The Least of Us: True Tales of America and Hope in the Time of Fentanyl and Meth

by Sam Quinones

Illicit fentanyl spread first through the midwestern and eastern states. By 2018 it was all over the West as well. Overdose deaths shot farther north; more Americans died yearly than in the entire Vietnam War. Cuyahoga County, where Cleveland is located, saw overdoses double from 2014 to 2017—from 353 to 727, with almost 500 deaths involving fentanyl. San Francisco saw a similar increase between 2018 and 2020, when three times as many people died of overdoses as of COVID-19. Philadelphia had long been a heroin town, but by 2019 90 percent of 1,150 fatal overdoses were due to fentanyl.

This methamphetamine, meanwhile, prompted strange obsessions—with bicycles, with flashlights, and with hoarding junk. In each of these places, it seemed mental illness was the problem. It was, but so much of it was induced by the new meth.

This made more sense as I read what neuroscience can now tell us: that every human brain has capacity for addiction. Isolation is part of why some people get addicted and some do not. So was trauma. Abuse, rape, neglect, PTSD, a parent’s drug use were as unspoken in America as addiction and as prevalent. The epidemic was revealing this.

The twelve months ending September 2020 tallied the highest number of overdose deaths in the country’s history—87,000, according to a preliminary estimate by the Centers for Disease Control and Prevention. Much of that was due to illicit street fentanyl.

For many years only Hells Angels and other biker gangs cooked methamphetamine. Their customers were working-class Whites.

another recipe for methamphetamine was rediscovered. Japanese researchers had invented it in 1919, synthesizing it from ephedrine, a natural substance from the ephedra plant—used for millennia as a stimulant and appetite suppressant that also clears the bronchial passages. During World War II methamphetamine was marketed in Japan as hiropon, a word that combines the Japanese terms for “fatigue” and “fly away.” Hiropon was given to Japanese soldiers and kamikaze pilots to help them over their fear of death.

In the postwar years, ephedrine was used legally as an antihistamine in the over-the-counter medicine Sudafed. The ephedrine method for meth, though, lay dormant for a long time. It was rediscovered by the underworld in the United States in the early 1980s. It democratized methamphetamine. One place this happened was in the San Diego area, largely due to a man by the name of Donald Stenger. Stenger, unlike the scattered bikers that cops by then were associating with meth, was middle class, smart, deliberate, and well organized. “He was the anomaly. He was a criminal genius, and he did a tremendous amount of research,” said Jim Clem, one of the now-retired San Diego police officers who pursued him. Up to that point, the method for cooking meth that bikers were using not only stank, but also complicated. Stenger saw that the ephedrine method was easier. All you had to do was tweak one molecule in ephedrine, and you had meth. It was just cooking, following a recipe—it didn’t really qualify as chemistry. And ephedrine was legal. Stenger had no interest in popularizing the formula, but it couldn’t be contained. By the mid-1980s, every meth lab that Clem and his colleagues busted was using ephedrine.

The pursuit of Donald Stenger lasted more than a year and ranged across the West, from California to Utah to Arizona, with Stenger eluding investigators in a high-speed chase by driving into Mexico, where he reportedly owned several gold mines. Along the way, agents seized cash, planes, and a helicopter that inaugurated the San Diego Police Department’s air unit. Clem finally arrested Stenger in 1986 in Colorado. He died in 1988 at thirty-two, in custody in San Diego County, when a packet of meth he’d inserted in his rectum broke open.

Among the most fertile scientific minds of the twentieth century belonged to a Belgian chemist named Dr. Paul Janssen. Janssen was among the first to marry chemistry and pharmacology in search of new drugs. He combined them with a relentless intellect and an enormous capacity for work, becoming by the time he died in 2003, at the age of seventy-seven, the world’s greatest drug inventor. His name was on 850 scientific papers; he presided over a hive of scientists in the Belgian village of Beerse, pop. 16,000, that was a world-class example of innovation through collaboration. Together they patented more than a hundred new medicines that have transformed our lives.

