It’s getting close to two years now since a NASA-funded team of scientists announced they had found a form of life that broke all the rules by using arsenic to build its DNA. It’s become something of an obsession for me. If you want to follow the saga, click here and start back at the earliest post. In July I live-blogged the announcement that other scientists had replicated the experiment and failed to find the same results. In some ways, that was the logical end to the story
My fascination with this story has been tempered from the start by a creepy feeling. As a science writer, I most enjoy reporting on advances in biology: the research that opens up the natural world a little bit wider to our minds. The “#arseniclife” affair was less about biology than about how science gets done and the ways it goes wrong: the serious questions it raised about peer review, replication, and science communication. That fierce debate did some collateral damage. The microbe in question, known as GFAJ-1, went from being the species that would force us to rewrite the biology textbooks to yet another bacterium that offered no serious challenge to the uniformity of life. It became boring.
But biology is not boring. Elephants and redwoods may both be made of the same elements, may both build genes from DNA, may both use the same genetic code book to build proteins–but they’re very different from each other in some respects, and, each in their own way, are most certainly not boring. Neither is GFAJ-1. And so it’s a pleasure to see a new paper in the latest issue of Nature in which a group of scientists pick apart the biology of the microbe and discover something very interesting.
The whole search for arsenic life got its start because arsenic, despite being toxic, is very similar to an essential element, phosphorus. Phosphorus is part of the backbone of DNA, for example, and it is an ingredient in the energy-storing molecule ATP–in each case in a form known as phosphate, with four oxygen atoms tacked on. Arsenate (arsenic linked to three oxygen atoms) is just about identical in size, has a similar charge to its oxygen atoms, and has many other chemical similarities to phosphate.
So the arsenic life team wondered if life might be able to survive with arsenic instead of phosphorus. One way to test that idea would be to rocket off to a planet where there is only arsenic and no phosphorus and look for life. Another would be to look for life on Earth that can swap arsenic for phosphorus. The arsenic life team opted for the latter and headed to Mono Lake in California, the waters of which are loaded with arsenic. They brought a strain of bacteria back to their lab, weaned it off of phosphorus, and supplied it with arsenic instead. The bacteria still grew. That fact and other studies they conducted convinced them that the bacteria had, indeed, become arsenic life.
The consensus today is that the scientists unwittingly fed the bacteria just enough phosphorus to survive, and the tests that seemed to indicate the arsenic was inside the DNA weren’t executed carefully enough.
But think about that for a moment. Imagine what it’s like for a microbe in Mono Lake, or in the lab of a particularly sadistic scientist. You’re drowning in arsenate, and in order to stay alive, to keep growing, you need to grab the precious few phosphate molecules drifting by.
Dan Tawfik, an expert on protein function at the Weizmann Institute in Israel, and his colleagues have uncovered some of GFAJ-1′s secrets to survival. GFAJ-1 and other bacteria absorb phosphate through their outer membrane, into a sandwiched layer of fluid called the periplasm. Once there, the phosphate is grabbed by so-called phosphate binding proteins, which then deliver the phosphate to the interior of the microbe. Tawfik and his colleagues examined these proteins in unprecedented detail to see how they work.
The scientists offered the proteins a mixture of arsenate and phosphorus. Even when they raised the ratio to 500 molecules of arsenate to every phosphate molecule, the proteins still managed to pluck out phosphate over half the time. The scientists then examined the proteins to figure out how they make such fine discriminations. When the proteins encounter a molecule of phosphate, they enfold it in a tight pocket, which ties down the phosphate with 12 different hydrogen bonds. When arsenate falls into that pocket, it doesn’t quite fit in, and the bond between one of the oxygen atoms in the arsenate and one of the hydrogen atoms in the protein gets twisted. It gets pushed to such an uncomfortable angle that the arsenate drops out.
This finding suggests that ordinary microbes are well-adapted to picking out phosphates when they’re scarce, using their fussy phosphate binding proteins to reject abundant arsenate. GFAJ-1 is stuck in a place where phosphate is always scarce and arsenate is always dangerously copious. Tawfik and his colleagues found that one form of their phosphate binding proteins is spectacularly fussy, preferring phosphates by a factor of 4,500. What’s more, GFAJ-1 produces many copies of this super-fussy protein. As a result, GFAJ-1 can thrive in Mono Lake. In fact, it can handle arsenate-to-phosphate ratios up to 3,000 times higher than found in the lake.
