Precision medicine is the future of healthcare, but to do it correctly, it must incorporate exposomics into it
‘Precision medicine’ is the future of healthcare and aims to tailor drug treatment according to a patient’s personal genetic profile. But few precision medicine programs incorporate the large body of research that has found environmental factors to be critical in disease risk and progression, says Robert O. Wright, MD, MPH, Co-Director of the Institute for Exposomic Research and the Ethel H. Wise Chair of the Department of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai.
“Most precision medicine programs don’t mention environment when they talk about how they will tailor treatments to each patient. But Mount Sinai is different. We know environment is important. What you eat, where you live, your occupation, the air you breathe, the water you drink — all those things play a role in your health. We’ve known it for a really long time. Genes don’t determine those factors. We can’t make medicine precise until we incorporate environment into our treatment plans. Even diseases we think of as purely genetic always have an environmental component. If you have a cystic fibrosis for example, which affects the lungs, you will be more sensitive to breathing air pollution than the average person.”
“Most precision medicine programs don’t mention environment when they talk about how they will tailor treatments to each patient. But Mount Sinai is different. We know environment is important. What you eat, where you live, your occupation, the air you breathe, the water you drink — all those things play a role in your health.
Robert O. Wright, MD, MPH
Many common diseases such as obesity, asthma, diabetes and Attention Deficit Hyperactivity Disorder (ADHD) are on the rise, which means non-genetic triggers must be to blame because a population’s genes can’t change in just 10-30 years. That means the increase has to be due to environment. Complex diseases like these are the major drivers of healthcare costs. To better prevent and treat these health problems, we must put into practice the role of exposomics, a patient’s environmental exposures across their life span, when we counsel patients on treatment and prevention options, he says. By doing so, we can factor in how those exposures trigger disease or worsen outcomes of existing disease. For example, a diabetic patient may want to avoid exposure to chemicals that affect metabolism, like certain plastics. The human body is already sensitive to changes in blood sugar, and the addition of chemicals that affect metabolism can worsen diabetes. People with diseases are more likely to be sensitive to these chemicals compared with healthy people.
Genes x Environment
Genes and environment also interact with each other. While genes are stable across your lifetime, people vary in their nutritional, social, chemical and physical profiles, which include such factors as vitamin and mineral levels, mixtures of chemicals, local air pollution, weak or strong social support networks and geographic altitude. It is the combination of genes that make you sensitive and environmental exposure that varies that predicts health. How person A reacts to a vitamin deficiency can be different from person B because of their genes. But remember, vitamin deficiency can vary between people with the same set of genes. If we only measures genes or only measure environment we miss the big picture. That is what is happening in precision medicine.
“Researchers often use studies that divide diseases into their genetic and environmental causes. This is expressed as ‘heritability.’ We say a study shows that a disease is 80% genetic and we think that means that 80% of people with the disease have a genetic cause. Biology doesn’t work by dividing genes and environment,” says Dr. Wright. “Biology integrates genes with environment. In fact, genes are inert without environment. Our genes react to air pollution, social stress, diet etc. They require environment to function. For this reason, heritability estimates aren’t helpful because they mislead people into thinking that their genes alone cause “X” percent of a disease and the remainder was caused by environment alone. If we’re going to do precision medicine correctly, we have to incorporate both exposomics and genomics into it. Otherwise, we miss what is happening biologically. For example, there are genetic traits that make you hyperabsorb iron and are a cause of iron overload. A heritability study in the US population may say that the disease in 80% genetic, because on average we eat a lot of red meat and a lot of iron. But you won’t get an iron overload disease even with these genes if you are a vegetarian. The same heritability study conducted in vegetarians would show that the disease is 0% genetic. If you only measure the genetic part of iron overload diseases and ignore diet, you won’t be able to figure out the cause.
Breakthroughs at Mount Sinai
Mount Sinai Institute for Exposomic Research scientists have been at the forefront of precision exposomics, discovering novel biomarkers of disease detectable years prior to diagnosis, through innovative methods to collect and analyze individual environmental exposure data. These breakthroughs in environmental health research offer wide application in treating existing disease, as well.
“A lot has happened in the past ten years,” says Dr. Wright.
Mount Sinai researchers have developed exposomic assays, or laboratory tests, that can measure thousands of chemicals in blood. ‘Wearables devices,’ such as cell phones and smart watches can synchronize data with satellites to measure highly localized air temperature and air pollution. Silicone bracelets can absorb thousands of chemical signatures. In the future, these data, along with heart rate and physical activity monitor data, could be downloaded to a patient’s electronic medical record to provide snapshots of a patient’s physical activity levels, exposures to toxic chemicals, access to healthy foods and green space, nearby traffic levels, and noise pollution, says Dr. Wright. An exposomic analysis of a patient’s urine or blood sample could be run, combined with their genetic profile, to help make risk scores relating to whether a patient will get a disease in the future or whether a new medication will be safe and effective.
“Exposomics is a new field, and there is an enormous amount of research that still needs to be done to figure out how environment impacts disease,” says Dr. Wright. “Some of it will seem obvious in retrospect, i.e., ‘Why aren’t we studying how lead exposure affects someone with Alzheimer’s disease? We know lead is ubiquitous and toxic to the brain.’ We need to do those studies. As another example, we can use wearable devices to monitor how a patient is responding to therapy. If someone’s getting chemotherapy, we can get granular data on how active they are. There may be an objective sign of a strong complication to chemotherapy if their activity falls too low. If someone with diabetes is having trouble regulating their blood sugar, an untargeted assay from the patient’s silicone bracelet, or from a urine test, can help identify a chemical in their environment that interferes with insulin. This is a space I think we need to live in because we can act on the findings to make people healthier. We can’t change our genes, but we can change our environment.”
The Future is Exposomics
Tomorrow’s precision medicine research will include studies that analyze groups of sick patients and their individualized, exposomic data. Such studies will deepen our understanding of all diseases, says Dr. Wright.
Taking a closer look at a patient’s exposome profile can also help doctors understand why the patient isn’t responding to a treatment. For example, a person living in an area with high levels of cardio-toxic chemicals in the air or water or food may be more likely to have a second heart attack
“Public health research has focused on vulnerable populations but has largely ignored what may be the largest vulnerable population — people with a disease,” says Dr. Wright. “People who are sick are likely to be very vulnerable to their environments, and we rarely study that. We’re very focused on why people get a disease and less focused on how they respond to treatment and whether progression of disease is affected by concurrent environment.”
“This is an exciting time to be an environmental scientist.” Dr. Wright says. “The big future advances will be in exposomics, because we can already sequence the genome. That work is done. The work in exposomics is just beginning. We need to understand environment in order to understand our genome and to understand how and why we get sick. That will complete the puzzle of precision medicine.”