Molecular Biology

MOLECULAR BIOLOGY

MOLECULAR BIOLOGY is the science, or cluster of scientific activities, that seeks to explain the phenomena of life through investigation of the molecules found in living things. The term was apparently invented in the late 1930s by Warren Weaver, a mathematician-turned official of the Rockefeller Foundation, who from 1933 through World War II (1939–1945) channeled much of this philanthropy's considerable resources into a program to promote medical advances by making the life sciences more like physics in intellectual rigor and technological sophistication. There is considerable debate about the extent to which Weaver successfully altered the intellectual direction of the wide range of life sciences with which he interacted. However, there can be little doubt that his program made important new instruments and methods available for biologists. For instance, Rockefeller support greatly furthered the development of X-ray crystallography, ultracentrifuge and electrophoresis instrumentation, and the electron microscope, all used for analyzing the structure and distribution in organisms of proteins, nucleic acids, and other large biomolecules. In the 1930s and 1940s, these biological macromolecules were studied not mainly by biochemists, since the traditional methods of biochemistry were adequate only for the study of compounds orders of magnitude smaller (with molecular weights in the hundreds), but rather by scientists from the ill-defined fields known as "biophysics" and "general physiology."

A general postwar enthusiasm for science made rich resources available to biologists from federal agencies such as the National Science Foundation and the National Institutes of Health. Thanks to this new funding, and also to a postatomic urge to make physics benefit mankind peacefully, the research topics and methods of biophysicists made great headway in the 1950s. New radioisotopes and accelerators spurred radiobiology. Electron microscopes were turned on cells and viruses. Protein structure was probed by crystallography, electrophoresis, and ultracentrifugation; furthermore, chemical methods were developed allowing determination of the sequence of the string of amino acids making up smaller proteins. This kind of macromolecule-focused research in the 1950s has been described as the "structural school of molecular biology" (or biophysics). In the immediate postwar era, another approach also developed around Max Delbrück, a physicist-turned-biologist fascinated since the 1930s with explaining the gene, who attracted many other physicists to biology. Now regarded as the beginning of molecular genetics, this style has been called the "informational school of molecular biology," since during the 1940s and 1950s the school probed the genetic behavior of viruses and bacteria without any attempt to purify and characterize genes chemically. To the surprise of many, largely through the combined efforts of James Watson and Francis Crick—a team representing both schools—in the mid-1950s, the gene was found to be a double-helical form of nucleic acid rather than a protein. From this point through the early 1960s, molecular geneticists concentrated much of their efforts on "cracking" the "code" by which sequences of nucleic acid specify the proteins that carry out the bulk of biological functions. After the "coding" problem was settled in the mid-1960s, they turned mainly to the mechanisms by which genes are activated under particular circumstances, at first in viruses and bacteria, and from the 1970s, in higher organisms. While the extent to which physics actually influenced the development of molecular biology is controversial, some impact can clearly be seen in the use of cybernetic concepts such as feedback in explaining genetic control, as well as in early thinking about genetics as a cryptographic problem.

Although many projects associated with biophysics flourished in the 1950s, the field as a whole did not. Rather, some areas pioneered by biophysicists, such as protein structure, were partly absorbed by biochemistry, while others split off in new disciplines. For example, electron microscopists studying cell structure split when they established cell biology, and radiobiologists largely left biophysics to join (with radiologists) in the newly emerging discipline of nuclear medicine. By the later 1960s, departments bearing the name "molecular biology" were becoming more common, typically including molecular genetics as well as certain types of "structural" biophysics. In the 1970s a new generation of convenient methods for identifying particular nucleic acids and proteins in biological samples (RNA and DNA hybridization techniques, monoclonal antibodies) brought the study of genes and their activation to virtually all the experimental life sciences, from population genetics to physiology to embryology. Also in the 1970s, methods to determine the sequence of nucleic acids making up genes began to be developed—culminating during the 1990s in the government-funded, international Human Genome Project—as well as methods for rearranging DNA sequences in an organism's chromosomes, and then reintroducing these altered sequences to living organisms, making it possible for molecular geneticists to embark upon "genetic engineering." In the early twenty-first century, there is virtually no branch of life science and medicine that is not "molecular," in that all explain biological phenomena partly in terms of nucleic acid sequences and protein structure. Thus, from its beginnings, molecular biology has resisted definition as a discipline. But however defined—as a style of investigation, a set of methods or questions, or a loosely knit and overlapping set of biological fields based in several disciplines—the enterprise of explaining life's properties through the behavior of its constituent molecules has, since its origins in the interwar era, become one of the most intellectually fruitful and medically useful movements ever to engage the life sciences.

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Nicolas Rasmussen

See also DNA ; Genetic Engineering ; Genetics ; Human Genome Project .