The Coming Plague

by Laurie Garrett

  Nigerian health officials reacted with considerable alarm. They had already had their fill of this terrible disease, which was named after the village of Lassa, located southeast of Jos, in the Yedseram River valley that runs along Nigeria’s eastern border with Cameroon. In 1969 an outbreak of the disease in Lassa had brought it sharply to Western attention for the first time when American nurses fell ill in the town’s Church of the Brethren Mission Hospital.

  It was a long chain of events, stretching back five years, that brought Mandrella, Brinkmann, and their colleagues to this moment of panic in Germany.

  On January 12, 1969, a sixty-nine-year-old mission nurse began complaining of a sharp backache. Laura Wine told her colleagues the pain was increasing as days went by, but assumed she’d done something to wrench her spine. Perhaps the daily rounds of bed changing and turning patients were the cause, she thought.3

  After a week, however, the nurse also had a throat so sore she couldn’t swallow, and her colleagues saw ulcers lining her pharynx. Assuming she was suffering from some bacterial infection, such as streptococcus, the hospital staff gave Wine penicillin.

  But the antibiotics did no good. Wine’s state escalated; fevers of 101°F, acute dehydration, unusual blood-clotting activity, a complete lack of proteins in her urine—these and other symptoms signaled that the woman was suffering from something wholly unlike the multitude of tropical diseases tolerated by residents of the grassland Yedseram River valley.

  WEST AFRICA

  Over the next four days Wine began to swell, her skin showed signs of hemorrhaging, her heartbeats became irregular, she grew disoriented and was unable to speak properly.

  On January 25 volunteer pilots flew Wine to Jos, rising from the hot grasslands at sea level up to the 4,000-foot-high town of Jos. As they made their journey the air cooled, the humidity dropped, and the tin mines around Jos came into view.

  Jos itself was inhabited by some 12,000 people, a large percentage of whom were European expatriates seeking refuge from the heat and malarial mosquitoes of Nigeria’s lowlands. Members of all three of Nigeria’s leading tribes—Hausa, Ibo, and Yoruba—lived in Jos, and the community had come through the tragic Biafran war fairly unscathed. Though tens of thousands of Nigerians died in the civil warfare of 1967–68 and thousands more were uprooted from their homes, Jos suffered only twenty-four hours of rioting and killing during that period.

  Dr. Jeanette Troup and nurse Lily Pinneo greeted Wine at the Jos landing field. Because radioed descriptions of Wine’s illness seemed to indicate cardiac problems, the pair immediately strapped an oxygen mask on the ailing nurse and rushed her to their Bingham Memorial Hospital emergency ward. There, Troup and her staff did everything possible to save Wine’s life.

  They failed. A day after arriving in Jos, Wine went into horrible convulsions and died.

  Three days later, a Jos hospital nurse who had tended to Wine felt chills, a headache, and dull pains in her back and legs. Forty-five-year-old Charlotte Shaw had gently dabbed Wine’s bleeding mouth with a gauze pad. When she too fell ill, Shaw remembered she had a tiny rose thorn cut on her finger—the very finger she had used to push the gauze along Wine’s mouth.

  Soon Shaw was experiencing the same symptoms that had claimed her patient: fevers, rashes, hemorrhaging, pains, swellings, heart irregularities. After eleven days of illness, she died.

  That night Dr. Jeanette, as she was called, performed an autopsy, assisted by her head nurse, fifty-two-year-old Pinneo.

  Pinneo, a Presbyterian missionary, had followed Shaw’s progress carefully, monitoring her lab results every day. Shaw and Pinneo had been close friends. As she donned her gown, gloves, and mask to assist in the autopsy, Pinneo thought, “How can I do this? How can I possibly face opening her up?”

  Troup and Pinneo gasped when they saw the devastation; every organ of Shaw’s body was seriously damaged. The heart was stopped up, with loads of blood cells and platelets piled well into the arteries and veins. Fluids and blood filled the lungs. Dead cells and fat droplets clogged the liver and spleen. The kidneys were so congested with dead cells and proteins that they had failed to function. When the team cut open Shaw’s lymph nodes they discovered with some shock that absolutely no lymphocytes—disease-fighting white blood cells—were inside. The nodes had been completely emptied.

