A debate that erupted 5 months ago over whether a bacterium incorporates arsenic into its DNA is about to start simmering again. Today online in Science eight research groups voice their concerns about a paper that appeared 2 December 2010 online in Science and will be published in next week's issue of the journal. The original article presented an exception to one of the fundamental rules of life on Earth. To survive, microbes, plants, and animals all require six essential elements: oxygen, carbon, nitrogen, hydrogen, sulfur, and phosphorus. But NASA astrobiology fellow Felisa Wolfe-Simon and her colleagues isolated a bacterium that, when grown with high arsenic concentrations and no added phosphorus, appears to replace some phosphorus with the chemically similar arsenic in key biomolecules, including DNA.
A startling discovery in and of itself, the finding became even more controversial because a NASA press announcement in December implied a connection to the search for extraterrestrial life. Yet many scientists were sharply critical of the paper, including several who blogged about their concerns in posts that drew hundreds of comments that offered additional attacks on the work. When journalists tried to follow up, Wolfe-Simon, then at the U.S. Geological Survey in Menlo Park, California, and her colleagues initially declined to respond, fueling speculations about the soundness of the research. The group eventually posted a response. And in a subsequent interview, Wolfe-Simon said she and her co-authors welcomed the debate but, "We wanted to be able to have that discourse in the scientific community, as a record."
That discourse has now begun with the so-called Technical Comments published today online by Science, along with a response by Wolfe-Simon and her colleagues. The exchange does not put forth new data on the matter, but centers on the original experiments in which Wolfe-Simon isolated bacteria from arsenic-laden Mono Lake, California, and then tried to grow them in cultures with large amounts of arsenic and no phosphorus, which is typically required for growth. One strain called GFAJ-1 still managed to multiply, despite the dearth of phosphorus, the original paper reported.
Several of the Technical Comments question whether contamination or background levels of phosphorus in the cultures could have fueled this growth. Another researcher worries that the DNA that was described as likely having arsenic incorporated in its structure might have been contaminated. Others suggest that arsenic compounds are too unstable to replace phosphorus compounds and be functional. "Their hypothesis that this microorganism contains DNA and other standard biomolecules in which arsenate atoms replace phosphorus atoms would, if true, set aside nearly a century of chemical data concerning arsenate and phosphate molecules," writes Steven Benner, an astrobiologist at the Foundation for Applied Molecular Evolution in Gainesville, Florida, in one of the Technical Comments.
Wolfe-Simon's team has acknowledged that there were indeed trace amounts of phosphorus in the media used, contributed by mineral salts—they even noted this in their paper. But Wolfe-Simons maintains there was not enough background phosphorus to drive the bacterial growth.
University of British Columbia microbiologist Rosie Redfield, the blogger most critical of Wolfe-Simon both personally and professionally, asserts in one of the Technical Comments that Wolfe-Simon did not go far enough in purifying DNA from GFAJ-1 before testing it for its arsenic components.
The issue of whether arsenic-containing molecules would be stable in a cell is the subject of three of the Technical Comments. In the cytoplasm, arsenate would be reduced to arsenite, which would not be able to substitute for phosphate, Barbara Schoepp-Cothenet, from the Bioénergétique et Ingénierie des Protéines in Marseilles, France, and colleagues, claim in one comment. Moreover, phosphates are incorporated into DNA early in a multistep process, and an arsenic substitute would be unlikely to survive that process intact, notes Benner.
In a response accompanying the Technical Comments, Wolfe-Simon and her co-authors point to work by others that suggests that these arsenic compounds would last longer when part of large biomolecules. Her group has proposed that the bacterium might sequester the arsenic compounds to protect them from breaking down. "In the comments, there were lots of good points that were raised," says Wolfe-Simon's co-author Samuel Webb, a biogeochemist at the Stanford Synchrotron Radiation Lightsource in Menlo Park, California. "With anything this intriguing or controversial, there will always be multiple sides."
In a note published along with the comments and the response, Bruce Alberts, Science's Editor-in-Chief, acknowledges that the debate over the bacterium is far from over, writing: "We recognize that some issues remain unresolved. However, the discussion published online today is only a step in a much longer process."