Hailed by The Nation as a “master of disaster prose,” author and activist Mike Davis addresses the imminent catastrophe of Avian influenza. In 1918, a pandemic strain of influenza killed at least forty million people in three months. Now, leading researchers believe, another global outbreak is all but inevitable.
A virus of astonishing lethality, known as H5N1, has become entrenched in the poultry and wild bird populations of East Asia. It kills two out of every three people it infects. The World Health Organization warns that it is on the verge of mutating into a super-contagious pandemic form that could visit several billion homes within two years.
In this urgent and alarming book, Mike Davis reconstructs the scientific and political history of a viral apocalypse in the making, exposing the central roles of agribusiness and the fast-food industries, abetted by corrupt governments, in creating the ecological conditions for the emergence of this new plague.
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About the Author
Historian Mike Davis, "America's most incendiary urban critic,"London Review of Books is the author of many books, including the bestselling City of Quartz and Ecology of Fear. The recipient of a MacArthur Fellowship and a professor at the University of California at Irvine, Davis lives in San Diego.
Read an Excerpt
Evolution's Fast Lane
In essence, it's a destructive form of molecular burglary; flu gets into the building, cracks the safe, takes what it wants; and wrecks the place on its way out.
The most ferocious of man-eaters is an innocuous companion of wild ducks and other waterfowl. At the end of every summer, as millions of ducks and geese mass in Canadian and Siberian lakes for their annual migration, influenza blooms. As researchers first discovered in 1974, the virus replicates harmlessly but vigorously in the intestinal tracts of juvenile birds and is copiously excreted into the water. Other birds ingest this viral soup until as many as one-third of the young ducks and geese are producing influenza. In northern lakes, moreover, diverse strains of influenza coexist in the same population, even within an individual duck; one study in Alberta found twenty-seven different subtypes in a community of mallards, pintails, and bluewinged teals.
During their migrations to the Gulf Coast and southern China, the birds continue to shed virus in their feces for as long as one month, increasing the likelihood of the infection spreading to other species of wild and domestic birds. By late fall, however, duck influenza fades to invisibility. Some virologists believe that enough smoldering infection survives in the birds to be rekindled the following August. Others surmise that influenza is tough enough to survive winter under lake ice. In any event, ducks and influenza both return to the same lakes year after year. The cycle, in fact, may be hundreds of thousands, perhaps millions, of years old. In the opinion of one textbook, it is "a classical example of an optimally adapted system." Influenza prospers while ducks remain otherwise unharmed.
Influenza in humans, pigs, and other mammals, on the other hand, is far from such a happy equilibrium; indeed, it is a radically different system of host–parasite interaction due to a variety of factors. In the first place, the virus usually infects the respiratory tract rather than the gut and spreads by an aerosol rather fecal–oral route. Second, it is highly pathogenic, causing an acute respiratory infection that sometimes kills the host. Third, in contrast to genetically stable wild-duck influenzas, the species-jumping versions are extraordinary shape-shifters that constantly alter their genomes to foil the powerful immune systems of human and mammalian hosts. The pandemic threat stems especially from this capacity for ultrafast evolutionary adaptation.
Influenzas are classified into three major genera: A, B, and C. Influenzas B and C have been domesticated by long circulation in human populations. "Genetic studies," a leading expert explains, "suggest that [they] ... diverged from the avian influenza A viruses many centuries ago." Influenza C is a cause of the so-called common cold, while B produces a classic winter flu, especially among children. Neither is a pandemic threat, although B is responsible for some of the annual influenza mortality in susceptible populations. Influenza A, on the other hand, is still wild and very dangerous. Although its primary reservoir remains among ducks and waterfowl, it is in the early stages of crossing over to humans and other bird and mammal species. Compared to other human pathogens, it is also evolving at record-breaking speed; from year to year its proteins change amino acids to create modified strains requiring new vaccines, a process called antigenic drift. Moreover, every human generation or so, a bird or pig version of influenza A will swap genes with a human type of influenza, or more drastically, acquire mutations that permit it to vault over the species barrier. This revolutionary event is called antigenic shift, and it signals the imminence of a pandemic. In effect, influenza A reinvents itself as a new disease against which we have no protective immunological memory. In epidemiological parlance (and in contrast to more stable viruses like smallpox), it is a "constantly emerging disease."
