The Coming Plague 1 Machupo BOLIVIAN HEMORRHAGIC FEVER Any attempt to shape the world and modify human personality in order to create a self-chosen pattern of life involves many unknown consequences. Human destiny is bound to remain a gamble, because at some unpredictable time and in some unforeseeable manner nature will strike back. --Mirage of Health, René Dubos, 1959     Karl Johnson fervently hoped that if this disease didn't kill him soon somebody would shoot him and put him out of his misery. The word "agony" wasn't strong enough. He was in hell. Every nerve ending of his skin was on full alert. He couldn't bear even the pressure of a sheet. When the nurses and doctors at Panama's Gorgas Hospital touched him or tried to draw blood samples, Johnson inwardly screamed or cried out. He was sweating with fever, and he felt the near-paralytic exhaustion and severe pain he imagined afflicted athletes who pushed their training much too far. When nurses on the Q ward first looked at Johnson lying beside his two colleagues they recoiled from the sight of his crimson blood-filled eyes. All over Johnson's body the tiny capillaries that acted as tributaries flowing to and from the veins' rivers of blood were leaking. Microscopic holes had appeared, out of which flowed water and blood proteins. His throat hurt so much he could barely speak or drink water, thanks to a raw and bleeding esophageal lining. Word around the hospital was that the three were victims of a strange and contagious new plague that felled them in Bolivia. In brief moments of lucidity Johnson would ask how many days had passed. When a nurse told him it was Day Five, he groaned. "If my immune system doesn't kick in fast, I'm a dead man," he thought. He'd seen it happen plenty of times in San Joaquin. Some of the people died in just four days, but most suffered over a week of this torture. Over and over he reviewed what he had seen in that isolated village on Bolivia's eastern frontier. He hoped to think of something that could help him recover and solve the San Joaquin mystery. It had all started exactly a year before--in July 1962. Johnson had justarrived at the Middle America Research Unit (MARU) in the Panama Canal Zone, having had his fill of cataloguing respiratory viruses at the U.S. government's National Institutes of Health in Bethesda, Maryland. Since 1956, then a young physician fresh from his medical training, Johnson had tediously studied viruses that caused common colds, bronchitis, and pneumonia. The work was getting plenty of praise, but Johnson, who was always impatient, was bored. When word got out that the National Institutes of Health was looking for a virologist to staff its MARU laboratory, he jumped at the chance. Shortly after Johnson arrived in Panama, his newfound MARU colleague, Ron MacKenzie, volunteered to assist a U.S. Department of Defense (DOD) team that was heading into Bolivia to conduct nutritional surveys. "A nutrition survey?" Johnson asked snidely. "Well, I could use the experience, and I've never been to Bolivia. So why not?" MacKenzie said. When MacKenzie and the DOD team met with Bolivia's Minister of Health in La Paz, the official said he had no problem authorizing their research plans, provided they first take care of a more pressing problem hundreds of miles away. "I need an expert in mysterious diseases to investigate an epidemic in the eastern part of the country." All eyes turned to MacKenzie, who, as a pediatrician and trained epidemiologist, came closest to fitting the bill. He shifted uncomfortably in his chair, mumbled something about not being able to speak Spanish, and tried to imagine what eastern Bolivia might look like. The minister went on to explain that the mysterious epidemic was fairly sizable, and two La Paz physicians had tentatively labeled it El Typho Negro --the Black Typhus. The following morning found the tall, somewhat gawky MacKenzie--dressed in a black suit, starched white shirt, and wing tips--standing on the La Paz tarmac, a briefcase at his feet. He greeted Bolivian physician Hugo Garrón, microbiologist Luis Valverde Chinel, and a local politician, and the quartet boarded an old B-24 bomber bound for the town of Magdalena, in the country's eastern frontier region. MacKenzie looked around for a seat: there were none. The plane had been stripped down for hauling meat, and the only passengers usually on board were sides of beef. So MacKenzie stood behind the pilot, holding on to the hull for dear life during the long acceleration down the gravel runway. Because La Paz was at an elevation of 13,000 feet, planes had to reach great speeds to gain enough lift for takeoff. After what seemed an extraordinary amount of time, the Bolivian Indian mechanic who was squatting between the pilot and the copilot pulled a lever in the cockpit floor, withdrawing the landing gear, and they took off. Like a tired old condor, the bomber circled La Paz slowly several times, spiraling upward to 16,000 feet, high enough to fly into a narrow passbetween the Andean peaks that towered around La Paz. MacKenzie found himself staring aghast at avalanches of ice cascading off dangerously close cliffs. When the plane escaped the claustrophobic mountain pass, it was enveloped in a dense fog which forced the pilots to fly by instruments alone: a magnetic compass, stopwatch, map, and notepad. MacKenzie figured this was already enough adventure. Just three years ago he had been patching broken bones and vaccinating kids in a bucolic town north of San Francisco. This new exploit was a bit more perilous than anything he had gambled on when he left private practice to go into public health. As the plane descended into the fog, MacKenzie began to feel the heat and humidity