Scientists Are Trying to Prove that Addiction Is a Genetic Disease

"There are the genes that control stress, genes that affect drug metabolism, and genes that affect how readily an addiction forms."

by Olivia Campbell
Jul 4 2017, 12:00pm

The idea that addiction is a disease is not new. References to chronic drunkenness as a sickness have been traced back as far as Ancient Greece and Egypt. The debate over whether or not addiction is a matter of biology or bad choices has been raging for centuries. Some even argue that the debate itself "prevents researchers from identifying effective treatment strategies."

No matter what you believe is the cause, the effects of drug abuse are devastating to families and communities across the country. And incredibly costly: According to the National Institute on Drug Abuse (NIDA), the crime, lost work productivity, and healthcare-related to abuse of tobacco, alcohol, and illicit drugs cost the US roughly $740 billion annually.

By working with mice, scientists at the Jackson Laboratory in Maine are in the process of bolstering the disease model of addiction. They are currently working on identifying the genes associated with addiction. Since addiction is a complex problem, treatment is not one type fits all by any stretch. But by uncovering the different genetic factors that can affect someone's vulnerability to addiction, it may lead to more tailored treatment approaches.

To find out more about this fascinating research into the biology of addiction, I spoke with Elissa Chesler, principal investigator at Jackson Laboratory's new Center for Systems Neurogenetics of Addiction, which is funded by the NIDA.

What do you think is the biggest misconception about addiction among the general public?
Like any disease, there are different extents to addiction, and variability in how it manifests. Some people can go into spontaneous remission, while others have a very hard time recovering. This diversity in addiction helps create a perception that it's a character flaw, a moral failing.

It's thought of as not a disease, but bad behavior. By not promoting access to treatment, public policies reflect the thinking that these are people behaving badly that deserve to be punished. But incarceration is not productive or effective.

In our work, we're looking at whether there is a common biology underlying these behaviors. We go back and forth between mice and humans: When we find something in mice, we go and look at how well that accounts for variability in humans. What we've found is that it's much easier to find biological mechanisms in mouse populations. The progress we're making using mice is incredible. We can really see how genes influence neurobehavioral traits.

Why is it controversial to call addiction a disease?
One of the issues is whether addiction is a disease or an extreme form of human behavior. We struggle with free will versus determinants—but in the case of compulsive drug-taking, free will is gone. There's something rooted in the biology of behavior with these intractable habits. Drug-seeking and taking become all-consuming.

We see lasting changes in the brain with addiction. Even some neuroscientists who see those brain changes say it's not a disease because people can spontaneously go into remission. But people recover on their own from the common cold all the time, and no one says a cold isn't an illness. We need to think about our philosophy of defining "disease."

How do you create addicts out of mice?
We train them to do work for drugs. Some are much more interested in doing the work, and they continue to do the work even when the drug is taken away. Then they start using drugs even more readily later when the drugs return. I work with two different genetic strains of mice. I'm not going to call one strain a problem or say it has bad behavior—both strains of mouse are blameless—there's some biological difference. I hope this work helps reduce the stigma of addiction.

Does it water down the meaning of the word "addiction" when we use it in everyday circumstances?
It's potentially damaging when we talk about much less harmful behaviors as "addictions"—chocolate, caffeine, technology—it's rare that you would need treatment to overcome such addictions. And the side effects typically don't fit into the constellation of impairments associated with drug and alcohol addiction.

In some ways, habits are normal. I brush my teeth every day, but it's not pathological. I'm not missing work to brush my teeth. What matters is when it becomes a problem that requires intervention.

When addiction runs in a family, what determines who may end up being affected?
Probability—people may not have inherited all the same genes—life experiences, environment. In identical twins, we often see shared substance abuse issues. It's also determined by the addiction potential of the drug: with more addictive drugs, addictions are more likely to be shared; weakly addictive substances are less likely to be shared across family members. Some people may have more difficult life experiences than their siblings. Peer groups also play a role. It may depend on whether you have a group of friends who approves or doesn't approve of drug use. More broadly, preference for drugs varies over time.

How realistic is it that we might one day genetically profile people to find and prevent potential addicts?
The biggest problem with behavioral genetics is that the genes identified with addiction might also lead to good behaviors as well. Entrepreneur, inventor—these are jobs where risk-taking behaviors are required, rewarded.

You don't necessarily want to tell people they are likely to become drug addicts because they might think: "well I may as well start now, since it's a foregone conclusion." You also see this in people when drug addiction runs in the family. The question is when is it most valuable to disclose this information; like can it help us understand the genetics underlying opioid addiction so we can see how best to treat it?

How close are we to pinpointing all of the genes involved in addiction?
Many are already known; the question is, how many are there. There are the genes that control stress responses, genes that affect how rapidly the drug is metabolized, and genes that affect how readily an addiction forms. These are the areas all addicts have in common: how likely you are to start, how the drug affects you, and how likely they are to form a habit. Even though we know some genes doesn't mean we can use that information to treat the addiction yet. There are many drugs, and for each drug, there are many genes.

I'm optimistic that genetics in lab mice will help us understand very specifically the biological mechanisms of human addiction. In mouse genetics, it's very clear which gene connects with which behavior.