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Proceedings
Day 1
April 18, 2007
WELCOME, INTRODUCTIONS, AND
WORKSHOP OBJECTIVES:
Dr. Alan Leshner
Dr. Leshner: Good morning everyone.
I am Alan Leshner. I am the CEO (Chief Executive Officer) of the
American Association for the Advancement of Science and Executive
Publisher of Science magazine, but I am here in my role as chair of the
Institute of Medicine’s (IOM’s) Forum on Neuroscience and Nervous
System Disorders.
I am delighted to welcome everyone. This is the workshop Autism
and the Environment: Challenges and Opportunities for Research.
The major purpose of this workshop is to work together to try to
figure out how we can do a better job to bring the full power of science
to bear on a public problem of tremendous magnitude and tremendous
import.
The IOM’s Forum on Neuroscience and Nervous System Disorders
has the purpose of building partnerships and discussions to further
understand the brain and the nervous system, to understand disorders and
their structure and function, as well as clinical prevention and treatment
strategies.
What the forum does is to bring together leaders from the public and
private sectors, including federal agencies, the pharmaceutical industry,
advocacy organizations, and the academic community to have conversa-
tions about these general critical issues.
5
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6 AUTISM AND THE ENVIRONMENT
In addition, we try to serve an educational function, educating the
press, the public, and policy makers about neuroscience and nervous
system disorders. One of the mechanisms through which we operate is
workshops like the one today that provide a venue for discussion about
key challenges and opportunities in the field.
The Forum was asked to host this workshop by the U.S. Secretary of
Health and Human Services, and William Raub will speak in a moment
to help explain its origins, but it came about as a result of a series of
discussions among members of the autism community, the Office of the
Secretary, and Dr. Harvey Fineberg, president of the Institute of
Medicine.
I do want to specifically thank Kelli Ann Davis, Jim Moody, and
Mark Blaxill—Mark has also been a member on our planning
committee—who were instrumental members of the advocacy
community in all of these discussions.
Let me say a few words about the format for today’s meeting. You
all have a copy of the agenda and I won’t read it to you, but let me just
reiterate that the workshop objectives are to look to the future, to look for
and try to identify the most promising scientific opportunities for
improving the understanding of potential environmental factors in
autism, to talk about what infrastructure, what tools and technologies are
available and what is needed, what kinds of interdisciplinary approaches
are needed and other kinds of infrastructure, investments and then to talk
about exploring potential partnerships that are needed to support and
conduct autism research.
The format that we are using, if you look at the agenda (Appendix
B), is to have a series of speakers in each of numerous settings. There
actually are way too many speakers for a normal workshop, but we were
unable to figure out how to keep this in proportion and make sure that we
covered this very complex issue fully. So, we are going to be rather
ruthless in maintaining the organization of the workshop.
Each speaker has been given 15 minutes. We will have one or two
minutes for what I will call critical questions of clarification right after
each talk, but really we mean critical clarification, not a discussion and
not a discourse. Then at the end of each session, we have allocated
actually a substantial amount of time for discussion among the session
participants and then we have allocated time at the end of the day for
continued discussion, but also an opportunity for members of the
audience to participate at that time as well.
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7
PROCEEDINGS
I would ask those people who are planning to ask questions or
develop questions over the course of the day’s events or the 2 days’
events, please, no statements, no long harangues. This is about questions.
This is a scientific meeting and we are looking for scientific
opportunities and ways that we can move the science forward. So, I
remind you of that, but I will surely remind you of that again.
Again, the purpose of the workshop is to stimulate discussion about
how best to move research on autism and the environment forward and I
need to make some, I apologize, bureaucratic announcements on behalf
of the IOM. One, this is not a consensus conference. We are not, in fact,
expecting to come to a consensus by the end of the meeting.
What we are expecting to do is to hear an array of opportunities,
an array of needs, an array of challenges that will be identified.
A proceeding of the workshop will be written. (NOTE: This is the pub-
lished document to which Dr. Leshner refers in his remarks.) It will not,
again, be an official consensus statement or consensus report of the
Institute of Medicine. It is outside our authority as a forum to produce
those kinds of reports, but, hopefully, what it will do is set the stage for a
research agenda moving forward, and that is really what our goal is
today.
I do want to thank the planning committee, which has been so
instrumental in this workshop. It could not have been done without the
joint activity of people from many different sectors with interest in this.
One request of the speakers before we move on and that is—and I
apologize for doing this late, but we are a little bit concerned that with all
the discussion and all the talk, it may be a bit difficult to capture each
speaker’s view of what a major opportunity or a major gap to be filled
might be. Therefore, if it is not too late to do that organizationally in
your head, if at the end of your talk you could articulate at least one, just
so the recorders can write down, here is one potential gap in scientific
knowledge or potential scientific opportunity that needs to be filled.
