Our Environment, Our Health: An NIEHS Perspective

(audience clapping) – So first of all, thank
you all for having me here. This is about the second
time I’ve been to Penn State. I really can’t remember. As I was saying to Gary, I’m gonna have to go back and look for when I was here before. But it’s really a pleasure. I will say thank you for yesterday, ’cause I flew in late yesterday,
and it was so beautiful. (audience chuckling) Can’t have that all the time. What I really wanna do today is give you a brief tour through, I’m not gonna be talking
about my own work, although sometimes I forget and move into something
that I’ve been doing, but I’m really gonna talk about who NIEH is, what we are, and what we do. And we’re a little bit of an odd duck. We are part of the National
Institutes of Health. We are the only institute of NIH that’s not headquartered
in Bethesda, Maryland. We are headquartered in
Research Triangle Park, North Carolina, and that was an example of when politics worked, ’cause we were paid back from
Jack Kennedy to Terry Sanford, the governor of North
Carolina, for delivering North Carolina to the
Kennedy wing in 1960. So that’s why we’re there. Like any NIH institute
we’ve got intramural labs that are doing basic biomedical research. We have a clinical research program and I was the first director,
or the fifth director, but I was the first one
to actually establish a clinical program onsite. They may be sending permanent travelers, but we still are running quite a number of clinical protocols onsite. We have obviously, like any NIH institute, where does most of our money go? I’m going to show you that
and it goes externally, both related to grants and
some contracts and stuff. Our focus is a little bit different. Much of the NIH is focused,
I would say not on health, but on medicine and is
focused on treatment and cures and our focus is on
prevention because if you know what it is in your environment
that’s causing a problem, you can do something about it. We have two programs that are unique. One is the National
Health Psychology Program, which is actually a
cross-departmental program that also involves part of FDA, part of the CDC, and other parts of NIH as well, but it is headquartered at NIEHS and when I wear that hat instead
of my NIEHS Director hat, I theoretically report to the head of HHS. The head of NIH doesn’t
like very much, but anyway. The other program, which
I don’t have up here, is that we have a
Superfund research program and our Superfund program
is not funded through the traditional health
and labor committees, but it’s funded through the
interior environment committee and when it was initially
established after circle was assigned in 1986, it actually came as a
pass through from EPA. That was not very successful
because every year EPA said we don’t want to give you the money, and congress said you’re supposed to pass through this money and
EPA said no, we want it. So some time in the mid 1990s that became direct funding line to us and so that is a problem-solving program, as is the NTP. Their objective is to
address specific issues and find solutions, not necessarily the basic
biomedical research. Okay so we did a strategic plan in 2012 and I will say we are living that plan, and I’m not going to vow
and say Gary and say Gary, tell me which part of our
strategic plan you fit into, but in fact pretty much
all of our work is captured in different parts of the strategic plan. And our mission is that
the mission of NIH is to discover how the
environment affects people, to promote healthcare laws, and our vision is to
provide local leadership for innovative research
that improves public health by preventing disease and disability. This is kind of the over-arching
themes that we deal with and originally this, let’s see if I can here, okay well you can’t really see it, but those arrows all move. It was very exciting and
that made the point that these things went together. Unfortunately that was not
good for someone with epilepsy. (audience laughing) So we stopped and we made it steady, but the point is is whether you’re doing fundamental research or exposure research or translational work or
focusing on health disparities and global training
education, communication, they all work together
and that you can’t do this without managing your
data and your knowledge and you have to have collaborative and integrative approaches. So those are our themes
and they’re cross-cut with our strategic goals and
we have 11 strategic goals and everybody wants to know
why 11 and it’s because my husband is a mathematician
and 11 is a prime number and 10 is not one. The goal one is the
big, basic science goal. This is the fundamental research
identifying, understanding fundamental shared mechanisms
of common pathways. Goal two is one that I’m
especially excited about and a lot of our focus
for the past year or two and I see in the coming
years is going to be understanding the
individual susceptibility across the lifespan, because when you’re a baby your susceptibility is very different than when you’re a teenager, very different than when you’re an adult. We’re very interested in
transforming exposure science. We really need to know what
are people being exposed to and new approaches to doing that. We’re very interested in
the issue of mixtures, and I’ll come back to this. Yesterday, yesterday, come back with your minutes, not only mixtures of chemicals, but mixtures of multiple
environmental kind of stressors and we’re very interested
in dealing with new threats that are emerging. So sometimes we still capture
fracking as an emerging threat and you here in Pennsylvania
can certainly tell me that it has well-emerged. We need to be dealing with it. Come back to some of these, and then we are very interested in the issue of health disparities because different groups, different populations have
very different environmental exposures and risks. Our goal seven is the
knowledge management goal and the need to actually develop interdisciplinary approaches. We have two goals that
are dealing with kind of education and training. Goal eight is kind of the goal to deal with people in the community, improve basic education. You know, scientific
literacy in our country is pretty horrific and
we really need to work on improving that and trying
to help people understand that certain kinds of
exposures are going to be associated with consequences. Goal nine is the
professional training goal and that it’s not only inspiring diverse, well-trained cadre of scientists and training the next generation. The important thing here is
bringing in different kinds of disciplines who before
haven’t been involved in doing environmental health research. So the engineers, the immunologists,
you know just think of, certainly the mathematicians. Goal ten is one that I am very
hot on and that is because currently the only thing
that talks is money and so we need to understand
what the economic impact of our policies and
behaviors are and we need research programs to try to
express that in monetary terms and then the eleventh
is absolutely essential. We scientists, whether you’re
an NIHS-er or anyone else, need to communicate with our stakeholders, with the public, you know,
with other scientists, and so it’s really important
that we increase the engagement with all of our different
stakeholder groups to go forward. Okay so this is just a
look at more background and this is, so our total budget in ’16 was about $750 million, no actually that’s 780, ’cause we got a couple
of other little things. And what you can see if
you look at the green, the Superfund was about 77
million in the grants program, the basic NIEH kind of Grants program was was about three and a quarter, so we have a little over 400 million, so we’re just over a
little half of our budget goes to grants, now that’s small percentage wise compared to many NIH institutes. And part of it is cause we
have two intramural programs, We have the basic
Biomedical research program and the national toxicology program. And we also spend $150 million on R and D, which is money that is also
going out to the community, but in a more targeted, usually problem-solving approach. So much of the work that NTP does is actually done by research
and development contracts, for example. Our intramural program, again as I said we have two programs, and because we’re not in Bethesda, we have to provide
