Interview with Frederick vom Saal, Ph.D.


Vom Saal is a Professor of Biological Sciences, University of Missouri. A leading researcher in the field of developmental biology, Vom Saal has studied the effects of both natural and synthetic hormones at extremely low doses. His studies have shown that extremely low doses of hormones can permanently alter development of the reproductive system in mice. He has also studied how manmade chemicals, including plastics, can mimic hormones at extremely low doses.

Interview conducted in February 1998 by Doug Hamilton, producer of FRONTLINE's "Fooling With Nature."

DH: You've said that the doses at which hormones affect the body are extremely low. Give me an example to make me understand that.

FvS: The issue of the amount of hormone that actually causes effects is very difficult for scientists to talk to people about because we're dealing with numbers that are outside of the frame of reference that anybody is going to be thinking about. We see changes, profound changes, in the course of development of essentially the whole body of experimental animals, and we're working with mice and rats, and we see these changes at fifty femtograms of the hormone per milliliter of blood. That's 0.05 trillionths of a gram of this hormone in a milliliter of blood.

DH: And what sort of effect does it have?

FvS: We see changes in the functioning of the prostate. We see dramatic change in the sprouting of glands within the fetal prostate. We see changes in testicular sperm production. We see changes in the structure of the endocrine control region in the brain, which is accompanied by changes in sex behavior, aggression, the way these animals behave towards infants, their whole social interaction, the way they age, the time that they enter puberty, the age at which they cease reproduction. It changes their entire life history, and these changes are capable of occurring at very low levels of hormones.

I remember when we first did this and I was a post doctoral fellow, and my advisor and I looked at the hormone levels and said, "My God, these levels are so staggeringly small and the consequences are so immense it's amazing." Even to biologists, it's amazing.

But what you have is the entire field of toxicology thinking of a millionth of a gram of a hormone or a chemical as being this staggeringly tiny amount, and to most people if I said there's only a millionth of a gram of it here you'd say, "How can it do anything?" A millionth of a gram of estradiol in blood is toxic. The natural hormone is actually operating at something like a hundred million times lower than that. So when you have a physiologist thinking of a millionth of a gram, you have that physiologist thinking this is a toxic high dose. When you are raised in the field of toxicology you are looking at that from the other perspective of "My gosh, that's such a tiny dose, it couldn't do anything."

So now what we have are two different fields coming into this issue and looking at a dose as either staggeringly high or staggeringly low, and it's not surprising that there is a clash occurring with regard to dose effects.

DH: Can you again describe the results, the developmental effects in your laboratory mice, that you are seeing with these unbelievably small changes in hormone levels?

FvS: We published a paper just a few months ago in the "Proceedings of the National Academy of Sciences" in which we experimentally elevated estradiol levels in mouse fetuses during the period when their reproductive organs were forming. And what we did was we experimentally elevated estradiol by one tenth of one trillionth of a gram of estradiol in a milliliter of blood. We estimate that we're increasing estradiol by about one molecule of estradiol per cell in the body. Okay? The consequence of this is that at the end of the first day of development of the prostate in the male fetuses we could see dramatic change in the sprouting of prostate glands. We rendered the prostate abnormally enlarged, and this was detectable within twenty-four hours of the beginning of its embryonic development. And when we looked at these treated animals as adults, that difference had persisted. They had abnormally enlarged prostates that were hyper-responsive to hormones.

Now, prostate disease is for every male in this country and for every male in the world a very, very serious concern. It's the largest bill to the medical community. It's the most prevalent disease of aging in humans. Seventy percent of men, by the time you're seventy years old, will have an abnormally enlarged prostate. We caused this to happen at the first day of embryonic life with that change in estradiol. That's how sensitive embryonic organs are to these staggeringly tiny changes in hormones.

DH: How might the changes you are seeing in mice relate to prostate disease?

FvS: With this experimental manipulation in mouse fetuses, we have caused the prostate of the mouse to become enlarged. And it would appear that this is an animal that's then going to have a higher probability of developing a clinically enlarged prostate that's going to cause it physical problems as it ages, because as the prostate gets bigger and bigger it squeezes down on the urethra and you can't urinate. And if you don't fix that you'll die.

