美国国家公共电台 NPR America's Opioid Epidemic（在线收听）

RAMTIN ARABLOUEI, HOST:

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ABDELFATAH: Lee County, Va., is located in the southwest corner of Appalachia. And at the turn of the 20th century, its economy was booming. The coal and rail industries were thriving. People were moving in. Houses were being built. Things were looking up.

ARABLOUEI: But by the turn of the 21st century, Lee County looked different. A lot of its buildings were abandoned. The coal mining industry was struggling. And many of its residents were hooked on opioids.

ABDELFATAH: One of those residents was Arnold Fayne McCauley.

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BETH MACY: This was a man in his '70s. He had been a full-time coal miner.

ABDELFATAH: For years, Arnold was the guy who got stuff done.

MACY: I asked his daughter what she remembered growing up. And she said, my memory of him was he worked.

ARABLOUEI: Coal mining is not an easy job. And Arnold suffered a lot of injuries at work, so he was no stranger to doctors.

MACY: Treated numerous times with immediate-release opioids and had always been able to get off.

ARABLOUEI: Then one day, he saw a new doctor who prescribed him a drug called OxyContin.

MACY: And this drug turned him into a nonfunctioning person. He loses his job, loses his family.

ARABLOUEI: He ends up dead, under shady circumstances, in his truck.

MACY: His truck overturned and pill bottles sort of, like, loose around him.

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ABDELFATAH: The thing is, in this county, Arnold's story wasn't that uncommon. Person after person walked into the doctor's office after being prescribed that drug...

MACY: They'd be like, doc, I lost my family. I lost my house. I lost my farm.

ABDELFATAH: ...With a strangely familiar story.

MACY: I lost my family. I lost my house. I lost my farm. That drug is my God.

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UNIDENTIFIED REPORTER #1: The opioid epidemic is getting worse.

UNIDENTIFIED REPORTER #2: More people are addicted to opioid painkillers than ever before.

UNIDENTIFIED REPORTER #3: On average, 130 Americans die every day from an opioid overdose.

UNIDENTIFIED REPORTER #4: The deadliest drug crisis in American history.

ELAINE QUIJANO: And there are virtually no signs of it getting better.

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ABDELFATAH: You're listening to THROUGHLINE from NPR.

ARABLOUEI: Where we go back in time...

ABDELFATAH: To understand the present.

Hey, I'm Rund Abdelfatah.

ARABLOUEI: I'm Ramtin Arablouei.

ABDELFATAH: And on this episode...

ARABLOUEI: America's opioid epidemic.

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ABDELFATAH: We hear a lot about opioids these days. The U.S. has been in the midst of an opioid crisis, and it's gotten worse in the past few years.

ARABLOUEI: About 400,000 people have died in the last two decades, making it the deadliest drug epidemic in American history.

ABDELFATAH: Entire communities, like Lee County, have been devastated by it. It feels like there's no end in sight.

ARABLOUEI: But how did we get into this mess? Where does this crisis actually begin? And how does it fit into America's longer history with opioids?

ABDELFATAH: After all, opioids aren't new. They've been around for thousands of years.

ARABLOUEI: Humans throughout history have turned to opium, which comes from the poppy plant, for things like pain relief.

ABDELFATAH: The ancient Greeks, Persians, Egyptians, Chinese all used it.

ARABLOUEI: Wars have been fought over it. Empires built, fortunes made.

ABDELFATAH: But America's opioid story is uniquely American.

ARABLOUEI: To understand today's opioid crisis, we need to explore the complicated relationship we've had with opioids for over a century now.

ABDELFATAH: While opioids can be addictive and dangerous, they've also provided very real relief for a lot of people.

ARABLOUEI: So we're going to tell you the story of three game-changing opioids.

ABDELFATAH: Morphine...

ARABLOUEI: Heroin...

ABDELFATAH: And OxyContin.

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ARABLOUEI: Part I - morphine.

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ABDELFATAH: In the early 1800s, a German pharmacist named Friedrich Serturner was hard at work conducting experiments on the opium poppy plant.

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ABDELFATAH: He was trying to figure out how to isolate its most valuable component - the alkaloid, the ingredient in the plant that gets you high and - more importantly for his research - provides pain relief. It was something no one had been able to do before.

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ABDELFATAH: For years, Serturner ran all sorts of tests in the lab on stray dogs and even on himself.

ARABLOUEI: Eventually, he cracked the code and managed to extract the alkaloid from the poppy plant. He called it morphine after the Greek god of dreams, Morpheus. And for the next few years, Serturner continued to study this new thing. And he started getting more and more nervous about how it might be used in the future.