everything for ourselves from the animals to the reagents to the security services. We have a beautiful campus and if you haven’t been to North Carolina, I invite you to join us sometime. And we have really a beautiful, almost our campus is bigger
than the whole Bethesda campus, which is really, really nice, but costs us a lot of money to maintain and have security for it. Oops, I did want to tell you, this kind of gives you an
idea of the grants portfolio, course it doesn’t include the Superfund. The Superfund is two very
large centers programs: the Superfund research program, which is funding 14 centers in different parts of the country, plus a small number of R01s dealing with, for example, hazardous waste sites and how to clean them up; and then the worker training program, completely non-NIHy, but we are mandated to provide training in hazardous waste and emergency response cleanup to workers, and we’ve trained over
three million workers in every state and territory
in the last 25 years. And so those are again our
totally Centers programs, but you can see that
of our regular budget, 73% is in research project grant line. So that’s primarily R01s,
and little bit R21s or R03s or R15s and so on. And then about 12% of our budget goes into our centers programs. We have environmental health core centers, we have children’s centers, health disparity centers. We have brain and breast cancer centers. I’m gonna forget some
of our other centers. At different times we have, oh we have oceans and human health, and can’t say the words
climate change anymore, but the impacts of extreme weather events on the oceans and health are also a centers program. And then we have specific
training programs like RT 32 programs and other research efforts and small business. We are mandated like all NIH institutes to spend approximately
3.5% of our grants funds on small business
innovative research grants. So those are the ones that are making new widgets and gadgets and so on. So what about the environmental
burden of disease? How much does it account for? According to WHO, about 23% of all deaths are
linked to the environment, which is close to actually
13 million a year. I think it’s important that 2/3 of those are really related to
non-communicable diseases. And I know that it’s really
interesting and exciting to study infectious diseases, but frankly, the non-communicable, chronic non-communicable
disease is the bigger cause of morbidity and mortality worldwide, not only in the United States
or developed countries, every year. And we know that, for example, seven million people die
a year from air pollution, about four million are related
to indoor air pollution. I’ll come back to that later. And we know that many
of those are children. And with healthier environments, would prevent a lot of that. And so that we know that
environmental risk factors such air, water, soil pollution, chemical exposure, oops, got a bad word, climate contribute toward 100 disease and injury types. So our research is focused on understanding the interaction of our genetic susceptibilities and our environmental exposures. So what do we mean by environment? And we mean the big E, by big E I mean, as I said, water, air, and soil pollution, pesticides and other agricultural chemicals, chemicals say in electronics, but also things like prescription drugs, cosmetics, all kinds of synthetics. What about nutrition,
food, psycho-social stress, all those things are
part of our environment and are important for us to be looking at. So should you or shouldn’t
you be concerned? Well I can give you lots
of other graphs here, but I think here are just
a couple of examples. So we know that since the late ’80s, actually starting before that, there was huge increase
in overweight and obesity. This is not really showing the increase, but as well as there are some great maps you can pull up on the CDC website that show the percent obesity
in say the ’80s, the ’90s, the 2000s, and now. It used to be that the
country was blue, light blue, and now it’s all dark orange, and it’s pretty much the whole country. Initially, at first was
like in the obesity belt that goes across the south and then it’s expanded. And so that’s increased. I think, well, cancer mortality is actually declined in the United States, not in other parts of the world. The prevalence is
actually still increasing. I think Alzheimer’s,
everyone knows it’s becoming, it’s a huge problem and it’s
only gonna become worse. And we really don’t have anything, very little about what might
be causing Alzheimer’s, although we do know that there may be some genetics involved, but we really don’t know
what we can do to treat it. There are very interesting
work published in Science about two months ago, showing that air pollution,
women with an 8.4 polymorphism were at greater risk for Alzheimer’s if they were exposed to
near roadway traffic. So that’s one of the first clear examples that I’ve seen for an
environmental gene interaction related to Alzheimer’s. And then I think another one which many people are very aware of is a tremendous increase
in autism prevalence. So 20 years ago, the risk of autism, the number of children was at one in 120 or
even higher than that, now it’s one in 68, and that’s been steady for
the past couple of years. The most recent statistical data we have from the CDC was 2012, takes a couple years
to get those analyses. But about four, 4 1/2 times
as many boys are impacted by or somewhere on the autism
spectrum than are girls. That should tell us something. I mean there are a lot
of health conditions that are more frequent in
one sex than in another, but that should give us some clues, not only to how to treat, but maybe what’s causing. But I could’ve shown you
slides of, for example, breast cancer incidents
is actually increasing, morbidity not because we have pretty good treatments for that, but many other, testicular
cancer in young men continues to increase, and that’s a worldwide phenomenon. ADHD in children, dramatic increases. I mean, I could go on. Our genes don’t change that fast. So in fact, one point that I wanna make is there’s nothing about our health that is just our genes. And there’s nothing about our health that is just environment. Everything is gonna be an
interaction between the two and in fact what I probably
should put on this slide is kinda just like maybe a balance scale, you know somethings will
be much more genetic and somethings will be
much more environmental. But we call that whole
roadmap initiative at NIH looking at the interactions between genes and the environment. And much of our focus,
and when I say ours, that’s the royal, our grant
teams are busy developing all kinds of sensors and other techniques to measure environmental exposures and early biological response. And many of those are now being used in epidemiology studies, and I’ll show you a couple at the end. So what are some of the other areas that are really, really important? And I’ve had a couple interesting
discussions already here with an understanding that you guys are as interested in the microbiome as we are, but I think for many years
we didn’t think much about what was in and on us. So the picture here is just
looking at external microbiomes. Often when people talk
about the microbiome, I wanna make the point, people are usually talking
about the gut microbiome and they’re usually talking about what they can recover from feces. There are multiple gut microbiomes. The one, for example, your oral cavity is different than the one
in your small intestine, different than in your large intestine. You’ve got microbiomes in your ears. You have microbiomes in your skin, depending where in your skin
you have different ones, and we need to start paying attention to what those bugs are doing both in terms of how they respond to different environmental stressors and how the environmental
stressor may be different as it gets passed through
the microbial metabolism. The other thing I wanted to make is that when people talk about microbiome, they’re usually talking
about the bacteriome. They’re not talking about
the biome or the mycome, or the parasitome, and
we’ve got all those too. And I think we may want to
begin to think more broadly about the microbiome, but I think we’ve known for a long time that say arsenic can be made
