Spillover: Animal Infections and the Next Human Pandemic (33 page)

Inside the viral capsid is usually nothing but genetic material, the set of instructions for creating new virions on the same pattern. Those instructions can only be implemented when they’re inserted into the works of a living cell. The material itself may be either DNA or RNA, depending on the family of virus. Both types of molecule are capable of recording and expressing information, though each has its advantages and its drawbacks. Herpesviruses, poxviruses, and papillomaviruses contain DNA; so do half a dozen viral families you’ve never heard of, such as the iridoviruses, the baculoviruses, and the hepadnaviruses (one of which causes hepatitis B). Others, including filoviruses, retroviruses (most notoriously, HIV-1), coronaviruses (SARS-CoV), and the families encompassing measles, mumps, Hendra, Nipah, yellow fever, dengue, West Nile, rabies, Machupo, Junin, Lassa, chikungunya, all the hantaviruses, all the influenzas, and the common cold viruses, store their genetic information in the form of RNA.

The different attributes of DNA and RNA account for one of the most crucial differences among viruses: rate of mutation. DNA is a double-stranded molecule, the famed double helix, and because its two strands fit together by way of those very specific relationships between pairs of nucleotide bases (adenine linking only with thymine, cytosine only with guanine), it generally repairs mistakes in the placement of bases as it replicates itself. This repair work is performed by DNA polymerase, the enzyme that helps catalyze construction of new DNA from single strands. If an adenine is mistakenly set in place to become linked with a guanine (not its correct partner), the polymerase recognizes that mistake, backtracks by one pair, fixes the mismatch, and then moves on. So the rate of mutation in most DNA viruses is relatively low. RNA viruses, coded by a single-strand molecule with no such corrective arrangement, no such buddy-buddy system, no such proofreading polymerase, sustain rates of mutation that may be thousands of times higher. (For the record, there’s also a smaller group of DNA viruses that code their genetics on single strands of DNA and suffer high mutation rates, as in RNA. And there’s a little group of double-stranded RNA viruses. To every rule, an exception. But we’re going to ignore those minor anomalies because this stuff is already complicated enough.) The basic point is so important I’ll repeat it: RNA viruses mutate profligately.

Mutation supplies new genetic variation. Variation is the raw material upon which natural selection operates. Most mutations are harmful, causing crucial dysfunctions and bringing the mutant forms to an evolutionary dead end. But occasionally a mutation happens to be useful and adaptive. And the more mutations occurring, the greater chance that good ones will turn up. (More mutations also mean more chance of harmful ones, lethal to the virus; this puts a cap on the maximum sustainable mutation rate.) RNA viruses therefore evolve quicker than perhaps any other class of organism on Earth. It’s what makes them so volatile, unpredictable, and pesky.

Notwithstanding the quip by Peter Medawar, not every virus is “a piece of bad news wrapped up in a protein”—or at least, it’s not bad news for every host infected. Sometimes the news is merely neutral. Sometimes it’s even good; certain viruses perform salubrious services for their hosts. “Infection” need not always entail any significant damage; the word merely means an established presence of some microbe. A virus doesn’t necessarily achieve anything by making its host sick. Its self-interest requires just replication and transmission. The virus enters cells, yes, and subverts their physiological machinery to make copies of itself, yes, and often destroys those cells as it exits, yes; but maybe not so many cells as to cause real harm. It may inhabit a host rather quietly, benignly, replicating at modest levels and getting transmitted from one individual to another without producing any symptoms. The relationship between a virus and its reservoir host, for instance, tends to involve such a truce, sometimes reached after long association and many generations of mutual evolutionary adjustment, the virus becoming less virulent, the host becoming more tolerant. That’s in part what defines a reservoir: no symptoms. Not every virus-host relationship evolves toward such amicable relations. It’s a special form of ecological equilibrium.

And like all forms of ecological equilibrium, it’s temporary, provisional, contingent. When spillover occurs, sending a virus into a new kind of host, the truce is canceled. The tolerance is nontransferable. The equilibrium is ruptured. An entirely new relationship occurs. Freshly established in an unfamiliar host, the virus may prove to be an innocuous passenger, or a moderate nuisance, or a scourge. It all depends.

