This is the sixth of 6 guest posts on infection and chronic disease.
By Courtney Cook
Kidney stone disease affects approximately 5% of Americans. While several risk factors are well-established, including genetic predisposition, metabolic diseases, lifestyle, and diet, there are still questions over the actual mechanism of calcium stone formation. Many cases do not have any kind of underlying disorder and therefore it is difficult to know how to treat these patients to prevent further stone formation.
This seemed to change when, in 1998, Kajandar and Ciftcioglu isolated an unusual microorganism in human kidney stones. Less than 100 nm across, the authors termed them "nanobacteria." They claimed to observe self-replication as well as to have identified a unique DNA sequence. This seemed to indicate a living entity that may be playing a role in stone formation. Are they?
(More after the jump...)
Nanobacteria have been found within mineralized "igloos" of apatite, a calcium-rich mineral. These structures were thought to possibly play a role in calcification in the kidney, as well as other structures within the body. Nanobacteria have been reported to be present in several pathological calcifications, including atherosclerosis, osteoarthritis, prostate stones, periodontal disease, as well as bodies in ovarian and mammary cancers. The actual mechanism of apatite formation by nanobacteria is unknown
Kajandar and Ciftcioglu have since taken the lead on nanobacteria research. They have further characterized nanobacteria as Gram-negative, ranging in size from 80-500 nm, and observable through transmission electron microscopy. They have also claimed to observe nanobacteria forming small colonies surrounded by their thick apatite coat under low nutrient and other extreme conditions. For example, a study based on increase in kidney stone formation in astronauts during and after long duration zero-gravity missions looked at growth of nanobacteria in microgravity, where it was determined that nanobacteria in simulated microgravity conditions had a significantly higher multiplication rate when compared to those in stationary or shaken culture conditions.
Specifically regarding kidney stone disease, results from several studies (most of which include Kajandar and/or Ciftcioglu as authors) suggest that nanobacteria may be associated with stone formation. An apparent dose-response relationship was observed when inoculating rats with nanobacteria - but that study was done with a sample size of four, bringing into question the power of such an experiment and whether any observations made would truly be significant.
Naturally, there is a great deal of controversy surrounding these ideas. Many question whether nanobacteria are even living in the first place. A study by Cisar et al directly brought Kajandar and Ciftcioglu's original results into question, suggesting that the DNA they found was actually a contaminant from a regular bacterium and there were no unique nucleic acids within the sequence. We would expect to see a unique DNA sequence if it was the DNA of nanobacteria being detected.
Contradictions also seem to arise when looking at methods used to detect the nanobacteria. Kajandar and Ciftcioglu use their own patented methods for culture of nanobacteria, but "traditional" microbiological method have failed to detect or culture nanobacteria. They have since turned these methods into financial gain, with the establishment of Nanobac Life Sciences, a company that develops and sells diagnostic kits for finding nanobacteria, as well as treatments for conditions that nanobacteria supposedly cause. This lucrative arrangement brings into question the true motives of the pair.
Right now it is really too soon to tell whether nanobacteria are causative agents for kidney stones and other conditions. Before identifying them as a cause, we first need to settle the debate surrounding their existence. With the lack of substantial evidence from multiple sources in either direction, more research is needed to try to determine the truth behind these mysterious entities.
Courtney Cook is a first year M.S. student in epidemiology, and currently holds a B.A. in mathematics. Her research interests involve infectious disease epidemiology, particularly in children. She hopes to apply these interests toward her ultimate career goal of practicing medicine, specializing in pediatrics.
Ciftcioglu N, Bjorklund M, Kuorikoski K, Bergstrom K, Kajandar EO. (1999). Nanobacteria: an infectious cause for kidney stone formation. Kidney International 56: 1893-1898. Link.
Ciftcioglu N, Haddad RS, Golden DC, Morrison DR, McKay DS. (2005). A potential cause for kidney stone formation during space flights: enhanced growth of nanobacteria in microgravity. Kidney International 67: 483-491. Link.
Hogan, J. (2004). Nanobacteria revelations provoke new controversy. New Scientist. Link.
Kajandar EO, Ciftcioglu N, Miller-Hjelle MA, Hjielle JT. (2001). Nanobacteria: controversial pathogens in nephrolithiasis and polycystic kidney disease. Current Opinion in Nephrology and Hypertension 10: 445-452. Link.
Kajandar EO, Ciftcioglu N, Aho K, Garcia-Cuerpo E. (2003). Characteristics of nanobacteria and their possible role in stone formation. Urol Res 31: 47-54. Link.
Urbano P, Urbano F. (2007). Nanobacteria: facts or fancies?. PLoS Pathog 3(5): 567-570. Link.
