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Two studies show 'weird life' microbe can't live on arsenic

Why was this such a big deal to begin with? In this "Last Word" video from December 2010, MSNBC's Lawrence O'Donnell discusses the arsenic-life controversy with Bill Nye the Science Guy.

A year and a half after one team of researchers claimed they had bred a type of bacteria that could live on arsenic, suggesting that life is weirder than we imagine, two other teams have found that the microbe really doesn't do anything with the arsenic after all.

These two teams say that the microbe, known as GFAJ-1, is somewhat weird, due to the fact that it can survive amid ultra-high concentrations of arsenic. But they confirm the widely held view among microbiologists that GFAJ-1 did not rewrite the existing rules of life — an extraordinary claim that was implied by the initial study, which made a huge splash in December 2010.

"The new research clearly shows that the bacterium, GFAJ-1, cannot substitute arsenic for phosphorus," the journal Science, which published the initial findings as well as today's follow-up studies, said in an editorial statement.

Case closed?
One of the authors of the new research, University of British Columbia microbiologist Rosie Redfield, was among the most outspoken critics of the original study — and she said that as far as she was concerned, today's publication closes the case. "This isn't an area I have any special interest in, or any funding for," she told me in an email.

Over the past 19 months, Redfield has focused on the analysis of GFAJ-1's DNA more as a case study in open science — a perspective that focuses on freely sharing the results of the research process as they come to light. The study that she and her colleagues authored has been available for months on the ArXiv pre-print website. (The other study, conducted by researchers at ETH Zurich in Switzerland, became public just today.)

Science's editors decided to time today's online publication of the two studies to coincide with a talk that Redfield was due to give at a conference in Ottawa on evolutionary biology. Redfield said last week on her blog that she'd be discussing the results of her group's research, including the Science paper, during her talk. When I contacted her on Friday about the impending publication, she expressed surprise that the journal accelerated its publishing schedule.

"What? No!" she wrote in an initial email. "Must be because of my Evolpalooza talk that night."

The print version of the papers released tonight are to appear in Science later this month.

In the past, the lead researcher for the original study of GFAJ-1, Felisa Wolfe-Simon, has declined to comment in detail about the follow-up experiments that have raised questions about her group's work. She has said such comments would have to wait until those experiments were described in peer-reviewed research articles. But due to the publication in Science, Wolfe-Simon responded to my emailed inquiries at greater length.

She acknowledged that the follow-up experiments failed to find evidence that compounds containing arsenic, known as arsenates, were being taken up into the molecular machinery of GFAJ-1's life processes, such as DNA. However, she said those experiments were apparently conducted under conditions that differed from those surrounding the original experiment.

"We do not know the history of the cells in these new papers," she wrote. "In general, it requires more evidence to publish something unexpected — e.g., that cells can thrive in arsenic and that arsenate is found inside the cells, than something that everyone expects — e.g. that arsenate is not found inside cells or DNA.

"Our original work and data was in fact given high scrutiny, as standards are almost always higher for evidence for things that are unexpected. We are actively following the arsenic in our cells and will know more in the next few months." (The full email exchange is laid out in a comment below.)

Sensationalism and skepticism
The original point of the arsenic-life experiment was to see whether organisms on Earth could be coaxed to use arsenic, which generally acts as a poison, in place of phosphorus, which is generally seen as one of the essential chemical building blocks of life. The structure of those two elements on the atomic level is similar, which is a big reason why substituting one for the other is so lethal.

If some types of organisms, even bacteria, could live on arsenic, that would upset the mainstream view of how life works. Such a finding, if confirmed, would potentially lead to a wider search for "weird life" — not only on Earth, but also in extraterrestrial environments such as the Martian subsurface or the hydrocarbon lakes of Titan.

Wolfe-Simon and her colleagues conducted their search for arsenic-eating life by taking samples from the arsenic-rich sediments of California's Mono Lake, then turning up the dial on the arsenic and turning down the dial on the phosphorus in their laboratory's cell cultures. They isolated a strain of bacteria that grew in a setting with ultra-high concentrations of arsenic and seemingly negligible amounts of phosphorus. (The strain's name, GFAJ-1, stands for "Give Felisa a Job.")

Analysis of the cells led them to conclude that arsenic was being used in place of phosphorus, even in GFAJ-1's DNA molecules. The findings created a sensation when they were announced. "We're talking about an organism that we think ... is replacing phosphorus with arsenic," Mary Voytek, the head of NASA's astrobiology program, said at the time. "This is a huge deal."

