Bacteria eat arsenic -- and survive!

Posted 5 December 2010 by

This week's issue of Science has a news article and a podcast about a USGS researcher who bred bacteria to live in an arsenic environment. If you do not subscribe to Science, you may read only slightly breathless articles in the New York Times and the Los Angeles Times. In brief, a team led by Felisa Wolfe-Simon of the the U.S. Geological Survey in Menlo Park, California, obtained some mud from Mono Lake, California, which has a high concentration of arsenic. They cultured bacteria from the mud and grew them in gradually increasing concentrations of arsenic and also decreased the concentration of phosphorus. Arsenic, which is directly below phosphorus in the periodic table, evidently replaced the phosphorus in the bacteria's chemistry. The bacteria survived on arsenic, though they grew better on phosphorus. The researchers found phosphorus in the proteins, lipids, and other constituents of the cell, as well as in the DNA. Although not everyone agrees, Wolfe-Simon and her team think that the bacteria actually use the arsenic to grow. Well, as they say on the Web, IANAB, but the result is precisely what any self-respecting adaptationist would have expected. What is interesting, however, is the empirical result that life can grow without phosphorus, and therefore by inference possibly without other elements that are also considered essential. I never thought otherwise, and in fact recall science-fiction writers from my dim, dark past postulating life based on silicon, which is directly below carbon in the periodic table. Evidently NASA has finally wakened up to such possibilities, since they trumpeted the discovery as "an astrobiology finding that will impact the search for evidence of extraterrestrial life."

82 Comments

Wheels · 5 December 2010

The next test for these bacteria will be to see if they can survive in elderberry wine.

Tom · 5 December 2010

I thought the real significance was that they used arsenic in their DNA in place of phosphorus, not that they ate it per se.

Zeno · 5 December 2010

I recall Isaac Asimov's essay(s) on the potential for biologies based on combinations of chemicals other than those we prefer to use. In particular, silicon was a reasonable alternative to carbon because of its structural similarities. The news from NASA and USGS is exciting and interesting, but not exactly a new idea to longtime sf readers.

Bob O'H · 5 December 2010

My wife is reading a review from 2003 about metabolism of arsenic by bacteria in the same lake.

The paper has also been taken apart by Rosie Redfield.

Matt Young · 5 December 2010

I thought the real significance was that they used arsenic in their DNA in place of phosphorus, not that they ate it per se.
Sorry -- "ate" might not have been the best word, but I needed a snappy title. Perhaps Science put it slightly better: "What Poison? Bacterium Uses Arsenic to Build DNA and Other Molecules." I think the point is that they found arsenic in a lot of places, and it was apparently functional.

Doc Bill · 5 December 2010

Most astounding of all is that when you magnify the bacteria they look like old lace.

Rosie Redfield · 5 December 2010

@Doc Bill,

The black gaps in the lace are the bacteria, and the big white blobs inside them are the granules of what is probably the energy-storage molecule polyhydroxybutyrate.

harold · 5 December 2010

P Z Myers has a pretty good discussion of this, under the title of "It's Not an Arsenic Based Life Form". Although some of the comments accuse PZ of an excessively skeptical tone, between his summary and the comments section, it's a good place to get more details.
I thought the real significance was that they used arsenic in their DNA in place of phosphorus, not that they ate it per se.
Actually, Matt Young was more correct than he gave himself credit for. In an environment with sufficient phosphorus, they use phosphorus the same way as any other bacteria. There is substantial evidence that in a phosphate deprived, arsenic enriched environment, they survive and reproduce, although not as well as well as in an environment with adequate supplies of phosphorus. In these special circumstances, the evidence indeed suggests that they may somehow be able to form stable nucleic acid molecules with arsenic atoms structurally substituting for at least some of the phosphorus atoms. I believe that this needs to be definitively confirmed, and that there is some skepticism from some biochemists, but that the evidence is very suggestive. Arsenic is a toxin because of its atomic similarity to phosphorus. This is a fascinating example of an extremophile adaptation - they have made the short but amazing biological trip from being poisoned because arsenic is similar to phosphorous, to, it would seem, being able to exploit those similarities. This research is only peripherally related to Origin of Life studies. For now, the overwhelmingly most rational hypothesis is that these highly specialized bacteria evolved from ancestors who don't make use of arsenic. Life on earth somehow originated at least once making extensive use of phosphate containing nucleotide molecules, both as the fundamental unit of energy exchange, and as the basis of the genetic code. Later, a tiny fraction of life evolved the ability to use arsenic as a substitute for phosphorus in some ways, although they are not as robust when forced to do so.

