The Failure of Decoding the Human Genome and the Future of Medicine

THE DECODING OF THE HUMAN GENOME at the dawn of the millennium carried the hope and promise of the beginning of the end of human suffering. However, after more than a decade of intense exploration of the human genome the burden of human disease and suffering has only increased across the globe. Heart disease, cancer, and diabetes as well as allergic and autoimmune disorders have all continued to skyrocket. Hope has given way to disappointment as scientists have recognized that, other than in single gene disorders likes Down’s syndrome, your genes don’t determine your fate.

In November of this year a review on Genomics, Type 2 Diabetes, and Obesity in the New England Journal of Medicine(i) sadly reported on how little correlation exists between obesity, diabetes, and your genes. There are associated patterns that confer small risks, but the authors lament the lack of stronger connections between genetic makeup and the biggest disease epidemic of our time (obesity and diabetes) with refrains such as “modest effect size”, “relatively few successes”, “remains far from clear”, “poorly captured by existing biologic knowledge.”

The story of your health is much more complex than genetic programming. It is ultimately determined by the dynamic interplay of the environment washing over genes creating the “you” of this moment. The good news is that this has been the year of discoveries about “omics”—epigenomics, exposomics, nutrigenomics and microbiomics, and toxigenomics—that do, in fact, hold the key to unlocking our health and disease mysteries.

Science is now proving what we all knew intuitively—that how we live, the quality of our relationships, the food we eat, how we use our bodies, and the environment that washes over us and determines much more than our genes ever will.

The Epigenome: Bypassing Darwin and Evolution

More important than our collection of genes, it now appears, is how those genes are controlled by both internal and external factors—our thoughts, stress, social connections, what we eat, our level of physical and mental activity, and our exposure to microbes and environmental toxins. These factors are switches that turn genes on and off and determine which proteins are expressed. The expressed proteins, in turn, trigger signals of disease or health.

What’s even more striking is that if your DNA is tagged by an environmental factor, such as a pesticide, the impact this environmental factor has on your genes can be passed down through generations. The “epigenome” become inheritable. That means if your grandmother ate too much sugar, or smoked, or was exposed to mercury from too much sushi, the genetic modifications she incurred from this exposure could affect you. Her epigenome would carry an increased risk of disease that could be passed down from generation to generation. Interestingly, the Darwinian and Lamarckian worldviews are intersecting in 2010.

The Exposome: Environmental Influences on Health and Disease

In October 2010 Science magazine(ii) published an important paper that reviewed the notion of the “exposome”—the idea that the environment in which your genes live is more important than your genes themselves. What this suggests is that applying genomics to treat disease is misguided because 70-90 percent of your disease risk is related to your environment exposures and the resultant alterations in molecules that wash over your genes.

The question then is how do we measure and change our “exposome”—or the totality of the impact of the environment on your genes. We must address not just one factor but the whole collection of interacting factors that determine health and disease—toxins, food, microbes, internal chemicals including all the biologically active molecules that control inflammation, oxidative stress, gut flora, and other natural processes.

Emerging biomarkers and analytic techniques will soon allow us to map our exposome from a drop of blood, and measure change over time. Using novel treatments that help identify and remove known external toxins (like pesticides and mercury) and strategies that change the internal environment including diet, nutrients, probiotics, and detoxification would help you change your “exposome” and lower your overall disease risk.

Once this new paradigm of understanding how a lifetime of interacting exposures interacts with your genes to determine your chronic disease risk, once the gene-environment interactions are mapped more carefully, then the promise of the genomic revolution can be fully realized.

Nutrigenome: Eating Your Way to Better Genes

The most important thing you do to control your genes every day is eat well. Food; and the combination and quality of macronutrients (protein, fat, carbohydrate), micronutrients (vitamins and minerals), fiber, and phytonutrients (plant-based bioactive compounds); all wash over your DNA every day turning on or off, up or down signals from your genes. This field, called nutrigenomics,(iii) offers a powerful way for you to control your destiny.

Researchers have found, for example, that depending on your genes, you may respond better to different diets—some do better with more fat and protein and less carbs, others may not. One of the most important discoveries of the decade is how food—whether it is plant-based, nutrient-rich, phytonutrients-rich food, or processed, high sugar, nutrient-depleted food—changes your gene expression in real time over the course of weeks to months. Dr. Dean Ornish showed how this works in his seminal prostate cancer research.(iv) He was able to beneficially affect over 500 cancer-controlling genes simply by having his patients eat a plant-based, whole foods diet.

Microbiome: The Most Important DNA in Your Body is Not Your Own

The human body hosts 100 trillion microorganisms. The DNA of the bugs living in and on you, outnumber your own DNA by 100 times. This is called the microbiome.(v) Our bodies are simply a host environment for bacteria. They use us for their own purposes. The molecules produced by the DNA of these bacteria have significant impact on our health. This is called “metaproteomics”.

This microbiome, particularly the ecosystem of nearly 500 bugs that live in your gut, have been linked to everything from obesity, to cancer, to autoimmune and allergic disorders and even heart disease and diabetes. Our modern lifestyle and diet and the overuse of antibiotics has changed the population of bacteria living in our guts and it has made us sick.(vi) Which bugs we grow in our intestine determine whether we will be fat or thin, inflamed or healthy. The critical discovery of this microbiome and its implications for influencing many of the diseases of the 21^st century will provide novel treatments involving changing our diets and the use of pre-and probiotics to shift the gut ecosystem into a health-promoting balance. We are only as healthy as our gut bacteria.

What the Future Holds

The giddy back-slapping decoding of the human genome, has given way to a more sober view of the limits of genomics and the remarkable understanding of what we all knew intuitively—that how we live, the quality of our relationships, the food we eat, how we use our bodies, and the environment that washes over us and determines much more than our genes ever will. The next decade will better characterize how the environment affects gene expression—the genome-exposome interactions—and our health, and provide us better ways to measure and improve those interactions and help us create the best expression of ourselves.

Now I’d like to know your thoughts on this subject.

Do you think your environment is as important as your genes in determining health or disease?

What actions do you plan to take to incorporate this new science into your life?

In the New Year would you consider changing your diet and lifestyle to improve your health? What changes do you plan to make?

Let me know your thoughts by leaving a comment below.

To your good health,

Mark Hyman, MD

References

(i) McCarthy, M.I. 2010. Genomics, type 2 diabetes, and obesity. N Engl J Med. 363(24): 2339–50. Review.

(ii) Rappapport, S., et al. 2010. Environment and disease risks. Science. 330: 460–461

(iii) Grayson, M. 2010. Nutrigenomics. Nature. 468(7327): S1.

(iv) Ornish, D., Magbanua, M.J., Weidner, G., et al. 2008. Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Proc Natl Acad Sci USA. 105(24): 8369–74.

(v) Caesar, R., Fak, F., Bäckhed F. 2010. Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. J Intern Med. 268(4): 320–8. doi: 10.1111 Review

(vi) De Filippo, C., Cavalieri, D., Di Paola, M., et al. 2010. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA. 107(33): 14691–6