Drugs kill more Americans than guns, cars and AIDS. How we got here.

Dr. Bill Fannin found his son unconscious in his bedroom. Medical training and a father’s love told him what to do.

Give him breath. Start his heart.

The Pikeville, Kentucky, physician cupped his son’s face and tried to resuscitate him on this October evening in 2011. He pushed down on his son’s chest.

Sean Fannin laid there, still unmoving.

“It was,” Fannin recalled, his voice fading as he spoke, “too late.”

COMPLETE COVERAGE: The science of opioids

He soon learned Sean had overdosed on a drug derived from the opium poppy.

It was a drug the doctor knew all too well, one he had prescribed to many patients to ease their pain.

'God's own medicine'

In Greek myth, when the goddess Aphrodite wept at the death of her lover, Adonis, her tears gave birth to a new plant. The colorful poppy contained a milky substance that promised to wash away sorrows.

The Greeks worshipped the opium poppy, and so did the Egyptians. Doctors, including Hippocrates, the “Father of Medicine,” discovered that opium seemed effective in fighting certain diseases.

But dangers followed. The Roman naturalist Pliny the Elder recorded fatal opium overdoses, and the Greek physician Erasistratus condemned the drug as a deadly poison.

Still, opium spread around the world.

Hoping to turn opium into a better medicine, German scientist Friedrich Serturner extracted a substance from the poppy in the early 1800s. He named the new drug “morphine” after Morpheus, the Greek god of dreams, dubbing it “God’s own medicine.”

Hospitals welcomed the painkiller and so did the battlefield, but by the end of the Civil War, so many soldiers were suffering from addiction that it became known as the “Army Disease.”

In response to that problem, Heinrich Dreser and others working for Bayer in Germany tried to develop a drug that would keep the medicine’s positive properties while removing its deadly and addictive nature.

Dreser tried the new drug out on animals. Then he tried it on himself and others, who reported the substance made them feel better. Even heroic.

He found that the new drug worked better than another opium-derived drug, codeine, on respiratory diseases. After trying the drug out on a number of people, he promised doctors it wasn’t addictive.

“It possesses many advantages over morphine,” he wrote in the Boston Medical and Surgical Journal. “There’s no danger of acquiring a habit.”

In 1898, Bayer began selling this supposed wonder drug, marketing it as a cough suppressant. Doctors also used the drug to treat pneumonia, tuberculosis, menstrual pain and even morphine addiction.

The new drug’s name? Heroin.

Within a year, Bayer was producing a ton of heroin, marketing it as a cough syrup for children and a medicine to fight pneumonia and bronchitis.

“With Bayer’s Heroin Syrup one manages to have a restful sleep,” promised one advertisement featuring children.

In reality, heroin turned out to be even more potent, addictive and deadly than morphine.

Some addicts crushed heroin pills and snorted the substance. Others injected the drug directly into their veins for a quicker high.

Hundreds of thousands of Americans became addicted to these opium-derived drugs, said David T. Courtwright, author of “Dark Paradise: A History of Opiate Addiction in America.”

The average addict was a middle- or upper-class white woman suffering from chronic pain, often introduced to the drug by her physician, he said.

In response to the epidemic, Congress gave the responsibility for protecting the nation’s food and medicine to a scientific bureau stuck in a basement of the Department of Agriculture building. The bureau became known as the Food and Drug Administration.

In 1914, Congress backed the Harrison Narcotics Tax Act, which regulated and taxed products derived from the opium plant and the coca leaves (used to produce cocaine). Patients now needed prescriptions from doctors to obtain powerful narcotics.

In the decades that followed, federal officials continued their crackdowns. They prohibited heroin from medical use and limited other opium-derived painkillers to patients recovering from surgery or other injuries or suffering from cancer or other terminal diseases.

Categories of pain

Growing up in Prestonsburg, Kentucky, Fannin spent lots of time in the woods and figured he would be a game biologist.

His father wanted him to practice medicine, but becoming a doctor seemed impossible.

After spending time in martial arts, he realized that by setting goals and working hard, he could achieve anything.

