A successful virus is one that doesn’t kill too well and can circulate widely. That’s what makes flu such a perennial threat. A typical flu renders its victims infectious for about a day before they get symptoms and for about a week after they recover, which turns every victim into a vector. The great Spanish flu of 1918 racked up a global death toll of tens of millions—some estimates put it as high as a hundred million—not by being especially lethal but by being persistent and highly transmissible. It killed only about 2.5 percent of victims, it is thought. Ebola would be more effective—and in the long run more dangerous—if it mutated a milder version that didn’t strike such panic into communities and made it easier for victims to mingle with unsuspecting others.

  That is, of course, no grounds for complacency. Ebola was only formally identified in the 1970s, and until recently all its outbreaks were isolated and short-lived, but in 2013 it spread to three countries—Guinea, Liberia, and Sierra Leone—where it infected twenty-eight thousand people and killed eleven thousand. That’s a big outbreak. On several occasions, thanks to air travel, it escaped to other countries, though fortunately in each instance it was contained. We may not always be so lucky. Hypervigilance makes it less likely diseases will spread, but it’s no guarantee that they won’t.

  It’s remarkable that bad things don’t happen more often. According to one estimate reported by Ed Yong in The Atlantic, the number of viruses in birds and mammals that have the potential to leap the species barrier and infect us may be as high as 800,000. That is a lot of potential danger.*2

  II

  IT IS SOMETIMES said, only partly in jest, that the worst health initiative in history was the invention of agriculture. Jared Diamond has called it “a catastrophe from which we have never recovered.”

  Perversely, farming didn’t bring improved diets but almost everywhere poorer ones. Focusing on a narrower range of staple foods meant most people suffered at least some dietary deficiencies, without necessarily being aware of it. Moreover, living in proximity to domesticated animals meant that their diseases became our diseases. Leprosy, plague, tuberculosis, typhus, diphtheria, measles, influenzas—all vaulted from goats and pigs and cows and the like straight into us. By one estimate, about 60 percent of all infectious diseases are zoonotic (that is, from animals). Farming led to the rise of commerce and literacy and the fruits of civilization but also gave us millennia of rotten teeth, stunted growth, and diminished health.

  We forget how devastating many diseases were until quite recent times. Take diphtheria. Into the 1920s, before the introduction of a vaccine, it struck down more than 200,000 people a year in America, killing 15,000 of them. Children were especially susceptible. It usually started with a mild temperature and a sore throat, so at first was easily mistaken for a cold, but it soon became much more serious as dead cells accumulated in the throat, forming a leathery coating (the term “diphtheria” comes from the Greek for “leather”; the disease, incidentally, is correctly pronounced “diff-theria,” not “dip-theria”) that made breathing increasingly difficult, and the disease spread through the body, shutting down organs one by one. Death tended to follow swiftly. There were many cases of parents losing all their children in a single outbreak. Today diphtheria has become so rare—just five cases in the United States in the most recent decade measured—that many doctors would struggle to recognize it.

  Typhoid fever was no less frightening and caused at least as much distress. The great French microbiologist Louis Pasteur understood pathogens better than anyone of his day but still lost three of his five children to typhoid fever.

  Typhoid and typhus have similar names and symptoms but are different diseases. Both are bacterial in origin and marked by sharp abdominal pain, listlessness, and a tendency to grow confused. Typhus is caused by a rickettsia bacillus; typhoid is caused by a type of salmonella bacillus and is the more serious of the two. A small proportion of people infected with typhoid—between 2 and 5 percent—are infectious but have no symptoms of illness, making them highly effective, if nearly always unwitting, vectors. The most famous such carrier was a shadowy cook and housekeeper named Mary Mallon who became notorious in the early years of the twentieth century as Typhoid Mary.

