Peter G. Shields, M.D. - Testimony Excerpts
23 (Witness sworn.)
24 DR. PETER SHIELDS
148
1 called as a witness in behalf of the Plaintiffs, being
2 first duly sworn upon his oath, was examined and
3 testified as follows:
4 DIRECT EXAMINATION
5 BY: MR. ZELCS
6 Q. Would you, please, state your name for the
7 record.
8 A. Peter Gary Shields.
9 Q. Where are you presently employed?
10 A. Georgetown University Medical Center.
11 Q. What departments do you work at Georgetown's
12 Medical School?
13 A. I am professor of --
14 MR. ZELCS: Your Honor, I will clean up around
15 here a little bit as well.
16 MR. TILLERY: I don't want to interrupt; Dr.
17 Harris is still back here.
18 THE COURT: Proceed. Go ahead.
19 MR. ZELCS: Q. I think you just told me what
20 departments you worked in at the Medical School, is that
21 right?
22 A. That's correct, in the Departments of Oncology
23 and Medicine.
24 Q. Within the Departments of Oncology and
149
1 Medicine, what specific areas do you work in?
2 A. I am the Director of the Division of Cancer
3 Genetics and Epidemiology, and I am also the associate
4 director for Cancer Control and Population Sciences.
5 THE COURT: Can you all hear him?
6 MR. TILLERY: Is that speaker on?
7 THE COURT: Speak in the speaker so that our
8 gallery, not just the attorneys, but our gallery they
9 are entitled to hear.
10 A. Can everyone hear me okay?
11 Q. (By Mr. Zelcs) Now that we're through that,
12 do you have any additional responsibilities at
13 Georgetown other than in the medical school?
14 A. Sure. I serve on a number of committees
15 there. I teach regularly, mentor faculty students,
16 faculty graduate students, post-doctorate fellows.
17 Q. Do you have anything to do with the Lombardi
18 Cancer Center?
19 A. Sure. Within the Lombardi Cancer Center what
20 I was mentioning before where I'm an associate director
21 for cancer control and population sciences. Under the
22 director there's three individuals that are responsible
23 for different areas of science: basic science, clinical
24 sciences and then cancer control and population
150
1 sciences?
2 Q. Would you tell the Court a little bit about
3 the Lombardi Cancer Center?
4 A. Sure. The Cancer Center is a National Cancer
5 Institute designated cancer center; it was established
6 about 1970. 1974 got that designation. What that is is
7 a peer-review process where the National Cancer
8 Institute brings in other scientists in the field and
9 reviews the science and the research going on in the
10 cancer center so you have to show that you do a large
11 number of research, that it is comprehensive, that it's
12 high quality, and that as a cancer center, you are
13 better than individual proponents within the cancer
14 center. Other cancer centers around the country include
15 MD Anderson, Johns Hopkins, Memorial Sloan Kettering,
16 probably about thirty throughout the whole country that
17 have this designation.
18 Q. There may be a unique reason why the Court
19 might be interested in what Lombardi Cancer Center is
20 named after.
21 A. I am not that big of a football fan. Vincent
22 Lombardi was actually treated at Georgetown University
23 Hospital; the Cancer Center was named after him. The
24 NFL still gives a certain percentage of penalties
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1 against the players to support the research.
2 Q. And is the Lombardi Cancer Center considered
3 by cancer specialists to be one of the leading cancer
4 centers in the world?
5 A. Absolutely.
6 Q. The Court has heard a number of witnesses over
7 the last couple of weeks talk about epidemiology, and I
8 won't ask you to tell the Court what epidemiology is,
9 but I do want you to tell the Court what biomarkers are
10 and what that means?
11 A. Well, a biomarker is basically any laboratory
12 test that one develops. It could be a test on any
13 biological tissue or fluid. That could include exhaled
14 air, hair, blood, biopsy tissue, basically when you go
15 to a doctor's office and they take a blood test or a
16 urine test from you, they're doing a biomarker test.
17 Q. You have told us a little bit about what you
18 do at the Lombardi Cancer Center; tell us a little bit
19 more about your actual teaching responsibilities at the
20 Georgetown Medical School.
21 A. There is different levels of teaching that one
22 can do. I run a course that is topics in molecular
23 epidemiology. I lecture frequently in other courses. I
24 sit on oversight committees for our tumor biology
152
1 program as well as our MD, PhD program and teach outside
2 the university all the time at other universities and
3 international conferences, that sort of thing.
4 Q. Are you regularly asked to speak at
5 universities throughout the United States and the world?
6 A. Yes. Almost monthly I am traveling somewhere
7 to give some sort of talk or presentation.
8 Q. By the way, let me just ask you something.
9 Other than this case, have you ever testified before in
10 any tobacco litigation?
11 A. I have been involved in -- I am involved now
12 currently in one case, which is Rivera v. Philip Morris.
______ _____________
13 I have given deposition testimony there; other than
14 that, I haven't testified in any other --
15 MR. HEPLER: What was the case?
16 A. Rivera versus Philip Morris.
______ _____________
17 Q. (By Mr. Zelcs) The point is, you are
18 relatively new to this process, a little nervous about
19 it?
20 A. I guess I would have to say yes.
21 Q. That's okay. We all are. Let's get back to
22 what you do. Does your current work also involve
23 treating patients?
24 A. Yes. At the Cancer Center I spent at least
153
1 twenty percent of my time caring for hematology and
2 oncology patients; I'm also active in the community.
3 For many years until a few years ago I was actually the
4 medical director of a free medical clinic that cares for
5 indigent patients and now actually president of the
6 board; I'm still fairly active there, more general
7 internal medicine.
8 Q. Before you came to Georgetown and the Lombardi
9 Cancer Center, where were you employed?
10 A. National Cancer Institute.
11 Q. What positions -- well, let me go back. How
12 long were you at the National Cancer Institute?
13 A. I started there sometime around 1987, '88.
14 Q. And until -- for how many years were you
15 there?
16 A. Until 2000 when I moved to the Lombardi Cancer
17 Center.
18 Q. And over those thirteen years or twelve years,
19 whatever the number was, what positions did you actually
20 hold with the National Cancer Institute?
21 A. Well, I started off there as a post-doctoral
22 fellow, and then I became what they consider a senior
23 clinical investigator, and then as I moved up through
24 the hierarchy, I became a section chief of the molecular
154
1 epidemiology section, which is in the laboratory of
2 human carcinogenesis. And around that time I was also
3 tenured, which is a very rigorous process, multi-level
4 peer-review process of both scientists inside the Cancer
5 Institute as well as external reviewers.
6 Q. As a tenured investigator, as a section chief,
7 as a senior clinical investigator, what areas were you
8 working at at the National Cancer Institute?
9 A. When I initially started, the program expanded
10 over the years as our research went on, but initially I
11 was focused on tobacco smoking and lung cancer and
12 development of different types of biomarkers, looking at
13 DNA damage, individual susceptibility, trying to answer
14 questions like why does one smoker get lung cancer,
15 another one doesn't.
16 We expanded that program to breast cancer using a
17 lot of the tools and techniques that we developed in the
18 lung cancer. Basically, it was a -- it's similar to
19 what I am doing now. It's a multi-disciplinary program
20 that includes basic scientists, epidemiologists,
21 statisticians, toxicologists, and we try to understand
22 carcinogenesis and why people actually get cancer.
23 Q. I think when you were running through your
24 positions at the National Cancer Institute, you
155
1 mentioned the Molecular Epidemiology Section. Would you
2 tell the Court what molecular epidemiology is. I said I
3 wasn't going to ask about epidemiology; I think that is
4 something the Court needs to know about.
5 A. Well, over the last ten or fifteen years as
6 our technology in the laboratory have gotten
7 substantially better, been able to apply a lot of
8 methodologies in epidemiology, incorporated more and
9 more biomarkers. At this point in time there's almost
10 no distinction between epidemiology and molecular
11 epidemiology. What we're saying is rather than the
12 traditional way of looking at someone's exposure, how
13 many cigarettes they smoked per day and how much lung
14 cancer they get, we really try to link the two
15 mechanistically.
16 We are using a variety of different biomarkers to
17 show the relationship of cigarettes going to the mouth,
18 smoke getting into the lungs, damage in the lungs, from
19 the damage in the lungs, how does that translate into
20 damage in the cells. At this point in time it is almost
21 impossible to get a grant funded from NIH doing just
22 pure epidemiology. You have to have a molecular and a
23 biological component.
24 Q. Let me see if I can get at the essence of what
156
1 you just said. Did I understand you correctly to say
2 that molecular epidemiology is what studies and looks
3 for the links between an exposure and an outcome?
4 A. That is fair; that is correct.
5 Q. Now, when you were at the molecular
6 epidemiology section at the NCI, what was the area of
7 work you focused on within that group at that time?
8 A. Well, as I mentioned before, we had a variety
9 of both laboratory as well as epidemiologic studies in
10 tobacco smoking and lung cancer expanded to tobacco
11 smoking and actually addiction and some of the genetics
12 of addiction and why people smoke the way they do, and
13 then we ended up with a fairly substantial project in
14 breast cancer as well.
15 Q. I think you also mentioned another area that
16 you worked in at the NCI was the division of basic
17 sciences; tell us what that area was focused on?
18 A. Well, our laboratory, which was the laboratory
19 of human carcinogenesis was seated in the division of
20 basic sciences so that's a hundred some odd laboratory
21 program, but what was important to understand about that
22 is that we were running an epidemiology program among
23 the group of basic scientists so we were really
24 emphasizing the biology and the links between the
157
1 biology and what happens to people in human health.
2 Q. During the time that you were employed at the
3 National Cancer Institute, did you also hold any
4 teaching positions?
5 A. Well, at that time I remained both active
6 teaching wise, as well as clinically active, through my
7 appointment to George Washington University Hospital.
8 Q. How many years did you serve on the faculty at
9 George Washington?
10 A. The entire time I was at the National Cancer
11 Institute so that would be a total of thirteen years.
12 Q. What divisions did you work in at George
13 Washington?
14 A. It was a clinical division, division of
15 hematology and oncology.
16 Q. And, ultimately, you became an associate
17 professor there, is that correct?
18 A. That is correct.
19 Q. Now, during your work at the National Cancer
20 Institute during the 1990's, did you develop a
21 particular expertise?
22 A. Yes.
23 Q. Tell us about what that expertise is.
24 A. So, the research program really led us to
158
1 think very carefully through, and this is really where I
2 developed the expertise into was both carcinogenesis,
3 how does cancer develop in people, trying to understand
4 what we learned in the laboratory, how we can apply that
5 to what is happening in people. It allowed me to
6 develop an expertise in epidemiology as well as
7 toxicology.
8 And then as we get into more particular
9 circumstances, it really led to expertise in terms of
10 understanding tobacco, tobacco use, how we use tobacco
11 products, how to evaluate tobacco products in terms of
12 cancer risk and carcinogenicity and toxicology.
13 Q. Have you published at all in your field of
14 expertise?
15 A. Sure.
16 Q. Tell us about what you published, how many
17 peer-review papers?
18 A. If you do a Medline search now and type my
19 name in, come up with ninety plus papers. I've probably
20 written thirty or forty review papers, currently editing
21 a book. I'm asked all the time to write review papers,
22 editorials, that sort of thing.
23 Q. Do you serve on any editorial boards or
24 journals that are related to your field of expertise?
159
1 A. I have and I still do. They include -- there
2 is one journal called Cancer Epidemiology Biomarkers,
3 Prevention, Journal of Carcinogenesis, Journal of
4 Oncology Reports, Journal of Pharmacogenetics.
5 Q. Have any journals asked you to serve as a peer
6 reviewer?
7 A. Probably at any given time, there are five or
8 six papers setting on my desk waiting to be reviewed.
9 Q. Tell us which journals have utilized you as a
10 peer reviewer in the past?
11 A. Well, including those journals that I serve on
12 their boards in some capacity, other journals have
13 included the Journal of the American Medical
14 Association, Journal of the National Cancer Institute,
15 Lancet, Nature, Cancer Research, American Journal of
16 Epidemiology. Dozens.
17 Q. You told us about Georgetown; you told us
18 about George Washington; you told us about the National
19 Cancer Institute. You told us about your publications,
20 peer-review work. What other work do you do with regard
21 to your areas of expertise?
22 A. Well, I also regularly sit on a variety of
23 committees for different organizations that help.
24 Sometimes we are asked to develop research agendas,
160
1 identify where funding priorities should go, for
2 example, for the National Cancer Institute, two of the
3 committees that I served on, one was called the lung
4 progress review group, the other was the tobacco
5 research implementation group where we were specifically
6 asked to provide guidance to the National Cancer
7 Institute in terms of where funding should go in these
8 areas. I have been on similar task force for breast
9 cancer. There is the Institute of Medicine Committee I
10 was on a couple of years ago.
11 Q. Stop there. There has been a lot of
12 discussion about that; tell the Court a little bit about
13 what the Institute of Medicine is.
14 A. Okay. So, the Institute of Medicine is part
15 of the National Academy of Scientists. This is an
16 agency that was established by congress, I don't know,
17 in the mid-1800's or something, and it's considered --
18 and it is an independent agency that is composed of
19 scientists and very highly-regarded engineers,
20 scientists, specialists in the field, and basically what
21 they do is when someone has got an important question
22 from the government to be asked, they will go to the
23 National Academy of Scientists or the Institute of
24 Medicine, whatever is appropriate, and that agency will
161
1 put together a panel to do -- to assess a variety of
2 data to do studies and then come out with conclusions
3 and recommendations.
4 Q. Have your peers ever chosen you to lead
5 scientific groups of molecular epidemiologists?
6 A. Sure. About three years or so ago, there was
7 a group within the American Cancer Association of
8 research which is 16, 18 thousand researchers. There
9 was a group of us who wanted to have our own sort of
10 mini-society within that group. And so we formulated
11 the molecular epidemiology group, like six or seven
12 hundred people, and I was actually elected the first to
13 chair that group.
14 Q. Was this considered the most prestigious
15 molecular epidemiology group in the United States?
16 A. Sure, probably the world.
17 Q. Have you consulted, or have you been asked to
18 consult, with anyone in your field of expertise?
19 A. Sure. I mean, there is different industry
20 that sometimes will ask me to work for them. In fact, a
21 couple of years ago Philip Morris had also asked me to
22 do some work.
23 Q. What did Philip Morris ask you to do?
24 A. Well, actually in a time that I was on the
162
1 Institute of Medicine committee, and Rick Stalana had
2 called me up and asked me to consider being the
3 principal investigator of their -- I'm not sure exactly
4 how they described it, smokers study, a large smokers
5 study that is either about to be in the field or in the
6 field now.
7 Q. What were you asked to do in this case?
8 A. Okay. I was asked to provide a number of
9 opinions on mutagenicity, how that relates to
10 carcinogenicity and how that relates to outcomes in
11 people, specifically looking through the Philip Morris
12 documents and considering their -- the testing they did
13 on the variety of cigarettes and cigarette products that
14 they used, what would be the implication for that on
15 animal studies of which they didn't do and then what was
16 the ultimate impact on people in terms of the effects of
17 what we see in terms of lung cancer.
18 MR. ZELCS: Your Honor, before I get into the
19 substance --
16 THE COURT: Okay. I think this is a good
17 point.
18 (Whereupon the Court was in recess.)
12 THE COURT: Be seated. Where's the witness?
13 THE WITNESS: Right here.
14 THE COURT: Oh, I'm sorry.
15 MR. ZELCS: Snuck in there.
16 THE COURT: I've been working too hard.
17 It's time to go to Florida again.
18 All right. You may resume.
19 MR. ZELCS: Thank you, your Honor.
20 PETER SHIELDS
21 resumed the stand, called as a witness on behalf of
22 the Plaintiffs, having been previously duly sworn, was
23 further examined and testified as follows:
24 DIRECT EXAMINATION (CTD.)
3
1 BY MR. ZELCS:
2 Q. Before the break you had just finished
3 answering a question about what you were asked to do
4 in this case. Let's proceed from there. You've been
5 studying cancer all your professional career. Please
6 tell us what cancer is and how it develops?
7 A. Okay. So cancer is an abnormal growth of
8 cells --
1 Q. (By Mr. Zelcs): Would you go ahead?
1 Q. (By Mr. Zelcs): Let me ask the question
2 again. I think you didn't finish. The question to
3 you was tell us what cancer is and how it develops?
4 A. Okay. So a cancer is an abnormal growth of
5 cells and basically what happens is that our normal
6 cells in the body depart different organs, lungs,
7 brain, whatever, they have normal functions, and we
8 live. You know, they help detoxify. The heart helps
9 pump the blood, but what happens is that there's a
10 genetic code in our genes that program these cells to
11 tell them what to do. So they function, they
12 function, and they go on functioning. Sometimes these
13 cells are programmed to also die and get replaced. At
14 this time will -- some will die. Others will
15 replicate and start new and accidental differentiate.
16 So what happens in a cancer though is that
17 genetic code gets messed up, and so rather than the
18 genetic code saying to the cells you know live, live,
19 live, function, function, function; what it says is
20 keep growing, get bigger, get bigger, get bigger,
21 reproduce, reproduce, reproduce and they never die.
22 And so eventually they just push out the normal
23 organs. I guess it's probably the best example would
24 be it's something like brain cancer where if you have
6
1 these tails that are growing bigger and more of them
2 in a brain, that's in all the brain that ultimately
3 that's how people die from cancer.
4 Q. Okay. You use the term "messed up." What
5 role, if anything, do mutations have in cancer?
6 A. Okay. So our DNA is basically a language.
7 It's like Morse code that helps code for different
8 functions within the cell. And what happens is that a
9 mutation is just a misreading of that code. So if
10 you're supposed to have one letter, it turns out a
11 different letter than the genetic code is for
12 something different, in which case it could turn off
13 that gene which would be important for having it
14 function normally.
15 The way those mutations happen that's a
16 salutation of their letters or we call the basis
17 within the DNA. Or sometimes you can break parts of
18 DNA off. You can have CFR what's called abnormal
19 breaks. And what happens is that you could have,
20 let's say a chemical can get into that cell, it can
21 attach to the DNA as part of the normal body's
22 function to try to get rid of a chemical that's not
23 supposed to be there, whether it's a medicine or
24 chemical or something that we make, it tries to
7
1 chemically convert these chemicals so that you can buy
2 them and excrete them through the urine, for example.
3 But sometimes that goes wrong, and the chemical
4 combines with DNA. When the cells reproduce and make
5 more DNA, the enzymes get confused and put the wrong
6 code back in or the wrong data and then you have the
7 cell programming is all messed up and you end up with
8 a cell that keeps growing uncontrollably.
9 Q. When you talk about cell programming and
10 mutations, what, if any, relationship is there between
11 a mutation and the way that a cell normally expresses
12 itself?
13 A. Well, what happens is that this genetic code
14 in the DNA programs for certain amino acids to come
15 together as a protein, and those proteins is really
16 what is cataloged as a chemical reaction themselves to
17 make them function normally.
18 So if you end up with a mutation in the
19 wrong base, you could end up with the wrong amino acid
20 or sometimes you can shut off any production of the
21 proteins so you don't have it at all and abnormal
22 functioning will become cancer.
23 In some cases those cells program, the cell
24 recognizes that it's been damaged very, very badly,
8
1 and the cell will die, which it doesn't go on to
2 cancer. But in other cases it messes it up just right
3 so that the cell loses its ability to control itself.
4 Q. And essentially, if I understand what you
5 just said, it's this uncontrolled cell growth that
6 basically causes cancer; is that right?
7 A. Well, that uncontrolled cell growth is what
8 cancer is.
9 Q. All right. Is cigarette smoke considered a
10 chemical?
11 A. Cigarette smoke is a very complex mixture of
12 thousands of chemicals.
13 Q. Are any of these chemicals that are in
14 cigarette smoke known or suspected carcinogens?
15 A. There's somewhere between 50 and 100 known
16 suspected probable, possible carcinogens.
17 Q. Based upon the work that you've done and the
18 education that you have, do you know whether there are
19 ways to determine if a chemical or groups of chemicals
20 such as those in cigarette smoke cause cancer?
21 A. There is a variety of studies and data that
22 we can look at. It's actually a fairly common
23 approach used by a lot of organizations, industries,
24 and universities where we test these chemicals in sort
9
1 of a step or stage process where we can look at both
2 just some basic chemistry and some cell culture
3 experiments in the laboratory, we do animal studies.
4 And really what we want is epidemiology. We want to
5 know what happens to people and I think that topic is
6 the most relevant. And when we head up epidemiologic
7 data, that's really the best evidence we can use for
8 related and exposure with cancer.
9 Q. Let me stop you and take you back. What I'm
10 asking is, is there a process that's regularly used to
11 determine whether such chemicals can cause cancer?
12 A. Yes.
13 Q. And what is that called? Is there a term
14 that's used for it or --
15 A. Sure. There's different ways, but it's
16 usually a multi-stepped process.
17 Q. I'm sorry?
18 A. A multi-stepped process.
19 Q. Okay. Tell me the components of the
20 multi-step process that's used?
21 A. Well, a lot of that is governed based on the
22 research question that you want to ask about that
23 exposure and possible cancer. But for a variety of
24 reasons people start off with either basic chemistry
10
1 studies or cell culture studies in the laboratory
2 which are generally easier to do quick and they're
3 considered to be screening or predictive for cancer in
4 animals and in people.
5 Q. Okay. So the first step of this multiple
6 step process is what you're calling cell culture
7 studies?
8 A. Cell culture or in vitro.
9 Q. And those are typically done in lab tests?
10 A. They are, yes.
11 Q. Okay. And later on I'm going to ask you
12 about the Ames test, and let me connect it up now. Is
13 the Ames test a cell culture test that's part of this
14 first test?
15 A. The Ames test is probably the most commonly
16 used one.
17 Q. Okay. Now, you were telling me earlier that
18 what you'd like to do is to be able to use
19 epidemiological data in evaluating a chemical or a new
20 product. Is that right?
21 A. That's right.
22 Q. Are there any problems in doing that?
23 A. Well, when you have epidemiological data
24 that should rule over everything else, and then you
11
1 would use other types of experiments to try to
2 understand what you deem in the epidemiology. The
3 problem is, is that if you have epidemiologic data
4 that means it's already too late. You've already got
5 a whole lot of people with cancer that you're now
6 studying, and so it's sort of like counting bodies
7 after the fact. What we really want to do from a
8 public health perspective is prevent the exposures
9 from happening so that we don't get to the
10 epidemiology.
11 Q. Can you tell the Court about some practical
12 examples that deal with this latency period that I
13 think you're referring to that makes it too late?
14 A. Sure. There's a lot of examples of that
15 including, you know, cigarette smoke and lung cancer
16 there's a latency of, you know, 20, 30, 40 years.
17 People that were smoking before that we're not getting
18 lung cancer. Another example would be asbestos and
19 lung cancer. Asbestos and mesothelioma, for asbestos
20 and mesothelioma, you know, probably a 50 to 60 year
21 latency period.
22 Q. Has the step wide process been a solution
23 with the development because of the inability to rely
24 upon epi. data for this purpose?
12
1 A. I would answer that question with a yes
2 since we're --
3 Q. It sounds like you need to explain
4 something. And it probably wasn't the best question.
5 Why don't you go ahead.
6 A. Well, I think we often make choices in life,
7 and we want to protect the public health so
8 recognizing that we don't have the epidemiologic data,
9 the solution we have chosen, although not necessarily
10 the perfect solution, is to go through this multi-step
11 process to try to understand what the risks are.
12 Q. You told us about the first step, the cell
13 culture step. Tell us what the next step is in this
14 multi-step process.
15 A. All right.
16 Q. And again we're looking at a process that
17 looks at chemicals to determine whether they cause
18 cancer; is that right?
19 A. That's right. And I guess from what -- the
20 other thing that I just want to clarify is that
21 sometimes traditionally, typically we go through a
22 multi-step process. Anyone that allows to bypass one
23 of the processes to the next advanced process. If you
24 want to go right to an animal study, you don't have to
13
1 do cell culture studies, if you want to do people
2 studies then --
3 Q. Tell the Judge what the second step is --
4 A. Got it.
5 Q. -- before we start talking about that.
6 A. So what typically happens is that people do
7 the cell culture studies to help them predict what
8 might be a possible problem in people. And if you
9 think that you have, based on your cell culture study,
10 that you've got a problem because you have more
11 mutations in your cell culture study, then typically
12 what people will do is they'll go to some sort of
13 animal experiment because animals, of course, are
14 closer to people as being half human and being half
15 mammal.
16 Q. Okay. That's the second step. What's the
17 third step?
18 A. Well, the third step then is once you
19 understand what's going in the animals then you can
20 make a decision about whether or not you want to
21 potentially expose people or whether there's a problem
22 with people or not. So you use the cell culture to
23 help you predict animal results and you use animal
24 results to help you predict human results.
14
1 Q. And that's why you call it a multi-step,
2 keep climbing up?
3 A. Right.
4 Q. But you can't go to humans right away?
5 A. It would depend on the research question.
6 If you're talking about potential exposure it would be
7 really foolish to go to people right away.
8 Q. Okay. Now, the step wide process that
9 you're telling the Court about, tell us who's adopted
10 this? Does industry follow it? Does science follow
11 it? Do regulatory agencies follow it? Tell the Court
12 about that.
13 A. All of that. There is a number of reasons
14 why that multi-step process is there, but it's
15 considered to be the quickest, easiest, and most
16 reliable methodologies to use and so chemical
17 industry, pharmaceutical industry, tobacco industry
18 certainly has used it. You can see that through the
19 Philip Morris documents, but other companies use that
20 process as well.
21 The government, the FDA, for example
22 requires that the EPA. It has a number of different
23 offices for the evaluation and treatment of water
24 chemicals and air pollution and that sort of thing.
15
1 Before they will allow chemicals to be released in the
2 environment, they want to see this type of data used.
3 Certainly in academics we use it all the time when
4 we're trying to identify carcinogens as well.
5 Q. Okay. Now, I apologize. You may have said
6 this, and I may not have caught it. Did you give the
7 Court examples of what industries use the step wide
8 process?
9 A. Sure. Chemical industry, pharmaceutical
10 industry, and then I said tobacco industry as well.
11 Q. Thank you. What about you, what experience
12 do you have using the step wide approach?
13 A. Well, when I was at the National Cancer
14 Institute and trying to understand the process for
15 lung cancer, particularly we became very interested in
16 a finding that was actually in China. And there's a
17 very high rate of lung cancer in Chinese women and
18 most of them don't smoke. And epidemiologically it
19 was linked to fumes or smoke that was coming off of
20 cooking oils. So they used, you know, wok cooking,
21 and they would turn the heat on really, really high so
22 all the smoke would come off, and we had reason to
23 believe that there was going to be carcinogens from
24 that tobacco smoke.
16
1 So to help us understand what the potential
2 carcinogens were and how to go about studying it, we
3 started off with a number of in vitro acids to help us
4 screen and identify which chemicals would be the
5 culprit. We did some animal studies, but in that
6 case, because we had these women who were continuing
7 to use the woks, we were able to go to the right
8 people and also do tests on humans as well.
