ROBERT MACNEIL: Dr. Herbert, how common in children with autism is a spectrum of biomedical problems, such as Nick has?
DR. MARTHA HERBERT: I think it's pretty common. I think it may be more common than not. Certainly, in my experience, it's been more common than not. People come to me because they know that I'm interested, but I think that probably the majority of people have some part of it.
ROBERT MACNEIL: How do those biomedical problems, gastrointestinal for example, affect the symptoms of autism?
DR. MARTHA HERBERT: Well, the simplest answer is they make it worse. But then the question is, how do they make it worse? That's the big question. Some people think it's because it's uncomfortable and painful, but the real action is in the brain and it's not affecting the real action of the brain; it's just a sideshow of discomfort.
Other people think that there's a much more profound connection between the gut and the brain. And there's a lot of research, not specifically in autism, but more generally in biology and neurobiology, about brain-gut connections. So that abnormalities in the gut -- inflammation, neurotransmitter differences -- can affect the way the brain functions.
ROBERT MACNEIL: These biomedical problems are treatable, many of them, with drugs. If you're treating those, how do they affect the symptoms of autism?
DR. MARTHA HERBERT: Well, that's a good question. It depends on the drug, and it's also a question of whether drugs are the only, or best, way of treating these problems. But if you treat these problems with drugs, you can get a diminution of symptoms. Let's say you have reflux. Reflux -- acid comes up from your stomach to your esophagus. That hurts.
Children with reflux can't say they have reflux if they have autism. What do they do? They bang their head against the wall, they have temper tantrums, they bite themselves, they attack other people. When you treat the pain from the reflux, they'll often stop those aggressive or self-destructive behaviors. They may sleep better. If you sleep better, everything goes better.
ROBERT MACNEIL: So are you, then, treating the autism or treating, in your case, the reflux?
DR. MARTHA HERBERT: Well, I think if you use a drug, you're probably treating the reflux. I think there are other things that you can do that may be more fundamentally treating the metabolic and immune imbalance that some of us think is going on in the whole system -- the gut, the immune system and the brain, and more -- all at the same time.
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: That's an interesting -- how do you explain the hostility?
ROBERT MACNEIL: The hostility -- medical hostility -- to it.
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.
ROBERT MACNEIL: Has the research into the biomedical side of autism been inhibited by the vaccine wars -- by the belief of some parents, many parents, that their child developed autism because of a vaccine?
DR. MARTHA HERBERT: I think the vaccine wars have made it really hard to pursue medical ideas about autism. I think many people in the research community feel that it's their responsibility to avoid giving ammunition to people who say that the GI or the immune thing comes from vaccines and nothing else but vaccines. And I've watched people try to restrict the discussion to things that happen before birth, or try to avoid the thing altogether.
I've tried to be a voice for expanding the idea of -- it used to be that people would say, it's genes or its vaccines. And vaccines was the only thing in the environment that people talked about. By now, it's finally expanded and people are looking at all kinds of other things in the environment that can play a role.
And they're also finding evidence that the bodily things -- the immune problems, the metabolic, the GI -- are really going on. And if you'd step two inches outside of the world of autism, you find that these things have thousands of papers showing that they're related to each other. So, I would really like it if people could just take a deep breath and say, let's just look at what we see.
ROBERT MACNEIL: Do you think vaccines have been exonerated by all the epidemiological studies, which say they are not implicated in autism?
DR. MARTHA HERBERT: Well, with vaccines, what I think is that in the last, let's say, 10 years, we've had such an explosion, particularly of immunology, that we're learning things about the immune system that we could never even have conceived. We have ways of measuring and studying that we've never even conceived. That these things could never possibly have been known when our vaccine system was designed and developed.
And I think we have a really great opportunity to apply this advanced science to making our ways of protecting the population from devastating, infectious disease really powerful and optimal in a way that was never conceivable before. So I think that we know, at the population level, what the statistics are. What we need to know now is what the biology is for each person.
ROBERT MACNEIL: Could there be a subset of children with a genetic predisposition to have a toxic reaction to vaccines that, for the rest of the children, have no adverse affect?
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 aren't necessarily designed to have the statistical power to find subgroups like that if the subgroups are small.
ROBERT MACNEIL: Yeah. How would you, now, say -- if you were asked what causes autism, where are you, in coming up with an answer to that?
DR. MARTHA HERBERT: Sometimes, I've thought about writing a book and calling it, "Autism and Everything"... 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 the kids have that 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.
ROBERT MACNEIL: We have introduced, in the last couple of generations, hundreds, if not thousands, of new chemicals into our households, our farms - everywhere. Could you see that change in our, how to put it neutrally, toxic environment as connected with the rise in autism?
DR. MARTHA HERBERT: I think that what you have is 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 jam up our receptors. Some of them damage our cell membranes. Many, many of them damage our mitochondria -- our energy factories in our cells.
