The cave had several shafts. The main shaft was about eight feet high. Because of all the mining activity, many of the bats had shifted their roosting preference “and went over to what we called the cobra shaft,” Amman later told me. The shaft was so called because, he said, “there was a black forest cobra in there.”
Or maybe a couple. It was a good dark habitat for a snake, with water and plenty of bats to eat. The miners showed Amman and Towner into the cave and led them to a chamber containing a body of brown, tepid water. Then the local fellows cleared out, leaving the scientists to explore on their own. They dropped down beside the brown lake and found that the chamber branched into three shafts, each of which seemed blocked by standing water. Peering into those shafts, they could see many more bats. The humidity was high and the temperature maybe 10 or 15 degrees hotter than outside. Their goggles fogged up. Their respirators became soggy and wouldn’t pass much oxygen. They were panting and sweating, zipped into their Tyvek suits, which felt like wearing a trash bag, and by now they were becoming “a little loopy,” Amman recalled. “We had to get out and cool off.” It was only their first underground excursion at Kitaka. They would make several.
On a later day, the team investigated a grim, remote chamber they dubbed the Cage. It was where one of the four infected miners had been working just before he got sick. This time Amman, Formenty, and Alan Kemp of the NICD went to the far recesses of the cave. The Cage itself could be entered only by crawling through a low gap at the base of a wall—like sliding under a garage door that hadn’t quite closed. Amman is a large man, six-foot-three and 220 pounds, and for him the gap was a tight squeeze; his helmet got stuck, and he had to pull it through separately. “You come out into this sort of blind room,” he said, “and the first thing you see is just hundreds of these dead bats.”
They were Egyptian fruit bats, the creature of interest, left in various stages of mummification and rot. Piles of dead and liquescent bats seemed a bad sign, potentially invalidating the hypothesis that Rousettus aegyptiacus might be a reservoir host of Marburg. If these bats had died of Marburg, suspicion would shift elsewhere—to another bat or maybe a rodent or a tick or a spider. Those other suspects might have to be investigated. Ticks, for instance: there were plenty of them in crevices near the bat roosts, waiting for a chance to drink some blood.
The men went to work, collecting. They stuffed dead bats into bags. They caught a few live bats and bagged them too. Then, back down on their bellies, they squeezed out through the low gap. “It was really unnerving,” Amman told me. “I’d probably never do it again. One little accident, a big rock rolls in the way, and that’s it. You’re trapped. Uganda is not famous for its mine rescue teams.”
By the end of this field trip, the scientists had collected about 800 bats. They dissected them and took samples of blood and tissue. Those samples went back to Atlanta, where Towner participated in the laboratory efforts to find traces of Marburg virus. One year later came a paper, authored by Towner, Amman, Rollin, and their WHO and NICD colleagues, announcing some important results. Not only did the team detect antibodies against Marburg and fragments of Marburg RNA, but they also did something more difficult and compelling. They found live virus.
Working in one of the CDC’s Biosafety Level 4 units (the highest level of containment security for pathogens), Towner and his coworkers had isolated viable, replicating Marburg virus from five different bats. Furthermore, the five strains of virus were genetically diverse, suggesting an extended history of viral presence and evolution within Egyptian fruit bats. That data, plus the fragmentary RNA, constituted strong evidence that the bat is a reservoir—if not the reservoir—of Marburg virus. The virus is definitely there, infecting about 5 percent of the bat population at a given time. Of the estimated 100,000 bats at Kitaka, therefore, the team could say that about 5,000 Marburg-infected bats flew out of the cave every night.
An interesting thought: 5,000 infected bats passing overhead. Where were they going? How far to the fruiting trees? Whose livestock or little gardens got shat upon as they went? The breadth of possible transmission is incalculable. And the Kitaka aggregation, Towner and his coauthors added, “is only one of many such cave populations throughout Africa.”
