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Soon after psychiatrist Leo Kanner first identified autism in the 1940s, he and his colleagues proposed a simple explanation for its cause: mothers’ “lack of genuine warmth” toward their children. Being raised by “refrigerator mothers,” the researchers explained, was what caused autistic people’s difficulties with social communication and sensory processing and their repetitive behaviors and interests.

But in the 1970s, studies of twins revealed that autism is highly heritable, not something that develops after birth. Thus began the search for the genes responsible. “We had rather simple views about what it might be” that caused autism, says Helen Tager-Flusberg, a professor emerita at Boston University. The idea in the 1990s, she recalls, was that “we’re talking about six to 10 genes.” Instead, researchers found hundreds.

No simple theory of autism has ever panned out, and the scientific community has moved on from the search for a simple answer. Researchers now know that autism develops from a staggeringly complex interplay between genes and factors that can influence development in utero. But attempts to pin the condition on one root cause abound, most famously in the disproven idea that vaccines cause autism. And earlier this year, U.S. Secretary of Health and Human Services Robert F. Kennedy, Jr., announced that he will reveal the “interventions” that are “almost certainly causing autism” in September.

While scientists rarely proclaim absolutes, autism researchers say that they are as sure as they can be that there’s no one cause of the condition. “It’s never going to be true,” says Tager-Flusberg; decades of data reveal that a complex (and highly variable) origin is the only logical conclusion.

The Genetic Picture

In the past 50 years, researchers have identified hundreds of genes linked to autism spectrum disorder. But which genes are involved varies greatly from person to person and can be much harder to pin down. About 10 to 15 percent of cases (some estimates are as high as 39 percent) involve genetic mutations that are new to a child—not inherited from their parents—explains Shafali Jeste, an autism researcher and pediatrician, who leads the neurology division at Children’s Hospital Los Angeles. In another approximately 50 percent of cases, autism is linked to the combination of many common variants of genes that were inherited from parents. In the remaining cases, the causes are murky

But even for new genetic mutations that are known to cause autism, the story is far from simple. The same mutations can be present in nonautistic people, too. “If you have this mutation, it doesn’t guarantee that you will have autism per se, but it increases the risk substantially,” says Jed Elison, who studies brain development and autism at the University of Minnesota. There are still other factors involved that researchers haven’t fully characterized—some that are likely genetic and some that are likely not.

Untangling genetic factors from nongenetic ones (which scientists call “environmental factors”) can be tricky. For example, studies have consistently shown that parental age at conception can play a role, with older parents being more likely to have autistic children. But that could be because of the effect of age on genes: people accumulate mutations with age and can pass these on to their kids. Other factors that have been linked to autism include people being born prematurely or through cesarean section, as well as pregnant people having obesity, using certain medications (such as the antiseizure drug valproate and the pain reliever acetaminophen, the active ingredient in Tylenol), and being exposed to air pollution. The strength of the evidence for these links varies, though, and the increases in risk tend to be small. The evidence is also only correlational, meaning it can’t establish what caused what.

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