In 1896, a British scientist named Ernest Hankin was astonished by something he observed in the waters of the Ganges and Yamuna rivers.
The rivers received the bodies of cholera victims. The water downstream was supposed to be laden with the curvilinear bacteria that Robert Koch identified in the early 1880s as the cause of the disease. There must be a widespread outbreak.
However, the outbreaks quickly faded. Apparently something in the river water is killing the cholera bacteria because it can wreak havoc. Hankin also noted that the effect was stronger in the Ganges than in the Yamuna, and that it was stronger in well water from nearby towns.
Hankin was unable to see the killer and found it was small enough to pass through a ceramic filter designed to contain bacteria. He guessed it was a chemical agent in the water and published his results.
Twenty years later, Frederick Tourte in England and Felix d’Herel in France described small viruses that infect and kill bacteria. D’Herel gave them the name phages, which means bacteria-eaters. That’s the name that stuck. These viruses that parasitize bacteria are the most widespread biological entities on the planet, outnumbering bacteria by approximately ten to one.
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Looking back, it’s tempting to wonder whether Hankin was the first person to find phages when he noticed something in the water. We will never know for sure, but it is an important question and not just for historical reasons. Cholera is still very much among us, even though we know what causes it and how to prevent it.
Cholera has caused seven epidemics in the past two centuries. The first began in 1817 around Jessore in the Ganges Delta. The seventh round began in 1961 in Sulawesi, and we are still in the middle of it. In 2023, the World Health Organization reported about 667,000 cases in five of its six regions. In the spring of 2022, a hospital in Bangladesh treated more than 42,000 patients in Dhaka in a single outbreak.
Bacteria-eating viruses accompanied cholera all those years. In the mid-2000s, researchers showed that as cholera bacteria multiplied in water during an outbreak, the number of viruses they preyed on also rose, seemingly ending the outbreak.
These viruses seem to make cholera less dangerous inside the body as well. A few years ago, researchers found that cholera patients who had high levels of cholera viruses that kill cholera bacteria in their stool suffered from moderate dehydration. On the other hand, patients with low ratios were sicker.
Now, two consecutive papers recently published in Nature add to the mutual complexity between these viruses and cholera.
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In one project, researchers watched a new antiviral defense system spread through a cholera population in Bangladesh in real time. Bacteria routinely pick up loose pieces of DNA from their surroundings, from other bacteria, and sometimes from the viruses they prey on. Some of these pieces carry instructions for useful survival tools. In a way, bacteria have their own “immune systems,” and may be the ancestors of many aspects of our immunity as well.
In September 2021, cholera bacteria in Bangladesh began carrying a new antiviral tool, which acts as a shield against viruses that eat the bacteria. Within nine months, the shield was found in 91% of cholera samples taken from patients because it gave them a survival advantage. By the time the outbreak occurred in Bangladesh in 2022, viruses from the patient’s stool were no longer able to kill the new protected cholera. Cholera bacteria were at the forefront, at least for a while.
But this advantage did not last either. Eleven months later, new viral strains emerged that were good at killing cholera bacteria. The viruses struck cholera bacteria.
The entire sequence reads like a spy novel on a microscopic level. Bacteria gain new defenses against viruses. The viruses that kill them come back with new tools. Then the bacteria try to get the upper hand, and the see-saw swings back and forth endlessly.
The second project published in Nature is equally interesting because it tells us about how cholera spreads. The researchers read the complete genetic blueprints of cholera samples from Bangladesh and northern India. Each cholera bacterium carries small genetic differences that accumulate as it spreads. Reading these differences and comparing them across thousands of samples allows scientists to draw a family tree of the disease, recording which strains they are related to and where they come from.
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According to this study, it appears that India, more than Bangladesh, is spreading the seeds of the outbreak elsewhere in the world. Kolkata is not far from Khulna in Bangladesh. Rivers, fish and birds ignore international borders. What about bacteria and viruses? The new work shows that cholera samples from Kolkata are more closely related to samples from northern India than to samples from Bangladesh. In other words, geographically close areas appear to carry somewhat different cholera bacteria depending on which country they originate in, India or Bangladesh.
It’s an interesting result, and not just for microbiologists. We have known since Koch and Hankin that cholera spreads in dirty water. But new research reinforces something we should also know about microbes. They follow the movement of people.
Anirban Mahapatra is a scientist and author. His latest book is When Medications Don’t Work. The opinions expressed are personal.
