The Cancer Letter: Two singular men shared an uncommon greatness: Waun Ki Hong and John Mendelsohn

Posted: Monday, February 11, 2019

Waun Ki Hong and John Mendelsohn were singular forces who combined to change the world of oncology

The Cancer Letter, 8 February 2019
Guest Editorial: Scott Lippman, Daniel D. Karp & James L. Abbruzzese

Waun Ki Hong and John Mendelsohn were singular forces who combined to change the world of oncology and, in the process, the lives of countless trainees, faculty, patients, and families.

After these giants of cancer research and treatment died last month—they died five days apart—much was said about their careers and awards, of which there were many. All of this was important, but it’s done, and now we can look at some of the timeless and instinctive leadership ingredients that shaped Ki’s and John’s success.

Through the course of many interactions, their approach to life synergized with each other, and they genuinely became the legends that they created. The relationship was not superficial. They were equals, and they took the time to learn from each other. They worked and played (tennis) together, they discussed programs and science, and in the end, they took care of each other. Whether they explicitly discussed leadership principles we may never know, but the closeness of the relationship suggests that they communicated deeply about how to work effectively in the context of complex academic and scientific systems to accomplish their personal goals while promoting institutional objectives and the work and careers of others.

Those of us lucky enough to have been mentees and colleagues of Ki and John experienced the unique dynamism and influence of each. What they did, and their impact, is a matter of public record; how they did it is another matter altogether.

Over the past month, we have deeply reflected on our history and experiences with Ki and John, and found ourselves researching little-known facets of their careers, gaining insights by tracking down students and colleagues who were delighted to reminisce and recall deeply etched, fond memories of these men, reaching as far back as the early 1970s.

We were struck by how Ki’s and John’s approaches, attitudes and outlook, decisions and dispositions made them the leaders they were. Though much is written on the science of leadership, Ki and John, through their individual and joint accomplishments, could have written a fine book on the applied art of leadership, a few of the themes of which are presented below.

While technology and scientific methodology dramatically changed over Ki’s and John’s careers, the leadership ingredients have stood the test of time…

You never know when a routine or chance meeting could become a career-defining moment

Both men made the most of even seemingly small opportunities when they presented themselves; and created their own breaks—such as when a Harvard undergraduate (John) knocked on the door of a new assistant professor named James Watson. Recognize that each encounter can leave an enduring impression. Cultivate “presence,” and preparation, to make small interactions noteworthy.

For Ki, it was a 1973 fellowship interview at Sloan Kettering, during which Irwin Krakoff, then chief of the Medical Oncology Service, could discern through the difficult English the intense passion, insight and focus that characterized Ki’s early career. Intrigued, Krakoff kept an eye on Ki during his fellowship and beginning of his faculty career at Boston Veterans Affairs; taking note of Ki’s incredible track-record of bringing precision and incisiveness to challenging clinical trials.

Krakoff was also impressed by Ki’s capacity to work (he often said, “I only consider myself of average intelligence, but I can out-work most people”); absorbing everything he could learn during fellowship from the likes of Joseph Burchenal, David Karnofsky, and Robert Wittes, as he embraced very difficult clinical problems. Ki’s early faculty career at the Boston VA, focused on head and neck cancer, developing a series of interrelated and innovative clinical trials designed to interrupt this disease process, ranging from neoadjuvant chemotherapy to chemoprevention, each at the cutting edge of translational research.

Krakoff was recruited to MD Anderson in 1983 to elevate the academic stature of the Division of Medicine; a year later (and 10 years after a memorable fellowship interview), Ki was recruited to bring rigor to the clinical trials program as chief of the Section of Head and Neck Medical Oncology, then Charles A. LeMaistre Distinguished Chair of the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson. On a related note, lasting impressions during his fellowship led Wittes, who had moved to the NCI Cancer Therapy Evaluation Program, to connect him several years later with surgeon Greg Wolf, who led the NCI Head and Neck Contracts Program HNCP-178, which set the stage for the pair to design and lead the landmark VACSP-268 laryngeal cancer preservation trial.

For John, it was during his residency at the Brigham and Women’s Hospital. A chance meeting with a visiting professor from NIH, Eugene Braunwald, would turn out to be a defining moment of his career.

Braunwald recognized early on that John had inherent leadership “gifts”: drive, vision, charisma. Several years later, while completing a hematology-oncology fellowship at Washington University, John received a call from Braunwald, who had moved to the University of California San Diego (UCSD) in 1968 as the founding chair of the Department of Medicine, where he wanted to build a strong presence in oncology.

He thought of John, introduced him to hematology division chief Mickey Goulian, who immediately recognized John’s talents and capabilities. They recruited John to UCSD in 1970, enticing him to break from his established Ivy League roots with the opportunity to literally “build oncology from the ground up” at this exciting, vibrant 2-year-old university.

Foster relationships with colleagues and competitors to build mutual respect and advance the field

Ki and John were masters at convincing and motivating people to join them and collaborate, using many strategies known to build relationships. John shaped and transformed three major cancer centers while launching and driving the era of targeted therapy.

