Genetically modified bacteria

Genetically modified bacteria were the first organisms to be modified in the laboratory, due to their simple genetics.^[1] These organisms are now used for several purposes, and are particularly important in producing large amounts of pure human proteins for use in medicine.^[2]

History

The first example of this occurred in 1978 when Herbert Boyer, working at a University of California laboratory, took a version of the human insulin gene and inserted into the bacterium Escherichia coli to produce synthetic "human" insulin. Four years later, it was approved by the U.S. Food and Drug Administration.

Pharmaceutical production

• The drug industry has made use of this discovery to produce medication for diabetes.^[3] Similar bacteria have been used to produce clotting factors to treat haemophilia,^[4] and human growth hormone to treat various forms of dwarfism.^[5][6] These recombinant proteins are safer than the products they replaced. Prior to recombinant protein products, several treatments were derived from cadavers or other donated body fluids and could transmit diseases.^[7] Indeed, transfusion of blood products had previously led to unintentional infection of haemophiliacs with HIV or hepatitis C; similarly, treatment with human growth hormone derived from cadaver pituitary glands may have led to outbreaks of Creutzfeldt–Jakob disease.^[7][8]*

Other uses

Genetically modified bacteria can serve various purposes beyond producing medicinal compounds. For instance, bacteria which generally cause tooth decay have been engineered to no longer produce tooth-corroding lactic acid.^[9] These transgenic bacteria, if allowed to colonize a person's mouth, could perhaps reduce the formation of cavities.^[10] Transgenic microbes have also been used in recent research to kill or hinder tumors, and to fight Crohn's disease.^[11] Genetically modified bacteria are also used in some soils to facilitate crop growth, and can also produce chemicals toxic to crop pests.

GM bacteria have also been developed to leach copper from ore,^[12] clean up mercury pollution^[13] and detect arsenic in drinking water.^[14]

Bacteria-synthesized transgenic products

• Insulin
• Hepatitis B vaccine
• Tissue plasminogen activator
• Human growth hormone
• Ice-minus bacteria
• Interferon
• Bt corn

References

1. Melo, Eduardo O.; Canavessi, Aurea M. O.; Franco, Mauricio M.; Rumpf, Rodolpho (2007). "Animal transgenesis: state of the art and applications". J. Appl. Genet. 48 (1): 47–61. doi:10.1007/BF03194657. PMID 17272861. Archived from the original (PDF) on 26 September 2009.
2. Leader, Benjamin; Baca, Qentin J.; Golan, David E. (January 2008). "Protein therapeutics: a summary and pharmacological classification". Nat Rev Drug Discov. A guide to drug discovery. 7 (1): 21–39. doi:10.1038/nrd2399. PMID 18097458.
   Leader 2008 — Fee required for access to full text.
3. Walsh, Gary (April 2005). "Therapeutic insulins and their large-scale manufacture". Appl. Microbiol. Biotechnol. 67 (2): 151–159. doi:10.1007/s00253-004-1809-x. PMID 15580495.
   Walsh 2005 — Fee required for access to full text.
4. Pipe, Steven W. (May 2008). "Recombinant clotting factors". Thromb. Haemost. 99 (5): 840–850. doi:10.1160/TH07-10-0593. PMID 18449413.
5. Bryant, Jackie; Baxter, Louise; Cave, Carolyn B.; Milne, Ruairidh (2007). "Recombinant growth hormone for idiopathic short stature in children and adolescents". Cochrane Database Syst Rev (3): CD004440. doi:10.1002/14651858.CD004440.pub2. PMID 17636758.
   Bryant 2007 — Fee required for access to full text.
6. Baxter L, Bryant J, Cave CB, Milne R (2007). "Recombinant growth hormone for children and adolescents with Turner syndrome". Cochrane Database Syst Rev (1): CD003887. doi:10.1002/14651858.CD003887.pub2. PMID 17253498.
7. Foster PR (October 2000). "Prions and blood products". Ann. Med. 32 (7): 501–13. doi:10.3109/07853890009002026. PMID 11087171.
8. Key NS, Negrier C (August 2007). "Coagulation factor concentrates: past, present, and future". Lancet. 370 (9585): 439–48. doi:10.1016/S0140-6736(07)61199-4. PMID 17679021.
9. Hillman JD (August 2002). "Genetically modified Streptococcus mutans for the prevention of dental caries". Antonie Van Leeuwenhoek. 82 (1-4): 361–6. doi:10.1023/A:1020695902160. PMID 12369203.
10. Hillman JD, Mo J, McDonell E, Cvitkovitch D, Hillman CH (May 2007). "Modification of an effector strain for replacement therapy of dental caries to enable clinical safety trials". J. Appl. Microbiol. 102 (5): 1209–19. doi:10.1111/j.1365-2672.2007.03316.x. PMID 17448156.
11. Braat, H (June 2006). "A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease". Clinical Gastroenterology and Hepatology. 4: 754–9. doi:10.1016/j.cgh.2006.03.028. PMID 16716759.
12. Valda, Daniela and Dowling, Julian (10 December 2010) Making Microbes Better Miners Business Chile Magazine, Accessed 21 march 2012
13. Ruiz, O. N.; Alvarez, D.; Gonzalez-Ruiz, G.; Torres, C. (2011). "Characterization of mercury bioremediation by transgenic bacteria expressing metallothionein and polyphosphate kinase". BMC Biotechnology. 11: 82. doi:10.1186/1472-6750-11-82. PMC 3180271. PMID 21838857.
14. Sanderson, Katherine (24 February 2012) New Portable Kit Detects Arsenic In Wells Chemical and Engineering News, Retrieved 23 January 2013

Further reading

• Karl Drlica. Understanding DNA and Gene Cloning: A Guide for the Curious (4th ed.). ISBN 978-0-471-43416-0.