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Arsenic and Odd Lace

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 e-mails, 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.

Today 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 [see addendum]. 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.

Addendum 1: 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.

Addendum 2: Detailed devastating critiques are appearing.

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.

My extended analysis: The Agency That Cried “Awesome!”

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.

Images: 1st, the vacuolated cells of the As-fed bacteria (Wolfe-Simon et al, Figure 2E); 2nd, the elements important to life; 3rd, Mono Lake (LA Times)

28 Responses to “Arsenic and Odd Lace”

  1. Asakiyume says:

    Thank you *so much* for this; it’s precisely what I was hoping for: a clear, complete explanation for what the parameters are and how this is new.

    I hadn’t realized/remembered the importance of phosphorus, and I only tuned in to the story at the point where people were admitting that it was phosphorus substitution, not straight reliance on arsenic, but all the while I was wondering why *phosphorus* was getting so much press–but thanks to your post, I now understand.

  2. Athena says:

    You’re most welcome! The romantic in me was harboring a guilty hope that this would prove to be indeed seismic. But the lack of leaks made me less and less hopeful. If this had been as huge a deal as they kept implying, someone would have broken under the strain and spilled the beans ahead of time.

  3. Sophy ZS Adani says:

    On one hand, I don’t blame NASA too much, not with all the budget cuttings. But I was a bit ticked off at the news. Extremophiles are cool, but I was hoping in my heart of hearts that it would be something truly alien they discovered. Something that would point to extraterrestrial life.

  4. Athena says:

    You and me both, Sophy!

  5. Peggy says:

    I agree too Sophy!

    I thought the paper was quite interesting and exciting, but after all the hoopla it felt like a bit of a letdown.

  6. Rose Lemberg says:

    What Francesca said – thank you very much for this clear, detailed explanation. It is disappointing that all they had to show for the noise was, basically, a trick experiment. It is still an important finding, but it does not live up to the hype, which diminishes its impact for the public. There is a Russian saying, “to make an elephant out of a fly,” which applies in this case, I think. Let’s hope for more exciting news sooner rather than later. I am still convinced that there is life in the universe besides us, and that we are likely to find some evidence of it in the Solar system.

  7. Athena says:

    A bit more than a fly but I agree with everyone that the hype was a bad idea. And I’m as convinced as you are that there is life elsewhere and it will be very different from us — although carbon and water are privileged components and may be prevalent, if not universal.

  8. Dr. Pierre Amiguet says:

    Contrary to what you say I overheard somebody saying that labeled AS was actually integrated into the DNA.
    Wright – wrong?
    Thanks, Pierre

  9. Athena says:

    The data in the paper are suggestive that this might be the case. Also, some forcing of As into the DNA would have to have occurred for the bacteria to continue propagating. Definitive proof would be some type of sequencing, although that’s admittedly hard to do without modifying current technology.

  10. Bob Keenan says:

    Good article. But one thing that bugs (like in bacteria) me is how the press is pushing this. “Alien life discovered in CA”. My local paper, the NASA website, and all the news stations are covering it likewise.

    But then I read the WSJ – my go to place for neutral if not boring news. And more was revealed.

    The experiment was to take these bacteria who have already adapted to a high arsenic low phosphorus environment in Mono lake…. BUT…. with normal DNA for that bacteria.

    Then in the lab, in petri dishes, slowly and methodically remove the phosphorus from the environment. And “Wha-LA. The bacteria is living in a nearly phosphorus free environment. AND they CLAIM that the DNA structure has changed to include arsenic as a substitute.

    SO…. no alien life in Mono lake. And the bacteria, if different, was altered in a lab by changing its environment.

    So you might conclude that life forms may be more adaptable than we thought…. But there is no new Alien life form.

    BTW NASA is a money sucking, parasitic, bureaucratic huge overhead on the future of space exploration. I am all for putting much more money into space exploration than we currently do but all NASA does is slow things down and get caught between, unions, lobby groups, and congressional actions. But that is another topic……

  11. Athena says:

    The substitution of phosphorus is the most important item in all this, because it was deemed an obligatory component for biomolecules. As for NASA, it was great once and it’s not the only research agency to be ground to dust by administrators and politicians.

  12. Path of Totality says:

    Thanks for the article. I watched the press release from NASA yesterday and as the video went on and the Biologist and Chemist “debated” I realized that the “ah-ha” moment was not “look what we found” but “what we made/did”. After that I read other articles from 2-5 years ago about the bacteria, when it was found and more about arsenic. Please note that I am not a Biologist but a Mechanical Engineer so a lot of things flew over my head. Your article here helped clarify things so again, Thanks. I didn’t see a new life form yesterday as anticipated but I am still comfortable in saying “it’s still cool stuff”. If nothing else I learned a little bit yesterday and today and that’s not a bad thing!

  13. Athena says:

    You’re very welcome! And I agree, the important point was what what they did — the announcement actually shortchanged the achievement!

