was first 10 diagnosed, in the first manifestation of his 11 disease was, in fact, an aplastic state, if I 12 understand you correctly, you are not 13 testifying that that means that benzene 14 couldn't have caused it. 15 A That's correct. 16 Q Is there a next step after the pathologic 17 differences? 18 A Well, I think the pathology, I suppose you 19 could divide that into really two areas. One 20 is morphology. In other words, what does the 21 bone marrow look like. 22 And the second would be, let's say, 23 other tests such as cytogenetics, the 24 chromosomal analysis that he had. And his 25 chromosome analysis was normal, as we 56 1 commented, which certainly does not exclude 2 benzene or other toxins, but it makes it less 3 likely. 4 Q When we were talking about exposure, 5 cumulative doses and things like that, you 6 used the terminology that there needed to be 7 an exposure sufficient to dent the marrow. 8 Do you remember using that word? 9 A Yes. 10 Q Tell me what you mean by that. 11 A Well, in general, when we look, for example, 12 at chemotherapy-induced myelodysplasia or 13 leukemia, what we find is that low levels of 14 chemotherapy is not frequently associated. 15 It's typically very high levels of 16 chemotherapy which result in significant 17 suppression of bone marrow function for a 18 period of time. 19 And what presumably is happening is 20 that you are damaging stem cells by producing 21 various changes in the DNA. And you may not 22 get that by low-level exposure, but you may 23 more easily get it by very high level or 24 intense exposure. 25 Q In use, let's say, with your analogy of 57 1 chemotherapy. If the chemotherapy is 2 successful and doesn't cause the death of the 3 patient, do the dents remain in place or do 4 they -- do the processes of the human body 5 repair those dents? 6 A Well, generally they're repaired. We 7 generally feel, and I believe the literature 8 supports that if a person, for example, gets 9 high doses of chemotherapy, there is a risk 10 period during which leukemia or bad things 11 may happen. And that peaks around 3 to 7 12 years. 13 But typically by about 11 or 12 14 years, the risk is gone and the bone marrow 15 has either gone bad during that period or it 16 has repaired itself. 17 Q. So in using the paradigm that we're talking 18 about of a very acute injury, short period of 19 time, high level, big dent. 20 A Yes. 21 Q That the extent to which that trauma, that 22 insult, that injury to the marrow is going to 23 develop aplasia, let's say, it would be a 24 relatively short period of time? I think you 25 said what? Seven to -- 58 1 A Well, from chemotherapy, I was talking about 2 acute leukemia, not aplasia. Aplastic anemia 3 from chemotherapy is not common. Like in the 4 benzene situation, we can induce leukemia all 5 right; but it's actually quite uncommon to 6 get aplastic anemia. We more likely get 7 dysplasias. 8 Q And why -- do you have an opinion or a theory 9 about why that is true? 10 A Well, it would be complete speculation. I 11 think that most people feel that in true 12 aplastic anemia, when the bone marrow 13 disappears entirely, what usually is 14 happening is there's some kind of an 15 immunologic set up such that the body is 16 starting to destroy its own cells. 17 That you didn't just kill them off 18 with your drug. You've done something to 19 jolt their immune system such that the body 20 perpetuates destruction. 21 Q And so now we're talking as opposed to 22 etiology, which would be the connection 23 between the agent and the disease, now you're 24 talking about the process, I guess, that 25 effectuates the disease or causes the 59 1 disease. 2 A Yes. Perhaps, yes. 3 Q What about benzene? How does benzene cause 4 the damage to the marrow? 5 A Well, I think that benzene is really very, 6 very close to the chemotherapy drugs we use. 7 The breakdown products of benzene, the 8 quinones, are inhibitors of an enzyme system 9 we call topoisomerase. And it's a DNA 10 remodeling enzyme system. 11 Q It does the repair. 12 A That does the repair. Well, it doesn't 13 exactly do the repair. What it does is 14 this: DNA is very tightly coiled. And in 15 order for the DNA to duplicate itself it has 16 to uncoil. And the topoisomerases allow the 17 DNA to uncoil. 18 Well, if you poison the 19 topoisomerases, you've now got the DNA with 20 its pants down; it can't get back together 21 properly, and defects occur. And depending 22 on how many of those defects occur, the body 23 can fix it. The body has an enormous 24 capacity to fix those things. But sometimes 25 you can overwhelm it. 60 1 So all of our drugs, even though 2 they're very diverse chemically, those that 3 are topoisomerase inhibitors are often 4 associated with what we call therapy-related 5 leukemia or secondary leukemia or 6 chemical-induced leukemia, whatever you might 7 call it. I think benzene is simply another 8 chemical that does that same thing. 9 Q In a general sense, would it be fair to 10 characterize what you're describing as a bone 11 marrow toxicity, a reaction in the bone 12 marrow just to the insult of the chemical? 13 A Yes. I think the chemical is interfering 14 with the normal maturation of cells; and in 15 so doing occasionally can cause a persistent 16 defect that gets you into trouble. 17 Q How is the aplasia different in this paradigm 18 that you and I are talking? How is the 19 aplasia different from leukemia? 20 A Well, by aplasia, what you have is simply a 21 lack of cells. In the case of leukemia, 22 what's happened is the bone marrow has 23 replaced the cell with blanks. Cells that 24 don't have any function. We call them 25 blasts. And those cells fill up the bone 61 1 marrow but they don't work. 2 And so you're prevented from making 3 normal cells. And you may have a situation 4 where the bone marrow is totally empty or a 5 situation where the bone marrow is full, but 6 to the body it makes no difference. There's 7 no blood production. In one case, it's 8 replaced by a cell that's not working and we 9 call it leukemia; and the other case it's 10 replaced by air or fat. 11 Q In both cases, though, the disease process is 12 a result of an insult to the marrow itself. 13 A Yes. 14 Q Do you have an opinion as to why in one case 15 or another the insult ultimately leads to the 16 fat or to the blanks? 17 A Well, I suppose in part it depends what 18 particular chromosomes are damaged, where the 19 damage occurs in the chromosome, how many of 20 the, what we call stem cells, which are the 21 cells that give rise to new blood, how many 22 of the stem cells are damaged. 23 It's probably a multifactorial 24 process. And I don't know that we know what 25 makes one person become, let's say, 62 1 myelodysplastic and another one become acute 2 leukemic. 3 Q In the long process that begins at the first 4 insult and ends with either aplasia or 5 leukemia, where along the line, you know, 6 does the decision tree? I mean, where do you 7 know whether you've got one or the other? 8 A I see. Well, here you make certain arbitrary 9 definitions. For example, we know that when 10 you look at a normal bone marrow only about 1 11 to 2 percent of the cells are what we call 12 blasts, very immature cells. They're good 13 blasts. Sometimes it's very hard to tell a 14 good blast from a bad one because they look 15 the same. But, anyway, there are very few in 16 a normal marrow. 17 Now, we say by definition that a 18 person with acute leukemia has greater than 19 25 percent blasts. But what about the fellow 20 who's got 15 percent blasts? He certainly 21 isn't normal, because that should only be 1 22 or 2. But, yet, he doesn't qualify for acute 23 leukemia; he doesn't have 25 percent. 24 So some people would use terms like 25 refractory anemia with increased blasts, and 63 1 various euphemisms for, Well, he's on the 2 road to leukemia. He hasn't quite got there 3 yet. So we make an arbitrary decision that 4 when there's so much blast population we can 5 make that diagnosis. And sometimes it isn't 6 exactly clear; it's not always easy. 7 Q What about with aplasia? 8 A With aplasia it's a little more clear, 9 because there what we're looking for are bone 10 marrows that have less than 20 percent of 11 normal total cellularity. With the cells 12 looking fairly normal, in the case of 13 classical aplastic anemia, in the case of 14 myelodysplasia-aplasia, even though the few 15 marrow cells that are there, they may look 16 very sick looking, very dysplastic. 17 Q Correct me if I'm wrong. It was my 18 impression that aplasias are often preceded 19 by a -- at some period of time by a -- I 20 don't know what term we're going to use today 21 to do it, but maybe not dysplasia but a 22 hyperplasia, where you've got bone marrow 23 function that is not really working right; 24 maybe your numbers are too high in some cases 25 clinically, and then you see the dropoffs. 64 1 A Well, that's more typical of the 2 chemical-induced type of aplastic anemia, the 3 drug -- the chemotherapy drug or benzene. 4 It's not typical of what we consider to be 5 drug-induced aplastic anemia. 6 (a Which is just -- you just see the drop. 7 A It drops immediately. Typically you get a 8 drug like Chloramphenicol, which is an 9 antibiotic. Your bone marrow is normal, you 10 get a very small amount of Chloramphenicol, 11 within two months time your bone marrow is 12 empty. And you've never gone through a 13 dysplastic phase. It just empties out. 14 Hepatitis is the same way. You 15 catch hepatitis; and as your jaundice is 16 fading away, suddenly your white cells 17 disappear. And within a matter of a month or 18 two you've got aplastic anemia. It occurs 19 very acutely. And that's the case of what 20 we've termed idiopathic aplastic anemia II. 21 Where we don't have drug; we don't 22 have hepatitis; we don't know why, but we 23 know the person had pretty good blood counts 24 a few months earlier and suddenly they're 25 gone. And we assume that something happened 65 1 in the preceding two or three months that did 2 it, but what that something was we don't 3 know. 4 Q Do you have an opinion about why the chemical 5 induced dysplasias are preceded by the 6 hyperplastic state? 7 A Yes. I think that their etiology is totally 8 different than what we call idiopathic 9 aplastic anemia. I think they're really 10 different diseases. I think in the case of 11 chemicals, chemotherapy agents, your cause 12 and development of a clone or a cohort of 13 cells in the bone marrow that are very sick 14 and eventually either become leukemic or die 15 out. 16 I think in the case of the 17 so-called idiopathic type or the hepatitis 18 type or the drug type, it has much more to do 19 with immunologic changes, and something 20 that's happened in your system. So your own 21 body is turning off the production as opposed 22 to having it turned off by a chemical that 23 you introduced. 24 Q And I want to make sure I'm clear so I 25 understand it. Do you believe that benzene 66 1 falls into that latter category or the first 2 category of chemicals that we discussed? 3 A I think the benzene falls into the 4 chemotherapy-type chemical that typically 5 acts by causing, as you put it, sometimes 6 increased cellularity. We call that 7 ineffective bone marrow or dysplastic bone 8 marrow. And then as that bone marrow gets 9 sicker and sicker, it may die out; it may die 10 out completely. So the bone marrow looks 11 totally aplastic. Or it may eventuate into 12 leukemia or it may sit and smolder with 10, 13 15 percent cellularity and very little blood 14 in the peripheral. 15 I think that's a very different 16 situation than what we call idiopathic 17 aplastic anemia, where there isn't this slow 18 development of aplastic anemia. It occurs 19 very abruptly. But the end stage is 20 indistinguishable. 21 Q The cytogenetics you referred to just is the 22 presence or absence of genetic aberrations or 23 abnormalities? 24 A Yes. 25 Q And if I understand what you're telling me, 67 1 in the idiopathic-type aplasias where the 2 bone marrow just in effect melts away, you 3 wouldn't expect to see genetic aberrations. 4 A That's correct. 5 Q But in the other types, chemotherapy, 6 benzene, chemical-type-induced aplasias, that 7 because your paradigm sees it as being an 8 insult that creates either -- to the stem 9 cells, it either makes the stem cell stop 10 functioning altogether or create clones that 11 you would expect to see genetic aberrations. 12 A Well, it wouldn't be 100 percent, but 13 frequently you would; I think would be the 14 term. 15 Q We went -- we were breaking down Step 4 into 16 A and B, morphology -17 A And then the chromosome study. 18 Q And the chromosome study. Is there a next 19 step? Is there a Step 5? 20 A Well, the laboratory -- there are other 21 laboratory tests that are occasionally 22 important. For example, one illness that 23 they tested this patient for was called PNH, 24 or paroxysmal nocturnal hemoglobinuria. 