increase, sweat built under his stiffly starched shirt, and when the fog cover broke, he watched seemingly endless grassy savannas pass beneath them. These were broken up by outcroppings of low, tree-covered alturas hills, and by long winding rivers lined with thin bandas strips of rain forest. "It looks just like Florida," MacKenzie thought. "Kind of like the Everglades." After two more long hours the plane landed in the little town of Magdalena, and MacKenzie couldn't believe his eyes. "My gosh," he exclaimed, "there must be two hundred people out there, standing around the plane." The women in the throng were dressed entirely in mourning; the men wore black armbands. The bereaved people of Magdalena had gathered to greet "the experts" who had come to end their epidemic. "Experts?" MacKenzie muttered, casting an uncomfortable glance at Valverde and Garrón. "Well, I'm it." With the grim entourage around them, the group dodged lumbering oxcarts as it made its way past a scattering of thatch-roofed adobe houses to the town plaza, a large courtyard surrounded by a circular arcade and the homes and stores of Magdalena. A sad, lethargic feeling pervaded everything. At Magdalena's tiny clinic MacKenzie found a dozen patients writhing in pain. "My God!" he exclaimed as he watched one after another vomit blood. MacKenzie shuddered, feeling the tremendous onus of his position and cursing the naivete with which he had walked into the situation. It seemed that only yesterday he was doling out antibiotics in a clinic in Sausalito to kids whose frolicking was briefly interrupted by sore throats. What MacKenzie saw on the ward forced him to push aside his pediatrics training and, for the moment, draw upon the lessons in courage and horror he had learned during World War II combat. He was told that most of the sick were outsiders from Orobayaya. Themere name of that distant village sent shivers through the Magdalenistas, who spoke of it with unconcealed fear. Soon the lanky MacKenzie, who towered over the Bolivians, was crouched in a dugout canoe making its way by moonlight upriver toward the plagued village. As they glided along MacKenzie kept spotting enormous "logs"--far larger than their canoe--sliding down the riverbanks toward them. The hair on the back of his neck stood up when he realized the "logs" were alligators. The next day the group rode forty kilometers on horseback to Orobayaya. It was deserted. The six hundred residents had fled days earlier in panic, leaving the village to pigs and chickens that scampered madly about in search of food. MacKenzie returned to Magdalena, collected some blood samples from local patients, and headed back to Panama, where he tried to convince MARU director Henry Beye and the NIH bosses in Bethesda that the Bolivian situation warranted further investigation. "It's probably just the flu," was the consensus from NIH officials. "It's something strange and dangerous," MacKenzie insisted. Both MacKenzie and Johnson thought the Bolivian villagers' symptoms resembled those brought on by a recently discovered Latin American virus, found near the Junin River in 1953 in Argentina. The Argentine virus was a close cousin of Tacaribe, which caused a disease of bats and rodents in Trinidad, also only recently discovered. While there was no evidence that Tacaribe could infect human beings, Junin was clearly lethal in many cases. In sparsely populated agricultural areas of Argentina's vast pampas, Junin appeared as if out of nowhere among men working the corn harvests. It too was a human killer that disrupted capillaries, causing people to bleed to death. Nobody was sure how the Argentines got Junin; there was speculation the virus might be airborne. No point in taking stupid chances, Johnson thought. Though the NIH had not approved a MARU investigation of the epidemic, he flew to the U.S. Army's Fort Detrick, in Maryland, to see Al Wieden. A pioneer in laboratory safety, Wieden had turned Fort Detrick into the world's premier center of research on deadly microbes. Johnson wanted something unheard of: a portable box of some sort so he could safely study Junin in the field--or whatever was wiping out the people of San Joaquin. At Fort Detrick there was a lot of research underway on "germ-free mice"--animals that had such weak immune systems that virtually any microbe could prove lethal to the mutant rodents. To keep the mice alive, scientists housed them inside airtight boxes that were constantly under positive pressure, pushing air past special filters to the mice, and then out again, toward the scientists. In this way, the mice breathed only sterile air. Scientists worked with the mice by inserting their hands into airtight rubber gloves that were built into the sides of the pressure box. The "gloveboxes," as the steel contraptions were called, were about the size of large coffins and weighed hundreds of pounds. Johnson's idea was to convert one of these contraptions from positive to negative pressure so that all air would go inward, toward samples of possibly dangerous animals or microbes. That way, he could work relatively safely in a portable laboratory. Such a portable laboratory had never before been used, and Wieden wasn't sure how to jury-rig the positive-pressure boxes. But, racing against time, Johnson and Wieden found a new, lighter-weight plastic glove box and surrounded it with a vast rib cage of aluminum poles to prevent the container from imploding when the pressure reversed from inside-out to outside-in. To their mutual delight, it worked. Meanwhile, MacKenzie still faced tough opposition in Bethesda, as well as at the Centers for Disease Control in Atlanta. Though he was a physician and had public health training, some higher-ups