At one time scientists believed our DNA held the key to preventing and reversing disease. But we now know that our environment—not our genes—is the primary driver of health and longevity.
The 20th century was the golden age of genetics. It ushered in the discovery of the double-helix structure of DNA, the polymerase chain reaction (PCR) method of amplifying DNA, and ultimately, the sequencing of the complete human genome.
Somewhat understandably, these remarkable discoveries led to “biological determinism,” the belief that human behavior and health is mostly—if not entirely—controlled by our genes. And it generated some pretty bold proclamations:
We now have the possibility of achieving all we ever hoped for from medicine.
Lord Sainsbury, Former UK Science Minister
Mapping the human genome has been compared with putting a man on the moon, but I believe it is more than that. This is the outstanding achievement not only of our lifetime, but in terms of human history.
Michael Dexter, The Welcome Trust
But it quickly became apparent that these heady promises weren’t going to pan out. Even Craig Venter, one of the first scientists to sequence the human genome, recognized the limitations of using genes to predict and prevent disease:
We simply don’t have enough genes for this idea of biological determinism to work.
Craig Venter, Chairman and CEO of J. Craig Venter Institute
We now know that genes account for about 10 percent of human disease.
So if our genes aren’t driving disease, what is?
The Exposome as the Primary Driver of Health and Disease
The “exposome” is a concept that was originally proposed by Dr. Christopher Wild in 2005. (1) It refers to the sum of all non-genetic exposures in an individual lifetime, starting from the moment of conception. It encompasses everything from the food we eat, to the water we drink, to the air we breathe, to the social interactions we have, to the lifestyle choices we make, to the health of our parents at the time of our conception.
In short, it’s the word scientists are using to describe the full range of environmental exposures that influence our health.
Genes may load the gun, but environment pulls the trigger.
The exposome has been broken down into the following three categories:
- Specific external environment: This includes diet, physical activity, water, consumer and personal care products, lifestyle choices like smoking, infectious agents, chemical pollutants, etc. It also includes our environment at the earliest stages of our life, including our mother and father’s health at the time of our conception and gestation, the method of our birth, whether we were breastfed or not, and our early life bond with our mother and other social and psychological influences.
- General external environment: This includes climate; urban vs. rural setting; traffic; our wider economic, social, and psychological influences including social status, education, financial status, and stress.
- Internal environment: This includes internal biological factors such as metabolism, the microbiome, inflammation, hormones, and oxidative stress. (2)
The reason the exposome is important as a concept is that we now know it is the primary driver of human health and disease. If genes cause less than 10 percent of disease, it follows that the exposome—our diet, lifestyle, and environment—drive the remaining 90 percent.
In fact, recent estimates suggest that about 50 percent of early death worldwide is attributable to just a few environmental factors, including diet, indoor and outdoor air pollution, and active and passive cigarette smoking. (3)
The Epigenome: Where Our Genes and Exposome Meet
The “nature vs. nurture” debate—the question of whether our genes (nature) or environment (nurture) are more important to determining our health—has raged for decades. But the relatively simple distinction we’ve made over the years between genes and environment, as if they are separate and unrelated factors, turns out to be inaccurate.
According to Dr. Randy Jirtle:
The nature vs. nurture argument is rapidly proving to be irrelevant, because we’re finding that the two forces interact in highly specific ways that alter gene behavior.
Dr. Jirtle is a pioneer in the field of epigenetics. Epigenetics, which literally means “on top of” genetics, is the study of modifications to our genetic material that change the way genes are switched on or off, but which don’t alter the underlying genes themselves.
We used to think our DNA was like a template or a mold: if you poured raw genetic material into this mold 100 times, you’d get 100 identical copies. This is consistent with the philosophy of “biological determinism” that was en vogue right around the time the human genome was sequenced.
But a better analogy for genes might be a script for a theater production or film. Our genes are like the script, and the exposome and epigenome are like the production and performance. The script of Romeo and Juliet doesn’t change from one production to the next, but how it is produced and performed can vary dramatically depending on the director, cast, crew, set design, costumes, and other factors. If a script is terrible, even a great performance can’t save it. On the other hand, the best script in the world won’t matter with a terrible production.
This explains why identical twins are similar, but not the same. They are matched for genes, age, sex, pre-gestational (and often post-gestational) environment, so we’d expect their risk of having the same diseases to be very high if genes were running the show. Yet in most cases the discordance rates between twins for even highly heritable diseases like schizophrenia can be up to 50 percent. (4) In other words, if one identical twin has schizophrenia, there’s only a 50 percent chance that the other twin will have it.
Dr. Francis Collins, director of the US National Institutes of Health, once summarized the relationship between genetics and the exposome in a single, pithy sentence:
Genes load the gun, but environment pulls the trigger.
Don’t get me wrong—genes do have a powerful influence on our susceptibility to disease, and there are situations where information about your particular genetic make-up can be useful. For example, there are genes (such as MTHFR, COMT, MTR, MTRR, etc.) that affect the methylation cycle, and mutations in these genes may lead to impaired detoxification, neurotransmitter metabolism, cellular energy production, and a range of symptoms such as depression, fatigue, and infertility. But in most cases, genetic predispositions will often only manifest in the presence of certain environmental factors.
The obesity epidemic is perhaps the clearest example of this. Our genes have not changed appreciably in the last 40 years, but during that time we’ve seen an explosion in the rates of obesity. This suggests that genetics are not the primary driver of obesity. However, we do know that there are genes that predispose some people to obesity more than others, and that not everyone is equally affected by exposure to the same environment. This suggests that genes do play an important role.
How to Fix Your Exposome
The recognition that environment, not genetics, is the primary driver of human health and disease carries with it a strong message of personal empowerment and responsibility. If our genes were the only determinant of our health, there wouldn’t be much motivation to optimize our environment. But since we know that the choices we make in our lifetime predict 90 percent of our risk of disease and early death, we have a strong reason to take action to improve our health.
But where do you start? With so many possible environmental influences, ranging from diet to chemical exposure to air pollution to personal care products, where do you get the biggest bang for your buck?
I believe that, for most people, the following four areas are the most important to focus on first:
- Physical activity
- Stress management
We have an overwhelming amount of research demonstrating the influence these four areas have on our health. And I’ve also seen the greatest impact from focusing on them in my work with hundreds of patients.
This is why I created the 14Four. It’s designed to help people optimize their diet, physical activity, sleep, and stress management in just 14 days.