The American Plague: The Untold Story of Yellow Fever, The Epidemic That Shaped Our Nation (30 page)

A new epidemic spreading among Africans gave Stokes and his partners fresh fever cases to work with. They drew blood from sick humans, storing it in a glass forest of vials and petri dishes in the lab, and injecting it into various lab animals, primarily monkeys. Their conclusions were mixed, and shipments of fresh monkeys and guinea pigs continued to arrive by boat and train at the lab.

The doctors were beginning to lose hope when they heard of a new outbreak of fever in Kpeve, Gold Coast—now Ghana—at the end of June. Much like Walter Reed and his Yellow Fever Commission had done in Cuba, the doctors hunted down the disease wherever outbreaks of fever occurred. Members of the commission traveled the 100 or so miles from Accra to Kpeve to see a European farmer and his wife—both of whom had been diagnosed with typhoid. Instead, they found yellow fever; or perhaps, yellow fever found them.

They also discovered an African man, twenty-eight years old, named Asibi. He was sitting on a stool, his head in his hands, his temperature 103 degrees.
Aedes aegypti
mosquitoes swarmed around him like sparks rising from a flame. The doctors took blood samples from several of the patients, including Asibi, and returned to their lab in Accra.

Asibi’s blood was injected into a marmoset, two guinea pigs and a monkey with the affectionate name Rhesus 253-A. The rhesus monkey arrived in a shipment from Asia; the doctors had discovered that African Old World monkeys seemed immune to the fever. Rhesus 253-A was the color of sand, with round, black eyes and a face like a human child. It was a lively, chattering monkey until it became ill a few days later. It grew quiet in its cage and soon died. Stokes autopsied the animal and found all the postmortem signs of yellow fever. It was their first major breakthrough. The doctors bled the monkey and injected the loaded blood into another monkey, Rhesus 253-B, and it too soon died of yellow fever. They passed the infected blood through a Berkefeld filter, and just like James Carroll, found nothing. No known bacteria or parasite had been caught in the filter. Whatever organism infected the blood of the monkeys had to be even smaller.

Mosquitoes fed on the blood of the sick monkeys, then the doctors bound healthy animals to boards, allowing the mosquitoes to bite, passing the virus from one monkey to the next, creating in the lab what nature had been accomplishing for centuries. If yellow fever could be passed effectively to monkeys, the possibilities were endless. Suddenly, the disease began to make more sense. Forest workers often returned from the bush with a case of yellow fever, in spite of the fact that they had not been in contact with any sick humans. If monkeys could harbor the virus, then the jungle itself was fueling the yellow fever virus, giving it refuge. It explained how endemic yellow fever lives quietly in the jungles, moving through monkey populations before exploding on urban, human ones. By 1935, an American doctor named Fred L. Soper would discover that monkeys also acted as hosts to the disease and that other mosquitoes could carry the virus as well. It became known as jungle yellow fever.

The discovery that the West Africa team had found a filterable virus passing through monkeys was met with controversy— particularly from a bacteriologist named Dr. Hideyo Noguchi. Noguchi, a doctor at the Rockefeller Institute with celebrity status in medical circles, believed he had found the
spirochete,
a rod-shaped bacteria, that spread yellow fever. What Noguchi lacked in physical stature, he made up for in intelligence and arrogance. He had been born to a Japanese servant family and changed his name to Hideyo, which means “great man of the world.” It became his personal mantra.

Noguchi was famous for working beneath the Rockefeller Institute’s director Simon Flexner. Most viewed Noguchi as either insane or a genius. He was well liked, but also egocentric, rabidly ambitious and a loner in medical research, preferring to conduct his experiments alone, and thus taking sole credit for them as well. His findings on yellow fever had been bold, but unsubstantiated and blasted by the likes of Aristides Agramonte—the only survivor from Walter Reed’s original team and now an old man. When Noguchi heard of the latest discovery in West Africa—one that discounted his bacteria—he decided to set up his own study there.

As Noguchi readied himself to travel to Africa that September, he was met with word that Adrian Stokes was ill with yellow fever. The doctors guessed that Stokes’s open wound on his hand had been infected with yellow fever blood. It was the first case of yellow fever transmission through skin. Stokes had retreated to his bungalow one night during dinner, where he began vomiting. Shortly thereafter, he moved into a hospital in Lagos, Nigeria. Ever the scientist, Stokes decided to personally take part in the experiments he had been performing on his monkeys. He insisted that his partners allow mosquitoes to bite him—200 in all. The doctors also drew blood from Stokes.