The dangers presented by zoonoses are real and severe, but the degree of uncertainty is also high. There’s not a hope in hell, for instance, as a great flu expert told me, of predicting the nature and timing of the next influenza pandemic. Too many factors vary randomly, or almost randomly, in that system. Prediction, in general, so far as all these diseases are concerned, is a tenuous proposition, more likely to yield false confidence than actionable intelligence.
But the difficulty of predicting precisely doesn’t oblige us to remain blind, unprepared, and fatalistic about emerging and reemerging zoonotic diseases. The practical alternative to soothsaying, as one expert put it, is “improving the scientific basis to improve readiness.” By “the scientific basis” he meant the understanding of which virus groups to watch, the field capabilities to detect spillovers in remote places before they become regional outbreaks, the organizational capacities to control outbreaks before they become pandemics, plus the laboratory tools and skills to recognize known viruses speedily, to characterize new viruses almost as fast, and to create vaccines and therapies without much delay. If we can’t predict a forthcoming influenza pandemic or any other newly emergent virus, we can at least be vigilant; we can be well prepared and quick to respond; we can be ingenious and scientifically sophisticated in the forms of our response.
To a considerable degree, such things are already being done. Ambitious networks and programs have been created by the WHO, the CDC, and other national and international agencies to address the danger of emerging zoonotic diseases. Because of concern over the potential of “bioterrorism,” even the U.S. Department of Homeland Security and the Defense Advanced Research Projects Agency (DARPA, whose motto is “Creating & Preventing Strategic Surprise”) of the U.S. Department of Defense have their hands in the mix. These efforts carry names and acronyms such as the Global Outbreak Alert and Response Network (GOARN, of the WHO), Prophecy (of DARPA), the Emerging Pandemic Threats program (EPT, of USAID), and the Special Pathogens Branch (SPB, of the CDC), all of which sound like programmatic boilerplate but which harbor some dedicated people working in field sites where spillovers happen and secure labs where new pathogens can be quickly studied. Private organizations such as EcoHealth Alliance (led by a former parasitologist named Peter Daszak) have also tackled the problem. There is an intriguing organization called Global Viral (GV), created by a scientist named Nathan Wolfe and financed in part by Google. GV gathers blood samples on small patches of filter paper from bushmeat hunters and other people across tropical Africa and Asia and screens those samples for new viruses, in a systematic effort to detect spillovers and stop the next pandemic before it begins to spread. At the Mailman School of Public Health, part of Columbia University, researchers in Ian Lipkin’s laboratory are developing new molecular diagnostic tools. Lipkin, trained as a physician as well as a molecular biologist, calls his métier “pathogen discovery” and uses techniques such as high-throughput sequencing (which can sequence thousands of DNA samples quickly and cheaply), MassTag-PCR (identifying amplified genome segments by mass spectrometry), and the GreeneChip diagnostic system, which can simultaneously screen for thousands of different pathogens. When a field biologist takes serum from flying foxes in Bangladesh or bleeds little bats in southern China, some of those samples go straight to Lipkin.
These scientists are on alert. They are our sentries. They watch the boundaries across which pathogens spill. When the next novel virus makes its way from a chimpanzee, a bat, a mouse, a duck, or a macaque into a human, and maybe from that human into another human, and thereupon begins causing a small cluster of lethal illnesses, they will see it—we hope they will, anyway—and raise the alarm.
During the early twentieth century, disease scientists from the
Rockefeller Foundation and other institutions conceived the ambitious goal of eradicating some infectious diseases entirely. They tried hard with yellow fever, spending millions of dollars and many years of effort, and failed. They tried with malaria and failed. They tried later with smallpox and succeeded. Why? The differences among those three diseases are many and complex, but probably the most crucial one is that smallpox resided neither in a reservoir host nor in a vector, such as a mosquito or tick. Its ecology was simple. It existed in humans—in humans only—and was therefore much easier to eradicate. The campaign to eradicate polio, begun in 1998 by the WHO and other institutions, is a realistic effort for the same reason: polio isn’t zoonotic. Eradicating a zoonotic disease, whether a directly transmitted one like Ebola or an insect-vectored one such as yellow fever, is much more complicated. Do you exterminate the pathogen by exterminating the species of bat or primate or mosquito in which it resides? Not easily, you don’t, and not without raising an outcry. The notion of eradicating chimpanzees as a step toward preventing the future spillover of another HIV would provoke a deep and bitter discussion, to put it mildly.
