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Autism Now: Dr. David Amaral Extended Interview

April 20, 2011 at 12:00 AM EDT

ROBERT MACNEIL:  Dr. Amaral, how close are we to finding the cause of autism?

DR. DAVID AMARAL: Well, I think we’re close to finding several causes for autism. But  I don’t think there’s going to be a single cause. Everything we know about autism is that there are multiple genes that confer risk. The children have various co-morbid problems. And everything we know looks like this is a multitude of disorders all under the umbrella that we call autism spectrum disorders.

ROBERT MACNEIL:  What is your best scientific hunch of where the leading clue will be found?

DR. DAVID AMARAL: Robert, I think there are many parallel pathways that people are pursuing at the moment. Some, I think, have more traction  than others. Clearly, 30 years ago, we didn’t know any genes that conferred risk of autism. Now, we know that there’s at least 20 or more that seem to be associated with autism.

The interesting, though, is that any particular gene that you might find that is related to autism, is only related to about 1 to 2 percent of the cases of autism. So I think what’s clear now is that there’s not going to be a single autism gene. But there are many, many.

And the reason that this is interesting is that there’s a race going on now. Trying to figure out now whether all of the genes, taken together, make sense. Whether they’re in some pathway that leads to, for example, the communication of information at synapses in the brain. If all of them were to affect that transmission of information, then we’d say, “Well, it doesn’t really matter which of these genes are involved. But they’re all damaging some ability of the brain to process information.” We’re not there yet. But I think it’s getting exciting. Because people are starting to look, instead of a single gene at a time, at networks of genes. So the genetics are very important.

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But I think what’s clear is that there’s — a reemergence of the idea that the immune system might also be involved in children with autism. But in a subset. We have found, here at the MIND Institute, work by Dr. Judy Van de Water, that about 12 to 14 percent of women who have children with autism have peculiar antibodies that are directed at the blood. And she’s pursuing the possibility that those antibodies, circulating during fetal life, in some way interact with the developing brain and that might be one path to autism.

We have other folks here that are looking at environmental factors. And again, we haven’t  found a smoking gun; one single environmental factor that causes autism over and over again. But I think there’s accumulating evidence that there are a lot of things in the environment that might increase the risk.

So at this point, I think we’re looking at genetics. We’re looking at  the immune system. We’re looking at environmental factors. Not a single one of those are going to be the answer. But there’s more evidence suggesting that all of them may contribute in some complex way.

ROBERT MACNEIL:  Some people in the field say that so much emphasis and funding– was put on finding a genetic pathway. That, looking at the environment was relatively impoverished by comparison. Do you feel that way?

DR. DAVID AMARAL:  Well,  I think that that was the case approximately 10 years ago.

I was involved in the first attempt by the National Institute of Health, to develop a strategic plan. It was called “The Matrix.” And that came out in 2003. And there wasn’t a lot about the environment in that strategic plan.

But over the successive years, as it became clearer and clearer that, first of all, genetics wasn’t  the only answer. Something else must but going on. And increasing evidence by a number of epidemiologists showing that there are environmental factors that seem to be conferring risk. That people are taking the environment much more seriously now.

And in the most recent iteration of the NIH strategic plans, environment  is near the top of the agenda, of where we should be putting some emphasis. So I think, transiently, a while ago, the environment wasn’t considered. But I think it is now.

ROBERT MACNEIL:  You mentioned in a talk in San Diego, that you can’t understand the genes in isolation. You said there are many routes through which environmental factors may exert consequences leading to autism. Like, what routes?

DR. DAVID AMARAL:  Yeah. So, for example, let’s say some of the genes that might be impacted in autism are genes that set up our immune system or allow our immune system to function properly. Well, if you were to have a child that had that gene and they were never to come into contact with something in the environment that would challenge the immune system it may never produce autism.

But given that our environment is incredibly, increasingly more complex. And that the immune system is actually increasingly more challenged. Both by chemicals that we’re putting into the environment that we’re creating. As well as things like pesticides and whatever.

