The Coming Plague (41 page)
Authors: Laurie Garrett
Harvard Medical School virologist Bernard Fields, who tried to perform studies of viral disease agents simultaneously on the micro, laboratory level and the macro, clinical scale, wondered just how relevant all this gene jumping was to human health. He likened viruses to spaceships on a voyage in to a hostile environment. Their payloadâthe viral DNA or RNA, replete with all its jumping gene and transposing potentialâwas hidden inside a delivery system that, in Fields's analogy, included propulsion and navigation systems and a protective capsule capable of withstanding the viral equivalent of an Apollo spacecraft's heated reentry into Earth's atmosphere. To gain access to its target cells in the human bloodstream, liver, brain, or whatever organ it was designed to infect, the virus had first to pass through significant hostile territory: the skin, intestinal lining, mucosal barriers in the reproductive tract, protective linings of the nose, mouth, and lungs, and the blood/brain barrier that barred entry to the central nervous system. Fields sought to keep concerns about the newly discovered viruses in check, insisting that the tiniest of microbes would die out if they mutated radically because they would, in the process of mutation, damage their vital payload and delivery systems.
A few scientists focused their attention on the origins of such viruses. Gallo, for example, forwarded the hypothesis that the HTLV-I and HTLV-II viruses made their way around the world along the shipping routes pioneered by Magellan and slave traders. He and Yamamoto asserted that the viruses originated in African monkeys, spread somehow into the human population, and then found their way around the world via sexual transmission between slaves.
27
An alternative theory was that the virus originated in Africa and was carried by Portuguese sailors to the port city of Kyushu during the sixteenth century.
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An alternative theory was that the virus originated in Africa and was carried by Portuguese sailors to the port city of Kyushu during the sixteenth century.
28
A few months before the discovery of HTLV-II was publicly announced, the U.S. National Cancer Institute and the Tokyo Cancer Institute held their 1982 annual Japanese-American cancer meeting, focusing on HTLV-I. The Japanese had trouble narrowing the pool of HTLV-I researchers down to the limit of seven participants who could attend the elite gathering. Research on HTLV-I had exploded in Japan, with over a dozen large laboratories attacking the scientific problem.
For the Americans, the reverse was the case. Besides Gallo and his staff at the National Cancer Institute, nobody was devoting much attention to HTLV-I, and many leading cancer experts in January 1982 pooh-poohed the significance of the virus. Since the meeting was to be chaired by the Americans, the National Cancer Institute was at pains to find a leader for the gathering who was generally familiar with cancer-causing retroviruses. The institute selected Harvard virologist Myron “Max” Essex, who was one of the world's experts on the feline leukemia virus (FeLV), a retrovirus that caused cancer in cats.
29
The Rhode Island-born Yankee was both a trained
veterinarian and microbiologist. At the time the Japanese-American meeting took place, Essex was the newly-appointed Chair of the Department of Cancer Biology at the Harvard School of Public Health.
29
The Rhode Island-born Yankee was both a trained
veterinarian and microbiologist. At the time the Japanese-American meeting took place, Essex was the newly-appointed Chair of the Department of Cancer Biology at the Harvard School of Public Health.
As the meeting unfolded it was clear that the Japanese were studying HTLV-I at a feverish pace, and had made impressive strides in elucidating the relationship between the virus and genesis of hairy-cell leukemia.
Gallo was not happy.
“I can't even get people in my own lab interested in working on this virus,” Gallo told Essex. “Nobody in the U.S. is taking this thing seriously, but the Japanese are working like crazy on it. They're pulling ahead of us.”
Essex acknowledged that the range and quality of data that various Japanese scientists had presented were quite good. Gallo leaned over and looked earnestly into Essex's eyes.
“Max, you've got to get involved.”
Essex protested that his lab was already overwhelmed with work on other cancer-causing viruses, notably FeLV and hepatitis B,
30
which produced liver tumors. But Gallo's insistence won him over.
30
which produced liver tumors. But Gallo's insistence won him over.
