Fentanyl, Inc.. Ben Westhoff
latest drugs aren’t conceived out of thin air. In fact, many are derived from the same naturally occurring chemicals our ancestors have been using for thousands of years. Fentanyl, for example, is a new plague, but its natural predecessor, the opium poppy, has been used (and abused) since at least the Mesopotamian era.
The story of fentanyl, however, can be traced to one man: Paul Janssen.
A Belgian chemist, Janssen was undoubtedly a genius. He could quote Homer in the Ancient Greek. During World War II he studied chemistry and other sciences at university in Namur, Belgium—enrolling secretly, despite the Nazi occupation—and in 1948, when he was twenty-two, he funded a trip to America in part by beating opponents in chess, at venues including the Manhattan Chess Club. What Janssen was best known for was creating medicines. Over his lifetime, he was responsible for some eighty new medical drugs, including fentanyl. One biographer called him “the most prolific drug inventor of all time.” His brilliance wasn’t just in coming up with new medicines but in realizing that new medicines could be created in the first place.
Janssen was born in 1926 in the small Belgian town of Turnhout. When she was four, Janssen’s younger sister died of tubercular meningitis, a then untreatable condition that can now be controlled with antibiotics. Janssen was in high school at the time, and his sorrow over his sister’s death inspired his journey into medicine. He was mentored by his father, a family doctor in Turnhout, who would operate on patients in their own homes. In these first decades of the twentieth century, rather than give patients the available medicines—organ extracts and tonics that are nowadays discredited—Janssen’s father gave them placebos. “And he was absolutely right to do so,” Paul Janssen later wrote. “Naturally, there was insulin, cardiac glycosides, aspirin and morphine, but where most of the other medicines were concerned, one could safely say they did more harm than good.” Janssen’s father nonetheless started his own medicine company. After the discovery of penicillin, his company sold the antibiotic and also produced its own products, which mainly were combinations of existing drugs. The enterprise’s success did little to impress the younger Janssen, at the time a precocious chemistry and medical student.
“Come up with something better yourself, then,” his father challenged him.
At age twenty-six, Janssen began pursuing new chemicals, with some help from his father, who fronted him money and lab space. But Janssen wasn’t interested in slapping new labels on old chemicals. He wanted to create new drugs that actually made people feel better—and that he could patent. The key to this, he learned, was playing around with chemical structures. Based on the work of Nobel Prize–winning German medical scientist Paul Ehrlich, Janssen knew that adjusting the chemical makeup of a known drug, even just slightly, could create something that could affect the human body in dramatically new ways.
A year later, in 1953, Paul Janssen founded his company, Janssen Pharmaceutica, initially working out of the third floor of his father’s building. “We didn’t even have a calculator, let alone a computer for the simplest calculations,” Janssen wrote in 2000. “To reduce expenditure we economized by performing simple tests on pieces of gut from newly slaughtered rabbits, which I collected early in the morning from a butcher in Turnhout.”
Despite its modest beginnings, the company hit the ground running with its discovery of a drug called ambucetamide, used to alleviate menstrual pain. Janssen would also invent loperamide (Imodium), for diarrhea, as well as chemicals that became critical to the fields of psychiatry, mycology, and parasitology. To spur his company’s ascent, he recruited star Belgian scientists from the Belgian Congo, after the political upheaval there that would lead to the country’s independence and the end of colonial rule. He was soon managing a large staff—its members called him Dr. Paul—but still closely involved with creating new chemicals. He literally daydreamed about molecules. “I often watched him at meetings,” wrote Sir James Black, a physiology and medicine Nobel laureate of King’s College London, “when bored with the proceedings, finding solace inside his head as he doodled new chemical compounds!”
One of these new chemicals was fentanyl, which Janssen and his team first synthesized in 1959 by experimenting with the chemical structure of an analgesic called pethidine. He was hoping to find an alternative to morphine, the reigning pain reliever of its time.
Derived naturally from the resin of the opium poppy, morphine was chemically isolated at the dawn of the nineteenth century by German pharmacist Friedrich Sertürner, who named it for Morpheus, the Greek god of dreams. Janssen tested the effectiveness of fentanyl on lab mice, placing the mice on hot plates and slowly turning up the heat to gauge their reactions.
Fentanyl was particularly profitable for Janssen Pharmaceutica. Doctors found it superior to morphine because of the way it acted. Like morphine, it bound with a receptor in the brain (which we now call the “mu” receptor) to cause pain relief. But fentanyl came on faster, was much more powerful, and wasn’t as likely to cause nausea. “Fentanyl,” Janssen later wrote, “made it possible for the first time to perform lengthy operations and, together with its successors, heralded a revolution in the operating theatre. Without this compound and its analogue, sufentanil, open-heart surgery [as performed today] would not be possible.”
The drug was a revelation, and it went on to become the world’s most widely used anesthetic. Janssen Pharmaceutica was purchased by American behemoth Johnson & Johnson in 1961, and Paul Janssen continued working for the company, tasked with developing other types of fentanyl, referred to as analogues. But almost from the start, fentanyl’s potential addictive dangers were recognized, and it was placed under international control by a United Nations agreement in 1964. This led countries including the United States and the United Kingdom, in 1971, to schedule it—that is, to ban its recreational use. Indeed, its euphoric qualities would prove too much for many users to resist. “Fentanyl is a good medicine but a bad drug,” Justice Tettey, chief of the Laboratory and Scientific Section at the United Nations Office on Drugs and Crime, summed up later. “It has excellent pain relieving properties, but is liable to abuse and can rapidly lead to dependency.”
Despite fentanyl’s quick success as a painkiller in Europe, during the 1960s it was almost blocked for sale in the United States by the Food and Drug Administration. One vocal opponent to the drug’s approval was University of Pennsylvania anesthesiology professor Robert Dripps. A rare outlier who believed fentanyl’s high potency could lead to abuse, he eventually agreed to a compromise after being lobbied by Paul Janssen himself: fentanyl would be available, but only when diluted with another drug called droperidol, a sedative—also patented by Janssen—that was believed to mitigate fentanyl’s detrimental effects. A ratio of fifty parts droperidol to one part fentanyl produced a “bad high” when taken recreationally, Dripps and Janssen agreed, and thus was unlikely to be abused. The FDA approved this combination in 1968. Fentanyl’s success boosted Janssen’s bottom line, which drove Paul Janssen and his colleagues to develop many other fentanyl analogues. Some, like alpha-methylfentanyl, were never turned into medicines that were sold. Others, however, made it to market, including sufentanil, used in long-lasting surgeries, and carfentanil, a veterinary medicine that is the strongest fentanyl analogue ever made commercially.
At the very end of the 1970s, a pair of overdose deaths in Orange County, California, stumped authorities. A few bits of information were known about the victims. They seemed likely to have both used heroin, as shown by their telltale scarring (tracks) and the heroin paraphernalia discovered with their bodies. But toxicology reports bizarrely didn’t turn up any known drugs in their system. Soon, a half dozen more people in the county had died under similar circumstances, and then twice as many.
Around the same time, police began discovering a new drug on the street, China White. Traditionally, dealers of China White touted their product as the finest heroin available—pale in color and originating in East or Southeast Asia. “To get connected with China White is a sort of fantasy for [opiate] addicts,” Darryl Inaba, director of the Haight-Ashbury Free Clinic of San Francisco, said in a report in US Navy Medicine. This new China White had no heroin in it, however, and rather than a fantasy it was a nightmare. Instead of pure heroin from Asia, laboratory analysis determined that it contained something called alpha-methylfentanyl—a fentanyl analogue.
Though