History of Molecular Biology

Biochemistry, Genetics, and Molecular BiologyAs a freshman biology major in undergrad, I was introduced to molecular biology with the following description: Molecular biology represents the intersection of genetics, biochemistry and cell biology. Some people, it turns out, add microbiology and virology into the mix. So molecular biology is often used as a catch-all, to describe a wide breadth of interests.

In its earliest manifestations, molecular biology – the name was coined by Warren Weaver of the Rockefeller Foundation in 1938 – was an ideal of physical and chemical explanations of life, rather than a coherent discipline. Following the advent of the Mendelian-chromosome theory of heredity in the 1910s and the maturation of atomic theory and quantum mechanics in the 1920s, such explanations seemed within reach. Weaver and others encouraged (and funded) research at the intersection of biology, chemistry and physics, while prominent physicists such as Niels Bohr and Erwin Schroedinger turned their attention to biological speculation. However, in the 1930s and 1940s it was by no means clear which – if any – cross-disciplinary research would bear fruit; work in colloid chemistry, biophysics and radiation biology, crystallography, and other emerging fields all seemed promising. Between the molecules studied by chemists and the tiny structures visible under the optical microscope, such as the cellular nucleus or the chromosomes, there was an obscure zone, “the world of the ignored dimensions,” as it was called by the chemical-physicist Wolfgang Ostwald.

1929 – Phoebus Levene at the Rockefeller Institute identified the components (the four bases, the sugar and the phosphate chain) and he showed that the components of DNA were linked in the order phosphate-sugar-base.
1940 – George Beadle and Edward Tatum demonstrated the existence of a precise relationship between genes and proteins.
1944 – Oswald Avery, working at the Rockefeller Institute of New York, demonstrated that genes are made up of DNA.
1952 – Alfred Hershey and Martha Chase confirmed that the genetic material of the bacteriophage, the virus which infects bacteria, is made up of DNA.
1953 – James Watson and Francis Crick discovered the double helical structure of the DNA molecule.
1957 – In an influential presentation, Crick laid out the “Central Dogma”, which foretold the relationship between DNA, RNA, and proteins, and articulated the “sequence hypothesis.”
1958 – Meselson-Stahl experiment proves that DNA replication was semiconservative, a critical confirmation of the replication mechanism that was implied by the double-helical structure.
1961 – Francois Jacob and Jacques Monod hypothesized the existence of an intermediary between DNA and its protein products, which they called messenger RNA.
1961 – The genetic code was deciphered. Crick and Brenner identified the triplet codon pattern, while Marshall Nirenberg and Heinrich J. Matthaei of the NIH cracked the codes for the first 54 out of the 64 codons.

At the beginning of the 1960s, Monod and Jacob also demonstrated how certain specific proteins, called regulative proteins, latch onto DNA at the edges of the genes and control the transcription of these genes into messenger RNA; they direct the “expression” of the genes.

This chronology really gets at the basic science underpinning molecular biology as a field of study. At it’s core is the so-called Central Dogma of Molecular Biology, where genetic material is transcribed into RNA and then translated into protein, despite being an oversimplified picture of molecular biology, still provides a good starting point for understanding the field. This picture, however, is undergoing revision in light of emerging novel roles for RNA. But aside from a few footnotes, the Central Dogma has become the basis for a revolution in the biological sciences.

More recently much work has been done at the interface of molecular biology and computer science in bioinformatics and computational biology. As of the early 2000s, the study of gene structure and function, molecular genetics, has been amongst the most prominent sub-field of molecular biology.

Increasingly many other fields of biology focus on molecules, either directly studying their interactions in their own right such as in cell biology and developmental biology, or indirectly, where the techniques of molecular biology are used to infer historical attributes of populations or species, as in fields in evolutionary biology such as population genetics and phylogenetics. There is also a long tradition of studying biomolecules “from the ground up” in biophysics.

Additionally, studying protein structures and folding has been a hot area of molecular biology for a long time. The study of protein folding began in 1910 with a famous paper by Henrietta Chick and C. J. Martin, in which they showed that the flocculation of a protein was composed of two distinct processes: the precipitation of a protein from solution was preceded by another process called denaturation, in which the protein became much less soluble, lost its enzymatic activity and became more chemically reactive.

Later, Linus Pauling championed the idea that protein structure was stabilized mainly by hydrogen bonds, an idea advanced initially by William Astbury (1933). Remarkably, Pauling’s incorrect theory about H-bonds resulted in his correct models for the secondary structure elements of proteins, the alpha helix and the beta sheet. Since then, how proteins fold and maintain structures has been studied extensively using every chemical and physical property of proteins that could be identified, and as of 2006, the Protein Data Bank has nearly 40,000 atomic-resolution structures of proteins.

You may have heard that some biologists have called the era from the 1960’s until now the “golden age of molecular biology,” and now you know a little bit why that is so.

See also:

  • Lily E. Kay, The Molecular Vision of Life: Caltech, the Rockefeller Foundation, and the Rise of the New Biology, Oxford University Press, Reprint 1996

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