more toxic by gut bacteria. It’s not the only, obviously,
compound that we know about. So another is the exposome, obviously ‘omes are big, you know. And it was first purposed by Chris Wild, who’s currently the head
of the International Agency for Research on Cancer, in 2005. And he basically defined it as the totality of human exposure. The problem is that’s almost
an impossible task to get that because what is in your body may vary from minute to minute, never mind day to day,
or time of day and so on. But when you look at the exposome, you’re really doing an untargeted
hypothesis free assessment of what the exposures are. So people have been doing for
the last 20 years or more, lots of biomonitoring, which is very, very helpful and important. But when you do biomonitoring, you’re looking under the lamp post. You’re looking at what you know about. When you start doing exposomic approaches, you’re starting to look at
things you don’t know about, which may in fact be very important. And so the metabolome, for example, is one part of the exposome. Your metabolome or rather
your endogenous metabolites present at orders of magnitude
higher concentration often than the environmental chemicals may be. And you can look at the exposome, you can look at the blood
exposome, for example, the urine exposome, usually do it in accessible tissues. And you can actually
use this as an approach to begin to understand the interactions of mixtures, both
chemical and non-chemical and the impacts on the microbiome. So in order to begin to do
more exposomic approaches, we developed a program that we funded at the end of 2015, which is actually a program that is trying to understand the impact
of environmental exposures focusing on children’s health and providing an infrastructure, infrastructure basically
laboratory capability to do both targeted and
untargeted monitoring of biological samples from any NIH funded studies that involve pregnant women or children. So it doesn’t have to be NIEHS funded. If you have funding
from any other institute and you had those characteristics, this consortium of six laboratories, a data center, which has developed a lot of new statistical
approaches and analysis and a coordinating
center is a place to go. So if you’re interested, just
go on the NIEH’s website, which is easy to find, niehs.nih.gov, and put in C-H-E-A-R, CHEAR, and you’ll get all the
information about this, but it’s a national resource that I think is going
to be very, very helpful and we’re very excited about it. So we all carry a chemical body burden. CDC issues a biannual report card of what they measure, and again, it’s targeted monitoring. But for example, chemicals
that you’ve all heard about, and there are some concern environmental BPA, PAH,
phthalates, and so on, you know there present
in pretty much all of us. There’s some studies that show most of these are present in pregnant women and all which means of course, that the developing fetus is being exposed and that many of these chemicals are also found in breast milk. The CDC measures that. Very little monitoring
is ever done of feces. And of course there’s totally
different chemicals present, for example, in urine than they do in feces and so on. What’s in feces is often
present in breast milk as well. But in cord blood, for example, there’s almost 300 chemicals that the CDC is looking for. That tells you nothing
about how many are there. But I think a really important point is everybody has a mixture
of these chemicals. Nobody is ever exposed
to one chemical alone. So how is everything
coordinated in our body? And I think we all know and there’s a lot of talk about endocrine disrupting chemicals, but we know the endocrine
system is extremely complex. It control basically our basic physiology. We sometimes forget that it absolutely controls development, and I’m gonna show you a slide about that in a moment. But the World Health Organization
in 2012 issued a report where they said that they
were becoming a global threat that needs to be addressed. And I think what we’re
finding more and more, and I think I have a slide about that, is we go low dosage, you’re having endocrine mechanisms. And endocrine, can be defined broadly, but it often involves nuclear
receptors attachments. So I think the point I wanna make and I’m gonna come back
to again and again, not only is endocrine disruptor
action life stage specific, but many effects are going
to be life stage specific. So while people have done a lot of the endocrine disrupting work looking at, for example,
estrogen or androgen effects and looking at effects on
the reproductive system, those are relatively high dose effects and in general may be reversible compared to what happens
during development where you have organizational effects often occurring at much lower doses. These effects often are not seen, for example, at birth. You may not see them
for a couple of years. You may not see them for
20 or 30 or 40 years, which is the latent period, and they are persistent. So when you perturb
something during development, you have long term impacts. So there’s this whole hypothesis
related to low does effects and one I think endocrine
disruptors have effects especially development at low dose. We see body burdens that are similar between animal studies and human studies, and when you look at your
epidemiology studies, you find that those are low doses. But the problem is, people mean different things
when they say low dose. So if you ever hear anyone
talk about a low dose study, you wanna ask them, what do you mean? How are defining this? Is that because it’s lower than was a traditional regulatory limit? Or is that because you’re
mimicking human exposure? And I usually define it by putting it in terms of human exposure, something that’s in the realm that the general population may face. To me, that’s a low dose
or it should be anyway. So I brought up this issue
about windows of susceptibility and longterm effects
of early life exposure, and this slide could be
much, much more complicated cause it’s not only what
happens during gestation that can impact all these life stages. But in fact, all these are
different susceptibility windows where you may have
differential susceptibility, which will mean different
things will happen. We often forget, for example,
that a pregnant woman, her body is rapidly
changing, rapidly developing, so she’s in a susceptible window, not only her fetus, for example. So I think those are important
things to think about. And so the fact that early life exposures have lasting effects has
led to a whole new field known as DOHaD, or the developing origins
of health and disease. Much of this came from the work that was done by David Barker in Southampton in the UK where he initially studied what was called the hunger winter or the famine in the Netherlands that occurring in 1944
during the Second World War. And children who are born, or had been in utero during that time, 40, 50, 60, 70 years later they’re still being followed. So they were undernourished in utero, had ended up with much higher rates of obesity, type two diabetes, cardiovascular disease, and cancer. And this impact has been
seen in numerous populations from the starvation that
occurred in Leningrad during the Second World War, to what occurred in the UK
during the Second World War, to Holocaust survivors,
a number of populations, this is a consistent finding. And so why is early life so sensitive? Because things are happening, genes expression programs
are being established. I’m not going to talk
about epigenetics guys, but if you’re not thinking
about epigenetics, that’s where a lot of the action is, especially related to a lot
of environmental exposures. Now I like the analogy that your genes are the score of a symphony, and epigenetics is the conductor turning things on and off. And so epigenetics is what controls when genes are turned on and off and it keeps getting more
and more complicated, but it’s clearly related to lots of different health and
disease states as well. And this is what’s during development you have lots of epigenetic
programing going on. And so again as I said a minute ago, changes occur during development permanently alter the organism. So here’s some examples of diseases that can be induced by early life exposure that we don’t see. So you can have things
