On the Monday of November 29, 2010, a news came out in a fairy bored way: NASA was going to hold a press conference in December 2, Thursday. Maybe just some routine reports from International Space Station. However, in that afternoon, NASA implied it was about a new life form. Suddenly, the internet exploded, everyone was asking if that would be the discovery of extraterrestrial life. 

I kept checking internet in the following two days. NASA did pretty good job to zip out any hint, leaving all the scientific speculators in anxiety. On Thursday, I went to lab in the morning but could not do anything other than refreshing my browser on computer continuously. Finally, it's 1PM, I got connected to NASA link instantly. Here we would find how the alien looked like!

When the PI of NASA-funded project, Felisa Wolfe-Simon, spoke, the mystery was revealed: she found a bacterium for which she claimed  arsenate as a substitute for phosphate in its DNA and other essential biomolecules. So, it's not an alien life in other planet, but a new life form on earth. The buzz in internet suddenly dissipated, but all the biologists got excited! 

I remember watched the press conference with awe-striking feeling. Felisa explained her crispy clear hypothesis: life may adapt the arsenic-rich environment by using arsenate instead of phosphate, since both elements are belonged to the same family in periodic table.  To test it, she led a team to screen bacteria thriving in the arsenic-rich Mono Lake, California, and identified a strain with arsenate-incorporated DNA. This was a beautiful result from a  process of scientific exploration. She gave a cute name to this new strain of bacterium, GFAJ-1, for "Give Felisa a Job".

The whole time of the press conference was full of victorious and cheering tones. However, there was a calm, even alarming, voice from one of the panelists, Steven Benner, a biochemist and evolutionary biologist, expressing the concern: the chemical bonds in arsenate are too weak to hold the backbone of DNA. However, his concern was dismissed by NASA and the journal that was publishing Felisa's paper. The sense of caution was submerged in the celebrating messages in the social media.  

Looking back, this was an bad omen of what was following.

Felisa's paper was published in Science in December 2nd, 2010, the Monday after the NASA press conference. It immediately took the field of biology by a storm. Everyone was talking about the "arsenic bacterium" and wondered if this opened the gate to find new life forms in exotic environment. The clip of Felisa speaking in the NASA conference was displayed in every news channel. She received many interviews by media and gave presentation in many conferences and seminars, and TED talk, or took part in the production of documentary of pop-science program NOVA of PBS.  Time magazine selected her as one of its Time 100, an annual list of “the most influential people in the world.” There was discussion if this discovery might deserve a Nobel Prize. 

On the other hand, many biologists felt very suspicious about the results and question the quality of this study. Following the publication of Felisa's paper, there were eight letters- mostly critical or questioning opinions on the study method- published in Science. Who knows how many others were submitted but not published.  Five commentary piece expressing concerns were published in Science and other journals, and many more were trying to publish their testing results on GFAJ-1. Felisa was fully confident about her discovery; she held the tone that the finding was a sure thing so all the criticisms were technical. She had no fear to send the sample of GFAJ-1 to any requester. Rosie Redfield, a microbiologist at the University of British Columbia, Canada, was very frustrated that she could not reproduce Felisa's results after many efforts. During the period, she led the criticism through her blog, RRResearch, which updated her observation or thoughts on the flaws of Felisa's paper at weekly or even daily basis. Redfield's criticism included that trace phosphorus in the culture media could have fueled GFAJ’s growth, and that Felisa had inadequately purified the DNA. 

Meanwhile, Felisa and NASA's PR team decided to avoid any debate while working on the analyses to answer the technical criticisms, so they stayed quiet. However, during this period of time Felisa still accepted the invitations to show up in the media or public events. Unfortunately, some commentators regarded this as an arrogant response, as they have been irritated by Felisa's defense- over-confidence and defensive, never considering to address the technical question, by their interpretation . The attacks aggravated at daily bases, including more evidence against Felisa's hypothesis, and I remembered feeling like witness the besiege of a city.

