On trail of a rare disease
By Tony Bartelme
The Post and Courier
Sunday, August 15, 2010
In September 2005, a letter landed on the desk of Dr. Jerry Gibson, the state’s top disease detective.
It came from a person who once worked on the sixth floor of the Medical University of South Carolina’s Children’s Hospital. In the letter, the person said that three colleagues who worked within steps of each other developed a rare disease called myasthenia gravis.
Myasthenia gravis means “grave muscle disease” in Latin. Though it’s rarely fatal, sufferers may lose muscle control in their arms and legs and may have trouble swallowing and talking. Scientists think it’s caused by an abnormal immune response but don’t know what triggers it. There is no cure.
Photo by Brad Nettles
The Post and Courier
MUSC Children’s Hospital is located on Ashley Avene at Sabin Street in Charleston.
Gibson was intrigued. As the state’s chief epidemiologist, he runs a department that tries to prevent as many diseases and health problems as his budget will allow. And scientists have long relied on the study of clusters to identify a mysterious disease’s cause and stop its spread. Gibson convened a committee to investigate the letter writer’s allegations.
What did and didn’t happen next is a story of detective work, mystery and frustration. On a deeper level, it’s about a world that scientists sometimes don’t understand well enough to determine cause and effect, and where the outcome isn’t always clear.
The red brick Children’s Hospital sits on the southern edge of MUSC’s campus and is the state’s largest pediatric health center. It was built in 1987 and has rooms for patients, offices and labs. To do tests and clean utensils in the lab, employees and students routinely use a laundry list of chemicals, including chloroform, formaldehyde and other known carcinogens, documents obtained by The Post and Courier show.
In the late 1990s, some of the labs’ hoods — air handlers that vent chemicals outside the building — went down for days at a time. Still, internal inspection reports reveal few violations of federal health and safety regulations, other than citations for failing to properly label hazardous chemicals. Heather Woolwine, MUSC media relations director, said that there have been “no reports of significant indoor air problems or chemical exposures in the Children’s Hospital facility.”
The myasthenia gravis letter in 2005, however, described at length employees’ concerns that they might have been exposed to something that triggered their illnesses. The letter writer said that three employees developed symptoms of myasthenia gravis during the late 1990s and that the facility had ventilation problems that may have exposed them to lab chemicals and other vapors.
The letter writer claimed to know of 25 other workers and researchers on the floor who had immune disorders, rare nerve disorders and other health problems. A fourth employee with possible myasthenia gravis would surface later. (Employees discussed in the letter to Gibson were not identified in documents obtained by The Post and Courier under the state’s Freedom of Information Act. Officials with DHEC declined to identify the patients, citing medical privacy laws.)
The letter writer noted that the disease was relatively rare. Estimates vary, but researchers think that 14 per 100,000 people in the United States have myasthenia gravis. That makes it more common than Lou Gehrig’s disease (Amyotrophic lateral sclerosis), which affects one or two people per 100,000, but not something doctors typically see.
“It’s not super rare, but it’s very uncommon,” Gibson said. “So we said, ‘Yeah, we need to look at this.’”
Gibson has gray hair, thick eyebrows and a reassuring voice that doesn’t hint at the pressures of his job. His office in downtown Columbia is in a building designed in the 1820s by noted architect Robert Mills, and Gibson says with a smile that it originally was built as an asylum for mental health patients. As a young man, he worked in the Peace Corps in what today is Malawi and was overwhelmed by the suffering and health problems he saw. Doctors could treat only so many people, he thought. “That’s where I got the idea that I wanted to do something about preventing diseases,” he said.
After receiving his medical degree, Gibson went into epidemiology, a field that identifies the risks and causes of diseases and seeks ways to prevent them and their spread. Today, he heads the state Department of Health and Environmental Control’s bureau of disease control, a division with responsibilities that range from preventing flu outbreaks to tracking down partners of people with sexually transmitted diseases.
Cluster investigations long have been an important tool for epidemiologists. One of the field’s defining moments happened in the mid-1800s in London during a cholera outbreak. At the time, people thought cholera was caused by “miasma in the atmosphere,” but a physician and scientist named John Snow theorized that it might be related to water contaminated with bacteria. He mapped cholera cases during a particularly deadly outbreak in his neighborhood.
