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Autism’s Causes: How Close Are We to Solving the Puzzle?

April 20, 2011 at 5:23 PM EDT
The rise in the number of reported autism cases has caused a surge in research to find the causes. For the latest thinking, Robert MacNeil speaks with four leading researchers about the issue. It's part three of the Autism Now series of reports.
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ROBERT MACNEIL: As we’ve reported, autism now affects one American child in a 110. Last month, a committee convened by public health officials in Washington called it a national health emergency. The dramatic rise in official figures over the last decade has generated a surge of scientific research to find what is causing autism.

Among the centers for such research is here, the University of California, Davis MIND Institute in Sacramento. Here and around the country, we’ve talked to leading researchers about where that effort now stands. Among them is the director of research at the MIND Institute, Dr. David Amaral.

DR. DAVID AMARAL, MIND Institute: Well, I think we’re close to finding several causes for autism. But there’s — I don’t think there’s going to be a single cause.

ROBERT MACNEIL: The science director of the Simons Foundation in New York, Dr. Gerald Fishbach; Dr. Martha Herbert, professor of neurology at Harvard Medical School; and Dr. Craig Newschaffer, professor of epidemiology and biostatistics at Drexel University in Philadelphia. First, I asked, how close are we to discovering the cause of autism?

DR. GERALD FISHBACH, Simons Foundation: I think we’re much closer now than we were five years ago. There’s been a tremendous amount of new information and discoveries. But with any disorder as complicated, as multifaceted as autism, I’m reluctant to say how close.

DR. DAVID AMARAL: 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.

DR. CRAIG NEWSCHAFFER, Drexel University: To begin with, I think there probably is no cause of autism. We’re probably talking about multiple causes. And I think we already have identified some causal components on the genetics front. But if I can interpret your question as complete understanding of all of these complex causes of autism, I think we’re still quite a ways away.

ROBERT MACNEIL: Some people we’ve talked to say we are on the verge of big discoveries. Others say we’re just scratching the surface. Where do you think we are?

DR. GERALD FISHBACH: I think we’re scratching the surface of big discoveries.

(LAUGHTER)

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DR. MARTHA HERBERT, Harvard Medical School: I think it’s somewhere in between. At the brain level, I think in the last five years, we’ve figured out that there’s a coordination problem of the different parts of the brain not hooking up in as synchronized of a fashion. The question for me is why is that happening?

ROBERT MACNEIL: The autism puzzle is proving to be immensely complex. But I asked what hunches they have on where the answer will be found.

DR. DAVID AMARAL: 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 thing, 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 there — I think what’s clear now is that there’s not going be a single autism gene. But there are many, many.

DR. GERALD FISHBACH: Well, I think many people feel that autism is a problem in communication between cells in the brain. Now that’s saying an obvious truth. The brain is a communicating organ. We take in sensory information. We put out motor actions. And in between, there’s the whole phenomena of perception, understanding and digestion of that information. It’s the phenomenon of synaptic transmission. And my belief is we will find root causes of autism at particular synapses in the brain.

DR. CRAIG NEWSCHAFFER: Well, I think it’s going to be a combination of continued good work on the genetic side of things. I also believe, however, that there are going be causal components that are nonheritable genetics, things that we refer to as environmental causes, with a capital E, environment-encompassing lifestyle factors — exposures, things of that nature. And those were, by the way, we’re still at the very beginning stages.

DR. MARTHA HERBERT: I don’t think there’s any one cause of autism. I would lay money that we will not find one thing. We certainly haven’t found one gene; we’re finding hundreds of genes. We’re finding boutique genes. We’re finding genes that kids have and the parents don’t have — their own parents. I think that there are a lot of things environmentally that are overwhelming our ability to cope, metabolically, that are overwhelming our immune system. And the synergy — the collective impact of that is to deplete our protective systems. And I think that’s what’s causing autism.

DR. CRAIG NEWSCHAFFER: But I think the emphasis on genetics probably has been correct, at least as we think about the unfolding of our understanding of what causes autism. And I think over time, we realized that in addition to these genetic components, there is room for and probably just cause for investigating the environmental. So we’re swinging around.

DR. GERALD FISHBACH:  First, there’s no question that autism is a genetic disorder. That does not mean the environment is not tremendously important, because it is also clear that the genetics are complex. We’re looking at the Simons Foundation for what are called de novo mutations — mutations that arise anew in the germ cells of one or the other parent, sperm or egg. Because it appears that these de novo mutations have a very big effect, a very profound effect. If you have the mutation, you have a great risk of developing autism.

