The Good Friday Meeting and mRNA

Messenger ribonucleic acid (mRNA) is in the news these days because of mRNA vaccines. But how was mRNA discovered? One reason I'm interested in this question is because mRNA (at least, our knowledge of mRNA) is almost the same age as I am: we were both born in 1960.

First, what role does mRNA play in biology? The central dogma of molecular biology is that DNA with its genetic code is stored in the cell nucleus. Transcription—where the base pairs in double stranded DNA are transcribed into bases in single-stranded mRNA—occurs in the nucleus, catalyzed by enzymes like RNA polymerase. Then, the mRNA leaves the nucleus and enters the cytoplasm. There, the mRNA attaches to the cell organelle called a ribosome (itself made from another type of RNA, rRNA) where the genetic code of base-pairs is translated into a string of amino acids in a protein. Yet another kind of RNA, tRNA, aids in this translation. In short:

DNA > transcription > mRNA > translation > Protein

Clearly mRNA plays a crucial role in all protein synthesis and is essential to life.

The Eighth Day of Creation,
by Horace Freeland Judson.

Russ Hobbie and I talk a little about DNA and proteins in Intermediate Physics for Medicine and Biology, but not much about mRNA. If you want to learn how mRNA was discovered, I suggest reading The Eighth Day of Creation: The Makers of the Revolution in Biology, by Horace Freeland Judson. It’s a long and complicated story, but a key moment was an informal meeting on April 15, 1960 (Good Friday), attended by biologists Francis Crick, Sydney Brenner, François Jacob, and others (Jacques Monod, a collaborator of Jacob, was not present) in Brenner’s rooms at Cambridge University. At that time, the structure of DNA and its role in creating proteins was already known, but the details of how that occurred was uncertain. Out of that meeting came the idea that mRNA was the messenger between DNA and Protein.

Judson writes

That fall, Jacob and Monod christened the unstable, information-bearing intermediate between gene and protein “messenger RNA.” Out of the amorphous biochemistry of RNA, three distinct anatomies had now been differentiated: rRNA, tRNA, mRNA. Two had begun their scientific careers as purely intellectual creations, function postulating structure. .Jacob and Monod wrote the idea of the messenger, and the term, into a theoretical summation they were preparing. Meanwhile, Brenner had written up the experimental work… At the end [of Jacob and Monod's article] they came to the function of the ribosome.

The property attributed to the structural messenger of being an unstable intermediate is one of the most specific and novel implications of this scheme… This leads to a new concept of the mechanism of information transfer, where the protein synthesizing centers (ribosomes) play the role of non-specific constituents which can synthesize different proteins, according to specific instructions which they receive from the genes through M-RNA.

There, in a sentence, was the first published statement of the pivotal realization that had come to Crick, Brenner, and Jacob in their conversation on Good Friday, eight months earlier….

Jacob and Monod titled their paper “Genetic Regulatory Mechanisms in the Synthesis of Proteins.” It reached The Journal of Molecular Biology on 28 December 1960.

So, next time you hear someone arguing about mRNA and vaccines and you aren’t sure what it is all about, go get a copy of The Eighth Day of Creation. At least you'll learn what mRNA is. Judson's book is one of the best about the history of science, and the absolute best I know of about the history of modern biology.