Matt Young · 5 December 2010

I just skimmed Professor Redfield's article, and it was largely Greek to me. Can you synthesize it in 25 words or less for those of us who have no idea what OD600 and cfu are? Where I come from, OD is your right eye. OK, OK, you may have more than 25 words.

harold · 5 December 2010

Based on the Rosie Redfield link, even what I described above may include a lot of very premature conclusions.

I do think that the adaptation of extremophiles to at a minimum tolerate fairly high concentrations of arsenic is interesting in itself.

John Kwok · 5 December 2010

Bob O'H said: The paper has also been taken apart by Rosie Redfield.
Assuming that Redfield's critique is true - and it looks as though it is - then Science didn't do a good job in peer review; this paper should have been held back until further results from the authors were substantiated, or outright rejected.

harold · 5 December 2010

Matt Young -

I will step back and let the real experts get started, but cfu = "colony forming units" and OD600 = optical density of a solution for a 600 nm wavelength of visible light. They are both, in this context, ways of estimating the density of bacteria per unit volume of a solution.

Matt Young · 5 December 2010

Can you synthesize it in 25 words or less for those of us who have no idea what OD600 and cfu are?
No idea why my last comment came up as a reply to a comment from Tom; in any case, by "you" I meant Professor Redfield.

Stephen P · 5 December 2010

IANAB either, but I note that biologists Jef Huisman and Hans Matthijs of the University of Amsterdam are pretty unimpressed by this paper. According to this weekend's NRC Handelsblad (up-market Dutch newspaper) they say that the evidence presented fails to demonstrate that phosphorus has been replaced by arsenic in the DNA.

Matt Young · 5 December 2010

but cfu = "colony forming units" and OD600 = optical density of a solution for a 600 nm wavelength of visible light. They are both, in this context, ways of estimating the density of bacteria per unit volume of a solution.
Yes, thanks! Come to think of it, where I come from, OD also means "optical density," but somehow it didn't register. OD is a logarithmic unit, incidentally, so it is perfectly consistent to plot OD on a linear scale and number of cells per milliliter on a logarithmic scale.

Jim Thomerson · 5 December 2010

As I understand it, Silicon bonds are quite rigid, in contrast to Carbon bonds, which are flexible and allow Carbon based molecules to bend and wiggle; a necessity for life as we know it. If so, life as we know it could not be Silicon based. Not a chemist, so I am open to correction.

Mike Elzinga · 5 December 2010

I assume these colonies were nurtured at pretty much the same temperature.

I am curious about the temperatures at which these “arsenic and phosphorus forms” are most viable.

Just looking at the difference in ionization potentials suggests that dropping the temperature for the arsenic form may make it more viable than the phosphorus form.

This doesn’t give any indication of what the bacteria actually “do” with the arsenic, but if it is temperature dependent, that may give some idea about where it is incorporated.

harold · 5 December 2010

Mike Elzinga -

Yes, you are correct on all counts.

The colonies were probably nurtured at temperatures that are similar to those in the lake, which, given its geographic location, are probably not very extreme (the fact that other "extremophiles" are adapted to temperature, rather than chemical, extremes, notwithstanding).

One source of contention seems to be physical chemistry related - whether it's even possible for nucleotide triphosphate structure to include one or more arsenic atoms in place of phosphorus atoms, and be stable, under reasonable conditions. I'm not sure whether this has been resolved, although it would seem to be an easily resolvable issue.