frankly doubted whether the thirty-seven-year-old MacKenzie had enough tropical experience to be able to recognize a new epidemic. They insisted it would be a waste of time and resources to deploy a team to investigate what would probably turn out to be some garden-variety bug such as influenza. In the fall of 1962 MacKenzie appealed to Bill Reeves, his old mentor from public health graduate studies at the University of California in Berkeley. He described Magdalena to Reeves, who insisted that MacKenzie "stand up to the Bethesda bureaucrats." "Go for it. You got something there. Don't let 'em discourage you," Reeves urged. On January 9, 1963, a meeting of the top brass in the NIH's infectious diseases division was held in Bethesda, and MacKenzie persuasively pleaded his case. It was decided that he and a MARU ecologist named Merl Kuns should first undertake a scouting mission to assess the extent of the epidemic, collect blood samples, and define the nature of the local ecology. The pair made their journey in March, and returned a week later even more firmly convinced that a serious epidemic was underway. Kuns, a University of Wisconsin-trained ecologist, was stunned by the thousands of bats that lived in the thatched roofs of towns like Magdalena, swooping out at night to forage for food. They were small bats, about the size of monarch butterflies, but they clustered in huge flocks that could suddenly fill the village sky. For his part, epidemiologist MacKenzie was convinced that nobody was actually getting infected in Magdalena, and the real epidemic was some fifty miles away in a town called San Joaquin. The pair returned to Panama with more than adequate evidence to gain approval for further investigation. With his new laboratory contraption in crates, Johnson headed to Bolivia in May 1963, along with MacKenzie and Kuns. After arriving in the capital, the team chartered an old USAF B-17 bomber and flew to the eastern edgeof the Andes, then down the eastern Andean foothills to the Itenez River, and from there to the river's Machupo tributary, eventually landing on a field outside San Joaquin. They then hauled their 10,000 pounds of equipment into the tiny town on mules. Nestled atop a sloping hill just above the Machupo's flood line, San Joaquin was, the flabbergasted Johnson thought, "the last frontier of the New World." Nothing in his scientific career had prepared him for conditions so primitive: no roads, no real health facilities, no fences, no electricity, no telephones, no running water. Cows outnumbered humans roughly two to one and roamed freely about the town. The people of San Joaquin were an evenly divided mix of pure Spanish, pure Indians, and mestizos whose ancestors had built the town in the seventeenth century. The wealthier citizens resided in tile-roofed, whitewashed adobe homes; the rest of the population lived in mud-stick houses with thatch roofs. Six thin strips of marsh formed the "roads" of San Joaquin, which converged in a modest central plaza. The Spanish people of San Joaquin were descended from cowboys who for a few generations had tended the large herds of a wealthy Brazilian family in control of an Amazon River fleet of refrigerated steamships. The ships took the beef out of San Joaquin, up the river system some 1,400 miles to the northwest, where the Amazon met the sea. From there the beef was shipped to Europe or North America, reaping excellent profits for the Brazilians. In tiny San Joaquin, however, the cowboys, their families, and the local Indians were entirely dependent on the "benevolence" of the Brazilian ranch owners and on the food and supplies that returning steamships brought to their remote town. In 1952 a revolution had brought the Movimiento Nacionalista Revolucionario to power. The land reform party stripped old Bolivian and Brazilian oligarchies of vast tracts of land, and the people of San Joaquin suddenly found themselves property owners. Unwilling to buy back from the local people the cattle they once owned, the Brazilians and their steamships left, never to return; and the villagers found themselves isolated, impoverished, and facing severe malnutrition unless they could grow crops to supplement the all too abundant supply of beef. When Johnson, MacKenzie, and Kuns arrived in San Joaquin they found a modest town of some 2,000 people managing to survive on beef, the yields of home vegetable gardens, and small rice and corn fields scattered throughout the savannas. A steady stream of travelers passed through the town on their way from even more remote areas in the savannas to larger Bolivian towns via the steamships that moored occasionally at the San Joaquin dock. Upon arrival, Johnson immediately set up his portable laboratory contraption, and the team set out to assess the extent of the mysterious outbreak. By then the epidemic had already been underway for some fourteen months,the people mourned every day when the church bell tolled another death, and fresh graves filled the cemetery. With the townspeople's eager help, the team mapped the area and painted numbers on all the adobe houses. Every family was interviewed extensively, and asked the questions most essential to the team: How many people in this house have had the disease? How many have died and how many have recovered? What were they doing in the days before they got sick? Is there any chance one family member gave the disease to another? Have any animals been sick? It became obvious immediately that nearly half the people had been infected, and, of those, nearly half had died of the disease. That was a terrifying finding because few microbes kill nearly 50 percent of those they infect. One family lost nine of eleven members in 1963. "That's almost