Spillover: Animal Infections and the Next Human Pandemic (26 page)

I watched over his shoulder as he worked with a small scissors, puncturing the skin and then zipping upward across the little bat’s chest. He spread the pelt back with his fingers—a light pull was enough—to reveal huge breast muscles, reddish purple as sirloin. This animal was built like Mighty Mouse. Aleksei cut through those flight muscles and then through the bones beneath, too delicate to give much resistance to his scissors. With a pointy aliquot, he drew some blood directly from the heart. He snipped out the liver and spleen, dropping them into separate tubes. And for these tasks, I noticed, the seatbelt analogy didn’t apply; in addition to his blue gloves, Aleksei donned an N95 mask. Still, it was very undramatic. Only later did I notice the connection between least horseshoe bats and what Wendong Li’s group had discovered. The least horseshoe bat is one of the suspected reservoir hosts of the virus.

Once finished, with the blood and organs preserved, Aleksei dropped the carcass into a Ziploc bag. He added the other bat carcass, after dissection, to the same bag. Where do those go? I asked. He pointed to a biohazardous waste box, specially designed for accepting suspect materials.

“But if they were food,” he added, “they’d go there,” indicating an ordinary trash basket against the wall. It was a shrug back toward our dinner discussions and the tangled matter of categorical lines: edible animals versus sacrosanct animals, safe animals versus infected animals, dangerous offal versus garbage. His point again was that such lines of division, especially in southern China, are arbitrarily and imperfectly drawn.

39

S
everal days later we traveled down to the city of Lipu, about seventy miles south of Guilin, to visit a rat farm that interested Aleksei. The trip took two hours on a rather luxurious bus—one offering seat belts and bottled water. At the bus station in Lipu, while waiting for our local contact to arrive, I noticed a sign stipulating security restrictions. The sign was in traditional Chinese characters but I could tell from the illustrations what was disallowed on board Lipu–Guilin busses: no bombs, no fireworks, no gasoline, no alcohol, no knives, and no snakes. We weren’t carrying any.

Mr. Wei Shangzheng eventually pulled up in a white van. He was a short, stocky, amiable man who laughed easily and often, especially after his own statements, not because he thought he was funny but from sheer joy at life’s curious sweetness. That’s the impression I took, anyway, as his words came translated by Guangjian and his attitude shone merrily through. We climbed into his van and rode six miles to a village northeast of Lipu, where Mr. Wei turned onto a narrow lane, then through a gate, above which was a line of calligraphy announcing:
SMALL HOUSE IN THE FIELD BAMBOO RAT RAISING FARM.
Beyond was a courtyard surrounded on three sides by cinderblock buildings. Two wings of the building were filled with low concrete pens. The pens contained silver-gray creatures, small-eyed and blunt-headed, that looked like gigantic guinea pigs: Chinese bamboo rats. Mr. Wei gave us a tour up and down the rows.

The pens were clean and well-drained, each furnished with a water dish and holding one to four animals. The Chinese bamboo rat
is native to southern China and thereabouts, and the chewed-upon stalks of bamboo in some cages signaled that its diet is true to its name. The front teeth are beaverlike, well suited for gnawing those stalks, but in disposition a bamboo rat is more comparable to a pussycat. Mr. Wei lifted one by the scruff of its neck, turned it over, and gently poked at its sizable scrotum. Don’t try that with a beaver. The animal barely wriggled. Up and down the line we could see adults, juveniles, one female nursing two mouse-size pups, a mounting in progress. They breed readily, Mr. Wei explained. He kept mostly females, plus a few good studs. Last month he sold two hundred rats, and now he was expanding his operation, building new sheds. Already he was the largest bamboo-rat farmer in southern China! he told us exuberantly. Southern China, yes, and maybe beyond! After the expansions, with capacity for five thousand animals, he might be the largest bamboo-rat farmer in all China! He stated this not to brag, it seemed, but in joyous amazement at the vagaries of fortune. Business was good. Life was good. He laughed—ha ha ha!—at the thought of life’s goodness. He’s famous! he told us. He had been featured on Chinese TV! We could Google him! His ventures in bamboo-rat husbandry began in 2001, when he lost his job at a factory and decided to try something new.

