Lee M. Nadler: Cancer’s Nemesis

Harvard dean Lee M. Nadler, my oncologist of three decades, has often shared with me his reverence for the most curious and courageous cancer scientists of our time: the probing risk-takers chasing their hypotheses to wherever they end. He applauds, and has been part of, studies resulting in profound new beginnings—with subsequent phases of rigorous discovery translated to the bedsides of patients.

We met, in 1992, after my local hematologist had the presence of mind to send me to an academic CLL expert for a second opinion. At the time, Lee (he insists patients call him Lee) was considered one of the country’s top physician-investigator experts for CLL, and had recently made full professor at Harvard Medical School—a rarity for a 43-year-old.

The Epitome of Tenacious Investigator

Lee has consistently pushed at a frenzied pace for over four decades, clocking many 100 hour weeks. Now in his early seventies, he shows no signs of slowing down.

His productivity and contribution to the cancer literature is remarkable; his byline appears on about 300 peer reviewed, published papers, many as first author.

Lee’s lab has been among the highest funded by the National Cancer Institute, enabling his steady path and pace of discovery. As a prolific inventor he has contributed to over 45 patents.

Discovery Highlights:

  • Lee’s lab discovered the human B-cell specific molecules CD19, CD20, CD21, CD22, and the costimulatory molecules B7-1 (CD80) and B7-2 (CD86).
  • His translational experiments established our understanding of human B-cell differentiation and led to the worldwide immunologic classification of human B-cell leukemias and lymphomas.
  • He was the first to administer a monoclonal antibody to a human and to use monoclonal antibodies to improve the outcome of human stem cell transplantation.
  • His discovery and characterization of the B1 molecule (CD20) led to the development of Rituxan that has significantly improved the survival of patients throughout the world with lymphomas and other B-cell diseases.

“His greatest gift is that he’s not tethered to reality. He sees where he wants to fly, and he goes there.” ~Dr. Barbara Bierer, senior vice president at Brigham and Women’s Hospital, a 30-year colleague of Lee.

A Street Kid with Humble Beginnings

Lee grew up in Queens; his family had little money and their fair share of challenges due to issues relating to his father’s mental health.

As a teenager, he found solace in the library. A librarian selected Pearl S. Buck’s The Good Earth when he told her he wanted to learn to read. Three years later he had Dostoevsky’s works under his belt.

At sixteen he was captivated by Arrowsmith by Sinclair Lewis—a novel whose characters have influenced many students to go into medicine.

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Though his family had no money for postsecondary education, Lee turned to the City University of New York who charged $34.00 for a semester.

This paved the way for a journey that is as inspirational as it is stirring.

The support of his girlfriend’s family—she later became his wife—grounded him, providing connections he’d missed as a child. He applied himself in high school, held down part-time jobs, and pressed onward.

Few students from the City University of New York became doctors; fewer went on to Harvard. These stats did not deter Lee and, after an unusual interview, Dr. Sanford Roth (interviewer) supported Lee’s admission.  The story involves Lee arriving at Harvard in 1968, drenched from having walked three miles in sleet, without a decent winter coat. While Lee argued with Dr. Roth about the Vietnam war, the prospective student disrobed and changed into scrubs, so that his clothes could be dried in the pathology dryer.

Physician, Humanitarian, Lifelong Learner

An accomplished professor, Lee’s had several incredible mentors throughout his career, and his medical students have no doubt helped shape his development. But it may be Lee’s patients who have influenced his work in the most profound ways.

As a longtime patient who, over the years, has conversed with others in Lee’s care, I’ve learned he considers the cancer survivors he has treated, managed, and befriended, among his most important ‘teachers’.

Throughout his academic medical career—regardless of how busy he has become as a professor and intrepid investigator—he’s continued seeing his patients in clinic one day each week at Dana-Farber Cancer Institute. He also personally sees each patient on every clinical trial he leads.

Skilled Healer, Skilled Listener

To be frank, Lee always has a lot to say. But he’s also an exceptionally skilled listener. He knows it is critical to understand each patient’s unique story and journey.

The human condition, and connection, matter to Lee: truly hearing patient stories, meeting family members, homing in on both the complex and unique physical, emotional, and vulnerable beings that appear in front of him. These highly personal encounters have spurred Lee’s unending commitment to translating new discoveries from the lab to patient bedside, and as expeditiously as humanly possible.

His encounters with patients, over decades, had led him to this observation: those having the strongest wills to survive tend to do the best.

Glenn Sabin and Lee Nadler, MD, standing side by side

Glenn Sabin and Lee M. Nadler, MD, Boston, 2014

Always Curious, Even About Integrative Oncology

While Lee is not an active proponent of integrative oncology, he has, for decades, been a participant in the core tenets of lifestyle medicine for his own health and wellbeing. Aside from work—and his growing collection of art and antique microscopes—diet and exercise have been constants in his life. These habits have arguably played a significant role in his fitness and sustained energy level.

At different points through the years, including my first appointment, Lee suggested that my healthy lifestyle  would have no influence—good or bad—on the CLL I was hosting. His thinking aligned with that of my local community hematologist.

As many experts have professed, CLL is genetic and plain bad luck. There was no acceptance of the thinking that healthy habits, including supplementation, would impact the cancer burden, or alter its progression.

