Welcome to the Hotel Influenza

While the CO₂ concentration itself is not a health hazard—even at much higher concentrations, like at a 2022 Maryland Public Health Association meeting he attended that had levels well over 2,000 parts per million—it’s a worrying sign. The amount of CO₂ in the air indicates the risk of infectious viruses floating around, according to a mathematical model Milton proposed with the late Stephen Rudnick of Harvard Medical School in an influential 2003 paper rejected by Science but published in Indoor Air.

Respiratory disease has shadowed Milton’s life. He grew up in the Baltimore area in the 1950s and ’60s, when factories and mills still crowded Sparrows Point and other parts of the city and belched pollution into the air far thicker than any hovering around Charm City today. As children, he and his two sisters watched their mother struggle with bronchiectasis, a condition that involves recurring, painful bouts of bronchitis and airway infection, and caused her death in 1995. “I think I may have gravitated toward studying respiratory issues from wondering as a child why my mother couldn’t get out of bed, what we could do to help her.”

He graduated from the University of Maryland, Baltimore County and Johns Hopkins University School of Medicine and later earned a doctorate in public health from Harvard. While serving as a practicing physician in environmental and occupational medicine, Milton began focusing on indoor air quality.

One tragedy in particular—the death of a woman who had been among several workers in a badly ventilated room who developed adult-onset asthma—galvanized his direction in medicine and public health. Her body was discovered in her home, clutching a rescue inhaler.

“That indelible image and the failure of medical treatments to save my patient keeps me focused on the importance of indoor air,” he says.

Photo by Stephanie S. Cordle

To prove his point about what’s in the air, he developed a machine, which he named Gesundheit II (left); the vaguely steampunk assemblage of tubes and gauges leads to a Victrola-like horn into which visitors to his Public Health AeroBiology Laboratory stick their faces so the machine can capture their breaths and extract viruses. In a 2013 study published in PloS Pathogens, he used it to demonstrate flu virus could be captured from infected people’s breath and cultivated. The paper also showed that surgical masks reduced the amount of influenza virus escaping into the air from an infected person by 70%.

A past collaborator of Milton’s, Raymond Tellier, an associate professor and microbiologist at McGill University in Montreal, says the backlash against Milton in part stems from scientific disputes stretching back to the early 20th century, when doctors fought unscientific beliefs about “miasma,” or unhealthy night air thought to cause everything from cholera to the bubonic plague. The idea led to measures that encouraged disease, such as buildings designed to prevent ventilation with outside air; while such thinking has been universally rejected, its echoes remain, he says.

“The idea of aerosols with virus particles was being lumped together with the old reaction against the miasma theory,” says Tellier, who adds that today those who refuse to consider Milton’s ideas are the ones ignoring science.

Milton also attributes some of the reaction to hospital administrators’ unwillingness to swallow the cost of air cleaning or issuing masks that are more protective—and expensive—than surgical masks. But the resistance is underlain by the idea that “this is how we’ve always done it,” he says.

“It’s dogma, not science,” he says. “I’m allergic to dogma.”

As the COVID-19 pandemic began, Milton watched with dismay as his work seemed to have little effect on what medical and public health authorities were telling people; masking was initially widely dismissed, and social distancing, handwashing and even wiping down supermarket purchases were presented as the best means to stay COVID-free.

Researchers and students from Milton’s lab test technology used to track participants in the flu study’s common room by playing a dancing video game. (Photo by Stephanie S. Cordle)

Unlike other controlled trials of virus transmission, the hotel-based one calls for flu recipients to quarantine in their rooms—reading, working remotely, watching TV—when they’re not being intentionally exposed to infected flu “donors.” Previous hospital-based studies that discount the importance of airborne transmission didn’t take steps to ensure people weren’t picking up the virus at home or elsewhere. As a result, they mean little, Milton contends.

In the Baltimore hotel study, participants are brought together in a common room at intervals throughout the day to play cards and board games, do yoga or belt out renditions of “Baby Got Back” and “I’ll Make a Man Out of You” from Disney’s “Mulan” in karaoke. Among other tightly controlled factors, Srebric and colleagues are testing different room ventilation rates to see if cleaner air results in fewer infections via the airborne route.

To examine other modes of infection, randomly chosen participants use hand sanitizer and wear face shields to prevent viruses from being propelled into their nose, eyes or mouth from coughs or sneezes, and to prevent them from touching their faces; others are unprotected. All participants are then instructed to pass digital devices and other common objects around to test touch as a route of infection.

Constant rapid PCR testing, using machines donated by the Balvi Filantropic Fund, keeps track of who has the flu and who doesn’t, while the Gesundheit II allows researchers to measure how much virus donors put in the air; molecular sequencing at NIH tracks what strain virus donors bring in.

A team led by School of Medicine Professor Wilbur Chen, an infectious disease physician-scientist, oversees the medical testing while keeping constant tabs on the well-being of participants; another led by mechanical engineering Professor Don Devoe focuses on creating novel testing devices and technology for analyzing airborne viruses.

Soon-to-graduate UMD student Priscila Terry was entertaining competing thoughts when she arrived in the sumptuous hotel lobby in February: The information science major was unhappy that her sick roommate had coughed freely around their apartment—including directly into a fan as she slept—the likely source of Terry’s flu. On the other hand, the payment involved—donor participants in the trial receive up to $1,900, while recipients can receive $2,500—would allow her to repay her parents for the fee they’d covered when she canceled a semester abroad to graduate early.

And she was wrestling with the complex ethics of medical trials, particularly those meant to induce illness: “I was always taught you should try avoiding coughing on people—it’s gross. It’s inconsiderate. But now I was supposed to make people sick.”

Qualms like Terry’s were unnecessary, says Lehua Gray, who also participated in a February quarantine. The 36-year-old digital user experience designer from Baltimore County first signed up for so-called “challenge trials”—where scientists manually infect participants—to help develop a COVID-19 vaccine, but was not chosen. While Milton’s airborne transmission hypothesis lacks the electricity of the high-stakes fight against the pandemic, the deep scientific and policy questions involved quickly grabbed her.

One of the most surprising aspects of the experience to Gray was the bond that the recipients developed during their activities over their two weeks—“like summer camp.” Several have since stayed in touch, even meeting for drinks and lobbying with administrators to check back in as a group this winter.

“I could randomly catch the flu going to the grocery store, and it wouldn’t help anything,” Gray says. “If I get it as part of this study at the hotel, maybe it will help science understand something we don’t understand as well as we thought we did.” TERP