MACY: He says, we must be very careful with this drug. And he warns people that calamity is around the corner.

ABDELFATAH: This is Beth Macy.

MACY: I'm a journalist and an author based in Roanoke, Va.

ABDELFATAH: Her latest book is called "Dopesick."

ARABLOUEI: So several decades after morphine is discovered, Serturner's fears are realized.

ABDELFATAH: Calamity strikes an ocean away in the United States.

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ABDELFATAH: The Civil War begins.

UNIDENTIFIED GROUP: (Yelling).

ARABLOUEI: It's an incredibly bloody war, the deadliest in American history.

ABDELFATAH: And most of those deaths actually happened off the battlefield.

ARABLOUEI: From things like disease and infection. But there was this great, new way of controlling pain.

ABDELFATAH: That new drug morphine. And the U.S. imported a lot of it. Many soldiers became hooked and stayed hooked after the war ended.

DAVID COURTWRIGHT: There's a saying or a cliche that morphine addiction in the late 19th century was the army disease or the soldier's disease.

ARABLOUEI: This is drug historian David Courtwright. And he says that nickname hides a significant detail.

COURTWRIGHT: Which is other evidence suggests very strongly that the majority of addicts were women.

ARABLOUEI: So Courtwright says while a lot of soldiers did return from the front addicted to morphine, it appears that as a century went on, women began to make up the majority of morphine addicts in the U.S.

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NANCY CAMPBELL: Why was morphine prescribed in the 19th century? It's prescribed for pain of all kinds, which women tended to be diagnosed with to a great - much greater degree than men.

ARABLOUEI: This is Nancy Campbell. She's a historian of drugs and drug addiction.

COURTWRIGHT: Men were expected to bear pain more stoically. They were not expected to seek out doctors for every ache and pain. There were also supposed racial differences in the ability to tolerate pain.

ABDELFATAH: So if you were a white woman who could afford prescription drugs and you went to the doctor for, say, a cough or menstrual cramps, you were way more likely to leave with a prescription for morphine than anyone else. One doctor, Frederick Heman Hubbard, wrote in 1881, uterine and ovarian complications cause more ladies to fall into the opium habit than all other diseases combined. So morphine was the catchall drug that doctors and pharmacists used for pretty much everything. And they prescribed it to women like Mrs. Matilda Webster.

CAMPBELL: Mother of nine children who suffered from neuralgia.

ARABLOUEI: Neuralgia's a condition where nerve pain causes a stabbing, burning sensation, usually in the head or face.

CAMPBELL: She sent, one night, one of her nine children to Boyd's, which was her usual South Brooklyn drug store. And the child reported to the druggist that her mother was in great pain - bodily pain and was asking for something to help her go to sleep. The druggist, who was pretty familiar with Mrs. Webster, packaged up a couple of doses of morphine consisting of one grain each. And Mrs. Webster, instead of doing what the druggist thought she would do, which is taking a little at a time until her pain was controlled, took everything - the whole supply. And she went into a coma, lingered in a comatose state and expired 24 hours later.

ARABLOUEI: She had overdosed on morphine. And the druggist who gave her the morphine was put on trial, which Campbell says was unusual because overdoses normally were reported as deaths by natural causes. But Matilda's husband wasn't willing to let go and eventually was given...

CAMPBELL: Five thousand dollars in, you know, 1868.

ABDELFATAH: 1868 - so not long after the Civil War ended, people were already starting to suspect that morphine was potentially dangerous.

MACY: Like, warning, warning. This drug is not safe.

ABDELFATAH: As the 19th century went on, on top of the thousands of veterans who'd become addicted during the war, thousands more people, many women, became addicted.

ARABLOUEI: Still, doctors kept prescribing morphine throughout the 1800s despite the warnings mostly because there just weren't many good alternatives. I mean, aspirin wasn't even marketed until 1899.

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ARABLOUEI: By the early 20th century, tens of thousands of Americans were addicted to narcotics like morphine. People were dying of overdoses, which sounds pretty familiar.

ABDELFATAH: Yeah, a lot like the crisis we're in today. People would go to the doctor's office, get a prescription for morphine, become addicted, maybe even die.

ARABLOUEI: And communities, who were mostly white, were left devastated. Remember; morphine was disproportionately prescribed to white women at the time.

ABDELFATAH: And just like now, it probably had a lot of people asking...

MACY: Oh, my Lord, what have we unleashed on this country?

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ABDELFATAH: One doctor wrote in 1884...

