Speaker 1:	First, can I ask you if you can hear me, yes? Great. Thank you. Thank you very much for that kind introduction, Peter, and I thank all the organizers of this series, that might be just Peter, I'm not sure or other people for inviting me to speak at this little mini symposium about silent spring. So I have a little bit of a confession to make before I start and I'm going to preface my confession with something that you ought to know about [inaudible 00:00:36] I know this about [inaudible 00:00:37] because I was one for a couple of years and because I've had the pleasure of teaching them for almost 20, and that is, when you give [inaudible 00:00:45] a reading list, they read the stuff on it, they do the reading. But I have to say that although I have always thought as Rachel Carson as one of my heroes and I've understood the importance of this book, I had actually never read it.
	Until I was asked to give this lecture and now I have done my reading. So I'm going to talk about the science of silent spring, one of the things that I want to thank the committee for, for asking me to do this talk and getting me to read this book is that I really, I really feel like I've gained a deep sort of affection for Rachel Carson and also an appreciation for her knowledge about biology. So Rachel Carson was educated at Chatham University, what is now Chatham University. She has a BA, had a BA in biology, she then went and got her masters at Johns Hopkins, she taught at John Hopkins, at the University of Maryland and she worked at [inaudible 00:01:46] and what is now the U.S. Fish and Wildlife Service. 
	But all this time she was writing as well and by the time she worked on Silent Spring, she was writing only. And what [inaudible 00:02:02] tells us about Rachel Carson in her book is that she never accepted second hand information but rather pursued a point to its source, communicating directly with a scientist or a doctor and obtaining her own copy of the findings. So I think we need to think about Rachel as surrounded by books and manuscripts and putting all of this stuff together in a story that could be appreciated by non scientists. And so this book is one that is known to have launched the modern environmental movement and I'm not putting that in quotes because so many people have said it, I now think of it as being in the public domain, we really do think of Rachel Carson in this way.
	Her book was a compilation of all sorts of studies done in the field, done in the lab, and it was unusual that it had references at the end, 55 pages of them. This was a first for Rachel Carson and also something fairly unusual in the works of that time. So I'm going to assume that some of you have not read this book either, or that you may have read it so long ago that you might be reminded about it's contents so I'll give you a brief synopsis about what she said in that book. So she begins by talking about pesticides. She's really concerned about pesticides, these chemicals that had been introduced into the environment and she said, we are waging a war on nature.
	These chemicals were designed to be herbicides, to protect our crops, to protect us from the embarrassment of having dandelions in our lawns. There were fungicides that were meant to protect yet other crops. There were insecticides that were meant to kill insects that were eating our crops or spreading disease. But the problem was that this was not the only thing that was happening. One of the poster children for these chemicals at that time was DDT. And DDT was discovered sort of by accident at the end of the 1800's but then it was brought back and researched and the person who actually worked on it as an insecticide got the Nobel prize for that work.
	Once DDT started being used, we started spraying it everywhere. So crops were dusted, forests were dusted, I have spoken to people who remember, in the summertime, trucks coming down their street in their neighborhood on a warm day, and running behind that truck and getting the moisture on them because it made them cool off. Housewives and all sorts of people found uses for DDT. And we were meant to think that DDT was good for us. It was good for us because it made our lives better and made us healthier. The problem of course is that we weren't very specific in who was being targeted by these chemicals. And the classic image from this era was pictures of eggs like these, with broken egg shells because the egg shells were so thin that even when the parents sat on them to incubate them, they broke.
	And so this is the place where Rachel Carson is going to speak to us, she says, is this too high a price to pay for a sproutless potato or a mosquito less patio. One of the other things that she understood very well is that evolutionary principles are at work all the time. And she says, the environment contained elements, that is long ago, that were hostile as well as supporting, given time, time not in years, but millennia, life adjusts and a balance has been reached. For time is the essential ingredient but in the modern world there is no time. So I've put this picture of stromatolites up here to remind us of the very first organisms that made oxygen on this planet and the fact that oxygen was in fact really toxic.
