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Sunday, June 6, 2010

Introduction to "Biotechnology"

Introduction to "Biotechnology"

Biotechnology generally refers to the use of microorganisms to produce certain chemical compounds. Long before the term "biotechnology" was coined for the process of using living organisms to produce improved commodities, people were utilizing living micro-organisms to produce valuable products. A list of early biotechnology applications follows below.
Proving bread with leaven prehistoric period
Fermentation of juices to alcoholic beverages prehistoric period
Knowledge of vinegar formation from fermented juices prehistoric period
Cultivation of vine before 2000 BC
Manufacture of beer in Babylonia and Egypt 3rd century BC
Wine growing promoted by Roman Emperor Marcus Aurelius Probus 3rd century AD
Production of spirits of wine (ethanol) 1150
Vinegar manufacturing industry 14th century
Discovery of the fermentation properties of yeast by Erxleben 1818
Description of lactic acid fermentation by Pasteur 1857
Detection of fermentation enzymes in yeast by Buchner 1897
Discovery of penicillin by Fleming 1928/29
Discovery of many other antibiotics from about 1945
Since then "biotechnology" has rapidly progressed and expanded. In the mid-forties, scale-up and commercial production of antibiotics such as penicillin occurred. The techniques used were (a) isolation of an organism producing the chemical of interest using screening/selection procedures, and (b) improvement of production yields via mutagenesis of the organism or optimization of media and fermentation conditions. This type of "antique" biotechnology is limited to chemicals produced in nature. It is also limited by its trial-and-error approach, and requires a lengthy timeframe (years or even decades) for yield improvement.
About two decades ago, biotechnology became much more of a science (rather than an art). Regions of DNA (called genes) were found to contain information that would lead to synthesis of specific proteins (which are strings of amino acids). Each of these proteins have their own identity and function; many catalyze (facilitate) chemical reactions, and others are structural components of entities in cells. If one now is able to express a natural gene in simple bacteria such as Escherichia coli (E. coli), a bacterium living in intestines that has become the model organism for much of biotechnology, one can have this bacterium make a lot of the protein coded for by the gene, regardless its source. The techniques used for this development include (a) isolation of the gene coding for a protein of interest, (b) cloning of this gene into an appropriate production host, and (c) improving expression by using better promoters, tighter regulation, etc.; together these techniques are known as recombinant DNA techniques. These will be discussed at some length in the course.
The commercial implications are that a large number of proteins, existing only in tiny quantities in nature, can now be mass-produced if needed. Also, the yields of (bio)chemicals to be produced can be increased much faster than was possible with classical fermentation. These modern biotechnology techniques started with the expression of human genes such as that coding for insulin, but have since been extended to mammalian, microbial, and plant genes. Also, the spectrum of "bioreactors" (organisms used for production) recently has been broadened to include a variety of animals and plants. As we will see, perceived needs and marketability, the researchers' imagination, ethics, and governmental regulations essentially are the major factors in setting the stage and boundaries for developments in biotechnology.
About a decade ago, "protein engineering" became possible as an offshoot of the recombinant DNA technology. Protein engineering differs from "classical" biotechnology in that it is concerned with producing new (man-made) proteins which have been modified or improved in some way. The techniques involved in protein engineering are more complicated than before, and involve (a) various types of mutagenesis (to cause changes in specific locations or regions of a gene to produce a new gene product), (b) expression of the new gene to form a stable protein, (c) characterization of the structure and function of the protein produced, and (d) selection of new locations or regions to modify as a result of this characterization.
In the mid-eighties and early-nineties, it has become possible to transform (genetically modify) plants and animals that are important for food production. "Transgenic" animals and plants, including cows, sheep, tomatoes, tobacco, potato, and cotton have now been obtained. Genes introduced may make the organism more resistant to disease, may influence the rate of fruit ripening, or may increase productivity. As this approach leads to release of genetically altered organisms into the environment, this part of biotechnology is quite strictly regulated at government levels. Recent advances in this area of modern biotechnology are numerous, and some will be highlighted in this course.

Below is an overview of recombinant DNA based biotechnology:
1953   Double helix structure of DNA is first described by Watson and Crick.
1973   Cohen and Boyer develop genetic engineering techniques to "cut and paste" DNA and to amplify the new DNA in bacteria.
1977   The first human protein (somatostatin) is produced in a bacterium (E. coli).
1982   The first recombinant protein (human insulin) appears on the market.
1983   Polymerase chain reaction (PCR) technique conceived.
1990   Launch of the Human Genome Project (HGP), an international effort to sequence the human genome.
1995   The first genome sequence of an organism (Haemophilus influenzae) is determined.
2000   A first draft of the human genome sequence is completed.
2005   Over 40 million gene sequences are in GenBank, and genome sequences of hundreds of prokaryotes and dozens of eukaryotes are finished or in draft stage.

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