MACY: Prompt action is then demanded lest our land should become stupefied by the direful effects of narcotics and thus disease physically, mentally and morally, the love of liberty swallowed up by the love of opium while the masses of our people would become fit subjects for a despot.

ARABLOUEI: But undoing this crisis would not be easy.

ABDELFATAH: Right. Like, how do you take so many addicted people and make them unhooked?

ARABLOUEI: Well, in the early 1900s, one pharmaceutical company came up with a new drug to try to do just that.

ABDELFATAH: And it would transform the landscape of drugs and drug addiction in the U.S.

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ARABLOUEI: In the process, they unleashed an even scarier monster - our next drug, heroin.

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COURTWRIGHT: Would you please say one, two, three, four?

UNIDENTIFIED PERSON #1: Yeah. One, two, three, four.

UNIDENTIFIED PERSON #2: Testing - one, two, three, four.

ABDELFATAH: Part II - heroin.

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COURTWRIGHT: Amparo, where were you born?

UNIDENTIFIED PERSON #3: (Speaking Spanish).

AMPARO: San Juan.

UNIDENTIFIED PERSON #3: San Juan, Puerto Rico.

COURTWRIGHT: When were you born?

UNIDENTIFIED PERSON #2: May 8, 1914 in old Harlem Hospital - 137th Street on Lenox Avenue in Harlem.

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ARABLOUEI: These are the voices of former heroin addicts who became hooked in the 1920s and '30s. David Courtwright talked to them in the 1980s.

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UNIDENTIFIED PERSON #4: One night, I walked in the bathroom. And I saw this girl sitting on the tub with this rubber band around her arm, a needle, and it scared me to death as I had never seen nothing like that before. And she said, oh, this is something. Try this.

UNIDENTIFIED PERSON #2: In 1921, I started using heroin. See?

UNIDENTIFIED PERSON #4: I said, I'll never use another needle. And I actually meant it.

COURTWRIGHT: Did you know that it was heroin?

UNIDENTIFIED PERSON #3: (Speaking Spanish).

AMPARO: (Speaking Spanish).

UNIDENTIFIED PERSON #5: Everybody was sick and puking and laying all over the curb (imitates vomiting).

UNIDENTIFIED PERSON #1: It only takes a few days of continuous use you get - to pick up a habit.

UNIDENTIFIED PERSON #2: Once you start with that, you can't stop.

ABDELFATAH: We know now that heroin is more potent, more likely to cause addiction, than morphine. But when it first appeared, heroin was seen as a safe alternative to morphine, the hero to end the morphine crisis.

ARABLOUEI: That initial perception of heroin as a safe alternative was no coincidence. In the late 1890s, the pharmaceutical company Bayer began marketing heroin...

CAMPBELL: As a non-addictive wonder drug.

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ARABLOUEI: They published ads claiming that heroin would relieve your cough, even marketing it to children.

ABDELFATAH: Heroin for kids - imagine that.

ARABLOUEI: And this whole marketing campaign was uncharted territory at the time - the idea that pharmaceutical companies could be big business in a way that, say, toys or textiles are.

CAMPBELL: Originally, pharmaceutical manufacturers were called ethical pharmaceutical houses.

ARABLOUEI: Again, Nancy Campbell.

CAMPBELL: And they did not market direct to consumers. Bayer did market direct to consumers.

COURTWRIGHT: But even so - even so, by the early 1900s, people are beginning to write articles for medical journals with titles like - and I quote - The Heroin Habit: Another Curse, in which they point out that, yeah, you can get addicted to this stuff too.

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ARABLOUEI: In 1906, the American Medical Association included heroin in its annual publication with this disclaimer. The habit is readily formed and leads to the most deplorable results. Despite that warning, heroin was readily available as an over-the-counter drug. And politicians became more and more suspicious of its supposed non-addictiveness.

ABDELFATAH: In 1914, a new law called the Harrison Act was passed. It put a tax on morphine and heroin and forced doctors to register drugs with the government to prevent doctors from over-prescribing them. See; even though there was growing awareness about the dangers of opioids, some doctors were still prescribing morphine. And the government didn't want to leave room for a repeat of the morphine epidemic with either morphine or any new opioid that came along. So they decided to step in.

COURTWRIGHT: The idea is to create a kind of closed system in which everything is transparent, and the narcotics are going only for legitimate medical purposes.

CAMPBELL: That act was important because it criminalized something that formerly was not thought to be a crime.

ABDELFATAH: Up until then, opioid addiction was seen as a medical problem, not a criminal one. The result of this new law was fewer and fewer doctors prescribing morphine and almost no doctors prescribing heroin. Problem solved, right?

