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Science / AAAS
A photomicrograph shows GFAJ-1 bacteria that were coaxed to grow in an arsenic-rich medium.
Did scientists really coax microbes found in a California lake to act like alien life forms? Last week I wrote that some scientists just couldn't believe the claims that were reported in the journal Science, and since then the controversy has only grown more contentious.
"This paper should not have been published," science writer Carl Zimmer quotes University of Colorado microbiologist Shelley Copley as saying in a roundup of highly critical commentary gathered for Slate.
The key claim in the Science paper was that a strain of salt-loving bacteria from California's Mono Lake, known as GFAJ-1, was weaned away from consuming phosporus and forced to use arsenic instead. The researchers said the experiment showed that arsenic -- which is poisonous to life as we know it -- could serve as a substitute for an element that is generally considered an essential for life.
The implication was that life forms may well exist in arsenic-rich environments on Mars or the moons of Jupiter or Saturn, and that they might go unnoticed unless we expand our view on what life requires.
That big-picture view still holds true: Few biologists would insist that the recipe for life elsewhere in the universe has to use Earth's main ingredients (carbon, hydrogen, oxygen, nitrogen, sulfur and phosphorus). But if last week's buzz focused on how bacteria could be taught alien tricks with arsenic, this week's buzz is about how the researchers may have left out some essential steps for making their case.
"Something's wrong," Steven Benner, an astrobiologist at the Foundation for Applied Molecular Evolution, told me last week. "This is a recipe for creating these kinds of confrontations."
Benner said the case of arsenic-based life might well end up like the case of cold fusion, or the case of Martian nanofossils, with researchers from different disciplines arguing for years over the details of how the experiments were done. There was some of that even last week: Benner contended that there was still just barely enough phosphorus left in the experiment to sustain the bacteria, but during a NASA news conference to discuss the results, lead researcher Felisa Wolfe-Simon of the U.S. Geological Survey said the trace amounts of phosphorus couldn't have kept the microbes alive.
Wolfe-Simon's colleague at USGS, Ron Oremland, repeated that view today during a NASA webcast about the research. "There's a smidgen of phosphorus in the medium ... but it's not enough to sustain growth," he said.
Oremland acknowledged that "we can't do everything" to make an ironclad case for arsenic-based life, and said it would be up to other scientists to repeat the experiment and assess the results. "They may prove us wrong, or they may reproduce the results and find new stuff," he said.
If the bacteria were still living off that "smidgen of phosphorus," why did they contain so much arsenic? The critics say that the arsenic was contamination, and they continue to doubt that the arsenic molecules were actually incorporated into GFAJ-1's cellular machinery. In a detailed blog posting over the weekend, University of British Columbia microbiologist Rosie Redfield said the researchers failed to give the DNA from the microbes a thorough enough cleaning to remove contaminants. That may have been why their analysis led them to claim that "arseno-DNA" had been created.
"If this data was presented by a Ph.D. student at their committee meeting, I'd send them back to the bench to do more cleanup and controls," Redfield wrote.
Other researchers said that if arsenic was truly incorporated into the DNA, the relatively unstable molecular bonds should have fallen apart when they came in contact with water.
All this is what led Benner to bet Wolfe-Simon $100 that the DNA was not arsenic-based after all. But that $100 may be in dispute for a while. In the Slate article, Zimmer quotes Wolfe-Simon as saying "any discourse will have to be peer-reviewed in the same manner as our paper whas, and go through a vetting process so that all discussion is properly moderated."
Which raises another question: If there's so much griping about the research now, why weren't these concerns raised during the peer-review process?
"I don't know whether the authors are just bad scientists or whether they're unscrupulously pushing NASA's 'There's life in outer space' agenda," Redfield wrote. "I hesitate to blame the reviewers, as their objections are likely to have been overruled by Science's editors in their eagerness to score such a high-impact publication."
Stay tuned to hear more about that angle in the days ahead. Meanwhile, here's a roundup of week-after reconsideration:
- Slate: 'This paper should not have been published'
- LiveScience: Debate over arsenic-based life gets lively
- Embargo Watch: An arsenic bacteria postmortem
- Wired Science: Doubts brew about arsenic life
- Nature News: Microbe gets toxic response
- CBC News: Arsenic microbe science slammed
- Seed Magazine: Death for 'arsenic-based life'?
- We, Beasties: Arsenate-based DNA: Big idea with big holes
- Highly Allochthonous: This is what peer review actually looks like
- The Observatory at CJR: The right place for scientific debate?