9 Q. You mentioned something earlier about the
10 tobacco industry, Philip Morris documents. I take it
11 that's part of your work in this case you used Philip
12 Morris documents to relate to the step wide process;
13 is that correct?
14 A. That's correct.
15 Q. Okay. And based upon your review of those
16 documents, what sense did you get of when in time it
17 was that Philip Morris first became aware of the step
18 wide process?
19 A. Well, they were -- in the 1960s, for
20 example, there were really not good in vitro tests, so
21 the step wide process back then started with animal
22 studies. And they were doing animal studies back
23 then. But in the '70s the in vitro tests, like the
24 Ames testing came along, they quickly adopted those
17
1 assays, and so the step wide approach then took a step
2 back and other industries were taking a step back.
3 Q. Okay. We've been talking about the first
4 step, the cell culture and all of that. I think it's
5 now time to tell the Court about what the Ames test is
6 and talk slowly and make sure you explain this because
7 it's not -- it's not an easy concept.
8 A. Okay. So basically it's a cell culture
9 assay. Cells in a dish. It was something that was
10 invented by Bruce Ames in the early '70s and his
11 co-workers. It is incredibly widely used. I mean
12 it's really groundbreaking in terms of in vitro
13 assays. A lot of other assays have come and gone, and
14 the Ames assay is still, you know, there as the one
15 that people almost always choose for their assessment.
16 So what it is, is they took this bacteria
17 and genetically engineered them so that they were
18 unable to use one of the amino acids that are part of
19 the protein of building blocks, as I mentioned before
20 are part of a normal cell function and because these
21 bacteria can't make their own histidine, what you have
22 to do is you have to grow them in a media or a broth
23 that contains histidine.
24 But what happens is that you take these cell
18
1 cultures and you expose them to certain mutagens. The
2 mutagen actually can change that genetic engineering
3 cause a mutation and reverts that need for histidine
4 so now they grow without histidine.
5 So in the dish what happens is you have
6 these cells minimally growing and needing to be fed
7 correctly, and then you put the mutagen in and all of
8 a sudden they don't need that histidine and they can
9 stop growing pretty wildly and then you can actually
10 see colonies in a dish just like you would see mold on
11 bread or something like that.
12 Q. Okay. Now, I've heard the term Salmonella/
13 microsome used in association with Ames. Tell the
14 Court what that relationship is about?
15 A. Well, the bacteria is Salmonella typhimurium
16 so -- and there's different strands that has developed
17 over time, but they're all Salmonella. And then the
18 microsome part comes, which is one of the
19 breakthroughs is that they realize that they just put
20 these mutagens in a dish with the cells often nothing
21 happens, but if you mix it with proteins from a liver
22 from a rat that mimic human proteins, then you can
23 help activate these mutagenics.
24 Q. Based upon the documents that you've looked
19
1 at as part of your work in this case, what is the
2 principal screening test that Philip Morris has been
3 using to test its cigarettes for the last 25 years in
4 terms of their potential for cancer causing effect?
5 A. There is no question it was the Ames test.
6 Number one through five of their ten choices was
7 always -- was always the Ames test. They had other
8 tests that they developed or on their own took or from
9 the literature and then used in the laboratory, those
10 came and went, and the Ames test just sort of stayed
11 through in experiment after experiment.
12 Q. Who other than Philip Morris has been using
13 the Ames test for that purpose?
14 A. Most -- most people do.
15 Q. When you say "people," the Court doesn't
16 know who you're referring?
17 A. Sorry. Researchers, industry, again,
18 required by the Federal government to go in with some
19 new products or new drugs through the FDA, to give
20 them reasons why you didn't choose the Ames avenue.
21 Q. Is there some limitation in terms of the
22 kind of chemicals that the Ames test can be used in
23 terms of testing or potential for cancer causing
24 effect?
20
1 A. Well, not all chemicals -- I'm sorry.
2 Again, there's different strands that have been
3 developed by Bruce Ames that are more responsive to
4 some type of chemicals than others, so there's no
5 single cell strand that would be predictive of every
6 possible chemical. So one of the limitations in these
7 assays is that you can get what we call false
8 negatives.so just because a test result is negative,
9 and the Ames test doesn't necessarily mean it's not
10 going to be a mutagen, an animal carcinogen, or a
11 human carcinogen.
12 Q. You used the term "mutagen," can you tell us
13 what that means?
14 A. Well a mutagen is the chemical that induces
15 that base change in the DNA so that you either shut
16 off the gene or you get the abnormal protein being
17 introduced.
18 Q. And the mutagen is the route or the term
19 mutagenicity; is that right?
20 A. Right.
21 Q. You also use the term revertant. Tell the
22 Court how that fits into a mutagenicity test, the Ames
23 test, --
24 A. Sure. One of the clever things about the
21
1 Ames assay is that it's genetically engineered to be
2 defective. So when you expose it to a mutagen, which
3 for us or for most organisms it's a bad thing. In
4 this case these cells it's a good thing because it
5 reverts back to a normal state because they're able to
6 use the histadine.
7 Q. Now, when you're testing a chemical for its
8 cancer causing effect in the Ames test, what
9 percentage of the chemicals that test positive in Ames
10 are thought to be animal carcinogens?
11 A. There's different criteria that you can use
12 for making that correlation, and so in some papers you
13 could see people drawing conclusions as high as 95
14 percent but I think it's still probably closer to 60
15 to 80 percent predictive rate.
16 Q. Okay. And we've been talking about Ames
17 being used to screen for a cancer causing effect. How
18 does one determine whether the potential for cancer is
19 real or not based upon a screening test result such as
20 that from the Ames test?
21 A. Okay. So I think that we can -- I think
22 it's pretty widely accepted that something like the
23 Ames test is very predictive of what would be an
24 animal carcinogen. The bigger step is what goes from
22
1 animal to people, and I think it's much more
2 complicated. There's many, many, many chemicals that
3 we test. Were doing that from a perspective of how to
4 protect the public health so we don't allow the
5 exposure. So it's much harder to show what chemicals
6 cause cancer in people because we don't have that
7 epidemiologic data, so we don't have the way to
8 correlate something like the Ames test to the animal
9 to the people through a public health perspective
10 they're not letting the people have it. So it is --
11 it's almost impossible to come up with the specific
12 predictive number of what is the relationship of the
13 animal carcinogen is to human carcinogens.
14 Q. What do you do next?
15 A. Well, I mean we've decided as a society, as
16 a public, you know, throughout our government, for
17 example, to consider possible human carcinogens based
18 upon just laboratory data, animal data, and that stuff
19 gets regulated so we don't get exposed.
20 Q. Okay. Let me go back. What I was asking
21 you is where do we go when we get a positive result in
22 an Ames test in terms of discussing whether or not the
23 potential for cancer is real or not. What's the next
24 step?
23
1 A. Well, what people do is they go to the
2 animal studies unless they have a specific research
3 question or basic data they can do on people.
4 Q. Let's focus on that. What are the types of
5 animal studies? Tell the Court about that?
6 A. Well you can do different mammals so you can
7 do mice, rats, some people use dogs. Hamsters are
8 common. Monkeys. And then you can use different
9 models within -- to those animals. So you can do
10 inhalation experiment, you can paint carcinogens on
11 their skin, you can do feeding studies. You can do
12 injection studies. There's a number of different ones
13 for tobacco smoke. In particular the most common ones
14 have been the skin painting and inhalation studies in
15 rodents.
16 Q. So the skin painting and inhalation studies
17 in rodents are examples of animal models that are
18 used. The second step in the step wide process; is
19 that right?
20 A. That's correct.
21 Q. Let's be specific. How does one determine
22 the potential of cigarette smoke to cause cancer?
23 A. Okay. So actually to this day one of the
24 best assessments of that really goes back to the 1964
24
1 Surgeon General's Report where the group of scientists
2 who are on that panel really evaluated, went through a
3 very careful and close evaluation and put very
4 cleverly housed -- how to present all that data to
5 make that decision. And basically they looked at
6 different data. And in that case they had an
7 epidemiologic data and they had animal data. They
8 didn't have the cell culture data. And they were able
9 to put it together by looking at a number of different
10 angles and looking for consistency within the
11 epidemiologic literature to look for, for example,
12 knowing that there's certain carcinogens in tobacco
13 smoke and those carcinogens cause cancer in laboratory
14 animals and seeing more of that exposure in humans
15 also causes cancer. So, for example, in the
16 occupational setting. By putting it altogether, it's
17 ultimately the way evidence is approached, they were
18 able to conclude that smoking causes cancer. Today we
19 still do much of the same thing, but we're so much
20 more sophisticated. We understand the biochemical
21 mechanisms that are going on in the cells when they
22 get exposed to carcinogens, how we compare these cells
23 to a -- what's going on in animals and what we see in
24 animal cancers that are also seen in human cancers.
25
1 Q. Is there any one set --
2 MR. LOMBARDI: Your Honor, we're looking at
3 our notes here to make sure. I think I would make an
4 objection on all the smoking and health stuff and we
5 just couldn't locate this. So I just wanted to
6 confirm that.
7 MR. ZELCS: We agree that they do.
8 THE COURT: Go ahead.
9 Q. (By Mr. Zelcs): Is there any consensus
10 about what a manufacturer of a consumer product should
11 do if a product modifications and design changes
12 increase the potential exposure to toxins or
13 biological activity?
14 A. I think anyone would say that they're doing
15 product design testing that is related to health and
16 safety of people, a bad result is a bad thing and it's
17 something you should do about it.
18 MR. LOMBARDI: And, your Honor, in addition
19 to what I have --
20 THE COURT: Yeah.
21 MR. LOMBARDI: This is my objection on
22 design defect as you anticipated, your Honor.
23 Q. (By Mr. Zelcs): As part of your work in
24 this case did you review the deposition of Dr. Solana
26
1 from Philip Morris?
2 A. Yes, I did.
3 MR. ZELCS: Could we have RS 60187001824.
4 MR. LOMBARDI: Before we do that, can I have
5 a page reference please?
6 MR. ZELCS: Yes. It's pages 18 and 19,
7 pages 56 of his deposition from June 18th, 2002.
8 MR. LOMBARDI: Page?
9 MR. ZELCS: Pages 18 and 19 and page 56.
10 (Whereupon, a film clip was played.)
11 "Our valuation process is to look at changes
12 that are proposed to products so that any
13 modifications we're considering making, you know, as I
14 said either at a minimum do not increase the overall
15 smoke chemistry or biological activity or were
16 intending to reduce the risk of smoking. That they --
17 that they do achieve that."
18 (Conclusion of film clip.)
19 MR. LOMBARDI: What was the next page?
20 MR. ZELCS: 56. 56, lines nine through 12.
21 (Whereupon, a film clip was played.)
22 "To further characterize it for this group
23 is one, in pursuing reduced risk of smoking, one clear
24 tool is in addition to pursuing change in smoke so
27
1 that it has less biological activity."
2 (Conclusion of film clip.)
16 Okay. Your Honor, the question starts at
17 line 21 of page 18.
18 "Does your responsibility include any
19 investigation into the products that Philip Morris
20 currently has for sale in the marketplace?
21 "Answer: Our valuation process is to look at
22 changes that are proposed to products so that any
23 modifications we're considering making, you know, as I
24 said either at a minimum do not increase the overall
28
1 smoke chemistry or biological activity or were
2 intending to reduce the risk of smoking. That they --
3 that they do achieve that."
4 Okay. That's the first piece.
5 MR. TILLERY: 56.
6 MR. ZELCS: Bear with me just a second
7 please. And the second clip, question, page 56, line
8 3.
9 "Will that group also deal with what I was
10 describing as the motivation for compensation?
11 "Answer: Let me just better characterize the
12 group would be the best answer because I leave it up
13 to the experts in the group to determine what it is
14 that they need to pull together to answer the
15 question. The question to further characterize it for
16 the group, for this group is to, one, in pursuing
17 reduced risk of smoking, one clear tool is in addition
18 to pursuing change in smoke so that it has less
19 biological activity. Another tool is can you design a
20 product in a way that smokers are exposed to less
21 smoke and, you know, and to best do that it would be
22 helpful for us to understand well, what are the
23 factors that determine for a smoker when, you know,
24 how much smoke they're going to take in in a day and
29
1 they could, you know, they could be many, but I didn't
2 want to create any preconceptions for the group. The
3 information would be used to help us move forward in
4 pursuing new design ideas."
5 Q. (By Mr. Zelcs): Is the testimony that was
6 on the screen, and the questions and answers that I
7 just read some of the material that you reviewed as
8 part of Mr. Solana's deposition?
9 A. Yes.
10 Q. What significance did that testimony have to
11 you in terms of whether or not Philip Morris
12 recognized this consensus mainly that a manufacturer
13 should at a minimum decrease potential exposure to
14 toxins and biological activities when making product
15 modifications or design changes?
16 MR. LOMBARDI: Your Honor, I'm going to
17 object to the foundation for the time frame. I think
18 there needs to be a foundation for the time frame for
19 the testimony.
20 THE COURT: Okay. Put the time frame.
21 Q. (By Mr. Zelcs): In reviewing the Philip
22 Morris documents and based upon your own knowledge in
23 terms of the industry consensus on the step wide
24 process, when in time was that consensus first reached
30
1 in industry in general and also with Philip Morris?
2 A. Okay. So clearly the step wide process was
3 incorporated and used easily into the early '70s and
4 probably -- probably before that. It really became
5 clearer when we had good in vitro models so I would
6 date it back at least to the early '70s, but
7 conceptually the concept was there that people wanted
8 to do ten, 20 years before that even.
9 Q. Let's go back to the step wide process.
10 What options does a consumer manufacturer such as
11 Philip Morris have after receiving screening test
12 results from tests like the Ames test that show
13 positive mutagenic activity?
14 A. Well, I think the operative word is that
15 it's a screening test, so you're interested in
16 evaluating a product design change, you're using a
17 screening test to predict whether or not it can cause
18 more harm and so you get your result back you have to
19 do something with it. So if you see more biological
20 activity, in this case more revertant mutagenicity in
21 the Ames test, and in this case in terms of product
22 design changes, you know, like increasing ventilation,
23 then -- or continuing the use of some of the low tar
24 products, then you have to make a choice. You either
31
1 say based on this adverse result I either abandon the
2 design change or I've got to figure this out to make
3 -- to learn from it, to ensure that it either is safe
4 for people or to understand the mechanism so that you
5 can change things enough to make it safe for people.
6 Q. Let me see if I understand what you just
7 told us. We're on the first step of the step wide
8 process. We've done an Ames test. We've got a
9 positive mutagenic activity result, and the options if
10 I understand what you just told the Court, the
11 manufacturer are to either abandon the process, throw
12 it out, or climb up to the next step and do some more
13 testing. Is that what you said?
14 A. That would be one of those two would be --
15 sorry. It would be appropriate to do one of those two
16 things.
7 MR. ZELCS: Okay.
8 Q. (By Mr. Zelcs): Let me focus you back on
9 where we were. You had just told me what the options
10 are for somebody if they get positive mutagenic
11 activity on the first level. Okay. Up or out I think
12 is the way you characterized it.
13 What are the potential consequences for a
14 manufacturer if after this first level test screening
15 results, positive screening results were received that
16 no additional or next step is taken, what are the
17 consequences?
18 A. Well, if you make a decision to ignore the
19 results of the screening test and then continue to
20 proceed with the use of your product design change and
21 expose people than the consequences obviously could be
22 awful. You could -- in this case you could induce
23 more cancer and more disease and more death.
24 Q. This determination to take no additional
34
1 step and not take the next step, I take it that that
2 has to be balanced in some way before a decision is
3 made. What goes into that mix? How do you balance
4 positive mutagenicity testing results in analyzing
5 whether to go forward, do more testing, or do nothing?
6 A. Well, it depends on what you're intended use
7 of the product is going to be. So if it's -- if you
8 get your positive screening result and you think that
9 it might cause more cancer, you then say well, is this
10 product important enough to go ahead with introduction
11 into the marketplace or more testing, or do you say
12 it's just not important enough and you just abandon
13 it.
14 So if you're, for example, a drug company
15 developing a medicine for migraine headaches and you
16 get a positive mutagenicity test, you're not going to
17 say I'm going to take this chance of causing cancer in
18 people, you know, because I really, really want to
19 treat their migraines. On the other hand, there are
20 times you may decide that you'll accept that risk, and
21 that's a conscious risk based on or a conscious
22 assessment of a risk based on lots of testing and
23 studies.
24 So, for example, you could have a fatal
35
1 cancer like Hodgkin's disease, that's a lymphoma, and
2 30 years ago that was a fatal illness and when
3 chemotherapy was developed, some of the best
4 chemotherapy for that actually can cause between a 5
5 and 10 percent chance of leukemia. And it was decided
6 that balancing the known fatality for lymphoma versus
7 the 5 or 10 percent chance of leukemia, we'll go for
8 the leukemia. And in fact, most people still take
9 those risks today.
10 Q. Okay. Let's go back and talk a little bit
11 more about the Ames test. I had you tell the Court
12 what a mutagen means, what a revertant means in that
13 context. What does dose response mean in the context
14 of the Ames test, if anything?
15 A. Okay. Sure. It's just a matter of taking
16 these Salmonella cells and exposing them to a mutagen.
17 It's actually a fairly well established criteria to
18 decide whether it's a positive test result or not.
19 And what you do is you use different doses, and as you
20 use different doses in different cell dishes, than you
21 should see more revertant. And you can apply this to
22 a test just to make sure it's not random or not, but
23 basically those response to is the more mutagen should
24 result in more revertant if you want to call it a
36
1 positive test.
2 Q. Once a dose response relationship is
3 demonstrated between a mutagen and a revertant, what
4 happens next? You said something about some physical
5 tests.
6 A. Right. So there is different physical tests
7 that people have used over time, but any of them what
8 you want to do is just make sure that you're not
9 looking at some random noise which is, you know, the
10 chance effect. So you apply statistics and say that
11 there is a bottom line, you want -- the threshold is
12 about a 95 percent probability that this is a correct
13 finding in the Ames test.
14 Q. Did Ames ever publish on the mutagenic
15 potential of cigarette smoke concentrate?
16 A. Yes. I believe it was in 1974, he had an
17 article on the proceedings of the National Academy of
18 Sciences on that very topic.
19 Q. I just want to flush this out. You've
20 already told us that Philip Morris was using the test
21 for 25 years. Was the Ames test considered reliable
22 by the scientific community?
23 A. Yes. The Ames test is something considered
24 to be very reproducible and there's been some
37
1 discussion over time about laboratory variation, but
2 for the most part it's considered a very, very good
3 test.
4 Q. Let me show you what's been marked as
5 Plaintiff's Exhibit 88. Do you have that in front of
6 you?
7 A. The Redbook 2000?
8 Q. Yes.
9 A. Yes.
10 Q. Okay. Showing you Exhibit 88, that's the
11 U.S. Food and Drug Administration, Center for Food
12 Safety & Applied Nutrition, Office of Premarket
13 Approval, Redbook 2000, Toxicological Principles for
14 the Safety of Food Ingredients, referred to as the
15 Redbook 2000. Let me direct your attention to that
16 document. Have you seen that before?
17 A. Yes.
18 Q. Okay. And are you familiar with section
19 Roman numeral IV.C.1.a, the bacterial reverse mutation
20 test?
21 A. Yes.
22 Q. All right. Does section IV.C.1.a include a
23 discussion of the uses of a bacterial reverse mutation
24 test or what is referred to as the Ames test?
38
1 A. Yes, it does.
2 Q. Why don't you read that into the record.
3 A. Okay. So this is -- thanks. This is a
4 guidance from the FDA for what they want to see in
5 terms of evaluation of food additives, and so under
6 that purpose for a it states that: "The bacterial
7 reverse mutation test uses amino acid-requiring
8 strains of Salmonella typhimurium and Escherichia coli
9 to detect point mutations, which involve substitution,
10 addition or deletion of one or a few DNA base pairs.
11 The principle of this bacterial reverse mutation test
12 is that it detects chemicals that induce mutations
13 which revert mutations present in the tester strains
14 and restore the functional capability of the bacteria
15 to synthesize an essential amino acid. The revertant
16 bacteria are detected by their ability to grow in the
17 absence of the amino acid required by the parent
18 tester strain."
1
5 Q. (By Mr. Zelcs): And let me interrupt you
6 for just a minute. What you've just read is a
7 definition essentially of how the Ames test works and
8 what you were trying to explain to the Court earlier;
9 is that correct?
10 A. That's correct.
11 Q. And in even more complicated language; is
12 that right?
13 A. I guess I will admit that, yes.
14 Q. Go ahead.
15 A. Okay. Then under B, it says, "Point
16 mutations are the cause of many human genetic diseases
17 and there is substantial evidence that point mutations
18 in oncogenes and tumor suppressor genes of somatic
19 cells are involved in tumor formation in humans and
20 experimental animals. The bacterial reverse mutation
21 test is rapid, inexpensive and relatively easy to
22 perform. Many of the tester strains have several
23 features that make them more sensitive for the
24 detection of mutations, including responsive DNA
40
1 sequences at the reversion sites, increased cell
2 permeability to large molecules and elimination of DNA
3 repair systems or enhancement of error-prone DNA
4 repair processes. The specificity of the tester
5 strains can provide some useful information on the
6 types of mutations that are induced by genotoxic
7 agents. A very large data base of results for a wide
8 variety of chemical structures is available for
9 bacterial reverse mutation tests and well-established
10 procedures have been developed for testing chemicals
11 with different physicochemical properties, including
12 volatile compounds."
13 Q. If I can ask you the next section please
14 read it slowly, please. Go ahead.
15 A. I'm done with that paragraph.
16 Q. All right. Could you bring up 900301- 01.
17 And that's second page of Exhibit 88. If you would
18 read that slowly please?
19 A. Okay. Under initial considerations, III B,
20 "The bacterial reverse mutation test is commonly
21 employed as an initial screen for genotoxic activity
22 and, in particular, for point mutation-inducing
23 activity. An extensive data base has demonstrated
24 that many chemicals that are positive in this test
41
1 also are genotox in other tests. There are examples
2 of mutagenic agents which are not detected by this
3 test; reasons for this shortcoming can be ascribed to
4 the specific nature of the endpoint detected,
5 differences in metabolic activation, or differences in
6 bioavailability."
7 Q. What is the significance of these passages
8 from the Redbook to your work and your opinions in
9 this case?
10 A. Okay. Well, these basically mimic what I
11 know to be true and what I said before, and I think
12 that this is something that's been accepted by the --
13 or put out by the FDA in the year 2000, but this could
14 easily have been written. It's been written by others
15 within the last 20 years, with the exception of a few
16 key words or a few fancy words in there, these are not
17 new principles. These have been around for 20 years.
18 Q. Are you familiar with any Philip Morris
19 documents that speak to its use of that same assay,
20 the Ames test?
21 A. Yes.
22 Q. I show you what's been marked as Plaintiff's
23 Exhibit 89. Let me show you what's been marked as
24 Exhibit 89, it's a meeting report entitled
42
1 "Recommendations on Data Production and Analysis Using
2 the Salmonella/Microsome Mutagenicity Assay." It
3 bears a Bates stamp of March 5th, 1979 and a file
4 stamp of T.S. Osdene. You've seen that document
5 before; is that correct?
6 A. That's right.
7 Q. Okay. And is this one of the documents from
8 the Philip Morris files that you've reviewed?
9 A. That's my understanding, yes.
10 Q. All right. Let me direct your attention to
11 pages eight and nine of that document. And I believe
12 that's CKT045926.
13 A. Okay.
14 Q. Hold on just a second until we get that up
15 on the screen. All right. Who is Tom or T.S. Osdene?
16 A. It's my understanding that he was a -- I
17 don't remember his exact title, but he's a senior
18 researcher at Philip Morris.
19 Q. Okay. And what kind of meeting did this
20 report speak to?
21 A. Well, this was a meeting that was held in
22 1978, and it was conducted or called together by a
23 group of researchers from the National Institute of
24 Environmental Health Sciences, and they brought these
43
1 experts together to discuss the uses of the Ames
2 testing and to think about how to standardize some of
3 the methodologies across different labs, across
4 different laboratories.
5 Q. Doctor, in that document bearing the 1979
6 date from Mr. Osdene's file, is there any discussion
7 about the reliability of the Ames test?
8 A. Yes.
9 Q. Okay. Could I have CKT45924-01. Okay. At
10 page 7 of Exhibit 89, do you see that?
11 A. Yes.
12 Q. Could you read that to the Court, please?
13 A. Sure. "In conclusion, the
14 Salmonella/microsome plate assay has proved to be an
15 invaluable test system in efforts to identify
16 mutagenic chemicals. With only minor modifications,
17 the protocol as published in 1975 is the protocol best
18 suited for the routine testing of chemicals."
19 This document or this meeting actually ended
20 up being published as a Ames summary in the Journal of
21 Science.
22 Q. And that's a fairly prestigious journal; is
23 that correct?
24 A. It's about as good as it gets.
44
1 Q. All right. Now, let me -- let me go back to
2 that and make sure we define something for the Court.
3 When you refer to -- when you talk about cigarette
4 smoke condensate, actually what are you talking about?
5 A. Well, sometimes people use the term in
6 different ways, but generally or conceptually there's
7 two different ways to think about it. One of them is
8 you put a cigarette on a machine and you suck the
9 smoke, you light the cigarette you suck the smoke
10 through the cigarette. And then you, as you're
11 pulling back the piston or a syringe and you suck the
12 smoke through a filter, and on the filter you will get
13 deposited basically tar. And so you can extract off
14 that tar and that's what some people will call
15 cigarette smoke condensate.
16 Another case what you can do is you can take
17 the smoke and you can bring it through a flask that is
18 chilled, and that trap will cause the smoke to come
19 out of the air and collect on the bottom of the flask
20 and that also would be called cigarette smoke
21 condensate.
22 Q. Cigarette smoke condensate is the particles
23 that are collected on the paper?
24 A. That's correct.
45
1 Q. Specific mutagenicity, what does that mean?
2 A. Well, it's a term actually I don't like
3 because people tend to get confused. But basically
4 what it means is you take that cigarette smoke
5 condensate, you put it into the Ames test, and you
6 figure out the amount of revertant per milligram of
7 the condensate.
8 Q. Who uses that test, the test that you've
9 just described for?
10 A. Virtually everyone who does cigarette smoke
11 testing.
12 Q. Has Philip Morris gone about testing
13 cigarette smoking condensate for differences in
14 specific mutagenicity using Ames test?
15 A. Repeatedly over 25 plus years.
16 Q. In your review of Philip Morris documents,
17 have you come across the name INBIFO?
18 A. Yes.
19 Q. All right. CKTO45900. I show you -- I'm
20 sorry. This has already been marked as Plaintiff's
21 Exhibit 20-O.
22 Let me show you what's been marked as --
23 previously marked and admitted as Plaintiff's 20-O.
