Exposome Perspectives Blog by Robert O. Wright, MD, MPH
“The fact that a trait is genetically determined does not mean that it cannot be changed.” — Richard Lewontin
I started my clinical career as a pediatric toxicologist. Most of my work involved acute poisoning: teenagers who overdosed, toddlers who accidentally swallowed a parent’s prescription drug, and the seemingly endless after-midnight calls from the poison control center.
But another part of my job was working in a lead poisoning clinic. Once a week, we gathered to teach the pediatric residents a few basic principles about the environment.
1) Older homes contain lead paint.
2) Toddlers are the perfect height to grab a windowsill, and that’s where lead-based paint-contaminated dust accumulates from the friction of opening and closing windows.
3) Toddlers also put their hands in their mouths, a completely normal behavior at age 2–3 that disappears as they age.
4) Age 2–3 is not just the peak age for lead poisoning risk; it also overlaps with a period of rapid brain development, when neural connections are actively pruned, refined, and sculpted into a more efficient brain network based on environmental inputs like love, education, and experiences. That network serves you for the rest of your life.
Lead works at the neurotransmission level to add noise to the signals that shape a child’s brain, disrupting their ability to develop proper attention, inhibitory control, planning, and learning. Lead, even at “low” doses, is the monkey wrench jamming up the machinery of development. Put all these puzzle pieces together and the reasons why lead exposure is so prevalent and so toxic in young children become clear. Toddlers are both the most exposed and the most vulnerable group for lead poisoning.
Chelation, which removes lead from the body, rarely changes these outcomes, except in the most severe poisoning cases, but that is likely because there is a lot of development after age 2–3. Child lead poisoning is not deterministic, and stopping environmental lead exposure is therefore actually a form of treatment. I would counsel parents that lead poisoning was not fate and that with help, guidance, and even tutoring, if possible, their child would likely return to a normal developmental trajectory. By removing the sources of lead from the child’s environment, we allowed normal brain development to reboot to a more normal setting. There are lessons in this approach for medicine in general, i.e., removing what is toxic from the environment and letting the body reset to homeostasis can work in other circumstances as well.
“Each human being is a multiplicity of miracles” — Thich Nhat Hanh
We are not all the same, and there was a second group of lead-poisoned patients for whom almost none of the above applied. Children with autism showed up in the lead clinic disproportionately, and their stories were different. I suspect that for many children with autism and lead poisoning, the lead poisoning was never found because the symptoms were assumed to be part of autism. These patients were typically older too, sometimes even teenagers, something otherwise unheard of in lead poisoning, making it even more unlikely that lead poisoning would cross anyone’s mind. The commonality of joint autism and lead poisoning was because many children with autism have pica, i.e., the behavioral eating of non-food substances. If there was lead in their environment, whether in house dust, magazine ink, cosmetics, fishing sinkers, or something else, they would find it and ingest it.
Their history typically went like this: parents described a child who had been functioning at a steady state and then gradually developed worsening behaviors: more irritability, more perseveration, sometimes self-injury or head banging. When a family persisted that something was different, eventually a blood lead level was checked and the explanation found—necessitating a referral to our clinic. We would start by doing a thorough index of the possible sources in the home to help families remove the source. I remember one older child whose lead poisoning was severe enough to require IV chelation. They needed to be sedated for the IV, but once the lead levels lowered, the anxiety and violent outbursts subsided—symptoms that parents had been told for months were just part of autism, even though they had never been this severe. Their child had returned.
“There are no right answers to the wrong questions” — Ursula K. Le Guin
By now, you might be wondering if I am about to bring up unproven relationships among lead, chelation, and autism. I should make two things clear. First, I am not arguing that lead poisoning causes autism. Autism can cause lead poisoning. I am observing that a child with autism is more likely to be exposed to lead than a child without autism. Second, I am not advocating chelation therapy for autism. Chelation is for severe lead poisoning, and it is not a treatment for autism. I am instead talking about situations in which lead and autism intersect. Those intersections are not just chance, as autism’s pica will increase the risk of lead poisoning. Yet, the exposure often remains invisible because the child seems too old for lead poisoning and because lead poisoning will cause symptoms often found in autism.
