One of the most controversial genetically altered microbes ever created was unveiled Wednesday — complete with instructions on how to engineer the hybrid flu virus in the lab.
The details, published in the journal Nature, have been under wraps for months because of fears they might be misused by bioterrorists.
The virus was created by a team led by Yoshihiro Kawaoka at the University of Wisconsin-Madison. The microbe and a second, even more contentious one engineered by Dutch researchers have triggered intense international debate about the creation of “doomsday” viruses in the lab.
“There is a lot of anxiety in the air,” said flu expert Earl Brown of the University of Ottawa, who is relieved freedom of scientific information has won out.
Brown said it was almost anti-climatic to finally see the details, but Kawaoka’s team does deliver “lots of flash and dash.”
Wednesday’s highly technical report describes how Kawaoka and his Japanese colleagues engineered a hybrid flu that indicates H5N1, the much-feared avian flu virus, has the potential to spread in mammals and cause a human pandemic.
Working in a secure lab, the researchers took a gene from H5N1 and gave it to H1N1, the flu virus that caused the human pandemic in 2009. The researchers then played with the hybrid in the lab to create four mutations that are contagious in ferrets, which are considered good proxies for humans.
The researchers “demonstrate that H5N1 viruses do have the potential to cause a human pandemic,” says a report accompanying the study in Nature.
While the virus is a “laboratory creation,” the Nature report says it might one day emerge naturally. The viruses used to make the hybrid are already in circulation and are known to readily mutate and swap genes.
A flu virus makes a genetic mutation every time it replicates, said Brown, who studies and manipulates the virulence of flu viruses in mice.
“When you have a little drip of mucus on the end of your nose when you’ve got the flu, you’ve got more than a million viruses in there,” he said. That’s more than enough to create the same four mutations used in the experiment.
What the experiment “hammers home” is that the right combination of mutations can create an avian virus that will transmit in animals and, presumably, in humans, said Brown.
The H5N1 now circulating is not contagious between people and does not often infect humans. But the virus is deadly. It has killed about half the people it’s infected, a much higher mortality rate than the Spanish flu that killed millions of people in the pandemic of 1918-1919.
If the H5N1 virus were to become contagious between people, the fear is it could unleash a deadly pandemic.
The U.S. National Institutes of Health funded the Wisconsin work and related experiments at Erasmus University Medical Center in the Netherlands. That group, expected to publish its work soon in the journal Science, reportedly has made the H5N1 virus contagious in ferrets — and presumably in humans — by adding five mutations.
Ron Fouchier, head of the Dutch team, kicked up an international furor last fall when he described his team’s creation as “probably one of the most dangerous viruses you can make.”
The U.S. National Science Advisory Board for Biosecurity stepped in and recommended in December that publication of the reports on the flu experiments be suppressed until certain details were withheld. The board and other observers were concerned terrorists would misuse the information to create bioweapons, or that the viruses would accidentally escape from a laboratory.
The World Health Organization disagreed and in February said the experiments should be published in full because the research could help lead to better anti-flu drugs and vaccines and better flu surveillance.
The U.S. biosecurity panel reconsidered and reversed itself in late March, saying the scientific reports “did not appear to provide information that would immediately enable misuse of the research in ways that would endanger public health or national security.” The reversal cleared the way for the publication of the reports.
The U.S. government also has released a new policy to review the potential risks of studies involving 15 “high consequence” pathogens and toxins, including H5N1. The WHO is working also on new biosafety guidelines.
Brown said an experienced virologist could take the information in the Nature paper, order up the necessary genes from a scientific supplier, and engineer hybrid flu viruses resembling the ones in the Wisconsin experiment.
“If you put your mind to it you could do it, but you would have to be good,” said Brown. But he added he doubts the virus would be much of a threat since the Wisconsin team found its hybrid virus, though scientifically intriguing, was not lethal when it was transmitted between ferrets.
“It is not probably not a bioterror agent,” said Brown.
In response to the controversy, the Public Health Agency of Canada announced in February that it would confine any mutated strains of H5N1 used in Canada to maximum-security laboratories.
Brown said he agrees with erring on the side of caution, but noted the research on pathogens is heavily regulated already and scientists have an incentive not to misuse pathogens with the potential to kill them.
There is also concern among researchers that calls for more regulation and restrictions on flu experiments could hinder research.
“If it gets too much heavier, it will really slow down the field,” said Brown.
Dr. Andrew Potter, director of the Vaccine and Infectious Disease Organization at the University of Saskatchewan, said it’s important to make the results of flu research public.
“I think it’s horrendously dangerous to keep this type of work secret,” Potter said in a statement. “These things do happen in nature, that’s how you get the deadly pandemics. They do happen.
“If we don’t do the research and publish the research, we will forever be in the situation of reacting to pandemics instead of being proactive.”
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