That it may be that genes that were defective or perturbed, leading to a perturbed immune system function. Are now actually undergoing more challenges in our environment. And that may be one of the reasons that we’re seeing an increase in autism.

So again, it’s not the entire answer. But that’s a genes-by-environment interaction. The genetic problem is there. But the genetic problem, in isolation, wouldn’t cause autism. It has to be the genetic problem and then being challenged by something in the environment.

ROBERT MACNEIL: What is your position today on vaccines and autism?

DR. DAVID AMARAL: So I think it’s pretty clear that, in general, vaccines are not the culprit. There  has been enough epidemiological evidence showing that if you look at children that receive the standard childhood vaccines that, if anything, those children are at slightly less risk of having autism than children that aren’t immunized.

And so, you know, I think it probably is a waste of effort at this time to try and understand vaccines as a major culprit for, or a major cause of, autism. It’s not to say, however, that  there is a small subset of children who may be particularly vulnerable to vaccines.

And in their case, having the vaccines, or particular vaccines, particularly in certain kinds of situations — if the child was ill, if the child had a precondition. Like a mitochondrial defect. Vaccinations for those children actually may be the environmental factor that tipped them over the edge of autism. And I think it is incredibly important, still, to try and figure out what, if any, vulnerabilities, in a small subset of children, might make them at risk for having certain vaccinations.

ROBERT MACNEIL: Which is what the committee that determines the strategic plan and recommends research, has just decided to recommend?


ROBERT MACNEIL: Small studies on those subpopulations that might be so vulnerable. Do you think that’s a sensible thing to do? Or is it just a response to continued public pressure?

DR. DAVID AMARAL: Yeah. So I think, personally, it’s a reasonable thing to do. Because I think that autism is ultimately going to have many, many causes. There are gonna be many, many subsets of children that are going to have different etiologies. Some of which are gonna be more environmental, some of which are gonna be more genetic. And I frankly don’t think that there’s going to be a large group of children that  — their autism is caused by their standard immunizations. But you know, it could be a small subset.

And I think, more importantly, what the whole vaccine issue has done. Has opened our eyes again to the idea that the immune system is an important component of autism. And I think, at least at the MIND Institute, some of our early parent advocates, who are very concerned about the vaccine issue. And rather than using all of our resources purely to look at vaccines we have — established a fairly extensive immune — analysis of autism.

Which in myriad differences are found in the in the children who have autism. Not all, again, but a subset. As well as the parents of children with autism. So I think the issue of the immune system and disregulation of the immune system has been an important — outcome of worrying about vaccines. I’d rather put our effort on understanding the immune system and how– beyond the small subset of children that might be damaged by vaccines. Some disregulation of the immune system might be causing autism.

ROBERT MACNEIL:  Some people believe that the huge controversy over vaccines has impeded research into the environment. Because it discouraged environmental research. Because everybody associated that with the vaccine controversy.

DR. DAVID AMARAL: I think it was sort of an uphill battle initially. I think we’re beyond that now. I think the field is beyond that now. And I think the field is more interested in neurotoxicants or chemical toxicants — pesticides, a variety of other things that are out there in the environment. I mean, vaccines are only one of the things that we do to ourselves. But there are myriad other kinds of  toxic chemicals that we’re putting into the environment.

And I think people now realize that they are very important to look at and to consider. So maybe transiently again, but  I don’t think there’s enough research on environmental factors. Frankly, I think it’s very expensive. It’s difficult research to do. Because again, you start — trying to develop a list of how many new things there are in the environment now, from 30 years ago. And it’ll be a very long list.

But I admire the epidemiologists who are trying to make sense of this. And we have one here that I believe you’ll be talking to later. Dr. Irva Hertz-Piccotto. And you know, it’s — women and families are concerned about these things. Questions, like, “Well, you know, doctor, I had pitocin when my child was being delivered, to enhance my delivery. Could that have caused autism?” Well, Irva’s looking into that. “I use flea and tick powder on my pets. You know, could that be causing autism?” Well, Irva’s looking into that. And you know, I think we need to do more of that kind of research.

