This 1991 article from National Geographic describes the work of epidemiologists, modern day “disease detectives,” who travel the world seeking the cause of both old and new infectious diseases.
The Disease Detectives
By Peter Jaret
“We live in muck and filthe,” they wrote to the London Times on July 3, 1849, in a letter signed by 54 of that city's poor. “We aint got no priviz, no dust bins, no drains, no water-splies, and no drain or suer in the hole place..... We all of us suffur, and numbers are ill, and if the Colera comes Lord help us.” Five years later, in 1854, cholera came with a vengeance.
A man waking in good health, it was said, could be dead by sundown. Within 250 yards of the intersection of Cambridge and Broad Streets, more than 500 people died in little more than a week. Carts groaned under the weight of corpses carried away for mass burial. Those who could, fled. Others locked themselves away in fear.
No one knew how or why contagions spread. Some blamed foul vapors. Others saw the work of divine retribution. Decades would pass before medical scientists accepted the idea that microbes too small to see were the cause of infection.
But a 41-year-old physician named John Snow believed he had found the source of the Broad Street contagion. On a map of London, Snow marked where victims died. Nearly all the deaths, he saw, had taken place near the Broad Street pump—one of many public water pumps in London.
But before he could be sure, Snow had to understand why ten deaths had occurred nearer another street pump. Amid the growing panic Snow visited the families of the deceased. Five of the distant victims, he learned, regularly sent for water from the pump at Broad Street, preferring its taste. Three others were children who attended a school near Broad Street's pump.
That was all he needed. On September 7, Snow appeared before the vestry of St. James's Parish, meeting in solemn consultation on the causes of the epidemic. His request astonished them. He asked that the Broad Street pump handle be removed. It was. Within days the outbreak of cholera ended.
Although Snow did not discover cholera's cause—a bacterium called Vibrio cholerae—his methodical work helped establish modern epidemiology, “the art and science,” as one of his present-day counterparts would put it, “of chasing epidemics.”
Today the Broad Street pump is gone. In its place I find the John Snow pub. I've come here to inaugurate a journalistic adventure. I am setting out to explore the nature of today's epidemics as well as the scientists who chase them. I've taken a crash course in epidemiology at the federal Centers for Disease Control (CDC) in Atlanta, Georgia, headquarters for the world's most famous medical sleuths. My honorary diploma in hand, I'm ready to follow in the footsteps of John Snow. Even as I raise my glass in the pub that bears his name, the CDC receives word that his old enemy, cholera, has struck again, this time in the small West African nation of Guinea-Bissau.
“Stop! Zona infectada cólera,” warns the handwritten sign strung on surgical gauze across the courtyard of Simão Mendes Hospital in Bissau, the nation's capital.
“Not very long ago this courtyard was crowded with cholera victims. Scores of new cases were arriving each day,” says my companion, a young physician named Nathan Shaffer. He is an officer with the Epidemic Intelligence Service (EIS), a corps of CDC disease detectives—some 65 doctors, nurses, and other experts in public health on call 24 hours a day for two years, ready at the first alarm to chase down an epidemic.
Vibrio cholerae infects the intestinal tract, releasing a toxin that causes severe diarrhea. Untreated, patients can become rapidly dehydrated and die. But drinking a simple solution of water, salts, and sugar usually heads off severe dehydration, giving the body a chance to eliminate the infection. So though the faces we pass in a cholera clinic are gaunt, these victims are safe. And the epidemic is ebbing.
Shaffer fills me in on his investigation. “Of course, I wondered about water—especially in a country that lacks even basic water sanitation. But the outbreaks didn't seem to be associated with particular wells. Here, you can see for yourself....”
He unfolds a map of Guinea-Bissau. Black marks indicate reported outbreaks of cholera. “The epidemic was spreading up and down the coast. Right away I suspected shellfish.”
Like John Snow, Shaffer went door-to-door through the hot, dusty streets of Guinea-Bissau. “An epidemiologist, like any good detective, begins by asking questions,” he tells me. “Who are the victims? What sets them apart from those who remain well? Where do they live, what do they eat and drink, when did they fall ill?”
Shaffer and I tour local markets, gathering shrimp and crabs to be tested for cholera. But even if the specimens harbor the cholera bacteria, one mystery remains.
