Got a fever, headache, sore throat and all the other lovely symptoms of influenza? You can blame it on the birds. The main reservoir for influenza viruses is wild birds, which can pass those microbes to domestic poultry, which can come into contact, and potentially infect, human beings. That is what has happened with the deadly H5N1 avian flu virus, which has killed at least 306 people during the past seven years, not to mention hundreds of millions of chickens and other birds. International heath authorities have increasingly focused on that viral intersection between birds and humans, reasoning that if H5N1 can be controlled in poultry, it won't be able to threaten people. That's a tall order, though: by one count there are as many as 70 billion chickens around the world, many of them in backyard shacks in the developing world, and the shifty flu virus often evades vaccination.
But what if there were a way to breed poultry that are genetically resistant to H5N1 or any other avian flu virus, thus severing a major link in the flu's evolutionary chain? That's what a team of scientists in Britain tried to do recently, and they were remarkably successful. The result, reported in a study in the Jan. 13 issue of Science, is genetically engineered chickens that, while they're still vulnerable to H5N1, don't seem to pass on the disease to other poultry. That's exciting news for chicken farmers who are trying to protect their flocks from a deadly virus, but it could also open the door to genetically engineering disease resistance into a host of other animals. "Genetic modification could be more effective than vaccination," says Helen Sang, a geneticist at the Roslin Institute at the University of Edinburgh and a co-author of the Science paper. "You wouldn't need to change the way you tackle each disease."
First the scientists had to figure out a gene that could interfere with the replication of the avian flu virus. Lawrence Tiley, a molecular virologist at Cambridge University and the lead author of the paper, indentified a gene that could make birds produce a piece of RNA that acts as a decoy to polymerase, an enzyme that is vital for viral replication. Rather than binding with the virus' genome, polymerase attaches itself to the decoy gene, preventing the virus from being able to replicate itself and spread.
Using Sang's transgenic techniques, the team was able to insert the decoy gene into chick embryos. When the GM chickens were exposed to the avian flu, they were still infected, getting sick and eventually dying, but they didn't pass on that virus to other chickens in close proximity, both transgenic birds and normal ones. Normally, once a few chickens have been infected with H5N1, the virus burns like wildfire through a flock, often with near 100% mortality. But the transgenic chickens effectively acted as firewalls for avian flu, stopping the spread cold. "The transgenic birds that are infected are shedding virus that seems to be defective in some ways," Tiley told Science.
While the ultimate goal would be to engineer poultry that are simply immune to the disease, the decoy target chosen by Tiley and his colleagues is a clever one. Flu viruses have eight gene segments, and polymerase has to bind to each of them during replication. To somehow evade the decoy, the flu virus would need to change parts of all eight gene segments. By comparison, a flu virus can evade a vaccine by changing just one gene, and since the flu mutates frequently, that's not hard to do. (Those genetic shifts in influenza are why we need a new vaccine every flu season.) Engineered correctly, a transgenic could be all but permanently protected from the flu, as would all their offspring, and they're otherwise normal. "You wouldn't be able to pick them out of a pen of chickens," says Sang.
Sang notes that this is just a small proof of principle study. "Commercial success is a long way off," she says. Transgenic chickens would also need to be approved by regulators and accepted by consumers, no guarantee, given the resistance to GM crops in much of the world. But regulators are already beginning to look at some GM animals, including a transgenic salmon that is able to grow faster in fish farms, and a GM pig that produces much less polluting waste. If we can protect ourselves from the next flu pandemic by tweaking our birds, the benefits might be worth the Frankenstein factor.