DH: These hormone levels you're talking about are inconceivably low, staggeringly low. How do we even begin to measure them?

FvS: For some chemicals, and for some hormones, the technical capacity to measure them is actually less sensitive than the body's ability to detect them. We've been working with a chemical, bisphenol-A. It's what polycarbonate plastic, hard plastics, are made out of: CD's, the plastic in your glasses' lens, milk containers, baby bottles. It's the chemical that they use to line cans with, it's the chemical they put on your teeth as a sealant and it is a very potent estrogen. It mimics the hormone that women produce in their ovaries, and it mimics this hormone estradiol that is actually being produced in fetuses and during pregnancy that is a major coordinator

or an alligator or any other animal.

Estradiol plays a critical role in development and then normal functioning of the body for the rest of an individual's life. The amount of estradiol you're exposed to throughout your life is also the best predictor of breast cancer. This chemical mimics that hormone. The body can't tell the difference between bisphenol-A and estradiol. In other words, it sees this chemical and it thinks it's getting exposed to its natural hormone.

DH: So you're saying that the hormone that has the clearest link to breast cancer, the hormone that is responsible for sexual development in any animal or human, is found in plastics?

FvS: Absolutely. The plastic materials, if they are polycarbonates, are made with this chemical bisphenol-A. And you can think of polycarbonate as a house made of bricks. Essentially you take this brick, this building block, which is bisphenol-A, and you link it together with other bisphenol-A molecules. That's a polymerization reaction. The bisphenol-A is the monomer used to construct these plastic materials. When it's attached to another one, that forms a polymer. And unfortunately in the process of making these plastics not all of the bisphenol-A gets linked together. So you put your food or other material in the plastic and it absorbs the unreacted bisphenol-A into it. And now in your food is a sex hormone.

DH: And what are you finding to be the effect?

FvS: Okay, the chemical bisphenol-A passes out of the plastic or out of the dental sealant that's put on your child's teeth or out of the lining of cans, into the food or liquid that's in contact with the plastic. Now the important point about detection by instrumentation of the bisphenol-A is that, based on our research, the ability of the current instruments used to monitor for bisphenol-A in food is a much lower level of detection than what our animals are able to detect. It's a huge difference as a matter of fact. So that you can put food that you have in contact with plastic into a chemical analysis and say there is no plastic material there. We extract from that same food, put it into animals and we get a big effect. The animals are more sensitive to the chemicals than the machinery. So detection limits, where people say our machine didn't detect this, doesn't mean it's not there and doesn't mean that it won't damage your baby. We have shown that in our experiments.

DH: So the plastics we use in daily life, the baby bottles, the food containers, leach chemicals into the food at levels that cause effects in lab animals?

FvS: One of the things that we started doing a number of years ago is we started looking at the effects of the materials that plastics are made out of in cell culture. We used human cells to see how responsive these cells were to these chemicals, and at what doses the chemicals could influence human cells to start growing and doing things differently. So, in other words, we're getting biological responses out of the cells and we were astonished at the incredibly small amounts of these chemicals that were actually able to alter human cell function.

So what we did in mice was based on the studies using human cells. We know that mouse cells are essentially identical to human cells in the way that they respond to these hormones. That's been known actually for quite a long time. So we used our information from human cells to then start treating animals with these very, very low doses of estrogenic chemicals found in plastics. So we had mechanistic information that really directed us towards very low doses.

Now one of the surprising things is that when we started looking into the literature concerning the amounts of these chemicals that were being released into food from plastic containers, and we compared that to the doses active in our cell culture studies, they were the same doses. But they were also doses that the toxicological community was saying were absolutely safe.

And so we looked into the bases of how could they say these doses were safe when our studies were saying that they wouldn't be safe. And the answer is they had never actually tested those doses. They had tested higher doses and then, based on assumptions about how the systems should work, they just said the lower doses must be safe. But there were no actual experiments that had ever tested to see if that was true. So we did something that had never been done. We started doing animal experiments at these very low doses, where our cell culture experiments had said these chemicals would cause effects. We actually administered these chemicals at the amount that we're consuming them. The average person in the United States is consuming these chemicals from plastics at the levels we administered them to pregnant mice.

