Weirdly Unweird: A Better End to the #Arseniclife Affair

By Carl Zimmer | October 3, 2012 5:59 pm

It’s getting close to two years now since a NASA-funded team of scientists announced they had found a form of life that broke all the rules by using arsenic to build its DNA. It’s become something of an obsession for me. If you want to follow the saga, click here and start back at the earliest post. In July I live-blogged the announcement that other scientists had replicated the experiment and failed to find the same results. In some ways, that was the logical end to the story

My fascination with this story has been tempered from the start by a creepy feeling. As a science writer, I most enjoy reporting on advances in biology: the research that opens up the natural world a little bit wider to our minds. The “#arseniclife” affair was less about biology than about how science gets done and the ways it goes wrong: the serious questions it raised about peer review, replication, and science communication. That fierce debate did some collateral damage. The microbe in question, known as GFAJ-1, went from being the species that would force us to rewrite the biology textbooks to yet another bacterium that offered no serious challenge to the uniformity of life. It became boring.

But biology is not boring. Elephants and redwoods may both be made of the same elements, may both build genes from DNA, may both use the same genetic code book to build proteins–but they’re very different from each other in some respects, and, each in their own way, are most certainly not boring. Neither is GFAJ-1. And so it’s a pleasure to see a new paper in the latest issue of Nature in which a group of scientists pick apart the biology of the microbe and discover something very interesting.

The whole search for arsenic life got its start because arsenic, despite being toxic, is very similar to an essential element, phosphorus. Phosphorus is part of the backbone of DNA, for example, and it is an ingredient in the energy-storing molecule ATP–in each case in a form known as phosphate, with four oxygen atoms tacked on. Arsenate (arsenic linked to three oxygen atoms) is just about identical in size, has a similar charge to its oxygen atoms, and has many other chemical similarities to phosphate.

So the arsenic life team wondered if life might be able to survive with arsenic instead of phosphorus. One way to test that idea would be to rocket off to a planet where there is only arsenic and no phosphorus and look for life. Another would be to look for life on Earth that can swap arsenic for phosphorus. The arsenic life team opted for the latter and headed to Mono Lake in California, the waters of which are loaded with arsenic. They brought a strain of bacteria back to their lab, weaned it off of phosphorus, and supplied it with arsenic instead. The bacteria still grew. That fact and other studies they conducted convinced them that the bacteria had, indeed, become arsenic life.

The consensus today is that the scientists unwittingly fed the bacteria just enough phosphorus to survive, and the tests that seemed to indicate the arsenic was inside the DNA weren’t executed carefully enough.

But think about that for a moment. Imagine what it’s like for a microbe in Mono Lake, or in the lab of a particularly sadistic scientist. You’re drowning in arsenate, and in order to stay alive, to keep growing, you need to grab the precious few phosphate molecules drifting by.

Dan Tawfik, an expert on protein function at the Weizmann Institute in Israel, and his colleagues have uncovered some of GFAJ-1′s secrets to survival.  GFAJ-1 and other bacteria absorb phosphate through their outer membrane, into a sandwiched layer of fluid called the periplasm. Once there, the phosphate is grabbed by so-called phosphate binding proteins, which then deliver the phosphate to the interior of the microbe. Tawfik and his colleagues examined these proteins in unprecedented detail to see how they work.

The scientists offered the proteins a mixture of arsenate and phosphorus. Even when they raised the ratio to 500 molecules of arsenate to every phosphate molecule, the proteins still managed to pluck out phosphate over half the time. The scientists then examined the proteins to figure out how they make such fine discriminations. When the proteins encounter a molecule of phosphate, they enfold it in a tight pocket, which ties down the phosphate with 12 different hydrogen bonds. When arsenate falls into that pocket, it doesn’t quite fit in, and the bond between one of the oxygen atoms in the arsenate and one of the hydrogen atoms in the protein gets twisted. It gets pushed to such an uncomfortable angle that the arsenate drops out.

This finding suggests that ordinary microbes are well-adapted to picking out phosphates when they’re scarce, using their fussy phosphate binding proteins to reject abundant arsenate. GFAJ-1 is stuck in a place where phosphate is always scarce and arsenate is always dangerously copious. Tawfik and his colleagues found that one form of their phosphate binding proteins is spectacularly fussy, preferring phosphates by a factor of 4,500. What’s more, GFAJ-1 produces many copies of this super-fussy protein. As a result, GFAJ-1 can thrive in Mono Lake. In fact, it can handle arsenate-to-phosphate ratios up to 3,000 times higher than found in the lake.

Finding alien life on Earth would have been grand. But seeing how life as we know it manages to adapt to our planet’s extremes is also a pleasure. And it’s a good place for the story of arsenic life to stop: at the point where new science begins.

[Update: Rosie Redfield, the University of British Columbia microbiologist who became a leading skeptic of arsenic life, Maneesh points out in the comments that phosphates are actually abundant in Mono Lake. Thanks for pointing that out, Rosie Maneesh!]

