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Summary
Summary
The story of the search for p53--the most important gene in medicine.
All of us have lurking in our DNA a most remarkable gene: it is known simply as p53 and its job is to protect us from cancer. p53: The Gene that Cracked the Cancer Code tells the story of the discovery of the gene and of medical science's mission to unravel its mysteries and get to the heart of what happens in our cells when they turn cancerous. When all is well, this gene constantly scans our cells to ensure that when they grow and divide as part of the routine maintenance of our bodies, they do so without mishap. If a cell makes a mistake in copying its DNA during the process of division, p53 stops it in its tracks, sending in the repair team before allowing the cell to carry on dividing. Cancer cannot develop unless p53 itself is damaged or handicapped by some other fault in the system. Not surprisingly, p53 is the most studied single gene in history.
Through the personal accounts of key researchers, the book reveals the excitement of the hunt for new cures--the hype, the enthusiasm, the lost opportunities, the blind alleys and the thrilling breakthroughs. As the long-anticipated revolution in cancer treatment tailored to each individual patient's symptoms starts to take off at last, p53 is at the cutting edge. This is a timely tale of scientific discovery and advances in our understanding of a disease that still affects more than one in three of us at some point in our lives.
Author Notes
Sue Armstrong is a science writer and foreign correspondent who has worked for a variety of media organizations, including New Scientist and BBC World Service. Since the 1980s, she has undertaken regular assignments for the World Health Organization (WHO) and UNAIDS, writing about women's health issues and the AIDS pandemic, among many other topics. The author of A Matter of Life and Death: Inside the Hidden World of the Pathologist , Armstrong lives in Edinburgh, Scotland.
Reviews (6)
Publisher's Weekly Review
Science writer Armstrong (A Matter of Life and Death: Inside the Hidden World of the Pathologist) conveys all the excitement and determination of the scientists who have relentlessly chipped away at the mystery of a workhorse gene known as p53, "the common denominator of cancers," in hopes of improving cancer research and treatment. Armstrong writes that scientists "working on the front line" of p53 research "believe we are on the threshold of a golden age in cancer prevention and cure." She makes accessible to the public a scientific mystery that she personally finds fascinating, speaking directly to many of the key players involved in p53 research and adeptly unwinding the difficulties confronting them since the gene's discovery in 1979. Armstrong takes fascinating side trips along the way, relating how p53 was used in "nailing Big Tobacco"-by proving the link between smoking and cancer-and revealing its role in the relationship between cancer and aging. She succeeds in her goal to "stand clear of those ledgers full of data as far as possible and tell the story of some of the curious, obsessive, competitive minds that to unravel the deepest mysteries of cancer." (Feb.) (c) Copyright PWxyz, LLC. All rights reserved.
Booklist Review
p53 is a sort of supergene that codes for a protein of great consequence in warding off cancer. Curiously, this gene can exhibit a split biological personality. Think Dr. Jekyll/Mr. Hyde on a molecular level. The normal p53 gene's main task is thwarting tumor formation when cellular DNA is damaged. When the gene functions properly as a tumor suppressor, a cell can't become cancerous. But if p53 is corrupted by a mutation, unruly cells are able to move toward malignant transformation. Under normal circumstances, the gene is described as the guardian of the genome. When p53 mutates, it is a common denominator of cancers. p53's activity is influenced by a variety of factors, including cellular stress, a protein known as Mdm2, and carcinogens. Incorporating interviews with the many scientists involved in the discovery and understanding of p53, science writer Armstrong adroitly untangles the complex story of this impressive gene. p53-based therapies for cancer treatment and its use as a biomarker to screen for early malignancies loom as amazing possibilities.--Miksanek, Tony Copyright 2010 Booklist
Choice Review
This book presents a historical perspective and fast-paced narrative of the race to characterize the role of the protein p53 in the development of cancer. Author/journalist Armstrong weaves a captivating story using personal anecdotes and interviews from leading researchers in cancer biology. She begins with the 1966 discovery of the Src gene from the cancer-causing Rous sarcoma virus as a model of the mechanics of cancer. The discovery of p53 followed as an inaugural example of a classification of "tumor suppressor" genes protecting against cancer onset. Surprisingly, p53 is defective in 50 percent of all cancers, acting as a central gatekeeper of the cell. Normally, p53 detects DNA damage and can destroy cells when mutations produce uncontrolled cellular proliferation. Defective p53 fails to signal, permitting cellular growth, tumor formation, and metastasis that allows the cancer cells to spread through the body. The author minimizes the use of scientific jargon throughout the text and focuses on the history and excitement of scientific discovery. Although her journalistic presentation of the p53 story is engrossing, a more complete bibliography including the many articles referenced in the interviews would be valuable for academic and educational purposes. Summing Up: Recommended. All library collections. --Dale L. Beach, Longwood University
