george gamow and rna--8/5/26

05 Aug 2026

george gamow and rna--8/5/26

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Today's selection-- from The Catalyst by Jonah Berger. George Gamow, a renowned theoretical physicist and cosmologist, and Soviet defector to the United States pioneered the study of the genetic code in the 1950s by proposing that nucleic acids use a combination of bases to sequence amino acids — among many other accomplishments. Along with James Watson (discoverer of the DNA double helix structure), he founded the famous RNA Tie Club, a group of elite scientists committed to deciphering how RNA builds proteins. Gamow was a well-known jokester, who reveled in practical jokes and humorous twists embedded in serious scientific publications:

“In biological terms, ‘deciphering the genetic code’ means understanding how DNA encodes proteins. Life is built from proteins, which are the main movers and shakers in every organism in our biosphere. In humans, some proteins form structures such as muscle fibers, skin, and hair. Some act as enzymes, breaking down the food we eat into its constituent components and then recycling these pieces to build up new cellular machines. Others punch holes in the envelopes that encase our cells, selectively allowing some salts or nutrients to enter the cell and expelling others. Other proteins act as signaling molecules, receiving information from the outside world and activating internal processes accordingly. Still others are antibodies, which protect us from foreign invaders such as viruses. In short, proteins are spectacularly diverse.

“Chemically speaking, proteins are polymers, strings of a hundred or even a thousand amino acids. These amino acid building blocks come in 20 types, with names such as lysine, valine, and phenylalanine. Each protein has a specific order, or sequence, of amino acids along its chain. This sequence determines how the protein folds into a three-dimensional entity that has a particular function, such as digesting food in the stomach or transmitting neuronal signals in the brain. Thus, even though we hear that we need to eat fish or tofu or an Impossible Burger ‘to get enough protein in our diet,’ there is not a protein but rather many thousands of different ones. And each is encoded by its own gene, which is made of DNA.

“Whereas proteins are built out of 20 amino acids, DNA is built out of the four bases. This leaves us with, on the one hand, the sequence of A’s, G's, T's, and C's in a gene made of DNA and, on the other hand, the sequence of 20 amino acids in the corresponding protein. Gamow sought to figure out how different arrangements of the four DNA bases specified, or encoded, each of the 20 amino acids. By 1954, he had recruited Watson, Crick, and an eclectic cadre of well-known scientists–20 in all, one for each amino acid–to direct their brain power to the coding problem.

Georgiy Antonovich Gamov

“Gamow had woolen ties, each embroidered with a strand of RNA, sewn for the members of this little fraternity of pointy-headed code breakers. He dubbed the group ‘the RNA Tie Club.’ Why not the ‘DNA Tie Club,’ you may ask? It was Jim Watson who convinced Gamow that they had to focus their code-breaking attention on RNA because of the basic structure of cells. Whereas DNA is found inside the cell's nucleus in higher organisms, proteins are made outside the nucleus, in the region known as the cytoplasm. This spatial separation mandated that some

sort of messenger must transport the information from DNA to the site of protein production. A number of forward-thinking scientists thought that RNA could be that messenger, as it was known to be abundant both in the nucleus and in the cytoplasm.

“Since the early 1900s, chemists had analyzed RNA and DNA and found that they were cut from the same biochemical cloth. Their full names–deoxyribonucleic acid and ribonucleic acid–reveal how closely related they are. "Deoxy" indicates that DNA has one fewer oxygen atom on each of its repeating units than RNA; the extra oxygen atom makes RNA chemically much less stable than DNA.

“For many decades, DNA and RNA were seen as chemical compounds without a function. They were far less interesting to scientists than proteins, whose roles as enzymes and as signaling molecules such as insulin seemed so exciting. DNA emerged as the centerpiece of biology only when the 1944 discovery by Oswald Avery and colleagues at the Rockefeller Institute that DNA is the molecule responsible for causing heritable changes in bacteria was coupled with the 1953 discovery by Watson and Crick of the double-helical structure of DNA. Because scientists had already theorized as early as 1947 that RNA was copied from DNA, they now assumed that RNA must also have an important role to play in the chemistry of life.

“Although RNA is typically single stranded and DNA is double helical, both speak the same language. Like DNA, RNA is written in a fourletter alphabet. The first three letters–A, G, and C–are the same as DNA’s. The fourth letter, U (uracil), occupies the same place in RNA's alphabet as T does in DNA's alphabet. So when RNA is copied from DNA, it carries the same information.

“Devoted as always to big, sweeping theories, Gamow first tried to work out a solution to the coding problem with nothing more than pencil, paper, and his brain. In 1953, the same year the double helix was discovered, he theorized that three bases might code for one amino acid. His reasoning was mathematical. If you took the four letters in the DNA or RNA alphabet and tried to create as many combinations of two letters as possible, you would get only 16 combinations–too few to specify the 20 amino acids that make up proteins. But if you tried to arrange the four letters of the DNA or RNA alphabet into as many three-letter combinations as possible, you would get 64 of these triplet codons–enough to specify 20 amino acids and then some. Longer groups of bases could do the job, but three were enough; it was the most economical format for the genetic code.

“But which groups of three bases encoded which amino acids? Even though Gamow had brought together some of the greatest geniuses of the twentieth century, ultimately the distinguished members of the RNA Tie Club succeeded only in tying themselves in knots. By the late 1950s, Gamow had given up trying to crack the code, convinced that the problem had ‘no solution’ that could be found on ‘the basis of pure theory.’

What Gamow really needed was the biological equivalent of the Rosetta Stone. Instead of a text written in both Egyptian hieroglyphics and Greek, it would display an amino acid sequence of a protein as well as the RNA sequence that encoded it. But there was no such stone; scientists would need to devise their own. And to do it, they would have to determine whether this hypothetical ‘messenger’ actually existed–whether RNA truly was the missing link between our genes and the protein building blocks of life.”