DH: And what did you find?

FvS: For the males, decreased sperm count and enlarged prostates. The treatment altered virtually every aspect of the reproductive system. The place next to the testes, the duct system called the epididymis where the sperm are stored prior to being ejaculated -- it was abnormally small, which could account also for lowered sperm count in the ejaculate. But we know also the testis is making fewer sperm. We see changes in growth rate as well. One of the interesting things is that these very low doses of estrogen increase rates of growth. The animals were actually growing larger than they would have normally. It was really quite a dramatic effect. The females went into puberty early. And we saw changes in behavior, changes in reactivity to the presence of other animals in the environment. Essentially the animals looked to be somewhat hyper-reactive to stimuli. We have, in other words, effects on brain and behavior. We're also seeing changes in liver enzyme activity which determines the way we respond to external chemicals, how fast we clear drugs, how we metabolize drugs.

In other words, in every aspect of physiology that we look for, we see effects. And they're permanent. And the important thing about what I'm talking about is we are only exposing babies to these chemicals for very, very short periods of time in development and the consequences are for the rest of the life of that individual. Once you change the development of an organ there is no way to undo that effect. It's a life sentence -- that's a lifetime consequence. Medical science can't undo the development of organs.

DH: And you're finding that organs are affected at levels as low as those that are leaching into our food from common plastics?

FvS: That's correct. The evidence provided by industry concerning the levels of plastic materials that are coming out of plastic into food that is put into a plastic container is, in fact, causing an effect in experimental studies. We're putting those levels into developing mice and we're altering, profoundly, the development of mice.

The reason the industry reported these data is that they were convinced that they could say, "Oh see, we're dealing with a billionth of a gram of these chemicals per gram of food." They thought it was such a small number that it couldn't possibly matter. Well, human cells respond to this chemical bisphenol-A at ten times lower than that. And that's been shown by at least four major independent academic laboratories and is now being repeated within the chemical industry itself. We understand now, with new techniques, that, in fact, cells are extremely responsive to these chemicals. This is information that people didn't have seven or eight years ago.

DH: But what you're saying stands what we currently know about toxicology on its head.

FvS: In science, this is called a paradigm inversion. The paradigm is the way people are doing things, and then periodically information comes along that says it's upside down, it's backwards, and if you ask the question a different way you get a totally different outcome. And whenever this happens, there is a convulsion in the field that is being turned upside down and there's a very documented series of responses because this has happened over and over through science. It's not the first time that the fundamental tenets of a field of science have been shown to be wrong, and the first thing is absolute denial. The second is a feeling that it may be true, but it's only true in very limited circumstances. The third is, it's true but the economic consequences are so great that we can't do anything about it. Just time after time, the response to these kinds of changes follows a very distinct pattern.

DH: And where are we now in that pattern?

FvS: Well, it's very interesting where we are in the progression. As of a year ago, people were saying the data from my colleagues and I stands alone and we can't believe it. In the last few months there have been a whole series of papers essentially confirming effects of this chemical bisphenol-A way below all of the published, absolutely "safe" level amounts that were in place in all the government regulatory agencies. So now, all of a sudden, we have three independent labs and also information coming out of institutions associated with the chemical industry that are saying, "Oops, got a problem here."

We have to be beyond the denial phase, because in science independent replication to the order of two, three, four times takes it out of the realm of impossible. When one person shows it, it may not replicate. Replication in science is critical. That's happened. So now what we're getting to is: well this is maybe true here but it can't be true everywhere else.

This is where you get to the issue of the endocrine system. It operates through mechanisms that are hard for people to really accept. The way estrogen works in a fish and the way it works in an alligator and a frog and a bird and a mouse and a woman is no different. That's been known for decades. Molecular biologists refer to this as incredible, extreme conservation of a fundamental system to life and you muck around with it and essentially it takes you out of existence. And so the assumption for this kind of system is that it's so profoundly central to life and reproduction that it has been subjected to only the most minor changes, so that this is a system that essentially works the same in everyone. And the important consequence of that is that if we're seeing these kinds of effects in experimental animals, we can't assume that humans aren't going to experience the same kind of consequence of this. And it also means that we have to begin thinking about the consequences of the amounts of these chemicals that humans are exposed to and the effects they can cause in people based on the work that we're now seeing in experimental animals.

