Wednesday, May 27, 2020

Beyond the Science – Reflections on Charles Graeber’s “The Breakthrough”

The subtitle of “The Breakthrough” is, “Immunotherapy and the race to cure cancer.”  Yes, the book is about the history of immunotherapy – in laymen’s terms, treatments that harness the body’s own immune system to stave off cancer.  But the subtitle does scarce justice to the richness of content and context that author Charles Graeber packs into 225 pages.  The book includes some truly compelling, sometimes moving, stories of researchers, doctors, patients and caregivers spanning more than a century starting from 1890 until a few years ago.  In a sense, the book is not about a race.  But rather, an extended marathon.  A marathon without a chalked-out route, without competing racers but rather, a relay.  The catch here is that the journey of the discoveries of immunotherapy was anything but a straightforward A to B to C route. 

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The baton of knowledge was not easily passed from researcher to indefatigable researcher and from one generation to the next.  That did not stem from an unwillingness to share.  It was more of a reflection of the dazzling array of complexities that marked this field for decades.  Even as studies in this field continue to pose newer, tougher questions, by and large, rock-solid foundations have been laid for an approach that has already been making a significant difference to the lives of those suffering from various types of cancer.  This book is a stupendously detailed account of all of the tireless efforts, frustrating setbacks, pleasant and unpleasant surprises, humbling disappointments and the rare but unforgettable moments of ecstasy in discovery and progress.  If one definition of breakthrough is, “a sudden advance,” another meaning of the word is, “an act or instance of moving beyond an obstacle.”  Doing justice to both these interpretations, this book sheds plenty of light on the method and the madness that led to the moments of magic.  And Graeber explains complex science in such simple terms replete with intuitive analogies, that the book is a very accessible read even for those that aren’t that familiar with the field of immunotherapy or its tremendous impact on oncology.

Some of the best parts of this book are in the chapter, “Glimmers in the Darkness.”  In this chapter, Graeber lays the building blocks of the immune system and how the deep understanding of the system came about piecemeal over time, not in one eureka moment.  More importantly, this chapter enlightens us on how researchers had to deal with skeptics.  A telling example is from a time when a researcher first presented information on the immune system comprising T cells in addition to B cells.  He was mocked in public with the comment that “B” and “T” were the first and last letters of the word, “bulls—t.”  It is a very revealing moment that shows us that the barriers to advancements aren’t always financial, logistical or scientific. 

The aforementioned chapter also details, with much incision and perspicacity, the need to disseminate information responsibly.  As much as there is a need to lucidly share important advances beyond the scientific community with the general public, of equal importance is balanced representation.  Nowhere is this more evident in the book than the section on Dr. Steve Rosenberg and the IL-2 news coverage in 1985.  A week before results from a small trial were due to be published in a journal, a Fortune magazine cover screamed, “Cancer Breakthrough.”  While the medicine itself marked definite progress in the field, the results of the trial did not actually measure up to the kind of hype it generated and worse, the blind hope that the headline offered patients and caregivers.  Seen one way, this book, especially this chapter, is not only a lesson in science but a lesson around science. 

The latter portions of the book offer insight into the game-changing discoveries in the field of checkpoint inhibition starting from CTLA-4 to anti-PD-1s/PD-L1s. (In light of what I just said, “game-changing” was a choice of term that I weighed carefully and used here only after being convinced of the enormity of the impact of these treatments.)  Let me hasten to add that these are not technically dense chapters.  As much as there is information on the science, there is an equal emphasis on how some patients stood (and continue to stand) to benefit from these newer treatments.  There are some deeply moving stories, some of delight, others of despair.  Even in his choice of the real-world stories, Graeber ensures that rays of light are appropriately tempered by clouds of unpredictability that continue to exist in the disease and its treatment.

Cancer, regardless of type, can be a very scarily complex disease.  Questions lead to answers that, in turn, lead to more questions.  We have a long way to go before the treatment of cancer, across the spectrum of afflicted patients, can be considered completely predictable and manageable.  This book is an important account of where the journey originated and where we are now.  John Lennon once said, “Everything will be okay in the end.  If it is not okay, it is not the end.”  Suffice to say that we are at the end…of just this write-up!