How small are the smallest living organisms? There seem to be many types of bacteria of 300 nm and upwards in diameter, but to many microbiologists it seems a rule of thumb that if something can get through a 0.2 µm filter (200 nm) it isn’t alive. Thus the discovery of so-called “nanobacteria”, with sizes between 50 nm and 200 nm, in the human blood-stream, and their putative association with a growing number of pathological conditions such as kidney stones and coronary artery disease, has been controversial. Finnish scientist Olavi Kajander, the discoverer of “nanobacteria”, presents the evidence that these objects are a hitherto undiscovered form of bacterial life in a contribution to a 1999 National Academies workshop on the size limits on very small organisms. But two recent papers give strong evidence that “nanobacteria” are simply naturally formed inorganic nanoparticles.
In the first of these papers, Nanobacteria Are Mineralo Fetuin Complexes, in the February 2008 issue of PLoS Pathogens, Didier Raoult, Patricio Renesto and their coworkers from Marseilles report a comprehensive analysis of “nanobacteria” cultured in calf serum. Their results show that “nanobacteria” are nanoparticles, predominantly of the mineral hydroxyapatite, associated with proteins, particularly a serum protein called fetuin. Crucially, though, they failed to find definitive evidence that the “nanobacteria” contained any DNA. In the absence of DNA, these objects cannot be bacteria. Instead, these authors say they are “self-propagating mineral-fetuin complexes that we propose to call “nanons.””
A more recent article, in the April 8 2008 edition of PNAS, Purported nanobacteria in human blood as calcium carbonate nanoparticles (abstract, subscription required for full article), casts further doubt on the nanobacteria hypothesis. These authors, Jan Martel and John Ding-E Young, from Chang Gung University in Taiwan and Rockefeller University, claim to be able to reproduce nanoparticles indistinguishable from “nanobacteria” simply by combining chemicals which precipitate calcium carbonate – chalk – in cell culture medium. Some added human serum is needed in the medium, suggesting that blood proteins are required to produce the characteristic “nanobacteria” morphology rather than a more conventional crystal form.
So, it seems the case is closed… “nanobacteria” are nothing more than naturally occurring, inorganic nanoparticles, in which the precipitation and growth of simple inorganic compounds such as calcium carbonate is modified by the adsorption of biomolecules at the growing surfaces to give particles with the appearance of very small single celled organisms. These natural nanoparticles may or may not have relevance to some human diseases. This conclusion does leave a more general question in my mind, though. It’s clear that the presence of nucleic acids is a powerful way of detecting hitherto unknown microorganisms, and the absence of nucleic acids here is powerful evidence that these nanoparticles are not in fact bacteria. But it’s possible to imagine a system that is alive, at least by some definitions, that has a system of replication that does not depend on DNA at all. Graham Cairns-Smith’s book Seven Clues to the Origin to Life offers some thought provoking possibilities for systems of this kind as precursors to life on earth, and exobiologists have contemplated the possibility of non-DNA based life on other planets. If some kind of primitive life without DNA, perhaps based on some kind of organic/inorganic hybrid system akin to Cairns-Smith’s proposal, did exist on earth today, we would be quite hard-pressed to detect it. I make no claim that these “nanobacteria” represent such a system, but the long controversy over their true nature does make it clear that deciding whether a system is being living or abiotic in the absence of evidence from nucleic acids could be quite difficult.