	Hard to believe because we can't live without it now and that really is a testament as to what can happen over evolutionary time that we can develop ways of dealing with these hostile elements and we can even work, we can develop ways in which we can actually use them to our benefit. So what she's saying here is that the toxicity of these chemicals is partly because we are introducing them so quickly and the organisms don't have a chance to evolve ways of detoxifying them. Another way that these evolutionary principles are at work she said is that, while it does take time for us to develop ways of handling these toxins, at the same time there are some animals, and plants that are able to develop resistance and this animal here is the Colorado potato beetle and it's probably the poster child for insecticide resistance. 
	Its resistant to almost everything that's out there. And Rachel Carson, when talking about pesticide resistance says, Darwin himself could scarcely have found a better example of the operation of natural selection than is provided by the way the mechanism of resistance operates. She went on to say that there were better ways of controlling pests in our environment and those better ways had to do with using the natural relationships that already existed. And so she says, the balance of nature is still there, she says, people seem to have forgotten this. A complex, precise, and highly integrated system of relationships between living things, which cannot safely be ignored then the law of gravity can be defied with impunity by a man perched on the edge of a cliff.
	And so what she advocated was biological controls, she advocated finding insects or other predators that specifically targeted the insect or whatever you were trying to get rid of and the idea was that they would target only that species and not the other ones in the environment. And what we see here is a tobacco horn worm that has been attacked by a parasitoid wasp that has laid eggs on the surface of the body and these eggs have developed and they are beginning to devour this horn worm and it will not survive this attack. Those parasitoids are really quite specific so they are targeting just this species or maybe a few species. We haven't always done so well with the biological control, so we haven't always chosen the right animals to do that and this is really a wonderful, no terrible example of a choice that was very poorly made.
	These are cane toads that were brought to Australia to control the [inaudible 00:08:58] in the cane. They were taken to this area right here and not only did they never eat the grubs at all because they didn't meet them they were active at different times, they have spread really widely and they have caused a lot of death of native wildlife. So it's a good idea but in practice it sometimes doesn't work quite as cleanly as we wish that it would. And one of the other things that Rachel Carson says, kind of indignantly she says, and the other thing is that many of these pests are there because we created the problem in the first place. And one of the things she knows about is the importance of diversity in the environment. 
	And what happens when we plant mono cultures like all of these beautiful elm trees that used to be so common on the streets of North American towns. When dutch elm disease came along it wiped out all of them. So if we plant just one species, if there's a disease or an insect that targets that species, they're all gone. And she realized that that was not a very stable situation. And so she says, the resort to weapons such as insecticides to control it is a proof of insufficient knowledge and of an incapacity so to guide the processes of nature, that brute force becomes unnecessary. And so she said, we really are just not using all of the intelligence that we have when we make some of our decisions.
	So Rachel Carson died in 1964, just two years after this book was published. She died of breast cancer and so her life was cut quite short. Today she would be 105, I think. And I think a lot of us have wondered what is it that Rachel Carson would be concerned about if she were alive today. And so what I want to spend the rest of this time talking about is some things we have learned since Rachel Carson's day and things that helped explain some of the things that she didn't understand. And the first person that I want to tell you about is Theo Colborn. Theo Colborn is a very interesting woman.
	She had a degree in pharmacy so she understood about how chemicals interacted with the body. She took some later degrees but only when she was a grandmother already at the age of 58 I believe, she got her PHD at the university of Wisconsin and then she went on to work with a lot of different conservation organizations but she is perhaps best known for this book, Our Stolen Future, and in the forward to Our Stolen Future, Al Gore says the following, he says, last year I wrote the forward to the 30th anniversary addition of Rachel Carson's classis work, Silent Spring. Little did I realize that I would so soon be writing a forward to a book that is in many respects it's sequel.
