Foundations in Medical Pharmacogenomics
Microbial genetics emerged in the mid-1940s, based upon Mendelian principles of heredity. The role of DNA advanced the understanding of the mechanisms of gene transfer between bacteria. The discovery of the structure of DNA by James Watson and Francis Crick, based in part on research carried out by Rosalind Franklin and Maurice Wilkins, illuminated the role of genetic expression at the molecular level. Experiments with bacteria, viruses, and plasmids established the foundations of molecular genetics, leading the way to further research on the role of DNA ligases, restriction enzymes, and recombinant DNA.
In 1971, Herbert Boyer and Stanley Cohen successfully spliced a toad gene between two recombined ends of bacterial DNA. Further experimentation with recombinant molecules and gene cloning formed the basis for emerging genetic engineering technologies. The term technology fusion was coined in the 1970s to describe the converging roles of food, drug, and industrial chemical industries in the corporate development of biotechnology and the manufacture of genetically modified products, setting the stage for a new bioeconomy. Boyer and Robert Swanson formed Genentech, a company devoted to the development and promotion of biotechnology and genetic engineering applications, in 1976. The bioeconomy of the early twenty-first century is driven by major life sciences corporations including Syngenta, Bayer, Monsanto, Dow, and DuPont.
In 1978, Boyer discovered a synthetic version of the human insulin gene and inserted it into Escherichia coli
(E. coli) bacteria. The E. coli served as cloning vectors to maintain and replicate large amounts of human insulin. This application of recombinant DNA technology to produce human insulin for diabetics was a foundation for the future of industrial applications of genetic engineering and biotechnology. The Eli Lilly company began manufacturing large quantities of human insulin by vector cloning in 1982. Growth hormones for children and antibodies for cancer patients were soon being similarly cloned in bacteria. The pharmaceutical industry was revolutionized.
The Human Genome Project
began in 1990. Since 1995, thousands of genomes have been sequenced, providing valuable data for comparative studies of genetic disorders. The human genome map has strengthened the clinician’s ability to profile illnesses and disorders more accurately based on genomic differences. Drug therapies are evolving to address those differences. Gene therapies hold great promise, but cell delivery strategies have not been sufficiently studied. Biologic (protein) drugs are similarly complex. Delivery systems must overcome differences in the molecular weight of genetic substances and the effect on the chemistry of plasma membranes. Nanoparticles may provide a workable transport system for the delivery of drugs, nutrients, and short interfering RNAs (siRNAs) to specific sites, with particular success in the treatment of cancer.
Cleaning Up Waste
Since the 1970s, numerous industrial processes have been based on applications of genetic engineering and biotechnology, ranging from the production of new medicines and foods to the manufacture of new materials for cleaning up the environment and enhancing natural resource recovery. These applications focus on industrial processes that reduce or eliminate the production of waste products and consume low amounts of energy and nonrenewable resources. The chemical, plastic, paper, textile, food, farming, and pharmaceutical industries are positively affected by biotechnology.
Genetic engineering methods are employed in myriad applications to help clean up waste and pollution worldwide. In 1972, Ananda Chakrabarty, a researcher at General Electric (who would later join the college of medicine at the University of Illinois at Chicago), applied for a patent on a genetically modified bacterium that could partially degrade crude oil. Other scientists quickly recognized that toxic wastes might be cleaned up by pollution-eating microorganisms. After a financial downturn for a number of years, a resurgence in bioremediation technology occurred in the late 1980s and early 1990s, when genetically engineered bacteria were produced that could accelerate the breakdown of oil, as well as a diversity of unnatural and synthetic compounds, such as plastics, chlorinated insecticides, herbicides, and fungicides. In 1987 and 1988, bacterial plasmid transfer was used to degrade a variety of hydrocarbons found in crude oil. In the 1990s naturally occurring and genetically altered bacteria were employed to degrade crude oil spills, such as the major spill that occurred in Alaska’s Prince William Sound after the Exxon Valdez accident.
Some genetically altered bacteria have been designed to concentrate or transform toxic metals into less toxic or nontoxic forms. In 1998 a gene from E. coli was successfully transferred into the bacterium D. radiodurans, allowing this microbe to resist high levels of radioactivity and convert toxic mercury II into less toxic elemental mercury. Other altered microbial genes have been added to this bacterium, allowing it to metabolize the toxic organic chemical toluene, a carcinogenic constituent of gasoline. Genetically altered plants have been produced that absorb toxic metals, including lead, arsenic, and mercury, from polluted soils and water. At Michigan State University, naturally occurring bacteria have been combined with genetically modified bacteria to degrade polychlorinated biphenyls (PCBs). A genetically altered fungus, one that helps clean up
toxic substances discharged when paper is manufactured, also produces methane as a by-product which can be used as a fuel. Synthetic biology is a newly emerging field with specific applications in the creation of biofuels and biocatalysts.
Biomass and Materials Science
Genetically altered microorganisms can transform animal and plant wastes into materials usable by humans. Bioengineered bacteria and fungi are being developed to convert biomass wastes, such as sewage solid wastes (paper, garbage), agricultural wastes (seeds, hulls, corn cobs), food industry by-products (cartilage, bones, whey), and products of biomass, such as sugars, starch, and cellulose, into useful products such as ethanol, hydrogen gas, and methane.
Commercial amounts of methane are generated from animal manure at cattle, poultry, and swine feed lots; sewage treatment plants; and landfills. Biofuels will be cleaner and generate less waste than fossil fuels. In a different application involving fuel technology, genetically modified microbes are used to reduce the pollution associated with fossil fuels by eating the sulfur content from these fuels.