Update for 5 p.m. ET Dec. 8: ScienceInsider's Elizabeth Pennisi passes along a statement that Wolfe-Simon posted to her website:
"My research team and I are aware that our peer-reviewed Science article has generated some technical questions and challenges from within the scientific community. Questions raised so far have been consistent with the range of issues outlined by journalist Elizabeth Pennisi in her Science news article, which was published along with our research. For instance, other scientists have asked whether the bacteria had truly incorporated arsenic into their DNA, and whether the microbes had completely stopped consuming phosphorus. Our manuscript was thoroughly reviewed and accepted for publication by Science; we presented our data and results and drew our conclusions based on what we showed. But we welcome lively debate since we recognize that scholarly discourse moves science forward. We've been concerned that some conclusions have been drawn based on claims not made in our paper. In response, it's our understanding that Science is in the process of making our article freely available to the public for the next two weeks to ensure that all researchers have full access to the findings. We invite others to read the paper and submit any responses to Science for review so that we can officially respond. Meanwhile, we are preparing a list of 'frequently asked questions' to help promote general understanding of our work."
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Here are extended comments from astrobiologist Steven Benner:
"This work provides an important system to advance our understanding of how terran life might adapt to environments rich in arsenate but scarce in phosphate", said Steven Benner, Distinguished Fellow of the Westheimer Institute at the Foundation for Applied Molecular Evolution in Gainesville Florida.
"The reported microbe may be an excellent system to learn the extent to which this adaptation reflects mechanisms to tolerate arsenate, whether the microbe has novel metabolic pathways or biostructures that incorporate arsenic and, most exciting, whether the organism has found ways to substitute arsenate for phosphate in standard biomolecules.
"The data in the paper report a remarkable feature of this organism, an ability to grow with added phosphate (without added arsenate), an ability to grow with added arsenate (without added phosphate), but an inability to grow in the absence of both added arsenate and added phosphate.
"Back of the envelope calculations suggest that the amount of phosphate that appears to be present when phosphate is not directly added (this phosphate presumably comes from contamination in the culture mixtures) is barely sufficient, if sufficient at all, to support the inventory of ribosomal RNA, transfer RNA, DNA, and metabolic phosphate required for standard cellular metabolism."
"How this organism has acquired this feature remains unknown. I do not see any simple explanation for the reported results that is broadly consistent with other information well known to chemistry.
"In particular, any hypothesis that arsenate might replace phosphate in biomolecules such as DNA (where arsenate diesters would replace phosphate diesters) or NADH and ATP (where pyroarsenate would replace pyrophosphate) must manage known rates for the hydrolysis of arsenate esters and arsenate anhydrides in water.
"Arsenate esters fall apart in water with half lives conveniently measured in minutes. Arsenate anhydrides fall apart in water with half lives measured in seconds. In contrast, the uncatalyzed rate of hydrolysis of phosphate diesters takes millennia. These rate constants are well measured, and are a cornerstone of physical organic theory that unifies much that is known about phosphates, arsenates, and the analogy between these two.
"While it is conceivable that a living system might have second and third molecules to interact with such novel arsenate-containing compounds to stabilize them within a cell, it is not clear that those interacting molecules would remain in contact with novel arsenate DNA following the procedures (phenol and chloroform extraction, ethanol precipitation) used to isolate products shown, for example, in the gel in Figure 2. Nor is it clear why the band in the gel would be so sharply defined if it were arseno-DNA associated with stabilizing molecules.
"Thus, it remains to be established that this bacterium uses arsenate as a replacement for phosphate in its DNA or in any other biomolecule found in 'standard' terran biology.
"If, however, the replacement hypothesized in this paper is established by chemical analysis, the result will have sweeping consequences. It will overturn a century of information about the comparative behavior of phosphates and arsenates. It will also demonstrate a type of continuity in biology between two structures having very different properties that is rarely seen.
"In this case, DNA with phosphate linkers, not requiring the stabilization of interacting molecules, will have continuously morphed into a DNA with arsenate linkers that requires many of these interacting molecules, functioning throughout the morphing process. From a biochemical perspective, this will be more than remarkable.
"Because the hypothesis of arseno-DNA contradicts expectations based on so many well established chemical facts, I expect that the hypothesis will be perfunctorily dismissed by most biological chemists", said Dr. Benner. "However, as noted in the book "Life, the Universe, and the Scientific Method", perfunctory dismissal of apparently fantastic hypotheses is a way of guaranteeing that even valid discoveries are overlooked, and therefore should not be done routinely. The book lays out a process that should be followed in managing such hypotheses.
"In this case, the process is easy to apply. The molecules isolated in the band boxed in lane 2 of the gel in Figure 1 A should be easily subject to standard tools used in chemistry to determine their structures, just as the structures of any other natural product have been determined. Is the band degraded by acid or base? Is it phosphorylated by DNA kinase? Is it digested by exonuclease? What fragments are generated by each of these processes.
"Any natural product that can be isolated as cleanly as the band in Figure 2A can have its structure determined.
"Until this happens, however, the hypothesis would seem to fall into the category of "exceptional" that, as Carl Sagan remarked, requires exceptional support."
