INTERVIEWEE: Dr. Marvin Legator (ML)
INTERVIEWER: David Todd (DT)
DATE: October 23, 2003
LOCATION: Galveston, Texas
TRANSCRIBERS: Melissa Balog and Robin Johnson
REELS: 2283 and 2284
Please note that the recording includes roughly 60 seconds of color bars and sound tone for technical settings at the outset of the recordings. Numbers correlate with the time codes on the VHS tape copy of the interview. “Misc.” refers to various off-camera conversation or background noise, unrelated to the interview.
DT: My name is David Todd. I’m here for the Conservation History Association of Texas. It’s October 23rd, 2003, we’re in Galveston at the University of Texas Medical Branch and we have the good fortune to be interviewing Dr. Marvin Legator who has worked for the United States Food and Drug Administration in their genetic toxicology branch and is currently professor of Preventative Medicine and Community Health here at the University of Texas and has done a great deal to help understand environmental health risks and to try and promote more understanding in the community about how to prevent health impacts. I wanted to take this chance to thank you for talking to us.
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ML: Glad to be here.
DT: Could you tell us how you got started in your interest in toxicology and environmental health?
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ML: Well, what really intrigued me about the area of toxicology is that it is one of the few areas that you can combine good science with the goal of trying to help people. In other words, you’re almost a public health advocate if you’re a toxicologist because we are very aware of our environment the way people are exposed to hazardous substances. And the whole thing is how can we modify or remove some of the substances that can play a major role as far as their health is concerned. So I guess from my early days even in high school up through college and my doctorate degree my emphasis really was on toxicology, but I found in those days there really wasn’t such a thing as a curricula for toxicology. In fact, most of my colleagues have come into toxicology from other areas whether it be genetics or physiology or pharmacology. And I basically came into this area from genetics and microbiology and that’s quite opposed to what we have now or we do have are really good structured programs in toxicology.
DT: Was there anybody you could point to who was a mentor, teacher or colleague that encouraged you a great deal?
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ML: Yeah, I was very intrigued by a figure in Sinclair Lewis’s book by the name of Goldsmith and he—Gotley, rather, and he was a cancer researcher and this was in Aerosmith, of course, and he was a researcher in cancer and I thought that was really the kind of person I would like to imitate. And then there are a series of books during my particular time of growth and in high school by Dr. Paul Lecruth and he also was a writer and a scientist and microbiologist and he played a real influence on my life too as I read through his various books. And then right after college I—when I had my PhD degree I worked for Shell Oil Company in Modesto, California, so there I had an extremely good experience of toxicology in industry and from that point I went to the Food and Drug Administration where I felt that we were almost covering most of the areas in toxicology. We had tools but the one area that we had completely overlooked and had no way of even determining if there was effect was the area of genetic toxicology. That is the area where
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chemicals interact with our genetic material and cause various aberrations. So I went from the—from Shell Oil in industry to the Food and Drug Administration where I headed the branch of genetic toxicology. Then I went on to Brown University and I came to Galveston really because of a extremely knowledgeable clinician who worked for Dow Chemical, which is just down the line here at Freeport and his name was Dr. Jack Killian and together we had this great ideal if—of—what if we could look at all the workers, their pre-employment physical and see what their chromosomal analysis looked like. That’s when we look at all their genetic materials in this packed area of a chromosome. And we felt that if we did that and then moved sequentially with the worker to see how indeed his—if indeed his cytogenetic would change at all as far as aberrations that this would be an extremely good method of making sure they were not—workers were not exposed to hazardous chemicals. And it’s interesting because we did that for many years.
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I moved to Texas because I wanted to be a part of the enterprise that was going on at Dow Chemical in Freeport and I thought this was the wave of the future and I still do, by the way. And what occurred was fascinating. After our—after our having some of the most sophisticated instruments a really good group in toxicology basically looking for mutations we found what we were looking for and that is we found that Benzene caused chromosome breaks. Now the interesting thing about this is we were probably one of the most well advertised groups in Dow Chemical as far as TV and radio, you know, the latest state of the art application of genetic toxicology in the work place, but when we found—when we found Benzene caused chromosomal aberrations in workers then we found the going was a little tough. In fact, I think I can say with—in terms of the timing, that shortly after our findings there no longer existed a toxicology group at Dow
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Chemical. It was simply phased out. But my interest, of course, in looking at populations with various procedures, especially some of our current procedures, would actually be the way of determining if indeed we had in the workplace hazardous substances that had yet to be identified.
DT: Can you talk about your career at the FDA and discuss the different pathways that people get exposed to toxins in the environment?
