Critics weigh in on arsenic life

Erika Check Hayden

Nearly six months after its online publication in Science1, the controversial suggestion that a newly discovered bacterium survives by incorporating arsenic atoms into its DNA and other biomolecules is facing a volley of terse critiques which appeared today on the journal's web site.

Many of the criticisms had already been aired through blogs and other publications. The arsenic paper's authors, who had previously defended their work, continue to do so in a technical response issued today alongside the critiques. They say they will distribute samples of the bacterium, GFAJ-1, so that other researchers can attempt to replicate their work.

Now the field is looking to independent researchers to take them up on that offer, to support - or refute - an overwhelming sense that the study suffers from flaws that undermine its conclusions. Some were frustrated that the authors did not release any new data in their response, noting that most of the critiques released today were submitted just days after the original paper was published, and had been aired publicly, allowing ample time for the authors to bolster their case with new data.

"I'm tired of rehashing these preliminary data," said John Helmann of Cornell University in Ithaca, New York, who critiqued the work in January on the Faculty of 1000 web site. "I look forward to the time when they or others in the field start doing the sort of rigorous experiments that need to be done to test this hypothesis."

The controversy first erupted in December, when NASA's press office issued a cryptic news release regarding an "astrobiology finding that will impact the search for evidence of extraterrestrial life." Once revealed, it quickly became apparent that the finding, if true, would be astonishing, because it would imply that an organism has evolved to incorporate the usually toxic element into its genetic backbone, possibly suggesting a broader range of molecular building blocks for life on Earth and beyond.

However, the work was quickly assailed by researchers, both for not living up to NASA's billing about relevance to extraterrestrial life, and for being marred by technical shortcomings that, they said, imperil its eye-popping conclusions.

"I have not found anybody outside of that laboratory who supports the work," says Barry Rosen of Florida International University in Miami, who published a critique of the work in BioEssays in March.

The comments published today include eight critiques of the original paper, whose first author was Felisa Wolfe-Simon of the NASA Astrobiology Institute and the U.S. Geological Survey in Menlo Park, Calif. Wolfe-Simon has previously defended her work both on her web site, and in the pages of the women's magazine Glamour , where she dispensed her "four laws of getting people to believe in you."

"We maintain that our interpretation of As [arsenic] substitution, based on multiple congruent lines of evidence, is viable," she and her colleagues write today.

In their study, the authors analyzed bacteria taken from Mono Lake in southern California. The bacteria were grown in the lab on a medium that, the authors said, contained arsenic but no phosphorus - the core constituent of the DNA double helix. The authors found that the bacteria reproduced, and integrated arsenic into their DNA.

The critiques attack multiple parts of the work. Several allege that the growth medium that supposedly only contained arsenic actually contained trace amounts of phosphorus - enough to support a few rounds of bacterial growth. Others say that the evidence purporting to show that arsenic integrated into the bacterium's DNA is flawed because the DNA was not properly purified.

Two authors in Hungary write2 that the authors used flawed methods to calculate the ratios of arsenic and phosphorus in their growth media. Many of the authors also said that there are alternative explanations for the fact that the bacteria could grow on a medium containing little or no phosphorus, such as the possibility that the medium selected for arsenic-tolerant bacteria that out-competed the non-tolerant microbes.

Some criticisms of the work come from within the same agencies that employ the authors; four of the authors of one critique are based at NASA's Jet Propulsion Laboratory, managed by the California Institute of Technology in Pasadena, Calif.

"GFAJ-1 appears to do all it can to harvest P atoms from the medium while drowning in As," they write3. "This suggests that GFAJ-1 is an extraordinary extremophile but does not support the more exceptional claim that As replaces the functions of P in this organism."

Steven Benner of the The Foundation for Applied Molecular Evolution in Gainesville, Fl., suggests a series of follow-up experiments that could be done to provide more solid evidence that arsenic has incorporated into the bacterium's DNA4. The big question for the field is whether and when independent labs will perform the necessary follow-up experiments to provide evidence that would support or rebut the critics' claims.

If GFAJ-1 is indeed utilizing arsenic as Wolfe-Simon and her coauthors suggest, Benner writes, the result would "set aside nearly a century of chemical data concerning arsenate and phosphate molecules." Benner cautions that inconsistent results should not be "discarded out of hand", however he criticizes the paper for not fully taking into account how much existing science would need to be rewritten to accommodate its extraordinary claim.

Rosemary Redfield of the University of British Columbia, who previously critiqued the arsenic paper on her blog and who published one of the commentaries released in Science today5, says that proving or disproving the work would not be difficult. She said it would be "relatively straightforward" to grow the bacteria in arsenic-containing media and analyze it using mass spectrometry to test whether arsenic is covalently bonded into the DNA backbone.

"The important thing to do is what the authors didn't do, which is meticulously clean up the DNA first," Redfield said.

She said that she would likely obtain samples of GFAJ-1 and is considering performing the follow-up experiments she describes, and is especially interested in getting a group of five of six laboratories to repeat the experiments independently and publish their results together.

However, most labs are too busy with their own work to spend time replicating work that they feel is fundamentally flawed, and it's not likely to be published in high-impact journals. So principal investigators are reluctant to spend their resources, and their students' time, replicating the work.

 
"If you extended the results to show there is no detectable arsenic, where could you publish that?" said Simon Silver of the University of Illinois at Chicago, who critiqued the work in FEMS Microbiology Letters in January and on 24 May at the annual meeting of the American Society for Microbiology in New Orleans. "How could the young person who was asked to do that work ever get a job?" Silver said.

Refuting another scientist's work also takes time that scientists could be spending on their own research. For instance, Helmann says he is in the process of installing a highly sensitive mass spectrometry machine capable of measuring very small amounts of elements. But, he says, "I've got my own science to do."

Helmann also points out that the bacterium is not yet available through cell repositories, and that researchers may be reluctant to sign the materials transfer agreement required to obtain it from the authors.

He and other researchers also said that the response released by the authors of the Science paper appear reluctant to accept that there may be alternative explanations for the phenomenon they observed.

"With so many mistakes pointed out, there should be at least some where the authors say, you're right, we should have done that but we didn't," Redfield says. "This as an entirely a 'we were right' response, and that's a bad sign in science." nature.com