Field of Science

Yet another reason why the Wolfe-Simon conclusion is so improbable

Experimental results need to be evaluated from two perspectives, the quality of the data and the probability of the explanation.  I and many others have critiqued the Wolfe-Simon results based on the poor quality of the data, and chemists have critiqued them based on the predicted instability of arsenic bonds in a DNA backbone.  But I don't think anyone has spelled out the improbability from an evolutionary perspective.  So here goes...

We're told that the authors originally thought they might have cultured a member of the hypothetical 'shadow biosphere'.  If such organisms existed they would be descendants of an evolutionary lineage that has been evolving independently of known organisms for billions of years.  Known organisms all belong to a single lineage, and the 'shadow biosphere organisms might either have originated independently of this lineage (A in the sketch below) or diverged from it shortly after its origin (B in the sketch below).
The organisms contained DNA, and PCR amplification using 'universal' primers for the 16S rRNA gene was successful.  This meant that the organisms could not be members of a type A shadow biosphere, as an independent origin wouldn't have produced either DNA or 16S rRNA genes.  But placing the 16S rRNA sequence in a phylogenetic tree showed that the organisms weren't members of a type B shadow biosphere either.  Instead they were members of a conventional group of bacteria, indicated by the dark wedge in the bacterial triangle.

Finding that a shadow biosphere organism had DNA with a backbone containing only arsenic (no phosphorus) would have been very surprising, both because we have no evidence that the shadow biosphere exists and because of the predicted instability of the arsenic ester bonds.  However, the claim that a conventional bacterium can function when its DNA backbone contains a mixture of arsenic and phosphorus is even more improbable.  Here's why:

Many different enzymes interact with DNA, and almost all of them need to do so with high precision.  They can do this because the DNA backbone has a very consistent structure.  Although the four bases that attach to the backbone have different shapes, they can occur with any sequence only because the nature of the base pair does not alter the backbone geometry.  The enzyme DNA polymerase is especially dependent on precise interactions with DNA, because it is responsible for accurate replication of the genetic material.  Typical measures of the fidelity of DNA replication by bacterial DNA polymerases show an error rate of about 10^-9.

The covalent radius of arsenic is about 11% larger than that of phosphorus (see this periodic table tool), and the As-O bond lengths reported in Table 3 are about 13% longer than the P-O bond lengths in DNA (Table S3).  No DNA polymerase could function on a template with such unpredictable geometry.  Even if it could bind to the template strand and proceed along it, the differing bond lengths it encountered would prevent the incoming nucleotides from forming the necessary bond with the growing end.   And even if it could create the backbone of the daughter strand, the error rate due to base mispairing would be so high that reproduction would fail.

Similar problems would affect every enzyme that contributes to production of the DNA and RNA precursors, to DNA and RNA synthesis, to DNA repair, and to energy metabolism.  No matter how stable the arsenic-substituted metabolites might be (and the chemists tell us they are mostly very unstable), the proteins that need to interact with them would not be able to cope with the unpredictability of usinging both arsenic and phosphorus versions.

The fundamental problem isn't that millions of generations would be needed to evolve enzymes that could tolerate a mixture of arsenic and phosphorus, but that the required adaptations are not compatible with the precision needed for function.


  1. In my opinion, as a non-scientist and general Average Joe, I think the whole point of the NASA press conference announcing this arsenic-based life-form, was given by the guy on the phone, Esler (sp?)
    He said we were running low on phosphorous.
    No phosphorous --> no fertilizer --> no food.
    He was telling us we can expect food shortages in the (near?) future. Perhaps massive food shortages. And all because there is a coming "phosphorous shortage."

    And, what do you know? Here's NASA to (perhaps) save the day. They happen to have just started to fund a ditzy scientist who has some crazy idea about discovering a "swopping-phosphorous-for-arsenic" type organism.

    Many scientists like to think we have an over-population problem. But, of course, it's always those other people, in distant lands, who are having too many children. Certainly not their own niche society, or their own family.

