Gene Machine: The Race to Decipher the Secrets of the Ribosome by Venki Ramakrishnan (PDF)

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A Nobel Prize-winning biologist tells the riveting story of his race to discover the inner workings of biology’s most important molecule “Ramakrishnan’s writing is so honest, lucid and engaging that I could not put this book down until I had read to the very end.” — Siddhartha Mukherjee, author of The Emperor of All Maladies and The Gene Everyone has heard of DNA. But by itself, DNA is just an inert blueprint for life. It is the ribosome — an enormous molecular machine made up of a million atoms — that makes DNA come to life, turning our genetic code into proteins and therefore into us. Gene Machine is an insider account of the race for the structure of the ribosome, a fundamental discovery that both advances our knowledge of all life and could lead to the development of better antibiotics against life-threatening diseases. But this is also a human story of Ramakrishnan’s unlikely journey, from his first fumbling experiments in a biology lab to being the dark horse in a fierce competition with some of the world’s best scientists. In the end, Gene Machine is a frank insider’s account of the pursuit of high-stakes science.

User’s Reviews

Editorial Reviews: Review “It is [Ramakrishnan’s] full embrace of the role of the antihero that makes Gene Machine so much fun to read and also serves as a reminder to us all of the beating human heart that lies at the center of every advance in science.”―Wall Street Journal “An engaging and witty memoir… This profoundly human story is written with honesty and humility… This lucid and highly readable account will be enjoyed by students in any of the sciences, by those interested in the history of science, or who love reading memoirs. But really, I think that anyone who is captivated by an absorbing story well told will find much to appreciate in this fascinating book.”―Forbes “[An] absorbing account.”―Scientific American “In Gene Machine, [Ramakrishnan] thoughtfully embeds his trajectory in a wider meditation on how scientists make the decisions that lead to success or failure–and on how they struggle to solve complex problems… anyone who wants to know how modern science really works should read it. It’s all here: the ambition, jealousy and factionalism–as well as the heroic late nights, crippling anxiety and disastrous mistakes–that underlie the apparently serene and objective surface represented by the published record.”―Nature Choice award for outstanding academic titles”An enchanting and invigorating work, Gene Machine casts a many-angled light on the world of science, the nature of discovery, and on one of the deepest mysteries of twentieth-century biology. Ramakrishnan, one of the key players in deciphering the molecular basis of protein translation, gives us both a rollicking scientific story and a profoundly human tale. In the tradition of The Double Helix, Gene Machine does not hesitate to highlight the process by which science advances: moving through fits and starts, often underscored by deep rivalries and contests, occasionally pitching towards error and misconception, but ultimately advancing towards profound and powerful truths. An outsider to the world of ribosome biology–an Indian immigrant, a physicist by training–Ramakrishnan retains his ‘outsider’s’ vision throughout the text, reminding us about the corrosive nature of scientific prizes, and the intensity of competition that drives researchers (both ideas, I suspect, will have a munificent effect on our current scientific culture). Ramakrishnan’s writing is so honest, lucid and engaging that I could not put this book down until I had read to the very end.”―Siddhartha Mukherjee”If someone had told me that one of the most witty and enthralling books I’d read this year would be on the quest to understand ribosomes, I believe I would have laughed in his face, but I would have been quite wrong. Gene Machine is beyond superb.” ―Bill Bryson”The ribosome, a structure of astonishing complexity, ‘lies at the crossroads of life’ and Venki Ramakrishnan played a key role in revealing its biological mysteries. His superb account lays out the science with great lucidity, but he also grants us the human face of science–the hard work and brilliant insights, of course, but also the role of luck, of personalities, jealousy, money, the roulette of major awards, and the further rewards heaped upon the fortunate. Science, in his glorious telling, becomes ‘a play, with good and bad characters.’ Competition and collaboration can appear inseparable, crucial figures get overlooked. It’s a wonderful book and a great corrective to the notion of science as dispassionate, untainted objectivity.”―Ian McEwan”The ribosome is the central processor that decodes the universal machine-code of life, and the history of its unravelling is on a par with that of DNA itself. You could think of Venki Ramakrishnan as a sort of ‘nice Jim Watson.’ His meticulously detailed and generous memoir has the same disarming frankness as The Double Helix. His personal honesty about the competitive ambition that drove him is tempered by his deeply thoughtful reflections on the potentially corrupting effect of big prizes. Gene Machine will be read and re-read as an important document in the history of science.”―Richard Dawkins”Gene Machine is a must-read for anyone interested in a glimpse of the messy business of how science happens.”―Times (UK)”Enlightening… one can’t help celebrating with Ramakrishnan when, near his story’s conclusion, the call from Stockholm arrives.”―Publishers Weekly “An enlightening and enjoyable picture of the human side of scientific research.”―New York Journal of Books”A skillful memoir… An entertaining account of a peripatetic career, academic infighting, and the colorful, charismatic, or eccentric mentors, colleagues, and competitors the author encountered as well as an often cynical view of the scientific establishment.”―Kirkus Reviews “Discovering the structure of the ribosome was a truly incredible moment in the history of humankind: this intricate, microscopic machine that lies at the heart of all life, made mostly of RNA, that mysterious material that pre-dates both DNA and protein. As its shape and moving parts came gradually into focus through ingenious applications of crystallography, it is extraordinary to think that this is a device vital to all life, yet which no living thing has seen or understood till now. In this detective story of a book, told with smiles and subtlety, Venki Ramakrishnan relates how he, an immigrant from India, managed to assemble the people, the ideas and the tools to achieve this remarkable feat, in collaboration and (sometimes sharp) competition with other scientific teams, culminating in a Nobel Prize. For students of how science actually happens, this is a book to be treasured and pored over.”―Matt Ridley”This exhilarating account of the race to understand the molecular machine that turns genes into flesh and blood is remarkable for its candid insights into the way science is really done, by human beings with all their talents and foibles. Venki Ramakrishnan, an outsider in the race, gives an insider’s view of the decades-long quest to map the million atoms in the machine to fathom the fundamentals of life, pave the way for new antibiotics, and share the glory of the Nobel prize.”―Roger Highfield”In Gene Machine, one of the world’s leading scientists reveals the reality of scientific discovery and the rivalry, collaboration and thrills that are involved. The result is a brilliant under-the-hood account of what it takes to win the Nobel Prize. Exciting and brutally honest, Venki’s book explains the dramatic turns in the race to describe the structure of the ribosome–an essential component of every cell that has ever lived. I laughed out loud, I shouted in disbelief, and I learned so much from reading this book.”―Matthew Cobb”Quite a ride. This is a riveting personal account of the race to decipher the structure of the ribosome, one of the most complex and fundamental machines in the cell. The book takes up the baton from Watson’s Double Helix, and like Watson, Ramakrishnan is disarmingly candid in tone, sometimes disquietingly so. His telling is laced with wisdom spun from a remarkable life story and the sharp lab anecdotes that are the lifeblood of everyday science.”―Nick Lane”This book is dynamite. Like no science book ever before, this is an honest, frank and simply jaw-dropping account of how a relative outsider ended up winning a Nobel Prize.”―Daniel M. Davis About the Author Venki Ramakrishnan shared the 2009 Nobel Prize in Chemistry for uncovering the structure of the ribosome. He is a senior scientist at the MRC Laboratory of Molecular Biology in Cambridge, UK, and also the president of the Royal Society in London.

Reviews from Amazon users which were colected at the time this book was published on the website:

⭐The mapping out of the ribosome was one of the big problems in biochemistry in the late 20th century for which the solution was awarded the Nobel prize in 2009. The recipients of the prize in that year were the author, Venki Ramakrishnan, Ada Yonath and Thomas Steitz. Gene Machine is the personal story of Venki’s life and how he tackled the problem and all of the challenges that came with it along with the stories of the strong rivalries that were perpetually driving everyone forward. This is a book of science history as well as of personal triumph and is quite entertaining.The author writes the book as an autobiography with a focus on the work that led to his receipt of the Nobel prize. Interestingly the author started his career as a physicist but immediately once minted with his Phd moved subject and tried to involve himself in biology. The story details his early graduate student days and how he met his wife. He then moves on to his early career and some of the big problems in biochemistry. The story of the ribosome is in an of itself quite interesting. After the discovery of DNA and progress was made incrementally on how protein synthesis occurred, it was becoming incrementally more clear that the ribosome was a key component in cellular protein dynamics and that it was of high importance. The author spends a lot of time on the subject of X-Ray crystallography. In fact, these techniques are what led to his results. The subject is quite technical but also vitally important in understanding why it is so hard to have known what cellular components like the ribosome actually look like. Starting with the basic concept of a microscope, the author discusses the challenges of peering into the molecular scale and the early solutions people discovered, namely electron microscopy and x-ray crystallography. When one moves to biological matter and crystals are not the natural structure of cellular components the techniques don’t work. Much of the race to understand the ribosome were dependent on coming up with acceptable crystals of the ribosome, which was a highly non-trivial endeavor. Ada Yonath pioneered the development of the crystals but got stuck on generating subsequent results, though the race seemed perpetually very close to all involved. The author goes through his path to generate ideal crystals for using crystallography to picture the ribosome. He made progress in many places including NY, Utah and seemingly most importantly Cambridge at the LMB, but throughout he was surrounded by graduate students who significantly helped achieve his goals. The story is quite interesting as were the rivalries. One is reminded that within science as like everywhere else, personalities can be big and combative and rivalries can run high. Some of the stories of the bickering between Yonath and others is quite remarkable as it just seems so childish but of course it isn’t that surprising when the stakes are the Nobel Prize.An all round interesting read if one wants to know the story of the ribosome and some of the key people involved in its discovery from the perspective of Ramakrishnan. Despite the remarkable achievement, techniques in electron-microscopy had developed within years of the Prize being awarded that could do the work of the crystallographers in a matter of days rather than years indicating that if techniques change then alternative solutions can be formed in a fraction of the time. Furthermore despite the understanding of the shape of the ribosome, the understanding of its functions continued to be a bigger topic for study as understanding the snapshot vs the movie of the ribosome were completely different things. Here again, new techniques can now do this. Quite an interesting story but also a reminder that in science, projects that took decades can often, a few decades later, be done in days!

⭐This book is details one award-winning Scientist’s journey from his days as an eager graduate-level student from India, through his post-doc researcher days, and well beyond, all geared towards a singular effort to understand one of the most important mechanisms in the human body (or non-human bodies for that matter) — the ribosome. On its face this might seem like a book that would be guaranteed to be dry and complex, basically a “slog” to get through, however it’s anything but. The author and editor do an excellent job of making things interesting and approachable, withouth dumbing them down too much. Some basic background in biology or chemistry wouldn’t hurt, but we’re talking HS level here, nothing crazy.One of the most surprising and interesting things I learned was just how “social” an endeavor scientific research really is. I don’t mean social in the over-used (and often mis-applied) sense of how we often describe Meta-face, twitter and other platforms. Far from just individuals and teams exerising their uber-brains and technical expertise, there’s a lot said about the different elements of competition, collaboration and how the two often intersect. Just as office politics exists, so “lab politics” can exist among the elite minds in the scientific community. Enough so in fact that the one minor down-side of the book is that at different points there are so many names and back-stories mentioned that it can be confusing.But beyond that many compelling descriptions of the scientific challenges, headaches, and small victories that take place over the course of decades, all ultimately in the pursuit of describing in molecular detail, just what the ribosome looks like and how it works. And all of it way before we had mega-puters with AI doing protein structure predictions without the need of x-rays and electron beams. Some of the ingenuity these folks displayed in trying to work this very complicated problem is nothing short of astounding. Gives one hope for the human race in the face of people like Donald Trump, who prefer to use their intelligence to manipulate and deceive, to the point of calling science a hoax and tell us that up is down and red is green.Maybe we need a few structural biologists and biochemists to run for high office! : )

⭐The ribosome is complex & complicated. This is the story of how the author worked to discover its structure & function. Not light reading if you don’t understand the biochemistry of protein formation.

