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.
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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:
- Diet
- Physical activity
- Sleep
- 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 last year. It’s designed to help people optimize their diet, physical activity, sleep, and stress management in just 14 days. I encourage all of you who’ve been procrastinating, or planning, or wishing, to try these 4 simple strategies for just 14 days.
When you join 14Four, you’ll also get access to our private Facebook support group, moderated by our fantastic Registered Dietitians (Kelsey & Laura).
Why make these changes as part of a group? Because research has shown that you dramatically increase your success at making consistently better day-to-day diet and lifestyle choices if you have social support. (5)
Click here to learn more about the 14Four challenge and join us in taking back your health!
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Great article, very uplifting as I am sure I was dealt mthfr. But what’s funny about your referance of putting a man on the moon…is that we didn’t. We were lied to. So…even more so your analogy is correct. Believing that our genes dictact our health is much like…men on the moon. A fallacy.
Emily, so sad that the latest comment to this outstanding article is by a “man on the moon denier”. Surely there are sites more pertinent to your belief system than this one.
So glad you, as the blog police set me straight.
If it was so horrific he wouldn’t have allowed it.
Blessings as you,
Emily
This is an extremely misleading article. Genetic Determinism is still very much in effect if we are to take the theater analogy seriously. Learner’s comment, which, I’ve noticed, no one has responded to, is relevant here. The script, is the bedrock of the play. Bad script, bad theater performance, period. Unless the “producer” is able to change the script, and make it better, the analogy is hardly inspiring. If you can show how environmental influences can reverse base level genetic mutations, you might be on to something. But so long as we accept the view of genes as the script, then genes are ruling the day, and no amount of Paleo is going to change that, nor is it going to give hope to those who have been told that they have genetic disorders.
You should read up on the Pottinger Cat Study of the 1940’s and see how genetics is influenced by diet over multiple generations.
Thank you for responding to my point. I have looked at this study. While the study certainly points out the incredible importance our diet has on our progenity, I don’t see how this invalidates my point. I’m not disputing that a poor diet can do damage to baseline DNA–we are not invincible, after all. What I am saying is that I don’t know how a good diet can repair damage that has already been done to baseline DNA—and this is something that the theater analogy implies. If the script is bad, regardless of cause, and there is no way to change the script, then production quality becomes moot, because we are still dealing with a bad script. If that makes sense. Understand, that I would like to be wrong, but I don’t see how I am given the information here. I look forward to further discussion.
Simply put; unless it can be demonstrated that the “script” can be repaired, and modified as need be, I don’t see how epigenetics can any meaningful way be “above” the genes, as the change is nonetheless restricted to whatever genes are available—even if the gene selection is limited, or at least, less than ideal. If that makes sense.
I understand your point, one of the things I see today is that we are being “born sick” and even though dietary changes may help, this is a multigenerational problem that we have to correct now, as you can see in the study, each generation worsens and it takes the same number of generations to correct the problem. We are seeing the 3rd generation of bad diet, we need to correct our children’s diet to ensure that their grandchildren can live relatively disease free.
That being said, our genome will function optimally for us if we don’t keep taxing it by giving it crap, maybe we can’t cure everything, but we can make it a good deal better.
Thank you once again for responding to my point. Certainly making positive changes will help improve things not only for us, but our lineage as well. That said, I found your response slightly ambiguous. I can’t tell if you we’re suggesting that positive dietary/environmental changes could help reverse baseline DNA damage to the genome over the course of multiple generations, or if you we’re conceding my point and pointing out that a good diet and environment would simply help us make the best of otherwise irreversible DNA damage—which I must say, is much more modest claim than to suggest that genes aren’t your destiny.
If you are indeed suggesting that environmental/dietary changes could indeed reverse baseline DNA damage, I would love to see literature on the subject. A stronger analogy would also be more apt 😉
Are not serious genetic disorders rare? Todays epidemic of diabetes, obesity, heart disease, cancer… has to have some other explanation besides faulty genetics.
I think you missed my point. And It depends on how you define disease. Just because many problems we have can’t be directly attributed to genes, doesn’t mean that genes don’t have an overriding effect on us. It’s like cooking a steak. Just because you are fully capable of cooking a steak bad, doesn’t mean you can turn a bad cut of beef into a good one. The result is the same; a less than ideal steak. But regardless, you can’t improve the cut of beef, no matter how good you cook it and seasons it—and as such, your steak will always be determined by the quality of the cut, if that makes sense.
