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Friday, February 03, 2012

The Arsenic Affair: No Arsenic in DNA!

The "arsenic affair" began with a NASA press conference on Dec. 2, 2010 announcing that a new species of bacteria had been discovered. The species was named GFAJ-1 (Get Felisa a Job), by the lead author Felisa Wolfe-Simon. GFAJ-1 was grown in a medium that lacked phosphate and contained high concentrations of arsenic. The paper, published that day on the Science website, claimed that arsenic was replacing phosphorus in many of the cell's molecules, including nucleic acids.

Here's a (bad) video of the press conference. The high quality version from NASA is no longer available and some other YouTube videos don't allow embedding.

Here's what Felisa Wolfe-Simon says beginning at 7:25 minutes into the press conference.
Then we found that the arsenic was associated specifically with a band of DNA—I think a lot of us have heard this kind of thing—and we measured that there was arsenic there. And then we could tell that the arsenic wasn't just stuck. it was in an analogous type of chemical environment or its nearest neighbors looked like it was behaving like phosphorus.
She then showed a video where the phosphorus atoms in the backbone of DNA are replaced by green arsenic atoms.

Felisa Wolfe-Simon continues...
So what we think is happening, all the evidence we've collected suggests that instead of the usual CHNOPS all these orange light balls [phosphorus] disappear and, represented by these green balls, we see that arsenic will be substituting for phosphorus in the backbone of DNA.
Later on in the the press conference, a "skeptic" explained the problems with such a replacement. There is absolutely no doubt that the main focus of the "discovery" was the finding that arsenic could replace phosphorus in DNA.

The paper itself says ....
These measurements therefore specifically demonstrated that the purified DNA extracted from +As/–P cells contained As. Our NanoSIMS analyses, combined with the evidence for intracellular arsenic by ICP-MS and our radiolabeled 73AsO43– experiments, indicated that intracellular AsO43– was incorporated into key biomolecules, specifically DNA.
Within days of the press release the paper had been thoroughly discredited by bloggers and science writers. Much of the criticism focused on the claim that arsenic replaced phosphorus in DNA. Rosie Redfield (University of British Columbia) got most of the attention because of the devastating takedown on her blog [Arsenic-associated bacteria (NASA's claims)].

The editors of Science were sensitive to the criticism in the blogosphere and they delayed publication in the paper version of the article until June. When the paper was published it was accompanied by eight comments that challenged the conclusions. The authors responded to the comments and part of what they said is ...
The DNA/RNA pellet was collected by centrifugation and washed with 70%ethanol, repelleted, dried, and resuspended in ultra-clean water (Fisherbrand, BP2484-100). After agarose gel loading buffer was mixed with the resuspended pellet, the DNA/RNA was electrophoresed on a 1% gel. Arsenate in the spent culture medium should have been removed by washing of the cells before extraction. Moreover, because both arsenate and DNA are negatively charged molecules, there should be little As sorbed to the DNA pellet after the purification process.

Our AsO43- experiment confirms that significant As is extracted into the organic fractions and that 11% of the total radiolabel associated with the cell pellet was associated specifically with the DNA/RNA fraction (1). This proportion of As seems too large to represent residual inorganic As contamination after multiple washing and extraction steps. Furthermore, our interpretation of our EXAFS data is that they are consistent with intracellular arsenic in the form of As(V) bound to about four O atoms and further bound to C atoms in secondary coordination shells, rather than being free in solution as an ion. Although it is possible that additional arsenic as residual inorganic arsenate was present in our whole-cell samples after washing, the spectra we obtained for GFAJ-1 indicate bond distances similar to phosphate bond distances in many phosphate biomolecules (Table 1) and are thus suggestive of As present in arsenoester-like compounds.
In other words, they defended their claim that the DNA backbone contained arsenic.

The comment from Editor-in-Chief Bruce Alberts is really quite extraordinary. I can't think of any other case where bloggers have had such an influence.
The Research Article “A bacterium that can grow by using arsenic instead of phosphorus” by F. Wolfe-Simon et al. [p. 1163, (1)] was the subject of extensive discussion and criticism following its online publication. Science received a wide range of correspondence that raised specific concerns about the Research Article's methods and interpretations. Eight Technical Comments that represent the main concerns, as well as a Technical Response by Wolfe-Simon et al., are published online with this issue at the addresses listed below (all were previously published in Science Express on 27 May). They have been peer-reviewed and revised according to Science's standard procedure.

The print version of the Wolfe-Simon et al. paper reflects minor clarifications and copyediting of the Science Express version. We hope that publication of this collection will allow readers to better assess the Research Article's original claims and the criticisms of them. Our procedures for Technical Comments and Responses are such that the original authors are given the last word, and we recognize that some issues remain unresolved. However, the discussion published today is only a step in a much longer process. Wolfe-Simon et al. are making bacterial strain GFAJ-1 available for others (2) to test their hypotheses in the usual way that science progresses.

Bruce Alberts, Editor-in-Chief
Rosie Redfield obtained the GFAJ-1 strain and carefully determined conditions under which the cells would grow in the presence of high concentrations of arsenic. She discovered that a low concentration of phosphorus was essential for growth and that the DNA contained no trace of arsenic when the cells were grown in arsenic. Her paper has been submitted to Science but you can see the draft here.

