Thomas R. Cech (W. W. Norton)
For 50 years, RNA was DNA’s undervalued sibling, but now it has jumped into the spotlight. This multifaceted molecule – which resembles DNA but can morph into a variety of shapes other than a double helix – brought us the most effective covid-19 vaccines and is key to CRISPR gene editing, one of the most powerful technologies in experimental biology.
Yet few of us have an in-depth understanding of the molecule and why it has suddenly become so important for research and medicine. Time for a biography of the rising star, and few could tell the tale more cogently than Thomas Cech, who shared the 1989 Nobel prize in chemistry for discovering that RNA – known mainly as a genetic messenger in cells – also possesses catalytic properties that make it an active participant in the core chemistry of life.
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Cech unpacks the story to date in his new book The Catalyst: RNA and the quest to unlock life’s deepest secrets, starting out by explaining exactly how RNA and DNA “are cut from the same biochemical cloth”. Each has a sugary backbone studded with nucleobases. In DNA, these are the familiar A, T, G and C of the genetic code. RNA differs by only a single letter – U in place of T – and its particular brand of sugar has one more oxygen atom, but this makes all the difference. Where DNA is long and stable, RNA tends to be short and volatile, allowing it to pull off wild stunts that make DNA “look like a one-trick pony”, says Cech.
In the late 1970s, when RNA first caught his attention, research was largely focused on the more stable sibling. Cech even refers to himself as “a DNA guy”. Although RNA had an important role, it was still seen as subordinate, useful only because it shared a language with DNA and could copy its genetic information into smaller “transcripts” that instructed the cell’s protein-making machinery. As Cech puts it, RNA was “DNA’s grunt”.
But he and his colleague Art Zaug were poised – if unwittingly – to add a new string to RNA’s bow. The pair were researching how RNA transcripts formed, and they thought they might catch this as it happened by isolating one from a single-celled organism named Tetrahymena thermophila. They became the first to see evidence of RNA catalysing a reaction, something thought to be unique to proteins. This shocker caused a major rethink of the status quo.
This sort of lab work involving test tubes and incubation flasks is hardly glamorous (let alone straightforward to explain), but Cech finds telling phrases and apt metaphors. He also knows how to explain what look like inscrutable decisions by researchers so that by the end of the book, you not only grasp the science, but also how it happened and why breakthroughs occurred when they did.
Take T. thermophila. It seems an obscure creature to be the source of such an important discovery – Cech himself called it “pond scum”. But he also shows why it was perfect: it has thousands of copies of certain genes, compared with the two or so in human cells. This makes it an ideal organism in which to find transcribed RNA, as the more copies of a gene there are, the more copies of its transcript there are too. It is, says Cech, “easier to find a needle in a haystack if there are 10,000 needles”.
This and other breakthroughs laid the groundwork for new uses of RNA, such as in the targeting system that tells CRISPR where to cut DNA or developing aptamers, RNAs that can bind to proteins to show how certain illnesses are progressing. Cech offers meticulous explanations and keeps us hooked with anecdotes about colleagues or the atmosphere in the lab after an unexpected result – all providing just the right amount of breathing space around the science.
One such moment of levity is his description of geneticist and lepidopterist François Michel, whose bushy beard made him look like he had “just emerged from the forest after a month’s-long butterfly hunt”.
All this makes The Catalyst a joy, from a writer who can’t help but be as endearing as he is authoritative. Cech displays a warm appreciation for past students and colleagues, and underlying the book is his passion for science, particularly when driven by curiosity. After all, without the freedom to investigate his “pond scum”, he might never have become an RNA guy.
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