by Azra Raza
Courtesy of Dr. Abdullah Ali
This pluralistic approach using actual human tissue is far more likely to be high yield compared to the reductionist approach prevalent for the past fifty years comprised of tweaking one or two genes at a time in the setting of mouse models. The strongest aspect of the tissue repository, besides the physical samples, is the clinical perspective it provides going back to 1984, making it possible to compare samples of thousands of patients who died early with thousands who survived more than five or ten years or longer. Sample collections started in the last decade cannot provide this unique retrospection. Imagine the staggering wealth of information that will emerge when we are able to examine multiple samples obtained serially at regular intervals from large numbers of patients showing biologic drifts in RNA, DNA, and protein expression as the disease evolves through its natural history. In addition, we can have a detailed understanding of how the patient’s immune system responded to these tectonic shifts since T cells from the peripheral blood of patients are simultaneously obtained and preserved in the tissue repository, cells viably frozen, which can be thawed out, regrown, and studied. The biomarker signatures thus developed can then be applied for early detection of MDS and AML in our aging population, the prime target of these diseases. But where is the support?
AND HOW MANY ZAINEBS?
I landed at the Qaid-e-Azam International Airport early one crisp December morning in 1992. I grew up in Karachi and moved to the United States immediately after graduating from medical school. As long as my parents were alive, I returned home frequently to see them. Each time I arrived back home at Gulistan-e-Raza, my mother would hand me a list of patients she had lined up for me to see. On the ride home during this particular visit, Ali Asghar, our driver, warned me that the list this time contained an emergency. “Begum Sahib is very anxious about a young woman dying of blood cancer, and she wants me to drive you there as soon as this afternoon.” Sure enough, my mother broached the subject within hours of my arrival. “Zaineb is only thirty-five-years old,” she said. “Her husband died in an accident last year. She has been doing cleaning jobs to support herself and her children. Suddenly, she got very weak and sick, and the government-run dispensary has been of no help to her. Poor thing cannot even get out of bed anymore. I heard of her through Bazm-e-Amna”—a charitable organization my mother was active in—“and offered your help. Please go see her today.”
As I arrived in the slum area and made my way to her little shanty, I was greeted by the sight of three skeletal little girls ranging from five to nine years outside the hut. The eldest looked particularly pale and listless. I asked her if she was okay, and she shook her head. I was scared to ask the obvious: if she had eaten. My older sister Atiya is not only a first-rate pediatrician and pediatric oncologist, she is also the president of the Human Development Foundation. She is on a mission to improve health care and primary education in deeply poverty-stricken areas of Pakistan and had asked one of the little girls in the school the same question: “Have you eaten today?” The six-year-old replied, “No. It was not my turn to have breakfast today.” That answer rang in my ears as I faced the three little ones outside Zaineb’s hut. Probably none of them had had a “turn” for any meals. For days, even.
How does one go in and talk to a thirty-five-year-old woman for whom dying from leukemia is only her second-biggest problem?
Cancer treatments such as CAR-T and other targeted therapies, stem cell transplants, and immune manipulations cost hundreds of thousands of dollars. They are bankrupting affluent, developed nations of the world. They are absolutely beyond the reach of someone like Zaineb. We cannot neglect our responsibility as a global society to develop an affordable answer that is universally applicable for the nearly eighteen million people diagnosed with cancer around the world each year.
Samuel K. Sia, professor of biomedical engineering at Columbia University, wants to do just that: develop an affordable diagnostic platform. Sam created a microfluidic chip that tests for multiple diseases, including sexually transmitted ones, and is eminently affordable, costing pennies. Referred to as the mChip and no larger than a credit card, it is a handheld device that takes a drop of blood and analyzes it for quick diagnosis of a variety of diseases. It has already received approval for diagnosis of prostate cancer in Europe. Our two labs at Columbia University are collaborating in an effort to develop an implantable chip that can be inserted under the skin for constant surveillance, detection, capture, and destruction of the first cancer cells. Early detection is the most compassionate and humane solution for the cancer problem.
LAURA AND THE IMPORTANCE OF ETIQUETTE
Between May and October of 2002, both Harvey Preisler and Per Bak were dead. The aftermath of Harvey’s death included a painful awakening about how inappropriate most people are when offering their condolences. One friend, while crying her eyes out, began by offering to take me out to a singles’ bar. A surprising and recurring comment, also supposedly well meaning, but one that left me baffled about how to respond, was, “Sorry to hear Harvey died. But you are looking well.” Perhaps the most patently absurd was a message left on my answering machine by a colleague saying how sorry she was that my husband was dead, but “don’t worry, you will join him soon, and then the two of you can live happily ever after in heaven.”