At "worst", these bacteria merely have a very high tolerance for environmental arsenic (ironically, high ability to exclude arsenic from "substituting" for phosphorus would be one conceivable mechanism of achieving this). At "best", they actually can sometimes use arsenic as an imperfect substitute for phosphorus, exploiting the atomic similarities that would cause poisoning for other lineages. Either of these is pretty damn interesting on its own. The latter could be said to be peripherally related to ideas about life in extra-terrestrial environments, if such environments were conjectured to be much like earth, but with more arsenic and less phosphorus (although that seems odd given the amounts of each of those elements in the universe).

The media claims have been silly. This finding is very neat, but is not in any way directly related to origin of life research, nor does it have any resemblance to a discovery of life with a different genetic code or fundamentally different biochemistry from the rest of life on earth.

Matt Young · 5 December 2010

As I understand it, Silicon bonds are quite rigid, in contrast to Carbon bonds, which are flexible and allow Carbon based molecules to bend and wiggle; a necessity for life as we know it. If so, life as we know it could not be Silicon based.
So I gather, but who said life as we know it? Perhaps silicones are not so rigid at higher temperatures. We need to get away from looking solely for life "as we know it," though I suppose that is a sensible first step.

co · 5 December 2010

Doc Bill said: Most astounding of all is that when you magnify the bacteria they look like old lace.
It's OK, Doc Bill. I got it.

Dale Husband · 5 December 2010

Jim Thomerson said: As I understand it, Silicon bonds are quite rigid, in contrast to Carbon bonds, which are flexible and allow Carbon based molecules to bend and wiggle; a necessity for life as we know it. If so, life as we know it could not be Silicon based. Not a chemist, so I am open to correction.
Sounds about right. Also, due to the heavier weight of the silicon atoms, anything made from them would have a higher melting or boiling point than similar molecules made from carbon atoms. That would explain why in science fiction, silicon based life forms are usually in extremely hot environments. Which leads to the next question: Could a planet like Venus have silicon based life?

harold · 5 December 2010

Life on earth is predominantly based on C, H, O, N, S and P, with ions of Na, Ca, Cl, K, and Mg playing important roles, and requirements for small amounts of some other metalic elements, most obviously Fe in metazoans that use a hemoglobin system, but other things as well.

If you just tried to substitute Si for the C, without making any other changes, it probably wouldn't work, to say the least.

Whether an entire similar system, based on heavier elements from the same columns (many of which are highly toxic to much of life on earth precisely because they can partly "mimic" similar but smaller atoms), could originate, and get to the point of individual reproducing cells enclosed in some kind of membrane, or something recognizably similar, is an interesting conjecture.

Of course, we still have a massive amount to learn about how life originated here on earth. (And as I noted above, the bacterial lineage under discussion here is not likely to be any more related to that question than any other bacterial lineage.)

Wheels · 5 December 2010

harold said: The media claims have been silly. This finding is very neat, but is not in any way directly related to origin of life research, nor does it have any resemblance to a discovery of life with a different genetic code or fundamentally different biochemistry from the rest of life on earth.
NASA has been largely responsible for playing up the exobiological significance. The media were all set to report on them finding actual aliens or something, so you can scarcely blame them for passing along the more tame news without being overly critical of is presentation from NASA.
Dale Husband said:
Jim Thomerson said: As I understand it, Silicon bonds are quite rigid, in contrast to Carbon bonds, which are flexible and allow Carbon based molecules to bend and wiggle; a necessity for life as we know it. If so, life as we know it could not be Silicon based. Not a chemist, so I am open to correction.
Sounds about right. Also, due to the heavier weight of the silicon atoms, anything made from them would have a higher melting or boiling point than similar molecules made from carbon atoms. That would explain why in science fiction, silicon based life forms are usually in extremely hot environments.
Not to mention that several of the workhorse carbon bonds in biology are far more stable and less easily broken if you're using silicon instead of carbon, which would tend to make it harder for life to pass silicon around as easily as carbon in the form of metabolisms. Carbon dioxide can be broken apart by pansies, but good luck finding a plant that can break down SiO2 (otherwise known as quartz) so easily. Finally, some key organic chemistry just isn't possible with silicon because Si either doesn't form the bond with that element, or only forms a single rather than double or triple bonds.