“I found,” he wrote later, “that nearly all the deaths had taken place within a short distance of the (area’s drinking water) pump.” The pump was disabled, and cholera cases in the area soon dropped.
But cluster investigations can be tricky.
“Random does not mean evenly distributed,” Gibson said. “Any random pattern of dots will look like it has clusters. The challenge is to distinguish clusters that happened from chance from the ones that have causes in space and time.”
The only proven cluster in South Carolina was discovered in the late 1990s when residents in Charleston’s Neck Area told DHEC they were concerned about the high number of cancers in their area. Using the state’s then-new cancer database, DHEC researchers found elevated rates of five types: colorectal, stomach, lung, laryngeal and pleural. The pleural cancers stood out the most. Researchers found four times as many as what typically would be expected in the area. And this type of cancer provided them with a key clue: It usually is triggered by asbestos exposure.
Researchers eventually found that two-thirds of the pleural cancer cases involved people who once worked around asbestos at the former Charleston Naval Shipyard. Six months after they began their investigation, cancer registry researchers determined that a cluster did exist and that it was related to the shipyard, not where people lived.
Gibson said that investigation was easier than most largely because of the asbestos connection. Other investigations require more work, and sometimes dumb luck. He said that a noted cluster investigation began in Boston after two doctors struck up a conversation in an elevator and one mentioned that he had several patients with an extremely rare form of vaginal cancer. The other said he did, too. From that conversation, doctors and researchers identified eight patients in the Boston area with the disease. After a painstaking investigation into the patients’ medical and family histories, researchers discovered that the mothers of all eight took high doses of an estrogen drug used in the 1940s and 1950s to prevent premature labor. “It’s a great detective story,” Gibson said.
The vast majority of cluster investigations, however, turn out to be busts. In the 1990s, the Centers for Disease Control performed one cluster investigation after another without finding causes of diseases.
“They concluded that it wasn’t a good use of tax dollars, not a high yield for the cost of the activity,” Gibson said. “But now and then you learn something really interesting and helpful. So they’re worth doing if you have the resources.”
That’s why Gibson thought it was worth investigating the letter writer’s concerns about myasthenia gravis at MUSC.
“There were three people who were working at MUSC and they appeared within a space of a few years to come down with a fairly unusual condition.” If it turned out to be a real cluster, perhaps there was something in the building that was causing the disease, he said. “There are two benefits there: Maybe you could get rid of what’s causing it — prevention — and secondly, myasthenia gravis is a big mystery; nobody has really figured out what triggers it. So it’s a chance to understand what one of the triggers might be. So there were a lot of benefits: You can make people feel better, prevent new cases, and understand the disease.”
After discussing the matter with his colleagues, Gibson asked the National Institute for Occupational Health to study the letter-writer’s allegations, but the agency declined. He then contacted Ray Greenberg, president of MUSC, who agreed to help with an investigation.
“Greenberg is a smart guy and understood that even if something was found that implicated something in the (building’s) environment, they were much better off finding it and correcting it than covering it up, so he immediately wrote back and said ‘yes, we’ll cooperate fully,’ ” Gibson said.
Gibson formed a committee. Because the state had no money set aside to fund such an investigation, all parties agreed to do it on a volunteer basis. Joining staffers from DHEC were researchers from the University of South Carolina Arnold School of Public Health, a representative from the federal Centers for Disease Control and Prevention, and Dr. Daniel Lackland, a professor in MUSC’s neurosciences department who specialized in epidemiology. All signed agreements that essentially put them under DHEC’s legal umbrella, a move to reduce their exposure to lawsuits should any arise from their work.
Gibson said the group talked about whether Lackland’s participation was a conflict of interest because of his position at MUSC.
“If he had been the only one (on the committee), it would have been a worry,” Gibson said. “But there were a number of people on the team, and that dilutes the worry. And it was important to have someone on site. You also have professional ethics here; your job is to find the truth, especially if you’re an academic public health person.”
In late 2005, Gibson e-mailed one of the people who claimed to have myasthenia gravis: “We propose to get in touch with a very senior doctor at MUSC, who we hope will be willing to take responsibility for looking into this situation seriously … We will keep you informed of the progress!”
