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The Song of the Cell: An Exploration of Medicine and the New Human

de Siddhartha Mukherjee

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5101845,283 (4.04)23
"From the author of The Emperor of All Maladies, winner of the Pulitzer Prize, and The Gene, a #1 New York Times bestseller, comes his most spectacular book yet, an exploration of medicine and our radical new ability to manipulate cells. Rich with Mukherjee's revelatory and exhilarating stories of scientists, doctors, and the patients whose lives may be saved by their work, The Song of the Cell is the third book in this extraordinary writer's exploration of what it means to be human. Mukherjee begins this magnificent story in the late 1600s, when a distinguished English polymath, Robert Hooke, and an eccentric Dutch cloth-merchant, Antonie van Leeuwenhoek looked down their handmade microscopes. What they saw introduced a radical concept that swept through biology and medicine, touching virtually every aspect of the two sciences, and altering both forever. It was the fact that complex living organisms are assemblages of tiny, self-contained, self-regulating units. Our organs, our physiology, our selves--hearts, blood, brains--are built from these compartments. Hooke christened them "cells". The discovery of cells--and the reframing of the human body as a cellular ecosystem--announced the birth of a new kind of medicine based on the therapeutic manipulations of cells. A hip fracture, a cardiac arrest, Alzheimer's dementia, AIDS, pneumonia, lung cancer, kidney failure, arthritis, COVID pneumonia--all could be reconceived as the results of cells, or systems of cells, functioning abnormally. And all could be perceived as loci of cellular therapies. In The Song of the Cell, Mukherjee tells the story of how scientists discovered cells, began to understand them, and are now using that knowledge to create new humans. He seduces you with writing so vivid, lucid, and suspenseful that complex science becomes thrilling. Told in six parts, laced with Mukherjee's own experience as a researcher, a doctor, and a prolific reader, The Song of the Cell is both panoramic and intimate--a masterpiece"--… (mais)
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Mostrando 1-5 de 17 (seguinte | mostrar todas)
The information in this book was really interesting and well presented. However it is information dense and I would recommend reading it slowly, not only to take it in, but to prevent yourself from getting burned out by it. I was reading it on a deadline and pushed through it which left me feeling a bit overwhelmed with the material at times. It is very readable and easy to understand so don't be put off by the science. Just take your time with it. ( )
  Iudita | Aug 19, 2023 |
Part science, part history, part autobiographical in scope, Mukherjee manages to cover single cell biology all the way through current immunotherapy. He doesn't talk down to the reader, nor does he simplify the science of cellular biology too much. He shows wary elation over progress that's been made in the field yet readily admits there's multitudes that isn't understood by researchers. Worthy of 10 stars, I read one chapter a day to soak the words in. ( )
  Ann_R | Aug 7, 2023 |
This is my third Mukherjee book. I’m a glutton for punishment! Being undeniably a non-scientist, I still find his books accessible and worth the struggle. He is a clever educator who piles on science history and supplements it with plot grabbing anecdotes. The stories mean little though without the science history. I particularly enjoy the analogies he finds to make his content more understandable to the lay person.
The CD4-positive T cell sits at the crossroads of cellular immunity. To call it a “helper” cell is to call Thomas Cromwell a mid-level bureaucrat; the CD4 cell is not so much a helper as it is the master machinator of the entire immune system, the coordinator, the central nexus through which virtually all immune information flows.
Loc 3800

I also appreciate that he summarizes at regular intervals to remind the novice reader what we've learned and where we are going next. I am glad I read it and would recommend it to curious readers and to those for whom medical science is their interest or vocation. ( )
  beebeereads | Jun 16, 2023 |
Undoubtedly, this book goes in-depth about the internals of a cell. This is the first book of Dr. Siddhartha Mukherjee that I've read and I'm inclined to read his previous books as well.

His analogies about the process of protein reaching its destination using a postal service and that of a human genome to a library helps etch the concepts in our minds. The write is so elegant and involved that many a times I was imagining these cell components as little lives living inside the 'fortress' of the cell city performing their job, mostly diligently - there are failures at times - just like us humans.

