The First Cell

by Azra Raza

  If hope can help individuals survive seemingly impossible odds, despair can galvanize efforts to seek solutions. The practice of Sufism consists entirely in welcoming and enduring affliction precisely for this reason. Negative emotions can be useful if they influence the future by serving as a motivation for transformation. In an ontological leap, affliction and despair lead to agency, seeking explicit solutions, exploring possibilities for a radically different future. An accounting of cancer’s unresolved scientific complexities alongside the toll of human suffering should serve as a tool with which to pry open new ways of critical thinking, a grander global vision, a positive outlook toward our world. A hope that of all possible outcomes in the future, alleviation of pain and distress from cancer can and will happen, positive change, both individual and societal, will occur.

  The burden of this book, from its opening paragraphs, has been to chronicle the intimacies of cancer kept confident by those who experience its anguish. The conceit is my absolute conviction that the engine driving social and scientific progress in quantum leaps, rather than in unbearably slow increments, is one fueled by empathy. Only the profound suffering of cancer patients has the power to ignite a brand of compassion necessary for demanding urgent and dramatic change. Only empathy can break the foolish consistency that is the hobgoblin of oncology and little minds. The future is in preventing cancer by identifying the earliest markers of the first cancer cell rather than chasing after the last. I have been saying this since 1984, and I will continue to say it until someone listens.

  For the individual with eyes, the dawn has already arrived.

  —ALI IBN ABI TALIB

  KHATAM SHUD

  Acknowledgments

  I WROTE THE INITIAL DRAFT OF THE FIRST CELL IN THREE MONTHS. My nephew Asad Raza pointed out, “Achi, you have been writing this book for thirty years. You just downloaded it in three months.” True. I owe TFC entirely to the profound impact that patients have had on my life for the past three decades. Sadly, for all the commitment and dedication, I have very little to show for it in terms of improvement in their treatment outcomes. So I begin this section by acknowledging my failures and apologizing to all the patients for not having done more to help.

  But tried I have. Every chance I got, I have spoken up about these issues, written extensively on various problematic aspects of the current cancer paradigm, appeared on radio and television, delivered a TEDx talk, given interviews and podcasts. To what end? I have not managed to change many minds. Everyone listens to me sympathetically, and then they go back to doing whatever they were doing before. I finally had a little break when I answered the 2014 annual Edge Foundation question, “What scientific idea is ready for retirement?” My answer—“Mouse models are the real elephants in the room”—was noticed by the media. It grabbed attention because of the controversial nature of my claims. Even a negative reaction is better than no reaction. Oscar Wilde said, “There is only one thing worse than being talked about, and that is not being talked about.” I was invited on NPR. I was interviewed on Freakonomics Radio. Sporadically, I started to receive notes of support. Alan Schechter from NIH and Robert Perlman from the University of Chicago applauded my efforts to unmask the problems with the reductionist approach and use of mouse models in cancer drug development.

  John Brockman, founder of the Edge Foundation, who “runs the world’s smartest website,” brought his wife, Katinka Matson, for dinner to my apartment one evening. “You want better answers for your cancer patients. You want researchers to stop fooling around with mouse models. You want oncologists to treat patients differently. You want nothing less than a paradigm shift in cancer studies and treatment. Write a book. Only someone like you, an insider in the field, can raise these issues. The public will take note if your message is compelling enough. A conversation could begin,” said sweet Katinka, gently encouraging me. John, on the other hand, known for his brutal bluntness, and not one to mince words, patted my back affectionately. “Put up or shut up, kid. Send us a proposal. By next week.”

  My first instinct, given the hectic work schedule I keep between seeing patients and supervising a very busy cancer research lab, as well as teaching and administrative duties, was to tell my story to a professional writer. I called Zara Houshmand, a dear friend, who has ghostwritten several hugely successful books, and she talked me right out of it. Thanks, Zara!