Finding alien life on Earth would have been grand. But seeing how life as we know it manages to adapt to our planet’s extremes is also a pleasure. And it’s a good place for the story of arsenic life to stop: at the point where new science begins.
Rosie Redfield, the University of British Columbia microbiologist who became a leading skeptic of arsenic life, Maneesh points out in the comments that phosphates are actually abundant in Mono Lake. Thanks for pointing that out, Rosie Maneesh!]
Like a number of other science writers, I’ve become increasingly interested (and concerned) about science’s ability to correct itself. (See my recent pieces about arsenic life, de-discovery, and dysfunctional science.) So I was intrigued by a new project launching today to encourage scientists to embrace the spirit of replication. I write about it at Slate. Check it out.
I’m going to be a guest during the second hour of Science Friday on National Public Radio tomorrow. Host Ira Flatow and I will be discussing the latest twist in the ever-intriguing arsenic life saga, and, more broadly, the rough-and-tumble way in which science corrects itself. If you miss the live show, you can listen to it here.
I’m spending the weekend in Ottawa, where a couple thousand scientists have gathered for the Joint Congress of Evolutionary Biology. I’m drowning in a torrent of fascinating talks, on everything from sexually cannibalistic crickets to the future of the Amazon’s biodiversity. In the evenings, the meeting features high-profile talks–Friday night, the science writer David Quammen spoke about his career, on the occasion of winning the Stephen Jay Gould Prize. I have a particular interest in tonight’s talk, so much so that I’m going to live-blog it. The speaker is one Rosie Redfield, and she’ll be talking about the endlessly intriguing case of Arsenic Life.
Before Redfield takes to the stage at 7:30 pm ET, I want to write a short preface. In December 2010, rumors swirled for a few days that NASA had discovered alien life. When they finally held a press conference, the world discovered that a team of scientists had found a species of bacteria at Mono Lake in California that appeared to be able to build DNA out of arsenic. If true, it would be unlike any known life on Earth.
Rosie Redfield, a microbiologist at the University of British Columbia, read the paper after the embargo at Science was lifted, and didn’t like it. After she posted her complaints on her blog, I got in touch with her, along with a number of other scientists to see what they thought. Most of them didn’t like the paper either. I wrote about their collective reaction in an article on Slate, which was called “‘This Paper Should Not Have Been Published.’” (That was a quote from one of the scientists I spoke to.)
The authors of the paper, who were willing to hold a big press conference, give TED talks, and so on, refused to provide me any comments. They declared that all discussion must be restricted to peer-reviewed channels. Six months later, when Science finally published the arsenic life paper in a print edition, they also published a number of comments from Redfield and other critics.
Redfield and others argued that the arsenic life study had been poorly carried out. To put a scientific claim to the test, critics can try to replicate it. But, as I wrote in the New York Times, that’s a pain in the neck, and a lot of researchers would rather spend their precious time doing something interesting, rather than cleaning up other scientists’ messes. But Redfield decided to replicate the arsenic life study anyway. She had another motivation for doing so: she’s a big fan of open science, and so she used her blog to chronicle her experiences, from receiving the bacteria from the original authors to failing to replicate their results to posting her paper on Arxiv to getting her paper accepted to Science, where it’s now in press.
As Redfield notes on her blog, tonight’s talk presents a certain complication to the traditional way that high-profile journals publish papers. Journals like Science keep their papers under strict embargo, meaning that people are supposed to keep their mouth shut until an appointed time. Science provides pre-publication copies of the papers to journalists, usually a week in advance, so they can write up articles that can appear once the embargo lifts. So…if Redfield talks about her research, what does that mean for her paper? And does the fact that you can download it already from Arxiv make all of this moot?
7:36: Getting started. Redfield’s getting introduced.
7:38: “Rosie Redfield led the charge that NASA got it wrong.”
