Preliminary Thoughts on the “Arsenic-Based Life” Paper

December 3rd, 2010

This is indeed an interesting paper.  I have some questions about it; maybe I am misreading things.  Pardon the terseness.  I’ll update this post later this weekend.

1.  What was the source of the arsenate used in the growth media?

I can’t find the vendor/product information in the paper or the SI.  I am inclined to agree with Steve Benner and his suspicion that there may be sufficient phosphate in the “–P” media to support growth.  Life has a nice ability to concentrate/pick out what it needs.

2.  How could you think that arsenic is in the backbone of the DNA?

This paper shows that arsenic(V) esters hydrolyze in water in seconds.  The authors hypothesize that the bacterium has mechanisms for coping with this, but how does that explain the fact that they see a nice, clean gel (with a single band) of the isolated DNA?  Shouldn’t that band streak like the Dickens?

3.  “Arsenic possesses a similar atomic radius [to phosphorus]”?

Is 15 picometers (P: 100 pm, As: 115 pm) really that similar?  That seems like miles to me (on the atomic scale).  It is bound to have profound implications for bond strength and molecular structure.

4.  Title:  “Using Arsenic” [vs. “Tolerating Arsenic”]

I am not convinced the data presented support the conclusion that these organisms are “using” arsenic.  It will definitely be interesting to see if future work can isolate and characterize biomolecules from this organism that include covalent bonds to As.  Regardless, this paper is interesting because it presents an organism that is very tolerant of arsenic.

26 Responses to “Preliminary Thoughts on the “Arsenic-Based Life” Paper”

  1. Curious Wavefunction Says:

    Good point about the gel band. It’s not only that. The concentrations of P are measured in femtograms and I hope the authors were zealously watchful about the error bars. Plus it’s worth making sure a million times that there is absolutely no phosphorus to sustain core life processes. It could very well be that there is enough P to do this, with the rest of the machinery being helped along by As. That would still be interesting but it certainly won’t be as revolutionary. Traces of P could come from virtually anywhere, from the media, from human bodies, from laboratory equipment. Rough analogy, but this sort of reminds me about those ‘transition metal-free’ reactions that turned out to be catalyzed by traces of transition metals.

    It just seems a very tall order to imagine that As substituted P in not just DNA but in ATP, cyclic-AMP, kinases and every other important molecular component and the bacteria did just fine. Life is resilient but not infinitely so.

  2. Paul Says:

    Yeah…I’ve done ICP before. Kind of tricky when you’re looking at very small concentrations. You’ve really got to watch things like drift in your torch. I wonder how careful they were about calibration (and how often they recalibrated).

  3. Paul Says:

    Also: I don’t have my copy of Skoog handy. How sensitive is ICP/flame photometry for P and As? My guess is low (relative to metals).

  4. Matt Says:

    What I would like to know is: what concentration of arsentate do you need in solution in order to make DNA with an arsenate backbone stable.
    While its true that arsenic (V) esters fall apart in water, can you make them stable in water saturated with arsenates? What is the arsenate concentration of the water at Mono Lake? What are the concentrations they used in their cultures?

  5. Flavio Ortigao Says:

    In this seminal paper of Prof. Westheimer “Why Nature chose phosphate” there is an excellent discussion about As as a substitute for P.

  6. Curious Wavefunction Says:

    Not an expert at all, but a preliminary perusal of the literature reveals ng levels of P detected by ICP/FP, the smallest ones I saw being 500 pG. I think you would have to be very careful talking about 9 fG of P. I am pretty sure there’s orders of magnitude more P on the tip of my thumb.

  7. Arson Nate Says:

    Natural abundance arsenic-75 is spin 3/2, and you can analyze it spectroscopically by NMR. An easy experiment would be isolating total bacterial DNA and taking an As-75 spectrum. Demonstrating that arsenic lived in different chemical environments (and comparing it to, say, a P-31 spectrum) would go a long way towards proving that arsenic was actually incorporated into the backbone.

  8. excimer Says:

    @Paul: According to this, the LOD of As and P are 50 and 30 ppb, respectively.

    The standard bond lengths of As-O and P-O are quite different as well, 178 pm for As-O vs 163 pm for P-O. That’s a big difference. It’ll be interesting to see what these critters are actually doing with the arsenic. I doubt they’re just ignoring it.