If we can focus in that way toward the future, I think we can make a
larger contribution than we could otherwise.
I don’t want to take too much time. We are already a bit constrained
and I, again, want to thank the members of the planning committee, who
did such a wonderful job of pulling this together. I want to thank all the
speakers, who will be with us today and tomorrow, and all of you who
are participating in this.
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8 AUTISM AND THE ENVIRONMENT
Let me turn now to Dr. William Raub, science advisor to the
Secretary of the Department of Health and Human Services (DHHS),
who just will make some additional comments about the workshop and
its origins and its particular charge.
CHARGE TO WORKSHOP PARTICIPANTS
Dr. William Raub
Dr. Raub: Good morning everyone. I add my welcome to Dr.
Leshner’s. I am delighted at the wonderful turnout.
The journey that brought us here began almost 2 years ago with a
protest action directed against the Executive Branch. Parents of autistic
children and other advocates were mindful of a reelection campaign
promise to eliminate mercury-based compounds from vaccines. Staff of
the Domestic Policy Council asked me to host a meeting whereby
representatives of the advocates could state their concerns in person. I
did so and had the privilege of meeting a group of impressive individu-
als, several of whom are here today.
I would like to be able to say that the protest event, the follow-up
meeting at Health and Human Services, and the subsequent communica-
tion from the Council back to the advocates left everyone satisfied. But
that was not the case, and deep divisions remain over the matter of
vaccine safety.
Nevertheless, several of the advocates asked if I would be amenable
to hosting further meetings, whereby they could lay out additional
concerns about how the institutions of science have approached the
problem of autism. I quickly agreed, having been moved deeply by the
quality of the advocates’ preparedness, the sincerity of their representa-
tions, and the power of their testimony regarding the crushing burden
that autism places on not only the affected children, but also the entire
family.
That led to a series of meetings with various combinations of repre-
sentatives from the autism advocacy community—but always focused on
what science has or has not done and what more it can or should do. Last
October, at one of those sessions, Dr. Harvey Fineberg, president of the
Institute of Medicine, joined Mark Blaxill, Kelli Ann Davis, Jim Moody,
and me to discuss the IOM’s studies of vaccine safety and related
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PROCEEDINGS
activities. Out of that meeting arose the notion that some sort of IOM-
anchored, autism-oriented event could make a uniquely important
contribution to shaping the research agenda against this dreaded disease.
During the weeks that followed, Dr. Fineberg and I posed this generic
concept to Dr. Thomas Insel, director of the National Institute of Mental
Health (NIMH) at the National Institutes of Health (NIH) and chairman
of the HHS Interagency Autism Coordinating Committee. Then we
widened the circle to include two other NIH leaders: Dr. David Schwartz,
director of the National Institute of Environmental Health Sciences
(NIEHS), and Dr. Duane Alexander, director of the National Institute of
Child Health and Human Development. This team quickly determined
that an IOM-hosted workshop focused on potential environmental factors
contributing to the etiology or pathogenesis of autism would make for a
highly desirable and value-added contribution to ongoing NIH-based
efforts to develop a strategic plan for autism research.
Without equivocation, Drs. Fineberg and Leshner affirmed that the
IOM neuroscience forum would host such a workshop. Drs. Bruce
Altevogt and Andrew Pope and their staff recruited and facilitated the
deliberations of a first-class planning committee. The three institutes that
I have already mentioned, plus the National Institute of Neurological
Disorders and Stroke and the Centers for Disease Control and Prevention
(CDC), agreed to provide the requisite funding.
As indicated by the agenda and the advanced materials on the IOM
website, the planning committee tried to ensure that no potentially
important environmental contributor to autism has been overlooked or
excluded. Although the workshop is not intended to reprise the analysis
of the epidemiological evidence related to vaccine safety, the planning
committee recognized that vaccine constituents, especially organic
chemicals used as preservatives or adjuvants, obviously qualify as
environmental agents that warrant attention. In other words, our research
agenda should include studies of any and all environmental agents that
plausibly might contribute to causing or exacerbating autism, irrespective
of the medium of exposure. I am hopeful that the next 2 days will prove
to be an important milestone for autism research—not only because this
workshop is addressing vitally important questions about the cause or
causes of the disease, but also because the agenda is the product of
collaboration between advocates for autistic children and their families
and the scientific community.
To be sure, other aspects of the autism challenge deserve similar
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10 AUTISM AND THE ENVIRONMENT
attention, especially the paucity of effective treatments, and autism
advocates and the scientific community have much further to go to
achieve the full measure of mutual understanding and trust. But our
challenge here and now is clear: to step together onto the path to a better
day, to set the stage for other important steps to come, and to make other
advocates and scientists want to be part of that advancing throng.
Thank you for being here.
