The Great Influenza (17 page)

One way to conceptualize antigen drift is to think of a football player wearing a uniform with white pants, a green shirt, and a white helmet with a green
V
emblazoned on it. The immune system can recognize this uniform instantly and attack it. If the uniform changes slightly (if, for example, a green stripe is added to the white pants while everything else remains the same) the immune system will continue to recognize the virus with little difficulty. But if the uniform goes from green shirt and white pants to white shirt with green pants, the immune system may not recognize the virus so easily.

Antigen drift can create epidemics. One study found nineteen discrete, identifiable epidemics in the United States in a thirty-three-year period - more than one every other year. Each one caused between ten thousand and forty thousand 'excess deaths' in the United States alone (an excess over and above the death toll usually caused by the disease). As a result influenza kills more people in the United States than any other infectious disease, including AIDS.

Public health experts monitor this drift and each year adjust the flu vaccine to try to keep pace. But they will never be able to match up perfectly, because even if they predict the direction of mutation, the fact that influenza viruses exist as mutating swarms means some will always be different enough to evade both the vaccine and the immune system.

But as serious as antigen drift can be, as lethal an influenza as that phenomenon can create, it does not cause great pandemics. It does not create firestorms of influenza that spread worldwide such as those in 1889-90, in 1918-19, in 1957, and in 1968.

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Pandemics generally develop only when a radical change in the hemagglutinin, or the neuraminidase, or both, occurs. When an entirely new gene coding for one or both replaces the old one, the shape of the new antigen bears little resemblance to the old one.

This is called 'antigen shift.'

To use the football-uniform analogy again, antigen shift is the equivalent of the virus changing from a green shirt and white pants to an orange shirt and black pants.

When antigen shift occurs, the immune system cannot recognize the antigen at all. Few people in the world will have antibodies that can protect them against this new virus, so the virus can spread through a population at an explosive rate.

Hemagglutinin occurs in fifteen known basic shapes, neuraminidase in nine, and they occur in different combinations with subtypes. Virologists use these antigens to identify what particular virus they are discussing or investigating. 'H1N1,' for example, is the name given the 1918 virus, currently found in swine. An 'H3N2' virus is circulating among people today.

Antigen shift occurs when a virus that normally infects birds attacks humans directly or indirectly. In Hong Kong in 1997 an influenza virus identified as 'H5N1' spread directly from chickens to people, infecting eighteen and killing six.

Birds and humans have different sialic-acid receptors, so a virus that binds to a bird's sialic-acid receptor will not normally bind to (and thus infect) a human cell. In Hong Kong what most likely happened was that the eighteen people who got sick were subjected to massive exposure to the virus. The swarm of these viruses, the quasi species, likely contained a mutation that could bind to human receptors, and the massive exposure allowed that mutation to gain a foothold in the victims. Yet the virus did not adapt itself to humans; all those who got sick were infected directly from chickens.

But the virus can adapt to man. It can do so directly, with an entire animal virus jumping to humans and adapting with a simple mutation. It can also happen indirectly. For one final and unusual attribute of the influenza virus makes it particularly adept at moving from species to species.

The influenza virus not only mutates rapidly, but it also has a 'segmented' genome. This means that its genes do not lie along a continuous strand of its nucleic acid, as do genes in most organisms, including most other viruses. Instead, influenza genes are carried in unconnected strands of RNA. Therefore, if two different influenza viruses infect the same cell, 'reassortment' of their genes becomes very possible.

Reassortment mixes some of the segments of the genes of one virus with some from the other. It is like shuffling two different decks of cards together, then making up a new deck with cards from each one. This creates an entirely new hybrid virus, which increases the chances of a virus jumping from one species to another.

If the Hong Kong chicken influenza had infected someone who was simultaneously infected with a human influenza virus, the two viruses might easily have reassorted their genes. They might have formed a new virus that could pass easily from person to person. And the lethal virus might have adapted to humans.

