Dr. Donald K. Milton has been trying to give people the flu for years.

During the last effort in 2024, the University of Maryland professor of environmental health put sick students and healthy volunteers in a downtown Baltimore hotel room hoping they’d pass the virus around.

This year, he plans to give them a regular dinner date in a special room in the engineering building on the College Park campus.

“You’d think this would be easy, but turns out it’s not,” said Milton, an expert in the transmission of respiratory viruses, including flu and COVID-19.

“At this point,” he said, “no one has been able to observe transmission under controlled conditions from one human being to another.”

What scientists like Milton know about how people get the flu comes from purposefully infecting people in a lab. The scientists, however, really want to capture precisely when and how flu naturally passes from one person to another.

The information isn’t just evidence in support of preventive measures, like masking and vaccinating. It’s critical to devising far more specific and effective means of preventing miserable and often dangerous infections.

Some of the challenges encountered by researchers are attributable to bad luck. In one recent study, researchers rented a floor of rooms in a hotel in January. But the flu season ended before then, and no one in the study got the flu that month to pass on.

Other issues were in the designs of the experiments. Milton now sees three problems in the 2024 study.

The first was choosing middle-aged people to catch the flu. They had really strong immune systems from years of vaccinations and infections. Researchers needed younger volunteers with less robust defenses.

The researchers also mixed the air, thinking it would spread virus around evenly to study subjects. But that just diluted the plumes of virus. They needed different controls.

And perhaps most importantly, the sick students didn’t cough much so they didn’t actively put concentrated virus in the air. Researchers needed students who developed the symptom.

It may seem counterintuitive that all the conditions matter so much in passing the flu, especially given that everyone seems to know someone, or is someone, with the flu these days.

But, Milton said, “if you think about it, it makes sense it’s hard to do this. We know about 20% get infected during robust flu seasons, so most people don’t get the flu.”

Still, one of the healthy volunteers from the 2024 study said she was surprised she evaded the seemingly ubiquitous malady.

Lehua Gray, a 38-year-old web designer, said she spent about 10 days in the Lord Baltimore Hotel near her Baltimore County home trying to get infected.

She and others passed around pens, played board games, watched movies and sang karaoke songs together over and over to fill the time in close quarters.

She’d signed up as a volunteer for trials during the coronavirus pandemic through the University of Maryland, Baltimore because she wanted to support science and figured she was exposed to all sorts of respiratory infections every year anyway.

“We put ourselves in harm’s way by existing,” she said. “I’m going to meet some friends at a concert in a few hours, and given the flu curve going crazy, that’s a risky thing. This way, as part of a study, I can help people.”

She spent her working hours during the last study on her computer doing her day job. After hours, she sang, danced and played games in a common area while a sick student lay ailing on a sofa.

She likened it to summer camp. And she ended up bonding with fellow volunteers, whom she still meets up with for karaoke.

“I just didn’t get sick,” said Gray, who remains in the pool of volunteers for more studies.

Gray’s efforts weren’t in vain, according to Milton, the principal investigator for the study, published Jan. 7 in the journal PLOS Pathogens. The team collected what he called circumstantial evidence about flu transmission, such as that air circulation is an effective preventive measure.

They will put all this to the test again when students return from winter break to College Park. This time, scientists will rely only on younger students, with their less robust immune protections and hectic lives.

Those who become sick — as well as those who remain healthy — will hunker down in their dorms by day and come together nightly in the engineering building prepared for optimal transmission by a team of engineers, including Jelena Srebric, a professor of mechanical engineering.

Two forms of equipment will monitor the interactions, a special camera to measure distance and orientation between people and a Gesundheit machine, which Milton helped develop to capture and analyze infectious viruses in the breath of people who are sick.

Srebric said they should be able to use data to calculate the chances of getting sick, for example, if someone coughs over one shoulder or in another direction. They should also be able to tell how long someone has to hang out in a plume of virus to become infected.

That could mean they know precisely how long a specific-sized school cafeteria or office space would have to run a certain-sized air purifier to prevent someone from passing on their infection to anyone.

She said they could also likely do the math for other infectious diseases, such as COVID-19 and RSV.

“Wouldn’t it be wonderful if we advance to a phase where we are all free of this stuff?” Srebric said.

But that would be possible, Milton said, only if “all the stars align” and study subjects actually get the flu this time.