The case sparked a huge backlash as well. Many scientists questioned the results — not only in comments to journalists, but also in blog postings and Twitter updates. Redfield suspected that the detection of arsenic was due to sample contamination rather than an uptake into DNA molecules. The experiment in which she was involved, conducted with Princeton's Marshall Louis Reaves as lead researcher, reported finding "only trace amounts of free arsenate" and no chemically bound arsenic compounds in the DNA samples they extracted from GFAJ-1.

In their Science paper, the researchers say the reason for the dramatically different results "is not clear," but they also note that "differences in DNA purity can readily explain" the discrepancies.

How GFAJ-1 works
The other study published today, with ETH Zurich's Tobias Erb as lead author, takes a wide-angle view of GFAJ-1, using mass spectrometry and other tools to trace the bacteria's chemical processes on the molecular level. They found that the microbes could grow with even less phosphorus than the tiny amount that was provided in the experiments by Wolfe-Simon and her colleagues. But when the phosphorus concentration was reduced to nearly nothing (less than 0.3 micromolar), no growth was observed.

Some arsenic compounds formed in the culture, but at a level that was more likely associated with non-biological chemical processes, Erb and his colleagues said. They noted that such compounds are also found in garden-variety E. coli bacteria when they're grown in cultures containing arsenic. This suggests that the detection of arsenic-containing compounds "might not be of physiological relevance," they wrote.

The two groups of researchers acknowledged that there was something extraordinary about GFAJ-1, in that it could grow amid ridiculously high concentrations of arsenic — roughly an order of magnitude higher than previously seen for other organisms, the Swiss-based scientists said. "The molecular basis for arsenate resistance in GFAJ-1 might be the subject of further investigations," they wrote.

It's also noteworthy that GFAJ-1 could survive amid ridiculously low concentrations of phosphorus. Wolfe-Simon and her colleagues said that was because the bacteria switched to metabolizing arsenic. But Reaves, Redfield and their colleagues said it was more likely that GFAJ-1 used a metabolic mechanism to enrich the tiny amount of phosphorus it could grab onto.

More research ahead
In her emails, Wolfe-Simon said the data reported in the newly published research did not contradict the thrust of her own studies, which are continuing. She said it's possible that the arsenic compounds taken up by GFAJ-1 become less stable "once cells are broken open."

"We expect to have our own results ready for publication in the next few months," she wrote. "We are focused on the questions, 'Where exactly is the arsenate going?' and 'How does this microbe survive in high arsenate?' These results will speak to the flexibility of the periodic table for life, so [they] merit the most thorough and careful analysis we can achieve."

In their statement, Science's editors took a different perspective.

"The new research shows that GFAJ-1 does not break the long-held rules of life, contrary to how Wolfe-Simon had interpreted her group's data," they said. "The scientific process is a naturally self-correcting one, as scientists attempt to replicate published results. Science is pleased to publish additional information on GFAJ-1, an extraordinarily resistant organism that should be of interest for further study, particularly related to arsenic-tolerant mechanisms."

Redfield agreed that GFAJ-1 was worthy of further study, even if she's not going to be doing it. "I think all organisms turn out to have interesting tweaks," she told me in her email. "We certainly know very little about the biology of GFAJ-1, and there are complications I never sorted out."

So just how big of a deal did the "arsenic life" controversy turn out to be? To my mind, the case seems likely to take its place among the other great disputed claims in science, ranging from cold fusion to Martian nanofossils and the missing-link primate. It also feeds into the debate over the best ways to distribute and verify scientific findings. Lots of folks will be weighing in on these questions over the next day or two, and you can have the last word in the comment section below.

Previous chapters in the weird-life saga:

In addition to Reaves and Redfield, the authors of "Absence of Detectable Arsenate in DNA from Arsenate-Grown GFAJ-1 Cells" include Sunita Sinha, Joshua D. Rabinowitz and Leonid Kruglyak.

In addition to Erb, the authors of "GFAJ-1 Is an Arsenate-Resistant, Phosphate-Dependent Organism" include Patrick Kiefer, Bodon Hattendorf, Detlef Günther and Julia A. Vorholt.

Science said the two papers, along with an editorial statement, were being released at 8 p.m. ET July 8 "to coincide with a related conference." That was a reference to Redfield's talk at the Evolution Ottawa conference.

Alan Boyle is msnbc.com's science editor. Connect with the Cosmic Log community by "liking" the log's Facebook page, following @b0yle on Twitter and adding the Cosmic Log page to your Google+ presence. You can also check out "The Case for Pluto," my book about the controversial dwarf planet and the search for new worlds.