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The Race to Decipher the Secrets of the Ribosome
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“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.
An Unexpected Change of Plans in America
WHEN I LEFT INDIA, I had my heart set on becoming a theoretical physicist. I was nineteen years old and had just graduated from Baroda University. It was customary to stay on to get a master’s degree in India before going abroad for a PhD, but I was eager to go to America as soon as I could. To me, it was not only the land of opportunity but also of rational heroes like Richard Feynman, whose famous Lectures on Physics had been part of my undergraduate curriculum. Besides, my parents were already there, as my father was taking a short sabbatical at the University of Illinois in Urbana.
Since this was a last-minute decision, I had not taken the GRE exam that is a requirement for American graduate schools, and most universities would not even consider my application. The physics department at the University of Illinois initially accepted me, but when the graduate college found out I was only nineteen, they said that at best I could join as an undergraduate with two years of college credit. No middle-class Indian then could afford the cost of tuition and living in America. In the meantime, my department chairman in Baroda showed me a letter from Ohio University asking him to let prospective graduate students know about its programme. I had never heard of Ohio University before but saw that the department had an IBM System/360 computer and a Van de Graaff accelerator and that its faculty had been trained at some of the best universities; that seemed good enough for me. They waived the usual GRE requirement and accepted me with financial support. After the typically nerve-racking interview for a student visa at the US consulate in Bombay, I bought my ticket to the promised land.
As soon as I had finished my final exams, I left the sweltering heat of India and set off for America. I had caught a fever and the flight seemed interminable, stopping at Beirut, Geneva, Paris, and London before landing in New York. I boarded a plane for Chicago and then took a short flight to Champaign-Urbana. As I stepped out onto the tarmac on the evening of May 17, 1971, I felt a blast of the coldest wind I had ever experienced.
My sudden immersion into American college life came as something of a shock. College life in India was fairly staid. Students were conservative in their attire and focused on their studies; many, like me, still lived with their parents. Dating, and especially premarital sex, was quite unusual. I arrived as a geeky student with a crew cut, glasses with thick black plastic frames, and orange suede shoes two sizes too large, into an America that in 1971 was a continuation of the sixties. American students seemed to belong to an entirely different species: the males in tattered jeans and hair even longer than the females, who in their hot pants and halter tops seemed almost naked compared to the Indian women I had just left behind. Campuses throughout America were protesting against the Vietnam War. One afternoon, out of a mixture of curiosity and sympathy, I attended a peace rally. I stuck out like a sore thumb but then found two older guys at the back, who like me had short hair and were dressed in the same cheap polyester trousers and shirts. I walked over to them and tried to be friendly, but they were rather curt and suspicious. Only later did I find out that they were FBI agents keeping an eye on the anti-war troublemakers.
I spent the summer taking courses at the University of Illinois, filling gaps in my education from Baroda. At the end of the summer, I drove with my parents and sister to the pretty and hilly university town of Athens in southern Ohio, which was to be my home for the next few years. The first problem was finding any home at all. Since I had to live on my teaching assistantship and was a vegetarian, I thought it would be best if I rented a small flat where I could cook my own meals. We scoured the newspaper for rental ads with little success. In one case, the landlady said the flat was available, but when we showed up to look at it only a few minutes later, she took one look at me and said it was ‘just taken.’ That was my first experience of racism in America. Unable to find a flat that weekend, I signed up for a dorm room and spent the first year living primarily on cheese sandwiches at the cafeteria.
Notwithstanding its culinary disadvantages, the dorm room had the great benefit of allowing me to instantly acquire a group of friends and avoid the feeling of isolation and ghettoization so common to foreigners. My dorm mates quickly helped me assimilate into American college life. The first Saturday, we went to a football game. The pomp, with cheerleaders, bands, and the loud PA system, seemed to dwarf the game itself.
The dorm also had the advantage of being close to the physics department, and several fellow graduate students lived in rooms nearby, so we were able to form a friendly study group and get used to graduate school together. Physics graduate students generally have to do a year or two of coursework followed by a comprehensive exam before they begin serious research. Although I finished my coursework and the written part of the comprehensive exam without too many problems, the oral part at the end gave me the first inkling that I did not have a burning desire to be a physicist. I was asked what recent interesting discoveries in physics I had read about. I couldn’t name even one, and only after some prodding could I even name an area I found interesting. They passed me anyway, and I decided to work under the supervision of Tomoyasu Tanaka, a well-regarded condensed matter theorist. By then, I had already become intrigued by biological questions, and I included some biological problems in my thesis proposal. Since neither Tomoyasu nor I knew the slightest thing about biology, these proposals were pure fantasy and I soon abandoned them.