Shaffer points out three black marks on his map—places where cholera has flared up far inland. Contaminated shellfish could have been carried from the coast. But there's a more macabre possibility. The bacteria may have traveled in bodies carried home for traditional funeral rites. Washing the bodies and preparing funeral feasts, often in unsanitary conditions, relatives and friends of the dead could have spread the disease.
We set out for the village of Quinsana, where cholera had claimed more than 80 victims. There we learn that a dockworker named Ocanti Te fell sick after returning from the capital. He died two days later. So did his 15-year-old son.
Villagers gather in the shade of the dockworker's porch.
“Who cared for the sick man and his son?” Shaffer asks them. “Was a funeral feast held? How were the victims buried?”
We learn little. The government has banned traditional funerals, and the village leader forbids talk about the burial.
Shaffer is disappointed. “An epidemiologist is part historian,” he explains. “We depend on people's memories and their willingness to tell what happened.”
For the next three weeks Shaffer continues his investigation. I visit him in Atlanta several months later, near the end of his EIS term, to discuss his findings. He has been seriously ill, not with cholera but with a rare parasitic infection he picked up in Guinea-Bissau—one risk of medical detective work.
But his persistence paid off. In another inland village where 11 had died, he proved his suspicion. The body of a dockworker had been smuggled home for burial. More than half the people who ate the funeral feast came down with cholera.
Shaffer adds a footnote. “When I went back through the data I gathered going door-to-door through the capital, I found an unexpected pattern. Families that possessed hand soap were far less likely to become infected than those without soap.”
Could something as simple as soap have slowed the epidemic? Almost certainly. John Snow himself wrote that “nothing has been found to favour the extension of cholera more than want of personal cleanliness....”
Strictly speaking, an epidemic is any unusual outbreak of illness,” Lyle Conrad of the CDC tells me. As director of field operations for the Division of Epidemiology, he has seen plenty. “There are as many as 3,000 outbreaks each year in the U. S. alone. No one knows how many more occur around the world.”
He shows me a list: hepatitis in a Washington, D. C., daycare center; measles at a small college in Colorado; an unexplained surge of tuberculosis in New York; Legionnaires' disease in Michigan.
Each year the CDC's laboratories receive hundreds of thousands of specimens—blood, tissue, puzzling microbes—illnesses in search of a diagnosis. Many are permanently stored here, part of a huge archive of maladies. Some are so deadly that scientists must don helmets and contamination-proof suits to enter the air lock of the maximum containment laboratory, where killer microbes reside.
“The same new technologies that have revolutionized modern medicine have also given us amazing powers of detection,” says Conrad. For instance, new instruments can search a single drop of blood for signs of dozens of diseases.
“But the science of epidemiology still owes much to John Snow,” he adds. Maps remain crucial. A pen and paper often come in handier than the fastest computer. The epidemiologist's laboratory is still the human community.
In the 1970s that laboratory was the wooded areas near Lyme, Connecticut.
A young mother named Polly Murray was among the first to notice. One by one her family had developed a baffling array of symptoms: rashes, headaches, pain and stiffness in their joints. “By the summer of 1975 my husband and two of the children were on crutches,” she recounts. “Meanwhile I kept hearing about other people, most of them children, with the same symptoms.” Alarmed, she contacted state health authorities.
At the time, epidemiologist Allen Steere had just settled down at Yale University to pursue a fellowship in rheumatology—the study of arthritis-like diseases. “Juvenile arthritis is rare,” Steere tells me. “And arthritis isn't known to be infectious.”
But in the Lyme area he found 39 children and 12 adults with swollen, painful joints. Along four rural roads, one in every ten children was affected. “I was astonished,” he recalls. “It seemed almost certain that we were looking at a new disease.”
But what was it? And how was it spreading?
All of the victims lived near wooded areas. Many first noticed their symptoms in summer or fall. Summer is insect time, and the woods around Lyme are a perfect breeding ground. Steere began to wonder if an insect could be transmitting the illness.
When he interviewed his patients, some mentioned an unusual bull's-eye rash that appeared weeks before their symptoms began. It was similar to a rash reported in Europe, thought to be caused by a tick bite.
“In 1977 one of my patients who happened to be an ecologist actually brought me the tick that had bitten him,” Steere remembers.
That tick was Ixodes dammini. And where it occurred—mostly on the east side of the Connecticut River—people were getting sick. To the west, where the tick was much rarer, the puzzling illness was far less prevalent.