Dr. Leshner: Thank you, Bill, and thank you very much for your
important efforts in getting this meeting organized, getting it stimulated,
and setting the appropriate stage for it. I do want to, again, thank the
planning committee. I neglected to mention that the importance of this
meeting from a scientific and a public health perspective is reflected by
the very large number of members of our forum, who came today, in
spite of it not being an official regular meeting of the forum. I really very
much appreciate the help and support. Almost the entire forum has come
today from many different sectors. I think that is an important statement.
I also want to reiterate William Raub’s thanks to Bruce Altevogt,
Sarah Hanson, and their colleagues from the IOM, who have done a
phenomenal amount of work putting this all together and making sure
that it happens.
Let me not take more time, but rather turn to Laura Bono, who has
been a member of our workshop planning committee, is a board member
of the National Autism Association, and has agreed to bring to the group
the perspectives of the advocacy community.
PERSPECTIVES OF THE ADVOCACY COMMUNITY1
Ms. Laura Bono
Ms. Bono: I am Laura Bono, founding board member and past chair
of the National Autism Association. I have been asked to talk about the
perspectives of the advocacy community. My time is short, so I will get
right to the point of what many in the advocacy community want and
think.
Declare autism a national health emergency under the Public Health
1
Throughout Ms. Bono’s presentation, she may refer to slides that can be found online
at http://www.iom.edu/?id=42455.
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Act and treat it with urgency. Thirty-six thousand children, who should
be living normal lives, will succumb to the diagnosis this year alone,
affecting the trajectory of their lives and that of their parents forever.
Autism is estimated to cost $3.2 million per child over a lifetime. Using
the conservative estimate in the United States of 500,000 children means
this epidemic will cost society close to $2 trillion.
Autism is both economically and emotionally devastating to the
children and their families. Many families are on the brink of bankruptcy
as they struggle to get insurance and the medical attention their children
need. Murder/suicides of parents and their autistic children are on the
rise.
I can’t discuss the perspectives of the advocacy community without
citing the failings of the CDC. We believe the CDC has a performance
and credibility problem. Their failure to declare an epidemic beginning
with the 1989 birth cohort to study the time trend data or to examine the
toxic and viral body burdens of children are why we are here today, over
15 years too late.
Julie Gerberding, director of the CDC, said recently in a February 8,
2007, CDC press release when they announced the 1-in-150 rate that she
wasn’t sure if the rates are truly rising or if they are getting better at
studies. “Our estimates are becoming better and more consistent, though
we can’t tell yet if there is a true increase in ASDs [autism spectrum
disorders] or if the changes are the result of our better studies.” This
denial thwarts research into environmental factors and just isn’t
acceptable. How many autistic individuals did you know when you were
under the age of 21?
Since it is impossible to have a genetic epidemic, literally hundreds
of millions of taxpayer dollars could have been appropriately directed to
gene–environment and other susceptibility initiatives. Even more could
have been spent on learning about the critical mechanisms involved in
response to environmental neurotoxicants. We could have been focusing
on what changed in the environment and when. We could have been
investigating the environmental trigger for years and successfully helping
suffering children. We urgently need to begin these initiatives now.
Many in the advocacy community are thankful because starting
today, the government is finally going to make environmental research a
priority, which will lead to better treatments and recovery. Because if
autism is environmental, then it is treatable and preventable. It is no
longer hopeless, or lifelong. It is hopeful, with a possible cure.
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12 AUTISM AND THE ENVIRONMENT
Recent clinical investigations have identified numerous comorbid
disease states in children with autism. These include immune system
abnormalities; inflammatory bowel disease; oxidative stress; disordered
urine and serum chemistries, including elevated porphyrins; methylation
disturbances; increased body burdens of metals, including mercury and
lead; chronic viral, fungal, and bacterial infections; and microglial
activation in the brain.
Studies must be initiated as soon as possible to increase the focus on
the identification of these comorbid disease states. Parents and clinicians
alike are reporting that when these problems are acknowledged and
treated, it can result in marked improvement in children’s learning and
behavior. Some children recover completely. This should be a wakeup
call to us all.
The research paradigm needs to shift from autistic children are
genetically defective to autistic children are sick and treatable. We
should only grant money to genetic vulnerability and epidemiology
studies that have a clear environmental hypothesis. Research
detoxification treatments; identify and validate biomarkers; study
biomedical imbalances and treatments that are working; investigate the
role of vaccines, including thimerosal, aluminum, and live viruses;
research the role of the immune, gastrointestinal, and endocrine systems;
and study the recovered children’s pre- and post-diagnosis medical files
for clues.
Because it is the environment, we need to leave no stone unturned.
There is a growing body of evidence implicating vaccine overload,
mercury and aluminum from vaccines. Thousands of parents agree with
this research. They watch their children regress after being vaccinated.
