Table of Contents:

Foreword

Introduction

I. Storm Gathering

1. 1918

2. Master of Metamorphosis

3. H5N1

4. Playing Chicken

5. Worse Than 1918?

6. When, Not If

II. When Animal Viruses Attack

1. The Third Age

2. Man Made

3. Livestock Revolution

4. Tracing the Flight Path

5. One Flu Over the Chicken's Nest

6. Coming Home to Roost

7. Guarding the Henhouse

III. Pandemic Preparedness

1. Cooping Up Bird Flu

2. Race Against Time

3. Tamiflu

IV. Surviving the Pandemic

1. Don't Wing It

2. Our Health in Our Hands

3. Be Prepared

V. Preventing Future Pandemics

1. Tinderbox

2. Reining in the Pale Horse

Topics

References 1-3,199

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The mad scientist scenario of intensive poultry production has been replicated around the globe. Viral transformations from harmless to deadly have been documented in the outbreaks in Pennsylvania in the 1980s, Mexico,1578 Australia, Pakistan,1579 and Italy in the 1990s, and in Chile, the Netherlands, and Canada since 2002.1580 These outbreaks have collectively led to the deaths of millions upon millions of chickens, but does this mean highly pathogenic bird flu viruses are more dangerous to humans? The CDC thinks this is likely the case.1581

Adaptation to land-based birds involves alterations of the virus in ways that may present increased human risk.1582 Any modification that enhances airborne transmission, for example, such as improved resistance to desiccation, could amplify risk to people. Certainly the mutation that allows the virus to rage throughout all organ systems may contribute to the ability of viruses like H5N1 to cross the species barrier into humans1583 and present a greater threat.1584 In order to create a human pandemic, though, the virus has to be able to bind effectively to human receptors.1585 That’s why we’ve been so concerned about pigs. Ducks have the 2,3 linkages, humans have the 2,6 linkages, and pigs have both. So, in a pig, the duck virus could theoretically accustom itself to our receptors and burst throughout the human population.1586 Unfortunately for the human race, researchers recently discovered that chickens have human 2,6 receptors in their lungs as well.1587

A pandemic virus faces a paradoxical twin challenge: It must be new to the human immune system, so there’s no pre-existing immunity, while at the same time being supremely well adapted to infect us.1588 Mikhail N. Matrosovich at the Russian Academy of Sciences in Moscow discovered what may be a critical piece of the pandemic puzzle by demonstrating that, unlike ducks, chickens can tightly bind human influenza viruses and vice versa. This, Matrosovich wrote, could lead to the emergence of bird flu viruses with “enhanced propensity for transmission to humans.”1589

In addition to the presence of human-like 2,6 linkages in the respiratory tracts of chickens, there’s evidence of a second sialic acid binding site on the virus, the significance of which is unknown. This second binding site is highly conserved in the aquatic bird reservoir, but lost in both chickens and humans—another similarity on a molecular level between the lungs of chickens and humans that may make viral adaptations to one applicable to the other.1590

A third line of molecular evidence that implicates chickens as the pale Trojan horse of the apocalypse has to do with the length of ganglioside sugar chains. Gangliosides are complex fatty molecules jutting out of our cell membranes that display chains of sugars. It is not enough for the influenza virus to hook onto the sialic acid receptors on one of our cells; the virus must then fuse with the cell and spill its nefarious contents inside to take over. The virus must not only dock, but pry open the bay doors. This may be where these ganglioside sugar chains come into play, facilitating the virus’s fusion and entry process.1591

The exact role gangliosides play remains speculative, but we do know that influenza viruses from different species have distinct binding preferences as to the length of these sugary chains. Duck viruses have an affinity for the short chains that are abundant in duck intestines, whereas human viruses have an affinity for the longer chains found in primate lung tissue. Part of the duck-human species barrier, then, may be that duck viruses prefer short chains, yet human cells exhibit more long chains. Chickens are in the middle.

As a duck virus circulates among chickens, there may be a selection pressure on the virus to attach to longer—and therefore more human-like—chains to better adapt and spread within and between chickens. H5N1, for example, which as a waterfowl virus presumably preferred short chains, has mutated in favor of an affinity for longer chicken chains, on a potential trajectory toward more efficient human infection. In fact, chicken flu viruses bind tighter to human cells than they do to duck cells. As a result of some strange twist of evolutionary fate, from the standpoint of the influenza virus, chickens may look more like people than they do like ducks. When waterfowl viruses that are essentially harmless infect chickens, they may start accumulating mutations that make them more dangerous to chickens and humans alike.1592 Evidence continues to build to support this hypothesis.1593 In developing a taste for chicken, these viruses may acquire a taste for us.

Analysis of the 1918 virus protein sequences suggests that the transformation into a pandemic virus may be easier than previously thought. Just a single point mutation may change a virus that binds duck 2,3 receptors to a virus that binds human 2,6 receptors.1594 The researchers who resurrected the 1918 virus found that the receptor binding site on the virus differed from the binding site of its presumed avian precursor by just one or two tiny amino acid substitutions, presumably all it needed to go human. Many experts expect H5N1 to similarly strike gold, line up the cherries, and cash in at our expense.

Adaptation to a human host requires more than just viral access into human cells. The internal viral machinery still has to evolve to best take over our cells, but viral entry is the first step. This surreptitious similarity between chicken and human receptors may better enable bird flu viruses like H5N1 to transition from infecting billions of chickens to infecting billions of humans. This may be thought of as an example of exaptation, a concept in evolutionary biology by which an adaptation in one context coincidentally predisposes success in an unrelated context. Legionnaire’s disease is the classic example.1595

Legionnaire’s is caused by bacteria whose primary evolutionary niche is the scum lining the rocks of natural hot springs. As it evolved to thrive within this warm, moist environment, it happened to be evolving to thrive within the warm, moist environment of the human lung as well. Of course, the bacteria had little occasion to find itself within our lungs, since we’re good about keeping water out of our windpipes (lest we drown). But then machines were invented, like air conditioners, which have the capacity to mist water into the air, as evidenced by the famous Philadelphia outbreak in 1976 at an American Legion convention in which the hotel ventilation system conditioned the air with bacteria now known as Legionella.1596 In the environment of the human respiratory tract, Legionella’s prior adaptations proved lethal. In the case of influenza viruses that may have pandemic potential like H5N1, chickens may be thought of as acting as both hot springs and air conditioner, providing the media by which the virus can adapt and propagate to the populace.

The evolutionary distance from duck to human seems too far for a direct jump by influenza, but with chickens sharing binding characteristics of each, they may act as stepping stones to bridge the huge species gap.1597 There is evidence that other land-based domesticated fowl, such as quail and pheasant, can also act as intermediaries and may play a minor role,1598 but we don’t tend to raise them like we do chickens. Although there was an outbreak of H5N2 on a farm raising more than 100,000 quail in Oregon in the 1980s, operations that size for birds other than chickens are the exception.1599 Indeed, chickens would seem the most threatening possible species to be exhibiting human virus binding attributes, as they are the one animal in the world we raise by the tens of billions every year. In nature, as a waterborne virus, influenza has been known to infect aquatic mammals like whales and seals,1600