  I wrote to my younger brother Abbas in Italy for advice. Abbas is the founder of the website 3 Quarks Daily. More importantly, he is my most trusted editor in chief. I have published original pieces at 3 Quarks Daily over the years, parts of several of which are included in this book (including Omar, Per, War on Cancer, Harvey, and Laura; a small portion of Lady N. appeared in the MDS Beacon). Abbas is extraordinarily well read and has an unparalleled instinct in matters related to both science and literature. He said, “Aps, I had to think really, really hard about your question of whether to listen to John and Katinka or not. For exactly three seconds. Yes. Of course they are right. Get on with it immediately.” Asad, the author of several amazing books on art and artists, said, “Achi, it is a badly needed book. From my experience, I can tell you it will take approximately eighteen months. Please start right now. Just write what you have been telling us over the years. That’s all. Do it.” I did. Here we are. Thanks, John, Katinka, and Max Brockman. Thanks, Abbas and Asad.

  When I was considering thalidomide for Harvey, I called Owen O’Connor, the chief of lymphoma service at Memorial Sloan Kettering Cancer Center in New York, to seek his advice. I had never met or spoken to Owen before, but after I told him the reason for my call, he gave me his home and cell numbers, urging me to call any time of day or night if I needed help. This was the reaction of practically every colleague around the country I contacted for advice throughout Harvey’s illness. Extraordinary compassion, incredible willingness to help, unconditional offers of their time and expertise. We traveled to Boston to see John Gribben at Dana-Farber and Bruce Chabner at Mass General; we consulted Ron Levy in California and called Harvey’s beloved, longtime best friend, Kanti Rai, in New York. Kanti found reasons to come to Chicago many times in the ensuing years, providing not just expert medical advice but much-needed and much-appreciated comfort at a personal level.

  Despite our habit of sorrow in those days, moments of such radical kindness and consideration from oncologists around the country and, more locally, from the nurses and medical staff, secretaries and lab assistants, scientific colleagues and administrative officers at Rush University lit up our lives with the comforting radiance of their acts. My deepest gratitude is owed to Lakshmi Venugopal, Sairah Alvi, Vila Ravanam, Suneel Mundle, Laurie Lisak, Minnie King, Beverly Burge, Chris Kasper, and Naomi and Uri Galili, who were ever present to help Harvey and to hold my hand and take care of business when Harvey and I were indisposed because of his illness. I cannot recall one single instance in almost five years of Harvey’s illness—innumerable tests, hundreds of clinic visits, and dozens of hospitalizations later—when we registered a complaint of even the slightest significance against the medical establishment, either privately or publicly. Everyone stepped up to do more than we’d expected. Drs. Steve Rosen, Hans Klingemann, Parameswaran Venugopal, Jamile Shammo, Seema Singhal, Jayesh Mehta, Stephanie Gregory, Sefer Gezer, Raphael Borok, and Phil Bonomi took care of Harvey as if he were a family member. Leo Henikoff, the president of Rush University, and his brilliant wife, Carole Travis Henikoff, were sources of extraordinary friendship and support at every level. Most loving and helpful was our dear friend, colleague, and an all-around wise person, the chairman of medicine at Rush, Stuart Levin. The manner in which Stu calmly and quietly provided strength and solace to both Harvey and me during five years of Harvey’s illness can never be repaid in words. As Harvey was taking his last breaths, the person I called was Stu. He was by my side in minutes. He stayed until the death certificate was signed and all the formalities were taken care of.

  Sol Barer, the founder of Celg
ene, and Jerry Zeldis, the chief medical officer, two visionary leaders who would transform the little, unknown company worth a few million dollars into a global biopharmaceutical behemoth worth tens of billions, stepped up to help when I most needed them by providing thalidomide and Revlimid on a compassionate basis for Harvey. They have remained dear friends these twenty years later, as has their successor, the talented and deeply empathetic Mark Alles. Mohamad Hussein at Celgene has been a rock-solid friend for decades.

  Seema and Vania’s presence was a godsend. They shared the happiest of times with us in Chicago and saw us through the heartbreak right to the end. Harvey gave instructions for his cremation to Vania. On the home front, I could not have survived in America without the unconditional love, nurturing, and benevolence of my beloved brother-in-law Tariq Khan, a superbly trained surgical oncologist with a second career as the best ER physician. In addition to Sarah, Mark, Vanessa, and my siblings, all of whom kept in touch constantly and made frequent visits to Chicago to see Harvey, it is to Irshad and Muhammad Mumtaz that I owe a profound debt of gratitude. The concept of daily existence without them in my life does not exist anymore. No one did more to help with Harvey when he became incapacitated than these two devoted souls.