25 And that, like chromosomal 68 1 abnormalities, suggests that a clone of 2 abnormal cells has been developed in the bone 3 marrow. And the PNH cells are very 4 susceptible to breakdown by certain agents. 5 And they usually imply that somehow an 6 abnormal clone is growing in the bone marrow 7 of cells. 8 So that would be additional 9 evidence that there's been some, let's say, 10 preceding damage going on before you've 11 suddenly recognized that aplasia. And the 12 tests for PNH were negative in this 13 particular case. 14 (a And that's similar to the cytogenetic tests. 15 A Similar. It's the same concept, but a 16 different marker, you could say, that you're 17 looking at. 18 fl Anything else? 19 A I think that generally covers it. I think 20 the response to treatment is hard to gauge in 21 this case because the patient didn't live 22 long enough. I think that in the case of 23 chemical-induced defects in the bone marrow, 24 they don't really respond to treatment as 25 well as someone who has idiopathic aplastic 69 1 anemia. 2 But in this case, that's not 3 helpful because the patient really died 4 before the therapy had a chance to influence 5 the course of the illness. 6 Q You mentioned in the course of the discussion 7 we just had a couple of agents; the 8 chemotherapeutic agents we've been 9 discussing. 10 Do you see anything, any indication 11 in the records that Mr. Frias received any 12 chemotherapy? 13 A No. 14 Q You also mentioned a drug called 15 Chloramphenicol. 16 A Chloramphenicol or Chloromycetin is the trade 17 name. That's an antibiotic. It's still in 18 use around the world -- and in the United 19 States, rarely -- that can cause aplastic 20 anemia. 21 Q Any indication that Mr. Frias had taken that 22 drug? 23 A No. 24 Q In our discussion of other agents, are there 25 any other specific agents that you have seen 70 1 any indication of in the medical records that 2 Mr. Frias might have been exposed to or been 3 taking his medication that you believe might 4 have caused his aplasia? 5 A No. There are many drugs that have been 6 associated with aplastic anemia, but we don't 7 have a history that he took any of those 8 compounds. 9 Q Let's talk about dents again. If I 10 understand the paradigm that we're talking 11 about, in a successful chemotherapeutic 12 treatment, we're going to dent the marrow but 13 we hope the marrow repairs itself. 14 A Correct. 15 Q And in the course of treatment over maybe a 16 number of years, a cancer patient might 17 receive a number of different treatments over 18 the years, correct? 19 A Yes. 20 Q And the hope is that they will each -- in 21 each instance be able to recover, I guess 22 with the possibility they might have to 23 receive treatment again later. 24 A Yes. 25 Q In chemotherapy, are there different 71 1 strengths,--levels of exposure, I guess, if 2 we're using the terminology that we're using 3 today? 4 A Well, yes and no. For example, in 5 chemotherapy for the most part, we're giving 6 these drugs to tolerance. So if I gave you a 7 treatment with chemotherapy and your white 8 cell count didn't drop, I'd say: Gee, I 9 didn't give you enough. Next time around I'm 10 going to give you more. 11 And so we design our programs to 12 make certain that we do reduce the counts. 13 So they're given to tolerance. So when we 14 say high dose, we may be talking about 15 different drugs, but they all are given at a 16 dose that could, as I put it, dent the bone 17 marrow. 18 Q And that's the whole point. 19 A That's the point. You're giving a drug to 20 tolerance. 21 Q In the example of benzene, chronic exposure 22 to benzene over a 20-year period, assuming 23 with me that you, in fact, get high levels of 24 exposure, as you've defined it, I think, 300 25 parts per million, at some point you get a 72 1 dent, right? Is that what we're talking 2 about? 3 A Yes. 4 Q Would you expect, then, over a period of time 5 as these dents occur, as in the model of 6 chemotherapy for, at least initially, the 7 body to respond and repair the dents? 8 A Yes. Frequently in benzene-induced 9 cytopenias, the cytopenia recovers after you 10 take the patient away from benzene; and 11 frequently the bone marrow will recover. The 12 white cell count, which is low, may come back 13 up to normal. 14 Q How quickly? 15 A Well, in general, as with most chemotherapy 16 drugs, it's about two weeks. 17 Q So let me pose a hypothetical for you. And 18 we're talking about a single dent now. I 19 walk out the door and somebody sprays me in 20 the face with benzene; 300 parts per million 21 I get zapped. 22 A Yes. 23 Q My bone marrow gets zapped. 24 A Yes. 25 Q If you tested me that day, did a full blood 73 1 workup, would you expect to see a change in 2 my peripheral blood counts? 3 A I would not expect to see a change in your 4 peripheral blood counts. I might see a 5 change in your urinary excretion of 6 metabolites, but not in the peripheral blood 7 counts. 8 Q When would you expect the change in 9 peripheral blood counts from that dent to be 10 evident clinically? 11 A Oh, anywhere from depending on how high the 12 dent was or how hard it was, anywhere from 13 about 8 days to about 21 days out. 14 Q That's when it would appear? 15 A That's when you might be able to detect the 16 low level, yes. 17 Q Then in the paradigm -18 MR. FAULK: I'm going to object 19 because this whole line of questioning 20 assumes -- and I think it's misleading to the 21 doctor -- that you're walking out getting 22 sprayed in the face with benzene can somehow 23 suppress your bone marrow in 8 to 21 days. I 24 don't think it's a fair question. I don't 25 quite understand what you're trying to get 74 1 at. How long did the spray take? 2 MR. THOMPSON: Well, I'm not asking 3 you, Rick. Is that an objection? 4 MR. FAULK: Yes, it's an objection; 5 because you're confusing the witness and 6 you're confusing me. 7 MR. THOMPSON: I don't think the 8 doctor is confused. 9 Q (By Mr. Thompson) This is a hypothetical, 10 Doctor. You understand that. 11 A Yes. 12 Q And the reason I picked the hypothetical I 13 did is because I don't want to spend five 14 minutes quarreling about, you know, some 15 example that would be sufficient to cause a 16 dent. 17 So maybe the easy thing to do is to 18 say you and I agree -- we'll agree that an 19 event occurs that you believe is sufficient 20 to cause the dent that we're referring to. 21 A Let's say a large amount of the compound in 22 question, in this case benzene, is introduced 23 in the body. Enough compound to interfere 24 with bone marrow function so the white cell 25 count will go down. 75 1 Q Got it. 2 A That count is going to go down probably about 3 8 to 21 days after the major exposure. 4 Q Understood. And then the second part of my 5 hypothetical is: Looking at benzene now as 6 opposed to chemotherapy, when would you 7 expect the counts to rebound if the body 8 responds and repairs the marrow? 9 A Well, that's somewhat variable in person to 10 person. But in general, in trying to relate 11 it to chemotherapy, which, of course, we have 12 exquisite data on, we don't have that good a 13 data on benzene. But in the case of 14 chemotherapy, typically our protocols are set 15 up so they're given every three to four 16 weeks. So we know that in about three or 17 four weeks those low white cell counts will 18 have recovered. 19 Q And I'm purposely asking you to try and apply 20 the chemotherapy model that we've discussed 21 to benzene. 22 A Yes. 23 Q Just so we understand that. So if we look at 24 a window from 8 to 21 days, when you would 25 first expect to see the blood -- peripheral 76 1 blood counts affected, and then I think you 2 said from what was it, three weeks? 3 A Usually by about three weeks they're back up. 4 Q So you've got a window that you would -- if a 5 dent occurred that you would expect to see 6 changes in the blood that would begin, let's 7 say, around eight days after this dent 8 occurred; and would close, say, three weeks 9 after the dent occurred. 10 A Yes. It would depend on the dose, what kind 11 of dent occurred, how severe the temporary 12 aplasia was, and so on. But as a general 13 rule, within three or four weeks, unless the 14 dose of chemotherapy was overwhelming, the 15 bone marrow would recover. 16 Q And so even if we have this hypothetical 17 dent, and I understand we're talking 18 hypothetically, before that time, before 19 around eight days and after the three-week 20 period, even though you know that that dent 21 has occurred, you would expect to see the 22 peripheral blood counts basically normal. 23 A Typically, yes. 24 Q Over a period of life, you know, whether 25 we're talking -- I guess on the one hand 77 1 we've talked about chemotherapy, repeated 2 therapy. Let's look at benzene for a 3 second. How many dents can a body repair? 4 A Well, I don't know the number, but it would 5 be a very large number. 6 Q What is it -- I mean, if I understand the 7 analogy, at some point the body just can't 8 fix the dents anymore? 9 A Well, I don't think that occurs. I think 10 what happens is you're presenting a certain 11 number of dents, and the body has the ability 12 to fix those. And at some point you may 13 statistically overwhelm the fixing 14 mechanism. And you will have a personal 15 defect. It's not necessarily cumulative. It 16 may be, but it's not necessarily cumulative. 17 But you may, by bad luck, that day you got a 18 defect that you couldn't fix. You had a bad 19 day. 20 Q So at some point, whether it's because of the 21 sheer number of dents or the combination of 22 the number of dents with how big the dents 23 were or how many dents you had in the last 24 two weeks, your body just can't respond. 25 A That's correct. And there may be genetic 78 1 variability with that. We think that some 2 people -- and we find that some people are 3 much more sensitive to chemotherapy than 4 others. And in some patients a dose that 5 wouldn't bother the next fellow makes their 6 blood counts disappear. So there's a lot of 7 variability. 8 Q Would you agree with me that that general 9 principle of variability is true also of 10 chemical exposure? 11 A I would think so, yes. 12 (1 Do you know or do you have any knowledge of 13 whether or not that was a medical, I guess, 14 piece of medical information or fact that was 15 taken into account in why the levels of 16 benzene -- occupational levels for benzene 17 exposure in fact were set very low? 18 MR. FAULK: If you know. 19 A Well, I don't know the reasoning. These 20 levels weren't set abruptly. They've been 21 changing over time. They were at one time 22 ten and now they're one in terms of parts per 23 million. It's been a state of gradual change 24 over the years. 25 Q (By Mr. Thompson) Do you have an opinion as 79 1 to what level of benzene exposure is safe? 2 A Well, one can say that smokers, for example, 3 get a substantial amount of benzene but at 4 low levels. The claim is they have about ten 5 times the exposure that nonsmokers do. And 6 yet, if we try to look for illnesses like 7 aplastic anemia, we can't identify that 8 smokers are higher risk than nonsmokers. 9 So therefore, very low levels or 10 moderate levels, at least in the case of 11 aplastic anemia, don't appear to be harmful 12 or operative. But exactly how low a level is 13 bad, I can't give you a number. 14 (a In your opinion, is there any safe level of a 15 substance like benzene? 16 A Well, probably, yes. Levels in which the 17 body can detoxify it and not have any adverse 18 effect, yes. 19 Q But you just don't have an opinion as to what 20 that level is? 21 A I don't have an opinion as to what that level 22 might be. 23 Q. I tried to get down to kind of the important 24 issues, and we've already talked about two 25 things. One is your opinion that Mr. Frias' 80 1 aplasia was idiopathic. 2 A Yes. 3 Q And the second is -- and it really is 4 related -- that it was not caused by benzene. 5 A That's correct. 6 Q And we spent some time talking about that. 7 A Yes. 8 Q Other than those two specific issues, are 9 there any other specific issues that you have 10 been asked to formulate or give testimony or 11 opinions in this case about? 12 A No. 13 MR. FAULK: Does that mean we're 14 done? 15 MR. THOMPSON: Not far from it. 16 Let's go off the record for a second. 17 (Discussion off the Record) 18 Q (By Mr. Thompson) Dr. Natelson, when we 19 started, we described the different documents 20 that you brought with you today, and one of 21 the documents or the pile of documents that 22 you've brought with you we have not marked 23 but we've identified as medical records. 24 For the record, though, let's just 25 make sure what else is in this pile. Could 81 1 you real quickly kind of flip through it with 2 me so that we can make sure we know what is 3 in -- and I'm going to cover over here, if 4 you don't mind just for a second. 