⭐Venki Ramakrishnan’s book is the story of the race to understand the structure and workings of the ribosome, and his part in that. He comes across as a modest, self-deprecating person, able to reveal his weaknesses as well as his strengths, and someone who is generous in acknowledging the contributions of others. As with many scientists of great aptitude, he lacks arrogance and at times comes across as quite diffident as to his abilities, fearing that others are better qualified than he is to solve this puzzle. His book does a wonderful job of conveying the combination of friendliness and rivalry that accompanies any scientific contest, no more so than when solving a problem of this importance. The journey is a roller coaster where one day his team seems to be ahead of his rivals, and the next a paper is published that suggests they are behind. He successfully expresses how his emotions rose and sank, as he continually tried to figure out where he was in relation to others in the race. In some respects, the book reminds me of The Double Helix by James Watson which recounts a similar, frantic rush to beat the competition to establish the structure of an important biological molecule.A chapter I found fascinating was one where Ramakrishnan discussed the politics of scientific awards, including the Nobel Prize, arguing that the system can become a closed-club where the same scientists repeatedly win prestigious honours. He was particularly critical of Nobel Prizes, writing: “Because many of the early Nobel laureates were giants in their field, the idea has taken hold – especially among non-scientists – that Nobel laureates are geniuses. In fact, the prize is not awarded for being a great scientist but rather for making a groundbreaking discovery or invention. Some of them may be extraordinarily brilliant, but others are just good scientists who were persistent or happened to stumble onto a major finding. Being in the right place at the right time often helped enormously”. He also blasted the rule that limits the number of winners to three. This may have been appropriate a century ago, but nowadays it doesn’t reflect the collaboration, intentional or otherwise, that marks most major scientific advances.He also writes about what he calls post-Nobelitis. As he puts it: “Suddenly, scientists are thrust into the limelight and bask in the public adulation that goes with it. They are asked for their opinion on everything under the sun, regardless of their own expertise, and it soon goes to their head. Some of them are long past their prime, having made their big discoveries decades earlier, and the renewed attention means that they spend their time wandering around the world, pontificating about all sorts of things”.Ramakrishnan knew that solving the mystery of the ribosome was worthy of a Nobel Prize but, with the rule of three in mind, he honestly admits that “I started worrying about my relative contribution and whether I would be perceived as a Johnny-come-lately rather than a pioneer”.Despite his cynicism about how the system works, Ramakrishnan comes across as extremely ambitious and someone who spent a lot of time fretting whether he would miss out on this ultimate scientific accolade. Would the ribosome really merit an award? And, if so, which three of the numerous scientists involved during something like 20 years of research would be named on the citation?A criticism I have of the book is that so many scientists are named that it is easy to lose track of who did what, where and when. Unfortunately, there is no index so when a name reappears there is no simple way of tracing when he or she was first mentioned. Furthermore, after they have been first introduced, Ramakrishnan often refers to scientists only by their first names, and the text is littered with references to Tom, Dick (actually Richard!) and Harry, which means that even having an index would be of limited value as an aide memoire. Perhaps a cast list might be better.Based on his personal experience, Ramakrishnan provides lots of interesting details about the mechanism of announcing and then awarding the Nobel Prizes. No doubt like many other recipients have been, he was very suspicious when he received the phone call from Sweden informing him that he’d won. Also, curiously, he tells us that the banquet after the ceremony is televised and shown live in Sweden. But he comments: “I wouldn’t have thought spending the evening watching a group of strangers eat would make for much drama, but there were speeches and entertainment”.The book is quite technical in places, notably in terms of crystallographic techniques. Nonetheless, it is not necessary to understand the details in order to enjoy this book because this is an account of how the race for a Nobel Prize is won, or, more often, lost. And therein lies the focus of the book.

⭐As a scientist, I was totally disappointed in this book. I was looking forward to reading the author’s scientific journey that helped unravel the mysteries of the Ribosome. Unfortunately, throughout the book the author attacks his fellow scientists and exposes their very personal details to the general public. I don’t think that is a particularly gracious attitude from a scientist that reached the pinnacle of his career by obtaining a Nobel prize.According to the author, he was badly treated by his peers and colleagues and the books appears to be his way of getting his revenge on his “enemies”. Many of the author”s published comments remind me of the unpleasant statements made by James Watson about Rosalind Franklin. One day his numerous negative comments about colleagues will come back to haunt this author, as they did for James Watson!