Essex applied the tools his lab had developed for studying T-lymphocyte responses to the cat virus to answer questions about how the human immune system reacted to HTLV-I. He soon demonstrated that, as was the case with FeLV in cats, humans infected with HTLV-I had aberrant immune systems. In particular, their T cells were suppressed or deficient in number, leading to an overall inadequacy of the entire immune system.
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Researchers from the Tokyo Cancer Institute showed that 100 percent of the Japanese islanders who had hairy-cell leukemias were infected with HTLV-I. But about 12 to 15 percent of the adult residents of the area were also infected, without having cancer: they did, however, suffer a range of immune system disorders.
Essex was convinced that these striking similarities between HTLV-I and FeLV pointed to some distant time when the viruses moved between host species. Similarly, he was convinced that hepatitis B viruses in various animal species all evolved from a common ancestor: the genes of the human virus were over 40 percent identical to those of a liver-cancer-causing virus found in, of all things, woodchucks.
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In both species, it would later be shown, the virus caused nearly all hepatocellular carcinomas; perhaps 100 percent of such tumors in the woodchucks and about 90 percent of those in human beings. Worldwide surveillance would eventually reveal that millions of people were infected with the hepatitis B virus, about 15 percent were chronically ill, and as a result, perhaps five million developed liver cancer every year.
33
Hepatitis B was not a retrovirus, of course, but a large virus whose genetic material was in organized segments of DNA. Scientists had no idea how the virus caused cancer, and there was no clear link between hepatitis B and any known oncogenes.
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Hepatitis B was not a retrovirus, of course, but a large virus whose genetic material was in organized segments of DNA. Scientists had no idea how the virus caused cancer, and there was no clear link between hepatitis B and any known oncogenes.
By 1980 there was also strong evidence linking some other DNA viruses to human cancer. As early as the 1960s, Denis Burkitt, a British physician working in Uganda, had noticed that a certain type of lymphoma was extremely common in East Africa, and that its distribution in the human population seemed to follow a clustering pattern: whole families or villages might be afflicted in one area, while virtually no cases of the cancer could be found in a nearby village. He hypothesized that the disease was caused by a transmissible virus.
34
British researchers Michael Epstein and Y. M. Barr discovered a new type of herpes virus in cells from Burkitt's lymphoma patients.
35
The tumor was dubbed Burkitt's lymphoma, the virus Epstein-Barr virus or EBV. Like hepatitis B, EBV was a fairly large DNA virus and scientists could find no immediate explanation for how it caused the lymphomas. Similarly, human papillomavirus was linked to genital cancers, particularly cervical carcinoma.
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British researchers Michael Epstein and Y. M. Barr discovered a new type of herpes virus in cells from Burkitt's lymphoma patients.
35
The tumor was dubbed Burkitt's lymphoma, the virus Epstein-Barr virus or EBV. Like hepatitis B, EBV was a fairly large DNA virus and scientists could find no immediate explanation for how it caused the lymphomas. Similarly, human papillomavirus was linked to genital cancers, particularly cervical carcinoma.
36
Though much about the connection between viruses and cancer remained obscure, it was an accepted tenet of biology by 1982 that viruses could directly, or perhaps through intermediary chemicals or host genes, cause the changes in cells that were the hallmarks of cancer. It was also generally accepted that such viruses might take years to produce clinically noticeable symptoms in those humans or animals who were infected. Thus, the concept of
slow
viruses had emergedâan idea epidemiologists found extremely challenging because of the difficulty of showing that a population of people have cancer today due to a virus they were exposed to ten or twenty years ago.
slow
viruses had emergedâan idea epidemiologists found extremely challenging because of the difficulty of showing that a population of people have cancer today due to a virus they were exposed to ten or twenty years ago.
The remarkable genetic similarities between oncogenes found in all animals, humans, even insects seemed to signal a commonly shared point of vulnerability in a huge range of the planet's fauna. If a virus adapted to infect, for example, a monkey and deftly switch on the simian's oncogene, could it not also, with some evolutionary or rapid mutation, gain the ability to enter human cells and switch on the nearly identical
Homo sapiens
oncogene?
Homo sapiens
oncogene?