5 A This first batch has to do with Mr. Frias' 6 on-the-job evaluations. There are certain 7 letters in here about his performance on the 8 job and whether he meets his various 9 criteria. There's a death certificate, 10 various funeral home arrangements. There are 11 financial records of capital accumulation of 12 various -13 Q Is any of this stuff that you have looked at 14 and relied upon with respect to the opinions 15 in this case? 16 A No, not in this particular material. There 17 are membership data. Weeks of absence and so 18 on. They primarily relate to evaluation of 19 this person on the job. 20 Q If you'll just kind of go on to the bottom of 21 the pile and make sure there's nothing in 22 there that's important. 23 A On the bottom of the pile are some medical 24 records from Kelsey-Seybold Clinic, I 25 believe. Yes, from Kelsey-Seybold Clinic. 82 1 And these are vaccination records. They look 2 like outpatient office visit records, 3 predominantly. 4 Q Is it your -- are you aware of whether 5 Kelsey-Seybold Clinic provided occupational 6 medicine services for Arco or Lyondell? 7 A I don't know for a fact. Apparently they 8 did, based on what's here. But I don't know 9 their arrangements. 10 Q In the rest of the records that we've got 11 here, you've got some tabs that we've 12 previously referred to. Can you tell me what 13 the tabs are and why you put them on there? 14 A Yes. 15 Q Not specifically, but in general. 16 A In general. 17 Q These are things that are important that 18 you've tabbed because they're significant or 19 you want to be able to refer to them? 20 A Yes. The first one -21 Q Just for the record, other than in the bound 22 files, it doesn't appear that there are any 23 tabs anyplace else. I don't see any tabs 24 anyplace else. 25 A That's correct. 83 1 Q Now, in order to speed this along, here's 2 what I would like to do, Doctor. These have 3 got -- they're identified on the cover. So 4 the first binder are records from -- medical 5 records from Memorial Health Network at 6 Lyondell. All right? Do you see that? 7 A Yes. 8 Q If you will, just flip through and describe 9 for me on the record the tabs that you've got 10 and why you tabbed that particular page. 11 A This first tab has to do with a urinary 12 phenol measurement that was done on May 10, 13 1990 that was negative. 14 The second tab is chemistry work 15 from 1987, 4/16/1987, indicating that the 16 blood count is -- the white cell count is 17 normal but that the SGPT, which is a liver 18 enzyme, is elevated. 19 (a Let me back up. I'm sorry. I don't mean to 20 interrupt. 21 On the 4/90 tab that you've got, 22 you note that the urinary phenol test is 23 within normal range, correct? 24 A Yes. 25 Q What is the normal range? What is your 84 1 understanding of the normal range for a 2 urinary phenol test? 3 A Well, the normal range can vary. For 4 purposes of benzene exposure, what you're 5 looking for are levels of 50 milligrams per 6 liter or in excess of that. And that is 7 suggestive that a person has had exposure: 8 It's claimed that you have to have 9 had at least 10 parts per million exposure to 10 see elevated levels. But if you see elevated 11 levels, a significant elevation is considered 12 to be 50 milligrams per liter. 13 Q Are there different ways to test urinary 14 phenol? 15 A I imagine there are. 16 Q Would the normal ranges vary depending on the 17 type of lab test actually employed? 18 A Well, I don't know that the normal range 19 would vary, but the chemistry of the analysis 20 might vary. 21 Q But isn't it -- I mean, it's my 22 understanding, from kind of reviewing medical 23 generally, that even from lab to lab normal 24 ranges might change depending on the test kit 25 they use. 85 1 A Well, perhaps. A person's blood sugar is a 2 person's blood sugar. It may be measured by 3 many, many different techniques; but a normal 4 value is a normal value. 5 Q What I'm getting to is: For you as a 6 physician to make a determination as to 7 whether a particular lab test is normal or 8 abnormal has got to be made with reference to 9 that lab's reference for that test. 10 A Well, I think that's important. In other 11 words, for example, on this particular slip 12 we're not given a number. We're simply told 13 that it's normal. So I have to assume it's 14 normal. 15 Now, if they gave me a particular 16 number, and that number was 5 milligrams per 17 liter, and I know that you have to have at 18 least 50 to be significant, I would know that 19 that's not a significant value. But here 20 we're not given a number. We're just told 21 that it's normal. 22 Q And so you're relying upon the reporting of 23 the -24 A The reporting agency to -- that they really 25 did a correct job and, in fact, reported a 86 1 correct value. 2 Q In your opinion, does a negative urinary 3 phenol test prove that somebody was not 4 exposed to benzene? 5 A No. Because it has a lot -- a lot of it has 6 to do with timing as to when the phenol was 7 collected relative to the exposure. And even 8 a high level doesn't prove exposure, because 9 there are foods that can contribute to that. 10 A level that's low would suggest that within 11 the 24 or 48-hour period prior to the time 12 the level was collected there was not a high 13 exposure. As we're getting into the second 14 tab, it had to do an elevated liver function 15 test in 1987. 16 Q 3/2 of 1987? 17 A 4/16/1987. 18 Q I'm sorry. Got it. 19 A Then the second -- third tab had to do with a 20 May 16, 1985. And again, the transaminase 21 values were elevated; the liver function 22 test. 23 The next tab was from 4/12/85, and 24 it's a history from, I guess you would call 25 it a history, from the Kelsey-Seybold 87 1 Clinic. And it's a reference for them as to 2 what chemicals the person might have been 3 exposed to. And under this list, it's listed 4 benzene, orthoxylene, toluene, perhexiline, 5 xylene, dripolene, and gasoline. So I assume 6 that these are all chemicals that Mr. Frias 7 is alleging that he might have been exposed 8 to. 9 Q And you're assuming that Mr. Frias is 10 reporting that? 11 A Well, that is an assumption. It may not be 12 true, but he has signed this. So I'm 13 assuming that he reported that, or agreed 14 with it, since he signed it. 15 Q Now, earlier we talked about the importance 16 of the history and physical -17 A Yes. 18 Q -- in diagnosing clinical disease. 19 In your review of these medical 20 records when you see multiple entries like 21 this that say: Here are the things that I'm 22 exposed to during the day, benzene, toluene, 23 perhexiline, xylene, dripolene and gasoline, 24 is that something that as a treating 25 physician, diagnosing physician, that you 88 1 would take into account? 2 A Well, you would always -- you would take into 3 account everything that you have from the 4 history and physical. It may not be valid 5 history. In other words, you don't know the 6 validity of looking at something like this, 7 but you put it into the computer along with 8 everything else. 9 Q What if that came from -- not from Mr. Frias 10 but came from his employer, from the 11 doctor -12 A The same thing. In other words, you wouldn't 13 know to what degree the exposure was. It 14 would be of interest, just as you would any 15 list of drugs the patient might be taking. 16 Q All right. 17 A The next tab is from 8/27/82; and here is 18 another phenol level, and it was zero. 19 Q 8/27? 20 A 8/27/82. 21 Q Okay. I'm sorry. Let me interrupt for a 22 second. 23 If Mr. Frias, hypothetically, was 24 exposed to a high level of benzene -- and 25 I'll let you -- high to your satisfaction -- 89 1 five days earlier, would you expect for that 2 urinary phenol to show elevated levels? 3 A Probably not. 4 The next tab is from 11/19/81, and 5 that's a blood count, which was normal. 6 The next tab is from 8/31/78, and 7 it's a combination of a blood count, which is 8 all right; but the liver enzyme again, the 9 SGOT is elevated. 10 The next one is from 7/21/77, and 11 it's a blood count, which is normal. 12 (a Now, in either of those two, do you see any 13 abnormalities in the red blood 14 characteristics? 15 A Well, the numbers are normal. In other 16 words, this man's hemoglobin is 15.9, which 17 is a certainly normal value for the red blood 18 cell count. Now, the MCV, which is a figure 19 for the mean corpuscular volume, in other 20 words the diameter of the red cells, that is 21 at the upper limits of normal according to 22 the range here that's given. It's 99, and 23 they have their normal as 83 to 99. I 24 wouldn't make much out of that. 25 (d All right. Next tab. 90 1 A The next one is 11/24/76. And, again, it's a 2 blood count, which is normal. 3 Here from 11/22/76 is a urinary 4 phenol, which is normal. 5 Q. Is there a note there about benzene on the 6 medical record itself? 7 A No. 8 The next note is from 6- -- wait. 9 Let's see. This is a note from 6/4/81, and 10 it says victim was accidentally showered with 11 some perhexiline. And it's an incident 12 report, I guess, is the best way to describe 13 it. 14 (a Do you know whether or not perhexiline has 15 benzene as a component? 16 A I don't. 17 Those are all the tabs from this. 18 (a And this being the medical records from 19 Memorial Health Care. All right. 20 Go to the next one. And if you 21 would, just look at the cover so we can 22 identify it. 23 A I'm sorry. This one is from MD Anderson 24 Hospital. It's medical records. 25 Q Volume 2 of 5. As we go through MD Anderson, 91 1 if I could, Doctor, there should be numbers 2 at the bottom. Will you refer to the number 3 of the page on which your tab appears? 4 A Yes. 5 Q Thank you, sir. 6 A The first one is page 314, and what it is is 7 a result of a white cell transfusion that was 8 done on 7/31/94. 9 (a And what is significant about that? 10 A Well, it was interesting to me because we 11 don't normally do white cell transfusions 12 anymore. And I was interested that they did 13 that in this patient. 14 The next is page 369. And it 15 indicates that the patient was placed on 16 corticosteroid therapy on 6/20/94. 17 Q And what's significant about that? 18 A Well, I have tabs in here that have to do 19 with the treatment that was rendered. Some 20 people feel that steroids are of some limited 21 benefit in aplastic anemia, and he was placed 22 on steroids at that time. 23 Q What would steroids do? What kind of benefit? 24 A Well, they reduce inflammation. Sometimes -25 this patient was requiring blood 92 1 transfusions, which often cause allergic 2 reactions; and the steroids may blunt those 3 allergic reactions. They cover a wide range 4 of evils, steroids do. 5 Q Okay. 6 A The next is on page 392, and it's the 7 treatment with antithymocyte globulin, or 8 ATHGAM that was given to the patient, which 9 began on 6/9/94. 10 Q And what's significant about that? 11 A Well, ATHGAM is our standard therapy for 12 aplastic anemia. And I was interested in the 13 dose and the duration that they used. 14 The next note is from page 400. It 15 has to do with the fact that the patient was 16 . . administered Dilantin. I was interested in 17 that because occasionally Dilantin can cause 18 aplastic anemia, and in this case they were 19 giving it to the patient to prevent seizures. 20 Q But it's not your opinion that the Dilantin 21 that he received at MD Anderson caused his 22 aplasia? 23 A No. No. Certainly he had the aplasia long 24 before that. 25 The final note in this group is on 93 1 page 402. And it's the fact that they 2 administered what we call colony stimulating 3 factor or G-CSF to the patient. 4 Q And that's trying to get some cells to start? 5 A Trying to stimulate his bone marrow. 6 Q All right. Let's go to the next volume. 7 A The next volume has-no entries. That's 8 Volume 3 of 5 from MD Anderson. 9 Q The next volume. 10 A The next volume has no entries. It's Volume 11 5 of 5 from MD Anderson. 12 Q Great. 13 A The next volume, which is the Bayshore 14 Medical Center records, and it's page 3, and 15 indicates -- it's a discharge summary from 16 that hospital, and indicates that the 17 patient's white blood cell count was 900, 18 platelet count 4,000 and hemoglobin 9. 19 Q And what is the significance of those 20 numbers? 21 A Those numbers are what we call pancytopenia, 22 meaning all three cell lines are reduced. 23 That's the only entry from this file. 24 Q Why is it important to you to note that on 25 discharge from Bayshore he was pancytopenic? 94 1 A Well, pancytopenic is the hallmark of 2 aplastic anemia. It certainly can be caused 3 by many other illnesses, but one typically 4 has a pancytopenia in severe aplastic anemia. 