Field of Science

"Arsenic bacteria": If you hadn't nailed 'im to the perch 'e'd be pushing up the daisies

Rosie Redfield (who blogs on this network) has just published an official, careful and decisive rebuttal to the "arsenic bacteria" fiasco in collaboration with a group at Princeton. The paper which will appear in Science is under embargo for now, but there is a copy available at that bastion of free publication arXiv. Readers may remember Redfield as the scientist who offered the most meticulous preliminary criticism of the original paper by Felisa Wolfe-Simon and others. Wolfe-Simon and the rest of the arsenic group refused to engage in debate with Redfield and other critics at the time, citing the "non-official" nature of the offered criticism and asking for publication in a more formal venue. Looks like they finally got their wish.

The abstract could not be clearer:

"A strain of Halomonas bacteria, GFAJ-1, has been reported to be able to use arsenate as a nutrient when phosphate is limiting, and to specifically incorporate arsenic into its DNA in place of phosphorus. However, we have found that arsenate does not contribute to growth of GFAJ-1 when phosphate is limiting and that DNA purified from cells grown with limiting phosphate and abundant arsenate does not exhibit the spontaneous hydrolysis expected of arsenate ester bonds. Furthermore, mass spectrometry showed that this DNA contains only trace amounts of free arsenate and no detectable covalently bound arsenate."

It's a fairly short paper but there are many observations in it which quite directly contradict the earlier results. The strain of bacteria that was claimed to grow only when arsenic was added to the medium was found to not grow at all. In fact it did not budge even when some phosphate was added, growing only after the addition of other nutrients. Trace element analysis using several techniques detected no arsenate in DNA monomers and polymers. This is about as definitive an argument as can be published indicating that the claims about the bacteria using arsenic instead of phosphorus in their essential biomolecules were simply incorrect. Much credit goes to Redfield who patiently and probingly pursued the counterargument, undoubtedly at the expense of other research in her lab. In addition she did open-science a great service and described all the ongoing research on the blog. She sets a standard for how science should be done, and we should hope to see more of this in the future.

Sociologically the episode is a treasure trove of lessons on how science should not be done. It checks off some standard "don'ts" in the practice of science. Don't fall prey to wishful thinking and confirmation bias that tells you exactly what you wanted to hear for years. Don't carry out science by press conference and then refuse to engage in debate in public venues. And of course, don't fail in providing extraordinary evidence when making extraordinary claims. If the original paper had been published cautiously and without hullabaloo, it would have become part of the standard scientific tradition of argument and counterargument. As it turned out, the publicity accompanying the paper made it a prime candidate for demolition by blogs and websites. If nothing it provided a taste of how one needs to be extra careful in this age of instant online dissemination. There's also some "do's" that deserve to be mentioned. The researchers did reply to criticism later and make their bacterial strains available to everyone who wanted to study them in a gesture of cooperation, but their earlier behavior left a bad taste in everyone's mouth and detracted from these later acts.

When the original paper came out, many of us were left gaping with eyes wide open at visions of DNA, ATP, phosphorylated proteins and lipids swirling around in a soup of arsenic, carrying out the exact same crucial biological processes that they were carrying out before without skipping a heartbeat. We just had a gut feeling that this couldn't be quite right, mainly because of the sheer magnitude of the biochemical gymnastics an organism would have to undergo in order to retool for this drastically different environment. Gut feelings are often wrong in science, but in this case it seems they made perfect sense.

What next? As often happens in science, I suspect that the defenders of the original paper will not outright capitulate but will fight a rearguard retreat until the whole episode drops off everyone's radar. But this paper here, it clinches the case for normal biochemistry as well as anything could. Good old phosphorus is still one of life's essential elements, and arsenic is not.

9 comments:

  1. I think that some people will write off this Science paper as "cheap" in the sense that the outcome of these experiments was not really in doubt and Science is almost obligated to publish these results. But the truth of the matter is that Redfield and coworkers have performed a valuable service to the community in taking the time to bury this controversy when everyone else had just left it for dead. When her paper is rightfully published in Science, it will be the official death certificate that everyone can reference in future work. Lord knows people won't be citing blogs (even Redfield's) in "serious" publications anytime soon.

    Also, fantastic post, Ash.

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    1. Thanks, and I agree. Official death certificates have a ring that proclamations of death, no matter how thunderous, don't. I for one am glad that this episode will go down in history as a textbook case of bad science.

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    2. With respect to citing blogs in serious publications, I did cite a couple of posts from my blog in a Persṕective ( http://dx.doi.org/10.1007/s10822-011-9515-0 ) written for the JCAMD 25th anniversary issue. I'll leave it to the readers of this column to decide whether that contribution should be considered to be serious.

      You may be interested to know that Philip Ball mentions his 'Water in Biology' blog ( http://waterinbiology.blogspot.com ) in his excellent 'Water as an Active Constituent in Cell Biology' Chemical Review ( http://dx.doi.org/10.1021/cr068037a ) although he does not actually cite specific blog posts.

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    3. Interesting. I do remember reading Ball's article but didn't notice the blog citations. His blog is quite good although he updates very rarely. Did the editor/reviewers have anything to say about your unusual citation sources?

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    4. There was no comment by the editors about my citing the blog. Originally the plan had only been to cite Á short rant about journal editors' since it reinforced my message that journals had to come to terms with sharing their ecosystem with forms of life that they consider to be inferior. It also gave me a chance to direct readers to a rather foolish and intemperate attack on bloggers by a journal editor who really should have known better. Writing about alkane/water partition coefficients got me thinking, "I'd written this before so why not just link Lipohilicity Teaser".

      Philip Ball mentions his blog (although doesn't cite specific posts) right at the end of his Chemical Review just before: '10. Note Added after ASAP Publication' and I think that it was a completely appropriate thing to do.

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  2. I wonder if she'll be updating her wikipedia page ( http://en.wikipedia.org/wiki/Felisa_Wolfe-Simon )

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    1. I started my own little experiment, editing the Wikipedia page to reflect the recent results. Wonder how long it would take for someone to object and remove the edits.

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    2. Keep us posted with the results of your experiment although remember that Arsenic will make you deader than Erwin's cat even if Werner is not so sure.

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  3. Patrick M. Dennis8:11 AM, June 05, 2012

    One more thing: Arsenic. I'll bet that if the metal had been antimony or bismuth we never would have heard of it in the popular press.

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