like learning differences and behavior, asthma, increase
sensitivity to infections, the whole testicular dysgenesis syndrome, this is the hypothesis that
environmental estrogens are leading to an increase
in cryptorchidism, hypospadias, testicular cancer. Things like infertility, obesity, there’s some data that says
that Parkinson’s disease may have an early life initiation as well as I’ve given
you an example of say cardiovascular disease and
so a wide range of things. So the point I wanna make
is it’s not only in utero that is a super sensitive window, but preconception is turning
out to be very important and why is that? Because what’s happening
preconceptionally, your germ cells are developing, there can be substrains for DNA damage. There can be changes in
mitochondrial integrity. You can have all kinds of things going on and the epigenome of the
germ cells can be altered. But the point that I wanna
make is that we now have data that shows preconceptional
exposure has impacts. For example, on the mother, that there are impacts
that are shown on obesity with maternal obesity
alters oocyte maturation and the offspring growth. That mom’s anxiety can impact the offspring
behavioral disorders. Preconceptional smoking is associated with increased risk of
congenital heart defects. We all know that smoking during pregnancy is really bad for the baby
for multiple health outcomes. But finding that, it’d
be better if you stopped before you even thought
of becoming pregnant. And then we know that there’s data from a number of persistent organics. associated with, for
example, low birth weight. Well, I got tired of talking
about women a little bit. And wanted to stress to you
all that dads matter too as far as preconceptional exposure. So we know that offspring, this is actually a rat study coming out of Oliver Rando’s work. Fed a low protein diet, have
impaired liver function. We know that offsprings
fed a high fat diet have diabetes and poor semen quality. And paternal obesity,
these are human studies, results in obese offspring and there’s an association
with increased rate of autism. So you know again, I was always very strict with my daughters and not so strict with my son about what he ate, no swordfish, gotta be careful of that ethyl mercury. Better be careful of things that would have PCBs and dioxins in them. And I kinda didn’t worry about the boys because I thought it’s all related to what you have in your
body when you’re pregnant. Anyway, he’s a good dad. (audience laughing) So I think the point is is
that the whole issue of DOHaD is that you have this
multigenerational risk cycle where, and this applies
to both men and women, so for example, if you
have a woman who is say, has a lot of health disparities,
might have a poor diet, not enough exercise and is overweight, might not be prepared for pregnancy, the infant for example isn’t breastfed, or breastfed very little
and a poor weaning diet and I can tell you, if you go into some of the more
economically deprived areas, you go to some of our tribal communities, you know kids are, what are they getting
in their baby bottles? Frequently they’re getting soda, like Coke and stuff like
that cause it fills them up. Anyway, the child is
going to be overweight and we know that that may be associated with neurocognitive development, the adolescent and it becomes a cycle. And this is really related to nutritional or is focused on nutritional, hands in development. Again from Southampton. So one of the issues here is
multigenerational effects, and I would say it is clear that there are effects
that can be inherited, at least up to the second generation to the grandchildren. I think what is less clear is are there things that actually go to the third, fourth,
and fifth generation. I don’t think that’s
clear from human studies. There are quite a few, and I should say that in males, you gotta go to the second
generation is transgenerational and in females it’s the third generation. Remember because in females, a girl child is born with every
egg she’s ever gonna have. So it was exposed, if there was exposure before she was born. So it happens to fit. So there from experimental animal studies there’s some of the data showing that some of these lovely compounds that we’re all familiar
with BPA, methoxychlor, which is a pesticide that’s an estrogen metabolized to a potent estrogen. DES, I don’t know, not a
lot of young people here, but DES was used extensively
in the ’50s, ’60s until 1971, Howard Bern
found adenocarcinoma in young women whose mothers had taken DES to prevent miscarriage. It didn’t really prevent miscarriage, but it’s had long term impacts, not only on those women, but on their daughters
and their grand daughters, as well as on their sons, there are DES sons as well. Vinclozolin, which is anti-antigen. The dioxins and tributyltin and all these things with
some mechanistic information about how we can explain these and these are all really
epigenetically immediate. So to give you some examples of effects for early life
exposure, for example, prenatal exposure to
phthalates is associated with an increase in asthma and you know it’s not all phthalates so there’s a huge number of phthalates and of course depending upon
the health impact you look for. This one is coming from dibutyl phthalate and dibenzyl phthalate, what you measure are
metabolites in the earth and you can see that those are the two that are causing the significant increase in asthma in children. But if you look at some
other health endpoints you may see other phthalates
that are problematic. Phthalates are all used as plasticizers in a lot of plastic tubing, used to be in rubber decking, some of them are still in rubber decking but not some of the high
molecular weight ones. So we know that there are immune effects, again, for early life exposure. Those are the two environmental exposures so prenatal exposure to the PFCs. Haven’t mentioned it before that that’s PFOA and PFOS
and a whole host of others. I don’t know whether they’re much of a problem in Pennsylvania. I know right in New York, there are loads of questions
about them right now. But we’re all exposed. Everybody carries these chemicals, about eight of them
actually, in our blood. But anyway, prenatal exposure, increased days with fever. Prenatal exposure, Philippe Grandjean, has shown that recurring POPs led to decreased white blood cell counts in five year olds. I think some of the most concerning stuff that we’re seeing not only from Grandjean but several other investigators have now shown both the PFCs and PCBs, the prenatal exposure is associated with decreased ability to
mount the vaccination response. In fact, about 20% of
Grandjean’s population in the Faroese Islands are below the level of having a health
protective antibody titer. The thing that I think is, two things are important about this. First of all, it’s exactly what we saw in our rodent models, exactly. Mice, the PCBs, you
expose them to the PFCs like PFOA or PFOS and they lose or they have greatly reduced ability to mount an antibody response. Now we’re seeing it so I think we need to begin to asking the question when you hear about an outbreak of pertussis or measles or chicken pox, is it because we’ve got people who don’t wanna vaccinate their kids or are they people who
are being vaccinated who are not able physiologically to mount a healthy antibody response? And then pesticides exposure here, higher adolescent body fat content. This is kind of on the wrong slide but anyway and girls appear
more susceptible than boys. This is actually dealing
with a genogram interaction. This example I believe is for PuroFoS which unfortunately was supposed to be banned totally from agricultural use and the new head of EPA
decided not to go forward with that recommendation. So I mentioned some of these things about obesogenic chemicals and those are chemicals
that are associated with an increased risk of obesity. Whether that’s a direct effect or happening via the micro biome I don’t think we know yet. But we know that nicotine acts like a developmental
obesogen in humans so I hope nobody in this room
is vaping with e-cigarettes because that’s just a
nicotine delivery device and we know that nicotine is a really potent developmental
toxicant in many ways but I think that this is, what’s really interesting is that girls who are exposed in