In applications involving the generation of new materials, a gene generated in genetically modified cotton can produce a polyester-like substance that has the texture of cotton, is even warmer, and is biodegradable. Other genetically engineered biopolymers are produced to replace synthetic fibers and fabrics. Polyhydroxybutyrate, a feedstock used in producing biodegradable plastics, is being manufactured from genetically modified plants and microbes. Natural protein polymers, very similar to spider silk and the adhesives generated by barnacles, are produced from the fermentation of genetically engineered microbes. Sugars produced by genetically altered field corn are converted into a biodegradable polyester-type material for use in manufacturing packaging materials, clothing, and bedding products. Genetically tailored yeasts can produce a variety of plastics. Such biotechnological advancements help reduce the prevalent use of petroleum-based chemicals that has been necessary in the creation of plastics and polyesters.
The fields of biotechnology and nanotechnology are merging in some materials science applications. Genetic codes discovered in microorganisms can be used as codes for nanostructures, such as task-specific silicon chips and microtransistors. Nanotech production of bioactive ceramics may provide new ways to purify water, since bacteria and viruses stick to these ceramic fibers. Recombinant DNA technology combined with nanotechnology provides the promise for the production of a variety of commercially useful polymers. Carbon nanotubes possessing great tensile strength may be used as computer switches and hydrogen energy storage devices for vehicles. When these nanotubes are coated with reaction specific biocatalysts, many other specialized applications are apparent. In the future, DNA fragments themselves may be used as electronic switching devices.
Natural Resource Recovery
Bioengineered microbes are being developed to extract and purify metals from mined ores and from seawater. The microbes obtain energy by oxidizing metals, which then come out of solution. Chemolithotrophic bacteria, such as Bacillus cereuss, are energized when they oxidize nickel, cobalt, and gold. They may be used to filter out and concentrate precious metals from seawater. Iron and sulfur-oxidizing bacteria can also concentrate and release precious metals from seawater. Genetically modified thermophilic bacteria
are being produced to extract precious metals from sands. Some genetically altered microorganisms can withstand extreme environments of high salinity, acidity, heavy metals, temperature, and/or pressure, such as those that exist around hydrothermal vents where precious minerals are present near the bottom of the ocean.
Genetically engineered strains of the bacteria Pseudomonas and Bacillus are being produced to extract oil from untapped reservoirs and store it rather than digest it. These bacteria can be extracted and processed to recover the oil. Other strains are being developed to absorb oil from the vast supplies of oil shale in North America. The process involves drilling into the oil shale and breaking it into pieces with chemical explosives. A solution of the bioengineered microbes would then be injected through a well into the rock fragments, where they would grow and absorb the oil. The solution would be pumped back to the surface through another well and the bacteria processed to remove the oil. Since this process would eliminate the need for large, open-pit oil shale mines, as well as the need to store oil shale at the surface, the negative environmental impact of oil recovery from shale would be greatly reduced.
Key Terms
biomass
:
any material formed either directly or indirectly by photosynthesis, including plants, trees, crops, garbage, crop residue, and animal waste
bioremediation
:
biologic treatment methods to clean up contaminated water and soils
cloning vector
:
a DNA molecule that maintains and replicates a foreign piece of DNA in a cell type of choice, typically the bacterium Escherichia coli
genetic transformation
:
the transfer of extracellular DNA among and between species
nanotechnology
:
ability to measure, see, manipulate, and manufacture things one to one hundred nanometers in size
pharmacogenomics
:
the study of inherited variation in drug disposition and response, focused on genetic polymorphisms
plasmids
:
small rings of DNA found naturally in bacteria and some other organisms, used as cloning vectors
recombinant DNA
:
a DNA molecule made up of sequences combined from different sources
synthetic biology
:
the application of engineering principles to fundamental biological components
technology fusion
:
a term used to describe the converging roles of food, drug, and industrial chemical industries in the corporate development of biotechnology for the manufacture of genetically modified products
Bibliography
Altman, Arie, and Paul Michael Hasegawa. Plant Biotechnology and Agriculture: Prospects for the 21st Century. Waltham: Academic, 2012. Print.
Bensaude-Vincent, Bernadette, and William R. Newman, eds. The Artificial and the Natural: An Evolving Polarity. Cambridge: MIT P, 2007. Print.
Das, Surajit, ed. Microbial Biodegradation and Bioremediation. Waltham: Elsevier, 2014. Print.
Erickson, Britt E. “Synthetic Biology: Rapidly Emerging Field Opens Many Opportunities but also Poses Difficult Challenges.” Chemical & Engineering News 87.31 (2009): 23–25. Print.
Evans, Gareth M. Environmental Biotechnology: Theory and Application. Hoboken: Wiley, 2003. Print.
Hindmarsh, Richard. Edging towards BioUtopia: A New Politics of Reordering Life and the Democratic Challenge. Crawley: U of Western Australia P, 2008. Print.
Hines, Ronald N., and D. Gail McCarver. “Pharmacogenomics and the Future of Drug Therapy.” Pediatric Clinics of North America 53.4 (2006): 591–619. Print.
Jasanoff, Sheila. Designs on Nature: Science and Democracy in Europe and the United States. Princeton: Princeton UP, 2005. Print.
Krimsky, Sheldon. Biotechnics and Society: The Rise of Industrial Genetics. New York: Praeger, 1991. Print.
Nicholl, Desmond S. T. An Introduction to Genetic Engineering. 2nd ed. New York: Cambridge UP, 2002. Print.
Schmidt, Markus, ed. Synthetic Biology: Industrial and Environmental Applications. Weinheim: Wiley, 2012. Print.
Sofer, William. Introduction to Genetic Engineering. Boston: Butterworth-Heinemann, 1991. Print.
No comments:
Post a Comment