  Early readers of the book to whom I am greatly indebted for invaluable feedback include my siblings Amera, Atiya, Tasnim, Javed, Sughra, and Abbas Raza and my sister-in-law Nazli Raza. Other early readers in the family and beloved friends include Zaineb Beams, Jaffer Kolb, Musa Raza, Zehra Raza, Carol Westbrook, Kanti Rai, Bob Gallo, Mary Jane Gallo, Naomi Galili, Seema Khan, Siddhartha Mukherjee, Darryl Pitt, Connie Young, Nermeen Shaikh, Stavroula Kousteni, Ellen Cole, David Steensma, Steve Rosen, Candi Rosen, Rafia Zakaria, Shan Rizvi, Nancy Bachrach, Susan Bates, Tito Fojo, and Anisa Hasan. Laura Claridge read the first chapter, gave me the green light, and has since supported me throughout. Ivana Cruz and Darryl Pitt helped clarify my thinking about the jacket design by producing some gorgeous alternate versions.

  Abdullah Ali is the son I did not have and, fortunately, the director of the MDS translational research program at Columbia University. He read the earliest version of TFC and gave brilliant suggestions, as did Naomi Galili, my most trusted, beloved friend and scientific colleague and the previous director of the MDS research program. Abdullah provides me with the strength to continue in my single-minded quest for the first cell and is equally motivated by the philosophy of only pursuing what is best for the patients. He is my right hand and my go-to scientific compass on a daily basis. I can never thank Abdullah enough, so I thank my lucky stars that brought him into my life when I was heartbroken over Naomi’s retirement. Naomi is supremely talented in the sciences and possesses a profoundly sensitive soul. She was a joy to have as a colleague in the lab, someone who got the centrality of the patient in even our most basic research endeavors.

  At Columbia University, I am grateful for the strong support I have received for a decade from the chairman of medicine, Don Landry; the dean, Lee Goldman; and, since he arrived, the chief of the division, Gary Schwartz. They have protected me from unnecessary bureaucratic entanglements and have wholeheartedly cheered my efforts on behalf of the patients. I am also deeply grateful for the collegiality and excellence of my medical and scientific colleagues. Over the years, some have become close personal friends: Greg Mears, Stavroula Kousteni, Connie Young, Emmanuelle Passegue, Joe Jurcic, Mark Heaney, Nicole Lamanna, Craig Blinderman, Hamza Habib, Riccardo Dalla-Favera, Emerson Lim, Chuck Drake, Susan Bates, Tito Fojo, Abbas Manji, and David Diuguid. A big thanks to the incredible staff of our offices and clinics, the nurses and administrative assistants, whose devotion and compassion for the patients strike awe in hearts. After the cancer patients themselves, it is to these selfless, dedicated medical staff that I owe the inspiration to write this book.

  Siddhartha Mukherjee and Sarah Sze are like family, or as Sid says, “Azra, you are a cross between my mother and my editor.” Writing a book about cancer after The Emperor of All Maladies is almost heretical, especially because I am Sid’s biggest admirer. It is one of the greatest joys in my life to spend time with Sid, whether we are batting scientific ideas back and forth, arguing in lab meetings, laughing at Bollywood jokes, or transported into ecstasy by Sid’s divine renditions of Indian classical vocals, accompanied by my adopted son, the great Ustad Ikhlaq Hussain, on sitar, lasting into the early morning hours.

  My dearest friend and coauthor of Ghalib: Epistemologies of Elegance, Sara Suleri Goodyear, read the earliest drafts, talked me through many difficult decisions, gave thoughtful, incredibly helpful suggestions, and gave me moral support when I was overcome with grief periodically while writing some parts of the book.

  I want to acknowledge the women who have influenced my way of thinking greatly over the course of a lifetime; my mother, Begum Zaheer Fatima; my younger sister Sughra Raza; my friends Seema Khan, Maliha Hussein, Sara Suleri Goodyear, and the great Urdu writer Qurratulain Hyder (Aini Apa), whose friendship meant the world to me. The four teachers with the biggest impact on my early thinking include Qamar Jehan, Farhat Aziz Muazzam, Nikhat Afroz, and Afroze Begum.