In 1981, while studying tickborne diseases with pathologist Jorge Benach, entomologist Willy Burgdorfer discovered that I. dammini was infected with a corkscrew-shaped bacterium called a spirochete.
“The Lyme disease spirochete has probably been infecting ticks for a long time,” contends Andrew Spielman, the Harvard University entomologist who first described I. dammini. A recent study noted that museum specimens of ticks collected on Long Island in the 1940s were infected. Since then tick populations in the Northeast have increased dramatically, triggering the epidemic.
Why are there more ticks? Many of the forests that had been felled in the region have returned. And deer populations, especially in the past few decades, have exploded. So have the numbers of I. dammini, which feed on deer.
Deer themselves do not become ill. But when a tick bite infects a human host, the result can be devastating disease, including crippling arthritis and memory loss. Last year more than 7,000 new cases of Lyme disease were reported. Efforts to find a vaccine are under way, but the infection continues to frighten much of the country each summer.
Each fall the CDC epidemiologists brace themselves for one of nature's most reliable epidemics—influenza. “Believe me, we have every reason to be afraid of this virus,” warns Alan Kendal, head of the CDC's influenza branch. “Every year it claims thousands of lives in the U. S. When a new strain appears, hundreds of thousands of people may die around the world.”
Periodically, devastating global epidemics develop. During the 1918-19 pandemic, flu killed at least 20 million people. “We don't know what made that flu so deadly,” Kendal admits. “And there is always the chance that another one will strike.”
Influenza viruses constantly evolve. And spread fast. A new strain emerging in Asia can circle the globe within months. Vaccines can protect, but a vaccine must be created for each strain. That means spotting mutations early.
“For flu hunters China is the most fertile ground,” Kendal tells me. “Virtually all new strains arise there. Pigs and ducks, common on Chinese farms, harbor the virus. Perhaps they serve as mixing vessels for new strains.”
Mutations may enable animal viruses to infect humans. Not just flu but also such diseases as tuberculosis and measles may have originated in animals.
“The sooner we spot a new strain of influenza, the sooner we can prepare a vaccine against it,” says Kendal.
He describes a flu-hunting mission to China he is planning for December. “Want to come along?” he asks.
Such a strange safari is irresistible, and a few months later we are touring the country in search of the latest virus. To our chagrin we can find none. In Beijing and Xian, to the west, we are told that 1987 is an unusually light year for flu. But the CDC has already reported the first outbreak of influenza back home—among a group of American tourists returning from China!
Persistent, we head to China's largest city, Shanghai. Our taxi ferries us through its crowded streets, past the bustling harbor filled with ships from around the world. We pass farmers with carts of produce from the countryside. So many people. So many comings and goings. So many opportunities to catch the flu.
We reach the Shanghai Hygiene and Anti-Epidemic Center, housed in a dilapidated building of European design—a reminder of this city's past. It is not heated, and for several very cold hours, while we warm our hands around cups of tea, Kendal tells the Chinese scientists that he hopes to procure freeze-drying equipment for them. That way they could mail specimens back to Atlanta, eliminating the need for trips such as this. He proposes an exchange with the CDC, to train students in genetic analysis techniques. Eventually their labs might simply fax a sheet of paper with information about the genetic structure of new viral strains. Still, for now we need live viruses.
We tour overcrowded laboratories, wearing down jackets beneath our medical gowns. I am convinced we will go home empty-handed. The meetings are finished. We are getting ready to leave, when Huang Yu Shun, deputy director of the center, holds out a shiny stainless-steel canister. Kendal opens it to find just what we came for: a dozen glass tubes filled with flu specimens from local hospitals.
A month later, back at the CDC, the viruses have been analyzed. We have caught a new strain: A/Shanghai/11/87. It has been transformed into a map of sorts.
Microbiologist Nancy Cox points to a sheet marked by rows of numbers and strange codes—Asn, Phe, Gly, Leu, Ser, amino acids that make up the proteins of a virus.
“Because the unique identity of a virus is determined by the specific order of amino acids in its proteins,” Cox explains, “we can use maps like these to compare different viral strains. And when a new strain like A/Shanghai/11/87 appears, we can alter the current vaccine to protect against it.”
