When I first meet Rita Woidislawsky at La Colombe, her favorite coffee shop steps from Philadelphia, Pennsylvania’s upscale Rittenhouse Square, she’s effusive and bracingly direct—hugging patrons she knows, waving to baristas, and quickly finding the one table that’s about to free up. She’s dressed in workout clothes and delights in looking younger than her 68 years, with curly hair and an Israeli accent that’s lingered since she emigrated in her late teens.
Hidden from view is what attracted world-renowned scientists to Woidislawsky, and why she and I are together now: her unusually elevated high-density lipoprotein (HDL), or “good” cholesterol, and her decision about 5 years ago to join a research project that’s studying people like her. Like millions of volunteers who give blood and a few hours of their time to scientists, the project had barely registered on her radar over the past couple years. And then last month came a startling discovery.
After a chance encounter with the lead scientist, she learned that the research group had published a paper in Science in which her case figured prominently (although only her age at the time of most recent data collection—67—was listed). Googling at home on her computer, she found my 6-week-old news story about the paper and read it with mounting alarm. My story began: “The 67-year-old woman had sky-high high-density lipoprotein (HDL), the form of cholesterol long seen as protective against heart disease, and yet her arteries were lined with plaque.” Displayed above this opener was a generically captioned stock photo of clogged arteries, which Woidislawsky mistakenly assumed were her own, because the study had included an arterial ultrasound. “My heart doesn’t look so good” was one of the first things she said to me, referring to the photo that wasn’t her heart at all.
As I detailed in my story and was also reported in The Philadelphia Inquirer and elsewhere, the researchers suspected that the high HDL Woidislawsky had always been proud of might be deleterious. They traced it to an extraordinarily rare gene mutation she carried, which they hypothesized made it more difficult for her liver to siphon HDL cholesterol out of the circulation. This, in turn, they suggested, could lead to an increased risk of plaque—and indeed, the paper reported, Woidislawsky had somewhat more arterial plaque than would be expected for someone her age.
All of this was news to Woidislawsky. A Ph.D. psychologist who treats young women with eating disorders, she was distressed and began hunting down and emailing HDL researchers all over the world in an attempt to learn more about her unusual biology.
She was also, I realized, at the nexus of two distinct quandaries in clinical research. What health information do researchers owe the volunteers in their studies, especially when it’s not clear what it means and whether or how to act on it? And should researchers notify volunteers of publications in which their individual story is chronicled, even if it’s impossible for others to identify them from what’s written? Woidislawsky’s experience shows that “the risks of publishing information about people are not just privacy,” says Christine Grady, chief of the bioethics department at the National Institutes of Health Clinical Center in Bethesda, Maryland. “They might learn something about themselves that they didn’t know.”
An HDL champion
Woidislawsky was in her 40s when she found out she had high HDL. Eventually it climbed to 152, about triple the norm. “It was always very fascinating,” she says. “I was sort of proud, wow, here I am walking around with high HDL, it’s very unusual.”
Her doctor at the time agreed, and suggested she connect with a research group at the nearby University of Pennsylvania (UPenn). In recent years HDL has been a source of confusion among biologists. Although high levels are associated with less heart disease, drugs that raise HDL have failed in clinical trials. Researchers know they’re missing something, and hope that people like Woidislawsky can help them understand what that might be.
I was hoping that the 67 year old woman was not me.
I was hoping that the 67 year old woman was not me.
“We didn’t really anticipate that we would get any results genetically that would be in any way relevant to the person’s health,” says Daniel Rader, the well-respected geneticist and lipidologist who leads the UPenn team. “When we started this study,” about 15 years ago, “that was absolutely the belief -- these people with high HDL, what a lucky thing to have, if we could only understand what causes this, we’d have great new insights.”
Rader was eager to include Woidislawsky in his genetics study. She signed the necessary forms, and a couple of researchers arrived on her doorstep to draw blood. DNA sequencing revealed a mutation in a gene called SCARB1, but, as is the custom of this group and many others, Woidislawsky wasn’t told because no one knew what, if anything, the mutation meant. Instead, the research team reached out to her again and asked whether she would be willing to undergo an ultrasound of her carotid arteries. She readily agreed.
Woidislawsky soon forgot all about the study. Then, sometime around early March, she says she ran into Rader at her usual haunt, La Colombe. The two chatted amiably, and she mentioned she had recently been diagnosed with high blood pressure. Rader suggested she make an appointment with him. (Her physician at UPenn had left the practice, and he offered to fill in.) The HDL study didn’t come up, she recalls.
But it was about to be published, along with news stories in several outlets. Woidislawsky had been the only person in the world whom Rader’s team could find with two copies of a mutation in the SCARB1 gene, one inherited from each parent. The scientists identified about 300 others with one copy.
Rader was uncertain what, if anything, to share with Woidislawsky. On 11 March, weeks before their appointment, he sent her an email. “I wanted to let you know that our manuscript describing the gene variant we found in you was published today in the journal Science,” he wrote. “It was written up in today’s Inquirer! You might want to take a look.” He added, “I can’t thank you enough for your gracious participation in our study.”
The message didn’t make much impression on Woidislawsky. It was the first she’d heard about having a gene variant, but she figured it had been found in thousands of other people, too. She read an account of the work in The Philadelphia Inquirer but didn’t connect its message—that high HDL in certain cases could be problematic—to herself. She assumed the 67-year-old woman with plaque in her arteries couldn’t possibly be her.
