Only a handful of scientists at Fred Hutchinson Cancer Center have been around longer than the institution itself; longtime public health researcher Ross Prentice, PhD, who retired at the end of 2022, is one of them.
“I came here in 1974, when ‘the Hutch’ was little more than a twinkle in Bill Hutchinson’s eye,” Prentice said in a recent interview. “Back then, Fred Hutch was a new institution and didn’t have a lot of infrastructure. Almost none. There really wasn’t even an annual budget process then. There were challenges — access to space, budget, recruitment resources — but at the same time, it was an invigorating environment; it was entrepreneurial. We needed to look after our own interests if we wanted to flourish.”
Unquestionably, Prentice flourished.
The biostatistician worked at Fred Hutch and the University of Washington for nearly 50 years, in a variety of roles, serving as a principal investigator of the Women’s Health Initiative and leading the effort to establish Fred Hutch as the WHI’s Clinical Coordinating Center. He served as senior vice president and director of the PHS Division for more than 25 years while at the same time making major contributions to population science and clinical research.
Over the course of his career, Prentice published over 500 scientific papers and 40 of them have at least 500 citations (few papers get over 100 citations). It was Prentice who first proposed the case-cohort study design and Prentice who was the first to establish the operational criteria for the use of surrogate endpoints in clinical trials.
A runner, a scientist, a born mentor and a “towering figure in statistics,” Prentice witnessed countless changes over the years, both at Fred Hutch and in the world of cancer research. But his compassionate leadership, his scientific rigor and his dedication to finding answers to life’s big questions remained a constant.
“Ross Prentice has been a remarkable team leader,” said Senior Vice President and PHS Director Garnet Anderson, PhD, holder of the Fred Hutch 40th Anniversary Endowed Chair. “He’s been inclusive and respective of the perspectives of multiple disciplines, courageous and persistent in the face of opposition, strategic and insightful in navigating complex situations, and always extremely generous in sharing credit. It has been my privilege to work for and with him these past 30 years.”
Born and educated in Canada, Prentice made the decision to come to Seattle soon after learning that a new cancer research center was forming.
He was quickly hired on and began working with physician-scientists like Noel Weiss, MD, Don Thomas, MD, and Rainer Storb, MD, learning not just the nuts and bolts of a pioneering new procedure called bone marrow transplantation and the challenges that came with it like graft-vs-host-disease, but also about the U.S. cancer research funding process.
“In Canada, there was nothing like that opportunity for getting sizable grants for big projects,” Prentice said. “We’re fortunate that we have a system that relies on the quality and promise of the research idea. The National Institutes of Health is the best grant awarding system in the world.”
Prentice used that system to Fred Hutch’s advantage, working with public health scientist and Fred Hutch President Robert Day, MD, to bolster research programs within the newly formed Public Health Sciences division.
And with every decade, he made his mark. Or as he put it, “it was a time to make hay.”
He was part of the team that created the first cancer prevention and control unit in the country, the Hutch’s Cancer Prevention Research Program, after the launch of the National Cancer Institute’s Division of Cancer Prevention and Control in 1983. He took over the leadership of PHS and grew the epidemiology and biostatistics program; he also helped launch the CARET trial to explore the efficacy of Carotene and Retinol for lung cancer prevention and with the encouragement of others, started exploring the link between nutrition and chronic disease.
“Bob Day stopped by my office one day and said the NCI was going to fund a study of low-fat diet for breast cancer prevention,” Prentice said in an interview published in Statistical Science. “He asked if we could apply for the coordinating center. I decided to try it and put in a successful proposal to form a statistical center for the initiative phase of what was called the Women’s Health Trial. That was a turning point with regard to my collaborative research.”
Prentice had no track record in that particular field, Anderson said, but nonetheless immersed himself in the research.
“That was the initiation of a nearly 10-year journey that led to his application in 1992 for the coordinating center for another, much larger effort, called the Women’s Health Initiative,” she said. “His leadership in nutrition and health represent an inspiring example of the impact that a statistician may have by engaging deeply, consistently, and creatively in a scientific area and, where needed, taking on responsibilities beyond the data.”
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Worst dietary culprit: Sodium. If you start studying the labels in grocery stores, you’ll find it’s very difficult to choose a low sodium diet. One tip: don’t use a lot of canned or packaged foods.
Best dietary friend: Veggies, fruits and grains. Grains are generally good as long as you don’t screw them up by adding too much junk.