Figure 1.1 The author as a graduate student in physics at Ohio University
As I began my thesis work, I realized that I could not quite see how to identify key questions, let alone how to approach them. Even worse, I didn’t find my work interesting. I retreated into my social life, playing on the university chess team, going hiking with my friend Sudhir Kaicker, learning about Western classical music from another friend, Tony Grimaldi, and generally doing anything except making progress on my graduate work. Tomoyasu was an almost stereotypically polite Japanese who would occasionally come into my office to delicately enquire about my progress, and I would tell him in a roundabout way that there hadn’t been any. This continued for a couple of years. I’ve often said that if I’d had students like me, I would have fired them!
Things suddenly changed when I met Vera Rosenberry, a recently separated woman with a four-year-old daughter. Some mutual friends decided that the two of us should meet, perhaps because we were both vegetarians – an oddity in 1970s southern Ohio. I was completely oblivious that our first meeting was a setup because we were part of a large Thanksgiving gathering. Observing my cluelessness, my friends decided I needed additional help and invited me to a dinner party with just one other couple. Vera struck me as both intelligent and classically good looking, but I assumed someone like her would be out of my league and couldn’t possibly be interested in me. So I tried to introduce her to a friend by inviting him to dinner along with Vera and her daughter, Tanya. I spent some of that time playing with Tanya so that my friend and Vera could be free to chat. It was my friend who had to point out that she seemed interested in me not him, and if anything, she probably became even more interested when she saw how well I got along with her daughter. Despite this comically inept start on my part, we began a stormy courtship that lasted less than a year and got married soon after her divorce became final. At the age of twenty-three, I found myself married and the stepfather of a five-year-old girl.
Marriage, however, focused my mind on my career. Vera wanted to have another child, so I faced the prospect of supporting a family without any idea of what I would do next. There seemed no question that if I stayed on in physics, I would spend the rest of my life doing boring and incremental calculations that wouldn’t result in any real advance in understanding. Biology, on the other hand, was undergoing the sort of dramatic transformation that physics had in the early twentieth century. The revolution in molecular biology that began with the structure of DNA was still going strong, and we were beginning to get fundamental insights into the molecular basis of biological processes that had puzzled us for centuries. Almost every single issue of Scientific American would report some major breakthrough in biology, and it seemed as if it could be done by mere mortals like me. My problem was that I knew only the most basic biology and had no idea what biological research entailed. So even before I had finished my physics PhD, I made the difficult decision to attend graduate school all over again, this time in biology, taking heart from the fact that many illustrious scientists like Max Perutz, Francis Crick, and Max Delbrück had made a similar transition.
I wrote to several top-tier universities, but many of them did not want to accept someone who already had a PhD into graduate school. Two replies were particularly memorable. The first, from Franklin Hutchinson at Yale, was a friendly letter saying that although they couldn’t accept me as a graduate student, he would send around my CV to his faculty in case someone was interested in hiring me as a postdoctoral research fellow. Two of them wrote back: Don Engelman and, ironically in hindsight, Tom Steitz. I thanked them both and said that I didn’t have enough background to be useful to them as a postdoc and would try to acquire some training first. At the opposite end of the spectrum from Hutchinson was James Bonner of Caltech. In my applications, I had written that because I was only twenty-three, I was young enough to go to graduate school again. Bonner berated me for bragging about my age, adding that he, too, was only twenty-three when he received his PhD and was considered backward in his family. He also said that the areas I had mentioned – allostery, membrane proteins, and neurobiology – were hardly surprising because they were the most fashionable areas of biology. If I wanted to work in them, he wrote, I had to first show that I could actually be competent in those areas, and certainly Caltech would not accept me as a student. Perhaps he had never read Catch-22. Fortunately for me, Dan Lindsley of UC San Diego was willing to accept me into the biology department as a graduate student with a fellowship. Even more fortunately, Vera and Tanya were game to move to California and continue living on a meagre graduate student’s stipend with the added burden of an infant – all without a car.
