Rosalind Wright: Mapping the Exposome
New research shows how environmental exposures accumulated throughout life could explain subtle cognitive deficits and profound neurological disease.
By Corey S. Powell
The modern world is a web of chemical and particulate pollutants. We accumulate exposures wherever we go. Credit: Alamy
It's well understood that air pollution affects the health of our bodies, but scientists are still learning about the impacts of pollution on our brains and our minds. Rosalind Wright is leading the effort to weed out the myths and to understand the real dangers. A major challenge, she says, is that all the various environmental factors hit us together, combining their effects and interacting in complex ways. Wright is a physician and professor of pediatrics and public health at the Icahn School of Medicine at Mount Sinai in New York City. She is also co-director of Mount Sinai's Institute for Exposomic Research. In this episode, she talks with OpenMind co-founder Corey S. Powell about emerging research that is identifying the neurological effects of airborne toxins. She also offers strategies that we can follow to reduce our risks. (This conversation has been edited for length and clarity.)
LISTEN TO THE PODCAST
READ THE INTERVIEW
We usually hear about potentially harmful exposures one at a time, but that’s not how risk really works. Can you explain your research focus on the exposome, the sum total of all our environmental exposures?
We're exposed to multiple things at a given time across the life span. And so we have been working to develop tools and analytic methods to more comprehensively look at those together. So, not only do we think about smoking and what chemicals might be in tobacco smoke, but about the air we breathe when we're outside in traffic and the things that might come from industries in our community, the foods we eat, the nutrients we take into our body, and how we emotionally experience our environment. It’s really a toxic soup impacting brain development, from the very young all the way up to older individuals in our society. We're finally there. We have the tools. We've made huge advances in the last five to 10 years, and we're on the cusp of translating it to better health outcomes and trajectories across the whole life span.
When I think of brain damage to children, the first thing I think about is lead—but in terms of that "toxic soup" you are describing, are other heavy metals involved?
We still look at lead, but now we think about lead in the context of a mixture of other metals in the environment. More contemporary research has linked the same problems to cadmium and arsenic. Some of those things show up in the type of wood that's used to build parks where kids might play. We know those metals can be toxic to the kids' brains; other metals, like manganese and mercury, can come from food.
How do you break down all the different pollutants, figuring out which ones people have been most heavily exposed to so that you can begin to connect them to specific health effects?
When we're measuring metals, for example, we have instruments in the laboratory where we gather up blood samples, urine samples, saliva samples and hair samples, without having to be invasive. Now we can measure a panel of tens of metals at a time. Eventually, we'll get to hundreds at a time. The same goes for man-made chemicals. We have tools that can measure thousands of chemicals in a single sample. When you think about air pollution, one thing you could do is get monitors, and then go out and monitor every individual place that you want to study. You could do it, but that's very work-intensive and very expensive. We're going to need other methods. A lot of folks in our institute are leaders in this area. For instance, they have already planted stationary monitors all over major cities (providing large-scale coverage). I could show you a map of these monitors all over New York City right now.
Yeah. I see those environmental monitors around my neighborhood in Brooklyn.
They are already measuring daily key pollutants regulated by the EPA. You can measure small particulate matter that comes from a lot of traffic-related pollutants, and you can break those measurements down into smaller and smaller constituents. Then there are air pollutants created by different chemical reactions that are going on in the air—from sunlight and humidity and things like this. Like ozone: We hear a lot about ozone and how that might affect health, particularly brain health.
Are the measurements detailed enough that you could tell me about my exposure?
We can do it based on an address, and we can link that address to an air pollution estimate that gets modeled.
That seems like a pretty nuanced job for ground monitors alone. What other ways are you gathering information on local environmental exposure?
We also have thousands of satellites up in space, all over the globe. We use data from them to calibrate to those ground monitors and to estimate the levels.
Does climate change also have an impact on the ways that pollutants affect us?
Temperature can change reactions between environmental toxins, depending on how high that heat is and how long you're spending in that heat. Higher temperatures can also lead to dehydration, so we have to account for that in our models.
What do we know about the ways that airborne pollutants affect cognition and the brain? How far have we come from the days when people first recognized the dangers of lead paint and leaded gasoline?
We're appreciating more and more that various toxins affect different pathways and processes in the brain. And depending on which exposures you have and when you have them, you might become more or less vulnerable to certain issues in the course of development. If you have those exposures as a 10-year-old or as a 40-year-old, after those systems are already pretty much laid down, you're not going to have the same impact that a young infant or a fetus might have. But there are certain parts of the brain—for instance, the prefrontal cortex—that we're learning from magnetic resonance imaging, MRI scans, that light up with exposure to the mixture of air pollutants. The prefrontal cortex area is interconnected to lots of different regions that have to talk back and forth with each other. Air pollution has a huge effect there, particularly in early development when you're talking about young children. It affects executive functions, such as your ability to pay attention to lay down working memory, so that as you get older and you take in information, you can start to see an impact. Then you will see an impact on IQ and higher-level cognitive functioning that the kid will need as they go across life. Life is going to be harder for a kid who gets started behind the eight ball because they've had these exposures.
