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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Understanding the ecology of the virus in its so-called “benign reservoir” is imperative if we hope to develop strategies to prevent future catastrophic outbreaks.1508 The primordial source of all influenza viruses—avian and mammalian—is aquatic birds.1509 In nature, the influenza virus has existed for millions of years as a harmless intestinal waterborne infection of waterfowl, particularly ducks.1510 The duck doesn’t get sick, because the virus doesn’t need to make the duck sick to spread. In fact, it may be in the virus’s best interest for the bird not to get sick so as to spread farther. Dead ducks don’t fly.

The influenza gene pool is really more of a gene pond. Every year, untold numbers of wild ducks congregate on the world’s lakes to mate, raise families, and spread the influenza virus to each other. The virus silently multiplies in the ducks’ intestinal lining and is then excreted into the pond water to lie in wait for other ducks to touch down for a drink. The ducks gobble down the virus and the cycle continues. This had been going on for perhaps 100 million years before the first person came down with the flu.1511

Most ducks are infected as ducklings. Studies of ducks on Canadian lakes show that up to 30% of juvenile birds are actively shedding the virus.1512 The ducks excrete such massive titers of virus1513 that researchers have been able to culture it straight out of a spoonful of lake water.1514 Under the right conditions, the virus is estimated to be able to persist for years in cold water.1515 With such high concentrations of virus, with such highly efficient transmission,1516 and with such environmental stability, scientists estimate that virtually all of the millions of ducks in the world become infected sometime within their lives.1517

The ducks aren’t infected for long.1518 Most only shed virus for a few days, but the fecal-oral route of infection for aquatic birds is so efficient that this is thought to be enough to keep the virus spreading throughout the millennia.1519 Millions of years of evolution have so tailored the parasite to its host, a so-called “optimally adapted system,” that the virus seems completely innocuous to the ducks.1520 The virus exists in an “evolutionary stasis” in waterfowl,1521 remaining unchanged despite its furious mutation rate.1522

Influenza viruses don’t tend to retain any new mutations in ducks because they found their perfect niche. Sharks, for example, have remained basically unchanged for 100 million years, even while other species evolved around them, presumably because sharks had already evolved to be such perfected killing machines.1523 Similarly, evolution doesn’t seem to be able to much improve influenza. The virus continues to churn out millions of mutants in wild ducks in an attempt to spread faster and farther, but since the virus-duck relationship seems so flawlessly fine-tuned, any deviant viral progeny are less successful and die out. The virus has achieved peak efficiency and is found ubiquitously throughout aquatic bird species around the world.1524

Because the influenza virus in its natural state is so finely attuned to its aquatic host, it not only doesn’t harm the carrier duck, but it also seems unable to cause serious disease in people. There are only two reports of human infection from wild bird viruses in the medical literature. One case involved a woman who kept ducks and got a piece of straw caught in her eye while cleaning out her duck house,1525 and the second was a laboratory field worker whose eye was sneezed in by a bird flu-infected seal.1526 Despite direct inoculations of virus, the worst the virus seemed able to do was cause a mild, self-limited case of conjunctivitis, commonly known as pinkeye.1527 Duck flu viruses don’t seem to grow well in humans (or other primates), and human flu viruses don’t seem to grow well in ducks.1528

Scientists have even attempted to directly infect human volunteers with waterfowl viruses, but to little avail. Test subjects snorted massive doses of virus—enough to infect up to a billion birds—yet most of the time the virus wouldn’t take hold at all, and when it had any effect, it typically produced nothing more than a transitory local reaction.1529 The evolutionary gulf between duck gut and human lung is so broad that an intermediate host is thought to be needed to act as a stepping stone for the virus.1530 “And poultry,” said a spokesperson for the Department of Homeland Security’s National Center for Foreign Animal and Zoonotic Disease Defense, “are likely to be that host.”1531