I wish they had read Laura Claridge’s insightful and engaging biography, Emily Post: Daughter of the Gilded Age, Mistress of Manners. Laura, introduced to us by my brother Abbas as a brilliant professor of English, rapidly became a beloved family friend. She makes two points very clear in this book: first, from birth to death, we humans need constant guidance about how to behave; and second, minding our manners can overcome even some of our most glaring deficiencies. One early review of Post’s Etiquette captured her spirit perfectly with the quotation from Mathew Arnold: “Conduct is three-fourths of life.” As Laura put it succinctly, “The subject hardly mattered: funerals or flower arrangements, broken hearts or broken glasses, Emily held her audience in esteem, and she meant to teach her readers, would-be ‘Best People,’ whatever their background, race or creed, to do likewise.” Deep down, the real meaning of manners, according to Ms. Post, is a demonstration of sensitivity to the feelings of others. “Best Society is not a fellowship, nor does it seek to exclude those who are not of exalted birth, but it is an association of gentle-folk [in which] charm of manner… and instinctive consideration for the feelings of others, are the credentials by which society the world over recognizes its chosen members.”
A few months after Harvey’s death, I received a brief but deeply sympathetic note from Harvey’s ex-wife, Angela. Beginning in 1977 when I first met Harvey, all the way up to 2002 when he died, I had met Angela only a handful of times and not seen her since 1982. I only have positive memories of her. The letter was remarkable because of its profound kindness and also because it contained a check for rather a large amount of money. Apparently, Harvey had not changed the name of the beneficiary in his retirement plan at Roswell Park Memorial Institute so that once his death was registered, the check was automatically sent to Angela. “This rightfully belongs to you and Sheherzad,” she simply said. Such are the acts of extraordinary decency, civility, and etiquette that Ms. Post is talking about.
I remember distinctly the evening when I was getting ready for Harvey’s memorial service, just a little over twenty-four hours after his death. The opaque, intricate mundanities of living were already starting to emerge in unexpected places. I picked up my wedding band and looked to my sisters for guidance.
“Should I still wear this?” I asked.
Sughra, my younger sister, who had been silently crying as she watched me getting ready, snatched up the ring and slipped it firmly on my finger.
“Yes, you will wear it tonight and for as long as you wish!”
As Laura writes, “Only Emily Post understood the power of routine to hold one’s raw emotions at bay.” No wonder Etiquette was “second only to the
Bible as the book most often stolen from public libraries.” Post counseled the bereaved wisely with these words: “At no time does solemnity so possess our souls as when we stand deserted at the brink of darkness into which our loved one has gone. And the last place in the world where we would look for comfort at such a time is in the seeming artificiality of etiquette; yet it is in the moment of deepest sorrow that etiquette performs its most vital and real service.”
While Laura was working on the Post biography, she was diagnosed with a particularly lethal form of brain tumor with little chance of survival beyond a few months. Despite the bleakest of outlooks (at one point, her ICU physician called me to request that I counsel the family to “let nature take its course with Laura now”), Laura not only defied all odds by surviving, she restarted her work on the book in a miraculously short period of time after her surgery. Even as her brain was being regularly assaulted by the insults of radiation and chemotherapy, Laura found her own grounding in meticulously researching and recounting another great woman’s life story. The book Emily Post, supported early for its merit by Harvard’s Nieman Foundation, is not only a fantastic personal achievement for Laura, it also stands as the finest testament to the indomitable sublimity of the human spirit. Both Post and Claridge transmuted tragedy into constructive pursuits, representing the best behavior in good times and bad.
Laura did not have a primary brain tumor. She had a lymphoma with multiple lesions in the brain. She underwent several surgical resections, repeated rounds of chemotherapy, radiation therapy, targeted therapy, and an autologous bone marrow transplant. Throughout these difficult times, Laura has continued writing; indeed, she writes now with greater clarity and verve than ever. Her latest book, The Lady with the Borzoi: Blanche Knopf, was published to great acclaim in 2017. She is now working on her first book of fiction.
Harvey died of the lymphoma. RIP, Harvey.
Per died from the complications of a stem cell transplant. RIP, Per.
Laura is alive with a lymphoma sixteen years after the diagnosis. She survived the stem cell transplant.
Laura is the reason oncologists don’t give up. We can’t give up.
Long live Laura.
MARK AT HARVEY’S MEMORIAL SERVICE:
Our dad was not a sentimental man. He was ever the scientist. Emotions clouded reason… and if you cannot see reason, you may as well be blind. But Dad did have a side few were lucky enough to see. While he was always practical, he truly was an emotional man. He stood up for his beliefs, and he never backed down. One of those beliefs was that it was important to die with dignity. No complaints, despite all the pain. He didn’t want to be a burden to his children or his wife. He never was. Azra said it best: taking care of him was an honor, never a burden. There’s a quote he often spoke of: “Death stared me in the face and I stared right back.” Dad, you certainly did.
More than anything, our father was a family man. He cherished us, and we cherished him. He often thanked us for all the days and nights spent by his side, but I told him there was no need for thanks. None of us could have been anywhere else. He and I often discussed his illness. He once asked me why he should keep fighting… what good was there in it? I told him his illness had brought our family much closer together. He smiled and said he was glad something good came of it.
Azra, he adored you. He often told me it was love at first sight. You two shared a love that only exists in fairy tales. Dad could be unconscious but still manage a smile when you walked into the room. I have never seen anything like it, and I feel privileged to have witnessed your devotion to each other. The way you took care of him is inspiring. You never left his side, and you refused to let him give up. No one could have done anything more for him, and he knew it. He was very lucky to find you.
