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The Race to Decipher the Secrets of the Ribosome

In case you didn’t know, the ribosome is what makes DNA come to life.

Venki Ramakrishnan calls it the Gene Machine.

And he tells it all about how its structure was discovered.

By him.

(Yup, he’s a Nobel Prize-winning biologist).

Who Should Read “Gene Machine”? And Why?

When the author of a book is a Nobel-Prize winner, you don’t ask questions such as the one above; you simply sit down and read the book, because in it you’ll inevitably find the utmost borders of human knowledge and accomplishments.

In this case, it’s even better: “an engaging and witty memoir,” Gene Machine is “a profoundly human story written with honesty and humility,” not merely about the discoveries (in this case, the structure of the ribosome), but also about how discoveries are reached.

“Anyone who is captivated by an absorbing story well told,” writes a Forbes review, “will find much to appreciate in this fascinating book.”

About Venkatraman Ramakrishnan

Venkatraman “Venki” Ramakrishnan is a British-American structural biologist and physicists of Indian descent.

After earning a Ph.D. in physics in 1976, Ramakrishnan decided to abruptly change his career focus, upon happening about an article on the ribosome in Scientific American.

He enrolled as a grad student at the UCSP and spent the next thirty years uncovering its structure and the functions of the ribosome, winning numerous prizes for his work. In 2009, he shared – with Thomas A. Steitz and Ada Yonath – the greatest one of them all, the Nobel Prize in Chemistry.

Even though knighted by the Queen for his services to science in 2012, Ramakrishnan almost never uses the honorific title “Sir.”

“Gene Machine PDF Summary”

Written by one of the foremost scientists alive – Nobel Prize winner Venkatraman “Venki” Ramakrishnan – Gene Machine is a memoir not that unlike James Watson’s renowned “personal account of the discovery of the structure of DNA,” The Double Helix.

In fact, it is so much like it that you’ll probably find in Gene Machine pretty much everything you can (and may have probably already found) in The Double Helix: personal ambition, discussions of the nature of scientific research, the race for recognition, and, last but not least, the structure of the magical inner computers of our body.

Considering the fact that, according to us, The Double Helix may be one of the best nonfiction books of all time, Gene Machine is in a pretty good company.

And though we’ll try our best, we kinda feel that our summary – or any summary for that matter – can’t do enough justice to this kind of a gem.

Beginnings in Physics and an Unexpected Change of Plans

“When I left India,” writes Venki Ramakrishnan at the beginning of his book, “I had my heart set on becoming a theoretical physicist.”

“I was nineteen years old,” he goes on,” 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 Ph.D., but I was eager to go to America as soon as I could.”

Why, you ask?

Well, for three reasons.

The first one – and the most obvious one – unlike India, the United States is a land of opportunities for young people.

The second one – and the most compelling one – Venki’s parents had already gone to the US because his father was taking a short sabbatical at the University of Illinois in Urbana.

The third one – and the one you’ll remember best – because the USA was the home of Richard Feynman, a certified genius and a hero for Venki and about a million other science-loving people out there.

Three things happened afterward.

First, in 1975, Ramakrishnan married Vera Rosenberry, a recently divorced woman with a daughter; “at the age of twenty-three,” he writes, “I found myself married and the stepfather of a five-year-old girl.”

Then, a year later, he obtained a Doctor of Philosophy degree in Physics from Ohio University.

And then, as soon as the latter happened, Venki realized that he doesn’t want to do “boring and incremental calculations that wouldn’t result in any real advance in understanding.”

So, he abruptly changed his career focus and enrolled as a graduate student in biology at the University of California, San Diego.

The reason?

Well, why don’t we say a couple of words about it in the next section.

The Ribosome, the Ultimate Code-Cracker

DNA and the Ribosome

“Mention DNA and almost everyone nods in understanding,” writes somewhat despondently Ramakrishnan.

“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,” Venki goes on, “and you will usually be met with a blank stare, even by most scientists.”

This is both pointless and scandalous, because to DNA, the ribosome is what your video codec is to the 1s and 0s which are packed in the mkv or avi file: the thing which makes sense of it all.

Or, in other words, the ribosome is the DNA interpreter, decoder, the molecular machine.

The Gene Machine.

The Ribosome (and Something About Eyes)

Defined in strictly biological terms, the ribosome is an organelle which can be found in absolutely every living cell, from bacteria to humans. It is essential for all life on Earth, and it is, consequently, as old; the information stored in the DNA molecules would be irrelevant in the absence of a ribosome to decode it.

Writing of its importance, Ramakrishnan shares an interesting anecdote:

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,” concludes Ramakrishnan, “is the culmination of one of the great triumphs of modern biology.”

Ramakrishnan and the Ribosome.

Now, by the late 1970s (when Venki Ramakrishnan decided to change his career focus), the structure of the DNA had already been determined and solved; but how the body decodes and uses this information to pass on traits from generation to generation was barely understood.

In fact, just about then – in 1974 more specifically – George Emil Palade, Albert Claude, and Christian de Duve were awarded the Nobel Prize in Physiology or Medicine for the discovery of the ribosome (something Palade first did about two decades before).

Ramakrishnan started working on something else though: in the laboratory of Mauricio Montal, Venki studied “proteins that let ions pass through the thin membranes of lipids that envelop all cells.”

However, one day, in the October 1976 issue of the Scientific American, he came across an article that would change his life.

The article – ‘Neutron-scattering Studies of the Ribosome,’ signed by Donald M. Engelman and Peter B. Moore, – “described how to locate the many different proteins on the ribosome using neutron scattering – a technique known to physicists but hardly used in biology.”

Ramakrishnan immediately wrote Don, but unfortunately, he had no vacancies left at the time of his inquiry. Fortunately, the neighboring laboratory of Peter Moore had one – and the rest, as they say, is history.

