New Frontiers in Addiction Medicine: Genetic Research and Biomarkers

0:00:22 William Moyers
Hello and welcome to Let's Talk, an award-winning series of podcasts produced and delivered by the Hazelden Betty Ford Foundation. Each podcast focuses on a topic related to addiction to alcohol and other drugs. From prevention, research, treatment, current events, advocacy, and of course, recovery from addiction to alcohol and other drugs. I'm your host, William Moyers, and today joining us is Dr. Marvin Seppala, the Chief Medical Officer of the Hazelden Betty Ford Foundation. Welcome, Marv!

0:00:52 Dr. Marv Seppala
Thanks a lot, William. Good to be here.

0:00:54 William Moyers
Nice to have you with us again. Here at the Betty Ford Center. On this podcast. And it's I think rather appropriate that our topic for today is talking about the collaboration with the Mayo Clinic on a couple of studies which I want you to talk about, but I think it's interesting that this collaboration is with Mayo Clinic and that's where a lot of your story comes from.

0:01:13 Dr. Marv Seppala
It sure does. I was—I got sober while I was working at the Mayo Clinic after high school. Actually before I graduated from high school 'cause I dropped out and I was working there. And able to get my diploma once I got sober. [laughs] 'Course they didn't really—I told the HR Department I hadn't graduated. [Moyers laughs] That nobody else really knew in the lab I worked in. [Both laugh heartily] So, somehow I still got a job without a high school diploma.

0:01:42 William Moyers
Wow.

0:01:42 Dr. Marv Seppala
And then I was absolutely influenced to go into medicine while working there.

0:01:47 William Moyers
And addiction medicine?

0:01:49 Dr. Marv Seppala
No. I was actually—I wanted to be a cardiac surgeon. 'Cause I worked with—in a cardiovascular research lab. And the primary person who influenced me was a Brazilian cardiac surgeon. And he—we would be doing surgery on these animals and he'd tell me all these stories of healing. From his work.

0:02:11 William Moyers
Hmm.

0:02:12 Dr. Marv Seppala
And just—I just wanna be like Joauo. That was my goal. [chuckles] So I thought I'd be a cardiac surgeon. Then halfway through medical school, back at Mayo, I still had that plan and I was doing clinical rotations, and all these patients had alcoholism or other type of addiction. And I had to identify that and bring it up with my attending, the physician on staff, and the residents. And they would listen to me and then tell me we're not gonna do anything about that, Marv. And we didn't put it in the chart. We didn't refer people for care, for consultation, nothing. [Moyers shakes head] And it was often the cause of the hospitalization and we were doing nothing about it. And I was complaining about this at AA, the meeting I attended weekly and after a few weeks, these two doctors in the meeting took me aside one night and said Marv, you have got to quit bitching about this and do something about it!

[Moyers laughs heartily]

0:03:13 Dr. Marv Seppala
And—and it kinda opened my eyes to possibility.

0:03:17 William Moyers
Yeah.

0:03:18 Dr. Marv Seppala
'Cause actually that discussion that resulted in me going into psychiatry and specializing in addiction.

0:03:26 William Moyers
Well we're glad that you did. It's been—

0:03:28 Dr. Marv Seppala
Me too!

0:03:28 William Moyers
—Many decades now.

0:03:29 Dr. Marv Seppala
It has, yeah.

0:03:30 William Moyers
And did you ever think that the day would come when the Hazelden Betty Ford Foundation would be collaborating with Mayo?

0:03:36 Dr. Marv Seppala
You know, I didn't. I had hoped so all along. But it just didn't happen, it didn't happen, so I kinda lost hope about it. And now here we are doing it.

0:03:44 William Moyers
Two studies! Tell us about 'em.

0:03:46 Dr. Marv Seppala
Yeah so we're doing an NIH grant-funded study that we partnered with Mayo Clinic on, the study of medication for alcohol use disorders. The medicine is Acamprosate. Which hardly gets used. 'Cause it only works for about ten percent of people with an alcohol use disorder. So for me as a Doc, it's hard to convince myself to prescribe it to somebody and especially hard to convince them to take it because it works so infrequently. You know in nine out of ten it doesn't work for. But there was always this underlying thought that it must be a genetic subtype of alcoholics.

