Medical Bioremediation
Medical bioremediation is the technique of utilizing microbial xenoenzymes for human therapy. The process involves screening for enzymes capable of catabolizing the target pathogenic substrate, engineering microbes to express sufficient quantities of the enzyme and finally delivering the enzyme to the appropriate tissue and cell types.
Introduction
Bioremediation is the technique of using organisms to catabolize toxic waste such as oil spills or industrial runoff. The most commonly used organisms are microbes, though phytoremediation is also used. 1 Wild-type microbes have proven capable of digesting highly toxic and stable compounds, but organisms can be genetically engineered to augment their ability. For example, Deinococcus radiodurans, the most radio-resistant organism known, has been modified to digest toluene and ionic mercury. 2
Microbes are the source of approximately 22,500 bioactive drug compounds. Of these, 17% were from unicellular bacteria (mainly Pseudomonas and Bacillus), 45% from filamentous bacteria (actinomycetes) and 38% from fungi. 3 Microbes are the predominant source of manufactured protein, ever since microbial human insulin production began 25 years ago. There are presently more than 130 protein therapeutics used worldwide and many more undergoing clinical trials. 4
Organic, energy-rich molecules introduced to the environment are potential microbial nutrients. The “microbial infallibility hypothesis,” coined by Ernest Gayle in 1952, 5 states that the buildup of compounds initially resistant to biodegradation exerts a strong selective pressure on nearby microbes to evolve to consume them.
Strategies for Engineered Negligible Senescence (SENS)
In 2002, Cambridge biogerontologist Aubrey de Grey theorized that the principles of bioremediation and Gayle’s hypothesis could be applied to human pathology as a part of his seven-part longevity protocol, Strategies for Engineered Negligible Senescence (SENS): 6
1. Cell loss or atrophy (without replacement) 7
2. Oncogenic nuclear mutations and epimutations 8
3. Cell senescence (death-resistant cells) 9
4. Mitochondrial mutations 10
5. Intracellular junk (particularly lysosomal aggregates) 11
6. Extracellular aggregates 9
7. Random extracellular cross-linking (Advanced glycation end products) 12
Medical bioremediation is applicable to protocols five, six and seven, termed “LysoSENS,” “AmyloSENS” and “GlycoSENS.” The SENS Foundation is funding research in these areas at their headquarters in Mountain View, California and externally, led by researchers such as David Spiegel at Yale, Chris Lowe at Cambridge, Sudhir Paul at the University of Texas-Houston Medical School, Brian O’Nuallain at Harvard, John Schloendorn at Arizona State University and Jacques Mathieu at Rice University.
Recognizing that bone is all that remains of the deceased in graveyards, de Grey made it obvious that there must be soil microbes capable of catabolizing all of the organic compounds comprising the human body. Certain such compounds are pathogenic, including amyloids, neurofibriliary tangles, cholesterol, lipofuscin, huntingtin, alpha-synuclein and many others. The rapid selective pressure on microbes in the presence of these pathogenic compounds as food sources may yield therapeutic new enzymes. De Grey coined the term “medical bioremediation” to describe this emerging therapy.
At right is a sample image insertion. It works for any image uploaded anywhere to MicrobeWiki. The insertion code consists of:
Double brackets: [[
Filename: PHIL_1181_lores.jpg
Thumbnail status: |thumb|
Pixel size: |300px|
Placement on page: |right|
Legend/credit: Electron micrograph of the Ebola Zaire virus. This was the first photo ever taken of the virus, on 10/13/1976. By Dr. F.A. Murphy, now at U.C. Davis, then at the CDC.
Closed double brackets: ]]
Other examples:
Bold
Italic
Subscript: H2O
Superscript: Fe3+
Section 1
Include some current research in each topic, with at least one figure showing data.
Section 2
Include some current research in each topic, with at least one figure showing data.
Section 3
Include some current research in each topic, with at least one figure showing data.
Conclusion
Overall paper length should be 3,000 words, with at least 3 figures.
References
[Sample reference]
1. Vidali, M. (2001) Bioremediation: An Overview. Pure Appl. Chem. 73 (7): 1163–1172.
2. Brim H. et al. 2000). Engineering Deinococcus radiodurans for metal remediation in radioactive mixed waste environments. Nature Biotechnology. 18 (1): 85–90.
3. Demain, A.L. (2009) Antibiotics: natural products essential for human health. Med. Res. Rev. 29: 821–841
4. Leader, B. et al. (2008) Protein therapeutics: a summary and pharmacological classification. Nat. Rev. Drug Discov. 7(1): 21–39
5. Gayle, E.F. (1952). The Chemical Activities of Bacteria. New York, Academic Press.
6. de Grey, A. et al. (2005) Medical bioremediation: Prospects for the application of microbial catabolic diversity to aging and several major age-related diseases. Ageing Res Rev. 4(3):315-38.
7. de Grey, A. (2005). A strategy for postponing aging indefinitely. Stud Health Technol Inform. 118: 209–19.
8. de Grey, A. et al. (2004). Total deletion of in vivo telomere elongation capacity: an ambitious but possibly ultimate cure for all age-related human cancers. Ann N Y Acad Sci. 1019: 147–70.
9. de Grey, A. (2006). Foreseeable pharmaceutical repair of age-related extracellular damage. Curr Drug Targets. 7 (11): 1469–77.
10. de Grey, A. (2004). Mitochondrial Mutations in Mammalian Aging: An Over-Hasty About-Turn? Rejuvenation Res. 7 (3): 171–4.
11. de Grey, A. (2002). Bioremediation meets biomedicine: therapeutic translation of microbial catabolism to the lysosome. Trends Biotechnol. 20, 452–455.
12. Furber, J.D. (2006). Extracellular glycation crosslinks: Prospects for removal. Rejuvenation Res. 9 (2): 274–278.
Edited by (your name here), a student of Nora Sullivan in BIOL187S (Microbial Life) in The Keck Science Department of the Claremont Colleges Spring 2013.
