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Biology

Heredity involves genes on chromosomes, but the details of how genetic information is used by cells are still being worked out.

Now we know:

The central dogma of molecular biology - DNA → RNA → protein - was proposed by Crick in 1957 and describes how genetic information flows in living cells. The genetic code was being deciphered through 1959–1961.

Disproven 1953

What changed?

When James Watson and Francis Crick published the double helix structure of DNA in April 1953, the central question of genetics changed form. The problem of what molecule carried hereditary information had been solved. The problem that replaced it was how that information worked, how the sequence of bases in a strand of DNA produced a living organism's proteins, structures, and functions.

The answer came in stages, through some of the most rapid and concentrated experimental work in the history of biology.

In June 1957, Crick delivered a lecture to the Society for Experimental Biology in London entitled 'On Protein Synthesis.' It contained, almost incidentally, a statement he called the Central Dogma of Molecular Biology: information flows from nucleic acids to proteins, but cannot flow from proteins back to nucleic acids. More specifically, DNA produces RNA, and RNA produces protein. The sequence of events was directional and irreversible. The diagram Crick sketched to illustrate it, three circles connected by arrows, with DNA and RNA connected to each other and both connected to protein, became one of the organizing frameworks of the entire discipline. Crick published a formal account of the dogma in Nature in 1970, clarifying what the principle did and did not claim.

The genetic code remained to be worked out. How did a sequence of four nucleotide bases specify which of twenty amino acids was incorporated into a growing protein chain? In 1954, the physicist George Gamow proposed that triplets of bases, codons, encoded individual amino acids; the combinatorial math worked out, since four bases taken three at a time yield sixty-four possible combinations, more than enough to specify twenty amino acids with room for redundancy and punctuation. It was an elegant hypothesis. Verifying it required experiment.

The critical breakthrough came in the summer of 1961. Marshall Nirenberg and his postdoctoral assistant Johann Heinrich Matthaei, at the National Institutes of Health in Bethesda, Maryland, set up a cell-free protein synthesis system, a test tube containing the cellular machinery for building proteins but no genetic material of its own. They introduced synthetic RNA composed entirely of the base uracil, repeated indefinitely: poly-U. The system produced a protein composed entirely of the amino acid phenylalanine. One triplet of uracil bases coded for one amino acid. The genetic code was crackable.

Nirenberg and Severo Ochoa, who had won the 1959 Nobel Prize in Physiology or Medicine for synthesizing RNA in vitro, raced to decode the remaining codons over the following years. By 1966, the full code was solved: every codon was mapped to its corresponding amino acid or stop signal. The information in DNA could now be read like a text in a known language.

This accumulation of knowledge happened extraordinarily fast. In little more than a decade, biology moved from uncertainty about the identity of the hereditary molecule to a nearly complete account of how that molecule's information was read and translated into protein. But the pace of academic publication was far faster than the pace of curriculum revision. High school biology textbooks typically lag the research frontier by a decade or more, and the molecular biology revolution reached classrooms unevenly.

Students in the late 1950s were taught that genes on chromosomes controlled traits, a framework still anchored in Mendelian genetics and chromosomal theory, without the underlying molecular account that made it explicable. The central dogma did not appear in most secondary biology curricula until well into the 1960s. Some state curricula did not incorporate the genetic code before the 1970s. The speed at which biology was rewriting its own foundations made the lag nearly unavoidable, but it produced a generation of graduates whose understanding of genetics stopped at the chromosome.

A diagram showing circles labeled DNA, RNA, and protein connected by arrows indicating the direction of information flow in the central dogma of molecular biology.
A reconstruction of Crick's original 1958 diagram of the Central Dogma of Molecular Biology, showing the directional flow of genetic information from DNA to RNA to protein, with additional possible transfers indicated. · Ragesoss - Public Domain

At a glance

Disproven
1953
Believed since
1945
Duration
8 years
Taught in schools
1959

Sources

  1. [1] Central Dogma of Molecular Biology - Crick, F.H.C., 1970
  2. [2] The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides - Nirenberg, M.W. and Matthaei, J.H., 1961