a Roman decimation," Johnson told his colleagues, referring to the great epidemics of ancient Rome's republican era when at least a quarter of the population was felled by a disease now thought to have been smallpox. The first order of business was to figure out what type of microbe was killing the people of San Joaquin: bacterium, virus, or parasite. Circumstances pointed to a virus, possibly spread by insects, so the team set up two small laboratories located seventy-five yards apart. The first, an existing tile-roofed adobe building, housed Johnson's glove-box contraption and a variety of other equipment and research animals used to isolate microscopic organisms from blood and tissue samples. The second laboratory was built to order by the local people out of lashed poles and thatching. It housed wild insects and animals Kuns and his assistants caught in the San Joaquin area. The team planned to study those animals to determine what species might be carrying the deadly microbes. The facilities were kept separate to avoid cross-contamination, and the buildings were fitted with window screens and tight doors. Finally, the laboratories were heavily doused with DDT and ringed with rodent traps to protect the scientists from whatever creatures might be carrying the disease. In June, after days of haggling with the San Joaquin community over the propriety of such things, Valverde convinced the local priest to allow MacKenzie to perform an autopsy on one of the recent victims of the epidemic. A few days later, a two-year-old boy died and from his spleen and brain the team was able to isolate a substance that, when injected into hamsters, produced the disease. Days after the boy died the team completed several more tests that proved the mysterious disease was caused by a virus: they ruled out a parasite or bacteria on the basis of both the minuscule size of filters through which the microbe readily passed and its ability to withstand antibiotics. They also showed the microbe could destroy human cells and cause disease in wild mice.1 Midway through the autopsy on the child, Hugo Garrón's scalpel slipped,flew across the autopsy table, and hit MacKenzie's hand. Looking at the blood that instantly filled his punctured glove, MacKenzie looked up at Garrón and predicted the worst. An anxious week passed without symptoms, and MacKenzie decided he was, indeed, a very lucky person. With greater care, he and Garrón performed several more autopsies and were struck by the level of devastation the mysterious microbe produced. Most alarming were the disease victims' brains: where clear cerebrospinal fluid should have been there was, instead, crimson blood; all of the meningeal protective layers around the brain were blood-soaked. Eerily, most of the hair fell off victims' heads before they died. Toward the end of June the town had a party, which the scientists used as an opportunity to celebrate their rapid discoveries. The next logical steps in their research would involve characterizing the virus and figuring out exactly how people got infected. Johnson, Kuns, and MacKenzie felt confident all the answers would soon reveal themselves, and enthusiastically joined the celebration, eating and drinking the local specialties. While all three men were in the mood for a fiesta, it was Johnson who, with characteristic gusto, threw himself into the spirit of the event, drinking, dancing, and joining in the local macho sport of telling tall tales. Though not a classically handsome man, Johnson carried himself with a mix of cowboy swagger and charisma that inspired other men and attracted women. MacKenzie too threw himself into the gaiety of the evening, while the shyer, more serious Kuns quietly observed the goings-on. On July 3 Johnson and MacKenzie were some twenty miles outside of San Joaquin gathering ticks from the bushes around a chaco , or small cattle ranch. They suspected the virus might be carried by insects and were collecting samples to take back to their field lab for analysis. When they began the long trek back to San Joaquin, the shorter Johnson kept having to slow down to avoid outpacing his usually athletic, longlegged colleague. By the time they reached the river and started to canoe downstream to San Joaquin, Johnson noticed he was pulling most of the weight. "I feel lousy. Really lousy," MacKenzie said as he staggered off to bed. The next morning Peace Corps nurse Rose Navarro, who had been sent in to help with translating, took one look at MacKenzie and pronounced his condition serious. She also noticed that Angel Muñoz, a Panamanian lab technician who had recently arrived from MARU to assist Kuns, had similar symptoms. Johnson and Kuns contacted Panama through a cumbersome radio relay system, and a USAF C-130 flew in that day--the Fourth of July--to evacuate the two ailing researchers. As he waved goodbye to MacKenzie, Johnson felt a feverish chill come over his body and thought, "Damn! I should have been on that plane too!" Over the next four days Johnson slowly hitchhiked his way, plane toplane, across Bolivia, Peru, and Colombia, finally reaching the Gorgas Hospital in Panama. And now here he was, bleeding to death. To his left lay MacKenzie, on the right Muñoz. Johnson could imagine his brief obituary: "promising young research physician, born in Terre Haute, Indiana, 1929. Dead, age 34. Unmarried." He knew there were two ways the virus could kill him. He'd seen it in San Joaquin. He might soon develop neurological symptoms, getting tremors and losing control of his muscles; eventually, he would have a grand mal seizure and die. Or the sheer volume of blood hemorrhaging from his capillaries would become so devastating that his body would go into shock and he'd die