7:41 Redfield is starting: this is a story about the process of science, that starts with a press conference.
7:42 Redfield glosses over the utterly insane week of speculation that NASA had found aliens. Hey, she’s a microbiologist.
7:43 Why was this done? “The researchers were looking for exactly what they found.” (Not always a good thing in science.)
7:44: Looking for alien life is very expensive. So NASA is looking for terrestrial life that can help the search.
7:44: 2009 paper in Astrobiology: arsenci life team pointed out that arsenic is similar to phosphorus. So maybe early life could have used arsenic instead of phosphorus (in DNA for example). And maybe they’re still around.
7:45: Origin of life. You can start forward from early Earth, or go back from life today to figure out what first life must have had.
7:46: Early earth: simple chemicals created complex ones. Also, early Earth was “stinky.”
7:47 Comets delivered dirty water, loaded with polycyclic hydrocarbons.
7:48 All life today is all related. All life descended from a common ancestor.
7:50 Common ancestor of all life today: DNA genome, cellular, lipid bilayer, protein synthesis, many modern biochemical pathways.
7:51 There’s a gap scientists have yet to bridge from prebiotic Earth to last common universal ancestor.
7:52 What properties are essential in living things? Reproduction, heredity, and heritable variation that affects survival or reproduction. Redfield: “That spells natural selection.”
7:53 Natural selection probably kicked in long before our last universal common ancestor. First life could have much simpler metabolism. May not have been based on DNA. Life could have started as RNA. (Check out this story I wrote for Discover.)
7:55 Today, proteins do much of the work of metabolism.
7:57 Creationists seized on this open question. Evolutionary biologists claimed evolution doesn’t include origin of life. But RNA world gets closer to the origin, via evolution.
7:58 Back to arsenic: Poisonous because cells sometimes take up arsenic, which screws things up.
7:59 “Shadow biosphere”–a cool name, but almost certainly wrong.
8:00 Shadow biosphere hypothesis: weird life exists even today, hiding from scientists. Redfield: “This is extremely cool.”
8:01 Redfield recaps arsenic life experiment. Mono Lake bacteria kept growing as arsenic was swapped for phosphorus in medium.
8:02 Once Felisa Wolf-Simon could grow bacteria, brought in other scientists. Sophisticated tests such as NanoSIMS to show arsenic in (or near) arsenic.
8:05 Redfield was suspicious. NASA’s track record was not good, given Martian meteorite debacle.
8:06 Whenever Redfield wants to think something through, she blogs.
8:07 Press release has just gone out on arsenic life. There are TWO papers refuting it.
8:09 Redfield: Medium in arsenic life had some phosphate in it–same as ocean water.
8:11 Arsenic bacteria got fat. They couldn’t divide any more, so they swelled up.
8:13 Redfield argues that DNA of arsenic life bacteria that was already dirty with arsenic–arsenic not part of DNA.
8:15 Dan Vergano at USA Today is reporting on the new papers. Arsenic life paper lead author Felisa Wolf-Simon declares, “There is nothing in the data of these new papers that contradicts our published data.”
8:17 I forgot to link to my database of the responses from many critics. Here it is.
8:18 For some reason, some people made fun of Redfield for her dyed hair. It’s just gray at the moment.
8:19 Arsenic in DNA would fall apart very quickly. A big problem.
8:19 The bacterium in the arsenic life paper was not part of the shadow biosphere. It was just a member of a well-known genus called Halomonas.
8:21 The bacterium, called GFAJ-1 (Get Felisa Wolf-Simons A Job), is very, very, closely related to other Halomonas. Not much exotic evolution to become arsenic life.
8:22 No reason to think there would be natural selection for arsenic use, since Mono Lake has a fair amount of phosphorus (although a lot of arsenic too).
8:24 NASA suddenly switched from big press conference to shutting up. Felisa Wolf-Simon “had been been tweeting up a storm.”
8:25 Six months after the press conference, paper published, plus criticisms. Response of authors: “We think our research is fine.” –Redfield.
8:27 Redfield’s “selfish reason” for focusing on arsenic life: she blogs about her work, pursing open science. Important that the public see how science is done.