Looking back, he recalled, “God had plans for me, it seems.”

A cousin who was a physician offered Fannin a job and soon became a role model. Fannin attended the University of Kentucky’s medical school and trained under a pain specialist.

He learned that pain fell into three categories: acute, cancer-related and chronic.

Doctors typically treated patients who suffered acute pain (for instance, after surgery or an accident) with a short-term prescription of opioids mixed with less powerful painkillers, such as aspirin or acetaminophen (coming under brand names such as Percodan, Vicodin, Percocet and Lortab).

Doctors typically treated patients suffering from cancer-related pain with opioids such as morphine. For patients with serious or terminal diseases, addiction was much less a concern.

Doctors hesitated to prescribe these powerful opioids to patients suffering from chronic pain (pain that lasts more than three months, such as lower back pain) because doctors feared these patients might become addicted after taking these opioids for so long.

Fannin understood some pain patients responded to physical therapy. Some could reduce their pain through biofeedback as patients began to learn from their bodies. Some could get help from chiropractors.

Pain, he realized, didn’t always need pills.

‘New class of addicts’

German scientists took another swing at the morphine molecule, and they came up with oxycodone. The opioid seemed to have fewer side effects, but it was no less addictive.

In 1950, the FDA approved Percodan, which combined oxycodone with aspirin. Nearly a quarter-century later, Percocet — a combination of oxycodone and acetaminophen — followed.

Those opioids began to be abused. By 1962, doctors had prescribed nearly 36 million Percodan in California, with the chief narcotics enforcement official complaining that people were “eating Percodan as though it were popcorn,” and the state’s attorney general concluding that the drug was creating a “new class of addicts composed of otherwise honest, not criminally inclined persons.”

Addicts eventually included singer Elvis Presley, who died of a drug overdose in 1977, and comedian Jerry Lewis, who received the opioid after a spinal injury and became addicted for 13 years.

In the 1980s, some doctors, including pain specialist Dr. Russell Portenoy, called attention to millions of Americans suffering from “untreated pain,” saying opioids offered the solution. He became the first president of the American Pain Society, which drugmakers helped fund.

The society campaigned for health care providers to make pain the “fifth vital sign,” joining blood pressure, temperature, heartbeat and breathing.

“We had to destigmatize these (opioids),” Portenoy told The Wall Street Journal. “We had to bring them out of the cold into the mainstream medical practice. We had to have doctors think in terms of risk and benefit instead of thinking of these consequences that are so scary — like addiction and death.”

In 1989, the Texas Medical Board adopted language to support wider use of painkillers by doctors. Other states followed.

The Federation of State Medical Boards, which received up to $2 million from drugmakers, recommended doctors not face punishment for prescribing large amounts of opioids and called on those boards to punish doctors who “undertreated” pain.

By the 1990s, juries awarded more than $16 million to patients and families whose loved ones suffered from pain, concluding that the nursing homes, nurses and doctors that failed to give opioids were guilty of negligence.

Addiction specialist Dr. Drew Pinsky said this development made doctors wary about failing to prescribe opioids to any patient who complained of pain. From that point forward, he said he began to refer pain patients to pain clinics.

‘The fifth vital sign’

By the mid-1990s, Fannin, who served in the Army in Vietnam, was working part time at a Veterans Affairs clinic in Prestonsburg, treating war veterans.

That was where he first heard doctors call pain “the fifth vital sign.”

It seemed odd to equate pain with something like breathing, but he understood the need to “dignify” and take care of pain.

He noticed that doctors seemed too willing to prescribe these opioid pills for chronic pain, patients seemed too willing to take them, and insurers seemed too willing to pay.

“Pain as the fifth vital sign” became policy at the VA clinic where he worked as well as VA hospitals across the U.S.

The Joint Commission began requiring hospitals to assess all patients for pain on a scale of 1 to 10, which some claimed caused more doctors to prescribe opioids.

Purdue gave the commission a grant to produce a pain assessment and management manual.

Officials from the commission and Purdue denied the company had anything to do with the content of the manual, co-written by Dr. June Dahl, who served on the speakers bureau for Purdue.

