Arsenic and Odd Lace

It was clever of NASA to disclose its "amazing astrobiology discovery" right around budget-cutting time. But they should have better managed the hype -- and kept squarely in their memory the tale of the boy who cried wolf.
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When you hear about lots of cherries, bring a small basket. ~ Greek proverb

About a week ago, I started receiving a steady and progressively swelling stream of emails, asking me if I knew anything about the hush-hush "amazing astrobiology discovery" that NASA would announce on December 2. I replied I would opine when I read the associated paper, embargoed by Science until after the press conference. I also added that my bets were on a terrestrial extremophile that pushes the exotic envelope. Many bloggers and news sites disagreed, posting entries with titles and guesses taken straight from the pulp SF era.

Thursday NASA made its announcement and Science released the paper. To give you the punchline first, the results indeed concern a terrestrial extremophile and show that bacteria are very flexible and will adapt to suboptimal conditions. This is not exactly news, although the findings do push the envelope... slightly.

What the results decidedly do not show is a different biochemistry, an independent genesis or evidence for a shadow biosphere, contrary to co-author Paul Davies' attempts to shoehorn that into the conclusions of an earlier (2008) related paper. It's not arsenic-based life, it's not an arsenic-eating bacterium and the biology textbooks don't need to be rewritten.

The experiment is actually very clever in that it follows a given to its logical conclusion. The researchers took an inoculum from the hypersaline, alkaline Mono lake and grew it in serial dilutions so that the medium contained progressively increasing amounts of arsenic (As) substituting for phosphorus (P). Lake Mono has arsenic levels several orders of magnitude above the usual, so bacteria living in it have already adapted to tolerate it.

The bacteria that grew in severely P-depleted and As-enriched conditions were identified as members of a halophile (salt-loving) family already known to accumulate intracellular As. When deprived of P, they grew slowly and appeared bloated because they were full of structures that look like vacuoles, cellular organelles that manage waste and grow larger and more numerous when cells are under stress. Additionally, there was still some phosphorus in the growth medium (it's almost impossible to leach it completely) and there is no direct proof that As was incorporated into the bacterial DNA. So essentially the bacteria were trying to do business as usual under trying circumstances.

Phosphorus means "lightbringer" because the element glows faintly under illumination, giving its name to Venus when it's the Morning Star. It is deemed to be among the six elements vital for life (in alphabetical order: carbon, hydrogen, nitrogen, oxygen, phosphorus, sulfur; often acronymed as CHNOPS, which sounds like the name of an Egyptian pharaoh). Indeed P appears in all three classes of biomolecules. It's obligatory in nucleic acids (DNA, RNA) and phospholipids, the primary components of cell membranes; phosphate groups are crucial covalent additions to proteins, regulating their activity and ligand affinities; it's also the energy currency of cells, primarily in the form of ATP (adenosine triphosphate). On the scale of organisms, bones contain phosphorus in apatite form and it's also an essential nutrient for plants, though P excess is as much a problem as its lack.

Arsenic is directly below phosphorus in the periodic table, just as silicon is directly below carbon. Arsenic is highly toxic to lifeforms precisely because it looks similar enough to phosphorus in terms of atomic radius and reactivity that it is occasionally incorporated in metabolic intermediates, short-circuiting later steps in cascades. [This, incidentally, is not true for silicon vis-à-vis carbon, for those who are contemplating welcoming silicon overlords. Silicon is even more inferior than arsenic in its relative attributes.] Arsenic was used in pesti-, herbi- and insecticides (and in stealth murders), until it became clear that even minute amounts leaching into the water table posed a serious health problem.

The tables in the Science paper are eloquent on how reluctant even hardy extremophiles are to use As instead of P. Under normal growth conditions, the As:P ratio in their biomass was 1:500. When P was rigorously excluded and As had been raised to three times the level in lake Mono, the As:P ratio remained at a measly 7:1. Furthermore, upon fractionation As segregated almost entirely into the organic phase. Very little was in the aqueous phase that contains the nucleic acids. This means that under extreme pressure the bacteria will harbor intracellular As, but they will do their utmost to exclude it from the vital chains of the genetic material.

As I wrote elsewhere, we biologists are limited in our forecasts by having a single life sample. So we don't know what is universal and what is parochial and our searches are unavoidably biased in terms of their setup and possible interpretations. The results from this work do not extend the life sample number. Nor do they tell us anything about terrestrial evolution, because they showcase a context-driven re-adaptation, not a de novo alternative biochemistry. However, they hint that at least one of the CHNOPS brigade may be substitutable in truly extreme (by our circumscribed definition) conditions.

On the larger canvas, it was clever of NASA to disclose this right around budget (cutting) time. But it would have been even cleverer if they had managed to calibrate the hype volume correctly -- and kept squarely in their memory the tale of the boy who cried wolf.

The paper: Wolfe-Simon F, Blum JS, Kulp TR, Gordon GW, Hoeft SE, Pett-Ridge J, Stolz JF, Webb SM, Weber PK, Davies PCW, Anbar AD, Oremland RS (2010) A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus. Science DOI: 10.1126/science.1197258.

Note: This article is also on the author's blog, with relevant images.

Note for young(er) readers: the title is a take off on Arsenic and Old Lace, Joseph Kesselring's black comedy about decorous yet murderous old ladies, later made into a film by Frank Capra starring Cary Grant.

Addendum: The paper has evidence that the DNA of the final isolate contains 11% of the total arsenic by incorporation of radioactivity and mass spectrometry comparison studies. However, important controls and/or purification steps seem to be missing. The crucial questions are: exactly where is arsenic located, how much substitution has occurred in the DNA, if any, and how does it affect the layers of DNA function (un/folding, replication, transcription, translation)? Definitive answers will require at minimum direct sequencing and/or crystallographic data. The leading author, Felisa Wolfe-Simon, said that this is fertile ground for thirty years of future work -- and in that, at least, she's right.

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