of cardiac arrest. Either death could strike in a matter of hours, or days. In any event, there was no cure, no antitoxin. There was just lying and waiting. After several more days of agony all three men showed signs of improvement, thanks largely to the efforts of an Army doctor flown in especially for them from Washington, D.C. Though he had never treated this particular ailment, the doctor had handled dozens of cases of another viral hemorrhagic disease called Seoul Hantaan, which first came to the attention of Westerners when 121 trench-bound American soldiers fighting in the Korean War died bleeding deaths that were not unlike the one threatening Johnson. (Nearly 2,500 U.S. soldiers suffered the Hantaan disease from 1951 to 1955.)2 Nobody had yet identified the Hantaan virus and it wasn't clear how the disease was transmitted, but U.S. Army doctors had discovered that patients' chances of recovery were greatly enhanced by careful supervision of their electrolytes and fluids. In all hemorrhaging diseases, as the capillaries leaked out precious fluids and proteins, the delicate chemical balances of vital organs such as kidneys, hearts, livers, and spleens were severely disrupted. Long before the immune system had a chance to mount a counterattack against the Hantaan virus, the organs would cease functioning and the patient would either convulse or go into shock. Also in from Bethesda was Pat Webb, Johnson's petite fiancée. Born in England and trained in both medicine and virology, Webb was doing research at NIH and had planned to move to Panama soon to join Johnson. Short, thin, and prematurely graying, Webb had an often caustic, opinionated style of speech. But for those who persevered, knowing Webb meant experiencing a woman possessed of a profound sense of humanity that infused her medical and research work. Now she sat beside her future husband and caressed, kissed, or embraced him whenever he could tolerate the pain of being touched. By deliberately touching Johnson to illustrate there was no danger, she hoped to allay the fears of the frightened hospital staff.3 Webb's fear was not the virus, but that Johnson would die, and a couple of times his condition seemed so grave she was convinced he wasn't going to make it. The Army physician's efforts, however, paid off. Johnson survived. As soon as he was up and about, Johnson started studying samples of the San Joaquin virus brought back to Panama with MacKenzie and Muñoz. He was able to confirm in the sophisticated MARU facilities what had tentatively been discovered in his glove-box contraption on the Bolivian frontier: the disease was caused by a virus that was similar to, but not the same as, Junin and Tacaribe. With Johnson safely recuperating, Webb headed back to Washington in late August. It had been two weeks, the worst was over, and it was time she got back to work. On board the plane she was suddenly seized by a pounding headache, muscle pains, and waves of shaking chills. The symptoms escalated until Webb knew that, despite all her protestations to the Gorgas nursing staff, she had gotten the virus from kissing and embracing her fiancé. She was treated at the NIH hospital and, after ten distressing days, had recovered enough to go home. A few weeks later, Webb moved to Panama and eagerly joined in the detective work. Though they had no way of knowing whether their painful illnesses had actually made them immune to the virus, Muñoz, MacKenzie, and Johnson made the journey back to San Joaquín in September, traveling now aboard USAF planes. They were quite naturally nervous, even fearful, but they felt compelled to return to the danger zone. The men shared a powerful scientific curiosity that pushed both doubt and fear aside, replacing them with a sleuthing urge every bit as powerful as that of a detective hunting down a serial killer. They needed to find out how the virus was transmitted in order to stop its spread. On the way, Johnson and MacKenzie reviewed all the possible ways the three of them could have become infected. Since the infections seemed to have been simultaneous, it was unlikely they were due to accidents or carelessness in their primitive field laboratories. The window screens and DDT had probably protected them from any virus-carrying insects that might lurk in San Joaquín. And the fact that many family members who tended to dying relatives were not ill seemed to rule out person-to-person transmission of the virus. Of course, Webb's illness forced an opposite conclusion. The only experience the three had shared shortly before becoming ill was the town party. But what possible association could there have been between the party and their near-deaths? In their absence Kuns had remained in San Joaquín, painstakingly capturing samples of every species of insect and mammal--from bedbugs to teeth-baring bats and slithering anacondas--he could get his hands on, all the while aware of the need to handle the animals with extreme care. As the wild rats tried to claw at him, or mosquitoes dove for his vulnerable flesh, Kuns deftly manipulated the creatures. "I understand the ways of animals," Kuns told his Bolivian assistants. He had a Ph. D. in veterinary sciences, specializing in the study of diseasesthat affected both humans and animals, and he had minored in wildlife ecology studies. Kuns was a details man; his training reinforced a natural tendency toward searching for answers by tediously sifting through mountains of minutiae. He and Johnson--the impatient man of action--were a study in contrasts. While the rest of the MARU team recuperated in Panama, Kuns organized forty San Joaquin men to assist in the capture of local creatures. All the men were volunteers who believed they had already