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Honoring Jack Fowler

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Honoring the Legacy of Jack Fowler

Jack Fowler

John “Jack” Fowler, a giant figure in the field of radiation biology and oncology and professor emeritus of human oncology and medical physics at the University of Wisconsin School of Medicine and Public Health, died in December at age 91. On February 24, UW colleagues gathered to celebrate his scientific contributions and his lasting impact as a mentor, colleague and friend.

Fowler served a joint appointment in the school from 1988 until 1994 and again from 1999 until 2003 after a long and successful career in England.

Much of his work helped bridge the gap between radiation biology and the radiation oncology clinic. By mathematically modeling how radiation interacts with tissue, he advanced the concept of dose fractionation—dividing a radiation therapy dose into several small doses to maximize the therapeutic effects and minimize damage to healthy tissue.

He helped define the “biologically effective dose” to better describe radiation treatment schedules. This has become the standard for predicting radiation damage when the dose rate and dose-per-fraction rate are altered.

Fowler’s influence and lasting legacy were abundantly evident at the Professor John “Jack” Fowler Celebration Symposium, which highlighted the breadth of his contributions and subsequent research that his work has stimulated.

Translational research pioneer

Before coming to UW–Madison, Fowler was director of the Gray Laboratory in the UK, where he guided and influenced the work of many leading radiobiologists and radiation oncologists. Among them was Dr. George Wilson, now a professor of radiation biology at Beaumont Health System.

At the symposium, Wilson highlighted Fowler and colleagues’ work with Tpot (tumor potential doubling time)—a means to measure the potential growth rate of tumor cells during treatment to help select patients for altered fractionation treatment. While this particular measure was ultimately found to be insufficiently helpful to warrant widespread adoption, it was this kind of work that showed Fowler’s affinity for translational research—work that bridges the gap between the lab and the clinic.

Wilson also showed a cartoon about translational research that Fowler had drawn in 1992 that depicted a bridge between mice and people. “Jack was a real pioneer because in those days no one knew what translational research was, but Jack was already onto that,” Wilson said. “The cartoon is a testament to how far ahead of his time he really was.”

New paradigm for treating prostate cancer

Fowler was a mentor to Dr. Mark Ritter, DHO professor of human oncology, who said Fowler “helped open a whole new paradigm for treating prostate cancer.” This approach uses hypofractionation, dividing the total radiation dose into larger doses over a shorter period of time than standard radiation therapy.

Ritter embarked on a series of clinical studies based on Fowler’s work and influence and is currently studying very short, large fraction size treatments that also further dose escalate to prostate tumors found on MRI imaging.

“Jack Fowler was a profound influence on the field, on the department and on myself personally during his time with the department,” Ritter said. “He has been an extraordinary mentor and teacher throughout his career and set a tremendous example for all of us to try to emulate.”

LQ Model

Dr. Bert van der Kogel, visiting professor of human oncology, highlighted Fowler’s work on the use of the linear-quadratic (LQ) model to calculate cell and tissue repair after radiation therapy.

This work is significant because it shows that patients undergoing more than one fraction per day lose some repair capacity, which has important implications for designing radiation treatment plans.

HDR Cervical Brachytherapy

Dr. Kristin Bradley, DHO associate professor, talked about how Fowler’s work laid the cornerstone for development of high dose rate (HDR) cervical brachytherapy.

In the past, treatment of cervical cancer involved low dose rate (LDR) brachytherapy—insertion of radioactive material directly into or near a tumor. Fowler and his colleagues helped optimize fractionation schedules for high dose rate (HDR) brachytherapy, which could provide more precise placement of sources and highly customizable dose distributions.

The move to HDR brachytherapy and image-guided adaptive brachytherapy has demonstrated improvement in cervical cancer outcomes, Bradley said.

“Jack has been an inspiration to me. He was always so curious, always wondering, questioning. And he was so excited about what he did,” Bradley said. “I hope that we as a department continue to move this excitement forward.”

Targeted radionuclide therapy

Dr. Bryan Bednarz, associate professor of medical physics, never met Jack Fowler personally but his work with targeted radionuclide therapy is a continuation of Fowler’s legacy.

Targeted radioactive therapy is the systemic delivery of a radioactive molecule that shows preferential uptake in tumors. Bednarz is developing tools in his lab to enable more accurate measurement and dose description of this type of treatment, which, unlike external beam radiotherapy, can target distant metastases.

Combining radiation and immunotherapy

Dr. Zach Morris, DHO assistant professor, is building on Fowler’s work by studying the how the use of radiation affects the immune susceptibility of tumors.

In addition to causing double strand DNA damage, radiation may also interact with immune response. Morris is studying cells that survive irradiation, which may increase the expression of markers that impact their susceptibility to immunotherapy.

Radiation may also play a role in eliminating cells that suppress the immune response to tumors, Morris said.

“This work ties together questions of timing, dose and fractionation,” Morris said. “We’re just beginning to scratch the surface of these issues in the context of immunotherapy. There is still lot of work to be done here, and I imagine that Jack would have a lot of thoughts about how to encourage this and track down answers.”

MRI-guided radiotherapy

Dr. Mike Bassetti, DHO assistant professor, highlighted the department’s work in MRI-guided radiotherapy, which also builds on Fowler’s work.

The advantage of MRI is that it provides better delineation of soft tissues. The department’s ViewRay machine, which uses MRI to guide treatment, enables clinicians to monitor mobile tumors during treatment and can be combined with a breath hold technique to deliver radiation only when the tumor is within a defined position.

High-quality imaging of soft tissues helps improve patient alignment and increases confidence in using high doses near normal tissues that move or are very sensitive to radiation, Bassetti said.

MRI-guide radiotherapy will also enable adaptive therapy—the ability to re-plan a radiation dose in real time.

“The other thing I’m really excited about looking at how treatment response can tell us about the underlying biology during treatment and perhaps predict during treatment who’s going to respond who’s not going to respond,” Bassetti said.

Energetic researcher and mentor

In addition to highlighting Fowler’s many scientific contributions, speakers at the symposium emphasized how much they enjoyed working with this energetic, prolific and passionate colleague.

“Jack was a remarkably enthusiastic person, a thinking person,” said Dr. Paul Harari, DHO chairman and the Jack Fowler Professor of Human Oncology. “He loved, loved, loved to talk about research, and it didn’t matter to him if you were an 18-year-old high school senior or the dean of the medical school, he gave equal time. There was no hierarchy for Jack.”

Fowler’s energy and productivity are legendary, as Dr. Steven Howard, DHO professor, illustrated in an anecdote about collaborating with him.

Early in his career Howard had an idea on reducing dose rate to deliver radiation more safely. One morning, he shared the idea with Fowler, who said, “That’s a good idea. I’ll think about that.”

Howard then went to the clinic and at around 3 o’clock, Fowler said, “Steve, I’d like you to come to my home for dinner tonight. By the way, stop by my office because I’ve graphed this all out. It’s all modeled.”

They didn’t talk much about science that evening. Instead, they spent about three-and-a-half hours listening to jazz, drinking beer and enjoying the lamb dinner Fowler’s wife Anna prepared.

At around 9:45, Fowler said, “Let’s write the paper,” Howard recalled.

Howard demurred and suggested working on it the following day and Fowler agreed. The next morning, Fowler handed Howard the completed manuscript. Fowler then submitted the paper, and it was published without the need for revisions.