⭐This book is written in an accessible way and I enjoyed it but the non-scientist may like to know that this book is about a very specific structure in our cells – the ribosome. It is interspersed with the author’s own life and research, and micro stories of his work in the lab and his working relationship with his fellow researchers, all of which relieved the mundane for the non-scientist. Although it is accessible, there is a great deal of biological jargon that may defeat most lay readers. For example, it will take a while to figure out: ‘The site for the tRNA that holds the growing protein chain is called the P site and the one with the decoding center that binds the tRNA bringing the new amino acid is called the A site. In these crystals of the 30S subunit, a piece of RNA from a 30S subunit called the spur was sticking into the P site of its neighbour. If we added mRNA and tRNA to the 30S subunit before crystallization, the complex would block the contact with the spur from the neighbouring molecule and the crystal would never form’.

⭐DNA has lodged itself in the public imagination as the “blueprint” of life and as other, often slightly deceiving, metaphors. But what happens next? How do organisms actually get anything done with the information coded in DNA? For biologists, this is standard textbook fare: DNA is copied into single-stranded RNA which is then translated, three letters at a time, into amino acids that, when strung together, make up the workhorses of the cell: proteins. The cell organ, or organelle, that does the latter part is the ribosome, which Venki Ramakrishnan introduces here in Gene Machine. He has written a riveting first-hand account of the academic race to describe its structure, and how, in the process, he bagged a shared Nobel Prize in Chemistry in 2009.Ramakrishnan initially intended to become a theoretical physicist, but soon became fascinated with biology. After finishing his PhD in physics he started over as a biology graduate. The bulk of this book describes how he became enamoured with learning more about the ribosome and spent decades studying it, going from student to postdoc to professorship, all the while recruiting brilliant students and colleagues to collaborate with. But he did not operate alone. As the decades progressed and more of the ribosome’s structure was clarified, competition for publication in top-tier journals intensified. Various research groups around the world were working in parallel towards the same goal: a complete, detailed structural description of all the protein and RNA elements making up a ribosome.Ramakrishnan has purposefully decided to make this book foremost a personal memoir of his contributions during those decades of research, and of those of his collaborators and competitors. He describes the many pitfalls, mistakes, tensions, and rivalries with disarming honesty and gives a very good picture of what real science looks like “in the wild”.If you were hoping for an accessible overview of the current state of ribosome biology, this book might leave you wanting more. For example, Ramakrishnan almost off-handedly mentions how we have come to learn that “the” ribosome doesn’t exist, but there seem to be many types, something which he does not elaborate on. Another interesting observation is that the core of ribosomes consists entirely of RNA, with various clusters of proteins on the outside. Since many scientists think that life started off as single-stranded RNA acquiring the ability to self-replicate (see Life from an RNA World: The Ancestor within), this could point to how the ribosome evolved. By the time the structure of the ribosome was finally elucidated by x-ray crystallography, further technical developments in electron microscopy made it possible to use that technique instead, with superior results. This is very reminiscent of the rapid developments in DNA sequencing, where the first efforts were herculean and incredibly costly, after which new developments accelerated and eased the process tremendously.I would have loved to know more about these and other details, especially as there is no good popular science book on ribosomes so far – instead DNA gets all the love (see for example The Gene: An Intimate History, She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity, or Blueprint: How DNA Makes Us Who We Are). I am convinced that Ramakrishnan could have written a fantastically readable overview, as he does a good job of familiarising readers with his method of choice, x-ray crystallography, and with the function and structure of the ribosome, making good use of illustrations.As a science memoir, however, the book is a great read that I could barely put down, and gives an honest insider’s account of the competitive nature of scientific research.

⭐I’m not a scientist but, while I’m sure that a knowledge of the subject and a familiarity with the world of science would enhance the enjoyment of this book, my lack of both certainly did not detract from mine. This is a well written book detailing a fascinating, exciting story. The author brilliantly captures the joys, frustrations, intrigues and feelings, associated with the competitive search for understanding of a key component of the process of biological evolution. He generously and humbly recognises the contributions made by the members of his research teams, his competitors and of the scientists on whose work and discoveries he and his teams depended. His honest insights into the world of recognition and rewards associated with the scientific community is also very interesting.

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