The manual told health care facilities the side effects of opioids had been exaggerated and that physical dependence had been wrongly confused with addiction. “There is no evidence that addiction is a significant issue when persons are given opioids for pain control,” the manual said.

Purdue officials explained that studies on opioid addiction depended on many factors, including mental health. They cited a 2008 article by Dr. David Fishbain of the University of Miami, who analyzed 79 published studies, saying he concluded the prevalence of abuse or addiction was 3.27 percent, or 0.19 percent for those with no past addiction.

Fishbain responded that his study was misinterpreted and that addiction could be anywhere between 3.27 and 20.4 percent.

Commission officials denied its new standards encouraged doctors to prescribe more opioids, blaming drug trafficking as well as diversion and abuse by individuals.

At that time, the “evidence was broadly supported by experts across the spectrum that pain was undertreated and a serious problem leading to poor clinical outcomes,” the commission said.

The commission concluded that “millions of people in the United States suffer from pain, and failure to treat their pain is inhumane.”

The painkiller market

Since 1987, Purdue Pharma had been selling a timed-release drug named MS Contin, the company’s version of morphine. Seven years later, annual sales topped $88 million — the best performing painkiller Purdue officials had — but they faced problems.

Doctors knew how addictive morphine could be, and most were reluctant to prescribe MS Contin to patients suffering from chronic pain.

The even bigger problem? MS Contin’s patent would expire soon.

That meant generic drug manufacturers could make their own versions of MS Contin and eat into Purdue’s share of the painkiller market.

A generation earlier, Arthur Sackler, the brother of Purdue’s owners, had marketed Valium and other tranquilizers to women experiencing anxiety, tension or countless other symptoms. The drug broke all sales records, turning many women into addicts and Sackler into a multimillionaire.

The Sackler family planned to repeat that success with a timed-release version of OxyContin, the company’s version of oxycodone.

In internal Purdue documents obtained by the USA TODAY NETWORK, company officials gushed that OxyContin could become a hit in “the $462 million Class II opioid marketplace.”

These documents detail their strategy: They would first market OxyContin strictly for cancer pain, where doctors were familiar with oxycodone.

Then the company would pivot to the lucrative market of chronic pain, which afflicted at least 25 million Americans.

Purdue’s plan included targeting primary care physicians, surgeons, obstetricians and dentists. The company even targeted home care and hospice care nurses who would “rate the patients’ pain and make a recommendation on the type of opioid and dosage for pain control.”

The plan also included targeting patients and caregivers through Purdue’s “Partners Against Pain” program. “You are the pain authority,” the website reassured patients. “You are the expert on your own pain.”

The website declared that “there are 75 million Americans living with pain, although pain management experts say they don’t have to,” reassuring patients that doctors could control their pain “through the relatively simple means of pain medications” and that the risk of addiction to opioids “very rarely occurs when under medical supervision to relieve pain.”

To ensure that OxyContin became a hit, Purdue sponsored more than 20,000 educational programs to encourage health care providers to prescribe the new drug and sent videos to 15,000 doctors.

The company also hosted dozens of all-expenses-paid national pain management conferences, where more than 5,000 physicians, pharmacists and nurses were trained for the company’s national speakers bureau.

By 2001, Purdue was spending $200 million on marketing and promotion and had doubled its sales force to 671. Before the year ended, sales bonuses reached $40 million.

Addiction knowledge: ‘zip’

Fannin remembers sales reps from Purdue flooding doctors’ offices in Appalachia, where poverty and pain are constant realities.

The reps gave away fishing hats, stuffed toys and music CDs titled “Get in the Swing with OxyContin.”

“Every time you turned around, you saw their faces,” Fannin said. “We had a population of doctors with very little grounding in pain, and I think Purdue took advantage of that.”

Many doctors knew about oxycodone from Percocet, which combined a small dosage of the potent opioid with 325 mg of acetaminophen.

What many of those doctors didn’t realize was that oxycodone was nearly twice as powerful as morphine, delivering a powerful high to those who use the drug.

