Manufacturing depression Page 7
Taken alone, this discovery would probably not have changed the course of medicine. Sleeping sickness, after all, is a rare disease, and one that mostly afflicts people in impoverished parts of the world. But in 1905, a colleague of Ehrlich’s at the Charité had discovered another spiral-shaped pathogen, a spirochete, and this one was responsible for a plague that at the turn of the century had infected as much as 10 percent of Europe’s population, ravaging the lives of common folk and kings and artists alike: syphilis.
Known to the French as the disease of Naples, to the Italians as the French disease, to the Russians as the Polish disease, to the Japanese as the Chinese disease, to the English as the Spanish disease, and to all concerned as a scourge, syphilis, or the great pox, first appeared in the late fifteenth century, not long after Christopher Columbus returned from the New World. When Europeans weren’t blaming one another for the disease, they speculated that its true origins were the savages that Columbus and his men met (and then some) on his voyage.
John Hunter, the eighteenth-century British physician, was one of the blame-America-first crowd. He also believed, against the prevailing wisdom of the time, that syphilis was caused by a “putrid liquid” contained in the pus that exuded from a chancre. In 1767, he injected some of that liquid, obtained from a patient’s penis, into his own. His intent was to determine whether gonorrhea and syphilis were variants of one illness. He didn’t consider the possibility that his patient could have both illnesses, so when he developed symptoms of each, he concluded that “gonorrhea and the chancre are the effects of the same poison.” Even if he had this wrong, however, he did manage to report accurately on the natural course of venereal diseases—although when his aorta burst twenty-six years later, he probably didn’t know that his experiment had killed him.
Hunter treated himself by cauterizing and applying mercury to his chancres and to the sores that erupted elsewhere in the disease’s later stages. Mercury had been the treatment of choice for the pox from the beginning—probably because physicians since Galen had used it with some success to heal skin conditions. Doctors rubbed mercury on patients’ genitals, injected it into their veins, vaporized it so they could breathe in the vapors, served it up as a chewing gum, dissolved it into alcohol to be imbibed, infused it into their rectums, and even, at least in Italy, coated their underpants with it. (The treatment gave rise to a rueful adage: “A night with Venus is followed by a year with Mercury.”) Mercury did seem to have some effect, and physicians learned to recognize the symptoms of mercury poisoning, like salivation, before it killed their patients, but doctors’ ability to publicize themselves as healers of the pox, which they did in slick pamphlets promising effectiveness and discretion, generally far surpassed their ability to actually do so.
With the success of the smallpox inoculation, some nineteenth-century doctors thought that the great pox would also be controlled by vaccine, but they soon found that infected people could get reinfected, making the disease unsuitable for that treatment. Public health measures also foundered—on both the distaste for talking openly about sex and on the near impossibility of controlling people’s sexual behavior. By midcentury, at least one doctor saw syphilis as making a mockery of progress.
Nineteenth century man has managed to do away with long distances, tunnel through mountains, harness the power of fire, and yet he has not thus far managed to preserve himself against disease. As a conqueror of matter, a new Icarus, he sets out boldly heavenwards; as the threadbare king of creation he…falls prey to a disease which the simplest precautions would enable him to avoid.
And in 1875, a French scientist gave even more reason for concern: syphilis, he said, was even worse than already thought, for it not only caused the genital chancres of its primary stages, and the blisters and fevers of its secondary stages, but a third, more horrifying stage, characterized by tabes dorsalis, a condition that caused people to lose muscle control and balance, and general paresis, a form of insanity. By one count, nearly half of the patients in Europe’s mental hospitals were suffering from tertiary syphilis.
A pale spiral-shaped organism had been spotted in chancres as early as 1837. But it was hard to make out in the microscopes of the time, and germ theory was still a twinkle in Pasteur’s eye, so there was little interest in isolating and identifying the bug until Ehrlich’s colleagues found it in blood and tissues as well as syphilitic sores. Because it vaguely resembled the spiraling trypanosomes, it made sense to see whether compound 418, which had killed those germs so well, would also attack the syphilis spirochete. The answer, unfortunately, was no, but Ehrlich and Hoechst were convinced that they were on the right track, and eventually Ehrlich’s 606th compound did the trick, killing the syphilis bug in infected rabbits.