Guardian Review
'A cure for cancer" - the phrase is so often repeated, surely it must finally materialise? To anyone not familiar with the developing story of cancer research, the position seems tragically unsatisfactory. Billions of pounds and decades of work by thousands of researchers have produced much better prognoses for some cancers, but harsh forms of chemotherapy and radiotherapy are still the standard treatment and the much sought-after magic cure remains tantalisingly out of reach. As Sue Armstrong points out at the beginning of her book, while we may naively wonder why so many people get cancer, researchers are asking "Why so few?". Every time a cell divides - skin and digestive-tract cells are constantly proliferating - there is a possibility of genetic errors. For cancer to develop, it requires the control mechanism in just one cell to be thrown into disorder, resulting in unlimited replication of that rogue cell. Considering the stupendous number of cell divisions occurring in the human body the development of cancer is rare. Scientists have long suspected that there is a very powerful protective mechanism at work. P53 (the name refers to a protein of molecular weight 53 kilodaltons) is the cancer prophylactic for most multicellular organisms; it has been dubbed the guardian of the genome. While cancer has many causes and can be insidiously malignant throughout the body, p53 is the single most unifying factor in the disease: for most kinds of cancer to develop, p53's suppressor activity has to have been disabled. It has taken scientists a long time to establish some of the basic facts about cancer. In 1911 the pathologist Peyton Rous reported a virus that caused cancer in chickens. For decades this finding was dismissed: cancer, according to the official line, could not be caused by a virus. Rous lived long enough to see Francis Crick and James Watson's double helix structure of 1953 establish DNA's role at the heart of life and for his own theory to be subsequently vindicated; he received the Nobel prize in 1966 for his pioneering work. How did we come to probe these minute molecular workings of nature? Most popular texts on genomics and molecular biology blithely report the results without offering any insight into how the scientists have reached their conclusions. Armstrong's book has one of the best accounts I've read of how science is actually performed. She asks, what can they actually see? When it comes to a gene, which is only two nanometres wide, the answer is "nothing"; they work by inferring from experiments on things that they can see. As she says: "It is the 'unseeable' nature of molecular biology . . . that makes it so difficult to grasp." She quotes one of her scientists, Peter Hall: "it's based on faith, ultimately." And even when scientists have a good sense of what their experiments are telling them, they're up against the fact that life is an immensely complicated process: we can land a probe on a distant comet after a 10-year flight because the Newtonian clockwork of bodies in space is predictable, but all-embracing laws of biology are hard to find. The process of discovery goes like this (and p53 is a classic example): something unexpected and odd turns up; investigation begins; its character gradually becomes clearer but its purpose remains a mystery; then evidence accumulates to suggest a function. That evidence is often misleading and, in the case of p53, a function diametrically opposed to the true one was ascribed to it for 10 years: it was thought to be a cancer-causing protein. Then came the moment of clarity and the potentially great unifying principle was born: in 1989, P53 was revealed as the master tumour suppressor - an order was established at last. There are great hopes that our knowledge of p53 will lead to novel cancer treatments, but the pattern has grown much more complicated since then. In some situations p53 can cause cancer. For cancers to grow they need a mutated and disabled p53: in science, these cycles of discovery go on forever, and so will the battle between cancer and p53. But progress is being made. One of the brightest hopes for therapy using p53 is in families with a predisposition to cancer. The reason for this blight is that the family members have each inherited a mutant copy of p53 and are therefore without the normal protection it provides. An experimental gene therapy (Advexin) already exists to correct this, but in 2008 the US regulatory body refused to license the treatment. A similar product, Gendicine, is licensed in China and approval for its clinical use is being sought in the US. One