Their autistic children have been diagnosed with heavy metal poisoning
and immune system dysfunction and when treated, get better. Regardless
of controversy surrounding any theory, we must research and produce
successful antioxidant, methylation, and blood-brain barrier chelation
treatments, as well as immune system, detoxification, and inflammation
interventions.
I want to remind you that you are tasked with setting in motion the
crucial environmental research that hundreds of thousands of children are
silently waiting for now. The guiding principles should be to pursue
research and treatments that will impact the most lives as quickly as
possible and follow clues provided by treatments currently working in
children. Such an agenda would best be served by a translational research
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PROCEEDINGS
protocol where clinicians who care for children with autism advise
research into the most promising areas of intervention.
It is imperative that the working group proceed with urgency and
follow the truth wherever it leads. Recovery happens every day to some,
but our goal should be for all. We need to accelerate environmental
research; demand even more money to address the problem; issue RFAs
[request for applications] and have research proposals scored according
to autism matrix goals; get answers; interpret them expediently; and
continue to work the problem until we beat it.
We can do this. And our hope starts with you. Thank you.
Dr. Leshner: Thank you very much for your very powerful
statement setting the stage. I would like to respond that we share the
sense of urgency. We share the sense that science and research will be
the hope, and we of course share the goal of bringing the full power of
science to bear on this public health problem of great urgency in
tremendous proportion.
I hope that we will live up to the charge that you have just given us
to look at the full array of environmental factors and the ways in which
they can cause this disorder, affect its progression and then, of course,
the variety of ways in which we can approach it. I think that your point
about the need to both inform clinical practice, but also to listen to
clinical practice is a very important charge and I assure you that we are
planning to take advantage of that and listen to that carefully.
So, I really tremendously appreciate the statement you have just
made and I promise you that we will do our best to respond to it.
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Session I
Autism—The Clinical Problem:
“What Do We Know? What Do We Need?”
Dr. Leshner: I would like to turn to a discussion of the clinical
problem and introduce Sarah Spence, who will serve as the session chair.
I would like to point out that we are on time. So, don’t feel any pressure,
Dr. Spence, or speakers in this session.
Dr. Spence is staff clinician at NIMH, where she works in the
Pediatrics and Developmental Neuropsychiatry Branch. Thank you.
Dr. Spence: Thank you, Dr. Leshner.
I think we may have one of the most difficult sessions to do, which is
to introduce the clinical problem and do it in an hour and 20 minutes and
no more. So, I am not going to spend a lot of time on the introduction. I
think the most important thing to keep in mind during this session is that
it is about what we know and what we need. It is about introducing the
main issues to set the stage for a productive discussion later on today and
getting a diverse audience, kind of onto a level playing field about what
the issues are.
So, to start with the clinical problem, I am going to introduce my
boss, Dr. Susan Swedo, the chief of the branch that I work in at the
NIMH.
CLINICAL OVERVIEW:
HOW CAN THE CLINICAL MANIFESTATIONS OF AUTISM
SHED LIGHT ON POTENTIAL ENVIRONMENTAL
ETIOLOGIES?2
Dr. Susan Swedo
Dr. Swedo: Since I only have 15 minutes today to describe all of
autism to you and why we believe that the environment plays such a
crucial role in this disorder, I’m going to be using videos to show you in
a few seconds what it would take me a very long time to try to explain.
2
Throughout Dr. Swedo’s presentation, she may refer to slides that can be found online
at http://www.iom.edu/?id=42456.
15
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154 AUTISM AND THE ENVIRONMENT
do, anyway.
I would propose from a sociological point of view that there could be
usefully some support for the self-organization of the parents and some
of the treating physicians, like the DAN docs, like Nancy and others, to
have more support to build a platform of communicating what classes of
data are available, a status report of what is being collected.
It is not enough for you to stand up and say for 30 seconds that you
have these kind of data. I think it would be really nice if we could have
support for a description in more detail of what is going on, focusing in
classes of data to facilitate the interface with NDAR and other kinds of
data collection mechanisms.
I’m not clear that it would work coming from NDAR to the parent
and treating community. I think there needs to be some support for the
treating community, which is exhausted and overworked beyond all
description with this incredible burden of cases. It is not just people
coming in and mining data. There needs to be preparation for that, so that
there is some kind of a systematic approach.
So I think to make this happen, in order to meet in the middle, there
can be a transitional infrastructure of setting up what it would mean to do
that. Otherwise the activation energy to make it start happening isn’t
going to happen.
Dr. Beaudet: It seems to me that it would be interesting to know if
the two camps could come together around a truly blind chelation trial, in
which certain patients got infusions of placebo, and this went on for a
year. Some parents would have to take the risk that their child might or
might not be on placebo chelation for a year. But I think this would take
considerable investment of both sides to agree to something like that.