To appreciate the true genius of influenza A, it is necessary to know a little about its macromolecules and their stunning evolutionary capabilities. Like all viruses, influenza is a parasitic genome traveling in the company of clever proteins. Under an electron microscope it is revealed to be a spheroid bristling with tiny spikes and mushrooms, rather like an infinitesimal dandelion. The spikes consist of three intertwined molecules of hemagglutinin, an amazing protein that derives its name from its ability to agglutinate red blood cells. The square-headed mushrooms, fewer in number, are powerful enzymes known as neuraminidase. The outer surface of the virus also has a few M2 proteins that function as proton pumps; these allow the virus to adjust the relative acidity of its interior. Inside the virus's lipid jacket — stolen from a host cell — is its strange genome. All living cells, of course, are programmed by the instructions contained in their DNA double helices. Influenza's genetic software, however, consists of single-stranded RNA packaged in eight separate segments known as ribonucleo-protein complexes (RNPs). Inside each of these complexes, an RNA molecule is coiled tightly around a nucleoprotein and bound together with the polymerases required for its synthesis. Inside the host, the virus also produces a nonstructural protein (NS1) which interferes with the cellular interferon-based immune response. Finally, a matrix protein called M1 fills the remaining space, cushioning the RNPs like so much styrofoam popcorn.
This highly competent little assembly is chemically inert until the hemagglutinin spikes make contact with appropriate receptors (actually sialic acid residues) on the surface of certain cells. While hemagglutinin (hence: HA) is the molecular key that influenza uses to unlock and enter host cells, different key configurations are needed to open different cells. Avian influenza HA, for example, generally only unlocks the intestinal cells of waterfowl, while human HA has been refashioned to break into cells in the mucous lining of the respiratory system. This difference in lock and key configurations is generally considered to be the species barrier that prevents avian influenzas from easily circulating among mammals. Recent research has shown, however, that slight amino substitutions in avian HA — perhaps even the change of a single glutamine to leucine — may suffice to unlock human cells.
Once influenza's HA has docked with a host cell, actual entry requires that the big HA molecule be cleaved down the middle to expose key amino acid complexes; some virologists compare this to opening a Swiss army knife. This cleavage is catalyzed by proteases, protein-hungry enzymes in the host organism. Most influenza HAs are fussy in choosing proteases, but some are more promiscuous. The latter probably have faster rates of attack and are correspondingly more virulent. In any case, HA's success at breaking and entering is the sine qua non of an influenza infection, and it is the primary target (or antigen) of immune response and vaccination. Pandemic influenza is usually defined as the emergence or reappearance of an HA subtype against which most people have no prior immunity.
After HA turns the lock, the influenza virus enters the host cell clothed in some of the host's own plasma membrane. The M2 channel protein then pumps ions into the interior of this capsule (endosome). The increased acidity dissolves the membrane and releases influenza's genome segments (the RNPs) into the host cell. The RNPs then flock to the nucleus, where viral RNA replication takes place. Like all viruses, influenza hijacks the host's biosynthetic machinery to produce several hundred copies of itself; in human influenza, the virus also issues instructions to stop making the proteins that the host cell requires for its own survival.
The complex details of RNA transcription and replication are best left to a good virology textbook, but two general aspects of influenza's reproduction are key to understanding its success as a pathogen. First, RNA synthesis is radically error prone. All cellular life (as well as some viruses) depends upon the scrupulous accuracy of DNA polymerase in duplicating genetic information; like an obsessive scholar, it proofreads and corrects every copy of DNA, and the resulting error rate (in bacteria and humans) is thus less than one mistake in every billion nucleotides copied. RNA polymerases, on the other hand, are careless hacks who do not proof or correct their copy. As a result, the error rates in influenza and some other RNA viruses are 1 million times greater than in DNA-based genomes. Each new strand of RNA is a mutant, differing on average from its parental template by at least one nucleotide. (Its progeny are often characterized as a "mutant swarm" or "quasi species" because of their extreme variability.) Influenza, in fact, lives at the very edge of what evolutionary biologists call "error catastrophe." If the error rate were any higher, information integrity would be lost, and the genome would decay into utter gibberish.
To aficionados of complexity theory, then, influenza is an outstanding example of a self-organized system on the edge of chaos. Such perilous fine-tuning is supposed to optimize complexity and enhance evolutionary fitness, but for what purpose? In wild ducks, genetic hypervariability has seemingly lost its raison d'être; older strains of influenza find it easy to earn a living, and different subtypes can coexist peacefully with another. Evolution, according to Robert Webster and William Bean, has resulted in stasis as "the long-term survival of the avian viruses appears to favor those that have not changed, and selection is primarily negative." In humans and other secondary hosts, however, influenza comes under ferocious attack from sophisticated immune systems. This generates intense selective pressure, which in turn kicks evolution into fast forward. "The molecular clocks of RNA viruses," writes evolutionary biologist John Holland, "can spin at blinding speeds as compared to those of their hosts." Indeed, their rates of evolution "proceed up to millions-fold faster than that of their hosts."