Divalent · 5 December 2010

Whether a life form *could* be based on arsenic rather than phosphorus is separate from the question of whether one would arise on it's own in a replay of the onset of life. And that is a separate question of whether a life form based on phosphorus could evolve to one based on arsenic. I suspect the answer to the latter two questions would be no. It's unlikely to start out the arsenic way because, although they are chemically similar, phosphorus is present in the universe at levels that are several thousand times higher than arsenic.

And given that life as we know it is now so critically dependent on phosphate, is likely that a particular strain of bacteria could, at this point, only develop a tolerance for arsenate, not switch completely. And my gut tells me it’s more likely to respond to the presence of arsenate by developing an ability to better discriminate against it, rather than developing the ability to interchangeably substitute arsenate for phosphate. That is, its more likely that natural selection would enhance an organisms ability to prevent arsenic from interfering with normal biochemistry via selection for phosphate-processing enzymes that are even more selective for phosphate over arsenate.

It would be an interesting experiment to do long term evolution studies to see how good enzymes could get.

Chris Lawson · 5 December 2010

Divalent,

I think life has more evolutionary potential than you give it credit for. Already on our own planet we see life forms capable of adapting to an extraordinary array of environments. Once upon a time oxygen was a waste product that caused horrendous chemical damage inside cells, now it is an essential element for almost all of the Eukarya and many of the Bacteria and Archea.

Chris Lawson · 5 December 2010

Actually, I should have said that oxygen is still a waste product that causes damage to cells, but it is now also essential to many organisms.

Mike Elzinga · 6 December 2010

Today’s (Dec. 6, 2010) Astronomy Picture of the Day has a picture of Lake Mono with an inset of the bacteria.

th · 6 December 2010

Doc Bill said: Most astounding of all is that when you magnify the bacteria they look like old lace.
Heheh

j a higginbotham · 6 December 2010

People show quite a range of reaction to arsenic exposure (a common water contaminant in parts of the Indian subcontitnent)

There is a significant inter-individual variability in susceptibility to progression from arsenic exposure to clinical manifestations of arsenic toxicity (e.g. skin, lung, liver and bladder cancers). Several observational as well as biochemical studies have led to a prevalent hypothesis that nutritional status may account for a substantial portion of this variability, though no controlled clinical studies have addressed this important hypothesis. http://www.mailman.columbia.edu/our-faculty/profile?uni=mvg7

Wheels' points of SiO2 stability and lack of varied silicon chemistry are pretty big hurdles to overcome. The chances of silicon based life seem pretty slim.

fnxtr · 6 December 2010

I love the post title. There was an actual Enquirer (I think) headline back in the '80's that read "Man Cuts Off His Head With Chainsaw And Lives!".

eric · 6 December 2010

[NASA] trumpeted the discovery as “an astrobiology finding that will impact the search for evidence of extraterrestrial life.”
In more ways than one. This is kind of a double-edged discovery; while it means we might expect to find life in a wider variety of conditions, IMO it also means we have to be even more careful of contamination than we are now. That arsenic-using critter your probe finds may have been a hitchhiker.

John Harshman · 6 December 2010

Unfortunately, Science and Nature are all too prone to publish sensational-sounding results without delving too much into their actual merit. Anyone who's ever had a paper rejected by either should feel simultaneous annoyance and schadenfreude over the reaction. I know I do.

John Kwok · 6 December 2010

This was a paper that was worthy of rejection, based on the recent comments I have read from Rosie Redfield and another commentator also posting online:
John Harshman said: Unfortunately, Science and Nature are all too prone to publish sensational-sounding results without delving too much into their actual merit. Anyone who's ever had a paper rejected by either should feel simultaneous annoyance and schadenfreude over the reaction. I know I do.

John Kwok · 6 December 2010

I have a sickening feeling in my stomach that this could be as "memorable" as cold fusion:
John Harshman said: Unfortunately, Science and Nature are all too prone to publish sensational-sounding results without delving too much into their actual merit. Anyone who's ever had a paper rejected by either should feel simultaneous annoyance and schadenfreude over the reaction. I know I do.

