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The First Cell

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Azra Raza is a professor of medicine at Columbia University and a practising oncologist. She specializes in and researches myelodysplastic syndromes (MDS), which the Canadian Cancer Society describes as “a group of diseases in which the bone marrow doesn’t make enough healthy mature blood cells.” Immature blood cells—blasts—don’t function properly, and they build up in the bone marrow and blood. Healthy red blood cells, white blood cells, and platelets are crowded out; there are fewer of them to do their vital work. MDS patients, who are usually older, often have debilitating anemia and require frequent blood transfusions, though some can be successfully treated with thalidomide. MDS used to be thought of as disease of low malignant potential, pre-leukaemia, but the syndrome is now considered blood cancer. One third of MDS patients go on to develop acute myeloid leukaemia (AML), another disease researched and treated by the author.

In over three decades of practice, Dr. Raza has cared for thousands of people with blood cancers. In her book, she tells the stories of several of these patients, as well as providing accounts of bright young people with other cancers—one, an intellectually gifted family acquaintance diagnosed with an aggressive sarcoma of the shoulder; the other, her daughter’s close friend, a young man in his early twenties, stricken with a lethal glioblastoma of the spinal cord. In a tender touch, she provides photographs of these patients, making them even more real and present for the reader. She documents how they negotiated their illness, made medical decisions, and confronted their end.

The author notes that over the years the billions of dollars directed towards cancer research have yielded valuable knowledge about its biology, but medicine has frustratingly little to show for this enormous investment in terms of actual treatments. Most of what is offered to the AML patients she sees (as well as to those with the most common types of cancer) has changed very little over the last forty to fifty years. Raza’s husband, cancer researcher Dr. Harvey Preisler—who himself succumbed to lymphoma in the early 2000s and whose suffering she describes in one chapter of her book—received the same combination of drugs that was used in 1977. Only about five percent of new cancer drugs are actually approved, and 70 percent of those provide no improvement in survival rates and are even harmful to patients. (America’s FDA is willing to approve an agent if it can prolong survival by 2.5 months over existing treatments—even if that additional couple of months is a living hell.) Treatments that are deemed “successful” employ the same old “slash-poison-burn approach” to cancer that’s always been used. While some novel immune therapies for lung cancer, lymphoma, and melanoma have come on the scene in recent years, they benefit only a few, and their cost is prohibitive. Even families with insurance plans frequently lose their life savings pursuing treatment for an afflicted loved one. Recent declines in cancer mortality rates are due to early detection—as is seen with colon and cervical cancer, for example—and smoking cessation. Given these realities, it’s not at all surprising that Raza’s impassioned main argument in the book is that cancer research needs to radically change.

The author aptly describes cancer as an example of malevolent “intelligence at a molecular level”. Perceiving its environment, it “takes actions that maximize its chances of survival,” becoming “stronger, smarter, and more dangerous with each successive cell division.” Many cancers are are still only diagnosed when they are quite advanced and extremely complex, having quickly transformed themselves, eliminating genes and entire chromosomes and acquiring multiple mutations. At this point, they are next-to-impossible to successfully treat. What is needed, says the author, is a commitment “to stop chasing after the last cancer cell and focus on eliminating the first” or, even better, “prevent the appearance of the first cancer cell by finding its earliest footprints.” She points out that oncologists and researchers are “already using sophisticated technologies to detect residues of disease that linger after treatment.” Why not harness and redirect these technologies to discover cancer early before it has laid waste to the body, she asks, pointing to the work of Bert Vogelstein’s team at Johns Hopkins, whose members are looking for the earliest markers (mutations, molecules, and metabolites) of breast, colon, lung, and pancreatic cancers in body fluids.

Early in her career, Dr. Raza treated a woman her age, a young mother in her thirties, who was terminally ill with acute myeloid leukaemia. Heartbroken that she could do little for a patient she had quickly grown to love, she took a decisive step in 1984: She began to build an MDS-AML tissue repository, banking samples from bone-marrow biopsies in order to study how these blood cancers evolve. Her tissue bank, which contains over 60,000 samples from thousands of patients, is the world’s oldest one created by a single doctor. A great challenge for Dr. Raza is actually gaining the research funds to carry out her work. She often has to court celebrities and hold benefits to get the financial backing needed to keep her project going.

