Azra RazaCríticas

Dr Azra has a point of view about early detection of cancer and whether or not animal testing can translate to treatment for humans. Not as relatable, for me, as Being Mortal by Atul Gawande.

The Myth Of (Cancer) Experience. This book actually does a phenomenal job of using both hard data and anecdotal case studies to show what the current state of cancer research and treatment is - and why it is costing us far too much in both lives and dollars. This is a cancer doc/ researcher who has been in the field longer than this reader has been alive, and yet she attacks the problem in a way that genuinely makes sense: if cancer is effectively a group of cells that begin replicating uncontrollably, the best way to eliminate this phenomenon is to detect these cells as early as possible and eliminate them before they become problematic. Using several patient case studies - including her husband, who apparently started out as her boss, and her daughter's best friend among them - Raza does an excellent job of providing names and faces (yes, the book has pictures of the patients as well) to go along with the alarming yet decently documented data. (Roughly 18% of the book is bibliography, which is perhaps a touch low - 25-30% is more typical - but is better than one might expect from such a case study driven narrative.) Ultimately this book actually makes the case for The Myth of Experience better than the authors of the book by that title did, which is actually fairly interesting to this reader. :) And the Urdu poetry (with English translations as well) was a nice touch to lighten a text that could otherwise be a bit dreary. Very much recommended.

Important, but just not very readable. It rambles and meanders from personal experience, densely scientific information, terribly sad bad-death stories, and glittering social gala fundraisers, and back again. Important because she paints a clear-eyed and damning picture of the useless "moonshot for the cure" approach to cancer, fueled by a never-ending quest for drugs: obscenely expensive, tested in ways that are meaningless for real-life treatment in human beings, and providing marginal (if any) benefit: average life extension is twelve weeks. If she had stayed with that, with a few well-chosen patient stories, it would have been a much better (and shorter) book, and perhaps a wider readership. Better to read Atul Gawande's "Being Mortal" for the end-of-life choices.

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.

The First Cell 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.

Subtitle: And The Human Costs of Pursuing Cancer to the Last

Azra Raza is an oncologist and researcher, primarily specializing in MDS (myelodysplasic syndromes), which frequently lead to acute myeloid leukemia, a deadly cancer. Her primary thesis is that we need to change the paradigm for cancer research and treatments. Currently, research focuses on making tiny incremental changes in survival rates. Barely any progress has been made in cancer survival rates in the last 50 years, other than progress made as the result of early detection.

Interspersed with the facts and the arguments she presents to support her thesis are stories of many of the cancer patients she has treated over the years, as well as the personal story of her and her husband who passed away from cancer at a relatively young age.

In her view, "Prevention will be the only compassionate, universally applicable care," for cancer. By "prevention", she is not referring to life style changes etc., but to the identification and eradication of transformed cancer cells at their inception. In her words, "We should not be aiming for weeks of improved survival." No more "mouse models." She is arguing for a huge about face in how scientists approach cancer research and treatment.

She makes this point repetitively, over and over. Unfortunately, she doesn't really present much information on how this is to be accomplished, and I am at a loss as to what she is arguing for scientists/doctors to do. So we are left with a book that points out problems, but does not provide solutions. And, I found that even identifying the problems was done in a somewhat disorganized way. The inclusion of the personal stories of her patients, while interesting to me, were not particularly necessary to presenting her arguments, other than showing the hell current treatments for cancer can put patients through, and ended up disrupting the flow of her arguments. It seemed to me there were two books here: personal cancer stories and a scientific argument, and neither helped the other much when they were put together.

A much better book I read several years ago about problems in cancer research is The Truth in Small Doses by Clifton Leaf, which I would recommend if you are interested in the subject. The First Cell, not so much.

2 stars

Oddly refreshing critique-cum-memoir given the macabre topic. Raza is an oncologist specialising in MDS, a blood disorder which can lead to the aggressive leukemia AML. She alternates between vignettes of her patients; advocacy of a holistic rather than reductionist approach to cancer research; and various accounts of cancer progression and treatment.