While going through his wallet, I was shocked to find a piece of paper folded up in the back. On it were two quotes written in his own pen. I’d like to share one with you. “There isn’t much more to say. I have had no joy, but a little satisfaction from this long ordeal. I have often wondered why I kept going. That, at least I have learned and I know it now at the end. There could be no hope, no reward. I always recognized that bitter truth. But I am a man and a man is responsible for himself.” (The words of George Gaylord Simpson.) Our father died Sunday, May 19, at 3:20 in the afternoon. His family lives on with a love and closeness that will make him proud. Pop, we love you. You were our best friend. We will miss you every day.
IN HONOR OF Harvey’s lifelong dedication to science and to finding a solution for his cancer patients, an annual lecture was started in his name. Below are remarks from Sheherzad at the Tenth Harvey Preisler Memorial Symposium in 2012:
I recall that last morning on May 19, 2002, as he lay dying. At 7:00 a.m., my mom came into my room where I was sleeping with my sister Sarah and told us that Dad wanted to see us. I ran into his room with the sinking instinctive certainty of an eight-year-old that all was not well, only to find him sitting up in bed, smiling and stretching his wasted arms out to hug me. We spent the next several hours with me alternately reading to him from my various favorite books, jumping on his bed, running away with his walker, having a serious discussion with him about Madagascar frogs, and taking his “tenchapur” with the thermometer I loved to play with. And each time, he would oblige me by smiling sweetly. Finally, Vania, a family friend came and took me out to the park with his daughter and my best friend, Salpi. This was the last time I saw my father.
It was only several years later that Mom told me how Dad had woken up at 5:00 a.m. that morning, saw that he was bleeding from multiple sites, recognized that he had DIC (disseminated intravascular coagulation), and announced calmly that he was going to die that day. After Mom cleaned him up and changed his dressings around the port, all he wanted to do in the last hours was to spend time with the family, even as he got more and more short of breath and his lungs filled up with blood. Dad calmed himself in those last hours by watching me play, listening to me chatter on endlessly, reading, and discussing biological facts about my pet frogs.
Amor Fati at its best.
AND THUS HARVEY lived, and thus he died. Proud to the end. He took his last labored, agonal breaths in my arms on a clear, sunny May afternoon in Chicago. His composure and his comportment until the final conscious moments was nothing short of heroic.
Stop all the clocks, cut off the telephone,
Prevent the dog from barking with a juicy bone,
Silence the pianos and with muffled drum
Bring out the coffin, let the mourners come.
Let aeroplanes circle moaning overhead
Scribbling on the sky the message “He is Dead.”
—W. H. AUDEN, “FUNERAL BLUES.”
AFTERMATH
GIVE SORROW WORDS
NAHEED. ALENA.
Some sorrows are unfathomable, language incapable of expressing them. What combination of letters could possibly speak the unspoken thoughts of the mothers Naheed and Alena as they bid unhurried farewells to the serially dying parts of the creatures they birthed and nurtured for decades? The anguish has no beginning and no end, no relief, no ascent or descent, no respite, collapsing past, present, and future into one bottomless pit.
A new language needs invention to encompass the defenselessness, the vulnerability of these two mothers who, with utmost delicacy, eased their boys into the grave, one piece at a time, each over a period of sixteen months, tormented until their child’s last breaths about how to make the bewildering segmented departure less painful. Omar had seven surgeries to remove slices of arms and lungs, a cancer-filled shoulder. In Andrew’s case, first the limbs went, followed by the bowel and bladder, then his eyesight, and in a final insult, he could swallow no more. To dare to mourn with Naheed and Alena, one must own the sorrows of the universe. No linguistic hyperbole can do justice. Language itself becomes speechless, vocabulary held hostage by the raw agony of such incalculable scales. The infinite care with which Alena washed, scrubbed, and
dressed the wasted, limp body of her twenty-three-year old, or the relentless, whacking, blistering, piercing, frightful terrors haunting Naheed in every waking hour, and in sleep, deplete the hubris of death, elevate the status of motherhood to where the stars lower their gaze. One spark of pain in the heart of these mothers eclipses the glory of the sun. Dust raised by their agitation conceals deserts, their tears forcing a river to recede, dragging its forehead obsessively in front of their grief.
Hota hay nehaan gard mein sehra meray peechay
Ghista hay jabeen khaak pe darya meray aagay
—GHALIB: EPISTEMOLOGIES OF ELEGANCE
Next to me, the wilderness is shamed into hiding in dust
The servile river grovels in the dust before me
OMAR AND ANDREW: WHAT WERE THEIR CHOICES?
Classic Greek canon places great emphasis on choice. In the Oresteia by Aeschylus, every character had a personal choice to make. Agamemnon did not have to kill his daughter Iphigenia. Clytemnestra did not have to kill Agamemnon in revenge for her daughter’s murder. Orestes did not have to kill his mother Clytemnestra to avenge his father Agamemnon. Everyone had a choice.
