A Dysentery Sample From A WWI Soldier Sheds Light On Drug Resistance

Enlarge this image toggle caption Courtesy of Genome Research Ltd Courtesy of Genome Research Ltd

In the early months of World War I, British Pvt. Ernest Cable was a member of the 2nd Battalion of the East Surrey Regiment. Records show that in early 1915, his regiment was fighting in the trenches of Flanders, Belgium.

But by March of that year, Cable, 28, was in a hospital in the northern French coastal town of Wimereux. On the 13th he died from dysentery, a diarrheal disease caused by the bacterium Shigella flexneri. Spread by poor hygiene and lack of sanitation, dysentery stalked the water-logged trenches of WWI, killing hundreds of thousands on both sides.

Now a sample of the very bug that felled Pvt. Cable 99 years ago may provide a boost to efforts to find a vaccine to prevent the disease, which is highly contagious and kills hundreds of thousands of children a year, mainly in developing countries. It's also wholly resistant to antibiotics.

When Cable died, a bacteriologist collected a sample of the microbe, which was sent to London and preserved at Public Health England's National Collection of Type Cultures, essentially a repository of bacteria.

Cable was certainly not the first British soldier to die from dysentery, but his sample was among the first collected and preserved. "It is the oldest living available strain," says Alison Mather, a researcher at the Wellcome Trust Sanger Institute, a genome research lab near Cambridge. She did the detective work that determined that the strain almost certainly came from Cable.

Earlier this year, Mather's colleagues at Sanger and researchers from the London School of Hygiene and Tropical Medicine began using new, sophisticated gene-sequencing technology to reconstruct Cable's S. flexneri genome and compare it to its modern samples. Their studies were reported in a special First World War edition of The Lancet, published Nov. 8.

The sample's genome had been reconstructed before, but a new technology allows whole strands of DNA to be sequenced without having to shred it into hundreds of pieces and put it back together like a jigsaw puzzle, says Kate Baker, one of the Sanger researchers. That's allowed investigators to see more precisely how the bug evolved and determine parts that remained unchanged — useful knowledge for development of a vaccine.

It turns out that only two percent of the genome differs from its modern equivalent. "That is a conservative amount of change," Baker says. "But the two percent that did change was the important elements that make it resistant to antibiotics. It was the right two percent."

Penicillin had yet to be discovered in 1915, but even it would have been ineffective against the so-called "Cable strain" of S. flexneri. To ward off dangers in the environment, the bacterium had evolved a gene that breaks down molds of the type used to make penicillin. Baker says the dysentery bacterium will probably always remain immune to antibiotics, which is why creating a vaccine is so important.

Each year, some 760,000 children under age 5 die from diarrheal diseases, and dysentery is one of the top four causes. S. flexneri is the bacterium responsible for two-thirds of dysentery cases.

A 2010 German study determined that 155,000 German soldiers were hospitalized with the bug during the war, but that's almost certainly a "tremendous undercount," Mather says. Not all the ill were likely hospitalized and many cases probably went undiagnosed.

Not much is known about Cable, who joined the army in 1911. But Mather discovered a memorial website for the fallen soldier, run by Michael Norman, a former Royal Air Force serviceman now in his 70s. Before the war, Cable had worked for Norman's grandfather and rented a room from him. Norman's father was a toddler at the time. When Cable died, an official memorial plaque, usually sent to next-of-kin, was sent instead to Norman's grandmother, an indication that Cable had no family. The plaque was then given to Norman's father.

"It's very moving that he [Cable] is still remembered today," Mather says. "It was important to locate the human side of this story as a way to memorialize the soldiers who died in the First World War."