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2008

Honey Bees Give Clues on Virus Spread
“Dissection” column, Wired.com, 2/22/08

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Everyone likes a medical mystery -- even more so when the mystery in question is solved. When a few people in Queens developed fevers in 1999, scientists pinpointed an American strain of West Nile virus. When people in East Asia began to get particularly wicked coughs in 2003, scientists discovered an entirely new virus called SARS. As much as we admire the ingenuity that went into solving these medical enigmas, that doesn't mean we should ignore the medical-sleuthing stories that haven't yet reached a satisfying ending. Their very mystery actually says something important about how nature works.

Last spring, U.S. beekeepers realized that one-third of their hives had collapsed. Honeybees were simply flying away to die. This strange phenomenon, now called Colony Collapse Disorder, threatens more than the honey industry. Fifteen billion dollars worth of U.S. crops such as almonds and apples simply will not grow if honeybees don't pollinate them.

To find the cause of Colony Collapse Disorder, or CCD, a team of scientists mashed up honeybees from stricken hives as well as normal ones. Using a new method called metagenomics, they searched the honeybee purée for the DNA of parasites. In September, they announced that they found the DNA of a particular virus in 25 of 30 sick colonies. Only 1 out of 21 healthy hives had it.

The virus, known as Israeli acute paralytic virus, was already known to make bees sick. Named for its origin of discovery, it had also been found in a few other countries, but never before in the United States. The scientists observed that one of those other countries was Australia. They suggested that it might be no coincidence that when, in 2004, U.S. beekeepers started importing Australian bees, the earliest reports of declining hives ensued. Perhaps, the scientists suggested, the virus came along too.

Now, as farmers wait anxiously to see if the honeybees will suffer again this spring, the true cause of CCD remains murky. Skeptics have raised many reasons to doubt that Australian viruses are to blame. In Australia, bees that get Israeli acute paralytic virus don't get sick, and the country has had no reports of CCD. And in places where honeybee colonies are collapsing -- Greece, Poland, Spain -- there are no imported Australian bees. These are not the sort of patterns you'd expect, the skeptics say, if Australian viruses were killing American bees.

It even turns out that Israeli acute paralysis virus is not the newcomer it seemed back in September. Yanping Chen and Jay Evans of the USDA's Bee Research Laboratory recently reported discovering the virus in bees collected as far back as 2002 -- two years before Australian honeybees arrived on our shores (.pdf). New research is revealing dozens of strains of the virus circulating among the honeybees of North America. Some are more closely related to the Australian strains, but some are closer to viruses found in Israel. There's no evidence yet that a single deadly strain of the virus recently arrived in the United States and swept across the country, single-handedly causing Colony Collapse Disorder.

In the 19th century, doctors began to solve medical mysteries with a simple experiment. They isolated a pathogen from a sick individual and injected it into a healthy one. If the same disease developed, they knew they had found the cause. It's still the gold standard for pinpointing diseases, but for some diseases it doesn't work well. CCD is one of those diseases. A bee injected in a lab with Israel acute paralytic virus might well die. But it might be overdosed with far more viruses than a bee in the wild might pick up. And if the bee doesn't die, scientists wouldn't rule out the possibility that the virus actually does cause CCD. It might only cause the disease in bees already weakened by pesticides, for example.

It gets worse. Scientists actually have a hard time finding a hive that's not infected with some kind of virus. Bees are not sterile petri dishes, but homes for many organisms including other viruses and bacteria, fungi and even mites. Scientists can't rule out the possibility that a bee must first be infected by some combination of these pathogens before Israeli acute paralytic virus -- or just one strain of it -- can kill it. On the other hand, the virus may just be an opportunistic latecomer that infects bees that are already sick.

All this probably gives beekeepers little comfort. But it reveals an important lesson that metagenomics is teaching us again and again. Whether scientists look inside a honeybee or look at the entire biosphere, nature is proving to be awesomely intricate. In the oceans and the soil, metagenomics is revealing millions of different kinds of microbes, with an almost inconceivable diversity of viruses shuttling between them, carrying genes from host to host. But we have almost no idea how these menageries work together, either in the biosphere or inside a host like a honeybee -- or a human. Many of the microbes that metagenomics is revealing are entirely new to science. As genetic databases fill with DNA sequences from millions of new species, our scientific wisdom lags far behind.

In a sense, metagenomics is taking us back to the early days of medical research ... back to when Louis Pasteur first established the germ theory of disease. He did it by grinding up insects as well -- not honeybees, but silkworms. In 1865, France's giant silk industry was in peril because silkworms were dying. Pasteur discovered that germs were making the silkworms sick, then a radical notion. By spreading the ground-up remains of sick silkworms on mulberry leaves, he could infect healthy silkworms that nibbled the plants. Pasteur drafted new rules to keep silkworm nurseries clean and prevent sick worms from infecting new ones. The silk industry roared back to life.

It was a tremendous discovery -- one of the greatest detective stories in the history of medicine. But it took Pasteur six years to solve the silkworm mystery. And we must not forget just how ignorant Pasteur was at the beginning of his quest. He freely admitted that he knew little about diseases, and even less about animals. When he arrived in the south of France to save the silkworms, a local entomologist handed him a silkworm cocoon. Pasteur held it up to his ear and shook it.

"It makes a sound!" he said with surprise. "Is there something inside?"

Today we are shaking the cocoon of life by our ear once more, wondering what's going on in there.

Copyright 2008 Carl Zimmer
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