Even before Ehrlich had satisfied himself that his results were not a fluke, word about 606 got out—and so, thanks to Hoechst, did samples of the drug. Doctors in Italy and Russia reported good results with early stage syphilitics, a Swiss physician reported that in addition to successful treatment of syphilitics he’d used 606 to cure a case of leukemia, and Alexander Fleming, a British doctor not yet famous for stumbling onto penicillin, reported that the drug had a “remarkable effect” on syphilis.
In April 1910, Ehrlich officially announced his success at a Wiesbaden medical conference. Almost immediately, he was besieged with requests for 606. Patients showed up at his research offices, hoping for a shot. By September, more than ten thousand patients had been treated, a number that had tripled by November. By year’s end Hoechst had distributed 65,500 free doses to doctors all over the world—virtually everywhere but the United States, where doctors warned that having a cure for the disease might encourage promiscuity. Headlines soon trumpeted the success of Salvarsan, the household-friendly name Hoechst settled on instead of 606 or the even less mellifluous dihydroxydiaminoarsenobenzene. By year’s end the company had put more than 375,000 doses into the pharmacies and was the proud owner of the world’s first scientifically proven wonder drug—a magic bullet aimed directly at the heart of one of the worst diseases known to humankind.
Shortly after Salvarsan’s release, a German magazine ran an article that included this clever encomium to the drug:
There’s hardly a child who believes in the gods,
They’ve vanished without a trace;
Even those who serve at Venus’s court
Now laugh in Mercury’s face.
This enthusiasm was misplaced, as wonder drug enthusiasm often is. Salvarsan promised to make the world safe for adultery and fornication, but even in successful cases, treatment could drag on for months or years of repeated, painful injections and debilitating side effects. Sometimes it made people sick or even killed them—it was, after all, made from arsenic. Some doctors stopped laughing at Mercury and started augmenting Salvarsan with old-fashioned quicksilver ointments. The treatment ultimately came to be seen, as one doctor put it, as “a long, slow, painful, and expensive grind,” and the world’s enthusiasm, at least when it came to syphilis treatments, eventually moved on to the next wonder drug, Fleming’s penicillin.
But the quatrain’s optimism was, in another sense, spot-on. Salvarsan finished the job that Hippocrates started. After two millennia of stumbling around in the humoral darkness, doctors and drug companies were ready to displace the gods entirely from the clinic by taking direct aim at disease and killing it at its source. And even if the drug itself was only a qualified success, the idea behind it was a blockbuster. Soon enough, Ehrlich’s magic-bullet promises came true in ways that exceeded imagination.
To cite just three familiar examples: scientists identified the lack of insulin as the culprit in diabetes in 1921; in 1922 a team in Toronto successfully treated a fourteen-year-old diabetic boy; and in that same year Eli Lilly and Company devised a method for mass-producing human-ready insulin from the pancreas of a cow. In 1942, chemists at Charles Pfizer and Company, which made its first fortune by producing citric acid, figured out a way to gro
w penicillin in fermenting corn liquor, allowing a drug previously great in promise but short in supply to be mass manufactured in time to treat the wounds (and syphilis) of World War II soldiers. In the late 1950s, researchers at Merck discovered that chlorothiazide, another benzene compound, could change blood chemistry enough to lower blood pressure, and Diuril was born. By the turn of the twenty-first century, Oliver Wendell Holmes’s prophecy had come true, but in a way he couldn’t have expected: the fishes were indeed suffering from the modern materia medica, but only because millions of people living better through chemistry were flushing the metabolized remains (and unused pills) down the toilet and out into the sea.
