Flu to be the “Rodney Dangerfield of diseases,” as Tim Uyeki puts it. Uyeki is a flu epidemiologist at the Centers for Disease Control and Prevention (CDC) in Atlanta, and he's been concerned that for years people didn't give influenza the respect it deserved. But now flu has all the attention any germ can get. First, there was a flu vaccine shortage over the winter, prompting long lines and provoking rage from people who couldn't get their shots. Later, bird flu mesmerized the world, with the CDC and the World Health Organization (WHO) keeping up a steady drumbeat: A flu pandemic―overdue for decades―would be upon us at any moment. Finally, it was announced that a pandemic flu strain had been accidentally sent to influenza labs around the world as part of a testing kit by Meridian Bioscience, a contractor for the College of American Pathologists. The jittery WHO, poised for catastrophe, insisted on the immediate destruction of the strain, for fear of accidental release. And while the threat posed by Meridian's error is far less than initial reports suggested, the reality is that lab accidents do happen. What's more, the feverish anxiety of public health officials to head off a new influenza pandemic may be generating the greatest influenza threat we face. The threat is man-made. Scientists in the United States and Great Britain are studying the deadliest flu epidemic of the last century, the 1918 pandemic. In order to learn what made it kill so many, they are working on producing artificial viruses that replace common human flu genes with 1918 genes. An accidental release of one of their constructs could make the Meridian error look as menacing as a cauliflower.   The flu strain sent out by Meridian is known as H2N2/Japan. H2N2 strains first appeared in 1957, causing a world-wide pandemic. But H2N2/Japan is what virologists call a “reference reagent,” regularly used in laboratory tests. It's already in the freezers of every serious flu researcher, says virologist Earl Brown of the University of Ottawa. Furthermore, calling the H2N2/Japan strain a “killer” ― as news reports across the globe have done ― makes little sense. It is no deadlier than any other new strain, and may actually be less so. According to microbiologist and pathologist Jared N. Schwartz, of the College of American Pathologists, H2N2/Japan has been through lab processes that typically weaken the virus. No one has contracted H2N2/ Japan from these lab kits. This is not surprising. As flu researcher Adolfo Garcia Sastre of the Mount Sinai School of Medicine in New York puts it, you'd have to aerosolize the virus in some way in order to catch it―not something that is likely to be done with a reference strain. Following the pandemic of 1957, which killed perhaps a million people, most of them elderly, H2N2 became the dominant human flu virus for 11 years. In 1968, a new strain, called H3N2, caused a new pandemic, and H2N2 mysteriously vanished. People born after 1968 may have partial immunity because of the N2 component of the virus, common also to the currently circulating H3N2 strain. Still, no one born after 1968 has full immunity, so WHO flu experts are concerned that a lab accident could cause another pandemic. But H2N2, like most flu strains, is disproportionately deadly to the elderly― precisely the group most likely to have some immunity. The WHO's frenzied demands that laboratories destroy this strain seem like an overreaction. Apparently, WHO wants to show a nervous world that it is taking action. But this mania to do something―anything―to stave off a pandemic has been building for years and led to the imprudent decision to re-create the dangerous 1918 strain.         The 1918 flu evolved its lethality on World War I's Western Front. This was no accident. According to Carol Byerly, a historian of military medicine and author of a new book, “Fever of War: The Influenza Epidemic in the U.S. Army During World War I,” the 1918 flu built up its unique virulence in the trenches and the hospitals, the trains and trucks of the front, where the deathly ill lay beside the uninfected, allowing lethal strains to be easily passed on. Tissue samples that prescient World War I Army physicians stored away, combined with flu RNA taken from the partially frozen corpse of an Inuit woman in Brevig Mission, Alaska, have yielded enough genetic information to allow the sequencing of all eight genes in the 1918 influenza virus genome. Molecular pathologist Jeffery Taubenberger and his colleagues from the Armed Forces Institute of Pathology have brought these lost genes from 1918 back from the dead; they've sequenced five of the genes, and are close to completing the last three as well.