The virus may also adapt indirectly, through an intermediary. Some virologists theorize that pigs provide a perfect 'mixing bowl,' because the sialic-acid receptors on their cells can bind to both bird and human viruses. Whenever an avian virus infects swine at the same time that a human virus does, reassortment of the two viruses can occur. And an entirely new virus can emerge that can infect man. In 1918 veterinarians noted outbreaks of influenza in pigs and other mammals, and pigs today still get influenza from a direct descendant of the 1918 virus. But it is not clear whether pigs caught the disease from man or man caught it from pigs.

And Dr. Peter Palese at Mount Sinai Medical Center in New York, one of the world's leading experts on influenza viruses, considers the mixing-bowl theory unnecessary to explain antigen shift: 'It's equally likely that co-infection of avian and human virus in a human in one cell in the lung [gives] rise to the virus' . There's no reason why mixing couldn't occur in the lung, whether in pig or man. It's not absolute that there are no sialic acid receptors of those types in other species. It's not absolute that the avian receptor is really that different from the human, and, with one single amino acid change, the virus can go much better in another host.'
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Antigen shift, this radical departure from existing antigens, led to major pandemics long before modern transportation allowed rapid movement of people. There is mixed opinion as to whether several pandemics in the fifteenth and sixteenth centuries were influenza although most medical historians believe that they were, largely because of the speed of their movement and the number of people who fell ill. In 1510 a pandemic of pulmonary disease came from Africa and 'attacked at once and raged all over Europe not missing a family and scarce a person.' In 1580 another pandemic started in Asia, then spread to Africa, Europe, and America. It was so fierce 'that in the space of six weeks it afflicted almost all the nations of Europe, of whom hardly the twentieth person was free of the disease,' and some Spanish cities were 'nearly entirely depopulated by the disease.'

There is no dispute, though, that other pandemics in the past were influenza. In 1688, the year of the Glorious Revolution, influenza struck England, Ireland, and Virginia. In these places 'the people dyed' as in a plague.' Five years later, influenza spread again across Europe: 'all conditions of persons were attacked' . [T]hose who were very strong and hardy were taken in the same manner as the weak and spoiled,' the youngest as well as the oldest.' In January 1699 in Massachusetts, Cotton Mather wrote, 'The sickness extended to allmost all families. Few or none escaped, and many dyed especially in Boston, and some dyed in a strange or unusual manner, in some families all weer sick together, in some towns allmost all weer sick so that it was a time of disease.'

At least three and possibly six pandemics struck Europe in the eighteenth century, and at least four struck in the nineteenth century. In 1847 and 1848 in London, more people died from influenza than died of cholera during the great cholera epidemic of 1832. And in 1889 and 1890, a great and violent worldwide pandemic (although nothing that even approached 1918 in violence) struck again. In the twentieth century, three pandemics struck. Each was caused by an antigen shift, by radical changes in either the hemagglutinin or the neuraminidase antigens, or both, or by changes in some other gene or genes.

Influenza pandemics generally infect from 15 to 40 percent of a population; any influenza virus infecting that many people and killing a significant percentage would be beyond a nightmare. In recent years public health authorities have at least twice identified a new virus infecting humans but successfully prevented it from adapting to man. To prevent the 1997 Hong Kong virus, which killed six of eighteen people infected, from adapting to people, public health authorities had every single chicken then in Hong Kong, 1.2 million of them, slaughtered. (The action did not wipe out this H5N1 virus. It survives in chickens and in 2003 it infected two more people, killing one. A vaccine for this particular virus has been developed, although it has not been stockpiled.)

An even greater slaughter of animals occurred in the spring of 2003 when a new H7N7 virus appeared in poultry farms in the Netherlands, Belgium, and Germany. This virus infected eighty-three people and killed one, and it also infected pigs. So public health authorities killed nearly thirty million poultry and some swine.

This costly and dreadful slaughter was done to prevent what happened in 1918. It was done to stop either of these influenza viruses from adapting to, and killing, man.