utero to cigarette smoke that may be small for
gestational age when they’re born but by the age of 10 are more likely to be overweight or obese
and by the age of 20 are more likely to have
developed type two diabetes. So another negative of cigarette smoking. BPA effects insulin release and cellular signaling
in pancreatic cells. There’s an association between diabetes and dioxins in certain PCBs. (audience laughing) Okay and multiple classes of pesticides may affect risk factors
for diabetes and obesity so that there are many compounds now showing associations. So this is just a little
bit of information about exposure to BPA. May be associated with obesity in a child. Prenatal exposure is associated with increased body fat and waist size in inner city children in age seven and that was related to
the prenatal exposure, not their exposure once they were born. So again, yes infancy
can be a sensitive window but it’s really dependent
what you will get. But at least for obesity
it appears to be in utero. Here Leah Trasande of NYU has estimated that the BPA exposure just associated with obesity resulted in
almost 28 million dollars in additional child health care costs. So just another one on BPA and this is just showing you some of the forest plots but we review studies that were done over a four year time period and for every endpoint, whether it was glucose homeostasis, diabetes or overweight and obesity, there was significant
increased risk through BPA. Now I’m not going to talk
much about neurodevelopment. I mentioned ASD at the beginning. I mentioned ADHD but what we’re finding, this is some of the data
showing the increase in ASD and some people will say the increase in autism, oh it’s just better
differential diagnosis. That explains 30 to 40 percent, at most. Most of it is real. I think the point is that
we know that many compounds, not only with ASD, but
with ADHD and cognitive, with learning ability, that BPA and guess what guys, if you have those new water bottles that says BPA free, you
got something else in them and guess what, we’re finding that those other things may
be equally as problematic. The brominated flame retardants, we’ve known for years that house dust and office dust is a
big source of say lead and we’ve thought about that but it’s only recently
that we’ve begun to say oh what else is in the
house dust and exposing us. Phthalates, which I said, are in lots of plastics and stuff as well as lots of food containers. So in fact, a lot of food has high levels of phthalates in them. PFCs I’ve mentioned. Perchlorate, which is used in rocket fuel, real problem in certain areas and problematic during pregnancy related to thyroid homeostasis if you don’t have accurate iodine intake. I just stuck on this slide some of the metals and nevertheless, I forgot to put on cadmium or for example, which is also
developmentally neurotoxic. I think you all know about methylmercury being developmentally, lead. Science is just a clear example of environmental injustice. Fluoride, now many of us have sung the praises of fluoride at least with our kids not having as many cavities as we did. But there’s not much of a margin of safety between the levels of
fluoride in drinking water and the levels where developmental impacts on cognition have been
reported from the Chinese and from three studies
which should be published. One this month, one next month and several others that are coming up. So I think we need to think about that. Arsenic, many of you probably know the Arsenic and Old Lace, that Agatha Christie where obviously there was a neurological impact as well as high doses killed them. But very low doses of arsenic, doses below the regulatory limit are being shown to be associated with lower learning and memory. A study was done by Joe Graziano in Maine where he recruited school children and most Maine kids are on wells and many of the wells had
elevated arsenic levels and I’m not sure they’re
phenomenally elevated but the regulatory limit
is 10 parts per billion and above five parts per billion, the kids had lower IQs,
the population was shifted. So I think we need to think about that. Manganese is another one and I could go on but the point is I’m becoming convinced that metals have no safe level. You want to get them, certainly
we know that for lead, and I think the more we study, the more we find, the less you can have with exposure to these, the better. So I’m not going to talk
much about air pollution but guess what, air pollution does it all. In this country today, our air doesn’t look like Beijing or Delhi or many other places in the world. But we’re still finding effects at levels below the
current regulatory limit and these are just some of
the effects that we see. Now I can remember 20 years ago, thinking oh air pollution, it was all about ozone and it’s all about pulmonary effects. Well guess what, it’s not just ozone. There are other pollutants
like SO2 and NOX and carbon monoxide and so on and PM and then it was PM10. Well it’s not just PM10. There’s PM2 the smaller particles, tend to get more and more toxic as PM2.5 and then to the
nanosized PM particles as well. Not just pulmonary, cardiovascular and then we’re finding things like developmental exposure associated with decreased IQ, increased
respiratory infections, behavioral effects, increase
in ADHD for example. There are at least 12 studies
that are now published. 12 observational studies in humans showing increase in autism associated with heavy traffic pollution. Problems with autoimmunity,
obviously asthma and associations with diabetes. So lots of things that air pollution does. Most of our focus is on
ambient air pollution and that’s because
that’s what’s regulated, at least in this country. But I can tell you the
most dangerous place to be is indoors and in many parts of the world we have people who are
cooking with biomass on various primitive kinds of stoves but we have 16 million people who are cooking and heating with wood in this country who are also at risk. If you’re gonna burn biomass of any type, there’s no way you can
burn it clean enough to get to basically your
PM levels down low enough. You can get better. One of our grantees, let’s
see do I have it up here. This, the increased risk
of low birth weight, respiratory infant mortality, this is Jim Tielsch’s study but Kirk Smith has been
working in Guatemala for the last 25 years doing a study called Respire and he has shown that if he uses a modern or a more modern wood burning stove, he can drop the PM levels and he can reduce the
severity of pneumonia in the kids but not the incidence. So they’re still getting it. So right now NIH has
finally gotten some funding from the Gates Foundation and from the Global Alliance
For Clean Cookstoves and we’re part of this, several of the other institutes and are conducting some
intervention trials we’re actually providing electric or propane fueled stoves to people to see what we can do
and whether it impacts on their health as well. So I’m not gonna have time to go through the specifics there. So we also know a lot of what we know about environmental impacts are kind of based on how
the poisoning scenarios and I’ve included smoking in that, smoking during pregnancy. But they’re recommending, we all know about the
developmental effects because of mini model series. We know about lead. I sometimes wanna think and I was mentioning to some
of our colleagues last night, we should be thinking about what about the elevated lead because lead is associated with cardiovascular
disease and renal disease and I tell you 40 years ago the average lead level in the US was 15 micrograms per deciliter. Today, CDC is about to drop
the level of concern to three. So where is all that lead? It’s stored in your bones. What happens when you get old? You start mobilizing, as your
bones start breaking down, you start mobilizing the lead and nobody’s thinking about that. I mentioned DES as the drug. PCB contamination of rice oil. Everybody in this room has PCBs. PCBs were banned in the US in 1977. Every single one has. PCB levels came down until about the 1990s and now they have kind of
stabilized in the environment and part of that is because 70% of the PCBs that were ever made are still out there and you have constant, we have micro contamination
of the food supply so you get your dose every
