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Nanobacterium

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Structures found on meteorite fragment ALH84001

Nanobacteria is the name of a possible class of living organisms; specifically cell-walled microorganisms with a size much smaller than the generally accepted lower limits for life, about 200 nanometres for bacteria. 200 nm happens to be the size of the smallest object which could be resolved in a standard light microscope. In 1996, the size was supposedly derived from the smallest volume required by known organisms, where nanobacteria were unknown.

Reports of them being living organisms are controversial.[1] If they are living, there is speculation that they may be a newly discovered form of life, rather than bacteria[2] and may be capable of synthetizing a matrix or biofilm. The term calcifying nanoparticles (CNPs) has also been used, side-stepping the question of their formal status as a life form. Although nanobes are sometimes associated with nanobacteria and sometimes mistakenly synonymized with nanobacteria, it is not known whether they are really related, although their morphology is quite different.

1981-1992 discoveries

In 1981 Torella and Morita described very small cells called ultramicrobacteria. Defined as being smaller than 300 nm, by 1982 MacDonell and Hood found that some could pass through a 200 nm membrane. Early in 1989, geologist Robert L. Folk found what he later identified as nannobacteria (written with two "n"s instead of one), that is, nanoparticles isolated from geological specimens[3] in travertine from hot springs of Viterbo, Italy. Initially searching for a bacterial cause for travertine deposition, scanning electron microscope examination of the mineral where no bacteria were detectable revealed extremely small objects which appeared to be biological. His first oral presentation "elicited mostly a stony silence", at the 1992 Geological Society of America's annual convention.[1] He proposed that nanobacteria are the principal agents of precipitation of all mineral and crystals on Earth formed in liquid water, they also cause all oxidation of metals, and are abundant in many biological specimens.

1996 Martian meteorite claims

Structures in the Martian meteorite ALH84001 have been interpreted by some as fossilized nanobacteria, but the origin of the structures is disputed.

1998–2000 claims

Nanobacterium sanguineum was proposed in 1998 as an explanation of certain kinds of pathologic calcification (apatite in kidney stones) by Finnish researcher Olavi Kajander and Turkish researcher Neva Ciftcioglu, working at the University of Kuopio in Finland. According to the researchers the particles self-replicated in microbiological culture, and the researchers further reported having identified DNA in these structures by staining.[4]

A paper published in 2000 by a team led by a dentist John Cisar USNIH stated that the "self-replication" was, in fact, an unusual form of crystalline growth, and that the only DNA detected in these cultures was contamination from environmental bacteria.[5] However, the Cisar group did not as part of their study examine nanobacteria samples from the Kajander group, therefore critics stated that without such a control sample the phenomenon studied by Cisar et al. may differ from that seen by the Kajander group.

Drs. Olavi Kajander & Neva Ciftcioglu set up a company in Finland in 2000 "Nanobac Oy" later absorbed in 2003 by a publicly traded Nanobacteria research company in Tampa, Florida founded by Nanobiotic developer Gary Mezo, 'Nanobac Pharmaceuticals, Inc.', to market medical diagnostic kits for identifying nanobacteria to medical researchers, and are developing prescription medical treatments for calcification-associated diseases. This has raised doubts concerning their impartiality.

April 2004 claims

In a press release, Nanobac Pharmaceuticals, Inc. reports that a strong correlation has been found between antibodies to nanobacteria and coronary artery calcification (associated with increased risk of coronary artery disease). The results were obtained using a testing kit produced by Nanobac. Tests on 198 patients were led by top Endovascular Researcher & Cardiovascular Researcher Stephen Epstein, MD, PhD, FACC, Director of the Cardiovascular Research Institute, Washington Hospital Center, Washington, D.C.

May 2004 claims

In 2004 a Mayo Clinic team led by infectious disease expert, Franklin Cockerill, MD, PhD, John Lieske, MD, and Virginia M. Miller, PhD. at the Mayo Clinic in Minnesota reports to have isolated nanobacteria in diseased human arteries and kidney stones. Their results were accepted and published in 2004 and 2006 respectively.[6][7] These findings were confirmed in 2005 by László Puskás, PhD at the DNA Lab, University of Szeged, Hungary. Dr. Puskás identified these particles in cultures obtained from human atherosclerotic aortic walls and blood samples of atherosclerotic patients but the group was unable to detect DNA in these samples.[8] For historical interest it has to be noted that the content of the referred paper was originally submitted to Nature as "Letter to Editor" for fast publication several years earlier. It was rejected after almost four months of peer-review process on the basis of the lack of detection of any kind of genetic material.

Unlike the Finnish nanobacteria researchers (discoverers), those at the Mayo Clinic apparently have no linked commercial interests. Working with particles less than 200 nanometres in size, they found indirect evidence that the particles had self-replicated, and found that they had a cell-like appearance under an electron microscope. They also believe that the particles are producing RNA, since they incorporated one of its building blocks, uridine, in greater quantities than would be expected in the case of pure absorption (by crystals such as apatite). Using an antibody produced by the Finnish researchers, the particles were found to bind to diseased arterial tissue, and to the same sites to which a DNA stain bound. The researchers now plan to isolate RNA and DNA from the nanobacteria.