Yet not everyone who is exposed to pollutants has an equally intense reaction. Can you explain why?
For one thing, the exposome interacts with your genetics. If you have an underlying genetic predisposition, say to depression or anxiety because it's being transmitted through family history, that gene may also be impacted more heavily by the toxic exposome that you're seeing. It might interact with temperature and air pollution. They multiply each other's effect. That's sort of the traditional way we think about gene-environment interaction.
Can your exposome change your genome?
It doesn't change the genetic code; that takes generations. But there can be a chemical change in gene expression, we call it methylation. If that happens during development, if pollution turns a gene off or on, depending on how that happens, it might be protective for that kid, or it might enhance the effect.
Is there any way to counteract the harmful ways that pollution can switch our genes on or off? Can we make targeted changes in our environment, for example?
Based on the knowledge we have and the tools we have, we can overlay the environment on top of the genomics and we can actually do that on a huge scale. Once we can do that, we can start to get a little bit more precise. Someday, I'm going to be able to have a patient sitting in front of me, get his data and be able to say, "Well, you know, based on this, we need to change some things that might be impacting you right now." We might recommend healthy intakes of antioxidants in your diet to offset lots of air pollution, for instance. There are a number of nutrients we could talk about to offset these toxic effects. Foods with polyunsaturated fatty acids are another. Supplements are another. Now, not everybody has equal access to a lot of these things, just as they might be disproportionately exposed to more of the toxins. So maybe we need to give them vouchers. Honestly, we need to bring dietitians and nutritionists back to every area of medicine to be counseling our patients in the clinical realm, because data is telling us that's an important part of countering some of these environmental factors.
What exactly is happening in the brain when pollutants are affecting us? I'm trying to understand why interventions such as antioxidants and diet can be effective.
There are common central mechanisms that get disrupted when you breathe in an air pollutant. It can change the way your immune system is functioning. It can change the optimal balance of the oxidative-antioxidative pathway. You may have heard that it's good to eat blueberries because they have a lot of antioxidants. Well, there's a reason for that; we have detoxifying enzyme systems in our bodies that are meant to help you live in the environment. It knows you're going to be exposed to harmful things and it can detoxify them to some level. But if you're in an environment where you're constantly getting bombarded by high levels of toxins, you overwhelm those systems. At some point, you are unable to detoxify everything.
What happens when the body's natural detox systems get overwhelmed?
Your body has to reset to keep that oxidative-antioxidative system in balance. A big mechanism (that happens when things are out of balance) is oxidative stress, which talks back and forth to your autonomic nervous system.
Tell me more about the effects of oxidative stress, the chemical reactions that result from many types of pollution exposure.
So you breathe in air pollution, it crosses through your lungs, and it has a local inflammatory impact and causes oxidative stress in the lungs. But it also gets through into the bloodstream and travels all over the body and crosses the blood-brain barrier. Once in the brain, it can actually really rev up these inflammatory pathways and oxidative stress pathways. So it has both systemic and local effects.
What do these pollution stress responses do to the brain?
Later in life, they accelerate the decline in cognitive functioning. They enhance changes in parts of the brain that are important to things like Parkinson's disease. We need more data there, but evidence suggests that air pollution plays a role in other chronic diseases as well. In animal studies, we can see changes happening in the brain.
How are you and your colleagues getting to the bottom of this, so that we can understand how pollution affects our thinking and our brain health?
In the past, when we tried connecting diseases such as Parkinson's and Alzheimer's to PM2.5 particles (fine particles less than 2.5 microns wide), or connecting low IQ to lead exposure, we were thinking about one chemical at a time. But now, with the exposome, we have to start looking at bigger mixtures. We must have the high-performance computing capability to manage all that data. Data scientists now can go beyond my human brain and what I can keep and model myself. So we're using tools such as artificial intelligence and machine learning, which folks have heard a lot about in medicine and out of medicine. This is a big wave that's hitting us on all levels. You can think about machine learning as being able to digest bigger and bigger mixtures of (datasets about) air pollutants, put together with things like temperature, your nutritional intake, and then connect the dots, see which things are correlated and traveling together and driving a health effect.
You alluded earlier to the role of socioeconomic factors. Not everybody is exposed to air pollution equally, right?