I would be pretty impressed if such a study could show something
is going on.
Dr. Swedo: I just wanted to say that such a trial has been developed
in collaboration with the DAN practitioners. We are using their protocol
and breaking those elements down. The gluten-free, casein-free diet is
already under investigation at one of the START centers as well.
So I think the individual components, the hard question and the thing
we really have to grapple with is this issue of—it appears that one of the
successes of the DAN approach is that it is very broad and deep. There
are a lot of things going on with those kids all at the same time, so trying
to figure out which components of it are useful is something that is going
to take some more work.
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Dr. Oberdorfer: Just to follow up on Martha Herbert’s point, when
you have observational studies that you are going to be undertaking that
you haven’t planned yet, if you do what you suggest, you are going to
see what sort of samples that you can take from a number of different
studies in a much more global sense. That way you would have some
commonality in a tool kit.
Right now, my impression is that they are going in cross purposes.
They are not collected in the same ways, they are not in the same times,
but they are moving in that direction. It seems to me that even if the
studies go in different directions, you will have samples that you can
compare homogeneously. I think that is very important, these kinds of
toolboxes. We can do that now.
Dr. Lipkin: Alan, this is not a comment. Maybe if Sue Swedo could
summarize for us what is going on, we might save some questions. We
are continually going back to asking what is being done at NIMH. If you
could just summarize what is being done in terms of treatment, then
maybe some of these questions would already be addressed.
Dr. Swedo: All right. The new intramural research program is about
a year old. We started with two major types of studies. One is an in-depth
phenotyping effort, making use of the anecdotal literature and the clinical
experience from clinicians across the country, but also the CHARGE,
CADDRE, and other data that had been collected. It is everything from
family history of medical illness and environmental exposures to
neuroimaging, genetics, and other evaluations.
Within that, we have a regressions substudy that looks at children
specifically with regression for additional factors, such as microbial
triggers or inflammatory responses. We also have a treatment compo-
nent. Intramural does best novel treatments. Tom Insel called us a SWAT
team. We go where we see a lead. For example, we are using meno-
cycline for its effects on NF kappa B to try and see if that would decrease
neuro inflammation.
We have a trial in antiglutamate agents, seeing what effect that
would have not only in repetitive behaviors, but overall autistic
behaviors. The chelation study is currently on hold because of some
recent reports of a rat study that reported cognitive deficits in DMSA-
alone treated animals. We are going back to the IRB (Institutional
Review Board) on May 1 to look at that question.
That is what we are doing in-house. My colleagues from extramural
can talk about the new A centers. But I think that many of the things that
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156 AUTISM AND THE ENVIRONMENT
are happening, some of them are underway. Probably the most important
is this issue of common measures and trying to get as much richness of
clinical data as we can from every subject that is studied with NIH
funding. That includes, as I mentioned, standardized diagnostic
assessments, behavioral assessments, neuroimaging if it is being done on
a common platform, as well as obtaining genetic material and biological
samples.
Dr. Lipkin: A constellation of toolboxes.
Dr. Swedo: Right. I think we have already heard about some of the
ongoing efforts in which supplements are being done to get the same
kind of biological data. Now one of the questions is how do we organize
it and go after the hypotheses.
Participant: My name is Becky Peters. I have worked in the autism
community for the last 5 years. I missed the very beginning, but I don’t
think until Sue Swedo just mentioned it that I have heard anything about
the possibility of food allergies.
I read a lot about and heard lectures on things like the gluten- and
casein-free diet, the specific carbohydrate diet, and how for some
children with autism, it has not only improved some, but even caused
recovery in some.
So I was just wondering if anyone in the research community is
looking into the possibility that food allergies or certain foods that maybe
children are genetically predisposed to be more sensitive to could be
environmental factors in causing autism.
Dr. Leshner: Does somebody have a very brief answer?
Participant: A brief answer is the recent data on microflora
associated with obesity, for instance. It is something that occurs in
response to a specific diet. We are finding that there is increasing
research that tells us that you can change metabolism and adipose
cytokines and adipose tissue can change in response to the diet in
conjunction with the microflora.
We have the opportunity now with the tools that exist to begin to
explore those types of issues. It may not be the standard allergies. It
could also be other models that we need to also think about.
Participant: Claudia Miller from U.T. (University of Texas) Health
Sciences Center in San Antonio. We have worked extensively with
adults with food intolerances and environmental intolerances. Until you
eliminate all of the things that bother that particular person, you don’t see
the problems reversed.
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Now we have started doing the same things in autism. The caution is
that if you start doing a few things and just gluten and just casein, you
may get some reversal but you may not get all of it. You may get other
intolerances that develop, which is why you have to have a very
comorbidity protocol.