At one point, eighteen of Janssen’s innovations were on the World Health Organization’s Model List of Essential Medicines. Janssen invented haloperidol—known commercially as Haldol—which calms the hallucinations of schizophrenics and allows them to be treated at home. The drug effectively ended the era of the insane asylum by convincing policymakers to release thousands of institutionalized mental patients who up to then could only be treated in a hospital. Janssen’s Center for Molecular Design eventually came up with anti-HIV compounds. His antifungal ketoconazole has been a godsend for those, like me, with flare-ups from athlete’s foot. Another drug, levamisole, kills hookworms and helps in the treatment of colon cancer.

Janssen abhorred hierarchies. Instead, he created an environment in which ideas seeped up from the people he hired. “Good scientists do not need to be supervised,” he once said. He walked daily through the Beerse compound of Janssen Pharmaceutica, alighting in one lab after another to ask, “What’s new?” He recruited heavily around the world, and his company opened labs worldwide.

(In 1961 Janssen sold his company to Johnson & Johnson, while retaining control over his research laboratory. For years he was Johnson & Johnson’s largest shareholder.)

They theorized that our brains contain receptors—tiny way stations residing on each neuron in our brains. One of these way stations—the mμ receptor—controls pain, our bowels, and our breathing. Mμ receptors were later called “opioid receptors” because drugs derived from the opium poppy seem to fit on them and produce extraordinary effects: constipation, slower breathing, sometimes euphoria, and reduced pain.

Nature’s morphine molecule—found in the opium poppy—works because it penetrates the barrier of protective fat surrounding the brain, locks onto the receptor, and stifles feelings of pain. But it does this slowly and inefficiently. Half the morphine molecules don’t make it through the fat barrier to the brain.

Studying the molecular structure of morphine and other opiates, Janssen learned that they had in common a six-sided section of their molecules known as the piperidine ring. This hexagon had a nitrogen atom attached. The combination, he surmised, must be essential to the molecule’s ability to attach to the receptor. So he did what medicinal chemists do: he manipulated the structure over and over, adding atoms to it, deleting portions, in an arduous trial and error. Finally, in 1959, he came up with a molecule that, tests showed, made its way through the brain’s protective barrier. His invention also fit on the receptor far more snugly and efficiently than did the morphine molecule. “A substantial portion of morphine doesn’t make it past that barrier in the brain,” said Carlos Valdez, a chemist at Lawrence Livermore National Laboratory in California, with whom I spoke as I tried to understand what Janssen had invented. “Heroin crosses the barrier much more easily, but then it partially converts into morphine once inside the brain tissue, slowing its absorption. The new molecule that Janssen invented crossed the blood-brain barrier very effectively, and most importantly, it wasn’t ...

On fentanyl, patients could be conscious during surgery, with blood pressure normal. Fentanyl was short-acting and could be reversed quickly with naloxone. People were in and out of it, without lingering aftereffects.

Janssen riffed off the piperidine ring over the next two decades, finding new molecules to hit the opioid receptors no matter where they were in the body. One place they reside is our bowels, which is why opiates create constipation. (Thus diarrhea is a common symptom of opiate withdrawal, as the body rebalances without the drug.) Janssen surmised that the piperidine ring might also be the basis for an antidiarrheal medicine. Trial and error led him to discover loperamide (brand name: Imodium), an opiate that attaches to receptors in our bowels but cannot cross the blood barrier into the brain and thus does not produce euphoria.

In 1974 Janssen scientists synthesized a molecule with an entirely new level of efficiency in reaching the brain. They called it carfentanil. Carfentanil was ten thousand times more potent than morphine. It had no valid use on humans, they believed, but they saw that it sedated elephants, rhinoceroses, and other large mammals. In the United States, later, carfentanil was made legal only for zoo veterinarians to possess. (UK scientists concluded that in 2002 the Russian government used carfentanil to attack Chechen rebels who had taken over a Moscow theater, dispersing it through the building’s air duct. At least 170 people died, including 121 hostages. The UK scientists based their conclusions on tests of items of clothing and blood belonging to British citizens who were near an exit and thus among the hostages revived by a Russian assault team that day. The Russian government has never commented on what it pumped through the theater beyond to say that it was a “mixture based on derivatives of fentanyl.”)

A year after Purdue’s guilty plea, overdoses surpassed car fatalities as the country’s leading cause of accidental death. Yet Americans considered it a minor problem, involving somebody else: junkies who flouted common sense and deserved what they got or, in Appalachia, hapless hillbillies who were to blame for their continued dysfunction.