Bird flu viruses only “heat up,” in the words of Dutch virologist Albert Osterhaus, the virologist whose lab first identified human H5N1 infection, “when they pass from wild birds to poultry.”1532 Drs. E. Fuller Torrey, director of the Stanley Medical Research Institute, and Robert H. Yolken, a neurovirologist at Johns Hopkins University School of Medicine, concluded in their book, Beasts of the Earth: Animals, Humans, and Disease, “If ducks had not been domesticated, we might not even be aware of the existence of influenza….”1533 H5N1 discoverer Kennedy Shortridge agrees: “When you domesticate the duck,” he said, “you unwittingly bring the flu virus to humans.”1534

Although for a brief period of the year remote Canadian lakes can swarm with virus,1535 a greater danger for humans may lie in the raising of domesticated ducks year-round on southern China rice paddies, leading to what Shortridge calls a “virus soup” of stagnant water and duck feces.”1536 Iowa State University’s Center for Food Security and Public Health wrote: “Humans have altered the natural ecosystems of birds through captivity, domestication, industrial agriculture, and nontraditional raising practices. This has created new niches for AI [avian influenza] viruses….”1537 The combination of what may be the greatest concentration of virus in the world with densely domesticated poultry and pigs to act as stepping stones may have been what enabled influenza to take on the human species.1538

For a virus so perfectly adapted to the gut of wild waterfowl, the human lung is a long way from home. What is influenza, an intestinal waterborne duck virus, doing in a human cough? Imagine an infected duck transported to a live poultry market. The duck is crammed into a cage stacked high enough to splatter virus-laden droppings everywhere. Even if the vendor or customer were hit directly by the infected feces, humans might be too alien for the unmutated duck virus to take hold. But what if the virus reached land-based birds like quail or chickens? Terrestrial birds are not natural hosts for influenza,1539 but they are recognizable enough by the virus to infect them. The virus then faces a problem, and the solution may be hazardous to human health.

All viruses must spread or perish. Like a fish out of water, when the influenza virus finds itself in the gut of a chicken, it no longer has the luxury of easy aquatic spread. It can no longer remain a strictly waterborne virus. Although the virus can still spread through feces when chickens peck at each other’s droppings, in the open air, it must, for example, resist dehydration better.1540 The virus must also presumably adapt to the novel body temperature and pH of its new environment.1541

In aquatic birds, the virus is and has been in total evolutionary stasis.1542 But, when thrown into a new environment, it quickly starts accumulating mutations to try to adapt to the new host.1543 The virus must mutate or die.1544 “Unless it mutates,” said one renowned flu researcher, “and unless a new mutant is selected, it’s going to disappear.”1545 Thankfully for the virus, mutating is what influenza does best.1546 And, given enough time and enough hosts within which to mutate, some bird flu viruses can learn how to invade other organs in search of a new mode of travel. Sometimes, they find the lungs.

In ducks, the virus keeps itself in check. The virus relies on a healthy host to fly it from lake to lake. To protect its natural host, the virus has seemed to have evolved a built-in, fail-safe mechanism that allows the virus to replicate only in the intestine, so as not to infect other tissues and potentially hurt the duck. To prevent itself from replicating outside the digestive tract, millions of years of evolution seem to have engendered an activation step.

Before the virus can become infectious, its hemagglutinin spike first has to be cleaved in half to activate it. This cleavage is done by specific host enzymes found only in certain tissues, like the intestinal tract. In its natural state, the influenza virus essentially gets permission from the host before tissue infection. The limited bodily distribution of the specific cleavage enzyme restricts the virus to safe areas like the gut. It would not be able to replicate in the brain or other vital organs that lack the specific cleavage enzyme required for activation. This is a restriction the virus has seemingly imposed upon itself, evolving harmlessness to best pass on and spread its genes.1547 But once it finds itself in unfamiliar species, all bets are off. Researchers have shown that H5N1 seemed to enter chicken populations as an intestinal virus but left as more of a respiratory virus.1548