  14. andy says:

    Well definitely an interesting discovery, pity the announcement was made to imply it is astrobiology-related, when the connection to astrobiology is somewhat tenuous.

    On a different tack, what do you make of this paper about hypothetical chlorinic photosynthesis? Unfortunately I only have access to the abstract, but not being a biologist or chemist I’m not particularly sure how much sodium chloride I should take with it.

  15. Athena says:

    I’ll see if I can gain access to the text of the article, Andy. A priori, monovalent ions are less versatile, but I’ll have to see their argument in its entirety.

  16. […] 4 Dec 2010 Update: Great posts on the newly-created arsenic eating bacteria are popping up, now that Science has released the article. In addition to Sarah Goslee’s post, above, we now have Athena Andreadis, a biomedical researcher and blogger, on the science and what it all means, in her post “Arsenic and Odd Lace.”. […]

  17. Mike says:

    NASA doth shout “there be wolves about!”
    but all that was found was a quail
    many felt let down
    and faces shaped frowns
    but the quail did have a nice tale

  18. Walter L Johnson says:

    The news reports beg the question to be asked–Can this bacterium be used to remove arsenic from common water sources contaminated with arsenic, such as a large portion of all the water wells in Bangladesh. The Homestake Gold Mine that used to operate in Lead, SD, used a custom bacteria to recover cyanide used in gold ore processing. See: http://freepages.history.rootsweb.ancestry.com/~gtusa/usa/sd/homestake.htm and if such a recovery approach could be used underground especially to cheaply remove arsenic it would be of huge benefit in all location were wells are contaminated by arsenic.

  19. Susan says:

    Sounds like a resilient little bacterium. I feel sorry for it.

  20. Athena says:

    Not a bad attempt at a limerick, Mike!

    Walter, that’s a very good question. It would be like the proposed use of hydrocarbon-metabolizing bacteria for cleaning oil spills.

    Susan, bacteria are amazing creatures. They adapt to cope with whatever we throw at them. Without their baseline flexibility, nothing else would be here today. However, it’s interesting to note that this particular adaptation (as many others) is predicated on an oxygen-dependent biochemistry. Another blow to the attempt to portray this as a remnant of the shadow biosphere.

  21. Excellent post, and very much ahead of the curve in seeing the flaws of this work!

  22. Athena says:

    Thank you, Rosie! I thought your analysis was terrific and I very much want to see Science’s reaction to all the letters to the editor (including yours) that point these things out.

  23. Walden2 says:

    Does anyone else recall the 2000 announcement from NASA about something big regarding Mars, only to have it turn out to be that liquid water might be running on that planet’s surface? Yes, that is news, but most people were being led to believe that actual life had been found. And now there are those who argue that the Martian sands are made of very fine powder that almost flows like a liquid and could explain those recent flows on the planet.

    And as for another Mars announcement of old, what has become of the so-called “fossils” in the famous Martian meteorite ALH84001? I recall a recent news item that perhaps the evidence does aim towards signs of life on that old rock. Plus that the Vikings may have detected life after all. Athena, do you have any information on these things? Thanks and thanks for reminding the media and other institutions about the facts and doing their homework.

  24. Athena says:

    I haven’t followed the two projects step by step, Larry but I know that 1) Dirk Schulze-Makuch, among others, argued that if life existed on Mars, some of the Viking experimental protocols might have inadvertently destroyed it and 2) the pendulum has swung towards the middle regarding the biogenic provenance of the formations in ALH84001. In short, the scientists haven’t reached consensus even after reassessment with more advanced techniques. Final resolution of these questions will require more missions.

  25. Walden2 says:

    My next nieve question is, why would NASA do this knowing that professional biologists would tear it apart if there were errors?

    http://www.dailymail.co.uk/sciencetech/article-1336752/Nasas-bacteria-lived-arsenic-discovery-dismissed-flim-flam-scientists.html

    I still contend that the news item which came out at the same time that there are three times more stars in the Universe than previously thought is more relevant to the possibility of extraterrestrial life, especially the kind we can communicate with.

  26. Athena says:

    “Those whom the gods wish to destroy they first turn mad.”

    It’s the only explanation I can come up with. More soon, in an upcoming essay.

  27. Walden2 says:

    Speaking of Mars life, ever see this from Walt Disney made in 1957? Amazing even if its only true on other worlds in other solar systems:

    http://www.youtube.com/watch?v=d76fiWRobU4

    My opinion is that any actual life on Mars is way underground, something no current mission plan can reach. NASA should be focusing on Europa and Titan if they want a better chance of finding life. And as a nod to David Grinspoon, the atmosphere of Venus needs better examining, too. Too many are still hung up on the idea of Mars as the only other place for life, though that is slowly changing.

  28. Athena says:

    I had seen it once before, but it never grows stale. Far more interesting and imaginative than Hawking’s Discovery program (especially given the relative dates).

    Indeed, the consensus is that Martian life, if extant, will be underground. And I agree, NASA should be looking at the other possibilities… if it can screw its head on straight.