time you eat animal products. Just a little bit but many
of them are very long lived. So the rice oil
contamination is a high level that occurred was unfortunate. The same kind of situation
occurred in Taiwan. That was ’69 and ’78 and
what’s really interesting in both of those
populations their children and now their grandchildren
are now being followed and they’re seeing
second generation effects in the grandchildren. There was an episode in Michigan
where unfortunately PBB, it was called Firemaster 560 and it was a flame retardant and accidentally got
mixed in with the feed and thousands and thousands
of domestic animals and cattle and sheep had to die, therefore had to be slaughtered. Unfortunately many of the
farm families in Michigan ate their livestock before they realized there was a problem and those children and grandchildren continue to be followed by Michelle Marcus at Emory. There are impacts on them. Then RC contamination of drinking water. In the US, we do have
over 16 million people who are at levels that exceed, or on municipal water systems that exceed the 10 nanograms per liter, the PTB level but then there are
people on private wells. You have areas of the country
like parts of New England, the southwest, that have
very high arsenic levels in the drinking water. If your levels in drinking water are low, that’s the good news but you might want to consider your rice because rice can be a major source depending where the rice was grown. Since none of us can
tell in the United States where your rice came from, I can tell you that basmati rice has less than some of the
long grain and wild rice. So what about the cost? Well these are just some estimates that Prasami did in the past two years. This was work that he did for the EU and so when you look at the health effect or you look at the type of
chemical that you look at, we’ll take pesticides, you’re talking about hundreds of billions of euros a year of cost and this is the kind of analysis I think that we really need more of to try to make the point. I know the estimates are for lost IQ due to lead is over a
trillion dollars a year. Just for lead. So how are we approaching some of the toxicity work
that needs to be done? There’s no way that we
can ever test ourselves out of concern. So we can only do maybe one to three epidemiology studies a year. There are only a couple
of environmental exposures that you can actually do clinical trials with cause you’re not
going to intentionally expose someone to something that you know could cause a big problem. We do it a little bit with air pollution. We do a little ozone exposure, a little PM exposure and
so on but never where- They’re usually short term exposures and not at levels where we expect. But it’s very difficult. You’re never gonna intentionally, today, you’re never
gonna give chlorpyrifos to anyone intentionally or PCBs to anyone intentionally. So we have a standard
work and tox test here. I can tell you that the long term studies, there are really only two places in the world they are being done. One is at NTP and one is
at the Ramazzini Institute in Bologna and maybe we’re doing three to five or maybe eight chemicals a year at three to five million
dollars per chemical. Obviously you can’t do very many of those. We’re doing more and more work with alternative animal models. So drosophila, worms, zebra fish, I have to tell you zebra
fish is my favorite. I don’t know if anyone here is working. But I love them because you got all the genetics and the genomics of them. You got all kinds of
ways to manipulate them. You can use 396 well plates and each one is an individual zebra fish. In the first five days of development, they only live for three months, but the first five days
they’re totally transparent, so you can watch everything forming and that’s pretty cool to see that. We’re doing lots of work looking at biochemical cell based assays. We can run ten thousand chemicals at over a relatively short period of time through batteries of 70
to 100 assays for example. We can identify toxicity pathways and do a lot of computational work. So we have to be moving in the direction to do better testing quicker. So some of the things that
I think are important. I’ll start with the bottom one because this is related
to looking at pathways of computational which
is harnessing big data and open sharing of the data. We all are going to, right now if you’re doing any genomics and you’re funded by NIH, you gotta enter your data
within three months into DCath. I can tell you for environmental exposure the same thing is coming. Data is gonna have to be freely available. The other two are two really great things. One is, I often say to people, okay you wanna rat that will
never get breast cancer? I got a rat for you. You want a rat that will
always get breast cancer? I got a rat for you. Which will represent the human population? Both. So what many of our experimental studies are done with inbred strains of animal, you could be missing the
effect that you wanna study. So working with inbred animals is really good when you’re
trying to get to mechanism. But when you wanna try to understand does a species have an effect, cause you really wanna take
it to homo sapiens then, I think there are better models. So one is the Diversity Outbred Mouse and Collaborative Cross
which span the genetics of mousedom and when using
the diversity outbred, NTD did a study, it was
published about two years ago, where they looked at benzene, a very, very well known
toxicant and carcinogen and they were able to show
just doing a 28 day exposure, almost a 300 fold
differential susceptibility between a most sensitive mouse and the least sensitive mouse and they did it two times. Robust, it repeated very nicely and then we did a study using the thousand genomes project which is there are 10,086 human lymphoblastoid cell lines that come from nine ethnic
groups in five continents. I was getting my numbers reversed. There aren’t nine continents, right? Okay, they’re a cancer cell line but they’re the same kind of cell line and we looked at just the toxicity measure with 179 different chemicals in these thousand cells
and what did we find? A 200 to 300 fold variability
and susceptibility. Not to all the chemicals but
to some of the chemicals. So I think that we need to keep that in the back of our minds
that we already know that Megann and I aren’t
the same genetically or historically or anything else. But we need to think about that and we need to think about that when we’re doing our
animal models as well. So there’s a lot of new approaches that I think can be used. Then I mentioned some
of the exposure tools cause exposure is so important. Those little wristbands that are actually being used in epistudies right now. They’re silicone wrist bands that come in multiple colors and they’re embedded with sensors that can pick up at least a thousand different air pollutants that are actually it discriminates 25 different
PAHs which is pretty cool. The only problem we’ve had is that they’re used in
some of our children studies and they kids don’t wanna give
back their pretty bracelets. So it’s a simple solution though we just give them pretty bracelets without sensors in them. They don’t know the difference
and we have the data. More and more personal monitors are being developed to be worn like for air pollution. Much air pollution data
is based upon sensors which are just set outside. We really wanna know
what’s personal measuring. It used to be that it
was a heavy backpack. That doesn’t work for a four
year old or five year old. So we’re developing
things that are based on the size of a deck of cards and those that can fit in a pocket and what we’ve been
able, world we, not me, grantees, have been able
to show, for example, that the highest exposure that kids get is when they’re waiting
for the school bus. Now I don’t know if they’ve done this standing outside waiting for soccer moms to pick them up and you
have the idling cars but that’s a real issue about pollution. So I think a lot of new techniques that are being developed. Another thing is, you can’t do environmental health work without engaging the community and we’re moving more and more, not only having all of our synergists have community engagement cores that are absolutely
essential to do the work. But doing a lot of citizen science and we have a whole bunch of programs. This is just giving you
