Rethinking Autism’s Origins

Beyond the Genome

The spike in autism over just one generation is hard to ignore. In 2000, the rate among 8-year-old children was 1 in 150 children in the US. In 2022, the incidence among 8-year-old children is 1 in 32. That spike can’t be fully explained by changes in diagnosis, growing awareness or genetics; genes evolve slowly—on the scale of hundreds to thousands of years. Those factors matter—but they don’t tell the whole story. Something else is happening, and we need to look harder at the world around us.

For 30 years, I’ve studied how toxic chemicals—lead, air pollution, pesticides—affect children’s brain development. My wife, a developmental pediatrician, works with children with behavioral conditions, including autism. Like many people drawn to this field, we have a personal stake: our granddaughter has autism.

The Limits of Genetics

Most autism research has focused on genes. Twin studies are often cited: identical twins are more likely to both have autism than fraternal twins. From that, people often say autism is “80 percent genetic.” It sounds like genes are the main cause—but that’s a misunderstanding. The number doesn’t mean genes cause autism in 80 percent of cases. It means that, in today’s world, genes help explain who develops autism. Change the environment, and that number could change too.

If everyone is exposed to the same stew of chemicals, then genes appear to matter more than environment. But most children who are genetically vulnerable only show symptoms when exposed to certain environmental triggers.

This is where most genetic studies fall short. They rarely ask how genes and environment interact. It’s like listening to only one half of a conversation and calling it a full story.

And yet, the genome has remained an alluring place to search for answers. Rare genetic mutations account for only 5 to 10 percent of autism cases. More common variants may raise the risk, but if they’re so common, why doesn’t everyone develop autism? The answer: genes don’t act alone.

A child may inherit a vulnerability, but whether it is expressed depends on what the developing brain is exposed to during development. That’s where genes and environment meet—and where we should be looking.

A Toxic World

We’ve learned some hard lessons from environmental disasters. Lead, mercury, PCBs—were once considered safe. Now we know they can damage the developing brain in ways that lasts a lifetime.

Today, we’re all exposed to hundreds of synthetic chemicals. Some of them—pesticides, air pollution, flame retardants, PFAS (so-called “forever chemicals”)—are known to interfere with brain development.

Over the past two decades, scientists have discovered troubling links between prenatal exposure to toxic chemicals and autism.

Take air pollution. Numerous studies have found that children with the highest prenatal exposure—especially from traffic—are more likely to have autism. One study found that children with the highest prenatal exposure were twice as likely to be diagnosed with autism. Pollutants like nitrogen dioxide and polycyclic aromatic hydrocarbons can inflame the developing brain and alter its chemistry.

Pesticides tells a similar story. Chlorpyrifos, once widely used in homes and still used in agriculture, harms the developing nervous system. Children born to mothers living near fields sprayed with chlorpyrifos and glyphosate had higher autism rates.

Phthalates, found in plastics and personal care products, disrupt hormones and are particularly risky during fetal development. Higher prenatal exposure, especially in boys, has been linked to autistic traits.

Different chemicals, same pattern: exposures to toxic chemicals during critical stages of brain development appear to raise the risk of autism.

Folate: A Line of Defense

Amid the risks, one protective factor stands out: folate, or vitamin B9. It’s essential for DNA synthesis and brain development. Women who take folic acid before conception or early in pregnancy lower their child’s risk of autism.

Many forces can block folate or make it less available. Maternal diabetes or infection—which increase the risk for autism—stress the body and make it harder to use folate efficiently. Some genetic variants reduce the body’s ability to process folate. Some chemicals interfere with how folate works. Valproic acid (an anti-seizure drug which was linked with autism), tobacco smoke, and arsenic can block or deplete folate. When these factors combine, the risk of autism rises sharply.

A Wider Lens

When studies examine both genes and environment together, the signals grow stronger. When a high-risk genotype met a high-risk exposure—like air pollution or no prenatal vitamins—the risk of autism rose threefold to sevenfold. That’s the kind of gene-environment interaction we should be studying more closely.

But most studies aren’t designed that way. We’ve been searching for autism triggers with a microscope; we need a wider lens.

Enter the exposome—the total sum of environmental exposures we experience throughout life, starting before birth. Chemicals transfer across through the placenta and shape the brain in ways we are just beginning to understand.

Maybe we’ve been looking in the wrong place. Maybe what’s “hidden” isn’t deep in the genome—it’s in the space between our genes and the world we’ve made.

Asking Better Questions

The real mystery isn’t whether the environment matters. It’s why we’ve been so reluctant to study it seriously. Genes feel safe—impersonal, fixed, beyond our control. The environment is messier. It forces us to ask harder questions about responsibility. It leads us to industry practices, weak regulations, and who should be held accountable.

If we want to understand autism in all its complexity, we need to ask better questions. What’s in our air? Our water? Our food? Our homes? Our bodies? Who bears the greatest burden of exposure—and who gets to avoid it?

The next chapter of autism research must begin at the intersection of biology and chemistry, where genes meet the chemical world.

We don’t need to wait for perfect knowledge to act. We already know enough to reduce the risk or severity of autism, ADHD, and other brain-based conditions:

· Start folic acid or folate supplements before or early in pregnancy

· Avoid tobacco and alcohol

· Minimize exposure to traffic pollution

· Use HEPA air cleaners in the home

· Choose organic foods when possible

· Limit pesticide use around your home

· Avoid heavily processed foods and plastic packaging

Of course, not every family has equal access to these choices. And even people like me who study toxic chemicals can’t protect our grandchildren. That’s why personal action must be paired with public policy. We need to modernize chemical safety laws, tighten pollution limits, and invest in safer alternatives. We need to treat early brain development as both a public health priority and an issue of environmental justice.

We’ve spent decades fixated on genes. It’s time we turn our attention to the environment—and how it interacts with those genes—to understand what’s really going on and what we can do to change it.