Brief History Of Modern Biochemistry Molecular Biology

Just as macromolecular entities such as proteins can be detected, purified, and characterized based on their inherent biological properties (i.e., molecular size, ionic charge at certain pHs), so, too, can micro-molecular entities such as nucleic acids (DNA and RNA). In fact, since the core biological properties of DNA and RNA were reported in the 1950s and 1960s, a number of molecular purification and characterization techniques have been developed which take advantage of these properties. The advent of these molecular techniques, first viewed as tools of biochemistry, has led to the emergence of a new and related field of study known as molecular biology. Noting the recent advent of genomics and proteomics, advancements in this field continue to occur at a pace which rivals that of the electronics industry.

Currently, there is much support hailing the discovery of the double helix by Watson and Crick as the beginning of modern biochemistry and molecular biology (9). Others stress that it was the later-proven speculation by Watson and Crick that the pairing arrangement of bases in the double helix implied the existence of an information-carrying genetic code (or "copying mechanism," as they called it). One could just as easily argue that modern biochemistry arose from the work of Hershey and Chase, that demonstrated that DNA was the material of heredity, and shifted much focus away from protein. It would seem to most, though, that the works of Hershey and Chase, Watson and Crick, Messelson and Stahl, Jacob and Monod, and Nirenberg and Leder, as a whole, during 1953-1964, set the foundation for modern biochemistry and molecular biology.

Following the elucidation of the genetic code, the 1970s were witness to a number of important advances in relation to the study of DNA. Right away, the first restriction enzyme was isolated from Hemophilus influenzae by Smith and Wilcox (1970) (14). Three years later, Cohen and Boyer utilized restriction enzyme technology in developing DNA cloning and recombinant DNA (15). Ed Southern (1975) developed a DNA detection technique (later named after him) that employed blotting DNA to a membrane and hybridizing radio-labeled DNA probes that were complementary to specific sequences (16). In 1977, Sanger developed a rapid technique for manually sequencing DNA in vitro (17).

Similarly, the rapid pace of scientific advancement in microbiology continued during the 1980s and 1990s, and continues right up to the present time. In 1980, the U.S. Supreme Court decreed that life forms, such as genetically-modified organisms, could be patented. This decision facilitated the emergence of numerous biotechnology companies, such as Amgen. The 1980s also saw the invention of the polymerase chain reaction (PCR) technique for amplification of DNA sequences by Kary Mullis (18) and the development of the first genetically-modified crop, a tobacco (19). Soon after, during the late 1980s and early 1990s, Leroy Hood and colleagues developed the first automated DNA sequencer and protocols utilizing fluorescent dyes that could be read automatically (20). In the mid-1990s, J. Craig Venter developed a rapid technique for genomic sequencing known as "shotgun" sequencing, in which genomic DNA is broken into smaller fragments for sequencing and afterwards the resulting sequences are put back in order for further genetic analyses (21). Meanwhile, at Stanford University, Patrick Brown and colleagues were busy developing an automated method for quantitative gene expression, later to be known as the DNA microarray (22). In 1997, the first successfully cloned animal was born in Scotland, a sheep named Dolly (23). And finally, in 2001, after nearly 10 years of tense competition, two research groups, one privately funded and one publicly funded, published the first drafts of the human genome sequence (24,25).

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