February 2005 NASA Results

Nanobac Pharmaceuticals' researcher, Neva Ciftcioglu, PhD and her Nanobacteria research team at NASA announced the results of an experiment in which a bioreactor chamber that simulates conditions of space travel was used to culture nanobacteria suspected of rapidly forming kidney stones in astronauts. In this microgravity environment, they were found to multiply five times faster than in normal Earth gravity. The study concluded that nanobacteria may need to be screened for in crews pre-flight.[9]

November 2006 Video Footage

Nanobac Pharmaceuticals released the first ever live video footage of calcifying particles on November 2, 2006 in Tampa, Florida using a new high definition Nikon microscope. In addition, the video showed a decalcifying agent dissolving calcified structures and inorganic crystals. Before the recent release of the new technology from Aetos Technologies which allows real-time tracking of calcifying nanoparticles (CNPs), observing live processes was impossible.[10]

"Although preliminary, this is a significant scientific and medical finding," stated Dr. Arnold Mandell, a professor emeritus at UCSD School of Medicine, research professor at the Emory University School of Medicine and a MacArthur Prize Fellow in the medical sciences.

"While these are early findings, we believe they merit serious investigation," explained Nanobac Co-chairman Dr. Benedict Maniscalco.

2008 articles

The February 2008 PLoS PATHOGENS article focused on the comprehensive characterization of nanobacteria. The results of the article ruled out the existence of nanobacteria as living entities. However, the study revealed that they are a unique self-propagating entity similar to prions - corresponding to self-propagating mineral-fetuin complexes.[11]

The April 2008 PNAS article suggests that reported blood nanobacteria do not exist in terms of the classical requirements for bacterial status and reports: "CaCO3 precipitates prepared in vitro are remarkably similar to purported nanobacteria in terms of their uniformly sized, membrane-delineated vesicular shapes, with cellular division-like formations and aggregations in the form of colonies."[12] Researchers at a workshop hosted by the National Academy of Sciences for this specific reason concluded that the minimal cellular size of life on Earth must exceed 200 nm in diameter in order to contain the cellular machinery based on DNA replication. But nanobacteria can be as small as 80 nm so, unless they contain some novel replicating mechanism, it seems unlikely that they constitute a form of life.[13]

See also

References

  1. ^ Kajander E (2006). "Nanobacteria--propagating calcifying nanoparticles". Lett Appl Microbiol. 42 (6): 549–52. PMID 16706890.
  2. ^ Ciftcioglu N, McKay D, Mathew G, Kajander E (2006). "Nanobacteria: fact or fiction? Characteristics, detection, and medical importance of novel self-replicating, calcifying nanoparticles". J Investig Med. 54 (7): 385–94. doi:10.2310/6650.2006.06018. PMID 17169260.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ A convention has been adopted between researchers to name -or spell- the nanoparticles isolated from geological specimens as nannobacteria , and those from biological specimens: nanobacteria.
  4. ^ Kajander E, Ciftçioglu N (1998). "Nanobacteria: an alternative mechanism for pathogenic intra- and extracellular calcification and stone formation". Proc Natl Acad Sci U S A. 95 (14): 8274–9. doi:10.1073/pnas.95.14.8274. PMID 9653177.
  5. ^ Cisar J, Xu D, Thompson J, Swaim W, Hu L, Kopecko D (2000). "An alternative interpretation of nanobacteria-induced biomineralization". Proc Natl Acad Sci U S A. 97 (21): 11511–5. doi:10.1073/pnas.97.21.11511. PMID 11027350.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Miller V, Rodgers G, Charlesworth J, Kirkland B, Severson S, Rasmussen T, Yagubyan M, Rodgers J, Cockerill F, Folk R, Rzewuska-Lech E, Kumar V, Farell-Baril G, Lieske J (2004). "Evidence of nanobacterial-like structures in calcified human arteries and cardiac valves". Am J Physiol Heart Circ Physiol. 287 (3): H1115-24. doi:10.1152/ajpheart.00075.2004. PMID 15142839.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Kumar V, Farell G, Yu S, Harrington S, Fitzpatrick L, Rzewuska E, Miller VM, Lieske JC. (2006). "Cell biology of pathologic renal calcification: contribution of crystal transcytosis, cell-mediated calcification, and nanoparticles". Journal of Invstigative Medicine. 54 (7): 412–424. PMID 17169263.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Puskás L, Tiszlavicz L, Rázga Z, Torday L, Krenács T, Papp J (2005). "Detection of nanobacteria-like particles in human atherosclerotic plaques". Acta Biol Hung. 56 (3–4): 233–45. doi:10.1556/ABiol.56.2005.3-4.7. PMID 16196199.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Ciftçioglu N, Haddad R, Golden D, Morrison D, McKay D (2005). "A potential cause for kidney stone formation during space flights: enhanced growth of nanobacteria in microgravity". Kidney Int. 67 (2): 483–91. doi:10.1111/j.1523-1755.2005.67105.x. PMID 15673296.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ "First Live Video of Calcifying Nanoparticles Provides Possible Key to Chronic Disease Condition" (Press release). November 2 2006. {{cite press release}}: Check date values in: |date= (help)
  11. ^ PLoS Pathogen article
  12. ^ Purported nanobacteria in human blood as calcium carbonate nanoparticles
  13. ^ PNAS article review


Additional reading