had the strange disease and their survival presumably rendered them immune. Over a year's time Kuns and his volunteers would collect some 10,000 mammals of dozens of species, all of which had to be identified and studied for viral contamination. Even more insects were amassed, and Kuns pored over microscopes, used field texts to figure out just what species each and every creature represented, and trained his assistants to do the same. When identity was impossible to ascertain, Kuns shipped samples to the Smithsonian in Washington, D.C., or the Field Museum of Natural History in Chicago, where experts made the final judgment calls. In coming months Kuns would complete one of the most exhaustive ecology surveys ever conducted in South America, all done in the pressure-cooker atmosphere of an epidemic. Having flown bombing missions over Germany in World War II, Kuns had no trouble staying cool, though he never forgot that any insect or animal he held in his hands might carry the deadly virus. The team went to enormous lengths to find the culprit. A typical rectangular thatched/wattle house was purchased and meticulously deconstructed pole by pole, every insect and animal scraped off and analyzed. By night Kuns and MacKenzie, wearing miner's headlamps, waded into knee-deep water to collect nocturnal animals such as vampire bats and night mosquitoes. Even though they tried to maintain a modicum of nonchalance on such occasions, MacKenzie couldn't help but feel chills when he would turn suddenly and spot beady red eyes staring at him. After a few nights on such forays, Kuns and MacKenzie figured out that the eyes belonged to giant constrictor snakes, anacondas, one of which they measured at over eighteen feet in length. The townspeople were anxious to help, and Kuns had to warn people not to handle the animals unless they had already survived the disease. One afternoon the leader of Kuns's volunteer ecology army, Einar Dorado, held a big gray mouse in his hands while Merl tried to jab the beast with a needle in order to withdraw a blood sample. The angry animal squirmed, bit Dorado, and urinated over his hands. Two weeks later Dorado was dead. His prior ailment had probably been the flu and he was not immune to the mysterious virus. Kuns thought about that large gray mouse--a type of rodent that was pervasive throughout San Joaquin. He remembered visiting a small home in the middle of town and spotting a six-year-old girl asleep atop a cowhidelaid across the dirt floor. When the girl awoke, Kuns lifted the hide and dozens of those same big gray mice raced out of a nest in the floor. As soon as Johnson and MacKenzie arrived in San Joaquin, the team spread word that they would give money to anybody who captured sick wild animals. Despite the strong monetary incentive, villagers were able to bring in only five sick animals over the next ten months, all large gray mice. The rodents were of a wild Calomys species normally found in the bush. Three of the animals died, suffering symptoms similar to those seen among the people of San Joaquin. The other two recovered and became virus carriers. The mysterious virus, which the team had dubbed Machupo after the local river, was found in the blood, spleens, or brains of the five animals. The team hypothesized that the disease was carried the same way as the plague: by insects that inhabited the fur of the rodents. An alternative idea held that mosquitoes or ticks that fed on the mice might, in turn, feed on human blood and thereby spread the virus. In either case, an insect carrier had to be found. From September 1963 to November 1964, the team, now including Webb, made numerous frustrating trips back and forth between San Joaquin and their Panama laboratories. They captured thousands of insects, ranging from tiny fleas and mites to larger ticks and mosquitoes. The insects were mashed up and their extracts scoured for Machupo virus. None was found. Night after late night in the Panama laboratory Johnson complained to Webb, "I can't tell what the hell is going on. I'm running out of ideas here." After having solved the first parts of the mystery with awesome speed, the team was now mired in confusion. Kuns was convinced that better insect traps and more extensive forays in the foothills around San Joaquin would eventually smoke out the culprit, but Johnson was dubious.4 Some villagers in San Joaquin were downright fed up with the investigation, and the Americans became targets of wholesale theft of critical supplies, such as the diesel fuel for their generator. Things became so unstable that the Bolivian government declared martial law in the area, flying in fifty-five soldiers to maintain order. Thirty-seven of those soldiers eventually got the disease. The team's work was further delayed by angry anti-American uprisings in Panama that erupted into full-scale riots, forcing closure of the Canal Zone airport and delaying return trips by Johnson, Webb, MacKenzie, and Kuns. One hot June day in 1964 Johnson and Webb were going over their laboratory records in Panama and noticed an odd disease pattern among the hamsters they had infected experimentally. If they injected the virus into baby hamsters, the animals almost always died and the adult hamsters would eat the bodies. The adults would then become infected at a lowlevel, but would survive. The adults, however, would pass on lethal infections to previously disease-free baby hamsters. How had these babies become infected? Johnson and Webb, now married, happily spent long hours together in the laboratory, isolating viral samples from hamster blood. There were no shortcuts, no ways to get around the long tedious hours and days of work required to get a tiny pellet of viruses from