Chapter 1. The Molecular Biotechnology Revolution
I. What it is II. Brief history III. Commercialization IV. Biotechnology and society V. Biotechnology literature
I. What it is
II. Brief history
III. Commercialization
IV. Biotechnology and society
V. Biotechnology literature
Note: The figures and tables referred to in these web notes are in the course textbook.
I. What is biotechnology?
Technology. The application of science, especially to industrial or commercial objectives.
Biotechnology. "...the application of scientific and engineering principles to processing of material by biologic agents (e. g. microorganisms, plants and animals) to provide goods and services." (your text)
Molecular biotechnology. Employs the tools of molecular biology (recombinant DNA, gene cloning) to engineer the genetic information/blueprint of living organisms to produce useful, marketable products.
Overview of Molecular Biotechnology
Before it was possible to manipulate DNA in the laboratory, biotechnology was limited by the species barrier which blocked movement of genes from one organism to another.
The techniques of basic molecular biology have enabled manipulation of the genetic material outside the cell and its introduction back into the cells of the same or a different organism. This recently developed capability has opened the door for genetic engineering of an organism to improve existing biotechnology applications as well as the use of previously impossible approaches to solving some of the problems facing mankind.
Why is biotechnology important and how does it benefit society?
Health (New and better antibiotics, drugs and vaccines, diagnosis of disease, gene therapy) Nutrition (Production of more nutritious foods: e.g. vitamins, amino acids, proteins) Agriculture (Increased crop and livestock production, disease resistance, better pesticides) Energy (Production of fuels from renewable resources, cleaner fuels) Chemicals (Production methods that produce less pollution) Environment (Bioremediation of pollution)
Health (New and better antibiotics, drugs and vaccines, diagnosis of disease, gene therapy)
Nutrition (Production of more nutritious foods: e.g. vitamins, amino acids, proteins)
Agriculture (Increased crop and livestock production, disease resistance, better pesticides)
Energy (Production of fuels from renewable resources, cleaner fuels)
Chemicals (Production methods that produce less pollution)
Environment (Bioremediation of pollution)
II. History
See Table 1.1 Some highlights that made molecular biotechnology possible 1944 DNA discovered as the genetic material (Avery, Macleod, McCarty) 1953 Structure of DNA determined (Watson, Crick, Franklin and Wilkins) 1961-66 Genetic code deciphered 1973 Recombinant DNA technology established (see below) 1975 Monoclonal antibody production methods (Kholer and Milstein) 1976 DNA sequencing techniques developed (Sanger, Maxim and Gilbert) 1995 First genome of free-living organism completely sequenced Haemophilus influenzae (1,830,137 nucleotides) 1997 First mammal cloned (Dolly the sheep) 2000 First draft of the sequence of the human genome (~3,300,000,000 nucleotides)
See Table 1.1
Some highlights that made molecular biotechnology possible
pSC109 is a recombinant plasmid that was created in vitro from two different plasmids using a restriction enzyme to catalyze cleavage of the plasmids and DNA ligase to catalyze formation of phosphodiester bonds between the fragments. E. coli cells containing pSC109 were resistant to both streptomycin and tetracycline.
United States Patent 4,237,224 Dec. 2, 1980
Process for producing biologically functional molecular chimeras
Abstract
Method and compositions are provided for replication and expression of exogenous genes in microorganisms. Plasmids or virus DNA are cleaved to provide linear DNA having ligatable termini to which is inserted a gene having complementary termini, to provide a biologically functional replicon with a desired phenotypical property. The replicon is inserted into a microorganism cell by transformation. Isolation of the transformants provides cells for replication and expression of the DNA molecules present in the modified plasmid. The method provides a convenient and efficient way to introduce genetic capability into microorganisms for the production of nucleic acids and proteins, such as medically or commercially useful enzymes, which may have direct usefulness, or may find expression in the production of drugs, such as hormones, antibiotics, or the like, fixation of nitrogen, fermentation, utilization of specific feedstocks, or the like.