Somehow, I scraped together enough work to produce a passable thesis just in time. Our son Raman was born just a month after my PhD exam. A couple of weeks later, a friend and I drove from Ohio to California in a Ryder truck with all our belongings, and Vera and the children flew in with my mother-in-law a week later. Once we had settled in, I began my studies in earnest in the autumn of 1976.
The thing that immediately struck me about biology was how many facts you have to know. The introductory lectures for new graduate students were full of jargon I didn’t understand at all. To catch up, I took a full load of undergraduate courses in genetics, biochemistry, and cell biology, in addition to doing first-year graduate student rotations, which are short six-week projects that American grad students typically do before they settle into a lab for their PhD research. Because my physics research had been entirely theoretical, I was totally ignorant of laboratory work. This was brought home to me during a rotation in Milton Saier’s lab, which worked on sugar uptake by bacteria. The experiment entailed adding a certain amount of radioactive glucose to a culture of bacteria at time zero, and then measuring how much glucose had entered the bacteria at various time points. The amount of the glucose to be added was much smaller than anything I had encountered before – only about twenty microlitres (less than 1 per cent of the volume of a teaspoon). How could you measure such a small volume? I asked. The technician who was training me very pleasantly showed me a device called a Pipetman, which is essentially a tube with a piston that can be set so that it can go up or down by a precise amount. She showed me how to set the volume on the dial, how to draw up the right amount, and how to give the knob a little extra push at the end to make sure all the sample had been ejected. That was all there was to it, she said. I took the device and plunged it into the radioactive glucose, and she exclaimed, ‘What the hell are you doing? You have to use tips!’ The devices were so commonplace that she’d forgotten to mention the narrow disposable plastic tips that needed to be attached to the end of the Pipetman so that it never got contaminated by contact with the sample.
Moving with a young child and an infant was not exactly conducive to learning a new field. However, I was extremely lucky that Vera, who was starting her own career as a children’s book illustrator, could work from home. She did almost all of the childcare and housework, allowing me to focus on my studies. I ended the first year feeling optimistic that I had a broad enough background in biology and fairly varied lab experience. In my second year, I began work with Mauricio Montal, who was studying proteins that let ions pass through the thin membranes of lipids that envelop all cells. As it turned out, I wouldn’t stay in his lab very long. Almost entirely by chance, I would move across the country yet again to begin work on one of the oldest and most central molecules of life.
Stumbling into the Ribosome
MENTION DNA AND ALMOST EVERYONE nods in understanding. We all know – or think we know – what DNA means. It determines the essence of who we are and what we pass on to our children. DNA has become a metaphor for the fundamental qualities of almost anything. ‘It is not in their DNA,’ we say, even when referring to a corporation.
But mention the word ribosome and you will usually be met with a blank stare, even by most scientists. A few years ago, I was told by Quentin Cooper on the BBC radio programme Material World that the previous week’s guest had been outraged that the eye only merited half a programme when an entire episode was planned for a mere molecule like the ribosome. Of course, not only are most of the components of the eye made by the ribosome, but virtually every molecule in every cell in every form of life is either made by the ribosome or made by enzymes that are themselves made by the ribosome. In fact, by the time you read this page, the ribosomes in each of the trillions of cells in your body will have churned out thousands of proteins. Millions of life forms exist without eyes, but every one of them needs ribosomes. The discovery of the ribosome and its role in making proteins is the culmination of one of the great triumphs of modern biology.
When I arrived in California to learn biology, like most physicists, I had no idea what the ribosome was and only the vaguest idea of what a gene was. I knew genes carried the traits we inherited from our ancestors and passed on to our offspring. But I learned that genes are much more. They are the units of information that allow a whole organism to develop from a single cell like a fertilized egg. Although nearly all cells contain a full set of genes, different sets of genes are turned on or off in different tissues, so a hair or skin cell is very different from a liver or brain cell. But what actually are genes?
Broadly speaking, a gene is a stretch of DNA that contains information on how and when to make a protein. Proteins carry out thousands of functions in life. For example, they are what make muscles move. They let us sense light, touch, and heat and help us fight off diseases. They carry oxygen from our lungs to our muscles. Even thinking and remembering is made possible by proteins. Many proteins called enzymes catalyse the chemical reactions that make the thousands of other molecules in the cell. So ultimately, proteins not only give a cell its structure and shape but also enable it to function.
