A fowl clue to flu

Much anguish has been expended lately about the next plague that is scheduled to sweep our species - will it be Ebola or something utterly new that emerges from the remaining fragments of rainforest?

Pete Davies's important and fascinating book lays out the reasons for expecting that the next great pandemic will be nothing so exotic. It is, on the basis of recent history, far more likely to be a new and devastating form of influenza.

He begins his story with the frightening 1997 outbreak of bird influenza that took place in Hong Kong (and presumably in southern China as well).

Eighteen people came down with a new kind of virus, all apparently through contact with chickens or other fowl, and six died. The mounting number of cases triggered a surprisingly firm response from the Hong Kong government. Almost two million chickens and other birds were slaughtered. Perhaps more important,the filthy and festering poultry markets of the city were cleaned up after more than a century of neglect.

It is unclear whether these draconian measures stopped the outbreak, or whether it was halted because the new virus is apparently unable to spread from one human to another. Either way, the fact that this new virus could be identified so quickly using new molecular methods gave the scientists on the front lines unparalleled power to pick up its traces in each patient.

Influenza is a disease that is not confined to humans. Interchanges of virus between pigs and humans, or between birds and domestic animals, are common.

The virus contains eight pieces of DNA that can mix and match between different viral strains. This ability to recombine, coupled with a high mutation rate, makes the virus a resourceful and rapidly evolving foe.

Changes in the virus can normally be tracked with sufficient accuracy that the most likely outbreak of each winter season can be anticipated the previous autumn. But any unanticipated genetic recombination, taking place in some poultry farm in southern China, can throw a wild card into the viral mix.

This seems to be what happened in Hong Kong, which was the first time that virus genes had been able to make the leap directly from birds to humans. Can they do so again, and will the next event lead to another great influenza pandemic?

Davies explores the various possibilities with mixture of vivid on-the-scene reporting and accurate accounts of the scientists' efforts that do not simplify the science.

In this century there has not been an influenza outbreak to match the great "Spanish" flu of 1918. It swept around the world and killed 40 million people, many of them vigorous adults in the prime of life.

Surprisingly little has been written about it - in part, Davies thinks, because the horrors of the Great War dominated contemporary reporting to the exclusion of everything else. He resurrects many tales of bravery and terror from that time.

One way or another, the outbreak affected everybody. It was with a frisson of astonishment that I read of the deaths of Edna, Albert and William Wills, inhabitants of Toronto and possibly relations of mine.

Perhaps my father was born in Toronto and taken to England before the outbreak of the war, leaving a number of since-deceased Wills relatives behind. If there were any connections between me and the tragic branch of the Wills clan that Davies has resurrected, they have unfortunately now frayed into invisibility. But, coincidence or not, the unexpected appearance of my unusual family name brought home to me the universality of this plague.

To understand the 1918 outbreak, Davies traces not just the history of the outbreak itself but also the recent attempts to resurrect the virus that caused the damage. Preserved specimens at the US Armed Forces Institute of Pathology (Afip), and bodies dug up in Alaska by the remarkable Swedish sleuth Johan Hultin, provided bits of the fragile RNA that coded the genetic information of the virus. These bits were rescued by Jeffery Taubenberger of Afip, using the magic of the polymerase chain reaction. He has recovered one important gene from the virus in its entirety, and others are on the way.

Even if the entire sequence is resurrected, the reason that the virus was so deadly will almost certainly continue to elude us. The virus has moved on, and so have we. But the gene that Taubenberger has rescued has haunting similarities to the same gene in the bird virus, perhaps helping to bring the story full circle to present day Hong Kong.

Davies brings us up to date on the scientific story with commendable thoroughness. Drugs are on the way that are likely to help. And a chain of laboratories is being established in southern China that can give earlier warning of an outbreak. The next time a flu pandemic breaks out, we will not be pushovers.

It is, of course, the reviewer's job to find some things to fault in a book. In this instance, far too much time is spent here on failed attempts to find the virus in frozen bodies in northern Norway - the bodies were buried above the permafrost and are now nothing but bones.

Also, the notes at the end of the book are cursory and of little use. More thorough documentation would have been helpful to the reader who would like to follow the story further and perhaps would have enabled me to track down Edna, Albert and William Wills!

Christopher Wills is professor of biology, University of California, San Diego.