Given the slow pace of the disease process produced by such viruses, and the ability of some to hide inside animal or human DNA, these microbes were extremely difficult to detect.
How many more might exist in nature?
How many types of cancer might prove to be caused by such viruses? Were there other diseases slow viruses might be causing right under the medical establishment's nose?
In a very short time scientists would unearth frightening answers to their collective inquiry.
Microbe Magnets
URBAN CENTERS OF DISEASE
When one comes into a city to which he is a stranger, he ought to consider its situation, how it lies as to the winds and the rising of the sun; for its influence is not the same whether it lies to the north or to the south, to the rising or to the setting sun. These things one ought to consider most attentively, and concerning the waters which the inhabitants use, whether they be marshy and soft, or hard and running from elevated and rocky situations, and then if saltish and unfit for cooking; and the ground, whether it be naked and deficient in water, or wooded and well-watered, and whether it lies in a hollow, confined situation, or is elevated and cold â¦
From these things he must proceed to investigate everything else. For if one knows all these things well, or at least the greater part of them, he cannot miss knowing, when he comes into a strange city, either the diseases peculiar to the place, or the particular nature of the common diseases, so that he will not be in doubt as to the treatment of the diseases, or commit mistakes, as is likely to be the case provided one had not previously considered these matters. And in particular, as the season and year advances, he can tell what epidemic disease will attack the city, either in the summer or the winter, and what each individual will be in danger of experiencing from the change of regimen.
âHippocrates,
On Airs, Waters, and Places, c
. 400 B.C.
1
On Airs, Waters, and Places, c
. 400 B.C.
1
In 6000 B.C. there were fewer humans on earth than now occupy New York and Tokyo. Earth's roughly 30 million prehistoric residents were scattered over vast expanses of the warmer parts of the planet, and few of them ever
ventured far from their birthplace. According to what little archaeological information and scientific conjecture is available, their microbial threats came primarily from parasites in their food and water or were carried by local insects.
ventured far from their birthplace. According to what little archaeological information and scientific conjecture is available, their microbial threats came primarily from parasites in their food and water or were carried by local insects.
Over the next 4,000 years the human population slowly increased and people congregated around rivers, ocean ports, and sites of rich food resources. Trade routes emerged, connecting the nascent urban centers, and the city's residents thrived off their merchants' exploits and the taxes they levied on their poorer rural subjects.
By the time the Egyptians ceased building pyramids, around 2000 B.C., there were several cities with thousands of inhabitants each: Memphis, Thebes, Urâthe religious or political capitals of empires. And by 60 B.C. the vast empires of Rome and China boasted urban centers of tens of thousands of people, which functioned as the hubs of trade and culture for the planet's 300 million residents.
By 5 B.C. Rome's 1 million residents consumed 6,000 tons of grains a week. After the fall of the Roman Empire, no city would again attain such a size for 1,800 years, when London would become the largest metropolis in history up to that time.
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Cities afforded the microorganisms a range of opportunities unavailable in rural settings. The more
Homo sapiens
per square mile, the more ways a microorganism could pass from one hapless human to another. People would pass the agent to other people in hundreds of ways every minute of every day as they touched or breathed upon one another, prepared food, defecated or urinated into bodies of water with multiple uses, traveled to distant places taking the microbes with them, built centers for sexual activity that allowed microbes to exploit another method of transmission, produced prodigious quantities of waste that could serve as food for rodent and insect vectors, dammed rivers and unwittingly left cisterns of rain water about to create breeding pools for disease-carrying mosquitoes, and often responded to epidemics in hysterical ways that ended up assisting the persistent microbes.
Homo sapiens
per square mile, the more ways a microorganism could pass from one hapless human to another. People would pass the agent to other people in hundreds of ways every minute of every day as they touched or breathed upon one another, prepared food, defecated or urinated into bodies of water with multiple uses, traveled to distant places taking the microbes with them, built centers for sexual activity that allowed microbes to exploit another method of transmission, produced prodigious quantities of waste that could serve as food for rodent and insect vectors, dammed rivers and unwittingly left cisterns of rain water about to create breeding pools for disease-carrying mosquitoes, and often responded to epidemics in hysterical ways that ended up assisting the persistent microbes.