What would John Snow have made of such a map? A simple street plan of London had helped him track down cholera. Now molecular epidemiologists are using genetic maps to extend the search for patterns deep into the building blocks of life itself.
And disease detectives have stretched the boundaries of epidemiology in other directions, taking on new illnesses like heart disease and cancer, diseases that may develop over a lifetime.
“The whole point of Framingham was to begin when people were healthy,” physician William Castelli tells me at the Framingham Heart Study clinic. In 1948 epidemiologists descended on Framingham, Massachusetts, population 28,000. Some 5,000 volunteers were recruited for the initial study. Every two years since then they have undergone physicals and answered dozens of questions. “As our subjects developed heart disease, as some inevitably did, we began to understand what factors put people at risk.”
Indeed, much of what we know about the risks of heart disease—high blood pressure, elevated cholesterol levels, cigarette smoking, lack of exercise—has been learned here.
But ending the epidemic of heart disease, says Castelli, won't be easy. “The causes of chronic diseases like cancer and heart disease are complex, rooted in how we live. It would be nice to think that all we have to do is locate the pump and remove the handle. But our job is much tougher.”
Nowhere is the challenge greater than in an epidemic that runs wild through the streets of the nation's inner cities. One Saturday night in an emergency room at Atlanta's Grady Memorial Hospital, I witness its toll.
Just after eleven o'clock the call comes. An ambulance is on its way, carrying a black male, 18, shot through the back.
I watch from the corner of the operating room while doctors and nurses try to save him, connecting IV tubes, transfusing blood, probing the wound. “I'm not getting a pressure on him,” someone says.
The flow of blood can't be stemmed. The bullet has torn his heart. Forty minutes later Edward Smith is dead.
“A black male born in the U. S. today has a one-in-27 chance of being murdered,” CDC epidemiologist Mark Rosenberg tells me. He shakes his head in outrage. “One in 27. And most of those victims will be young.”
Traditionally, violence has been a matter for the police, not medical sleuths. But Rosenberg believes classic methods of disease detection can help curb violence.
“If we can find a pattern,” he says, “we can find ways to intervene. Kids who are at risk can learn to stop arguments before they escalate into violence. Public-health people can begin to recognize behaviors that lead to spouse abuse. Communities can learn to spot the warning signs of teenage suicide.”
Rosenberg is no dreamer. He knows the causes of violence and suicide—poverty, drugs, hopelessness—run deep. “But it wasn't long ago that smallpox was considered a fact of life in most parts of the world, something that people simply accepted,” he reminds me. “We've eradicated smallpox, wiped it off the face of the earth. Today people think violence is a fact of life. I don't believe we have to accept that.”
In truth smallpox remains, sequestered in two laboratories—one in Atlanta, the other in Moscow. Scientists still debate whether to exterminate these last viruses or preserve them for study.
But there's no doubt that the end of smallpox represents one of the greatest triumphs in public health. Indeed, until this past decade, it seemed as if most infectious diseases were being tamed, at least in the developed world. Until 1981—when we first realized that a new, appallingly destructive disease was silently spreading. That disease was AIDS.
“Classic epidemiology was all we had to go on,” recalls James Curran, who directed the CDC's first investigations in the early 1980s and now leads the agency's continuing battle against AIDS. “Week by week the reports came in of a bewildering array of puzzling infections. An unusual and often deadly form of pneumonia. Skin cancer so rare that most physicians had never seen it.”
Epidemiologists quickly traced the disease to sexual contact. Then the first hemophiliac with AIDS was diagnosed, and it became clear that contaminated blood could also transmit the illness. Soon an infant was born to an infected mother, proving the disease could spread from mother to child. Researchers also realized that it could lurk in the bloodstream for years before producing any symptoms.
In July 1981 Curran and his staff reviewed local medical records for rare cancers and infections going back to 1976. “Nothing showed up in 1976 or 1977,” he remembers. “Then in 1978 we began to find isolated cases of the symptoms we are seeing now. No one knew what to make of them back then. Now we know we were looking at the birth of a new disease.”
Recently medical detectives have tracked AIDS surprisingly deeper into the past. At the Manchester Royal Infirmary in England, British physician Trevor Stretton still recalls vividly the 25-year-old sailor who appeared in the clinic in 1959. “He was feverish, losing weight, wasting away,” says Stretton, who was himself a young physician in training at the time. “Sores covered his skin. Nothing we could do seemed to help. He died before our eyes. We hadn't the slightest idea why.”
