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Guest Essay

The Long-Overlooked Molecule That Will Define a Generation of Science

By Thomas Cech

Dr. Cech is a biochemist and the author of the forthcoming book “The Catalyst: RNA and the Quest to Unlock Life’s Deepest Secrets,” from which this essay is adapted.

From E=mc² to splitting the atom to the invention of the transistor, the first half of the 20th century was dominated by breakthroughs in physics.

Then, in the early 1950s, biology began to nudge physics out of the scientific spotlight — and when I say “biology,” what I really mean is DNA. The momentous discovery of the DNA double helix in 1953 more or less ushered in a new era in science that culminated in the Human Genome Project, completed in 2003, which decoded all of our DNA into a biological blueprint of humankind.

DNA has received an immense amount of attention. And while the double helix was certainly groundbreaking in its time, the current generation of scientific history will be defined by a different (and, until recently, lesser-known) molecule — one that I believe will play an even bigger role in furthering our understanding of human life: RNA.

You may remember learning about RNA (ribonucleic acid) back in your high school biology class as the messenger that carries information stored in DNA to instruct the formation of proteins. Such messenger RNA, mRNA for short, recently entered the mainstream conversation thanks to the role they played in the Covid-19 vaccines. But RNA is much more than a messenger, as critical as that function may be.

Other types of RNA, called “noncoding” RNAs, are a tiny biological powerhouse that can help to treat and cure deadly diseases, unlock the potential of the human genome and solve one of the most enduring mysteries of science: explaining the origins of all life on our planet.

Though it is a linchpin of every living thing on Earth, RNA was misunderstood and underappreciated for decades — often dismissed as nothing more than a biochemical backup singer, slaving away in obscurity in the shadows of the diva, DNA. I know that firsthand: I was slaving away in obscurity on its behalf.

In the early 1980s, when I was much younger and most of the promise of RNA was still unimagined, I set up my lab at the University of Colorado, Boulder. After two years of false leads and frustration, my research group discovered that the RNA we’d been studying had catalytic power. This means that the RNA could cut and join biochemical bonds all by itself — the sort of activity that had been thought to be the sole purview of protein enzymes. This gave us a tantalizing glimpse at our deepest origins: If RNA could both hold information and orchestrate the assembly of molecules, it was very likely that the first living things to spring out of the primordial ooze were RNA-based organisms.

That breakthrough at my lab — along with independent observations of RNA catalysis by Sidney Altman at Yale — was recognized with a Nobel Prize in 1989. The attention generated by the prize helped lead to an efflorescence of research that continued to expand our idea of what RNA could do.

In recent years, our understanding of RNA has begun to advance even more rapidly. Since 2000, RNA-related breakthroughs have led to 11 Nobel Prizes. In the same period, the number of scientific journal articles and patents generated annually by RNA research has quadrupled. There are more than 400 RNA-based drugs in development, beyond the ones that are already in use. And in 2022 alone, more than $1 billion in private equity funds was invested in biotechnology start-ups to explore frontiers in RNA research.

What’s driving the RNA age is this molecule’s dazzling versatility. Yes, RNA can store genetic information, just like DNA. As a case in point, many of the viruses (from influenza to Ebola to SARS-CoV-2) that plague us don’t bother with DNA at all; their genes are made of RNA, which suits them perfectly well. But storing information is only the first chapter in RNA’s playbook.

Unlike DNA, RNA plays numerous active roles in living cells. It acts as an enzyme, splicing and dicing other RNA molecules or assembling proteins — the stuff of which all life is built — from amino acid building blocks. It keeps stem cells active and forestalls aging by building out the DNA at the ends of our chromosomes.

RNA discoveries have led to new therapies, such as the use of antisense RNA to help treat children afflicted with the devastating disease spinal muscular atrophy. The mRNA vaccines, which saved millions of lives during the Covid pandemic, are being reformulated to attack other diseases, including some cancers . RNA research may also be helping us rewrite the future; the genetic scissors that give CRISPR its breathtaking power to edit genes are guided to their sites of action by RNAs.

Although most scientists now agree on RNA's bright promise, we are still only beginning to unlock its potential. Consider, for instance, that some 75 percent of the human genome consists of dark matter that is copied into RNAs of unknown function. While some researchers have dismissed this dark matter as junk or noise, I expect it will be the source of even more exciting breakthroughs.

We don’t know yet how many of these possibilities will prove true. But if the past 40 years of research have taught me anything, it is never to underestimate this little molecule. The age of RNA is just getting started.

Thomas Cech is a biochemist at the University of Colorado, Boulder; a recipient of the Nobel Prize in Chemistry in 1989 for his work with RNA; and the author of “The Catalyst: RNA and the Quest to Unlock Life’s Deepest Secrets,” from which this essay is adapted.

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