How scientists traced a mysterious covid case back to six toilets

This article first appeared in The Checkup, MIT Technology Review's weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

This week I have a mystery for you. It's the story of how a team of researchers traced a covid variant in Wisconsin from a wastewater plant to six toilets at a single company. But it's also a story about privacy concerns that arise when you use sewers to track rare viruses back to their source.

That virus likely came from a single employee who happened to be shedding an enormous quantity of a very weird variant. The researchers would desperately like to find that person. But what if that person doesn't want to be found?

A few years ago, Marc Johnson, a virologist at the University of Missouri, became obsessed with weird covid variants he was seeing in wastewater samples. The ones that caught his eye were odd in a couple of different ways: they didn't match any of the common variants, and they didn't circulate. They would pop up in a single location, persist for some length of time, and then often disappear-a blip. Johnson found his first blip in Missouri. It drove me nuts," he says. I was like, What the hell was going on here?'"

Then he teamed up with colleagues in New York, and they found a few more.

Hoping to pin down even more lineages, Johnson put a call out on Twitter (now X) for wastewater. In January 2022, he got another hit in a wastewater sample shipped from a Wisconsin treatment plant. He and David O'Connor, a virologist at the University of Wisconsin, started working with state health officials to track the signal-from the treatment plant to a pumping station and then to the outskirts of the city, one manhole at a time," Johnson says. Every time there was a branch in the road, we would check which branch [the signal] was coming from."

They chased some questionable leads. The researchers were suspicious the virus might be coming from an animal. At one point O'Connor took people from his lab to a dog park to ask dog owners for poop samples. There were so many red herrings," Johnson says.

Finally, after sampling about 50 manholes, the researchers found the manhole, the last one on the branch that had the variant. They got lucky. The only source was this company," Johnson says. Their results came out in March in Lancet Microbe.

Wastewater surveillance might seem like a relatively new phenomenon, born of the pandemic, but it goes back decades. A team of Canadian researchers outlines several historical examples in this story. In one example, a public health official traced a 1946 typhoid outbreak to the wife of a man who sold ice cream at the beach. Even then, the researcher expressed some hesitation. The study didn't name the wife or the town, and he cautioned that infections probably shouldn't be traced back to an individual except in the presence of an outbreak."

In a similar study published in 1959, scientists traced another typhoid epidemic to one woman, who was then banned from food service and eventually talked into having her gallbladder removed to eliminate the infection. Such publicity can have a devastating effect on the carrier," they remarked in their write-up of the case. From being a quiet and respected citizen, she becomes a social pariah."

When Johnson and O'Connor traced the virus to that last manhole, things got sticky. Until that point, the researchers had suspected these cryptic lineages were coming from animals. Johnson had even developed a theory involving organic fertilizer from a source further upstream. Now they were down to a single building housing a company with about 30 employees. They didn't want to stigmatize anyone or invade their privacy. But someone at the company was shedding an awful lot of virus. Is it ethical to not tell them at that point?" Johnson wondered.

O'Connor and Johnson had been working with state health officials from the very beginning. They decided the best path forward would be to approach the company, explain the situation, and ask if they could offer voluntary testing. The decision wasn't easy. We didn't want to cause panic and say there's a dangerous new variant lurking in our community," Ryan Westergaard, the state epidemiologist for communicable diseases at the Wisconsin Department of Health Services, told Nature. But they also wanted to try to help the person who was infected.

The company agreed to testing, and 19 of its 30 employees turned up for nasal swabs. They were all negative.

That may mean one of the people who didn't test was carrying the infection. Or could it mean that the massive covid infection in the gut didn't show up on a nasal swab? This is where I would use the shrug emoji if we were doing this over email," O'Connor says.

At the time, the researchers had the ability to test stool samples for the virus, but they didn't have approval. Now they do, and they're hoping stool will lead them to an individual infected with one of these strange viruses who can help answer some of their questions. Johnson has identified about 50 of these cryptic covid variants in wastewater. The more I study these lineages, the more I am convinced that they are replicating in the GI tract," Johnson says. It wouldn't surprise me at all if that's the only place they were replicating."

But how far should they go to find these people? That's still an open question. O'Connor can imagine a dizzying array of problems that might arise if they did identify an individual shedding one of these rare variants. The most plausible hypothesis is that the lineages arise in individuals who have immune disorders that make it difficult for them to eliminate the infection. That raises a whole host of other thorny questions: what if that person had a compromised immune system due to HIV in addition to the strange covid variant? What if that person didn't know they were HIV positive, or didn't want to divulge their HIV status? What if the researchers told them about the infection, but the person couldn't access treatment? If you imagine what the worst-case scenarios are, they're pretty bad," O'Connor says.

On the other hand, O'Connor says, they think there are a lot of these people around the country and the world. Isn't there also an ethical obligation to try to learn what we can so that we can try to help people who are harboring these viruses?" he asks.

Now read the rest of The CheckupMore from MIT Technology Review

Longevity specialists aim to help people live longer and healthier lives. But they have yet to establish themselves as a credible medical field. Expensive longevity clinics that cater to the wealthy worried well aren't helping. Jessica Hamzelou takes us inside the quest to legitimize longevity medicine.

Drug developers bet big on AI to help speed drug development. But when will we see our first generative drug? Antonio Regalado has the story.

Read more from MIT Technology Review's archive

The covid pandemic brought the tension between privacy and public health into sharp relief, wrote Karen Hao in 2020.

That same year Genevieve Bell argued that we can reimagine contact tracing in a way that protects privacy.

In 2021, Antonio Regalado covered some of the first efforts to track the spread of covid variants using wastewater.

Earlier this year I wrote about using wastewater to track measles.

From around the web

Surgeons have transplanted a kidney from a genetically engineered pig into a 62-year-old man in Boston. (New York Times)
Surgeons transplanted a similar kidney into a brain-dead patient in 2021. (MIT Technology Review)
Researchers are also looking into how to transplant other organs. Just a few months ago, surgeons connected a genetically engineered pig liver to another brain-dead patient. (MIT Technology Review)

The FDA has approved a new gene therapy for a rare but fatal genetic disorder in children. Its $4.25 million price tag will make it the world's most expensive medicine, but it promises to give children with the disease a shot at a normal life. (CNN)
Read Antonio Regalado's take on the curse of the costliest drug. (MIT Technology Review)

People who practice intermittent fasting have an increased risk of dying of heart disease, according to new research presented at the American Heart Association meeting in Chicago. There are, of course, caveats. (Washington Post and Stat)

Some parents aren't waiting to give their young kids the new miracle drug to treat cystic fibrosis. They're starting the treatment in utero. (The Atlantic)