Profiles in Cancer Research
Dr. Sholom Wacholder
Senior Investigator, Biostatistics Branch
NCI’s Division of Cancer Epidemiology and Genetics
Dr. Sholom Wacholder has used three criteria in guiding his career choices: “Are you good at it? Are you having fun? Are you making a difference?”
A talented biostatistician who is revered by colleagues, he is credited with contributing to numerous seminal epidemiologic studies, so he’s hit on the first and third marks.
But it may be surprising to learn that an area he has found to be difficult and therefore not always fun—communication—is central to the work that he does.
“I’m not a natural writer, and I have to work hard to communicate effectively,” he admitted. “But, really, communication is critical for this job. I always paraphrase Robert Hoover [the NCI epidemiologist], who said that good science that nobody understands or nobody can learn from isn’t doing the job.”
Points of Interest
“Like most every kid, I had no idea what I wanted to do with my life,” said Dr. Wacholder. “I just knew that I didn’t want a career that would require me to write papers.” He said that his excitement about math first emerged during a sophomore-year honors math course at the University of Cincinnati, where he enjoyed the practice of proving abstract theorems.
He turned his attention to the more practical applications of his skills when a friend of the family, a radiologist, suggested that he contact a colleague in the University of Cincinnati’s department of epidemiology and biostatistics. From there, Dr. Wacholder went to graduate school to study biostatistics at the University of Washington in Seattle, and he joined the Biostatistics Branch at NCI in 1986.
“What I try to do in much of my work is think about the clinical impact,” Dr. Wacholder said.
“The point is to improve public health.” Means to that end often begin with an observation from his own research.
For example, the March 27 issue of the British Medical Journal (BMJ) published a study that Dr. Wacholder led on HPV vaccine safety. The analysis used data on pregnancy loss pooled from two randomized controlled trials of the HPV vaccine Cervarix. “Overall, vaccinated women did not appear to have a higher risk of miscarriage,” explained Dr. Wacholder, “but concern remains for a possible effect in women who conceived within 90 days after vaccination.” Based in part on the data in the BMJ publication, the FDA asked the manufacturer for post-licensure studies on risk of miscarriage, because “even a tiny effect in a small subset of women adds up to a large number of possible miscarriages in tens of millions of women to be vaccinated,” explained Dr. Wacholder.
In the mid-1990s, Dr. Wacholder conducted a study on the risk of breast cancer among women of Ashkenazi Jewish descent who had BRCA mutations. Previous studies reported an 85 percent risk of breast cancer for these women before the age of 70. Dr. Wacholder and his colleagues surveyed more than 5,000 Ashkenazi Jewish women and men in the Washington, DC, area using the “kin-cohort” method—an approach that Wacholder developed in which risk is estimated from the cancer history of family members. Using this new approach, he found the risk of breast cancer in BRCA carriers to be closer to 50 percent.
“All of the previous data had come from families with a number of breast cancer cases,” he said. “Our population-based study found many carriers had no or minimal family history, and, hence, our estimates of rates in carriers are much lower than most earlier estimates. Subsequent studies confirmed our results. I told the Wall Street Journal that this was the difference between a sure thing and a coin flip.”
Teaching to Learn
Dr. Wacholder smiles often as he speaks about his work. At times he sounds philosophical. Echoing Einstein, Wacholder believes: If I can’t explain it simply, I don’t understand it well enough.
“I never feel I truly understand something if I can’t explain it to someone else, orally or in writing,” he said. “The teaching part of what I do is essential to my work.” The biggest challenge, he explained, is boiling down the extraordinary range of details to those few essential points. “To communicate, you have to think of the audience, and not just what excites you.”
Collaboration is key to his work, he said. “I spend a lot of time in person-to-person and group settings,” he said. “A big part of my job is to make sure my collaborators understand and appreciate the statistical and methodological issues.” Dr. Wacholder also spends a lot of time mentoring other scientists. One mentee stands out in his mind.
“Nilanjan Chatterjee was a graduate student when we first met. When he came here as a post-doc, everyone recognized him as extremely talented. And now he’s my boss,” said Dr. Wacholder, laughing.
Dr. Chatterjee remembers the generosity of his former mentor. “Sholom allowed me to work independently and gave me advice,” he said. He also described Dr. Wacholder as a visionary when it comes to thinking about the big picture of a research question and all the elements—study design, false positives, and genetic applications, for example—that will come along with it.
“The way he thinks about selecting a problem, the criteria that he uses, is something you can’t learn from books,” said Dr. Chatterjee. “You can only learn it from seeing someone else do it. So I was really fortunate to be one of his mentees because, even now, when I think about taking on a project and I have to prioritize, what I learned from him helps me.”
Looking back at the three criteria he uses to guide his career, Dr. Wacholder’s résumé speaks to both his professional success and his impact on public health: the Chinese benzene workers study and other occupational hazard research; more than 20 years working on HPV and cervical cancer research; and recently, a report on the impact of inherited genetic variation on breast cancer risk in clinical settings. His teaching and communication skills have continued to develop through his work as a statistics editor for the Journal of the National Cancer Institute and in editorial positions at Epidemiology, Cancer Epidemiology Biomarkers and Prevention, and the American Journal of Epidemiology.
The “fun” element is clearly present as evidenced by his total absorption in his subject matter. Dr. Wacholder talks about his research with visible joy and awe. It’s also clear that he is always learning and teaching and that, for him, the two are one and the same.