a list of some of them. For example the Research
to Action is one community. These are community driven efforts. The Research to Action. We have programs in
climate- Gotta change that. Climate and Human Health. I mentioned Global Alliance
For Clean Cookstoves. I didn’t mention some of
our long term LP studies, our internal studies. We’re doing Study Sisters. Almost 51,000 women who are sisters of women who had breast cancer. This is a sister study. Recruitment started in 2004 to 2009. So some women have been in
the study now over 10 years. About 2000 of these women have gone on to develop breast cancer. Partly they were recruited because we know that women whose sisters had breast cancer are at increased risk
themselves for breast cancer. We’ve always said it’s genetic. We’re now gonna step back and say, you know most sisters grew
up in a similar environment. What role is that playing? So we’re trying to understand what are some of the risk factors for breast cancer there. Just many other studies. I hold community forum. I usually hold two or three
a year in different places. I held one in Prevolito last week. That was not the most
difficult one I ever had but it was in a community that was living on a former dumpsite where they filled in a 400 foot wide canal between two lagoons. Every time there’s a heavy rain, the houses flood with a whole toxic stew and also a lot of sewage. So I go to learn about this. One of the most interesting ones I did was on St. Lawrence Island in Anchorage. Some of you may remember when a former vice presidential candidate mentioned that she could see Russia. She couldn’t from Wasilla. But St. Lawrence Island is about the size of Puerto Rico that is located almost on the international date
line in the Bering Sea and it is 30 miles from Russia and on a clear day, which
doesn’t happen too often, you can actually see
the coastline of Russia. Her husband was stationed
there in the US Air Force so that’s probably where she, anyway. This was a very interesting, two communities about 1500 Yupik, secondary Yupik native people who are tremendously
disadvantaged health wise and environmentally wise. It was both because where do environmental pollutants go when they go up into the atmosphere? They go up in temperate climes and then they come down in the Arctic and what is their traditional diet? Their traditional diet
is, not so much fish, whales, walrus, that kind of thing, which are heavily contaminated. So we’re trying to
improve how you evaluate environmental health for clinical studies. We know from big general systematic review for a long time. When you’re doing environment, you can’t just look at clinical studies because we don’t have
them most of the time. But we have epidemiology, we have animal, we have mechanistic and
we’re trying to develop transparent and complete approaches to pull all the data together to try to understand what
the real hazard may be. Some of the other key
issues we’re dealing with are global environmental health, health disparities,
environmental health literacy, communication issues and I have to change this
one, climate effects. We’re also as a nation before our goal five is emerging issues. And emerging issues,
these are just a couple of examples, obviously you recognize 9/11. That was a hurricane. That was the result of super storm Sam. You remember a few years ago. I forget what the other two were. But we actually developed
a whole new approach. We call it the DR2 approach, if you’re interested in finding it, just go on the National
Library of Medicine website who we work with and we’ve got that 300 drop down protocols. Some of them awarded them through our IRU approval as well as some of our grantees approval so that when the next emergency hits, whether it’s national or industrial cause, we can get people in the field, on the scene immediately. I think that that’s really exciting and I’m just about through. Zika, okay, Zika it caused
all that microcephaly and microcephaly in Brazil. Not nearly so much in some of the other countries
where it’s happening. Puerto Rico is ground
zero in the US for Zika. There have been over
40,000 confirmed cases. What we’re finding from
some of the studies is that only 20% of
people who ever had Zika even know they had it. So maybe there have been
five times 40,000 so far. You don’t have a lot of infection in the dry season cause you don’t have a lot of mosquitoes then. So we’re kind of expecting it to come roaring back this summer. The real concern with Zika, I think it’s not only the microcephaly but we’re finding that there are other neurological effects which are not evident when the child is born. That often, they’re finding a kid six years old that’s not
developing normally and so on. So I think we just don’t know. We are part of a consortium with Nationals to validate infectious diseases and the National Child Health Institute recruiting over 10,000
babies in Puerto Rico, Brazil, Colombia, Guatemala and Nicaragua in the first trimester of pregnancy and we’re gonna be following them and their children to try
to get a better handle on the health effects. I should say that Tony Fauci and his group are really, they found a vaccine which looks like it might be pretty good. So hopefully they’re, but
we’re always for looking in NTP at some of the pesticides that are being used in the areas where we’ve seen microcephaly. So this is one, in Miami
that are using Naled and that makes me really scared because that’s a brominated, chlorinated redonal phosphate. Not a pretty chemical. Okay so as I mentioned
before, this is it guys, prevention is the key. Genetic and environmental
factors both interact. What happens depends
when you were exposed. Both chemical hazard and exposure are both critical components and if we can identify
the environmental factors we can do something about them because you can’t change your genes but you can change your environment. So thank you. (audience applauding) Okay so I’m happy to answer any questions. What I talked about or something else. – Can you address about how pharmaceuticals in the environment? Is that something that we (muffled) – It is beginning to be. For a long time, it was a drug so it was verboten but what we’re finding people are being exposed to drugs through their drinking water exactly. It’s also interesting as we move to use gray water more and more, we really need to understand whether we’re getting rid of the personal care products and the pharmaceuticals
in the drinking water. I know in Israel they
use a lot of gray water. They found elevated levels of Prozac and cucumbers and some other, I forget what other kind
of vegetable was taken up. – Is it healthy? – I don’t think they looked
at the health effects. Other questions? – I think you were
using the term obesogen. I’ve never heard that before. I was really curious about (muffled) How does that work? – Mechanistically I don’t think we know. We have better information on tributyltin and some other chemicals. As I said it may be the changes in the microbiome but the important thing that you just highlighted was, guess what, different things happen in adults to children or fetuses and we need to be alert to that so we need to not expect it. The other thing that I
didn’t talk much about. There were a few examples on the slides, is that boys and girls
respond differently too and for years I can tell you lots of people in our animal studies we’d only use male rats or mice because they didn’t have to deal with the estrus cycle. It was much easier. Well guess what? Frequently now we’re finding that females respond differently and that’s very true related to some obesogens, it’s true related to some
neurodevelopmental impacts. It’s true related to some immune effects. So NIH now is basically requiring you, if you’re only gonna use one
sex in your animal model, you have to justify why
you’re only looking at one. Obviously if you’re studying
testicular development, you’re okay. – Can tell me some more
about the bracelets? – Sure they’ve been developed by Kim Anderson at Oregon State University out of Corvallis, Oregon and they are, I believe actually she
may have formed a company and is actually selling them. But if you’re interested, I would google Kim Anderson or Oregon State University. They’re developed in our
Superfund center out there. – Kim Anderson?
