How Our Choices Change Our DNA

I’m Bill Kraus. I’m a cardiologist, I deal with prevention, and I also do research in the genetics of cardiovascular disease. I think that there’s a misperception in the general community about how important genetics are to determining disease. There are some conditions where one simple variant in a gene can lead to disease, but most of the diseases that I’m dealing with, which are lifestyle diseases, involve multiple genes, and so any one genetic variant has very little contribution to actual development of that disease.

We know that lifestyle can [be] a very strong determinant [of] whether one develops disease, given a given genetic background. In particular, diet, exercise, eating habits, sleep habits, all can modify genetic responses. And there are strong interactions between what people do as behavior and their genetic background. I like to think about the influences of lifestyle or environment on gene expression and on cell behavior kind of like a piano. So, a piano has 88 keys, its structure based upon 88 keys, every piano has 88 keys. But how that piano is tuned, and how the person interacts with that piano, is what determines the music.

It’s the same thing with genes. The gene code is fixed for an individual, but how that gene is modified by behavior and environment can determine, actually, how the cell behaves that contains that gene. So for complex diseases, with which I ideal, or with metabolic responses, which are very important for exercise, the contribution of genetics is probably about 1/4 to 1/2. That means behavior, or the environmental component, is a very strong determinant of what actually happens.

The way the way cells work is that they have a certain genetic code contained within them, but we have to figure out how to turn those genes on, and create proteins from those genes, and how to turn the genes off in an appropriate contextual way. One way the cell does this is by methylating genes when they want to turn them off. When they turn them off, it’s like a switch. The gene can no longer code for RNA, no longer code for protein, doesn’t express that gene.

We are learning a lot about epigenetics now – what can influence that. It’s clear that environment is a very strong predictor. In particular, exercise, we know – one single bout of exercise, can differentially methylate genes, or turn that switch on and off to the favorable benefit of the individual. That is, one exposure to exercise can cause a whole program of genes to be induced that can increase one’s fitness level, for example. Now, how long those switches are on, what turns them off, what kind of exercise is better, those are all questions that we have to look at going forward. So of course, everyone’s looking for the exercise drug, that is, a medicinal that can mimic the very profound and systemic effects of exercise. I’m a firm believer that that will never happen. That said, drugs can interact with genes as well to influence the response of a cell. For example, an individual that has a certain genetic makeup could have a very different response to a drug than those with a different genetic makeup.

Likewise, lifestyle can interact with drugs, and with genes, to create responses. And so that has been the focus of my work recently, and will be for the next period of time. If someone were to ask me “Are we more than our genes?” I would say absolutely – that in medicine, our behavior, our environment, more than our genes determine our fate. That is, the diseases we get and the responses to those diseases. In addition, our environment, the pills we take, the choices we make, determine our medical future.

So, how does personalized medicine work, and how does genomics fit in? There’s a dream, and I think at this stage we’re rather like someone who has an idea for a revolutionary new business. Maybe you’re Thomas Edison, and you’ve invented the lightbulb, and it’s the late 1800’s, but there are no street lamps, and there are no electric power stations, here’s nothing, you have a view. What you do is at the early stages you talk it up, and you pretend that you’ve created the thing that really is just in the back of your mind. And you talk it up, and you hope that you venture capitalist or someone that can fund and believe. You keep talking, people keep believing, you don’t quite have it yet. And eventually, if you’re fortunate and you work hard, the thing that you have been talking up but wasn’t really there, eventually it appears, and everyone’s amazed. And when it appears, it isn’t even the thing that you imagined. So I think we’re still at the “talking it up” stage of the impact of genomics and personalized medicine. Probably, we need to know a billion times more to be able to really see how it will work when it actually works, instead of mostly talk with the very occasional simple use case that works. It truly will be revolutionary, it will be in ways that we can’t predict ahead of time, so all we can predict is that it will change the world.

So one of the dreams of personalized medicine is [that] based on information about your genome, information about all sorts of other things, your metabolic profile, et cetera, you can find the right treatments for the right people, and that ideally you can prevent diseases before they start with the right diet, with the right vitamins, etc, who knows. I think we are years and years from from that.