NASAs announcement of a news conference "that will impact the search for evidence of extraterrestrial life" was criticized as sensationalistic and misleading; an editorial in New Scientist' commented "although the discovery of alien life, if it ever happens, would be one of the biggest stories imaginable, this was light-years from that".
In addition, many experts who have evaluated the paper have concluded that the reported studies do not provide enough evidence to support the claims made by the authors. In an online article on Slate, science writer Carl Zimmer discussed the skepticism of several scientists: "I reached out to a dozen experts ... Almost unanimously, they think the NASA scientists have failed to make their case". Chemist Steven A. Benner has expressed doubts that arsenate has replaced phosphate in the DNA of this organism. He suggested that the trace contaminants in the growth medium used by Wolfe-Simon in her laboratory cultures are sufficient to supply the phosphorus needed for the cells DNA. He believes that it is more likely that arsenic is being sequestered elsewhere in the cells. University of British Columbia microbiologist Rosemary Redfield said that the paper "doesnt present any convincing evidence that arsenic has been incorporated into DNA or any other biological molecule", and suggests that the experiments lacked the washing steps and controls necessary to properly validate their conclusions. Harvard microbiologist Alex Bradley said that arsenic-containing DNA would be so unstable in water it could not have survived the analysis procedure.
On 8 December 2010, Science published a response by Wolfe-Simon, in which she stated that criticism of the research was expected. In response, a "Frequently Asked Questions" page to improve understanding of the work was posted on 16 December 2010. The team plans to deposit the GFAJ-1 strain in the ATCC and DSMZ culture collections to allow widespread distribution. In late May 2011 the strain was made available upon request directly from the laboratory of the authors.  Science has made the article freely available. The article was published in print six months after acceptance in the 3 June 2011 issue of Science.  The publication was accompanied by eight technical comments addressing various concerns regarding the articles experimental procedure and conclusion, as well as a response by the authors to these concerns. The editor in chief Bruce Alberts has indicated that some issues remain and that their resolution is likely to be a long process. A review by Rosen et al., in the March 2011 issue of the journal BioEssays discusses the technical issues with the Science' paper, provides alternative explanations, and highlights known biochemistry of other arsenic resistant and arsenic utilizing microbes.
On 27 May 2011, Wolfe-Simon and her team responded to the criticism in a follow-up Science journal publication. Then in January 2012 a group of researchers led by Rosie Redfield at the University of British Columbia analyzed the DNA of GFAJ-1 using liquid chromatography–mass spectrometry and could not detect any arsenic, which Redfield calls a "clear refutation" of the original paper's findings. Following the publication of the analysis, Wolfe-Simon stated that she and her colleagues "expect to publish new information in the next few months", but as of 2024 has not submitted any new publications since 2011.
A simple explanation for the GFAJ-1 growth in medium supplied with arsenate instead of phosphate was provided by a team of researchers at the University of Miami in Florida.  After labeling the ribosomes of a laboratory strain of Escherichia coli with radioactive isotopes (forming a radioactive tracer), they followed bacterial growth in medium containing arsenate but no phosphate.  They found that arsenate induces massive degradation of ribosomes, thus providing sufficient phosphate for the slow growth of arsenate tolerant bacteria.  Similarly, they suggest, GFAJ-1 cells grow by recycling phosphate from degraded ribosomes, rather than by replacing it with arsenate.
Following the publication of the articles challenging the conclusions of the original Science article first describing GFAJ-1, the website Retraction Watch argued that the original article should be retracted because of misrepresentation of critical data. , the paper had not been retracted.