Especially since – and interestingly enough – Moore’s close collaborator was Thomas Steitz, Ramakrishnan’s fiercest competitor in the race for the discovery of the structure of the ribosome.

Four decades later, and the guys would end up sharing the Nobel Prize.

The Race and the Competitors

But first, let us introduce you to the nature of this race and the competitors at the beginning of Ramakrishnan’s biology career.

The objective: to obtain three-dimensional crystals or images of ribosomal particles; the prospect: somewhat bleak; the existing methods: producing splotches rather than images (in fact, Venki and his colleagues explicitly and scathingly referred to crystallography as “blobology.”)

And then a pediatrician named Hasko Paradies appeared out of nowhere, publishing an article in which he claimed to have crystallized tRNA before anyone else.

It turned out that he was lying, but, as Ramakrishnan writes, “often, just being told something is possible breaks down a huge psychological barrier and spurs people to try things.”

And the people who started trying things?

Well, dozens mentioned and hundreds of unmentioned and unsung heroes.

Here are the main guys:

• Joachim Frank, “a tall, courteous, and somewhat reserved person with a deep love of art and literature… working away in relative isolation at the Wadsworth Center in Albany for years;” Frank won a Nobel Prize in Chemistry in 2017;
• Harry Noller, “the Sage of Santa Cruz,” a bearded, long-haired jeans-wearing guy with a fondness for motorcycles and Ferraris and the “demeanor of a mellow, pot-smoking California hippie;”
• Brian Wimberly, “the Ferrari Boy,” called that way because he rejoiced at the early maps of the ribosome just like a teenager would at the keys of a Ferrari;
• Thomas A. Steitz; the guy already mentioned, “a burly, imposing figure” with Amish-like chin-strap beard and immense knowledge; direct in his approach and married to Joan A. Steitz, “a top molecular biologist;”
• Ada Yonath, an Israeli crystallographer with “exactly the right combination of ambition and tenacity” needed for the project; and
• Venki Ramakrishnan, the “dark horse” of the race.

The Politics of Recognition and the Collaborative Nature of Science

In 2009, the last three – sometime rivals, most of the time friends – would end up sharing the Nobel Prize for Chemistry.

“I thought you had to be really smart to win one of those,” said Vera Ramakrishnan to the author upon finding out the news.

But there may be a deeper point behind this joke.

Ramakrishnan constantly insists on the fact that it’s merely a coincidence that these three – and not some other three guys – won the Nobel Prize.

Why?

Because science is a constant pursuit by the multitude and not something that an individual does.

True, Ramakrishnan worked tirelessly, but so did thousands and thousands of other people, whose studies opened his – or his colleagues’ – eyes to some new discovery.

Science is not the story of great men, but the story of collaborative humankind:

So I don’t subscribe to the heroic narrative of science. Rather, some of us are fortunate enough to be the agents of important discoveries that would have been made anyway, sometimes not even that much later. But this cold analytical view does not sit well with our emotional selves. We humans tend to personify everything we touch. We give names to theories and theorems, discoveries, laboratories, even pieces of apparatus. Science becomes a play, with heroes and villains. So even if discoveries are inevitable, we recognize that it is individuals who make them happen, and we like to honor those who took that first leap into the unknown, to go just beyond what was thought to be possible. And when someone like Newton or Einstein sees much further than others, or Watson and Crick synthesize in one stroke the essential features of DNA that might have dribbled out in pieces, we tend to immortalize them.

Key Lessons from “Gene Machine”

1.      The Ribosome Is a DNA Decoder
2.      Venki Ramakrishnan is a Physicist – and He Won a Nobel Prize in Chemistry
3.      Science Is a Collaborative Field

The Ribosome Is a DNA Decoder

The DNA is a blueprint for all life: it’s where the important all the genetic instructions are written.

However, without the ribosome, that information would be unusable: the ribosome is a molecular machine which reads the info from the DNA and turns the code into proteins and, therefore, us.

In other words, a DNA without a ribosome is pretty much a BD without a Blu-ray Disc player: neither is enough in itself, but, in combination, they work wonders!

Venki Ramakrishnan is a Physicist – and He Won a Nobel Prize in Chemistry

In 1976, Venki Ramakrishnan obtained a Ph.D. in physics from Ohio University.

Most people would consider that the summit of their scientific pursuit, but for Venki it was merely the beginning of something else: he enrolled as a grad student in biology at the UCSD, in an attempt to find a practical use for his physics-related knowledge.

In 2009, Ramakrishnan won a Nobel Prize – in Chemistry!

Science Is a Collaborative Field

Venkatraman Ramakrishnan shared the Nobel Prize in Chemistry with two other people – Ada Yonath and Thomas A. Steitz.

Nothing surprising: not merely because, since about two decades ago, it’s only normal for these scientific Nobel Prizes to be awarded to three people, but also because that makes much sense.

“If I have seen further,” wrote Newton in 1675, “it is by standing on the shoulders of Giants.”

Ramakrishnan admits that he was in that position exactly; and that even if he hadn’t existed, someone else would have discovered what he did.

And that’s the collaborative nature of science for you.

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“Gene Machine Quotes”

Our Critical Review

Part-memoir, part-detective story, Gene Machine is an engaging, wittily written, immensely important and – to quote our beloved Bill Bryson – “beyond superb” gem of a book.

Richard Dawkins compares its “disarming frankness” (justly) to The Double Helix, noting that “Gene Machine will be read and re-read as an important document in the history of science.”

It is also unputdownable – so, just pick it up as soon as you find the time!

Emir Zecovic

Emir is the Head of Marketing at 12min. In his spare time, he loves to meditate and play soccer.