ARABLOUEI: Well, yes and no. On the one hand, morphine use dramatically decreased. But on the other hand, this law had unintended consequences.

CAMPBELL: It began to move both morphine and heroin, really, into the fringes of the underworld.

ARABLOUEI: After all, if people couldn't get what they needed from a doctor, they were probably going to look for it somewhere else.

MACY: The moment they were prescribed and that prescription ran out, they were soon experiencing that feeling of dope sickness.

ARABLOUEI: Again, Beth Macy.

MACY: That excruciating withdrawal that's like the worst flu times a hundred. And then they're going to the black market for heroin or for pills.

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UNIDENTIFIED PERSON #6: They want your sweet, innocent girls to take the bull so they can be enticed into honky-tonks.

ABDELFATAH: Not long after that, in 1920, prohibition began, banning alcohol throughout the country.

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UNIDENTIFIED PERSON #6: I say alcohol must go.

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CAMPBELL: And during that time, organized crime, also called the syndicate, begins to grow.

ABDELFATAH: Underground networks of alcohol smugglers began popping up everywhere, importing alcohol from countries around the world. And those networks made it easy to smuggle in other things, too.

CAMPBELL: So you begin to get markets for illicit products.

ABDELFATAH: Products like heroin. So heroin started to be seen as a drug of the underworld - a quote, unquote, "street drug." And in 1924, the government outlawed heroin altogether, making it completely illegal, even for medicinal use, pushing the heroin market even further underground.

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ARABLOUEI: Fast forward to the 1940s. World War II is coming to an end.

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ARABLOUEI: And a lot like the post-Civil War period, opioids became a big issue in post-World War II America.

CAMPBELL: Yes. Every war has its drug. And what typically happens is, after wars end, that drug becomes a domestic problem. We have not thought well about how the practice of war seems to require so much pharmaceutical support.

ARABLOUEI: During the war, the supply of opioids dried up. But after the war ended, opioids began flooding into the black market through illicit networks.

CAMPBELL: You begin to see heroin traffic heat up.

ABDELFATAH: These black markets were mostly concentrated in big cities, where a lot of the drug routes pass through. So by this time, the average opioid addict looked different.

CAMPBELL: The median age falls to age 20 or so. It's more frequently someone from a community of color - African-Americans, Puerto Ricans in New York.

COURTWRIGHT: So by the 1940s and 1950s, narcotic addiction in the United States is mainly centered on big cities and it's mainly a matter of drug traffickers smuggling the drug, heroin, into the country and distributing it through various illicit networks.

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UNIDENTIFIED REPORTER #5: U.S. Customs officers and police are having another drive to round up dope smugglers. And here's some of the swag. Concealed in barrels of olive oil, they find millions of dollars' worth of deadly heroin, enough, they say, to kill six million people.

CAMPBELL: So in 1951, Congress is concerned enough about the situation that they passed the first mandatory minimum sentences for drug use.

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ARABLOUEI: Otherwise known as the Boggs Act.

CAMPBELL: They cannot say these are innocent teenagers who are preyed upon by dealers. They have to sentence them to five, 10, 15 years, depending upon the quantity they possess at the time of the arrest.

ARABLOUEI: And keep in mind, these heroin markets were in majority black and brown neighborhoods in cities. So the Boggs Act disproportionately affected those communities.

COURTWRIGHT: What we think about addicts depends very much on who is addicted. Again and again, in the literature, you'll see this distinction being made between medical users or medical addicts and pleasure users or recreational users, and they were generally considered to be more blameworthy.

ARABLOUEI: Morphine addicts were seen as medical users, heroin addicts as recreational users.

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UNIDENTIFIED PERSON #7: But there's one sure thing. This is one game nobody beats. If you use narcotics, before long, you'll have the habit.

COURTWRIGHT: Another way to say this is that if the composition of the addict population hadn't changed - if we had the same pattern of mostly medical, mostly female, mostly morphine addicts that we'd had in 1870, then I don't think American drug policy would have taken the punitive turn that it did.

ABDELFATAH: In the 1950s, that punitive approach got even more intense. Hearings were held in 14 major cities across the country. Politicians declared war on heroin.

CAMPBELL: And Congress decides to stiffen those penalties, allow for deportation of foreign nationals and the death penalty to dealers.

COURTWRIGHT: It wasn't the drug problem in the United States. It was the heroin problem.

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UNIDENTIFIED PERSON #8: Most of the known addicts are addicted to heroin. Here is heroin - this white powder.

COURTWRIGHT: As far as the policymakers in Washington were concerned and as far as the police in most American big cities were concerned, heroin was the drug to worry about in the '50s and the '60s and early '70s.