24 Its a document entitled "Draft, Guidelines for the New
46
1 Assay Approval Committee."
2 Is this something that you reviewed as part
3 of your work in this case?
4 A. Yes.
5 Q. And were you able to determine from
6 reviewing this document who generated these draft
7 guidelines?
8 A. Well, this is a document that was generated
9 apparently by Rick Solana to a committee, and my
10 understanding of this document from reading it
11 indicates that what Philip Morris was doing was trying
12 to come up with guidelines to which in vitro test they
13 wanted to use to test various products.
14 Q. Could I have 45907-01. And let me direct
15 your attention to CKT45907 on that document.
16 A. Yes.
17 Q. Does that document have any dates on it?
18 A. Yes. So what you're looking at is the
19 INBIFO portion of this document from Cologne, Germany,
20 and the date is June 18th, 2001.
21 Q. If you could drop back. At the very top
22 portion under number one where it says assay. What
23 does it say there?
24 A. Salmonella Reverse Mutation Assay.
47
1 Q. And, again, this is what's commonly called
2 the Ames test; is that right?
3 A. That's right.
4 Q. Okay. Does that document have an assessment
5 or a recommendation with regards to the use of the
6 Ames test?
7 A. Yes. The committee by Rick Solana and
8 Philip Morris had some guidelines for what they wanted
9 to see for their testing, and this document that
10 accompanies it is the one that they put together for
11 the Ames testing.
12 MR. ZELCS: Could I have 45911-01, please?
13 Q. (By Mr. Zelcs): Could you read into the
14 record and for the Court what it says there?
15 A. Before the Ames test, their overall
16 assessment and recommendation was, The assay is
17 sensitive for detection of mutagenicity of cigarette
18 smoke condensate, robust, widely used, and accepted.
19 It is routinely used at INBIFO for the reproducible
20 discrimination of different cigarette types."
21 Q. Okay. And from your review of Philip Morris
22 documents in this case, did you develop an
23 understanding of the relationship between INBIFO and
24 Philip Morris?
48
1 A. Well, my understanding was that INBIFO was
2 one of its research institutions.
3 Q. All right. You testified earlier that
4 Philip Morris had been using Ames tests for over 25
5 years. From your review of the Philip Morris
6 documents that you've looked at, what did Philip
7 Morris learn from the Ames tests that they have been
8 conducting for over the Past 25 years?
9 A. Well, they were testing a number of
10 different cigarettes, cigarette like products and a
11 number of different design changes. And one of the
12 things that was incredibly consistent through
13 experiment after experiment after experiment was the
14 role of ventilation in the filter and increased
15 mutagenic.
16 Q. Okay. As to ventilation, -- I'm sorry. And
17 as to those documents was there any specific
18 information they learned about low tar or light
19 cigarettes?
20 A. Sure. Well, initially, as they started the
21 experimentation they were testing the low tar or light
22 cigarettes, including some that were similar to the
23 Marlboro Lights, and they saw that there was increased
24 mutagenic activity from those cigarette products. And
49
1 then over a series of experiments they identified and
2 really nailed down the issue that the ventilation was
3 -- was a major contributor, if not the major
4 contributor.
5 Q. Now, let me go back. We talked about it
6 being 25 years that they've been using Ames tests. We
7 talked about the testing results. Are you talking
8 about one, two, three? How many test results are you
9 talking about?
10 A. The blank look is it's kind of hard to count
11 all of them. I could think of separately three, four,
12 five, six very discrete, different -- different series
13 of studies over different years and different
14 locations, and they all provided the same answer.
15 Q. Did this repeated testing establish why low
16 tar reference cigarettes were higher in specific
17 mutagenicity than full flavored?
18 A. I wanted to establish the only reason why
19 was clearly the ventilation was the major contributor
20 to that.
21 Q. Have you reviewed Philip Morris documents
22 that speak to this connection?
23 A. Yes.
24 MR. ZELCS: All right. Could I have 004936
50
1 up on the screen, please? This has already been
2 previously marked as Plaintiff's 25.
3 Q. (By Mr. Zelcs): You've reviewed this
4 before; is that right?
5 A. That's correct.
6 Q. Okay. And what -- there's a reference there
7 to project 6906.
8 MR. ZELCS: Could I have 4940-01 on the
9 screen?
10 Q. (By Mr. Zelcs): What was 6906? What was
11 that project focused on?
12 A. Okay. Well, this document is an annual
13 report summarizing the results from that project. A
14 whole bunch of research done that year. And you could
15 see the objectives of the project which are to -- it
16 says, " The objectives of this project are: (a) to
17 develop a battery of in vitro assays to evaluate the
18 biological effects of cigarette smoke products; and to
19 apply those assays to study activity as a function of
20 cigarette, chemical, and/or biological parameters so
21 as to understand the nature of the activity and how it
22 can be controlled."
23 Q. Let's link this up. Ames is an in vitro?
24 A. Correct.
51
1 Q. Okay. Does this document have a summary?
2 A. Yes, it does.
3 MR. ZELCS: All right. Could I have 4939-01
4 on the screen?
5 Q. (By Mr. Zelcs): And could you read into the
6 record and to the Court that language from the
7 summary?
8 A. Sure. So this '78 document says, "A
9 cigarette parameter, filter dilution, was also shown
10 to influence WSC activity," which is whole smoke
11 condensates.
12 Q. That's what you had defined earlier for the
13 Court?
14 A. That's right.
15 Q. And -- I'm sorry. Go ahead and complete
16 reading that section.
17 A. This says, "This implies that the way a
18 cigarette burns or is smoked can also affect WSC
19 activity."
20 Q. All right. Now what's the significance of
21 that comment in that summary in that document to you
22 written in 1978?
23 A. Well, in 1978 they already had clearly
24 implicated that product design change of increased
52
1 filter dilution, and I think also very importantly is
2 it shows that they were thinking that people smoked
3 these products differently and so these -- well, so
4 people smoked these products differently and -- I'm
5 sorry.
6 Q. Take your time. Slow down. Take your time.
7 A. Try to articulate. Right. My inclination
8 is to read back the sentence because I think it kind
9 of speaks for itself. Basically what's clear to them
10 and what's clear to the reader is that they understand
11 that smokers can smoke these products differently and
12 get exposed to different rebel mutagens.
13 Q. All right. Let me show you what's been
14 marked as Plaintiff's Exhibit 90. Exhibit 90, you've
15 reviewed that document as part of your work in this
16 case?
17 A. Yes.
18 Q. All right. And what is that?
19 A. This is an INBIFO document summarizing yet
20 another whole other set of research.
21 Q. Okay. Tell us a little bit more about the
22 research that that document summarizes.
23 A. Okay. In this case this was a series of
24 experiments that was focused, if I remember correctly,
53
1 exclusively on the issue of ventilation and
2 mutagenicity.
3 Q. Okay. Now, let me ask you something, what
4 cigarettes were studied in this report?
5 A. Well, it was cigarettes they manufactured
6 with different levels of ventilation.
7 Q. Okay. Does this report discuss the results
8 of the study?
9 A. Yes.
10 Q. Okay. And where does it do that? Is there
11 a table?
12 A. Yes.
13 Q. Okay. Let me ask you to bring up 900316 and
14 could I ask you to -- there you go.
15 A. So what this --
16 Q. Why don't you tell the Court what that data
17 shows?
18 A. Okay. What this table is, is giving you
19 results of the Ames test. So under the mutagenic
20 effect you see frameshift mutation and base-pair
21 substitution. Those are two different Salmonella
22 strengths. The TA98 is the first one and the TA100 is
23 the second one. Then they're showing us their code
24 for the cigarettes and for each cigarette we're seeing
54
1 the ventilation.
2 Q. Let's just stop. The code column is -- and
3 maybe we can do it that way. Right there.
4 A. Right.
5 Q. Low tech. And here's your ventilation
6 column; is that right?
7 A. That's correct.
8 Q. All right.
9 A. Okay. And then going over to more, there's
10 a column that's entitled, "Mean Specific
11 Mutagenicity." Thank you. Whoever is doing that.
12 And then lastly, the last column is a physical test to
13 see whether or not the result for that particular
14 cigarette is different than the one without
15 ventilation.
16 Q. Okay. And, again, what's the significance
17 of this data to you?
18 A. What they're doing is they're doing some
19 very nicely designed experiments to define the role of
20 ventilation in -- to the extent that ventilation
21 causes increased mutagenicity.
22 Q. I show you what's been marked as Plaintiff's
23 Exhibit 91. This is a document dated October 4th,
24 1991. It's entitled, "Philip Morris U.S.A.
55
1 Interoffice Correspondence." It's from Mr. Hellams to
2 Mr. Izac, and the subject is, "Proposal for a
3 Systematic Study of Varied Cigarette Construction
4 Parameters to Determine the Effect on Biological
5 Activity."
6 Have you reviewed that document as part of
7 your work in the case?
8 A. Yes.
9 Q. What is it?
10 A. Okay. So over ten, 15 years of earlier
11 studies, what these Philip Morris researchers decided
12 to do was to come up with a -- yet a better, more
13 definitely designed study, so this is a proposal to do
14 exactly that.
15 Q. Okay. Now, I read from the subject line,
16 the reference to varied cigarette construction
17 parameters. What do you understand that to be a
18 reference to? Tell the Court.
19 A. Well, one of them was ventilation. They're
20 also looking at filter efficiency and other -- there's
21 some additives that are there as well.
22 MR. ZELCS: Could I have 4744-01 up on the
23 screen, please?
24 Q. (By Mr. Zelcs): All right. Does the
56
1 proposal discuss comparisons of the mutagenicity of
2 smoke from low tar and regular referenced cigarettes?
3 A. Sure. As part of their introduction and
4 rationale, they're summarizing the PM research from
5 earlier years. And you can see from the highlights
6 there it says, "As a result of the study with Model I
7 cigarettes" --
8 Q. Let me just -- let me just, for the record,
9 you're reading now from that document?
10 A. Correct.
11 Q. And at what page is it --
12 A. Page 18, 004744.
13 Q. Thank you.
14 A. "As a result of the study with Model I
15 cigarettes, it was noted that the cigarette smoke
16 condensate of a low tar reference cigarette was not
17 statistically as active in the Salmonella mutation
18 assay as the burley cigarette smoke condensate, but
19 was statistically more active than the cigarette smoke
20 condensate from the 2RI Kentucky Reference cigarette."
21 Q. Now, I suspect that's mumbo-jumbo to a lot
22 of people in here. Tell the Court what a Kentucky
23 Reference cigarette is?
24 A. Okay. There were several cigarettes that
57
1 were designed to be used in research that would be
2 sort of constant overtime so you can compare one
3 experiment to the next.
4 Q. What was it that a Kentucky Reference
5 cigarette was supposed to approximate?
6 A. Okay. Well that's a full flavored
7 approximated cigarette and that's to compare it to the
8 low tar reference, which would be compared to
9 something more like the Marlboro Lights.
10 Q. Okay. And the Kentucky Reference cigarette
11 was something that was used by Philip Morris; is that
12 right?
13 A. That's absolutely true.
14 Q. Okay. Now, does the proposal also speak to
15 the impact of filter ventilation on the biological
16 activity in low tar cigarette smoke?
17 A. Yes, it does.
18 MR. ZELCS: 4746-02, please.
19 A. Here it says that the --
20 MR. LOMBARDI: I'm sorry. If you could just
21 read the page number of the document it would be -- it
22 would just be helpful for me to follow along with you.
23 MR. ZELCS: Yeah, the -- do you want the
24 Bates stamp or the CKT number?
58
1 MR. LOMBARDI: Use the number in the
2 document itself.
3 MR. ZELCS: The bad news is the document has
4 no page numbers.
5 MR. LOMBARDI: Okay. I'll take the Bates
6 number.
7 MR. ZELCS: Okay. 2023949731.
8 MR. LOMBARDI: Thank you.
9 MR. ZELCS: You're welcome.
10 Q. (By Mr. Zelcs): Go ahead.
11 A. Okay. So here it says that, "The cigarette
12 parameter studies and their effect on CSCs as measured
13 by the Salmonella mutation assay in the BCR Division
14 over the last 15 years have been varied in regard to
15 fillers, cigarette wrappers, and filters."
16 Q. Read the next sentence slowly, please.
17 A. All right. "From these studies, filter
18 ventilation appears to be the outstanding cigarette
19 parameter which affects cigarette smoke condensate
20 Salmonella activity the most."
21 Q. Okay. Now, let's translate for the Court.
22 What's CSC stand for?
23 A. That's cigarette smoke condensate.
24 Q. What's S/M activity refer to?
59
1 A. That's the Ames -- the Ames assay.
2 Q. Let me show you what's been previously
3 marked as Plaintiff's 20N. This is a document from
4 INBIFO entitled, Report P 0500/3198, dated July 13th,
5 '94, entitled, Mutagenicity of the Mainstream Smoke
6 Condensate of the Research Cigarettes X6D2EYL,
7 X6D2EYM, X6D2EYN, and X6D2EYO in the Salmonella" --
8 Pronounce that for me, if you will.
9 A. Typhimurium.
10 Q. Thank you. "Strains TA98 and TA100." Have
11 you reviewed this document?
12 A. Yes, I have.
13 Q. All right. What is it?
14 A. So this is yet another series of studies.
15 In this case they want to examine the role of
16 different paper around cigarettes to see whether or
17 not that increased or affected the mutagenicity. As
18 part of those studies that they did with the other
19 studies, they also incorporated an assessment of
20 ventilation issues that remained the outstanding
21 parameters of the impact.
22 Q. Okay. Could I have --
23 THE COURT: Excuse me. What did you do your
24 graduate, your educational work?
60
1 THE WITNESS: Undergrad at University of
2 Pennsylvania.
20 THE COURT: I'm sorry. Go ahead.
21 MR. ZELCS: That's all right.
22 Could I have 017625? And could I blow that
23 up? Thank you very much.
24 Q. (By Mr. Zelcs): Could you -- could you
61
1 discuss that or read that into the record, please?
2 A. Okay. So that's a -- one of two sentences
3 -- two sentences from the abstract which is
4 summarizing these series of experiments. And in this
5 case it says, "The specific mutagenicity of the
6 mainstream smoke condensate of the nonventilated
7 reference cigarette X6D2EYL was statistically
8 significantly lower than that of the ventilated
9 reference cigarette X6D2EYM in strain TA98."
10 Q. Okay. Light or I'm sorry. Go ahead.
11 A. "In strain TA100, it was only numerically
12 lower."
13 Q. Light or low tar cigarettes are ventilated;
14 is that correct?
15 A. Light or low tar cigarettes are ventilated.
16 That's correct.
17 Q. Could I also have 017630P? I guessed wrong.
18 That's not what I need. Let's try this one. I
19 apologize. 17637-01.
20 A. Have it.
21 MR. ZELCS: Could you blow that up a little
22 bit?
23 A. Okay. So as part of these series of
24 experiments they also tested those Kentucky referenced
62
1 cigarettes, so the 1R4F is equivalent to the low tar
2 and the 2R1 is equivalent to the high tar. And here
3 they state, "For the 1R4F, assayed under standard
4 conditions for the first time at INBIFO, the specific
5 mutagenicity of the MSC-I was approximately 30 percent
6 higher than that of the 2R1 which up to now has been
7 used as the internal control."
8 Q. Now, in that document, is there a
9 ventilation rate that's reported?
10 A. I believe so. Are we talking -- are you
11 talking about for these two cigarettes or for the test
12 cigarettes?
13 Q. I may have it wrong. I may be on the wrong
14 document. Just take a quick look at it. If it's not
15 there, I'll move on.
16 A. No, I'll just refer to this here. Okay. I
17 got it.
18 Q. Hold on just a second. I think I'm catching
19 up. Why don't you --
20 A. It's 17630.
21 Q. Thank you very much.
22 MR. ZELCS: Could you blow that up, please?
23 Thank you.
24 A. So here in this document they were comparing
63
1 these different cigarettes, and you can see under
2 ventilation percent, which is if you go down to smoke,
3 cigarette, paper, filter, ventilation, you could see
4 that the nonventilated are zero and you could see that
5 the ventilated was 28 percent. And that was
6 significantly significant in the nonventilated
7 cigarettes. Marlboro Lights is somewhere around 25
8 percent.
9 Q. What does that tell you?
10 A. What that's saying is at a level of 28
11 percent ventilation, they're getting a significant
12 increase in mutagenicity. I'm sorry for talking so
13 fast.
14 Q. Let me show you what's been marked as
15 Plaintiff's Exhibit 92. It's a document called the
16 Brands (Ames). You've seen this document as part of
17 your work in this case, right?
18 A. Yes, I have.
19 Q. What is it?
20 A. This is yet another series of experiments
21 where they're discussing the mutagenicity, and this
22 time in relationship to actual Marlboro versus
23 Marlboro Lights as well as other commercial products.
24 MR. ZELCS: Could I ask you to bring up
64
1 59982?
2 Q. (By Mr. Zelcs): Is that the right chart?
3 A. Yes.
4 Q. Okay. Could you explain what that is and
5 what its significance is to you in terms of your work?
6 A. Okay. What they're doing here is comparing
7 mutagenicity for each of these cigarettes, and they're
8 comparing two different smoking machine parameters.
9 One is what they say is ISO, but that's the same as
10 the FTC, and the second one is the Massachusetts
11 smoking protocol.
12 Q. Let's stop there. ISO is another machine
13 smoking method that's used outside of the United
14 States?
15 A. Yes, but it's the FTC method.
16 Q. And it's essentially the same as the FTC?
17 A. Correct.
18 Q. Okay.
19 A. So basically the difference between the two
20 methodologies is there's some difference in puffs per
21 minute as well as a little bit of difference in the
22 puff volume, but what they also do in the
23 Massachusetts protocol is cover over half the holes so
24 they reduce the ventilation. Okay. And what you can
65
1 see is the dark black bars is the FTC method. The
2 lighter grayish bars is the ones where you cover over
3 the holes and you reduce the ventilation. What you
4 can see is on every one of those cigarettes, the
5 mutagenicity for the cigarettes that have more
6 ventilation is higher.
7 Q. Is that the teaching point for us to take
8 home from that --
9 A. Yes.
10 Q. -- this document?
11 A. Yes.
12 Q. This exhibit has been previously marked as
13 Plaintiff's 20-M. It's a document entitled, "In Vivo
14 Mutagenicity of Mainstream Smoke Condensate of 30
15 Research Cigarettes with Differences in 6 Parameters."
16 MR. TILLERY: In vitro.
17 Q. (By Mr. Zelcs): In vivo. I'm sorry. I
18 stand corrected. In vitro.
19 Have you reviewed that document as part of
20 your work in this case?
21 A. Yes, I have.
22 Q. Where did it come from?
23 A. Okay. What looks to me --
24 Q. Hold on. Hold on. Where did it come from?
66
1 A. Well, it's a Philip Morris document.
2 Q. Tell us what it describes.
3 A. Okay. It looks to me like this is the
4 summary of that proposal that we saw earlier on the 30
5 different cigarettes. So we saw the proposal and the
6 rationale for needing a large study of 30 research
7 cigarettes with different parameters and these are the
8 results.
9 Q. Does this document include a summary?
10 A. Yes.
11 MR. ZELCS: Could I have 46122-03? Would
12 you blow that up, please? Thank you.
13 Q. (By Mr. Zelcs): What -- I'm sorry. Go
14 ahead and go through that and explain it to the Court
15 if you would?
16 A. Okay. So under the summary they gather, you
17 know, they report basically the results of their data
18 and reflectionality, and what they're saying here is
19 that the mutagenicity of the mainstream smoke
20 condensate is influenced by, and there's several
21 factors here. We have highlighted the filter
22 ventilation and that's because that's really the major
23 difference between the Marlboro Reds and the Marlboro
24 Lights.
67
1 MR. ZELCS: Okay. Let me ask you to bring
2 up 46.
3 THE COURT: What was the date of the
4 document?
5 THE WITNESS: It looks like there's a 1-95
6 on the top left.
7 THE COURT: Oh, is that the date? Okay.
8 MR. ZELCS: I believe that's right, your
9 Honor.
10 MR. ZELCS: All right. Could you blow up
11 the conclusion?
12 Q. (By Mr. Zelcs): Please read into the record
13 these points?
14 A. "Conclusion. The results of the study
15 enable us to specifically modify a given cigarette to
16 get lower mutagenic activity."
17 Q. What's the significance of that statement,
18 that conclusion to you?
19 A. Well, they're telling us the -- what they
20 have been doing and what industry in general does is
21 basically product line testing with the goal of
22 getting something that they think will have less of an
23 adverse effect. In this case, mutagenic activity.
24 Q. Have you reviewed any Philip Morris
68
1 documents that speak to their knowledge that lights,
2 such as Marlboro Lights and Cambridge Lights, are not
3 only higher in specific mutagenicity but that their
4 increased filter ventilation dilution design feature
5 results in increased mutagenicity?
6 A. Yes.
7 Q. It's been previously marked as Plaintiff's
8 20-L. It's another INBIFO document. January 28th,
9 1994. It's actually correspondence. It's from
10 someone that's been designated, I believe by the
11 defendants, as a potential witness. Wolf Reininghaus
12 to Cathy Ellis.
13 And you've reviewed this as part of your
14 work; is that right?
15 A. That's right.
16 Q. What is this letter?
17 A. Okay. So this is a correspondence to a
18 doctor Cathy Ellis from Dr. Reininghaus, and it's
19 dated January 28th, 1994.
20 Q. Does this letter speak to their knowledge of
21 the link between increased ventilation and dilution in
22 light and increased mutagenicity?
23 A. Yeah, we have --
24 Q. Let me ask for something to be called up now
69
1 that you've answered it.
2 MR. ZELCS: 046543-01.
3 Q. (By Mr. Zelcs): Could you read that into
4 the record?
5 A. Sure. It says, "Increased porosity and
6 ventilation will lower the air flow through the cone
7 and increase the specific mutagenicity."
8 Q. Okay. What's the significance of that
9 statement to you?
10 A. Well, we have seen the -- either the raw
11 research data or the summaries of the research now are
12 being -- we're seeing correspondence among different
13 Philip Morris scientists which basically demonstrate
14 how widespread this knowledge was.
15 Q. I'm going to show you what's been marked as
16 Plaintiff's 93. It's a memo, a Philip Morris memo
17 from a Richard -- R. A. Carchman to a Dr. Leyden,
18 April 6, 1992. And the subject is 1992 Tobacco
19 Biochemistry Program Operation Plan--Update. Have you
20 seen this document as far as your work in this case?
21 A. Yes, I have.
22 Q. Can you tell us what it is?
23 A. So initially we saw that 30 brand cigarette
24 proposal, we saw the results. This is the interim
70
1 progress report from Dr. Carchman.
2 Q. Is there any reference in this document as
3 to how cigarette construction affects biological
4 activity?
5 A. Yes.
6 MR. ZELCS: Could I have 46512-01?
7 Q. (By Mr. Zelcs): Could you read that into
8 the record please?
9 A. Sure. It says, "Previous non-systematic
10 studies have suggested that cigarette smoke condensate
11 from a low tar reference cigarette was more active
12 than cigarette smoke condensate from the Kentucky
13 Reference cigarette."
14 Q. Let me interrupt you again at this point.
15 The Kentucky Reference cigarette again is what again
16 for the Court's benefit?
17 A. This is the high tar cigarette that's meant
18 to approximate something like the Marlboro Reds.
19 Q. Something akin to a full flavored?
20 A. Correct.
21 Q. Okay. Go ahead.
22 A. And then it says, "But the low tar reference
23 cigarette had a high efficiency cellulose acetate
24 filter, high porosity paper and a 47 percent filter
71
1 dilution. Other studies suggested that filter
2 dilution was a critical factor in determining
3 bioactivity."
4 Q. What's the import of that statement to you?
5 A. Well, again, we're seeing a number of Philip
6 Morris scientists continue to report out their
7 findings, which actually summarize research over the
8 early 20 years.
9 Q. Did Philip Morris and the Ames testing
10 program suggest anything as to whether they thought
11 that the Ames test predicted carcinogenicity?
12 A. Yes.
13 Q. I show you what's previously been marked as
14 Plaintiffs' 20-B. It's a document that the first page
15 appears to be the personal notepad of someone named
16 Robert B. Seligman. Have you seen this document as
17 part of your work in this case?
18 A. Yes.
19 Q. What does it appear to be based upon your
20 review?
21 A. Well, these are handwritten notes from
22 Robert Seligman, and it looks to be like it's either
23 he was doing a presentation or he was taking notes
24 from a presentation and --
72
1 Q. Let me interrupt you if I may just for a
2 second. Who was Robert Seligman?
3 A. My understanding is that he was a senior
4 Philip Morris researcher.
5 Q. Okay. Go ahead. I didn't mean to interrupt
6 you.
7 A. And so he has been -- summarized a large
8 amount of data that's related to both in vitro as well
9 as in vivo animal testing.
10 Q. Do these notes, Seligman's notes summarize
11 any findings on Ames testing?
12 A. Yes, they do.
13 MR. ZELCS: 31670-01. Could you blow it up?
14 Q. (By Mr. Zelcs): Okay. Go ahead.
15 A. So under summary of findings for the
16 Salmonella typhimurium, he wrote, "Generally good
17 correlation with skin painting results."
18 Q. What does that mean?
19 A. Okay. So --
20 Q. Wait. Let's go back.
21 MR. ZELCS: Could you take off just the
22 highlighted section for the time being. Step back.
23 There you go.
24 Q. (By Mr. Zelcs): That's under the heading of
73
1 what, Salmonella?
2 A. Typhimurium.
3 Q. Okay. And what again is that?
4 A. That's the Ames assay.
5 Q. Okay. So that's another term for Ames,
6 right?
7 A. Correct.
8 Q. And underneath that they're saying what?
9 A. "Generally good correlation with skin
10 painting results."
11 Q. All right. Now, let's go back because we
12 were talking fast, both you and I. We earlier talked
13 about skin painting as being the second step, the in
14 vivo step? Is that right?
15 A. That's right.
16 Q. Okay. What's the significance to you of a
17 statement in Seligman's notes under a discussion of
18 findings involving the Ames testing that there's
19 generally a good correlation with skin painting
20 results?
21 A. Well, it could mean one of several things.
22 The skin painting assay was commonly used. It was --
23 especially for cigarette smoke condensate and he's
24 either telling us that he knows Ames testing in
74
1 general is well correlated with skin painting results,
2 or what I think based upon other documents as well is
3 that they're actually reporting to us results of their
4 animal testing, which was either done way before the
5 Ames test or some time just recently before this
6 document was written.
7 Q. Is this way of giving somebody a heads up
8 that there's a link between these two things?
16 Q. (By Mr. Zelcs): Does that suggest to you
17 that there's a link being stated in that?
18 MR. LOMBARDI: The same objection, your
19 Honor.
20 MR. ZELCS: I'm asking him based upon --
21 THE COURT: Well I'll overrule that.
22 A. Okay. Well, what it says to me is that he's
23 acknowledging that the Ames test is predictive of skin
24 painting animal studies.
