Here's a historical perspective on bird flu and on pandemic influenza.

Some basic facts:

—Type A flu viruses cause pandemic flu. A pandemic is the worldwide spread, in humans, of a flu virus to which most people have no natural immunity. This can happen when an old flu virus reappears after a generations-long absence. It can also happen when a flu virus new to humans acquires the ability to spread easily from person to person.

—Type A flu viruses are subtyped according to proteins on their surfaces. There are 16 different H proteins and nine different N proteins. All H and N proteins occur in birds.

—Human disease has traditionally been caused by three H subtypes — H1, H2, and H3

—Recently, humans have become ill after catching new H subtypes — H5, H7, and H9 — from birds. It's feared that one of these subtypes will emerge as the next flu pandemic — particularly the H5N1 virus causing an unprecedented global epidemic among domestic and wild birds.

—Bird flu viruses come in two varieties, depending on how efficiently they kill birds. Low pathogenicity avian influenza (LPAI) is not as deadly. High pathogenicity avian influenza (HPAI) — apparently limited to the H5 and H7 viruses — kills up to 100 percent of infected birds. The current H5N1 bird flu virus is an HPAI virus.

—In a typical flu season — the seasonal flu, not pandemic flu — there are 30,000 to 50,000 deaths in the U.S. and 20 to 30 times that number of flu deaths worldwide.

Flu Time Line

1580 — First recorded influenza pandemic began in Europe and spread to Asia and Africa.

1700s — Influenza pandemics in 1729-1730, 1732-1733, 1781-1782.

1878 — A disease causing high mortality in poultry becomes known as the "fowl plague." Fowl plague is now called HPAI avian influenza.

1800s — Influenza pandemics in 1830-1831, 1833-1834, and 1889-1890. The last of the three — called the Russian flu — spread through Europe and reached North America in 1890.

1918-1919 — The "Spanish flu" circles the globe (though some experts think it may have started in the U.S.). Caused by an H1N1 flu virus, it is the worst influenza epidemic to date. There are more than half a million U.S. deaths; worldwide death estimates range from 20 million to 100 million. The pandemic comes before the era of antibiotics — which are now essential in treating the secondary bacterial infections that often kill flu-weakened patients — so it's difficult to say whether this flu would have the same dreadful impact in the modern world. But it is a very frightening disease, with very high death rates among young, previously healthy adults.

1924 — The first outbreak of HPAI avian influenza — bird flu — in the U.S. It does not spread among humans.

Flu in the Mid-20th Century

1957-1958 — The "Asian flu" causes the second pandemic of the 20th century. Caused by an H2N2 virus, it begins in China and kills 1 million people worldwide, including 70,000 Americans.

1968-1969 — The "Hong Kong" flu causes the last flu pandemic. It was caused by an H3N2 virus and killed some 34,000 Americans. The relatively low death toll is thought to have been due to two factors. First, the virus contained the N2 protein humans had been exposed to before. Second, an H3 virus circulated around the turn of the century, giving some immune protection to elderly people who'd caught the flu back then.

Mid-1970s — Researchers realize that enormous pools of influenza virus continuously circulate in wild birds.

1976 — Swine flu breaks out among a handful of soldiers stationed at Fort Dix, N.J. One dies. It's an H1N1 virus, and health officials worry that they are seeing the return of the 1918 H1N1 Spanish flu pandemic.

As the virus is circulating among U.S. pigs, President Gerald Ford calls for a crash vaccination program. Despite delays, a vaccine is made and a quarter of the U.S. population is inoculated. There were 25 deaths from a rare paralytic complication of the vaccination (Guillain-Barre syndrome). Nobody else died of swine flu, which never caused an epidemic.

1983 — The second HPAI outbreak in the U.S. Caused by an H5N2 virus, it does not spread among humans. However, this severe poultry epidemic strikes chickens, turkeys, and guinea fowl in Pennsylvania and Virginia. It is finally brought under control after the destruction of 17 million birds.

1996 — HPAI H5N1 bird flu is isolated from a farmed goose in Guangdong, China.

May 1997 — The first person known to catch H5N1 bird flu dies in Hong Kong. The virus has been causing an epidemic among poultry in the city.

November-December 1997 — There are 18 new human cases of H5N1 bird flu in Hong Kong, 12 with direct contact with infected poultry. Six people die. Officials destroy 1.4 million chickens and ducks.

Recent Flu Events

April 2003 — The Netherlands reports H7N7 bird flu in over 80 human cases with the death of one veterinarian.

Mid-2003 — H5N1 bird flu spreads in Asia, but it is either undetected or unreported.

December 2003 — Tigers and leopards in a Thailand zoo die of H5N1 bird flu after eating fresh chickens. It's the first time bird flu has been seen in large felines.

Jan. 11, 2004 — Humans in Vietnam come down with H5N1 bird flu caught from poultry. There is a high death rate among infected people, but the disease does not spread from person to person.

Jan. 23, 2004 — Thailand reports human H5N1 bird flu infections.

February 2004 — The last HPAI outbreak among U.S. poultry. A flock of chickens in Texas comes down with an H5N2 virus. A quick response by state and federal officials keeps the virus from spreading beyond this one small flock. There are no human cases.

Feb. 1, 2004 — Vietnam investigates a family cluster of H5N1 cases. Person-to-person spread cannot be ruled out, but the virus is not spreading among humans.

Feb. 20, 2004 — Thailand reports H5N1 infection of domestic cats in a single household.

Oct. 11, 2004 — H5N1 infection spreads among tigers in a Thai zoo.

Feb. 2, 2005 — Cambodia reports its first human case of H5N1 bird flu. It is fatal.

April 30, 2005 — China reports that wild birds are dying at a lake in central China. The lake is a major stop along migratory pathways. Within weeks, more than 6,300 wild birds are dead.

July 21, 2005 — Indonesia reports its first human case of H5N1 bird flu.

October 2005 — H5N1 is reported in poultry in Turkey and Romania and in wild birds in Greece and Croatia.

Nov. 1, 2005 — The WHO's official count of human cases of H5N1 reaches 122, with 62 deaths, in Vietnam, Thailand, Indonesia, and Cambodia.

By Daniel J. DeNoon, reviewed By Louise Chang, MD

SOURCES: Infectious Diseases Society of America. World Health Organization.Nature web site. European Society for Veterinary Virology web site. Indiana State Department of Health web site. U.S. Health and Human Services web site. CDC web site.