Tackling a Killer on a Molecular Level

Jeffery Taubenberger

Alumnus delves into the genetic makeup of the flu and other diseases

Mason alumnus Jeffery Taubenberger, B.A. Biology ’82, has, along with his colleagues, accomplished ground- breaking work in deciphering the genetic makeup of flu viruses, “one of the largest killers in the world.” And although Taubenberger recommends annual flu shots, the chief of molecular pathology at the Armed Forces Institute of Pathology (AFIP) says that many people’s attitude toward the flu is rather blasé.

Taubenberger’s interest in performing immunology research was already in place when he graduated from Mason, and it was a reason he attended the Medical College of Virginia in a combined M.D. and Ph.D. program. He completed his residency in pathology at the National Cancer Institute of the National Institutes of Health and stayed on there as a staff pathologist. In 1993, the AFIP recruited him to set up a molecular diagnosis laboratory.

Part of the work facing Taubenberger at the lab’s outset was to develop techniques for extracting genetic material out of fixed tissue. “It is easy to get genetic material out of frozen or fresh tissue,” he says. “But if you take that tissue and process it the way pathologists normally do, it becomes difficult to get genetic material out of those tissues.” Taubenberger and his colleagues, however, eventually worked out the techniques to do just that. They decided to highlight those techniques and the AFIP’s extensive collection of human autopsy samples—that date back to the Civil War—by looking into the particularly lethal virus that caused the worldwide 1918 flu pandemic that claimed an estimated 40 million to 50 million lives in about six months.

“ One of the weird things about the 1918 virus is that it had the propensity to kill young healthy adults in just a couple of days,” says Taubenberger. “People who tend to die of flu infection are the elderly, people with chronic illnesses.” About 20,000 to 30,000 Americans die of the flu every year; in 1918, the flu killed 700,000 Americans.

One of the things making Taubenberger’s research challenging is the fact that flu viruses are not stable genetically. “Once the virus has gone through the population, the population builds up immunity to that particular strain,” he says. “If the virus is going to survive, it has to mutate itself in a way to escape the immunity that already exists.” The 1918 virus, therefore, only existed in 1918. Fortunately, the AFIP’s collection had lung tissue from soldiers who died of the flu during that year.

Taubenberger says that teasing the bits of influenza genes from the tissue is difficult and tedious because the genetic material is so fragile. “Having gone through the process of being fixed with formalin and stored for 84 years, it is very degraded and only present in tiny fragments in tiny amounts, so we cannot just read the sequence of the virus at one time.” Once the whole sequence of the virus has been read, Taubenberger hopes to discover where the virus came from and why it was so lethal.

At this point, researchers think the genes came from a bird virus that spent time adapting in some other host before infecting humans. They are comparing what they have of the 1918 virus gene sequence with the gene sequences of flu viruses from birds, animals, and people. Through a collaborative study with scientists at the Smithsonian’s Natural History Museum in Washington, D.C. (which has its own unique collection—hundreds of birds stored in alcohol), they were able to find the same type of virus as the 1918 one in a goose collected in Alaska in 1917.

One theory as to why the virus was so lethal is that the protein in a flu virus that blocks a person’s immune response when he or she is first infected was especially effective in the 1918 strain, says Taubenberger. Another is that people of the age group for whom the virus was most deadly had an immune response to the virus that ended up harming them.

Taubenberger says the work has generated a good deal of publicity. “There’s this sort of ‘Frankensteinian’ element—one of the samples we have is from a frozen body in Alaska.” The research has been the subject of some books and articles in the New York Times, the Washington Post, National Geographic, Newsweek, and Time magazine.

Taubenberger notes that the research is more than just a look at a historical curiosity. It attempts to answer some real medical questions: What happened, and can we use that knowledge to help prevent something like this from ever happening again?