I am instead pointing out something fundamental about autism that gets lost in the debate about “nature vs nurture”. Children with autism live in the same world as everyone else. They are exposed to lead, as well as pesticides, PFAS, microplastics, air pollution, ultra-processed foods, social media messages, and countless other environmental contaminants and factors. This is a fact, but we never ask: “Are they affected in the same way as everyone else?”
I suspect many, if not most, of us believe our modern environment (wildfires, forever chemicals, microplastics, etc.) directly impacts our health. Are these exposures also common in autism? More importantly, are people with autism more sensitive to them? We honestly don’t know because we haven’t studied these questions. This is one of the costs of a gene-centric worldview.
Most lead screening programs stop around age six. That one-size-fits-all approach may make sense for the average child but not for children with autism. We are likely missing cases of lead poisoning in children with autism, not to mention a host of other environmental factors. We have fallen into the trap of accepting that all a child’s symptoms are due to their “genetics,” i.e., they are predetermined. We don’t consider that the environment impacts behavior in everyone—even someone with autism. We don’t know the extent to which this occurs, because the question has never been rigorously studied.
Which raises a larger question: why not?
“You’ve got to start with the customer experience and work backwards to the technology. You can’t start with the technology and try to figure out where you’re going to try to sell it. ” — Steve Jobs
Notice that this post is not about what causes autism. This post is about what affects people who already have autism and what they need. That may seem like a subtle distinction, but it is a tectonic shift in the way we do autism research. First, this type of environmental study starts after someone is diagnosed—it accepts the world as it is without seeking causation, then tries to address what can be done given that constraint. Second, a study proposing to screen autistic children for lead, pesticides, metals, or other environmental exposures might be viewed as managing symptoms rather than directly addressing the disorder—therefore it is flawed. But is that really a flaw?
A genomic study aimed at identifying biological pathways that could someday be leveraged to develop a new drug treatment, on the other hand, may be hailed as targeting autism at its root cause. My counter is that the environmental approach, even to a genetic disease, could be implemented today. The genomics-alone approach to autism has already taken over two decades waiting to be completed and validated, with no treatments on the horizon. The result is a research landscape that eagerly investigates the genomic causes of autism in search of a distant future drug therapy, while paying little attention to environmental factors that may shape the day-to-day health and well-being of people who already have it.
How often do we as researchers ask what our patients need today? Do we factor in what it is like to be told to wait 20 years for a new treatment? Too often, researchers start with an approach that looks like: “What can we do with this amazing technological tool to create a new treatment? Sure, it will take a long time, but it will be worth it.” Patients may not have 20 years left to wait. Perhaps instead we could ask simpler, more practical research questions, like: “Are people with autism more sensitive to environmental factors than the general population?” Maybe their environments are exacerbating symptoms, and if so, we could intervene by modifying their environments—something we know quite a lot about already.
If we measured the exposome of autistic children, we could catalogue which environmental exposures worsen unwanted or harmful symptoms or which exposures reduce those symptoms. We could then understand to what degree children with autism are vulnerable to pollutants. This kind of research question won’t lead to a blockbuster drug or a patentable technology, but it could matter deeply in the daily lives of people living with autism. Better yet, it can be implemented quickly, because the necessary knowledge about exposure reduction already exists.
No, this approach of studying people with autism won’t prevent autism, nor will it “cure” autism, but there is no guarantee that genomics will deliver a cure either. Get back to me in 2046 with that answer.
Finally, this is not a call to abandon genomics. We can study the impact of the exposome on people with autism and still look for cures using genetics and gene-environment interactions. We forget that science has shown repeatedly that our genes are not our fate. Our environment is constantly modifying the effects of our genes, even in autism. Our genes may constrain how we respond to our environment, but we still have the ability to change that environment. Regardless of whether or not you believe autism is purely genetic, you have to acknowledge that our world is not a neutral backdrop and environments vary dramatically even among people with autism. If environmental factors are contributing to suffering in people with autism, then choosing not to look for them is both a scientific and ethical failure. For too long, the idea that autism is purely genetic, and therefore everything about it is predetermined, has been promoted as a scientific conclusion, but it is not. Nothing is purely genetic, just as nothing is purely environmental. As Leonard Cohen once sang—let’s let some light in.
“Ring the bells that still can ring
Forget your perfect offering
There is a crack, a crack in everything
That’s how the light gets in”
Leonard Cohen (Anthem)