The idea of actually harnessing new technology to look at “disease-caused perturbations” years ahead of their clinical appearance is not yet widely embraced by a “sclerotic” cancer industry. Over the years a huge bureaucracy and byzantine funding process has developed around in vitro and animal studies, even though these have yielded little of practical value to patients with cancer. Raza does not advocate for the abandonment of these studies, but she does offer an illuminating explanation of their limitations. Cultured cells are grown in controlled environments, quite unlike their natural ones, and the cells are forced to adapt to this hostile habitat. In time, they diverge wildly from their parents, genetically and in form and structure. Their doubling time is also much faster. While animal models may offer cell lines an environment more comparable to a human’s than petri dishes do, the complexity of the human environment is not fully understood and consequently can’t be replicated. Mice and human lineages diverged approximately 85 million years ago, and human and mice genomes are only about 50 percent identical. The life cycle of a mouse is short (three years), and the animal reaches sexual maturity at six to eight weeks. Furthermore, its metabolic rate is seven times faster than a human’s, so drugs are very rapidly metabolized in mice. Doses for clinical trials have to be drastically reduced because of the much slower metabolism of humans. Perhaps most critically, the immune system of mice evolved to be very different from that of humans. Ours developed to combat airborne pathogens and mice’s to handle earth-borne ones. A target lab mouse is healthy—not debilitated, as a human cancer patient is. Its immune system would naturally reject transplanted human cells; therefore, its immune system has to be destroyed before human cells are introduced. Needless to say, the tiny bodies of immunocompromised creatures hardly resemble the ones in which human cancer cells thrive. Yet, writes Raza, scientists have expected these transplanted cells to help them identify useful drugs for cancer patients.

<i><b>The First Cell</i></b> is an ambitious, rich, and informative book. It is also a demanding one at times. It will reward the persistent and motivated lay reader. My chief criticism is that it is occasionally repetitive. I believe some judicious cuts would have served the book well. As a lover of literature, Dr. Raza includes passages from great novelists and poets, but I’ll admit to having struggled at times with their pertinence. However, these are relatively minor complaints about an illuminating book that I’m glad to have read—one with a message that deserves to be heard.

Thanks to the publisher and to Net Galley for providing me with a digital copy for review purposes.

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I think just about everyone has known or knows of someone suffering from cancer. I really don't believe the disease is beatable. A friend of mine once told me, cancer may go into remission, but it's just hiding somewhere in a person's body, waiting for another round of attacking it. Her mother had died of cancer. I've known too many people myself who have been treated for it. One, an aunt, upon finding her cancer had returned, rejected further treatment a second time. She said she'd rather die an easier death then go through the treatment again. I think this book is a book for everyone. It's factual and informative.

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Get this book and read it. This book is about why we need to change the way cancer research is done. The ultimate goal is, of course, a finding a cure to cancer. The key is to find the first cancer cell, eradicate it before it becomes damaging or the cure just as damaging.

Research needs to be funded, to work towards this goal, of how to detect those first cancer cells. Perhaps if enough people talk about a better way then the turn may happen.

This book is an emotional one, but also filled with compassion. I hope this book will make the change.

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Author provides in depth description of the development of cancer cells, including the genetics, the politics of research, which is directly related to money, and the drugs, which offer little in the way of a cure to most people, but suffering for all. Personal relationships with patients and professional relationships with colleagues are interspersed with the history of cancer treatment, which hasn't changed over the years. The overall theme is the small amount of time the aggressive drugs provide, while lowering the patient's quality of life a patient and incurring the financial ruin for most. Honest. Realistic. Thorough.

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I learned so much from this book. Everyone is touched by cancer. This book was very informative and stresses that early detection is crucial to fighting this disease. I think everyone should read this well written book. I highly recommend it. I have ordered the book for the library and will encourage others to read it.

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Columbia University oncologist and cancer researcher Azra Raza is angry—angry about the current “protocol of surgery, chemotherapy, and radiation—the slash-poison-burn approach to treating cancer” which she calls “an embarrassment”; angry about the state of cancer research, which prioritizes mouse models and animal cancer research over research to “prevent the appearance of the first cancer cell by finding its earliest footprints”; angry about the cancer deaths of her patients and, most personally, her husband; and angry about whether, having failed to give her cancer patients a better life, she and other oncologists could have given them a better death. Raza wants “nothing less than a paradigm shift in cancer studies and treatment” and “The First Cell” is her manifesto for how it should happen.

This is not an exhaustive scholarly study of cancer (although at times I did struggle to keep up with the science)—if you’re looking for that book, try The Emperor of All Maladies by Siddhartha Mukherjee, a colleague and close friend of Raza’s. “The First Cell” is a far more personal (and for me, more affecting) book, focusing as it does on the problems with current treatment protocols as demonstrated through the personal stories of many of Raza’s patients and their families, who are given a chance to tell their experiences in their own voices. Anyone who has watched a loved one suffer through cancer treatment will be nodding their heads in agreement, as I was, throughout these sections, which prove better than anything else could how high the stakes Raza is fighting for are. “To begin the ending,” she says, “we must end the beginning. Prevention will be the only compassionate, universally applicable cure.” I finished this book rooting for her and hoping her mission to completely shift the paradigm of cancer treatment succeeds.

