There are many rousing lyrics in Les Misérables, probably my favorite of all musicals -- with some competition from Wicked, and Man of La Mancha. Among them is this: it is time for us all to decide who we are.
In Les Mis, this is a question pertaining to rather fundamental matters of, well, let's call them: liberty, equality, and fraternity. The line is followed by: Do we fight for the right to a night at the opera now?
A lead article in today's New York Times invites us all to confront the same existential decision, but under a rather different set of circumstances. The article, full of promise no doubt dosed to coincide with the inchoate New Year, is about seeking genetic mutations to help fight chronic diseases.
This is elaborated in the article as something of an about face for the genomic venture. The venture began with dual goals: map the normal human genome, and use that normal template as a way of identifying troublesome anomalies. The hopes went beyond just detecting genes associated with the major causes of years lost from life, and life lost from years -- and extended to the elusive power of fixing them. The basic idea was to associate such scourges as dementia, diabetes, cancer and heart disease with their particular genetic defects, and then harness the power of our science to remediate the wayward DNA.
Some 15 years or so later, none of that has played out as hoped. For the most part, the hyperendemic chronic diseases are complexly polygenic. Not only are multiple genes inevitably involved, but different combinations of multiple genetic defects account for similar diseases in dissimilar people. And then, even if we could pin a bad outcome on some consistent malefactor in the genetic code, we have not yet devised means to rewrite that code. Fixing genes we don't like remains, more often than not, an aspiration.
After 15 years, though, aspirations unfulfilled invite frustration or innovation, and in this case almost certainly both. The innovation is the stuff of today's article.
In families where a particular chronic disease -- Alzheimer's, for instance -- is prevalent, something truly useful might be learned from those family members who don't get it. So goes the hopeful, logical, and laudable thinking of scientists committed to this new endeavor. If the genes that protect against serious diseases among an obviously, and exceptionally vulnerable cohort can be identified, then...
Then what? The answer provided in the article is this: "By understanding how protective mutations work, [the scientists involved] hope to develop drugs that mimic them and protect everyone."
Which leads me back to the provocation with which I began: it is time for us all to decide who we are.
As recently as last week, a peer-reviewed paper was published reminding us what the "actual" causes of years lost from life and life lost from years really are in our culture. Yes, of course, genetic vulnerability is in the mix. But of course, it is the genes that deny us gills that make us vulnerable to drowning; that doesn't make drowning a genetic disease.
In much the same way, there is genetic vulnerability -- and variation in that vulnerability -- for heart disease, cancer, diabetes, dementia, obesity, and so on. But that doesn't make these genetic diseases either. There are whole populations that get them routinely, and whole populations that avoid them. More provocatively, there are studies to show that the very same people with the very same genes routinely get these diseases when they live where and how we do (in the U.S.), but don't get them when they live like the cultures from whence they hail.
The new paper is about the built environment -- from buildings that entice use of elevators while concealing stairs; to suburbs that encourage drive-through everything; to potentially calamitous intercourses between high-speed motorists and distracted pedestrians -- and how it relates to the actual causes of premature death. Those causes, in turn, have been catalogued again, and again, and again -- for literal decades.
What are they? The full list extends to ten factors, and includes things like how we drive, the sex we have, and how we use guns. But fully 80 percent of the action is the first three entries, and those are: tobacco, poor diet, and lack of physical activity. Or, as I like to put it: bad use of feet, forks, and fingers.
And just as the genetic focus has now shifted from what imperils us to what might protect us, so too did the literature on lifestyle factors years ago. As reliably as we know what accounts for 80 percent of all chronic disease, we know how to prevent it. That literature, too, has been like the percussion of a drum -- again, and again, and again -- pointing out the possible. The possible extends to favorable alterations in gene expression.
The question is: who are we? Are we a culture that would rather take drugs that "protect everyone" by mimicking the actions of salubrious genes? Are we a culture that prefers to wait and hope for that advance? Are we a culture comfortable with the idea that we need drugs to "protect everyone" in the first place? Are we comfortable with the inevitable costs -- in dollars, and failures, and likely side effects? Are we comfortable with all of this while having, and squandering, the means to prevent 80 percent of all chronic disease right now, no drugs required?
That last one is the crux of the matter. I am a research scientist; I am not here to argue against the hopeful line of inquiry lauded today in the Times. I commend the effort. But the devotion of resources to the pursuit of a lesser solution we don't yet own, while neglecting the one we do -- is a dubious proposition. And it raises vexing questions about who we are as a culture.
We are apparently a culture willing to market multicolored marshmallows to our children as part of a complete breakfast, then blame their diabetes on iniquitous genes and prescribe them a drug.
Or not. I think it's time for us all to decide.
The evidence is clear from that literature spanning decades, and the shining example of Blue Zone populations in the world today, that how we live defines our destiny more reliably than the genes we happen to have. DNA, for the most part, is not destiny. Dinner, to a propitious extent, is.
As I have pointed out before, we can each try to live well in a culture that tends to propagate every alternative. With will, and skill -- it can be done. But it's hard work. Why should the pursuit of health be in opposition to the prevailing winds and currents of our culture? Unlike DNA, culture is ours to direct as we choose. We can redirect it -- and I intend to do my utmost to try.
Finding and fixing flawed stretches of DNA was a laudable goal all along. Finding defenses lurking in the double helix is another.
But with years in lives, and life in years at stake right now -- it says something about who we are if we neglect the means already at our disposal to eradicate 80 percent of all chronic disease while holding out for some wonder drug. What it says is none too flattering.
It's that time of year. It's time for us all to decide who we are. The opera is optional.
David L. Katz, MD, MPH, FACPM, FACP has a genetic condition that prevents him from breathing under water. He has never been to the opera.
Director, Yale University Prevention Research Center; Griffin Hospital
President, American College of Lifestyle Medicine
Editor-in-Chief, Childhood Obesity
Author: Disease Proof