The American Plague: The Untold Story of Yellow Fever, the Epidemic that Shaped Our History - Molly Caldwell Crosby (2006)

Part IV. United States, Present Day

Chapter 26. The Vaccine

The yellow fever virus, from its earliest beginnings in the African forests and savannah, to its widespread epidemics on the other side of the world, to the hundreds of thousands of its victims, has been connected by one thing: blood. It is blood in monkeys that harbors the virus. It is blood that passes the virus into the body of a mosquito. It is blood that connected 5,000 deaths in Memphis to Walter Reed’s human experiments twenty years later. Blood is the medium that allows the virus to travel distance and time, passing from species to species. And it was in the blood that science finally found a way to fight the virus.

Max Theiler did not look like a man who would achieve greatness. He did not have the English charm and graciousness of Adrian Stokes. He did not have the larger-than-life self-confidence of Hideyo Noguchi. For one thing, Theiler was five two. For another, he did not have a stellar academic record. Theiler had been born to Swiss parents in South Africa; he was schooled in London and lived in New York. Theiler never actually received a degree as a doctor in medicine or science, in spite of attending courses at the Royal College of Physicians and the London School of Tropical Medicine and Hygiene. When colleagues mistakenly called him “doctor,” he never bothered to correct them, not because it embarrassed him, but because it didn’t. “You can’t educate a person; you can only create an environment in which he can educate himself,” Theiler once said of his background.

Theiler was young, shy and kept to himself. His lab was littered with ashtrays and boxes of Chesterfields. He loved to read, enjoyed art galleries and found no interest in practicing medicine because there was too little to be done for the patient. In 1922, when asked if he would like to join the staff of Harvard Medical School, Theiler said, “Sure, fine.”

Though many doctors were still searching for bacteria in the blood that could be linked to yellow fever, Theiler began to have ideas of his own. For decades a long list of skilled bacteriologists that included names like Sternberg, Sanarelli and more recently Noguchi had been searching for the bacteria that caused yellow fever—this, in spite of the fact that James Carroll had shown that yellow fever blood passes through a filter without catching any known bacteria. Theiler began to wonder if there wasn’t something even smaller, something that could pass through a filter, something incapable of living in dead cells.

During the summer of 1929, Max Theiler’s boss at the lab in Boston went on vacation, and Theiler decided to try his own experiment. Since monkeys were costly at fifteen dollars each, he opted for mice, which cost only a few cents. First, Theiler injected bits of yellow fever-tainted liver into the brains of mice.

They did not develop yellow fever, but died nonetheless, developing a sort of encephalitis. Next, he tried injecting the same blood into the abdominal cavity of the mice—they lived. Each time, he drew new blood from the mouse. He purchased three rhesus monkeys and injected each with the mice blood. The first monkey died of yellow fever, the second developed a fever but survived, the third developed nothing at all. The yellow fever virus, it seemed, had been turned upside down and inside out—it was killing mice that were not supposed to be able to contract yellow fever, and it was not killing the monkeys that were highly susceptible to it. In Theiler’s hands, the virus could become more deadly in one animal and less so in another. What Theiler had was a vaccine in the making.

Theiler cannot be credited with this line of thinking. After all, Edward Jenner is considered the first to have achieved this with cowpox at the end of the eighteenth century. Jenner named the process vaccine from the Latin word for cow—vacca. But the basic premise was the same: a virus can be manipulated, taking something harmful, and creating out of it something protective. As the virus is passed into another animal it adapts to its new host, it mutates into a less harmful form. The scientist becomes God and the virus his subject. The danger comes in the fact that a virus, ever mindful of evolution and its survival, has its own methods of defense. If man can manipulate the virus, the virus can manipulate man.

Aside from its brute force in taking over cells, the other major weapon in a virus’s assault on the body is the ability to mutate. Complex creatures, like humans, store their genetic material in DNA, which is more stable and less likely to change. Viruses are often made of RNA, an unstable store of genetic material, which can produce errors when it replicates known as mutations. The mutations can work against the virus, hindering it or even killing it; in other cases, they enable the virus to kill more efficiently.

HIV is a prime example of a virus’s skill at changing forms and mutating easily. Just when the body produces the right antibodies to fight a viral strain, the virus alters its outer coating just slightly. The key will no longer fit into the lock. That is why a flu vaccine, made up of several different influenza strains, is a yearly vaccine and not one that produces lifelong immunity. That is also why an influenza pandemic would prove so deadly. In the six months it would take to isolate the virus, grow it in chicken eggs and create the vaccine, the virus may have spread through the population decimating millions of people.