Cities, in short, were microbe heavens, or, as British biochemist John Cairns put it, “graveyards of mankind.”
3
The most devastating scourges of the past attained horrific proportions only when the microbes reached urban centers, where population density instantaneously magnified any minor contagion that might have originated in the provinces. And microbes successfully exploited the new urban ecologies to create altogether novel disease threats.
3
The most devastating scourges of the past attained horrific proportions only when the microbes reached urban centers, where population density instantaneously magnified any minor contagion that might have originated in the provinces. And microbes successfully exploited the new urban ecologies to create altogether novel disease threats.
Warfare, trade, the occasional need to put down local peasant uprisings during times of elevated taxation or famine, religious pilgrimages, and the seductive lure of the city for adventurous youth guaranteed that continuous
cycles of new microbial invasions would beset urban populations which generally lacked protective immunity.
cycles of new microbial invasions would beset urban populations which generally lacked protective immunity.
The microbes' transmissive success was guaranteed among a city's poor, and every urban center had its marginalized neighborhoods where malnourished, immunodeficient people lived in high-density squalor. Urban poverty and disease went hand in hand not only because insufficient diets weakened people's immune systems but also because of their living conditions. If the Roman patricians occasionally suffered dysentery because of bacteria in the aqueducts, the plebeians downstream were guaranteed a doubled exposure due to the additional bacterial burden of the patrician's contaminated waste.
The life expectancy of ancient Rome's populace was far shorter than that of the Empire's citizens in rural Mediterranean or North African areas. Only about one of every three Roman residents saw the ripe old age of thirty, compared with 70 percent of their rural counterparts. Virtually nobody in the city lived to eighty, whereas about 15 percent of the pastoral citizens attained that goal.
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Ancient urbanites recognized some of these special hazards. Accounts going back 2,000 to 4,000 years tell of scourges carried by lice, bedbugs, and ticksâall disease-associated insects that the writers noted were more abundant in the dense housing conditions of the cities. Though their understanding of the relationship between these insects and specific diseases was muddy, writers in ancient Egypt, Greece, Rome, India, and China all drew attention to the insect problem. Similarly, Galen in Athens and Herodotus in Rome recognized a connection between the expansion of their cities into marshy areas and the increase in malaria.
5
Chinese records dating back to 243 B.C. also noted massive epidemicsâclaiming millions of livesâwhich arose constantly from the cities of China's far-flung empire.
6
5
Chinese records dating back to 243 B.C. also noted massive epidemicsâclaiming millions of livesâwhich arose constantly from the cities of China's far-flung empire.
6
On the basis of historical accounts from Greece, Rome, Europe, and the post-Columbian Americas, twentieth-century scholars have tried to interpret which diseases plagued ancient urban centers. For example, during the Peloponnesian War of 430 B.C. a devastating epidemic hit Athens, probably imported by returning soldiers. Thucydides said of it, “No scourge so destructive of human life is anywhere on record. The physicians had to treat it without knowing its nature, and it was among them that the greatest mortality occurred.”
It was later thought that the epidemic, which Thucydides said caused illness in every Athenian and killed up to half the population, was either typhus, the plague, or smallpox.
7
Hundreds of great global pandemics followed. Four diseases that seemed to William McNeill and other medical historians of the 1970s to have gained particular benefit from the urban ecology over the previous 2,000 years were pneumonic plague, leprosy (Hansen's disease), tuberculosis, and syphilis. As far as could be discerned
from historical records, these were rarelyâif everâseen prior to the establishment of urban societies, and all four exploited to their advantage human conditions unique to cities.
7
Hundreds of great global pandemics followed. Four diseases that seemed to William McNeill and other medical historians of the 1970s to have gained particular benefit from the urban ecology over the previous 2,000 years were pneumonic plague, leprosy (Hansen's disease), tuberculosis, and syphilis. As far as could be discerned
from historical records, these were rarelyâif everâseen prior to the establishment of urban societies, and all four exploited to their advantage human conditions unique to cities.