DH: Could I just get you to repeat that in simpler terms?

FvS: OK. If you look at the fish or the human or the frog or the bird at the earliest stages of embryonic development, when the reproductive organs are forming, you're hard pressed to tell them apart. And if I were to show you the developing prostate in a human at the very beginning of its development, and the developing prostate in a mouse at the beginning of its development, you wouldn't tell them apart. And at the functional level they're essentially identical.

DH: One of your colleagues actually stumbled onto this problem with plastics. How did that happen?

FvS: Well, it's a fascinating detective story. At Tufts University, they were doing the same types of studies that we have been doing with human cells: culturing them and then looking at the ability of the cells to respond to chemicals in the environment. They had purchased some new test tubes and the test tubes were made of polystyrene plastic, and the cells that we're using to detect estrogens require estrogens to grow and to proliferate, to go through development. And they put the cells in these test tubes and they started growing. And so the natural assumption was, "Somebody spilled some chemical in the lab that is infiltrating all of our cultures, and oh my gosh this is a disaster." Contaminated labs are a real serious problem.

Instead, after months and months of work, they realized that the lab was absolutely clean and that it was the test tube that was causing the cells to grow. So they called up Dow Corning, from whom they had purchased these test tubes, and said, "Your test tubes are causing our estrogen-responsive cells to grow. They must be releasing an estrogen. What could that be?" And Dow Corning said, "We won't tell you. We won't tell anybody what's in our products." And I'll come back to this because this is an extremely critical issue with regard to knowing what chemicals we're exposed to. Because the chemical industry will not inform scientists or the public what the chemicals in the products we're using are, and so it took months of work, of chemical analysis of these plastics, to realize that it's an additive material.

It's an antioxidant that stops discoloration of the plastic and it's added to the plastic to stop it from discoloring, and it's present in soaps, detergents, hand creams, vaginal creams. It's used in loads of different types of products. This same chemical is also used as an antioxidant in plastics. And it's a potent enough estrogen that when you put human cells into a plastic material made of polystyrene, but it's got this additive material in it, it can cause human breast cells to start proliferating. That's not a good thing.

DH: Could it be cancer causing?

FvS: Well, you can't have breast cancer if you don't have enough estrogen to cause the breast cells to undergo differentiation in development. Women who, at a young age, have their ovaries taken out and their estrogen levels reduced don't get breast cancer. It's an estrogen-dependent disease, and the amount of estrogen you're exposed to through your life is the best predictor of the likelihood of getting breast cancer. So from an epidemiological point of view, if you can account for something in the environment that's going to elevate a woman's lifetime exposure to estrogen, the evidence is clear that that is a risk factor. We don't understand what causes breast cancer, but it is a factor in the probability of getting breast cancer.

DH: And this is coming from soaps, creams, plastics that are in our daily lives?

FvS: That's correct When you take this plastic material at levels way below what the government in the United States and in Europe has deemed a safe daily intake amount, and for just eleven days you administer that to a rat, you get dramatic increases in breast proliferation, in breast cell proliferation. And the conclusion of these authors who just published this in a major scientific journal a few months ago is that there is absolutely no doubt that extensive proliferation of breast cells is a recognized risk factor for breast cancer.

DH This issue can't be talked about without getting into politics, it seems. Why is that?

FvS: The political aspects of dealing with the endocrine disrupter issue have really altered the course of what is happening dramatically. If we were dealing with a topic that didn't have incredible economic consequences, there wouldn't be the kind of resistance to what we're talking about right now. Paradigm shifts in science are always difficult, but if they only impact a scientific issue that impacts a few scientists that are wedded to an idea, the general scientific community is going to look at it and say, "Gosh, this really makes sense." The transition is going to be relatively easy.

