Flu That Leapt From Birds to Seals Is Studied for Human Threat

Four times in the past century, a new strain of flu has emerged that can spread quickly in humans. One of those strains, which emerged in 1918, killed an estimated 50 million people.

All human flu strains evolved from flu viruses that live in birds. To understand how these transitions happen, scientists have recently been tinkering with a strain of bird flu to see how many mutations it takes until its spreads from mammal to mammal.

When news of their efforts emerged last fall, a fierce debate broke out about the wisdom of publishing the experiments in full.

Eventually, the scientists got the go-ahead from a federal advisory board, and earlier this year they described how a few mutations of a strain called H5N1 enabled it to spread among ferrets. But the controversy still rages: Responding to worries about an accidental release of an engineered virus, leading flu scientists agreed in January to a moratorium on further research, and experts are debating when it should be lifted.

Scientists may respect moratoriums, but nature does not. Evolution recently carried out an influenza experiment of its own on the coast of New England. Last fall, 162 dead harbor seal pups washed up on the beaches of New Hampshire and Massachusetts.

In a paper published Tuesday in the journal mBio, a team of scientists reports that the pups were killed by a new strain of influenza. Their research indicates that the virus evolved from bird flu, gaining the ability to spread from seal to seal — a real-life example of the transformation that scientists have been exploring in their labs.

“It’s a beautiful study,” said Eddie Holmes, an expert on flu evolution at Penn State who was not involved in the research. He praised the scientists’ speed in identifying the new virus and convincingly tying it to the seal die-off.

Dr. Holmes believes the new virus needs to be carefully monitored to see what sort of threat, if any, it poses. “The question mark is what it means for seals, and what it means for us,” he said.

Waterfowl like ducks and geese carry a wide range of flu strains. These bird flu viruses sometimes infect mammals, but they rarely, if ever, spread from one mammal to the next.

Since 2003, H5N1, the most worrisome subtype of bird flu, has spread across Asia and Africa. But hospitals have recorded only 607 cases of H5N1 infection in humans.

In rare cases, a bird flu virus strain gains the mutations necessary to multiply quickly inside a mammal and spread to others. Flu viruses have adapted to several mammal species, including pigs, dogs and horses.

In September 2011, beachgoers noticed dead seal pups on New Hampshire beaches. “Surfers were surfing into seals floating in the water,” said Katie Pugliares, a senior biologist with the New England Aquarium’s rescue program.

Unlike typical seal cadavers, the seals were not malnourished, suggesting they had died suddenly.

An examination of tissues from the seals pointed to a respiratory infection. To identify the pathogen, tissue samples from five pups were sent to the Center for Infection and Immunity at Columbia University. Simon Anthony, a postdoctoral researcher at the center, led a search for viral genes in the tissue.

Within 24 hours, Dr. Anthony and his colleagues had discovered that all five seals carried an influenza virus. There have been a few documented flu outbreaks in seals, the most recent having hit in 1992. As far as scientists can tell, these outbreaks came directly from birds; the virus could not spread from mammal to mammal.

Within another 24 hours, the researchers had determined that the virus was a strain of the flu never seen in seals. The virus belongs to a flu subtype known as H3N8. H3N8 viruses have crossed over from birds to dogs and horses several times since 1960.

Dr. Anthony and his colleagues found flu genes at high concentrations in the lining of the seals’ airways. From such evidence, the scientists concluded that H3N8, no innocent bystander, had killed the seals.

“Now we have a nice legal case against this virus,” said W. Ian Lipkin, director of the Center for Infection and Immunity and an author of the study.

The scientists then searched for the origin of the seal virus. Its closest relative is a virus isolated in Ohio in 2002 from a species of duck called the blue-winged teal.

They identified 37 mutations that set the seal virus apart from bird flu. A number of the mutations have been previously documented as important for flu viruses to adapt to mammal hosts.

A new strain that can spread among seals is a reason for serious concern, Dr. Anthony said. “What we fear is that it would allow the virus to persist within the seal population,” he said. “And if it persists, who knows what other changes may accumulate over time?”

“If it adapts better to mammal hosts, it may well start to move into humans,” Dr. Lipkin said. “This is clearly a virus for which we need some surveillance.”

Pigs, Dr. Lipkin noted, are especially good at producing new flu strains because they can be infected by bird flu and mammal flu at the same time. Two kinds of virus can combine, giving rise to new hybrid strains.

Dr. Lipkin and his colleagues found evidence that seal cells can also be invaded by both kinds of viruses — raising the possibility that they could produce new hybrid flu strains as well.

“It could be the equivalent of an aquatic pig,” Dr. Lipkin said.

Dr. Holmes wanted to see more evidence for the idea that flu viruses can mix in seals. He also pointed out that H3N8 has never crossed from dogs or horses to people.

“Just because we find a seal with mammal-adapted H3N8 does not mean we’re going to get a human pandemic,” Dr. Holmes said. “At the moment, it’s hard to say what the threat really is.”

Still, Dr. Pugliares will be on the lookout for a new outbreak in September on the beaches of New England. And she and her colleagues will be taking extra precautions with any seals that show signs of the flu.

“We are going to definitely step it up a notch,” she said.