“It’s more like heroin,” explained Dr. Andrew Kolodny, co-director of the Opioid Policy Research Collaborative at Brandeis University. “It crosses the blood-brain barrier more quickly.”

But the sales reps never mentioned that. Instead, they said OxyContin didn’t create highs like other opioids and was less likely to get people addicted.

Fannin recalled sales reps calling OxyContin “a revolution in pain care” and “much more effective” than the old drugs.

They also talked of studies, citing one that found only four of 11,882 patients — less than 1 percent — became addicted after using opioids. Portenoy and others repeatedly cited this research, with some calling it a “landmark study.”

The truth is it wasn’t even a study. It was a five-sentence letter to the editor that a doctor wrote the New England Journal of Medicine.

For the most part, Fannin believed what the sales reps were telling him, and so did other doctors in the region.

“Our knowledge about addiction,” he said, “was about zip.”

So they spread the opioid with their prescription pads, and it settled into the Appalachian mountains like the ever-present morning fog.

OxyContin, which some hailed as a “miracle drug,” became the blockbuster in 2001 that Purdue officials dreamed of, with more than 7 million in prescriptions and nearly $3 billion in revenue.

By 2015, the Sackler family, who owned Purdue, had made $14 billion, joining Forbes’ 2015 list of America’s richest families, edging out the Rockefellers.

‘It was a setup’

Believing he was easing pain, Fannin turned increasingly to OxyContin.

He typically prescribed it for people suffering for more than a year from chronic, non-cancer pain. He considered it “a good tool” for patients with serious back injuries, estimating that 150 or more of his patients took OxyContin back then.

“Some doctors were more conservative” about prescribing the pills, he said. “Some prescribed them more freely.”

Fannin believes doctors bore part of the blame for overprescribing OxyContin, but he believes Purdue bore blame, too.

“From the get-go, it was a setup,” he said. “This drug got turned loose in eastern Kentucky.”

A nation addicted

The trickle of OxyContin turned into a flood across the U.S. In five years, the drug’s prescriptions for chronic, non-cancer pain shot up almost tenfold from about 670,000 in 1997 to 6.2 million in 2002.

At a conference sponsored by Purdue, Dr. Jeffrey Summers, a pain specialist in Flowood, Mississippi, recalled a law enforcement officer insisting that OxyContin couldn’t be abused, and that was why it had almost no street value.

When the doctor asked one of Purdue’s experts about this, he said the expert replied that OxyContin couldn’t be abused by crushing or chewing because “the oxycodone would be released all at once.”

Summers said that instant release “became the primary reason OxyContin was abused,” producing a heroin-like high for abusers.

Admitted abusers of OxyContin jumped from 400,000 in 1999 to nearly 3 million in 2003. By 2009, abuse of prescription painkillers had played a role in the nation’s record 1.2 million emergency room visits.

Former Mississippi Attorney General Mike Moore, who led the litigation against tobacco companies and is now involved in the litigation against opioids makers, said a Purdue salesman told him that each morning he would look at reports detailing doctors in his territory who had prescribed OxyContin or other opioids.

Moore said the salesman told these doctors that OxyContin was less addictive, that it lasted 12 hours and that it was OK to increase the dosage to 40 mg to ensure that pain was controlled.

“Sales skyrocketed,” Moore said, “and a nation became addicted.”

Getting hooked

It didn’t take long for Fannin to realize something was wrong. Instead of reporting less pain over time and needing less OxyContin, patients complained of worse pain and asked for more pills as their bodies grew more tolerant to the drug.

They were getting hooked.

Scientific studies countered Purdue’s claim of a “less than 1 percent” addiction rate, showing that as many as 1 in 4 who took prescription opioids long term for non-cancer pain struggled with addiction.

In the years that followed, more than 2 million Americans began to abuse prescription opioids or become dependent on them, including some of Fannin’s patients.

“I would’ve put a lot fewer people on that medicine if I knew then what I know now,” Fannin said. “I created problems and I didn’t know it. I created problems for people because of my ignorance.”

