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Scientists Say Bottoms Up to Find the Connection Between Genes and Addiction

December 13, 2012 at 12:00 AM EDT
Scientists have not found one master alcoholism gene in DNA but rather several that may affect a person's susceptibility. Science correspondent Miles O'Brien goes under the influence to examine the genetic science behind alcoholism and other addictions, and how the answers point to great challenges in curing substance abuse.
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JUDY WOODRUFF: Next: addiction and the role of genetics.

NewsHour science correspondent Miles O’Brien provides a personal take as he hones in on those connections and the latest research.

MILES O’BRIEN: So far as I know, there’s no law against reporting under the influence.

Here we go. Party. So, here goes something. That wasn’t too bad.

A stiff dose of 30 grams of pure ethanol, mixed with Diet Coke, the equivalent of three stiff drinks chugged in eight minutes or less.

MAN: And give it a blow. Good. Perfect. Just keep blowing, keep blowing.

MILES O’BRIEN: A bottoms-up moment to help get to the bottom of the link between addiction and our genes.

Marc Schuckit is a professor of psychiatry at the University of California, San Diego.

DR. MARC SCHUCKIT, University of California, San Diego: What were our major findings regarding predictors of the pattern of maximum drinks over time?

MILES O’BRIEN: He’s been studying the genetic links to alcoholism for more than 35 years.

Can you look at a genetic array right now and identify the potential alcoholics? Are we at that point yet?

DR. MARC SCHUCKIT: No. It’s a great question. We haven’t come to the major pathway of greatest interest to me. Each of them — each of the sets of genes operate in different pathways, and each of those are only explaining part of the pathway itself.

MILES O’BRIEN: But he and others are getting close. The current conventional wisdom: The risk of alcoholism is about 50 percent to 60 percent rooted in our genetic code. And researchers have identified at least six genes that impact our sensitivity to alcohol.

This idea that many people might have that there is some sort of master alcoholic gene doesn’t exist?

DR. MARC SCHUCKIT: I doubt it. I doubt a master alcoholic gene exists. Of course, I could be wrong.

DAVID CARR, The New York Times: Do you think there’s going to be any news out of Zuckerland (ph) any time soon? Come on!

MILES O’BRIEN: Whatever the genetic recipe is, New York Times media reporter and columnist David Carr is certain it is wired into his DNA.

Did you come close to dying?

DAVID CARR: Yes, quite a few times.

MILES O’BRIEN: Carr has been clean and sober for 20 years now, but nearly lost everything after years of drug and alcohol addiction, all of it chronicled in his lyrical 2008 memoir “The Night of the Gun.”

So you think there’s probably some genes inside you that make you want this more than others?

DAVID CARR: Since I have been 3 or 4 years old, I have, like — I would spin around until I got dizzy and then fall down. I think the desire to feel different than I feel right at this moment is, yes, pretty much baked into me.

MILES O’BRIEN: Which brings us back to Dr. Schuckit’s scientific saloon.

Cheers.

The tests I take under the influence will determine how sensitive I am to alcohol.

That was messy, messy.

DR. MARC SCHUCKIT: No, it’s not.

MILES O’BRIEN: He designed the regime for a long-term study of 450 men. It’s been under way for 30 years now.

DR. MARC SCHUCKIT: It’s wrapped around you.

MILES O’BRIEN: Schuckit found those who get tipsy easily are about three times less likely to become alcoholics, but those who have to drink a lot before they feel buzzed are at much greater risk. They have a 45 percent chance of becoming an alcoholic, 60 percent if they come from a family of alcoholics.

DR. MARC SCHUCKIT: All right, perfect.

MILES O’BRIEN: Oh, wow. That’s so interesting.

DR. MARC SCHUCKIT: So, this low response, no matter what the mechanism might be regarding what’s going on in the environment, whatever the mechanism might be is increasing the risk for heavy drinking and alcohol problems.

MILES O’BRIEN: If you drink one glass and you get drunk and you do that all the time, you’re just as much an alcoholic as the person who needs to drink 10 glasses, right? Is alcohol about the volume imbibed or the net effect?

DR. MARC SCHUCKIT: The real question is, do you want to get intoxicated or not? And if you want to get intoxicated and you have to drink a lot, then you spend a lot of time drinking, hang out with people who spend a lot of time drinking. You don’t hang out with me because I don’t spend that much time drinking.

And you change the way you look at alcohol and you start increasing ever more the amount of alcohol that you’re taking.

MILES O’BRIEN: David Carr will drink to that — metaphorically, of course.

It’s not just nature. It’s nature and nurture, or it’s genes and the environment that come at play. Would you agree with that?