Influenza A's extraordinary heterogeneity thus becomes a resource for resisting the immune-system onslaught. As rapidly as antibodies defeat one influenza strain, others, more resistant, emerge to take its place — a single amino acid substitution can suffice to thwart an antibody attack. This irresistible drift of influenza's antigenic characteristics ensures its survival in the face of the antibody blitz. Indeed, according to leading researchers, "it may be that human influenza A is unique in that it is able to produce a series of antigenically selected mutants that are as fit as the parental population and is the only virus that undergoes true antigenic drift." Yet if these point mutations ensure influenza viability as a disease from season to season, they do not totally outwit immunological memory. "[T]he high level of partial immunity remaining in the community," Dorothy Crawford explains, "ensures that antigenic drift will not cause a pandemic."
The influenza genome, however, has a second, even more extraordinary, trick up its sleeve: because its RNA is packaged in separate segments, a co-infection of a host cell by two different subtypes of influenza can result in a reassortment of their constituent genes. Under the right circumstances, influenzas can trade replicating RNPs like kids swap baseball cards, with the resulting hybrids having gene segments from different parents. Thus the pandemic Asian flu of 1957 contained three avian segments (including a novel HA) along with five RNPs from the previously circulating human subtype. Likewise, the pandemic Hong Kong subtype of 1968 retained six segments of the 1957 genome while adding new avian genes for HA and one of the polymerases. In both cases, the reassortants combined avian surface proteins with human-adapted internal proteins; this enabled them to overcome what Taubenberger and Reid characterize as "the twin challenges of being 'new' to its host, while being supremely well adapted to it."
But, given the species barrier raised by HA specificity, how do co-infections of avian and human viruses ever occur? Until the 1997 outbreak, it was generally believed that antigenic shift required the intermediary of pigs: "[F]or influenza viruses, the species barrier to pigs is relatively low when compared with the barrier between birds and humans." Cells in the respiratory systems of swine have the right receptors for both avian and human HA and thus can contract diverse subtypes of influenza A — they are ideal viral blenders. Their critical role, moreover, is supported by epidemiological history: influenza epidemics and pandemics usually emerge first in southern China (especially in Guangdong and the Pearl River Delta) where huge numbers of pigs, domestic ducks, and wild waterfowl live in traditional ecological intimacy.
It should be stressed, however, that reassortment, like mutational drift, is a scattershot process. As a leading researcher at the National Institutes of Health explains, "the vast majority of reassortants between avian and human (or mammalian) influenza viruses contain a gene ... or gene constellation that prevents the virus replicating efficiently in primates." Nevertheless, "some 25 percent of the resulting recombinant viruses would still be potentially virulent for humans if one of the two parents is a human influenza virus." On rare occasions, it is also possible for novel influenza subtypes to emerge through recombination: the splicing together of parts of genes (coding for the same protein) from different species. In a controversial 2001 article in Science, three Australian researchers proposed that the devastating 1918 pandemic was triggered by a recombination event involving the HA gene. The spike head, they argued, derived from a swine lineage, while the stalk was encoded by a human gene. This recombinant hemagglutinin, they suggest, may have had "an unusual tissue specificity, such that it spread from the upper respiratory tract to the lungs." (Later, to make matters more complex, we will examine two other possible mechanisms of pandemic emergence: dormancy and direct species jump.)
Whether or not recombination is part of influenza A's repertoire, few other human pathogens — apart from the HIV retrovirus (world champion at wily mutation) and the chief malaria parasite, Plasmodium falciparum, seem so invincible. Yet influenza does have its weak points, as can be seen as we complete our sketch of its progress through a host: next, the progeny viruses must be assembled and then execute their escape from the dying host cell. Although research shows that the M1 protein is probably the "major virus assembly organizer," the complex choreography that produces new viral particles out of the separately replicated gene strands and proteins is incompletely understood. The final assembly takes the form of a budding of the new viruses from the cellular membrane. This is sticky business; the problem is that the strong affinity of the HA molecules for the external neuraminic acid residues — the very property that made viral entry possible — now blocks the exit. Neuraminidase (henceforth: NA) overcomes this dilemma by attacking and removing the neuraminic acid residues — if HA is the burglar, NA is the escape artist. Their complementary roles are so important that virologists classify influenza A subtypes by their specific HA and NA: the formula adapted in 1980 is HxNy. (Please remember this. It will avoid confusion later on when you meet a series of bad characters named H3N2, H9N1, H5N1, and so on.)
