The Exposome: Finally, a way to measure nature vs. nurture.

15 12 2010

Today I attended The Sixth Annual Symposium on Predictive Health, Human Health: Molecules to Mankind at the Emory Conference Center.   The tagline was ambitious and meant to inspire:  “THE END of DISEASE, the BEGINNING of a NEW KIND of HEALTH CARE.” I was only able to go to Session V “Ethical Manipulation of the Human Exposome.”

The Exposo-wha??? Let’s back up.  Remember the genome? Remember when we sequenced the human genome 7 years ago, and people were really excited because this meant now we would not only understand what it meant to be human, but also how to predict and prevent every disease from which humans suffer?  Goodbye aging, goodbye sickness. Hello, ever-lasting health and answers to the previously unanswerable questions about humanity. Why didn’t that happen?

Well it goes back to nature vs. nurture.  You are the cumulative result of your genes and your environment.  Genes might give you a prediction about your susceptibility to developing diseases, but they rarely independently genuinely cause a disease. Given that environments are so complex and so varied from person to person, it’s staggeringly difficult to fully understand what the consequences of all these variables will be with your genes.  Enter the Exposome.  The exposome is a new body of generalizable data that explicitly talks about the intersection of your genes and your environment.  The exposome is a map of all your environmental exposures.

One example of the exposome is the metabolome, or a map of stuff your body has metabolized. A metabolite, represents something that has passed through your body’s cellular processes and can be measured by taking a blood, urine, or plasma samples. By collecting your metabolite profile, researchers are able to get a map of clues to your environmental exposures, and then possibly predict what diseases you may develop or what may have caused you to develop a disease. These data can be combined with your genetic data  to better understand how your body’s genes made you (in)capable of metabolizing agents in your environment (whether it be emotional stress or plant pesticides).  As you can imagine, your body responds to a number of agents at any given moment and can also be influenced by the current circumstances of your exposure (e.g. are you already sick, are you young, are you old, are you a healthy eater, etc). Actually, clearly isolating one culprit in disease causality isn’t as easy as it seems, even with the human genome sequenced. In addition, some things are metabolized and are quickly broken down, leaving barely a trace. Some things leave a longer lasting trace and others leave a temporary trace that you might only see at night or early in the morning.  Finding the right window to detect metabolites can also present a challenge.

Despite these challenges, we shouldn’t underestimate the power of combining the data from the Human Genome Project and now the Human Metabolome Database can potentially have amazing consequences on health care and the way we live.

At today’s symposium, some researchers stated that they were a bit puzzled about why they were asked to discuss the ethical implications of their work stating “I’m not an ethicist” or made statements that they felt their job as *public health* researchers was to put a wall between their research and how their data might affect legislation. They weren’t the first scientists who had their laundry list of excuses to not get involved with ethics. While I was a bit disappointed with these responses, I was glad there was interest enough to devote one of their sessions to ethical discourse.  Ethics sessions like these are necessary to ensure that public health researchers are not  blind-sighted by how their findings might actually hurt, not help the public if they don’t understand how to maximize the benefits of their work. While some interesting points were brought up during the session, I still wanted to know their thoughts, as public health researchers, on how this might actually change or lead to “a NEW KIND of HEALTH CARE” as inspired from their flier.

The Department of Health and Human Services (who is in charge of helping to determine your health and healthcare) have a mission to generate not only preventative, but personalized medicine.  Metabolomics could fit very nicely with these goals.  Metabolomics could tell you how to prevent certain diseases by unintentional exposure to toxins such as pesticides in the environment.  Metabolomics could also tell you how to prevent diseases by preventing behaviors that tipped your genetically vulnerable self into a state of disease.  It could revolutionize the way we live into healthier, longer-living, happier humans.

But what else could it do? What are other ways, the exposome could impact the way I live?

First, we need to better understand exactly how strong the predictive power of “metabolomics” for humans is.  Don’t these studies tell us more about association than actual causation? Many follow-up basic research studies will need to be done to confirm causality. And what  if my metabolic profile as an adult tells a sad story: my unfortunate environmental exposure profile has destined me to get a terrible incurable disease- what will I do with that information?   Should I just take the cyanide pill and warn my children not to make the same mistakes? Would the average citizen know how to interpret their metabolome results, or would hospitals now need to have a staff of genetic and metabolomic counselors?  Will my health insurance need to be informed of my pre-exisiting metabolome condition? Should my healthcare provider know this information?  After all, wouldn’t it help my doctors to give me better treatments and more personalized medicine?  Would I be required to tell my life insurance agent, my employer, or my employer’s lawyer? Extreme care will be needed to ensure that exposome data is secure and in the right hands.

How will this change the way we view “disease” and  accountability?  Environmental toxins like lead, or pesticides are not the only bad things you’re exposed to in your environment. Certainly everyone wants big business, Pharma, the military, and industry to be held accountable for the exposure that the public will unknowingly gets. What about the known, voluntary exposure to toxins?  The passive suicide cocktail of bad eating habits, smoking, and not controlling their stress or exercising?  This will  all show up in your metabolome.  Remember when drug abuse and depression were thought of as moral failures?  Sure some people still think this, but the popular mind has grown to understand that these conditions actually have a physiological substrate just like any other bonafide disease.  Let’s look at Parkinson’s disease or Alzheimer’s disease.  This is a disease where people don’t generally assume you have due to a moral deficit.  Parkinson’s disease is linked to unknowing, involuntary environmental exposure to pesticides.  What if it was linked to a series of voluntary choices?  Would we then say things like, “You gave yourself Parkinson’s disease?” How these data could and should be used will need to be clearly expressed to the public.

In fact, one could argue that all your activities in your history from your emotions to your ingestion of foods will be identified in your metabolome,  maybe even replace a fingerprint. Who should have access or own this information? Would certain exposome patterns be used to predict bad behavior?  If growing up in low socio-economic areas resulted in poor nutritional patterns, predicting subsequent criminal behavior, should preventative measures be taken?  The session at today’s symposium was about *manipulation* of the human exposome– should we manipulate this person’s exposome to try to then change or pre-empt his/her undesired behavior? Can this even be done?  These are the types of  basic research model experiments that are needed that need to be done in parallel to the human studies.  Not just asking, what are the associated changes in the exposome, but can we change them, and what would changing them do for people and society.  This information will also be required for making new health care policy changes. It is critical that the researchers doing this work be able to translate these data for public audiences. Researchers need to think more deeply about the ethical consequences of their work.  You don’t need to be an ethicist to do this, you just need to think critically and genuinely care.

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