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ML: Yeah, my reason, by the way, for going to the Food and Drug from Shell is because this was about the late 60’s, 1970, where we just had the Thalidomide disaster. Now I don’t know if any of you are old enough to remember Thalidomide, but Thalidomide was a chemical that was given to treat pain and various other conditions and it caused a condition called Phocomelia and that’s where children were born without arms and legs. And it was that chemical and it was easy to detect because of the rare outcome that this chemical caused. It was shortly after that period that I said well, we now have procedures for determining Teratogenicity that is the malformations in children induced by chemicals that we now have some procedures for doing that but the one thing we don’t have is looking at mutations, genetic changes that lead to cancer and actually can lead to various malformations. So I looked around and said where would be the best place to start something like this? And at that time the Food and Drug Administration had a fairly hefty budget and I actually went to the Food and Drug Administration with the mandate to develop a research group in this new area of genetic toxicology, which we foresee it to do.
DT: What was your work at Brown?
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ML: Right. From the Food and Drug Administration where I think we had one of the better genetic toxicology groups, in fact, one of the few toxicology groups in our country. I thought it was time to get into the academic life because I felt I had industrial experience. I had experience with a regulatory agency in government. Now would be the time to do some education and it was interesting because a very senior scientist and administrator for Brown University was with me on a airline coming home from Switzerland and we both attended this meeting. And he proposed that I come to Brown University and it was a fairly good offer and so by the time we landed I had accepted a job at Brown University.
DT: What sort of courses did you teach and what sort of students did you have there?
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ML: Yeah, right, and at Brown University I did the same thing except the course is teaching but still—my research was in genetic toxicology.
DT: You mentioned Thalidomide. Was this also the time when Silent Spring was published?
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ML: I don’t know how much of that was in Silent Spring. I believe Thalidomide was mentioned in what I consider one of the successors to Silent Spring; that’s Our Stolen Future. Thalidomide was certainly in that and it’s, you know, its been widely publicized. Again, this occurred about 65 to 69.
DT: You mentioned that the industrial managers at Dow were shocked and discouraged when they heard that you were seeing toxicological effects from chemicals in the environment. What other sorts of reactions did you see among people when they were starting to realize that there are these problems?
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ML: Yeah, it was amazing because up to that time you could walk into an embryology department and ask whoever was in charge if they knew anything about chemical inducing malformations and, yeah, yeah, they would shake their hands. They had never heard about it. We were very fortunate with—with Phocomelia and Thalidomide because it’s such a rare thing. This was really picked up by a clinician, an Australian clinician, and we could pick it up because they had never seen it before. But our problems in the area of developmental toxicology is the fact that when we are exposed to chemicals what they usually do is simply add to the already burden we have. But what made Thalidomide so easy to detect and really extre—exceptional was the fact that this was unique. Most things are not rare or unique. They simply add to our background noise.
DT: Why wasn’t there some suspicion early on that these new chemicals might have little resistance in humans and others kinds of animals?
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ML: Yeah, this is kind of a sad story but a few years back there was a National Academy of Science meeting on what classes of Asians have been tested sufficiently to say that they were a threat or that they were safe, whatever safe means. And this was called the Upton Committee. It was a—the former director of the National Cancer Institute, Charlie Upton headed this committee and what they found was rather interesting if not frightening. When you look at drugs, okay, about 25 percent of the drugs had not been fully tested for hazardous effects, 25. If you look at industrial chemicals it’s exactly the reverse. Seventy two percent had never been tested. So that means that we have been exposed to many, many chemicals that have never been evaluated for toxicity in any great detail. Now this has a extremely important meaning to us today because as I go around the country, as I interact with certain individuals who are exposed to toxic chemicals I notice that the one thing that they all tell me is that they had
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a federal or state official addressing them at a meeting and saying that there is no evidence that this chemical is dangerous. They’re exactly right. The only part of it is they never say what the flip side of it is. That there’s no evidence that this chemical is safe. In fact, its never been tested. So there’s a tremendous difference between a negative result in a well conducted experiment and something that’s never been tested at all. But you see the problem we now have is that a chemical that has not been tested is considered safe just as if it had been tested. And this probably is one of the major, major mistakes I think that is made continually by lay individuals is that they’re hearing correctly from the state, federal and so forth guy, but they’re not understanding that he says or she said that there is no evidence but that doesn’t mean it was ever tested. And if I—this is the biggest myth I think we have to explore and it’s much easier for a—somebody from EPA or what have you to say that there’s no evidence that this compound will cause you a danger. And they usually will not be asked has it been tested? So if I do anything else today what I’d like to do is they never take this ideal that there’s no evidence ask where has it been tested, how has it been tested and can I see the data? So if—if we do that we’ve accomplished an awful lot.
DT: Why do you think it is that there wasn’t a burden of proof placed on the companies that introduced new chemicals into the environment to show that they were safe and why is the burden of proof different for companies that introduce food or drug products where I understand they’ve got higher burden of proof and yet companies that are producing chemicals as byproducts of industrial processes have less burden?
