Monday, June 4, 2012

It's Not a Game

It would be disingenuous of me to claim that my current desire to change careers is motivated by the career and not by own circumstances, and the problems with me are detailed in previous posts. But still, the current state of the profession doesn't help. It is one thing to work very, very hard to get to that first hint of a great discovery. It's another to work very, very hard to ensure that your science is of exceptional quality, especially when no one's looking that carefully. When this is the case, it's easy to feel like the people winning the game aren't doing so by playing within the rules. A recent commentary in Nature (483:509) alluded to the large number of sloppy mistakes that are creeping into papers. When the goal is to push out publications as quickly as possible, the ugly reality is that the incentives are often in the wrong direction: being sloppy can work to the benefit of the laboratory publishing the paper.

Two high profile examples of this have recently appeared: the finding that the effects of an "anti-aging" gene disappear when the controls are done carefully (Nature 477:482), and the whole debacle surrounding the infamous "arsenic bacteria" story. Now that the refutation of the conclusions of the original paper have been accepted, it's worth taking a step back and recalling that NASA originally pitched this as being relevant to the study of extraterrestrial life. There isn't any bigger splash you could make with the popular press. When the paper was made available and it was clear what it was really about, I think the public was somewhat disappointed. Let's just be clear that this had nothing to do with extraterrestrials. The idea that a living thing using something other than the CHNOPS elements (carbon, hydrogen, nitrogen, oxygen, phosphorous, sulphur) has anything to do with alien life is frankly confusing.

Still, the conclusions of the paper were pretty astonishing to those within the community. One of the universal principles of life, perhaps the universal principle, is in the structure of DNA itself. The "backbone" of DNA is always the same, even though the sequence can encode a nearly infinite amount of information. The language of life is universal, it's the words that are written with that language that make organisms different from each other. Even so, it seems any rule in biology has exceptions, so even arsenic-containing DNA seems plausible.

Like - I suspect - most of the molecular biology community, I read the title and abstract of the paper and skimmed the figures. Since most of what Science publishes is pretty solid, and it isn't my field, I felt that would be sufficient. Boy was I wrong. In a now-famous blogpost, Dr. Rosie Redfield thoroughly destroyed the papers conclusions based on the data and methods provided. While the criticisms of the paper called into serious questions the conclusions, they also didn't really say that these bacteria don't have arsenic in their DNA. This required more work, and Dr. Redfield and her collaborators set out to test this directly using mass spectrometry. These results are the subject of the current submission would seem to put the nail in the coffin for arsenic-containing DNA.

So where does that leave the story that was supposedly about extra-terrestrial life?
  • Undoubtedly, this bacterium can grow unusually well in the presence of arsenic. This is a significant finding, but one that in the end is not all that surprising. Where there are extreme conditions on this planet, some type of life form - usually a bacterium - will find a way to live there.
  • NASA and Science Magazine each deserve a share of the blame for the amount of hype and publicity this paper received. A papers that makes as bold a claim as "a bacterium that can use arsenic instead of phosphorous" (emphasis mine) deserves a high level of scrutiny. We will never know whether the reviewers had the same reservations as many readers did and were simply overruled by the editors. 
  • There is more to being a scientist than publishing the most papers in the best journals. When you publish something, you stake a part of reputation on it. It isn't a game to get it past the reviewers.
  • The last I heard, Dr. Felisa Wolfe-Simon, the lead author of original paper, was standing by her discovery. She gave the bacterium the name GFAJ-1 which stands for "give Felisa a job". The last I heard, that hadn't happened either. I feel bad for her in a way (apparently, she is a fellow oboist, so we share that). There are tonnes of bad papers out there, and most authors will never have to answer for it the way she has. Still, as Michael Eisen pointed out: 
    The acid test of a scientist is how they respond when their work is criticized. The best scientists listen and consider what is being said, defend the things they still believe and, most importantly, recognize where their work fell short and use criticism to make their work better. This is, of course, not always so simple. It’s easy to get defensive instead – to view criticism as an attack, see sinister motives in its sources, and ignore its substance. But I think the worst response is to view criticism as a kind of virtue. And there were signs in Wolfe-Simon’s talk that she is beginning to relish the role of the iconoclast. She appears to see herself as someone who has unconventional ideas that the scientific community can’t deal with. And that criticism of her work is not an effort to get at the truth but a conspiracy to suppress it. At several points she made reference to other scientists whose ideas were not accepted when they were proposed, but which turned out in the long run to be correct. The problem is that many people get stuck this way – and being iconoclastic becomes their whole scientific identity (we can all think of people like this….).
  • Yes, there is danger that what everyone will take away from all this is that it's dangerous to have a new idea. But, I think, it should be dangerous to have a new idea. You want to bat with big boys, then be prepared to take the fall. It's fine to be wrong. Science moves forward by people being wrong. But to not take seriously the task of needing reason and proof, is to fall far too close to "it's right because I say it's right". For this reason, I hope Felisa doesn't get job. There are just too many other people who deserve it more.

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