Scientist again pursuing a microbe Physician at Hopkins finds Pfiesteria case is echo of her past

A puzzling illness suddenly begins robbing people of their short-term memory. A single-cell marine organism is implicated. Scientists and physicians work under intense public scrutiny to find people who were poisoned and to block future outbreaks.

For Dr. Trish M. Perl of the Johns Hopkins University School of Medicine, it's not just a medical mystery. It's an uncanny echo of her past.


In fall 1987, it was Perl, a young physician working for the Laboratory Centre for Disease Control in Canada, who traced TC deadly illness to blue mussels harvested in a single river on Prince Edward Island.

Now Perl, 40, is one of a team of University of Maryland and Hopkins scientists tracking the potential human health effects of Pfiesteria, a single-cell organism blamed for killing millions of fish along the Atlantic coast in the past six years.


So Perl finds herself, for the second time in a decade, in the middle of a politically sensitive investigation of a maverick microbe. She seems well-suited for the task.

"I think people that meet her for the first time are struck by the fact that she's incredibly kinetic, very straightforward," said Dr. John G. Bartlett, director of the infectious disease division of the Hopkins medical school, who asked her to join the team.

"And she's very goal-directed, so that she identifies problems and tends to map strategies that will be successful," he added. "She sometimes gets frustrated by people around her who don't operate at her speed and efficiency."

Perl is the oldest of three children in a family where health care was part of the dinner conversation -- her father was a professor of medicine, and her mother a speech pathologist.

As an undergraduate at the University of North Carolina, she majored in French literature -- "just to prove I wasn't going to be a physician" like her father, she said.

Taking a year off from school, she decided she wanted to become a pediatrician after all. But her experience as a UNC medical student persuaded her otherwise.

"When I was on the pediatric ward, I cried every day," said Perl, whose office door is plastered with pictures of her three daughters.

After getting her medical degree in 1983, she went to McGill University in Montreal for her postgraduate training because, she said, Canadian society was more accepting of women doctors.


Five years later, she went to the University of Iowa, and became an expert in tracking staphylococcal and other blood infections. Hopkins hired her as hospital epidemiologist in January 1996, charged with containing in-hospital outbreaks of infectious disease.

Her 1987 mussels detective work came when she was working at Royal Victoria Hospital in Montreal and in a second job as an investigator with Canada's CDC. On her regular hospital rounds one Friday in November, she was approached by several other young doctors.

"They said, 'We have this wild one up in the intensive care unit,' " she recalled.

An 84-year-old businessman had eaten mussels for lunch in a restaurant in a shopping center he owned. Within 24 hours, he developed stomach cramps and began forgetting things.

By the time Perl saw him, he was in a coma. His blood pressure fluctuated wildly, surging to dangerous levels and then plummeting. He couldn't breathe without a respirator.

The standard tests for pathogens turned up nothing.


Perl had been working for the CDC only two months. But when she learned the patient had eaten mussels, she immediately suspected food poisoning and frantically called contacts at other intensive care units in Montreal.

Cases began popping up. Three days later, she learned that a 71-year-old man who had cooked mussels at home was in a coma. She tracked down the man's wife and asked her to retrieve the shells from the garbage.

Those shells yielded crucial evidence. A government laboratory in Ottawa scraped off the fibers holding the top shell to the bottom, ground up the fibers and injected the puree into mice.

Perl suspected saxitoxin, one of the deadliest poisons known. It's produced by algae off both coasts of North America. When mussels and other filter-feeding shellfish eat the algae, the toxin collects in their tissues. When people eat the shellfish, it causes paralytic shellfish poisoning, or PSP.

Mice injected with the mussel extract scratched themselves on the ears compulsively until they lost their balance and flipped over. This didn't look anything like PSP intoxication. It didn't resemble anything known.

Meanwhile, the clock ticked. The number of people in Montreal intensive care units rose to seven. Scores of other cases were turning up across Canada.


Perl and other Canadian CDC scientists held a meeting late at night with a high-ranking federal official to decide what to do. Canadian mussel beds were routinely tested for PSP, considered the most likely culprit, and those tests had all turned up negative. Still, there was strong circumstantial evidence that mussels harbored a deadly illness.

After a lengthy debate, Perl asked the scientists a simple question: Would anyone there eat mussels that evening?

"None of us would," she recalled. That clinched it. Investigators called federal food safety authorities. By Thursday, the government had pulled all mussels off the market.

It wasn't a popular edict. "Mussels are kind of like crab cakes in Baltimore," she said. Worse, Canadian authorities feared devastating the nation's mussel aquaculture industry. Perl and other health officials had to act swiftly.

She interviewed family members of the victims and pored through records from 40 restaurants and 32 distributors. She flew to Prince Edward Island's eastern coast. There, she spent four days talking with mussel farmers and touring chilly North Atlantic estuaries.

Relatively few residents of the island had reported getting sick, but Perl soon learned why. "They had a very stoic population there," she said. "They probably had more cases than they admitted."


Finally, she sorted through her mountain of notes, drawing flow charts of mussel sales. All but one of the cases, she found, could be tied to mussels harvested in early November from two farms on the Cardigan River.

Meanwhile, scientists analyzed the contaminated mussels and identified the toxin: domoic acid, an obscure poison linked to mushrooms and algae, first described in Japan. Water samples yielded a species of diatom, a type of phytoplankton with a hard, shell-like cell wall that had never been seen in the area. The investigators also found traces of domoic acid.

In all, 107 people fell sick in the outbreak; 19 were hospitalized. Of those, three died and several suffered permanent brain damage. The 84-year-old shopping center owner survived. Doctors came to call the disease amnesiac shellfish poisoning.

To prevent outbreaks, the Canadian government began monitoring mussel beds for domoic acid. The toxin has appeared elsewhere. In 1991, it was blamed for the illness of at least 20 people in Washington and Oregon who had eaten razor clams.

Like others on the Pfiesteria team, Perl was dubious in August when asked to help study suspected cases of Pfiesteria poisoning.

"It sounded at the time like it was a nothing illness," she said.


She quickly changed her mind after the team conducted a battery of neurocognitive tests that showed an uncannily consistent pattern of severe, short-term memory loss. Positive emission tomography (PET) scans, which depict metabolic activity in the brain, showed a striking pattern in those victims.

While still working full time on hospital duties, Perl ran the state's Pfiesteria hot line out of her office for two weeks. Now she's seeking money to launch a more extensive study of Pfiesteria on the Eastern Shore.

"We really want to see long term what's going on," she said. "We want to find out what are important exposures."

Domoic acid seems far more dangerous to humans than Pfiesteria's toxins. A lethal dose of Pfiesteria's toxins doesn't seem to exist, at least not in lab rats. While domoic acid strikes people who eat tainted shellfish, Pfiesteria seems to affect only bTC those who come in contact with waters where the microbe is active.

Both investigations represent a critical opportunity: the chance to learn enough about an emerging disease to stop it in its tracks.

"You have a moment to seize," she said.


Pub Date: 10/23/97