text: Arsenic-based life debate continues | The Scientist Magazine®
  Arsenic-based life debate continues
  More than a dozen researchers voice their concerns about a 2010 paper that claims bacteria can use arsenic in place of phosphorus in its DNA and other biomolecules, such as proteins.
  By Jessica P. Johnson | June 2, 2011
  Mono Lake, CaliforniaiMAGE: IMAGE © 2010 HENRY BORTMAN
  Scientists are questioning the validity of a high-profile paper that claimed to have discovered a strain of bacteria from Mono Lake, California, that can use arsenic in place of phosphorus in its DNA and other biomolecules, such as proteins.
  The paper, which appeared online in ScienceExpress last December, immediately sparked a hot debate among the scientific community. Now, fifteen researchers have articulated their concerns in the form of eight technical comments published in ScienceExpress last week (May 27), and, for the first time since its publication, the authors of the controversial study have written a formal response to their critics.
  In general, the criticisms highlight poor experimental techniques and point to more likely explanations for the results than a straightforward replacement of phosphorous with arsenic in biomolecules.
  "It's like finding a unicorn in your back garden," said Rosemary Redfield, professor of microbiology at the University of British Columbia and an author of one of the eight published comments. "The chances of it being an actual unicorn are small, but if the experiments had been really well done, then they would have been convincing. In fact, the experiments were quite badly done. It's like having a blurry picture of the unicorn. It's unlikely that it's actually a unicorn."
  Specifically, Redfield takes issue with the DNA extraction protocol, claiming that the genetic material was not purified properly before being tested for arsenic content. Furthermore, the supposedly phosphate-free growth medium on which the bacteria were cultured actually did contain phosphate, the phosphorus-based molecule of DNA backbones, which, Redfield argued, the bacteria may have been using to survive. To be absolutely sure that the bacteria were indeed using arsenate (the arsenic equivalent of phosphate) as the authors claimed, she said, the strain must be cultured without any phosphate.
  Felisa Wolfe-Simon, a fellow at NASA's Astrobiology Institute and lead author on the original study, and her colleagues defended their DNA purification techniques, and said that they were transparent in revealing the presence of small quantities of phosphate in the medium. But, she argued, the low levels were not enough to sustain growth, as supported by lack of growth in control cultures in media that contained similar amounts of phosphate but no arsenate.
  But James Cotner, environmental microbiologist at the University of Minnesota and one of the published commenters, contends that the authors overestimate the minimum amount of phosphorous required for cell survival, noting that many species of bacteria naturally survive on the low levels present in the study.
  Furthermore, researchers argue that there are simpler possible explanations for why the bacteria cultured with arsenate survived and grew. Patricia Foster, professor of biology at Indiana University, said it's possible that the bacterial strain, called GFAJ-1, can only bring phosphate into its cells when it is exposed to a stimulant such as arsenate. Therefore, the control cultures don't prove that GFAJ-1 grows by incorporating arsenate into its DNA, just that arsenate needs to be present in order for the bacteria to grow. She also said that if the cells were actively growing and incorporating arsenate into their DNA, then their DNA should have contained a higher percentage of arsenic than the researchers found.
  Much of the skepticism stems from the longstanding belief that arsenate is extremely unstable. In his comment, Steven Benner, distinguished fellow at the Foundation for Applied Molecular Evolution and another comment author, calculated that each arsenate linkage inside a hypothetical arseno-DNA molecule would hydrolyze (degrade) after only 1 minute in the environment of Mono Lake while phosphate-DNA can survive approximately 30 million years.
  Though the specific criticisms vary, the sentiment is clear -- more research is needed to conclusively demonstrate that the bacteria actually incorporate arsenic into their biomolecules. "The experiments weren't done to the standards of a controversial issue," said Cotner.
  Wolfe-Simon and her colleagues plan to continue follow-up experiments, and though they have new data on the organism, Science declined to publish it with the authors' response to comments. They have also made GFAJ-1 available for study by other labs. "We weren't particularly happy with all of the hoopla," said Wolfe-Simon. "But you have to embrace your critics. It gives you the opportunity to be more scholarly."
  phosphorus, phosphate, NASA, Mono Lake, microbiology, GFAJ-1, Felisa Wolfe-Simon, biomolecules, astrobiology, arseno-DNA, arsenic and arsenate
  Glycolysis runs even faster with arseniate(V) than phosphate, that is known since the 70's, though the sugar-arseniate analogs of glycolysis are prone to hydrolysis than the natural sugar -phosphate. Pigs can grow faster and heavier with a little arseniate(V), but they die younger. Since the "discovery of arsenic-loving bacteria" was made in a pond not free of phosphate, I wonder where did the "discoverer of this extraterrestrial bacteria" studied general biochemistry.
  DFSpencer
  It mystifies me as to why these purported discoveries cannot be refuted in very simple terms. There is really no need to criticize experimental sloppiness (even if it may be justified), nor to do any other hand waving about arsenate being required for phosphate import (which may also be true) and so on.