    It is my belief we have enough food for everyone, it is just the distribution of food that is at fault. How many dumpsters full of cast-off food do you find in countries who have a high rate of starvation? And here, in Western countries, we have overflowing dumpsters containing enough food to feed people and their families, if only it were better distributed before spoilage.

    I realize my comment has ranged far from the discussion at hand. And yet, I will return to my original point: NASA is telling us, asking us to believe, that phosphorous levels are rapidly decreasing. That was the whole point of the news conference. Please do not take this in the wrong light but I believe you specialized scientists are lost in your fascination with the trees, failing to see the entire forest.

    I believe NASA knew Wolfe-Simon's research was deeply flawed. They knew it would be skewered by those more in-the-know, such as Rosie Redmond. The interesting question is why would 12 other scientists add their name to the paper, and why a so-called impeccable journal publish it?

    This is a set-up job. The whole point was to get the word out that phosphorous levels are (supposedly) rapidly decreasing and NASA might have serendipitously found an answer proffered by, holy smokes, someone they are funding! What luck! Don't forget, people, NASA is an arm of the military, and the military is foremost invested in geo-politics.

    In my opinion, Wolfe-Simon is a useful idiot. Her "discovery" of this life-form was most likely directed by others above her who happened to direct her attention towards Mono Lake.

    NASA wants us to get used to the idea of "other" life-forms entirely based upon principles beyond our ken (or kin.) To what purpose? Who knows? They most assuredly know many things not said in news conferences.

    That is all I have to say. Please ignore this post for it has nothing to do with the scientific questions and doubt most ably put forward by Dr. Redmond.

  2. Please forgive my misspelling of Redfield.

  3. @anonymous:
    Sure, why not. Makes as much sense as most of the posts on this blog.

  4. and its equally substantiated!

  5. What would seem even more miraculous from an evolutionary and functional standpoint would be that the 16S RNA from this Halomonas would have remained unchanged (as implied by the phylogenetic tree) in its base sequence while accommodating systematic or statistical replacement of phosphorus by arsenic.

    Unless the bug also encodes a second version of the 16S gene specialized for arsenic, one may safely predict that this element is actively avoided in the making of GFAJ ribosomes.

    For the sake of science, let's hope that the Mono Lake miracle will be fully confirmed or fully dismissed with nô delay. Otherwise, the academic tribe might be forced to attend the equivalent of San Gennaro's yearly ordeal of blood liquefaction :

    Science is the discipline of reproductible miracles.

  6. "phosphorous levels are (supposedly) rapidly decreasing"

    I don't know what "phosphorous levels" are, and this is OT. But shortly: the constraint of CHNOPS cells in nature is often phosphorous, which is then provided to plants as fertilizers. Fresh manufactured fertilizer is currently made from some useful sedimentary minerals, and those are in limited supply.

    If you go with the popular but totally market denying model of "peak supply", it is estimated to happen anywhere between decades (peak modelers) and centuries (suppliers). [See Wikipedia on the element.]

    But there are plenty of potential phosphorus sources as phosphorous is a common ingredient of the mantle, _which is basically why cells use it and not arsenic_. If you realize we have markets and technology, this element may some day be mined with similar methods that electrochemically refine aluminum from rock.

    Also, I have a hard time visualizing arsenic plants for food or arsenic wood for buildings and furniture!

  7. This is anonymous 3:17. I asked the question about PCR. Thanks this post clarified why it couldn't work.

    I don't remember ever reading in their paper about a hypothetical 'shadow biosphere.'

    But even if this was a recent adaptation, what I don't get is what is the selective force? Mono Lake seems to have a sufficient amount of phosphate that there would be no reason to substitute As into any of the constituent biomolecules.

  8. @3:17 The authors aren't saying the bacteria do this in Mono Lake but that they are able to do it when put in an environment with high As but no P. Possibly a vestigal ability that they retain from an ancestor that evolved in a hydrothermal vent or some other strange environment. They don't claim that this organism represents a shadow biosphere.