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ABDELFATAH: Despite all these efforts, heroin remained on the streets. And drug users continued to be treated as criminals.

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RICHARD NIXON: America's public enemy number one, in the United States, is drug abuse.

ARABLOUEI: Until a new opioid appeared on the scene.

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ABDELFATAH: Part III - OxyContin.

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ARABLOUEI: OK, first question. Have you ever heard the name Sackler? It probably sounds familiar because it pops up on buildings everywhere.

PATRICK KEEFE: On universities and hospital buildings and medical facilities and art museums the world over.

ARABLOUEI: Plus it's been in the headlines a lot lately for multiple lawsuits. The Sacklers are one of the richest families in America. And for generations now, they've had a real sweet spot for philanthropy. And you may be wondering...

KEEFE: Well, where did all that money come from?

ARABLOUEI: The answer to that question gets at the thing that the Sacklers are facing lawsuits over - whether they bear some responsibility for the opioid epidemic.

KEEFE: There's a kind of conversation I think we have in America where we realize that a lot of our great cultural and educational institutions were built on money that we would now think of as tainted money.

ARABLOUEI: This is Patrick Radden Keefe. He writes for The New Yorker. And Patrick spent months investigating the history of the Sacklers for a piece called "The Family That Built An Empire Of Pain." He says the story of how the Sacklers made their money is also the story of how the drug at the center of today's opioid crisis, OxyContin, came to be.

ABDELFATAH: It all begins in the 1950s...

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ABDELFATAH: ...With three brothers in Brooklyn.

KEEFE: Arthur and Mortimer and Raymond Sackler.

ABDELFATAH: They're from an immigrant family.

KEEFE: They're - grow up in the Great Depression.

ABDELFATAH: And all three of them...

KEEFE: All three brothers train as doctors.

ABDELFATAH: The oldest brother, Arthur Sackler, is kind of the patriarch of the family.

KEEFE: He's this gap-toothed, brilliant, brilliant guy who becomes a doctor.

ABDELFATAH: Specializes in psychiatry.

KEEFE: Does a huge amount of pathbreaking medical research in the 1950s.

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ABDELFATAH: Arthur and his brothers authored more than a hundred studies on the biochemical roots of mental illness. In other words, they challenged a lot of Sigmund Freud's ideas. Despite his success in that field, Arthur Sackler began to get restless. After all, he was a natural-born entrepreneur. So...

KEEFE: On the side...

ABDELFATAH: ...Arthur joined and later bought an ad agency that specialized in medical advertising.

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JOHN HAMM: (As Don Draper) It's clean. It's simple. And it's tantalizingly incomplete. What's missing?

ARABLOUEI: I thought of him was almost a kind of Don Draper figure, where, in the 1950s, you have this revolution in advertising in which all of these new persuasive techniques are being brought to bear to sell everything from gym socks to Ford convertibles. And Arthur Sackler has this revelation, which is, what if we applied some of those bells and whistles to the way we sell drugs, the way we sell medicine? He's the father of modern pharmaceutical marketing.

DAVID HERZBERG: I don't mean to, you know, rain on a parade or anything, but I've been a little bit surprised to hear him credited as the inventor of this phenomenon, which seemed to me to be everywhere in the 1950s.

ARABLOUEI: This is David Herzberg. He's a professor of history at the University at Buffalo.

HERZBERG: There was this purposeful turn in the 1950s to really institutionalize and expand consumer markets in all their various forms and guises, from real estate to pharmaceuticals.

ARABLOUEI: Arthur Sackler may not have been the only one breaking into the medical advertising game at the time, but he was definitely one of the best because his approach was innovative. Back in the early 1900s when Bayer tried advertising heroin, their marketing campaigns were basic.

CAMPBELL: If you look at any of these early-20th-century ads that Bayer puts out...

ARABLOUEI: Again, Nancy Campbell.

CAMPBELL: It's not really made visual in the ways that we think of advertising as being visual.

ARABLOUEI: In other words, they were pretty boring.

ABDELFATAH: And what Arthur realized that the people at Bayer hadn't was that advertising a drug is an art of seduction. And it doesn't actually begin with the consumer - the patient.

PATRICK RADDEN KEEFE: The first person you need to seduce is the doctor.

ABDELFATAH: Why?

KEEFE: People trust doctors. And he trusted doctors. And so if you have an endorsement from a doctor, it's like putting Mickey Mantle on a box of Wheaties.

ABDELFATAH: So he started developing ad campaigns...

KEEFE: Brilliant and very persuasive advertising campaigns.