  Almost nothing is known of her beginnings. She was variously reported in her own day as being from Ireland, England, or the United States. All that can be said for certain is that from young adulthood Mary worked in a number of well-to-do households, mostly in the New York City area, and wherever she went, two things always happened: people came down with typhoid, and Mary abruptly disappeared. In 1907, after a particularly bad outbreak, she was tracked down and tested and in the process became the first person to be confirmed as an asymptomatic carrier—that is, was infectious but had no symptoms herself. So fearsome did this make her that she was held in protective custody, very much against her will, for three years.

  She was released when she promised never again to take a job handling food. Mary, alas, was not the most trustworthy of souls. Almost immediately she began working in kitchens again, spreading typhoid to a number of new locations. She managed to elude capture until 1915, when twenty-five people developed typhoid at the Sloane Hospital for Women in Manhattan, where Mary had been working under an assumed name as a cook. Two of the victims died. Mary fled but was recaptured and spent the remaining twenty-three years of her life under house arrest on North Brother Island in the East River until her death in 1938. She was personally responsible for at least fifty-three cases of typhoid and three confirmed deaths, but possibly many more. The particular tragedy of it is that she could have spared her unfortunate victims if she had just washed her hands before handling food.

  Typhoid may not worry people as it once did, but it still affects more than 20 million people a year around the world and kills between 200,000 and 600,000, depending on whose figures you rely on. The United States has an estimated 5,750 cases each year, about two-thirds brought in from abroad but nearly 2,000 acquired domestically.

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  —

  If you want to imagine what a disease might do if it became bad in every possible way, you could do no better than consider the case of smallpox. Smallpox is almost certainly the most devastating disease in the history of humankind. It infected nearly everyone who was exposed to it and killed about 30 percent of victims. The death toll in the twentieth century alone is thought to have been around 500 million. Smallpox’s astounding infectiousness was vividly demonstrated in Germany in 1970 after a youthful tourist developed it upon returning home from a trip to Pakistan. He was placed in hospital quarantine but opened his window one day to sneak a cigarette. This, it has been reported, was enough to infect seventeen others, some two floors away.

  Smallpox only infects humans, and that proved to be its fatal weakness. Other infectious diseases—flus notably—can disappear from human populations but rest up, as it were, among birds or pigs or other animals. Smallpox had no such reservoir to retreat to as humans gradually persecuted it into smaller and smaller patches of the planet. At some point in the distant past, it had lost the ability to infect other animals in order to focus exclusively on humans. As it turned out, it chose the wrong enemy.

  Now the only way any human can get smallpox is if we inflict it upon ourselves. Unfortunately, that has happened. In 1978, at the University of Birmingham in England, a medical photographer named Janet Parker went home from work early one afternoon in late summer complaining of a blinding headache. Soon she was very ill indeed—fevered, delirious, and covered in pustules. She had contracted smallpox via an air duct from a lab one floor below her office. There, a virologist named Henry Bedson had been studying one of the last smallpox samples on Earth still allowed for research. He was frantically working against a deadline before his own stocks were to be destroyed and evidently grew careless in keeping them safe. Poor Janet Parker died about two weeks after being exposed and in so doing became the last person on Earth to be killed by smallpox. She had actually been vaccinated against the disease twelve years earlier, but smallpox vaccine doesn’t last. When Bedson learned that smallpox had escaped from his lab and killed an innocent person, he went out to his garden shed and committed suicide, so in a sense he was smallpox’s last victim. The hospital ward on which Parker was treated was sealed off for five years.

  Two years after Parker’s terrible death, on May 8, 1980, the World Health Organization announced that smallpox had been eradicated from Earth, the first and so far only human disease to be made extinct. Officially just two stocks of smallpox remain in the world now—in government freezers at the Centers for Disease Control in Atlanta, Georgia, and at a Russian virology institute near Novosibirsk in Siberia. Both countries have several times promised to destroy the remaining stocks but never have. In 2002, the CIA claimed there were probably also stocks in France, Iraq, and North Korea. No one can say whether, or how many, samples may survive accidentally as well. In 2014, someone looking through a storage area at a Food and Drug Administration facility in Bethesda, Maryland, found vials of smallpox dating from the 1950s but still viable. The vials were destroyed, but it was an unnerving reminder of how easily such samples can be overlooked.