That’s the salubrious thing about zoonotic diseases: they remind us, as Saint Francis did, that we humans are inseparable from the natural world. In fact, there is no “natural world”; it’s a bad and artificial phrase. There is only the world. Humankind is part of that world, as are the ebolaviruses, as are the influenzas and the HIVs, as are Marburg and Nipah and SARS, as are chimpanzees and palm civets and Egyptian fruit bats, as is the next murderous virus—the one we haven’t yet detected. And while humans don’t evolve nearly as fast and as variously as an RNA virus does, we may—let me repeat that word, may—be able to keep such threats at bay, fighting them off, forestalling the more cataclysmic of the dire scenarios they present, for one reason: at our best, we’re smarter than they are.
OLIVER SACKS
Altered States
FROM The New Yorker
TO LIVE ON a day-to-day basis is insufficient for human beings; we need to transcend, transport, escape; we need meaning, understanding, and explanation; we need to see overall patterns in our lives. We need hope, the sense of a future. And we need freedom (or, at least, the illusion of freedom) to get beyond ourselves, whether with telescopes and microscopes and our ever-burgeoning technology, or in states of mind that allow us to travel to other worlds, to rise above our immediate surroundings.
We may seek, too, a relaxing of inhibitions that makes it easier to bond with each other or transports that make our consciousness of time and mortality easier to bear. We seek a holiday from our inner and outer restrictions, a more intense sense of the here and now, the beauty and value of the world we live in.
Many of us find Wordsworthian “intimations of immortality” in nature, art, creative thinking, or religion; some people can reach transcendent states through meditation or similar trance-inducing techniques, or through prayer and spiritual exercises. But drugs offer a shortcut; they promise transcendence on demand. These shortcuts are possible because certain chemicals can directly stimulate many complex brain functions.
Every culture has found such chemical means of transcendence, and at some point the use of such intoxicants becomes institutionalized at a magical or sacramental level. The sacramental use of psychoactive plant substances has a long history and continues to the present day in various shamanic and religious rites around the world.
At a humbler level, drugs are used not so much to illuminate or expand or concentrate the mind but for the sense of pleasure and euphoria they can provide. Even the pioneer Mormons, forbidden to use tea or coffee, on their long march to Utah found by the roadside a simple herb, Mormon tea, whose infusions refreshed and stimulated the weary pilgrims. This was ephedra, which contains ephedrine, chemically and pharmacologically akin to the amphetamines.
Many people experiment with drugs, hallucinogenic and otherwise, in their teenage or college years. I did not try them until I was thirty and a neurology resident. This long virginity was not due to lack of interest. I had read the great classics—De Quincey’s Confessions of an English Opium Eater and Baudelaire’s Artificial Paradises—at school. I read about the French writer Théophile Gautier, who in 1845 paid a visit to the recently founded Club des Hashischins, in a quiet corner of the Île Saint-Louis. Hashish, in the form of a greenish paste, had recently been introduced from Algeria and was all the rage in Paris. At the salon, Gautier consumed a substantial piece of hash. At first he felt nothing out of the ordinary, but soon, he wrote, “everything seemed larger, richer, more splendid,” and then more specific changes occurred:
An enigmatic personage suddenly appeared before me . . . His nose was bent like the beak of a bird, his green eyes, which he wiped frequently with a large handkerchief, were encircled with three brown rings, and caught in the knot of a high white starched collar was a visiting card which read: Daucus-Carota, du Pot d’or . . . Little by little the salon was filled with extraordinary figures, such as are found only in the etchings of Callot or the aquatints of Goya; a pêle-mêle of rags and tatters, bestial and human shapes.