ML: Yeah, well as you know it’s called the Food and Drug Information—Food and Drug Administration just for that reason; it looks at foods and it looks at drugs. And at foods it doesn’t look at that critically, but when it comes to industrial chemicals they were kind of the orphan for many, many years. And it was only in the mid 60’s or so that we really started to take a look at industrial chemicals and—and even today the amount of testing that has to be done in terms of industrial chemicals is nowhere near what we have to do in terms of drugs. So it was kind of the orphan and let me just give you some ideas of what this really meant. Even to this minute if you and I were sitting here and talking three years ago or four and you would ask me what is the permissible exposure level of an industrial chemical called Butadiene? This is used in the manufacturer of synthetic rubber. I would say to you, oh, it’s about a thousand parts per million, okay?
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As we sit here today and I was asked that question I’d say it’s one part per million just to show you the difference that we had. Imagine, four years ago it was a thousand parts per million permissible exposure to the workers. Now it’s one (inaudible). The same thing has occurred with chemical after chemical. As we get to know more about these chemicals we really learn their effects and how in fact they aren’t safe. So that’s just a commentary and the frightening thing as I said earlier the majority of industrial chemicals have not been tested or tested in a very non confident way to where you wouldn’t feel confident that the results were really meaningful.
DT: Why wasn’t there pressure to do more testing?
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ML: Well, I guess it’s economics, of course. Look at the Dibromochloropropane. This is a classic. It’s called DBCP. It was manufactured by Dow and Shell. Again, I’d say in—in the 60’s and 70’s and it was a nematicide. It killed worms in a soil. And it was on the market for 16 years. Sixteen years workers were exposed to it. And I like this story because we had two workers allegedly drinking a glass of beer together and they both discovered that as much as they tried they couldn’t have kids. These are the workers themselves. Now they then went back to their fellow employees and found that none of them had families and this is 16 years later after they’ve all been exposed. And then they finally went over to the University of California to a scientist by the name of Wharton who tested them and found they were all deficient in sperm or lacking in numbers. And
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that led to the ban of DBCP. Now that leads to any number of questions because if there is any simple wh—thing that one could do is to look at sperm counts. I mean this was not a, yeah, a fantastic DNA kind of a solution that you were looking for some rare basis. I mean this was just sperm, looking at sperm. And the other question that one has to ask, if you have a company doctor like Dow and Shell did where in blazes was he? I mean if he just in his interview asked about, you know, how many kids do you have, it would have been apparent, but yet it never came out. And to my knowledge I have never really heard a reason fr—why this really happened. And we have, I’m sure, many instances like this occurring frequently. Again, this was just a lucky find where the workers themselves discovered it.
DT: Is it that the companies complain we could never test 70,000 substances. We would have to go bankrupt if we had to do that. Is it that they just don’t want to factor that into their bottom line?
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ML: You’re right. And my feeling is, of course, economics enters into it, but I think the major thing is what I said earlier. When I say that if it’s considered safe, you know, unless proven otherwise then certainly there’s no incentive to testing. I mean if I test this product and I’m only interested in the bottom line, the only thing that testing can do for me is hurt that product. And if it has a wide economic base, boy, I’m not going to look at that for sure. So certainly that is part of the reason. We’re doing better now. We do have some laws. I think perhaps our level of consciousness has been raised and we do—I’m—I—I feel we are doing better. But still we have so many, many things that haven’t been evaluated. We have so many problems to look at. Major things like cancer are so difficult. You have a two year animal test. It’s extremely difficult to find any really good results in epidemiological studies. So there are many problems. The things like c—cancer, developmental effects, etc. in the target species man are extremely difficult and require a lot of resources. So that too is part of the equation.
DT: It sounds like a lot of the evidence that’s coming out about toxicological problems is coming out from effects in people that are exposed.
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ML: I’m afraid that’s all and, you know, I often wonder what we can do to help people who are victims of chemical exposure. This is why I wrote the book Chemical Alert. Because if you take a community that’s exposed to chemicals where do you find these communities? You find them next to an industrial complex. You find them next to a hazardous waste site and usually these are communities in poverty. These are communities who have very little access to resources. You can bet your bottom dollar that they’ve been told by state and federal officials that there’s really no problem for the reasons I’ve—I’ve given. And what can these people do? This is really a real bur—this is really a problem that we are faced with and have very few answers. Probably we can take a lesson from going back to Love Canal, which is the beginning of a lot of this waste
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disposal problem, and there they had a terrific group called the Homeowners Association. I’ve never met a group of people and I still am in contact with some of them, that have been so effective. They took courses on how to handle the media. They were able to bring the President of the United States down to this little area in upstate New York. And they were able to actually have their land and homes purchased so they could relocate, but that’s a unusual group. It’s really an unusual group. It’s really hard work to organize communities so they can be effective and so they can get some results, so they can get some sort of medical treatment. We have helped, I hope, many communities by coming out with our book that says how do you really organize, what do you look for, what is important? And we ourselves carry on community surveys just to see indeed what is the really key effects in terms of their adverse health outcome?