75
1 Q. (By Mr. Zelcs): And, again, skin painting
2 is one of the in vivo tests that would be considered
3 the next step above Ames as you work your way up the
4 step wide process, right?
5 A. That's correct.
6 Q. Let me ask you, --
23 MR. ZELCS: Bear with me just a second here
24 if you would. All right. Could we have 31669 up on
76
1 the screen, please? 3. Correct. Beautiful. And
2 could we --
3 Q. (By Mr. Zelcs): All right. What does this
4 talk about?
5 A. Okay. This is in the same presentation
6 under the same section of summary of findings, but
7 here we're looking at skin painting results.
8 Q. Okay. So we've got the section here that
9 deals with results relating to skin painting, right?
10 A. Correct.
11 MR. ZELCS: Let's drop down to the last line
12 under that skin painting section. Beautiful. If you
13 would blow that up.
14 Q. (By Mr. Zelcs): What does that say?
15 A. It says, "Specific activity is not lowered
16 by filters."
17 Q. What does that mean?
18 A. Well, we see between the other page about
19 the Ames correlation of skin painting, and now he's
20 reporting results of skin painting data by filters.
21 He's trying to see some hint that Philip Morris may
22 have done what would have been the appropriate thing
23 to do which would be to do animal studies on these
24 products.
77
1 MR. ZELCS: Now, help me out here if you
2 would. Could you call up 31657?
3 Q. (By Mr. Zelcs): Okay. And this has a
4 series of dates on it, does it not?
5 A. That's correct.
6 Q. And what's the last date that's on there?
7 A. 1977.
8 Q. Okay. From the documents that you reviewed
9 for this case, did you see any indication that Philip
10 Morris had done skin painting tests relating to smoke
11 condensate?
12 A. Among all the documents that I've seen, I've
13 actually -- we have one page of results of a summary
14 of a skin painting experiment from Philip Morris.
15 MR. ZELCS: Could I have CKTO3169 up?
16 Q. (By Mr. Zelcs): This has been marked as
17 Plaintiffs' Exhibit Number 94. It's a document
18 entitled "Low Tar Reference Cigarette, X6D7AKJ. Did
19 you review this document as part of your work in this
20 case?
21 A. Yes, I did.
22 Q. What's the significance of that document to
23 you?
24 A. Okay. So they're providing results as it
78
1 says, Gross findings from experiments that look like
2 they were done in 1977 being reported out in 1979.
3 Q. Let me interrupt you -- let me interrupt for
4 a second.
5 MR. ZELCS: Could we go to the top line,
6 I-A, highlight that.
7 Q. (By Mr. Zelcs): And could you tell the
8 Court what that says?
9 A. Okay. It says mouse skin painting study,
10 INBIFO, 1977.
11 Q. Okay. Go ahead.
12 A. So here they're comparing two cigarettes,
13 the X6D7AKJ is their low tar equivalent cigarette, and
14 the 2R1 is the full flavored cigarette, the high tar
15 cigarette. And you can see that where we've got
16 highlighted yellows we have the equivalent doses of
17 the one to one dilution. And on the tumor -- on the
18 tumor rates you can see that the low tar reference
19 cigarettes had 54 percent or 54.2 tumor, whereas the
20 high tar cigarettes less tumors, the 42.6 percent
21 tumors. So there were more tumors here with the low
22 tar reference than the high tar reference.
23 Q. Are you aware of any in vitro testing prior
24 to the Ames testing done by Philip Morris that
79
1 indicated any difference between low tar and regular
2 cigarettes?
3 A. Yes.
4 Q. This will be Plaintiffs' Exhibit 95.
5 MR. ZELCS: If you would just bear with me,
6 your Honor.
7 THE COURT: Take your time.
8 MR. ZELCS: It's not one that I haven't --
9 Do you need some water?
10 THE WITNESS: I've got my own. Well,
11 actually it would be great to get a little more.
12 MR. TILLERY: I'll get you some.
13 Q. (By Mr. Zelcs): I show you what's been
14 marked as Plaintiffs' Exhibit 95.
8 THE COURT: All right.
9 MR. ZELCS: -- it was listed on Sunday as
10 one of the documents this witness was testifying
11 about. I don't have the reliance sheet in front of me
12 right now, so before I make any representations
13 regarding that, let me check.
14 We'll go ahead and mark this as 96 for the
15 time being.
16 Q. (By Mr. Zelcs): I show you what's been
17 marked as Plaintiffs' Exhibit 96, Philip Morris
18 interoffice memo dated April 19, 1998 from McCoy to
19 Penn. Is this a document that you've seen as part of
20 your work in this case?
21 A. Yes.
22 Q. What is it?
23 A. It's a Philip Morris memorandum dated April
24 19th, 1988, and it's a summary of a meeting that Mr.
81
1 or Dr. McCoy had attended on March 27th through 31,
2 1988. It's a meeting of the Environmental Mutagen
3 Society.
4 Q. All right. Does McCoy -- What does McCoy do
5 in that memo?
6 A. He's summarizing the data that was presented
7 at this national meeting, international meeting I'm
8 showing.
9 Q. Does he report on any correlations discussed
10 at this meeting of the Mutagen Society relating to
11 Ames Salmonella Assays?
12 A. Yes, he does.
13 MR. ZELCS: 55417-01. Would you blow that
14 up, please? That's fine.
15 Q. (By Mr. Zelcs): Could you read that in the
16 record?
17 A. "There appeared to be a correlation between
18 the level of response in the Ames/Salmonella assay and
19 the pattern of positive carcinogenicity findings."
20 Q. What's the significance of that document to
21 you?
22 A. Well, we've seen the primary research data,
23 we've seen the correspondence of all Philip Morris
24 employees, and now we're seeing the interaction of
82
1 Philip Morris scientists with the general scientific
2 community. And again saying exactly the same thing
3 that we've seen in the PM documents by their own
4 research scientists that there's a high correlation --
5 that there's a high correlation between the Ames
6 testing and carcinogenicity tests.
7 Q. Plaintiffs' 97. It's a document dated March
8 6, 1980 from Ferguson and Pages, a Philip Morris
9 interoffice correspondence to Mr. Kuhn. Have you seen
10 this before as part of your work in this case?
11 A. Yes.
12 Q. Tell us what this document is.
13 A. Okay. So this is a March 6th, 1980
14 memorandum that's also a trip report summarizing their
15 monthly meeting of the DKHEW Subcommittee on
16 Environmental Mutagenesis, MIH. And at that meeting
17 there was a number of highly regarded, quite famous
18 researchers and tobacco epidemiology and
19 carcinogenists.
20 Q. Now, this report, does it comment at all on
21 Ames testing?
22 A. Yes.
23 MR. ZELCS: 45952-01.
24 Q. (By Mr. Zelcs): Could you read that into
83
1 the record?
2 A. Yes. It says, "From all information
3 available at present they believe that all chemicals
4 which are active in both the Ames and the Williams
5 tests," that's another in vitro test by Gary Williams,
6 "are potent carcinogens and any such chemicals should
7 be immediate candidates for chronic lifetime bioassay
8 in rodents (step four below) without requiring any
9 further short-term testing."
10 Q. Now, there's a further notation in that
11 document, is there not?
12 A. Yes.
13 Q. Now, I want you to read that very slowly.
14 A. Okay. It says, "No prudent person would
15 seriously propose bypassing step four with a compound
16 that would be expected to have widespread use and/or
17 exposure to humans."
18 Q. The people that wrote this Ferguson page,
19 who were they?
20 A. These were Philip Morris employees.
21 Q. Were they senior research leaders?
22 A. That's my understanding.
23 Q. How does Philip Morris respond -- I'm sorry.
24 How did Philip Morris' response to the results of its
84
1 Ames testing on ventilated cigarettes compare with
2 this statement by Ferguson and Page?
3 MR. LOMBARDI: I object, your Honor. This
4 goes back to the idea that there's testing, different
5 tests we should have done. I apologize. I think you
6 gave me a standing objection on that. I apologize,
7 your Honor.
8 A. Well, this document also articulates the
9 multi step testing process that one would do and --
10 Q. (By Mr. Zelcs): Let me interrupt you.
11 A. Yes.
12 Q. Are you saying it refers to the step wide
13 process --
14 A. That's right.
15 Q. -- that we were talking about earlier how
16 you keep climbing?
17 A. That's correct.
18 Q. Out or up?
19 A. That's right. And what the document clearly
20 says, what these authors clearly say is that it
21 actually doesn't even matter once you have -- once you
22 have a positive in vitro test or you decide not to do
23 an in vitro test, you have to do animal studies before
24 you introduce these products to humans. And in the
85
1 Philip Morris case, we see all in vitro testing. We
2 don't see the animal -- we don't see the animal
3 testing that shows that these products were -- these
4 product design changes were a benefit to smokers.
5 Q. Did Philip Morris take any steps that would
6 suggest that they appreciated the Ames test
7 mutagenicity levels were predictive carcinogenicity?
8 A. I'm sorry. Say that question again.
9 Q. Did Philip Morris take any steps that would
10 suggest that they appreciated the Ames test
11 mutagenicity levels were predictive of
12 carcinogenicity?
13 MR. LOMBARDI: I object to trying to define
14 the intentions or mental state of Philip Morris
15 employees.
16 THE COURT: Overruled.
17 A. Well, they kept doing the same experiments
18 over and over again.
19 Q. (By Mr. Zelcs): In their work, did they
20 emphasize the need to decrease mutagenicity scores in
21 terms of their efforts to develop a so-called less
22 harmful cigarette?
23 A. Yes.
24 Q. Have you seen any evidence or reviewed any
86
1 documents that speak to this need to decrease
2 mutagenicity scores while developing a less harmful
3 cigarette?
4 A. Yes.
5 Q. Have you read the deposition of Harold
6 Burnley?
7 A. Yes.
17 THE COURT: Okay. A fifteen minute break.
18 (A fifteen minute recess was taken.)
19 THE COURT: You may be seated. Have you
20 disclosed the whole exhibit?
21 MR. ZELCS: Your Honor, this was one of the
22 documents that had been produced in the last two weeks
23 before we commenced the trial. That's the basis.
24 THE COURT: All right.
87
14 MR. ZELCS: And this had been previously
15 marked as 95 and given to everyone. I'll use the
16 follow up of this. This isn't part of our --
17 Q. (By Mr. Zelcs): Dr. Shields, let me show
18 you what's been marked as Plaintiffs' Exhibit 95. You
19 reviewed that document recently as part of your work
20 in this case; is that correct?
21 A. That's correct.
22 Q. Tell us what it is?
23 A. It's a document that is reporting results
24 from June 1970 to June 1971 on the biological effects
89
1 of smoke. The title is biological effects of smoke
2 and it's part of the 9606 project.
3 Q. All right. And what was the purpose of that
4 study?
5 A. Well, it says that: "The objectives of this
6 project are to find meaningful tests for the
7 biological effects of cigarette smoke with relevance
8 in biological systems in general. To try to
9 anticipate the direction of future attacks on the
10 effects of cigarette smoke and to experimentally
11 evaluate published procedures on the biological effect
12 of cigarette smoke."
13 Q. Now to put that all back into context for
14 the Court, when I originally introduced this document,
15 we were talking about Ames tests and documents showing
16 how Philip Morris had been using that. And my
17 question to you on this document is and I'll repeat it
18 now. Even before the advent of Ames testing at Philip
19 Morris, did you see documents evidencing in vitro
20 testing of cigarette smoke?
21 A. Yes. This was, as you just said it's before
22 the Ames test was used, and they were summarizing
23 their research to try to identify other in vitro acids
24 that they could use, not yet knowing that the Ames
90
1 test was going to come along.
2 Q. And this document dates back to 1971, right?
3 A. That's correct.
4 Q. I think you wanted to talk about Table I; is
5 that correct?
6 A. That's correct.
7 Q. Tell the Court what Table I is?
8 A. Okay. So this is a summary of data from
9 actually some very interesting state of the art type
10 experiments at the time where they were culturing lung
11 cells of people and putting them in a dish and looking
12 at responses to the different exposures of the puff
13 smoke. And so what we see here is actual Philip
14 Morris products being tested. It wasn't until 19 --
15 2000 and something that we got to see actual products
16 being tested again. And --
17 Q. Let me interrupt you if I may. To make sure
18 the Court understands what you're saying here. And
19 correct me if I'm wrong. Are you saying that back in
20 1971 they were testing, based upon that table, actual
21 products that they sold people, and they stopped doing
22 it and didn't test them again until sometime around
23 1998, 1999, or 2000?
24 A. That's my understanding, yes.
91
1 Q. Go ahead.
2 A. So what they did is they exposed these cells
3 to the whole smoke, and they looked at the glycolysis
4 rate. That's basically a glucose utilization and
5 energy consumption test. And what you can see among
6 all these different products they tested is that the
7 single highest value, which is much higher than all
8 the others, is the one that says E L -- EOLR-60%
9 mechanically diluted. So the one that has the
10 filtered dilution provides the highest response. That
11 suggests to me that at the time they were already
12 aware that they were going to have different
13 biological activity from these products of high
14 dilution.
15 Q. And this, again, was in July -- June of
16 1971?
17 A. That's correct.
18 Q. And do you know whether or not the Marlboro
19 Lights was introduced in the fall of 1971?
20 A. That's my understanding.
21 Q. All right. Just before the break we were --
22 I was trying to find the transcript for the Burnley
23 deposition, and we were successful in that effort,
24 your Honor. What I would like to do now is show a
92
1 clip that's from Burnley testimony at page 48 and I
2 will -- I will read the question and answer and then
3 we'll show the clip if that's okay. Line six.
4 "Question: And the goal of the biological
5 testing obviously is to identify what decreases the
6 biological testing score rather than increases that
7 score; is that right?"
8 Mr. Wagner objected to form.
9 "Answer: Well, the biological testing is used to
10 determine the suitability of a product change.
11 Certainly you don't want to do anything that will make
12 a product more hazardous or more risky or increase the
13 likelihood that people who use that product would get
14 sick."
15 And then going on.
16 "So the goal would be, if you make a change, the
17 biological testing scores should go down rather than
18 up?
19 "MR. WAGNER: Object to the form.
20 "MR. SWEDLOW: Is that right?
21 "Or stay the same.
22 "And if a biological testing score went up, more
23 investigation would be needed; is that correct?
24 "That's right."
93
1 MR. ZELCS: And then the additional section
2 that I'd like to read would be on page 55.
3 THE COURT: What is the answer with the
4 designation would be?
5 MR. ZELCS: The line -- the question starts
6 at line 21, and the answer starts at line 24 and
7 continues through -- I'm sorry. 21 through 24.
8 The question, "And all other things are
9 equal, more mutagenicity is worse rather than better;
10 is that right?
11 "ANSWER: It may be, yes. I'll give you your
12 point."
13 MR. ZELCS: Could we read the clip please or
14 play the clip?
15 (Whereupon the following proceedings were
16 taken down from the video clip.)
17 "Well, the biological testing is used to
18 determine the suitability of a product change.
19 Certainly you don't want to do anything that will make
20 a product more hazardous or more risky or increase the
21 likelihood that people who use that product would get
22 sick."
23 "And if a biological testing score went up, more
24 investigation would be needed; is that correct?
94
1 "That's right."
2 "And all other things are equal, more
3 mutagenicity is worse rather than better; is that
4 right?
5 "It may be, yes. I'll give you your point."
6 (Conclusion of video clip.)
7 Q. (By Mr. Zelcs): You read that testimony,
8 the entire deposition?
9 A. Yes.
10 Q. And you relied upon it in performing your
11 opinions in this case?
12 A. Yes.
13 Q. What's the significance of that testimony to
14 you?
15 A. Well, it's clear that this individual, who
16 is employed by Philip Morris, is basically saying the
17 same thing I've been saying in my testimony which we
18 also know is true through a consensus of the
19 scientific and public health community that more is
20 worse and that it would indicate that their light
21 cigarettes are not linked.
22 Q. Did you also review the testimony of Jerry
23 Whidby, one of the fellows, the two fellows designated
24 so in the Philip Morris research and development
95
1 department?
2 A. Yes.
3 MR. ZELCS: And, again, your Honor, I'll
4 read the testimony first. I'll have to read back a
5 couple of questions because there's some objections.
6 This starts on page 58 and at line 23. And what I'm
7 reading in does.
8 "Question: Let me strike that question and ask a
9 different one. If you learn that there was testing
10 being done of components, biological data, and the
11 results just showed that this was really bad in terms
12 of mutagenicity or anything else, as somebody that
13 knows and design cigarettes, you wouldn't -- you
14 ultimately wouldn't learn of that information, they
15 wouldn't hide that information or keep you from
16 learning it, would they?
17 "MR. LOMBARDI: Objection to form, foundation.
18 "No, they would not, and I can tell you what they
19 actually did.
20 "Question: Okay.
21 "Answer: What we actually did by example was if
22 we were making a modification of the product or you
23 want to make a modification of a product, what we
24 typically did was to test a product that was not
96
1 modified and test the same product as identical as
2 possible except for modification. For example, if we
3 wanted to change the type of paper on a particular
4 cigarette, we would evaluate from a biological testing
5 point of view and also a chemical point of view the
6 cigarette before it was modified and the cigarette
7 after it was modified, and in some instances that I
8 was involved in we found the biological activity was
9 increased and, therefore, we did not implement those
10 changes."
11 MR. ZELCS: The second piece is on page 62.
12 And, again, I have to go back and read a preceding
13 question that actually starts on 61, line 13.
14 "Question: I'm with you. Here's what I'm trying
15 to get at, but if I understood it correctly what you
16 would be doing is it would be like if you had a Chevy
17 Malibu, and if it had a certain type of fuel injection
18 on it and you were going to change the fuel injection
19 on it, the way you would test that is you would work
20 up the Chevy Malibu with the changed fuel injection
21 and test it against the existing one and see how the
22 performance differs. Well, from a chemical as well as
23 a biological point of view and if you got results that
24 made you this achieves it better whatever you're
97
1 trying to work for, in that case the ignition
2 propensity that was less but if there was a biological
3 activity piece of it that was bad news you might not
4 go forward?
5 "Answer: We wouldn't go forward, but that's kind
6 of the way it would work using my Chevy Malibu as an
7 example instead of a cigarette.
8 "MR. LOMBARDI: Objection to the form to the
9 deponent. That's an example.
10 "Okay. And so you were involved in that
11 sort of work" -- question -- "or knew of that sort of
12 work or proposed modification as to a component of an
13 existing product tested to see how it might all,
14 right?
15 "Yes.
16 "And, okay, what you were trying to do there was
17 to test the product that would be as identical as
18 possible with this modified version?
19 "Right. "
20 MR. ZELCS: And that's the section that I've
21 read and played to the Court.
22 (Whereupon the following proceedings
23 were reported from the video clip.)
24 "In some cases that I was involved in we found
98
1 the biological activity was increased and, therefore,
2 we did not implement those changes. But if there was
3 a biological activity piece of it that was bad news,
4 if someone told you that increased air dilution or
5 increased ventilation in cigarettes also increased
6 biological activity, would that change your conduct at
7 all in terms of designing cigarettes with more
8 ventilation and air dilution?
9 If that were a fact borne out by science, and it
10 was agreed upon that that was really the case, I think
11 using ventilation, increased ventilation would be
12 under question."
4 Q. (By Mr. Zelcs): Let me go back to the
5 question. Did you read Mr. Whidby's testimony as part
6 of your work in this case?
20 Q. (By Mr. Zelcs): You read that testimony?
21 A. Yes.
22 Q. What was the significance of that testimony
23 to you in terms of your opinions in this case?
24 A. Well, it said pretty clearly that he was
100
1 involved in product design changes, and when they had
2 product design changes that if they had an adverse
3 effect they abandoned them, and he said that that
4 would also be true for ventilation and that's what he
5 learned. And in fact over the 25 years as a Philip
6 Morris knew was that the ventilation was worse and yet
7 they continued to go ahead with their product.
8 Q. Did Mr. Whidby's testimony suggest to you
9 that Philip Morris appreciated the main testing of
10 carcinogenicity levels?
11 A. Leading.
12 THE COURT: Overruled.
13 A. Well, clearly he said they were making
14 product design changes on the basis of the
15 mutagenicity, and that's related to, you know, cancer
16 risk in people.
17 Q. (By Mr. Zelcs): Now, let's move forward.
18 After getting consistent test results demonstrating
19 increased specific mutagenicity resulting from this
20 increased filter dilution or ventilation, whatever you
21 call it, what, if anything, did Philip Morris do based
22 upon your review of the materials?
23 MR. LOMBARDI: Objection. Foundation and
24 relevance.
101
1 THE COURT: Due to regard with what? With
2 regard as a result of this test?
3 MR. ZELCS: Yes.
4 Q. (By Mr. Zelcs): What did they do with
5 regard to following the step wide process that they
6 were aware of.
7 THE COURT: Well, overruled.
8 A. Okay. Well, with the exception of the one
9 page document summarizing the skin painting tests, I
10 don't see any evidence in the documents that they did
11 anything with the results, which is a contrast to
12 continuing to produce and market the light cigarettes,
13 and, of course, ultimately making the leading
14 satellite cigarette.
15 Q. Did the documents suggest to you that they
16 continued to utilize the same design matter, namely
17 increased ventilation?
18 A. Yeah. They kept testing it over and over
19 and over again.
20 Q. And getting the same results?
21 A. Absolutely.
22 Q. And, again, the ventilation feature that I'm
23 talking about is the one that's used in Marlboro Light
24 and Cambridge Light cigarettes?
102
1 A. My understanding is that's the predominant
2 difference in these cigarettes.
3 Q. Now, this notion that despite getting all
4 these test results they kept on doing the same thing,
5 is that also borne out by evidence or documents that
6 you looked at?
7 A. Sure.
8 Q. Okay. Did you read the testimony of Mr.
9 Solana in this case?
10 A. Yes.
11 Q. Okay. Let's go to page 66 of Mr. Solana's
12 deposition. I believe -- I believe this clip captures
13 an entire question and answer so it won't be necessary
14 for me to read them. Why don't we go to that first.
15 This is at page 66, line two through six.
16 (Whereupon, a film clip was played,
17 where the following proceedings were
18 took down.)
19 "To your knowledge, has any of the data on the
20 mutagenicity of low tar smoke resulted in a change in
21 a product that Philip Morris sells?
22 No. We also talked about the need to take the
23 data as a whole, the weight of evidence."
24 (Conclusion of video clip.)
103
1 MR. LOMBARDI: And, Judge, he continues his
2 answer. The question says right.
3 THE COURT: Yeah, it was interrupted there.
4 MR. ZELCS: Your Honor, the -- I'll read --
5 THE COURT: Just go ahead and read it.
6 MR. ZELCS: I'll read the rest of it. That
7 was his complete answer. There was an extra question
8 that says right, and he then went on and said, "And so
9 this would be very important to do. If you know James
10 assay, a simple screening assay is to get a sense of
11 interaction of the smoke of DNA that bacteria and
12 cells information that's relevant to smokers,
13 different it's bacteria and even it is it was it's not
14 human cells and if it were human cells and even if it
15 were a human other than we take into account actual
16 smoke. And ultimately what we have to do is that it
17 does take all that into account and is the most
18 definitive at that at that. It's the data on risk in
19 the sense of lung cancer epidemiology. So you have to
20 take the entire situation of evidence if you want to
21 ask a question about low tar cigarettes taking one
22 piece of data and culture. I know we're
23 overemphasizing without considering all the other data
24 it would be an irresponsible way to interpret the
104
1 signs."
2 Q. (By Mr. Zelcs): What's the significance of
3 that testimony to you?
4 A. Well, I really couldn't agree more with Rick
5 Solana. I think he's absolutely right that the
6 responsible thing to do is to examine the weight of
7 evidence when you get a result -- when you get a test
8 result like that, you need to weigh the evidence. The
9 fact is that Philip Morris had no weight. They just
10 kept doing the same test over and over again.
11 Q. In your opinion as someone with expertise in
12 mutagenicity, cancer, and DNA damage and carcinogens,
13 what should they have done?
14 MR. LOMBARDI: Objection, your Honor. This
15 is not relevant to any issue in this lawsuit, and I
16 have my standing objection also on preemption and
17 warning and omission.
18 MR. ZELCS: Again, your Honor, it's tied
19 into the notion --
20 THE COURT: Go ahead. I'll overruled that.
21 Go ahead. Overruled.
22 Q. (By Mr. Zelcs): Do you need the question
23 back?
24 A. Yes, please.
105
1 Q. In your opinion as someone with expertise in
2 mutagenicity, cancer, DNA damage, and carcinogenicity,
3 what should they have done?
4 A. Well, they were testing design changes on a
5 product that when used as intended was dangerous.
6 They had results that showed that their product design
7 change could make it more dangerous in people. They
8 had really two clear choices. One of them was to
9 abandon the design change, not go through it in terms
10 of either introducing it to the market or taking it
11 off the market.
12 Actually, they could have done three things.
13 They could have done the testing that they needed to
14 decide that fact that this was an okay change after
15 all and a benefit to people, or they could also have
16 started working with the public health community and
17 scientists to try to figure out this problem as
18 quickly as possible.
19 I don't think the choice that would have
20 been acceptable was to just keep doing the same
21 testing over and over again and making a harmful
22 product potentially more harmful.
23 Q. Is it your opinion that they didn't do the
24 additional testing, they should have taken the product
106
1 off the market?
17 A. Could you say the question again? I'm
18 sorry.
19 Q. (By Mr. Zelcs): If they didn't do any
20 additional testing, should they have taken the product
21 off the market?
22 MR. LOMBARDI: The same objection.
23 THE COURT: Overruled.
24 A. Yes.
107
1 Q. (By Mr. Zelcs): And is that an opinion that
2 you hold within a reasonable degree of scientific and
3 medical certainty?
4 A. Yes.
5 MR. LOMBARDI: The same objection, your
6 Honor.
7 THE COURT: Overruled.
8 Q. (By Mr. Zelcs): You've talked about some
9 isolated references to skin painting; is that correct?
10 A. That's correct. In the Philip Morris
11 document.
12 Q. Right. Other than those isolated
13 references, did Philip Morris conduct any additional
14 experimental animal testing after getting 25 years of
15 these results on Ames assays with regard to filter
16 ventilation and higher mutagenicity levels?
17 A. There also were some isolated references to
18 inhalation testing, but I could not find results for
19 any of that data.
20 Q. Are you suggesting that if any such work was
21 actually done by Philip Morris it should have been
22 publicized or published?
23 MR. LOMBARDI: The same objection to some
24 kind of publicized --
108
1 THE COURT: Well, --
2 MR. ZELCS: Okay.
3 THE COURT: Yeah, I'll sustain that
4 objection.
5 Q. (By Mr. Zelcs): Was any of this information
6 available to the public health community?
7 A. I'm not aware of any information in Philip
8 Morris in this regard with regard to the public health
9 community.
24 THE COURT: You may ask the question.
110
1 Q. (By Mr. Zelcs): As a medical doctor and a
2 scientist, was this -- in your opinion, was this data
3 from these tests important information?