Belgian winters are cold and gray, and in 1975 the Janssen compound at Beerse had little charm. The buildings were white, unremarkable; inside, their concrete corridors were lit by fluorescent tubes running along the ceiling. Yet for a week that winter, a young pharmacology professor named Gary Henderson from the University of California, Davis, walked through the compound feeling as though he’d been transported to some kind of chemistry Shangri-la. Laboratory after laboratory was crammed with the most intelligent, unassuming scientists, paid what an assistant professor in the United States might earn, yet every one of them absorbed in creating new chemicals that might be used by medicine to treat mental illness, diarrhea, or tropical fungus infection. Even the secretaries spoke four languages. “It was such a different world,” Henderson remembered. “They were people doing world-class research and living very modestly.” It was as if the research was so intellectually fulfilling that interest in material possessions wasn’t important.

Janssen spoke of a deal to distribute fentanyl in China. Chinese officials, he said, wanted a joint venture through which they could learn how to make the drug. Eventually the sides agreed. Janssen got access to the huge Chinese market and the assurance that pharmaceutical fentanyl would be manufactured at high quality. That joint venture marks the moment when China learned to make fentanyl. In 1985 Janssen opened the first Western pharmaceutical factory in China. Since then, Henderson said, “China has had the technology for producing fentanyl at an industrial level.”

Could the professor develop a test for the presence of fentanyl in a horse? Actually, the director used the term “elephant juice,” as the drug was called in the racing world, since it reputedly could stop an elephant. Hovering at the edges of the racing industry, the director explained, was a shady class of people constantly looking for chemicals that could “hop a horse or stop a horse”—make it run faster, or slower. Fentanyl, he said, did the former. The drug was a narcotic when administered to humans; it doped them, slowed them, sent them into a stupor. But it threw horses into a manic rage—cats, too, for that matter. Opioids, in fact, tend to produce strange effects in mammals other than humans. Fentanyl will turn a rat stiff, to the point where you can stand him on his head. A horse on fentanyl will tear up a stall. On the track, the drug pushed the horse to extremes.

The fentanyl-death outbreak of 2006 ceased with the closure of Distribuidora Talios. When supply halted, deaths fell. By 2007, the worst US fentanyl crisis up to that point ended. It was an example of supply reduction as the best harm reduction.

Back in the United States, meanwhile, overdoses were now the leading cause of accidental death. People addicted to prescription pain pills began switching to cheap, potent Mexican heroin. In 2016 Rapaszky took over the DEA office on Cape Cod in Massachusetts. He watched as street fentanyl became the opioid epidemic’s third phase, crowding out heroin—just as it had briefly done in south Chicago in 2006. The national death toll consequently set new annual records. On Cape Cod, every addict had had a hockey injury, or was injured on a fishing boat; either way, the doctors prescribed them opioids for the pain, and years later they were addicted and buying off the street what they thought was heroin. It was fentanyl, and many died.

Unions, meanwhile, kept asking for higher wages, unable to imagine a world competing with workers in Oklahoma, much less Asia.

In the literature of psychology, giving stuff away is a quick route to getting people to like you.

As agents busted these sites in those first years of street fentanyl, they discovered one of the reasons for this surging mortality. The amateur fentanyl mixers’ tool of choice, it turned out, was the most successful product in the history of infomercials: the Magic Bullet blender.

Still, fentanyl spread. It did so because it was the drug underworld’s great democratizer, and the Magic Bullet was some part of that. A more complicated, expensive, hard-to-find mixing machine might have deterred many of these new fentanyl dealers. Instead, the Magic Bullet was cheap—$29.95 at any Target, Walmart, or Best Buy. Its very name seemed to promise a solution to all of one’s problems. It enclosed the mixture in a plastic bulb; you didn’t need to use an open bowl from which you might inhale the product’s dust. Each dealer appeared to imagine that this tiny appliance was not only great for making smoothies and salsa, but also all he needed to rake in millions from a synthetic substitute for heroin.