  Karachi life is unthinkable without my cousin Qasim Raza; my sister-in-law Arfa Raza; my friends Seema Khan, Anisa Asim Haider, Mansoora Ahmed Sheikh, Meher Fatima, Nigar Khan, Anisa Hussain Hasan, Shakeela Khan, Farrukh Seir, Tahir Alvi, Mehro Hamid, Tariq Shakoor, Rashid Jooma, and Sheena and Jamil (Jimmy) Malik.

  New York felt like home from the moment Sheherzad and I moved here in 2007 because of the friendship, warmth, and protection provided by Anees and Rafat Mahdi and Marina and Shaukat Fareed.

  At Basic Books, Liz Stein edited the first draft of the book, and I thank her for her incredible effort and sympathetic reading. Liz Wetzel, Kelsey Odorczyk, Rachel Field, Melissa Veronesi, and my copy editors Sara and Chris Ensey have been unbelievably thorough and supportive.

  TJ Kelleher, my editor, recognized that the patient stories were worth telling, the message compelling and timely, from the moment he read my book proposal, all the way up to this final version, overseeing every aspect of editing. While I was regularly astounded by the depth of TJ’s scientific understanding, it is his exquisite sensitivity that helped me polish some of the rust off dense sentences upon many rounds of rereading and editing. Lara Heimert, our publisher, is sui generis; incredibly brilliant, she is quick to spot the good and the bad. Lara stepped in at crucial moments to weigh in with suggestions, commands, and appropriate hand-holding as required.

  Thanks to all the present and future patients who continue to humble us every day with unparalleled grace. Know that there are thousands of devoted oncologists ready to listen to you, advocate for you, and thousands of scientists moving heaven and earth to find solutions to your problems. Thanks to all the clinical and basic cancer researchers and the incredibly hardworking, dedicated oncologists spread throughout the country, working night and day to help cancer patients. I have had the great good fortune to interact with many extraordinary colleagues in these last three decades. So much of what this book says is owed to what they have taught me.

  My best teacher, one who shaped my personality and my thinking in profound ways, is of course Harvey. I was fortunate to find so unique a mentor when I was barely twenty-four, one who insisted that the only things that matter are excellence and a serious pursuit of truth, and that after all is said and done, the most beautiful thing in life is still an adult intimate relationship.

  Lastly, I thank my daughter, Sheherzad, whose unconditional love for and confidence in me and whose intellect and courage are so totally Harvey that it is frightening. She has sustained me through some rough patches in the last two decades. Above all, Sheher has witnessed the ravages of cancer at a deeply personal level, as she watched her father and her best friend succumb in excruciating and painful installments to its exacting malevolence. Here’s to hoping she will continue to promote the mission of her parents by serving cancer patients in every capacity possible and always w
ith sensitivity and humility.

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  CHAD HUNT

  AZRA RAZA is the Chan Soon-Shiong Professor of Medicine and director of the MDS Center at Columbia University. In addition to publishing widely in basic and clinical cancer research, Raza is also the coauthor of Ghalib: Epistemologies of Elegance and the coeditor of the highly acclaimed website 3QuarksDaily.com. She and her daughter, Sheherzad, live in New York City. Her website is https://azraraza.com.

  Bibliography

  NOTE: Sources in the bibliography coincide with the order in which they appear in the text.

  INTRODUCTION: FROM LAST TO FIRST

  DeVita, Vincent T., Jr., Alexander M. M. Eggermont, Samuel Hellman, and David J. Kerr. “Clinical Cancer Research: The Past, Present and the Future.” Nature Reviews Clinical Oncology. 11, no. 11 (2014): 663–669.

  Horgan, John. “Sorry, but So Far War on Cancer Has Been a Bust.” Scientific American, May 21, 2014.

  El-Deiry, Wafik S. “Are We Losing the War on Cancer?” Cancer Biology & Therapy 14, no. 12 (2013): 1189–1190.

  Davis, Devra. The Secret History of the War on Cancer. New York: Basic Books, 2007.