4 A. I think this was a major red flag in the
5 context of their product design testing and what was
6 going on at the time.
7 Q. And why was the status so important?
8 A. Because there -- the public was switching to
9 these -- to this product with their perception it was
10 better. We in the public health community were giving
11 the message that if you can't stop smoking, then you
12 ought to go to this product. And at the same time
13 there was data that was generated by Philip Morris, it
14 was their screening test, it was their test that they
15 used over and over and over again. And a result of
16 their screening test said that all may not be true,
17 that this is not a better alternative for people who
18 can't stop smoking.
19 Q. And if the information that Philip Morris
20 had that this wasn't true in terms of light cigarettes
21 and the ventilation features of light cigarettes, if
22 that information had been available to other doctors
23 and scientists, do you have any opinion as to how that
24 would have impacted them?
111
18 Q. (By Mr. Zelcs): You can go ahead and
19 answer.
20 A. I'm sorry. Can you ask the question again?
21 Q. (By Mr. Zelcs): What do you think
22 scientists and medical doctors would have done with
23 this data if it was made available to them?
24 MR. LOMBARDI: The same objection, your
112
1 Honor. Just for the record.
2 THE COURT: Yeah, overruled.
3 A. Okay. The public health community was
4 clearly aware of the implications of their
5 recommendation. They knew that with the issues of
6 competition and potential product design changes that
7 if there were adverse effects to either of those, then
8 their recommendations could be quite dangerous. So
9 they were actually actively asking for data to shed
10 light on that subject.
11 Q. In your -- based upon your work in the
12 fields of mutagenicity, cancer risk, DNA damage, and
13 as a medical doctor, do you have any opinion within a
14 reasonable degree of medical and scientific as to
15 whether Philip Morris should have disclosed this data?
16 A. Yes.
17 MR. LOMBARDI: The same objection, your
18 Honor. This has now turned into a --
19 THE COURT: Well, you haven't disclosed. Is
20 this in connection with warning or what?
21 MR. ZELCS: It's in connection with making
22 the information available to the public health
23 community.
24 THE COURT: Well, why don't you couch the
113
1 question that way.
2 Q. (By Mr. Zelcs): Do you have any opinion
3 within a reasonable degree of scientific and medical
4 certainty, Doctor, as to whether or not Philip Morris
5 should have shared this information with the public
6 health community?
22 Q. (By Mr. Zelcs): Would you please state your
23 opinion on this point?
24 A. Yes. It's my opinion that the screening
114
1 test that Philip Morris did, the identification that
2 ventilation increases mutagenicity, the knowledge at
3 the time that mutagenicity was particular of animal
4 carcinogenicity, and knowing that we do animal testing
5 as a way of protecting the public health, and ignoring
6 results from either mutagenicity or any such studies
7 could harm the public. I mean it's my opinion what
8 they did was wrong.
9 Q. When you say wrong, will you elaborate on
10 that?
11 MR. LOMBARDI: And I would object. Now
12 we're asking the doctor to elaborate what is wrong in
13 some nonlegal, undefined sense. It's not relevant to
14 this lawsuit and it shouldn't be permitted.
15 THE COURT: Well, let's see what his answer
16 is.
17 MR. ZELCS: Your Honor, I'm asking how he
18 viewed it.
19 THE COURT: I'm overruling the objection.
20 A. I'm sorry. Ask your question again.
21 Q. (By Mr. Zelcs): The question is how was it
22 wrong based upon your expertise as a medical doctor
23 and a scientist?
24 A. Well, they initially started out doing the
115
1 right thing, which is to assess their product design
2 changes and the effects on mutagenicity, the screening
3 test. To then do nothing with those results and allow
4 the public health community to make recommendations
5 that Philip Morris clearly had indications were wrong.
6 I mean I think that's absolutely, you know, dangerous,
7 reckless, and obviously immoral.
6 Q. (By Mr. Zelcs): Do you have any opinion as
7 to what were the --
24 Q. (By Mr. Zelcs): You indicated that --
117
1 THE COURT: Okay. I'm sorry.
2 Q. (By Mr. Zelcs): You indicated that their
3 conduct was wrong, immoral. Do you have any opinion
4 as to what would have happened if this information had
5 been shared with the public health community?
14 MR. ZELCS: -- in the science industry, the
15 government, and everywhere else.
=
17 Q. (By Mr. Zelcs): Please answer the question?
18 A. Well, I've been practicing medicine and
19 doing research for just about 20 years and so a lot of
20 this information is not brand new today. I think that
21 my contemporaneous people as well as my mentors would
22 certainly have thought very seriously and would have
23 been very concerned to learn that tar is not tar, and
24 that at the time that data on competition was coming
119
1 out everyone just thought it was just you're getting
2 more of the same thing. Now, we have data from Philip
3 Morris that shows that at that time they understood
4 that that is that tar was not tar and that the tar in
5 the light cigarettes in their screening tests was
6 predicted to be more dangerous than the higher tar
7 cigarettes.
8 Q. (By Mr. Zelcs): Let's move to a different
9 point. Do the light cigarettes have any impact on
10 lung cancer?
11 A. Yes.
12 Q. Tell the Court about that.
13 A. Looking at a variety of different types of
14 data, the weight of the evidence, you can piece
15 together a number of areas of science to see the net
16 result of the increased use of light cigarettes over
17 time. We start off with knowing that these light
18 cigarettes have higher mutagenicity per tar. There
19 has also been data that's been published that light
20 cigarettes over time have had different chemical
21 compositions and, in fact, when you smoke light
22 cigarettes in a compensating way which means you're
23 inhaling tar and other parts of composition, you
24 actually also change the smoke chemistry. What
120
1 happens is that those chemicals are known to affect
2 different parts of the lung. At the same time we know
3 that as people inhale deeper from their light
4 cigarettes, they're now exposing their outer parts of
5 their lungs with cigarette smoke.
6 I mean it's pretty obvious when you take a
7 deep breath, you're now puffing air out into the
8 periphery. We know that over time we're now seeing
9 lung cancers happen in people more so out in periphery
10 than the central parts. The type of lung cancer has
11 changed. It used to be, you know, 15 to 1, 20 to 1
12 squamous cell cancers compared to adenocarcinomas.
13 Now, adenocarcinomas are more common than squamous
14 cell carcinomas. The adenocarcinomas happen to be the
15 peripheral cancers.
16 Going back to what I was talking about
17 before about the different types of smoke chemistry,
18 as it turns out those type of carcinogens that are
19 increased actually affect the type of lung cells in a
20 more peripheral and also realize that in the periphery
21 of the lungs we have less defense mechanism. We don't
22 have cilia and that sort of thing. So we see a change
23 in the balance of the chemicals. We see a change in
24 histology, we have coincident animal data to show that
121
1 those type of chemicals that are now increased more
2 typically cause the types of cancers that we see in
3 people. So when you piece this altogether, it's my
4 opinion and that the increased use of light cigarettes
5 over time has -- can be clearly seen in an effect on
6 people.
7 Q. And is there any data that speaks to the
8 question of whether or not the risk of getting
9 adenocarcinomas from cigarettes has increased since
10 light cigarettes have come to market?
11 A. Yes.
12 Q. Tell the Court about that.
13 A. Well, for example, that's Michael Thun's
14 publication, but there are other publications as well
15 which shows that over time bad adenocarcinomas have
16 been increasing over smokers.
2 MR. ZELCS: -- some testimony out from Dr.
3 Shields on this point.
4 Q. (By Mr. Zelcs): Briefly summarize some of
5 the studies that suggest to you that the risk of
6 adenocarcinomas from light cigarettes is increasing
7 over time?
8 A. Well, there is, as I said, Michael Thun's
9 data. In the paperwork he actually looked at two
10 separate populations at the same time which makes it a
11 much more powerful paper, but comparing the earlier
12 cohort to a later cohort, also showing that the
13 adenocarcinoma rate has been increasing over time in
14 Connecticut. There's other studies as well that have
15 absolutely found the same thing, listed the same thing
16 as that. And as I mentioned also just the observation
17 that we have increasing adenocarcinomas in comparison
18 to the squamous cell cancers and a number of other.
19 Q. Are there any other design changes in light
20 cigarettes that cause more cancers?
21 A. Not that I'm aware of.
22 Q. What impact does the presence of additional
23 tobacco specific nitrosamines have in terms of light
24 cigarettes?
123
1 A. Well, that's the -- one of the chemical
2 classes that has increased and it increases further
3 when you basically suck harder on cigarettes.
4 Co-workers have known that. And it's those
5 nitrosamines that we know in the animal studies more
6 commonly cause adenocarcinomas. And we believe that
7 the cells in the periphery of the lung, which are a
8 different type of cells, are more sensitive to the
9 nitrosamines. I guess there's one other thing that I
10 can mention too is that tobacco specific nitrosamines
11 in particular is in the animal studies are really,
12 really very solid because it's very cell specific
13 target organisms and carcinogens.
14 Q. Other than what you've already told us,
15 based upon your review of the materials and the
16 evidence in this case that you've looked at, are there
17 any additional opinions that you formed within a
18 reasonable degree of medical and scientific certainty?
19 MR. LOMBARDI: Is that just kind of an open
20 invitation to provide an opinion on anything he wants
21 to? It's inviting a narrative. What kind of question
22 is that? I object to the form, your Honor.
23 THE COURT: Do you want to repeat the
24 question?
124
1 (The reporter read back the question.)
2 THE COURT: Along with the capacity of
3 information, information capacity of this doctor, this
4 could end up taking an hour to answer that.
5 MR. ZELCS: Fair enough.
6 THE COURT: I'm going to sustain the
7 objection.
8 MR. ZELCS: Thank you.
9 A. That was a compliment.
10 MR. ZELCS: Sorry.
11 A. I said that was a compliment.
12 Q. (By Mr. Zelcs): Your discussion about the
13 risks of adenocarcinoma as related to light cigarettes
14 and your opinion relating to that, is that something
15 you hold within a reasonable degree of medical and
16 scientific certainty?
17 A. Yes.
18 MR. ZELCS: Your Honor, at this point in
19 time I move for Exhibits 88, 89, 90, 91, 92, 93, 94,
20 95, 97 into evidence.
21 MR. LOMBARDI: It's kind of difficult, your
22 Honor, when you just get a listing like that.
23 MR. ZELCS: Well, 88 is the Redbook.
24 THE COURT: Well, just like a trip around
125
1 the world, start with the first step. All right. 88,
2 take a look at it.
3 MR. LOMBARDI: That was the FDA Redbook. I
4 had an objection that I articulated at the time,
5 Judge, to the relevance.
6 THE COURT: Okay. I recall. That will be
7 admitted over objection.
8 89.
9 MR. ZELCS: Yes. It's the meeting report,
10 recommendations on data production and analysis.
11 That's from Mr. Osdene's file in 1979.
12 MR. LOMBARDI: No objection.
13 THE COURT: Be admitted.
14 MR. ZELCS: The next one is the expose, the
15 INBIFO report.
16 MR. LOMBARDI: What was the number? I'm
17 sorry.
18 MR. ZELCS: The number on that was 90.
19 Study of mutagenicity of whole smoke condensate.
20 MR. LOMBARDI: Can you give me a date on
21 that? Oh, I've got it. I've got it. No objection.
22 THE COURT: Admitted.
23 MR. ZELCS: The next one is 91, and that's a
24 1991. That's the proposal for a systematic study of
126
1 very cigarette parameters to determine their effect on
2 biological activity.
3 MR. LOMBARDI: I assume they're subject to
4 my objection I made at the beginning of the testimony
5 about mutagenicity generally.
6 THE COURT: Well, you don't waive that
7 objection.
8 MR. LOMBARDI: And those documents would
9 fall within that, but other than that, I have no
10 further objection to 91.
11 THE COURT: All right. They will be
12 admitted. What happened to 96?
13 MR. ZELCS: That's a good point, your Honor.
14 I -- I missed that in my reading and it's in the pile.
15 We'll cover that.
16 92, the brand. Ames document with the
17 chart, comparing the ISOs and FTC.
18 MR. LOMBARDI: Within, you know, the bounds
19 of my prior objections that we articulated at the
20 beginning of this testimony, no further --
21 THE COURT: Okay. Subject to that, it will
22 be admitted.
23 THE COURT: Number 9 is Dr. Carchman's study
24 regarding the biochemistry -- his memo regarding the
127
1 biochemistry program.
2 MR. LOMBARDI: And the same objections we
3 articulated at the beginning of our testimony, Judge,
4 but nothing further.
5 THE COURT: Same on the ruling.
6 MR. ZELCS: 94 is the low tar reference
7 cigarette document regarding the mouse skin paintings
8 back in 1977.
9 MR. LOMBARDI: I thought that one was
10 already in. I thought you had marked that with your
11 own. Did that wrong?
12 MR. ZELCS: Well, I --
13 THE COURT: He did testify in that area, but
14 -- no, I don't think that one is in. That was another
15 document.
16 MR. LOMBARDI: I thought it was part of a
17 group exhibit, your Honor.
18 THE COURT: Oh, now that could be.
19 MR. LOMBARDI: I could be wrong.
20 MR. ZELCS: I don't think -- I don't think
21 we got it in. I'll make that representation.
22 THE COURT: Yeah, because I didn't look at
23 all the pages so he is -- okay. Go ahead.
24 MR. LOMBARDI: Other than the objections I
128
1 articulated, --
2 THE COURT: The same ruling.
3 MR. LOMBARDI: -- no further.
4 THE COURT: Be admitted.
5 MR. ZELCS: Okay. 95 is the 1971 anaerobic
6 glycolsis study.
7 MR. LOMBARDI: And, Judge, I have my
8 objection which I've articulated and my same
9 objections --
10 THE COURT: Okay. On that one there I'm
11 going to note that it was within that group from the
12 last few weeks, and I won't allow it for that reason.
13 All right. 96 is --
14 MR. ZELCS: 96 is the meeting report.
15 MR. LOMBARDI: And --
16 THE COURT: Did he testify on that?
17 MR. ZELCS: Yes, he did.
18 THE COURT: Okay.
19 MR. LOMBARDI: And again, Judge, subject to
20 the same objection I made at the beginning, no further
21 objection.
22 THE COURT: The same ruling.
23 MR. ZELCS: 97 is another meeting report.
24 MR. LOMBARDI: And that's subject to the
129
1 same objections at the beginning, no further.
2 THE COURT: The same ruling.
3 MR. ZELCS: That covers them all, your
4 Honor.
5 THE COURT: Okay.
6 MR. ZELCS: No further questions.
7 THE COURT: No further questions? You may
8 cross-examine.
18 CROSS-EXAMINATION
19 BY MR. LOMBARDI:
20 Q. Good morning, Doctor. My name is George
21 Lombardi. We have not met, have we?
22 A. No, we have not.
23 Q. Doctor, you are here as an expert on
24 biological testing at Philip Morris; is that correct?
130
1 A. I am here to give my opinion about the data
2 that I've seen from the Philip Morris documents.
3 Q. Okay. And is it your intention in
4 testifying here to provide the Court with a full and
5 complete picture of the testing that's been done at
6 Philip Morris?
7 A. Yes.
8 Q. And it's your intention in doing so to
9 present the Court with a full and complete picture of
10 the documents that you've reviewed; is that right?
11 A. That's correct.
12 Q. And it's your intention to provide the Court
13 with your best information on all the scientists that
14 you talked about here today?
15 A. Yes.
16 Q. For instance, you talked about a fellow
17 named McCoy, didn't you?
18 A. That's correct.
19 Q. Who was he?
20 A. He's one of the Philip Morris scientists.
21 Q. What were his research interests at Philip
22 Morris?
23 A. I can't tell you the full scope of the
24 research interests other than what he wrote in his
131
1 documents.
2 Q. And those documents, the documents you
3 showed today are documents you got from plaintiffs'
4 counsel, isn't that right, Doctor?
5 A. That's correct.
6 Q. And the documents that you got for your
7 reliance materials, you got from plaintiffs' counsel;
8 is that right?
9 A. That's right.
10 Q. And you presented a subset of your reliance
11 documents today in court; is that right?
12 A. I presented the documents that I thought
13 were representative of other documents that I've seen.
14 Q. And you took little snippets from those
15 documents and put them on the screen and read them to
16 the Court; is that right?
17 A. Are you talking about little in terms of
18 size?
19 Q. In size. Like a sentence here and there; is
20 that fair?
21 A. That's fair.
22 Q. Okay. And it's your testimony that that
23 provides a fair picture of the biological testing,
24 mutagenicity testing, that was done at Philip Morris;
132
1 is that right?
2 A. To the best of my ability, yes.
3 Q. And this is the first time that you've done
4 this kind of testimony; is that right?
5 A. That's correct.
6 Q. Okay. You are not a historian by training;
7 is that right?
8 A. Undergraduate I had my major in American
9 Civilization which is --
10 Q. Are you an historian by training?
11 A. Well, I have an undergraduate degree --
12 Q. Doctor, I'm asking you are you an expert in
13 historian?
14 A. I have an undergraduate degree in American
15 Civilization.
16 Q. Okay. We'll call you a historian. All
17 right. Now, these kinds of -- you talked about step
18 wide testing; is that right?
19 A. That's correct.
20 Q. And as I understand it, and correct me if
21 I'm wrong, the first step was something called in
22 vitro. Do I have that right?
23 A. Well, in vitro is the correct word. It's
24 not entirely in vitro. That's not a correct
133
1 characterization.
2 Q. What's a better characterization?
3 A. Well, in vitro involves a chemical
4 composition study.
5 Q. Okay. In vitro is a chemical composition?
6 A. Right.
7 Q. And in vitro literally, what's that, Latin
8 you said?
9 A. Yes.
10 Q. In vitro refers to glass; is that right?
11 A. Actually I don't know what the Latin
12 translation is, but it means cell culture.
13 Q. Okay. But it basically refers to things you
14 do in a test tube or a Petri dish or something like
15 that; is that fair?
16 A. That's right.
17 Q. All right. Okay. What was the second step?
18 A. The in vivo animal studies.
19 Q. Okay. And in vivo basically refers to?
20 A. In life.
21 Q. In life. So live animals is what you're
22 talking about?
23 A. Correct.
24 Q. Like mouse skin painting is a live mouse; is
134
1 that right?
2 A. That's right.
3 Q. And then the third one was?
4 A. Well, then you go to human investigations?
5 Q. Human investigations.
6 A. Of some sort, yes.
7 Q. All right. Did Dr. Solana do any
8 mutagenicity testing himself?
9 A. I don't know.
10 Q. Do you know what his position was in 1978?
11 A. I might have, but I don't recall.
12 Q. How about Pages? What was his position in
13 1978?
14 A. I'm sorry.
15 Q. Pages. Do you remember that name, don't
16 you?
17 A. Yeah, I don't know what his position was.
18 Q. Human investigations would include things
19 like what?
20 A. It could be clinical trials. You could --
21 in this case, you could have done some trials with
22 people using the actual cigarette products or the
23 epidemiology.
24 Q. Okay. And I think you said epidemiology
135
1 with lung cancer -- I want to make sure I got your
2 words right here, Doctor. Epidemiology is the best
3 for cancer; is that right?
4 MR. ZELCS: Objection to the extent that
5 you're mischaracterizing his testimony.
6 Q. (By Mr. Lombardi): I'm asking you, Doctor,
7 the best what? The best test and best study of cancer
8 in humans? Do you remember that?
9 A. Food epidemiologic studies then that is the
10 word were wins over other types of testing.
11 Q. And that's what I was trying to -- and I
12 think you said if you have good epidemiology, then you
13 can rule out the other type of tests and use them to
14 determine things like mechanism; is that right?
15 A. That's correct.
16 Q. Okay. Now, this step wide approach you said
17 was in place in the 1970s; is that right?
18 A. That's right.
19 Q. The Ames test came into play in 1974; is
20 that right?
21 A. More or less that's when the publications
22 were coming out.
23 Q. And I won't hold you to an exact date, --
24 A. Right.
136
1 Q. -- but mid to early '70s; is that fair?
2 A. Yes.
3 Q. Sometime after 1971?
4 A. That's right.
5 Q. What were the characteristics of the EOLR
6 cigarette?
7 A. That particular cigarette, I would have to
8 look at a document, but they were testing different
9 paper types of a round of tobacco.
10 Q. Do you know what the characteristics of the
11 EOLR cigarette that you testified to earlier today
12 are?
13 A. I know what is in the document.
14 Q. You know what's in the document?
15 A. No, I know what -- the information that I
16 have about that cigarette is what was available in the
17 document.
18 Q. Okay. Do you know anything more about it as
19 you sit here today?
20 A. I don't recall any other reference to this
21 -- to that study.
22 Q. Okay. Who is Mr. Ferguson?
23 A. Again, I don't know what his position was.
24 Q. How much mutagenicity testing did Ferguson
137
1 do?
2 A. I don't know. Most of these documents are
3 summaries of their data.
4 Q. How about Penn? Did he do any mutagenicity
5 testing?
6 A. Can you refresh my memory as to where that
7 name is from?
8 Q. Just asking you. It's from one of the
9 documents you used this morning.
10 A. Okay. I don't recall.
11 Q. Okay. Now, you said with Exhibit -- let me
12 make sure I have the right number, Doctor. 20-D. Do
13 you have that still up there?
14 A. My exhibits are not numbered so you'll have
15 to show me.
16 Q. It's the one. It looks like this.
17 A. The Seligman notes. Okay. Okay.
18 Q. Now, did you intend to give the Court a full
19 understanding of the information that was set forth in
20 Exhibit 20-D?
21 A. Yes.
22 Q. Okay. And just to make sure I've got this
23 right, Doctor, you looked -- well, there have been
24 developments over time in mutagenicity testing; is
138
1 that right?
2 A. More or less.
3 Q. And is it fair to say that Philip Morris'
4 view of results of mutagenicity testing has changed
5 over time?
6 A. I don't know if I agree with that.
7 Q. Okay. We'll go and look at it then. But
8 anyhow, let's look at Exhibit 20-D, which was one that
9 you talked about this morning. Let's remember the
10 part that you --
11 This part, just to remind everybody, is I
12 think the main thing you looked at. You said
13 Salmonella, and I have trouble with that word too. Is
14 it type --
15 A. Typhimurium.
16 Q. Typhimurium?
17 A. Yeah.
18 Q. Okay. I'm going to say Salmonella; is that
19 okay with you?
20 A. That's fair.
21 Q. Okay. You pointed out it's a generally good
22 correlation with skin painting results. And are you
23 able to read that next part that looks like it's added
24 in?
139
1 A. I can read it if you like.
2 Q. Why don't you go ahead for the sake of
3 completeness.
4 A. When used with microsomal activation.
5 Q. Now, what was -- who wrote this document?
6 A. It says a note from Robert B. Seligman, so I
7 assume that he wrote it.
8 Q. Do you recognize his handwriting there?
9 A. I don't know what his handwriting looks
10 like.
11 Q. Do you know, is he referring to data there?
12 A. He's definitely referring to data.
13 Q. What data is he referring to?
14 A. That I can't tell you.
15 Q. Can you tell from what he's written there
16 whether there actually is a good correlation in the
17 data you looked at or can you tell anything about the
18 data he's looking at?
19 A. The only thing I can tell you is what his
20 statement is.
21 Q. Okay. Just that -- just that one sentence.
22 That's your whole basis for saying that Philip Morris
23 at this time believes there's a good correlation with
24 skin painting results?
140
1 MR. ZELCS: Objection to the extent that
2 you're mischaracterizing his testimony.
3 THE COURT: Yeah, that will be sustained.
4 Q. (By Mr. Lombardi): Okay, Doctor, there was
5 other information in this document about the results
6 of testing, wasn't there?
7 A. This is a summary document, that's correct.
8 Q. And surely you saw the bottom of the page,
9 didn't you, before coming here to testify? Did you
10 see this?
11 A. Yes.
12 Q. And you didn't read this to the Court, but
13 it says, tell me if I'm right, "Filters, dilution
14 systems, paper, reconstituted tobacco, and some
15 additives which are effective in lowering the delivery
16 of TPM and/or gas phase components are effective in
17 reducing activity." You read that to be biological
18 activity, sir?
19 A. Sure.
20 Q. That means mutagenicity did take form of a
21 biological activity test?
22 A. That's correct.
23 Q. "On a per cigarette basis, although they may
24 have no effect on a per gram of condensate basis." Do
141
1 you see that?
2 A. Yes.
3 Q. That's information that's relevant to what
4 Philip Morris thought about mutagenicity and
5 biological activity back at the time this was written;
6 is that correct?
7 A. That's correct.
8 Q. You said that the AKJ -- Do you know what
9 the AKJ is, right?
10 A. The test cigarette.
11 Q. Yeah.
12 A. Correct.
13 Q. Well, you said that was a low tar cigarette;
14 is that right?
15 A. That is one of the tests -- this was one of
16 their test cigarettes that was representing low tar.
17 That's correct.
18 Q. What was the delivery of that cigarette?
19 MR. ZELCS: What are you asking about in
20 time?
21 Q. (By Mr. Lombardi): I'm asking about the
22 time when you talked about it Doctor?
23 A. The tar load -- can I refer back to the
24 document?
142
1 Q. If you need to.
2 A. I prefer to give an exact number.
3 MR. ZELCS: Is there a specific document,
4 just to save a little bit of time here?
5 MR. LOMBARDI: Well, the doctor referred to
6 it, and I frankly don't know which document the doctor
7 was referring to.
8 A. Okay. Here.
9 Q. (By Mr. Lombardi): Now, Doctor, I've got a
10 limited amount of time so just let me ask --
11 THE COURT: I won't count. Go ahead.
12 MR. LOMBARDI: Okay. If I've got a waiver
13 from the Court, then that's good enough for me.
14 A. I'm reasonably sure it's in one of these
15 documents.
16 MR. LOMBARDI: Your Honor, I have no desire
17 to prolong this.
18 THE COURT: What was the question again?
19 MR. LOMBARDI: I wanted to know what the tar
20 delivery was of one of the cigarettes he testified to
21 this morning or this afternoon. The AKJ cigarette was
22 a low tar cigarette, and I wondered how low the tar
23 was in that cigarette?
24 A. I clearly recall it was in the low tar
143
1 category.
2 Q. Well, let me just --
3 MR. LOMBARDI: Your Honor, I'll retract the
4 questioning and do another one. I have no desire to
5 slow things down here.
6 Q. (By Mr. Lombardi): Doctor, that's okay.
7 The AKJ cigarette, what was the dilution of the AKJ
8 cigarette?
9 A. It was -- again, I really need to see the
10 data. My recollection it was more than a Marlboro
11 Light and it was less than 50 percent.
12 Q. Okay. And a Marlboro Light -- what was the
13 Marlboro Light dilution in 1978?
14 A. I actually only know the light dilution, the
15 Marlboro Light dilution in 2001.
16 Q. Now, wouldn't it be important in evaluating
17 the in vitro, the mutagenicity testing to know what
18 the dilution of the cigarettes was that Philip Morris
19 was testing at that time? Wouldn't that be an
20 important point?