ABDELFATAH: ...With doctors at the center of them.

KEEFE: You want to sell a lot of a drug, you sell it to these doctors who will then prescribe it to their patients.

ARABLOUEI: Which sounds pretty similar to how morphine spread.

ABDELFATAH: Right. But in this case, the business model was much more deliberate.

KEEFE: And this ended up becoming, I think, a really key aspect of how we got to where we are with the opioid crisis is that - it's one thing to go out on a street corner and try and find some sketchy person who's going to sell you something in an alley. It's another thing altogether to go into your doctor's office and have your doctor write you a prescription.

ARABLOUEI: But doctors were skeptical of prescribing opioids.

HERZBERG: Physicians and patients have now learned their lesson. And so...

ARABLOUEI: Arthur, along with other pharmaceutical companies at the time, turned to two different classes of drugs called barbiturates and benzodiazepines.

HERZBERG: Which were not opioids and were - they're not derived from plants, so their manufacture and circulation was relatively controlled. They didn't seem like they posed a problem. And as a result...

CAMPBELL: We've had a new acceptance of the idea that there is a pill for every ill and that taking pills can support productive everyday lives.

ARABLOUEI: And Arthur Sackler's marketing techniques played a big part in that shift.

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KEEFE: He develops his first real fortune marketing drugs like Valium. And he sort of brings along his brothers, Mortimer and Raymond. And they end up having a - buying a small pharmaceutical company called - at the time, it was called Purdue Frederick. And the company starts developing a succession of drugs.

ABDELFATAH: During the 1950s and '60s, Arthur and his brothers began making so much money. We're talking millions and millions of dollars.

ARABLOUEI: They were a company that knew how to market their products really well, which is the goal of any business.

ABDELFATAH: And a lot of people did benefit from these drugs.

ARABLOUEI: But their success and the growing pharmaceutical industry made some politicians suspicious. So Congress held a hearing about the pharmaceutical industry and called Arthur Sackler to testify.

KEEFE: And he was a genius. I mean, he was a really brilliant guy. And he just - I've read the transcripts. And he dances circles around these guys.

ARABLOUEI: In Keefe's New Yorker piece, he quotes from a Congressional staffer's memo. "The Sackler empire is a completely integrated operation in that it can devise a new drug in its drug development enterprise, have the drug clinically tested and secure favorable reports on the drug from the various hospitals with which they have connections."

KEEFE: It's like they have drugs that they're developing and then medical journals that can run articles about the drugs and then doctors who can go out and promote those drugs. So it becomes this extraordinarily sophisticated, self-serving system.

ABDELFATAH: Arthur and his brothers came out of the hearing unscathed. Their drugs kept selling. They kept making money. Doctors and pharmaceutical companies became more and more intertwined. And that idea - that there's a pill for every ill - became the new status quo. But almost none of those pills were opioids. Remember; after morphine and heroin, doctors were resistant to prescribing opioids in any form because they turned out to be really addictive.

HERZBERG: Heroin was criminalized in 1924 and sales of morphine and other familiar opioids were restricted robustly. The pharmaceutical industry tried to introduce new blockbuster opioids every few years for the next 70 years, but these kinds of campaigns were never allowed to come to fruition. There was a very fierce counterattack against any idea that there could be such a thing as a non-addictive opioid.

ARABLOUEI: But in the 1990s, that started to change. In fact, pain itself was redefined.

MACY: Yeah. So early to mid-'90s physicians, pharmaceutical companies, pain groups funded by pharmaceutical companies...

ABDELFATAH: Again, Beth Macy.

MACY: ...Started pushing this notion that we had this epidemic of untreated pain.

ARABLOUEI: Pain became reclassified as a fifth vital sign, like blood pressure, heart rate, temperature.

HERZBERG: You also began to get different ideas about the safety and applicability of opioids for people experiencing pain in the 1990s that comes out of a few, at first, marginal figures in the pain reform movement. But these marginal figures, with shocking rapidity, become dominant figures who are claiming that opioids are, in fact, terribly underused, that they are one of the best and first-line treatments for a much wider range of pain. And the reason that these quite radical reinterpretations of opioids go from the margins to the mainstream so rapidly is because of funding from people like the Sacklers, who give them a megaphone for their voices.

ABDELFATAH: At the same time, Purdue Pharma was developing a new drug based on the opioid oxycodone. By this time, Arthur Sackler had passed away. And Richard Sackler - Arthur's nephew - was a leader in the company now called Purdue Pharma. And in 1996...

ARABLOUEI: Purdue released OxyContin.