Naloxone is better known today by the brand name Narcan. It stops overdoses to opioids like heroin, fentanyl, or oxycodone. Naloxone immediately revives a person who is overdosing. However, the large doses that paramedics must apply to those overdosing on the street often send the person into withdrawal, the symptoms of which are, among other things, shaking, shivering, and anxiety. Today, naloxone is widely available as a lifesaver for heroin and fentanyl overdoses.

The American Heart Association would set guidelines for how much daily sugar consumption was healthy (six teaspoons for women; nine for men). Still, the food and drink industries urged Americans on to ever-greater consumption of sugar, made cheap by government subsidies. Within a decade, one Frappuccino would come larded with more than double the daily sugar intake recommended by those AHA guidelines. Processed food, designed in laboratories, massed ever-greater amounts of sugar, sometimes bundling it unnaturally with fat (sugar and fat are not found together in nature). Companies sold it in the form of cereals, cookies, cakes, sodas, sweet teas, condiments, and more. It was a commercial assault of an addictive substance that was likely without equal—other than alcohol and nicotine, of course.

Dentists, too, were prescribing large bottles of narcotic painkillers—thirty days’ worth of pills for pain that dentists knew would last two or three days. This was standard now. Every year, 48 million routine surgeries took place in America. Virtually every patient during those years left with renewable prescriptions for big bottles of thirty, sixty, or ninety pain pills of one brand or another. Thus a firehose of prescription narcotics blasted at the US public for close to two decades. Routine surgeries became a gateway to addiction. The removal of wisdom teeth from what the American Dental Association estimates as five million Americans every year was part of that. Dentists feared losing patients should anyone feel pain from the operation; parents feared their kids might suffer from the surgery. Most of those dental patients took home bottles of sixty pain pills at a time. Thus wisdom-tooth removal led many into addiction, particularly young people.

Later, some people would claim that the opioid addiction epidemic was only getting attention because the great majority of its victims were middle-class White people. That was true. The other truth was that the plague hid for years because so many of its victims were middle-class Whites. Families seared by the loss also had to navigate the shame. They covered up, mortified at how their loved ones had died, afraid to stain their memories. Newspaper obituaries reported that a twenty-seven-year-old died of a “heart attack”; a middle-aged brother “died suddenly” at home. Amid this nationwide silence the plague festered, metastasized, and, like a virus, took on a life of its own.

Jim Rauh, who through the years visiting China had formed such kinship with the Chinese people, feels differently toward their government: “I see this as a chemical attack on the United States, with the Chinese government’s complicity. They’re pushing this material in what I consider to be the third Opium War, just this time by Chinese against us and other Western countries, and fentanyl is its weapon of mass destruction.”

In the People’s Republic of China, the principal law enforcement agency is known as the Ministry of Public Security (MPS). It employs two million people and is housed in central Beijing in an enormous rectangular building next to the National Museum of China, which in turn overlooks Tiananmen Square.

As the Chinese government made one drug illegal, the Zhengs were astute enough to change its molecular structure, rendering their new product technically legal to sell in China. If he’s not selling anything illegal here, the officials said, we can’t arrest him.

in August 2018, federal prosecutors in Cleveland went public with the indictment against the Zhengs. US officials shut down their websites and froze their assets; the US Treasury designated the Zhengs as drug kingpins. Nine months later, the Chinese government banned all forms of fentanyl, except that produced by companies the government licenses to manufacture it. With that, China’s role as a provider of illicit fentanyl faded.

“Always Be Closing.” That motto is gospel to salespeople. It comes from Glengarry Glen Ross, a 1992 movie starring Al Pacino, Jack Lemmon, Alec Baldwin, and Kevin Spacey. The movie is about a suburban office of hapless salesmen hawking shady real-estate investments. To keep their jobs, “Always Be Closing” is the mindset they must adopt with clients, a pitiless approach to an unfair world made up of winners and everyone else. In the office sweepstakes, “first prize is a Cadillac Eldorado,” Baldwin, a boss in from downtown, tells the staff. “Second prize, a set of steak knives. Third prize is you’re fired.”

Harrell is from Dallas, an amateur painter and a thin, soft-spoken fellow who you must sometimes lean forward to hear. When you do, you perceive a lawyerly care to avoid inflammatory, adjective-laden language; to stick to the facts that documents reveal and, above all, not speak outside what he calls “the four corners of the complaint” against any company under investigation, particularly when talking to a journalist.