0:04:23 William Moyers
Mmm.

0:04:24 Dr. Marv Seppala
So that respond to it. So, what we've decided with Mayo is to find out if that's true because one of the main researchers there who I actually knew since I worked in that lab as a kid, Dick Weinshilboum, he helped develop technologies for examining genetic and metabolic biomarkers. Which are just kinda the whole human genome kinda testing that to see if an individual is gonna respond to medicine or not. But also these metabolic biomarkers are just normal metabolic byproducts floating around in our blood. So it can take simple blood test and check it out to see who responds to the medicine and who doesn't. And as a result of determining that, we put it into artificial intelligence computers to examine the characteristics of those biomarkers in those who respond versus those who don't. And he started with these studies with cancer chemotherapeutic agents. And now if you go to Mayo with certain cancers, they just take a blood test and they'll tell ya well this is the one you should take. This is the medicine you should take 'cause it'll work for you. Where this one won't. Which is a tremendous help in decision-making. Really personalized medicine.

0:05:42 William Moyers
Mmm-hmm.

0:05:43 Dr. Marv Seppala
And then he worked on some antidepressant medications in the same manner, same kinda biomarkers, to—simple blood test to tell who responds and who doesn't. Or who has side effects versus who doesn't. And—and he decided you know alcoholism is such a huge problem all around the world, it's the next place I wanna spend my time. And so we're doing this study. And it will give physicians and other prescribers the ability to meet somebody with an alcohol use disorder and determine if this medicine makes sense or not. And it'll be the first time that's—that kind of decision-making's available in the addiction field.

0:06:21 William Moyers
How long's it gonna take before we get some results?

0:06:25 Dr. Marv Seppala
Probably another three to four years. It takes—we need 800 patients with an alcohol use disorder. Half of whom will get a placebo, half of whom will get the real medication. To be able to compare response rates and figure out who's who. And then using the artificial intelligence stuff too. There's another aspect of this study that's like science fiction.

0:06:48 William Moyers
Tell us!

0:06:48 Dr. Marv Seppala
So, every patient that volunteers for this will have a little bit of their blood shipped down to Mayo. And a woman there will take certain cells, these that are called pluripotent stem cells—you've heard of stem cells.

0:07:05 William Moyers
Sure!

0:07:06 Dr. Marv Seppala
Well pluripotent stem cells can turn into any kinda cell. So she'll turn—it takes three months but she'll turn them into neurons. So brain cells.

0:07:15 William Moyers
[chuckles] Oh!

0:07:16 Dr. Marv Seppala
Yeah. [chuckles] And—and so well first she'll just take the regular cells, three months to turn into pluripotent stem cell, three more months to turn into a neuron. So actually it's like she's growing these mini brains in a petri dish. [chuckles] In the Mayo Clinic. And—and then we can test to see if the medicine—

0:07:37 William Moyers
Sure. Yeah. [nodding] 

0:07:38 Dr. Marv Seppala
—As we're doing these other, this other research, if it actually does really work on that person's brain cells—

0:07:41 William Moyers
Uh-huh.

0:07:43 Dr. Marv Seppala
—Without even being in touch with that individual.

0:07:46 William Moyers
Huh.

0:07:46 Dr. Marv Seppala
Which is really unusual. And really fascinating and it's just been a treat to be involved and to learn about.

0:07:52 William Moyers
Well tell us about the other study.

0:07:54 Dr. Marv Seppala
So the other study is basically the same kinda thing only for opioid use disorders. And—

0:07:59 William Moyers
Hmm.

0:08:00 Dr. Marv Seppala
—We got a grant from a Minnesota businessman, Mayo got the grant initially, he said he'll only give it in partnership with us which was kinda nice—

0:08:09 William Moyers
Yes.