Participant: My question is about it being part of the etiology. I
know that diet is out there and it is helping people, but I don’t feel like
anybody here has addressed the possibility of the food allergies causing
that problem. I was just wondering if anyone is considering that, or if
that is not on the table for research.
Participant: I am Dr. Richard Deth from Northeastern University in
Boston. There is something missing here from this discussion that unifies
many of the observations and the questions that have come up during this
afternoon’s discussion.
That is reflecting some of the work that we did and we continue to
do on the dopamine D4 receptor. The D4 dopamine receptor is involved
in methylating membranes of neurons. It uses methyl groups from the
folate pathway through the enzyme methionine synthase. We discovered
that a certain number of years ago.
The D4 dopamine receptor is linked to ADHD, and is now recog-
nized as the most important genetic risk factor for ADHD. The D4
dopamine receptor is linked to lead toxicity and the role of lead in
contributing to ADHD. The D4 receptor is linked to IQ. It is a risk factor
for IQ reductions. So it has all the characteristics of a candidate receptor,
dopamine included.
This is the only receptor that utilizes sulfur pathways. It uses the
enzyme methionine synthase that is turned off by oxidative stress. When
oxidative stress occurs, be it mercury or be it pollutants or be it
pesticides, that enzyme turns off to make more glutathione and robs that
system of its methylation ability.
The role of the D4 receptor is to synchronize that gamma synchrony
that is gamma-frequency synchronized, synchronization of the brain
during attention, a system that is deficient during autism as well as
ADHD.
As we have pursued this line of investigation, we have recently
found that there is alternative splicing of the gene from the mRNA from
methionine synthase in the human cortex. We have found that this
alternative splicing is related to aging; it is complete in 80-year-olds, and
it is incomplete in 20-year-olds.
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158 AUTISM AND THE ENVIRONMENT
As a result of recognizing the central role of this process, I think you
can find mechanisms to explore. The enzyme methionine synthase
utilizes methyl B12, which is a treatment that approximately 30 percent of
people respond to.
So I would say that there are all the elements here to start building
from, even though it might not be a complete story. I just recommend
that area of science to the panel members, because it can unify many of
the things that they are concerned about.
Dr. Leshner: Have you published it?
Participant: I published several papers. The first paper about the
D4 receptor was published in Molecular Psychiatry. The second paper
was about methionine synthase being inhibited by ethanol, mercury,
lead, thimerosal, because glutathione levels are low and methyl B12
synthesis is impaired. There is a lot to know about this. You just have to
look into it.
Dr. Leshner: Thank you. We will put that onto the list. Very
helpful.
Participant: I am from CDC. I want to make three points and try to
make them quickly. The first is, I hope that everyone will be here
tomorrow morning, because there will be several epidemiologic studies
that will be presented, and they can be built upon in terms of specific
environmental questions that are not being addressed. The CHARGE
study will be presented and the CDC CADDRE study will be presented.
It sounds like a lot of the questions that people are asking about studies
and cohorts might be answered tomorrow morning.
The second point is, Dr. Schwartz was asking about large cohorts
that are available for study. I wanted to mention one in China. These are
children of mothers that received folic acid. These children are about 12
years old now. There are about 200,000 children that are going to be
characterized for autism. So I just wanted to go on the record to say that
is a cohort that could be studied.
The third point is to talk about the National Children’s Study a little
bit more. Dr. Landrigan did mention that study, but there are a lot of
environmental agents that are going to be studied as part of that study in
terms of levels in the children, and autism is an outcome.
There will be a research protocol that will be available for public
comment. If that study is not addressing some of the questions that
people have, if we don’t have the right chemicals identified, if we don’t
have the right confounders, mediators, and modifiers described in the
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study, then I would encourage people who are here today to comment
upon that. That study was designed to answer a lot of these questions
about specific environmental exposures.
So I just wanted to remind people that there are some studies in
addition to the ones that Sue Swedo had mentioned within NIH. There
are some studies underway that might be able to shed some light on some
of these questions.
Dr. Leshner: I’ll just reiterate your point about tomorrow morning.
A lot of very important talks are going to touch on an array of these
issues that we have been talking about already. But we allow free talking.
Thank you.
Participant: My name is Harold Grahams. I am a private practi-
tioner in Pennsylvania.
To address Dr. Insel’s issue about the urgency of a biomarker, there
is a tool that has come across my radar a few years ago that has been
used in chemistry labs and hospitals and university settings all across the
world that has been underutilized in autism. It is a high-performance
liquid chromatography. There is a gentleman, Wayne Madsen, from PSA
Labs who did work with lead studies 20, 30 years ago. Wayne Madsen
did some unpublished studies with a controversial group up in the
Philadelphia area probably about 10 years ago. I think it is a tool that
might answer a lot of questions that all of us as practitioners and
anybody could use as a reliable biomarker.