  With smallpox gone, tuberculosis is today the deadliest infectious disease on the planet. Between 1.5 and 2 million people die of it every year. It is another disease that we have mostly forgotten, but only a couple of generations ago it was devastating. Lewis Thomas, writing in The New York Review of Books in 1978, recalled how hopeless all treatments for TB were in the 1930s when he was a medical student. Anyone could catch it, he noted, and there was really nothing you could do to make yourself safe from infection. If you got it, that was it. “The hardest part of the disease, for both the patient and the family, was that it took so long to die,” Thomas wrote. “The only relief was a curious phenomenon near the end, known as spes phthisica, when the patient suddenly became optimistic and hopeful, even mildly elated. This was the worst of signs; spes phthisica meant that death was coming soon.”

  As a scourge, TB actually got worse as time passed. Until late in the nineteenth century, it was known as consumption and was believed to be inherited. But when Robert Koch discovered the tubercle bacillus in 1882, the medical community realized beyond doubt that it was infectious—a far more unnerving proposition to loved ones and carers alike—and it became more widely known as tuberculosis. Victims were previously sent to sanatoriums entirely for their own sake; now there was a more urgent sense of exile.

  Almost everywhere patients were subjected to harsh regimens. At some institutions, doctors reduced patients’ lung capacity by cutting nerves to their diaphragm (a process known as a phrenic crush) or by injecting gas into their chest cavity so that the lungs couldn’t fully inflate. At Frimley Sanatorium in England, authorities tried the opposite tack. Inmates were given pickaxes and made to do hard, pointless labor in the belief that that would strengthen their wearied lungs. None of these did, or possibly could do, the slightest bit of good. In most places, however, the approach was simply to keep patients very quiet to try to stop the disease from spreading from their lungs to other parts of their bodies. Patients were forbidden to talk, write letters, or even read books or newspapers for fear that the content would unnecessarily excite them. Betty MacDonald, in her popular and still very readable 1948 book, The Plague and I, about her own experiences in a TB sanatorium in Washington State, recorded that she and other inmates were allowed visits by their children just once a month for ten minutes and by spouses and other adults for two hours on Thursdays and Sundays. Patients were not allowed to talk or laugh unnecessarily or to sing ever. They were ordered to lie perfectly still for most of their waking day and not permitted to bend over or reach for things.

  If TB is off the radar for most of us, that’s because 95 percent of its more than a million and a half annual deaths are in low- or middle-income countries. About one in every three people on the planet carries the TB bacterium, but only a small proportion of those contract the disease. But it is still around. About seven hundred people a year die from tuberculosis in America. Some boroughs of London now have rates of infection that nearly match those of Nigeria or Brazil. No less alarmingly, drug-resistant strains of TB now account for 10 percent of new cases. It is entirely possible that we could one day in the not too distant future be facing an epidemic of TB that medicine cannot treat.

  Lots of historically formidable diseases are still out there, not quite entirely vanquished. Even bubonic plague is still around, believe it or not. The United States averages seven cases a year. Most years there are one or two deaths. And there are lots of diseases in the wider world from which most of us in the developed world are spared—diseases like leishmaniasis, trachoma, and yaws, which few of us have even heard of. Those three and fifteen others, known collectively as neglected tropical diseases, affect more than a billion people worldwide. More than 120 million people, to take just one example, suffer from lymphatic filariasis, a disfiguring parasitic infection. What is particularly unfortunate is that a simple compound added to table salt could eliminate the filariasis wherever it appears. Many of the other neglected tropical diseases are beyond horrible. Guinea worms grow up to a meter long inside the bodies of their victims, then escape by burrowing out of their skin. The only treatment, even now, is to speed the process of exit by winding the worms onto a stick as they emerge.