Many thanks to NetGalley and Basic Books/Hachette Book Group for providing me with an ARC of this title in exchange for my honest review,

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Poetic. Thought-provoking. Impossible to put down. These are not the words I expected to write in a review of a book written by a person expert in and deeply experienced with cancer in her career and in her marriage. In the excellent THE FIRST CELL, Raza succeeds brilliantly in shining a clear light into the approach, process, and system of cancer treatment. For all the supposed advances in the battle of this devious, complex, changeable malady, there have been few significant advances in halting the inevitable, painful, life-sucking progress of cancer. Raza proposes a different approach that acknowledges complexity, pain, and focuses on wellness and genuine wellbeing. An essential read for the thinking person. I am grateful to the author for sharing her experience, perspective, and poetic turn of phrase, to the publisher and Netgalley for an advance copy of this book in exchange for my honest review.

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The war against cancer: of course we know about it, of course we care about it, of course we cheer this week's victories … except maybe the war is false. Oncologist Azra Raza, specialist in myeloid leukemia, has spent a lifetime on the frontlines of the war against cancer, and "The First Cell: And the Human Costs of Pursuing Cancer to the Last" is both her professional life story but also a very human plea against oncology's ruling worldview. This is an extraordinary work, somehow combining real tales of cancer battlers, her own memoir that revolves around the death from cancer of her husband, Harvey Preisler, himself an oncologist, and also a powerful plea to rethink the decades-long, no-holds-barred war. She is convinced the world should switch "from chasing after the last cell to identifying the footprints of the first."
I first came upon an oncologist's disquiet in the closing pages of Siddhartha Mukherjee's magisterial "The Emperor of All Maladies." Perhaps, Mukherjee whispered, the war is being lost. Since then, I've observed friends enveloped by institutional cancer "battle" cycles - the ops, the chemotherapy, the radiotherapy, and (the latest) the immunotherapy. My unease festered. Now Azra Raza confirms my intellectual and emotional unrest. Lab-tested cancer drugs, she writes, fail with humans 95% of the time and the successful 5% see their lives only extended by a few months at most. In spite of progress with some cancers, in broad terms, overall "war against cancer" statistics flatline over the last three decades. "No one is winning the war on cancer. It is mostly hype, the same rhetoric from the same self-important voices for half a century." Oncologists' "inevitable slash-poison-burn cycles" hold out hope but mostly don't deliver, in fact Raza cites a number of highly personal case studies that question whether the collateral suffering was at all effective or humane.
"The First Cell" is compulsory reading from a talented writer and a first-hand participant in history. Embrace it for an emotional rollercoaster and to open your eyes. Whatever your final judgement - it's hard to jettison the "war against cancer" hopes - at least your reading will offer more choices when the Big C hits you or your family or your friends.

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Amazing perspective of an oncologist dealing with first hand cancer experience. As a physician, I like to always challenge dogma, because we don’t really know everything. This is another physician that also doesn’t really believe that we are always doing what is best and also pushing the envelope for more.

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Raza is an oncologist who has had a first-hand look at cancer through the eyes of both her patients and her husband, who died of cancer. She has seen death up close through these patients and recounts the stories of a number of them. This book is a personal memoir but is also a great discussion of the history of cancer research and treatment. Raza sees that most research funding has not been very well spent. Drugs have been developed that cost huge amounts of money, have many negative side effects, and often extend life very little. She states that the current medical model of cancer treatment of slash/poison/burn (surgery/chemotherapy/radiation) is not curing most cancers.
Raza decided to focus on studying cancers in the earliest stages, including precancels in order figure out how to arrest the disease before it progresses. A quote: "there is much exciting work going on the area of detecting the first rather than the last cancer cell".
This book was a difficult read because it does not whitewash all of the negative symptoms faced by her patients. I took a course on nutrition for cancer during my nutrition program. My interest in cancer treatments through nutrition were revitalized this year when my husband was diagnosed with precancerous esophageal dysplasia. This book solidified my desire to prevent cancer with natural methods and, if cancer is found, help combat it with natural treatments, including diet.

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“We are all tested. But it is never in the way we prefer, not at the time we expect.”—Dr. Azra Raza’s husband, Harvey, discussing the disease that killed him

“The prevention I am talking about is through identification and eradication of transformed cancerous cells at their inception, before they have had a chance to organize into a bona fide malignant, incurable disease.”

Are current methods to treat cancer making a difference in the lives of patients? The First Cell would say hell no, and within the first pages the book argues we need to start looking at treating this disease through a prevention-based strategy that acknowledges that diet and exercise are not enough to stop cancer.