12 cases in Charleston
Lackland is a respected epidemiologist who has spent years investigating why South Carolinians have higher than normal rates of stroke and hypertension and why these rates are higher among black patients.
An epidemiologist has “to be comfortable with complexity and uncertainty, and that can be frustrating sometimes,” he said, and the investigation into myasthenia gravis at MUSC would be filled with both.
The first step was to verify whether employees on the floor in fact had myasthenia gravis.
To determine this, researchers needed detailed reviews of patients’ medical and work histories.
He and Gibson said that one patient was extremely cooperative but that two others declined to release the needed records or do in-depth interviews.
“They weren’t comfortable releasing their medical records, so in the end it was a dead-end,” Gibson said.
Despite the inability to obtain the employees’ medical records and cooperation, other members of the committee acquired data on medical records from the state Office of Research and Statistics, which records diagnoses of diseases throughout the state.
The database search generated some possible new clues: Between 1996 and 2005, 73 patients had myasthenia gravis in South Carolina. And of those 73, eight cases — 11 percent — involved MUSC employees.
Meanwhile, Charleston and Richland counties each recorded 12 cases, far more than any other counties in the state. That’s roughly twice as the state’s average rate, said Khosrow Heidari, a top DHEC epidemiologist also on the team.
Still, Heidari cautioned that it’s difficult to draw statistical conclusions from such a small number of cases. Gibson added that although Charleston had 12 cases, that number was still within what normally is found in other parts of the country with similar population levels.
By late 2006, the investigation was losing steam, mainly because the committee couldn’t verify the myasthenia gravis diagnoses, and therefore, whether there was in fact a verifiable cluster at the Children’s Hospital.
“There were dwindling levels of enthusiasm,” Lackland said.
The investigation chugged along for two years. Investigators learned that a fourth employee in the Children’s Hospital also may have myasthenia gravis, but they weren’t able to verify that diagnosis, either. In an e-mail to Gibson in 2008, Erik Svendsen, a USC professor, wrote that he didn’t think the numbers, statistically speaking, constituted a cluster.
“This still appears to be just a few unfortunate cases who happen to share the same employer,” he wrote. “I still do not believe that this small cluster alarm warrants a public health investigation, especially given the current economic constraints which our government and agency are currently facing — this could likely be a waste of valuable time and resources which could be better spent on public health issues which threaten larger populations in S.C.”
In the end, Lackland said the team “gave it our best effort. Even though we’re all volunteers, we were all very dedicated, (but) it just didn’t build up and get legs. Is there something we missed? Possibly. But I didn’t see it. Clusters sometimes just happen.”
In recent decades, disease clusters, especially those related to pollution, have made international headlines. A few cluster investigations have been made into popular books and movies (“Erin Brockovich” and “A Civil Action”). This comes amid a rising tide of cancer — every year more than 1.2 million cases are diagnosed — and another trend: an ever-increasing number of chemicals in commercial products, most of which have yet to be tested for their long-term affects on human health. The Environmental Protection Agency has required testing of only 200 of the 80,000 chemicals in use.
A report by the U.S. Public Interest Research Group Education Fund in 2002 found that health departments across the country receive more than 1,000 requests for cluster investigations a year and are “just one sign of the broad public concern about the role environmental factors play in the development of chronic disease.”
Amid all of these chemicals, new diagnoses and media attention, it’s easy for the public to connect the dots, whether the dots show something or not.
“We don’t want things to happen randomly,” Gibson said. “It’s a human reaction. We want there to be a reason for things.” But, he added, “It can be very harmful if people find the wrong reason,” a situation akin to charging an innocent person with a crime and allowing the true perpetrator to remain at large.
Since the letter landed on Gibson’s desk five years ago, the myasthenia case investigation has become the epidemiological equivalent of a cold case. MUSC has made extensive repairs to the Children’s Hospital. Labs on the sixth floor were converted into office space. As in any large organization, many employees have moved on. Trying to reconstruct what might or might not have happened in the late 1990s would be a massive research undertaking. Only the questions about what did or didn’t happen in the building remain.
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