Is fat friend or foe? A high-fat diet is to be avoided partly because it tends to correspond to a high-calorie diet. Avoid trans fat and limit your saturated fat, but don’t replace it with other fat. Carbohydrates are a better replacement choice.
Advice for the research world? Be more open to change.
This early involvement in nutrition and chronic disease risk was when Prentice first began to investigate, and question, the methodology used in this field of study.
“I became slowly convinced that observational nutritional epidemiology, as practiced at that time, using self-reported dietary data, was not likely to yield reliable information on topics of great public health importance,” he said.
Food frequency questionnaires, he saw, were only as reliable as participants’ memories and research showed many people undercounted their calories, particularly if they were obese or overweight.
He and other Fred Hutch scientists began exploring the use of measurable biomarkers — from blood, urine and other body fluids — as a way to glean more dependable data about dietary intake and its relationship with disease. For example, Prentice’s research on micronutrients and their impact on health, conducted with Hutch colleagues Marian Neuhouser, PhD, and Johanna Lampe, PhD, studied effects of at alpha-carotene; beta-carotene; carotenoids and vitamin E.
This biomarker work will continue after his retirement. In fact, Prentice believes nutritional epidemiology — how the food we eat affects our health (for better and for worse) — is actually still in its infancy.
“We simply do not have reliable data on how many calories you consume and how that relates to chronic disease,” he said. “There are well-documented problems with current approaches. It’s time to try additional approaches, along with what’s already being done.” Read more about Prentice’s thoughts on nutritional epidemiology.
— Senior Vice President and Director, Public Health Sciences Division Dr. Garnet Anderson
Research within the Women’s Health Initiative, perhaps Prentice’s largest and most successful effort, also still continues unabated.
Launched by the first woman director of the NIH, Bernadette Healy, MD, the WHI was a national health study that focused on strategies for preventing heart disease, breast and colorectal cancer and osteoporosis in postmenopausal women, in part as an effort to make up for a lack of research in this area (women and minorities weren’t well represented in most clinical research until the NIH made it a requirement in 1993).
The effort, sponsored by the NIH’s National Heart, Lung and Blood Institute, included a randomized controlled clinical trial, a large observational study and a community prevention study. Ancillary studies and additional analyses continue to this day.
The multi-faceted WHI clinical trial, which enrolled nearly 70,000 postmenopausal women, included a component to rigorously assess the risks and benefits of combined hormone therapy used mainly for menopausal symptom control. This trial component was terminated early by a safety monitoring committee because the overall risks of hormone treatment were considered to outweigh the benefits.
“Our 2002 JAMA publication was a defining moment for WHI,” Prentice recalled in his Statistical Science interview. “There was an elevation of breast cancer incidence in the active hormone randomization group, in conjunction with some elevation in coronary heart disease and a noteworthy elevation in stroke.”
The response was profound — and much of it negative — particularly from the gynecologic community, which was suddenly inundated with phone calls from women asking for advice. There was also pushback from the cardiovascular community who believed hormone therapy was beneficial, Prentice said, and from the pharmaceutical companies that made the popular combined hormone therapy.
But the FDA and other regulatory agencies took the results seriously and combined hormone therapy soon started to come with health warnings. More importantly, 70% of American women using these preparations stopped taking them. As a result of this one WHI finding, breast cancer incidence has been reduced by 15,000 to 20,000 women per year in the U.S. since the data was published.
“That one trial also saved many billions of dollars in health care costs, due to the sea change in the use of menopausal hormones that these trials induced,” Prentice said.
The WHI trial also offered valuable lessons for how to dovetail good science with good communication: when a subsequent WHI trial of estrogens alone was stopped early due to stroke risk, Prentice and his team gave professional societies a heads-up before results were published so they could adequately prepare.
Prentice would like to see today’s NIH develop a similar focus on prevention — complete with large randomized controlled trials, or RCTs. Many of the diseases that plague us are preventable in a much larger way, he said, pointing to the 20 to 25% reduction in coronary heart disease that came about as a result of focused disease prevention research and trials conducted in the 1980s and 90s.
A coordinated research agenda for chronic disease prevention is much needed, he said.
“We need to have additional compelling approaches to preventing major cancers, heart disease, obesity and diabetes,” he said. “Lifestyle interventions are what you want to get to, but these need to be effective in terms of health benefits versus risks. But the NIH, as good as it is, is not highly supportive of this type of prevention research. It’s an extremely hard-sell.”
The WHI provided a great model, he said, since it “conducted research that had outcomes across the entire spectrum of chronic disease.” It also helped researchers from a variety of fields connect and collaborate, learning from each other along the way.
