Searching for a killer: Inside CDC’s scramble to solve mysterious vaping disease

Scientists were ecstatic. The test results were in. For the first time, the lab team at the Centers for Disease Control and Prevention had direct evidence that a chemical compound, vitamin E acetate, was a likely culprit in the disease that has sickened nearly 2,300 people and killed 47. Officials set a date to share the news.

But as the lab team raced to test a last batch of lung fluid samples, the tool needed for the chemical analysis suddenly crashed. Scientists feared their precious samples would be destroyed. “My stomach dropped,” recalled Jim Pirkle, who oversees CDC’s chemical lab analyses. “Since we have limited volume (of fluid samples), it could mean we weren’t going to be able to analyze them.”

The equipment failure in early November was one of countless challenges confronted by the more than 100 CDC scientists who have been working around the clock on the agency’s Chamblee campus in Atlanta scrambling to create new investigative tools and techniques as they seek to prevent additional injuries and deaths from a vaping-related illness.

The devastating lung illness was reported for the first time this summer among previously healthy young people in the Midwest. Doctors believed it was linked to e-cigarettes, battery-powered devices that mimic smoking by heating liquids containing nicotine or marijuana, among other substances. But the devices had been sold for more than a decade without reports of such a disease. Why was this happening now?

Over the past three months, teams of scientists working to solve the mystery developed extensive lab tests and built a new data collection system on the fly. They even relied on 3D printers to manufacture custom parts so that vaping devices could be fit into the CDC’s special smoking machines, enabling them to “puff” on the devices to test the aerosols that are released.

In many infectious disease outbreaks, disease detectives have some idea of the likely culprit or at least a sense of how to approach the investigation. The challenge in this case was that no one had any idea what might be making so many people so sick.

Even more daunting, federal and state health officials were dealing with a vast number of possible suspects that included several hundred e-cigarette or vaping devices and thousands, if not more, e-liquids, many of which contain more than one ingredient. Supply chains for the vaping products also appear to vary state to state. “The level of difficulty on this one is probably a 9 out of 10,” said Pirkle, director of the laboratory science division at the CDC’s National Center for Environmental Health.

Diagnosis of a new disease that presented itself in different ways also was confounding, said Peter Briss, medical director at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, who helped lead the investigation. Many patients had chest pain and shortness of breath. Others reported nausea and vomiting or fever and chills.

Pirkle said only two other investigations he participated in during his nearly four decades at the CDC were more difficult. One involved a toxic oil syndrome in the 1980s involving contaminated oil fraudulently sold as olive oil in Spain that killed hundreds and sickened thousands. That took several years to solve, he said. The other involved developing a way to measure levels of dioxin in Vietnam War veterans who had been exposed to Agent Orange.

That also took several years “to get a methodology that was sensitive enough,” he said. “What we have done here, we have done in weeks,” he said, crediting scientists working 14- to 15-hour days. Among the earliest challenges was gathering data. The illnesses first appeared in Wisconsin and Illinois in July. When the CDC got involved in August, officials had no idea how big or widespread the outbreak would become.

The agency relied on a version of a system used to track food-borne outbreaks, said Macarena Garcia, chief data scientist for the investigation. But as one state after another reported cases, she realized the system couldn’t be scaled up fast enough. Information from the states also was arriving in different formats, she said, making it difficult for federal officials to quickly analyze the national picture.

Lab tests turned out to be even more challenging. In early fall, New York’s Wadsworth Center laboratory and the Food and Drug Administration began analyzing vaping products collected from sick patients and found vitamin E acetate in those containing THC – the ingredient in marijuana that produces a high. But it was the CDC’s analysis of lung fluid from sick patients that provided the first direct evidence of the oil as a common factor in their damaged lungs.

Vitamin E acetate, an oil from the vitamin, is in many foods, nutritional supplements and cosmetics. It also is an additive used to dilute THC in black-market vape cartridges. The oil does not usually cause harm when swallowed as a supplement or applied to the skin. When inhaled, research suggests it might disrupt normal lung function.

Developing reliable and accurate tests took time – about three weeks – because scientists wanted to ensure that their methods were sensitive enough to detect the wide array of substances being investigated, said Eric Blank, chief program officer at the Association of Public Health Laboratories. Scientists are “looking for things you wouldn’t normally see in these (lung) specimens,” he added.

By early November – more than three months after the first cases had been reported – a team of 25 scientists had found vitamin E acetate in lung fluid from 19 patients. More remarkable, the scientists found no evidence of other chemicals or compounds on the list of possible suspects. The labor-intensive and meticulous process involved more than 1,000 measurements just to rule out many plant oils as culprits, Pirkle said.

Still, “We needed to get results fast,” Pirkle recalled. “We couldn’t keep having people getting sick and dying.” To buttress their case, the team sought to test 10 more samples. But the night before the analysis was to take place, a software failure crashed the chemical analysis tool called a mass spectrometer.

“It was tense,” Pirkle said. The CDC had already begun writing a report detailing its findings. The deadline was less than 12 hours away. Technicians fixed the tool, and the new samples provided even stronger confirmation. When the results came back positive for vitamin E acetate in those, as well – now 29 out of 29 samples – team members were so tired, “We just went home,” Pirkle said.

Two days later, Anne Schuchat, the CDC’s principal deputy director, announced that vitamin E acetate was “a very strong culprit of concern” in the outbreak. The evidence, while not yet definitive, has helped public health experts better understand how the puzzle pieces might fit together.

The findings reinforced health warnings against e-cigarette or vaping products that contain THC, especially those bought off the street. But because a small population of sick patients insist they used only nicotine-containing products, the CDC is maintaining its recommendation that consumers consider refraining from using all vaping and e-cigarette products, including those with nicotine.

Investigators also are trying to find out what other toxins might be flowing into people’s lungs as they vape. Federal health officials have said the outbreak may have more than one cause. “It’s possible the harmful thing doesn’t even get produced until fluid is vaped” or heated, Pirkle said.

To understand what other substances are being inhaled, the CDC began testing aerosols from vaping devices linked to sick patients. The agency is relying on 13 smoking machines used in the past to study toxic chemicals in conventional cigarettes. But the machines have round holes, whereas many vaping devices have rectangular mouthpieces. So the CDC scientists used 3D printers to create “custom interfaces” to fit on the mouthpieces and connect them to the machines.

“You’re literally putting a square peg in a round hole,” Pirkle said. The machines puff at different voltages and for different lengths of time just like “all the things people do” when they’re vaping, he said. Scientists will analyze whether higher temperature and dosages make a difference. Filters will collect the aerosol and any lipid-containing droplets.

“We’ll be looking to see if we get anything unusual,” Pirkle said. Most of the sick patients vaped THC, but many used multiple products. “It could be one thing caused the problem and two or more others didn’t. But we still have to analyze all of them.”