Environmental impact of genetically altered bacteria

DEFINITION: Bacteria that humans have manipulated at the genetic level to possess specific properties or carry out certain functions

The genetic modification of bacteria has made possible the manufacture of medically important human proteins such as insulin and growth hormone. Genetically altered bacteria have also been used as a means to introduce into plants genetic material that increases their resistance to disease, pests, or freezing.

The ability to alter genetically is the outcome of several independent discoveries. In 1944, Oswald Avery and his coworkers demonstrated gene transfer among bacteria using purified deoxyribonucleic acid (DNA), a process called transformation. In the 1960s, the discovery of restriction enzymes permitted the creation of hybrid molecules of DNA. Such enzymes cut DNA molecules at specific sites, allowing fragments from different sources to be joined within the same piece of genetic machinery. Restriction enzymes are not species-specific in choosing their targets. Therefore, DNA from any source, when treated with the same restriction enzyme, will generate identical cuts. The treated DNA molecules are allowed to bind with each other, while a second set of enzymes called ligases are used to fuse the hybrids. The recombinant molecules may then be introduced into bacteria cells through transformation. In this manner, the cell acquires whatever genetic information is found in the DNA. Descendants of the transformed cells will be genetically identical, forming clones of the original.

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The most common forms of genetically altered DNA are bacterial plasmids, small circular molecules separate from the cell chromosome. Plasmids may be altered to serve as appropriate vectors for genetic engineering, usually containing an gene for selection of only those cells that have incorporated the DNA. Once the cell has incorporated the plasmid, it acquires the ability to produce any gene product encoded on the molecule. The resulting artificially produced DNA is called recombinant DNA. The first bacterium to be genetically altered through recombinant DNA technology for medical purposes, Escherichia coli, contained the gene for the production of human insulin. Prior to creation of the insulin-producing bacterium in the 1970s, diabetics were dependent on insulin purified from animals. In addition to being relatively expensive, insulin obtained from animals produced allergic reactions among some diabetes patients. Insulin obtained from genetically altered bacteria, by contrast, is identical to human insulin. Subsequent recombinant DNA research has led to the manufacture of a variety of human proteins, including human growth hormone, parathyroid hormone, several kinds of interferons, many monoclonal antibodies, hepatitis B surface antigen, clotting factors, and granulocyte colony-stimulating factor.

Genetically altered bacteria may also serve as vectors for the introduction of genes into plants. The bacterium Agrobacterium tumefaciens, the etiological agent for a plant disease called crown gall, contains a known as Ti. Following infection of the plant cell by the bacterium, the plasmid is integrated into the host chromosome, becoming part of the plant’s genetic material. Any genes that were part of the plasmid are integrated as well. Desired genes can be introduced into the plasmid, promoting or disease resistance within plants infected by the bacterium.

In April 1987, scientists in California sprayed strawberry plants with genetically altered bacteria to improve the plants’ freeze resistance; this event marked the first deliberate of genetically altered organisms in the United States to be sanctioned by the Environmental Protection Agency (EPA). The release of the bacteria represented the climax of more than a decade of public debate over what would happen when the first products of became commercially available. Fears centered on the creation of bacteria that might radically alter the through elaboration of gene products not normally found in such cells. Other concerns included the creation of super bacteria with unusual resistance to conventional medical treatment.

Despite these fears, approval for further releases of genetically altered bacteria soon followed, and the restrictions on release were greatly relaxed. By 1991, permits for field tests of more than 180 genetically altered plants and microorganisms had been granted. Between 1987 and 2004, more than 10,000 trials were conducted at more than 39,000 sites, and more than sixty biotechnology products entered the market. Included among clinical trials underway in 2023 was the use of a modified Streptococcus mutans in fighting dental cavities. Scientists have modified this bacterium, responsible for tooth decay in its unaltered form, so that it does not produce the lactic acid that ordinarily erodes tooth enamel. In animal tests, it has been found that the modified bacterium eventually replaces the S. mutans naturally occurring in the mouth. The US Food and Drug Administration began issuing approvals for genetically altered bacterial products in 2022, approving several treatments for diseases in the gastrointestinal system, a place already rife with microbiota. The FDA also issued approvals for vaccines targeting cholera and typhoid fever. Several clinical trials were underway in 2023 testing whether genetically altered bacteria could help combat diseases from diabetes to cancer.    

In general, “red biotechnology” (the application of biotechnology in medicine) tends to generate less controversy than “green biotechnology” (use of biotechnology in food production). In the United States, anyone intending to produce or import genetically altered microorganisms for commercial purposes must submit a notice to the EPA, which assesses whether the constitutes an unreasonable to human health or the environment.

Bibliography

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Food and Agriculture Organization and World Health Organization. Safety Assessment of Foods Derived from Genetically Modified Microorganisms. Geneva: World Health Organization, 2001.

Gulig, Paul, Scott Swindle, Mark Fields, and Daniel Eisenman. "A Review of Clinical Trials Involving Genetically Modified Bacteria, Bacteriophages and Their Associated Risk Assessments." Applied Biosafety, 8 May 2024, doi.org/10.1089/apb.2024.0002. Accessed 19 July 2024.

Han, Lei. “Genetically Modified Microorganisms: Development and Applications.” In The GMO Handbook: Genetically Modified Animals, Microbes, and Plants in Biotechnology, edited by Sarad R. Parekh. Totowa, N.J.: Humana Press, 2004.

Iacopetta, Domenico, et al. “Diarylureas: New Promising Small Molecules Against Streptococcus Mutans for the Treatment of Dental Caries.” Antibiotics, vol. 12, no. 1, Jan. 2023, p. 112., doi.org/10.3390/antibiotics12010112. Accessed 19 July 2024.

Stemke, Douglas J. “Genetically Modified Organisms: Biosafety and Ethical Issues.” In The GMO Handbook: Genetically Modified Animals, Microbes, and Plants in Biotechnology, edited by Sarad R. Parekh. Totowa, N.J.: Humana Press, 2004.

Watson, James D., et al. Recombinant DNA: Genes and Genomes—A Short Course. 3d ed. New York: W. H. Freeman, 2007.