5 Q All right. Do you recall -- when 6 Dr. Quraishi referred Mr. Frias over to MD 7 Anderson, from your review of the records, do 8 you recall what he specifically asked MD 9 Anderson to do? What the priority was? 10 A I believe he was referred there for 11 consideration for a bone marrow 12 transplantation. 13 Q And, in fact, in your review of the medical 14 records, what they were about at MD Anderson 15 was trying to figure out whether they could 16 treat this man's aplasia with a bone marrow 17 transplant? 18 A Well, that was part of what they did, yes. 19 They referred this patient to treat his 20 aplastic anemia. That might or might not 21 involve a marrow transplant. 22 Q Okay. Next volume. 23 A The next volume is Volume 1 of 5 from MD 24 Anderson Hospital. And it is page 30 from 25 6/28/94. And it's a discharge summary that's 95 1 labeled Bone Marrow Transplant. I assume 2 that's their bone marrow transplant team. 3 And I've marked this because it contains the 4 statement: The remainder of the workup for 5 aplastic anemia was completed and no specific 6 etiology was noted. 7 Q Now, is that the statement upon which you 8 base your opinion that MD Anderson diagnosed 9 it as idiopathic? 10 A No, not entirely. There are more statements 11 that say the same thing in that chart. 12 Q And here they just say that no specific 13 etiology was noted. 14 A In this particular -- in this particular page 15 they say that, yes. 16 Q All right. Go on. And that was page 30, 17 right? 18 A Yes. 19 This is page 36. And it indicates 20 that the patient received cyclosporin on 21 7/14/94, which is another drug we use for 22 aplastic anemia. 23 (a So again, you're just noting the treatment. 24 A Yes. 25 The next is page 37, and it has to 96 1 do with the death summary. 2 Q And what is significant about the death 3 summary? 4 A Just the time of death and what happened at 5 the time of his death. 6 Q Based on your review of the medical records, 7 and I guess your understanding of the disease 8 aplastic anemia, in general, how is it that 9 Mr. Frias actually died? What caused him to 10 die? 11 A Well, he was administered the drug 12 antithymocyte globulin, and the drug 13 cyclosporin and the colony stimulating 14 factor. Those are three things that have 15 helped patients with aplastic anemia. But 16 generally what you find is those drugs are 17 very slow acting. And to really get a good 18 response from those drugs often requires 19 months. And he didn't live long enough to 20 get that kind of response. And so what 21 happened was he sustained a series of 22 infections and also got bleeding from the low 23 platelet count. 24 So his death was related to 25 infection and bleeding, and indirectly 97 1 related to the aplastic anemia, which caused 2 the infection and bleeding. 3 Q What kind of infections did he have? 4 A He was thought to have a disseminated fungal 5 infection. 6 Q In his chest? 7 A If he had it in his chest he probably had it 8 in many other places. 9 Q I think there's some notation of pleural 10 fusion someplace? 11 A Yes. 12 Q That would relate to what? 13 A It could be any one of a number of things. 14 Q Could it have been blood in his lung? 15 A It could have been blood in his lungs. It 16 could have been infection that causes fluid. 17 It could have been heart failure. It could 18 have been any one of a number of things. 19 Q Specifically, what kind of bleeding do you 20 recall? 21 A Well, he had intracerebral bleeding. He had 22 bleeding in his head. 23 Q In his brain? 24 A Yes. 25 Q I mean, what does that do to -- where does 98 1 the blood go if you're bleeding in the brain? 2 A Well, it can't go very far. The skull is 3 fairly rigid, and the brain is very soft. 4 And it's all packaged very tightly in there. 5 And if you put just a small amount of blood 6 into the brain it gets squashed, and you die 7 very quickly. 8 Q Why does aplastic anemia lead to this 9 bleeding that you've described? 10 A Well, for a number of reasons. One, the 11 platelet count is very low; and platelets 12 sustain blood vessels. One of the functions 13 of the platelet is to migrate into the blood 14 vessel each day and keep it from being too 15 porous. And if you take the platelets away, 16 the blood vessels start to leak. 17 In addition, when you get 18 infections, particularly fungal infections, 19 that seems to damage the wall of the blood 20 vessel, make it leak even more easily. So 21 the combination of a bad infection and no 22 platelets often leads to bleeding. 23 Q And so in Mr. Frias' case, he clearly had 24 bleeding inside of his brain and perhaps 25 bleeding actually in his lungs and in his 99 1 chest. 2 A Yes. 3 Q The next tab. 4 A The next tab is page 44, and it indicates 5 that HLA testing was done on the patient's 6 family. There's a comment that his siblings 7 did not match. 8 Q What does that mean? 9 A Well, generally, marrow transplants can be 10 done from a variety of sources; that is to 11 say, that the donor cells can come from a 12 variety of sources. But the best source is a 13 brother or sister who is a close match, and 14 they didn't find that. 15 Q Does the failure to have a match in the 16 family have any impact upon your previous 17 opinions about the etiology of the aplastic 18 anemia? 19 A No. 20 Q We've talked a little bit about similarities 21 between -- and differences between aplasia 22 and leukemia. 23 A Yes. 24 Q And I guess one of the fundamental 25 differences, maybe the fundamental 100 1 difference, is one is I guess technically a 2 malignancy, leukemia; and the other is not. 3 A That's true. 4 Q But in our earlier discussions, we kind of 5 talked about the disease process in the blood 6 itself as being in many ways a continuum that 7 starts with insult and may end up in either 8 of those type of disease states. 9 A Yes. 10 Q Leukemia, even though it's cancer, can be 11 treated, correct? 12 A Yes. 13 Q And we've talked at some length about 14 chemotherapy, and that's one of the 15 treatments that is commonly used for 16 leukemia. 17 A That's correct. 18 Q Is there -- what are the chances of survival 19 if somebody, say, Mr. Frias' age -- I think 20 he was, what, 52, 53? I can't remember. 21 A Something like that. 22 Q Middle-aged. 23 A Yes. 24 Q -- is diagnosed with leukemia and you're able 25 to treat it? Is there some chance of 101 1 survival? 2 A Yes. 3 Q But in his case, his aplasia was so acute and 4 so severe that I think your testimony is 5 there really wasn't even a chance to treat 6 him. 7 A Well, I suppose you would have to say this: 8 In today's world, if you have two patients, 9 one with aplastic anemia and one with acute 10 leukemia, statistically the patient with the 11 aplastic anemia is going to do better than 12 the acute leukemia patient. 13 In this -- and one might have 14 expected this patient to do better than 15 someone with acute leukemia, but 16 unfortunately he got badly infected and the 17 treatment just didn't get a chance to gel. 18 He just didn't survive long enough for the 19 treatment to do its work; so that he died. 20 And that is the case in many 21 patients with aplastic anemia. The general 22 date of these days from various series is 23 that probably anywhere from 50 to 60 percent 24 of people with aplastic anemia get over their 25 illness with treatment. Some series even 102 1 higher. 2 Q 50 to 60 percent? 3 A In most cases. A lot depends on whether or 4 not you have a match in the case of a 5 transplant. But I would say 60 percent would 6 be a reasonable figure that would do well 7 with treatment. 8 Q And is this true of the aplasia that like 9 Mr. Frias' that end up with literally no 10 cells, with just fat? 11 A Well, in general, that's true. Some 12 people -- we generally call severe aplastic 13 anemia something that has lower than 500 14 granulocytes a type of white cell. And some 15 people call unusually severe aplastic anemia 16 if they only have 200 granulocytes. 17 I believe he was in the 500 18 granulocyte variety. And so he had severe 19 disease, but a very significant chance of 20 doing better. And I've certainly treated 21 people who have had just as abnormal blood 22 counts as he has that have done quite well. 23 Q But, again, the fundamental difference, I 24 guess, that we've discussed already is that 25 in aplasia you end up really with no cells 103 1 being produced in the marrow as opposed to a 2 leukemia where you've got cells being 3 produced but they're bad cells, blanks, as 4 you described. 5 A They're blanks, yes. 6 !1 In some ways would you agree with me that 7 aplastic anemia can be worse than leukemia in 8 terms of the clinical presentation? 9 A Well, of course, there are many kinds of 10 leukemia. Let's assume you're talking about 11 acute myeloblastic leukemia. In certain 12 cases, like in this fellow's case, he was 13 certainly in a bad spot. I mean, in his case 14 he was sicker than most people we see with 15 acute leukemia. But that's usually not the 16 case. 17 In other words, as a general rule, 18 you would have to say that an aplastic anemia 19 patient today would have a better chance of 20 long-term survival than a typical acute 21 leukemia patient. 22 Q But in Mr. Frias' specific case, that wasn't 23 the case. 24 A That's true. 25 (1 All right. Let's go on. 104 1 A Next is page 185, and it's an admission 2 note. And it's commented that he was 3 referred to the MD Anderson center for 4 evaluation for possible bone marrow 5 transplant patient due to suspected aplastic 6 anemia. 7 Q You just noted that because that was the 8 admission reports? 9 A I just noted it because that was the 10 admission data. 11 And page 188 comments that the bone 12 marrow carrier type or the bone marrow 13 chromosomes were normal. 14 Q That's the genetic -- cryogenetic testing 15 that you referred to earlier. 16 A Yes. 17 The next note is page 196, and it 18 says: Workup negative for secondary causes 19 of aplastic. 20 Q And what does that mean to you? 21 A Well, let me finish the sentence. It says: 22 Workup negative for secondary causes of 23 aplastic -- I guess they left out the 24 anemia -- and most consistent with primary 25 aplastic anemia; which I would consider to be 105 1 idiopathic. 2 Q And so that specifically when you were 3 referring to MD Anderson's conclusion that it 4 was idiopathic, these are the reports you 5 were referring to? 6 A These are the reports. That and that other 7 discharge summary, I think, we commented 8 about. 9 Q Okay. 10 A The next is page 212. And it comments again 11 that his cytogenetics are normal, and also 12 comments that -- it states: I have reviewed 13 his HLA typing. His HLA typing shows that 14 for the three siblings tested to date none of 15 them match. 16 Then on page 223, there's a comment 17 in here somewhere. Let me see if I can find 18 it. There's a comment in here that his 19 hepatitis B Surface Antigen was negative. 20 Hepatitis C Core Antigen was negative. His 21 HIV test was negative. His transaminases 22 were a little elevated. 23 Q Those are the liver function tests you 24 referred to? 25 A Yes. 106 1 The last one is on page 226, and is 2 another -- Primary Medical Evaluation is the 3 title of this page. And it comments about 4 his history of bleeding from dental 5 extractions. It also comments that he was 6 taking no medications at the time of 7 admission. It claims that he has been 8 exposed to benzene during his work at a 9 refinery. That's the only thing I noted on 10 that group of records. 11 Q And in that last report, was there a specific 12 conclusion about etiology made? 13 A I think it comments they're going to pursue 14 the workup. I think that was a 15 preliminary -- it was an admission history 16 and physical, so there wasn't a conclusion. 17 The next is records from Dr. Arturo 18 Gonzales. I have no marks there. Records 19 from the McGregor Dental Center, no marks 20 there. Records from Dr. Quraishi, I have no 21 marks there. Additional records from MD 22 Anderson Hospital, I have no marks there. 23 This mark is a test that they did 24 for cytotoxic antibodies. 25 Q What's the page number? 107 1 A I'm sorry. Page 850 under MD Anderson Volume 2 4 of 5. This has to do with part of the HLA 3 testing. 4 There's a note on page 869. It's a 5 test for PNH, which was negative. 6 Q What's PNH? 7 A PNH is paroxysmal nocturnal hemoglobinuria, 8 and it's sort of a clonal disease of the bone 9 marrow that you might see in myelodysplastic 10 patients. 11 Q And we referred to that as kind of a -- not 12 quite the same as the cytogenetic testing but 13 similar? 14 A Similar kind of thing. 15 Q All right. 16 A The next is page 907, and it's the official 17 chromosome report indicating that it was 18 normal. 19 Next is page 911, and it's testing 20 for hepatitis. For hepatitis B and C, and 21 these were negative. 22 Q But I believe you commented earlier they 23 didn't test for hepatitis G? 24 A That's correct. 