DT: Is there much value to testing lab animals; mice, rats, fruit flies, whatever?
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ML: Of course, of course, if we indeed realize that—how difficult it is to do human experiments, especially—let me give you an example of what you’re faced with. Let’s say we have a youngster who has ringworm—ringworm of the scalp, okay? And we treat this youngster for three months, whatever, with a chemical called Griseofulvin, which is a antifungal material. And let’s say that 15 years after that treatment this child comes down with a malignancy. Now ask yourself what is the chance of ever figuring out that that Griseofulvin that he had as a youngster was due—what’s caused his cancer when now he’s a grown adult? Almost nil. It’s—it’s a difficult, difficult thing. If we look at cancer with a 15 year or more wait and see period it’s a really hard thing. Most of the times that we have found that we have a human carcinogen is in the occupational setting where we can get thousands of workers where we can really do some big studies. I don’t think we’re going to see too many more big studies like we have in the past. Hopefully,
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it’s because our level is reduced but also because our resources are needed. So I would say that animals have to be our first line of defense. I—I just don’t see how we can get away with it. And thing—one thing that I can say that I think is rather encouraging is every known human carcinogen does cause cancers in animals. So a two year animal study with complete pathology is still our gold standard right now and certainly if we have evidence that this chemical causes cancer, causes mutations and so on in animals then we should really think very strongly of leaving it on the market. Now the ability to take a compound off the market is exactly proportional to its economic status. When I first started out working this area at the Food and Drug Administration I said well, if I don’t want to get into any political debate, if I don’t want to have any problems in terms of the meaningfulness of my work I said I’ll do it with a chemical called Aflatoxin.
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Aflatoxin is a product pr—a product of a mold and there’s no constituency for a mold, so I didn’t have anything to worry about because this appears in brown nut and other products, but this was something, you know, everybody was willing to do something about. But most of the time when we s—studied chemicals we looked to study those kind of chemicals where a number of people are exposed and this sometimes becomes tough. I mean there’s no getting away from the fact that as in toxicology as many areas of public health you usually run afoul of some of our larger corporations and so on and it’s a fact of life. Some of our large companies are doing a better job than others. So it’s a mixed bag.
DT: When we were talking about animal testing how confident do you feel about scaling up from what are suspected to be safe levels for a half pound animal to a hundred and fifty pound adult?
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ML: Yeah, th—this is, of course, a problem and believe it or not we have examples now of chemicals that are more active in humans than they are in animals. So this is always not a fact. Let me—let me first say this. When you test animals, if you have a concentration and can use 50 animals, this is a big experiment, okay? And yet you’re trying to extrapolate from those 50 animals when there may be millions of humans who are exposed to it. So look at the disparity between the number of animals that you can use and the exposed population. So what does a person—what does a scientist do? He says well let’s go look at those response curves. In other words, the higher we go that will somehow compensate for the difference in numbers, the disparity in numbers. Well, what we’re really finding out, which is fascinating, the cornerstone of toxicology was always at those response curve. The higher you go the more the effect. Well, we’re finding out with, you know, estrogens, with other chemicals that that doesn’t necessarily
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hold. We get a U-shape curve now. We’re finding that the higher concentrations may be less toxic than the lower concentrations. And there’s a number of reasons that we can go into for that. So with some of our recent evidence, especially with the Zeno-Estrogens, it may be that our Dose-Response relationship is really not holding. And a while ago we looked at three chemicals, Benzene, Vinyl Chloride and I forget the other one. Anyhow, with three chemicals we found indeed that the higher you go after a certain point the less effect you get. Butadiene was the third chemical. So we’re not that—those response curve may not really hold for all chemicals. This, by the way, will really have an effect on our regulatory colleagues.
DT: And I guess conversely lower doses necessarily don’t cause less response in that you can’t extrapolate down to some safe level. Is that…
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ML: That’s right. You’re ab—exactly right because we’re finding at the higher dose what you’re doing is you’re inducing another set of enzymes that detoxify the chemical faster than at a low dose, so the balance is kind of shifted. So it—it’s fascinating but we still have a long way to go. Many of our chemicals have not been tested or tested adequately. We’re finding that when we get more data we usually find that the chemical is far more dangerous than we thought. And there’s a lot of, I believe, myths floating around like this extrapolation from animals. Like why aren’t we testing? All these are—are things that we have—encounter and have to do something about.