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T
he virus known informally as herpes B (and more precisely now as Macacine herpesvirus 1, referring to its natural reservoirs, macaques) sprang from obscurity to medical attention in 1932, after a laboratory mishap at New York University. A young scientist named William Brebner was doing research toward a polio vaccine. Monkeys were important for such work, and the animal of choice was the rhesus macaque (
Macaca mulatta
), which belongs to the cercopithecine family. Because poliovirus hadn’t yet been cultured in glass (that would eventually be possible, but only when living cells could be maintained in the medium as viral hosts), rhesus macaques typically served both as incubators of the virus and as test subjects. Poliomyelitis is not a zoonosis; it doesn’t naturally affect any animals other than humans; but with the help of a hypodermic needle, it could be made to grow in monkeys. An experimenter would take the poliovirus from one animal, which had been artificially infected, and inject that into the brain or the spinal cord of another, keeping the chain of infection continuous and observing effects on the monkeys along the way. One day, handling a monkey, William Brebner got bitten.

It wasn’t a bad bite, just a nip across the ring finger and the pinkie of his left hand. Brebner dosed the wounds with iodine, then with alcohol, and kept working. The monkey seemed normal and healthy, though understandably cantankerous, and if it was already carrying polio, that doesn’t seem to have concerned Brebner. Soon afterward the monkey died (under ether, during another experimental procedure), and it wasn’t necropsied.

Three days later, Brebner noticed “
pain, redness, and slight swelling
” around the bite. Another three days passed and he was admitted to Bellevue Hospital. His symptoms developed slowly—tender lymph nodes, abdominal cramps, paralysis of his legs, inability to urinate, tingling numbness in his arms, and then a high fever and hiccupping—until, after two weeks, he was very sick indeed. His breathing became labored and he turned blue. Put into a respirator, he convulsed and lost consciousness. Frothy liquid came wheezing out of his mouth and nostrils. Five hours later, William Brebner was dead at the age of twenty-nine.

What killed him? Was it polio? Was it rabies? A fellow researcher in the same NYU lab, just out of medical school but bright and ambitious, assisted at Brebner’s autopsy and then made a further investigation, using bits of Brebner’s brain, spinal cord, lymph nodes, and spleen. This man was Albert B. Sabin, decades before his fame as creator of an oral polio vaccine. Sabin and a colleague injected an emulsion from Brebner’s brain back into monkeys; they also injected some mice, guinea pigs, and dogs. None of those animals showed signs of what Brebner had suffered. But rabbits, likewise injected, did. Their legs went limp, they died of respiratory failure, their spleens and livers were damaged. From the rabbits, Sabin and his partner extracted a filtered essence capable of causing the same course of infection again.
They called it simply “the B virus,”
after Brebner. Other work showed that it was a herpesvirus.

Herpes B is a very rare infection in humans but a nasty one, with a case fatality rate of almost 70 percent among those few dozen people infected during the twentieth century (before recent breakthroughs in antiviral pharmaceutics) and almost 50 percent even since then. When it doesn’t kill, it often leaves survivors with neurological damage. It’s an occupational hazard of scientists and technicians who work with laboratory macaques. Among the macaques themselves it’s common, but merely an annoyance. It abides within nerve ganglia and emerges intermittently to cause mild lesions, usually in or around the monkey’s mouth, like cold sores or canker sores from herpes simplex in humans. The monkey sores come and go. Not so with herpes B in people. In the decades since Brebner’s death, forty-two other human cases have been diagnosed, all involving scientists or laboratory technicians or other animal-handlers who had contact with macaques in captivity.

The number of human cases rose quickly during the era of fervid research toward a polio vaccine, in the 1950s, probably because those efforts entailed such a sharp increase in the use of rhesus macaques. Conditions of caging and handling were primitive, compared with standards for medical research on primates today. Between 1949 and 1951, a single project within the overall effort financed by the National Foundation for Infantile Paralysis (aka the March of Dimes) consumed seventeen thousand monkeys. The foundation maintained a sort of clearinghouse for imported monkeys in South Carolina, from which one leading researcher had a standing order of fifty macaques per month, at $26 apiece, delivered. Nobody knows exactly how many macaques were “sacrificed” in the labs of Albert Sabin and Jonas Salk, let alone other researchers, but the incidence of herpes B infections peaked in 1957–1958, just as the polio vaccine quest came to its crescendo. Most of those cases occurred in the United States, the rest in Canada and Britain, places where rhesus macaques were thousands of miles removed from their natural habitat but medical research was intensive.