Inventors: Cohen; Stanley N. (Portola Valley, CA); Boyer; Herbert W. (Mill Valley, CA). Assignee: Board of Trustees of the Leland Stanford Jr. University (Stanford, CA). Appl. No.: 1,021 Filed: Jan. 4, 1979
III. Commercialization of molecular biotechnology (Fig. 1.2)
Microorganisms were the first organisms to be genetically engineered with recombinant DNA technology to produce commercial products
Stages of the Industrial Use of Microorganisms to Produce a Commercial Product.
1. Upstream processing. Preparation of the food source for growth of the microorganism.
Ex. Corn syrup as carbon and energy source.
2. Fermentation. Large-scale growth of microorganisms and transformation of food source to desired product(s).
Ex. Ethanol, antibiotics, hormones (human insulin), dyes (indigo), proteases (detergnets).
3. Downstream processing. Product purification from cells or fermentation medium and further refinement if necessary to produce an acceptable, marketable product.
To be profitable, a biotechnological application must maxamize efficiency...
-Greatest amount of product from the -Cheapest raw materials in the -Shortest time with -Minimal downstream processing
...through improvements in:
-Bioreactor design, control, monitoring -Growth media -Organism (focus of this course)
-Bioreactor design, control, monitoring
-Growth media
-Organism (focus of this course)
Many potential benefits However there are some concerns -Potential to cause harm to individuals or the environment. E.g. Spread of toxin or cancer-causing genes to benign organisms Spread of antibiotic resistance genes to pathogens Spread of herbicide-resistance genes to weed plants -Can't "recall" microorganisms after they have been released to the environment. -Morality of genetic engineering of humans. -Knowledge of predisposition to disease may influence personal decisions or availability of health insurance. -Patenting genetic material and living organisms. -Deliberate misuse (biological warfare, terrorism)
Many potential benefits
However there are some concerns
-Potential to cause harm to individuals or the environment.
E.g. Spread of toxin or cancer-causing genes to benign organisms Spread of antibiotic resistance genes to pathogens Spread of herbicide-resistance genes to weed plants
E.g. Spread of toxin or cancer-causing genes to benign organisms
Spread of antibiotic resistance genes to pathogens
Spread of herbicide-resistance genes to weed plants
-Can't "recall" microorganisms after they have been released to the environment.
-Morality of genetic engineering of humans.
-Knowledge of predisposition to disease may influence personal decisions or availability of health insurance.
-Patenting genetic material and living organisms.
-Deliberate misuse (biological warfare, terrorism)
V. Some Biotechnology Literature
Books
1. Molecular Biotechnology. 2003. 3rd edition. B.R. Glick and J.J. Pasternak. American Society for Microbiology. Washington, DC.
2. Microbial Biotechnology. 1995. A.N. Glazer and H. Nikaido. W.H. Freeman and Co. New York.
3. Molecular Biotechnology. 1991. S.B. Primrose. Blackwell Scientific Publications. London.
4. Engineered Organisms in the Environment: Scientific Issues. 1985. H. O Halvorson, D. Pramer and M. Rogul (Eds.). American Society for Microbiology. Washington, DC.
5. Manual of Industrial Microbiology and Biotechnology. 1999. 2nd Edition. A. L. Demain and J. E. Davies (Eds.). American Society for Microbiology. Washington, DC.
6. Recombinant DNA. 1992. J. D. Watson, M. Gilman, J. Witkowski and M. Zoller. W. H. Freeman and Company. New York.
Journals/News/Internet
Science
Nature
Journal of Industrial Microbiology and Biotechnology
Applied and Environmental Microbiology
Applied Microbiology and Biotechnology
Bio/Technology
BioTechniques
Genetic Engineering News
Chemical and Engineering News
ASM News
Biotechnology Progress
Biotechnology and Bioengineering
The Scientist
Nature Biotechnology
Bio Online http://www.bio.com
Bio 101 http://www.ultranet.com/~jkimball/BiologyPages
Internet Directory of Biotechnology http://biotech.che
Transgenic Crops http://www.colostate.edu/programs/lifesciences/TransgenicCrops/
Genomic Art http://www.geneart.org/community.html
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