The opioid epidemic : Short Wave Over the last 25 years, the opioid epidemic has been devastating to families and communities all over the U.S., and has caused half a million deaths. But it started as a way to treat severe pain. Today, host Emily Kwong talks to Patrick Radden Keefe, author of the book Empire of Pain: The Secret History of the Sackler Dynasty, about what went wrong in science to make the opioid epidemic what it is today.

The opioid epidemic

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MADDIE SOFIA, BYLINE: You're listening to SHORT WAVE from NPR.

EMILY KWONG, HOST:

The opioid epidemic has had a lot of faces over the last 25 years.

PATRICK RADDEN KEEFE: It really started as a prescription painkiller crisis and morphed into a heroin crisis and then more recently into a fentanyl crisis. So it has evolved over that time.

KWONG: Patrick Radden Keefe is a staff writer at The New Yorker who wrote "Empire Of Pain: The Secret History Of The Sackler Dynasty," which came out this year.

KEEFE: You basically have a public health crisis that has unfolded over a quarter of a century now, really starting in the mid-1990s and has resulted in hundreds of thousands of deaths, I mean, you know, conservatively, half a million deaths.

KWONG: And this estimate, half a million deaths, doesn't also capture the millions of people across the U.S. right now living with an opioid use disorder. It's been going on so long that it's easy to forget where this all started - in medical offices, with doctors back in the 1980s in the U.K. and the U.S. wanting to break from this old-school attitude towards pain.

KEEFE: There was a tendency to just sort of say, hey, grin and bear it. You're going to have to deal with this pain. And a lot of these revisionist doctors who are making this case argue that part of the reason the pain wasn't aggressively treated is that you had this amazing solution, which was the opioids, which was a kind of class of drug that derived from the opium poppy, but that physicians had been too reluctant to prescribe these drugs because of a fear of their addictiveness.

KWONG: Back in those days, doctors were administering the opioid morphine intravenously - so through a tube in patients' veins. And that required people to come into the doctor's office on a regular basis. So Keefe says a British drug company now called Napp Pharmaceuticals Limited had an idea. What if they figured out a way to put a big dose of morphine in a pill?

KEEFE: And then have a coating that would slowly release the drug into your bloodstream over a matter of hours. And so you didn't need the doses often. If you were a cancer patient, it meant that you could go home, for instance. And so this drug was called MS Contin.

KWONG: MS Contin. That was the first-ever extended-release morphine product. And its developer, Napp Pharmaceuticals, was then owned by the Sackler family, the same family that owned Purdue Pharma. And executives at Purdue were really interested in making this new pill marketable in the U.S.

KEEFE: There was an executive at Purdue Pharma who talked about how different drugs have personalities. This was sort of a marketing thesis that he had. The problem was that morphine was associated in people's mind with death, with end-of-life care. You know, if your grandmother was going on morphine, that meant she was going to die. And so part of what they did with the MS Contin is they kind of - they created a more approachable, less threatening, you know, take it at home with a glass of water version of morphine.

KWONG: And Keefe says that was the seed of the opioid crisis - when medicine joined up with marketing. Today on the show, Patrick Radden Keefe and I take a step back to talk about what went wrong in science, from the chem lab to corporate boardrooms, to make the U.S. opioid epidemic what it is today. This is SHORT WAVE, the daily science podcast from NPR.

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KWONG: In 1984, when MS Contin, this slow-release morphine pill, debuted, it did what Purdue Pharma wanted - helped patients manage pain, made money. But after a few years, the drug was approaching the precipice of what's known as a patent cliff.

KEEFE: So at a certain point, the patent on MS Contin was running out. And there were these discussions inside Purdue at very high levels about, what do we replace this with? You know, our profits are really going to take a slide, and we need to find something new. And they really liked that Contin coating system they'd come up with, the idea of a slow-release coating on a pill. So the question then became, are there other opioids that we could use the Contin coating system with? And they came up with the idea of using oxycodone, which is another opioid, been around for a long time. You know, oxycodone itself was generic, not patented. It was cheap.