You're absolutely right. It's not uniformly distributed. The different factors in your exposome depend on where you live, eat, play and go to school. And a lot of that depends on the community where you live. There's more disinvestment in certain communities. You have fewer resources to provide safe transportation and living in certain communities. Communities of lower income might be someplace where people feel they can more readily place a polluting industry or have heavy traffic go through. Some of this goes back to "redlining" policies and practices starting in the 1930s until about the 1970s, when legislation started to intervene, that designated some communities as desirable and others as deteriorating and hazardous. Those policies were deliberately discriminatory, particularly against minority populations. That was the history of our country. Those were chronically disinvested-in communities, with dilapidated housing. There, you have more exposure indoors to molds and cockroaches and other things that affect the immune system and cause health problems.
Poor, polluted neighborhoods also tend to be stressful places to live. You've said that stress itself is a kind of toxin, right?
When you have financial strain, there's a lot of psychological stress that comes from that. There's more crime and violence in communities that have health impacts. And when those go together with air pollution, there are going to be compounding and synergistic and magnifying effects. Even though redlining policies have been gone for so long, almost 75% of the communities that were redlined through those practices to this day remain segregated, with largely lower to moderate-income ethnic minorities. These same communities are disproportionately burdened by environmental toxins, including air pollution. We did a map recently of our populations here in New York City and in the Boston metropolitan area, overlaid on a map with those redlining communities from way back when, and showed where most of the air pollution is. It's still disproportionately in those historically redlined communities. So they're still being impacted today.
I'd like to talk more about prevention strategies. You mentioned that eating foods with antioxidants can help. What else can we do to reduce our risks?
This country has seen an epidemic of loneliness. People talk all the time about being disconnected. That really scares me, because the literature in our own work shows that connectedness is an important buffer, not only to psychological stress but also to oxidative stress and ongoing inflammation, just as getting rid of an air pollutant would be.
Well it would be great if you could help us feel more connected! What about the chemical aspects of risk? Can your detailed studies of exposomics help individual people reduce their exposures, or weed out specific pollutants?
We're working on these things. The idea would be to, to come up with a screen of the exposome for a given individual or group of individuals and come up with a profile that, that a physician can look at. Maybe we could turn the knob up on this one. Maybe we can work on these things, and try to make them more prevalent. And that might be changing your diet, or reducing stove-top cooking, or increasing ventilation. Changing how you heat your home. If you look globally, people are burning biomass fuels to heat their homes. Well, that's causing a lot of the indoor air pollution and health problems we see.
Is it really possible that we could be monitoring our exposures at the individual level in the near future?
There are already little silicone bracelets that you can put on your wrist and you wear it for seven days. You can take a shower with it. You go everywhere with it. You're in your home, you're at work, you're out in the community. And then you can ship that back to the lab here, and they can do a scan of hundreds and thousands of chemicals on that get taken up in that bracelet and they can show you a map. If it's in the summertime, we might see people are putting mosquito spray on themselves, right? Or you might live in a community where they use chemicals on the lawns. Then we can say: Here are some alternative companies that you might want to switch to. When people see it, they say, "Oh my goodness, I didn't even know."
Where do you see exposome research going next? How can we do better at collecting the right kind of data, and then applying it to improve the health of our bodies and our brains?
There are folks around who want to map and measure more and more of the exposome, so let's have open science and bring this together. Then maybe we can use it here at Mount Sinai to treat patients across the boroughs of New York City and beyond. We may then be able to say, boy, there's a lot of asthma over here and it does seem to be that A, B and C are the priority things that seem to be driving a lot of the morbidity related to that and more visits to your doctor, more visits to the ER. And then tailor prevention and intervention strategies in that way. I think that's going to be very important.
We are developing new methods like that silicone bracelet I mentioned. Now we have people in the laboratory who can analyze a single strand of hair. Hair grows about a centimeter a month, so when we get a strand of hair right at the nape of the neck, we can go back in time. If you are a pregnant woman, and you have long hair, we can go nine months back and say, "Here's what your exposure looked like (while your fetus was developing). What does that make us think of? What do we need to do now?" That kind of thing.
Hold on: You can reconstruct a person's pollution exposure back to the time before they were born.
People are doing it with teeth, too. Teeth grow like rings in a tree, one day every day. You're still doing it. You lay down a ring (in your baby teeth) that starts in pregnancy, in about the second trimester. Then a kid loses their tooth at age 6, say. You can take that tooth and use laser ablation to go back in time (analyzing its internal chemistry). You can recreate the exposomic history going all the way back to the womb. Why do I do all this work starting in pregnancy? Because I want to identify early markers of who's at risk and what can we do about it. Maybe with new interventions and new therapies, we can put people back on track.
This podcast and Q&A are part of a series of OpenMind essays, podcasts and videos supported by a generous grant from the Pulitzer Center's Truth Decay initiative.
February 1, 2024