DT: This last case that you gave us of the U-shape curve versus the S-shape curve, does this kind of relate over to chronic and acute exposure where you might have an occupational exposure at very low level for many years being actually more toxic than somebody getting a brief…
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ML: We’ve always said concentration times time equal effect, okay? We’re not quite so sure now of that concentration. I should mention another thing. When you do studies on animals you’re doing studies usually with animals in which you know or can predict their background tumor incidence. These are animals that have been specifically bred for the cancer bioassay because they have a known background, lower than 15 percent say and above five percent; something in a narrow range. When we go into humans we are not that genetically precise and so you have tremendous variability in humans and that variability is not accounted for (?) animal study. So you know my old professor used to say are we—is man more like a rat or a mouse? The answer is what man because we almost mimic every—there is a subset of us that will mimic the animal metabolism. So when we get into humans it’s a far
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more different effect because of the individual’s susceptibility. I like to point out the Burns Factor. Here we have George Burns, okay, who smoked every day, womanized every day, drank every day from what I understand, and you know when his—when it was asked by a journalist why his doctors hadn’t told him to stop it his answer was my doctors are dead and this is exactly right. Here is a s—here he did everything that you would think would destroy longevity and yet he lived to almost a hundred and why? Well, the George Burns Factor is obviously he had a very rare way of metabolizing these chemicals that most of us do not have, so human susceptibility is a very, very wide range. We’re now beginning to look at it with various assays that we have, but this also adds to the complexity of the kinds of things we’re doing.
DT: If you have been exposed for five years to something already, they say when you give up smoking every year you stop smoking you get back ten years of your life, for example, but if you’ve been exposed for five years, ten years to this can it be filtered out of your body? Do you have to be cleansed?
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ML: Well, you know once somebody comes in with a say a central nervous system disorder, which we see from so many chemicals, there is no difference in treating that person with a chemically induced CNS than there is with a person who may have gotten it because of genetic problems. So once the disease is there the medical treatment is the same, you know, there’s no—there’s no difference. The only difference is you may have to be able to identify that chemical and you may be able to say well, if this chemical causes blood dyscrasias or causes a number of cancers in the metabolic system well then we’ll do some human monitoring to see if we can find it at the earliest state to help these people. But once the disease occurs, and as I say this is usually just the increase of our background rate, there’s no difference in treatment if it’s chemical or non chemical.
DT: So for those men who were exposed to the DBCP, take them away from it, get it out of their system and three years later are they producing children? I guess that’s the question.
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ML: Yeah, well the—the DBCP story is that if indeed they were exposed to certain concentration of the chemical it is irreparable—irreversible. Others you may be able to build up slightly, but there will always be a deficiency.
DT: My understanding is that a lot of toxicological data is based on what it takes to kill half of a population.
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DT: And I’m wondering if that’s useful in extrapolating from those kind of figures to what causes some kind of mutation, some kind of less serious disease in a smaller part of the population?
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ML: Absolutely not. I mean one thing about an animal study you should be able to ask the right question, okay? We may not be able to ask the right question in humans. It’s interesting. Humans we can’t ask the right questions but we can get a good answer and it’s just the opposite in animals. We can get a good answer but we may not get the right question. But the truth of the matter is if you’re looking for mutations, if you’re looking for cancer, if you’re looking for developmental effects there are specific procedures in each of these areas that are totally different than looking at LD50 or even kidney effects. So it has to be a battery of tests that have been pretty well designed we use in the drug field, although it’s not perfect, but there are tools in all these areas that can be used. And one good thing is I—I—I know that the chemicals now, even industrial chemicals, are tested to a greater extent than they were say even 10, 15 years ago. But unfortunately we have a tremendous backload of chemicals that have been with us say since the early 60’s and even now they’re still are some holes in our testing.
DT: You said a moment ago that the mice and rats that might be used for testing the effects of some chemical have very well understood strengths and weaknesses.
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ML: Yeah, yeah.
DT: And I was wondering if they also have very well understood background loads?
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ML: Yeah, they—they are—they are selected in cause of a known background in terms of their tumors. That’s, you know, partially why you select them.
DT: How do you distinguish the effects of individual chemicals?
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ML: Here’s our future as I see it. We are now being a lot better—have much better techniques than we had when I wanted to start—when I did start testing the people at Dow Chemical using Cytogenetics. We are now be—we are now able to h—to look at people with a series of biomarkers that really will—will predict their sensitivity. In fact, the Cytogenetic assays will predict if they’re more likely to have cancer. I mean you’re not able to say that this test means you’re going to have cancer because heck, somebody can walk out the door and get run over by a car, but you can say that this is from what we can tell looking at his genetics that he’s more likely to get cancer or than—than somebody who is not at that level. So we have a number of biomarkers
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coming out now. Cytogenetics has really taken a great, great turn where we’ve made tremendous advancements and we can say these people are a great risk for cancer right at the present time or are not. And if they are exposed to chemical A, B and C we can say the risk correlates with their exposure. So we’re getting much better at being able to look at our population and say which is a high risk population versus a population that has a lower risk, and I think that’s our future. We’re fortunate enough at this time to have a lot of tools looking at our target species man, which we didn’t have in the past. And the real trick now is to use it, that’s it.