Show me that we can reverse baseline genetic DNA errors, and THEN we can say that genes aren’t your destiny/
A study from San Francisco using men with prostate cancer undergoing no treatment, just watch and wait, showed that external factors can turn genes on or off. So that is akin to changing the script.
if true, that’s what the analogy needs to address to satisfy sim who makes an excellent point. hope that the script can be altered enough to matter.
loaded guns dont kill people. chemically stressed out imbalances kill people. loaded guns require special care/handling/holsters, strict safety protocols, etc.. enough of that.
let me take a stab at revising the analogy that adds the complexity sim is asking for:
any 500 year old script can be tweaked by a director into any modern form by adding this or subtracting that re instruments and lighting fx, props, extras and more. even the script can be modified so modern people can understand what in hell is being said in long form shakespearean and thereby, making ‘the story’ more accessible/enjoyable to wider audiences aka ‘tweaking all we can to optimize/update the old script’.
one could argue forever ‘but then its not romeo and juliet’ anymore when it still is.
romeo and juliet has or will be renditioned in multiple languages, in slang, with text on a screen, with everyone nude, without dialog, without actors, with robots or cartoons, etc. and while the script and title code remain untouched, the rendition can obviously be tweaked and hacked to no end ala bio-hacking ala nutrigenomics.
i have also heard/read that one can change a mutation aka eventually cure/heal it aka switch a gene off, etc..
if stress can make a genetic rendition worse/accelerate its expression, then reverse engineering it could make it better, reverse the damage.
every law/script/code can be modified, even if it seems either near impossible or blasphemous to do so. why would this one code be any different from any other?
also, consider that functional doctors like kris kresser and amy nett say they’ve “seen numerous cases” of people with ample mutations actually methylating optimally, and many without significant mutations who have very poor methylation function. so obviously, genes alone could not be the limiter.
Of course when the dna is damaged it could be hard to talk about fixing, but the point of the article regards the damage that we provoke to our body with bad habits, which seems to be the actual issue. With the right diet you can improve many issues, and that’s what really matters.
Thank you…
Chris, you perfectly hit the point, are we a faulty creature which would be unable to live without technology, or we are just part of nature and we can thrive if we comply with its requirements? How could we have lived for more than two millions years without the modern stuff around us? If genes have to be blamed, why hunter gatherers societies are actually healthy. Please folks open your eyes, you just have to look around you, you don’t need a supercomputer to perceive how nature actually works, please wake up!!
Sim please, you didn’t understand how nature actually works…
My goal is to lose this last 10-15 lbs. of fat. So far, I have gone from 245 lbs. down to 185 lbs. but find some weeks I may lose a couple of pounds and others none. I eat pretty much like this six days a week and the seventh day my lunch is a cheat meal to eat whatever I want. I also drink a gallon of water throughout the day and take both a multi-vitamin and fish oil. I followed also this http://die-lard.com/xtreme-fat-loss-diet-review/ which is designed to do just that. Yeah, I done it. I love it when people that I haven’t seen for ages, don’t even recognize me.
Well if you stop the fish oil you will lower your insulin resistance and may lose those last few pounds.
Dr. Jeff,
What makes Fish Oil the new villain ??
Please back your statement with facts and scientific explanation.
Most people on Fish diet are the leanest amongst cohorts.
Exactly. Dr. Jeff spews this science but yet in reality those who eat the most fish are super trim. This is what I also hate about science it doesn’t always match reality.
Dr. Jeff, Are you joking? Fish oil & healthy fats (cold pressed coconut oil, grass fed butter (like Kerrygold), avocados, & olive oil (only cook with @ Low temp.) Improve insulin resistance & help with weight loss. Carbs, Not fat’s are the primary driver of weight gain. The best way to get fish oil is by eating the actual wild-caught fish. (Cook on Low temperature). Fish oils are fragile, so to get the benefits you need to research brands that clearly document extraction methods (No heat or chemical extraction…) & are tested by an unrelated company for purity. Quality fish oil capsules are not cheap. For example, I don’t place trust in Sam’s brand of fish oil capsules. If you do buy fish oil capsules, they should be refrigerated. When in doubt, eat directly from the source: Wild caught fatty fish, such as salmon.
This is my first time encountering the concept “exposome”. The discovery has definitely made me feel both empowered and yet overwhelmed. I hope more people will learn about this concept and be active on caring for the environment that we live in.
Very interesting studies here. I’m glad that genes don’t determine so much that one is unable to do anything about their health! Thanks for sharing.
Great article Chris! I finally got to understand epigenetics at last.