What Wayne Madsen found with a group of kids is that we could
give him bloodwork, and he could tell us—if we give him the blood
tubes, he could run it through his chromatography, look at all these
metabolites. What he could then spit back was that this was a cerebral
palsy kid, this was a Down syndrome kid, or this was an autistic kid, just
from those metabolites.
The nice thing about it—yes, pretty impressive, right? But it was
unpublished.
Participant: How do we see it? How do we see the data?
Dr. Leshner: People have to get the data into the system.
Participant: I understand that.
Dr. Leshner: I questioned unknowingly before about publication.
Particularly in this field I think we have to be extremely careful that we
not lead families astray, lead the scientific enterprise astray. So if you
could tell Sue Swedo or somebody, people who are actively involved
about this, maybe they can get access to the data.
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I am a journal publisher, so I am obsessed with peer review and
publication and making sure that whatever it is that we communicate is
going to be as scientifically rigorous and credible as possible, lest we
lead people astray.
Participant: Oh, I understand that. I hate to stand up here and say
there is this fabulous tool that has not been worked. But just to throw it
out, that it is a tool that has been preliminarily looked at with maybe 100
or so kids. I think it also allows us—the tool also has the fingerprint for
the individual child. So what Martha Herbert was talking about, as
having a way to track our treatments, I think we should as physicians be
allowed the freedom to do whatever we do, because each doctor may be
fixing a certain subset of children, but if we don’t know, that is the
frustrating world of the clinician.
Dr. Leshner: I agree with that. I would just urge you to somehow
get the individual attached to these networks that are developing, because
we don’t want to lose the opportunity if there is something particularly in
this. So perhaps you could refer the physician to the networks that are
developing.
Participant: That is my frustration as a clinician. How do we know
whether what we are doing is valuable and have the time to collect the
data that the scientific community—when I went to UC–Davis (Univer-
sity of California–Davis) too many years ago, I know the rigors that
science wants, and we just don’t have it available, but we are doing
something. So while we are doing something, we might as well be
collecting a yardstick so we can measure what anybody is doing, and we
don’t have that kind of biomarker. But I think this is a potential tool.
Participant: One model that might apply here, and maybe we can
talk about it more tomorrow, is the cystic fibrosis (CF) model, in which
they started with a few very focused research centers, encouraged them
to begin the training. That very rapidly got out to regional centers, and
the regional centers began to work with the private physicians, and they
markedly improved survival rates for individuals with CF.
So I would be very thrilled to try to help spearhead that effort.
Obviously it is going to be a major undertaking, but I think working
together we can probably get that done.
Participant: The bloods are already being collected so you don’t
need a whole lot of blood.
Participant: Right. We would need to make sure that the diagnoses
were accurate and blinding was done. So I think the testing of that
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particular hypothesis, absolutely, that can happen very quickly. The
larger question is how physicians can be providing feedback and families
can be providing information. It is something I think we need to organize
both sides in at the same time.
Participant: I am a grandparent of two autistic grandsons. I thank
you for inviting the public. I hope to be one of the taxpayers and voters
who gets you the funding to go on with your research.
I must say, when I saw the advertisement for this on the Internet, I
was distressed to see that mercury was not going to be discussed in the
context of vaccines. I thought there was going to be a white elephant
roaming around in the middle there, and everybody would avert their
gaze. But I see that there is frank discussion on that, and I am very
encouraged. I think the pursuit of science, obviously you have to go
where the truth leads you.
Also, as a taxpayer funding this research, I think it is very important
for you to understand that the people who are going to be out there
getting political want some basic questions answered. They want you to
look at the mercury hypothesis and tell them why it is not mercury, why
it is not repeated environmental insults, and the number of shots they get.
It is mercury and it is an immune assault to get these inoculations, and
there are so many of them. So they need an explanation for why that is
not the cause.
I think we can’t move beyond and do good research until we answer
that question, put that one to bed. So let’s not ignore it. Let’s address it
head on, and tell parents why they needn’t feel guilty. There are so many
emotional issues involved here.
Another thing is, people don’t really trust their government all that
much anymore, CDC, FDA, and beyond. They need to trust their
government more in their research by knowing that certain areas are not
off limits.
If we do not allow an explanation for mercury and vaccines, it will
be like doing lung cancer research and saying, but let’s not say ciga-
rettes. Nobody would believe it, and they would know their money was
wasted. So that needs to be on the table.
I have another tack altogether. Psychology doesn’t seem to be
represented here. I know that is perhaps not a good fit with environ-
mental issues, but it is something that should participate in any funding
for autism.
In our situation we have gotten a lot more bang for the buck with the
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biomedical. We have pretty much given up a lot of the behavioral
therapies. They have been good, but they haven’t been as good as the
other. So we need guidance.