I found the text fascinating, enlightening and illustrative on the topic of "What a cell actually does". ( )
  nmarun | Jun 2, 2023 |
This is the third book I have read by this author. He always writes very well, and knows how to enliven the science with personal stories, dramatic clinical histories, and personal facts about the scientists discussed. I think his approach is formulaic, in a sense. All of his scientists are introduced with some tidbit about their outside interests ("rowing fanatic"), habits, appearance, idiosyncrasies, and usually some explanatory biography that motivated them to study a certain topic. The discoveries are always sudden and "breathtaking", although all of them are peering through microscopes at cell cultures. A lot of graduate students and post-docs are involved, and the question of credit for fundamental discoveries comes up often, but the poverty wages of post-docs are never discussed. I am in awe of Mukherjee's genius and productivity, although I do not see how he can be a writer, a clinician, a basic cell biology scientist, a husband and parent, without a large research staff. It woiuld take me a year or two to read all the articles and books he cites. His cell biology history and description is not comprehensive, and he is clearly more familiar with developments in his field of oncology.
I marked many interesting points in his book:
p. 50 - 1858 Rudoph Virchow's doctrine of the cells - omnis cellula ex cellula
p. 98 - 1878 Walther Flemming describing mitosis in salamandar eggs
p. 109 -1968 Robert Edwards & Walter Steptoe (with usual modern nurse who does not get a Nobel) pioneer in vitro fertilization
p. 124 - 2018 "JK", the Chinese scientist who sensationally implanted genetically altered human embryos
p. 137 - 1200 or so, Albertus Magnus described animal and bird embryos
p. 141 - 1920 or so, microtransplantation of embryo parts creates two headed tadpoles
p. 143 - 1961 thalidomide birth defects and FDA scientist Frances Kelsey blocking approval in the US
p. 155 - 150 AD Galen and black bile causing cancer and depression (black bile in Latin is melan-cholia)
p. 165 - 1881 Giulio Bizzonero describes platelets and their role in clotting
p. 178 - 2020 At the shrine of the Indian godess Shitala in Kolkatta, describing variolation for smallpox
p. 211 - 1987 Alain Townsend describing immune function based on class I MHC molecules - structure looking like an open bun for an antigen hot dog
p. 214 - 1990s Class I MHC antigens from inside cells recognized by T8 cells, and peptides in lysozomes loaded on Class II MHC sensed by T4 lymphocytes
p. 227 - 1500 BC or so, Vedic philosophy "atman" (self) and "Brahman" (universal, multitudinous self)
p. 239 - 1994 Immune checkpoint inhibitor CTLA4
p. 252 - 2020 SARS-COV2 stops infected cells from secreting interferon type 1 that signals early infection to T cells
p. 278 - Ramon y Cajal drawings of nerve cells and synaptic boutons
p. 292 - 2003 Helen Mayberg deep brain stimulation in Brodmann area 25 (subcallosum cingulate gyrus) for treatment of depression
p. 300 - 1920 Frederick Banting and the discovery of insulin, in the islets of Langerhan (described in 1869)
p. 321 - 1960 Till and McCulloch paper showing the existence of bone marrow stem cells
p. 324 - 1963 graft vs host disease ( )
  neurodrew | May 3, 2023 |
Mostrando 1-5 de 17 (seguinte | mostrar todas)
The rise of the ‘new human’ – how stem cells are revolutionising medicine.

Siddhartha Mukherjee's brilliant The Song of The Cell explains how these building blocks will upend our understanding of life itself.
very cell in your body, from toenail to brain, comes from a single original cell: the fertilized egg that was you at conception. So every different organ and tissue in the human body can in principle be produced by an embryonic cell, or stem cell. That being the case, why don’t we grow new limbs after injury, like salamanders and starfish do? Alas, our cells don’t always do what we’d wish. At least, not yet.

The prospect of the kind of “cellular engineering” that might make such therapies possible is one among many themes of The Song of The Cell, whose author, the oncologist Siddhartha Mukherjee, previously wrote the bestselling The Emperor of All Maladies: A Biography of Cancer (2010). Cancer itself is a recurring thread here too, being another way in which our cells can rebel against our hopes and desires. (There are some particularly moving scenes at the bedside of a friend and patient of the author’s.) What can make the disease so intractable, he explains, is that a single tumour can contain cells that have mutated in different ways, so that it is “an assemblage of nonidentical diseases”. So even novel therapies that sequence a tumour’s genome are not guaranteed to succeed.

No one knows how the planet’s first biological cell – the shared ancestor of all living things, from magic mushrooms to Liz Truss – constructed itself, billions of years ago. But somehow a bunch of proto-genetic material surrounded itself with a protective bubble and life got going. Later, single cells decided it might be worth getting together – perhaps huddling for defence, though again no one really knows – and so multicellular organisms such as shrubs and lizards were eventually made possible. As Mukherjee explains, cells have evolved into exquisite nanobots, packed with all sorts of machinery for energy production, replication, and – in the case of immune cells – hunting and killing.