She sent Rader an email: “I never think of myself as a Narcissist but I was hoping that the 67 year old woman was not me. You will explain more about the results when I see you.”
Several weeks later, Rader did. On a Friday in late April, she arrived at his office for her appointment. There, because she’d asked, he broke the news that she was the woman in the article. “And let me talk about what it means for you,” Rader recalls saying. He assured her that he felt she had nothing to worry about, but because of the modest increase in arterial plaque, he prescribed Crestor, a cholesterol-lowering drug, as a precaution.
Woidislawsky struggled to process this turn of events. “I was sad,” she says. “I was so startled.” She didn’t know what to say, and could only wonder how she had “clogged arteries” but was so outwardly healthy, a devotee of pilates, yoga, weight-lifting, and aerobics.
“After the appointment, that weekend that’s all I wanted to talk about,” she says. “I researched more about the genetics, those mutations. … I want to know what else I can do that I don’t do” to protect her health. Her two adult daughters were shocked by the revelation. They are considering getting tested for the same genetic variant, about which almost nothing is known.
Lessons all around
Woidislawsky’s story holds lessons for researchers like Rader, for the ethicists who guide them, and even, I came to believe, for journalists like myself who communicate new findings. “In general, we don’t do a good job of giving people who have volunteered in research any feedback on the study,” says Grady, who urges, “give people results more often, even in the aggregate.” Grady wonders, too, whether research volunteers understand that a primary goal of scientists is to publish their results. “There’s a lot of consent forms that don’t say anything about publication,” Grady says.
Woidislawsky stresses that she likes Rader and doesn’t want a negative article about him. That said, she sensed that the scientists were there when she had something they wanted -- but not when the converse was true. “They call you lots of times to get the bloodwork and they’re at your doorstep, but when it’s time to really say what’s it all about, they’re gone,” she says.
Because Woidislawsky was singled out in the paper, Grady says, it “seems respectful” to share that with her. Had there been even one or two others with two mutated copies of the gene, “it would be different. … The information would be less directly about her.”
Rader now says he’d been uncertain how to address the situation. Although not a case study, “this article was so sort of dependent on the initial discovery of her,” he says. He wondered “if the right thing is to let her know that the article is about her. … On the other hand, a case can be made that it’s reporting research results that the person didn’t sign up” to learn about. The consent form Woidislawsky signed said nothing about returning results, whether they were published or not.
Journals don’t offer much guidance. When it comes to case studies, some, like The Journal of the American Medical Association and The BMJ, require that the subject sign off on it prior to publication—but only if he or she can be identified from the manuscript, which wasn’t the case for Woidislawsky. Science has no specific guidelines for case studies.
Today, researchers increasingly lean toward returning medically relevant findings, and the studies Rader runs now include a question for those enrolling: Do you want to know of any findings that may be of interest to you? But even under these guidelines, would the findings about Woidislawsky have met the bar for return? When it comes to the SCARB1 mutation, probably not; it isn’t on the list of 56 genes that the American College of Medical Genetics and Genomics suggests giving back to study volunteers. And “everybody has plaque in their arteries,” points out Barbara Koenig, a medical anthropologist at the University of California, San Francisco, who studies the return of research results.
“I really think we need to start a much bigger conversation about this and get some collective ideas from patients about how to handle this,” Koenig says. “The patients want to be partners,” and Koenig’s work has shown that most want “everything back—they don’t care if it’s uncertain,” which is something that worries her because those findings can be so difficult to interpret.
Woidislawsky found my news story, and me, a few days after her appointment with Rader. She wanted to know whether I could connect her with other researchers in the field. As our conversation progressed and we made plans to meet, she grew intrigued by the idea of publicly sharing her story. And I began considering the lessons her tale might hold for journalists. Despite singling her out in the research paper, the authors were relatively circumspect about her cardiac health. They wrote that the thickness of her carotid artery wall was above the 75th percentile for women her age (which doesn’t necessarily indicate a blockage), and that she had “detectable plaque” in the left internal carotid artery. “I was cognizant that this was an n of 1,” Rader told me last week, “and that the carotid plaque was not that impressive.” The paper also included a wealth of other data, like mouse studies.
I began to wonder, as we talked and I felt a powerful urge to reassure her, whether my news story had overplayed Woidislawsky’s individual tale in order to more dramatically suggest that HDL might not always be advantageous. Other reporters had gravitated to this narrative as well. One story described Woidislawsky as a “Jewish grandma” and said that despite high HDL, “her arteries are still as thick and gummed up as an old rusty pipe.” What was in the press about her coronary arteries was enough to induce palpitations in anyone.
In fact, several HDL researchers to whom Woidislawsky reached out assured her that the findings are preliminary and that she should follow the usual directive: exercise and control low-density lipoprotein cholesterol. “Stick with the red wine and exercise—I think you will be fine!” one researcher not involved in Rader’s study told her, when she explained how much she loved red wine and that she hoped she wouldn’t have to give it up.
Rader now plans to see Woidislawsky again soon, recognizing that she needs more reassurance and whatever additional information he can offer. She’s planning on a cardiac stress test, and hopes that his earlier promise stays true. “I said to Dr. Rader, ‘When am I going to have a heart attack?’” she tells me. “And he said, ‘Not before 100.’”