25 Q And do you commonly test for hepatitis G? 108 1 A Well, we do now, because it's a newly derived 2 test. And it's only recently been shown that 3 this virus exists, No. 1. And it's also been 4 surprisingly found in several people with 5 aplastic anemia. 6 So today, if I had a patient with 7 aplastic anemia, I would make the effort to 8 get that test. Five years ago I wouldn't 9 have heard of it. 10 Q But you wouldn't have expected MD Anderson to 11 have run that test? 12 A Not in 1994. 13 Q Is there a specific article in here that 14 refers to hepatitis G? 15 A Yes. 16 Q Why don't we talk about that when we get 17 there. 18 A The last is a chest x-ray report indicating 19 that he's got terrible looking lungs. That's 20 page 1119. 21 Q Is that towards the end? 22 A That's the last entry. 23 Q And again, terrible looking. Does that refer 24 to the effusions and spots that we talked 25 about? 109 1 A And that's called consolidation, meaning that 2 there's -- the lungs are dense on the 3 x-rays. Not necessarily with fluid; it may 4 be pus or fungus or something in there. But 5 it probably isn't fluid. That's the last of 6 these notes. I think we've already looked at 7 these notes. 8 fl That's that. All right. I want to make sure 9 I understand. Your statement in your report, 10 which is Exhibit 4, that states the 11 physicians at MD Anderson determined that he 12 had no potentially significant recent drug or 13 toxic exposures, and their test for hepatitis 14 markers gave negative results. 15 You are -- I mean, it is your 16 opinion that the MD Anderson people decided 17 that his benzene exposure was not significant. 18 A They concluded that. 19 Q And it's based on the report that you referred 20 to. 21 A Yes. 22 (a And so it is also your opinion that they 23 concluded that it was idiopathic. 24 A Yes. 25 (1 Why don't you take a minute and look through 110 1 your report real quickly and see if there are 2 any general issues that we've just not 3 touched on yet. 4 MR. FAULK: It's been two and a 5 half hours. I don't know that that's a fair 6 question. I object to that for that purpose. 7 MR. THOMPSON: So noted. 8 MR. FAULK: There are probably a 9 number of issues. 10 A I'm not sure what you're referring to. I'm 11 familiar with the letter since I wrote it. 12 But what specifically are you asking me? 13 (A recess was taken) 14 Q (By Mr. Thompson) Dr. Natelson, we have 15 previously marked your copy of the 16 Toxicological Profile for Benzene, Exhibit 17 5. I flipped through it. There are some 18 handwritten notes in there. Are all the 19 handwritten notes on that document yours? 20 A Yes. 21 Q If I go through and if there's underlining or 22 exclamation marks or stars or whatever, those 23 are made by you, Dr. Natelson? 24 A That is correct. 25 Q And you just did that as you read through the 111 1 document? 2 A Uh-huh. 3 Q At the tab that I stuck on there -- open 4 that, if you would -- there's a section that 5 addresses urinary phenol testing. 6 A Yes. 7 Q And you've, I think, put a line beside it 8 over there on the right-hand margin. Why did 9 you do that? 10 A Well, I was interested to know the value of 11 urinary phenol testing and what might 12 influence it; and this paragraph has to do 13 with that. 14 Q What in that paragraph, in the ATSDR 15 document, do they indicate as the range for 16 elevated urinary phenol test results? 17 A That's not on this page. 18 Q Maybe it is the next page. 19 A The next page. It says the ACGIH has 20 established 50 milligrams of phenol per liter 21 as what they call the BEI for benzene 22 exposure. 23 Q Any reference in there to a range that begins 24 at 5 milligrams per liter in that section of 25 the document? 112 1 A Not that I can see. 2 Q We talked a little bit about whether you had 3 reviewed any industrial hygiene monitoring 4 data, and I just want to make sure it is 5 clear. Everything that's here today that 6 we've gone through is what you've reviewed? 7 A That's correct. 8 Q You've reviewed nothing else? 9 A Nothing else. 10 Q So you did not review -- you don't recall 11 reviewing any MSDS documents with respect to 12 the products that were shipped at the docks? 13 A I don't recall that. 14 Q In your report, Exhibit 4, you note that 15 Mr. Frias was a smoker. 16 A Yes. 17 Q On what basis do you make that report? 18 A I believe in these work records it is 19 commented on that he smokes. I think in the 20 MD Anderson history and physical that it said 21 that he didn't, but the work records claim 22 that he was a smoker. 23 Q Do you know what his smoking history was? 24 A I may have at one time. I don't recall it 25 today. 113 1 Q Was it significant, in your opinion? 2 A In terms of causation of aplastic anemia? 3 Q True. 4 A No. 5 Q What's macrocytosis? 6 A Macrocytosis means large blood cells. 7 Q Is macrocytosis a manifestation that is 8 related in any way to -- insult to the blood 9 by chemical toxins? 10 A It can be. 11 Q And is it a -- when we talked earlier about 12 lab tests and indicators in lab tests and 13 possible insult to the marrow, is that one of 14 those indicators? 15 A Well, it conceivably could be. It is not -16 typically when we're talking about insult by 17 chemicals, we more commonly look at the white 18 blood cell count and platelet count. But 19 chemicals -- marrow toxin could certainly 20 alter the MCV. 21 Q You are familiar with a phrase called 22 "latency period," correct? 23 A Yes. 24 Q Most commonly we talk about latency in the 25 context of cancers and malignancies. 114 1 A Yes. 2 Q Is it your opinion that in examining a 3 patient with aplastic anemia, a nonmalignant 4 state, that the concept of latency is also 5 significant? 6 A Well, it may be. 7 Q How? 8 A Well, if you could demonstrate that the 9 patient had a dysplastic marrow; in other 10 words, that they had abnormal blood counts 11 that were progressively getting worse and 12 eventuated into aplastic anemia, then I think 13 that would be significant. 14 Q In your opinion, does there need to be -- is 15 there some accepted relationship between the 16 insults that we've talk about, kind of in 17 general, the dents over a series of years to 18 the marrow and the manifestation of disease 19 with respect to aplastic anemia? 20 A Well, in the case of chemical exposure, there 21 might be. There doesn't necessarily have to 22 be. 23 Q So there's no hard and fast rule as to 24 when -- you know, what window you would look 25 to to say the disease would have to develop 115 1 or you would expect the disease to develop in 2 this time frame? 3 A No. The general, when we look at a 4 drug-induced aplastic anemia or 5 hepatitis-induced aplastic anemia, we're 6 looking at a relatively short time between 7 the onset of the drug. I suppose drugs are 8 best -- are most -- best characterized 9 because we know when the person took the drug 10 and we know when the aplastic anemia was 11 evident by blood counts, and that typically 12 is a relatively short interval. 13 Q Is that also true in chronic exposure 14 situations, like the benzene model we've 15 looked at? 16 A Well, in chronic exposures, as we've said 17 before, you often go through a phase where 18 you don't have a normal marrow but you don't 19 have aplastic anemia either. You have a 20 dysplastic phase, and that phase could last 21 for some years. 22 Q You don't have -- you are not going to 23 express an opinion in this case that one of 24 the ways you've ruled out benzene as a cause 25 is that somehow Mr. Frias' disease doesn't 116 1 fit a latency model of some sort? 2 A Well, I don't see that we have any evidence 3 that he had myelodysplasia preceding the 4 development of acute -- of aplastic anemia, 5 and that that combination is frequently seen 6 in benzene-induced aplastic anemia. 7 (a Is it your opinion that for the aplastic 8 anemia to be -- to have been caused by 9 benzene exposure, that it would necessarily 10 have to be preceded by myelodysplasia? 11 A No. I don't think it would have to be. 12 fl Assuming that levels of exposure reached the 13 levels that you have discussed about where 14 you would be comfortable that there are 15 damages to the marrow, dents to the marrow, 16 over a period of time, say 18, 20 years, how 17 long -- if the process is a continual 18 process -- would you expect for it to take 19 for the damage to be so severe that you would 20 become aplastic or see a manifestation of 21 disease? 22 A I don't know that I could put a number on 23 that. As I commented before, we know that in 24 chemotherapy-induced myelodysplasia and 25 leukemias that typically we look at peak 117 1 windows around three to seven years. It 2 might occur as early as a year and a half; it 3 might occur as late as 11 years or so. But 4 by 12 years, the window is typically closed 5 and the effect doesn't occur. 6 Q When you talk about, you know, any period of 7 time, twelve years, three years, seven years, 8 what are you using to measure that window? 9 From what? From the exposure? 10 A From -- usually it's from the last exposure. 11 Some people look at it from the first 12 exposure. Typically with chemotherapy we're 13 not giving these drugs for an indefinite 14 period. We're typically giving them for, 15 let's say, six months or occasionally as long 16 as eight months. And so you could look at it 17 from the beginning of that treatment program 18 or the end of the treatment program. There's 19 not a great deal of difference to the time of 20 the onset of the chemo. 21 Q In the context of a chronic exposure 22 situation, how does that model that you've 23 just described, the chemotherapeutic model, 24 you know, inform you in any way as to how to 25 look at a chronic exposure situation where 118 1 you have, say, continual or repeated 2 exposures over a long period of time? 3 A Well, in the chemotherapy model we 4 generally -- in people who have taken drugs 5 for a long period of time, we typically use 6 the time they took the last dose of drug to 7 the onset of whatever the illness is we're 8 looking at. 9 Q But in the case of somebody who -- again, 10 chronic exposure, occupational setting 11 assuming that there's a continual exposure 12 going on, you're not saying, I don't think, 13 that you wouldn't expect disease to manifest 14 itself until somehow you stopped being 15 exposed so that you could -- I mean, if the 16 exposure was continual, you would expect at 17 some point disease to develop? 18 MR. FAULK: Exposure continual, 19 assuming the dose that you've previously 20 mentioned? Continual exposure without a dose 21 doesn't mean anything. 22 A Well, it's hard to answer that because you 23 might -- your situation in many forms, let's 24 say of chemotherapy-induced leukemia, is that 25 the drugs are given in very high dosages and 119 1 the blood counts may look fairly normal for a 2 couple of years, and then all of a sudden the 3 leukemia appears. 4 There may be changes in the marrow 5 that you have trouble recognizing. They 6 haven't dropped the blood counts a great 7 deal, or the changes may suddenly abruptly 8 develop six years out. So I don't know if 9 I've answered your question. 10 (a (By Mr. Thompson) Probably not. 11 A I think that's a difficult question to 12 answer. 13 (a It was a bad question. 14 MR. FAULK: I agree. 15 (a (By Mr. Thompson) Assume with me for a 16 minute that Mr. Frias was exposed to benzene 17 from the day he walked on to the property of 18 the refinery in 1974, at some level, until 19 the day he was diagnosed with aplastic 20 anemia -- or the day he left the plant before 21 he was diagnosed with aplastic anemia in 22 1994, 20 years. And that during that time 23 period there were intermittent but repeated 24 high-level doses. 25 Is his development of aplastic 120 1 anemia in 1994 any way inconsistent with that 2 exposure model? 3 MR. FAULK: I'm going to object to 4 the form of the question. 5 A Well, I would say that you've made a 6 hypothetical model for him; but you have to 7 say that he is not the only person in the 8 world or in his company that might have these 9 kinds of exposures. 10 Q (By Mr. Thompson) And I understand that. I 11 want only for you to focus on the 12 hypothetical Mr. Frias. 13 A Well, I would say to my way of thinking about 14 the situation is that I don't believe that 15 chronic low-level exposures, what I would 16 consider low-level exposures, albeit they may 17 be higher than the one milligram per liter or 18 the one part per million that we have 19 regulations. I don't believe that chronic 20 low-level exposure would likely give you 21 aplastic anemia. 22 Q You've already said that you believe that it 23 requires some high-level exposure sufficient 24 to dent the marrow. 25 A Yes. 121 1 Q How many-times? 2 A I don't know. 3 Q One? 4 A I would say it is doubtful that one. But 5 whether it would be two or three, I couldn't 6 give you a number. 7 Q But one, doubtful; two more likely? 8 A You could kill a person with one exposure. 