Science Stays Alert, Part I: Birds Under Scrutiny

There's about one bird per square foot in the chicken house at Double Trouble farm in Rhodesdale, Maryland; about 40,000 birds in all. A veterinarian clad in white plastic coveralls, booties, gloves, an elastic cap, and a surgical mask wades through the crowd and plucks a test subject. During the visit he'll swab the throats of 11 representative birds to test for the highly pathogenic avian influenza called H5N1. It's customary to check every commercial flock about to head to market in the United States. If flu is found in one bird, the entire house would be killed on the spot.

A chicken house at Double Trouble Farm. © Jason Lelchuk for AMNH

A chicken house at Double Trouble Farm.

© Jason Lelchuk for AMNH

H5N1 is a virus that primarily affects birds, but like other influenzas, it can also transmit between species. The biosecurity clothes mainly help prevent Don Ritter, the poultry veterinarian, from spreading viruses from one house to the next. But they protect him, too.

As of April 2007, testing U.S. poultry for avian flu has yielded nothing out of the ordinary. "Highly pathogenic H5N1 virus has never been found in North or South America, and I mean never been found in a duck, in a chicken, in a goose, in a turkey," says Ritter. Called H5N1 for its combination of surface proteins, this flu subtype has managed to hop from birds to humans in limited instances. As of April 11, 2007, the World Health Organization has confirmed 291 human cases of H5N1 in 12 different countries. When influenza transmits from one species to a different species that has no immunity to it, the new host can be blindsided. More than half of the 291 human victims of H5N1 have died—an extraordinarily high rate—succumbing to rapid fever, difficult breathing, bleeding of the lungs, and other dreadful symptoms.

Humans and animals live in close quarters on this ever more-crowded Earth. In many places around the world, commercial farms like Double Trouble are so large that one outbreak can rapidly infect tens of thousands of animals. The ease with which people move about the planet also makes it easy for viruses to transmit, mingle, adapt, and evolve. "I think that some aspects of modern society have made us at greater risk for these novel viruses," says influenza researcher Jeffery Taubenberger of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

In a handful of cases, humans have contracted H5N1 from birds and then passed the virus to other humans. But in general, H5N1 is not yet spreading efficiently between people. Doctors and scientists like Ritter and Taubenberger are taking great pains to prepare for the possibility of such a pandemic.

Shuffling a Genetic Deck

In late 1997, doctors first discovered H5N1 in 18 Hong Kong residents, its first human victims. The virus, it turns out, was rampant in local, crowded, multispecies poultry markets. About 1.5 million birds were killed to try to control the disease, but variants of the virus remained in chicken farms in southern China. Within two years, they evolved into a new strain of H5N1 through two methods: antigenic drift and reassortment.

If influenza's 14,000 nucleotides are individual cards in the deck of its RNA, then antigenic drift and reassortment are the mechanisms whereby the suits and sequence of the cards change over time. In antigenic drift, individual nucleotides change randomly due to errors when the virus replicates, so new mutations appear. In reassortment, the virus exchanges nucleotides with another virus present in the same animal or human host.

The "H" in H5N1 stands for a surface protein called hemagglutinin, and the "N" stands for another, neuraminidase. Scientists have tallied 16 types of H's and nine types of N's, which can mix and match to make a range of subtypes. The influenza subtypes that generally infect humans are H1's, H2's, and H3's. The rest are largely seen in animals. But scientists have their eye on H5 and H7, as these seem the most likely subtypes to adapt to humans. They may do this by acquiring additional mutations through antigenic drift or by reassorting with H1, H2, or H3 subtypes that already have human-adapted nucleotide sequences. "Only if the virus actually acquires the ability to spread efficiently from one person to another can you maintain a chain of infection," says Taubenberger.

Wild Origins...Wild Future?

Scientists believe the original source of H5N1 was wild aquatic birds. Wild birds still carry the virus, and they are very mobile. In early 2006, an unusually cold weather front in eastern Europe forced infected wild swans to divert their migrations from eastern to western Europe. There, they mingled with backyard chicken flocks and passed along the virus to new avian—and human—hosts.

In the United States, species like mallards, Canada geese, and blue geese fly north in summer, mingling in northern Canada with birds from Asia. In April 2006, the U.S. Departments of Agriculture and Interior launched a major effort to test wild birds in all 50 states for H5N1. Technicians capture and test sample birds migrating south, hoping to intercept the virus before the wild birds further associate with domestic ones. As of April 2007, the program has tested nearly 116,000 live and dead wild birds from the millions that migrate to and from all 50 states. Not one had highly pathogenic H5N1.

"We'll never be free of infectious diseases," says Andrea Morgan, an administrator at the Agriculture Department's Animal and Plant Health Inspection Service. "Though as time marches on, we're getting more sophisticated in our ability to detect them, respond to them, and manage them to secure ourselves from the potential of devastating pandemics."

For more about how researchers are preparing for possible pandemic by analyzing historical events and developing vaccines, see "Science Stays Alert: Past Pandemics and Future Vaccines."