DAVID CARR: When you’re fully engaged in the alcoholic or addictive lifestyle, you’re constantly looking for the same, or maybe a guy who’s just a little farther down the gutter, so you can feel OK about yourself. So you tend to sort of channel yourself into groups where what you’re doing seems or feels normal.

MILES O’BRIEN: I know what you are thinking. This reminds you the fruit fly Drosophila, right? Well, actually, it does if you are neuroscientist and fruit fly expert Ulrike Heberlein at the Howard Hughes Medical Institute’s Janelia Farm Research campus near Washington, D.C.

Do you love studying fruit flies? Do you love fruit flies?

ULRIKE HEBERLEIN, Howard Hughes Medical Institute: I love fruit flies, particularly drunk fruit flies. Quite honestly, I didn’t know what we were doing back then, but when I saw the very first drunk fruit fly, I said, this is it.

MILES O’BRIEN: Dr. Heberlein and her team use fruit flies as a model for studying alcoholism. When the flies breathe ethanol vapor, they get hyper, bump into the walls, become unable to fly, and then pass out.

So, what you really saw was the arc of a human buzz?

ULRIKE HEBERLEIN: Absolutely.

MILES O’BRIEN: In something that buzzes?

ULRIKE HEBERLEIN: In something — very, very, very good.

(LAUGHTER)

MILES O’BRIEN: Here, they are homing in on specific addiction genes. Mutant fly strains are named Cheap Date, Happy Hour and Tank, depending on their genes and how they control the hankering for booze.

The researchers are also looking at how outside influences can encourage flies to become barflies. After male fruit flies are spurned by females not interested in mating, they drink twice as much alcohol as those who just had sex with a receptive female.

ULRIKE HEBERLEIN: They may compensate by drinking to normalize their sort of reward system.

MILES O’BRIEN: Key to the reward system for fruit flies and humans are molecules called neuropeptides. They travel from neuron to neuron, allowing brain cells to communicate with each other.

ULRIKE HEBERLEIN: Rejection reduced the levels of neuropeptide F, and mating increased the levels. And we were able to show that reducing the levels of neuropeptide F leads to enhanced drinking. The converse, elevating levels of NPF, led to reduced drinking.

MILES O’BRIEN: But neuropeptides are just part of the internal chemistry of reward and its link addiction. Psychiatrist Nora Volkow is director of the National Institute on Drug Abuse.

She is running down a pathway toward learning more about dopamine, our internally produced feel-good drug, the chemical designed to reward behavior that is important for survival, like eating, procreating or even a brisk morning run.

NORA VOLKOW, Director, National Institute on Drug Abuse: When you take a drug or the drug hijacks that reward system, its system — basically, it stimulates it in a much more potent way than any natural rewards.

And that starts this cycle that, the more you take drugs, the higher it gets. The higher it gets, the worse you feel, when the normal rewards are no longer motivating to your behavior.

MILES O’BRIEN: Volkow has imaged the brains of cocaine addicts while they view a photo of someone using the drug. Just the image can increase an addict’s dopamine production.

Just the sight of it gets things going?

NORA VOLKOW: Yes, it gets — exactly. Just the sight of it gets things going. But, now, the more they actually increase dopamine when they see these images, the more they decide to take the drug, and the more they are motivated to go and engage in behaviors to get the drug.

MILES O’BRIEN: The more scientists understand addiction, the more intractable the problem seems. After all, it is fueled by some processes that are fundamental to human survival.

That is not stopping scientists from searching for drugs to counteract the disease. Just don’t expect a silver bullet.

Is this something that could be solved with a pill?

DAVID CARR: I mean, that’s the myth that drives all addictions, is that whatever is going on with you can be a erased if you just find this mythical level of, if I take this inhibitor and I take this one that looks after my mood, that somehow I will find — I have been doing that math all my life. It has never worked.

So, my — my own take would be is, if there was a pill to prevent addiction, I wouldn’t get involved in it, because I’m — I have already tried that route.

MILES O’BRIEN: Now for a confession. Like David Carr, my family tree is filled with alcoholics. So, I took the Marc Schuckit booze challenge with some trepidation. Learning that I was one of those “drink them under the table” guys would be, well, sobering, to say the least.

DR. MARC SCHUCKIT: What’s your level of response? How do you react to the alcohol? And you’re about average.

MILES O’BRIEN: So, while I may have the genes of an Irish pub crawler, my chances of becoming an alcoholic are slightly less.

It’s enough to make me think twice at the end of a long day, when the siren call of dopamine tells me it’s time for a taste.