Much like her friend and colleague Siddhartha Mukherjee's The Emperor of All Maladies, Raza tries to combine a literary and emotive writing style with scientific narrative, but unlike Mukherjee she is focused on one goal. She believes clinicians and researchers should work more closely with each other and with cross-functional experts to achieve more ambitious results. Spending billions of dollars on cancers grown on petri dishes and in rodents for paltry returns is a dead end. Reductionist approaches do not work as the "seed" (cancer cells) and "soil" (microenvironment) are both important. Instead, analysis of human tissues, cancer progression and biological markers to root out the first cancer cell rather than the last is more likely to yield dividends.

Raza argues against treatment that is often worse than the illness. The slash-poison-burn regimen of surgery-chemotherapy-radiation lends itself, by a form of natural selection, to the emergence of resistant and metastasising cancer. While I'm convinced the current paradigm is broken, Raza isn't able to convince me hunting the first cell the way she envisages is the solution. The author herself mentions many times the challenges of finding early stage cancer, or tracing the pattern of mutations which lead to cancer. Raza shares some of the worrying statistics detailed in H. Gilbert Welch's eye-opening Overdiagnosed, which shows how the current trend towards more powerful / frequent scanning or narrower acceptable ranges has diminishing returns, or may even cause more problems than it solves.

Once found, there is then the challenge of targeting a small number of cancerous cells. Raza outlines an approach or two to tackle the problem, but it all seems very distant. She imagines a chip which will monitor blood and alert when hallmarks of cancer are found, then a way to isolate cancerous cells by their markers. It may well happen, but I would also have liked to hear about the influence of comorbidities, or the importance of nutrition and exercise to avert the obesity epidemic. The hope, which Raza acknowledges, is artificial intelligence and big data expertise can bridge the gap between current research endeavours and her dream.

Raza is pretentious at times. The constant name dropping and plethora of quotes become grating. We learn that Raza can recite dozens of lines of poetry (English or Urdu works); she once ordered a collection of 100 classic books to distract herself; her family (and patients!) are all brilliant geniuses. On the positive side, she expresses humility early on when she admits cancer treatment is currently a failure. Some of this blame is shared with "the system" which gives patients unwarranted hope. She gives a nod to Atul Gawande: "giving in" to cancer is in no way a failure. Fighting a lost battle to the last is debilitating all round, physically, emotionally and financially.

I can look past a style of writing I deem pretentious, because it does not detract from the power of The First Cell. Sure, the ideas here may not be novel. But the vision is put forward forcefully and eloquently in a manner digestible by a layperson like myself. For me, that's good enough.

This book, written by an oncologist, describes how we have lost the “war” on cancer. We have certainly improved survival rates for some cancers, and others stand a much better chance of being cured completely in a patient. But the treatment options differ little from the advances made in the 1970s; they cause agonizing physical, emotional and financial difficulties for patients and their families; and they don’t even win that much more time. Dr. Raza argues that instead of seeking solutions that treat cancer after it’s shown up, that we need to be investing in measures that detect the first cell to turn cancerous—stop the cancer in its tracks before it has a chance to develop.

I knew this would be an emotional read because it was likened to When Breath Becomes Air, by Paul Kalanithi, and Dr. Raza’s own husband, Harvey, died of cancer, and this story was covered in the book. But I wasn’t expecting to read this sentence:

“I treat and study a bone marrow preleukemic condition known as myelodysplastic syndromes (MDS) as well as acute myeloid leukemia (AML), which develops in a third of MDS patients.”

My grandfather, who died almost 3 years ago, had this very syndrome and required regular blood transfusions. As far as I’m aware, it never progressed to leukemia—it was just managed with the transfusions. He did have shots of some other drug at one point, but it was expensive and ended up stopping working properly. So to see this sentence in print, at the time I did, was overwhelming.

Dr. Raza marshals her facts and experiences thoroughly. She has built strong relationships with her patients, many of whom agreed to tell their stories with their real names, and even with their photos. She is candid about the failures of the system and about patients where she feels she has let them down. And she is aware that the system as built will be very slow to change, but that doesn’t stop the change from needing to be made.

I highly recommend this book, with the caveat that the writing is on the more technical side, especially when it talks about specific cells and inhibitors and that sort of mechanism at the cellular level.½