In spite of carrying a single, simple strand of RNA, yellow fever does not mutate easily. Instead, flaviviruses like yellow fever somehow disable the body’s immune response—a process that continues to elude science. When the body encounters the virus, it mounts a mass campaign against the foreign invader on two fronts. White blood cells known as B cells create antibodies that cleave to the virus and mark the virus for destruction. At the same time, Killer T cells search out infected cells and destroy them. During the several days it takes to organize and implement this counterattack, the virus courses through the body, taking over kidney cells, liver cells, breaking down blood vessels until the organs themselves fail, and blood flows uncontrollably. There is no way to stop it unless the body can mobilize its forces before the virus has taken hold—that is what a vaccine does. The vaccine is a milder but live form of yellow fever that activates both arms of immune response—in advance.

Max Theiler’s work in Boston caught the attention of some scientists working with the Rockefeller Foundation—one of which was Dr. Wilbur Sawyer. The Rockefeller Foundation offered Theiler double his salary at Harvard to join their yellow fever lab. Theiler accepted and began work with Sawyer on a vaccine to inoculate the doctors who worked in labs—doctors who continued to die from their work with yellow fever. Theiler himself had contracted yellow fever in the lab in 1929, but recovered, developing immunity. Recently, three other doctors had also developed yellow fever in their work in the United States and in Lagos; one had died. A vaccine would finally give the scientists trying to conquer yellow fever a fighting chance.

Sawyer and Theiler developed a makeshift vaccine combining the infected mouse-brain tissue with blood from a human immune to yellow fever. Then, they took the amalgam of virus and antibodies and injected it into a man named Bruce Wilson. Wilson, who had earned fame as a public health field director fighting against malaria, had just returned from Brazil. He was checked into a screened room at the Rockefeller Institute, where he was injected with this new vaccine. His temperature and pulse were monitored constantly, and to pass the time, Wilson taught his night nurse how to play poker. Wilson never grew ill, and instead, developed immunity to yellow fever.

They now decided to turn their attention to developing a large-scale, safe vaccine. French studies using Theiler’s mouse strain had produced some negative reactions. Even Sawyer had seen the occasional case of fatal encephalitis during his test studies on monkeys. They decided to try an entirely new vaccine using milder strains of yellow fever taken directly from monkeys, forgetting the mice all together. An extensive laboratory was set up in which thousands of flasks, a factory line of glass tubes, housed the virus—part of the Asibi strain—and reproduced it in various forms. They experimented with mouse embryos, then chicken embryos. With time, they developed what became known as the 17-D vaccine, grown in a chicken embryo and named for the seventeenth series of experiments and the type of tissue used. The only complication wasn’t really a complication at all: The virus required a little human nonimmune blood, a serum, to survive. The doctors therefore added about 10 percent human blood to the vaccine. It was cheap and safe—it seemed simple enough. But man continually underestimates nature, and as a result, nature occasionally makes folly out of man’s triumphs.

Scientists had now been working on a vaccine for nearly ten years. Throughout the 1930s, as America fell into a deep depression, the doctors locked themselves away in labs and engaged in this viral fertility study. They nurtured the yellow fever virus, disciplined it, fed it blood and grew it in the surrogate confines of a chicken egg.

By 1941, it seemed clear that America would soon be at war, and as every war in the past had taught, disease could be far more devastating than the enemy. Dr. Wilbur Sawyer worked on a mass production of the vaccine to inoculate American soldiers as they left to fight. Theiler had some reservations about the new vaccine though. He wanted to try a serum-free vaccine, one that could be used without introducing human blood into the mix. Sawyer thought it was a good idea in theory, but added that there simply wasn’t time. America was headed for war, and soldiers were headed into countries where yellow fever was rampant—particularly Africa. “You are courting disaster,” Theiler told him.

In the fall of 1941, the yellow fever vaccine was given to all troops departing for the tropics, and by 1942 seven million doses had been issued by the International Health Division to the U.S. Army, Navy and the British fighting in Africa. But, complications began to arise—infectious hepatitis was reported among soldiers. At first, it was sporadic; then, it became epidemic. The soldiers seemed jaundiced, complained of headaches, nausea and dizziness. There were a few fatalities. It did not take long for the blame to fall on the new yellow fever vaccine—the blood that fed the virus in the vaccine had been taken from several hundred volunteers. A few of those—maybe 2 percent—reported a history of jaundice. Their blood had been pooled, and roughly 400,000 doses of the vaccine had been tainted. It became known as “Rockefeller disease” and “serum hepatitis.”

In the end, there were close to 50,000 cases and 84 deaths. But there was not a single yellow fever case in an American soldier. Dr. Wilbur Sawyer took complete responsibility for the hepatitis epidemic, as well as for the notable absence of yellow fever among the troops. He would be remembered for the former, not the latter.

It was October 15, 1951, when Max Theiler received a cablegram at his lab in New York. He had been awarded the Nobel Prize in Medicine for his “discoveries concerning yellow fever and how to combat it.” When asked what he would do with his $32,000 prize money, Theiler responded: “Buy a case of Scotch and watch the Dodgers.”

Max Theiler is the only scientist ever to receive the Nobel Prize in connection with yellow fever.