In May 27, 2011- about half year after publication of GFAJ-1- Felisa and the team published the responses to the technical criticisms in Science. They admitted that there was trace amount of phosphate in the salt ingredient of the culture medium (~ 3 uM); however, the bacterium grew when the arsenate was added into the phosphate-depleted medium. Moreover, the detoxification reaction of arsenate was not detected, so arsenate was likely incorporated into the macromolecules at the phosphate position. Three other questions were also responded.

Up to this point, some of the researchers no longer trusted any results generated from Felisa's studies. They aimed to debunk it, so all kinds of experiments were in cooking. In August, 2012, two papers that intended to reproduce Felisa's results and investigated why they could not were published side-by-side in Science. One was performed by Julia Vorholt Lab, the other by, eh, Felisa's "Nemesis",  Rosie Redfield. Both studies showed that GFAJ-1 could tolerate high concentration of toxic arsenate, but definitely needed phosphate to grow, even at very low level (~1.6 uM, notice it 50% lower than the phosphate contamination value in Felisa's study). Also, trace of free arsenate may stick with the DNA but there was no evidence of substitution of phosphate. These were the last two nails for the coffin of GFAJ-1 as the arsenic life form.

Studies on GFAJ-1 continued in many groups. This bacterium strain becomes a microbe model of arsenate tolerance or resistance, and you can find studies using it published very recently.  However, one year after the two refuting papers published, Felisa was obviously exhausted and left the NASA-funded research job. Based on her LinkedIn profile, she did some kind of freelance works for a few years, and then did teaching and laboratory management for another few years. I would be saddened very much if she exiled herself from scientific research. Luckily, I found that she joined a research institute as a PI this year, which is a cheerful news for me.

Felisa made mistakes in the GFAJ-1 study, and her over-zealous confidence to the phosphate substitute theory, and overwhelmingly surging fame, blinded her and the team from taking the right approach for new tests and response to criticism. However, the piling criticisms in the period can be described as over-reacting emotionally. Even in 2021, nine years after the two refuting papers published, there was still calling to retract the GFAJ-1 paper. It is not fair that all the fingers pointing only to Felisa. The biggest issue in that study was so obvious, as Steven Benner pointed out, that the arsenate bond was easily hydrolyzed in aqueous solution. In fact, that's why arsenate is toxic; it's just too reactive. Some biophysical study had shown that the half life of the arsenate-based DNA was only minutes. So obvious that every biochemist should know, why the manuscript passed review process? Should not the editors and reviewers take responsibilities? Were NASA and the journal too eager in publishing the paper anyway, thus ignoring all the problems? If that was the case, what is the meaning of peer review?

Other than papers deliberately made by fraud, this was not the first time the top-tier journals published studies that made mistakes. It is so well-known that we have a problem of reproducibility in the current biomedical research. Why do the scientific community or the journals not check those papers one by one and ask the authors to respond? It is supposed a good thing to do, but this is done only to Felisa's paper. Is that a double standard? I have no intention to defend Felisa, but her incidence may expose some deeper issues in the current biomedical research.

I am also very concerned that the harsh treatment given to Felisa may signal the future researcher: only do "safe" research, do not challenge the paradigm- that's exactly why Felisa's paper got so much scrutiny. Yes, she made mistake. However, was the mistake so bad to kill her full idea: life can be developed in a flexible way in different environment? I want to ask this question: could the arsenate-based DNA be stable enough in different kind of solution- for example, organic solvent, or in very low temperature?

Is this question relevant? I think so. Titan, the biggest moon in solar system, has rivers and lakes full of methane under the low temperature. As Felisa's paper was killed, do we miss the chance to find exotic DNA in another corner of solar system?

Reference:

Scientist in a Strange Land

A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus

Response to Comments on “A Bacterium That Can Grow Using Arsenic Instead of Phosphorus”

GFAJ-1 Is an Arsenate-Resistant, Phosphate-Dependent Organism

Absence of Detectable Arsenate in DNA from Arsenate-Grown GFAJ-1 Cells

Why nature really chose phosphate