Dr Herbert: There are 85 000 or God knows how many new-to- nature chemicals in the environment, not to speak of other stressor, such as infectious and electromagnetic agents. We don't have an intrinsic or new physiological pathway for every single chemical that is invented. They basically come into your body, and your body has certain ways to respond. Any one substance can stress out a range of pathways-and you can have problems way before you hit what has been called "toxic." Combinations of such sub-stances synergize, so that you can get a cumulative effect that's noxious, toxic, impairing, and hurtful even if no one substance crosses the so-called line that somebody decided was safe or not safe. Which gets back to the question of, says who? And with what level of technology and sensitivity? With emerging knowledge of epigenetics and endocrine disruption and more, we are seeing an unprecedented ability to measure and mechanistically understand much more subtle changes that can happen in gene expression and in metabolism. In this setting the old idea of a threshold between what's safe and not safe is becoming meaningless.

So what if it doesn't kill half the laboratory animals? That's not the level at which the problems we're talking about are occur-ring. We're babes in the woods with regard to how the regulatory apparatus can cope with what our advances in science are allowing us to understand about what we really might be doing with our "advanced" way of life. The idea that you study one thing at a time and each input is separate seemed so logical and systematic, but it isn't really good for understanding what's going on with our health.

This gets to an existential question. This is something I wrote about last December in an article called "Time to Get a Grip" in the Autism Advocate. In a special issue on environmental health and autism, I wrote that we've set up a situation right now where we really didn't think things through, producing all these chemicals because "we"-that is, the people who decide what is impor-tant and who need to have it be "scientific" or else it doesn't exist-didn't know that we were making a mess because we didn't know how to measure it. Now the measurements are revealing embarrassing information. And interestingly, the Bush administra-tion is closing down the Environmental Protection Agency libraries and not letting people even look at data. They're closing librar-ies and packing up the information. You would think that at this point in time, when we really need to see the information because we're in trouble, it would be even more available, but instead it is being put away. Closing these libraries is a crisis for democracy in a scientific world. I think that the closing of libraries reflects that the information is becoming damning.

The complexity and huge diversity we are starting to be able to measure is outstripping our simple models in many domains. I love to listen to Jeff Bland, when he talks about the incredible explosion of knowledge, for example, of the thousands of phytonutri-ents and the things we are learning that they do. There's incredible diversity. I read the interview with the ethnobotanist Jim Duke in the March/April issue of Alternative Therapies that addresses the same thing. With this incredible diversity of natural substances, combined with genetic individuality and individual variations in state, it seems to me that it's becoming meaningless to talk about standard dosing recommendations for nutrients or safety limits for toxins.

Basically, we are not equipped to get final certitude on the level of complexity that we're coming to appreciate is in play. Au-tism is so complicated-and so is other environmental illness and so is the planetary situation right now-that we're going to have to use some kind of good judgment way before we can have scientific certitude and comprehensive precision about these things-which indeed we won't ever get, realistically. We're going to have to transition how we make our decisions from a model of pre-cise science as the arbiter of what is permissible to think and what is not, to the use of science as a kind of tool to check our judg-ment. Our standards will need to come from a more healthful approach as a fundamental basis as opposed to assuming things are safe and then requiring precision science to prove otherwise for one exposure at a time.

The final common pathway argument takes you here because you realize that we've created a production system that hits us with a huge number of exposures, with which we're basically trashing supportive body pathways and body systems, even if we don't know specifically what's doing the metabolic damage. And if you have any kind of genetic vulnerability in any of those pathways, you're going to be a sitting duck to suffer. In this regard, one of the models going around now in autism is that these kids just have more genetic vulnerability, and they'll need fewer environmental hits than their less genetically vulnerable neighbors to overtly suffer from exposures. There are other people in the autism debates who think maybe you don't even need that genetic vulnerability if the exposures are sufficiently strong. So no one has resolved this discussion at this point because we've just started to ask those questions, and there's almost no data because the research programs in place so far have not been designed to answer those kinds of questions.

AT: It sounds like we won't be at a point of resolution anytime soon.

Dr Herbert: No, and meanwhile, we have to handle the situation now: this one and many others. We're going to have to handle these situations on the basis of something other than the results of the next 40-year perspective study. We can't sit around doing nothing while we wait for these data to come in.

AT: And yet that premise, as you mentioned, flies directly in the face of using the science and the research as the traditional arbiter of the decision-making and regulatory processes.

Dr Herbert: That's exactly right. But this is a colossal epistemological crisis on top of the environmental crisis. Even some of my closest friends and allies want to base decision making on what we call "sound science." The problem here is that the term "sound science" can be defined in different ways that carry different motivational and ideological loads. It's very important to seek the best scientific understanding that we can have, but at the same time, we want to use science as a guide, a tool, but not as a censor, as a bully.