DT: You are talking a little bit there about how to distinguish the effects of an individual chemical from the background loads. What about how to understand the risks from a single chemical in synergistic effects with other chemicals?
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ML: Yeah, that’s a—that’s of course another major problem. When we do our testing in animals we do it with a single chemical. There’s not—I don’t think any of us are exposed to a single carcinogen during our lifetime. In fact, I like to analogize our—our experience to something I call the road to cancer. And the road to cancer for me puts everything in a fairly good perspective. I say let’s visualize a road. At the end of that road is cancer. One third of us are going to reach the end of that road and that’s a given. Now where we start on that road depends on our genetic background. Let’s say that we already have a genetic problem; Downs Syndrome or what have you. Instead of starting at the beginning of that road you’re halfway down that road at birth, okay? Now everything you do to yourself determines how fast you go down that road. If you’re a smoker you’re going to get in the fast lane. If you’re a
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smoker and are exposed to Benzene now you’re really zooming down that road. So if you take my road to cancer you can see that everything we do including our lifestyle, our exposure to chemicals, our genetic heritage, all are integrated into our reaching the end of that road or not. Now by saying that I am saying that if we have a malignancy it’s probably not due to a single factor. It’s not due to Benzene alone or smoking alone. It’s due to the integration of our whole lifestyle and everything we do to ourselves that gives us that malignancy and chemicals play a major role in that.
DT: How do you both recognize that there are legitimate synergistic effects and yet give some credence to the fact that some of these chemicals are a problem?
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ML: Yep, the simple answer and of course we’ve had experience with this with Johnson and Johnson and ethylene oxide where they didn’t want to expose women because its cause supposedly may effect the child and genetic screening, we’re worried about that. You know I talked about how we can pick up susceptible individuals. Well, when we pick those up does that mean he’s not going to be allowed to work? So this is a lot of problems and the simple answer to that is the workplace should be safe for all these people. That there’s no reason for somebody who may be genetically susceptible to a chemical, okay, not to be protected by that company from exposure, so the answer is the workplace should be a safe place to work where even a subset of sensitive individuals can work without increasing their problems.
DT: Just a moment ago you gave the example of the road to cancer and that some of us start farther down the road and some of us go faster down the road. My understanding is that a lot of toxicological testing is done for what would be safe exposures for mature young adults, I guess, but there are more sensitive populations such as children and elderly as I understand. How do you protect those other populations?
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ML: Well, it’s actually the—the sick, the young and the old. Those are your three most sensitive populations and those are c—by the way, you know there is such a thing as a Healthy Worker Effect and a Healthy Worker Effect says that in industry you have selected the least susceptible group of people to work. So when you do a study in a workplace you should not be looking at say overall averages for the country, but you should be looking at another group of workers who aren’t exposed to that chemical. Anyhow, that’s the Healthy Worker Effect, but you are absol—you’re absolutely right. We’ve always looked at individuals, usually young adults who are healthy in many of our studies, and we are just coming to grips with that right now where we’re starting to look at children, where we’re starting to have different kinds of regulatory laws for children versus adults. So the—the ch—the child group now is
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being singled out for greater protection than ever before, but probably the—the most susceptible entity that you can find is the developing embryo and there we’ve still got a lot to go, a lot to do. We are seeing now a group of chemicals if given to the adult can cause mutations in the embryo. So you have the transmission through spermatogenesis from a male to the female of the offspring and we’re seeing that in terms of cancer and also in terms of some malformations. That’s a very comp—you can see how complicated this area can get very quickly.
DT: How can you do meaningful toxicological testing when some of these effects may take more than one generation to appear?
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ML: Difficult, difficult even in animals. We do have a three generation animal testing that the Food and Drug does right now. You can—you’re all—you’re going to be able to detect something like Phocomelia if it’s rare enough to stand out, okay? As I said most things are just adding to the background noise we have. Epidemiology is a very insensitive tool, so it—it’s a tough deal. You want to do as many meaningful studies as you can in animals and then you want to use biomarkers to the greatest extent available to determine possible or potential outcomes in man and that’s about where we are now.
DT: I understand that there is a lot of hormonal disruptions that people have been starting to see in the last decade or more. Do you think that those are significant as the cancer causing chemicals that we’ve worried about for many years?