In the case of the endocrine disrupter issue, where the chemical that we're publishing about happens to be one of the fifty top chemicals made in the United States, it is worth billions of dollars to a few major corporations such as General Electric, Shell Oil, Dow Chemical. Each of them makes billions of dollars from this chemical. That's what I hear. And the consequence of that is that if there is a shift in the government's approach to regulating this chemical, it could impact billions of dollars of profits. So instead of just looking at the scientific issues, now you have this huge force that has tremendous influence over the way our government operates -- and everybody recognizes the amount of money spent in lobbying is somehow related to legislation. I don't think that's a wild assumption anymore. And so you have this tremendous infrastructure of industry trade groups arguing that we don't know enough yet to do anything of a regulatory nature based on the scientific findings.

And my response to that is for billions of dollars of products and profits, how much information will you ever need to get to the point where you know enough? And my attitude is, essentially, as far as those industries are concerned, never. And the model for that is tobacco. Because it has been clearly known within the tobacco institutes and the tobacco manufacturers for at least, now we know, three decades that these are cancer causing. It's addictive, but that wasn't going to be a factor in them doing business.

DH: There's just not enough known here to assume that the industry is following those traditional patterns.

FvS: There is an important distinction between what we're doing right now and what was done by the tobacco industry thirty years ago. For thirty years, let's say, the tobacco manufacturers have clearly understood the extreme negative health consequences of smoking, and they lied and they hid that from the public. It's very clear that the people who manufactured these plastic materials twenty years ago thought they were safe.

What we are now in is this paradigm inversion that I've taken you through, where what you do is you step through these sequences of denial: now we accept it, but it's limited, but it's going to cost too much. What you have now is clearly enough scientific information to warrant concern and a change in the regulatory approach to these chemicals. You have at least six major laboratories essentially concordant with the findings concerning how potent, one, this chemical really is.

If that information had been known at the time that this chemical was first put into commerce, it would not have been put into commerce, alright? But because it already is in commerce, and chemical industries have a huge stake in maintaining their market share using this chemical, how do they now respond to evidence that it really is not a chemical that you would want your baby to be exposed to? We're still in the attack phase.

Dow Chemical sent a representative down to my lab a number of months ago and essentially asked if there were a mutually beneficial outcome that we could arrive at where I held off publishing the information about this chemical until they had repeated my studies, and after repeating my studies approval for publication was received by all the plastic manufacturers.

DH: They were trying to buy you off?

FvS: We didn't get to anywhere beyond that. My response was, "Do you have a scientific criticism that would justify not publishing this paper?" Because if anybody can ever provide a valid scientific criticism on the research that I've done, that would be a reason not to publish an article. But this was research funded through the National Institutes of Health. I have an absolute obligation to take public money and report the findings from research conducted with those public funds. To not do so would be a gross violation of professional ethics, and I don't need to tell you would be totally inappropriate.

So I don't know what mutually beneficial outcome they were thinking about, but there was no beneficial outcome that I would have found acceptable and so I simply shut that conversation off. But clearly that was an example where they would have preferred that the information not be seen by the general community, and not be discussed about in this format.

DH: Dow Chemical said this didn't happen. There may have been a misunderstanding, or whatever, but they certainly weren't trying to influence your research.

FvS: Well, if you say that Dow says this didn't happen, there were a number of other people in the room during this conversation and I wrote a letter to the Food and Drug Administration documenting the conversation in detail. Quite a detailed letter that was sent to the government with copies all through my university hierarchy.

I never received a letter back from anybody at Dow suggesting that there was anything in that letter that wasn't exactly as it had happened which, again, was also witnessed by numerous other people. If they have any problem with what I am saying here, they can deal with that however they want. What I am saying is exactly what happened and could be corroborated by a number of other people who were in the room and heard this.

DH: Why would they do this?

FvS: I was stunned. I can't answer for the people who would have made that decision. It was a stupid decision as far as I am concerned. I can't imagine how they would have thought I would do something like that. It was totally inappropriate. Scientists simply don't put away their findings until industry lawyers decide it is appropriate for them to publish.

But it does raise an absolutely critical issue that when an industry funds "science" -- I put "science" in quotes there because there is an inherent contradiction. Science is the pursuit of knowledge and the dissemination of that knowledge. Industry typically puts constraints on the ability to disseminate that information.