“Some of my most valued colleagues work in cardiovascular disease, endocrinology, bone disease or diabetes, all through WHI,” he said. “These collaborations give one insights as to what might contribute to overall health benefit versus risk for our U.S. population.”
Collaboration has long been a hallmark of Prentice’s career and was the inspiration behind the Ross L. Prentice Endowed Professorship of Biostatistical Collaboration, one of the many honors bestowed on the scientist.
“At every turn, Ross fostered a collaborative spirit between the Hutch and UW,” Thomas R. Fleming, PhD, a UW professor of biostatistics and former department chair, said in a recent UW news story. “And in recognition of his achievements, of his dedication and of his leadership, the UW and Fred Hutch jointly established the Ross Prentice Endowed Professorship of Biostatistical Collaboration in 2005.”
Mentorship has also been a significant part of Prentice’s career.
Fred Hutch biostatistician Li Hsu, PhD, who first started working with him as a student at the UW, said she found him to be kind, patient and thoughtful.
“Ross was my PhD advisor and when I did my dissertation with him, he gave me a lot of space,” she said. “Whatever ideas I brought to him, he always listened carefully and showed interest.”
Hsu said in hindsight, many of her ideas and thoughts were probably “naïve or wrong” but Prentice never once discouraged or disparaged her.
“He would instead discuss and explore these ideas with me and guide me into the right direction without me even realizing it at that time,” she said.
Understandably, Prentice’s many contributions to science have garnered him dozens of awards and honors. He holds an honorary doctorate in mathematics from the University of Waterloo, where he received his Bachelor of Science degree; the Nathan Mantel Lifetime Acheivement Award from the American Statistical Association; the Mortimer Spiegelman Award from the American Public Health Association; the Committee of Presidents of Statistical Societies Presidents’ Award; the Marvin Zelen Leadership Award in Statistical Science from Harvard University; the American Association of Cancer Research/American Cancer Society Award for Research Excellence in Cancer Epidemiology and Prevention; and the American Association for Cancer Research Team Science Award. In 1990, he was elected to the Institute of Medicine/National Academy of Medicine. Even part of the Public Health Sciences building is named for him — the Ross L. Prentice Atrium.
Despite this “celebrity scientist” status, Prentice is very approachable, said Ruth Etzioni, PhD, who was selected as a Prentice professor in 2018.
Although it took a while for her to discover this.
“I watched Ross from a distance for the bulk of my years at Fred Hutch, but was always starstruck,” she said. “He wasn’t just a giant in statistics and methodology, but a giant in epidemiology, as well. He literally wrote the book on survival analysis.”
Etzioni, holder of the Rosalie and Harold Rea Brown Endowed Chair, said she worried about presenting a worthy enough lecture all during the year in which she held the Prentice professorship before finally working up the courage to ask Prentice to lunch to discuss her chosen topic.
“It was like all of these walls I’d envisioned between him and me vanished,” she said. “I discovered that he’s mischievous and funny and spiritual and humble while at the same time confident, which he should be. He’s just a genuinely kind person.”
Many others agree, including colleague Charles Kooperberg, PhD, who’s worked with Prentice since the early days of the WHI.
“Ross is a great leader and colleague,” he said. “I've learned a lot from him over the years. We all have. He has accomplished so much and positively influenced so many in his lifetime.”
What plans does Prentice have for the future now that he’s retired?
There will be a bit of consulting work at Fred Hutch, he said. There will be extended stays in Hawaii, where he regularly vacations with his wife, Didi, and more time spent with his daughters, sons-in-law and four grandchildren.
And there will be more involvement in the church, something that’s become more meaningful to him over the years.
“For me, the spiritual side is a central part of human existence,” he said, scoffing at the notion that science and spirituality don’t mix. “If you look back, early scientists were often theologians and deeply involved in faith. For me, there’s no inconsistency there.”
Science focuses on learning about our physical world and physical person, Prentice said, “but there’s more to the human being than that. There’s the notion of life beyond the life that we are currently part of. There’s the possibility that God may choose to interact directly with you on a one-to-one basis. Not by you taking a bunch of measurements of what’s been created, but by listening.
“I do find it terribly exciting that we might be able to interact in a meaningful way with the creator of the universe,” he said.
As usual, Prentice is off to look for answers to life’s big questions.
Diane Mapes is a staff writer at Fred Hutchinson Cancer Center. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor, she blogs at doublewhammied.com and tweets @double_whammied. Email her at email@example.com. Just diagnosed and need information and resources?
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