The customary autopsy was performed. Tissue samples from different organs were preserved in blocks of paraffin and stored—but not forgotten. The unsolved case haunted Stretton and his colleagues.
Then in the early 1980s young men in San Francisco, New York, Los Angeles began to sicken and die—wracked with fever, gasping for breath, bodies often covered with strange sores.
Could the sailor, Stretton wondered, have died of AIDS? No one dreamed AIDS was afoot in the 1950s. If so, could it be proved? No blood samples had been saved. Pathologist George Williams, who performed the original autopsy, located the tissue specimens. But when virologists at nearby University of Manchester examined them, they found no sign of the AIDS virus.
And there the case might have ended. But in the 1980s American scientists developed a disease detection technique of extraordinary sensitivity. Called polymerase chain reaction (PCR), it allows researchers to detect a mere fragment of a virus lurking within tissue and then make millions of copies to analyze. Using PCR, the Manchester virologists identified the AIDS virus in four of the six tissue specimens. Thus, three decades after he had helplessly watched the young sailor die, Stretton was able to make his diagnosis....
In 1989 the CDC began random and anonymous testing of blood samples from 26 hospitals around the country. One out of every 75 patients was found to be infected with the AIDS virus.
Some areas of the nation are harder hit than others. In one New Jersey hospital one in every four men admitted between the ages of 25 and 44 years old is infected.
And AIDS continues to spread. Based on a military study, the CDC estimates that as many as 40,000 adolescents and young adults become infected each year. It also reports that some 2,000 babies were born in 1989 carrying the virus.
What spawned AIDS?
I put that question to Max Essex, director of the Harvard AIDS Institute and one of the world's leading experts on the origins of the AIDS virus. “One possibility is that AIDS has been around for a long time, hidden away in some remote human community,” he explains. “Then, as travel and contact increased, the virus began to spread. But I think there's a more likely explanation.”
The AIDS virus, called human immunodeficiency virus, or HIV, may have existed for centuries in African monkeys and apes.
“African chimpanzees can be infected with HIV, but they don't develop the disease,” Essex tells me. “That suggests that chimpanzees have developed protective immunity.”
Then, perhaps as recently as 40 years ago, this virus crossed from monkey into man. Was there a small genetic change in the virus? Or was there simply more contact between monkeys and people as human populations encroached on jungle areas?
“When a new disease infects a previously unexposed population, the impact is often devastating,” says Essex. “Smallpox, carried to the New World by European explorers, decimated the native peoples.
“But it never pays to kill off your host, even for a virus. Evolution favors a truce. Viruses become less virulent. Hosts eventually develop immunity. Explosive epidemics are often just the first stage in the evolution of a new disease. Eventually AIDS too will probably evolve into a milder, even harmless disease,” says Essex. “But that will require centuries.”
Long before then, some researchers worry, new diseases, perhaps even deadlier than AIDS, will emerge. “An epidemic is an experiment of nature,” explains virus expert Stephen Morse of Rockefeller University. “Like all living things, viruses and bacteria are constantly evolving. At the same time, human communities are changing, creating new ways for diseases to spread.”
Morse believes we may be inadvertently creating ideal conditions for new epidemics. Rapidly increasing human populations provide a fertile breeding ground for microbes. And as the planet becomes more crowded, the distances that separate us seem smaller. “Today it takes a matter of hours to travel by plane from Sierra Leone to New York,” Morse points out. “In the rush to get from here to there, we're opening up unprecedented highways for viral traffic.”
In some cases, literal highways. “The recent completion of a major road through the Amazon rain forest of Brazil led to outbreaks of malaria in the region,” he says. “In Kenya, AIDS almost certainly traveled the Mombasa-Nairobi highway.”
Commerce too provides routes for new disease agents. In 1985 used tires imported into Houston, Texas, from eastern Asia carried larvae of the Asian tiger mosquito. Virtually unknown in this country until then, this mosquito can be a dangerous vector for serious tropical diseases—including dengue fever, which kills as many as 5,000 children worldwide each year. Today the Asian tiger mosquito has established itself in 17 states.
Ironically, even lifesaving medical technologies pose a threat. Blood transfusions have provided an unforeseen path for viruses, spreading both hepatitis and AIDS.