Understanding how the information in a piece of DNA could be used to make a protein was the culmination of an exciting decade that began with the classic 1953 paper on the double-helical structure of DNA by James Watson and Francis Crick. Often, the structure of a molecule does not immediately explain how it works. Not so with DNA, which immediately suggested both how it could carry information and how it could reproduce itself. It had long been a mystery how information in a cell is duplicated when it divides or how offspring inherit this information when an organism reproduces.
In each molecule, the two strands of DNA that intertwine to form a double helix run in opposite directions. Each strand has a backbone of alternating sugar and phosphate groups, and one of four types of bases – A, T, C, or G – is attached to the sugar and faces the inside of the helix. While playing with cardboard cutouts of the bases, Watson arrived at a brilliant insight: he realized that an A on one strand could chemically bond or pair to a T on the other but not to any of the other bases, while a G on one strand could similarly pair with a C on the other. In doing so, the shape of each base pair, whether it was AT or CG, was about the same, which meant that regardless of the order of the bases, the overall shape and dimensions of the double helix was about the same. This formation of base pairs meant that the order of the bases on one strand would precisely specify the order on the other strand. When cells divided, the two strands would separate, and each would have the information to serve as a template to make the other strand, resulting in two copies of the DNA molecule from one. In this way, genes were able to duplicate themselves. After centuries, we finally understood in molecular terms how hereditary traits could be transmitted from generation to generation.
Figure 2.1 DNA structure
Figure 2.2 Proteins
The structure immediately suggested how genes could be duplicated and passed on but not how the information in our genes could actually be used to make proteins. The problem was that each strand of DNA was a long chain made up of building blocks containing the four types of bases. But proteins are completely different chains made up of amino acids, and their chemical linkage is completely different. Their enormous variety comes from the fact that there are twenty types of amino acids, which have a wide range of chemical properties. The length and order of amino acids in each protein chain is unique, and amazingly it contains the information needed for the chain to fold up into its own unique shape, which allows it to carry out its special function. Crick realized that the order of bases in DNA coded for the order of amino acids in a protein, but the question was how.
Figure 2.3 Transcription: copying a gene in DNA to messenger RNA
Lots of people worked on this problem for well over a decade. It turns out that a stretch of DNA containing a gene is copied into a related molecule called messenger RNA or mRNA, so-called because the molecule carries the genetic ‘message’ to where it is needed. RNA, which stands for ribonucleic acid, differs from DNA or deoxyribonucleic acid by having an extra oxygen in the sugar ring. It, too, has four bases, but the base thymine (T) in DNA is replaced by a very similar base, uracil (U), in RNA, which, like T, also base pairs with A.
How do you go from four types of bases to twenty types of amino acids? It would be like following a long sentence of instructions written in code using a foreign alphabet. It turns out that the bases are read in groups of three at a time, and each group is called a codon. The way they are read – something predicted by Crick – is that another RNA molecule called transfer RNA or tRNA has an appropriate amino acid attached at one end and a group of three bases called an anticodon at the other end. The anticodon and codon form base pairs just like the ones between the two strands of DNA. The next codon is recognized by a different tRNA, which brings along its amino acid, and so on.
Figure 2.4 Transfer RNA: the adaptor molecules that bring amino acids and read the code on messenger RNA
The next big discovery was that this doesn’t happen by itself. Cell biologists discovered particles in cells where the mRNA is read and proteins are made. The particles were tiny by normal standards – you could pack four thousand of them in the width of a human hair. There were thousands of them in every cell, from bacteria to humans. But they were enormous in molecular terms. Each of them contained about fifty proteins and three large pieces of their own RNA – a third type of RNA (after mRNA and tRNA). Initially, scientists referred to the particles as ‘ribonucleoprotein particles of the microsomal fraction’ because they were made up of both RNA and protein and were isolated from cellular fragments known as microsomes. This was quite a mouthful to say; so in the late 1950s at a conference, Howard Dintzis suggested the name ribosome, which it has been called ever since. Dintzis was also the first person to figure out the direction in which a protein chain is made. Embarrassingly, even after working for thirty years in the field, I didn’t know Dintzis or his work. When I finally met him in 2009 at Johns Hopkins University, where I had been invited to give a lecture named after him, he was still justifiably proud of having coined the word.