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One more thing makes influenza unusual. When a new influenza virus emerges, it is highly competitive, even cannibalistic. It usually drives older types into extinction. This happens because infection stimulates the body's immune system to generate all its defenses against all influenza viruses to which the body has ever been exposed. When older viruses attempt to infect someone, they cannot gain a foothold. They cease replicating. They die out. So, unlike practically every other known virus, only one type (one swarm or quasi species) of influenza virus dominates at any given time. This itself helps prepare the way for a new pandemic, since the more time passes the fewer people's immune systems will recognize other antigens.

Not all pandemics are lethal. Antigen shift guarantees that the new virus will infect huge numbers of people, but it does not guarantee that it will kill large numbers. The twentieth century saw three pandemics.

The most recent new virus attacked in 1968, when the H3N2 'Hong Kong flu' spread worldwide with high morbidity but very low mortality - that is, it made many sick, but killed few. The 'Asian flu,' an H2N2 virus, came in 1957; while nothing like 1918, this was still a violent pandemic. Then of course there was the H1N1 virus of 1918, the virus that created its own killing fields.

Part III

THE TINDERBOX

CHAPTER NINE

I
N THE SPRING OF
1918 death was no stranger to the world. Indeed, by then the bodies of more than five million soldiers had already been fed into what was called 'the sausage factory' by generals whose stupidity was matched only by their brutality.

German generals, for example, had decided to bleed France into submission by matching it death for death at Verdun, believing that Germany's greater population would leave it victorious. The French later replied with their own massive offensive, believing that their
élan vital
would triumph.

Only slaughter triumphed. Finally one French regiment refused orders to make a suicidal charge. The mutiny spread to fifty-four divisions, stopped only by mass arrests, the conviction of twenty-three thousand men for mutiny, with four hundred sentenced to death and fifty-five actually executed.

Yet nothing expressed the brutality of this war as did a sanitation report on the planned eradication of rats in the trenches to prevent the spread of disease. A major noted, 'Certain unexpected problems are involved in the rat problem' . The rat serves one useful function - he consumes the corpses on No Man's Land, a job which the rat alone is willing to undertake. For this reason it has been found desirable to control rather than eliminate the rat population.'

All of Europe was weary of the war. Only in the United States Anglophiles and Francophiles, most of them concentrated on the East Coast and many of them holding positions of power or influence, were not weary. Only in the United States Anglophiles and Francophiles still regarded war as glorious. And they put intense pressure on President Woodrow Wilson to enter the war.

The war had begun in 1914. Wilson had withstood this pressure. A German submarine had sunk the
Lusitania
in 1915 and he had not gone to war despite outrage in the press, instead winning a German commitment to limit submarine warfare. He had resisted other justifications for war. He could fairly campaign for reelection in 1916 on the slogan 'He Kept Us Out of War.' And he warned, 'If you elect my opponent, you elect a war.'

On election night he went to bed believing he had lost, but woke up reelected by one of the narrowest margins in history.

Then Germany took a great gamble. On January 31, 1917, giving only twenty-four hours' notice, it announced unrestricted submarine warfare against neutral and merchant vessels. It believed that it could starve Britain and France into submission before the United States (if the United States did at last declare war) could help. The action utterly outraged the nation.

Still Wilson did not go to war.

Then came the Zimmermann note: captured documents revealed that the German foreign minister had proposed to Mexico that it join Germany in war against the United States and reconquer parts of New Mexico, Texas, and Arizona.

Wilson's critics sputtered in fury at his pusillanimity. In a famous essay, pacifist and socialist Randolph Bourne, who later died in the influenza epidemic, lamented, 'The war sentiment, begun so gradually but so perseveringly by the preparedness advocates who come from the ranks of big business, caught hold of one after another of the intellectual groups. With the aid of [Theodore] Roosevelt, the murmurs became a monotonous chant, and finally a chorus so mighty that to be out of it was at first to be disreputable and finally almost obscene. And slowly a strident rant was worked up against Germany.'