The chemical industry has shown an absolute unwillingness to give any money not attached to strings where they control the process of putting together the experiments and then publishing the experiments. And that is just unacceptable. And this is a perfect example of what would happen if I had a contractual arrangement with them that allowed them to shut me down in terms of providing you with the information I am providing to you.

What we have been calling for, in the scientific community, for a number of years is for the chemical industry to set up a mechanism to give money to address the basic issues of how chemicals work without controlling the design of the experiments and the ability to publish the work once the research has been done

DH: Do you think that Steve Safe is close-minded to the truth?

FvS: I think what you have is a complex web where what is the cause of what behavior is impossible to sort out. He was adamantly opposed to the concept of endocrine disrupters. So who did the chemical industry give money to? Stephen Safe. They are not funding me. So one of the important issues here is, did the fact that he then received that money in any way contribute to his unwillingness to look at the accumulation of scientific evidence and alter this absolute position that he had locked himself into?

Science is the pursuit of knowledge. Nobody has a crystal ball to look down the line and see where the science is going. And if, in fact, over the last four years all of these experiments that people are probably talking about on this program had been negative, with regard to effects of endocrine disrupters, we probably wouldn't be here having this conversation. Because there would be nothing to talk about.

But Steve Safe, while taking money from the chemical industry, still rejects entirely the possibility of endocrine disruption, if you in fact believe what he wrote in "The New England Journal of Medicine" where he refers to the possibility of this as a phobia -- an irrational fear. I think that most scientists looking at the totality of data here would certainly not call concern about endocrine disruption an irrational fear.

So let's say you get a million dollars and it comes into your lab and you set up an infrastructure based on that million dollars. And people's jobs depend on you. There are pressures associated with maintaining the funding and keeping that environment going, and anybody who would claim that getting money has no influence on your behavior I just think is not making a credible argument. I don't think anybody would accept that as a legitimate argument.

The next issue, then, does it cause you to lie? And I am not suggesting that anybody is overtly lying. You don't need to do that in science. It is very easy for someone who understands the way a system works to set up an experiment to find exactly what you want to find.

When the amendments to the Safe Drinking Water Act were passed and the Food Quality Protection Act was passed, industry knew that there was a mandate that within a two-year period of time there had to be a whole new method of testing environmental endocrine structures. Not because industry wanted to, but because Congress said, "This must be on our desk in two years or there is going to be hell to pay."

What you have is something very different when the chemical industry is funding people to provide information about chemicals in commerce, and then that information goes into determining whether that chemical is actually allowed to be used in products or not allowed to be used in products -- when that is based on the outcome of those experiments. And that is the type of research we want separated from industry control. The industry should also be putting money into basic mechanisms of which systems are appropriate to test chemicals and these sort of foundation issues.

The problem is that all chemical screening is controlled by industry hiring contract labs to screen those chemicals, and then that information doesn't go through intermediates. It goes directly to corporations through their legal departments. And then they decide whether to provide it to the government or not. They decide whether the outcomes are adverse. That could be very subjective. And they just say, "Well, we didn't provide this information because we didn't think it was a problem."

I essentially don't trust the system because every time you look into it, you find that there is abuse. Because we are dealing with chemicals that are worth billions of dollars, and that kind of money inherently corrupts.

DH: Steve Safe says if he has had any PR impact it is only infinitesimal compared to the effect that others, including yourself, have had in this issue of endocrine disruption.

FvS: The issue of impact is very difficult to assess. What is very clear to me is that what industry has done is they have found a very effective spokesman in one person who travels extensively around the world presenting this issue as being debated broadly by members of the scientific community who disagree with the possibility that chemicals in the environment may pose a threat to health, and other scientists who think there could be a problem.

DH: There are an awful lot of dissenting voices: Nobel Laureates that we have talked to, others who think it is an interesting hypothesis but don't feel that there is anywhere near enough information now to completely accept this hypothesis. We are still very much in a discovery process.