Immunotherapy – the re-education of a patient’s own immune cells, the better to target cancer or other disease – is one of the cutting-edge medical interventions that really interest Mukherjee, and he relates some fascinating case studies of how it can work or fail. The problem is often that the supercharged immune cells go after other innocent organs (say, the liver) as well as the enemy. In a short but excellent chapter on the covid-19 pandemic, meanwhile, Mukherjee explains the especially vicious cellular effects of the Sars-Cov-2 virus’s hijacking and subverting of the immune system itself. Still it isn’t known how exactly this is done. “The monotony of answers is humbling, maddening,” the author writes. “We don’t know. We don’t know. We don’t know.”

What we do know, however, is already impressive. The fact that living tissues are made from cells was first discovered only in the late 17th century, by microscope-building investigators such as Robert Hooke and the Dutch cloth merchant Antonie Van Leeuwenhoek. (Hooke called them “cells” because their structure reminded him of monks’ rooms.) Two hundred years later, it was still common for surgeons who dropped a scalpel on a blood-and-pus-soaked floor simply to wipe it off on their gowns for reuse. (Pus was thought to have splendid healing powers.) And now, a mere 150 years later, we can rewrite the DNA inside cells to cure some kinds of vision or hearing loss.
By engaging in such medical magic, Mukherjee argues that we are in a sense creating “new humans”, which might be thought a slight overstatement, but one cannot begrudge him his delight in his chosen science. Indeed, the subject of the cell is so vast in his hands – covering not only the anatomy of single cells, but also everything from IVF and heart attacks to battlefield medicine, deep-brain stimulation for depression, the Thalidomide disaster, the discovery of insulin, and gene-edited babies – that he has effectively attempted to write a book about the entirety of human biology and modern medicine. The guiding metaphor of “new humans”, as we allegedly shall be once immunological and genetic engineering becomes routine, is therefore structurally useful if not altogether convincing.

It is fortunate, then, that Mukherjee he is such an engaging writer, alert to both nanoscopic beauty and the potential deceptions of metaphor. After a particularly gruelling hospital episode, he comments: “Ever since that evening, I never use the word ‘bloodbath’ casually.” The most immediate parts of the book, indeed, are the periodic case studies from the author’s clinical practice, written with compassionate warmth and humour, and the personal glimpses into an ordinary scientific life and the dedication that goes with it. At one lovely point, he relates how he spends Monday mornings alone in a darkened room at his hospital, looking at blood samples under a microscope. It’s his favourite time of day. “I love looking at cells, in the way a gardener loves looking at plants.”

He also has an amusing habit of describing British places (Oxford, Oldham) as interminably rainy or foggy purgatories in which scientists must nonetheless doggedly pursue the truth, with wry asides at “the English habit of deadly euphemism” he encountered as a student. One scientific mentor, he relates, had a habit of reacting to an idea he thought ludicrous by calling it “subtle”. Mukherjee remembers: “At lab meetings, I must confess, I was often rather subtle.” In a more flattering sense of that term, he still is.
adicionado por AntonioGallo | editarThe Telegraph
 
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In the sum of the parts, there are only the parts. The world must be measured by eye. - Wallace Stevens
[Life] is a continuing rhythmic movement, of the pulse, of the gait, even of the cells. - Friedrich Nietzsche
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(Prelude) The conversation took place over dinner in October 1837.
Introduction) In November 2017, I watched my friend Sam P. die because his cells had rebelled against his body.
Both of us, you and I, began as single cells.
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"On August 6, 1945, at about eight fifteen in the morning, thirty-one ­thousand feet above the Japanese city of Hiroshima, an atomic bomb nick­named Little Boy was dropped from an American military aircraft, a B-29 bomber nicknamed the Enola Gay. The bomb took about forty-five seconds to descend, and then detonated in midair, nineteen hundred feet above the Shima Surgical Hospital, where nurses and doctors were at work, and pa­tients still in their beds. It released about the energetic equivalent of fifteen kilotons of TNT -- about thirty-five thousand car bombs going off at once. A circle of fire, more than four miles in radius, spread out from the epicenter, destroying everything in its wake. The tar on the streets boiled. Glass flowed like liquid. Houses were flicked into oblivion, as if by a giant, incinerating hand. Outside the stone steps of Sumitomo bank, a man or woman who was vaporized instantly left a shadow of herself on the stone that had been blistered white by the conflagration.

"The waves of death that followed had three crests. About seventy thousand to eighty thousand people -- nearly 30 percent of the city's population -- were broiled to death almost instantly. 'I was trying to describe the mushroom [cloud], this turbulent mass,' one of the tail gunners of the aircraft wrote: 'I saw fires springing up in different places, like flames shooting up on a bed of coals [ ... ] it looked like lava or molasses covering the whole city, and it seemed to flow outward into the foothills where the little valleys would come into the plain, with fires starting up all over.'

