1986

In the stool of people with diarrhoea, a small, unknown virus turns up. It sits there alongside rotavirus and norovirus, the familiar culprits. The conclusion is drawn quickly: this is another one of those, and it will attack the intestinal wall.

The virus cannot be cultured in the lab, so no one can test that hypothesis. For forty years, it holds up.

2024

A lab in St. Louis studies Caenorhabditis elegans, a roundworm widely used in genetic research. Among the worm material is genetic material from picobirnaviruses.

What do a worm and a human have in common? Bacteria. Worms eat them, humans carry trillions of them. Does this virus infect bacteria, then?

2025

To test that, you need a system in which the virus can actually grow. First author Tianyu Gan introduces human stool into mice without their own gut flora. Then he cultures the virus in laboratory dishes with gut bacteria, without oxygen.

Human cells do not survive without oxygen. Bacteria do. The virus grows for twenty days. As soon as antibiotics are added, the growth stops.

2026

They find the virus again in a hitherto undescribed gut bacterium, Candidatus Anaerotignum faecalis. The study appears in Nature Microbiology. From that moment on, picobirnaviruses are the third known group of RNA viruses that infect bacteria.

It changes the picture of the gut virome, the whole of the viruses in your digestive tract. Most of it has not yet been classified, and what we understood of it was often based on the same assumption: a virus in the gut is a virus for humans.

Perhaps many of those viruses hunt bacteria and influence our health indirectly, through the composition of the gut flora or through immune responses.

Wang himself remains cautious. The virus has been linked to acute diarrhoea, graft-versus-host disease and type 1 diabetes, but presence is not cause. It could be a marker, a sign that something is wrong without being the culprit itself.

What stays with me most about this story is the thinking error that preceded the discovery. The virus was found in the place where things went wrong, next to viruses known to make things go wrong. That proximity was read as proof.

The researchers of the time are hardly to blame. It is a pattern that recurs everywhere: we see something at the site of the problem and call it the cause. Sometimes that is right. Often it is a bystander.

For forty years, the question was which disease this virus causes. The first question should be: what does this infect, and what does it live on? Only after that can you talk about disease. The answer was bacteria, all those forty years.

Source: 40-year mystery solved: Common gut virus infects bacteria, not human cells — WashU Medicine; paper: Nature Microbiology.