I think we need to use science flexibly and adaptively to ferret out the treatable biology in autism and other environmentally modulated illnesses. How do you test treatments when people are so different from each other? Once you acknowledge that, you have to be humble about the results of treatment trials. It's really complicated because of course you don't want to introduce inter-ventions that hurt people, and you don't want to do things that waste people's time and money. At the same time, how do you make judgment? I think we're going to have to take on a systematic re-evaluation of the judgments and gate keeping involved here.

AT: Why are we seeing such a rise in autism? Is this real or simply an artifact due to broader definitions and better reporting?

Dr Herbert: Certainly, there's more awareness and more reporting. The more affected people you have, the more you're going to see it and the more you'll report it. And it's on the news all the time. There were children I saw during my residency whom we would now call autistic, but we didn't then. In these cases, the problem back then was awareness. Regarding broader definitions, I don't think the diagnostic criteria have changed a lot in the past 15 years-certainly not enough to explain the 10-fold increase in the numbers. Some people say, "Oh, they haven't changed lately, but it takes people time to learn what the new ones are." Then other people say, "Well, people get called autistic because that's how they get services, even if they aren't really autistic."

I think all of this is true, to one degree or another, but it begs the question, do all of those lines of arguments exhaustively ex-plain how the numbers shot up from 3 to 4 in 10 thousand in the mid 1980s to current figures of 1 in 150 or even more? A recent UK report said 1 in 86 children are on the autism spectrum. You'd have to be pretty confident that all those inferences explaining these numbers away, such as "It's just better diagnosis" and so forth, were absolutely, solidly, the only possible explanation for such striking increases. And if you are not absolutely clear about the reasons why, then you had better treat this as a public health emergency until proven otherwise.

I think there's an emotional issue going on here, too, that people are conservative, and they don't want to say something alarmist if it's wrong. There is also cognitive dissonance-how could a genetic disease truly increase? People don't realize how tenuous the evidence is for this truly being "genetic" so they treat the genetic model of this condition as fact. Many of my col-leagues who will not consider the possibility of an epidemic have no vested interest in anything that would bias their judgments except that this is what they believe and it's very hard for them to entertain anything else. To consider that we may have an epi-demic of autism and childhood neurodevelopmental disorders is emotionally painful because it raises profound questions about our environment, our progress, our way of life, and what we deeply trust. To avoid asking those painful questions, people try to main-tain the assumption that nothing significant is changing.

But if you look at graphs of the number of new-to-nature molecules that the chemical industry has produced, you get an aston-ishing, exponential increase in substances on the planet that we've never seen before. That's just the physical substances, the chemicals. The next thing that happens, when you start thinking about this, is that it becomes so overwhelming that you go back to genetics because it feels like at least we can study that in an organized fashion, whereas looking at environmental factors would be total chaos. This argument is one of the standard talking points of some of my genetics researcher colleagues.

Advanced scientists should start to realize that the only way they can maintain this point of view is to advocate advanced techniques to study genetics and old-fashioned insensitive techniques to study environment. They need to partition their intellects to do this. As I've already said, we're learning so many more sensitive ways of measuring things, including the impacts of these new environmental inputs, and this is so new that we have hardly had time to think of how to apply these things. One of the ex-pressions around this that I like is, "Absence of evidence is not the same as evidence of absence." The intellectually honest thing to say is not that there is no evidence, but that we have hardly started to look. Then, when you get interested in looking, you see that there isn't a lot of support for such investigations, and there is a fair amount of resistance. This becomes a political and economic question as well as a scientific question. Who's going to fund it, and who's going to get paid by which vested interest to shoot down whatever you say, who's going to sue you if you uncover anything that sheds a bad light or creates potential liability, and all the other related considerations? Given all these potential challenges, it's ever so important to think carefully and strategically about how to proceed.

My personal opinion is that while it may take years to sort out exposures and which ones may have strong impacts, there is a lot we can do right now with the knowledge we already have about the physiology of vulnerability to environmental impacts. My interest is in helping to figure out the points of intervention that can help people do better now, and in helping others to understand that this is a critical area of work. That's where I want to focus my energy. It's important to point out that there are destructive connections between chemicals and our health, and it's important to substantiate these connections, but we really need to under-stand the mechanisms of how health is impacted in order to be able to help people who are already affected right now. I would like to work on this area, which has been a black box in my field, and make it not a black box anymore but an area that's richly differ-entiated with carefully made observations.