8:29 Redfield lacked all the expertise required for trying to replicate arsenic life. Blog post led to collaboration with experts who could do the job. (Actually, they volunteered their grad student!)
8:30 Redfield spent a month trying to get bacteria to grow, blogging all the way. Trouble with amino acids. Eventually, figured it out.
8:32 Redfield used better reagents with much less phosphate. Arsenic didn’t help growth. Arsenic life team was wrong.
8:33 Her DNA was stable for a couple months. Couldn’t have arsenic in it.
8:35 Redfield et al wrote up a paper, submitted to Science, and uploaded to Arxiv–because this is open science.
8:36 Science planned to publish on July 26.
8:36 Journals use embargoes to control how research is publicized. For more, read Embargo Watch.
8:38 Embargoes enforced by “vague threats.”
8:38 Weirdness of paper being on Arxiv for months and Science enforcing embargo. Redfield informed that embargo being lifted tonight.
8:39 I just told Redfield her paper has been up for half an hour. Applause breaks out.
8:40 Redfield: This is a story of serial failure. Lead author convinced of evidence without good research, senior authors didn’t provide supervision. Co-authors should have accepted responsibility. Reviewers failed, missed a lot of problems. Science failed in selecting reviewers.
8:42 “And finally, NASA failed big time.”
8:42 But the process of science did not fail.
8:45 Talk over. Question–will this episode change science? Redfield: If you blog about it, you mark that it’s your idea.
8:47 Peer review like democracy (as described by Churchill), is terrible, but the best we have.
8:48 Redfield: lots of “seriously flaky” stuff gets published, so we don’t have to worry about strangling science.
8:49 Idea of arsenic life “unlikely to be true,” but an “okay hypothesis.” You always fall in love with your own ideas. “It’s the ultimate high in science.” But you need self-discipline to test your hypothesis and see if it’s wrong.
8:52 That’s it, folks. Good night!
Today marks the one-year anniversary of the Arsenic Life Affair. On December 2, 2010, NASA-funded scientists announced that they had discovered a microbe in Mono Lake that broke the rules of biology. They claimed it could build DNA from arsenic rather than phosophorus. It was a sensational claim, and it was greeted by a spectacular backlash.
Alan Boyle takes a close look at arsenic life on its first birthday over at MSNBC. Other scientists have yet to report whether they can replicate the results or not (the bet of many experts is on not). Meanwhile, other researchers are studying its biology, sequencing its genome, and otherwise investigating it as they would any new microbe. It seems as if the arsenic life affair is morphing into regular science. Which may be about as good of an ending as one could hope.
The year has been an intriguing one for me as a journalist–I’ve found writing about arsenic life as both science and the sociology of science to be very satisfying. Here’s a round-up of my main pieces:
1.Of Arsenic and Aliens, The Loom, 12/2/10
This was the first post I wrote, on the day of the announcement, explaining why arsenic life would be a big deal if it were true.
2. “This Paper Should Not Have Been Published,” Slate, 12/5/10
Over the next couple days, I encountered deep doubts among experts. I summarized their objections in a piece for Slate.
3. Of Arsenic and Aliens: What the Critics Said, The Loom, 12/8/10
I could not delve into the full details of the objections in my Slate piece, but I wanted to make sure readers could see that the critics were not shooting from the hip. So I posted their complete responses on my blog.
4. The Discovery of Arsenic-Based Twitter, Slate, May 27, 2011
Nearly six months after arsenic life was announced, Science finally published the paper, along with lengthy criticisms. It felt fairly anti-climatic to me; at Slate, I wrote about what I thought was the important outcome of the whole affair: an experiment in open science and post-publication peer review.
5. It’s Science, But It’s Not Necessarily Right, The New York Times, June 26, 2011
As the Arsenic Life Affair was unfolding, several other high-profile papers were also under siege. Together, they got me interested in how science progresses: how scientific ideas are tested, and how difficult it can be for the wrong ones to be “de-discovered.”