9 So -- if it's high enough. 10 Q Well, at one level -- one exposure, what 11 level would be high enough to sufficiently 12 damage the marrow? 13 A I don't know on a single exposure. It would 14 be the level high enough to lower the white 15 cell count. I would expect to see, if you've 16 given -- it's like when we talked about 17 giving chemotherapy. If I don't dent your 18 white count with chemotherapy, I didn't give 19 you enough. If you didn't get your white 20 count dented by benzene, you didn't get 21 enough that gives you aplastic anemia. 22 Q Got it. I understand. 23 What about two? If you've got two, 24 does the level that you are talking about now 25 become lower? Two dents? 122 1 MR. FAULK: I'm going to object to 2 the question. You are not separating it by 3 time or chronology. The question is vague 4 and ambiguous and impossible to answer. 5 Q (By Mr. Thompson) Do you understand the 6 question, Doctor? 7 A I understand the question, and I don't know 8 if I could answer that. 9 Q Well, you said low-level chronic exposure, in 10 your opinion, is not enough. 11 A That's correct. 12 Q We have agreed that it is your opinion that 13 in addition to that you would require some, 14 quote, high-level exposure; and I think you 15 have said in your opinion that is at least, 16 what, around 300 parts per million? 17 A Generally, the cases -- for example, it's 18 commented on in this text -- those kinds of 19 levels that have been associated with 20 aplastic anemia, and I believe they quote in 21 here, persist in exposures around 3 to 500 22 parts per million. 23 Q But can we use 3? 24 A Say 300. All right. 25 Q It is my understanding it is your opinion 123 1 that you would require some high level of 2 exposure during this chronic period. 3 A Yes. 4 Q And my question to you is we're trying to 5 figure out at what point do you draw the 6 line, Dr. Natelson? You said one, probably 7 not, right? 8 A Well, if I said that, I'm not certain that I 9 meant that in the case that -- one that did 10 what? One that didn't affect the blood 11 counts or one that did? 12 MR. FAULK: I'm going to object to 13 that. 14 Q (By Mr. Thompson) How do you know? 15 A Well -16 MR. FAULK: Just a minute. Just a 17 minute. I'm going to object to the whole 18 line of questioning because you're saying one 19 and you are not defining how long, how 20 intense. You are simplifying it beyond the 21 possibility of answering, and it is 22 misleading. It is unfair to the doctor. 23 If you are going to ask him a 24 hypothetical question, give him the courtesy 25 of giving him a reasonable question that's 124 1 defined and specific. 2 Q (By Mr. Thompson) Doctor, do you understand 3 my question? 4 A Well, I'm not certain; but I think that I 5 have the idea. 6 MR. FAULK: Wait. I'm going to 7 instruct you not to answer a question that 8 you are not certain you understand. 9 THE WITNESS: All right. 10 Q (By Mr. Thompson) What don't you understand 11 about my question? 12 MR. FAULK: I'm going to ask -- I'm 13 going to instruct you not to answer that 14 question. You are entitled to a good 15 question from Mr. Thompson, not one that you 16 have to explain to him. 17 Q (By Mr. Thompson) How many times, in your 18 opinion, does somebody need to be exposed to 19 high levels of benzene before you are 20 comfortable that it can cause aplastic 21 anemia? 22 A Well, it can be one time if that time is 23 sustained. In other words, if a person is 24 exposed to high levels chronically, perhaps 25 for months, that might well be enough. 125 1 (1 What if the exposure is just a matter of 2 hours? 3 A Probably not. 4 (a How many exposures that last only a matter of 5 hours would you require? 6 MR. FAULK: I'll again object as 7 not quantifying the dose. The question is 8 vague and ambiguous. The entire line of 9 questioning is misleading. 10 A Well, I would say that it would have to be 11 enough to damage the bone marrow; and the way 12 you would assess that damage would be 13 reductions in the white blood cell count that 14 were substantial and measurable. 15 (a (By Mr. Thompson) But it's your opinion that 16 a high dose of benzene doesn't necessarily 17 mean it damaged the bone marrow? 18 A Well, there are different susceptibilities 19 people have, probably on a genetic basis. So 20 a single dose that didn't affect the blood 21 count might well not affect the bone marrow 22 either. 23 Q So you just aren't -- you can't make a 24 determination -- you don't have an opinion 25 about how many times somebody needs to be 126 1 exposed to 300 parts per million or higher in 2 order to develop aplastic anemia? 3 MR. FAULK: I'm objecting because 4 that mischaracterizes his testimony. The 5 question has been asked and answered. He 6 stated that he doesn't have an opinion with 7 respect to any of the unreasonable 8 hypotheticals that you've given him. 9 A In other words -- if the question is: If 10 this room were filled with benzene at 300 11 parts per million and you walked into this 12 room a number of times during the day, how 13 many times would you have to walk into this 14 room to get sick? I have no idea. 15 (a (By Mr. Thompson) So how do you know? How 16 do you -- how would you make a 17 determination? If I asked you to look at 18 Mr. Frias' records and say -- and determine 19 whether or not benzene was the cause of his 20 aplastic anemia, what would you be looking 21 for in his records to satisfy yourself that 22 he had sufficient exposure? 23 MR. FAULK: Objection; asked and 24 answered. That's what the last three hours 25 of his deposition have been about. 127 1 MR. THOMPSON: Rick, we can get out 2 of here -3 MR. FAULK: I'm tired of sitting 4 here and having you replow old ground. He 5 has given you five separate items that you 6 went through in some detail as to why he 7 thinks this aplastic anemia clinically is not 8 caused by benzene. 9 MR. THOMPSON: I understand. 10 MR. FAULK: I don't see the point 11 in going on. I'm giving you some leeway. 12 MR. THOMPSON: Are you instructing 13 him not to answer? 14 MR. FAULK: No. I'm giving you 15 some leeway, but let's get it over with. 16 A Well, what I would have liked to have seen in 17 these records as we went through these 18 various blood counts that he had, and I 19 didn't see that he ever had a low white blood 20 cell count, and I would have liked to have 21 seen, at least on one occasion, that he had 22 an abnormal blood count, abnormal white blood 23 cell count. 24 Q (By Mr. Thompson) In your opinion, that 25 would indicate an exposure sufficient to have 128 1 caused marrow damage? 2 A It might have. It might not be sufficient. 3 But at least it might be suggestive, if he 4 had enough exposure, to lower a white cell 5 count. 6 Q Let's assume for a second that in our 7 hypothetical that the exposure is sufficient 8 to cause a change in the peripheral blood 9 count. White blood cells, in your example. 10 How many times would you require that before 11 you would be willing to say the aplastic 12 anemia was caused by these? 13 A I don't know that you could pick a number and 14 say that. It is just that if you could show 15 me in these records that at one time he had 16 an exposure and the white cell count dropped 17 to 2,000 and perhaps stayed there for a week 18 or two and then recovered, I would say: 19 Well, that doesn't prove his aplasia is from 20 benzene, but that increases the likelihood 21 that it is. 22 It puts him in a higher risk group 23 because he has had evidence of a dent in his 24 bone marrow by the benzene, but I don't see 25 any evidence of that in these records. 129 1 Q Remember when we talked earlier about your 2 patient who had myelodysplasia that you 3 thought might be related to benzene? 4 A Yes. 5 Q Did you see any medical testing, any medical 6 monitoring, that was done during his work 7 experience that you saw that indicated 8 abnormal blood tests? 9 A I really can't answer that. I did have some 10 records on him, and I just don't recall. I 11 kind of think that he did, in fact, have 12 abnormal blood counts; but I can't really 13 recall that -- those numbers. 14 Q On your report, you've got footnotes for, I 15 think, ten articles. 16 A Yes. 17 Q They're not all here. The last two are not 18 here, which were the two that deal with 19 hepatitis G? 20 A I believe they're all there. You've got them 21 right there. There's only one page. These 22 two articles right here, Aplastic Anemia and 23 Hepatitis G Infection. 24 Q They're both on one page? 25 A Yeah. Because there are two articles, one on 130 1 the other side; Hepatitis G Associated 2 Aplastic Anemia. 3 Q I see. So are these -- are these studies? 4 A These are recent reports. 5 Q Case reports. 6 A These are case reports. That's correct. 7 Q As opposed -- what's the difference between a 8 case report and, say, an article? 9 A Well, you have a single patient with a 10 problem; it is a case report. If you have 11 two, it is a series. That's the difference. 12 Q Are your case reports there peer-reviewed? 13 A Yes. This is a peer-reviewed journal? This 14 is from the Lancet which is sort of the 15 British equivalent of the New England Journal 16 of Medicine. 17 Q How are case reports peer-reviewed? 18 A Well, you provide data to the -- to the 19 editor. And typically what the editor does 20 is looks through that, sends it to an expert 21 in the field. The expert in the field looks 22 at it and says: Well, this is not right. 23 That's not right. Shorten this, take out 24 that. This shouldn't even be a paper. It 25 needs to be a case report. This shouldn't 131 1 even be a case report. It needs to be a 2 letter. And eventually something gets 3 published. 4 Now, the editor doesn't go to the 5 hospital and say: Was this fellow's 6 hemoglobin really three? They're not checked 7 on to that degree. You assume honesty on the 8 part of the reporting physician. 9 Q I see. Have you done any kind of a Medline 10 search or anything to determine whether there 11 are any other case reports or articles about 12 hepatitis G? 13 A Oh, there are because some of these reference 14 other reports. If you look at the end of 15 those articles, they'll have footnotes; and 16 they are referencing other cases. The 17 first -- in other words, the first case of 18 hepatitis G was discovered in a patient with 19 aplastic anemia, and that's not either one of 20 these case reports here. That's a third one. 21 Q So there are three case reports? 22 A There may be more. I don't know how many 23 there are, but they're starting to accumulate 24 because this is a recently recognized 25 phenomenon. So we suddenly are now starting 132 1 to do the testing; and this may be the first 2 three cases we'll find, and the only three 3 cases in this century. Or it may be that 4 this will turn out to be a major cause of 5 aplastic anemia. 6 Q And just so I understand, each case report 7 reports on one patient? 8 A Generally speaking. I'll have to look at 9 that again and see if they are commenting 10 about one or more patients. 11 This first one on this side talks 12 about a 26-year-old man. So that's a single 13 case. And the one on the other side is a 14 19-year-old. They reference other articles 15 and I don't have the other articles. But, 16 you see, this virus was first isolated in 17 1995. So we're not going to have a lot of 18 articles for a few years on this treatment. 19 Q Just so I'm clear, it's not your opinion that 20 Mr. Frias had hepatitis G? 21 A Oh, I have no idea if he did have it. He 22 wasn't tested for it, and I have no idea 23 whether he did or didn't. 24 Q Can you tell me what the other clinical 25 manifestations of somebody suffering from 133 1 hepatitis G would be? 2 A Well, they're described, at least in those 3 couple of patients, their clinical 4 presentation is described. But as in any 5 person with hepatitis, the infection may be 6 subchnical and you may have no symptoms 7 whatsoever or you might be quite jaundiced 8 and quite ill. 9 (a With respect to idiosyncratic -- idiopathic 10 aplastic anemia, is it true that 11 idiopathic -- cases reported as idiopathic 12 tend to be those cases reported in younger 13 and older patients? 14 A I'm sorry. Who else are there besides 15 younger and older people? 16 MR. FAULK: Object to the form. 17 Q. (By Mr. Thompson) The people in the 18 middle-age, you know. 19 A Okay. Well, as you look at -- any age can be 20 affected by aplastic anemia. As you look at 21 some of these studies, there is some 22 suggestion that there is a younger group and 23 an older group; but there are also plenty in 24 the middle. They are not two well-defined 25 categories. 134 1 Q So you knew what I meant when I asked about 2 younger and older, notwithstanding 3 Mr. Faulk's -4 A Yes. I didn't initially; but I realized what 5 you said afterwards, yes. 6 Q In fact, there are studies that report on 7 that phenomena, aren't there? 