thousands of hamster cells. Once the infected animal red blood cells were grown in petri dishes, the virus had to be purified out by a series of fractionization techniques. First, they mixed the hamster cells and blood with ammonium sulfate, which created a salted-out layer of gunk that sat at the bottom of a test tube. The fluid was poured off, and the virus-contaminated mass at the bottom was mixed with an alcohol, creating another layering. The virally infected layer, now smaller and purer, was spun about at low speed in a centrifuge; objects in the test tube migrated under spin to various positions according to their weights. The garbage--extraneous bits of hamster cells--formed a visible band in the tube, which was removed. Then the tube was spun again, this time at a very high speed, adequate to separate objects that differed only slightly in weight. A pellet would be left, at long last, at the tube's bottom--a nearly pure sample of concentrated, deadly Machupo viruses. Johnson and Webb discovered that the adult hamsters were shedding virus in their urine. They then bred wild mice from San Joaquin and found the same thing--the animals actively urinated Machupo virus. The baby rodents had become infected because they were caged in an atmosphere of wood chips and sawdust drenched in Machupo virus. Johnson felt the archetypical cartoon lightbulb flash above his head and heard himself shout, "Aha!" He returned to San Joaquin and did a very simple experiment: He divided the town in half. On one side he set five-cent mousetraps throughout houses and corn storage areas. The other half of San Joaquin was left alone. One woman living in the trap side of town begged Kuns to give her as many traps as possible; he could only spare three. In a single night she caught twenty-two mice in her home, proudly presenting them all to an astonished Kuns the following morning. Within two weeks the difference was obvious. While the epidemic continued at the same pace on one side of town, no new Machupo virus cases occurred where mousetraps had been set. Two weeks later, having set traps throughout San Joaquin, Johnson's team stopped the Machupo epidemic. "This is unbelievable," Johnson proudly said to himself. "Within just eighteen months we isolated the virus, discovered its mechanism of transmission, and stopped it cold." Between 1962 and 1964 over 40 percent of the residents of the San Joaquin region were sick with Machupo virus; some 10 to 20 percent of the villagers died of the disease. If the region hadn't been so sparselypopulated, the impact could have been devastating. As it was, for the people of San Joaquin, Magdalena, and the surrounding area, Machupo virus was a scourge that claimed at least one member of every family and was carried aboard mouse-infested supply carts to remote parts of the eastern frontier. Its impact on people's lives would not soon be forgotten. Over the next three years the Panama-based researchers would fill in some of the remaining pieces of the Machupo puzzle, and successfully stop a second outbreak of the disease deeper in the Bolivian savannas.5 Johnson put together a best-guess history of Machupo virus, and together with MacKenzie, Kuns, and Webb published several scientific papers between 1964 and 1966 describing most aspects of the virus. He decided the epidemic's roots lay in Bolivia's social revolution of 1952, when the people of the San Joaquin area suddenly found themselves without an employer or steady source of food supplies. In their haste to grow corn and other vegetables, they chopped down dense jungle areas of the alturas and bandas wherever the land naturally formed a relatively flat mesa above the Machupo River flood line. In so doing, they unwittingly disrupted the natural habitat of the Calomys field mouse and provided the rodent with a superior new food source: corn. The mouse population swelled during the 1950s and the rodents literally invaded the town of San Joaquin in the early 1960s. By the time the first cases of Bolivian hemorrhagic fever (as the disease was now dubbed) surfaced, the mice could be found anyplace the townspeople stored food and grain. And each night while the mice nibbled away at the humans' food supplies, they urinated. The virus could be eaten or inhaled or could gain entry through cuts in the skin; in any event, Machupo could be lethal. Johnson noticed that there was a ritual common to every household in San Joaquin. Before dawn the mothers and grandmothers would awaken and quietly prepare breakfast for the men and children. While pots boiled, the women would sweep their dirt and clay floors. "And each time they sweep that broom," Johnson realized, "they're sending mouse urine-infected dust and crumbs drifting all about in the air." Every time the families of San Joaquin assembled for breakfast, they shared virus-contaminated air. Johnson also decided that he, Ron, and Angel got sick as a result of eating contaminated food at the San Joaquin party. Researchers from the Rockefeller Foundation Laboratories in New York City and the University of Buenos Aires eventually reached a similar set of conclusions about the Argentine Junin virus. An Argentine team led by Dr. A. S. Parodi concluded that another species of wild Calomys mouse had been flushed out of its pampas habitat by post-World War II changes in local agricultural practices. Farmers had long had difficulty growing profitable crops of corn because short broad-leafed weeds had invaded thefields. After World War II, herbicides effectively eliminated the short grasses and dramatically increased crop yields.6 As harvest time approached, however, taller grasses that were not affected by herbicides would grow in the corn fields, thriving just when humans