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ML: I think so. Oh, I think that certainly if I was living near a waste disposal site where they have a lot of chemicals like we had (?) down the road here or where we’re near a chemical complex like you are in Beaumont and Port Arthur. I think there is good reason there to worry, really, because you’re looking at a number of different chemicals many of whom that have not been evaluated correctly or intensely and that—that’s just the fact of life. There are ways of trying to say how bad a situation is. Air monitoring, we’re doing something good right now with a data base that the EPA puts out where it tells what each plant puts out into the environment and to any of the (?). The trouble is it is a self reporting deal. In other words, (?) reports what
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it’s putting out in terms of contamination and we don’t really know how accurate that is. That’s a TRI data. So I think we’re moving in the right direction but ever so slowly and it’s—it’s tough to be exposed to a chemical and know your neighbors are and to figure out a course of action. I—I’ve been in so many communities that just don’t have any hope of doing anything. That’s just a—that’s just where we’re at right now and I hope we’re going to improve.
DT: My understanding is that some drugs and chemicals were tested in past years on African Americans, prison populations and I think even Jews without their permission or consent and without their knowledge sometimes. What do you do with that kind of data? It’s useful but is it tainted?
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ML: I’ve never been faced with that—that particular problem. But it seems to me that if that data is available and there’s nothing you can do about turning back history then it would be rather silly not to use it to see if it can tell you anything if we can get something out of it. I’m just trying to think of—as I said I can’t think of any—any time I’ve encountered that particular problem. Certainly we’ve met—at this day we would never do something like that. I mean we have the IRB’s and so forth in every university, so you never really encounter that kind of a problem. I know when I was with the FDA the place where everything was tested whether you were with prisoners or in Yugoslavia for some reason but I think we’ve gotten away from that.
DT: How useful are the Effects Screening Levels and how did they come about?
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ML: I know some—a individual who has often said to me who’s in the business of risk assessment he said that God created astrol—astrology to make risk assessors look good and I just think there’s a lot of truth to that. Risk assessment is extremely difficult. What really is absolutely wrong is for the risk assessor to say that this chemical will lead to so many cancers in so many individuals per year; absolutely ridiculous. There’s no way that we can do it. It’s a extremely uncertain science with many factors that we take into account probably wrongly and I’ve already mentioned how due to dying four or five years ago was a thousand parts per million by the risk assessors and now it’s one. So risk assessment is extremely difficult and the way I use risk assessment if I use it at all is to think of broad categories. Certainly I can tell
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the difference between sacharrin, which is used as a sweetener and asmicotoxin. I was talking about Aflatoxin. So I like to—to say okay, I will not pay any attention to the numerical numbers. They’re really meaningless. I’ll try to put things into classes; A, B, C and D and not go any further than that. The ESL levels that you mentioned, Environmental Safety Levels, are basically based on some of the old workplace standards. Even though you put a factor in they are totally wrong, completely wrong, so I hope we get away from looking at risk assessment as such an exact area like putting on specific numbers when the best we can do, you know, and even that isn’t very satisfying, is to talk about some major categories; A, B or C. So risk assessment and the modeling is difficult. If we see many more U-shape curves it’ll almost be inconsequential in terms of the precision that you—we think we have in risk assessment to the realities.
DT: With risk assessment some people sometimes compare the kind of chemical exposures that you get in the workplace with other kinds of risks that seem to me to be quite distinct whether it’s driving a car or flying in an airplane; things that are taken on voluntarily. Do you see a qualitative difference there?
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ML: No, I—I really don’t. When they, you know, when we compare chemical risk factors and we try to talk about risks of driving a car or risks in flying a airplane, two things, when a community or workers are exposed, okay, they don’t know it. They don’t know what’s happening to them, okay? That’s quite different than making a voluntary deal like getting in a car or smoking a cigarette. That’s perfect—that’s tremendously different. The other thing that I—I see is, you know, we have fire departments not because we have a fire every day but they’re there to protect us and the same thing here. If this compound is carcinogenic you should know it so you could protect yourself. I mean many things we do is to avoid risk even though that risk may not be great, it may be minimal. In the workplace we have involuntary exposures to toxic compounds, which is quite different.
DT: Could you give us a couple of examples of epidemiological work?