8 A Yes. 9 Q And studies report that of the large 10 percentage of aplastic anemia cases that are 11 reported as idiopathic, they tend to occur in 12 people who are young, young people, 13 preadolescent people, or in people that are 14 older than, say, 60? 15 A Some haven't found that relationship, but 16 there is mention in the literature and some 17 of these cases, case reports or studies that 18 I have here, deal with that. There is some 19 suggestion that there's a bimodal pattern, 20 but it's not very well defined. 21 Q But it is something that is in the literature 22 and that you would take into account in 23 trying to go through the decision tree that 24 you and I discussed earlier today. Your 25 differential diagnosis. 135 1 A I really don't know that age would affect me 2 too much in terms of a differential 3 diagnosis. You take everything into 4 consideration, but that would be one fact 5 that I don't know that I would lend great 6 store by. 7 Q Do you know Dr. Quraishi? 8 A No. 9 (a Are you familiar with his practice at all? 10 A No. 11 Q Do you have any reason to believe that --and 12 I know you've already expressed your opinion 13 that each doctor has to look at the record 14 and decide for himself, but you have no 15 reason to believe that he is not a competent 16 hematologist? 17 A No. 18 (1 Do you know Dr. Gardner? 19 A Yes. 20 Q Have you ever worked with Dr. Gardner? 21 A Well, we've had some patients that we worked 22 together with. I can recall one just about a 23 year ago that the two of us saw together. I 24 don't know that I've ever worked directly 25 with him on any projects that I can think 136 1 of. From time to time, he's requested slides 2 from me on patients with aplastic anemia. So 3 I've had dealings with him; and I usually see 4 him about every other month at one of our 5 hematology meetings. 6 Q But your experience with Dr. Gardner has been 7 generally that he is -- you know, knows what 8 he is doing and is competent? 9 A He is a very experienced hematologist. He's 10 the former chairman of the department at the 11 medical school in Galveston. 12 Q And you've had a chance to review 13 Dr. Gardner's deposition? 14 A Yes, I have. 15 Q I don't want to go through line-by-line. I 16 don't want to take the time. Are there any 17 very specific things after reviewing his 18 deposition that you -- you know, critiques, 19 comments, criticisms of Dr. Gardner, what he 20 said about specifically this case? 21 A Well, I might comment -- and you've alluded 22 to it, too, this question of the mean 23 corpuscular volume and the significance of 24 that. In some of the studies, in fact 25 they're referenced in here, a few patients 137 1 with benzene-induced problems have had 2 elevated mean corpuscular volume levels. And 3 I believe Dr. Gardner commented something to 4 the effect that that might be an early 5 manifestation of benzene toxicity. 6 But elevated mean corpuscular 7 volume levels are generally the rule in 8 people with liver disease. And the next 9 hundred people I see with an elevated mean 10 corpuscular volume, at least 50 are going to 11 have some form of liver disease; and none of 12 them are going to have benzene poisoning. 13 So that in this particular case, 14 the fact that we know that on a routine basis 15 virtually every time he had chemistries done, 16 his liver function tests were abnormal. 17 There's a ready explanation for any elevated 18 mean corpuscular volume; and, in fact, the 19 elevations that he had are trivial and 20 generally within the normal range on the lab 21 slips reported there. So that I would say to 22 attach any significance to the mean 23 corpuscular volume, I can't think that that's 24 of any usefulness. 25 In terms of other things that he 138 1 commented on, I don't remember any specific 2 detail what he said that I might make comment 3 on. We've already commented on the fact that 4 he mentioned that he has not cared for people 5 with benzene-induced aplastic anemia. That 6 would speak to the rarity of the problem. I 7 don't think there's anything else I could 8 comment on in that deposition. 9 Q Let me take a minute and go through your CV 10 that we've identified as Exhibit 2. 11 You list your present title as 12 director of medical education and director of 13 transitional -- of the transitional 14 internship program at St. Joseph's Hospital, 15 correct? 16 A Yes. 17 Q How long have you been in that position? 18 A Well, I've been director of the transitional 19 internship program since about 1975, and the 20 director of medical education in the hospital 21 for probably the last nine or ten years. 22 Q Sometime in the eighties? Mid-eighties? 23 A Yes. 24 Q So currently you've got a full-time position 25 at St. Joseph's? 139 1 A Well, no. I split my time between private 2 practice and the hospital. I have two 3 offices, one in the hospital and one in a 4 professional building. 5 (1 Prior to -- tell me just briefly what you do 6 in your duties as a director of the medical 7 education program. 8 A Well, with respect to the transitional 9 internship program, we have 12 transitional 10 interns that spend a year at the hospital and 11 then go off on various residency programs; 12 and I'm in charge -- I'm a committee of one 13 that selects all of these interns and, if you 14 will, hires them. 15 And I'm in charge of their 16 education during the course of the year. 17 They rotate on various services and end up 18 going into glamour specialties like 19 ophthalmology, things like that; and they end 20 up driving Mercedes. 21 The other aspects of my duties are 22 that we have five residency programs, four in 23 additional to the transitional program; and I 24 am in charge in a titular way of those 25 programs. In other words, each program has a 140 1 subdirector. We have a director of our 2 surgery program, but theoretically I'm that 3 person's boss. So we review the data from 4 our surgery residents and so on. 5 So there are a lot of 6 administrative things, numerous meetings to 7 attend, that have to do with maintaining our 8 residency programs at the hospital. 9 Q Do you do any specific teaching? 10 A Yes. 11 Q What do you teach? 12 A Well, I teach hematology. In other words, 13 these residents will rotate on hematology; 14 and for that month, all they do is see our 15 patients and work them up, do bone marrows, 16 do whatever all we're doing. So they're 17 getting, let's say, on-the-job teaching. 18 Q It's in a clinical context? 19 A It is in a clinical context, yes. 20 Q Do you do any lecturing? 21 A Yes. We give lectures at grand rounds, and 22 we present conferences. From time to time, I 23 give didactic lectures at the two medical 24 schools. So that within our hospital, I 25 function as what is a usual function for a 141 1 director of medical education. 2 Q And the lectures at grand rounds or the 3 lectures that you've referred to, do any of 4 those specifically involve discussing 5 aplastic anemia and the causes of that 6 disease? 7 A I have discussed that in the past and 8 presented cases with aplastic anemia. I'm 9 trying to -- it would have to be not in the 10 last two or three years. I don't recall 11 presenting that subject, but I have in the 12 past. 13 Q When did you first have any association with 14 the hospital? You said 1975? 15 A 1975. Because prior to that, I was on the 16 faculty at Baylor College of Medicine. And 17 then in 1975, I defected to the University of 18 Texas and I was stationed -19 Q Made you popular? 20 A Made it popular. And I was stationed down at 21 St. Joseph's Hospital. 22 Q You also have a private practice? 23 A Yes. 24 Q You've had a private practice during this 25 whole time you've practiced medicine? 142 1 A Yes. 2 (1 Tell me about your private practice today. 3 What kind of practice? 4 A What does it consist of? Well, I'm officed 5 with a group of cancer physicians. We have 6 three surgeons, one dermatologist and another 7 internist like myself. And our group 8 primarily specializes in cancer work, 9 although my particular practice, probably 10 about 60 percent of the patients have some 11 form of cancer and about 40 percent don't. 12 So I do standard classical hematology. 13 Q Mostly care and treatment of people who were 14 referred to you with blood disorders? 15 A Yes. Leukemia patients, multiple myeloma, 16 lymphomas, in the case of malignancies; and 17 in the hematology side, people with bleeding 18 disorders, anemias, that kind of thing. 19 (a How many patients -- do you go to your 20 clinical practice every day? 21 A No. Sometimes it's necessary because people 22 drag into the clinic. But what I try to do 23 is see patients on Tuesdays and Thursdays. 24 And I'll typically see in the outpatient 25 clinic, oh, 15 patients on each one of those 143 1 days. So I might see, let's say, 30 patients 2 a day in our clinic; and then I also have 3 some inpatients in the hospital that I round 4 on, see consults in the hospital and so on. 5 (a Have you ever performed services as -- I 6 guess that would be described as relating to 7 industrial medicine or occupational 8 medicine? 9 A No. 10 Q Have you ever been part of a team who was 11 designated by an employer to do work on their 12 employees? 13 A No. 14 (1 Of the patients you see, do you have a feel 15 for how many of your patients come from, you 16 know, blue-collar or working-class type 17 environment? 18 A Well, these days, much of our patients come 19 through various managed care plans, and they 20 can really come from anywhere. I would say 21 we see people from all walks of life. It 22 would be pretty hard to put a number on 23 that -- blue collar. We certainly see 24 industrial workers and mechanics, and then we 25 also see white-collar patients. 144 1 Q In your practice today, when a patient 2 presents as part of your history and 3 physical, do you routinely go into their work 4 history? 5 A Generally. Particularly if they have any 6 sort of a malignancy, or let's say a 7 suppressed bone marrow for any particular 8 reason. We ask them if they have any unusual 9 hobbies. Do-they work with any chemicals. 10 What do they do for a living. Do they 11 smoke. Do they drink alcohol. What drugs 12 are they taking. Those are the kind of 13 things we ask. What the family history is. 14 Are there other people in the family with 15 that diagnosis or something similar. 16 (a All of those things to help in your 17 differential diagnosis? 18 A Yes. 19 (1 Have you always been that careful during your 20 whole medical practice of asking about 21 occupational background? 22 A Well, I must admit that when I first went 23 into medicine in some respects I was more 24 thorough than I am today; but then I think I 25 know a little more today. So I can have the 145 1 luxury of being a little less thorough. 2 So that we still do ask them about 3 all of these exposures, but I think at this 4 stage of my career I have a feel for which 5 particular exposures I'm interested in and 6 which I'm not. 7 (a With respect to blood disorders, which are 8 the exposures that you are most interested 9 in? 10 A Well, I can give you an example. I saw a 11 lady the other day with abnormal blood 12 counts, which she wanted to relate to an 13 episode of dysentery when she was a 14 stewardess and went to Panama in 1950. 15 So I decided that that wasn't very 16 important information. I wasn't interested 17 in what happened in 1950 when she was a 18 stewardess. But I was interested in the fact 19 that she's been an alcoholic for about the 20 last ten years. So that it just depends on 21 the patient. 22 (a If you would, take a second and look through 23 the publications on your resume. 24 A Yes. 25 (1 Are there any -- there's quite a few, but 146 1 what I'm mostly interested in is articles 2 that you, based on your best recollection, 3 have discussed specifically aplastic anemia 4 and/or benzene-related blood disorders. 5 A Well, in reference No. 38, I talked about 6 treatment of iron overload in patients with 7 chronic anemias. Several of those patients 8 had aplastic anemia, which is -- an iron 9 overload is a problem in those that have to 10 get lots of blood transfusions, and that 11 article dealt with how to treat that. 12 No. 52 was an article on current 13 therapy of aplastic anemia. That was written 14 in 1985. That article cited several cases 15 that I was following. 16 No. 55 had to do with marrow 17 aplasia from allopurinol. 18 Q What kind of -- is it a drug? 19 A That's a drug, yes. 20 Q What kind of drug? 21 A It's a drug that reduces the uric acid 22 level. It's used for gout and occasionally 23 can cause aplastic anemia. 24 I have an article, No. 59, that has 25 to do with PNH, or paroxysmal nocturnal 147 1 hemoglobinuria, which is a subject you 2 mentioned, which is frequently seen in 3 patients with aplastic anemia. 4 Q That was a test that we discussed that was 5 negative? 