AVIAN FLU: PREVENTING A PANDEMIC
Avian Virus Caused
The 1918 Pandemic,
New Studies Show
By BETSY MCKAY
Staff Reporter of THE WALL STREET JOURNAL
October 6, 2005; Page B1
There is a new reason to worry that the avian-flu virus could erupt with little notice into a global pandemic that kills millions of people: It happened already.
After nearly a decade of research, teams of scientists said yesterday that they had re-created the historic influenza virus that by some estimates killed 50 million people world-wide in 1918 and 1919. The scientists concluded that the virus originated as an avian bug and then adapted and spread in humans by undergoing much simpler changes than many experts had previously thought were needed for a pandemic.
Some mutations of the 1918 virus have been detected in the current avian-flu virus, suggesting the bug "might be going down a similar path that led to 1918," says Jeffery Taubenberger, chief of molecular pathology at the U.S. Armed Forces Institute of Pathology, who led one of two studies.
The studies, published yesterday in the journals Nature and Science by researchers from the Armed Forces institute, the Centers for Disease Control and Prevention, and Mount Sinai School of Medicine, suggest that a bird-flu pandemic could erupt in more ways than previously thought -- and could be as lethal as its predecessor. Unlocking the mysteries of the 1918 bug "has taken on new urgency," says Dr. Taubenberger.
The findings could also help researchers hone their efforts to develop vaccines and treatments for avian flu by pinpointing which pieces of the virus made it so virulent. CDC researchers narrowed in on a gene in the re-created 1918 virus that allows the bug to attach itself to cells and multiply. With the gene, the virus was highly lethal; it lost its virulence when researchers removed it. Those findings and the genetic makeup of the virus will now be publicly available. The U.S. National Science Advisory Board for Biosecurity endorsed making the genetic information public to promote development of tests, treatments and preventive measures, the CDC said.
Deciphering clues from the bug has never been so urgent. Avian flu continues to spread in poultry flocks and is jumping to humans with increasing frequency. The lethal strain has claimed 60 lives in Indonesia, Vietnam, Thailand and Cambodia since late 2003.
Most of those cases occurred in people who had direct contact with infected poultry. But health officials are concerned that the virus could mutate and begin spreading between humans, and that when it does, it will rapidly sweep the globe. On Tuesday, President Bush unexpectedly announced he would consider using the military to enforce quarantines in the event of an outbreak in the U.S.
"If 1918 happened like this, why couldn't or shouldn't 2005 happen like this?" says Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, who has warned in several papers that the H5N1 virus could morph into a 1918-like pandemic. "These viruses are kissing cousins."
Precisely why and how the 1918 virus killed so many people has been considered one of the greatest remaining secrets of virology, and the team led by Dr. Taubenberger has spent the past nine years trying to decipher it. According to historical accounts, suffocating victims turned deep shades of blue; many hemorrhaged, bleeding even from their eyes and ears. More people died during the pandemic than in World War I. Unlike with most flu epidemics, most of the casualties were otherwise-healthy people ranging in age from 15 to 34.
But studying the virus was nearly impossible until recently because virus samples weren't preserved at the time. In February 2004, Dr. Taubenberger and his team published sequences for five of the 1918 virus's eight genes, using material preserved from the lungs of U.S. soldiers killed by the flu, as well as the body of an Inuit woman exhumed in 1997 from the Alaskan permafrost. The team completed sequencing the remaining three genes, and their work is published this week in Nature.
They concluded that the pandemic was caused by an avian virus. The scientists also discovered 10 changes in amino acids that distinguish the 1918 virus from avian bugs, suggesting that the virus mutated on its own, without mixing with another virus, to become transmissible in humans, they say. The current avian bug has made five of the 10 changes found in the 1918 virus. (Emphasis added by DM.)
In the study in Science, researchers from the CDC, Mount Sinai, and others then re-created the virus using a process known as reverse genetics to determine which of its features made it so lethal. The virus was then injected into embryonated chicken eggs and mice and was found to be "exceptionally virulent," says Terrence Tumpey, a senior scientist at the CDC who led the effort. The team also found that the bug had an unusual ability to penetrate cells that flu viruses don't usually reach deep in the lungs, providing some clues as to why the disease's symptoms were so severe.
While the research advances scientists' understanding of the avian-flu threat, it raises questions about how to keep the virus from escaping from a laboratory or falling into the hands of bioterrorists. Not only has the virus now been created in a CDC lab, but its genetic information will be published in GenBank, a public genetic-sequence database maintained by the National Institutes of Health.
Dr. Tumpey says the experiments were approved by two CDC committees with internal and external experts, and were conducted under strict safety and security standards inside a CDC lab.
The 1918 flu virus would be unlikely to cause a pandemic today, Dr. Tumpey says. This virus is in the same family as the seasonal influenza viruses that have been circulating for several years. Many people today have some immune protection from these types of viruses because they have been exposed to the seasonal flu viruses either through natural infection or vaccination.
The researchers say they are pushing ahead with their work. Dr. Tumpey says he and his colleagues plan to analyze the remaining four of the eight genes whose virulence they didn't study, with the hope of identifying more virus proteins. Dr. Taubenberger of the Armed Forces Institute says his team's goal is to create a "checklist" that would help researchers tracking viruses determine which mutations are important and which are minor.
"We hope to work out in the future the rules of how this happens, how a bird virus becomes a human virus," he says.