Enterprising and innovative, Mr. Wei now also had two pairs of large, rather menacing porcupines, which sulked in larger pens at the end of one room. He was diversifying. He had begun to breed them and, yes, their offspring too would be sold as food. A special product for special occasions, targeting the wealthier, more jaded epicure. A pair of porcupines was worth $1,000, Mr. Wei said. He did not lift one and poke its scrotum.

I noticed several hypodermic syringes lying ready along the edge of a pen. Was he concerned about the health of his bamboo rats? I asked. Yes, very, said Mr. Wei, especially regarding viruses. They’re invisible. They’re dangerous. And you can’t run a bamboo-rat farm if the animals are sick. He showed us how he would inject an ailing rat on the inside of its calf. He didn’t mention what sort of medicine he injected, and most likely it was an antibiotic (therefore useless against viruses), not a newly developed SARS vaccine already available at the level of bamboo-rat wholesaling. But at least Mr. Wei’s animals might be free of common bacterial infections at time of sale. What they encountered thereafter—confined to their cages among tenements of other creatures, coughed upon, peed upon, shat upon by bats or civets or raccoon dogs in a warehouse or a wet market—that was a different matter.

After the tour, Mr. Wei insisted we stay for dinner. He had commanded his family to prepare a small banquet. We sat at a low table on tiny chairs with an electric burner amid us, atop which Mr. Wei’s elderly mother assembled a formidable hotpot. Into the boiling broth she slid portions of chopped pork, chopped duck, some sort of potatolike tuber, enoki mushrooms, bean sprouts, bok choy, and greens from a plant related to morning glory. She stirred. She added dabs of salt. The ingredients cooked quickly, floated up, and combined to a savory stew, which we picked at with chopsticks and ladled into our rice bowls. Separately, on a cool platter, she offered us roasted gobbets of bamboo rat.

The rat meat was mild, subtle, faintly sweet. There were many small femurs and ribs. One eats bamboo-rat hocks with one’s fingers, I learned, sucking clean the bones and piling them politely on the table beside one’s bowl, or else dropping them on the floor (the preferred method of Mr. Wei’s father, a shirtless old man seated to my left), where they would be scavenged by the skinny cat who slept under the table. The hotpot was scorching. Mr. Wei, an exemplary host, brought out some big bottles of Liquan beer, Guilin’s finest brew, nicely chilled. After a few glasses, I got into the spirit of the meal and found myself turning back to the rat platter, browsing for choice morsels.

I had begun to see Aleksei’s point: If you’re a carnivore, you’re a carnivore, so what’s the merit of fine distinctions? And if you’re going to eat bamboo rat, I figured, best to do it here, at the source—before the poor animals get shipped, stacked amid other animals, and sick. Wild Flavor doesn’t need to be seasoned with virus.

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A
part from the aftershock cases in early 2004, SARS hasn’t recurred . . . so far. The known events of the 2003 outbreak are still being interpreted. Many bits aren’t known. Many questions remain unanswered. Are bats the sole reservoir hosts of SARS-like coronavirus? If so, which kinds of bats? Is the coronavirus that was detected in least horseshoe bats the direct ancestor of SARS-CoV as found in humans? If so, how did the original spillover occur? Was it just a single transmission—from one bat into one civet—or several such happenings? And from civet into human—how many occurrences, how many independent spillovers? Did a cage full of infected civets, sold one by one in a market, send the disease off in multiple directions at once? What exactly happened on the ninth floor of the Metropole Hotel? Did Professor Liu vomit in the corridor, or did he merely sneeze, merely cough—merely exhale? How did the virus evolve during its passage through 8,098 humans? What role did the unique culinary culture of southern China play in bringing a dangerous pathogen out to Hong Kong and then to the world? Where do Mr. Wei’s bamboo rats go after leaving the Small House in the Field Bamboo Rat Raising Farm? How are they handled, amid what other animals, what piles of cages, what flying excretions, before reaching the restaurants of Guilin, Guangzhou, and Shenzhen? Why are some people superspreaders, when infected with this virus, but not others? What is the numerical value of
R
0
for SARS? When will the virus emerge again? Aleksei Chmura is just one researcher among many trying to add new data to the dossier in which these questions reside.