I was, however, one of those strong-willed patients that Lee has described. I was curious as well, and knew I was facing the most profound challenge of my life. Respectful of the experts placed in my path, I never had unrealistic expectations of my conventionally-trained academic CLL expert… even if he was Lee Nadler.

Just as I’ve never leaned on my integrative physician for an expert opinion on the therapeutic drug pipeline for treating CLL, I would not expect informed anticancer lifestyle behavior advice from Lee.

Through the decades, Lee would dutifully ask me about self-care and lifestyle activities I was following, including supplementation. Everything was captured in my medical record. He never once dissuaded me from doing all of the things that became my evolving regimen.

I was, and remain, primarily focused on lifestyle behavior—nutrition, movement, stress reduction, sleep, hydration, reducing environmental toxins, along with well-informed supplementation.

I visited Lee in the summer of 2003 when, for the first time in a dozen years, the CLL had become acute and debilitating—I was suffering with full-blown leukemia.

He looked me in the eye and said: “You are headed over a cliff… you need to be treated, like yesterday.”

I reminded Lee that the standard of care he was offering, called R-CHOP, was not provided with curative intent. It was palliative. I would relapse. And at that point I would be resistant to the same combination of chemo and monoclonal antibody.

Even if his lab did help create the remarkable monoclonal antibody, rituximab—that was the ‘R’ in R-CHOP—I played it to him straight.

“So what are you going to do?” he asked.

I didn’t have an answer just then, so I told him that I’d figure it out and let him know. I would ultimately be seen twice each week, locally, for bloodwork, while continuing my informal experiment.

When I was eventually successful in getting to a partial remission (no leukemia evidenced in bloodstream, but still active in marrow) without conventional therapy, I went to Boston to see Lee in his clinic.

He could not believe the reversal from such an acute period of leukemia to the point of remission, and that an auto-immune hemolytic anemia had resolved without steroids; a first in the medical literature.

And in the style of a lifelong, intrepid learner, Lee wanted to know each and every detail of what I did, from the time I was extremely ill and saw him at Dana-Farber, and up to the point when my blood counts were completely normal.

He was incredibly curious. We talked for an hour. He did not dismiss me as an aberration, an outlier, an anecdote, which, frankly, I am—even with the case report covering my clinical journey peer reviewed and published (here).

Not only was Lee impressed with what he had seen happen, he endorsed me in writing a letter to the National Institutes of Health to support a research grant I was exploring.

Several years later we earnestly discussed developing a pilot trial at Dana-Farber that would include a top biostatistician and their CLL expert team members.

The caveat was that Lee was only interested in investigating one variable: the impact of green tea extract on a population of CLL patients with a specific immunoglobulin profile that had never been treated with conventional therapy. This was not much different than a study Mayo Clinic was doing.

As incredible as it would have been to work on a research project in which Lee was involved, what he was describing, in terms of the proposed design, did not fully reflect what I had been doing during all those years. It was too reductive. My program was quite comprehensive; it was multi-interventional—way beyond just a green tea extract supplement. In this case, the biostatistician would be required to do some heavy lifting.

Though a pilot trial was not meant to be, this did not deter Lee’s interest in me or mine in him.

“I never treated Glenn. He decided he would come to me not as a ‘treater’, but as a credible assessment.” ~Lee M. Nadler, MD

This is true. I have not been treated conventionally for CLL, but did achieve a complete pathological remission—clearing of leukemic cells from the bone marrow—almost 10 years ago. Nonetheless, I have been the beneficiary of top diagnostics and monitoring of the CLL I hosted for decades by a major cancer institute, and followed by a top clinician-researcher. I am deeply grateful for my longtime relationship with Lee.

A couple years ago Lee connected me with Isaac Kohane, MD, PhD. Dr. Kohane is the Chair of the Department of Biomedical Informatics at Harvard Medical School. In 2019, Kohane launched a study called NEER—Network of Enigmatic Exceptional Responders. NEER would retrospectively engage in studying those patients who had experienced remarkable responses to therapy across various populations of malignancy—mostly advanced, metastatic disease.

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An exception was made for me to enroll in NEER, given I had never undergone conventional therapy. I would also go on to personally recruit approximately 10 percent of NEER’s small number of initial participants.

Lee championed NEER as a Harvard Catalyst project. He founded Harvard Catalyst in 2008 and continues his role as principal investigator for its research portfolio.

His support of NEER, and keen interest in individual ‘outlier’ cases of exceptional responders, is quite different to that of many oncologists and clinician-researchers. Whereas most see aberrations and anecdotes not worthy of further investigation, the most inquisitive—like Lee and Kohane—ask the critical questions of ‘how?’ and ‘why?’ NEER is a result of that level of curiosity. I eagerly look forward to further development of the NEER project, and to getting a copy of the data they are collecting on my case.

“In the study of the profession to which he had looked forward all his life he found irritation and vacuity as well as serene wisdom; he saw no one clear path to Truth but a thousand paths to a thousand truths far-off and doubtful.” ~from Arrowsmith, by Sinclair Lewis

Thank you, Lee. Stay curious, my friend.

Watch Lee Nadler publicly discuss Glenn’s case for the first time in 2019.