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. So I think that's one of the big factors. I'm also concerned about the way we've been treating our gut bugs, where the gut micro-biome -- what we're learning so much in the last few years about how much the organisms in our gut affect our whole health.
ROBERT MACNEIL: That's the bacteria that are naturally in our digestive system.
DR. MARTHA HERBERT: The bacteria that live in our guts turn out to play so many important roles in our metabolism. And they they do work for us. They digest things for us. They make vitamins for us. And if they're not balanced right, they may make things -- not make things we need or make things we don't need. So I think that's another problem. And some of that is toxins and some of that is just feeling that we have to kill all the bugs, and we don't realize that we actually have to live with the bugs.
ROBERT MACNEIL: Where are we - where have we arrived in understanding autism? Some people say we're on the verge of great discoveries; other people say we're only scratching the surface. What do you think?
DR. MARTHA HERBERT: 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? I want to look underneath the recordings showing that it happens to understand what's happening in the brain tissue that's interfering with the ability of the brain to coordinate.
There was a wonderful study by a friend of mine, David Beversdorf -- gave people with autism a drug called propranolol, which many people use for blood pressure, but it's also a stage-fright medicine. And he found that with that drug, their connectivity improved. He interpreted this that when you take the stress away, the brain can access more remote networks. So I think that's a clue that, right there. You give the drug, you see improved function. That's like, it's not necessarily broken; it's obstructed.
We also have people looking at the biology -- things that could be wrong, not only in the body, but in the brain -- the inflammation, the oxidative stress, the problems at the cellular-metabolism level, the inflammation and the cellular over-excitation -- that could create a chemical environment in the brain where the cells don't fire in a normal way.
But mostly, you've got people over here in science describing the brain patterns and people in a different corner describing the cells, and they're not working together. So my feeling is, we have the pieces for a breakthrough, but the pieces aren't connecting yet. So we have a connectivity problem in the brain in autism and you have a connectivity problem in the science.
ROBERT MACNEIL: Should the public efforts in this matter be directed by a National Institute for Mental Health, or should they be directed by a different institute or some working party bringing them all together that - in other words, does it need a different kind of direction? Some people say it's a national health emergency, a crisis. It needs an autism czar to coordinate. What is your feeling about that?
DR. MARTHA HERBERT: Well, I think it needs a systems team. No one point of view can possibly take care of this. We have a buzzword in science - transdisciplinarity. It's a big word. We've got to pull that off. We have to have people sitting together, working to coordinate. I think that the way we're funding autism research in general is part of the problem here. People are competing for money to do their little projects that have to be defined very narrowly.
The people with autism, meanwhile, have lots and lots of problems all at one time. Why don't we collaborate amongst many people with different ways of measuring those problems and thoroughly study the different dimensions that are troubling individuals all at one time? So how do the brain problems relate to the gut problems? How do the gut problems relate to the immune problems? How do they relate to gene expression in those kids? And then, for the kids who actually get better, how do those change when they get better?
I think we need a collaborative model, not a competitive, fragmented model.And we need people who understand systems biology, 21st-century science, in order to pull that off.
ROBERT MACNEIL: Who said, in all my practice, I have never met a child with autism with gastrointestinal problems.
DR. MARTHA HERBERT: Well, I heard that. I heard about that. Right. Some of the psychiatrists - some of the studies with the lowest figures for how much GI involvement there is in autism were retrospective chart reviews. So a psychiatrist or psychologist didn't write down that there was a GI problem. Well, maybe they didn't ask. Maybe they didn't know how to ask. So how much does that really count?
ROBERT MACNEIL: Is our wonderful science implicated in creating such changes in the environment that it could be, in part, responsible for creating autism?
DR. MARTHA HERBERT: Yes. I think our science has created changes in the environment that go beyond the capacity of our bodies and our planet to cope. And when you're pushed past the point of coping, you pull back into systems that you can handle. Everybody gets repetitive and they do the same thing over and over again when they're stressed. If you look at an autistic child, person, narrowing their field, it's a stress response.
But our cells are stressed, too. Everything is stressed. We have too many chemicals coming in; we have too much information coming in, much of it pointless. And so I think we've created a glut of new chemicals, information and quick fixes that are not optimal. And people are caving. They're not handling it. And the autistic children are caving really young and really dramatically.
The hopeful thing about it is that some of these people are turning around. And when you see someone who was told they had a hopeless condition make, sometimes not all-that-complicated changes - diet and a few other things - and do a fair bit better, it gives me hope that if we catch ourselves in time, we might be able to right our course. Because if organisms - if kids can get better, maybe the rest of us can get better and we can live more intelligently and in a way that makes us healthy, not sick.
ROBERT MACNEIL: Can you explain to us how the systems in the body affect the brain, which we consider to be autism? I liked your line that the brain is a wet organ.
DR. MARTHA HERBERT: Right. The brain is wet. It's not a computer. It's not a silicon chip. It's wet. It gets blood. The things from the blood have to get into the brain. So you've got to feed the brain the nutrients that it needs. It needs a lot of oxygen. It uses up 20 percent of the oxygen energy in the body.