They have since turned these methods into financial gain, with the establishment of Nanobac Life Sciences, a company that develops and sells diagnostic kits for finding nanobacteria, as well as treatments for conditions that nanobacteria supposedly cause.
Looking at Nanobac's website, they seem to be very close to the edge of promoting an unapproved drug. For example, this page claims their Cal-DETOX system "Helps Clear The Body Of Excessive Calcium Crystals In The Heart, Prostate, Kidney, Joints, And Other Areas." It qualifies this with the standard FDA disclaimer for supplements: "These statements have not been evaluated by the Food and Drug Adminstration. This product is not intended to diagnose, treat, cure, or prevent any disease."
But further down the page, they ask "Who needs Cal-DETOX?" followed by a bulleted list containing many diseases, including Alzheimer's, arthritis, cancer, diabetes, etc. They don't specifically SAY that Cal-DETOX is supposed to do anything for these diseases, or even that these patients should take it. But it's very strongly implied.
I think if FDA reviewed this stuff, they'd conclude it violated federal drug laws. However, from Nanobac's 2007 annual report, it appears they don't actually sell this "supplement" any more anyway.
Nevertheless, a pretty shady looking outfit, IMO.
Nanobacteria or maybe "Nanobacteria-like particles" were on the cover of PNAS last week:
Purported nanobacteria in human blood as calcium carbonate nanoparticles
Jan Martel, and John Ding-E Young
PNAS | April 8, 2008 | vol. 105 | no. 14 | 5549-5554
These guys present a case that these are abiotic particles of calcium carbonate whose apparent growth and division are influenced by incubation conditions of the serum they are grown in and that the Nanobac antibodies are specific for binding human serum albumin. The lack of an apparent effect of huge doses of radioactivity also seems to indicate that if these are actual living organisms they are way different than anything else alive today, but is no big shakes if they are just CaCO3 particles.
The nanobacteria story has been interesting to follow over the last few years and would be really cool if real, but it's been getting harder and harder to buy, even aside from the fact that the small size is incompatible with known biosynthetic size requirements for transcription, translation and replication.
If it looks like woo, walks like woo, and quacks like woo, then it's probably woo!
Fascinating subject that I heretofore knew nothing about. Nice post.
Thanks for the succinct overview. I have to say I am irresistibly reminded of cold fusion.
I have been following this story for a long time. From excitement about the first PNAS paper describing them (http://www.pnas.org/cgi/content/full/95/14/8274), to disappointment about the continued lack of confirmatory evidence from other labs(how about a genome sequence) and the founding of a company that sells expensive, nonFDA approved "supplements" to treat them.
At first, I was worried that you would present only Kajandar's and Ciftcioglu's interpretation of their data that these objects are living organisms.I was happy to see that you told the larger story and remained appropriately skeptical.
More microscopic bullshit. On par with prions, another bogus entity that garnered a Nobel Prize for Stanley Prusiner, even though they likely don't even exist.
These people really, really, have no shame. They look through electron microscopes, see stuff that appears new to them, but have no idea how to interpret what they are seeing, nor the significance.
Nano-bacteria, my arse! Pure quackery.
Looks like there's more against nanobacteria:
From Nature news:
Nanobacteria theory takes a hit - They look like tiny bacteria, have been implicated in several diseases and have even been hailed as a completely overlooked branch of the tree of life. But are 'nanobacteria' genuinely alive? New research suggests that the answer is probably no. Read On
You think Prions are Bullshit? I think CJD and BSE are pretty well documented and characterized diseases...
Hi Michael who are
Appears me every body here says nanobac is bogus.
Brian said "You think Prions are Bullshit? I think CJD and BSE are pretty well documented and characterized diseases..."
No, no, no Brian - they are not. Are they chaperone molecules gone bad? Or is nothing more than the wrong metal ions in particular circumstances sufficient to cause protein misfolding? Open your mind Brian.
Prions and nanobacteria...going where no man has gone before....
Makes me think about the pictures of planets taken by the space probes (which I love to see). I don't know how they figure out what chemicals make up the atmosphere on Venus or Saturn, but I definitely do not want to visit there!
Note on another Tara blog entry-Politicians have to straddle some mighty high fences with the vaccine/autism thing, sounds to me like they are 'riding the rail' very well this year!
Is there a possibility of Nanobacteria or other unknown organisms. Yes. Could it be bacteria that are causing the stones. Maybe. If you look back at how medicine was started and the belief systems they had, you would see there is still plenty to learn. Blood letting, taking a pic and ramming up your nose and scrambling your brain, Vioxx( side effect kills you), and many more.
Honestly, I am still surprised we are still alive despite the medications that people take, antibiotics, eating genetically modified food that produces herbicides and pesticides, additives, preservatives, food coloring, etc. Any wonder why America is one of the lowest ranking in all industrialized nations as far as health is concerned?