Figure 2.5 Composition of ribosomes
The whole ribosome has over a million atoms. Because it is the link between our genes and the proteins they specify, the ribosome lies at the very crossroads of life. Even though everyone knew this, nobody had any idea what ribosomes looked like other than that they were blobs consisting of two parts. And that was a real problem. Somehow, the ribosome bound mRNA and stitched together the amino acids brought by the tRNAs into a protein. But without knowing what it looked like, how could we possibly understand how it all worked?
Imagine you are a Martian peering at earth from above. You observe tiny objects on the surface that move mainly in straight lines, occasionally turning at right angles. If you were able to get a little closer, you might see that these objects move only when even smaller objects enter them and stop moving when they leave. If you have sensors, you could tell that they consume hydrocarbons and oxygen and emit carbon dioxide and water along with some pollutants and heat. But you would have absolutely no idea what these objects really are, let alone how they work. Only by knowing the detailed construction of the object would you be able to see that it is made of hundreds of components that work together and that it has an engine connected to a crankshaft that makes the wheels turn. You would need to see even more detail to know that the engine itself has chambers with pistons and draws in a mixture of fuel and oxygen that is ignited with a spark plug, which drives the piston forward.
Figure 2.6 Alfred Tissières and James Watson, two early pioneers of ribosome research (courtesy of Cold Spring Harbor Laboratory)
It is the same with understanding molecules. Knowing the detailed structure of DNA revolutionized our understanding of how it works to store, transmit, and replicate genetic information. But the ribosome was not a simple molecule like DNA. It was enormous and complex and seemed just too daunting and intractable.
Many great scientists like Crick, who had played key roles in figuring out how information in DNA is encoded, simply gave up on the ribosome and left for other fields. Sydney Brenner, an equally eminent colleague of Crick’s who was one of the discoverers of mRNA, said in the 1960s that the structure of the ribosome was a trivial problem and there was no need to work on it in Cambridge since that sort of work would, of course, be done by Americans. This reminds me of Senator George Aiken saying of the intractable Vietnam War that the ‘US should declare victory and get out.’ One of the early molecular biologists who persisted on the ribosome was Watson, who worked on the problem with Alfred Tissières, a biochemist from Geneva who was visiting his lab. Nearly forty years later, at a meeting in Cold Spring Harbor in 2001, Watson recalled those early days, saying that when he realized how complex the ribosome was, he automatically knew that we would never know its structure.
The ribosome was far from my mind as I settled into Mauricio Montal’s lab, but after I had only been there a few months, I came across an article on the ribosome in Scientific American that would change my life. It described how to locate the many different proteins on the ribosome using neutron scattering – a technique known to physicists but hardly used in biology. The two authors were Don Engelman and Peter Moore, and I remembered that Don was one of the people who had expressed interest in having me as a postdoc when I was trying to switch from physics to biology. I thought if he’d wanted me with no biological background at all, he might be even more interested now that I had learned some biology and had over a year of lab experience. It also occurred to me that I had already learned enough biology to do research in the field, and there was no need to get a second PhD in biology.
So I wrote to Don reminding him of our previous correspondence, saying I was now more prepared for a postdoc. Since I knew Don’s main interest, like Mauricio’s, was in membranes and proteins in membranes, I told him I would like to work on them in his lab. He wrote back saying that he didn’t have any positions but his collaborator Peter Moore did, and if I came there and worked on ribosomes, I could then do some membrane work in my spare time. By that time, I knew that ribosomes were fundamentally important, so I said that was fine with me. As it turned out, the ‘spare time’ was non-existent.
Peter soon wrote saying he was visiting San Diego for a conference and would be happy to meet me. When I went downtown to see him, he was dressed in his characteristically preppy clothes with a brown corduroy jacket, and his thick glasses and manner completed the stereotype of an Ivy League intellectual. Which indeed he was. He entered the fast track early in life and never left it, and I was never sure whether he really understood what it was like not to have been in elite institutions all your life. His father had made pioneering contributions to transplantation surgery at Harvard, and Peter himself had studied at a private school and then Yale before going to Harvard for grad school, where he worked with Watson on the ribosome. After that, he went to work with Watson’s friend and collaborator Alfred Tissières in Geneva, who by then was a leader in the ribosome field. There he set about purifying the different proteins that made up the ribosome.
- "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
- On Sale
- Nov 6, 2018
- Page Count
- 288 pages
- Basic Books