Landing in foreign territory, not only is it advantageous to find new ways to spread, but the virus also faces a hostile immune response and finds itself fighting for its life. It’s either you or me, it “reasons,” so in certain cases, the virus is able to eliminate the fail-safe mechanism that restricts it to the gut. The hemagglutinin spike of H5 and H7 viruses can mutate over time to be activated by enzymes in any organ in the body, allowing the virus to go on a rampage and essentially liquefy the bird from the inside—the “flubola” phenomenon of highly pathogenic avian influenza.1549

Of course, viruses don’t reason. This is an example of high-speed natural selection. Even in ducks, influenza viruses exist as a swarm of mutants, each subtly different from the others. Since time immemorial, though, the same perfected, harmless mutant has won out over all the others time and time again. Deadly mutants find themselves grounded by the shore in a dying bird never to propagate to other locales. Harmful viruses are dead ducks.

Like other parasites, viruses tend to evolve toward a common agenda over time. Only when backed into a corner in new hostile territory might it be beneficial for the parasite to kill its host. The virus can be forced into what evolutionary biologists call an “acute life strategy” in which its only choice may be to rapidly overwhelm the host to gain a foothold.1550

Syphilis, for example, emerged more than 500 years ago as an acute, severe, debilitating disease, but has evolved into the milder, chronic form. Known in Renaissance Europe as the Great Pox, it had the ability to ulcerate faces off victims like leprosy and form great abscesses of pus. “Boils are exploding in groins like shells,” read one contemporary description, “and purulent jets of clap vie with the fountains in the Piazza Navona.”1551 For a sexually transmitted disease, however, virulence may not be conducive to transmissibility. Overt manifestations—like losing one’s nose—may tip off and turn off potential sexual partners, reducing the selective advantage of aggressive strains of the disease.1552

The best studied example of this phenomenon is the intentional introduction of the rabbitpox virus into Australia. In the 1950s, rabbits were introduced for hunting purposes, but lacking natural predators, they rapidly populated the continent.1553 To kill off the rabbits, scientists introduced a rabbitpox virus isolated from a Brazilian rabbit species to which the virus had co-evolved an aggressive symbiosis.1554 Within a year, the virus had spread a thousand miles in each direction, killing millions of rabbits with a 99.8% mortality rate.1555 To the bane of the farmers (but the benefit of the bunnies), by the second year, the mortality rate was down to 90% and eventually dropped to only 25%, frustrating attempts to eradicate the cotton-tailed menace.1556

The rabbitpox virus was faced with a trade-off. On the level of a single, individual host, it was presumably in the virus’s best interest to attain maximal virulence, replicating and destroying at full bore to overwhelm the rabbit’s immune defenses in hopes of spreading outward to other rabbits. If the immune system got the upper hand first, there was little chance the virus could pass on its genes. This tendency towards maximum virulence, though, was counterbalanced by the need for effective transmission on a population level. By rapidly overcoming the host, the virus may have won the battle but lost the war.1557

If a virus kills the host too quickly, there is less opportunity to spread in both time and space. Just as dead ducks don’t fly, dead rabbits don’t hop. Unless farmers could cram rabbits by the thousands into some kind of bunny barn, viral mutants with diminished lethality may have an overall advantage since the host may stay alive longer and have more occasion to pass on the virus. This is a risky strategy for the virus—if it becomes too weak, the hosts’ defenses may quash it completely. Natural selection mediates this evolutionary process, choosing over time the virus with the perfect balance of lethality and contagion.1558

This doesn’t always mean a transition toward lesser virulence. “If predator-like variants of a pathogen population out-produce and out-transmit benign pathogens,” wrote one evolutionary medicine pioneer, “then peaceful coexistence and long-term stability may be precluded much as it is often precluded in predator-prey systems.”1559 H5N1, in this case, seems the model predator.

The tendency of the influenza virus, finding itself locked in a host as unfamiliar as a chicken, may be to become as virulent as possible to overpower the bird’s defenses.1560