But what they did then was they said MS Contin was a big success, but it was a success for cancer pain. And there's only so many people who have cancer. And wouldn't it be great if we could position this new drug, OxyContin, not just for cancer pain and not just for severe pain, but even for moderate pain? They actually had a marketing tagline for OxyContin, where they said it's the one to start with and the one to stay with.

KWONG: Wow, OK. They were trying to create at that point kind of an all-purpose painkiller. And what is the difference chemically between oxycodone, the chemical in OxyContin, versus morphine, what they were using before?

KEEFE: Yeah, so this is part of what's interesting. I mean, they're chemical cousins. And they're chemical cousins, you know, with heroin. They're both opioids. But when Purdue was getting ready to to launch OxyContin, they discovered that doctors thought that oxycodone was weaker than morphine. And the crazy thing is it's about twice as strong as morphine.

KWONG: Oh, wow.

KEEFE: And they knew this inside the company. And so there's this amazing email traffic where they say, we have to make sure we don't do anything to disabuse them of this.

KWONG: Wow. Did anyone push back in that email thread and say, guys, I don't know if, ethically, this is right?

KEEFE: Yeah, not that I saw there.

KWONG: Wow 'cause that would have been the moment. That would have been the moment to change history.

KEEFE: It would have been, yeah. And I should say none of which is to say that OxyContin should not have been sold and marketed to pain patients. You know, it is a drug that makes a big difference in the lives of a lot of people. The crime in my mind here is not putting the drug on the market. It's how you market it and how deceptive you are about its properties. I think the thing that was interesting is that the drug starts going until early '96. And you have all these sales reps going out and basically saying for thousands of years, humans have known that the opium poppy can produce these amazing therapeutic benefits which can make pain go away. But there's always been this attendant danger, which is addiction. And what they're saying is, like, we at Purdue Pharma have hacked it. Like, we figured out a way to uncouple those two things. So you get all the up - all the therapeutic upside and none of the downside.

KWONG: By 2007, Purdue admits it deceptively marketed OxyContin as safer and less addictive than other prescription opioids. But in those early days, doctors, thinking it less potent than morphine, were prescribing OxyContin in huge doses.

KEEFE: So there was an 80 mg pill. For a time, there was 160 mg pill. They ended up...

KWONG: Whoa, 160 milligrams?

KEEFE: It's insane. It's insane. They - and they ended up taking that one off the market, having had conversations about how, you know, if a kid took one of those, one pill could kill you.

KWONG: Yes.

KEEFE: And what would happen is that people - there was this kind of perverse thing in which the labeling on the bottle said, whatever you do, don't chew or grind up the pills because if you do, you'll override the slow-release mechanism and you'll get the whole hit all at once, which (laughter) - I mean, it's good that they put that warning there. But you can also see how, for some people, that probably had a perverse effect of being kind of an instruction manual on how to override that mechanism.

KWONG: The walls have come down on Purdue Pharma. In the last 14 years, the company has pleaded guilty to misleading doctors and patients about how addictive OxyContin is. It's important to note the Sacklers have never been charged with any crime, and members of the family who led the company say they did nothing wrong. In verifying the claims in Keefe's book, we reached out to representatives of the different branches of the Sackler family. The Mortimer Sackler branch said, our focus is on concluding a resolution that will provide help to people and communities in need rather than on this book. The Raymond Sackler branch has previously rebutted Keefe's depiction of their role in the opioid crisis and denied that they had swayed researchers and doctors with money.

But when it comes to Purdue Pharma, the company pleaded guilty again to federal criminal charges last year relating to its OxyContin marketing. A lot of public health experts think the company's deception led many down a path of harder drugs, like fentanyl and heroin. And we're dealing with that today. For this story, we also reached out to attorneys representing Purdue Pharma. They said, Purdue deeply regrets and has accepted responsibility for specified misconduct that took place before June 2017. So my question to Patrick Radden Keefe as a science show was this.

Patrick, help me understand this. How did so many knowledgeable people - scientists, doctors, trained federal regulators at the FDA and DEA - let this crisis happen? Like, what went wrong as far as the medical and science community in not stopping this?