It's encouraging that the media is reporting on the recent results instead of ignoring the followup experiments as they usually do. The report in ScienceNews [Arsenic-based life finding fails follow-up] is particularly interesting because it contains the following ...
Wolfe-Simon, who says she can’t comment in detail until Redfield’s results appear in a peer-reviewed journal, wrote in an email that her original paper never actually claimed that arsenate was being incorporated in GFAJ-1’s DNA, but that others had jumped to that conclusion. “As far as we know, all the data in our paper still stand,” she wrote. “Yet, it may take some time to accurately establish where the [arsenic] ends up.”
I'm with Jonathan Eisen when he says, "WTF"? [2010 "Arsenic found in DNA", 2012 "We never claimed arsenic was in the DNA" WTF?]

There's one more troubling aspect to this story. The Science paper has twelve authors and all twelve of them signed the rebuttal that was published in June. However, it appears they are content to leave all the heavy lifting to Felisa Wolfe-Simon when it comes to defending their work. This is not acceptable. Either they stand by their own paper or they don't and it's very difficult to see how they can avoid taking some responsibility for this disaster. Rosie Redfield has found a wonderful comment about this from David Dobbs. You should go to her blog and read it [Authorship without responsibility?].

Arsenic and Bacteria
DNA, Phosphorus, and Arsenic
More than a Blog?

Wolfe-Simon, F., Switzer Blum, J., Kulp, T.R., Gordon, G.W., Hoeft, S.E., Pett-Ridge, J., Stolz, J.F., Webb, S.M., Weber, P.K., Davies, P.C.W., Anbar, A.D. and Oremland, R.S. (2011) A bacterium that can grow by using arsenic instead of phosphorus. Science. 332:1163-1166. Published online 2 December 2010; published in Science magazine Jun 3, 2011 [doi: 10.1126/science.1197258]

Wolfe-Simon, F., Switzer Blum, J., Kulp, T.R., Gordon, G.W., Hoeft, S.E., Pett-Ridge, J., Stolz, J.F., Webb, S.M., Weber, P.K., Davies, P.C.W., Anbar, A.D. and Oremland, R.S. (2011) Response to comments on "A bacterium that can grow by using arsenic instead of phosphorus". Science. 332:1149. [doi: 10.1126/science.1202098]


Schenck said...

It's really awesome that Redfield's group did this, a lot of people were just rejecting the NASA claims in theory, so it's really great to see that someone actually investigated it and attempted to confirm/reproduce the results. Even more fantastic that Redfield's initial suspicions were publically aired on her blog, so great to see such an open version of science with a high impact publication to follow up.

It's unfortunate that the co-Author's on Wolfe-Simon's paper seemed to have left it's defense to her. It's also unfortunate that her group didn't seem to want to debate anyone outside of a series of peer-reviewed articles too.

Matt G said...

One of the co-authors of the original paper is the ID creationist Paul Davies. He said something recently about how being "unencumbered by knowledge" (paraphrasing) helped him to wrap his mind around the paper. How/why he was a co-author is a mystery to me since molecular biology is not his field. Anyhow, good riddance to bad science!

Brian Malow said...

Jonathan Eisen found this version on NASATV's YouTube channel (and it's embeddable, if you want to grab the code):

Joachim Dagg said...

Haven't followed this affair. But it seems to me that the question she asked in the first place lead her astray, because a microbe surviving in a lake with high arsenic could as well detoxifying arsenic somehow rather than replacing it for phosphorus. Seems to be a case of not taking all possible alternatives into consideration and therefore misinterpreting data.

But that would just be normal human fallibility. I think what irated the skeptics and got her in for a thorough bashing is her vainglory announcing things lke "stay tuned fot the enxt 15 years ..." combined with the media hype. Otherwise such papers are being published and simply forgotten and no affair ever arises.

DK said...

her original paper never actually claimed that arsenate was being incorporated in GFAJ-1’s DNA, but that others had jumped to that conclusion.

From her paper's title: "using arsenic instead of phosphorus". Does she know the meaning of the word "instead"?

Verdict: Dishonesty coupled with incompetence.

Torbjörn Larsson said...

Interesting how the polarization among critics follow the cold fusion pathological science pathway, some notes that the bacteria simply lives well on phosphorous, some claims that arsenic uptake isn't invalidated. (Actually both groups seem to agree on the result, they just choose to interpret the context differently.)

@ Matt G:

I'm interested in "the ID creationist Paul Davies" stance in as much as it affects his astrobiology as it does his physics. He seems to be a deist, reading his physics books and seeing his Templeton success there.

But he has been outspoken against ID. What is your reference?

Matt G said...


Davies appears to be of the "god is in quantum mechanics," or "god is in the laws of physics" ilk. He may criticize ID, but since when has that ever deterred a creationist from nevertheless embracing it, albeit in another form? Cognitive dissonance is part and parcel of ID. Check out posts by Jerry Coyne about comments by Davies, and look at Davies' statements on the "Speaking of Faith" program. Davies can't claim to be a theistic evolutionist, I don't think.


Torbjörn Larsson said...

Thanks Matt, those look promising!

Anonymous said...

If the authors signed the rebuttal that was published, then that is their response. Why do they owe you an appearance on Judge Judy? When new results are *published* Oremland has said that he is likely to respond to them. As of now that has not happened.