People,
So I promised to counter “smack downs” of my NYT oped on autism. My rebuttal is disappointingly simple and boring. As I told Wired.com, talk to scientists. See what they say about this research, and about my piece. Check it out with them.
Paul Patterson, who pioneered much of the prenatal-inflammation-autism research, has made this quite easy. He has a blog. (I did not know this when I wrote the oped.)
He writes about new work in the field, and answers questions. It’s really a remarkable resource — a direct line to a scientist — and highly unusual. My guess — although it’s not my hope — is that the sheer number of people writing in will eventually surpass his ability to respond to everyone.
But for now, he does. So go ask him questions.
A few points that bear mentioning. I’ve gotten whiffs of people — mothers perhaps — considering acquiring helminth infections to prevent who-knows-what. That’s an extremely bad idea. Why? First and most important, that approach hasn’t been proven to work or prevent anything.
Second and just as important, given what the research is telling us — that maternal immune equilibrium is important for fetal health — the experiment could backfire. The immunoregulation scientists think is so important for preventing allergies or autoimmune disease occurs with chronic infection with a certain quantity of parasites, not necessarily a recently acquired infection consisting of the wrong amount.
In fact, when you’re first colonized by a helminth, your initial response may be quite inflammatory. And that’s what we’re trying to avoid. Moreover, if you haven’t grown up with parasite infections, your response isn’t likely to be the same as someone who has — at least not at at first. It may be more intense. Again, that’s something to steer clear of.
So do not under any circumstances do this. Let science 1) show it actually works, and 2) provide something safe.
Onto some FAQs.
Aren’t you making another version of the vaccines-cause-autism argument?
Not at all. A few distinctions worth making: The vaccine-autism claim went unreplicated, and extensive epidemiological studies failed to support a link. The Lancet eventually retracted the 1998 paper positing that the MMR vaccine might trigger autism.
The research I refer to in the NYT piece—and much more that wasn’t mentioned—has progressed in a way that’s the mirror opposite. Different groups around the world keep finding evidence of inflammation in this subset of autism, and at every level—the cellular, the transcriptome, the periphery, the brain, the spinal fluid, the womb.
Scientists working in parallel on animal models find they can reproduce many of these phenomena with prenatal inflammation. And the epidemiology—prenatal infections, maternal autoimmune disease, asthma, metabolic syndrome—all support a role for immune dysregulation in the womb.
This body of science has snowballed just as good science should.
If this argument is true, how come I’ve never heard of it?
Scientists have heard of it. Many bloggers out there have as well. Teams of people around the world are working on it. They’re all familiar with it. That’s why I keep saying, Go ask the scientists.
But it’s not proven…
The science, I think, has advanced beyond some — although not all — of the debate points I see in the blogosphere. Is inflammation a cause or effect? some ask, and rightly so. But the scientists are already finding they can improve some autistic symptoms with anti-inflammatories.
Another such study is in the works.
A test is in development, meanwhile, for those fetal brain-directed antibodies, presumably to flush them out.
The science is moving toward prevention and treatment.
Your oped was depressing
The underlying message should be one of hope. The idea: Some subset of autism associated with prenatal inflammation may be preventable. Ongoing inflammation, which often correlates with symptom severity, may be treatable. Paul Patterson and Alan Brown, who’s done great work on prenatal infection and schizophrenia, have said this outright regarding schizophrenia. With the proper foresight and planning, the subset of schizophrenia cases associated with prenatal infection could be prevented.
This idea of prevention is more difficult with immune dysregulation that occurs on its own, as in autoimmune disease. At this point, allopathic medicine just isn’t very good at treating autoimmune disease. That said, at least the subset associated with those fetal brain directed antibodies may be preventable once scientists figure out how to flush them out.
And it may be that a pregnancy-safe NSAID, like in this mouse study, help immensely when the problem stems from more generalized inflammation.
In this study, for example, women who had fevers while pregnant, and treated their fevers with anti-pyretics, didn’t have an increased risk of a child with autism. But children born to mothers who didn’t treat their fevers did have children at increased risk for ASD.