Much has been written about SARS in the scientific literature since spring of 2003. Most of those papers are narrowly technical, addressing the details of molecular evolution, reservoir relationships, or epidemiology, but some take a broader view, asking
What is it that makes this virus unusual?
and
What have we learned from the SARS experience?
One thought that turns up in the latter sort is that “
humankind has had a lucky escape
.” The scenario could have been very much worse. SARS in 2003 was an outbreak, not a global pandemic. Eight thousand cases are relatively few, for such an explosive infection; 774 people died, not 7 million. Several factors contributed to limiting the scope and the impact of the outbreak, of which humanity’s good luck was only one. Another was the speed and excellence of the laboratory diagnostics—finding the virus and identifying it—performed by Malik Peiris, Guan Yi, their partners in Hong Kong, and their colleagues and competitors in the United States, China, and Europe. Still another was the brisk efficiency with which cases were isolated, contacts were traced, and quarantine measures were instituted in southern China (after some early confusion and denial), Hong Kong, Singapore, Hanoi, and Toronto; and the rigor of infection-control efforts within hospitals, such as those overseen by Brenda Ang at Tan Tock Seng. If the virus had arrived in a different sort of big city—more loosely governed, full of poor people, lacking first-rate medical institutions—it might have escaped containment and burned through a much larger segment of humanity.

One further factor, possibly the most crucial, was inherent to the way SARS-CoV affects the human body: Symptoms tend to appear in a person before, rather than after, that person becomes highly infectious. The headache, the fever, and the chills—maybe even the cough—precede the major discharge of virus toward other people. Even among some of the superspreaders, in 2003, this seems to have been true. That order of events allowed many SARS cases to be recognized, hospitalized, and placed in isolation before they hit their peak of infectivity. The downside was that hospital staff took the first big blasts of secondary infection; the upside was that those blasts generally weren’t emitted by people still feeling healthy enough to ride a bus or a subway to work. This was an enormously consequential factor in the SARS episode—not just lucky but salvational. With influenza and many other diseases the order is reversed, high infectivity preceding symptoms by a matter of days. A perverse pattern: the danger, then the warning. That probably helped account for the scale of worldwide misery and death during the 1918–1919 influenza: high infectivity among cases before they experienced the most obvious and debilitating stages of illness. The bug traveled ahead of the sense of alarm. And that infamous global pandemic, remember, occurred in the era
before
globalization. Everything nowadays moves around the planet faster, including viruses. If SARS had conformed to the perverse pattern of presymptomatic infectivity, its 2003 emergence wouldn’t be a case history in good luck and effective outbreak response. It would be a much darker story.

The much darker story remains to be told, probably not about this virus but about another. When the Next Big One comes, we can guess, it will likely conform to the same perverse pattern, high infectivity preceding notable symptoms. That will help it to move through cities and airports like an angel of death.

Two days after our dinner at the rat farm, I rose early in Guilin, said my farewell to Aleksei Chmura, and caught a plane back to Guangzhou. I killed some hours in the airport there, paying more yuans for a ham sandwich and two lattes than I’d spent on a week’s meals in the cafés and noodle parlors of Guilin. Then I boarded my onward flight. In the row beside me were two young Japanese tourists, a couple, possibly returning from a romantic vacation amid the hotels, parks, malls, markets, restaurants, and crowded streets of Guangzhou or other cities of southern China. They took their seats unobtrusively and settled in for the short ride to Hong Kong. Maybe they felt a bit cowed by their own adventurousness and relieved to be headed home to a tidier nation; maybe they remembered the news stories about SARS. I didn’t intrude on them with questions. I wouldn’t have noticed them at all, except they were both wearing surgical masks.

Yes, I thought, if only it were that simple.

V

THE DEER, THE PARROT,
AND THE KID NEXT DOOR

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A
lthough the drumbeat has quickened in recent decades, the emergence of new zoonotic diseases isn’t unique to our era. Three stories exemplify that point.