Then one more thing. I have a natural experiment to suggest. Rho-
negative mothers are subjected to a standard of care that calls for a
RhoGAM injection at 5 months of gestation, so we give them a little
extra environmental assault and a little extra mercury there.
I understand that Rho-negative mothers have a higher percentage of
autistic children than others, so what is the explanation for that? Is it
Rho-negative mothers? I don’t know. These are some questions we
would like answered.
Thank you very much.
Participant: I would like to comment on the RhoGAM issue. There
is a small study which is not very well done, and it shows this kind of
finding. Since then there has been a more systematic study which I hope
is in press. I can’t give more details, but it is from somewhere very
respected in the United States, which has done a large sample in a study
of that kind, and it showed there was no association between RhoGAM
and being the mother of an autistic child. It is in press.
Participant: Just going back to something both Mark Blaxill and
Mark Noble said before, we are looking at first of all a very complex set
of circumstances here. I don’t think there is going to be one thing that is
found. I think it is going to be multifactorial, and I think this group is
saying that.
But I think as we address that from a clinical point of view, we have
to look at not just one treatment modality, but also what the child is
experiencing overall. When we look at what Jill James was showing us
between the gut and the immune system and the brain, looking at all of
those factors before we say, how does chelation affect a child?
I think as we set up the studies that Sue Swedo is doing, for instance,
if we set it up in such a way that we are just looking at the effects of
DMSA on a child without looking at whether that child has had and still
has gut or immunologic abnormalities, we would have very different
outcomes than if we look at a child that is otherwise healthy and then
looking at how chelation does it.
So it is a very messy set of data and we have to look at all those
parameters going in and coming out, or else we are going to have data
that show us nothing.
Participant: My name is Heather Elias. There is a subgroup of
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children with autism, and a critical factor in treating them is regulating
their hormone levels, particularly their testosterone levels. We know that
boys are more likely to have autism than girls, but the girls tend to be
more severely affected by the autism. That also makes me think that
testosterone plays a big effect on how these children’s treatment should
go.
We know that Risparitol, Lepran, Spironolactone, all pharmaceutical
drugs, are effective treatments for certain behaviors associated with
hormone levels. I am curious if any of the scientists here are doing any
kind of research on the hormones and how it affects the behaviors of
people with autism and regulating those, how it helps them, if there is
any kind of study going on about that.
Participant: The study that we will be describing tomorrow, one of
the domains of research that we are investigating, is related to hormone
abnormalities.
Dr. Leshner: Good, that will make you come back tomorrow.
Participant: It will be including also immune dysfunction, which
will address a lot of the other issues that have been raised today.
Participant: There is someone in the United Kingdom whose name
is Simon Cohen, who has been doing studies in relation to autistic
symptoms or traits in the children who are born from these pregnancies.
He has shown some relationship. It is very preliminary. It is not looking
at autism as a disorder, as an outcome.
Participant: I just also wanted to mention, I have a daughter who
has autism, and we have followed the DAN protocol, and I am so
grateful for these doctors doing all of this research. But we now are
looking at the data. Just keep in mind that the parents have basically
spent thousands of dollars to get these tests done, and they have really
sacrificed a lot to get that information. So just remember the children
when you are looking at the data.
Thank you.
Dr. Leshner: That is what this is about. You can be the last word.
Participant: My name is Scott Bono. I live in Durham, North
Carolina. I thank the panel for convening and taking up this topic. It is
deeply personal. Last month I filed to retain guardianship of my 18-year-
old son. I have two other children in college, and I never expected that
when my son was born I would have to do this at age 18. It is very
personal. I know what happened to my son was inexplicable, but you all
are looking into it, and I appreciate that.
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The most relevant question that has been asked today was asked by
Dr. Choi. That is, for 15 years nobody has been looking at the urine and
the blood of the children that we are talking about right now.
Most parents, when they go to a pediatrician and they are told that
their child is autistic, they are dismissed. That child’s illness is dismissed
on the basis of behavior. I am so grateful that each of you is looking into
some of the systems that have gone wrong in my son and so many other
children.
Treatment should always be what is in your mind as you proceed
here, because I want my son back. Everybody wants their child back. I
really want to thank all of you for coming. And Jackson thanks you.
Dr. Leshner: Thank you, sir, and thank you for reminding us. We
are going to stop for the day. This has been from my perspective a
wonderful day. I want to thank the speakers, I want to thank the
audience. This was for me a very—I guess the right word is dramatic, but
it was a wonderful example of how the patient and family community
and the scientific community can work together. You have to come back
tomorrow. I am really tough, so if you don’t come back tomorrow I am
going to chase you.
But I didn’t want to leave without making the comment that I am not
sure that I have seen as good an interaction between the scientific
community and the patient and family community, and I really appreci-
ate it greatly. I am very grateful to the family members for coming and
sharing your experience and your insight with us.