It is nearly impossible to overstate the impact of Ehrlich’s idea. It has turned the suppliers of magic bullets into wealthy and powerful corporations, and doctors into dead-aim gunslingers possessed of an authority that Hippocrates could only dream of. It has also turned diseases into afflictions with specific causes that can be located in our biochemistry. By revolutionizing our view of sickness and health, in short, it has ushered in a new climate of opinion about suffering and its remedy, and even more about who we are and why we suffer: not the descendants of Job, awaiting the next inexplicable misery, but people with a biochemical essence that can be known and, when it goes wrong, corrected.
And that’s not all. If scientists can figure out how to make a beautiful color the first time, every time—and out of industrial waste no less, no mucking about with snails or bats—and use that knowledge not only to make the ladies of Paris happy but also to cure the great pox, then the prospects for humankind are suddenly and dramatically enhanced. Petitioning Yahweh for an account of the wherefores of suffering—and falling into resignation or despair when no answers are forthcoming—is unnecessary when doctors can peer into the recesses of the body, find the answers in its molecules, and send the chemicals in to the rescue. The promise of a boundless future that originated with the Enlightenment and began to come to fruit in the Industrial Revolution has perhaps no better expression than in the birth of scientific medicine.
But that promise also created a temptation, one that eventually would prove irresistible. To the manufacturers of drugs, diseases are markets. The continued growth and success of the pharmaceutical industry depends on a proliferation of those markets. It was only a matter of time before doctors and drug companies started to improve upon nature in yet another way: by creating the diseases for which their potions are the cures.
Indeed, even as Ehrlich was working in Berlin, in another corner of the same hospital, another doctor was beginning to do just that. He wouldn’t have described his work that way, of course. As he mapped the landscape of psychic suffering, he thought he was discovering diseases, not inventing them, and he had no intention of curing his patients. Still, simply by insisting that there were mental illnesses in nature and that he knew how to find them, Emil Kraepelin set the machinery of depression in motion.
CHAPTER 4
THE DANGERS OF EMPATHY
When my doctor at Mass General went to determine whether or not I was minorly depressed, he did what nearly any researcher in any clinical trial for a psychiatric condition does. He sat down across his desk from me and opened up a big loose-leaf binder. In it was the script for the Structured Clinical Interview for DSM-IV (SCID), a test derived from the DSM’s diagnostic criteria. The procedure is very simple. To find out if you satisfy the two-weeks-of-sadness requirement, the doctor asks you if you have been sad for two weeks. To find out if you have lost interest in the activities that usually bring you pleasure, he asks if you have lost interest in the activities that usually bring you pleasure. This goes on for forty-five minutes or so, the questions shunting you from one slot to another, like a coin in a sorter, until you drop into the drawer with all the other pennies.
What the doctor doesn’t do as he scores your SCID is pay much attention to how you are actually behaving, the words you use to express yourself, or the way you come across in person—in short, the qualities that we usually think make us who we are. In fact, my doctor didn’t even have my name right. He kept calling me Greg. I would have corrected him, but I didn’t want to embarrass him.
In the old days—which is to say back when psychiatrists paid attention to your own account of your interior life—the fact that I didn’t want to embarrass my doctor, had it somehow come up in the interview, would have mattered. A clinician might have seen it as a reflection of some aspect of my personality—a fear of conflict, perhaps, or disguised hostility, or even some compulsive need to take care of others. My suffering would have been seen as the outgrowth of that fear or need, the question of how I came to feel that way would have been central, and the diagnosis would have depended in part on the answer to that question. The symptoms alone, in other words, would not have been enough to render a diagnosis. The doctor would have needed to understand the context and meaning of my symptoms, and my illness would have been seen as at least partly a matter of biography.