 More: 

The paper

C & EN article

Nature News

[Image of Mono Lake by .Bala via Flickr, under Creative Commons License]

CATEGORIZED UNDER: Arsenic life, Top posts

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Comments (15)

  1. The problem with the NASA study was that their experiments did not justify the conclusion that they reached. This was (or should have been) obvious from the original paper. When the correct experiments were performed, it became easy to rule out the hypothesis that GFAJ-1 incorporates As into DNA.

    I know it’s a subtle point, but I think it’s an important one: the Redfield study didn’t “repeat the experiment”. They performed an entirely different experiment. The reason I think this is important is that the take-home about what went wrong is different.

    If an experiment failed to repeat (ie the results were faulty), it would indicate either seriously sloppy bench-work or misconduct. The editors, the reviewers, and perhaps the more senior authors on the paper would not be at fault.

    OTOH, if the conclusion was unjustified – based on data that was available for everyone to see – this underscores a disturbing trend towards scientists having to act as salesman for their research, and trying to make the biggest splash rather than doing work that is incremental but well-grounded. Dr. Wolfe-Simon is certainly guilty of this, but so is Science, NASA, and ALL of the authors on the original paper.

  2. “Arsenate (arsenic linked to three oxygen atoms)”

    Arsenate and phosphate have four oxygen atoms, not three. They are arranged in a tetrahedron around the group 5 cation, and the whole complex has a -3 charge.

    The phosphate complez is a major building block of DNA, ATP, and other crucial biomolecules. It is also the natural occurance in terrestrial minerals.

    An arsenic atom with three oxygens is an Arsenite. The phosphorus equivalent, phosphite, is much less stable, but can be synthesized (sort of).

    [CZ: Gah! Sorry for the mix-up. Fixed.]

  3. Thanks for the link love, Carl. I’ve always thought the #arseniclife paper, despite its now well-known issues, was masterfully framed around a fundamental question for chemistry- ‘what are the elemental limits of life?’ This new find, the subtle strategy (from a chemistry standpoint) thathelps ensure survival, made me think a big question to ask is ‘will scientists’ abilities to manipulate matter ever approach the level of nature’s?’

  4. Tim

    I totally agree with Casey. Redfield’s been overconfident but it’s hard to seriously blame a reseacher for that. The fault entirely lies with Nature editors.

  5. Tim

    I totally agree with Casey. Wolfe-Simons’s been overconfident but it’s hard to seriously blame a reseacher for that. The fault entirely lies with Nature editors.

  6. @Casey,

    The first part of our work was an attempt to closely replicate the culture conditions used by Wolfe-Simon et al. – the conditions that, they claimed, caused GFAJ-1 to incorporate arsenic in place of phosphate in its molecules. The second part was different – we used different/better methods to purify and analyze the cells’ DNA, and these methods showed that the DNA did not contain significant arsenic.

  7. Maneesh

    [posted yesterday, but my comment seems to have been eaten or might still be in moderation]

    Hi Carl,
    Your article suggests that phosphate is scarce relative to arsenate in Mono Lake:

    “Imagine what it’s like for a microbe in Mono Lake, or in the lab of a particularly sadistic scientist. You’re drowning in arsenate, and in order to stay alive, to keep growing, you need to grab the precious few phosphate molecules drifting by.”

    ” GFAJ-1 is stuck in a place where phosphate is always scarce and arsenate is always dangerously copious.”

    A paper (by Oremland):

    http://www.monobasinresearch.org/research/arsenic/Mono_Arsenic_Review_Reprint.pdf

    tells us that the concentration of phosphate is about twice that of arsenate in Mono Lake (Fig 1). This was at least partial motivation behind the skepticism as to why this bacteria would supposedly evolve a (profound) mechanism to deal with phosphate scarcity. GFAJ-1 may have 99 problems, phosphate scarcity ain’t one!

  8. Marine cyanobacteria (and some phytoplankton) CAN “distinguish” arsenic from phosphorus in phosphorus-limited environments, like the surface of the subtropical gyres. Arsenic is actually not too abundant in the surface ocean, but nutrients are even more scarce, so this is an issue for them.
    Arbitrarily chosen example: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201022/

  9. Chris Lawson

    Sad that Wolfe-Simon and her team had a really neat idea about arsenic in biology and discovered something quite interesting, but over-reached in their conclusions. This had the makings of a solid paper. Even if they had responded sensibly to the early criticisms, they could have come out looking good.

  10. MarkB

    Just a thought – that hashtag thing has already been beaten to death. I would have said ‘jumped the shark,’ but that expression has…. well, you know.

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The Loom

A blog about life, past and future. Written by DISCOVER contributing editor and columnist Carl Zimmer.

About Carl Zimmer

Carl Zimmer writes about science regularly for The New York Times and magazines such as DISCOVER, which also hosts his blog, The LoomHe is the author of 12 books, the most recent of which is Science Ink: Tattoos of the Science Obsessed.

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