In just one year, from 1918 to 1919, as many as 50 million people around the world succumbed to the flu pandemic. For decades, speculation abounded about what exactly caused the catastrophic outbreak.
Now, scientists in the United States led by Dr. Jeffery Taubenberger, of the Armed Forces Institute in Washington, and Terrence Tumpey, of the Centers for Disease Control in Atlanta, say they have resolved one of the great medical mysteries of the 20th century. And the timing couldn’t be more grimly appropriate.
The researchers have proven what had long been suspected and feared: The 1918 pandemic was caused directly by bird flu.
John Oxford, a top British virologist, calls this finding the biggest breakthrough of its kind in many years. But he said it is especially alarming because it means the current outbreaks of bird flu in Asia and Russia are even more likely to morph into a human flu pandemic than scientists had previously believed.
Until the U.S. findings were released, scientists thought the bird flu virus would first have to mix with a human flu virus for it to become an effective human pandemic agent. That is what happened during the less serious flu pandemics of 1957 and 1968.
But what researchers have now proven is that the far more deadly 1918 pandemic was caused by a pure bird flu virus that jumped into the human population directly. No transition phase was necessary.
The current bird flu virus that is mostly circulating around Asia but is spreading westward -- H5N1 -- has already shown it can infect humans. It has only killed some 60 people so far. But if it suddenly mutates, as happened in 1918, it could become a killer on a grand scale.
"The current situation is fairly dangerous with the H5N1 [virus], the chicken flu in Southeast Asia. And this report by the American group, Taubenberger's group, heightens that worry quite significantly, because in its essence, what it shows is that in 1918, a virus not so different from H5N1 came across as a single package," Oxford said. "It leapt across from a chicken or a goose or a duck in its entirety, infected humans and then broke into a great world epidemic that killed 50 million people."
Taubenberger’s group achieved its breakthrough after 10 years of pioneering research that recalls the popular movie “Jurassic Park.”
The scientists managed to piece together the exact genetic sequence of the 1918 virus. They did this using tissue samples from people who died in the epidemic. One of the samples came from a woman who died in a remote Alaskan village that was wiped out by the disease. She had been buried in a mass grave and her body remained intact thanks to the northern permafrost.
Researchers at the Centers for Disease Control then infected various laboratory animals with the virus, taking out and adding genes, to measure its exact effect.
They found that changing just 20 to 30 out of the 4,000 amino acids contained in the original bird flu viral proteins made it into a human killer. In other words, the mutation that turned the virus from a bird killer into a human killer was very small.
What happened in the lead-up to the 1918 pandemic, according to Oxford, was similar to where we find ourselves now. Disease-carrying migratory birds from Asia appeared in Europe. Small outbreaks began.
"In 1917-1918, [the birds] would have overflown England, overflown France. The war was going on. There were little outbreaks -- just like at the moment, actually, in Southeast Asia," Oxford said. "There were not huge amounts of people dying, but groups of 50 people dying, groups of 60 people dying in the great army camps on the Western Front. And I think now, looking back, that's where the virus had its genesis -- not in Spain, not in Asia as such and not in the United States, but there in France. And then the great movement of young people in 1918 -- in October 1918, when the war was ending -- gave the virus its opportunity to spread around the world."
In recent weeks, scientists at the World Health Organization have expressed growing alarm at the potential for H5N1 to turn into a killer pandemic. This week, U.S. President George W. Bush also said America needed to prepare for a possible outbreak.
Oxford says it’s time the world woke up.
"Forget bioterrorism. Forget Iraq. Forget all this," Oxford said. "What could threaten us all is Mother Nature in the form of a great infectious disease. So, if anything, this study and other studies reawaken that possibility -- and it's a very distinct possibility -- that this virus, this current virus, this H5N1, could break out and sweep around the world."
Fortunately, unlike in 1918, preventive measures can be taken. But it will require political initiative from world governments. Ordinary annual flu shots will do nothing to protect people from a pandemic.
And the 1918 outbreak, unlike ordinary influenzas that hit the sick and elderly hardest, killed a disproportionate number of young, otherwise healthy adults.
But the good news is that a new generation of antiviral drugs can be mass produced and stockpiled and should be effective in combating an outbreak. A specific human vaccine against H5N1 can and should be developed, according to Oxford.
"That's the No. 1 preventative strategy: to build up that class of drugs," Oxford said. "This is new technology. This is a new discovery in the last five, six, seven years. And we must exploit that to the full extent. As regards vaccines, it's fair enough that the virus from Asia at the moment -- the H5N1 -- may not emerge. Maybe another one will. But I still think this is important enough for us to conclude at the moment that this is the threat. And so make the vaccine now against H5N1. If it doesn't emerge, throw the vaccine away and make another batch."
Several European countries have begun to stockpile antiviral medication. The big questions now is whether other world leaders will also heed scientists’ calls -- while there is still time.