The world has experienced at least two great pandemics of bubonic/ pneumonic plague, a disease caused by the
Yersinia pestis
bacteriumâcarried by fleas which resided on rodents, particularly rats. Though the bacterium has never been eradicated, ideal ecological conditions for its rapid spread among
Homo sapiens
occurred only a handful of times in recorded human history. Once Y. pestis got into the human bloodstream, either via a flea or rat bite or by inhalation of the bacterium, it quickly made its way into the lymphatic system. There, the bacterium killed massive numbers of cells, giving rise to formation of often grotesque pustules and pus-filled boils. Bacteria produced in these infected sites then migrated to the liver, spleen, and brain, causing hemorrhagic destruction of the organs and demented behavior that during the Middle Ages was interpreted as intervention by Satan.
Yersinia pestis
bacteriumâcarried by fleas which resided on rodents, particularly rats. Though the bacterium has never been eradicated, ideal ecological conditions for its rapid spread among
Homo sapiens
occurred only a handful of times in recorded human history. Once Y. pestis got into the human bloodstream, either via a flea or rat bite or by inhalation of the bacterium, it quickly made its way into the lymphatic system. There, the bacterium killed massive numbers of cells, giving rise to formation of often grotesque pustules and pus-filled boils. Bacteria produced in these infected sites then migrated to the liver, spleen, and brain, causing hemorrhagic destruction of the organs and demented behavior that during the Middle Ages was interpreted as intervention by Satan.
The occasional case of plague was seen during the twentieth century,
8
but well before humanity had invented antibiotics to treat it, the disease had ceased to threaten further pandemics.
8
but well before humanity had invented antibiotics to treat it, the disease had ceased to threaten further pandemics.
Sometime around 1346 the Black Death began on the steppes of Mongolia: infected fleas infested millions of rodents which, in turn, raided human dwellings in search of food. Why the disease emerged that particular year was never clear, though scientists in the 1980s speculated that the weather may have favored a rodent population explosion. The disease made its way rapidly across Asia, carried by fleas that hid in the pelts of fur traders, the blankets and clothing of travelers, and the fur of rodents that stowed away aboard caravans and barges crisscrossing the continent. Rumors of the Asian scourge preceded its arrival in Europe, and it was said that India, China, and Asia Minor were literally covered with dead bodies.
9
The Chinese population plummeted from 123 million in 1200 to 65 million in 1393, probably due to the plague and the famine that followed.
9
The Chinese population plummeted from 123 million in 1200 to 65 million in 1393, probably due to the plague and the famine that followed.
It reached the prosperous European trading port of Messina, Sicily, in the fall of 1347 aboard an Italian ship returning from the Crimea, and immediately exploited the city's ecology. Rats from the plagued ship joined the abundant local rodent population. Ailing men from the ship passed the bacteria on to the Messina citizenry directly, exhaling lethal microbes with their dying gasps.
As the plague made its way across Europe and North Africa, each city anticipated its arrival and tried by a variety of means to protect itself. Travelers were barred entry, drawbridges were raised to seal the wealthy urbanites off from their less fortunate peasantry, great purges and outright slaughter of tens of thousands of Jews and alleged devil worshippers were staged. The city of Strasbourg alone savagely slew 16,000 of its Jewish residents, blaming them for spreading the Black Death.
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Some who had no scapegoats blamed the plague on their own lack of piety. The Brotherhood of Flagellants were Christian men who daily beat themselves to the edge of death to purge the sins that were responsible for their disease. All over Europe, these men, encouraged by crowds of crazed aristocrats and peasants alike, would thrash themselves with leather whips embedded with small iron spikes.
The terrorized European population did everything save what might have spared them: ridding their cities of rodents and fleas. The cities fell not only because of rat infestations but also due to both human population density and hygienic conditions. Bathing was thought to be dangerous, and few Europeans ever washed, making them fertile ground for flea and lice infestation.