From that 1950s peak, the rate of accidental infections declined, possibly because lab techs began taking better precautions, such as wearing gloves and masks, and tranquilizing monkeys before handling them. In the 1980s came a small second uptick in herpes B incidents, correlated with another increase in the use of macaques, this time for research on AIDS.

The most recent case occurred at the Yerkes National Primate Research Center, in Atlanta, in late 1997. On October 29, a young woman working among the captive monkeys was splashed in the eye with some sort of bodily gook from a rhesus macaque. It may have been urine, or feces, or spit; nobody seems to know. She wiped her eye with a paper towel, soldiering on through her chores, and almost an hour later found time to rinse the eye briefly with water. That wasn’t enough. She filed no incident report, but ten days later the eye was red and swollen. She went to an ER, where the physician on duty prescribed antibiotic eyedrops. Thanks a lot. When the eye inflammation worsened, she saw an ophthalmologist. More days passed, and another ophthalmologist examined her, before she was hospitalized for suspected herpes B. Now they put her on strong antiviral drugs. Meanwhile, cultures taken from swabbing her eyes were quietly retrieved from the commercial laboratories to which they had been sent for analysis—um, never mind, we’ll just take those back. Her cultures had belatedly been deemed too dangerous for ordinary lab workers to handle.

The young woman seemed to improve slightly and left the hospital. But she woke the next morning with worsening symptoms—abdominal pain, inability to urinate, weakness in her right foot—and went back. At the end of the month, she began having seizures. Then came pneumonia. She died of respiratory failure on December 10, 1997. Despite the fact that her own father was an infectious-disease doctor, her mother was a nurse, and Yerkes was full of people who knew about herpes B, modern medicine hadn’t been able to save her.

This pathetic mishap put some people on edge. The probability of cross-species transmission might be low—very low, under normal circumstances—but the consequences were high. Several years later, when eleven rhesus macaques at a “safari park” in England tested positive for herpes B antibodies, management decided to exterminate the entire colony. This decision was driven by the fact that Britain’s Advisory Committee on Dangerous Pathogens had lately reclassified herpes B into biohazard level 4, placing it in the elite company of Ebola, Marburg, and the virus that causes Crimean-Congo hemorrhagic fever. National regulations specified that any animals infected with a level-4 agent had to be either handled under BSL-4 containment (meaning space suits, triple gloves, airlock doors, and all the rest, not quite practicable at a tourist attraction for viewing wildlife) or destroyed. Of course, positive results on antibody tests meant only that those eleven monkeys had been exposed to the virus, not that they were presently infected, let alone shedding herpes B. But that scientific distinction didn’t stop the cull. Hired shooters killed all 215 animals at the safari park, using silenced .22 rifles, in a single day. Two weeks later, another animal park in the English countryside followed suit, killing their hundred macaques after some tested positive for herpes B antibodies. The law was the law, and macaques (infected or not) were probably now bad for business. A more sensitive question, raised by primatologists who considered such cullings grotesque and unnecessary, was whether herpes B does or doesn’t belong in level 4. Some arguments suggest that it doesn’t.

The rhesus macaque isn’t the only monkey that carries herpes B. The same virus has been found in other Asian monkeys, including the long-tailed macaque (
Macaca fascicularis
)
within its native range in Indonesia. In the wild, though, neither rhesus macaques nor the others have passed any known herpes B infections to humans, not even in situations where the monkeys come into close contact with people. For this there’s no easy explanation, because the opportunities do seem to exist. Both rhesus macaques and long-tailed macaques are opportunistic creatures, largely unafraid of humans or human environments. As the chainsaws and machetes of humanity’s advance guard have driven them out of their native forest habitats—in India, Southeast Asia, Indonesia, and the Philippines—they have been only more willing to take their chances scavenging, stealing, and panhandling at the edges of civilization. They live anywhere they can find food and a modicum of tolerance. You can see rhesus macaques lurking along the parapets of government buildings in Delhi. You can glimpse long-tailed macaques scrounging garbage from the corridors of dormitories at a university not far from Kuala Lumpur. And because both the Hindu and Buddhist religions embrace gentle attitudes toward animals in general, toward nonhuman primates in particular, macaques have become abundantly, boldly present at many temples around their native regions, especially where any such temple stands near or within a remnant of forest.