In 2010, Wolfe-Simon led a team that discovered GFAJ-1, an extremophile bacterium that they claimed was capable of substituting arsenic for a small percentage of its phosphorus to sustain its growth, thus advancing the remarkable possibility of non-RNA/DNA-based genetics.

[6] She received her Doctor of Philosophy in oceanography from the Institute of Marine and Coastal Sciences at Rutgers University in 2006 with a dissertation titled The Role and Evolution of Superoxide Dismutases in Algae.

At a conference in 2008 and subsequent 2009 paper, Wolfe-Simon, Paul Davies and Ariel Anbar proposed that arsenate (AsO3−4) could serve as a substitute for phosphate (PO3−4) in various forms of biochemistry.

This search led to the discovery of the bacterium GFAJ-1, which her team claimed in a Science on-line article in December 2010 was able to incorporate arsenate as a substitute for a small percentage of the typical phosphate in its DNA and other essential biomolecules.

[29] She briefly worked at Lawrence Berkeley National Laboratory but the GFAJ-1 controversy impaired her ability to obtain funding and she left the research career-path.

[22] She subsequently worked mainly as a performer and teacher of the oboe, and partly in science-adjacent roles including organising seminars at Mills College at Northeastern University, consulting for biotech startups, and industrial microbiology for bakeries.