there was strong consensus on the first issue, but the others remain open. The six geneticists and cell biologists in Panel I reached consensus on the smallest size likely to be attained by organisms of modern biochemical complexity. Free-living organisms require a minimum of 250 to 450 proteins along with the genes and ribosomes necessary for their synthesis. A sphere capable of holding this minimal molecular complement would be 250 to 300 nm in diameter,1 including its bounding membrane. Given the uncertainties inherent in this estimate, the panel agreed that 250 ± 50 nm constitutes a reasonable lower size limit for life as we know it. At this minute size, membranes have sufficient biophysical integrity to contain interior structures without the need for a cell wall, but only if the organism is spherical and has an osmotic pressure not much above that of its environment.

Panel 2 consisted of microbial ecologists asked to elucidate the smallest sizes actually observed in free-living organisms. Once again, consensus emerged from the panel's discussion. Consistent with the theoretical limits articulated by Panel 1, members of Panel 2 reported that bacteria with a diameter of 300 to 500 nm are common in oligotrophic environments, but that smaller cells are not. Nanobacteria2 reported from human and cow blood fall near the lower size limit suggested by cell biologists; however, the much smaller (ca. 50 nm) bodies found in association with these cells may not, themselves, be viable organisms. Observations on archaea indicate that, in general, they have size limits similar to those for bacteria.

Two problems constrain discussions of minimal cell size in natural environments. Commonly used methods of measuring cell size have inherent uncertainties or possibilities of error. Perhaps more important, most cells found in nature cannot be cultivated. Thus, ignorance about biological diversity at small sizes remains large. These problems notwithstanding, it appears that very small size in modern organisms is an adaptation for specific environmental circumstances, including stress and scarcity of resources. Primordial organisms may or may not have been tiny, but the smallest organisms known today reside on relatively late branches of the RNA phylogeny.

Whereas Panels 1 and 2 indicated that a cell operating by known molecular rules—with DNA or maybe RNA, ribosomes, protein catalysts, and other conventional cell machinery—would have a lower size limit of 200 to 300 nm in diameter, Panel 4 suggested that primitive microorganisms based on a single-polymer system could be as small as a sphere 50 nm in diameter. There is no assurance that primordial cells would have been this small or, if they were, that such minute cells would have been more than transitory features of early evolution. Nonetheless, unless one is willing to posit that everywhere it has arisen, life has evolved a biochemical machinery comparable to that seen on Earth, the rules that govern minimum cell size may not be universal.

In fact, as explored by Panel 3, there axe a number of ways that living cells or fossils might fall below the minimum size deemed likely by cell biologists and ecologists. On Mars or Europa, fossils might preserve a record of biological systems different from those we understand—perhaps early products of evolution that made do with a small complement of functional molecules. Organisms of modern biochemistry might become small by being pathogens or living in consortia—that is, by using the products of another organism's genes. Or, fossils might preserve remains that shrank after death, or parts of organisms rather than complete cells—both are common in the terrestrial record.


Contributors to the workshop have usually described relevant scale sizes or dimensions in units of nanometers (nm) or micrometers (mm), depending on the context and the features being described. For an indication of the range of relevant scale sizes, see Figure I in the paper by Jack Farmer, Panel 3, p. 94.


While biologists have yet to agree on a precise meaning for this term, it is generally used to refer to any single-celled microorganism proposed to have a maximum diameter in the range of tens to a few hundreds of nanometers.

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