– With an O. – I have two questions. The first is about the coated rice. Is this the old story
of some radical research about some new rice, golden rice, called or true door so the experiment
was not approved by NIH? So there’s a research method, data experiments you cannot, talking about NIH policy
in research methods so what’s your opinion about the national cooperation research? – Well I think that we
live in a very small world and we have to work together. I can tell you currently funding by the NIH or by US government of work in other countries is being seen as foreign aid not as research so it’s gonna be a little more difficult. But I think there’s great
work coming out of China and India and Japan, Korea. Lots of partners throughout the world and we can’t, we shouldn’t ignore it and we should be partnered with people. – (muffled) Is this part of a new law? (audience laughing) – So the president
released a skinny budget. That’s what it was called
about two weeks ago. And that called for a least
an 18% decrease to NIH. It’s actually more than that because NIH has to absorb AHRQ without any funding and they have the 21st Century Cures money fortunately a million dollars which
was already appropriated this year under a separate legislation has to come out of the budget. So it’s closer to a 20 to 23 percent cut depending upon your institute. Now I don’t have a crystal ball but none of us think
that those cuts will hold but I think some cuts will hold. In other words I think that, I don’t expect that we’re gonna review the 20% cut at NIH because
everybody loves NIH. There isn’t a congressman who doesn’t have an NIH grantee living in his district. I think it’s our opportunities to educate our legislators
about the importance of health research and
how it improves lives and its scale, it’s innovation and so on. So, sorry, no more information. – So you probably can answer in terms of what do you think is gonna happen with the NIH budget
but if you some insight that would be helpful
and then to what extent- – So let me answer that first.
– Yeah sure. – So I think that if this were to happen, we’re looking at at least 10% cuts of competing grants,
of non competing grants and probably drop in the
pay line in the foreground. – And then my other question is some of the NTP testing that you’re doing. I wonder to what extent, before even putting new
chemicals on the market, the private industry could
bear some of those cost, bear that responsibility. – I could say we have the
best government money can buy. But that probably
wouldn’t be very helpful. Toxco was recently revised after trying for about 20 years, to require industry to sponsor some testing. But it’s, I think, five chemicals a year. It’s not a huge number. There are over a dozen chemicals, that’s just in commerce, that’s not including lots of other stuff. So it would be nice if industry would do some of the
testing but I don’t expect great increases there and I would say you have to always look- You know you sometimes only
find what you look for? And a lot of the testing,
the required testing is based on studies that were developed study protocols in the ’70s and the ’80s. I want to know why I’m not
using 21st century methods. There and then there. – What methods of communication do you think are most effective for influencing support of science either among citizens or
among government officials, whichever answer you choose to give. – Well I think to inform
our fellow citizens, I think social media is
really important today. That’s how information is shared. I think as far as our legislators, we all have the opportunity
to educate them. I can even educate my
legislators as a private citizen. I just have to take off my government hat. I think if we can get
to them on the phone, that’s not always possible,
you can write to them, you can email them. I think actually written things have more of an impact than
email at this point in time. You have an opportunity, you can visit your congressman, either their local office or through marching in
Washington for Earth Day. Of course there are gonna be about 284 marches around the country. You don’t have to go to Washington. I bet there’s one. For the March of Science on Earth Day. Frank? – [Frank] I have a question
on the Chlorpyrifos I find particularly entertaining. Not in a good way and also maybe atrazine thrown in on top of that so with so much evidence from
science for so many years, why do we never hear that maybe FDA or USDA via the pesticide data program, why wouldn’t they actually have an ability to keep that off crops? Why does it fall under just EPA and how can one person basically- – It depends upon, so our regulation of our food supply, and I’m not an expert on
this, it’s pretty distributed. So I remember there was a study where there was lots of contamination found in some chickens in I think it was the late ’70s and trying to find out what
was the source of that, which we did within a month, it was pretty exciting actually. But the point was is USDA controlled, was responsible for regulating, and I may have this but
it was USDA, FDA and EPA and one controlled the chicken and one controlled the egg and one controlled I
think the chicken feed. Something like that and they were differentially regulated. You got some of the same
issue with pesticides. If you have pesticide residues in food, then that becomes the Center
for Food Safety and Additives, sustained responsibility. But the major exposure like for a purophosphate, remember it was banned for residential use in about 2002 and the major exposure today is the agricultural use on
fields and on golf courses. Then it drifts out into the,
pesticides don’t stay put. They drift and so there have been quite a number of studies that have shown elevated levels in little kids, elevated levels in cord blood of women who are living near areas where propurophos was sprayed. Atrazine, I think it’s
about 60 something percent of the population is exposed to atrazine everyday in drinking water. Clearly problematic. I think the data, but the
regulations are just not there. FDA has a very stringent
regulatory system. They’re very afraid of litigation so they’re afraid to do anything. So okay, well thank you all. (audience applauding)

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