Q fever. Sixty years before Hendra, sixty years before Vic Rail’s horses started dying in that suburb of Brisbane, a very different sort of pathogen made its first recognized spillover in almost the same locale. It wasn’t a virus, though in some measure it behaved like one. It was a bacterium, but unlike most other bacteria. (An ordinary bacterium differs from a virus in several obvious ways: It’s a cellular organism, not a subcellular particle; it’s much larger than a virus; it reproduces by fission, not by invading a cell and commandeering the cell’s machinery of genetic copying; and it can usually be killed by antibiotics.) This new bug caused an illness that resembled influenza or maybe typhus. The earliest cases, occurring in 1933, were among abattoir workers in Brisbane, whose jobs involved slaughtering cattle and sheep. The affliction they suffered,
known initially as “abattoir fever”
among the doctors who treated them, acquired a more opaque name that stuck: Q fever. Never mind, for the moment, the origin of that name. The most notable thing about Q fever is that, even now in the age of antibiotics, for reasons related to its anomalous biology, it’s still capable of causing serious devilment.

Psittacosis. Around the same time as Q fever emerged, in the 1930s, another peculiar bacterial zoonosis hit the news. This one also had links to Australia, but its scope was global, and it seems to have first reached the United States by way of a shipment of diseased parrots from South America. That was in late 1929, just in time for the Christmas season of parrot-giving. One unlucky recipient was Lillian Martin, of Annapolis, Maryland, whose husband bought her a parrot from a pet store in Baltimore. The bird keeled over dead on Christmas Day, a bad omen, and Mrs. Martin started feeling ill about five days later. Psittacosis is the medical name for the ailment she contracted; it passes from birds (especially those of the order Psittaciformes, meaning parrots and their kin) to humans, causing fever, aches, chills, pneumonia, and sometimes death. “Parrot fever” was the label under which it raised alarm in the United States during early 1930, when people exposed to those unhealthy imported birds started getting sick, especially in Maryland.
PARROT FEVER HITS TRIO AT ANNAPOLIS
was a typical headline, bruiting a story that ran in
The Washington Post
, on January 8, about Lillian Martin and two of her close relatives. Three days later, also in
The Post
:
BALTIMORE WOMAN’S DEATH BLAMED ON PARROT DISEASE.
Over the next several months psittacosis would become a national concern, causing enough reaction or overreaction that one commentator called the whole thing
an example of
“public hysteria,” commensurate with flagellation zeal and St. John’s fire in the Middle Ages.

And then there’s Lyme disease. This seems to be a more recent version of the spooky-new-bacteria phenomenon. In the mid-1970s, two alert mothers in Lyme, Connecticut, near Long Island Sound, noticed that not only their children but a high incidence of other youngsters nearby had been diagnosed with juvenile rheumatoid arthritis. The odds were against any such concentration of cases occurring by chance. Once the Connecticut Department of Health and the Yale University School of Medicine had been alerted, researchers noticed that these arthritis diagnoses coincided with a particular pattern of skin rash—a red ring, spreading outward from a point—known to occur sometimes around tick bites. Ticks of the genus
Ixodes,
commonly called “deer ticks,” were abundant in the forests of eastern Connecticut and surrounding areas. In the early 1980s, a microbiologist named Willy Burgdorfer found a new bacterium in the guts of some
Ixodes
ticks, a likely suspect as the causative agent. It was a spirochete, a long spiral form, closely resembling other spirochetes of the genus
Borrelia.
After further research confirmed its role in the arthritis-like syndrome, that bacterium was named
Borrelia burgdorferi
in honor of its principal discoverer. Lyme disease is now the most common tick-borne disease in North America and one of the fastest-increasing infectious diseases of any sort, especially in New England, the mid-Atlantic states, and Wisconsin. Part of what makes it problematic is that the life history of
Borrelia burgdorferi
is very complex, involving much more than ticks and people.

Lyme disease, psittacosis, Q fever: These three differ wildly in their particulars but share two traits in common. They are all zoonotic and they are all bacterial. They stand as reminders that not every bad, stubborn, new bug is a virus.