Did the anti-pyretic drugs prevent interference in fetal brain development? Obviously, we need more research before we can answer that question definitively. But if prevention is that simple—wow.
The hygiene hypothesis is so controversial…
Really, it’s not. It has graduated from hypothesis to theory, in fact. (See my ~350-page book for the full proof.)
But some misunderstand what the hypothesis says, and how it has evolved since it was first posited by the epidemiologist David Strachan in 1989. That partly stems from the phrasing — “the hygiene hypothesis.” We’re not talking about showers. And we’re not talking about bringing back smallpox. Some more accurate renditions: “the microbial deprivation hypothesis”, or the “old friends” hypothesis.
Whatever you call the idea, few researchers who’ve been following its evolution think acute infections — measles, smallpox, the flu, common cold viruses — help us in any way. That’s because these infections—crowd disease that mostly originated from animals relatively recently—don’t change our immune systems favorably. They prompt a major inflammatory response, which is not what we’re looking for. We’re looking for immunoregulation.
It’s the microbes inside us — the microbiota — and a few parasites that are important for immune calibration. You’ll notice a commonality: Organisms that help us generally take up long-term residence in our body. And they also have a special relationship with our immune system. They’ve probably been with us for a long, long time — since the Paleolithic.
As a principle, the fact of mammalian dependence on microbes for “education” has been proven beyond a reasonable doubt. The most dramatic illustration is simply what happens to animals that have no microbes — germ-free mice. They really don’t have immune systems at all. Their lymphoid tissue fails to grow. Their t-cell repertoires are all off. They have insufficient regulatory t-cells. They’re more prone to asthma and colitis. Their intestines are under developed. Their hearts are shrunken. They need to eat more food than germy mice to survive.
They basically don’t look at all how they should.
More recently, scientists have shown that the “germ-free” brain is also different. Genes are “on” that should be “off.” The mice have less anxiety (maladaptive for a rodent that numerous predators are itching to eat).
And even more recently, scientists at Harvard demonstrated that the microbes that prime the immune system are species-specific. A mouse’s gut doesn’t recognize human microbes. It needs mice-specific bacteria. Meaning that, as mammals, we’ve coevolved with particular microbial communities, so any old bug won’t do. We need our native bugs.
So no, the principles underlying the “old friends” hypothesis are hardly controversial at this point. The only question is how — and when — we’ll actually be able to marshal this new understanding to improve our health. It’s not quite ready yet. But we’re getting much much closer.
In fact, I’ll wager that even some of my critics buy into this idea. Although I can’t find the link, I seem to remember one mentioning that s/he used probiotics after laying into my oped. Why the probiotics? Because s/he thinks live organisms will benefit her. S/he thinks they’ll change how his/her immune system works for the better. That’s a fundamental tenet of the hygiene hypothesis.
S/he buys into the idea she sought to discredit. And good. Because it’s true.
About those worms
It’s simple. They secrete immune suppressants–part of their bag of tricks for parasitizing you. We’ve evolved with these immune suppressants constantly injected into us. Run the following experiment in your head. You have 1000 people, administer immune suppressants to them chronically, and drop them in a jungle with lots of very deadly pathogens. Wait 1000 generations. What will happen? Only those able to fight off acute infections with their immune systems depressed will reproduce. Those who can’t won’t.
After 1000 generations, you end up with people who manage to have ‘normal’ immune function in the context of constant immune suppression by parasites. Now imagine suddenly removing those immune suppressants. The immune system is now too pro-inflammatory. It becomes hyper-reactive.
That’s what David Pritchard, whom I talk about in the book, calls a “hangover” from parasitism.
So the anti-inflammatory drugs of the future may not be worms themselves, but maybe worm-based drugs. This Scottish group is already working with a secretory product isolated from tissue-dwelling filarial worms. It has shown benefit in a mouse model of rheumatoid arthritis.
Think the notion of drugs from parasites strange? A Warfarin-like anti-coagulant has been tested on people. What’s its provenance? The dog hookworm—ancylostoma caninum.
Here’s a list of drugs derived from mammal-feeding invertebrates.