In an age of technological wonders, few can equal the life-altering and life-saving drugs that have poured forth from laboratories and research teams in the 20th and early 21st centuries. Anti-psychotic drugs have emptied mental hospitals. Antibiotics have added years to average life expectancy. Birth control pills have transformed sex lives—and mores. Seeming miracles can feel almost routine: Jimmy Carter, after being diagnosed with metastatic melanoma in 2015, took a recently approved drug called pembrolizumab, which redirected his immune system and played a decisive role in ridding him of cancer.
In “Ten Drugs: How Plants, Powders, and Pills Have Shaped the History of Medicine,” Thomas Hager, a veteran science writer, chronicles a range of drug-related breakthroughs, tracking the experimental efforts, occasional missteps and eureka moments that preceded them. The story, though filled with remarkable achievements, is of course not entirely a triumphalist one.
Opium, for instance, derived from the poppy plant, has been in use for at least 10,000 years, making it one of the oldest drugs known to man, and it has been an important trading item since Roman times. As Mr. Hager emphasizes, opium and its derivatives and synthetic forms—most recently fentanyl—have freed millions from intractable pain, but they have also condemned millions to the travails of addiction and to early death. In the 19th century, with a quarter of its population addicted, China resisted the importation of opium, leading to two wars with Britain, the principal player in the opium trade. Enormous resources have been poured into decoupling the pain-killing power of opiates from their powerful addictive nature, Mr. Hager notes, but so far without success.
For millennia, drugs were found in nature, from plants most of all. But in the 1830s the first non-natural drug was developed in a laboratory, and the modern drug industry was born. That drug was the sedative chloral hydrate, from which chloroform, one of the first anesthetics, was derived.
Mr. Hager introduces us to the German chemist Justus von Liebig (1803-73), “a true genius, a great teacher, who was passionate about applying chemistry to everything—especially living processes.” It was Liebig’s investigations—as he was “playing with molecules, learning what transformed one into another”—that led him to turn chloral hydrate into a sweet-smelling liquid whose fumes, as it happened, induced a loss of consciousness. A couple of decades later chloroform was being used in surgery. But like so many drugs, chloral hydrate was liable to misuse. When combined with alcohol, it produced so-called knock-out drops, what Mr. Hager calls “the original date-rape drug.” The same combination—supposedly used for fleecing customers and credited to a Chicago saloon keeper—became the fabled “Mickey Finn.”
Other discoveries, as Mr. Hager shows, emerged from more deliberate pursuit. In the 1960s, a Japanese college student, Akira Endo, having read a biography of Alexander Fleming, the discoverer of penicillin, wondered whether mold might yield not only antibiotics but drugs that would lower cholesterol in the blood. A decade later, as a research scientist, he pursued the idea. He went through almost 4,000 molds, Mr. Hager says, before finding what he was looking for—in a mold that was spoiling a bag of rice in a Kyoto grain shop. Another member of the genus Penicillium, it produced the first statin, a class of drugs now taken by tens of millions of people every day.
One of the revelations of Mr. Hager’s chronicle is the role that serendipity can play. A mid-20th-century French surgeon named Henri Laborit wanted a drug that would calm his patients before their operations and prevent surgical shock. At the time, antihistamines were being investigated for their ability to help hay-fever and cold sufferers. But antihistamines had side effects, one of which was to make patients drowsy. Laborit thought this side effect might be just what he needed. He asked the French drug company Rhône-Poulenc for help. As luck would have it, Rhône-Poulenc had been trying to find better antihistamines and had a number of failures on the shelf. One of them, called RP-4560, was especially ineffective. It didn’t stop runny noses, but it did make patients drowsy. It was all side effect.
Laborit tried it, and it worked wonders keeping patients calm. One day, Laborit happened to be talking with the head of psychiatry at his hospital, who was bemoaning the need to keep so many of his patients in restraints to prevent them from harming themselves or others. Laborit suggested RP-4560. A patient who had been admitted twice for violent irrational behavior was given a dose 10 times what Laborit used on his surgical patients. The patient fell asleep after a few hours, and when he woke up he stayed calm for an additional 18 hours. After three weeks of treatment, he was, Mr. Hager writes, “rational enough to play bridge.” Thus was born the first anti-psychotic drug.
While sticking mostly to history, Mr. Hager touches on the economics of the drug industry. It costs billions of dollars to bring a drug to market, he reminds us, and many candidates never make it, pushing up the price of those that do. When a blockbuster drug does erupt, it can be enormously profitable. The statin Lipitor “became the most commercially successful drug in history,” with sales of more than $120 billion between 1996 and 2011. Rare diseases, because the potential return on investment is so much lower, get short shrift.
Mr. Hager previews the wonders yet to come, such as drugs with sensors that send a signal when they are taken, helping the elderly or the mentally ill to keep their doses on a strict schedule. Super computers allow the modeling of ever more complex molecules, speeding up drug development. The ability to read the genomes of individual patients and manipulate their DNA holds out enormous promise. If Mr. Hager’s well-written and engaging chronicle is any guide, there may be unforeseen downsides to such developments, but the upside will certainly be worth celebrating.