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ML: Yeah, we have just recently concluded a study, I like to call a symptom survey, because epis a—you know, epidemiology is very difficult. So we just concluded a symptom survey in the Port Arthur Beaumont area and that was interesting and we compared it to Galveston, by the way. And we found in about 12 different categories and this was simply a—a survey that was carried out by asking questions of the citizens of Port Arthur and Beaumont. What we found that in literally every care—every area we looked at CNS effects, a central nervous system effects, kidney effects, liver effects, blood dyscrasias on and on, that the Port Arthur Beaumont area was many, many times greater than the Galveston area. So it was statistically positive for almost everything we looked at in that area. We could not look in that kind of study
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at obviously cancer or reproductive, that takes much—many more numbers. So we were just looking as—and we do this very frequently as a kind of a descriptive study to say really are these people correct when they say they have all these symptoms. And we did that with a hundred people in Port Arthur Beaumont and a control group and we think this is a very effective instrument; nothing else to point out the real problems and why it exists. For instance, we did another study near—in a community actually where they lived right near a kiln. I forgot the name. I think in Waxahachie, but it was where they were right near a kiln and there we found by a symptom survey that their major effect was respiratory problems, which made perfectly good sense because of the particular matter that they were inhaling from that partic—from the particular kiln that was there. So we’ve done quite a bit of—of those kinds of studies.
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But what I really like to do because I think it’s the most definitive thing that we can do is do the chromosomal studies or mutation studies, especially in a workers population and I already mentioned the fact that we did—not we, but studies were carried out at Dow Chemical with Benzene where it was found to be chromosome breakage. We did recently excellent studies with Butadiene where we showed how they effect the genetic material of exposed workers.
[End of Reel 2283]
DT: If you could resume with your story about the Waxahachie situation.
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ML: Right. Yeah, we published on that in the (?) Journal and I hope we had some influence in that community, you know, in making both them aware and also the—the regulatory agency. And I believe we have been able to reduce the particulate emissions from that particular plant. Then—then we—I should say a group of my colleagues did a study on Butadiene and—in a workplace, and the outcome of that was truly a positive in that the outcome with Butadiene was one of the factors in reducing the exposure from, you know, I told you a thousand (?) to about one to two parts to one part per million, so that was kind of satisfying. So we—we do have I think many times positive outcomes from our studies. The reason is data is lacking and if you supply the data you can make some intelligent judgments.
DT: Do you have any advice for either your fellow researchers or the government or for effected communities on how they can…
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ML: I’d—I’d like to see our regulatory agencies become closer aligned with the populations that they are supposedly monitoring. There’s often a disconnect between a community and the regulators. And many times if you go into a community and you ask who the villain is believe it or not it’s not the toxic waste generator it’s the officials from the state and federal agencies who they think are there to protect them and very quickly learn that they don’t. And so that’s where the greatest animosity comes almost in every community I’ve been to—at. And again, the reason is because of this deception about there is no problem when these people know they’re having a problem. So I’d like to see the government agencies do a better job of interacting
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with communities than we’re doing really right now. I would obviously like to see something we call the Precautionary Principle come into use. The Precautionary Principle says that if indeed you don’t have the safety data you don’t have a market. In other words, we get the data before people are exposed, but that’ll be a long time in coming I’m afraid. And the good news is we have some extremely good tools that have developed because of molecular biology that allow us to have more information than we ever would dream possible five, ten years ago.
DT: Has it either been rewarding or frustrating to have to ride that boundary between sick people who you know and data that they say lies or is misleading.
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ML: Yeah, good point. I mean if you were—if you were a government official sitting in North Carolina and putting pins on a map you’re not going to be nearly as excited about the pins on a map as if you were down there actually talking to these people and listening to them. So there’s a tremendous disconnect between that. The second thing that I think—I hate to say it, but I think plays a very key role. If you look at a government employee of which I was one and you look at these poor people here with not many resources and you know that if you say anything that’ll antagonize the large toxic waste generator there may be hell to pay from your superior. We see this happening with whistle blowers all the time. So you don’t have
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any—anything to worry about here, but you sure as hell do if you really involve the toxic waste generators. And, you know, we often talk about the revolving door and this is operating beautifully now. Usually if you’re in government and do the right thing you will get a job in one of the industries that you regulated. We see this going all the time. So there’s—there’s many reasons, not appropriate ones, but there are many reasons why the individuals who are exposed do not get the attention and do not get the programs that they really need.
DT: Do you feel that in your long and successful career you’ve paid a price that these things have been leveled against you but you would do it again anyway or not so?
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ML: Well, I—I—I think the answer is yes and I think it really—it really is a point of judgment, okay? You don’t rush out with something that you think may be not really factual, but if you come out with good data, pure reviewed stuff, it’s very hard to refute. And—and that’s basically our—our—our really—our lifeline is publishing in credible journals and then going from there.
DT: Well thank you.
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ML: One of the dismal failures of toxicology that I hope some day will be corrected is the fact that our medical students get almost no toxicology while they’re going through medical school. And I think this has a tremendous meaning. If we could get to the medical students and show them the importance of toxicology before they’re out there practicing I think we’d have a whole new advocacy group.
[End of Reel 2284]
[End of Interview with Marvin Legator]