Yet, we highlight Ki’s approach to this principle because of its uniqueness as a tactic in academic medicine. Though we doubt Ki ever read a leadership book, he clearly understood the techniques embodied in the genius of Abraham Lincoln, as outlined in the Team of Rivals by Doris Kearns Goodwin.

Ki had the innate ability to cultivate relationships with colleagues and competitors by simultaneously competing with and promoting the interests of these individuals. With deep political intuition, Ki built a team of trusted friends, colleagues and even rivals to advance cancer research and care.

He found a way to allow each of his competitors—including detractors—to contribute to cancer medicine, where they could achieve personal success, thereby advancing the field and, intended or not, simultaneously enhancing Ki’s stature. Throughout his career, Ki devoted considerable time and effort to elevating the careers of others—nominating and passionately advocating colleagues and competitors alike for major awards and accolades.

This tactic was simultaneously a selfless act, yet also one with great returns on investment, generating longstanding mutual respect and admiration. The success of this strategy was iterated throughout his career, and with each success became a self-reinforcing aspect of Ki’s highly effective interactions with others. This was a political genius on par with that of Lincoln.

Think broadly, look ahead, recognize and promote talent

John was recruited to UCSD to build an oncology program, but his expertise was as a hematology physician-scientist with additional fellowship training at the NIH, leading a large basic lab effort.

He knew he needed to bring a national leader in solid tumor clinical trials, so in 1976, the year John became the founding UCSD Cancer Center Director, he recruited the late Mark Green, one of the most highly respected oncologists in the United States, famous for his encyclopedic knowledge of clinical oncology (and memorizing medical record numbers of his patients.)

John was always looking for ways to expand the breadth and depth of the UCSD Cancer Center within his modest budget. He successfully promoted and leveraged academic and academic-industry partnerships, and passionately engaged community leaders.

His broad vision is illustrated by his early years at UCSD, building the cancer program and center to encompass very basic studies of T-cell receptor biology, advancing disruptive monoclonal technology and establishing a nascent effort in community engagement.

In 1981, John recruited Georgia Sadler to be the associate director for administration, also realizing that her doctoral training in public health would be a real asset in helping him to expand the breadth of the center.

He supported her efforts to create public education and awareness programs highlighting the importance of cancer prevention and clinical trial participation. This outreach effort had a strong regional focus on reducing cancer disparities, placing meaningful value on what we now call “catchment area,” making John one of the nation’s first directors of an NCI-designated cancer center to use community-campus partnerships as an effective cancer control strategy.

Embrace difficult challenges that address simple, compelling, and worthy questions

Ki and John developed groundbreaking, yet straightforward, simple and compelling research hypotheses that addressed meaningful problems.
While simple in retrospect, each breakthrough was incredibly difficult and challenging to operationalize and implement, requiring tenacity, resilience and creativity in the face of opposition and scientific concerns regarding the validity of their research ideas and feasibility.

For example, though the idea behind Ki’s Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) study was simple and compelling—base targeted drug selection on current tumor biology—it was unprecedented and prompted vigorous debate, skepticism, and even ethical resistance.

The controversy centered on the risk of the core needle re-biopsy required to base drug selection on current biology in the second line setting, versus the risk of inaccurately selecting drug therapy or pathway targets from archival diagnostic tissue.

Despite the skepticism, BATTLE established the feasibility of a challenging precision therapy protocol design that has become an established approach in cancer medicine.

Related to his principle of simple, straightforward hypotheses, Ki designed trials to answer important questions, contributing valuable information, regardless of the result—this was his “no lose approach” to cancer research.

In 1980, John’s groundbreaking hypothesis that launched the era of targeted therapy was, at its core, quite simple—make an antibody to prevent the growth factor-receptor connection, in this case epidermal growth factor receptor (EGFR) to block cell proliferation.

The hypothesis, however, was based on circumstantial evidence, including basic studies of transferrin- and acetylcholine-receptor biology, but no direct experimental data. In fact, prevailing data revealed that monoclonal antibodies functioned as agonists in this setting. Unprecedented, uncertain, and unfunded, John partnered with Gordon Sato, to push the idea to reality through initially scraping together funds for preliminary hybridoma studies, screening thousands of antibodies over several years to find a lead compound (225) with strong antagonist, blocking activity. John moved to Sloan Kettering in 1985, continuing his 225 work, and led seminal studies driving the development of 4D5 and Herceptin with Rakesh Kumar and José Baselga.

These are but a few examples of the approach to leadership embodied and employed by these two great men. There were many similarly important principles in other aspects of their careers, including seamlessly integrating education and training into the fabric of cancer research and care: creatively designed and funded innovative and transformational training mechanisms such as an advanced scholars program.

Having the incredible fortune to work with them over many years, as well as listening to the stories told by former students and colleagues, was exciting and compelling. Ki and John didn’t write an actual book about their leadership experiences, but they “wrote the book,” figuratively, and that bears noting—and retelling.

Read more

For a more in-depth look at the lives of these two extraordinary and inspirational individuals, please read our tribute in Cancer Cell, Feb. 11, 2019.

Copyright (c) 2018 The Cancer Letter Inc.