21 A. Yes.
22 Q. And it's important because a Marlboro Lights
23 dilution might be different than the dilution of some
24 of the cigarettes that were being tested; is that
144
1 right?
2 A. That could be true. That's correct.
3 Q. Let me ask you something. Who is -- who is
4 Mr. Kuhn? C-U -- K-U-H-N. He's one of the folks on
5 the memo as you testified about.
6 A. I don't know.
7 Q. Didn't he do mutagenicity testing?
8 A. I don't know whether he was in the lab or
9 not.
10 Q. Do you know what he thought about whether
11 there was a correlation or not between mutagenicity
12 and skin painting?
13 A. Not that I recall here.
14 Q. Okay. You can get, when you do this whole
15 step wide type of testing, you can get inconsistent
16 results within any given category, can't you?
17 A. Yes.
18 Q. And so, for instance, you can do an Ames
19 Salmonella mutagenicity test and get one set of
20 results and you could do a different kind of
21 mutagenicity testing and get a different set of
22 results; isn't that true?
23 A. That's true.
24 Q. And you could actually -- the Ames tests
145
1 there are different strains of the Ames bacteria that
2 can be used in those tests, isn't that right?
3 A. That's right.
4 Q. And even among different strains of the Ames
5 test, you can get different results, isn't that right?
6 A. Different strains, that's correct.
7 Q. And an investigator or a scientist should
8 take into account when there are inconsistent results,
9 shouldn't he?
10 A. I guess you need to define take into account
11 for what?
12 Q. Well, in determining the toxicity of the
13 substance that he or she is working with?
14 A. Usually you're going to review the raw data
15 that you have.
16 Q. Yeah. You want to take into account all the
17 data, don't you?
18 A. That's kind of important. You'll evaluate
19 what data you have available.
20 Q. Okay. Let me show you another document that
21 you put up 20-I. And I'll put it up on the screen if
22 you don't -- it's kind of inconvenient if you don't
23 have the numbers there, Doctor, but --
24 A. All right. I've got it.
146
1 Q. Did you see the date on that one?
2 A. The 1978 document, right?
3 Q. May 4th, 1978.
4 A. Right.
5 Q. You have it?
6 A. Yeah.
7 Q. I'm sorry. Okay. And I believe that you
8 looked at the summary page, and you read something
9 about filter dilution being shown to influence WSC
10 activity there. That was in the middle of the summary
11 page.
12 A. That's correct.
13 Q. I'll just put it up here so we can see it.
14 It starts right there, doesn't it? "A cigarette
15 parameter, filter dilution, was also shown to
16 influence WSC activity."
17 A. Yes.
18 Q. What was the extent of dilution that had
19 been shown to influence WSC activity?
20 A. I'm just going back to the tables. 47
21 percent.
22 Q. 47 percent?
23 A. Correct.
24 Q. Now, you didn't point that out to the Court
147
1 earlier; is that right?
2 A. I don't recall whether I did or I didn't.
3 Q. But that in any event is considerably more
4 dilution than the Marlboro Light cigarette; is that
5 right? At least the Marlboro Lights you're aware of,
6 the Marlboro Lights of today?
7 A. Well, a 25 percent dilution.
8 Q. So an increase of 22 percent dilution?
9 A. Correct.
10 Q. That could make a difference in a
11 mutagenicity test, couldn't it, Doctor?
12 A. Every -- virtually every, if not all, tests
13 that I saw included the more dilution, the more
14 mutagenicity.
15 Q. It could make a difference in mutagenicity
16 testing?
17 A. I would think that it would likely make a
18 difference in mutagenicity.
19 Q. Okay. Now in this document as well in
20 addition to being about a 47 percent dilution
21 cigarette, it points out something about results in
22 other assays, doesn't it?
23 A. I believe that's correct.
24 Q. What's an E. coli assay?
148
1 A. It's a different type of in vitro test.
2 Q. Do you see where -- I'm sorry, Doctor. It's
3 page 23.
4 MR. ZELCS: The same document?
5 MR. LOMBARDI: Same document.
6 A. Page 23. Okay.
7 Q. (By Mr. Lombardi): Where it says Model II
8 WSC activities?
9 A. Okay.
10 Q. What's the WSC, Doctor?
11 A. That's the whole smoke condensate.
12 Q. Okay. And does this report the results of
13 E. coli test, a test done in E. coli assay?
14 A. Yes.
15 Q. And it notes that these results show that
16 the E. coli assay, like the Salmonella/microsome
17 assay, recognizes the WSC prepared from the CIG
18 cigarette. Do you know that cigarette from your
19 travels through these documents?
20 A. Yes.
21 Q. What was the dilution of that cigarette?
22 A. Hang on a second. If I remember correctly
23 there was no dilution, but hold on a second.
24 A. Okay. The CIG was actually -- I'm sorry.
149
1 The -- that's the one with the 47 percent dilution.
2 Q. It had 47 percent dilution?
3 A. That's right.
4 Q. Okay. So "the WSC prepared from the CIG
5 cigarette, which has filter dilution, as being
6 significantly different in activity. In contrast to
7 the Salmonella assay, however, the E. coli assay shows
8 that WSC to be significantly less active." Do you see
9 that?
10 A. Yes.
11 Q. That was inconsistent results, is that
12 right, Doctor, from the ones that you read from the
13 same document?
14 A. Using the E. coli assay that was a negative
15 result, whereas the Ames assay was a positive result.
16 Q. Okay. And, Doctor, in the 1970s you were in
17 college?
18 A. I was in college. That's correct.
19 Q. Were you part, in addition to being a
20 historian, Doctor, were you part of the public health
21 community then?
22 A. Well, if you consider my volunteering on an
23 ambulance squad being part of the public health
24 community, I would be, yes.
150
1 Q. Well, in your role in volunteering with the
2 ambulance squad, did you poll the members of the
3 public health community about their belief about
4 mutagenicity tests?
5 A. No.
6 Q. Did you check into what they thought about
7 tumorgenicity tests?
8 A. At that time, no.
9 Q. Do you -- do you know who made up the
10 consensus that came to the 1981 Surgeon General's
11 report?
12 A. Do you mean -- are you talking about who
13 were the individuals on the committee that wrote the
14 report?
15 Q. No. Well, are you aware of the Surgeon
16 General's report that represents the scientific
17 consensus?
18 A. I would say that's more illustrative.
19 Q. Okay. Well, do you think it wasn't true in
20 1981?
21 A. No. I think that those reports are written
22 by panels of experts who review literature and they
23 are independent panels. I would say that there can't
24 be any time when they haven't represented a consensus,
151
1 but I'm not sure that that was their charge was to
2 identify these contentions.
3 Q. Well, you would agree there were a bunch of
4 people involved in that 1911 Surgeon General's report;
5 is that correct?
6 A. Correct.
7 Q. And that 1981 Surgeon General's report took
8 into account the beliefs of numerous people and
9 organizations in coming to that scientific consensus;
10 is that right?
11 A. Coming to the consensus of that committee
12 who wrote that report.
13 Q. Right. Do you agree with that?
14 A. Yes.
15 Q. Okay. And you have not gone back and polled
16 those people to determine anything about their beliefs
17 for purposes of your testimony in this case; is that
18 right?
19 A. I have not gone back and polled individuals
20 in reference to this case. I might know some of them
21 and might have had discussions with them about these
22 issues.
23 Q. But no poll? That's what my question was,
24 Doctor.
152
1 A. No.
2 Q. Doctor, let me show you another document. I
3 don't think you showed this one this morning. This is
4 marked as 5065. Have you seen this one before,
5 Doctor?
6 A. This one looks familiar to me.
7 Q. Okay. Just to identify for the record,
8 Doctor, tell me if I've got this right. It's the
9 December 11th, 1978 memo, indicating it's a Philip
10 Morris internal memo, from Page to Kuhn, K-U-H-N,
11 concerning charge number 6906. Is that -- did I get
12 that correct?
13 A. That's correct.
14 Q. And that's the document you have in front of
15 you?
16 A. That's right.
17 Q. This is 1978?
18 A. That's correct.
19 Q. And this is a document -- you recall this
20 document from having looked at it in preparation for
21 this case, didn't you?
22 A. I believe that's true.
23 Q. And this is a document that talks about
24 results of other tests; is that right? Other tests
153
1 meaning other than the Salmonella test; is that right?
2 A. That's right.
3 Q. And, in addition, it does talk about the
4 Salmonella test results; is that right?
5 A. Yes.
6 MR. LOMBARDI: 5605, please.
7 Q. (By Mr. Lombardi): Yeah. Okay. Doctor,
8 December 11th, 1978. And the first thing they mention
9 is a mouse cell mutation assay. Are you familiar with
10 that?
11 A. I'm generally familiar with it.
12 Q. And that is generally a mutagenicity assay;
13 is that right?
14 A. It's another in vitro assay for
15 mutagenicity, that's correct.
16 Q. Okay. And it shows in that highlighted
17 portion, "Experiments conducted on replicate
18 preparations of the four Model II IT WSCs."
19 What's a Model II?
20 A. Philip Morris had a series of cigarettes
21 that they were testing, and they were grouping them.
22 There was initially Model I. And based on the results
23 of Model I, they identified Model II and then you know
24 they went on to Model III.
154
1 Q. What was the dilution of the Model II
2 cigarettes?
3 A. I would have to look.
4 Q. Well, do you know?
5 A. I don't want to give -- I don't want to give
6 inaccurate numbers.
7 Q. Okay. Well, I don't want -- I don't want to
8 spend the time looking through documents right now,
9 Doctor, but you don't know as you're sitting here
10 right now; is that right?
11 A. The Model II had a range of dilutions.
12 Q. Okay. "Experiments conducted on replicate
13 preparations of the four Model II IT WSCs" -- that's
14 whole smoke condensate again, right?
15 A. That's right.
16 Q. -- "showed that this assay was not able to
17 detect significant differences in WSC activity which
18 could be associated with changes in physical cigarette
19 parameters such as filtration, paper porosity, and
20 filter dilution." Do you see that?
21 A. Yes.
22 Q. Okay. Let's go to the next one. The next
23 one is mammalian cell transformation.
24 A. It's actually a Philip Morris document.
155
1 Q. You've not heard of it before that?
2 A. I don't -- it's a very general term. Oh,
3 I'm sorry. It's the hamster. Hamster embryo cells
4 transformation assay, so sure.
5 Q. Would you call this a type of mutagenicity
6 test or something else?
7 A. Yes.
8 Q. Okay. It's a mutagenicity test. All right.
9 Let's look at this one. It says, "All of the whole
10 smoke condensates were active, but due to the low
11 number of transformants observed, no significant
12 differences in activity could be demonstrated." Using
13 the Model I cigarette; is that right?
14 A. That's correct.
15 Q. What's the dilution of the Model I
16 cigarette?
17 A. They use several different cigarettes.
18 There was like eight or twelve different cigarettes.
19 Q. Okay. You don't know as you're sitting
20 right here now?
21 A. I could open up the table and give you the
22 answer.
23 Q. I don't want to waste the time, Doctor.
24 Let's go to number three. It says, the yeast mitotic
156
1 -- Did I say that right?
2 A. That's correct.
3 Q. Mitotic gene conversion. Do you know what
4 that is?
5 A. Yes.
6 Q. Is that another assay, a mutagenicity type
7 of assay?
8 A. It's measuring -- it doesn't really measure
9 the mutations but the intent of the assay was the same
10 sort of in vitro screening to predict carcinogenicity.
11 Q. Okay. Let's go to the next page and see
12 what the results of this one were. "The yeast assay
13 was also found to be capable of detecting significant
14 differences in whole smoke condensate activities among
15 the Model II cigarettes." And I'm going to go on.
16 "Incorporation of a high efficiency filter and filter
17 dilution were found to decrease WSC activity."
18 Do you see that?
19 A. That's right.
20 Q. That means that WSC or whole smoke
21 condensate activity was going down; is that right?
22 A. In that assay.
23 Q. With filter dilution; is that right?
24 A. That's what it says.
157
1 Q. Okay. This is inconsistent with the
2 mutagenicity testing you referred to this morning,
3 isn't that correct?
4 A. I don't think I would be using the word
5 inconsistent. You're getting different results for
6 the test and measuring different things.
7 Q. Okay. Let's go to the E. coli differential
8 toxicity test. Do you know what that test is?
9 A. I learned about it from these documents.
10 Q. Is it another type of mutagenicity test?
11 A. Well, it says here, "An arbitrarily selected
12 new assay protocol." I think the answer is yes, it
13 is.
14 Q. Okay. And we're using Model II cigarettes
15 again?
16 A. They use Model I and Model II.
17 Q. Okay. And then it says, "The Model II
18 results showed show that filtration and filter
19 dilution were associated with a decrease in whole
20 smoke condensate activity." Is that right?
21 A. That's right.
22 Q. So in those assays, filter dilution was
23 having the effect of lowering whole smoke condensate
24 activity; is that right?
158
1 A. Only some of them.
2 Q. Okay. Well, in E. coli assay; is that
3 right?
4 A. I'm sorry. I'm looking for the quote again.
5 Yes.
6 Q. Okay. I'll give you another document. In
7 this same general time frame, Doctor. This has been
8 marked as 5604. This is a -- why don't you state it
9 for the record and so we've got it identified, Doctor.
10 You tell me if I've got it right. June 4th, 1979
11 Philip Morris interoffice memo from Rapp, R-A-P-P, to
12 Pages. Is that right?
13 A. That's correct.
14 Q. And you've seen this document before; is
15 that right?
16 A. I believe I have.
17 Q. This was in your reliance materials, wasn't
18 it?
19 A. I've seen it before so, therefore, it would
20 be in the reliance materials.
21 Q. Okay. And this is a document that you did
22 not go through this morning with the Court; is that
23 right?
24 A. That's correct.
159
1 Q. Okay. Let's take a look at it. Now, we
2 have if you look at this subject line. We have Model
3 III cigarettes. Do you know what the filter dilution
4 of the Model III cigarettes was?
5 A. Well, as the other models they have several
6 cigarettes with a range.
7 Q. Okay. Do you know what that range was?
8 A. They have tested four cigarettes. One had
9 no dilution, one had 20-24 percent, one of them had 36
10 to 44 percent, and the fourth one had 55 to 60
11 percent.
12 Q. Okay. Let's look at the introduction. It
13 says, "Previous results obtained by testing the whole
14 smoke condensate obtained from the Model II cigarettes
15 indicated that the incorporation of a filter dilution
16 into a cigarette was associated with a significant
17 increase in whole smoke condensate specific activity
18 in the Salmonella/microsome assay." And I think you
19 referred to that testing this morning; is that right?
20 A. Yes.
21 Q. Okay. Now, let's look at the rest of it.
22 The Model III cigarettes, which are described more
23 fully in Table 1, were designed to differ only in
24 their degree of filter dilution. The results to be
160
1 presented below indicate that high filter dilution (55
2 to 60 percent) is associated with a significant
3 increase in WSC specific activity in the
4 Salmonella/microsome assay."
5 Do you see that?
6 A. Yes.
7 Q. That's what Philip Morris was reporting on
8 June 4th of 1979; is that right?
9 A. That's what they reported in their series of
10 experiments, that's correct.
11 Q. Okay. And this dilution for the cigarette
12 they're specifically talking about here is 35 to, what
13 is it, 30 to 35 percent higher than the dilution for
14 what you know Marlboro Lights to be today; is that
15 right?
16 A. That's probably right.
17 Q. I'm sorry?
18 A. That's probably right.
19 MR. LOMBARDI: Okay. The next page please.
20 Q. (By Mr. Lombardi): "In the case of the
21 Model III cigarettes reported here, there were no
22 significant differences between the WSC activities of
23 the 0, 20-24%, and 36-44% diluted cigarettes."
24 Do you see that?
161
1 A. Yes.
2 Q. That means that for cigarettes with around
3 25 percent dilution, there was no significant
4 difference in WSC activities?
5 A. Only in this study. Not in the study we
6 discussed this morning.
7 Q. Well, I know that, but you didn't talk to
8 the Court about this study.
9 A. I did not present this evidence this
10 morning. That's correct.
11 Q. Okay. And I don't think you told the Court
12 about the dilution of the study you talked about this
13 morning, did you?
14 A. We -- we discussed two studies where the
15 dilution was reported to have been as low as 25 or 27
16 percent dilution.
17 Q. Okay. I'm talking about --
18 A. I did discuss it this morning, yes.
19 Q. Okay. It's 1979 we're talking about,
20 Doctor.
21 A. Okay.
22 Q. And then it says, "The WSC from the 55-60%
23 diluted cigarette however was 30% more active than the
24 nondiluted control, 25.5% more active than the 20-24%
162
1 diluted cigarette and 20.5% more active than the
2 36-44% diluted cigarette." Do you see that?
3 A. Yes.
4 Q. And they're reporting that that 55-60%
5 diluted cigarette is significantly more active than
6 the other levels of dilution; is that right?
7 A. Can you say that question again?
8 Q. They're reporting that the 55-60% diluted
9 cigarette is considerably more active than the
10 dilutions of the other cigarettes -- than the other
11 diluted cigarettes; is that right?
12 A. I guess.
13 Q. It's on page two.
14 A. No, I can read it. I'm just not sure when
15 you say considerably, are we talking --
16 Q. You can look right at what it says. It says
17 it's 30% more active than the nondiluted control.
18 A. Right.
19 Q. 25.5% more active than the 20-24% diluted
20 cigarette, right?
21 A. Correct.
22 Q. That's where the Marlboro Lights would fit
23 approximately today given your understanding of its
24 dilution today; is that right?
163
1 A. That's correct.
2 Q. You don't know its dilution back then; is
3 that right?
4 A. That's correct.
5 Q. And 20.5 percent more active than the 36-44%
6 diluted cigarette; is that right?
7 A. That's what it says. That's correct.
8 Q. And then it goes on to say, "Why there
9 exists an apparent threshold in filter dilution which
10 leads to an increase in whose smoke condensate
11 activity is a phenomenon worthy of further study."
12 And it goes on from there. Do you see that?
13 A. Yes.
14 Q. So at this point on June 4th, 1979, you
15 would agree that these scientists at Philip Morris
16 believed that there was an apparent threshold where
17 the activity of a cigarette picked up based on its
18 dilution; is that right?
19 A. I don't know that I would infer that. They
20 have threshold in quotes.
21 Q. Well, they said threshold; is that right?
22 A. They have threshold in quotes.
23 MR. ZELCS: Judge, it's threshold in quotes.
24 Q. (By Mr. Lombardi): Well, that's just fine.
164
1 They have threshold in quotes, Doctor. Do you agree
2 with that?
3 A. They did write that.
4 Q. They apparently said that at that time; is
5 that right?
6 A. They wrote that in quotes, that's correct.
7 Q. Okay. And does the fact that it's in quotes
8 indicate to you that they didn't believe that was
9 true, Doctor?
10 A. That tells me that they had some doubts
11 about whether or not there was a threshold.
12 Q. And did you talk to which -- who wrote this
13 memo?
14 A. I think you said before Mr. or Dr. Rapp.
15 Q. Okay. Have you talked to him before?
16 A. No.
17 Q. Have you seen any indication what he meant
18 by putting this in quotes?
19 A. No. I can just interpret the data and
20 interpret -- and look at what he wrote and see how he
21 --
22 Q. You can speculate on what he might have
23 meant?
24 A. Right. Or I can look at the data and draw
165
1 my own conclusion.
2 Q. Okay. And the data shows that the 55-60%
3 has a substantial jump over the other dilutions, isn't
4 that right?
5 A. Substantial is a relative term. It has more
6 revertance and a physically significantly increase
7 over the other cigarettes.
8 Q. Okay. Well, I don't want to make you
9 uncomfortable with a relative term, Doctor. Look at
10 the ads here, the last line. It says, "In examining
11 these results however it should be kept in mind that
12 the differences being measured are extremely small and
13 are probably at or near the limits of sensitivity of
14 the Salmonella/microsome assay."
15 Do you see that?
16 A. Yes.
17 Q. There's a statistic -- there's this idea of
18 statistical significance in these tests? Right,
19 Doctor?
20 A. That's right.
21 Q. And statistical significance essentially is
22 a -- if it's a statistically significant difference,
23 then the tester can conclude that the difference is
24 not due to some random variations; is that right?
166
1 A. That's why you use the whole test. That's
2 correct.
3 Q. Okay. But even if something is
4 statistically significant, if there's a statistically
5 significant difference, that doesn't necessarily mean
6 there's a big difference, does it? Does it?
7 A. I'm sorry. A big difference in terms of
8 what?
9 Q. In terms of the results that you're
10 reporting.
11 A. These are the quantitative difference?
12 Q. Right.
13 A. No. The point of the physical test is to
14 identify whatever that difference, whether it's big or
15 small is happening by random chance or not.
16 Q. Okay. And the mere fact that you have a
17 difference doesn't mean that there's any biological
18 significance to the difference that you have, isn't
19 that right?
20 A. That is possible. That's correct.
21 Q. Okay. Doctor, did you continue to follow
22 the Philip Morris testing into the early 1980s?
23 A. I think so, yes.
24 Q. Okay. Do you know someone named Levins?
167
1 A. Not personally.
2 Q. Do you know the name?
3 A. I don't recall either way.
4 Q. Does it -- does it -- do you remember that
5 as the name of a person at Philip Morris?
6 A. I read 15 to 20 inches worth of documents.
7 Each memo probably had a different name so I don't
8 know that I've --
9 Q. Well, let me be more specific. Do you
10 remember that as a person at Philip Morris who worked
11 on mutagenicity testing?
12 A. I don't recall either way.
13 Q. Okay. I handed you what's been marked as
14 5607. And here's an extra copy. And just so I've got
15 it right on the record, Doctor, this is an October
16 16th, 1984 report with a title, "6908 Smoke Condensate
17 Studies, 1984 Annual Report." Do you see that?
18 A. That's right.
19 Q. Okay. Have you seen this one before?
20 A. I believe I've seen it.
21 Q. Okay. This is not one that you talked about
22 this morning; is that right?
23 A. That's correct.
24 Q. I ask you to turn -- I'll find the page for
168
1 you, Doctor. To page 14 of the document. Tell me
2 when you have page 14, Doctor.
3 A. I do.
4 Q. Okay. Do you see it says, "Low Tar
5 Reference Cigarette Study"?
6 A. Correct.
7 Q. All right. And it's got R. Levins in
8 parens?
9 A. Right.
10 Q. Do you interpret that as being R. Levins did
11 this study?
12 A. He might have.
13 Q. Okay.
14 A. He might not have. Maybe he was just the
15 author.
16 Q. Okay. Let's go to page 15.
17 A. Okay.
18 Q. It's talking about an LTR cigarette, right?
19 Low tar reference?
20 A. Right.
21 Q. The L -- there at the top of the first
22 sentence, "The LTR cigarette differed from the other
23 models in the MS PAH study in two significant ways:
24 cigarette construction, paren, (LTR incorporates 50%
169
1 air dilution via a mechanically perforated filter),
2 closed paren., and blend composition."
3 Do you see that?
4 A. Yes.
5 Q. What is a mechanically perforated filter,
6 Doctor?
7 A. That's, you know, a filter with holes in it.
8 Q. What's it mean to say it's mechanically
9 perforated?
10 A. It's perforations of the hole.
11 Q. How?
12 A. It's the actual --
13 MR. ZELCS: How as to what?
14 Q. (By Mr. Lombardi): How are they perforated?
15 A. How do they manufacture it?
16 Q. How are they perforated?
17 A. I don't know the actual mechanism for doing
18 that. I just know that they are perforated with
19 holes.
20 Q. Okay. So this cigarette is 50 percent air
21 dilution. Do you see that?
22 A. Yes.
23 Q. Okay. Let's go to the bottom of that
24 paragraph. "It was concluded that high air dilution
170
1 was not a major factor contributing to the high
2 activity of the LTR cigarette."
3 Do you see that?
4 A. I see that. I have to read the whole
5 paragraph.
6 Q. I'm sorry. I couldn't hear you, Doctor.
7 A. Yes, I see that. I was just trying to get
8 the context within the context.
9 Q. Okay. Well, this was a report that was
10 prepared October 16th, 1984, Doctor.
11 MR. ZELCS: Why don't you let him read the
12 paragraph?
13 MR. LOMBARDI: Because I have limited time,
14 Judge.
15 THE COURT: Let him ask the question.
16 Q. (By Mr. Lombardi): This is an October 16th,
17 1984 report, Doctor?
18 A. That's correct.
19 Q. And as of October 16th, 1984, R. Levins was
20 reporting that high air dilution was not a major
21 factor contributing to the high activity of the LTR
22 cigarette?
23 A. They're talking about isolated fractions
24 here, so I'm not sure if they're referring to the
171
1 entire cigarette or just a section of the smoke that
2 was coming off.
3 Q. Doctor, can you conclude that the high air
4 dilution was not a factor?
5 MR. ZELCS: Objection. He answered the
6 question. He indicated --
7 MR. LOMBARDI: He didn't answer the
8 question.
9 THE COURT: Overruled.
10 A. I'm sorry. Ask the question again.
11 Q. (By Mr. Lombardi): Did it conclude that
12 high air dilution was not a major factor contributing
13 to the high activity of the LTR cigarette?
14 A. That's what they looked.
15 Q. And the dilution in that case, Doctor, as
16 you know was 50 percent; is that right?
17 A. I have not looked through this document.
18 For example, 50 percent I would have to see what it
19 says in the table.
20 Q. Well, it said in the paragraph that we just
21 looked at, didn't it, Doctor?
22 A. Okay. Fine. Correct.
23 Q. Twice as much as what you now believe the
24 Marlboro Lights ventilation to be?
172
1 A. That is correct.
2 Q. Okay. Now, Doctor, it would be fair, you as
3 a historian, Doctor, in order to be fair would want --
18 Q. (By Mr. Lombardi): Doctor, to be fair, --
19 A. Yeah.
20 Q. -- to be fair about what Philip Morris knew
21 and was thinking in the late 1970s and early 1980s, it
22 would be fair to look at documents out there in the
23 scientific community too, wouldn't it?
24 A. Yes.
173
1 Q. That would help provide a context, wouldn't
2 it?
3 A. Yes.
4 Q. Did you do that kind of search for this
5 case?
6 A. Yes.
7 Q. Okay. Did you look at something called the
8 TWG?
9 A. The Tobacco Working Group?
10 Q. Very good. Yes. Did you look at that?
11 A. Well, there's a lot of things in the Tobacco
12 Worker Group.
13 Q. Did you know what kind of work they were
14 doing relating to biological testing, biological
15 activity testing in the 1970s?
16 A. I understand that that's what they were
17 doing.
18 Q. Okay. Well, then maybe you'll know about
19 this. Before we get there, Doctor, let me just,
20 again, try to identify this for the record. And I'm
21 not expecting you to look through the whole document,
22 Doctor, but at least on its face, does that appear to
23 be Report No. 4 Toward Less Hazardous Cigarettes, The
24 Fourth Set of Experimental Cigarettes?
174
1 A. Yes.
2 Q. Okay. And have you seen this one before?
3 A. I'm actually -- I don't think I've actually
4 seen this document before.