6. #ArsenicLife Goes Longform, And History Gets Squished, The Loom, 9/30/2011
The first big feature on arsenic life appeared in Popular Science. I warned that a folk tale about everything being the fault of those pesky bloggers was taking root. (Soon after, the author, Tom Clynes, sent a long message to me, which I posted on the blog.)
Along with Boyle’s piece, you can also plunge into Bora Zivkovic’s epic link round-up for more reading.
Yesterday I wrote about the arsenic life saga, prompted by a long retrospective feature by Tom Clynes in Popular Science. While I recommend the piece, I expressed reservations because it passed along the “scientists besieged by bloggers” spin on the events, when the actual history doesn’t support that.
Clynes (whom I’ve never met) emailed me in the evening with this comments, which he allowed me to share:
Thanks for your comment on my Popular Science feature on Felisa Wolfe-Simon’s arsenic-life saga. In some ways, I think you’re on target, though I would like to provide a bit of clarification: Throughout the story, when I convey an argument made by someone who’s on one side of the issue or another, it doesn’t mean that I necessarily buy into that argument.
To that end, I’d like to add a bit of context to a paragraph that you quote, regarding the storm of criticism and the paper’s authors going “underground.” You follow the excerpt with your comment that “Clynes has us believe that this barrage of extraordinary, brutal criticism (or perhaps questions from journalists) forced Wolf-Simon and her colleagues to go into witness protection.”
Actually, I don’t believe that, nor would I have my readers believe it. I think it would have been useful to your readers for you to have included my next paragraph, which makes it clear that I am in fact spotlighting both sides of a polarized dialogue regarding this particular point:
Microbiologist Jonathan Eisen of the University of California at Davis called the lack of response “absurd” and told Carl Zimmer from Slate, “They carried out science by press release and press conference. They are now hypocritical if they say that the only response should be in the scientific literature.”
Though I didn’t state my opinion in the story (better for readers to decide for themselves), I will here: I think that Eisen is on the money here.
Some other opinions: Do I think that the arsenic-life paper was flawed? Yes. Do I think it that some of its conclusions will be dissolved by further investigation? Yes. Do I believe that NASA’s hyped-up approach to publicizing what was actually a rather understated paper was ham-handed, and damaging to everyone involved? Big time.
Do I think the paper never should have been published? No. In a profession where young scientists are advised to avoid controversy as they build their careers, Wolfe-Simon pushed against a paradigm and sought answers to some very big questions. She passed through the same peer-review hoops (imperfect as they may be) at Science as other scientists must. Yes, her research was imperfect and yes, she likely overreached—but plenty of scientific papers are flawed, and many young researchers go too far. If scientists aren’t willing to subject themselves to the possibility of failure, science can’t possibly progress.
Critically, there’s nothing to indicate that Wolfe-Simon did anything unethical, which might have justified the shrill tone and sweeping proportions of the response—and the fact that she was singled out among the paper’s 11 authors. True, she was the lead author, and it was her hypothesis. But it’s surprising that Ron Oremland, the lab director and principal investigator, is rarely mentioned in the criticisms.
If my story has a bottom line, it’s in this quote by the University of Colorado’s Alan Townsend: “Absent major ethical violations, no junior scientist full of passion for an idea deserves crucifixion for a professional failure or two. If a paper is flawed, it should be dismissed. The scientist should not.”
Rosie Redfield of the University of British Columbia has steadfastly raised doubts about the headline-grabbing news about arsenic-based life last November. (If neither arsenic life nor Rosie Redfield ring any bells for you, check out my two pieces for Slate, in December and June.) Redfield then did something exceptional: she set out to replicate the initial findings, getting the original bacteria and seeing whether they can build DNA from arsenic when deprived of phosphorus.
And then she did something quite unique: she started to chronicle her experiences on her blog. It’s a fascinating peek into the lab notebook of a practicing scientist. Today’s post is especially intriguing:
Among other things, Redfield reports that the bacteria seem to be able to grow at very low levels of phosphorus–levels that the original scientists claimed were too low to sustain the growth they saw.
Of course, Redfield has a lot of work left to do. She will have to run this experiment to its bitter end, write up the results, submit a paper to a journal, get it past peer review, and publish it in a peer-reviewed journal. But we can all watch her journey in real time.