  To say that much of our progress against these diseases has been hard won is to put it mildly. Consider the contribution of the great German parasitologist Theodor Bilharz (1825–62), who is often called the father of tropical medicine. His entire career was devoted, at constant risk to himself, to trying to understand and conquer some of the world’s worst infectious diseases. Wishing to better understand the truly horrid disease schistosomiasis—also now sometimes called bilharzia in his honor—Bilharz bandaged the pupae of cercariae worms to his stomach and took careful notes over the following days as they burrowed through his skin en route to invading his liver. He survived that experience but died soon afterward, aged just thirty-seven, while trying to help stop a typhus epidemic in Cairo. Similarly, Howard Taylor Ricketts (1871–1910), the American discoverer of the bacterial group rickettsia, went to Mexico to study typhus but contracted the disease himself and died. His fellow American Jesse Lazear (1866–1900), from the Johns Hopkins Medical School, went to Cuba in 1900 to try to prove that yellow fever was spread by mosquitoes, caught the disease—probably by intentionally infecting himself—and died. Stanislaus von Prowazek (1875–1915), of Bohemia, traveled the world studying infectious diseases, and found the agent behind trachoma, before succumbing to typhus himself in 1915 while working on an outbreak at a German prison. I could go on and on. Medical science has never produced a more noble and selfless group of investigators than the pathologists and parasitologists who risked and all too often lost their lives in trying to conquer the most pernicious of the world’s diseases in the late nineteenth and early twentieth centuries. There ought to be a monument to them somewhere.

  III

  IF WE DON’T die so much from communicable diseases anymore, plenty of other maladies have stepped in to fill the gap. Two types of diseases in particular are more visible now than they were in times past, in part at least because we aren’t being killed off by other things first.

  One is genetic diseases. Twenty years ago, about five thousand genetic diseases were known. Today it is seven thousand. The number of genetic diseases is constant. What has changed is our ability to identify them. Sometimes one rogue gene can cause a breakdown, as with Huntington’s disease, which used to be known as Huntington’s chorea, from the Greek for “dance,” a strange and decidedly insensitive reference to the jerky movements of Huntington’s sufferers. It is a thoroughly wretched disease, affecting about one person in every ten thousand. Symptoms usually first appear when the victim is in his or her thirties or forties, and progress ineluctably to senility and premature death. It is all because of one mutation in the HTT gene, which produces a protein called huntingtin, one of the largest and most complex proteins in the human body, and we have no idea what huntingtin is for.

  Far more often, multiple genes are at play, usually in ways too complex to fully understand. The number of genes that have been implicated in inflammatory bowel disease, for instance, is comfortably over a hundred. At least forty have been linked to type 2 diabetes, and that is before you start to factor in other determinants like health and lifestyle. Most diseases have a complex array of triggers.

  That means that it is often impossible to pinpoint a cause. Take multiple sclerosis, a disease of the central nervous system in which sufferers experience a gradual onset of paralysis and loss of motor control, nearly always beginning before the age of forty. It is indubitably genetic, but it also has a geographical element that no one can quite explain. People from northern Europe get it much more often than people from warmer climes. As David Bainbridge has observed, “Why a temperate climate should make you attack your own spinal cord is not so obvious. Yet the effect is clear, and it has even been shown that if you are a northerner you can reduce your risk by relocating southward before puberty.” It also affects women disproportionately, again for no reason that anyone has yet determined.

  Mercifully, most genetic diseases are quite rare, often vanishingly so. One of the more famous sufferers of a rare genetic disorder was the artist Henri de Toulouse-Lautrec, who is thought to have suffered from pycnodysostosis. Toulouse-Lautrec was normally proportioned until puberty, but then his legs stopped growing while his trunk continued growing to normal adult size. In consequence, when standing, he looked as if he were on his knees. Only about two hundred cases of the disorder have ever been recorded.