Denise Grady & Donald G. Mcneil Jr.
Recent reports that two teams of scientists had genetically altered a deadly flu virus to make it more contagious have provoked fear, even outrage, in some quarters.
Biosecurity advisers to the US government, which helped fund the research, have urged that full details not be published for fear that terrorists could make use of them. The World Health Organization warned on Friday that while such studies were important, they also could have deadly consequences.
Some scientists argue the research should not have been done since the modified virus could slip out of a lab and spark an epidemic. Others contend such experiments are essential to learning what naturally occurring changes in flu viruses are the most dangerous. The results could aid efforts to predict epidemics, they say, and to develop antiviral drugs and vaccines.
There is one point on which the factions agree: the ability of a virus to spread easily from person to person is the key to determining if it can cause a pandemic.
There is much scientists do not know about what makes a virus transmissible — and much they must learn before they are able to prevent another flu pandemic. Contagion depends on a complex interplay between a virus and its victim, including where it enters the body, the types of cells in which it can reproduce and whether it can then escape to reach another human.
The virus that scientists made more contagious was the A(H5N1) avian flu. In its natural form, it is known to have infected only about 600 people since its discovery in 1997, but it killed more than half of them. Humans almost never transmit it to one another. But if that ever were to change, bird flu could become one of history’s worst pandemics.
The work to make the virus more transmissible was done by two separate groups, one at Erasmus Medical Center in Rotterdam, the Netherlands, and the other at the University of Wisconsin. The experiments were performed on ferrets because flu behaves in them almost exactly as it does in humans.
In Rotterdam, a team led by Dr. Ron Fouchier made a strain of bird flu that could drift through the air into nearby cages and infect other ferrets. Although that result has set off worldwide concern, some researchers say the modified virus might not behave the same way in people because ferrets are not a perfect model for human transmission.
The new virus does not seem as contagious as either the 1918 Spanish flu or the 2009 swine flu, Fouchier said. To become airborne, the virus required a range of genetic modifications — “a combination of everything,” he said.
In humans, bird flu lives best in the lower lungs, he said, which makes it harder for it to escape in sneezes and coughs. If it could replicate in the upper airways, it would be more likely to be released as an aerosol and might become more transmissible.
If the virus were shed, or expelled, as individual particles instead of in clumps, Fouchier said, it would be more easily spewed out in the droplets of a cough.
“It also may help if the virus induces coughing or sneezing,” he added.
Modifications to any of these viral traits may help make the bird flu virus more contagious. In fact, it took only a few mutations to make the new virus, he said.
Fouchier declined to describe them in detail. But other scientists said increased transmissibility usually depends on changes in at least two of eight genes: one that helps the virus invade cells, and one that helps it copy itself.
In birds, flu is primarily a gut disease, shed in feces, whereas in people it is primarily a nose, throat and lung disease, shed in saliva and mucus. The main risk factor for catching bird flu is working at a chicken farm or a live bird market. Powdery dry feces can be inhaled; a finger that touches a countertop or water contaminated with wet feces can transfer it into a nostril or an eye.
The rare cases of apparent human-to-human transmissions have usually involved long, close contact, such as a mother caring for a sick daughter. That suggests the child might have coughed up so much virus that droplets drifted deep into the mother’s lungs.
But there have also been some anomalous cases, including a group of diners in Vietnam who apparently were infected by raw duck blood pudding, and the handlers of fighting cocks who were stricken after sucking blood and mucus out of their birds’ beaks.
Experts disagree about just how people can become infected with bird flu.
Ram Sasisekharan, a Massachusetts Institute of Technology researcher on a team that did a 2009 study that made a bird flu more transmissible in ferrets, argued that, at least in theory, humans could get the virus by ingesting it. From there, the virus could travel throughout the body; it could reach the brain and cause fatal encephalitis, for example.
But Dr. Joseph Bresee, chief of epidemiology at the flu division of the Centers for Disease Control and Prevention, argued that the virus must enter humans through the nose, throat or lungs.
In anomalous cases — like the blood pudding and roosters — he said the virus must have made subtle contact with the respiratory tract. He also said it was unlikely that a flu virus could make its way through blood to the lungs or brain. Studies done for blood banks to see if donors with flu could infect recipients show that “it’s really durn hard to ever find flu virus in the blood.”
There is one reassuring note in the unsettling findings from Rotterdam and Wisconsin. Fearsome though it may be, the new virus appears to be vulnerable to existing vaccines and flu drugs.
The New York Times
Denise Grady & Donald G. Mcneil Jr.