So if you're not bringing in the right nutrients, that's a problem. If you're inflamed, that causes a problem because there's a barrier between the blood and the brain, and that barrier opens up and things get into the brain that irritate the brain. So if the brain is wet and it's also supposed to be protected from things in the body that shouldn't get in, things can get in that, maybe, shouldn't be there. So let me try and recap that because that's still a little bit, you know, wandering.
ROBERT MACNEIL: How do the functions of the rest of the body affect the brain?
DR. MARTHA HERBERT: The brain gets substances from the body - nutrients, hormones, chemicals. If you give a drug, it affects your brain functioning, so we know things get into the brain. The brain is either well-nourished or irritated. It gets signals and it gets confused. Let me try that again. I still don't like that. What's the general principle that would really sum this up?
ROBERT MACNEIL: We're coming back to systems.
DR. MARTHA HERBERT: So in autism, let's talk about the gut and the immune system and the energy systems. So, there are three body systems that are examples of what can affect the brain. The immune system can affect the brain if it has - if the immune system puts you in a state of inflammation, which is common in autism.
There are chemicals that get into the brain that make it too excited. If the brain is too excited, sensory experience is irritable, you may have trouble sleeping and you may even have seizures. The gut is full of bacteria, and under ideal circumstances, they would be good for us. But if they're imbalanced, some of these bacteria produce chemicals that act like neurotransmitters, like dopamine, for example. That can affect your behavior.
If your energy metabolism is awry; if your mitochondria are not working right; if they've been injured by some of these toxic chemicals or by inflammation, you won't be able to make enough energy to carry out the work of connecting your brain cells from one to another because that takes a ton of energy.
So all of these things degrade and confuse the quality of signal in the brain. The chemicals from the body degrade and confuse the signals in the brain. And I think that, that's what the problem is. So taking a whole-body approach to autism, trying to optimize the state of the body so the chemicals it produces are good for the signals in the brain should be a treatment strategy.
DR. MARTHA HERBERT: I mean, it's bad enough that there's a controversy about vaccines; imagine if there's a controversy about antibiotics. I mean - and look at where we're putting so much antibiotic into the food supply for the farm animals. And then it gets into the water and into our...
ROBERT MACNEIL: And hormones.
DR. MARTHA HERBERT: Yeah. So all of these things, they are confusing to the body. I think we're confusing the signaling systems. We're confusing the information properties of our bodies and our brains.
I mean, in the past, we didn't have a concept that there were information systems that you could confuse.
ROBERT MACNEIL: I'm particularly interested in this, and it would be easy to take it too far - this idea that we have so dramatically changed the environment. I've read numbers like 12,000 new chemicals that have been introduced - maybe it's many more than that -- into all the various aspects of life, from the farm to food to some that are known to be neurotoxic, like fire-retardant chemicals in sofa cushions and that sort of thing, which are required. And their toxicity was discovered because California passed one of the most progressive fire-retardant laws in the country.
DR. MARTHA HERBERT: My choice has been that I think we need to look at the environmental factors in relation to how the body is vulnerable to them. I want to have a glutathione t-shirt. It's the glutathione. It's this chemical that's the biggest detoxifier, the biggest anti-oxidant. And every time you're exposed to something -- not all somethings, but many somethings.
ROBERT MACNEIL: Your body produces it naturally?
DR. MARTHA HERBERT: Well, you wear it out. You wear it down and you don't have enough. So the more cumulative, even little, exposures, the more you deplete it. And the sum total of all the little things add up to a big problem with glutathione. So many different chemicals will deplete glutathione.
ROBERT MACNEIL: Other researchers have said that it's very difficult to get research proposals accepted in the environment, whereas you can be specific about a proposal for a genetic study because you can - as you said earlier, you can be very precise about it. How are you precise about the environment when it's everything around us? And how do you narrow down a group?
DR. MARTHA HERBERT: Well, there are computer tools now, which link genes and chemicals and pathways. So that's one way of doing it. But let me turn that around. You can be specific about a gene, but has that given us big answers?
ROBERT MACNEIL: No.
DR. MARTHA HERBERT: So maybe the genes are also much more complicated and we just had ways of narrowing them down, and you could get away with it because everybody believed that it was going to add up to something. That doesn't mean that it's the right approach.
ROBERT MACNEIL: Yeah, the silver bullet, which, five years ago, I guess they believed they were going to find quite quickly after the human genome was ... autism?
DR. MARTHA HERBERT: I think we probably have biomarkers that suggest risk. They wouldn't be diagnostic, in my view, because they wouldn't be specific. But I think what they would do is say that this child is at risk for something.
ROBERT MACNEIL: Fragile X, for example?
DR. MARTHA HERBERT: Um, fragile X - well, no. I mean, I'm thinking of immune and oxidative-stress problems. I have a study going with babies and we're measuring those things starting at two weeks.