	And really I think that this is the way that many of us think about this book. Like Silent Spring, Our Stolen Future contains information compiled from all sorts of sources and again I think we need to envision Colborn surrounded by piles and piles of manuscripts. She's really trying to put together a story that has lots of different facts, lots of different things she's trying to integrate together. And she also has annotated her book with lots of references. So in this way quite similar to Silent Spring. So one of the things that Rachel Carson was trying to figure out was the effects of pesticides on reproduction.
	So we had lots of evidence that this was happening and she was trying to figure out how that worked. And one of the things that was discovered around that time is that people finally figured out how metabolism worked at the molecular level inside cells. She was very excited about that finding and she also knew that a few pesticides actually disrupted that process and so, the way she put this story together for herself was well, if these pesticides are disrupting metabolism then that could really explain all of these problems. The small testes that we're seeing in some of these wild animals, well that was just because the didn't have enough energy to grow.
	And the young couldn't grow normally because they weren't getting enough energy. And we also knew something about the livers, the very metabolically active organ, and we know that the liver has something to do with maintaining the proper balance of sex hormones so this somehow is probably what explains what is happening with reproduction and why these pesticides are so toxic to reproduction. So she was kind of getting to the right place when she started talking about sex hormones, but it was really Theo Colborn who for the public put together this story of what's really going on. And her big message is that these pesticides are effecting reproduction because they are mimicking hormones. 
	And so I'm gonna give you a quick little lesson in how hormones work so that we can understand how the pesticides are disrupting that process. Okay, so the first step with hormone action is that the hormone binds with the receptor. So here's our little hormone and it's coming in and binding with our receptor and the idea here is that the two of them fit together really nicely. So that's the first part, once they bind, then a change of events is initiated and the receptor travels down to the DNA and it sits there and remember that the DNA has the instructions for the cell, what it's to make, what it's to do etc. and once that receptor has bound there we get instructions being read out. These instructions might be things like, what kind of a cell are you to become, another kind of instruction might be, what things to make or how to respond to something in the environment.
	And since organs are made up of cells and were affecting cell function, that means that we are affecting organ function and really all the way up to behavior. And I always think about, if I wonder about if all of these things are true I just say, think of myself walking into a middle school and observing what's happening there for about 10 minutes and I will be confirmed in my conviction about what these hormones are doing. Okay, so now we want to ask the question, what things can bind with this hormone receptor. So here's the receptor, here's the hormone that our bodies makes, but what about these other molecules.
	Can they bind there too. Well here's one that doesn't look like the native hormone but it has just enough of the right shape to fit in that receptor just very nicely. And so if that happens, what's gonna happen is again, the receptor moves to the DNA and we get our effects, just as if the native hormone had bound with that receptor. Okay, so we know this one binds, that one binds of course, what about that one and that one. Well these are all different shapes but they all have that geometry that allows them to fit in here. So really it doesn't matter what's on the rest of that molecule, there could be a peacock feather sticking out of there, something like that, but again, it can bind and it goes and binds on the DNA and it causes the cell effects.
	Okay. So the answer to that question, what can bind, is anything that fits there. Alright, so we've looked at those examples, now let's look at this example right here. And a molecule that fits kind of. So we can see that it fits here pretty well but the match isn't perfect and when that happens we can have a couple of things happen next. One is nothing, it can just sort of sit there. Sometimes it will go to the next step and actually bind with the DNA but again these shapes aren't really quite the right thing to make everything happen and there's no effect. So this molecule is not only preventing anything from happening, it keeps this normal hormone from binding there, okay? So what we say is that these molecules can have pro hormone or anti hormone effects.
	And so the estrogen receptor happens to be a receptor that we have created a lot of molecules unwittingly that bind to it and so I'm just going to take this example, we've got the estrogen receptor, an estrogen that binds there, and we've got these molecules that act like estrogen, so they are estrogenic and we have these that act like estrogen enough to bind there but then block all the effects after that and we call those anti-estrogenic. Okay, one more thing that we need to know and that is, the relationship between androgen and estrogen. It turns out that if we ever want to make estrogen, we've got to make androgen, testosterone in particular, first.
