Exploring the Exposome

I ran into the term "exposome" (pronounced ex PO some, with the "some" rhyming with "dome") about a month ago when trying to keep up with scientific research being done on autism spectrum disorders ("ASD's"). The field of ASD studies is so interesting, among other reasons, because it tries to tease out, from the complexity of influences on a child, the precise causes of and treatment for the ASD experienced by the child. Growing ever stronger in ASD studies in the past decade has been the philosophy that many of these ASD's might be "environmentally" caused. While the term "environmental" is itself a fairly opaque word, it is being used to contrast with the word "genetic."*

[*I will try to deal with the notion of what an environmental influence is below].

Thus, the recent work on ASD's is increasingly trying to say that it isn't simply tinkering with the child's or person's genetic makeup that will enable treating or even "recovering" of ASD-affected individuals, but it is through an understanding of the complex web of "environmental" influences on an ASD person that most help is probably going to come.

Mix In Personal Medicine

Combined with this relatively recent emphasis on "environment" in causing ASDs is a somewhat unrelated movement called "individualized medicine." Individualized medicine is driven by the ready availability of internet technology, the ease in getting one's own medical records, and the commitment to tailoring medical treatment, as well as almost everything else we do in life, to the individual. Ever since Starbucks introduced, in the early 1990s, the reality that one's coffee could be completely individualized, Americans have been on a quest for individualizing everything. We want personal financial consultants, exercise consultants, and tutors in a variety of fields. It only stands to reason that the time would come when we would want to be able to put our medical records in the hands not just of our local doctor but, potentially, of the world's expert in the field so that we could get "personalized" medicine from the one involved in shaping the field that is most related to our distress(es).

Marrying the Two Concepts

When you join these two ideas which, at first glance, have little to do with each other, you have the germ of the new concept called the "exposome." In a few words, scientists interested in studying the "exposome" are interested in documenting and calibrating life-course environmental exposures (including lifestyle factors) from the prenatal period onward. The exposome is, according to a summary of the first-ever exposome conference (held in Feb. 2010), "a comprehensive measurement of all exposure events (exogenous and endogenous) from conception to death." A summary of that conference appears in the June 2010 newsletter of the Standing Committee on Use of Emerging Science for Environmental Health Decisions.

The exposome is, at this stage, more of a mental concept than an actual reality. Scientists interested in studying it (and pride of place for coining the term goes to England's Dr. Christopher Wild, in a 2005 article) are discussing two key issues now: (1) how to define "environment" in the phrase "environmental exposures;" and (2) how to measure these exposures for individuals rather than for "large populations." The hope of those answering these questions is that concrete results might help us to determine not simply generic susceptibility to disease (and many of the first generation of "exposure scientists" are cancer researchers) but to identify specific factors in the life of the individual that makes him/her susceptible to disease. The rest of this essay will focus on the ambition, and problems, with this new "exposure science."

Ambitions

The almost breathtaking scope of exposure science's ambitions should be readily apparent. Just as the human genome was decoded and sequenced from about 1990-2003, with the result that we have had for the past few years a sequencing of the approximately 20,500 genes in human beings--with the hope that further study on gene expression will provide clues to how diseases are caused--so the hope of measuring and calibrating all the environmental influences on a person may contribute even more to identifying and healing diseases. Scientists now conclude that up to 90% of diseases are "environmentally" rather than "genetically" triggered; thus there is the urgent need for a "exposome" project as ambitious and well-funded as the genome project. The strength of the ambition is related to the clarity of the goal--you have a better chance at understanding and healing disease and chronic illness if you can identify the precise factors leading to the disease in an individual. Thus, the marriage of interest in the 'environment' behind contemporary ailments, as well as the philosophy of 'individualized medicine' make this a project whose time seems to have come.

And, on an interesting note, we have an unlikely group of funders waiting in the wings to help support the effort. Which group? A consortium of chemical companies. Why is this an unlikely group? Because they are generally viewed as the culprits in the proliferation of environmentally-caused illnesses and diseases. Their manufacture of incompletely-tested chemicals, and their combining of these chemicals with other incompletely-tested chemicals has led many people to point fingers at them as responsible for the "big four" childhood epidemics (ADHD, autism, obesity, asthma). But they, in fact, think they are innocent of all charges and would like to put in some money to prove this is so. Of course, this brings us into the problem that is ever-present for scientific research in our day--it is often funded by the very interests who have much to gain by results coming out in a certain way.

Limitations

If the ambitions of the project are daunting, the challenges are no less so. Indeed, at this point, the development of measuring tools and agreed-upon definitions are the greatest needs. Let's me conclude this essay by mentioning just the latter. The central issue here is what constitutes "environmental." Thinking about this issue for a while leads you to a seemingly Catch-22 situation. If you define environment in a crisp and easily-definable way--say the amount of exposures that a person might receive from levels of certain carcinogens or other possibly dangerous chemicals, you run the risk of eliminating tremendously important factors in the etiology of disease. For example, what if you have two people, one of whom is of a rather morose or even worrying temperament, and he responds to an assault of some kind of carcinogen or other external exposure in a way that puts an excessive strain on his system, leading him to a disease, while another person, more robust in mind, experiences the same exposures and is spared any significant life trauma.

In order to handle this problem, you have to define the concept of "environment" broadly, to include the totality of influences on a person, including a variety of psychic, stress-related, or other internal tendencies that may be impossible to measure but essential to understand the "make up" of this person. So, if it will be difficult to calibrate the physical exposures a person has had over a lifetime, just think how impossible it would be to identify the nature of the psychic strains or psychic makeup of each person given these exposure realities. Thus, the Catch-22.

Exposure scientists respond to this concern by saying that they don't need to have the entire "sequencing" of environmental exposures in order to get a detailed-enough understanding of the individual to do some real good. Indeed, Dr. Stephen Rappaport, of the University of CA Berkeley, likens the quantum of information needed by exposure scientists to the whole of exposures of an individual to the relationship of a trailer for a movie to the movie itself. The "trailer," one of many 'trailers' which play in theaters for the first 30 minutes of the time that the billed film was supposed to have been playing (and lawsuits to get theaters to stop doing this have, obviously, failed) only gives us a short "snapshot" of the entire film, but we can ascertain from the trailer some of the leading features of the film. Thus, in the same way, Rappaport argues, an imperfect exposure record for an individual is much better than nothing at all. Don't let your lofty ambitions mean that you can realize nothing except the full ambition.

Conclusion

We are philosophically prepared for this new movement. The human genome project was completed with great fanfare but has revealed that there is so much more that needs to be done until we have a fuller understanding of disease and its eradication. We are "ready," then, for people to come along and tell us that similar measures of the "environment" are the next step in moving us toward the goal of a healthier society and world. For this alone, the movement will get a lot of notice and funding. I can't help but think, however, that once we leave the so-called "hard" or "fixed" science of genetics (and, of course, we are discovering that even these seemingly most 'stable' things in our make-up, our genes, are anything but stable--witness the rapid explosion of the field of "epigenetics"), we are dealing with so much "softness" and unpredictability, that only minimal progress can be made. That isn't an argument for doing nothing; it just suggests that billions more will go into this project before we discover how really little we actually know..

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