5 Q. Do you recognize this as in the form of
6 reports issued by the Tobacco Working Group in the
7 1970s?
8 A. I'm not sure what it is.
9 Q. Okay. Now, Doctor, before we get into the
10 text of it, the document, we were talking about the
11 three levels here and you said you could jump from one
12 level up; is that right? For instance, you could say
13 I'm not going to do any more in vitro, I'll go
14 directly to in vivo testing; is that right?
15 A. You could do that.
16 Q. Or you could go in vivo directly to human
17 investigations like epidemiology; is that right?
18 A. One could do that.
19 Q. Okay. All right. Now, mouse skin painting
20 is at this second level, in vivo; is that right?
21 A. That's right.
22 Q. Now, if you could turn to page four of the
23 document itself, Doctor.
19 Q. (By Mr. Lombardi): Did you get to page
20 four, Doctor?
21 A. Yes.
22 Q. Okay. And you see on that page, let's go to
23 the second from the bottom highlighted part. Right
24 there. Thank you. Do you see that paragraph I'm
176
1 looking at?
2 A. Yes.
3 Q. "The air dilution filter proved to be
4 effective in reducing the tumorigenicity."
5 Now, what does tumorigenicity mean?
6 A. That's the number of tumors that you get in
7 an animal study.
8 Q. So, for instance, in a mouse skin painting
9 study lowering the tumorigenicity would be a good
10 thing; is that right, Doctor?
11 A. That's right.
12 Q. "The air dilution filter proved to be
13 effective in reducing the tumorigenicity of the
14 cigarette condensate applied on an equivalent weight
15 basis."
16 Do you see that?
17 A. I see that.
18 Q. Okay. Now, the Judge pointed out, you go
19 back to the acknowledgements which is Roman Number IX,
20 5206.10. Do you have that? There's a list of
21 individuals?
22 A. Yes.
23 Q. And do you see on there Robert Seligman?
24 A. Yes.
177
1 Q. Who's he?
2 A. He's -- I'm assuming he's the same
3 individual that we looked at his notes from Philip
4 Morris.
5 Q. Now, you don't -- you don't know for sure I
6 take it; is that right?
7 A. That's correct.
8 Q. Okay. Do you know whether Robert Seligman
9 was involved in the tumorigenicity testing that was
10 done at the TWG in the 1970s?
11 A. I don't know that.
12 Q. Do you know whether he talked to any of the
13 people listed here as being in the Tobacco Working
14 Group about tumorigenicity studies in the 1970s at the
15 TWG?
16 A. I don't know that either way.
17 Q. But in any rate the tumorigenicity studies,
18 Doctor, -- Doctor, --
19 A. Yes.
20 Q. -- are down here at level two; is that
21 right?
22 A. That's correct.
23 Q. That's a step up from the mutagenicity
24 studies you talked about; is that right?
178
1 A. It's the next level step.
2 Q. Okay. You've had a chance to read the
3 Surgeon General's Report from 1981, haven't you?
4 A. Yes.
5 Q. Okay. Doctor, I've handed you what's been
6 marked as 7078, and can you tell that that is the 1981
7 Surgeon General's Report?
8 A. That's correct. That's what it is.
9 Q. Okay. Let's go to page 18 of the report,
10 Doctor. 7078.36 please.
11 A. I'm sorry. What page?
12 Q. Page -- I'm sorry. 18. I said eight I
13 think. Page 18.
14 A. Okay.
15 Q. And tell me when you got it?
16 A. I've got it.
17 Q. Okay. I'm looking down at the bottom down
18 at number eight. Do you see conclusion eight?
19 A. Yes.
20 Q. "The tar content of smoke condensate of
21 today's cigarettes is less tumorigenic to mouse skin
22 than that of cigarettes of 30 years ago."
23 Do you see that?
24 A. That's right.
179
1 Q. Okay. Do you have any reason to doubt that
2 the Surgeon General had it right about the
3 tumorigenicity of cigarettes of that day?
17 Q. (By Mr. Lombardi): Doctor, I'm sure you
18 don't remember the question at this point. Is that
19 fair? First of all, have you found the part at page
20 18 that I was referring to?
21 A. Yes.
22 Q. Okay. And you found there that it makes
23 reference to the fact that the smoke condensates of
24 today's cigarette is less tumorigenic to mouse skin
184
1 than that of cigarettes of 30 years ago?
2 A. That's correct.
3 Q. And at page 34, -- do you have page 34,
4 Doctor?
5 A. Not yet. Okay.
6 Q. Page 34, 7078.52. I'm sorry. That's a
7 reference so they can get it on the screen, Doctor.
8 A. All right.
9 Q. You see another reference, they're talking
10 about animal models for lung cancer. Do you see that?
11 A. Yes.
12 Q. And they say, "The mouse skin carcinogenesis
13 assay is thus far the most fruitful method of
14 evaluating smoke condensates from different types of
15 cigarettes for carcinogenic potency for the human
16 lung."
17 Do you see that?
18 A. That's correct.
19 Q. Okay.
12 Q. (By Mr. Lombardi): Doctor, let's look at
13 Plaintiffs' 91, and you don't have numbers I guess.
14 This one. Okay.
15 Okay. And that is a document you looked at
16 earlier today; is that right?
17 A. That's correct.
18 Q. And I'm going to refer you, I think, to the
19 pages you looked at. This is an October 4th, 1991
20 memo from Hellams, H-E-L-L-A-M-S to Izac, I-Z-A-C. Is
21 that right?
22 A. Yes.
23 Q. Who was Dr. Izac?
24 A. I presume that's someone who was working for
186
1 Philip Morris.
2 Q. What other mutagenicity testing did he do
3 other than the testing you referred to this morning?
4 A. The only thing that I know is what's
5 contained in this document.
6 Q. How about Dr. Hellams? Who's he?
7 A. That I presume is an employee of Philip
8 Morris because it's Philip Morris letterhead.
9 Q. Okay. Let's go -- I think you were on the
10 second page of that document. 3403.1. And I believe
11 what you read -- just do the whole top paragraph,
12 please for now. I think you just read the first
13 sentence there, didn't you, Doctor?
14 A. That's correct.
15 Q. Where he says, "As a result of the study
16 with Model I cigarettes, it was noted that the CSC" --
17 What's that?
18 A. Cigarette smoke condensate.
19 Q. "Of a low reference tar cigarette was not
20 statistically as active in the Salmonella assay as the
21 burley CSC, but was statistically more active than the
22 CSC from the 2R1 Kentucky Reference cigarette." Do
23 you see that?
24 A. Yes, sir.
187
1 Q. Okay. Now, the next line you didn't read,
2 did you?
3 A. No.
4 Q. The Model I low tar reference cigarette,
5 that's the AKJ you were talking about before; is that
6 right?
7 A. That's right.
8 Q. Differed from the other Model I cigarettes
9 in its physical parameters. It had a high efficiency
10 cellulose acetate filter, high porosity paper, and how
11 much dilution, Doctor?
12 A. 47 percent.
13 Q. And does that refresh your recollection that
14 the AKJ was at 47 percent?
15 A. Yes.
16 Q. Okay. Let's go down the page. "With the
17 Model II cigarettes it was found that among the three
18 physical cigarette parameters studied, high porosity
19 paper, high efficiency CA filter." What's CA?
20 A. Cellulose acetate.
21 Q. That's a type of filter?
22 A. Yes.
23 Q. And filter dilution, approximately 47%, only
24 filter dilution had a significant affect on CSC
188
1 activity in the Salmonella assay. Based on these
2 results, a Model III set of cigarettes -- I won't even
3 read that, all those letters, but with a particular
4 kind of filter were fabricated --
5 A. Filler, not filter.
6 Q. Filler. Thank you, Doctor. Were fabricated
7 with CA filters with filter dilutions of 20-24%,
8 36-44%, and 55-60%. The control cigarette was without
9 a filter, and then here's the result. Only the CSCs,
10 that's the condensates, right, Doctor?
11 A. That's right.
12 Q. From the 55 to 60% diluted cigarette was
13 statistically more significant than the other three
14 cigarettes; is that right?
15 A. This is the same study that we just talked
16 about a few minutes ago.
17 Q. Well, this is 1991.
18 A. But they're still summarizing the earlier
19 data.
20 Q. Going back to '79. Okay. And there it is.
21 It's talking about the 55 to 60% being the only one
22 that has a statistically significant difference. And
23 that's the result that you didn't point out to the
24 Court this morning; is that correct?
189
13 Q. (By Mr. Lombardi): Let's see. You've got
14 20-L, Doctor, and that one is this. I just want to
15 make sure you've got it.
16 A. I've got that one, yes. Okay.
17 Q. Do you know -- well, let me just state for
18 the record 20-L is a letter to Cathy Ellis from Wolf
19 Reininghaus; is that right.
20 THE COURT: What are we looking at now?
21 MR. LOMBARDI: I'm sorry, Judge. This is
22 Plaintiffs' 20-L that we looked at earlier.
23 THE COURT: Oh, yeah.
24 Q. (By Mr. Lombardi): From Wolf Reininghaus;
190
1 is that correct?
2 A. That's correct.
3 Q. And while the Judge is looking, I'll spell
4 it for the court reporter.
5 THE COURT: No, go ahead.
6 Q. (By Mr. Lombardi): All right. And this is
7 a letter and you pointed out, I guess, I'll take the
8 headnote here. I think you pointed out this part at
9 the beginning; is that right?
10 A. That's right.
11 Q. Of the second page, subsequent page.
12 "Increased porosity and ventilation will lower the air
13 flow through the cone and increase the specific
14 mutagenicity." That's what you pointed out; is that
15 right?
16 A. That's right.
17 Q. How much ventilation was Dr. Reininghaus
18 referring to there?
19 A. I don't recall offhand, but I think he was
20 talking about those Model III cigarettes, but I'm
21 actually not seeing that stated in here.
22 Q. Is it fair to say you don't know, Doctor?
23 A. If you give me a couple of minutes I'll find
24 it to refresh my memory.
191
1 THE COURT: When we talked about it, it
2 raised my curiosity as to the difference between
3 mutagenicity and cytotoxicity.
4 MR. LOMBARDI: I can ask the Doctor about
5 that. Judge, I think we can clear it up. Can I let
6 him finish his search first and then we'll clear that
7 up for you.
8 A. I guess he doesn't state in here which
9 earlier PM data he was referring to.
10 Q. Now, it also says the cytotoxicity will not
11 be changed; is that right?
12 A. That's right.
13 Q. Cytotoxicity refers to another type of in
14 vitro test; is that right?
15 A. Sure.
16 Q. Okay. And I guess I'll state it like a
17 layman, Doctor, and I'll see if you can accept it.
18 Cytotoxicity is a test that measures cell depth as
19 opposed to mutagenicity which measures cell mutation;
20 is that right?
21 A. That's right.
22 Q. So when you do the cytotoxicity test, you're
23 determining how many cells have died as a result of
24 exposure to a substance. Is that right?
192
1 A. That's correct.
2 Q. And so you would read this as saying that
3 cytotoxicity would not be changed by increased
4 porosity or ventilation?
5 A. That's correct.
6 Q. And incidentally, Doctor, this in vitro test
7 level, you would suggest doing a battery of tests, not
8 just one test; is that right?
9 A. When you're starting off your evaluation,
10 you would do a battery of tests.
11 Q. Okay. And I'm sorry. Were you finished?
12 A. Yes. But I was going to say once you have a
13 positive result like in the Ames Salmonella and one
14 strand, you don't need to do the other one.
15 Q. But by battery of tests you mean a whole
16 group of tests and you try to draw as much information
17 as you can based on having done a whole group of
18 tests; is that right?
19 A. Well, you have to do that because you want
20 to make sure -- you want to make sure that you're not
21 going to get all false negatives. Some in vitro
22 assays are better for predicting a specificity
23 chemical versus another. So if you just shoot one,
24 you haven't chosen the wrong model, then you're going
193
1 to make a false conclusion. So you do a battery to
2 make sure that you cover a wide range that if there is
3 one positive, you know you've got a positive
4 mutagenicity that you have to deal with.
5 Q. And cytotoxicity could be one of the battery
6 of tests that you do under in vitro testing; is that
7 right?
8 A. That's definitely not correct. Actually, I
9 take that back. You could make some inferences about
10 the results, but it is not an assay use for a
11 prediction of carcingenicity in animals.
12 Q. And actually one of the things you've done
13 in very recent years is you've been part of an
14 organization that has proposed that a battery of
15 assays be developed for testing cigarettes; is that
16 right?
17 A. Well, a battery of assays, not that they
18 were developed new, but identified them.
19 Q. I didn't mean new tests, Doctor.
20 A. Right.
21 Q. That isn't what I was trying to convey,
22 Doctor. I meant that you were suggesting with others
23 that there be a group of tests identified to use for
24 testing cigarettes; is that right?
194
1 A. That's correct.
2 Q. But you didn't specify which tests would be
3 used; is that correct?
4 A. That's correct.
5 Q. And to date, to your knowledge Burns and the
6 United States government hasn't specified the battery
7 of tests that should be used at this in vitro level;
8 is that correct?
9 A. No. I think different agencies actually
10 have made very specific recommendations on some of
11 them that they need to see. The point is as long as
12 you have a well designed battery, no one needs to say
13 you have to do these, you know, three or five tests.
14 Q. All right. Doctor, 20-M, and let me show
15 you which one that was. Let me know when you've got
16 it, Doctor?
17 A. Okay.
18 Q. This was another one you put up and I'll
19 just put it on the screen. This is -- it's for
20 identification. It's Plaintiffs' 20-M and it's titled
21 "In Vitro-Mutagenicity of Mainstream Smoke Condensate
22 of 30 Research Cigarettes with Differences in 6
23 Parameters." Do you see that?
24 A. Yes.
195
1 Q. Okay. And I have this, right? Let me make
2 sure I've got the pages right. I think the pages you
3 showed were the summary which is toward the second
4 page from the back. That's right. This is one of the
5 pages you talked about, isn't it?
6 A. Yes.
7 Q. This is where you talked about mutagenicity
8 of mainstream smoke condensate is influenced by filter
9 ventilation among other things; is that right?
10 A. That's right.
11 Q. And then you showed the last page I believe,
12 is that right, the conclusion?
13 A. Yes. That's correct.
14 Q. The results of the study enable us to
15 specifically modify -- and you read this part -- to
16 specifically modify a given cigarette to get lower
17 mutagenic activity?
18 A. That's right.
19 Q. And elsewhere in the report, and the part
20 that we didn't see earlier, they show some eight for
21 the effects of various parameters of design on
22 mutagenicity; is that right?
23 A. That's correct.
24 Q. And that's at the page that ends in Bates
196
1 number 379, isn't it, Doctor?
2 A. Yes.
3 Q. All right. We'll go a little wider.
4 There's a table there called weight coefficient of
5 each parameter?
6 A. That's right.
7 Q. And by parameter you understand that to
8 refer to one of the cigarette design features; is that
9 right?
10 A. That's right.
11 Q. Okay. And it lists them going down that
12 left hand column?
13 A. That's right.
14 Q. And the weight coefficient, that's based on
15 what's called a regression analysis?
16 A. That's correct.
17 Q. And what it shows here is -- well, it shows
18 that actually the filler, that's the tobacco that goes
19 in the rod, is that right, Doctor?
20 A. That's right.
21 Q. It shows that filler has the greatest effect
22 on mutagenicity; is that right?
23 A. That would be a reasonable conclusion.
24 Q. That's because it's at 43.8 plus or minus;
197
1 is that right?
2 A. Yeah, it gets a little bit difficult to
3 interpret this type of data this way, but I think that
4 roughly is correct.
5 Q. Okay. And then it says paper porosity
6 negative 6.32. Do you see that?
7 A. Yes.
8 Q. And when it says negative 6.32 that means
9 that paper porosity tends to decrease the
10 mutagenicity; is that right?
11 A. That's right.
12 Q. Okay. And then if you skip down you see
13 filter efficiency has a 15 percent or a 15.2 is its
14 coefficient. Do you see that?
15 A. Yes, I do.
16 Q. And then down there at the bottom it says
17 filter ventilation has a 7.76 weight coefficient. Do
18 you see that?
19 A. That's correct.
20 Q. So the filter ventilation is not having the
21 biggest effect on the mutagenicity in this study; is
22 that correct?
23 A. The way they design these test cigarettes,
24 that would be a reasonable conclusion.
198
1 Q. Okay. And, in fact, the filter ventilation,
2 its weight coefficient is barely more than the
3 negative coefficient of paper porosity; is that right?
4 A. The numbers are similar. It also depends on
5 how you define the range of the parameters that you
6 want to test.
7 Q. Well, do you know how they defined them?
8 A. Well, I do have a table here. That's
9 correct.
10 Q. Okay. And so -- well, do you know, Doctor,
11 did Marlboro Lights cigarettes have porous paper?
12 A. My understanding is that they have porous
13 paper.
14 Q. So if you have porous paper in a light
15 cigarette, that tends to reduce the mutagenicity; is
16 that right?
17 A. It's my understanding -- when I used this
18 document this morning, it's my understanding that the
19 difference between the Lights and the Reds are
20 essentially ventilation and that the other parameters
21 are a --
22 Q. Well, but that wasn't my question. My
23 question was do you understand that Marlboro Lights
24 has porous paper?
199
1 A. It's my understanding that it has porous
2 paper.
3 Q. And to the extent it has porous paper, the
4 porous paper offsets, virtually offsets, according to
5 this study at least, the increased mutagenicity of
6 filter ventilation; is that right?
7 A. I'm not sure you can -- no, I don't think
8 you can make that conclusion from this table because
9 they're presenting a model for one, two, three, four,
10 five, six different parameters. If you wanted to
11 compare one to another, you would have to do a very
12 different model.
13 Q. Okay. Well, you're the one that put this
14 study up for the conclusions, right?
15 A. That's correct.
16 Q. And we're just going back here and looking
17 at the data that they compiled to get to those
18 conclusions; is that right?
19 A. That's right.
20 Q. And what this shows is that the increase in
21 mutagenicity due to filter ventilation is about the
22 same, a little bit higher, than the decrease in
23 mutagenicity attributable to the paper porosity?
24 A. I don't agree with that conclusion. I don't
200
1 think you can draw that from this table.
2 Q. Okay. Doctor, you also looked at Exhibit 92
3 and that's this one.
4 A. Brands study. Okay.
5 Q. This is another document that you showed; is
6 that right?
7 A. That's right.
8 Q. And I may have been confused on pages,
9 Doctor. I was trying to keep up, but I'm going to put
10 up a page and you tell me if I'm wrong, but I think
11 this is the right page that you showed earlier.
12 A. Yes.
13 Q. Okay. And you were explaining -- when was
14 this study done by the way?
15 A. The last few years.
16 Q. Do you know when specifically?
17 A. The last few years.
18 Q. If that's as specific as you can be?
19 A. I think 2001, but it would be plus or minus
20 one to two years.
21 Q. Okay. And you know based on your
22 investigation that this is a study that Philip Morris
23 was preparing for publication? Do you know that from
24 your investigation?
201
1 A. I have read the original document from this.
2 I don't recall whether they said they were going to
3 publish it or not.
4 Q. Okay. And you pointed this out. Up in the
5 corner it indicates that it's reporting the results
6 for ISO and then MCTSP. Do you see that?
7 A. Right.
8 Q. ISO is actually not the FTC test; is that
9 right?
10 A. It's the parameters are essentially the
11 same.
12 Q. It's similar but it's a test that's used in
13 Europe; is that right?
14 A. It's used in Europe, but I think the
15 parameters are identical.
16 Q. Do you think they are identical?
17 A. That's my recollection that they are.
18 Q. All right. Well, we'll check on that later,
19 but MCTSP -- did I get all those initials? It's
20 getting late.
21 A. Yes.
22 Q. I couldn't tell. That's referring to the
23 Massachusetts protocol; is that right?
24 A. That's right.
202
1 Q. Where they cover up vent holes and smoke the
2 cigarettes differently than they do in either the FTC
3 or the ISO; is that right?
4 A. That's correct.
5 Q. Now, tell me, are the results reported on
6 this chart, do they indicate statistically significant
7 differences between Marlboro Lights and Marlboro
8 regulars?
9 A. They didn't put the data here, but when you
10 go back to the raw data, they fairly significantly
11 make that link.
12 Q. Okay. Where did you find the data that
13 you're referring to?
14 A. In one of the documents that was provided to
15 us by PM.
16 Q. Okay. Doctor, now, it shows that Marlboro
17 Lights is above Marlboro Reds on the T90 -- TA98
18 strain, is that right, as to this particular chart?
19 A. That's right.
20 Q. And there are other charts in here as well;
21 is that right?
22 A. That's right.
23 Q. And, Doctor, do you see the Bates number?
24 The Bates number is kind of running along the side
203
1 right there. And it's the one that ends 253 that I've
2 turned to.
3 A. Okay.
4 Q. All right. Let's put this one up. This is
5 another one of the charts that are in there?
6 A. Right.
7 Q. Okay. And this is the TA98 on a per
8 cigarette basis. Do you see that?
9 A. That's right.
10 Q. So they're measuring the mutagenicity on a
11 per cigarette basis?
12 A. They're calculating that. That's correct.
13 Q. And on each of the tests the Marlboro Light
14 is less than the Marlboro regular; is that right?
15 A. Comparing ISO to ISO and then Massachusetts
16 to Massachusetts, that is correct. They are
17 numerically lower.
18 Q. Okay. Now, Doctor, you talked a little bit
19 earlier, actually later in your testimony about
20 adenocarcinoma. Am I saying that right? I never know
21 whether I am.
22 A. Actually some people do but I say
23 adenocarcinomas.
24 Q. Okay. Then I'm going to say adeno then. I
204
1 have never known, Doctor. And so you were talking
2 about some developments in the histo pathology of lung
3 cancer; is that right?
4 A. Yes.
5 Q. Now the first publication that indicated
6 this change in the increase in adenocarcinoma was
7 1997; is that right?
8 A. The first publication ever?
9 Q. The first -- the publication you first
10 referred to was Dr. Thun, isn't that right?
11 A. That's correct.
12 Q. And that was a publication in 1997; is that
13 right?
14 A. That's correct.
15 Q. And I take it, Doctor, that you accept
16 Monograph 13 as reflecting the medical consensus these
17 days?
18 A. I would agree with that statement.
19 MR. LOMBARDI: Okay. I take it you don't
20 need Monograph 13.
21 MR. ZELCS: What would you do if I told you
22 that I do?
23 MR. LOMBARDI: I would not believe you.
24 Q. (By Mr. Lombardi): I don't remember whether
205
1 the Doctor has Monograph 13?
2 A. I don't have it in front of me now.
3 Q. I'll give you one, Doctor.
4 MR. ZELCS: Get you some water?
5 THE WITNESS: Yeah, that would be great.
6 MR. TILLERY: I'll get it.
7 Q. (By Mr. Lombardi): And I'll hand you -- I'm
8 sorry.
9 MR. TILLERY: He needs some water.
10 MR. LOMBARDI: Oh, that's fine.
11 Q. (By Mr. Lombardi): I'll hand you the
12 Monograph in the meantime, Doctor. And I will wait
13 until you have your water.
14 A. No. That's fine. Let's go.
15 Q. The Monograph does reference
16 adenocarcinomas; is that right?
17 A. I believe it discusses adenocarcinomas.
18 Q. I'm sorry. I couldn't hear you?
19 A. I said I believe it discusses
20 adenocarcinomas.
21 Q. And I'm going to refer you to a specific
22 page.
23 A. Okay.
24 Q. Page 110.
206
1 A. Okay.
2 Q. And that's at 7109.125. And if you could
3 highlight the last paragraph there. Do you see that
4 last paragraph, Doctor?
5 A. Yes.
6 Q. And so the Monograph says, "Changes in
7 pattern of deposition of smoke aerosol have been
8 postulated." And that's one of the things you're
9 talking about with respect to adenocarcinomas; is that
10 right?
11 A. That's right.
12 Q. "Have been postulated as one mechanism
13 underlying the dramatic increase in adenocarcinoma
14 seen over the last several decades in the United
15 States and other countries."
16 Do you see that?
17 A. Yes.
18 Q. And do you agree that the Monograph is
19 reflecting that the increase in adenocarcinoma and its
20 relationship to low tar cigarettes is something that
21 has been postulated?
22 A. I'm sorry. Say that again.
23 Q. Do you agree that the Monograph indicates
24 the medical consensus as of the time of the Monograph
207
1 13 indicates that the increase in adenocarcinoma was
2 postulated to be related to low tar cigarettes?
3 A. Well, they say the changes in pattern of
4 deposition is postulated as one mechanism.
5 Q. Okay. Well, let's go to the next page. And
6 just that top part. Not the chart, but the text.
7 Thank you.
8 And then it says about halfway through that,
9 Doctor, "Increased levels of tobacco-specific
10 nitrosamines." Those are TSAs, is that right?
11 A. That's right.
12 Q. "Have the potential to make cigarettes
13 manufactured after the 1960s more carcinogenic and may
14 have contributed to the rise in adenocarcinoma." Do
15 you see that?
16 A. Yes, I do.
17 Q. And the Monograph is pointing out that it's
18 possible that the rise in adenocarcinoma is due to low
19 tar cigarettes, but it's saying it hasn't been
20 scientifically determined yet; is that right?
21 A. I don't see anything about scientific
22 determination as saying that those cigarettes have the
23 potential to make them more carcinogenic.
24 Q. And that's my point. They have the
208
1 potential; is that right?
2 A. The potential is the word they use. That's
3 correct.
4 Q. And actually even with the rise in
5 adenocarcinoma, you know that lung cancer rates have
6 been going down, is that right, as a whole?
7 A. Adenocarcinoma rates have been going up.
8 Q. I said lung cancer is, Doctor. Did you
9 understand what I'm saying? Lung cancer rates as a
10 whole have been going down; is that right?
11 A. If you look at all the types of lung cancers
12 together, that's correct.
13 Q. And they have actually in data that's not
14 reflected in the Monograph, they've continued to fall
15 further than they had even at the time of the
16 Monograph, isn't that correct?
17 A. They are still trimming downward.
18 Q. Doctor, you said that the public health
19 community would have changed its view of low tar
20 cigarettes had it known about Philip Morris'
21 ventilation studies, mutagenicity studies on
22 ventilation. Was that your testimony?
23 A. That's correct.
24 Q. And actually, Doctor, the public health
209
1 community has known about a relationship between
2 ventilation and increased mutagenicity, hasn't it?
3 A. I'm sorry. From when?
4 Q. At any time, has that ever been something
5 reported publicly?
6 A. They certainly know about it today.
7 Q. Any time before today?
8 A. It was -- I'm sorry. Are you talking about
9 specifically the ventilation itself in the filters?
10 Q. Yes.
11 A. I'm sorry. I lost track of your question.
12 Q. Okay. Has the public health community --
13 have there been scientific articles written about the
14 effect of ventilation in cigarettes on mutagenicity?