	And there's an enzyme, aromatase, that is responsible for causing that conversion to happen. So what we now know is that pesticides can mess with almost every part of this little relationship. They can mimic androgens, they can mimic estrogens and they can change the activity of aromatase. That's playing with fire, all of those things. Okay, let's talk about lawns. So back to Rachel Carson's lawns, she says the [inaudible 00:19:21] of suburbia now dictate that crabgrass must grow at whatever cost. Sacks containing chemicals designed to rid the lawn of such despised vegetation have become almost a status symbol. And in fact you can go to pretty much any hardware store, you can go to Home Depot and you can pick yourself up some atrazine or some compound that contains atrazine.
	Okay, atrazine has an effect on this relationship that I just told you about. Atrazine increases the production of aromatase. So what that means is we're going to be making more estrogen. And because we're making estrogen from androgen, we're going to have less androgen around. Okay, so that sets the stage. This is the next person I want to introduce you to, this is Tyrone Hayes. He is a professor at Burkley and he studies frogs. Right there. And he has been giving a lecture for awhile called from Silent Spring, to silent night, and he's talking about his frogs that call at night. Frogs are in trouble these days and Tyrone has been working on ways to figure out what's going on and he has been working specifically on atrazine. 
	So one of the things he's done in the field is he's gone to places where there are atrazine contaminated waters and he's been collecting these frogs and here is the cross section of a testis that he pulled from one of these frogs. And what you can see here is some tissue that looks like it belongs in a [inaudible 00:21:10] and then there's this and that and that. Those are eggs. They don't belong there. Okay, so that was the first publication back in 2003, more recently he came across some frogs that had gone one step further and this is not all the frogs that live in atrazine contaminated waters but it is a substantial fraction of them. And what he's showing here is a frog that you would think is a female but he looked at the chromosomes and he knows it's a genetic male.
	And what we see here, now this is all yellow because it's been stained. That's not it's normal color. What we see here, those are eggs. Lots and lots of them. So this looks to be a pretty radically feminized male. Here's one of these atrazine induced females, the big one on the bottom copulating with one of her male siblings that was not exposed to atrazine. So they're doing that behavior and she is releasing all these eggs and those are going to hatch into tadpoles and survive to adulthood, amazing. Rachel Carson had an incline about this kind of thing going on. She says, mosquitoes exposed to DDT for several generations turned into strange creatures called [inaudible 00:22:40] part male and part female.
	So this is really following on this observation that she had made but hadn't really been able to put together with the molecular biology to understand how it worked. So there's another thing about atrazine and that is the link with breast cancer. So one of the things that we know is that estrogen can stimulate some cancers to go. And we call these estrogen sensitive cancers, and what you can imagine is if you have lots of aromatase activity you're going to get more estrogen and the risk of getting an estrogen sensitive cancer is increased. And so atrazine is not just a problem as frogs, it's a problem for us as well. And one of the ways that we can see that this principal is valid is looking at a drug that women with breast cancer are given to treat it.
	They're given a drug called letrozole sometimes and it's job is to do the opposite of atrazine. To inhibit aromatase activity and therefore decrease the estrogen production. So one of the reasons that I wanted to talk about Tyrone Hayes is that he is unlike Rachel Carson and Theo Colborn in that he is not a writer as such, he is a scientist who's producing data in the lab and in the field but he cares about frogs and he cares about women and it got to the point that he felt like he couldn't not speak out. And so to him it was so obvious, atrazine should be banned and we should do it right now, but when that subject was brought up people would say, well the data are very equivocal, some people say that atrazine harms the gonads and some people don't.
	And so really, we don't think there's enough conclusive evidence to get us to make this decision now. So he went out and he did a study of these studies, a meta study and there were 15 of them. Some of them said it was harmful, some of them said it wasn't. And so the question was what was the difference between these studies. And what it looked like is that who funded this study made a big difference. And if you look, every time we've got a non profit funding, here, National Science Foundation, World Wildlife fund, Howard Hughes, W Alton Jones, the answer is yes. And every time Syngenta funds the study the answer is no. What does Syngenta do? They make atrazine, that's right.
