Dr Martha Herbert - Interview on Autism as a Metabolic Condition

20 Apr 2011 - PBS Newshour

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The following are some excerpts from an extended interview given to PBS Newshour by Dr Martha Herbert.

These illustrate some of the huge gaps that still exist between the findings from scientific research into autism (and related conditions) and the way that these conditions are still primarily viewed by the medical establishment, which influences current priorities in both research and clinical practice.

Emphasis has been added here to some of the key points made in this extract from Dr Herbert's interview

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ROBERT MACNEIL: How do you explain the hostility in a lot of the medical community to the treatments that parents of autistic children are using to treat these biomedical conditions?

DR. MARTHA HERBERT: I think that there are a number of different levels for hostility.

One of them is, medical doctors are trained to believe that drugs are more efficacious than remedies like diet. There's a strong prejudice against diet and nutritional interventions.

Another thing is that the parents are not doing this under the control or guidance of their medical professionals. And that is a problem.

It feels like it's an out-of-control situation, I think, to doctors. I think that most doctors don't really have an understanding, from what they've learned of autism -- if they're not specializing in it, they don't hear about the advances in the science and they have no reason to think that this could have anything to do with what they conceive of as a devastating, lifelong, inborn brain error.

ROBERT MACNEIL: Because autism is still diagnosed and given its correct number for insurance purposes in the diagnostic manual drawn up by psychiatrists.

DR. MARTHA HERBERT: That's right. And if you think of it as a brain disorder that's a miswiring from birth, then what the parents are doing is utterly insane or incongruous. But if you think of the brain as being affected by the whole body, then when you affect the body, you can affect the brain. And that's the rationale of what the parents are doing. The parents are doing, in my view, systems biology.

ROBERT MACNEIL: What does that mean?

DR. MARTHA HERBERT: That means they're looking at the organism as an integrated whole with underlying, genetic gene expression and metabolism patterns that don't know organ boundaries. 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. To be honest with you, I think that parents have beat medicine to systems biology.

ROBERT MACNEIL: How do you describe autism now? How do you define it?

DR. MARTHA HERBERT: I've taken a number of steps in how I define autism. The first step that I took was realizing that autism was not so much a brain disorder as a disorder that affects the brain. So then the question is what's affecting the brain? The immune system is affecting the brain; changes in chemistry are affecting the brain; changes in the microorganisms in our guts are affecting the brain. All of those things -- brain, gut, microorganisms -- are very central right now in systems biology.

Then I began to think, well, if the brain is affected by the body, then what's wrong with the brain? 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. The most dramatic reason is there are more and more reports, some of them published in the literature, of 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, will be interactive, will relate. You see that sometimes with children on antibiotics. A child who would have been really out of touch will become connected, and then it will go away. Another one is steroids. A child with autism and asthma has an asthma attack, gets some steroids, starts to talk and relate immediately.

It doesn't take a whole long learning process. It's as though there was an obstruction, you lifted the obstruction and the underlying capability was there. We haven't figured out how all of these instances of temporary relief of the obstruction can be made more permanent, although there are cases where persistent effort does create a permanent change.

But seeing the underlying capabilities be there. And also, some children who recover from autism will start telling their parents stories of things they remember from when it looked like they were totally out of it, indicating that they were recording and observing. The book by Portia Iversen, "Strange Son," a really remarkable book about her son and about Tito Mukhopadhyay, who is a very high-functioning but nonverbal person with autism, when her son, Dov -- when they first gave him a communication device, he was doing fourth-grade math and he could read Hebrew and English.

And they didn't even know he could do any of this. So his mental computer was operating, but the interface wasn't working. So if the computer is operating, it's not an impairment; it's not a mental retardation. It's something about coordination and interface that's being blocked, or the settings are off.

ROBERT MACNEIL: You've had a varied career, but can you remember the moment about autism when you suddenly said, hey, we've got this all wrong -- this isn't just a brain disorder, this is a whole system disorder?

DR. MARTHA HERBERT: Sure. Well, the build-up to the moment was seeing patients over a number of years, after my residency, where I was trained to work up psychiatric patients for rare metabolic diseases. And I would perform these work-ups and I would almost never find anything, which is the usual. But then, why was everybody sick? Why were they all having allergies? Why was I getting this story of people being -- you know, diarrhea all the time?