ROBERT MACNEIL:  What particular area are you personally, as a researcher, focusing on?

DR. DAVID AMARAL:  Robert, I’m a neuroanatomist by training. So I’m actually interested in what parts of the brain are particularly impacted in autism. And I’m also interested in knowing whether you see the same pattern of brain changes in autism. Now, on the one we do — magnetic resonance imaging studies of children with autism. And we also are doing, and in those MRI studies, we call them, we’re trying to chart of the course of brain development in autism.

And what we’ve found is that– there are certain parts of the brain. The frontal lobe, right– behind the forehead– in particular. As well as a small structure that’s about two inches in from you ear, called the amigdala. Both of these structures actually grow too quickly. They get to the adult size too quickly in children with autism. Now, you might say, “Well, so, that’s not so bad. You know, if it gets, you know, there too quickly.”

But the brain is actually like a symphony. Its development is like a symphony, where everything has to be playing in tempo and in time. And if a part of the brain like the frontal lobe grows, matures too rapidly. One possible outcome is that, when it sends out its connections to other parts of the brain that it communicates with. Those other parts of the brain are not ready for those connections. Basically reject them. And then the frontal lobe starts trying to communicate with other parts of the brain.

And in fact, there’s a strong current of thinking in autism that it may be a disorder of communication, of connections in the brain. So we’re trying to chart in very young children with autism. We start with children diagnosed at two years of age. And then — have the children come back annually to have an MRI. We do this at night when they’re sleeping so that there’s no anesthesia. And the parents love it because — they get to see their children’s brains. And there’s actually no impact on the children whatsoever.

And what we found is, yes, these parts of the brain, the frontal lobe and the amygdala, are growing too rapidly. But not, again, in all children with autism. For the kids who have the large frontal lobe, we see it in about 40 to 50 percent of the children with autism. The rest of the children with autism, we see no differences whatsoever in the way their brains are developing. They map entirely on top of typically developing kids.

But what’s interesting is that then we can start asking, “Well, what is different about the kids who have the big frontal lobes compared to the kids who have the normal-sized frontal lobes?” And one of the things that we’ve most recently found is that the kids who have the big frontal lobes are the kids who have the regressive form of autism. So just to be clear, there’s really– if you think about when does autism start? There’s a bunch of kids who probably have autism right from the get-go. Right from conception or very early on. So that if you look at those children when they’re 12 months old, they already are showing the signs and symptoms of autism. They’re not enjoying the interactions in their birthday parties, those kinds of things. But there’s another group and we would call those the early-onset form of autism.

There’s another group of kids who, at 12 months old, they look fine. They’re communicating, they’re engaging socially. But then, some time between 18 and 24 months, they lose social behavior. They lose language. And they regress back into autism. Now, that’s what — that’s the only thing that we knew. We knew, behaviorally, there were those two kinds of autism.

But now, we’re showing that the kids who regress into autism, for whatever reason, are the ones who have the rapidly growing brains. So that’s a clue. I mean, it doesn’t tell us all that much. And it doesn’t tell us how to treat those two kids differently, but it’s beginning to provide evidence that there really are biologically different subsets of kids of autism. And I think, once we actually define that there are different subsets, we can start going after the causes of each one of those subsets.

ROBERT MACNEIL: One of the researchers we talked to said, speaking of disconnections, that there’s, in science, a certain disconnection. Because some people are studying the patterns in the brain.


ROBERT MACNEIL:  Other people are studying the biology and the cells.


ROBERT MACNEIL: And the two are not connecting as they should.

DR. DAVID AMARAL:  I think that that was more the case before. I think now, big science, like autism science, is collaboration. And at places like the MIND Institute, we have cellular neuroscientists who are studying the minute details of how neurons communicate with each other.

But they’re interacting with people who are actually doing the epidemiological work. In our case, we have Irva Hertz-Piccotto, who’s doing the epidemiological work, working with a neurotoxicologist, a guy named Isaac Pessah. He does cell cultures of individual neurons. And she’s actually finding out what things in the environment might be damaging to the brain. And then he takes those things and looks to see whether they might be impacting  the neurons.

