Autism Revisited: Three Potential Drivers

Andrey Rzhetsky, a new breed of biologist, brought up in Russia’s third largest city, Novosibirsk, is a big deal—tenured at the University of Chicago, director of the Conte Center for Computational Neuropsychiatric Genomics, and senior fellow of the Institute for Genomics & Systems Biology and Computation Institute. Never one to shy away from controversial and difficult subjects, he takes on big, complex, controversial topics like what’s behind the autism epidemic.1

While most biologists spend hours in a lab, Rzhetsky thinks there is more than enough macro and micro data available already; he queried 100 million medical records trying to figure out the best correlations between environmental changes and autism, and concluded that autism might just be a milder form of extensive chemical poisoning.

It was already known that when certain chemicals, such as thalidomide, enter the human body, particularly during crucial periods like gestation, they can seriously deform various body parts. So Rzhetsky began searching for various extreme malformations, especially in boys, since they are far more prone to autism. These kinds of conditions, like micropenises and undescended testicles, are rare, occurring in only 0.27 percent of the male population. But wherever Rzhetsky found a cluster of these congenital malformation cases, he could also predict a massive increase in the incidence of autism in the surrounding community.2

In some parts of the world, the trends are more than a little worrisome. In Korea (2000–2005), the rates of undescended testes increased 348 percent. Malformations were far more common near chemical parks than near nonindustrial areas: 198 cases per 10,000 births in the petrochemical-plagued Yeocheon versus 11 cases in the city of Chuncheon.3 Less than a year after these data were published, the first major Korean autism study found three times more cases of autism per capita than occur in the United States.4 (And remember the United States is already in the throes of a massive autism epidemic.)

According to Rzhetsky’s correlations, the closer you get to certain chemical clusters, the likelier you are to see a population with devastating birth defects, and the likelier a far larger percentage of the population will be affected by autism. Deformities increase substantially if mothers are janitors, maids, landscapers, or farmers. If Rzhetsky’s correlations are right, then wherever you see an uptick in serious deformities you should see an explosion in autism cases. It might pay to keep a close eye on parts of Brazil, given the extraordinary rates of micropenises, especially in boys whose parents worked with or near pesticides.5

We live in a far more complex and varied chemical environment than our ancestors did. A single grad student can now synthesize hundreds of novel chemicals in a month, whereas it used to take a great chemist years to come up with a few new molecules. New chemical disruptors may be changing how the human brain develops, but because human clinical trials for such things would be unethical, and the variety and interactions of various chemicals is so extensive, it’s very hard to trace exactly which chemicals, in what combinations, alter the brain. We do know that children are far more sensitive to certain chemicals and medicines than adults are. A child’s brain grows to 80 percent of an adult-size brain during the first two years of life, and many of its initial connections are established during gestation and early childhood. Perhaps some of the materials we use every day—in our homes, such as clothes, foods, and utensils; or in the course of other activities—are having serious disruptive effects on the brains of young boys.

In a sense, boys seem to be acting like the proverbial canary in a coal mine, especially vulnerable to environmental insults from the pesticides, plasticizers, sex-hormone analogues, drugs, synthetic molecules, and other chemicals that surround us. Even overall sex ratios may be affected by these agents; Russian pesticide workers exposed to dioxins father fewer boys.6 Something similar is occurring in Taiwan.7 And in heavily industrialized Sarnia, Ontario, the reduction was even more brutal: Just one baby in three was male.8 Overall, mothers seem less affected by most chemicals, and the same is true of daughters. (And in the United States, boys are diagnosed with autism 4.5 times more frequently than girls.) So Rzhetsky advocates measuring specific chemicals to test whether, as parents expose their bodies and their children’s bodies to more and more chemicals, one of the immediate and cumulative effects is that their kids suffer autism.

Not everyone agrees with Rzhetsky. A second major research camp believes parents have so modified their bodies and breeding habits that they themselves are the primary cause of the autism explosion. In 1900, in the United States, fewer than 1 in 5 women entered the workforce. Today it’s almost 4 out of 5. Working women have fewer offspring, and the children they have are born later in life. Late conception increases the likelihood and prevalence of some birth defects.9 Many of these new mothers might not have been able to conceive naturally, so they flooded their bodies with synthetic hormones. In 2009, more than 6 percent of U.S. births came after ovulation treatments.10 The specific chemicals used to induce childbearing past the age when your body naturally says, “It may be too late” may also have unintended side effects on the development of infants’ brains.11 Add to this a bevy of stereotypical macho men, the ones over age sixty, with the new convertibles and young wives, who are also fathering kids later—not always a smart idea, given that their sperm accumulate an average of two new mutations per year.12 These unfortunate combinations result in kids who are far likelier to suffer autism, schizophrenia, and cognitive impairment.13

A third major faction in autism research is focused on gastric disorders; many autistic children seem especially prone to stomach troubles.14 The question is, how does this relate to brain development? Well, it turns out “gut instinct” is absolutely real; one of the oddest of anatomical discoveries is the number and reach of neurons scattered throughout your digestive tract. At least 500 million neurons stretch from your throat to your . . . ahem, rear end. The existence of this “enteric nervous system” means you have the equivalent of 6.6 mouse brains lying outside your skull telling your body what to do, what to eat, and how to react.15 Having a partially decentralized brain helps you decide how to digest, what to expel, what to crave, but the import of this enteric system goes far beyond food. The neurons in your gut generate as much dopamine as your brain; this is the key neurotransmitter that helps control the body’s reward and pleasure sensors as well as emotional responses.16 Furthermore, up to 95 percent of the serotonin in your body, the neurotransmitter that inhibits appetite, controls sexual behavior, and reduces pain also resides within your enteric system.17 Celiac disease increases the probability of having an autistic child by 350 percent. So when the gut-neuronal system is disrupted, there can be serious consequences, including an increase in the chances of getting autism.

Various other factors that disrupt early neuronal development may also be driving autism. Mothers hospitalized for viral infections during their first trimester triple their chances of having a child with autism. But, ironically, some communities plagued with infectious diseases have lower incidences of autism, so part of the inflammatory epidemic may be due to our living in ever more sanitized and pristine environments where our own immune systems less frequently fight off infections and parasites.18 And beyond these explanations are still others such as antibiotics, gene mutations, TV exposure, premature birth, assortative mating, obesity . . .

Whichever of these explanations, or combination of explanations, turns out to be right, we are still left with a mass of open questions: How are we so quickly altering our descendants’ brain circuits? Is it a cumulative exposure to more and different chemicals so that what our grandparents and parents were exposed to is now affecting our children? After generations of low-level chemical exposure, have we accumulated a “memory” of this toxicity in our bodies so that now we somehow transmit a torrent of acquired nonrandom mutations to our children? Or is there one particular new class of chemicals whose use is growing fast? We don’t know. We do know we have an epidemic on our hands. Our children’s brains are evolving fast.