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ABDELFATAH: To market OxyContin, Arthur Sackler's living relatives and Purdue Pharma took his approach to a whole new level.

ARABLOUEI: Starting with the FDA.

KEEFE: There was a evil-genius sophistication to the whole arsenal of tricks that were employed to persuade the FDA.

ABDELFATAH: When the FDA approved OxyContin in 1995, it approved a claim that Oxycontin was safer than other, similar drugs on the market with this wording, quote, "delayed absorption, as provided by OxyContin tablets, is believed to reduce the abuse liability of a drug," end quote.

ARABLOUEI: Oxycontin's biggest selling point was that it had a time-release mechanism built into it. So if you took one pill, the drug would be slowly released over the course of 12 hours, offering you longer-lasting pain relief and supposedly...

ABDELFATAH: Supposedly.

ARABLOUEI: ...Making it less addictive.

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HERZBERG: There was no research behind that claim, but it seemed to make sense.

ARABLOUEI: Purdue Pharma didn't provide any clinical studies on how addictive its drug might be.

ABDELFATAH: Persuading the FDA was just the first step. The next step...

KEEFE: Persuade doctors and patients not only that this drug wasn't addictive, but that it was actually a safer bet than some of the other drugs on the market.

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UNIDENTIFIED PERSON #9: We doctors were wrong in thinking that opioids can't be used long-term. They can be and they should be.

ABDELFATAH: They aired ads like this one promoting OxyContin.

ARABLOUEI: They hired an army of pharmaceutical sales reps to travel across the country, marketing OxyContin. They flew doctors to tropical destinations for weekend getaways.

ABDELFATAH: They targeted doctors in rural and poor communities who were already prescribing other opioids.

HERZBERG: OxyContin had this nickname. They called it hillbilly heroin.

KEEFE: Which means - initially, at least - their customer base was majority white. Drugs like Oxycontin...

HERZBERG: Were prescribed primarily to white patients, number one, because of access to the medical system, which was unequal along lines of race, but number two, public panic over heroin addiction, which was closely associated with racial minorities living in some of the larger cities. And so the idea of addiction, at this time, had become both popularly and politically associated with non-white racial groups. And as a result, there was a reluctance on the part of physicians to prescribe potentially addictive medications to those populations.

ARABLOUEI: In other words, David is saying that heroin exaggerated an already-existing racial bias among doctors. Because heroin was seen as a black and brown problem, doctors tended to believe those populations were more likely to become hooked on Oxycontin or, really, any prescription pill, and were, therefore, much less likely to prescribe it to those populations.

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ABDELFATAH: Within just a few years, it was clear to many doctors and, of course, to many patients, that OxyContin was addictive. In 2007, Purdue Pharma even pleaded guilty to criminal charges that it misbranded OxyContin in marketing by misrepresenting its risk of addiction and its ability to be abused. But by then, small communities were shaken by it, with people of almost all ages becoming addicted and thousands dying.

ARABLOUEI: Plus, doctors and researchers were finding that it led to heroin use. Just like with morphine, when the prescription ran out, heroin became the Plan B, pushing people to seek out heroin, as well as fentanyl, on the black market.

ABDELFATAH: What started out as a, quote, unquote, "hillbilly drug" now...

KEEFE: Crosses ethnic, geographic, regional, socioeconomic lines.

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ARABLOUEI: Now, it might be easy to forget about the Sacklers in all of this. But lately, they're becoming harder to ignore. Some museums have even been rejecting their donations.

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CINDY HSU: Dozens storm the Guggenheim Museum to protest a donor's alleged ties to the opioid crisis.

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RICK SANCHEZ: Yesterday, the National Portrait Gallery in London canceled a million-dollar donation. How dirty does someone's money have to be for a charity to turn down a donation of $1 million?

ABDELFATAH: Along with Purdue Pharma, members of the Sackler family are facing multiple lawsuits over OxyContin.

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UNIDENTIFIED REPORTER #6: Several members of the billionaire Sackler family...

UNIDENTIFIED REPORTER #7: Today, the attorney general of Massachusetts pushed for the release of more documents from Purdue Pharma...

ANDREW NAPOLITANO: The Sackler family purporting to, as lawyers like to say, pierce the corporate veil.

ARABLOUEI: In documents released in these court cases, we've learned that the company is accused of not reporting illegal activity to the government, like improper prescribing by doctors. For example, it's alleged a Purdue sales manager wrote to a company official that Purdue was circulating opioids to an illegal pill mill. The employee wrote, quote, "I feel very certain this is an organized drug ring. Shouldn't the DEA be contacted about this?", end quote. Purdue allegedly did nothing about that email for two years.