0:08:09 Dr. Marv Seppala
'Cause working together like this is working out really well. And what we're doing is looking at Naltrexone and Buprenorphine, two of the three main medicines for opioid use disorder, and trying to same kind of biomarkers that will predict who responds the best to which medication. And right now, they both work. They both—you know, like any medicine, one's gonna work better for one person than another, but we have no clues, no predictors, of any kind. So it's just you know it's a coin toss right now which medicine you give people. We use certain characteristics to try to decide but in general, we just don't have the information. And so after four or five more years and a lot of people, we're gonna get the same kinda situation where a simple blood test will tell us which medicine will work for that individual.

0:08:59 William Moyers
Ahhh. What's the ultimate goal with all of these kinds of studies? What do you as a doctor but also you as a man in long-term recovery—what do you aspire or hope happens here?

0:09:12 Dr. Marv Seppala
You know, the ideal is just better and better outcomes for people with substance use disorders. So that when they come into treatment, simple blood test defines which medicine would work for them and that will give them the best outcome of the medicines available. We add all the psychotherapies, you know, the Twelve Step facilitation therapy, get 'em involved in recovery-oriented systems of care and peer support. And if we do everything right, it's a lot more likely they're gonna stay sober. And that's the goal, you know? Increase the likelihood that people are sober.

0:09:46 William Moyers
And they always talk about recovery being a program where strength in numbers matters, but in the addiction treatment field and in the research field, strength in numbers through collaborations is important as well.

0:09:58 Dr. Marv Seppala
It really is. 'Cause in this case with Mayo, they've got this tremendous genetics lab, you know? And all this technology and all these people involved with other medicines long before they got involved in addiction. And it's kinda plug 'n play for them. They've done it before, this is just a different group of medicines and a different illness. And we've got all these patients with substance use disorders.

0:10:22 William Moyers
Mmm-hmm.

0:10:23 Dr. Marv Seppala
So we kinda supply patients and the recovery you know treatment—treatment programs, everything else they need. Ongoing involvement, they supply the manpower behind all that research. And then they use actually an artificial intelligence system from a university in Indiana.

0:10:47 William Moyers
Hmm.

0:10:47 Dr. Marv Seppala
So—so we've got three different systems involved actually. Yeah.

0:10:51 William Moyers
So science, medicine, collaboration. And so there's great hope on those—on those fronts for people who are struggling with addiction.

0:10:59 Dr. Marv Seppala
There really are. And you know the rates of recovery are still you know basically on the low side.

0:11:08 William Moyers
Mmm-hmm. Yes.

0:11:08 Dr. Marv Seppala
You know when you look at it compared to other major illnesses. And so the better we can define who gets what medicine, the better we can define who gets what psychotherapy, you know? The more we do in that way, the better the outcomes will get. And it's again, you know, the main goal.

0:11:24 William Moyers
Hope.

0:11:25 Dr. Marv Seppala
Yeah! Yeah. Give people hope. 'Cause you know right now, when you talk to most people on the street, they say well addiction treatment doesn't really work, does it?

0:11:32 William Moyers
Right. Right. [nodding]

0:11:32 Dr. Marv Seppala
You know, and so you give people hope, they're more likely to seek treatment or they're more likely to have their family member seek treatment.

0:11:40 William Moyers
Mmm-hmm.

0:11:41 Dr. Marv Seppala
Because it's—it's probably gonna work!

0:11:42 William Moyers
Mmm-hmm.

0:11:43 Dr. Marv Seppala
You know, that's a whole different mindset.

0:11:46 William Moyers
Thanks for taking the time to be with us today and instilling with our viewers and our listeners that sense of hope that with innovation and collaboration in addiction treatment can come better outcomes and more people can recover.

0:11:57 Dr. Marv Seppala
Well thanks a lot, William. Glad to be here.

0:11:59 William Moyers
Dr. Marvin Seppala, Chief Medical Officer of the Hazelden Betty Ford Foundation and our guest today on another edition of Let's Talk, a series of podcasts on the issues that matter to us, the issues that we know matter to you, too. Please if you like this program, please share it with your friends and collaborators. Your colleagues, your families, and let them know that there is great hope through these series of podcasts. We hope you'll join us again. Thank you.