FvS: You are saying you are interviewing Nobel Laureates, for instance. One of the problems is in this field the information is moving extremely quickly. If you don't do this type of work, you may know what is currently going on behind the scenes in your field, but none of the people you are talking to probably are, themselves, involved in research in this field. And so they are playing catch-up with information that may be two years out of date.

Because what we are finding is that people come in with an immense amount of skepticism, do an experiment, and go, "My god, I never would have imagined getting this outcome." And then they change their ideas when they see the data.

DH: Isn't it hard to assess where this issue really stands, from where you sit? You certainly are at the cutting edge, which is an exciting place to be in science. But people who are the deepest into it don't always have the clearest perspective. Might you be in the wrong position to really know where we are?

FvS: Is the fact that you are involved on a daily basis in studying a subject and learning about it, is that going to put you in a position to not be able to understand where this information fits in the larger picture? There is always a concern that you can buy into an idea and begin to ignore reality. All right. But that is definitely going to get obvious in a very, very short order of time because people are replicating studies and moving forward very quickly in this field.

What is important is clearly that information that is presented by one group be replicated by another group, and information extended. And this is the case with our finding concerning bisphenyl-A that we only published one year ago, where we said that this is a chemical that operates at very, very low doses and can have profound effects that were not predicted based on the way chemical testing was done. And in the last six months, two other studies from major independent laboratories have come to exactly the same conclusion. Now, all of a sudden, it is not just me anymore. And that is the kind of information that wins over the scientific community. Now we are up to three independent replications coming to the same conclusion.

The question I have is: who is looking at that series of replications and saying, "I still don't believe that anything can happen"? Because the scientific process says that as replications occur, the degree of confidence goes up dramatically. And so I would say they may just not be aware that the replications occurred. Because if they were aware of it, I think that skepticism would decrease dramatically. How could three studies, independent of each other... Apparently none of us knew the other people were working with this chemical, and the outcomes are all the same. That is very compelling. We had no agenda, with regard to economic outcome, of finding one chemical dangerous and one chemical not dangerous.

DH: You are both an advocate for this issue and a scientist. Do you see any conflict between those two roles?

FvS: I don't see myself as an advocate for any position other than the results of my experiments. What I am doing is, I am saying that we took a chemical that is deemed to be safe at fifty parts per million: fifty millionths of a gram per gram of your body weight. If you eat that much, you are absolutely "safe". We dropped that down 25,000 times, and just totally perturbed the whole course of fetal development. Because of that, I say, "That concerns me." All right?

Now we did it with a whole series of chemicals. Every time we challenge the model of "here is a safe amount, anything below that should do nothing", we find out that the safe amount as published in the government registry is wrong. We started giving low doses to animals, and it was only after that that we were absolutely astonished to find that nobody had ever done that.

I am a developmental biologist studying the effects of natural hormones on development. I had been doing that for twenty years before I got into this, and had no intention of actually ending up working in toxicology. That was the farthest thought from where I was ten years ago. I have lots of other questions in science that I am very interested in, and the last thing I want to do with my scientific career is waste my time working on something that ten years from now is going to be looked at as nonsense. Why would I want to do that?

And so I have a reputation because I have conducted experiments that were reporting new information that were thought of as controversial, and then turned out to be replicated and extended and, in fact, are now totally accepted. Because of the weight of evidence that has accumulated.

If you have industry throwing bricks at you, saying, "This is untrue. This person is incompetent. This is junk science," and you are brand new, you are vulnerable. But it is very easy not to find something. The trick is to find that needle in the haystack. It is very easy not to find it.

DH: I think the impression that's often put out there is that industry is spending all this money to try to influence science and influence the media. Their point of view is that there are also an awful lot of groups, environmental groups, that are working with these scientists -- and they're using some of the same PR tactics that industry is. Are they right that PR is just a necessary way that you get a message out?

FvS: I don't know of very many scientists who have actually been involved in PR activities in an overt sense. What I have been willing to do is sit down with reporters, just as we are right now, and I've been willing to discuss the findings from my experiments. Now if that is considered PR, then... I think that disseminating the information that you have to the public is an important part of the scientific process, as long as it's not done prematurely.

