In recent years, much attention has been given to concerns over the possible spread of deadly new varieties of “bird flu” from avian populations to human ones. The truth is that, for practical purposes, all flu is bird flu. More specifically, duck flu. Ducks and other waterfowl are now considered to be the essential biological reservoir for influenza viruses, including all strains of influenza A. If there were no ducks, there would be no flu. No seasonal flu, wreaking its quiet toll on aged and immunocompromised humans; no explosive global flu pandemics, carrying off innocent millions.
It is senseless to hold this against the ducks, tempting as that is. Human flu doesn’t come directly from them anyway. When ducks pick up the flu bug, they exchange it amongst themselves, and distribute different strains across continents, but they remain asymptomatic. The various strains of influenza have “learned,” by natural selection, to live peaceably within their migrating host. It’s when the virus passes from the duck to other animals not innately immune to flu—notably pigs, chickens and turkeys—that it undergoes gene reassortment and begins evolving more quickly under high-selection pressures from immune systems. That’s where the danger begins, according to current virological dogma.
The key figure in working all of this out, the discoverer of the “duck reservoir,” is the celebrated New Zealand-born virologist Robert Webster. Holder of a chair at St. Jude’s Children’s Research Hospital in Memphis, Tenn., Webster has been called “the godfather of influenza research.” Some of his most important work was done on lakes and ponds around Edmonton, with assistance from the Canadian Wildlife Service. Webster recalls making annual visits, beginning in 1976, for longitudinal data-gathering that established the ubiquity of influenza in young-duck habitats. “For the first year, [CWS staff] were very skeptical of this silly guy sticking swabs up the back end or down the throats of ducks,” he says, “but they sort of tolerated me.”
Visiting proteges of Webster are still continuing his work in northern Alberta. And by an uncanny geographical coincidence, two researchers at the nearby University of Alberta, biology professor Katharine Magor and Ph.D. student Megan Barber, have now added an important piece to Webster’s picture of the life cycle of influenza. Although the “duck reservoir” hypothesis is mostly taken for granted now, nobody knew precisely why chickens get sick from influenza and ducks don’t. In a preprint paper released online on March 22 by the Proceedings of the National Academy of Sciences, Magor and Barber produce evidence for a new hypothesis.
It turns out that ducks possess a genetic influenza “sensor” called RIG-I that chickens must have lost somewhere in their evolutionary history, probably before their domestication in Asia more than 10,000 years ago. Demonstrating this—with the help of Webster and St. Jude’s colleague Jerry Aldridge Jr., who are co-authors on the paper—involved Sherlockian subtlety. Specific genes for RIG-I had to be identified in living ducks, and analogues sought in chickens by means of genetic “probes”—bits of DNA with telltale radioactivity added. To expose ducks to highly pathogenic strains of H5N1 flu not stored in any Canadian facility, Magor and Barber had to retrace Webster’s historic steps in reverse, leaving Alberta to go annoy unwitting Anatidae at his St. Jude’s laboratory.
Having established that chickens have no RIG-I, the Alberta duo went on to show that the RIG-I sensor can be spliced into the genes of chicken cells and that it fights flu there, in vitro. The natural next step would be the creation—for research, and perhaps even commerce—of a flu-resistant transgenic chicken. Magor and Barber have applied for a patent on the means of creating one. “We believe we could do it,” says Magor. “It would be such a cool experiment.”
But the pair is not about to go mad-scientist and start creating a super-chicken army anytime soon. Making chickens flu-proof like ducks might limit the pervasiveness of flu in human populations by cutting off a major avenue for transmission—but it also might achieve nothing beyond turning the “duck reservoir” into a supersized “duck-and-chicken reservoir.” Practical applications for this new knowledge must await a better understanding of the still-emerging, still-confusing details of influenza’s natural history.