Many other area doctors did the same. And a small percentage actually pushed the drug for profit, opening so-called “pill mills” where people could get OxyContin for cash just by asking, even with no medical need.

Though these physicians were “looked down upon,” Fannin said, “we didn’t police our own ranks.”

Gradually, pills spilled onto the streets. Addicts sold them to fuel their habits. Poor patients in real pain sold some to stay afloat. Children and teens raided medicine cabinets and sold them at school.

‘Unleashed … dangerous drug’

Soon America was awash in OxyContin, and other opioids followed.

Those prescriptions had consequences. By 2001, the number of deaths related to oxycodone had risen fivefold.

In 2007, Purdue’s holding company pleaded guilty to “misbranding” OxyContin, admitting that sales reps “with intent to defraud or mislead” had promoted the drug as less addictive and less likely to be abused than other opioid painkillers.

“With its OxyContin, Purdue unleashed a highly abusable, addictive and potentially dangerous drug on an unsuspecting and unknowing public,” U.S. Attorney John Brownlee of Virginia announced.

Purdue, a privately held company in Stamford, Connecticut, paid a $600 million fine, and three executives pleaded guilty to misbranding, paying nearly $35 million in fines.

Despite their pleas, Purdue insisted the executives had not been guilty of misleading anybody. “To the contrary,” the company’s statement said, “they took steps to prevent any misstatements in the marketing or promotion of OxyContin.”

At the sentencings, the judge gave the executives probation and community service.

Some present praised OxyContin for killing their pain. Others said the drug had killed their teenage children. One mother held up a jar that contained the ashes of her late son.

Treatment, sobriety, relapse

By then pills were everywhere — and easy for Fannin’s son to find.

Sean Fannin, the younger of two boys, was a smart kid who preferred skilled trades to medicine, telling his dad he wanted to be a welder. He would grow up to work in the coal mines for a time, like his grandfather.

As he came of age, Fannin later learned, Sean was smoking pot, drinking and eventually abusing pills. Fannin and his wife thought he had attention deficit hyperactivity disorder or a mood problem until a University of Kentucky doctor diagnosed his addiction. A psychotherapist advised residential care.

“It made me angry that I missed it,” Fannin said, “especially being a doctor.”

On the long drive to a teen recovery center in the Tennessee woods, Sean confessed his drug use to his parents. He was around 14 at the time, and this stint in recovery was the first of many.

The family filled the next several years with periods of treatment, sobriety and relapses.

The ordeal gave Fannin a new perspective on addiction.

For much of his life he hadn’t believed it was a disease. But watching his son suffer made him realize he needed to fight it like any other malady. And not just on a personal level.

While supporting Sean’s recovery, Fannin began helping others trapped by addiction — first by covering shifts for another doctor doing recovery work at a Pikeville hospital. Eventually, he became one of the few board-certified addiction specialists in eastern Kentucky.

In his family practice, meanwhile, Fannin prescribed far less OxyContin and required any patients on opioids to undergo urine screens and pill counts. He also checked their prescription history through the state’s electronic prescription drug monitoring system.

He was determined not to fuel any more addiction in his community, but he was unable to pry his son from addiction’s grip.

‘Healers become dealers’

Opioids kill first by slowing down breathing, then by depriving the brain and body of oxygen, the very stuff of life.

By 2009, drug overdose deaths had become the leading cause of accidental deaths in the U.S., surpassing traffic fatalities. The Centers for Disease Control and Prevention declared that the nation faced an opioid epidemic.

Overprescribing has fueled much of this epidemic, said Dr. Anna Lembke, an associate professor of psychiatry, behavioral sciences and anesthesiology at the Stanford University School of Medicine.

“So how did healers become dealers?” she asked.

It happened as medicine became an industry, she said, with doctors practicing “assembly-line medicine” in “health care factories.”

Factories do well with things like knee replacements, but the system breaks down when it comes to addiction, said the psychiatrist, who runs Stanford’s Addiction Medicine Dual Diagnosis Clinic. “I can make more money spending five minutes with a patient and prescribing a pill than I can spending an hour with the patient in psychotherapy.”