	Okay, I don't have time to talk more about how these differences can come about but if you're interested here's the reference and I guess I would just like to say that scientific evidence isn't always enough. That there needs to be a political and social will as well for these changes to come about. I just want to put in a plug for the college. The college has recently gone over to having an organic lawn. They became concerned about the chemicals they were using and they've made the switch over. They're working hard at that and I really want to applaud what they are doing. Okay, so endocrine disruptors I think is something that Rachel Carson would definitely be writing about if she were alive in this age. Another thing that she mentions, she says these important studies establish the fact that the insecticidal poison effect a generation once removed from initial contact with it.
	So I want to talk now about trans generational effects. And I want to talk about a fungicide called vinclozolin. It's commonly used on vegetables and especially in vineyards. And I want to tell you about an experience with vinclozolin in which we've got some rats. We start with a female rat who is treated with vinclozolin. She's treated after she's gotten pregnant from mating with this other male and she then has a whole bunch of offspring and we take her sons and we mate them with females who are descended from unexposed females. We take there sons, we do the same thing, we go all the way down to the great, great, grandsons. And now we're going to ask about whether this exposure to vinclozolin, only in this one female, not in any of these other animals shows up in the later generations.
	And it does. It shows up as impaired sperm production. And so if we look at the testes of a healthy controlled male, this is what the testes of a fertile male looks like. So we're looking at cross sections of these seminiferous tubules and in the center of the heads of the sperm are sort of lodged in here and there tails are sort of what you see here, these threads sticking out. And so that's what a good healthy testes looks like. If you look at the testes from these descendants now of that one vinclozolin treated female, what you see is something that looks not at all like a normal testes. I don't really see any sperm tails in there at all. If we look at things like, how many sperm you have and whether they swim or not, a sperm is no good if it doesn't swim. 
	We find that even in these later generations, in every case, the descendants of that vinclozolin treated female have lower sperm number or less fewer [inaudible 00:28:47] sperm than controls that never had any exposure in any of their ancestry. So this stuff is being passed down and you can see that it isn't really lessening with age or with generation. That effect is still there and it's very strong. So vinclozolin it turns out is an anti androgen and that makes sense with what we've seen as far as the testes development and sperm production is concerned. But there's more to reproduction than just the physiology and the testes and all that stuff, there's also behavior. So an experiment that's sort of like a speed dating for rats was set up and we're now testing the sexual attractiveness of rats that are descended from vinclozolin treated females or descended from females that have never seen any vinclozolin.
	So we set up a cage, on one side we've got a descendant of a vinclozolin treated female on the other side a control. And then we put our lucky test rat in the middle and we asked that rat to choose which one do you like better. And generation after generation what we found, or what they found is that the females preferred the males that were not descended from the vinclozolin treated females. It turns out the males were not very choosy, but the females did choose reliably and they preferred the ones that had not had the pesticide exposure in there ancestral history. So really this is being passed on from generation to generation and the question is, how does that happen? And the answer comes to us from a field that has really been developing speed and growing by leaps and bounds, it's the field of epigenetics.
	We used to think that the only important thing was which genes you got from your parents. But we understand now that it's more than just which genes you have, it's which genes are actually read, which are expressed, and those two things are not the same. And it turns out that there are ways to silence genes that you have and one of the ways is to wind them up really tightly into little balls like this so that it is impossible for the machinery that reads those genes to get in there and read them. So that's the first thing. And that machinery slides along this DNA strand and another way that you can keep those genes from being read is to tap on little bits of molecules here. These are methyl groups and that machinery can't go passed them.
	So that's another way to silence these and it turns out that that methylation pattern can be transmitted from a parent to a offspring to the next generation to the next generation. So this is what we think is going on here. So epigenetics I think would be another thing that Rachel Carson would love to know about and to write about. The last thing that I want to talk about is fat and obesity. And I think we've all heard this, this is not news, obesity is a growing health epidemic. I'm going to show you a series of graphs that are made by the CDC each year, the centers for disease control. And this is a graph of what percent of people in each state exceed the obesity standard, okay. 