15 A. Yes, there have.
16 Q. Okay. And, in fact, one of them was written
17 in 1995 and published, wasn't it?
18 A. It would be helpful if you showed it to me.
19 I'll assume it's correct.
20 Q. Do you remember the Steele study?
21 A. I'm aware of the Steele study.
22 Q. I've handed you again, Doctor -- I just want
23 to make sure we've got the same thing for purposes of
24 the record, 4376, which is an article titled, "A
210
1 comparison of the mutagenicity of mainstream cigarette
2 smoke condensates from a representative sample of the
3 US cigarette market with a Kentucky Reference
4 Cigarette K1R4F." Do we have the same article in
5 front of us?
6 A. Yes, we do.
7 Q. Okay. And this is what you understand to be
8 the Steele study; is that right?
9 A. That's right.
10 Q. And the Steele study in fact does publicly
11 report information about the relationship between
12 mutagenicity and dilution in cigarettes; is that
13 right?
14 A. That is my recollection.
15 Q. Okay. How long has it been since you've
16 seen this document?
17 A. Oh, I've looked at it some time over the
18 last couple of weeks.
19 Q. Okay. Let's look -- it's page 186 of the
20 article itself, Doctor. And let's -- the paragraph
21 that starts at the end of column two is what I'm
22 looking at. Do you have that, Doctor? Okay. And
23 this is where they start to report on mutagenicity
24 results with cigarettes; is that right?
211
1 A. I'll take -- I'm sorry. Did you ask me
2 about whether they start to talk about mutagenicity?
3 Q. We can go through it, Doctor.
4 A. Yeah.
5 Q. "Data were available to examine the
6 relationship between mutagenicity and the weight of
7 tobacco burned, milligrams of condensate per
8 cigarette, cigarette rod length, and air dilution for
9 a subset of 24 of the brands." Do you see that?
10 A. That's right.
11 Q. "Nonlinear mutagenicity estimates and the
12 square root transformation were used," and it refers
13 to a table, correct?
14 A. That's correct.
15 Q. And then it says, "The variables most highly
16 correlated with mutagenicity on a revertants per
17 milligram condensate basis." And just so we're clear,
18 revertants per milligram condensate basis is the
19 measurement we've seen throughout your testimony; is
20 that right?
21 A. That's right.
22 Q. "Were milligram per condensate/cigarette and
23 air dilation, with milligram condensate per cigarette
24 being negatively correlated and air dilution being
212
1 positively correlated." Do you see that?
2 A. Exact.
3 Q. "One hypothesis is that increased air
4 dilution, which generally produces cigarettes with
5 lower milligram condensate per cigarette, alters the
6 way the cigarette burns. Increased air dilution
7 results in increased oxygen being available during
8 pyrolysis and could yield slightly more mutagenic
9 condensate." Do you see that?
10 A. Yes.
11 Q. "However, mutagenicity on a per cigarette
12 basis is lower for the low condensate products since
13 total condensate yielded is lower." And it goes
14 through all those words like revertants again. Do you
15 see that?
16 A. Yes. That's right.
17 Q. Okay. And so it's reporting a relationship
18 between dilution and increased mutagenicity; is that
19 correct?
20 A. That's right. Using the smoking machine,
21 that's correct.
22 Q. Okay. And this was in 1995; is that right?
23 A. That's right.
24 Q. And you did not mean to suggest to the Court
213
1 that the public health community didn't have -- there
2 wasn't literature out there that made this connection
3 between mutagenicity and air dilution in cigarettes,
4 did you?
5 A. Well, I certainly didn't mean to imply that
6 in '95 that wasn't there.
7 Q. So it was there in '95, right?
8 A. Correct. We were generally talking about in
9 the '70s and '80s.
10 Q. Okay. Well, you also had some documents
11 from the '90s too, didn't you, Doctor?
12 A. That's correct.
13 Q. And you know there was a later article on
14 the same subject, correct?
15 A. I don't know that to be the case.
16 Q. Do you know of Chepiga?
17 A. The name is not ringing a bell right now.
18 Q. Okay. That's C-H-E-P-I-G-A. Doctor, again
19 for identification purposes this is marked as 4377,
20 and it's an article titled a comparison of the
21 mainstream smoke chemistry and mutagenicity of a
22 representative sample of the US cigarette market with
23 two Kentucky reference cigarettes. And then it
24 identifies those.
214
1 Have you -- Now, I have this in front of
2 you. First of all, did I identify that correctly?
3 A. Yes.
4 Q. And now that I have it in front of you, do
5 you recognize the document?
6 A. Yes.
7 Q. Okay. You have seen that one before?
8 A. Yes.
9 Q. Okay. And the main author is a man or woman
10 named Chepiga; is that right?
11 A. It's a man or a woman. That's correct.
12 Q. Okay. That's fairly inclusive I guess. All
13 right. Let's go back to the discussion section which
14 is, Doctor, page 960 of the article itself.
15 And you see there at the bottom it's talking
16 again about the relationship between cigarette types
17 and mutagenicity; is that right?
18 A. That's right.
19 Q. Okay. And it says, "As illustrated in
20 Figure 2, there is a reasonably strong positive
21 correlation between mainstream smoke condensate
22 activity level on a revertant per cigarette basis and
23 "tar" delivery activity increased as "tar" delivery
24 increased." Interestingly, on a revertant per
215
1 milligram "tar" basis, there is a weak tendency for
2 the converse." Do you see that?
3 A. I see that.
4 Q. And when it says a weak tendency for the
5 converse, it's saying that the revertant per milligram
6 of tar tend to increase as the tar delivery decreases;
7 is that right?
8 A. That's correct.
9 Q. Okay. And it says that's a weak tendency,
10 but it's a tendency, correct?
11 A. That's what it says.
12 Q. Okay. And then it refers to the Steele
13 article, correct?
14 A. That's correct.
15 Q. And it refers to the result in the Steele
16 article that says, "There's a negative correlation
17 between specific activity (mutagenicity on a revertant
18 per milligram condensate basis and milligram per
19 condensate cigarette in the Salmonella assay for 24 US
20 market brands." Do you see that?
21 A. I see that.
22 Q. And it goes on to report the result we were
23 just talking about. "Steele, et al. also observed a
24 positive correlation between mutagenicity and air
216
1 dilution."
2 A. Right.
3 Q. "They hypothesized that increased air
4 dilution, which generally results in cigarettes with a
5 lower yield of condensate per cigarette, might alter
6 the way the cigarettes burn and could yield a slightly
7 more mutagenic condensate." Do you see that?
8 A. Yeah.
9 Q. "However, similar to the results observed in
10 the present study, mutagenicity on a per cigarette
11 basis was lower for low condensate products in the
12 Steele et al. report since total condensate yielded
13 was lower." Do you see that?
14 A. Yes.
15 Q. And that's also consistent with what you
16 reported from that Philip Morris brand study, isn't
17 it, Doctor?
18 A. That's right.
19 Q. Okay.
20 A. Wait. I'm sorry. Say that question again.
21 Q. Let's see if I can. It's also consistent
22 with what you reported seeing in that Philip Morris
23 brands study you discussed?
24 A. The revertant per cigarette was numerically
217
1 lower in the brand study and that's what they're
2 reporting here.
3 Q. Okay. Now, Doctor, when we're talking, this
4 article is 1999; is that right?
5 A. 2000.
6 Q. I'm sorry. You're right. You're right.
7 This article, the Chepiga article was 2000, and the
8 Steele article was 1995; is that right?
9 A. That's right.
10 Q. Now, those articles still fit in up here
11 under in vitro; is that right?
12 A. That's right.
13 Q. And down here in the epidemiology you've
14 already told us was the best study of human, effect on
15 humans; is that right?
16 A. If you have well defined epidemiological
17 studies, then that's correct.
18 Q. Okay. And tell the Court -- well, the
19 Monograph, Monograph Number 13 is the -- kind of the
20 encyclopedia of the science related to low tar
21 cigarettes. The best current information; is that
22 right, Doctor? At least as of the time it was
23 written. How about that?
24 A. Yeah. I guess I'm not clear on how you're
218
1 characterizing that. I mean to me the encyclopedia,
2 I'm not sure --
3 Q. Okay. I don't want to make it difficult
4 with words that are subject to interpretation, but you
5 accept the Monograph that was released in November
6 2001 as being reflective of the scientific consensus
7 at that time about low tar cigarettes; is that right?
8 A. That's correct.
9 Q. Okay. And in the Monograph it talked about
10 tumorigenicity studies; is that right?
11 A. That's right.
12 Q. Of low tar cigarettes; is that right?
13 A. That's right.
14 Q. It talked about epidemiology studies of low
15 tar cigarettes?
16 A. That's right.
17 Q. It didn't say a word about mutagenicity
18 studies, did it, Doctor?
19 A. I guess I don't recall either way.
20 Q. You don't know one way or the other?
21 A. I would have to refresh my memory first.
22 MR. LOMBARDI: If I may have a moment, your
23 Honor.
24 No further questions, your Honor.
219
9 Q. (By Mr. Lombardi): Okay. We talked about
10 two ways of measuring, Doctor, today essentially. One
11 was on a per cigarette basis --
12 A. Right.
13 Q. -- and one is on a per milligram basis; is
14 that right?
15 A. That's right.
16 Q. And when you're talking about a per
17 milligram basis, you're talking about how mutagenic
18 for that particular weight of your tar sample; is that
19 right?
20 A. The way it's standardized in your results
21 from cigarette to cigarette so you can compare one to
22 the next.
23 Q. Yeah. But the idea is you take a milligram
24 of tar and you count how many -- how mutagenic that
220
1 milligram is?
2 A. That's correct.
3 Q. Then when you go on a per cigarette basis
4 you smoke the whole cigarette and then you add up how
5 much mutagenicity there is for all the puffs you take
6 in the cigarette; is that right?
7 A. You add that up on a machine without taking
8 into account how people smoke cigarettes.
9 Q. Okay. But when you say on a per cigarette
10 basis, you're taking -- smoking from the time you
11 light that cigarette on the machine until the time you
12 stop smoking on the machine and you come up with a
13 measure of mutagenicity for the total; is that right?
14 Excuse me.
15 A. That's correct.
16 MR. LOMBARDI: Did that clear it up, Judge?
17 THE COURT: (Nodding.)
18 MR. LOMBARDI: Thank you.
19 REDIRECT EXAMINATION
20 BY MR. ZELCS:
21 Q. Let me follow up with a couple of questions
22 on that. Did I understand you correctly that per
23 cigarette analysis does not consider compensation or
24 how people really smoke a cigarette; is that correct?
221
1 A. That's absolutely correct. I mean so the
2 comparisons that you make in the brand study is not
3 the comparison of the ISO to ISO or Massachusetts to
4 Massachusetts. What you do is you consider
5 compensation, and so even though lower tar might have
6 less revertants for the total cigarette, in fact, to
7 compare it to a person who's smoking a Red if they
8 went to a Light, the number of revertants they would
9 actually get per cigarette would substantially
10 increase because of the compensation, which is why
11 it's a more dangerous product.
12 Q. Okay. And I think there was another
13 instance where Mr. Lombardi was asking you questions
14 that really didn't deal with the way people really
15 smoked. When you're talking about an ISO and Mass
16 now, that doesn't take into account compensation
17 either, does it?
18 A. Well, it would take into account if you
19 happened to be that individual that happened to smoke
20 like the Massachusetts protocol, but in the population
21 we have a wide range of the way we smoke our
22 cigarettes so it's correct. It's not really
23 representative.
24 MR. ZELCS: Could I have CKT4960, please?
222
1 Q. (By Mr. Zelcs): Mr. Lombardi in his
2 questioning to you was suggesting that even if these
3 Ames tests were getting certain results, if there were
4 other assays that Philip Morris was using that maybe
5 trumped it and was a better analysis, --
15 Q. (By Mr. Zelcs): Let me direct your
16 attention to the bottom portion here and one of the
17 assays he talks about was the E. coli assay. Would
18 you magnify that? Do you see where they say if we are
19 to continue to use the E. coli assay?
20 A. That's right.
21 Q. Does that suggest to you that Philip Morris
22 had a high level of confidence in the validity of the
23 E. coli assay?
24 MR. LOMBARDI: Object. Leading.
223
1 THE COURT: Overruled.
2 A. Okay. In fact, there wasn't a high level of
3 confidence and, in fact, almost all of them, maybe all
4 of those assays that he mentioned were actually
5 abandoned by Philip Morris and in contrast to the Ames
6 testing which existed all the way through 2001. If
7 you look at the brands you don't see any of those
8 other individual assays, and that's because over time
9 they have dropped out and not been determined to
10 provide the same quality information as the Ames
11 testing.
12 Q. So basically he was running you through a
13 bunch of assays that Philip Morris on its own had
14 realized weren't the ones that they wanted to use
15 later on in time; is that right?
16 MR. LOMBARDI: I object to the form and I
17 object to lack of foundation, and I object to the
18 characterization, your Honor.
19 THE COURT: Well, --
20 MR. ZELCS: It's a fair characterization.
21 MR. LOMBARDI: Yeah.
22 THE COURT: Overruled.
23 A. The way -- Philip Morris clearly abandoned
24 the test. And they actually abandoned the test for a
224
1 good reason which is they had the positive Ames
2 result. Once they have the positive Ames result, they
3 needed to deal with that. Okay. Even if they have a
4 million other in vitro tests that say it's not
5 mutagenic, the fact is in that test it's mutagenic,
6 they need to know why it's mutagenic in that test
7 system.
8 So if you're starting off with an unknown,
9 you do a battery of tests because there are some times
10 that maybe the mouse controlled assay would have been
11 positive and the Ames negative. In which case you've
12 got to run with the mouse and a ball bat saying
13 figure out what's going on there. In this case, they
14 have the positive Ames test. They needed to deal with
15 that result.
16 Q. Likewise Mr. Lombardi asked a bunch of
17 questions about well, there's this strain you can use
18 in Ames and this strain and it might get you different
19 results and all of that, right? Do you remember that?
20 A. Right. Right.
21 Q. No matter what strain they used, whether it
22 was the TA98 or the TA100, did Philip Morris always
23 get results pointing in the same direction when they
24 tested using the Ames assay?
225
1 A. Using these two strains that they chose to
2 test, repeatedly they had the positive results.
3 Q. And for 25 years they kept using --
4 A. I was just going to say they were times that
5 you would have -- you would not have a statistical
6 significance, but when you always see the trend in
7 that direction, it is likely that if they had designed
8 the study using, for example, more cultures or more
9 replicates, it's pretty likely that stuff would have
10 tested positive as well.
11 Q. And for 25 years they kept going with the
12 TA98 and the TA100, right?
13 A. That's correct.
14 Q. And they kept getting results pointing in
15 the same direction?
16 A. They kept getting the same results over and
17 over again.
18 Q. Do you consider that pretty consistent?
19 MR. LOMBARDI: Objection.
20 A. They were actually -- at some point they
21 actually started using it to test their systems so if
22 they got new media in or they had questions about
23 their assays, they would go back and do that same
24 study over again to make sure they got the same
226
1 results.
2 Q. What you're telling the Court is that it was
3 so consistent that they were using it as a reference
4 tool, right?
5 A. That's right.
6 MR. LOMBARDI: Objection. Leading, Judge.
7 THE COURT: Well, overruled. Overruled.
8 You know, you're leading somebody that's not very
9 astute. It doesn't make that much difference in these
10 kinds of cases.
11 MR. ZELCS: I won't pull the exhibits out.
12 I'll just talk about them.
13 Q. (By Mr. Zelcs): He also showed you, and I
14 believe it's 20-M, an exhibit where he pointed out
15 that ventilation wasn't really the big actor, that it
16 was the paper and all this other stuff, right?
17 A. Right. Right.
18 Q. Okay. And you tried to explain something,
19 but he pointed out to you that's not my question. I
20 want to go into that right now.
21 Assume that a Marlboro Light and a Marlboro
22 Red, with the exception of the dilution, are
23 essentially the same in terms of their tobacco blend
24 paper and everything else, would the role that the
227
1 filter ventilation played be pretty meaningful in that
2 context?
3 A. Absolutely.
4 Q. Would it be the most meaningful actor in
5 that context?
6 A. Well, you would clearly see a difference in
7 mutagenicity and that would be the only explanation.
8 Q. The only explanation?
9 A. Right.
10 Q. Does the fact that he found a study in 2000
11 or one in 1995 that acknowledged a linkage between
12 filter dilution and increased mutagenicity, change in
13 any way any of the opinions you've given regarding
14 what Philip Morris should have done based upon the
15 years of all these test results?
16 A. No. I mean I was aware of those studies.
17 It was also clear what the public health community was
18 recommending at the time and what they didn't know.
19 Q. Let's talk a little bit about these mouse
20 skin painting tests and the nonfiltered cigarettes
21 that he asked you about. How do mouse skin painting
22 tests of nonfiltered cigarettes from the 1950s have
23 any relevance at all to the relative mutagenicity of
24 Marlboro Lights versus regular Marlboros or Cambridge
228
1 Lights versus regular Cambridges?
2 A. Well, the short answer is I really don't
3 consider it relevant at all. The explanation is that
4 in the '50s and '60s the tobacco blends were
5 different. You had different chemicals coming off
6 here with substantially more tar. And so in that
7 report they're talking about studies that were done in
8 the '50s and '60s versus more recently. The
9 cigarettes where the tar was different, there were so
10 many differences that were substantial, that I think
11 that when you try to understand the difference between
12 a Marlboro Light and a Marlboro Red, it just is not
13 the same thing.
14 Q. You also talked about adenocarcinoma or
15 however you want to pronounce it. Mr. Lombardi
16 offered some documents or he asked you whether or not
17 the lung cancer rates that were going down generally
18 and I want to follow up on that. Is there any basis
19 to conclude that light cigarettes have reduced the
20 incidence of lung cancer?
21 A. I would say no.
22 Q. I think you've already told us Philip Morris
23 had test results spanning 25 years indicating that
24 cigarette ventilation increased biological activity,
229
1 right?
2 A. That's right.
3 Q. Based on those results you have seen and
4 taking into account each and every one of the
5 additional studies that Mr. Lombardi asked you about,
6 do you have an opinion as to whether Philip Morris
7 should have engaged in additional testing before it
8 sold either Marlboro Lights or Cambridge Light
9 cigarettes?
10 A. Yes.
11 Q. And what is that opinion?
1 Q. (By Mr. Zelcs): Would you please answer the
2 question, Doctor?
3 A. The documents he showed looking at the 50
4 percent ventilation with things like threshold in
5 quotes, okay, in fact, you may not have the physical
6 significance, you have the trends if you design the
7 studies right, you may see a slight physical
8 significance, but I think what's important is we then
9 see Philip Morris continuing to do the studies to try
10 to figure out what it is.
11 I mean if they really thought that at 50
12 percent that was it, then they didn't need to go any
13 further, they didn't need to continue to do that
14 testing. But in fact they also had other studies
15 which I had mentioned, for example, the one with the
16 HANSA cigarette which was down to, you know, 27-28
17 percent which is right smack in the range of the
18 Marlboro Lights. And then, in fact, you see the
19 comparison of Marlboro Reds to Marlboro Lights and
20 they're significantly different.
21 Q. Is that an opinion that you hold to a
22 reasonable degree of medical and scientific certainty?
23 A. Yes.
24 MR. ZELCS: I have no further questions.
231
1 THE COURT: Recross.
2 MR. LOMBARDI: Yes, sir.
3 RECROSS-EXAMINATION
4 BY MR. LOMBARDI:
5 Q. Actually that HANSA study, the statistical
6 significance was at 33 percent, wasn't it, Doctor?
7 A. I don't think that's correct.
8 Q. Do you want to find it up there?
9 A. Sure. No. It's at 23 percent actually.
10 Q. Do you want to look at page 9-4 of the
11 document?
12 MR. ZELCS: What exhibit are you referring
13 to?
14 MR. LOMBARDI: The HANSA document.
15 Plaintiffs' 90.
16 A. 94. I'm not seeing pages.
17 Q. It's 9-4 in the upper right. It's a funny
18 system.
19 A. Okay. Okay.
20 Q. And it says there that for the cigarettes
21 HANSA 4, 6, and 8 the difference was statistically
22 significant. Do you see that?
23 MR. ZELCS: Mr. Lombardi, could I have the
24 page reference again, please.
232
1 MR. LOMBARDI: 9-4.
2 MR. ZELCS: Thank you, sir.
3 A. I see where you're referring to.
4 Q. (By Mr. Lombardi): Okay. And then if you
5 go back to the table. Doctor.
6 A. 11.1?
7 Q. The table on 1-3.
8 A. I'm sorry?
9 Q. The table on 1-3.
10 A. Oh, okay.
11 Q. The lowest amount of ventilation that was
12 statistically significant was HANSA-4 which was 33
13 percent?
14 A. That is not correct. The substitution of -3
15 has a plus next to it. It's a 23 percent ventilation.
16 Q. But do you see where it says for the
17 cigarette HANSA 4, 6, and 8 this difference was
18 statistically significant due to their differences
19 between substudies 1 and 2, no significance is given
20 for the cigarettes HANSA 3, 10, and 11?
21 A. I'm sorry?
22 Q. I'm talking about 9-4, Doctor, under
23 specific mutagenicity.
24 A. Well, they have results for both of them so
233
1 I really need you to clarify.
2 Q. Look at page 9-4. At 9-4, do you agree with
3 me -- I'll just show you. There you go. I'll get it
4 closer, Doctor. You've got that page, don't you?
5 A. Yes.
6 Q. And it says that due to the differences
7 between substudies one and two, no significance is
8 given for the cigarettes HANSA-3, 10, and 11. Do you
9 see that?
10 A. I see that.
11 Q. Okay. And then we go back to the table.
12 Here you go, Doctor. HANSA-3 was the 23 percent; is
13 that right?
14 A. In the bottom part of the table, that's
15 correct.
16 Q. And the top part of the table HANSA-3 is 23
17 percent?
18 A. That's correct.
19 Q. And that's what the text just said that it's
20 not statistically significant?
21 A. For the top part of the table. The bottom
22 part of the table, the text does say that it's
23 statistically significant on the next page.
24 Q. Well, in fairness to the Court, you didn't
234
1 report that there were some results for the 23 percent
2 that were not statistically significant, did you,
3 Doctor?
4 A. I would say yes, that's correct. I don't
5 know whether that was --
6 Q. So you don't object to my pointing out --
7 MR. ZELCS: Objection. Let him finish the
8 answer before you go.
9 MR. LOMBARDI: I thought he had finished.
10 Q. (By Mr. Lombardi): Doctor, --
11 A. I thought I was fairly representing the data
12 in this table.
13 Q. But it's fair to say, Doctor, based on the
14 text, that it is not -- the 23 percent is not
15 statistically significant for all tests, isn't that
16 correct?
17 A. That is correct. For all tests it is not
18 statistically significant.
19 Q. Thank you. And one of the things that you
20 were again shown, the brand study, and I wanted to ask
21 you one other thing. Incidentally you weren't meaning
22 to be critical of machine testing of cigarettes when
23 you were talking about ISO and the Massachusetts
24 method as being just machine tests, were you?
235
1 A. I'm trying to think about my intent. Why
2 don't I just clarify what I meant, which was that the
3 machine testing is not representative of what happens
4 with people when they smoke.
5 Q. But people still think machine testing is
6 worth doing to find out information about cigarettes;
7 isn't that right?
8 A. There is some information that you can get
9 from machine testing.
10 Q. That's why the Commonwealth of Massachusetts
11 came up with the Massachusetts test, correct?
12 A. That's right.
13 Q. And they came up with that test within the
14 last few years, correct?
15 A. That's correct.
16 Q. And that test was intended to be closer to
17 the way people really smoked cigarettes than ISO, the
18 international method, or the FTC method, is that
19 right?
20 A. That test was intended to be closer but
21 clearly understood not to be representative of the
22 general public.
23 Q. And the way they made it closer was they
24 covered some vent holes; is that right?
236
1 A. That's right.
2 Q. And the puff was more intense; is that
3 right?
4 A. The -- there was more volume to the puff.
5 Q. Okay. Well, if you look and that was --
6 that was thought at least to be more representative of
7 the way smokers smoked than FTC or ISO methods; is
8 that right?
9 A. That's correct.
10 Q. And if you look at -- this is the chart you
11 were on again, and if you look at the Marlboro under
12 the ISO method, which is the darker one, right?
13 A. The Marlboro ISO, correct.
14 Q. Do you see that? And that's the far -- the
15 far left. The Marlboro --
16 A. Yeah.
17 Q. -- excuse me -- under the ISO method. And
18 then you look at the Marlboro Light when it's smoked
19 in a way that's considered more similar to the way
20 people smoke, -- Can you do that comparison for me?
21 A. Yes.
22 Q. It actually shows the Marlboro Light is less
23 under that measure than the Marlboro regular is.
24 A. All you've done is by covering up the holes
237
1 --
2 Q. Well, can you answer my question?
3 A. It looks to be numerically lower.
4 Q. And what's going on is the Marlboro is being
5 smoked one way and the Marlboro Light is being smoked
6 more intensely if you look at that comparison under
7 the two machines, right?
8 A. Under this specific machine condition,
9 that's correct.
10 Q. And so under this specific machine condition
11 if you smoke -- well, you've heard people say that
12 Marlboro Lights would be smoked more intensely by
13 somebody who switched down from Marlboro regulars,
14 haven't you?
15 A. That's correct.
16 Q. And so under this particular machine
17 comparison, you would see that the Marlboro Lights had
18 less mutagenicity when smoked more intensely than the
19 Marlboro regulars would?
20 A. If you took a Marlboro --
21 Q. Is the answer yes, Doctor?
22 A. I'm sorry. Then you'll have to ask the
23 question again because I wanted to try to answer it
24 accurately.
238
1 Q. Is this -- Does this chart show that if you
2 smoked a Marlboro Light more intensely, as indicated
3 by the Massachusetts test, than the Marlboro regular,
4 the mutagenicity of the Marlboro Light is lower on a
5 per milligram basis? Does the chart show that?
6 A. If you smoke like a machine, then the
7 numbers are low.
8 Q. For Marlboro Lights?
9 A. Right.
10 Q. Thank you.
11 MR. LOMBARDI: Nothing further, your Honor.
12 MR. ZELCS: Could you leave that on for just
13 a second, please?
14 MR. LOMBARDI: Sure.
15 REDIRECT EXAMINATION
16 BY MR. ZELCS:
17 Q. Does less ventilation have a role in
18 explaining the result that Mr. Lombardi just talked
19 about?
20 A. That's exactly what it is. I mean they
21 basically took the Lights and made it into a regular.
22 MR. ZELCS: No further questions.
23 MR. LOMBARDI: No questions, your Honor.
24 THE COURT: Okay. Are we done with the
239
1 Doctor?
2 MR. TILLERY: We are, your Honor.
3 THE COURT: All right. Thank you, Doctor.
4 You will be excused, sir.
5 THE WITNESS: Thank you.
6 (Witness excused.)