  A week after assisting in the autopsy, nurse Pinneo also fell ill. This time the medical staff took the case seriously, admitting their colleague to the hospital with the first signs of fever.

  It was February 21, 1969, and panic began sweeping over the Jos hospital as Pinneo’s colleagues stood by helplessly and watched their friend deteriorate from her early symptoms of a mild fever, reddened tonsils, and some liver tenderness.

  Hoping Pinneo had a bacterial infection, Dr. Troup gave the nurse huge injections of penicillin. But the antibiotic proved useless, and on February 26 Troup contacted Dr. John Frame at Columbia University in New York. Frame was a tropical disease expert and director of medical services for Sudan Interior Mission (SIM), which operated a chain of Christian hospitals in West Africa.

  Frame saw no alternative: it was imperative that Pinneo, along with blood and tissue samples from her dead colleagues, be flown to New York immediately. While Pinneo was en route from Jos to the Nigerian capital of Lagos, Frame contacted laboratory scientist Jordi Casals at Yale University.

  As early as 1955 Frame had been hearing reports of strange illnesses among the mission hospital staff and members of their families. That year eight children of Nigerian missionaries suffered high fevers and convulsions. Though the children survived, they all had some degree of permanent brain damage.

  With odd disease reports continuing in subsequent years, Frame hatched the idea of using missionaries as epidemic early-warning systems.

  Though most of his colleagues espoused the 1960s concept of a health transition, Frame wasn’t at all convinced it was time to close the book on infectious diseases; he had reviewed too many strange medical charts forwarded from nurses and doctors in the field.

  In the mid-1960s, Frame met with Wilbur Downs, director of the Yale arbovirus laboratory and Jordi Casals’s boss. They decided to test the blood of all missionaries who had recently suffered unexplained prolonged fevers.

  Casals screened the blood of sixty-five such cases and was able to ascribe illness in half the missionaries to one or another virus he had in his vast Yale collection.

  But the inability to find an explanation for the illnesses of thirty-two cases seemed to prove Frame’s point: there were a lot of microbes yet to be discovered.

  In 1968 a screening system was put in place, and Troup and other mission hospital directors were told to send blood specimens from all mysterious cases to Columbia University. After a superficial perusal, Frame would pass the blood samples on to Casals for detailed analysis. The 1969 illness of Pinneo was the first real test of the system.

  As had been the case two years earlier with Marburg, Casals’s expertise in identifying mysterious viruses was needed. Casals agreed to accept the blood and tissue samples from the nurses, and told Frame, “It will just be a matter of routine to identify this agent.”

  When she arrived in Lagos, Pinneo was dangerously weak. Nigerian and American officials could not reach agreement on how best to transport the ailing nurse to New York, so she was placed in isolation for four days in a small shed near the Methodist Hospital.

  Pinneo was tended to by close friend Dorothy Davis, also a nurse. Authorities in Lagos placed the women in the pesthouse, a shed so full of mosquitoes that Davis was forever waving her arms frantically about in hopes of keeping the insects from biting her friend. Both Pinneo and Davis had already noticed that even the tiniest of mosquito bites seemed to bleed for several minutes: for some reason, Pinneo’s blood wasn’t clotting.

  During th
eir first night in the pesthouse temperatures in Lagos soared into the nineties—hotter still inside their tin-roofed hut. Beside Pinneo lay a tiny measles-ridden baby who was also fighting for its life. During the night the baby died, and its mother rocked back and forth for hours, wailing and sobbing.

  Fitfully, Pinneo went in and out of delirious sleep.

  For four long days Davis fretted over her friend and, knowing what had happened to Shaw after tending to Wine, couldn’t help but worry some about her own health. Both devout Christians, the nurses prayed for a miracle.

  Nigerian and American officials finally agreed on a way to transport Pinneo to New York after CDC investigator Lyle Conrad, who was coincidentally in Nigeria, intervened. He negotiated air passage for Pinneo aboard a Pan Am commercial jet, placing her, along with Davis and himself, in the otherwise empty first-class section. In the seat beside Pinneo was a box containing blood and brain tissue samples removed from the bodies of her friends Laura Wine and Charlotte Shaw.