ABDELFATAH: We've also learned that Richard Sackler seems to have been especially aggressive in pushing the marketing and sale of the drug. One of the lawsuits alleges that he badgered sales managers constantly - nights, weekends and holidays - pushing them to sell more. These campaigns were focused on getting doctors to prescribe higher doses to their patients.

ARABLOUEI: The thing is Purdue and the Sacklers have been in this position before. But in the past, even when they've been found guilty and forced to pay hundreds of millions of dollars in fines and damages...

MACY: It's like me giving you a hundred dollars.

ABDELFATAH: Just a drop in the bucket - not much harm done. But that could change.

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UNIDENTIFIED REPORTER #8: Purdue Pharma, the maker of OxyContin, agreed to pay $270 million to the state of Oklahoma. The settlement allows Purdue...

ABDELFATAH: There are currently more than 1,600 cases against Purdue Pharma in federal and state courts.

ARABLOUEI: We reached out to Purdue Pharma for comment. And they say, quote, "it is deeply flawed to suggest that activities that last occurred 18 years ago are responsible for today's complex and multifaceted opioid addiction crisis. The bulk of opioids prescribed are not and have never been OxyContin, which represents less than 2 percent of current opioid prescriptions, and in total, never exceeded 4 percent in any year."

KEEFE: Whatever they're telling themselves, the real legacy here is OxyContin and the opioid crisis.

HERZBERG: But I think that there's a risk to attributing it - too much of this to this one family. I mean, it does make for a good story, but it means that it's possible to lose sight of the broader dynamics and the broader structures that made them able to do what they did. You know, while they're clearly villains in this story - and you get no debate with me about that - the circumstances which made their villainy possible are, in some ways, more important to understand than the fact that those were bad guys.

ABDELFATAH: So David says the opioid story is bigger than the Sacklers or OxyContin or Purdue. It's about our relationship with pain and our very human desire to get rid of it - something people have been trying to solve for forever.

HERZBERG: Life involves a lot of suffering and pain. People desperately want relief for it. And so when you hear of something that's new and that there's people with MDs and PhDs after their name, saying, this might be different this time around - sure, if you existed in some pure form of rationalism, you might say, well, you know, that's a little unlikely. But if you're suffering and you want to believe - as, you know, I'm sure all of us have at various times - these things - it matters.

ARABLOUEI: The Sacklers and Purdue tapped into this need for pain relief and made enormous amounts of money in the process. But they aren't the only ones. Big Pharma is much more than one company. It's a vast network built on strategic pharmaceutical marketing, lack of government oversight and a whole lot of money.

ABDELFATAH: And I sort of feel like we've been grappling with a version of this problem going all the way back to the Civil War. I mean, sure, it's become this sophisticated system now. But the struggle to figure out what to do with new, better drugs for treating pain and how to deal with their unintended consequences - like, that's not new. Then and now, it raises the same questions. How do we know what pain to live with and what pain to treat? And what are the social costs of continuing to address pain with innovative but potentially addictive drugs?

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ABDELFATAH: That's it for this week's show. I'm Rund Abdelfatah.

ARABLOUEI: I'm Ramtin Arablouei.

ABDELFATAH: And you've been listening to THROUGHLINE from NPR.

ARABLOUEI: This episode was produced by Rund and I.

ABDELFATAH: Our team includes...

JAMIE YORK, BYLINE: Jamie York.

JORDANA HOCHMAN, BYLINE: Jordana Hochman.

LAWRENCE WU, BYLINE: Lawrence Wu.

NOOR WAZWAZ, BYLINE: Noor Wazwaz.

MICHELLE LANZ, BYLINE: Yo, yo, yo, it's Michelle Lanz. (Singing) Say my name, say my name.

N'JERI EATON, BYLINE: (Laughter) OK, smizing or somber? N'jeri Eaton.

ARABLOUEI: Thanks also to Anya Grundmann.

ABDELFATAH: Chris Turpin.

ARABLOUEI: Gisele Grayson.

ABDELFATAH: Andrea de Leon.

ARABLOUEI: Greta Pittenger.

ABDELFATAH: And Mark Memmott. Our music was composed by Kristina Reznikov and Drop Electric.

ARABLOUEI: And a special thank you to Columbia University Oral History Project and David Courtwright for letting us use the powerful interviews they did with people who struggled with addiction.

ABDELFATAH: If you like something you heard or you have an idea for an episode, please write us at [email protected] or hit us up on Twitter, @throughlinenpr.

ARABLOUEI: Thanks for listening.

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