So I think it used to be the case that there was all these silos. But people have smartened up to the fact that to solve these daunting, complex disorders like autism, you have to collaborate across levels. And people are doing it more and more.

ROBERT MACNEIL: And just to tip you off. I’m coming up to the point where I wanted you to talk about the heterogeneity..

So with– with all the amount of research effort, brain power, funding, going into this? Hundreds of scientists all over the world doing this.


ROBERT MACNEIL: What are the obstacles to finding the answers in autism?

DR. DAVID AMARAL: I think, you have to understand that autism is an incredibly complicated disorder. And we’ve been studying autism in a rigorous biomedical fashion only for a relatively short period of time.

Far less, for example, than something like Alzheimer’s disease. Alzheimer’s disease is actually much more straightforward, in a sense. We can actually look in the brain and see the lesions and now the target is how do you prevent the lesions or recover them? We don’t really have those kinds of lesions in the autistic brain.

So it’s a complicated disorder. When you think about what goes wrong in autism, it’s a disregulation of the most complex of human interactions, that’s social interactions. Very, very complicated. We don’t even understand, at this point, from basic neurobiology, how the social brain works. We’re still trying to figure out, what is the social brain? If you asked me, what part of the brain does memory? I could say, “Well, there’s the hippocampus. And the hippocampus is connected to this part and that part.” And I can tell you a whole story about how memories are made.

I can’t tell you a story of how we accomplish social behavior. So the fundamental function is extremely complicated, that we’re trying to understand. And so if you’re asking, “Well, where’s the pathology on top of that?” It’s pretty hard to find. But the other real problem about autism is that it’s not a single disease. It isn’t going to be something like Parkinson’s disease or Alzheimer’s disease.

It’s a disorder that is incredibly heterogeneous. I already mentioned that there’s not a single autism gene. There’s going to be many, many genes that are involved. And then when you look at the children or at the individuals who have autism. The complexity is mind-boggling.

30 percent of people with autism have epilepsy as well. But 70 percent don’t. 20 percent or so have big heads. But a large number don’t. And there’s even a small number of people with autism who have small heads and small brains. If you look at other things, like gastrointestinal problems. People say, “Well, what does gastrointestinal problems have to do with autism?” Well, a fair number of individuals with autism, probably more than the general population, certainly more than the general population and arguably, even more than children who have other developmental disorders, have chronic gastrointestinal problems.

And we’re trying to figure out, you know, is that a chicken or egg? Do the gastrointestinal problems potentially cause autism? Or does the autism cause the GI problems? But why does it only happen in a subset of kids with autism? Often times, when I’m talking to a lay audience, I say, “You know, if you put a pear and an apple and an orange in front of me and said, figure out those fruit,” I could do it. I could look at the genetics of each one of them.

But if you took them all and put them into a blender and asked me to figure out those fruit I wouldn’t basically know where to start. And what’s been hard at autism is that we have this potpourri of different causes, all of which have the behavioral signs and symptoms of autism.

And when they come into clinics, when they come into research, up until recently, people basically tried to figure them all out at the same time. And that was the losing proposition. And more and more, what people are trying to do now, is to say, “Well, let me look at the kids who have autism plus GI problems. Or autism plus epilepsy. Or autism plus big frontal lobes. And let me try and figure out those kids.”

So I think that the big issue was heterogeneity. We’re now just starting to come to terms with it. But the other issue is that we really haven’t been studying this disorder, this complex disorder, for very long. Unfortunately, I understand the parents are frantic to get the answers, and I appreciate that. But it’s a very, very complicated disorder.

ROBERT MACNEIL:  Is it frustrating as a scientist? To have so many clues, but so few answers?