Two days later, on September 17, Stokes felt better. He read books and spoke of going to his lab to work, but he also made his colleagues promise that if he should die, they would autopsy him for the study. Stokes’s temperature stayed around 101 degrees, while his pulse hovered at 70. His mind began to slip, at first just growing dull and later delirious. His skin grew yellow. Stokes died of yellow fever on September 19.

His colleagues, Bauer and Hudson, deliberated what to do next. They had promised to autopsy Stokes, but carving into their own friend an hour after his death seemed impossible. Bauer, with tears in his eyes, said he would do it. But Hudson, who performed all autopsies for the team, stopped him. “I will do it.”

The diagnosis was a clear case of yellow fever, and the doctors had shown that the virus could cause an infection through the skin—their friend and colleague, Adrian Stokes, had been proof of that.

Two months after Stokes’s death, on November 17, 1927, Hideyo Noguchi arrived in Accra to begin his work. Since there had been no new outbreaks of yellow fever, he would have to use blood samples from the Asibi strain and Stokes. Again working alone— and demanding a larger bungalow for his personal quarters— Noguchi went to work proving his bacteria theory, or at least proving that there might be different types of yellow fever. He used roughly 1,200 monkeys during his six-month stay, spending close to $20,000 on his subjects. In cables to New York, which could run $1,800 per month, Noguchi declared, “My work is so revolutionary that it is going to upset all our old ideas of yellow fever.”

By May, Noguchi had plans to return to the United States with his proof in tow. The other doctors found his data confusing and inconclusive, but he was not deterred by the opinions of less brilliant men. First, however, he wanted to visit the lab in Lagos to compare studies. As he boarded the boat, Noguchi complained of a chill. He looked tired and asked Hudson to draw some blood to test for malaria. No malarial parasites could be found. Noguchi made the overnight boat trip back to Accra, growing more ill. Another doctor housed Noguchi and cared for him during an illness that was looking more and more like yellow fever. As his temperature rose, and his pulse slowed, he began retching the telltale black vomit. He suffered from seizures and bit his tongue. Finally, on May 20, his kidneys failed, and he started convulsing. Noguchi died of an unmistakable case of yellow fever. The head of the West Africa commission, Dr. Beeuwkes, and a British doctor named William Young visited Noguchi’s lab while he was in the hospital. They found several monkeys dead in their cages; they killed the rest for safety. They also found
Aedes aeygpti
mosquitoes flying around the room; the insects had somehow freed themselves from their corner cage.

Ten days after Noguchi’s death, William Young died of yellow fever, presumably from the mosquitoes in Noguchi’s lab.

Yellow fever would also kill another famous physician. Dr. Paul Lewis was a quiet, brilliant doctor who had discovered that a virus was responsible for polio and had been one of the main doctors in the fight against the 1918 influenza epidemic. Lewis, on assignment for Simon Flexner, would die of yellow fever in a tropical lab in Brazil.

And, finally, the virus would take its last victim: Theodore B. Hayne. Hayne was a researcher working for the Rockefeller Foundation in 1930 when he was sent to Lagos, Nigeria. He was thirty-two years old when he died there.

Yellow fever had always been and always would be a disease that countered every gain with a substantial loss.

It seems only natural that a virus should fight for its own survival, and yellow fever had been hunting down and killing the scientists attempting to destroy it. First, the fever killed Jesse Lazear outright, and later, James Carroll from presumed complications. It had indirectly weakened the health of Walter Reed, who died within two years of his study linking yellow fever to mosquitoes.

When the plague hunters turned their attention to West Africa, the virus’s natural habitat, it struck again with just as much violence. Adrian Stokes, Hideyo Noguchi, William Young and Theodore B. Hayne died of yellow fever, even as they studied ways to control it. Then, Paul Lewis died in Brazil. During the Rockefeller Foundation’s fight to eradicate yellow fever, five doctors in all died of the fever, and a total of thirty-two scientists and technicians would contract the fever in the lab.

One doctor would later write: “I can think of no other disease that killed so many scientists studying it.”

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.