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 25. A Return to Africa

Dr. Adrian Stokes bound a monkey onto a cushioned board with gauze, keeping his head firmly strapped. For an hour, Stokes allowed Aedes aegypti mosquitoes to bite the monkey on his face, lips, ears. Then, he returned the monkey to its cage. It seemed a little cruel, but it was too dangerous for the doctors to hold the monkeys while loaded mosquitoes fed. Even with leather gloves on, the insects could bite through the stitching. Across the lab from the monkeys, in a cage with roughly six screens dividing it, mosquitoes hummed in their wire prison.

A forty-year-old doctor who worked in pathology at Guy’s Hospital Medical School in London, Stokes was a part of the Yellow Fever Commission sent to West Africa in 1920—the one William C. Gorgas was to be a part of when he died in London. Stokes was a graying Englishman—charming, a tennis player, loved by all those who worked with him. Stokes rarely wore gloves when he worked and took poor care of his hands and fingernails. One doctor had even noticed an open sore on Stokes’s finger from a monkey bite.

The commission’s lab was located in Yaba, not far from Lagos, Nigeria. Africa at the start of the twentieth century was still very much the “Dark Continent”—dark primarily because of colonial Europe’s inability to understand it. For centuries Europeans and Americans had landed on the coast of Africa to enslave Africans; now, they landed on the same shores to enlighten them. The white man, it seemed, would not stay out of Africa; but Africa would not have him. In The Coming Plague, Laurie Garrett wrote of the song African children sing championing yellow fever: “Only mosquito can save Nigeria, Only mosquito can save South Africa, Only mosquito can save Zimbabwe, Only Mosquito can save Africa, Only malaria can save Africa, Only yellow fever can save Africa.”

By the 1920s, after Reed’s proof of the mosquito vector and the vigorous campaign by Gorgas to eliminate yellow fever in urban environments, yellow fever, it seemed, would soon be conquered. Paul De Kruif, in his popular book, Microbe Hunters, wrote: “Because, in 1926, there is hardly enough of the poison of yellow fever left in the world to put on the points of six pins; in a few years there may not be a single speck of that virus left on earth.” Hubris. Arrogance. The lessons of the previous century diminished in the distance as the wheels of the Progressive Era rolled forward.

The same year that De Kruif wrote that statement, 1,000 people in an African village of only 5,000 became infected with yellow fever. Although the fever routinely hit nonimmune populations like British and French colonials, the colonial doctors had never seen an epidemic among native Africans before. It was as though an ember had been left smoldering in the jungle, and now fires were beginning to erupt.

America had entered the Progressive Era. Gone were Victorian ideals, heavy-laden tradition, elaborate ceremony and sentimentality. This was the age to move forward. Everything from home life to education to medicine took on a rational precision. For the first time in American history, more people lived in urban environments than on farms. Ideas, people and governments were compartmentalized—there were experts to lead the masses. Medicine had finally become a profession, and science was at the center of progressive thought. Greer Williams wrote that the old bacteriologist was not dead; he had merely “shaved his beard, put on horn-rimmed glasses, changed hats, and reappeared in a new branch of microbiology as a virologist.”

The Rockefeller Institute embodied all the ideas of the Progressive Era. Johns Hopkins had been the premier place for the study of medicine since the 1870s, and it had made monumental discoveries, much like the European institutions before it. They lifted the veil and unraveled the mystery around disease, adding name after name to the list of famous scientists. The Rockefeller Institute, which opened its first lab in 1904, would take a more aggressive tack. It would not model itself after European research and individual scientists, but instead make a departure from it, moving beyond the study of disease to the eradication of it. Like the Progressive Era itself, the institute would take the offensive, its mission “to promote the well-being of mankind throughout the world,” its vision “to cure evils at their source.” Over thirty years, the Rockefeller Foundation would spend fourteen million dollars in an effort to eradicate yellow fever. It would seek out the fever and control the natural world. And there was no place where the natural world was still so unconquered as in Africa, no place where the well-being of mankind was more at stake.

A large cast of American and British doctors was sent to Nigeria by various organizations, including the Rockefeller Foundation, to eradicate yellow fever. The Rockefeller team needed a good pathologist, and in 1927, Adrian Stokes was assigned to work with them. They were the plague hunters, and their aim was not only to see that yellow fever disappeared from North America but to destroy it entirely.

In spite of bubonic plague, malaria and yellow fever, the scientists from both countries made the most of their time in the tropics. They played croquet on the lawn and dined together. They kept gardens with orange bursts of marigold and salmon-colored hibiscus and sun-streaked zinnias. They visited nearby villages in the touring Dodge. But there were a few cultural differences. The Englishmen usually stopped working after 4:00 in the afternoon to enjoy cocktails or play golf or tennis. The British, in turn, found the Americans and their penchant for sunshine strange. The Americans were forever bareheaded in the sun or screening their bungalows and blocking the breeze.

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.”