  This all comes down to basic chemistry, and Steven Benner has in fact more or less addressed that. If someone were to propose (without any experimental basis for it) that arsenate could replace phosphate in nucleic acids (which implies also replacing at least the alpha phosphate in nucleotide and deoynucleotide precursors), talking with any decent chemist would solve the whole issue quickly, although the chemist would probably scold you soundly for being so ignorant of chemistry.
  Arsenic is in the same group as phosphorous in the periodic table but why would anyone imagine that implies they are interchangeable? The pKas of o-arsenic and o-phosphoric acids are fairly close and apparently arsenate can be a competitive inhibitor for phosphate in transporters, for some enzymes, etc. but it really shouldn't be a surprise that phosphorous and arsenic have different and often rather important chemical properties.
  To me what is most irritating is that the the critical information can be fairly easily found on the Internet, one reference being in a 1977 free online book titled "Arsenic: Medical and Biological Effects of Environmental Pollutants", available to read at the National Academies Press.
  QUOTE: "Because there are similarities between arsenic acid and phosphoric acid, the possibility that arsenate can replace the important phosphate group in biologically essential molecules (such as the monosaccharide phosphates and adenosine triphosphate) must be considered. However, arsenic acid esters are much more easily hydrolyzed than phosphoric acid esters."
  This is the point that Steven Brenner was making, that the phosphodiester bond in DNA in solution (and even in RNA under neutral conditions) is very stable whereas the arsenodiester bond is very unstable, as it happens the sulphodiester bond is as well.
  This doesn't even take into consideration all of the changes that would be required in presumably every cellular enzyme and complex involved in nucleic acid metabolism, the kinases, phosphatases, ligases, polymerases, nucleases, gyrases, topisomerases, etc. to accommodate the arsenic substitution. It also ignores the whole issue of RNA(s), ATP, and their synthesis and behavior because, for one thing, the deoxynucleotide precursors (dNTPs, well, dN-As-As-As or dN-As-P-P) have to get their 'As' from somewhere.
  This is too reminiscent to me, being of an age, to the notion floated about 40 or 50 years ago that alien life forms could be silicon- rather than carbon-based. That was as preposterous then as it is now.
  We are in a business that, first, recognizes that physics and chemistry have laws and biological systems are bound by them. Secondly, a principle of scientific-based thought is the ability to predict, based on the laws of the universe and accumulated observation. Pigs can't fly. Bumblebees can.
  True, but I'm sure that's not exactly what she meant. She's embracing the criticism as constructive, not implying that science does not have to be scholarly... I think you're just putting words in her mouth.
  In times like this it would be nice to see the referees' and editors comments during the peer review process.
  @d29d772ecdf79aa66b842f0a01bb2fe9:disqusÂ
  I think you're reading too much into an off the cuff remark-she basically means that criticism can make you think more deeply about issues you may not have considered and come up with new ways to test your hypotheses.
  Wolfe-Simon is quoted as saying, "...you have to embrace your critics. It gives you the opportunity to be more scholarly.â€쳌 More scholarly? This astonishes me. Under what circumstances does she think a scientist can be less than 100% "scholarly" ????? Am I the only one who is bothered by the attitude revealed by this quote?
  That foolish claim that aeronautical engineers or physicists can't explain how a bumblebee can fly (or that it violates physics) is just that, foolishness. There is ample information available explaining the origins of that myth that you can find by a simple Google search, such as this nice one:
  http://www.sciencenews.org/vie...
  The arsenic story is in fact more akin to some group claiming that they have trained a pig to fly (or witnessed it). You don't have to be a Ph.D. in Physics to know that is crap. And you shouldn't need too many advanced degrees in Biochemistry or Nucleic Acid Chemistry to recognize that arsenic cannot, from basic chemical principles, substitute for phosphorus in the diester bond that links deoxyriboses in DNA or conceivably, riboses in RNA.
  To apply your philosophy we should pander to the "brilliant" minds who insist that they have built a perpetual motion machine or an antigravity machine.
  The mantra of the scientist should not be that of the Queen in "Through the Looking Glass', "Why, sometimes I've believed as many as six impossible things before breakfast.'
  This is all fine, but it seems so close-minded. Pigs can't fly, of course. But as far as I know, our present understanding of aerodynamics cannot yet show why bumblebees can fly. And all of your pretty theories would be laid to rest by an unequivocal demonstration that arsenate can support bacterial growth.Â
  My point is that theory should never dissuade one from doing an experiment because theory is often wrong.
  maybe it is true. but now we need more data to support it. two or more than two ways to prove it.i believe the time will prove whether it exist.
  "Arsenic supports life?" is the name of the paper that says that they found arsenic where phosphorous should have been. In cell structure phosphate is a complete necessity. Life as we know it could not exist without phosphate. The idea of arsenic being a possible replacement is somewhat believable at first because phosphorus and arsenic have a lot in common but they also have a lot of differences. Arsenic is extremely unstable and could not support life. That is my opinion until more useful research is done.
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