common story in today's medical research is of remarkable possibilities constantly being blocked by a sluggish regulatory system and the skewed priorities of Big Pharma, which prefers to develop bestselling drugs that will have the widest use. Armstrong's book will offer many readers a sense of hope, but might also induce intense frustration at the long time it takes for discoveries in the lab to filter down to hospitals and the marketplace. Nevertheless, we can be sure that p53, even if it is not the "cure for cancer", will have an honourable role to play in our attempts to find one. 288pp, Bloomsbury Sigma, pounds 16.99 To order P53: The Gene that Cracked the Cancer Code for pounds 13.59 go to bookshop.theguardian.com or call 0330 333 6846. - Peter Forbes Caption: Captions: The tumour-suppressing protein How did we come to probe these minute molecular workings of nature? Most popular texts on genomics and molecular biology blithely report the results without offering any insight into how the scientists have reached their conclusions. [Sue Armstrong]'s book has one of the best accounts I've read of how science is actually performed. She asks, what can they actually see? When it comes to a gene, which is only two nanometres wide, the answer is "nothing"; they work by inferring from experiments on things that they can see. As she says: "It is the 'unseeable' nature of molecular biology . . . that makes it so difficult to grasp." She quotes one of her scientists, Peter Hall: "it's based on faith, ultimately." And even when scientists have a good sense of what their experiments are telling them, they're up against the fact that life is an immensely complicated process: we can land a probe on a distant comet after a 10-year flight because the Newtonian clockwork of bodies in space is predictable, but all-embracing laws of biology are hard to find. - Peter Forbes.
Kirkus Review
The scientific history of the gene that regulates cancer in humans. "Because most molecules are smaller than the wavelength of light," writes Armstrong (A Matter of Life and Death: Conversations with Pathologists, 2008, etc.), most of what transpires in molecular biology is unseen. However, with the discovery of the DNA double helix in 1953, under the right conditions, scientists suddenly had something visible to work with, enabling them to decipher the components of human cells and how they interact with one another. Armstrong details the extensive research that has gone into one gene in particular, p53, which regulates the body's ability to fend off cancer. First concretely identified in 1979, the scientific interest in p53 waxed and waned as researchers around the world, working in isolated labs, analyzed this gene in a variety of scenarios. Without excessive jargon or detail, the author leads readers through years of experiments conducted by exemplary scientists in their respective fields. Armstrong chronicles the numerous disappointments and eureka moments when the research yielded unexpected and significant discoveries on how and why p53 plays such a huge role in regulating the production of cancerous tumors. As scientists continue to work with and manipulate this gene, they learn more about how it functions, which will help them create courses for cancer treatment that are highly personalized to an individual's genetic background. This would ease many of the side effects currently suffered by cancer patients, such as hair loss and nausea. Armstrong's narrative is informative and entertaining for those with a medical or scientific background or readers who have an interest in scientific breakthroughs, but it may be less appealing for more general readers. A well-written examination of the complex world of scientific research, focusing on a specific gene in the human body. Copyright Kirkus Reviews, used with permission.
Library Journal Review
P53 is the body's oncologist: a tumor suppressor. When it works, it halts tumor replication millions of times a day. When it doesn't work, havoc ensues. But P53 doesn't just create devastation in its absence, it can mutate in such a way that it promotes growths different from those formed when it is simply knocked out. Mutant P53 can act like an oncogene (tumor promoter), or help generate misfolded proteins called prions, a discovery leading to a Nobel Prize for mad cow disease researcher Stanley Prusiner. The route to all this knowledge was circuitous. Scientists first hailed P53 as an oncogene and ignored research calling it a suppressor; then welcomed it as a suppressor and disregarded research identifying it as an oncogene. VERDICT This is a short, workmanlike overview of milestones in research on a key regulatory gene. Although the author is a science writer and journalist, the book is not written in a manner destined to inspire a general audience. It leaps too quickly from one researcher to the next to allow for meaningful personal development, and the science is described with more patience than passion. Still, graduate students and cancer literature buffs will be absorbed. Cynthia Fox, Brooklyn (c) Copyright 2014. Library Journals LLC, a wholly owned subsidiary of Media Source, Inc. No redistribution permitted.