Genetic engineering: Historical development
Foundations of Genetic Engineering (Genetics & Inherited Conditions)
Microbial genetics, which emerged in the mid-1940’s, was based upon the principles of heredity that were originally discovered by Gregor Mendel in the middle of the nineteenth century and the resulting elucidation of the principles of inheritance and genetic mapping during the first forty years of the twentieth century. Between the mid-1940’s and the early 1950’s, the role of DNA as genetic material became firmly established, and great advances occurred in understanding the mechanisms of gene transfer between bacteria. The discovery of the structure of DNA by James Watson and Francis Crick (aided by the X-ray photography of Rosalind Franklin) in 1953 provided the stimulus for the development of genetics at the molecular level, and, for the next few years, a period of intense activity and excitement evolved as the main features of the gene and its expression were determined. This work culminated with the establishment of the complete genetic code in 1966, which set the stage for later advancements in genetic engineering.
Initially, the term “genetic engineering” included any of a wide range of techniques for the manipulation or artificial modification of organisms through the processes of heredity and reproduction, including artificial selection, control of sex type through sperm selection, extrauterine development of an embryo, and development of whole organisms from cultured cells. However,...
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The Development of Genetic Engineering (Genetics & Inherited Conditions)
Molecular genetics originated during the late 1960’s and early 1970’s in experiments with bacteria, viruses, and free-floating rings of DNA found in bacteria, known as plasmids. In 1967, the enzyme DNA ligase was isolated. This enzyme can join two strands of DNA together, acting like a molecular glue. It is the prerequisite for the construction of recombinant DNA molecules, which are DNA molecules that are made up of sequences not normally joined together in nature.
The next major step in the development of genetic engineering came in 1970, when researchers discovered that bacteria make special enzymes called restriction endonucleases, more commonly known as restriction enzymes. Restriction enzymes recognize particular sequences of nucleotides arranged in a specific order and cut the DNA only at those specific sites, like a pair of molecular scissors. Whenever a particular restriction enzyme or set of restriction enzymes is used on DNA from the same source, the DNA is cut into the same number of pieces of the same length and composition. With a molecular tool kit that included isolated enzymes of molecular glue (ligase) and molecular scissors (restriction enzymes), it became possible to remove a piece of DNA from one organism’s chromosome and insert it into another organism’s chromosome in order to produce new combinations of genes (recombinant DNA) that may not exist in nature. For example, a...
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Human Genome Project (Genetics & Inherited Conditions)
The Human Genome Project was proposed in 1985 by Charles DeLisi, director of the Office of Health and Environmental Research at the Department of Energy (DOE), to better understand potential changes to human DNA in the aftermath of the atomic bombs dropped by the United States on Nagasaki and Hiroshima, Japan, to end World War II. Sequencing began in 1990 in an international effort to map all of the genes and 3.1 billion base pairs on the human set of twenty-three pairs of chromosomes. Since 1995, more than 180 organisms have been sequenced, providing valuable data for comparative studies of genetic disorders. In 2007, Sir Martin John Evans of Cardiff University was awarded the Nobel Prize for creating chimeric, or transgenic, mice genetically engineered to lack a targeted “knockout” gene, a model particularly useful for understanding the genetics of cancer and psychiatric disorders. In April, 2009, a research team led by Byeong-Chun Lee of Seoul National University in South Korea announced the cloning of the world’s first litter of transgenic puppies. Ruppy the ruby puppy and her littermates express a red fluorescent gene produced by sea anemones, allowing them to glow in the dark. The mapping of the dog genome sequence provides researchers new material for unraveling the mechanics of human disease. Data bioinformatics systems continue to provide complex arrays and algorithms for mapping genetic characteristics. On May...
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Impact and Applications (Genetics & Inherited Conditions)
The application of genetic engineering to gene therapy (the science of replacing defective genes with sound genes to prevent disease) is still in the formative stages of clinical trial. Early trials introducing genes straight into human cells often failed, intensifying a wary public distrust of gene therapies. On September 14, 1990, genetically engineered cells were infused into a four-year-old girl to treat her adenosine deaminase (ADA) deficiency, an inherited, life-threatening immune deficiency called severe combined immunodeficiency disorder (SCID). In January, 1991, gene therapy was used to treat skin cancer in two patients. In 1992, small plants were genetically engineered to produce small amounts of a biodegradable plastic, and other plants were manufactured to produce antibodies for use in medicines.
By the end of 1995, mutant genes responsible for common diseases, including forms of schizophrenia, Alzheimer’s disease, breast cancer, and prostate cancer, were mapped, and experimental treatments were developed for either replacing the defective genes with working copies or adding genes that allow the cells to fight the disease. During the sequencing of the human genome, genes were identified for cystic fibrosis, neurofibromatosis, Huntington’s disease, and breast cancer. In February, 1997, a lamb named Dolly was cloned from the DNA of an adult sheep’s mammary gland cell; it was the first time scientists...
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Further Reading (Genetics & Inherited Conditions)
Abeloff, Martin D., et al., eds. Abeloff’s Clinical Oncology. 4th ed. Philadelphia: Churchill Livingstone/Elsevier, 2008. This textbook introduces oncology and the role of molecular biology in preventive strategies.
Fredrickson, Donald S. The Recombinant DNA Controversy, a Memoir: Science, Politics, and the Public Interest, 1974-1981. Washington, D.C.: ASM Press, 2001. An overview of the initial concerns about potential hazards of recombinant DNA cloning.
Grace, Eric S. Biotechnology Unzipped: Promises and Reality. Washington, D.C.: National Academy Press, 1997. Provides a nontechnical history and explanation of biotechnology for general readers.
Judson, Horace Freeland. The Eighth Day of Creation. Rev. ed. Cold Harbor Spring, N.Y.: Cold Spring Harbor Laboratory Press, 1997. A noted and fascinating history of molecular biology that details the deciphering of the genetic code.
Lengauer, Thomas, ed. Bioinformatics: From Genomes to Therapies. 3 vols. Weinheim, Germany: Wiley-VCH, 2007. Intensive introduction to genetic and molecular theory and applications in medical testing, therapies, and bioinformatics systems.
Maas, Werner. Gene Action: A Historical Account. New York: Oxford University Press. 2001. This account explains the realization of how genes work, within three distinct periods of discovery and experiment.
Portugal, Franklin H.,...
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Web Sites of Interest (Genetics & Inherited Conditions)
Genome News Network. http://www.genomenewsnetwork.org/resources/timeline. A catalog of all sequenced organisms.
Human Genome Project Information. http://www.ornl.gov/hgmis/home.shtml. Provides a history of genome research and highlights of current applications.
National Health Museum, Biotech Chronicles. http://www.accessexcellence.org/ab/bc. Discusses the history of biotechnology and includes a time line, from 6000 b.c.e. to the present, with key figures and links.
National Human Genome Research Institute. http://www.genome.gov. Provides a catalog of published genome-wide association studies.
New Scientist. http://www.newscientist.com. Bulletin providing timely information on current topics in the life sciences.
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