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P
arrot fever was recognized as far back as 1880, when a Swiss physician named Ritter described a household outbreak, of something resembling typhus, in which seven people got sick and three died. Because the illness showed certain pneumonia-like aspects, suggesting airborne transmission, Dr. Ritter called it “pneumotyphus,”
but he was groping. Although he couldn’t identify what caused it, he did manage to pinpoint the site of common exposure: the house’s study. The only thing remarkable about that room was that it happened to contain a dozen caged birds, including finches and parrots.

A larger outbreak occurred in Paris in 1892, after two animal dealers received a shipment of five hundred parrots imported from Buenos Aires. The dealers became infected, several of their customers became infected, and then so did relatives, friends, and one doctor in attendance. Sixteen people died. Soon the disease had cropped up also in Germany, in New York, and at a department store (which sold birds) in Wilkes-Barre, Pennsylvania. In 1898 it struck the annual exhibition of the Berlin Union of Canary Fanciers, demonstrating that parrots and their kin weren’t the only birds capable of carrying this “parrot fever” microbe, whatever it was. (Canaries belong to the order Passeriformes, not to the Psittaciformes.) Half a dozen canary fanciers fell ill and, by an account in a Berlin newspaper, “
three died in agony
.”

Then came a hiatus, if not in the incidence of parrot-borne infections at least in the attention they received. The Great War, followed immediately by the great influenza, gave people a surfeit of death and disease to engage their sorrows and fears. The 1920s were decidedly more cheerful and carefree, until they weren’t. “
The year 1929 marked a turning point
in the revival of interest concerning the etiology of human psittacosis,” according to one historical survey of the disease. Etiology, that was the crux. Outbreaks might come and go. What differed in 1929, besides the Crash and a general lowering of spirits, was a sufficiency of parrot-fever cases to make studying the
cause
not only more practical but also more urgent.

Lillian Martin of Annapolis had been among the first of this new wave, and though she eventually recovered, others weren’t so lucky.
The Washington Post
continued to track the story, reporting parrot-fever fatalities in Maryland, Ohio, Pennsylvania, New York—and Hamburg, Germany. On January 13, the Surgeon General telegraphed health officials in nine states, asking for help in tracking the situation. Two weeks later, with cases now reported also from Minnesota, Florida, and California, President Hoover declared an embargo against imported parrots. The director of the Bureau of Bacteriology within Baltimore’s health department, who had been doing necropsies on infected birds, got sick and died. A laboratory technician at the Hygienic Laboratory, which was part of the US Public Health Service, got sick and died. That technician had been assisting a researcher, Charles Armstrong, with bird-to-bird transmission experiments in the laboratory basement. Their working conditions were less than ideal: two small basement rooms full of distressed parrots held in garbage cans, wire mesh over the tops, feathers and bird shit flying out, curtains soaked in disinfectant to contain the airborne drift. It wasn’t BSL-4. Charles Armstrong got sick but did not die. Nine other personnel of the Hygienic Laboratory also became infected, none of whom had even entered the basement bird rooms. The laboratory director, realizing that his building was broadly contaminated with whatever wafting agent caused psittacosis, closed the place down. Then he descended to the basement himself, chloroformed all the remaining parrots, chloroformed the guinea pigs and pigeons and monkeys and rats involved in the same experimental work, and threw their dead bodies into the incinerator. This forthright man, this hands-on administrator, described in one source as “
tall with a gnarled Lincolnian face
,” was Dr. George W. McCoy. For reasons explicable only in terms of the wonders of the immune system and the vagaries of fortune, Dr. McCoy didn’t get sick.

The psittacosis epidemic of 1930 was winding down, and probably also, though more slowly, the psittacine panic. On March 19, the Acting Secretary of the Navy issued a general order for sailors on shipboard to get rid of their parrots. George McCoy reopened the Hygienic Laboratory, Charles Armstrong returned from convalescence, and the search for a cause of the disease continued.