	And so they start actually well after Rachel Carson's time in 1985 but you will see that there's a bit of a difference between then and now. And what you will notice is that we basically need to keep adding new colors that indicate higher percentages of people who are considered obese. Colorado, holding out but there it goes it's not a blue state anymore, okay. So this goes up to 2010, I have no doubt that this trend is actually continuing that's what the data are telling us. And so why do we think that's happening and what's the connection with these pesticides that Rachel Carson was so concerned about. Well, when we're talking about adults it's kind of easy to explain, it has to do with lifestyle. It has to do with how much exercise you get, how much food you eat, what kinds of foods you eat, but the thing that's getting interesting is that it's not just in adults anymore, it's in children, it's showing up in infants, and here's the one that I find so interesting, it's showing up in pets, in lab animals, and in feral animals like rats that just live out in the environment.
	Near us but not being fed by us directly. So that suggests that there might be something else going on and I'm going to tell you about an experiment in a moment that gives us an idea of what that might be. So one of the things that we know about these pesticides and other compounds like them that are endocrine disruptors is that their fat salluible and that means that they lodge in our fat and they basically hang out there. They don't get flushed away in the way that other toxins can be flushed out of our bodies. And so as we go up the food chain here, what we know is that one of these individuals is going to have to eat at least 10 times it's body weight in these individuals to get the energy it needs. That all kind of flows through the body but the toxins stay there. And so as we go up we get these accumulated levels of toxins and the higher up you are, the higher concentration and the more in danger you are of being harmed by these substances.
	Now, Rachel Carson said something about this to she said, deposits may lie dormant like a slumbering volcano. And then she said something else which I'll get to in a moment. So the first idea was well maybe the body fat is kind of good because it's a way of sequestering those toxins. Body fat doesn't really do anything it's just sort of inert tissue and so what a great idea. We can just sequester those toxins there. So that's a very sanitized view. What we understand is that there are times when these toxins leak out and one of the main times is when you're undergoing some kind of a fat loss, those toxins are released and they're circulated around the body. 
	And some people believe now that that might actually be happening at low levels all the time, that we are leaking out little bits of those toxins. And so this gets us to the idea of the slumbering volcano. She says, deposits may lay dormant like a slumbering volcano, only to flare up in periods of physical stress when the body draws upon it's fat reserves. Okay, so we also know that obesity is a risk factor for all sorts of diseases including cancer and so one of the ideas is that maybe one of the risk factors has to do with the fact that the fat is storing up these toxins which then can lead to cancer later on. But I want to tell you now about a very recent experiment. It has to do with triflumizole which is a fungicide. 
	It is used on all sorts of crop plants and ornamentals. Here's a tomato plant with powdery mildew which is what this chemical is designed to kill and it tends to be found especially on leafy green vegetables. Okay, you may have noticed this piece in the New York Times not too long ago. It was called warnings from a flabby mouse. And this experiment that I'm going to tell you about is what this article, this piece, referred to. So I'm gonna tell you about two experiments that were done. The first experiment was done just with cells in a dish, okay? And there were two kinds of cells that had not yet experienced their ultimate fate.
	There were mouse pre fat cells. These are cells that are net yet fat cells but at some point they can become fat cells if they get the right signal to do that. Then we've got another group of cells, these are human stem cells. And these particular stem cells have the capability to form either fat cells or bone cells, depending on what signal they get. Alright. So now we're going to treat these fat cells with triflumizole and the interesting thing about this fungicide is that it had been believed to be, have a very low toxicity. So it had gone through all sorts of toxic testing and in this toxic testing they come up with a no observed adverse effects level. So that's basically just below the lowest effect level that gives you any effect at all.
