Public health’s new frontier: unlocking the exposome
Dean Andrea Baccarelli of the Harvard T.H. Chan School of Public Health argues that medicine is on the cusp of a breakthrough: We're moving from the genome to the exposome. The article discusses the future of public health by focusing on the exposome, a collection of exposures that affect individuals' health throughout their lifetime. The exposomal includes a process called DNA methylation, which adds atoms to specific spots in your DNA, which can trigger gene expression changes that can have profound effects on your health. The article suggests that while these changes can be applied to individual health, they will also be used to accurately estimate how many cigarettes an individual has smoked in her lifetime. Advances in genetic sequencing and data analysis have made it feasible. The science is still at an early stage, but powerful findings are already emerging. The potential improvements to public health could propel more widespread improvements in treatment and treatments for cancer.
Published : 2 months ago by Andrea Baccarelli in Health
In the not-too-distant future, your doctor might be able to tell from a few drops of blood if you’ve been exposed to damaging levels of toxic chemicals. She’ll be able to see if you’ve been ingesting harmful levels of microplastics or ultra-processed foods. She should even be able to tell if you’re doing too much sitting and too little walking.
A blood test is a remarkable tool: An inexpensive lab analysis can yield crucial information about your health, including your cardiovascular risk, liver function, and immune response. Now imagine if that were just the start.
These new tools will be game changers, not just for individual health but for population-level health as well. I expect they’ll demonstrate that damaging exposures affect all socioeconomic groups, all races, and all neighborhoods — although some will undeniably be harder hit than others.
My predictions build on two decades of work that I and other scientists around the globe have been doing to unlock the secrets of what we call the exposome.
The exposome refers to the huge but largely invisible collection of exposures that affect an individual’s health across their lifetime. Your mother’s diet when she was pregnant with you is part of your exposome. So is the lead paint on your childhood train set. The toxic chemicals in your drinking water. The soot you breathe while walking to work.
It may seem impossible to untangle such a diffuse cloud of influences, much less analyze their individual impact on a person’s or community’s health. However, vast improvements in genetic sequencing and data analysis have made it feasible.
The key is a process called DNA methylation — a common chemical reaction that adds a few atoms to specific spots in your DNA.
I often compare that reaction to the musical notations a composer makes on a score. These notations don’t change the music as written, but they do change the way the music sounds. The notation may direct the orchestra to play faster or slower, louder or softer. In the same way, DNA methylation directs the expression of genes — turning them on or off or instructing them to produce more or fewer proteins. And those changes in gene expression can have profound effects on your health.
As it turns out, DNA methylation is exquisitely sensitive to a wide array of environmental and behavioral exposures. It can be triggered by the chemicals you encounter and the lifestyle decisions you make. In effect, your exposome — the aggregation of all your exposures and behaviors — is recorded in a layer on top of your DNA called the epigenome.
Using relatively inexpensive technology that’s standard in many labs, scientists can now see how individuals’ epigenomes change in response to potentially hazardous exposures. More sophisticated equipment can identify changes at all 28 million potential methylation sites on the human epigenome. We can then map those changes against patient health records or behavioral surveys to identify patterns.
The science is still at an early stage, but powerful findings are already starting to emerge.
Several research teams that I’ve worked with have found that cigarette smoking is associated with DNA methylation at thousands of distinct sites in the genome, affecting the expression of more than 7,000 genes. To return to our musical analogy, that’s equivalent to the conductor making notations that change the way at least one-third of the notes in a symphony are played. In this case, those changes are due to exposure to the toxins in cigarettes.
Perhaps not surprisingly, the changes affect genes linked to numerous smoking-related diseases, from cancers to cardiovascular disease to pulmonary disorders to rheumatoid arthritis. Some of these changes appear to fade away if the smoker quits. Others are quite durable, persisting for decades after smoking cessation.
We also found that we could use these epigenetic changes to reliably estimate — from a few drops of blood — how many cigarettes an individual has smoked in her lifetime.
Colleagues and I have also identified epigenetic changes driven by exposure to car exhaust, poor diet, and psychological stress, among other factors. In time, we expect to be able to work backward from the chemical markers in a blood sample to estimate an individual patient’s exposure to all sorts of damaging toxins, just as we have done with cigarettes.
Why does this matter? Since the Human Genome Project kicked off nearly 35 years ago, the public, private, and nonprofit sectors have poured billions into decoding DNA. The investment transformed our understanding of human biology. The payoff for human health has included targeted cancer therapeutics and treatments for rare diseases.
But the science of the exposome holds the potential to propel more widespread health improvements by shifting our focus from treatment to prevention. The more we know about the damage caused by everyday exposures, the more we can do to protect against them.
These interventions could take the form of national initiatives that seek to protect the entire country, such as smarter nutrition policy, environmental regulation, and building design.
More targeted interventions — aimed at protecting local communities from their most damaging exposures — could also be highly effective, ushering in a new age of precision public health. For instance, a public health department could regularly test residents who live near a factory to see if its emissions are causing epigenetic changes that affect genes associated with cancer or other diseases. If such changes start to occur, the city could demand better pollution controls — and potentially prevent a wave of devastating illnesses in the community.
This dream could become a reality within a decade. What do we need to make it happen?
As the field accelerates, scientists will produce enormous quantities of data. We’ll need new artificial intelligence tools to analyze these efficiently. We must also invest in fields such as decision science, implementation science, and design thinking, which explore how to efficiently achieve important societal goals. Finally, we’ll need strong partnerships between scientists and policymakers — and excellent communicators to engage the public around these thrilling but complex ideas.
When our doctors can check our environmental exposures as quickly and easily as they can analyze our cholesterol, we’ll have a powerful tool for improving personal, public, and planetary health. I’m pushing hard for that day to arrive as soon as possible.
Dr. Andrea Baccarelli is the dean of the faculty at the Harvard T.H. Chan School of Public Health.
Topics: Social Issues