However the NA mushrooms are more vulnerable than are the HA spikes to antivirals that imitate neuraminic (sialic) acid residues and plug strategic portals in their three-dimensional structures. The development of powerful neuraminidase inhibitors — zanamivir (Relenza) in 1993 and oseltamivir (Tamiflu) in 1997 — has been a major breakthrough in the treatment of annual influenza. More importantly, zanamivir and oseltamivir are the only medications that are thus far effective in preventing or moderating the acute onset of avian flu (or, for that matter, lab-made clones of the deadly 1918 strain). Because of the difficulties of administering zanamivir — it requires an inhaler — oral oseltamivir tablets are seen as the only practical alternative for mass prophylaxis. Indeed, until (and if) avian flu vaccines become widely available, oseltamivir, as Science points out, "would be the world's only initial defense against a pandemic that could kill millions of people." For several years the world's top influenza experts have been urging a crash program to increase oseltamivir production; it is currently manufactured by Roche in a single factory in Switzerland. An international stockpile could then be set aside for emergency use by the WHO. These warnings, as we shall see later, have largely been ignored, and oseltamivir inventories remain woefully insufficient to meet the pandemic needs of a single American state, much less the entire nation or the rest of the world.(Continues…)
Excerpted from "The Monster at Our Door"
Copyright © 2005 Mike Davis.
Excerpted by permission of The New Press.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.
Table of Contents
1: Evolution's Fast Lane,
2: The Virulence of Poverty,
3: The Wrong Lessons,
4: Birds of Hong Kong,
5: A Messy Story,
6: Pandemic Surprise,
7: The Triangle of Doom,
8: Plague and Profit,
9: Edge of the Abyss,
10: Homeland Insecurity,
11: Structural Contradictions,
12: The Titanic Paradigm,
Conclusion: Year of the Rooster,
Most Helpful Customer Reviews
This book is a comprehensive look at just what bird (or avian) flu is all about, and what the world is, or is not, doing about it.Influenzas are divided into three major categories. Types B & C are relatively mild, leading to the common cold, or, at worst, the winter flu. But Type A is the unpredictable, and lethal, strain that is fully entrenched among the bird population of East Asia. It is very easy for the disease to jump from migratory birds, to ducks, to chickens, to swans and egrets, and back again, mutating along the way. Until now, the human deaths have come from direct contact with infected birds. But the time is coming when that last mutation will click into place, causing it to jump from person to person. A worldwide flu pandemic, with a death toll in the hundreds of millions, is, as one researcher put it, "late."What is America doing to prepare for the coming pandemic? Not much. Industrial chicken farms, with millions of chickens crowded into one building, are a wonderful breeding ground for diseases of all sorts, not just bird flu. Remember SARS from a couple of years ago? Among the reasons why it was contained is that the cities where it happened, Toronto and Hong Kong, are modern cities with modern health care systems. Imagine if SARS had shown up somewhere in Africa, with a much less modern health care system.The major drug companies have opposed moves to allow other countries to make cheap copies of flu vaccines, even though there are nowhere near enough doses of vaccines even for first responders, out of concern for their corporate bottom line. The Bush Administration is more interested in spending money preparing for a smallpox or anthrax outbreak, something which has much less chance of ever happening, than in spending it on bird flu, which is coming in the near future.This is a very spooky book, which I guess is the idea. It is written for the layman, and does a fine job at showing how unprepared America is for the next flu pandemic. It is very highly recommended.
I read this book in two days flat! It is very well researched. It gives a chronological account of the outbreaks that have occured from 1997 through 2005. It also compares and contrasts the influenza pandemics of 1918, 1957, and 1976. The book describes how the H5N1 virus jumped the species barrier, and why it is dangerous to humans. According to the author, the avian flu pandemic is behind schedule. Globalization, factory farming, and a failing world health care system make this a perfect storm. Governments need to make a deal with pharmaceutical companies to entice them to make a vaccine. This is a great read. This book will tell you everything about the Bird Flu that goverments and the press have been trying to hide.