VCU news

By Leah Small

Groundbreaking virologist and VCU alumnus Jeffery Taubenberger, M.D., Ph.D, talked during a VCU Libraries lecture Monday about the deadly reach of the 1918 flu pandemic, and his work to develop a vaccine steps ahead of the ever-mutating disease.

The lecture marked the centennial of the 1918 pandemic, demystified the mechanisms by which the disease thrives and spreads, and looked toward the future. The timely consideration of the disease comes as the federal Centers for Disease Control and Prevention announced last week that the flu was at epidemic levels in most states. This year’s flu vaccine is estimated to be about 36 percent effective overall and only roughly 25 percent effective against the H3N2 strains.

Taubenberger has found insights into combatting future flu epidemics by investigating the 1918 Spanish  flu, which he notes is the progenitor of modern-day strains. Conservative estimates put the worldwide death toll of the 1918 pandemic at 50 million, but many have estimated that it could have been as high as 100 million, he added.

“[The 1918 flu] stands out as one of the most significant public health or natural history disasters in all recorded history,” Taubenberger said.

A look to the past

The 1918 epidemic dawned at the height of U.S. involvement in World War I. Men in close quarters gearing up to fight on the western front provided ideal opportunities for the virus to spread. One such instance was an outbreak at Camp Devens, a training facility outside Boston. On Sept. 7, a man presented to camp medical staff with what was described as a respiratory illness. The next week, a dozen men reported similar symptoms and a week after that, three dozen. By the third week, 13,000 otherwise healthy 18- to 25-year-old men fell ill and one-third of the camp — 800 men — died.

Preeminent John Hopkins pathologist Henry Welch inspected the camp in the aftermath and wrote, “It must be some kind of new infection or plague.”

Of course, it wasn’t, even though scientists did not isolate the virus until the early 1930s. Centuries earlier George Washington had almost perished from the flu during his presidency and suspected cases had been reported in even earlier writings by European monks.

“The impact of the virus on military troops was devastating,” Taubenberger said. “Over 40 percent of U.S. troops that died of all causes in World War I died of the flu.”

The beginnings of the 1918 epidemic in the U.S. were reported on the East and West coasts and its path into the interior could be traced along railroad lines. In the first two weeks, it spread into New England and the Mid-Atlantic. Two weeks later it was across the country and by October, there were outbreaks in all 48 states.

The impact of the virus on military troops was devastating. Over 40 percent of U.S. troops that died of all causes in World War I died of the flu.

A little under 700,000 people died in the United States from the influenza virus, Taubenberger said. In Philadelphia, which was already a major city, 15,000 people died. Virginia saw roughly 17,000 to 18,000 deaths, about 1,200 of which were in Richmond. Most deaths were caused by secondary bacterial pneumonia.

“People in 1918 did everything they could to prevent the flu. They went to the movies wearing masks. They played baseball wearing masks. They served soup wearing masks,” Taubenberger said. “There were sights in American cities that I think the like of which had never been seen, that I think we all hope will never be seen again. There were huge lorries of coffins.”

People ages 20 to 40 suffered very high morbidity, in contrast to other flu epidemics that affected the elderly and young children. The reason is largely unknown, Taubenberger said. Average life expectancy for 1918 dropped by about 12 years as a result of the epidemic.

The virus even helped shape major world events. President Woodrow Wilson was so ill he left the Versailles Peace Conference, which set peace terms following WWI. Many historians believe his absence contributed to the disharmony in Europe after WWI and the rise of WWII.

Answers for today

Answers for why the flu was so widespread in 1918 did not come until years later, and as understanding grew, Taubenberger and other scientists used clues from the pandemic to inform modern treatments.

“[In 1918] the concept of viruses as agents of infectious disease was still relatively new. Influenza wasn’t known to exist,” he said.

Many believed the flu was instead caused by bacteria. In 1931, it was finally possible to isolate the flu virus.

Fast forward to the early 1990s. Taubenberger was working for the Armed Forces Institute of Pathology in a Washington, D.C., building that housed the largest archive of pathology material worldwide.

Taubenberger and his colleagues began searching for tissue samples from someone who died of the 1918 flu with the goal of piecing together clues about the pandemic. Eventually, they struck gold with what he describes as “a fingernail sized” piece of lung tissue from a soldier’s autopsy. The researchers were able to produce a partial sequence of the virus and the breakthrough was published in the journal Science in 1997.

Taubenberger later collaborated with pathologist Johan Hultin, who said he could locate larger samples of the virus. In the 1950s, Hultin had traveled to the Seward Peninsula in Alaska to extract DNA from victims of the 1918 flu in the village of Brevig Mission but wasn’t able to successfully culture the virus.

Hultin returned to the peninsula and exhumed and autopsied a flu victim nicknamed “Lucy.” He sent her lung tissue back to Taubenberger’s lab, where the material tested positive for the virus.

Taubenberger got to work piecing together an intricate puzzle. He used tissue and samples taken during autopsies of flu victims worldwide to sequence the entire genome of the virus. In 2005, multiple institutions partnered to produce copies of the virus to inform vaccine development. The discovery was lauded as the most significant breakthrough in flu research.

Looking to the future

The flu’s ability to adapt is what makes it so virulent and persistent, Taubenberger said. The virus continually mutates, can pass among species and thrives in multiple environments.

“If [a] bird virus is finding itself in the pig’s nose, any of those mutations will help it replicate. If you give an antiviral drug, any one of those mutations will help the virus escape from that drug,” he said. “If the patient has pre-existing immunity to the multiple strains of flu, maybe some of those mutations help viruses escape from that immunity and spread.”

Taubenberger and his team have found that the 1918 flu probably originated in birds before spreading to people. He said the coding sequences of modern bird flu viruses are similar to that of the 1918 virus.

The virologist said that rapid adaption of flu viruses means that vaccinations must be updated annually and are not totally effective. It takes at least a year to make a prediction about which strain to target and to manufacture the vaccine. In that time, the flu virus mutates.

“We have seen this year that this is not a good long-term strategy,” Taubenberger said. “The dream of the flu community and the public health community is to develop a vaccine that has broad protections.”

Taubenberger aims to start phase one trials on a vaccine in about a year.

“[A vaccine] every five to 10 years instead of a vaccine every year would be great,” he said. “If you had a vaccine that could prevent an acute pandemic, that would be remarkable.”