DR. DAVID AMARAL: Very frustrating. Yeah. Absolutely. It’s frustrating because I often go out and speak to speak to parents, and they get all excited about the fact that we’ve absolutely confirmed that there’s a subset of kids who have big frontal lobes. And then the parents will say, “Well, so what does that mean? How do I treat those kids?” You know, at this point, we don’t know what the implications are for treatment. We don’t even know whether those kids will fare better or worse with the standard treatments that are being done.

So on the one hand, I am frustrated. And on the other hand, I’m optimistic that if you had gone back 20 years ago, we wouldn’t know even about a fraction of the biological facts that we already know about this disorder. And I keep saying it’s a complicated disorder. I appreciate that we’re moving pretty fast, at this point.

You were mentioning the amount of money that goes into research in autism. It has increased dramatically over the last 10 years. Still a relatively small amount compared to other disorders like cancer and others that a lot more money is being spent on. So we’re making tremendous progress, but we still have a long way to go.

ROBERT MACNEIL: How important is this to you, personally, this search?

DR. DAVID AMARAL:  You know, up until 12 years or so ago, I was perfectly content to study the brain.  I was interested in the brain and memory. I was interested in the social brain. And I wasn’t all that interested in the clinical aspects or neuroscience. But then the MIND Institute was started. And– and I was fortunate to be here at the very beginning.

It was started by five families, all who have children with autism. And I got to know those families very well and since then have interacted with hundreds of families who have children with autism. And this has really captured me. I mean the founding parents said that, at one time, I was a plain vanilla neuroscientist. And now, I might amount to something. Because I’m going after autism.

I don’t know what it is about it. It’s something about the passion of the parents. This is an unusual group of individuals who are fighting for their children. And the disorder itself is so complex and and taps into what makes us human. You know, what makes us complex. So it has completely captivated me.

It’s altered my life because from, basically, just knowing very little about autism, I’ve become passionately dedicated to studying this disorder for the rest of my life. And I do hope that, at least in some ways, the MIND Institute and the work that we do here will contribute to an increased quality of life for children with autism.

ROBERT MACNEIL: The latest strategic plan from the NIMH– interagency coordinating committee called it a “national health emergency.”


ROBERT MACNEIL: Is that overstating it?

DR. DAVID AMARAL:  I don’t think so. Regardless of the debate about prevalence. And whether it’s changed. I’m not an expert. I’m not an epidemiologist. I’ve talked to clinicians who have been working in autism for the last 30, 40, 50 years. And their view is that there really has been an increase in the number of individuals with autism.

But regardless it’s 1 percent of the population in the United States now. 1 out of 100 children are being diagnosed with autism. And to me, that’s too many children to lose to this disorder. And it’s not the only disorder that we have to deal with. But it is incredibly prominent.

And you know, the thing is, that these children who are diagnosed at two or three years of age live a lifetime. And they live a lifetime that is often in need of constant care. And the families who have children with autism do everything they can for their children. Yet they worry. “What happens when I’m not here?” What happens to their children? We don’t have a system of supports for these children when they become adults.

And I do see sort of a wave of these children now going into adulthood. And I worry that we’re not prepared for that wave. It’s affecting our educational system, it’s going to affect our medical system. We need to do more.

I also think it’s forcing us to, again, like most disabilities, rethink our values. When we started the MIND Institute, parents wanted us to cure autism. And you know, I thought, “That’s great.” Here are these children that have these disabilities and their problems. In my early days, when I was very naïve about this, I would go out and talk about what we were trying to do to cure autism. And then after a while, people who have autism would come up to me afterwards. And they’d say– “You know, I don’t want to be cured.”

And there are individuals on the autism spectrum who, I think, cherish the fact that they have autism. What they really want is they want to lessen their disability. They want to be able to lead a fulfilled, full life. And so, I know as we see more and more of individuals with autism, and we have to deal with this as a society, we’re gonna have to figure out how to be more accepting of individuals that are different. You know, and oftentimes, better, but have problems, like we all do. So  I think that this is gonna challenge us in all kinds of different ways. But I’m excited about being a part of the process.

ROBERT MACNEIL: Well, thank you.

DR. DAVID AMARAL: Thank you.