Molecular pathologist has spent much of the past eight years immersed in the genetic analysis of the virus responsible for the 1918 influenza pandemic. Before he began his landmark investigation to decipher the virus’s mysteries, including where it originally came from and why it was so deadly, Taubenberger knew remarkably little about the virus and the outbreak. “The only thing I remembered was a brief passage from my medical school training that it was the worst pandemic in history and that at least 20 million people had died, but beyond that I had really sketchy details in my mind,” he recalls. “It is curious that the pandemic doesn’t seem to be part of the cultural memory, at least in the United States, although it was a huge event with a huge impact. Everyone hears at school about the Black Death in the 1300s, yet here was an infectious disease only 85 years ago that killed 40 million people and for some reason we don’t know about it.”
Taubenberger’s chief scientific interest, he says, is “basic immunology.” But the 1918 flu, he admits, is a “hobby that has kind of taken over my life.” His passion for understanding the virus began in large part because of circumstance. In 1983, Taubenberger left his previous job at the National Institutes of Health to take a position at the Armed Forces Institute of Pathology in Rockville, Maryland, to create a state-of-the-art molecular pathology laboratory. Traditionally, a pathologist will diagnose disease by examining tissue samples under a microscope to look for the distinctive cellular changes that mark a tumor cell, for example, and indicate that it is benign or malignant. “But molecular medicine has advanced so much that there are many conditions, including some tumors, that have particular genetic mutations associated with them, so you can make a diagnosis of cancer or leukemia by looking at the DNA for that particular mutation,” explains Taubenberger. “I was charged with setting up such a lab. As part of our work we developed techniques to recover nucleic acids” — the building blocks of our DNA strands — “from tissues that had been fixed in formaldehyde.” Although pathologists commonly study fixed tissues, molecular biologists prefer fresh blood and tissue samples because the preservation process can break up and damage DNA.
Those techniques allowed him to take advantage of a unique database. The Armed Forces Institute of Pathology, where Taubenberger is now chief of the Division of Molecular Pathology, has been in existence for more than 140 years and houses a vast collection of preserved tissue specimens — including, Taubenberger discovered, samples from victims of the 1918 influenza outbreak. “At some point around 1996 it occurred to me that it would be useful to look at the 1918 flu through the lens of molecular biology. Here was something that we thought was very medically relevant, it was an outbreak that had killed tens of millions of people, and nobody knew anything about it because viruses weren’t even known then to be human pathogens,” he says.
Taubenberger’s studies have proven to be more than “relevant.” He and his colleagues are on the verge of determining the 1918 strain’s entire genetic code and they’ve shed light on the origin of the virus and why it was so peculiarly deadly to young adults. As part of the work, he and his team
reconstructed the genes of the virus and inserted them individually into other viruses. Taubenberger bristles at the assertion by some activist groups that recreating, at least in part, the deadly 1918 virus would be considered bioterrorism if the work were done outside of the United States: “I’ve seen references like that but I don’t think the claims are appropriate. These people have never contacted me. They make references to papers and draw conclusions that have nothing to do with the papers they are referencing, so they are not looking at the science carefully.”
“I think one thing these people get excited about is that the Armed Forces Institute of Pathology belongs to the Department of Defense,” he adds. “But this is not a DOD-funded project. It is a project of my lab, being funded by the NIH. The sequences we generate are put into GenBank” — a storehouse of genetic sequence data that is publicly available. “It is clearly not a secret project.”
Furthermore, Taubenberger says, “the experiments that involve reconstructing viruses that contain 1918 genes are done in high biological containment with appropriate biosafety oversight. We don’t want to be cavalier and say there is nothing to worry about, no risk. What we want to say is that we think that working with this virus, trying to understand what happened in 1918 using the sequence of the virus, is really important work.”