entered the fields to reap the corn. As it turned out, a fairly rare species of field mouse naturally subsisted on the seeds of these tall grasses. As the grasses proliferated, so did the mice, until the once-rare species became the dominant rodent of the region. The mouse, of course, carried Junin virus, the cause of Argentine hemorrhagic fever.7 MacKenzie thought another Bolivian factor also played a role in the San Joaquin epidemic. On all his trips to Magdalena, Orobayaya, and San Joaquin, he was struck by the remarkable absence of cats in the villages. When he asked the people what had happened to the cats, he was told they all died. The feline die-off coincided with the rise in the mouse population, allowing the Calomys to take over the town without battling predatory cats. There were two theories about why the cats died: they were also killed by the virus, or the felines were DDT victims. Bolivia was in the midst of a massive DDT-spraying campaign to eliminate malaria, and the quantities used in the homes of these remote areas were often so great that all furniture and walls were coated with a thin white film of insecticide powder. MacKenzie did a simple experiment. He injected six cats with the virus and force-fed DDT to six others. The virus-treated cats were completely unaffected by the experiment, but the DDT-poisoned animals all died of symptoms identical to those seen among the domestic pets of San Joaquin. Valverde was so impressed with MacKenzie's hypothesis that he went on national radio to issue a call for donated cats. In June 1964 hundreds of cats were airlifted into San Joaquin, and the epidemic's halt soon followed. Kuns, the ecologist of the group, wasn't ready to buy either the cat die-off idea or Johnson's notion of a mouse invasion. "It's stupid! Absolutely stupid," Kuns said of the cat/DDT link, noting that felines killed only the weak and sick members of mouse colonies and rarely had an enormous impact on the overall size of a rodent population. He wasn't at all convinced people could get infected as a result of eating food contaminated with mouse urine either. To Johnson's theory that three of the scientists got the disease as a result of feasting at the fiesta he said, with a wink, "You ought to think about what you did after the fiesta, boys, not what you ate."8 Kuns believed the epidemic began when the virus itself changed and became more virulent. And he felt the exact mode of transmission of the disease from mouse to human was still unresolved. Kuns told the NIH that he wanted to put fluorescent chemicals in mousefood and then use ultraviolet lights to follow the animals' urine trails in San Joaquin. That, he hoped, would answer the question by showing where the animals' urine came in intimate contact with human noses, mouths, and inhalations. His hunch was that the rodents scampered around the villages while people slept, directly infecting the slumbering men, women, and children. But once the epidemic was abated the NIH withdrew all research funds and Kuns's efforts came to a full stop. "Hardly anything has ever disappointed me more in all my thirty-nine years than having to pull out of here without finishing the job," Kuns mumbled to himself as he packed up his microscope and thousands of animal samples. When a few cases of the disease appeared in San Joaquin a year later, Kuns told The Saturday Evening Post: "You might compare us to firemen. We've discovered the location of the blaze and we've put it out. But we still don't know where or when it could start again."9 For his part, however, Johnson was quite pleased. By the end of 1964 Johnson was able to look over his recent accomplishments with great pride. Together with MacKenzie, Kuns, and Webb, he had solved an intriguing mystery, stopped an epidemic, published in prominent scientific journals, and organized a crackerjack virology laboratory in Panama that was prepared to tackle anything that might surface in the Americas. Furthermore, the NIH promoted him to director of the whole MARU facility. He had also found love, honor, and a mission in life. He married Patricia Ann Webb, received the Decorated Order of the Condor from the Bolivian government, and discovered his personal call of the wild. He had survived a near-death experience and then gone on to defeat the enemy on its own turf. "That's enough for some people for a lifetime," thought the thirty-five-year-old. "But that's just the start for me." His life dreams now changed forever, Johnson sought ways to combine science, clinical medicine, and good old-fashioned detective work. Wherever he went, whatever epidemics might come his way, he knew these were the skills he would use, and the challenges he would relish. From then on, Johnson stressed the need for calm in the face of epidemics, for reason, science, sound clinical training, and the ability to work with a team of diverse expertise. These were lessons passed on first to those who worked with Johnson in Panama and later to a whole generation of infectious disease "cowboys." Over the next two decades Johnson and his "cowboys" would fight dozens of skirmishes and a few pitched battles with the microbes, always maintaining a healthy respect for both their microscopic enemies and the human bureaucracies, governments, and institutions whose rules Johnson would regularly defy. The war was on, and the battlefield was the entire planet. Copyright (c) 1994 by Laurie Garrett Excerpted from The Coming Plague: Newly Emerging Diseases in a World Out of Balance by Laurie Garrett All rights reserved by the original copyright owners. Excerpts are provided for display purposes only and may not be reproduced, reprinted or distributed without the written permission of the publisher.