KEEFE: It's such a great question. The first thing I should say, just to be really clear, is, you know, this book that I've written is about the Sackler family, and I think that they and their company deserve special blame for the role that they played, particularly early in the opioid crisis. But that's not to say that they deserve all the blame. You know, you don't get to more than half a million people dead with one set of bad actors. This is really a story of kind of larger system failure. And as your question suggests, it's, you know, a failure of the medical establishment, the scientific establishment, lots of people who, in theory, have patients' best interests in mind and who should know better. So how did that happen?

I think that, you know, in some instances, you had doctors who were simply corrupt. So that's one category of bad actors, people who basically just took the money and looked the other way and wrote too many prescriptions. And many of those people ended up getting prosecuted. I also think part of the problem is this company comes along, and they say, we have this amazing chemical panacea. And there were a lot of doctors, I think, who were very ready to believe that because they were idealistic. And they desperately wanted to help their patients. But I should also say that I think there's something else, too. So if you have kind of outright corruption. You have kind of idealism that was co-opted. And then, I think you get what I think of as soft corruption, which is OxyContin is a drug that's generated some $35 billion over the decades. And when you have that amount of money, I think it just trickles into everything. And you see the way in which industry money exerts influence at every level.

KWONG: I mean, this has really been backed up in documents that have come out since that Purdue Pharma has released. I know Mother Jones just published this whole kind of analysis of some of their payouts. And you wrote in your book a lot about how Purdue Pharma and the Sacklers influenced medical communities and academic communities with money. So I think it's a really important thing to talk about, this kind of intersection of science and capitalism.

KEEFE: I completely agree. And I think the - yeah. We have the receipts at this point. And the receipts are just kind of adding up.

KWONG: Yeah.

KEEFE: There's huge amount of documentation of the way in which this type of influence works. I should say that I think that there is a perception of physicians - and to some degree, this would be true of scientists as well - that they can be unimpeachable. And in a strange way, I feel as though nothing is a better breeding ground for corruption than the idea that any professional class is incorruptible, you know, that the kind of self-image of the medical profession was actually part of the problem here.

KWONG: So just broadly speaking, what do we owe those who experience pain and chronic pain?

KEEFE: Oh, it's...

KWONG: Because that is a very hard thing to live with.

KEEFE: It is. Yeah. And I think it's - I think that the - I think that we owe them good treatment. I think the critique in the 1990s - 1980s and 1990s that said doctors haven't really learned about the treatment of pain, it's not taught in medical schools in a serious way, you know, this is a problem in the field, I think that was a legitimate critique. I think that was correct. The problem is that into that vacuum rushed industry. What industry wanted to do, generally speaking, was teach people how to get onto these drugs and not how to get off of them. So I think at a minimum, we owe people that if there's going to be an on-ramp, there either has to be an off-ramp or there has to be, you know, a kind of a sensible plan for keeping people on in a way that feels responsible and is not going to cut them adrift.

KWONG: And it wasn't just, of course, Purdue Pharma that contributed to all of this. There were other drug companies that made and marketed opioids, you know?

KEEFE: Yeah. Absolutely. I mean, there's a lot of blame to go around. It was not just Purdue. There were other big companies that sold opioids and marketed them in similarly deceptive ways. There were the wholesalers. There were the pharmacy chains. There are a lot of bad actors in this story. I think that the specific role of OxyContin and the marketing for OxyContin is significant because they were really the first. That was the marketing campaign that changed the way these drugs were prescribed. And you had a bunch of other companies that came in afterwards. But in the words of one scientist who worked on OxyContin at Purdue and I - somebody I interviewed for my book, this person said, the thing about OxyContin was it was the tip of the spear.

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KWONG: Patrick, thank you so much for talking to me about all of this and explaining and breaking it all down.

KEEFE: Thanks for having me. It was a pleasure.

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KWONG: This episode was produced by Berly McCoy and edited by Sara Sarasohn. The fact-checkers were Indi Khera and Margaret Cirino. The audio engineer for this episode was Josh Newell. Special thanks to Brian Mann, who covers addiction for NPR, and to Micah Ratner. I'm Emily Kwong. Thank you for listening to SHORT WAVE, the daily science podcast from NPR.

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