If, in fact, you go through the proper channels of publishing scientific information and then you have industry saying this is junk science, I think sitting down with you and explaining my research findings to you is an appropriate part of the process of getting information out to the public that is actually accepted by the scientific community. I've never really thought of that as PR in some kind of marketing sense, but I suppose it really is. I'm engaging in public relations with regard to the research going on in my laboratory. But I'm not putting a spin on it, I'm simply telling you what I found.

MC: Steve Safe said to us that the levels of chemicals in the environment have all gone down.

FvS: DDT is at much lower levels in the United States today than it was in the 1970s. Of course it's also being used all over the world, and it's in the atmosphere. And the very current evidence is that while levels decreased after it was banned, we're now somewhat stabilizing. The same with PCBs.

Those two chemicals do not encompass endocrine disrupters. And we absolutely, desperately need Congress to fund broad monitoring studies of chemicals in the environment that are being identified as endocrine disrupters. This is all of the components of plastics. Every four years, one trillion pounds of plastics are made in the world. They are being thrown away in the landfill. They are leaching these products back into our water. No one is looking for them. So as a general statement, to say that all endocrine disrupting chemicals are at lower levels today than they would have been twenty years ago is just ludicrous. Because nobody's looked. Nobody knew they were endocrine disrupting chemicals.

DH: You've said that the doses at which hormones affect the body are extremely low. Give me an example to make me understand that.

FvS: The issue of the amount of hormone that actually causes effects is very difficult for scientists to talk to people about because we're dealing with numbers that are outside of the frame of reference that anybody is going to be thinking about. We see changes, profound changes, in the course of development of essentially the whole body of experimental animals, and we're working with mice and rats, and we see these changes at fifty femtograms of the hormone per milliliter of blood. That's 0.05 trillionths of a gram of this hormone in a milliliter of blood.

DH: And what sort of effect does it have?

FvS: We see changes in the functioning of the prostate. We see dramatic change in the sprouting of glands within the fetal prostate. We see changes in testicular sperm production. We see changes in the structure of the endocrine control region in the brain, which is accompanied by changes in sex behavior, aggression, the way these animals behave towards infants, their whole social interaction, the way they age, the time that they enter puberty, the age at which they cease reproduction. It changes their entire life history, and these changes are capable of occurring at very low levels of hormones.

I remember when we first did this and I was a post doctoral fellow, and my advisor and I looked at the hormone levels and said, "My God, these levels are so staggeringly small and the consequences are so immense it's amazing." Even to biologists, it's amazing.

But what you have is the entire field of toxicology thinking of a millionth of a gram of a hormone or a chemical as being this staggeringly tiny amount, and to most people if I said there's only a millionth of a gram of it here you'd say, "How can it do anything?" A millionth of a gram of estradiol in blood is toxic. The natural hormone is actually operating at something like a hundred million times lower than that. So when you have a physiologist thinking of a millionth of a gram, you have that physiologist thinking this is a toxic high dose. When you are raised in the field of toxicology you are looking at that from the other perspective of "My gosh, that's such a tiny dose, it couldn't do anything."

So now what we have are two different fields coming into this issue and looking at a dose as either staggeringly high or staggeringly low, and it's not surprising that there is a clash occurring with regard to dose effects.

DH: Can you again describe the results, the developmental effects in your laboratory mice, that you are seeing with these unbelievably small changes in hormone levels?

FvS: We published a paper just a few months ago in the "Proceedings of the National Academy of Sciences" in which we experimentally elevated estradiol levels in mouse fetuses during the period when their reproductive organs were forming. And what we did was we experimentally elevated estradiol by one tenth of one trillionth of a gram of estradiol in a milliliter of blood. We estimate that we're increasing estradiol by about one molecule of estradiol per cell in the body. Okay? The consequence of this is that at te components of plastics. Every four years, one trillion pounds of plastics are made in the world. They are being thrown away in the landfill. They are leaching these products back into our water. No one is looking for them. So as a general statement, to say that all endocrine disrupting chemicals are at lower levels today than they would have been twenty years ago is just ludicrous. Because nobody's looked. Nobody knew they were endocrine disrupting chemicals.

 

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