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W
ithin a month, a culprit had been identified. It was a small bacterium with some unusual properties, seemingly similar to the agent that causes typhus (
Rickettsia prowazekii
) and therefore given the name
Rickettsia psittaci.
Where did it come from? Argentina had been implicated as a source of sick birds at the start of the 1930 outbreak; President Hoover’s embargo would have stanched that source. But then latent psittacosis was detected in some commercial California aviaries, where parakeets for the domestic pet trade were produced—meaning that American breeders were harboring an endemic reservoir of the infection and distributing it by way of interstate commerce. So a proposal was made to destroy all those infected flocks and then reestablish the trade with healthy birds from Australia. This seemed to make sense on two counts. First, what we Americans call a “parakeet” is a native Australian bird, widespread and abundant in the wild, known to Australians as the budgerigar. Second, Australia itself (despite a high diversity of psittacine birds) was thought to be psittacosis-free. Starting over with wild birds might free the American bird trade of psittacosis. That was the idea, anyway.

A pair of American scientists got permission, despite the embargo, to import a consignment of two hundred Australian parakeets lately captured in the vicinity of Adelaide. They wanted to do an experiment. Their plan was to infect the imported birds, whose immune systems were assumed to be naïve, with American strains of psittacosis. But when one of the imports fell dead, not long after arrival, the scientists opened it up and found
Rickettsia psittaci
. They also noticed that some others of their birds, seemingly healthy, carried the bacterium
as a latent infection, like the birds in those California aviaries. That raised fresh concern about what might be lurking in other aviaries, in zoos, and in pet shops around America, and strongly suggested that Australia might not be as clean as it seemed.

This is where Frank Macfarlane Burnet, a great figure in Australian science, enters the story. Burnet was a complicated, brilliant, crotchety man and a signal character in the study of infectious diseases. Eventually he would earn a knighthood, a Nobel Prize, and a number of other fancy honors, but long before those he had made a name for himself in zoonoses. Born in 1899, second child among an eventual seven, he was a solitary, opinionated schoolboy who read H. G. Wells, disapproved of his own father’s shallow morality, preferred beetle collecting to more sociable activities, despised his roommates, read about Charles Darwin (who became one of his heroes) in an encyclopedia, forced himself (despite an inaptitude for sports) to achieve competence as a cricketer, and became an agnostic during his undergraduate years. Unfit for a career in the Church, ambivalent toward the law, he chose medicine. He trained as a doctor in Melbourne but then, recognizing his lack of empathy with patients, went to London for a PhD in virology. Declining a chair at the University of London, he returned to Australia to do research. He was a nationalist, stoutly Aussie. Much later in life, laden with honors and fame, Burnet kept his edge by publishing cranky pontifications on a wide range of subjects including euthanasia, infanticide for handicapped babies, Aboriginal land rights, population control, tobacco advertising, French nuclear testing in the Pacific, the futility of trying to cure cancer, and the merits (low, in his view) of molecular biology (as distinct from his discipline, microbiology). Burnet received his Nobel, in 1960, for helping illuminate the mechanisms of acquired immune tolerance. His role in understanding zoonotic diseases began much earlier. In 1934, as a young microbiologist based at the Walter and Eliza Hall Institute, back in Melbourne, he got interested in psittacosis.

Keying off the American study, Burnet ordered himself a crate of parrots and cockatoos from Adelaide. He found that a third of them were infected. He ordered another dozen from Melbourne. At least nine of those were probable carriers. Another two dozen from Melbourne yielded still more positives. So much for the myth of Australia as a prelapsarian psittacosis-free Eden.

But if the country’s wild bird populations were riddled with
this bacterium, how could the country’s people—so many of whom doted upon their pet budgerigars and talking cockatoos—be entirely as unaffected as they seemed? The likely answer, Burnet guessed, was not some magical form of immunity but ignorance and underdiagnosis. Australian doctors didn’t know psittacosis when it wheezed in their faces. To test that guess, Burnet started chasing down cases of human illness that
looked
like psittacosis but might have been diagnosed as influenza or typhoid. He and a co-investigator found seventeen people, sick with fever, cough, headache, pneumonia, et cetera, all of whom had been exposed to pet birds—either captive-bred budgerigars or parrots and cockatoos lately caught from the wild. His most interesting cluster was a group of twelve people infected from one batch of sulphur-crested cockatoos.