  9. Here is yet another, another reason their conclusions are so improbable.

  10. Okay, this has nothing to do with the conclusions of the paper. Nowhere in the actual publication is there even a suggestion of a shadow biosphere. Bash NASA's PR department all you want, they certainly deserve it (and not just for this most recent pile of BS); but don't lump the actual authors into it when they can't control what garbage the media is going to make up about their actual conclusions.

  11. Anonymous @ 5:03pm.

    Perhaps the authors didn't mention the shadow biosphere in the paper, however in her closing statements at the press conference Felicia Wolfe-Simon showed a somewhat over-the-top movie that put all known life in one 'tree of life', and her newly discovered bacteria in another. So, clearly the notion of the shadow biosphere is not just a NASA construct. It was developed, and fully supported by the authors of the paper.

  12. @ Anonymous (5:03):

    Did she really? But that's in complete contradiction of the phylogenetic analysis in her own paper, which puts GFAJ-1 smack-dab in the middle of the gamma-proteobacteria!

  13. I don't remember that in the press conference but at any rate lets stick to whats in the paper. Actually Redfield's point in this post is that the paper does not invoke a shadow biosphere.

  14. If the authors had simply reported the discovery of bacteria that tolerated extremely high levels of arsenic without any problems, they'd likely have been okay - but they certainly wouldn't have gotten the headlines.

    They didn't even look into the background, it seems - for example:

    "Planktonic microbes in low-P environments (e.g., the Sargasso Sea) are particularly frugal with P that they acquire from their environments. Phospholipids and nucleic acids appear to be the primary reservoirs of P within the planktonic cells in the open ocean (Van Mooy et al., 2006; recent work of author Van Mooy and Allan Devol, University of Washington, paper in review), and recent studies show that plankton have evolved mechanisms to economize on these biochemical P requirements."*

    It is true, however, that some marine bacteria replace their cell membrane phospholipids with sulfur/sugar lipids (S-lipids) (not with arsenic). Such discoveries, however, were carefully substantiated with biochemical assays, and have been seen in other microbial groups.

    The claims about a similar substitution taking place in DNA were apparently not based on anything other than speculation and the desire to get a paper in Science.

    Microbes and the Marine Phosphorus Cycle, Dyhrman, Ammerman, Van Moody, in Microbes and Major Elemental Cycles.

    This kind of thing is a growing problem in the corporate science world. Scientific accuracy takes second place - public relations comes first, and that means maximizing the hype - and the federal science agencies have become the worst offenders (outer space microbes! zero emission coal plants! etc.)

    It's somewhat reminiscent of claims by Lawrence Berkeley researchers that "all the oil has vanished from the Gulf of Mexico" - a claim based on another seriously flawed microbial study - take a look at that press release:

    The author of that (bogus) report also weighed in on the arsenic story for the SF Chronicle:

    "Terry C. Hazen, a specialist in microbial ecology at the Lawrence Berkeley National Laboratory, said the information provided by Wolfe-Simon and her colleagues "is quite convincing and provides potential new insights that many of us have not thought of.""

    All together, now.

  15. It does not matter how improbable a conclusion is. It only matters whether it is right or wrong.

  16. The shadow biosphere? Don't wast your time. Just as two organisms can not inhabit the same niche, two trees of life are unlikely to be able to inhabit the same biosphere.


  17. Somebody's jealous!

  18. Dr. I dont know if you have already mentioned it but all the polymerases we use for PCR will be unable to amplify any DNA that is contaminated with As. So I see only two propabilities

    1) Almost no arsenate on the DNA (Most likely)
    2) 1 atom of arsenate for like 1000 phospate molecules (Just a strain that is bad at removing As from DNA).


    What about RNA. Since bacteria in general have way more RNA than DNA it would make no sense to have As in DNA and not RNA. And I will "eat" my degrees if rRNA can work with As instead of Pi.

    The editors of Science that were responsible for this fiasco should be fired. Good science is better than rubbish science.

  19. Here are two peer-reviewed responses to the Wolfe-Simon paper in ACS Chemical Biology and Biochemistry journals. Makes for very interesting reading....

  20. Thanks for the refs - I;d seen the first but not the second.


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