I think one of the simple answers in terms of the amount of backlash and lack of critical peer reviews stems from the fact that the USGS is essentially releasing a paper on complex forensic DNA.
This is the equivalent of having chemists write a paper on tectonic plates. Granted, I'm sure she or one of her peers has some geochemistry background, but by and large, these are geologists folks!
D.Man: According to Wolfe-Simon's CV, she is a biochemist. She has the requisiste knowledge to do this work. You apparently didn't even try to find out who these people were and made comments which were totally offbase. These are NOT simply geologists and your analogy is so wrong it borders on slander.
So folks, you can ignore D.Man's comments.
All I want to know is did these other scientists try to re-create the experiment before they started nay-saying it or did they just read it and start pontificating.
Oh yeah please start making the e-mail addresses of people who leave ads on NewsVine public so I can flood their e-mail with useless junk mail.
I actually had a spammer complain to me because I commented saying everyone should mark his post as spam. I had seen him post on several different articles that day and was really sick of it. I don't know why they should be special and not follow the rules of the vine...
Eat Smidt!
Some Lame Name Here has a point. While this wouldn't be the first time that Science has been accused of publishing something that wouldn't make it past a normal PhD committee in the name of a great headline (see Searchinger et al. 2008), people should try to re-create the experiment before they denounce it as impossible. Poor research methodology increases the likelihood of errors occurring, but it doesn't ensure that they do.
Well, if I recall correctly Carl Sagan suggested for years before his passing to assume that all life must follow the rules for earth is both naive and stupid. Possibly not with that harsh of language, but still the point was he felt that putting such constraints on life is foolish at best.
As a non-scientist but very intersted observer I have to agree with Sagan on this one. Ever noticed that in Sci-fi the "good" aliens (with the exception of ET) always look "human" (even ET has Frank Sinatra's eyes) but the "bad" aliens are always monsters of some kind. (well, except maybe on "V").
Ok, my point is, it's Chauvinism. You can't have life it if doesn't fit our narrow definition.
What?
I really think that is foolish.
Not being a scientist I'm not qualified to comment on the original findings or what the critics are saying. But I think we need to open to the possibility of Methan-based or Arsenic-based life forms in the universse and how we might safely intereact with them if the opportunity should present itself.
Going into an experiment biased should be grounds for removal from said experiment. Scientists are supposed to be open minded!
Who says the scientists are biased? They have an objective; to prove a hypothesis. That is not bias. Not all projects can be "black box", very few people fund on the basis of "we have no preconceived notion as to what we will find"/
That said: Atomic absorption spectroscopy to detect Arsenic would be the way to go; that or trying to design an experimental system that would be phosphorus free. Maybe a long term culture with intermediate concentrations of Arsenic and enriched over time until phosphorus is severely diluted.
However, what the thing is in an high arsenic and low phosphorus environment, it takes a great deal of energy to to bring phosphorus back into useable condition. AMP's take energy to turn back into ATP. Trinucleotides are needed to elongate oligonucleotide as the mechanism is driven by pyrophosphate release. So even if they can survive on low phosphorus, the next question is how their mechanistic machinery can function at such high heavy metal concentrations to keep things going?
It would be a good time to screen the lysates and run them through the mass spec. If Arsenic is being substituted the m/z should change accordingly. Fun times and more papers coming out of this lab...!
Oh felis wolffe..you should have never hyped up the pose...sigh..it only leads to a love that can never last...
all good things...
if only you had kept it in your pants.
But then again, the allure of the ride is better than the reasonable response, it gives way to truth, after all. A world with no suffering would never separate the elizabeths from the Edwards..would that be fair? I think not. You know someone from definition in the face of adversity...a world of troubles, a tale of two cities, yet, in the mass of humanity, we see elizabeth, we see the poor man that goes out of his way to feed the homeless...and the meaning allows for beauty.
What a treacherous and tragic world, and yet, how beautiful. Sad be the world that takes away mans power for self determination and his suffering, for there is no grievance, and yet, no meaning..and no enjoyment..
Benner's a quack--he's a fellow of the institute he founded--Westheimer was his thesis advisor at Harvard--and Benner named the Institute after him
I just think it was an interesting experiment.
Does any one proof read the articles before they are published.... Whas.... really
paragraph 13
If only religion had such robust debate!!
Having recently attended RCIA (catholic conversion) classes I can assure you there is very robust debate in (educated) theology circles about all things religious.
You simply have to go in with an open mind (kind of like science actually), which exceedingly few people do. I spent my whole life thinking I had an open mind and that I knew what religion was about. I was wrong. Find a good priest and ask those questions that never made sense. You would be surprised at what you might learn. They seriously debate that stuff.
Yes that true been there done that and came out an atheist.