“There is a crisis in the field. The bizarreness of things we are doing both in clinical and basic science is effectively cloaked under important-sounding terms, conveying a reassuring sense of objectivity—best practices, evidence-based medicine, precision oncology, genetically engineered mice. Mostly euphemisms to sweeten the bitter truth that we don’t have better treatments than what we were offering fifty years ago.”

Dr. Raza is not an impartial observer, a fact she makes clear early on when discussing how she was trained by her husband, in the same exact field, to always remain impartial. Yet when he got cancer, she was the only doc he trusted, despite his wife’s obvious failure to meet his number one criterion. It’s hard to see how any of us could make it through the death of a spouse at the hands of our life’s inanimate nemesis.

She discusses young brilliant minds in the field and why they are deluded. It’s simple, really: cancer drugs tested in mice have no predictive value in terms of human efficacy. It’s easy to feel her frustration.

“Do other cancer patients experience variations on these themes, the vertigo pf evanescent, soul-destroying, irreducible suffering? Do they run their weary fingers through serrated edges of anguish, say farewells in unspoken, unheard of languages in the silence of sleepy nights?”

The author doesn’t hide the pain of losing her husband; rather, she uses this viewpoint as a family member left behind to move her search for better cancer prevention forward to spare others her pain.

About midway through her book, Dr. Raza discusses Zen and the Art of Motorcycle Maintenance, a book I tried to finish this year—and failed. Throughout she uses poetry and book quotes to illustrate ideas and points and she uses the Robert Pirsig classic to discuss dynamic quality. Her description of the book makes me want to try again to read it, as if missing out on its wisdom will impact me beyond just this section of her book.

She quotes the book, “the only Zen you find on tops of mountains is the Zen you bring there.”

This book will give me nightmares. JC, a 34-year-old who had an uncontrollable urge to sniff gasoline while pregnant—and who succumbed to leukemia when her twins were 2.5 as a result.

The First Cell will change your mind about cancer research. It’s frustrating that the American system is so useless. We’ll all be touched by cancer in this lifetime—and we all must push for a better system to fight it.

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A well written book about a physician who treats cancer but thinks the way we are doing things is not always best for the patient. Her patients become family to her and I hope if I ever get cancer, my oncologist cares for me in the same way. One thing that stuck with me is the use of chemo. She seems to think that poisoning the body to maybe gain another few months of life at the expense living your last few months the way you want without toxins flowing through your body resonated with me. She states the current research approach doesn't mimic our bodies and thus we haven't made many improvements in treatment commensurate with the money spent. A good book but heartbreaking for those going through cancer treatment.
Thank you Netgalley, Azra Raza, Perseus Books and Basic Books for the ARC for my honest opinion

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Part memoir, part manifesto; I enjoyed The First Cell by Azra Raza, although the book felt more like a collection of essays rather than a coherent story. Each chapter focused on one of Dr. Raza's patients that had an impact on 1) the way she lives, 2) the way she acts as a physician, and 3) the way she acts as a scientist. As a scientist myself, I agree with Dr. Raza's belief that much cancer research is performed on cell lines and in mice which have little to no resemblance to actual disease, and it is a relief to see these words published. However, I think she is too broadly dismissive, forgetting, for example that research on HeLa cells has been beneficial for society, and that PD1 immunotherapy was worked out in murine models. Dr. Raza's patient vignettes tell the side of the story that When Breath Becomes Air could not: that of the physician treating the cancer patient. Cancer has touched Dr. Raza's life so intimately, not only via the loss of family, but also the loss of her patients, which she treats as family. Her stories show how much the patient/doctor relationship has changed because of the rise of Dr Google, but also how they have stayed the same emotionally as well. I leave this book with a deeper appreciation for physicians, and oncologists especially. Overall, I would recommend this book to other scientists like myself, for its refreshing take on basic research, and its heartfelt tale of a physician touched by cancer from all angles.

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Love this book, truly. Wasn't sure what to expect and did also love Emperor of All Maladies.This gives a new, exciting, if painful, perspective on the whole cancer landscape. From her own first professional, then intensely personal experience with the relentlessness of the disease, the author is exemplary is her discussions.

Her detailed knowledge of the process of disease, diagnosis and treatment mirrors the clusterfuck having cancer in this day and age really is. From the pursuit of a cure - similar in many cases to locking the barn door after the horses have fled, to the shotgun of let's try everything, the approach has been backwards. With the knowledge we have now, looking at cancer from the first cell is only logical and reasonable.

I too have had cancer, and it did and continues to scare me....I can only hope that her voice and call resonate for all of us who have had and will have to face that situation. Nipping it in the bud is far and away more preferable than chasing errant, racing cells throughout the body, and laying waste to things in its path.

Thorough, detailed and thoughtful, thank you. I enthusiastically recommend and am gategelu for the advance copy.

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