  During her long flight Pinneo languished apathetically on her stretcher. Though she was fighting for her life, Pinneo’s outward appearance was that of an exhausted traveler, just a tad more wearied by jet lag than were most passengers.

  But inwardly Pinneo was reeling. Every defensive weapon her immune system could muster against the rapidly growing virus population was coursing through her bloodstream to pockets of confrontation. From her lymph nodes to her liver the battle raged.

  Meanwhile, Pinneo’s lassitude was striking—the result of having suffered a 101°F fever for six days. She stared blankly ahead and thought, “I don’t have time to be sick. I have so much to do. I need to fulfill the Lord’s will.”

  But she also trusted the Lord. “If He wants to take me away, it would be all right.”

  Just after midnight Pinneo was admitted to Columbia-Presbyterian Hospital, where she was placed in isolation inside a glass-walled room under twenty-four-hour direct observation by intensive-care nurses.

  When Frame arrived the following morning, he found the medical staff highly agitated, some clearly fearful. He tried to reason with Pinneo’s physician, asking, “What would you do if this were a case of pneumonic plague?”4

  “I’d die of fright!” was the answer.

  Frame, searching for a middle ground between the terror of the Black Death and the casualness inspired in hospital staff by routine bacterial infections, suggested that the physicians and nurses take precautions appropriate for handling scarlet fever. All personnel who attended Pinneo wore protective gloves, masks, gowns, and foot coverings and operated under strictest disease control procedures.5

  Pinneo was exhausted, severely dehydrated, and feverish. Her temperature was 101.2°F, her muscles ached, and her abdomen was tender. But she was often alert and able to assist the Columbia team with useful answers to their medical queries. Some members of the team were, in fact, so impressed by Pinneo’s lucidity and normal heart functions that they expressed the hopeful belief she had already seen the worst and would soon recover from the mysterious ailment.

  All hopes were dashed hours later when Pinneo’s fever skyrocketed to 107°F and her throat filled with lymphatic fluids. By March 6, Pinneo could no longer eat or swallow because her throat—the esophageal lining—was aflame with florid infection. The worried medical staff noted that Pinneo’s face and neck were swelling. Her lungs and chest were also filling with fluids, and X rays showed evidence that some organisms had invaded the linings of her lungs.

  Pinneo grew weaker. She became completely apathetic, no longer evidencing a will to fight the disease. On top of everything else, Pinneo developed malaria on March 7, undoubtedly due to a latent Plasmodium falciparum infection that was activated by the devastation of her immune system.

  Samples of the fluids from Pinneo’s throat were sent off to Casals in New Haven, along with the brain and blood samples from her dead colleagues.

  Meanwhile, Pinneo deteriorated further. By April 1, she lost control of her eye muscles, and her eyes began jiggling about uncontrollably in their sockets. Muscles all over her body were similarly subject to tics and trembling. A brain scan indicated the mystery virus was attacking her central nervous system.

  Ironically, whenever Pinneo was momentarily lucid she seemed more concerned about the fate of the nurses around her than about her own sorry state. “Oh, look at the poor dears, fumbling with those big rubber gloves. It’s so hard to make a bed with those things on,” she thought. Each time the nurses had to administer a local anesthetic to Pinneo’s ravaged throat before giving her a pill, Penny apologized. She was similarly contrite when day after day she remained unable to swallow food, and had to be maintained on intravenous fluids that required close attention from the hospital staff.

  Casals had no immediate answers. Whatever virus was tormenting Pinneo did not match any hemorrhagic agents in his Yale collection. He did know one thing: this organism was unusually tough.

  Miraculously, Pinneo began to recover by mid-April, and was well enough to walk—albeit at an odd rightward slant—out of her hospital room. On May 3 she was discharged from the hospital, but she continued to suffer severe headaches, dizziness, and vertigo until the end of the month.