My training had led me, in working up these metabolic disorders, to understand that a genetic problem that changes your metabolism affects your whole body, that more genes express in the brain than anywhere else, so something that affects your body will affect your brain. So that's the background.

I was in Rome in 1999 at a conference on autism to present my brain-imaging research. And another speaker got up and showed a slide of abnormal proteins in the urine of someone with autism -- a whole lot of extra spikes of proteins that are not found in a typical person. That's the kind of printout you see when you're working up a metabolic disorder. No one had ever shown me that kind of data for autism.

And I saw that and I said, this is a metabolic disorder. It has to be. Otherwise, you wouldn't have this problem. I don't know what kind of a metabolic disorder, but I took it from the basket of the brain and which regions of the brain are creating the behaviors to a systemic disorder where the metabolism is off, and it's affecting everything.

And it was just that one slide, and it fit right into my pediatric neurology training, but in a different way than I had been led to expect. And everything after that has been working out -- well, it's a lot of sleuth work. It isn't completely obvious how to play that out, but that was it. If you see that kind of metabolic abnormalities, it puts it in a different category.

ROBERT MACNEIL: Has the heavy emphasis on genetic research into autism delayed or inhibited possible research into the biomedical side of it?

DR. MARTHA HERBERT: So with genetic research, people are looking for genes that affect particular functions. But the people who are doing that work are mostly not the kind of physician that I was trained to be -- a child neurologist with a background, which you have to have, in metabolic disorders.

The first time I presented my lecture in my department's continuing medical education course on, is autism a brain disorder or a disorder that affects the brain, our residency director said, well, it's got to be that way. She said, I don't know exactly how it's going to be, but it has to be. That makes total sense. But she is a metabolic specialist. She understands how these things work.

When I talk to geneticists, I've had such a hard time talking about how genes affect pathways. Even a few years ago, people were looking at genes as if they weren't in pathways. Recently, people have been talking -- partly because of these software programs that locate genes in these networks, it's becoming more obvious that they're in pathways and that it's the pathway that does the work.

ROBERT MACNEIL: And the pathway can be proteins, can be other substances that are signaling substances?

DR. MARTHA HERBERT: Yeah. But you know, so there was one study out of Vanderbilt where they found this one gene -- the MET gene -- which was an interesting gene because it affected the brain, the immune system, the gut and it was environmentally vulnerable. So then they went to the pathway that MET was in to see if there were any other genes that were also present - gene abnormalities that were present more in autism. And they found several others, the idea being that it's the pathway. The product of the pathway when it shifts -- that's what the problem is.

I think that genes have become this abstraction divorced from the organism and we have to put the genes back in metabolism, back in physiology. And then we can see how genes and the system work together and interact with each other.

ROBERT MACNEIL: Could you give us a definition of metabolism, since you've used it a lot, that I can understand?

DR. MARTHA HERBERT: It's funny because my writer colleagues says she's been doing science reporting for the last 10 years, and no one's been able to define metabolism for her, which is funny because metabolism is basically like cooking: you turn one thing into another thing. You have a substance. It goes through a chemical reaction and it comes out different. And our bodies are our metabolic factories.

We have to be changing things from one to another. We build things up. We break things down. We create energy. We burn up energy. We do all these things. And we have to do it very carefully. I mean, you can't start a fire in yourself to get heat; you have to do it so nothing is damaged. So everything is done in these very careful, step-wise ways. When you're changing one thing to another, the enzyme that makes it go from one thing to another is shaped by a gene.

If the gene has a mutation, the change from A to B could be slower. It could be faster. It could not happen at all. What I was trained to look for was, the change from A to B is broken. It hardly happens at all. What I think we're seeing in autism is, the change is inefficient. So you have a baseline -- it's inefficient. Then along comes the environment -- some toxins, some exposure, maybe an infection. That vulnerable change from A to B now has another source of vulnerability that makes it even more inefficient, and it starts to break down in its function.

And I think that's where it's hard for geneticists to understand because they think the genes are doing almost everything and the environment is a few of the decorations on the icing on the cake. I think that it's really, really interactive all the way along. And I also think that the more we learn about gene expression, the more it's going to become obvious that that's the case.