“Nature is trying to tell you something.” Taken by itself, this quote from Nobel laureate and former Cold Spring Harbor Laboratory (CSHL) scientist Richard Roberts suggests that the solutions to any number of problems may be within earshot. If only things were so simple. The fact is, scientific experiments go awry all the time. When trying to answer complex questions, researchers often guess wrong—and keep guessing wrong—in hopes that every once in a while, something goes right.
In the 1970s, Richard Roberts’ lab was working on adenovirus, a common virus that causes colds and sore throats. Postdoc Rich Gelinas kept expecting to see 15 or 20 spots in his test results. Instead, he kept finding just one. When he repeated the test over and over and kept seeing the same mistake, Roberts considered that it might not be an error after all. It turned out that this time, he was right.
The ‘mistake’ ended up being the discovery of RNA splicing, a naturally occurring process whereby the parts of messenger RNA (mRNA) that contain cell instructions are kept and the non-coding sections are removed. In a monumental paper published in 1977, Roberts showed through adenovirus that one gene doesn’t necessarily contain the instructions for only one protein, as previously thought. Instead, pieces of information in a single gene can be arranged, or spliced, in different combinations to produce a variety of proteins.
Want to know more about how RNA splicing works? Watch this animated video. If only nature would speak so clearly!
Not only did RNA splicing help account for the genome’s tremendous complexity. It also pointed to the root cause of numerous diseases. The discovery set the stage for the creation of RNA splicing modifiers called antisense oligonucleotides, which have been used to treat spinal muscular atrophy (SMA), the leading genetic cause of death among infants. SMA is one of more than 200 diseases caused by errors in RNA splicing. In fact, Professor Adrian Krainer, who developed the first FDA-approved drug for SMA, was recruited to CSHL by Roberts himself. (But that’s a story for another day.)
In 1993, Roberts was awarded the Nobel Prize in Physiology or Medicine, along with Philip Sharp of MIT.
Years later, reflecting on his discovery, Roberts said, “Failure is a great thing. It [means] one of two things. Either you screwed up, or maybe nature is trying to tell you something. So, don’t ever be disheartened by failure.” Those are wise words for anyone. They also get at the heart of fundamental biology research. To turn science into medicine and technology, one must first know the ‘language’ that nature speaks. Uncovering that knowledge is the role of fundamental biology.
Written by: Jen A. Miller | publicaffairs@cshl.edu | 516-367-8455