	So that's a pretty low level and for this experiment they took 1/400th of that level. Okay? So let's see what happens. We're going to add this amount to these two different populations of cells and dishes and see what happens. And what happens is that compared with cells that have not been treated with triflumizole, we get many more fat cells, committed fat cells that are expressing the genes that are necessary to work as a fat cell. To accumulate fat and to do all the things that fat cells do. And for these cells, this is a slightly different case, these cells don't know in the beginning which they're going to be and what they found is that treating with triflumizole increased the ratio of fat cells, or cells that became fat cells to cells that became bone cells.
	So that was the cells in a dish experiment, and now I want to tell you about another experiment with this compound that was done partly with animals, whole animals. So in this experiment we had a female and she has some little pups and after eight weeks we weigh those pups and we also measure how much fat they have on their bodies. Then we take cells from those little mouse pups, well they're not pups anymore at eight weeks and then we see what happens to those stem cells. And these are like the human stem cells from the previous experiment so these can become either fat cells or bone cells. So we're going to treat only the mom with the triflumizole. Again we're going to use this 1/400th of a no observed adverse effects level.
	And then we're going to see what happens. So what happens is that when we weigh her pups, her offspring at eight weeks, we find that they aren't actually heavier than the controls who have not had a mother treated with this compound but they had a larger proportion of their body weight as fat. So that kind of makes sense if we think about the two possible fates of some of these cells. And when they put the cells in a dish, and remember they're not treating them again, we find that again, more of them form fat cells than bone cells when we compare those with the controls that have not come from mice that came from a mother that had been treated with triflumizole. So basically what this is telling us is that some part of this part of the system, when triflumizole is being administered here is programming what these cells do later in life.
	So this is a big idea that is also part of the idea of epigenetics. Not only can we program what happens and pass those things down to our offspring. But experiences that we have early on in life, especially that's a time when we are particularly vulnerable can cause these different patterns to be put in place and for particular genes to be expressed or not expressed later in life of that individual. So we can actually look at what these compounds are doing in terms of programming the future bodies of these individuals that are exposed when they are very young. So the connection with obesity is then that not only does obesity cause us to accumulate these chemical pollutants but some of these chemicals can in turn actually cause obesity. There's much more to be learned about this I'm sure but it is an extremely interesting idea.
	So I think that this is another thing that Rachel Carson would have wanted to write about to follow up on her earlier ideas. So I want to close by thinking about what are the things that we have gained in our knowledge since the time of Rachel Carson and what would she think of these gains. So the first thing I think we could say is we've increased our understanding of cellular and molecular mechanisms and I think that would have thrilled her. She says, so it is only when we bring our focus to bare first on the individual cells of the body, then of the minute structures within the cells, and finally on the ultimate reactions of molecules within these structures, only when we do this can we comprehend the most serious and far reaching effects of the hap hazard introduction of foreign chemicals into our internal environment.
	So I think that she would have been really thrilled to understand this better. I think she would have been dismayed to learn how quickly we have been filling the environment with more and more of these chemicals. And they are not just pesticides, they are pcv's, they are flame retardants, they are plastics, they are all sorts of chemicals that are having effects like this. One of the other things that we've learned along the way is that we need to think about toxicity in a different way. So originally what we were thinking was that birth defects and cancer really were the things we need to look out for. But now we understand we should also be testing to see if substances are endocrine disruptors or if they are obesogenous, substances that program our bodies to accumulate more fat.
	Or are some other kind of epigenetic programmers and we are moving very slowly in that direction but I would emphasize the slowly part. So I think what I would like to close with then is with two quotes from Rachel Carson. I think there are some things she said back then that she would say, apply equally well today. One of them is, life is a miracle beyond our comprehension and we should reverence it even where we have to struggle against it, humbleness is in order and there is no excuse for scientific conceit here. And lastly the question is whether any civilization can wage relentless war on life without destroying itself and without losing the right to be called civilized. So in the 50th year of Silent Spring I think there are many things still to be learned from this book and I would encourage you to read it if you haven't had a chance to.
	As I said in the beginning as a biologist I actually found it quite an exhilarating read to understand how much she knew and how much she was able to start putting together, given what was known at that time. So thank you very much and I'm happy to answer questions.