But perhaps most worrisome, says Morse, is disruptive environmental change. “We know already that deforestation and sweeping agricultural changes can unleash epidemics. Major outbreaks of Rift Valley fever followed the construction of the Aswan High Dam—most likely because breeding grounds were created for mosquitoes, which spread the disease. In Brazil the introduction of cacao farming coincided with epidemics of Oropouche fever—a disease linked to a biting insect that thrives in discarded hulls.”
Will the destruction of tropical rain forests release viruses that have long remained isolated? Will the sweeping changes predicted because of global warming alter animal habitats in ways that encourage the spread of new lethal diseases?
“Isolated outbreaks of exotic diseases are constantly occurring,” says Morse. Seven years ago, for instance, a mysterious epidemic of a swiftly fatal hemorrhagic fever killed a dozen children in rural Brazil. Other isolated outbreaks have followed. Researchers linked the disease to a common bacterium long known to cause conjunctivitis, a mild eye infection. A slight evolutionary mutation, they suspect, has transformed it into a killer. If the disease should reach densely populated São Paulo, it could prove disastrous.
“Ebola fever, swine flu, Marburg fever, Rocio encephalitis—these are all deadly diseases that have appeared and then, for no reason, disappeared again,” says Morse. “Any one of them, given the right circumstances, could break out and ignite global epidemics. That's the lesson of AIDS.”
Such lessons will have little meaning to a small boy I'll call Jerome.
Jerome is a Christmas baby, born December 25, 1985. But he has had few blessings. He began life infected with AIDS. Most of his short life will be spent here on the 17th floor of Harlem Hospital Center. Except for a few halting words, he has never learned to speak, and probably never will. His fingers have become clubbed, a sign that his lungs aren't taking in enough oxygen. His doctor tells me that he probably won't see another Christmas.
AIDS continues to spread fast among intravenous drug users. The epidemic of crack cocaine, which encourages prostitution and indiscriminate sexual behavior, has worsened the situation. Inadequate medical care in our country's inner cities allows other sexually transmitted diseases to go untreated, fostering an environment that may also speed the spread of AIDS. Warns Phyllis Kanki, a researcher with the Harvard AIDS Institute, “We are creating the conditions of poorest Africa right here in our own backyards.”
What is there to feel but despair?
For Michael Talbert, however, despair is a waste of time. I meet him one afternoon in Steve Swanson's senior English class at San Francisco's Riordan High School, six weeks before graduation. Today these students will learn a lesson as important as any they will take into the world.
Talbert, 37, has come to tell them about AIDS—which will eventually claim his life.
They seem wary at first, embarrassed. Talbert tells them that it has been three years since he was diagnosed with AIDS. “My hobby then was weight lifting,” he says. “I was pressing 350 pounds.”
The kids look startled. Talbert's body is so frail that he sometimes needs a cane to walk.
“I always thought bad things happened to other people. Other people got mono. Other people's girlfriends got pregnant. Then I got mono. My girlfriend got pregnant.”
The kids laugh. He has touched a nerve.
“That's what I thought about AIDS too,” he says quietly.
Later the students ask questions. “How do you think you got AIDS?””Most likely through sexual contact,” Talbert answers. “What did your friends say when you told them?””Some of them were very caring. Some of them were afraid,” he replies.
“Back when I got infected, people didn't know how to protect themselves,” he says. “We didn't have a chance. You do. You don't have to let this happen to you.”
In his small, determined way, I realize, Talbert is removing the pump handle.
Perhaps that is the most important lesson of AIDS. For if this devastating disease has taught us that epidemics will always threaten, it has also shown us that we are not helpless. Day by day, knowledge about AIDS is winning out over ignorance. Fear is giving way to compassion. Medications are slowing the disease's progress. Hopes for a vaccine grow. Moreover, in recent months intensive research has identified 13 ways the AIDS virus may be vulnerable to medical counterattack.
And around the world there are people like Michael Talbert.
“If I can keep just one of these kids from becoming infected,” he tells me after class, exhausted by the effort of speaking, “I've made a difference. I've won one small victory against this terrible virus.”
Source: National Geographic, January 1991.
Microsoft ® Encarta ® Encyclopedia 2002. © 1993-2001 Microsoft Corporation. All rights reserved.