"Then came a second wave -- from radiation sickness (or 'atomic bomb sickness' as it was initially called). As the psychiatrist Robert Jay Lifton said, 'Survivors began to notice in themselves a strange form of illness. It consisted of nausea, vomiting, and loss of appetite; diarrhea with amounts of blood in the stools; fever and weakness; purple spots on various parts of body from bleeding into the skin ... inflammation and ulceration of the mouth, throat, and gums.'

"But there was yet a third wave of devastation to come. Survivors who received the lowest doses of radiation began to develop bone marrow failure, resulting in chronic anemias. Their white cell counts sputtered, then declined and collapsed over a few months. As the scientists Irving Weiss­man and Judith Shizuru put it, 'those who died from the lowest lethal dose irradiation almost certainly died of hematopoietic [blood production] failure.' It wasn't the acute death of blood cells that killed these survivors. It was the inability to sustain the constant replenishment of blood; a collapse homeostasis of blood. The balance between regeneration and death had tipped. To paraphrase Bob Dylan: the cells not busy being born were dying.

"Macabre as it was, the bombing of Hiroshima provided proof that the human body possesses cells that continuously generate blood, not just in the moment, but for prolonged periods of time, through adulthood. If these cells are killed -- as they were in Hiroshima -- the entire blood system would eventually falter, unable to balance the rate of natural decay with the rate of rejuvenation. In time, these cells, capable of rejuvenating blood, would be termed 'blood-forming' -- or 'hematopoietic' -- 'stem and progenitor cells.'

"Our understanding of stem cells was born of a paradox: an unfathomably violent attack in an attempt to restore peace at the end of an unfathomably violent war. But stem cells are themselves a biological paradox. Their two principal functions seem, at face value, to be precisely opposed to each other. On one hand, a stem cell must generate functional 'differentiated' cells; a blood stem cell, for instance, must divide to give rise to the cells that form the mature elements of blood-white cells, red cells, platelets. But on the other hand, it must also divide to replenish itself -- i.e., a stem cell. If a stem cell achieved only the former function -- differentiation into mature, functional cells-the reservoir of replenishment would eventually be ex­hausted. Over the course of adulthood, our blood counts would keep falling year after year, until there were none left. In contrast, if it only achieved its own replenishment -- a phenomenon termed 'self-renewal' -- there would be no production of blood.

"It is the acrobatic balance between self-preservation and selflessness­ -- self-renewal and differentiation -- that makes the stem cell indispensable for an organism, and thereby enables the homeostasis of tissues such as blood. Cynthia Ozick, the essayist, once wrote that the ancients believed that the moist track of slime left behind by a snail in its trail was part of the snail's self. Bit by bit, as the slime rubs off, the snail is depleted, until the organism disappears altogether. A stem cell (or in the snail's case, a slime-producing cell) is a mechanism to ensure that the moist track of slime -- i.e., new cells -- are generated constantly and that the snail does not rub itself into oblivion."
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"From the author of The Emperor of All Maladies, winner of the Pulitzer Prize, and The Gene, a #1 New York Times bestseller, comes his most spectacular book yet, an exploration of medicine and our radical new ability to manipulate cells. Rich with Mukherjee's revelatory and exhilarating stories of scientists, doctors, and the patients whose lives may be saved by their work, The Song of the Cell is the third book in this extraordinary writer's exploration of what it means to be human. Mukherjee begins this magnificent story in the late 1600s, when a distinguished English polymath, Robert Hooke, and an eccentric Dutch cloth-merchant, Antonie van Leeuwenhoek looked down their handmade microscopes. What they saw introduced a radical concept that swept through biology and medicine, touching virtually every aspect of the two sciences, and altering both forever. It was the fact that complex living organisms are assemblages of tiny, self-contained, self-regulating units. Our organs, our physiology, our selves--hearts, blood, brains--are built from these compartments. Hooke christened them "cells". The discovery of cells--and the reframing of the human body as a cellular ecosystem--announced the birth of a new kind of medicine based on the therapeutic manipulations of cells. A hip fracture, a cardiac arrest, Alzheimer's dementia, AIDS, pneumonia, lung cancer, kidney failure, arthritis, COVID pneumonia--all could be reconceived as the results of cells, or systems of cells, functioning abnormally. And all could be perceived as loci of cellular therapies. In The Song of the Cell, Mukherjee tells the story of how scientists discovered cells, began to understand them, and are now using that knowledge to create new humans. He seduces you with writing so vivid, lucid, and suspenseful that complex science becomes thrilling. Told in six parts, laced with Mukherjee's own experience as a researcher, a doctor, and a prolific reader, The Song of the Cell is both panoramic and intimate--a masterpiece"--

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