By the 1890s, Westerners were also beginning to sample mescal, or peyote, previously used only as a sacrament in certain Native American traditions. As a freshman at Oxford, free to roam the shelves of the Radcliffe Science Library, I read the first published accounts of mescal intoxication, including those of Havelock Ellis and Silas Weir Mitchell. They were primarily medical men, not just literary ones, and this seemed to lend an extra weight and credibility to their descriptions. I was captivated by Mitchell’s dry tone and his nonchalance about taking what was then an unknown drug with unknown effects.
At one point, Mitchell wrote in an 1896 article for the British Medical Journal, he took a fair portion of an extract made from mescal buttons and followed it up with an additional dose. Although he noted that his face was flushed, his pupils were dilated, and he had “a tendency to talk, and now and then . . . misplaced a word,” he nevertheless went out on house calls and saw several patients. Afterward, following three further doses, he lay down quietly in a dark room, whereupon he experienced “an enchanted two hours,” full of chromatic effects:
Delicate floating films of colour—usually delightful neutral purples and pinks. These came and went—now here, now there. Then an abrupt rush of countless points of white light swept across the field of view, as if the unseen millions of the Milky Way were to flow a sparkling river before the eye.
Unlike Mitchell, who had focused on colored, geometric hallucinations, which he compared in part to those of migraine, Aldous Huxley, writing of mescaline in the 1950s, focused on the transfiguration of the visual world, its investment with luminous, divine beauty and significance. He compared such drug experiences to those of great visionaries and artists, though also to the psychotic experiences of some schizophrenics. Both genius and madness, Huxley hinted, lay in these extreme states of mind—a thought not so different from those expressed by De Quincey, Coleridge, and Baudelaire in relation to their own ambiguous experiences with opium and hashish (and explored at length in Moreau’s 1845 book Hashish and Mental Illness). I read Huxley’s The Doors of Perception and Heaven and Hell when they came out in the 1950s, and I was especially excited by his speaking of the geography of the imagination and its ultimate realm—the “antipodes of the mind.”
I had done a great deal of reading but had no experiences of my own with such drugs until 1953, when my childhood friend Eric Korn came up to Oxford. We read excitedly about Albert Hofmann’s discovery of LSD, and we ordered 50 micrograms of it from the manufacturer in Switzerland (it was still legal in the midfifties). Solemnly, even sacramentally, we divided it and took 25 micrograms each—not knowing what splendors or horrors awaited us—but, sadly, it had absolutely no effect on either of us. (We should have ordered 500 micrograms, not 50.)
By the time I qualified as a doctor at the end of 1958, I knew I wanted to be a neurologist, to know how the brain embodied con
sciousness and self and to understand its amazing powers of perception, imagery, memory, and hallucination. A new orientation was entering neurology and psychiatry at that time; it was the opening of a neurochemical age, with a glimpse of the range of chemical agents, neurotransmitters, which allowed nerve cells and different parts of the nervous system to communicate with one another. In the 1950s and ’60s, discoveries were coming from all directions, though it was far from clear how they fitted together. It had been found, for instance, that the Parkinsonian brain was low in dopamine, and that giving a dopamine precursor, L-dopa, could alleviate the symptoms of Parkinson’s disease; while tranquilizers, introduced in the early 1950s, could depress dopamine and cause a sort of chemical Parkinsonism. For about a century, the staple medication for Parkinsonism had been anticholinergic drugs. How did the dopamine and the acetylcholine systems interact? Why did opiates—or cannabis—have such strong effects? Did the brain have special opiate receptors and make opioids of its own? Was there a similar mechanism for cannabis receptors and cannabinoids? Why was LSD so enormously potent? Were all its effects explicable in terms of altering the serotonin in the brain? What transmitter systems governed wake-sleep cycles, and what might be the neurochemical background of dreams or hallucinations?