6 A Yes, the PIH test. 7 Those are -- those would be the 8 ones I would cite specifically to do with 9 aplastic anemia. I've not written anything 10 specific to benzene. 11 Q Have you done any research or special study 12 in the area of benzene-induced aplastic 13 anemia? 14 A No. 15 Q And I think you testified earlier, but I want 16 to make sure, that it's your recollection 17 that none of the aplastic anemias you treated 18 did you attribute to benzene exposure. 19 A That's correct. 20 Q How many aplastic anemias was it that you 21 estimate? 22 A Estimate. I think I said 20, because I can 23 think that I've treated about 10 people with 24 aplastic anemia with antithymocyte globulin, 25 as they did this case, and 2 with marrow 148 1 transplants, and then a number with neither 2 one of those modalities before either one was 3 available. So I would have to guess at least 4 20 patients, I'd say, with aplastic anemia. 5 (a You also do some consulting work. 6 A Yes. 7 (1 Tell me how much consulting work you do. Is 8 that part of your clinical practice or part 9 of your work at St. Joseph's or neither? 10 A Probably neither, depending on how you look 11 at it. I look at it as continuing medical 12 education. So like I said, that's part of my 13 St. Joseph's practice. 14 (1 What percentage of your time do you spend 15 doing your consulting work? 16 A A very small percentage. I would say less 17 than 5 percent. 18 (a Do you know what percentage of your income 19 you derive from consulting work? 20 A Very little. I would say certainly less than 21 5 percent. 22 Q What are your rates for your consulting work? 23 A Oh, I would say $200 an hour. 24 (a No matter what you are doing? 25 A Generally no matter what I'm doing. 149 1 Q And do you have any -- do you have an 2 estimate of how many hours you've spent on 3 this case so far? 4 A Oh, it would be more a guesstimate than an 5 estimate. But it could be four or five 6 hours. 7 Q And that would have been spent reviewing the 8 records? 9 A Reviewing some records, pulling things out of 10 my files, reviewing some slides, discussing 11 the situation with the attorney, a couple of 12 phone calls, those sorts of things. 13 Q How many times have you met with Mr. Faulk? 14 A We met either once or twice. I know we met 15 recently, perhaps a month ago. We must have 16 met before that; probably twice. 17 Q In your consulting practice, what I'm 18 obviously most concerned with is 19 litigation-related consulting. How many 20 cases have you been involved in performing 21 consulting services for? 22 A You are including malpractice cases? 23 Q Any kind of litigation-related consulting. 24 A Any kind of litigation? Gee, it would be 25 hard to put a number on that. I would say -- 150 1 oh, I might review perhaps at a maximum of 2 about six cases a year. Six to eight cases a 3 year. And many of those I don't give 4 testimony because they seem to vaporize. And 5 perhaps two or three times a year I've given 6 a deposition. And perhaps on average once a 7 year I might testify in some kind of a court 8 setting. 9 (1 So -- and this is over your entire career? 10 A Oh, probably over the last 15 years anyway. 11 Q So 15 years, about six per year, what -12 A I would say that would be a maximum. In the 13 early of those 15 years, it might be once or 14 twice a year; but I would say -- in the last 15 couple of years, I would say I've probably 16 reviewed about six to eight cases a year. 17 Q Of those cases, can you give me an idea of 18 how often you were engaged by the defendant 19 and how often you were engaged by a 20 plaintiff? 21 A Well, more are often the defendant; but I can 22 think of several where it was the plaintiff. 23 It's been, I would guess, probably 75 percent 24 for the defendant and 25 percent for the 25 plaintiff, something in that ballpark. 151 1 Q. Of this whole pool of cases, how many cases 2 involved, I guess, allegations of exposure to 3 chemicals? 4 A Well, several. I wouldn't say it would be 5 the majority, but I could think of several. 6 I mean, I would have to say it is probably 7 perhaps ten. That's just a rough guess. 8 Q And of those, how many involved 9 benzene-related allegations? 10 A Many of those. I would have to say probably 11 about 80 percent of those. 12 Q. In any of the benzene-related cases, have you 13 been asked to consult by the plaintiffs? 14 A No. Not that I can recall. 15 (1 Can you give -- can you tell me who your 16 clients have been on the benzene-related 17 cases? What companies? 18 A Well, I testified on one occasion for Amoco. 19 Actually, it was a patient that I had taken 20 care of who had chronic granulocytic leukemia 21 and claimed that it was a consequent to 22 benzene exposure. 23 I testified concerning a patient 24 with multiple myeloma; and I can't remember 25 at all who his family was suing, but the 152 1 allegation was that the benzene had caused 2 him to have multiple myeloma. 3 Q Do you remember the law firm? 4 A The first one was a firm out of Austin, 5 Flahive, Flahive and something. The second 6 one I seem to think was Baker & Botts, but I 7 wouldn't swear to that. I think that's 8 right. 9 Then I testified on a case of acute 10 lymphoblastic leukemia that was alleged to be 11 caused by benzene, and I remember the 12 attorney was Mr. Shoebotham. I think that's 13 Baker & Botts. I'm not certain about that. 14 Let's see, I reviewed other cases 15 where lymphomas have been alleged to be 16 caused by benzene; but I don't think I've 17 been asked to give any testimony in those 18 cases. 19 Q Do you remember who you were engaged by? 20 A I really can't. 21 Q Let's focus on deposition testimony then. 22 A Yes. 23 (1 How many times have you given deposition 24 testimony in cases that involve allegations 25 of benzene-related diseases? 153 1 A Well, I gave a deposition on the myeloma 2 patient case that I -mentioned. 3 Q Do you remember the name of the case or how 4 long ago it was? 5 A Poston, P-o-s-t-o-n. 6 Q P-o-s-t-o-n? 7 A Yes, Poston. 8 Q Where was the case pending? 9 A I assume here in Houston. 10 fl You gave a deposition? 11 A I'm quite certain that I did. 12 Q Did you testify at trial? 13 A There was no trial. The case was resolved 14 before trial. 15 Q That was multiple myeloma? 16 A That was multiple myeloma. 17 Q And you think Baker & Botts was the person -18 the law firm that hired you? 19 A I think so. It could have been Woodard, Hall 20 & Primm, but I -- it was probably one of 21 those two. 22 Q You don't remember a lawyer's name on that 23 one? 24 A No. 25 Q What other depositions have you given? 154 1 A On any subject? 2 Q On benzene. 3 A Benzene. 4 Q Allegations of benzene-related disease. 5 A I gave a deposition, I believe, on this case 6 with Mr. Shoebotham that had to do with acute 7 lymphoblastic leukemia and benzene. 8 Q Do you remember the case name? 9 A No. 10 Q Was that herein Harris County? 11 A Yes. The patient was seen at Methodist 12 Hospital, but I don't remember what the name 13 was. 14 Q Do you in your office, or anywhere, keep a 15 list of your depositions or copies of your 16 depositions? 17 A No. I do have a list of firms that I've 18 consulted for and the lawyers within those 19 firms that I've worked with, but I don't have 20 any -- if I give a deposition, I may review 21 it and then throw it away. I don't retain 22 any files of those. 23 Q That's very smart of you because you would 24 have to drag them to all of these things. 25 A What I look forward to is when I get a 155 1 railroad car full of this material, is to 2 find out that the case has been settled and 3 then I get to throw it all away. 4 Q If I could, I'd like to ask you to -- if you 5 could forward to Mr. Faulk that list. 6 A Yes. 7 Q That might help us a little bit here. 8 MR. FAULK: Let's go off the record 9 just a minute. 10 (Discussion off the Record) 11 Q (By Mr. Thompson) What I need to do is try 12 and determine in what cases you've given 13 testimony or written reports about 14 benzene-related diseases. So I'm trying to 15 find the quickest way to get down to that. 16 With respect to the ALL case you 17 refer to, you recall giving deposition 18 testimony but you don't know really the name 19 of the case? 20 A No. I gave deposition testimony and also 21 testified at a hearing on that case. And I 22 remember the judge, whose name was Green; but 23 that's about as close as I can get. 24 Q That was in Austin? 25 A No, that was here in Houston. 156 1 Q Houston. 2 A Actually, I've testified in front of Judge 3 Green twice, once in Galveston and once here 4 in Houston. Once on the chronic granulocytic 5 leukemia case I mentioned and once on this 6 acute lymphoblastic leukemia case. 7 Q Do you recall how long ago? 8 A Well, the one in Galveston I'm guessing about 9 five years ago. The one -- the acute 10 lymphoblastic leukemia probably two years 11 ago. 12 Q Any other testimony? 13 A Well, with respect to benzene, I can't recall 14 that I have given other testimony. 15 Q So three depositions? 16 A As best I can recall, I -- that's about as 17 best as I can recall, yes. 18 (1 And in each of those cases, was it your 19 conclusion that the benzene exposure did not 20 cause the disease in question? 21 A Yes. 22 Q In any of those cases, did you review 23 exposure monitoring data or anything like 24 that? 25 A There may well have been some of that data in 157 1 there. 2 Q Have you been asked to prepare any 3 demonstrative exhibits or aids for your 4 testimony at trial? 5 A No. 6 Q And it's my understanding you've brought with 7 you everything that you have prepared or 8 reviewed in preparation for your testimony in 9 this case? 10 A Yes. As I mentioned early on, there might be 11 something that we haven't discussed. Like if 12 you want to suddenly decide you want an 13 article on mean corpuscular volume, I could 14 find one in my files; but I don't have it 15 here today. 16 Q I understand. What I mean is to date, stuff 17 that you have specifically pulled out, 18 reviewed and referred to in preparing your 19 report making your notes and the various 20 things we've discussed today. 21 A Yes. That is correct. 22 MR. THOMPSON: I have no further 23 questions. 24 25 158 1 MR. FAULK: We'll reserve ours 2 until time of trial. 3 (Deposition concluded 5:36 p.m.) 4 5 ----6 7 THE STATE OF COUNTY OF 8 I, ETHAN A. NATELSON, M.D., hereby 9 certify that I have read the foregoing transcript of my testimony given in the 10 foregoing numbered and styled case and that same is true and correct to the best of my 11 knowledge and belief. I further certify that any and all 12 corrections have been made on a separate page and initialed by me. 13 This the day of 1996. 14 15 16 ETHAN A. NATELSON, M.D. 17 SUBSCRIBED AND SWORN TO BEFORE ME, this the day of , 18 1996. 19 20 Notary Public in and for 21 the State of 22 My Commission Expires 23 24 25 Job No. 1-25247 159 1 THE STATE OF TEXAS 2 I, JOHNNIE E. BARNHART, Certified Shorthand Reporter in and for the State of 3 Texas, hereby certify that this deposition transcript is a true record of the testimony 4 given by the witness named herein, after said witness was duly sworn or affirmed by me. 5 I further certify that I am neither 6 attorney nor counsel for, related to, nor employed by any of the parties to the action 7 in which this testimony was taken. Further, I am not a relative or employee of any 8 attorney of record in this cause, nor do I have a financial interest in the action. 9 Further certification requirements, 10 if any, pursuant to the Rules will be certified to in the Supplemental Certificate 11 after they have occurred. 12 Subscribed and sworn to on this, the day of , 1996. 13 14 15 JOHNNIE E. BARNHART, CSR Certificate No. 976 16 Expires December 31, 1996 17 18 19 20 21 22 23 24 25 160 1 NO. 94-38491 2 JESUS VALENTIN FRIAS : IN THE DISTRICT COURT OF 3 VS. : HARRIS COUNTY, T E X A S 4 SHELL OIL COMPANY, ET AL. :270TH JUDICIAL DISTRICT 5 6 REPORTER'S SUPPLEMENTAL CERTIFICATE TO DEPOSITION OF ETHAN A. NATELSON, M.D. 7 TAKEN ON SEPTEMBER 25, 1995 8 I, JOHNNIE E. BARNHART, Certified Shorthand 9 Reporter, hereby certify pursuant to the Rules and/or agreement of the parties present to the 10 following: 11 That $ is the charge for the 12 preparation of the completed deposition transcript and any copies of exhibits, charged to 13 14 State Bar No. 15 That the deposition transcript: 16 was submitted to the witness on for the witness 17 to examine, sign and return to CONTINENTAL COURT REPORTERS, INC., by 18 was not submitted to the witness for 19 examination and signature, same having been waived by the witness and all 20 parties present. 21 That the deposition transcript: 22 was returned, properly executed by the witness, to the deposition officer. 23 was returned unsigned because of illness 24 refusal to sign absence of witness 25 failure to accept delivery