For Redfield (whoever she is) to say that the authors are bad scientists is absurd and irresponsible. This research group has literally hundreds of high impact papers among them in the very best research journals during careers that in many cases span decades. These folks are some of the best reputations in the field despite any criticisms that one may have of the work in question, this relatively unknown researcher in Canada with a blog has no basis on which to question their integrity. They have rewritten the textbook several times on less fundamental topics, so give them a little respect. The experiments are there for people to try to reproduce. Time will tell.
Carl Sagan and others have said that if we ever find ET, it would never look like us. I never bought that argument. Considering that we still know next to nothing of extraterrestrial life, how can we tell? To say that the way life evolved on Earth is a fluke and that if it started again it would be different is only speculation. In the absence of any comparison, such statement cannot be proved or disproved. There are laws of chemistry and physics that apply to the universe, who's to say that there are no laws of biology that say that for a planet like Earth, with a similar sun, same gravity and so on, the probability of humanoid evolution would be higher than any other form of intelligent life. That wouldn't mean that the DNA would be compatible to our own. Again, who really knows what's out there? Sci-Fi has shown us myriads of human forms across the universe in movies and there are good reasons for that: it's a lot cheaper than creating something totally alien, and it helps the viewer relate to the characters. And besides, the best Sci-Fi is rarely about the future or real aliens. It's more of a comment on the human condition as it is now. For proof, compare the science-fiction of the 50s to that of today.
The bottom line is: Until we find real alien life, and a good enough sample of it, we're in the dark.
A planet just like ours would not only need the same size and gravity, but it would have to have the same elements in similar relative abundances to even give a chance of evolution occurring down the same line. I find no problem with the notion that other systems could exist for biology, since the laws of biology are the same laws as chemistry. If you can get weird chemistry in weird environments, you can possibly get weird biology.
life on earth works & fills every niche available from the top of everest to the bottom of the seas,under every easy or difficult condition;good reason to look at our experience as the optimum.let the mad scientist create their monsters,we don't need them to want to explore the cosmos;just get me there & show me how to grow a tomato!!
Until we see physical evidence that the nucleotide structures in the DNA of these bacteria actually contain arsenic groups instead of phosphate groups, this case will remain controversial. I say forget about trying to determine if there was enough phosphate in the media to sustain the bacteria - purify the DNA and perform some analysis on it to determine its structure. You could go further and try to construct arsenate containing nucleotides for use in DNA synthesis. If the DNA doesn't synthesize then that is a problem. If it does, construct a plasmid with the arsenate nucleotides, transform some bacteria with the plasmid and assay its function.
Also protein signaling cascades rely heavily on phosphate groups being added and removed from the proteins. Arsenate groups would have to be shown to function in a similar manner. Purify some proteins from the bacteria in their first experiment and use mass spec to screen for the presence of arsenate labelled peptides. If there are none, or if the proteins are shown to be labelled with phosphate there is a problem with their conclusions. You could also try to crystallize some kinase enzymes (the enzymes responsible for labeling proteins with phosphate) with arsenate groups present to see if they can coordinate the arsenate in their active sites.
I say wait and see, but do these follow ups, since without these types of experiments the conclusions are premature. There is plenty of work to be done.
Not only that, but the group that did the original experiement is waiting for independent verification before they call it definitive. It could have been a data error, the residual phosphates, or the bacteria was just simply unaffected by the arsenates, rather than incorporating them. But any scientist worth their salt should never decry something as impossible. Everything is possible, just very very very unlikely at times. Its possible I could sprout wings and fly away, improbable to the extreme, but still possible none the less, and concidering how little we know of this realm in which we exsist, that we call the Universe, I discount nothing.
In some ways, you'd think we were back in the 1600's and theories of heliocentricity are just starting to emerge. The outcry, though no where near as violent, is somewhat parallel
IF! you leave it to NASA they will find life on Uranus! they need to justify their jobs, and longevity! Never trust ANY science or research from a group who's well being and income depend on the outcome in any way or fashion. This is true of Government, Universities, Hospitals, labs, etc etc etc! IF they get Gov. $$$ , have any agenda for one sided opinion, or funded or sponsored by any organization with a position that will aid them, then you have to discount the outcomes! NOTHING can be trusted in the environment of big Gov. handouts, research, and political agendas! NOTHING.
We have corrupted our entire system of research and findings, and we are at peril because of it.
Conspiracy theories help no one. Government funded research, universities, labs throughout the previous century leading to some of our greatest advances -- atomic energy, lunar landing, computer technology, internet... the list goes on. Not to mention the numerous government-funded medical advances.
nuclear energy, i was a nuclear engineer, the PWR and BWR was the worst, worst idea for a power plant ever, and it was Gov. politics that made that decision, NOT science or engineering! and as for space, MOON? what moon landing? a flag and a golf-ball up their, wow thats advancing science, your stretching the facts, there are no facts, and we would have had the computer etc advancements without, NASA!