DR. MARTHA HERBERT: I think that what you have is, yes, definitely a question of toxics and toxics in our environment, that some of them act like our own molecules, like hormones, for example. That’s called endocrine disruption. Some of them get confused with neurotransmitters. Some of them damage our cell membranes. Many, many of them damage our mitochondria, our energy factories in our cells.

DR. CRAIG NEWSCHAFFER: Something that I think is important in thinking about these complex causes is thinking about the window of vulnerability. When are these causes most likely to act? And again, I believe that that prenatal, intrauterine period is going be very, very important. So things from maternal diet, infections that mothers may be exposed to in pregnancy, exogenous chemicals, chemicals in the environment that could be neuro-developmentally significant. All these are things — I think these things are likely to play a role. How large, how small, I think, is yet to be determined.

DR. GERALD FISHBACH: I don’t think this is an either-or effort. The issue is ideas and hypotheses. The genetics will facilitate work on the environment.

ROBERT MACNEIL: One issue science considered settled for years won’t go away: the parental belief that vaccines cause autism. Public health officials have steadily maintained there is no valid, scientific evidence of such a connection; all epidemiological studies have proved negative.  But now, bowing to public opinion, the body that sets priorities in autism research, The Inter Agency Coordinating Committee, has recommended studies to determine whether small subgroups might be more susceptible to environmental exposures, including vaccines.

DR. GERALD FISHBACH: Despite many, many, many epidemiological studies, no evidence that current vaccines in their present form have triggered autism. There are two prevalent things going on here: vaccination and autism. But trying to correlate those two have failed to date.

DR. DAVID AMARAL: So I think it’s pretty clear that, in general, vaccines are not the culprit. If you look at children that receive the standard childhood vaccines. If anything those children are at are at slightly less risk of having autism than children that aren’t immunized. It’s not to say, however, that there is a small subset of children who may be particularly vulnerable to vaccines 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’s — 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.

DR. MARTHA HERBERT: I think it’s possible that you could have a genetic subgroup. You also might have an immune subgroup. There are a variety of subgroups. But the problem with the population studies is they don’t they aren’t necessarily designed to have the statistical power to find subgroups like that if the subgroups are small.

DR. DAVID AMARAL: I think more importantly what the whole vaccine issue has done is has opened our eyes again to the idea that the immune system is an important component of autism.

DR. MARTHA HERBERT: The brain and the immune system and the gut are intimately related. The cells in those systems have common features. They work together seamlessly, and when you disregulate one, you disregulate all the others. And systems biology is a way of looking at how we work as an integrated whole. I think that’s 21st century biology. Is the brain miswired, or is it misregulated? And I’ve come to think the brain is misregulated. And there are several reasons for that. Short-term, dramatic changes in the functional level of people with autism. One of them is the improvements you see with fever. A child who gets a fever will start to make eye contact, be interactive, will relate. A child who would have been really out of touch will become connected, and then it will go away.

DR. DAVID AMARAL: You know, 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.

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.

DR. MARTHA HERBERT: When we were having this explosion of our chemical revolution, we didn’t have any way of knowing the subtle impacts on cellular function. We thought if it doesn’t kill you, it’s probably okay. But now we’re learning that it can alter your regulation way before it kills you.

ROBERT MACNEIL: There are many other areas of focus that researchers are pursuing.

DR. GERALD FISHBACH: Parents are having children at later ages. And there is a lot of evidence that children born of parents in the late 30′s and 40′s have a higher likelihood of developing autism.

DR. DAVID AMARAL: We’re trying to chart the course of the — 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 your ear, called the amygdala. Both of these structures actually grow too quickly. They get to the adult size too quickly in children with autism.

There’s a bunch of kids who probably have autism right from the get-go. Right– you know, right from conception or — very early on. There’s another group of kids who, at 12 months old, they look fine. They’re communicating, they’re having — engaging socially. But then sometime between 18 and 24 months, they lose social behavior. They lose language. And they regress back into 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 — 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 with 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: Are you at all discouraged that after so much effort, investment, some of the best minds in the world on this, that — that autism is still so baffling?

DR. GERALD FISHBACH: I’m not discouraged at all about that. I think we’re addressing one of the most profound problems in not only all of medicine but in all of human existence. We’re talking about the ability to relate to other people, to empathize in a certain way and to comprehend. And I think it’s the most worthwhile, most challenging effort in science that I’ve ever been involved in. So I’m not discouraged at all.

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