If “Always Be Closing” was an attitude Purdue reps were urged to adopt, so was the classic salesman advice “Never give someone more information than they need to act.”

Lubricating all this were cards the Tennessee attorneys also discovered, offering patients a $75 discount off the copay on their first five OxyContin prescriptions. Purdue sales reps took the cards to clinics for doctors and their staff, and to pharmacies, particularly independent pharmacies, where the cards helped boost essential traffic in the competition with chain pharmacies. A Purdue internal report showed that patients using these “opioid savings cards,” as the company called them, tended to stay on the drug longer than those who did not. Every $1 million the company invested in the cards, according to a company report, returned $4.28 million in OxyContin sales.

Medical studies have found that two-thirds of patients using opioid painkillers for more than ninety days were still using them five years later.

The savings cards prodded thousands of Americans to keep using OxyContin well past t...

once sales reps stopped calling on a doctor to promote OxyContin, that doctor stopped prescribing as much. The calculation was simple: more sales calls on doctors equaled more OxyContin prescriptions; fewer calls meant fewer prescriptions and lower profit. It resembled the problem facing fast-food or soft-drink manufacturers, whose products are known worldwide yet whose sales depend on relentless advertising and product placement.

“I believe in the beachhead,” Fisher told me. “You get people energized. It helps spread the glow. You start to create that village thing—you get that energy and vitality.”

In human brains, behind each ear and just above the brain stem, lies a blue spot that has helped guarantee our survival. It’s known as the locus coeruleus (Latin for “blue spot”), though those who study it just call it the LC. In humans, the LC evolved early, as it had to. The main job of the LC is to send a chemical—called noradrenaline—to other parts of the brain that ignite warnings of life-threatening menace. Noradrenaline helps sound the alarm, pushes the panic button, in a sense. Without it, we would have died off long ago. Opiates change a lot in our brains. One thing they do is stifle the LC. They shut it down. Under their influence, the LC can no longer send the chemical igniting panic. Smothered so completely, the LC, product of millennia of evolution, is muted, even as the drug sends the body into overdose. In fact, like some menacing extraterrestrial, opiates convince the LC that doing without them would be the life-threatening event. With opiates removed, the now-unbound LC leaps into action. Studies of the brain of an addict entering withdrawals show that the LC gets agitated, releasing outsize amounts of noradrenaline that produce alarm, panic, anxiety, and insomnia. The result amounts to, in effect, a chemical shriek that the addict must have the drug immediately or all is lost.

Dopamine rushes to a key node in the brain’s pleasure circuit known as the nucleus accumbens, where it creates feelings of motivation.

Reward is about self-gratification and the me-first impulse, but it is essential to human life. Seeking reward pushes us to achieve, to build. “Reward is the predominant driving force since Homo sapiens inhabited the planet,” wrote Dr. Robert Lustig, whose videotaped speeches and fantastic book The Hacking of the American Mind were part of my education.

The chemicals that transmit messages between one part of the brain and the other have a name. They’re called neurotransmitters. Dopamine and noradrenaline are among the brain’s many neurotransmitters. They help transmit messages between different parts of the brain. The way these neurotransmitters do this is by locking onto these receptor molecules, an action that produces these feelings—alarm, desire, pain, pleasure, reward. The list goes on. But the brain, always seeking equilibrium, creates neurotransmitters in only limited quantities. By some bizarre coincidence of nature, however, some plants produce molecules that when introduced to our bodies activate these receptors as well. Two of the most famous are the opium poppy and marijuana.

These receptors were discovered in the 1970s, and as scientists saw they were especially affected by opioids—morphine, heroin, other opium derivatives, as well as those synthetically produced, like fentanyl—they called them “opioid receptors.” The neurotransmitters that the brain produces naturally to attach to these receptors they termed “endorphins”—a combination of the words endogenous and morphine.

Marijuana, meanwhile, produces a chemical called THC that attaches to the second class of receptors (discovered in 1988). These receptors were then deemed “cannabinoid receptors,” and the brain chemicals that attach to them were called endocannabinoids (for endogenous cannabinoids).