  The doctors, in both Nigeria and New York, were at a loss to explain what had happened. The best guess was that Marburg disease was responsible, but Casals could find no evidence of Marburg in any of the nurses’ blood samples.

  Back in New Haven, Casals continued his search, working under state-of-the-art precautionary conditions. During the four days it took Pinneo to travel from Jos to New York, the dry ice in which the samples were packed had completely sublimated, and the blood was exposed to the hot, humid Nigerian climate. Nevertheless, the hardy viruses arrived intact. To protect his staff, Casals insisted that only he would attend to the mice that had been experimentally injected with the mystery agent. The rodents were kept in a special airtight room, which Casals never entered without first donning a mask, goggles, and gloves.

  Day after day, Casals injected samples of the nurse’s mystery microbe into test animals, searching for clues to the identity of the agent. His lab also grew cells from African green monkeys, called Vero cells, in petri dishes, poured in microbe-contaminated fluids, and watched the results. The final quick test they used mixed antibodies against Marburg and other viruses into test tubes full of Pinneo’s blood.

  When they studied their results under powerful microscopes, the mystery for Casals only deepened. None of his vast range of antivirus antibodies —including those that usually attacked the Marburg virus—seemed to lock on to the mysterious microbe. Antibody molecules are very specific; for scientists like Casals, an antibody/virus complementary relationship was as reliable a clue as a detective’s discovery of a culprit’s possession of the sole key to a safe-deposit box full of the victim’s diamonds.

  But none of the antibody “keys” in Casals’s vast collection fit the “lock” of Pinneo’s mysterious virus. Casals and colleague Robert Shope screened over 200 viral antibody types against the microbe before concluding it was “something new.”6

  Equally disturbing were the microscopic clues provided by studies of infected Vero and rodent cells; the enigmatic agent just didn’t look like Marburg, or any other pathogen with which Casals was familiar. Working with ace electron microscope expert Sonja Buckley, Casals searched for recognizable attributes of the microbe. They magnified their samples over 100,000 times to be able to visualize the tiny killers: what they saw were perfectly round balls or spheres, from which projected dark spikes.7 Inside the balls was the genetic material of the virus. Marburg, by contrast, was a long, thin, fuzzy virus that often coiled up into a tight spiral.

  The two viruses just didn’t look alike.

  Worse yet, Casals concluded tha
t this mystery microbe was lethal as hell. When Buckley diluted samples to a ratio of one drop of Pinneo’s blood to ten million drops of benign fluid, the concoction still killed half the Vero monkey cells she grew in her petri dishes within eight or nine days. Even Marburg didn’t do that.

  In late May, as Pinneo was recovering, Casals began working on his presentation for the upcoming WHO conference on Marburg disease. He was living in an apartment on Manhattan’s Upper West Side and commuting daily to New Haven. Preferring to do his writing at home, Casals gathered up papers around his office on June 3 and prepared to head into New York. But suddenly Casals felt a dramatic shivering sensation all over his body that lasted over an hour. He took two aspirin and it went away. The following morning he awoke to make his journey back to New Haven and felt lousy.

  On Saturday, Casals awoke to pain in his thigh muscles that was startling in its severity. “I never knew a muscle could hurt that much,” he thought, contemplating the scientific significance of the matter.

  He tried to get out of bed and walk, figuring he’d shake it out, but was startled to find the pain increased and his legs were almost too weak to hold up the rest of his body.

  Dazed, Casals went back to bed, and soon found himself watching the hours slip by without the slightest concern. He felt oddly lethargic and apathetic.

  “Probably just the flu,” he stubbornly concluded, despite symptoms that he knew indicated something else.

  Casals’s family had been away for the weekend, and when they returned on Sunday evening, mother and daughter were aghast. Jordi Casals had eaten nothing. The New York Times lay unread on the floor beside him. The usually energetic scientist seemed absolutely apathetic, as if he had decided to abandon himself to fate. He was extremely confused and kept mumbling something about the flu.

  “This is no damned flu!” his wife declared, quickly calling their family physician, Edgar Leifer. The doctor arrived swiftly, ruled out influenza immediately, and whisked Casals off to Columbia University’s Presbyterian Hospital.