Two centuries ago, pain was considered beneficial, boosting the immune system, she said. “Now we consider pain dangerous — something that if left untreated will leave people with psychic scars.”

The new thinking is that a patient in pain is an aggrieved party that doctors are supposed to fix, she said. “And if they don’t, they are not only lacking in knowledge and compassion, they are amoral.”

She said physicians are taught to “first, do no harm,” and automatically prescribing opioids over the long term not only exposes these pain patients to the risk of addiction, but she said the drugs may also exacerbate their pain and slow their healing.

With millions of Americans abusing prescription opioids, Mexican cartels found a new market for their cheap heroin. In 2001, fewer than 1,800 Americans died of a heroin overdose. By 2016, those deaths had topped 15,000.

And that heroin has often been laced with synthetic opioids such as fentanyl, which is 50 times more powerful than morphine, and carfentanyl, which is 10,000 times more powerful than morphine.

Fentanyl is used to treat breakthrough cancer pain. Carfentanyl is an elephant tranquilizer, and just a few grains can kill humans. In 2016, overdoses from these synthetic opioids surpassed 20,000 deaths.

Lembke said the U.S. faces a “modern plague” with addiction, which affects more than 40 million Americans if tobacco and alcohol are included. Addiction costs the nation $442 billion in a single year, according to the surgeon general.

“Karl Marx said religion is the opium of the masses,” she said. “We are at a point in history where opium has become the religion of the masses.”

‘It honors him’

Sean Fannin’s Pikeville funeral was standing room only.

Fannin finds it tough to talk about the loss of his child, about the overdose of OxyContin and the anti-anxiety medicine Xanax that killed him at just 28.

But he’ll share his experiences with addicted patients and their families.

“Still to this day, he’ll use Sean’s story to get through to somebody,” said his longtime office manager, Amy Hunt. “And he’ll cry at the drop of a hat when he talks about it.”

The pain of his death continues to haunt Fannin and his wife, an artist and quilter. But they also treasure their son’s living legacy — a 6-year-old daughter, born shortly before his death.

Fannin, who turns 70 in February, recently retired from family practice to devote more time to hospice work and addiction treatment.

At East Kentucky Rehabilitation Center in downtown Prestonsburg, he treats patients recovering with the help of medication such as Suboxone and Vivitrol. Before he sees them, he prays with Hunt. Not only have they worked together for years, but Fannin treated her late husband’s opioid addiction, which began after he took painkillers following a mine accident.

On a recent afternoon, patients gathered in a downstairs waiting room with family members. One sidled over to another to ask what he had been doing lately. A preschool girl played near an older relative, and Hunt stopped over, bent down and cheerfully remarked on how she had gotten bigger.

There are no strangers here. Fannin has been known to spend at least 45 minutes with each patient, even if that means staying late.

Sometimes, Fannin gets a glimpse of the difference he’s making. At a local Walmart last year, a former patient walked up to Fannin with her baby, asking if he remembered her. He did.

She pointed to her husband, another former patient, who was checking out fishing poles nearby. She told the doctor they were both staying clean and doing great. She’d been pregnant when he treated her, and now had two healthy kids.

Tears flowed as she spoke to the doctor. “I just wanted to thank you.”

Fannin knew that couple was among the lucky ones. Studies show that only 1 in 10 Americans are able to get treatment for addiction.

David Gearheart, the certified alcohol and drug counselor who owns the recovery center, said, “It’s getting to the point where we could be open seven days a week, 24 hours a day. People drive two to three hours to come here. There’s just not enough treatment out there.”

Fannin knows his job is far from over. The Vietnam veteran has lived long enough to see the drug scourge claim more lives in a single year than the entire Vietnam War.

He stared out the window over downtown Prestonsburg, aching, as he always does, for his own loss. But the memory of Sean infuses his work.

“The way I figure,” Fannin said, “it honors him.”

The doctor finished off the last of his sandwich and made his way downstairs to see another patient.

He wasn’t done. He would never be done, as long as there was someone else he might save.