Thomas R. Cech, PhD, is Distinguished Professor of Biochemistry at the University of Colorado Boulder and received the Nobel Prize in Chemistry in 1989. His book The Catalyst (2024) is available now in paperback. You can request an exam copy for your courses at the end of the article. 

I’ve taught several thousand college students over the decades, and I’ve taught at multiple levels: general chemistry to freshmen, biochemistry and molecular biology to PhD students, and origins of life to science nonmajors. I know how difficult it is to keep a class engaged. 

Active-learning techniques help. “Clickers,” small-group breakout sessions, and in-class demonstrations are a few active-learning methods that I’ve found useful. Now I’m preparing to try another experiment: engaging a class of biology or biochemistry students by telling stories of different RNA molecules, using my book The Catalyst: RNA and the Quest to Unlock Life’s Greatest Secrets. 

Why RNA?  

Isn’t it too narrow a topic for a course?  I’d argue that the topic is not overly focused, but rather allows exploration of a variety of diverse topics that can be presented at different levels, ranging from a nonmajors course to an advanced graduate course. Consider that you can’t talk about RNA without talking about its parent, DNA, or its children, the proteins that it encodes. So even though this is a special-topic course, it will tie in with what the students learned in high school or in a college introductory course. 

The other feature that makes RNA a great topic for a course is that it’s very much in the news. The mRNA vaccines have been heralded as saving many millions of lives, and at the same time are considered dangerous by others. Why are they now politically incorrect in the U.S.?  And RNA-guided CRISPR gene editing is often in the news, with the first gene therapies being recently approved. How are citizens to grapple with a technology that can save lives but also offer “the unthinkable power to control evolution” (J. A. Doudna and S. H. Sternberg, A Crack in Creation, Mariner Books, 2017)? 

Teaching the Nonmajors Course 

For a nonmajors course that students take to fulfill a general science requirement, The Catalyst is already written at an appropriate level. It assumes very little prior knowledge about the molecules responsible for genetic information. Much of it is written at the high school level, and the portions that are more challenging can be discussed in class or even skipped over. 

At one chapter per week, the 12 chapters would fill a one-semester course. The first chapter, about the history of mRNA, gives the students a chance to refresh their memory of DNA as the genetic material, how portions of it are copied into RNA, what a protein is, and how RNA codes for proteins. Chapter 2, about RNA splicing, can be used to spark in-class discussions of the circuitous paths of scientific discoveries. What is serendipity, and why is it credited with so many scientific discoveries? What is a hypothesis, and how does one go about testing it? Can we ever know that a scientific “fact” is, in fact, correct? 

Chapter 3 takes the students back in time and into my own research lab, recounting the discovery of catalytic RNA, or ribozymes. Because proteins are such spectacular catalysts of biochemical reactions, why do living systems need RNA catalysts? Are they just curiosities, or are they central to understanding how every protein on the planet is constructed? 

The many wonders of RNA stem from its ability to fold into a myriad of complex shapes, each suited to a specific cellular job. To help bring home the wonders of this “RNA origami,” the students can fold their own RNA structures using pipe cleaners. 

Other chapters lead the students to consider the medical utility of RNA. Now that they understand some of the natural qualities and functions of RNA, they’re ready to see how it can be repurposed for therapeutics. Small interfering RNAs, discovered in a tiny, transparent nematode worm, work in humans to inhibit the activity of disease-causing RNAs. Messenger RNAs, the workings of which have been understood in minute detail for over half a century, may open the door to vaccines against cancer. And could RNA-driven CRISPR gene editing lead to “designer babies” in the future? 

The goal here is to stimulate class discussion by showing the students that RNA is a real-world topic that they’ll continue to encounter. 

Teaching Advanced Courses 

Turning the page: How could The Catalyst provide the framework for an advanced course, where the students already know the basics of molecular biology? Here the book would be used in a very different way.  I would challenge the students to fill in all the exciting details that the book glossed over. And these shortcomings are numerous, given that I wrote the book for a nonscientist audience.  

For example, Chapter 2 simplified the cut-and-paste process of mRNA splicing, leaving out key technical details. What is the biochemical mechanism of mRNA splicing, and how does it produce novel lariat-shaped RNAs? What is the spliceosome, and how is it transformed during the reaction cycle? How is alternative RNA splicing possible, and how do cells regulate it?  Where is the leading edge of this field now? Answering these questions will take the students far beyond The Catalyst and draw them into the peer-reviewed scientific literature. 

Moving on to the therapeutic RNA chapters: Why has RNA ignited the passion of biotechnology companies?  What advantages and limitations do therapeutic small interfering RNAs or mRNAs have over traditional small-molecule and catalytic-antibody modalities? What RNA therapies have been approved since the book was written?  What might the future hold? One assignment can involve the student choosing a disease for which there’s currently no therapy and specifying the sequence of A’s, G’s, C’s and U’s in an RNA that could be tested as a therapeutic. 

The goal for an advanced course is to cut across bioscience material the students have already had in an orthogonal direction, thereby cementing their learning while at the same time revealing biotechnology topics they’ll encounter in their future careers in medicine, industry, or academia. 

Engaging with Storytelling 

Many bioscience textbooks include historical vignettes in boxes, walled off from the flow of the facts. It’s as if to say, “Read the box if you wish, but it’s not central to understanding the material.” I’m planning to turn that approach on its head, using stories of discovery to organize and incentivize learning. One could even say the stories will act as the catalyst for learning.  

Interested in reviewing a copy of The Catalyst for your course? Request a paperback copy here. 

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