  9. sam Says:

    Don’t be so cynical. This is the most amazing discovery of the past thousand years. And it’s in Science, so it can’t be wrong.

  10. Abid Says:


    200 uM

  11. David P Says:

    This made it into XKCD today!

  12. Emily Says:

    I’m not sure about their As source, but they did measure the amount of P in their medium and concluded it was below the level necessary to sustain life. (With no As subsitution, that is!) They also tried growing this strain in an As-/P- medium and found no growth.

    That DNA gel is whacky. They don’t specify what it is (the whole genome? a fragment?), how big it is, why the bands from the As+/P- and As-/P+ media look so different from each other.

    Re: tolerating vs using, they also don’t seem to comment on how the huge vesicles they see in the cells growing in As+/P- medium might affect the measured intracellular As concentration. Presumably their analysis of phenol/chloroform extracted cell bits is evidence that As is actually in the DNA and proteins, but their preps seemed pretty dirty (proteins and other metabolites in the same fraction–why not clean it up?).

  13. yonemoto Says:

    I have posted this before in many places, but they really do need go all old school and use an caesium chloride gradient ultracentrifugation to prove the DNA is getting denser due to arsenic. I will accept no experimental substitute.

    Basically, this experiment:

  14. Yonemoto Says:

    Eric Kool laughs at your 15 angstroms! Mwahahaha!

  15. Yonemoto Says:

    urg, I meant .15 angstroms.

  16. Curious Wavefunction Says:

    An excellent and exhaustive critique of the “arsenic-based” life paper. Basically the ugly question of whether there was enough phosphorus in the medium to support core life processes is still unresolved.

  17. Matt Says:

    @abid, Thanks.
    200uM seems pretty small to alter the dissociation rate of these complexes in water. But, I could be wrong. Until there is a structure, I think a lot of people are going to have a difficult time with this one. It could be that this As concentration is enough. Or it could be that there is a different backbone structure. Or it could be phosphorus. Need to do the experiments.
    As far as the amount of P in the cells. I don’t know that you can be that hard on them. If its in fg, it’s probably per cell. So, they have to do an estimate of the number of cells they’re sampling. They are also measuring a signal that is much larger than fg in mass. I’m sure these are just extrapolations. It seems to me that the order of magnitude could be OK if they 1) have an accurate cell concentration and 2) are measuring P concentrations in of the proper magnitude.

  18. cookingwithsolvents Says:

    I thought the acute toxicity of As was due to it being used to make As-ATP followed by hydrolysis upon leaving the active site and the carcinogenic nature due to incorporation into DNA.

    With that in mind, I wouldn’t be surprised to see P-based DNA backbones and use of something other than ATP to store/transfer energy.

  19. Yonemoto Says:

    i bet both the toxicity and carcinogenicity of arsenate have to do with it blocking active sites of enzymes, not replacing parts of biomolecules.

  20. CR Says:

    More importantly, who cares? More NASA “research” to try and survive R&D cuts. Can bacteria survive with arsenic? Whether they survive in arsenic or Tang, no big deal…

  21. Curious Wavefunction Says:

    Another great critique

  22. Yonemoto Says:


    “Any cellular machinery that stabilized arsenate-DNA was removed.”

    How do you know? This is in no way definite. There are certainly protein that can survive phenol-chloroform extraction, although they are few and far between.

    “In the absence of biochemistry, pure chemistry takes over”

    WTF? WTF?

  23. Claire Says:

    For ICP-MS, detection limits of As and P can be quite low, with clean preparation. The limits of 30 and 50 ppb given above are more typical for less sensitive ICP techniques, like ICP-OES or flame AA. From my experience (Agilent 7500cx), I prefer not to use ICP-MS for P, if I can help it, due to poor ionization in the plasma, but colleagues claim to measure at least below 10 ppb with accuracy. As, on the other hand, regularly has good response down to 0.5-1 ppb, and if I had a clean room in which to prepare samples and standards, I think the background is low enough that concentrations of 0.1 ppb could be readily measured. Agilent suggests LODs of ~0.05 ppb for both, under ideal conditions and sample matrices.

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