American Scientist

THE CATALYST: RNA and the Quest to Unlock Life’s Deepest Secrets. Thomas R. Cech. 304 pp. W. W. Norton, 2024. $28.99.

Never underestimate RNA. A simple adage that is the central message of The Catalyst: RNA and the Quest to Unlock Life’s Deepest Secrets, by Thomas R. Cech, a biochemist whose career has centered on tackling the mysteries of RNA—work that earned him the Nobel Prize in Chemistry in 1989.

Not long ago, RNA stood in the shadows as a “biochemical backup singer,” as Cech writes; it was believed to be a mere messenger whose responsibility was to relay DNA’s instructions to eventually make proteins. RNA would have likely remained an ignored talent, relative to DNA, were it not for the COVID-19 pandemic. The events that shut down the world in 2020 simultaneously brought RNA into the limelight. Although the genetic backbone of the SARS-CoV-2 coronavirus is RNA, the spotlight was due to the development of RNA-based vaccines.

Cech states that “breakthroughs in RNA research represent one of the most transformative scientific achievements since the discovery of the DNA double helix,” while lamenting the general lack of knowledge about RNA. The book, then, can be seen as a guide for citizens to better understand RNA: After all, he reasons, much of the research on RNA has been financed by tax dollars, and the public deserves an update on their investment.

RNA stores information just like DNA—but it can also play different roles within living cells, whereas DNA cannot.

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So what is RNA? RNA stores information just like DNA—but it can also play different roles within living cells, whereas DNA cannot. As Cech explains, almost with a sense of reverence:

It can act 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 the aging process by building out the DNA at the ends of our chromosomes. By guiding the gene-editing machinery of CRISPR, it empowers us to rewrite the code of life. Many scientists believe RNA even holds the secret of how life on our planet began.

In the first part of the book, Cech walks readers through the story of RNA and how its potential slowly came to light through RNA-related discoveries: early characterization work, how it has supported lifeforms across the ages, and its now recognizable influence on crucial cellular processes. He also introduces readers to the work his own lab did, and the discovery of ribozymes, or RNA molecules that can act like enzymes, that led to the Nobel Prize. Until that point, the assumption was that enzymes need to be proteins. This discovery was the start of scientists seeing RNA as more than a messenger. The second section focuses on applications of RNA in improving human health and extending life, but also on the different ways it can harm life. And, of course, Cech addresses how scientists can use RNA as a tool in biomedical engineering.

Cech uses foundational discoveries as mileposts, such as the story of when his lab uncovered RNA’s catalytic ability using a tiny organism, Tetrahymena, that lives in pond scum. Similarly, he describes how mapping key structural properties of ribosomes—molecular machines that make proteins—again placed RNA on center stage, with proteins playing supporting roles. These ideas were so radical early on that very few scientists pursued them for about a decade.

RNA is multifaceted; Cech even refers to it as “a changeling.” It is a molecule of many shapes and talents. Differential joining of RNA segments, known as alternative splicing, means that the output of a single gene can be different RNA products, creating a rich diversity of different proteins. This versatility to form different RNAs from a single gene, plus RNA’s nifty ability to form many structures, results in a complex milieu that influences different cell functions and cell type identities. This means that control of RNA, including alternative splicing, can differ from cell type to cell type so that the final protein products in, and the functions of, immune cells are different from that in brain cells, with no change in the sequence of DNA. This knowledge has helped scientists to unravel how RNA defects, dysfunctions, qualities, and derived tools impact disease.

Cech writes about work exploring how RNA is associated with life’s origins, eventually coming to an uneasy conclusion that although it may look like the origins of life come from RNA, “science will never be able to prove whether life started with RNA.”

Although RNA might play a key role in life’s history, it definitely plays a role in the future of life and medicine. Cech goes on to detail how RNA is involved with viruses, and how the viruses that are behind dangerous pandemics are driven almost entirely by RNA. Which is why, he explains, the ideal way to fight an RNA-based virus is with an RNA-based vaccine, as we saw with the COVID-19 pandemic. This explanation serves as the perfect segue to Cech’s exploration of the development of RNA-based medicines and treatments. But at the same time, he is cautious: “Are we on the cusp of an mRNA therapeutics revolution? The truth is we don’t yet know.”

RNA is also at the center of the CRISPR-Cas9 genome editing toolkit that has already revolutionized medical and environmental technology. CRISPR is a powerful technology that can edit or remove entire genes in a cell. RNA guides the targeting machinery to the area within a cell’s DNA that is to be edited with striking precision, using its ability to base pair with nucleic acids. Although Cech sees the promise of CRISPR therapy, he is also well aware that clinical trials are needed to assess the benefits and safety of these therapies. It’s not just the medical sphere that could be revolutionized by CRISPR, though: There is also the possibility that it might be used to fight climate change and other environmental issues that pose public health problems, like mosquitos and malaria, and to help make crop plants more resistant to heat and drought.

The Catalyst is an accessible narrative detailing how RNA has rightly emerged from the shadow of DNA to be recognized for its roles in the origins of life, evolution, aging, and disease. Cech deftly braids stories of key scientific discoveries with tales of scientists’ tenacity in working to understand RNA. These stories, along with sharing his own journey within RNA research, leave us with ethically centered hopes for how RNA is poised to impact human health, and curiosity about discoveries yet to be made.