The pneumonic form of the plague, which rarely spread in less populated rural areas, was easily transmitted inside the densely populated medieval cities. Once a rat-driven bubonic form took hold, pneumonic cases in humans soon appeared, spreading the disease with terrifying rapidity.
Each city would be in the grip of the disease for four or five months, until the susceptible rats and humans had died. The survivors would then face famine and economic collapse, caused by the sharp reduction in workforces.
The daily death rates were staggering: 400 in Avignon; 800 in Paris; for Pisa, 500; Vienna buried or burned 600 bodies per day; and Givry, France, 1,500 daily. By the end, London, with a pre-plague population of 60,000, had lost 35,000. Half of Hamburg's and two-thirds of Bremen's populations perished. Most historians believe that at least one-third of Europe's total human population (20 to 30 million people) died of the plague between 1346 and 1350.
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The highest per capita losses were consistently in the cities.
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The highest per capita losses were consistently in the cities.
Over subsequent centuries, there were numerous outbreaks of urban plague in Europe, Asia, and the Middle East, though few spread far beyond the cities due to quarantines and to slow improvements in hygienic conditions.
In 1665, London suffered the Great Plague, a
Yersinia
epidemic that claimed over 100,000 lives in a year's time. The epidemic began a year earlier, probably in Turkey, and was carried by trading ships to Amsterdam and Rotterdam and on to London during the winter of 1664â65. By that summer as many as 3,000 of the city's residents perished each day.
Yersinia
epidemic that claimed over 100,000 lives in a year's time. The epidemic began a year earlier, probably in Turkey, and was carried by trading ships to Amsterdam and Rotterdam and on to London during the winter of 1664â65. By that summer as many as 3,000 of the city's residents perished each day.
The royal family and the aristocracy fled at the first sign of pestilence, taking up residence in the English countryside. The residents of London, the world's largest and most densely populated city, were left to fend for themselves. They lived in thatch-roofed, brick, and wood row houses: an ecology made in heaven for rats.
In considering the pestilence a generation later, Daniel Defoe recommended that city authorities in the future
⦠not let such a contagion as this, which is indeed chiefly dangerous to collected bodies of people, find a million of people in a body together, as was very near the case before ⦠. The plague, like a great fire, if a few houses only are contiguous where it happens, can only burn a few houses; or if it begins in a single, or, as we call it, a lone house, can only burn that lone house where it begins. But if it begins in a close-built town or city and gets a head, there its fury increases: it rages over the whole place, and consumes all it can reach.
Â
Shortly after the plague subsided, in 1666, London was overcome by a real fire that engulfed most of the city. McNeill believed it was the Great Fire which stopped the Great Plague, burning off the thatch roofs, which were replaced with tile and slate.
Leprosy, as it was then called, claimed only a fraction of the lives felled by the plague, but was no less feared. Throughout history leprosy was dreaded more for its disfiguring and crippling effects on the human body than for its slow capacity to kill.
By the 1970s leprosy would be referred to as Hansen's disease (named after Armauer Hansen, who in 1873 described the first definitive differential diagnosis of the disease) by those who wished to separate the bacterial ailment from the centuries of horror and prejudice that went with the word “leper.”
There was great debate in the latter half of the twentieth century about the age of the
Mycobacterium leprae
organism and how long it had been producing significant disease in human beings. Though the Bible referred to ancient Hebrews suffering disfiguring diseases often translated as leprosy, the usually meticulous records of Egyptian scribes bore no hint of it. Searching for evidence of bone damage produced by the gnawing bacteria, studies of skeletons revealed no sign anywhere in the world prior to A.D. 500, when apparently leprotic bones were buried in the graveyards of Cairo, Alexandria, and parts of England and France.
Mycobacterium leprae
organism and how long it had been producing significant disease in human beings. Though the Bible referred to ancient Hebrews suffering disfiguring diseases often translated as leprosy, the usually meticulous records of Egyptian scribes bore no hint of it. Searching for evidence of bone damage produced by the gnawing bacteria, studies of skeletons revealed no sign anywhere in the world prior to A.D. 500, when apparently leprotic bones were buried in the graveyards of Cairo, Alexandria, and parts of England and France.
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