It’s not hard to understand why diagnosis doesn’t work that way anymore. Reaching that kind of conclusion requires open-ended conversation and liberal interpretation, which would be very hard to map onto a troubleshooting chart. That’s an inefficient process, and it would yield an unscientific result. The difficulties raised by this approach to diagnosis reached a crisis point in the early 1970s. In addition to the Rosenhan study, psychiatrists were confronted with research that showed that they often disagreed about what mental illness a given person had. Diagnostic trends varied from country to country, from city to city, even from hospital to hospital, and diagnoses began to seem more like folk stories than medical categories. Even worse for the industry’s credibility, in 1973, after years of subjecting homosexuals to all manner of “treatment,” the American Psychiatric Association voted homosexuality out of the DSM. Developments like these seemed to indicate that psychiatrists didn’t know how to define mental illness to begin with. That kind of confusion could have been very bad for business.
So just a few years before Prozac came along, psychiatrists turned to what they called a descriptive nosology. In a development I’ll describe in detail later on, they came out with an entirely revamped DSM, one that focused not on personalities or causes of mental illnesses but on lists of symptoms like the one that my doctor was using to diagnose me. These lists featured more or less objective criteria—duration of unhappiness, changes in weight, length of sleep. They were designed to meet statistical standards like interrater reliability, which made them much more friendly to the quantitative tests and measures that we equate with science. And they worked. It turns out that if you standardize the questions you ask, you will come up with standardized answers. Or, to put this another way, if you go into the interview looking for what you already know, then you are very likely to see it.
The trick with the descriptive approach to diagnosis is to keep your eye on the loose-leaf notebook and not on the patient. That’s why it didn’t really matter whether my doctor knew my name or noticed that I was cracking jokes, engaging him in relatively sophisticated conversation about neurochemistry, talking about sad things but not being sad—or, for that matter, that I had driven eighty miles, shown up almost on time (the subway was a little slow), was dressed and groomed, and so on. Details like these would have been inconvenient, to say the least. Clinical trials are hard to fill. Even more important, the mental health industry’s commitment to the DSM and the SCID is its best hope for maintaining its sometimes tenuous place among the disciplines of scientific medicine. If the SCID spits out a diagnosis that just doesn’t fit the patient, then what would that mean about the psychiatric enterprise?
The problem here is that all those descriptors, in all their detail and specificity, don’t necessarily add up to a disease. A good doctor would never conclude that a person with a sore throat and fever necessarily has a streptococcal infection, and a good scientist would not say that the disease of strep throat is constituted solely by a sore throat and
fever. Both would insist that a bacteria must be present to complete the diagnosis. This is the great advance in diagnostics brought on by magic-bullet medicine: the symptoms of a disease are only the signs of the disease, not the disease itself.
Except in psychiatry, where the symptoms constitute the disease and the disease comprises the symptoms. William James had this tautology in mind when, remarking on another disease that doctors no longer believe to exist, he wrote, “The name hysteria, it must be remembered, is not an explanation of anything, but merely the title of a new set of problems.” To say that a person who suffers from sadness and lethargy and sleeplessness and the loss of appetite and interest in pleasure is depressed is merely to give his suffering a new title—at least so long as depression is no more or less than the condition in which a person suffers in this fashion.
Psychiatrists would no doubt love to be able to skip even the SCID’s superficial questions in order to diagnose depression. They would simply look into a microscope, at which point it wouldn’t matter what the patient said, or what the psychiatrist thought about what he said any more than it would matter what a cancer patient said. The industry is working hard to eliminate the human element from psychiatry, but for now the best it can do is to circle the answers in notebooks and train practitioners to ignore what’s in front of their eyes.
If this approach seems a little unsophisticated, a little primitive, and a little inhumane, there’s a reason for that. When the APA turned to a descriptive nomenclature, they weren’t exactly making an innovation. In fact, they were turning back nearly a century, to a nearly forgotten diagnostic system developed by Emil Kraepelin, a German doctor who was much more interested in weeding out the mentally ill than in curing them. Resurrecting Emil Kraepelin’s system, psychiatrists also dusted off his solution to the problem that William James had noted: act as if there is science behind your nosology, and eventually the name of the disease will seem to be an explanation of everything.