History of molecular biology

The history of molecular biology begins in the 1930's with the convergence of various, previously distinct and unrelated, branches of biology: biochemistry, genetics, microbiology, and virology. Numerous physicists and chemists also took an interest in this new material.

As its name indicates, this new branch of biology attempts to explain the phenomena of life starting from the macromolecular properties that generate them. Two categories of macromolecules in particular are the focus of the molecular biologist: 1) nucleic acids, among which the most famous is deoxyribonucleic acid (or DNA), the constituent of genes, and 2) proteins, which are the active agents of living organisms. The scope of molecular biology therefore is to characterize the structure, function and relationships between these two types of macromolecules. This relatively limited definition will suffice to allow us to establish a date for the so-called "molecular revolution", or at least to establish a chronology of its most fundamental developments.

In 1940, George Beadle and Edward Tatum demonstrated the existence of a precise relationship between genes and proteins. In 1944, Oswald Avery, working at the Rockefeller Institute of New York, demonstrated that genes are made up of DNA. In 1952, Alfred Hershey and Martha Chase confirmed that the genetic material of the bacteriophage, the virus which infects bacteria, is made up of DNA. In 1953, James Watson and Francis Crick discovered the double helical structure of the DNA molecule. In 1961, Francois Jacob and Jacques Monod hypothesized the existence of an intermediary between DNA and its protein products, which they called messenger RNA. Between 1961 and 1965, the relationship between the information contained in DNA and the structure of proteins was determined: there is a code, the genetic code, which creates a correspondence between the succession of nucleotides in the DNA sequence and a series of amino acids in proteins. At the beginning of the 1960's, 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.

The chief discoveries of molecular biology took place in a period of only about twenty-five years. Another fifteen years were required before new and more sophisticated technologies, united today under the name of genetic engineering, would permit the isolation and characterization of genes, in particular those of highly complex organisms.

The exploration of the molecular dominion

If we evaluate the molecular revolution within the context of biological history, it is easy to note that is it the culmination of a long process which began with the first observations through a microscope in the 18th century. The aim of these early researchers was to understand the functioning of living organisms by describing their organization at the microscopic level. From the end of the 18th century, the characterization of the chemical molecules which make up living beings gained increasingly greater attention, along with the birth of physiological chemistry in the 19th century, developed by the German chemist Justus von Leibig and following the birth of biochemistry at the beginning of the 20th, thanks to another German chemist Eduard Buchner. 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. This world is populated by colloids, chemical compounds whose structure and properties were not well defined.

The successes of molecular biology derived from the exploration of that unknown world by means of the new technologies developed by chemists and physicists: X-ray diffraction, electron microscopy, ultracentrifugization, and electrophoresis. These studies revealed the structure and function of the macromolecules.

A milestone in that process was the work of Dr. Linus Pauling, which for the first time linked the specific genetic mutation in patients with sickle cell disease to a demonstrated change in an individual protein, the hemoglobin in the erythrocytes of heterozygous or homozygous individuals.

The encounter between biochemistry and genetics

The development of molecular biology is also the encounter of two disciplines which made considerable progress in the course of the first thirty years of the twentieth century: biochemistry and genetics. The first studies the structure and function of the molecules which make up living things. Between 1900 and 1940, the central processes of metabolism were described: the process of digestion and the absorption of the nutritive elements derived from alimentation, such as the sugars. Every one of these processes is catalyzed by a particular enzyme. Enzymes are proteins, like the antibodies present in blood or the proteins responsible for muscular contraction. As a consequence, the study of proteins, of their structure and synthesis, became one of the principal objectives of biochemists.

The second discipline of biology which developed at the beginning of the 20th century is genetics. After the rediscovery of the laws of Mendel through the studies of Hugo de Vries, Carl Correns and Erich von Tschermack in 1900, this science began to take shape thanks to the adoption by Thomas Hunt Morgan, in 1910, of a model organism for genetic studies, the famous fruit fly (Drosophila melanogaster). Shortly after, Morgan showed that the genes are localized on chromosomes. Following this discovery, he continued working with Drosophila and, along with numerous other research groups, confirmed the importance of the gene in the life and development of organisms. Nevertheless, the chemical nature of genes and their mechanisms of action remained a mystery. Molecular biologists committed themselves to the determination of the structure, and the description of the complex relations between, genes and proteins.

The development of molecular biology was not just the fruit of some sort of intrinsic "necessity" in the history of ideas, but was a characteristically historical phenomenon, with all of its unknowns, imponderables and contingencies: the remarkable developments in physics at the beginning of the 20th century highlighted the relative lateness in development in biology, which became the "new frontier" in the search for knowledge about the empirical world. Moreover, the developments of the theory of information and cybernetics in the 1940s, in response to military exigencies, brought to the new biology a significant number of fertile ideas and, especially, metaphors.

The choice of bacteria and of its virus, the bacteriophage, as models for the study of the fundamental mechanisms of life was almost natural - they are the smallest living organisms known to exist - and at the same time the fruit of individual choices. This model owes its success, above all, to the fame and the sense of organization of Max Delbrück, a German physicist, who was able to create a dynamic research group, based in the United States, whose exclusive scope was the study of the bacteriophage: the School of the Phage.

The geographic panorama of the developments of the new biology was conditioned above all by preceding work. The US, where genetics had developed the most rapidly, and the UK, where there was a coexistence of both genetics and biochemical research of highly advanced levels, were in the avant-garde. Germany, the cradle of the revolutions in physics, with the best minds and the most advanced laboratories of genetics in the world, should have had a primary role in the development of molecular biology. But history decided differently: the arrival of the Nazis in 1933 - and, to a less extreme degree, the rigidification of totalitarian measures in fascist Italy - caused the emigration of a large number of Jewish and non-Jewish scientists. The majority of them fled to the US or the UK, providing an extra impulse to the scientific dynamism of those nations. These movements ultimately made molecular biology a truly international science from the very beginnings.

References

• Fruton, Joseph. Proteins, Genes, Enzymes: The Interplay of Chemistry and Biology. New Haven: Yale University Press. 1999. ISBN 0-300-07608-8
• Morange, Michel. A History of Molecular Biology. Cambridge, MA: Harvard University Press. 1998.