Gary Hurd · 6 December 2010

The research was featured at the recent teleconferecne by the NASA Astrobiology Institute. We tried to host a post-conference discussion here at PT. The conference organizers, even announced this to the conference members, and some did try to respond to questions.

All (almost all) of the presentations were available on line, including Felisa's. It still is- "Alternative Biochemistry and Arsenic, or Life as We Might Not Expect It," Felisa Wolfe-Simon, US Geological Survey.

You all could have been weeks ahead of the newspapers, and broadcasts.

Left Coast Bernard · 6 December 2010

I'm an old guy, so I have no idea what this means

"Well, as they say on the Web, IANAB,..."

Sorry.

By the way, I've been wondering why your header illustration with the words "Panda's Thumb" in big letters has a photograph of a panda's head. Please show a photograph of a panda's thumb, which I've never seen.

Matt Young · 6 December 2010

I'm an old guy,
Me too.
so I have no idea what this means "Well, as they say on the Web, IANAB,..."
I am not a biologist. It descended with modification from IANAL, I am not a lawyer.
Please show a photograph of a panda's thumb, which I've never seen.
Good idea! I will see if I can find one.

harold · 6 December 2010

John Kwok -

I hope that this is an over-hyped but very worthwhile discovery.

At worse, it seems to be a bacterial lineage with a very interesting adaptation to an environmental compound that is toxic to most life. That's true even if it's just an arsenic-tolerating extremophile, and even more true if it can utilize arsenic as a substitute for phosphorus under limited conditions. Figuring out the mechanism of tolerance will be of great interest, and it could even have applications.

It's unfortunate that all of this "Arsenic-based Invaders From Uranus" type publicity (the authors' own fault, and so is the preliminary nature of the data and the possibility of some claims that may not stand up) got started, but the discovery itself may still turn out to be of great interest.

Gary Hurd -

Yes, there was some interesting stuff discussed here with respect to that conference. Mostly OOL stuff (this bacterial strain is an adaptation of unequivocal standard terrestrial cellular life, of course).

I think that this particular discovery has very, very limited implications for either OOL or extraterrestrial life, but on the other hand, it seems cool.

Doing biological research in extreme terrestrial environments seems like a perfectly good thing for NASA to do.

Mike Elzinga · 6 December 2010

harold said: It's unfortunate that all of this "Arsenic-based Invaders From Uranus" type publicity (the authors' own fault, and so is the preliminary nature of the data and the possibility of some claims that may not stand up) got started, but the discovery itself may still turn out to be of great interest.
This has been a problem with reporters for as long as I can remember. I remember I and my colleagues cringing when a reporter got wing of our research and wanted to interview someone about it. Not one person I have ever worked with in my entire career with ever wanted to talk to a reporter. It was always the case that a reporter or his editor wanted to inject some catchy phrase or “human interest” paragraph that made the whole article look ridiculous. Most scientists know their results are subject to being overturned. They would rather have the crucible of peer-review and crosschecking by other scientist take care of this process rather than have it sensationalized with ludicrous science fiction mixed in.

John Kwok · 6 December 2010

But NASA bears some of the blame for playing this up too:
Mike Elzinga said:
harold said: It's unfortunate that all of this "Arsenic-based Invaders From Uranus" type publicity (the authors' own fault, and so is the preliminary nature of the data and the possibility of some claims that may not stand up) got started, but the discovery itself may still turn out to be of great interest.
This has been a problem with reporters for as long as I can remember. I remember I and my colleagues cringing when a reporter got wing of our research and wanted to interview someone about it. Not one person I have ever worked with in my entire career with ever wanted to talk to a reporter. It was always the case that a reporter or his editor wanted to inject some catchy phrase or “human interest” paragraph that made the whole article look ridiculous. Most scientists know their results are subject to being overturned. They would rather have the crucible of peer-review and crosschecking by other scientist take care of this process rather than have it sensationalized with ludicrous science fiction mixed in.

John Kwok · 6 December 2010

I am wondering if how much of the results were due to accidental contamination by arsenic. While not trained in biochemistry or cell biology, I would say that Redfield's critique may be on the mark, simply for the sloppy nature of the research and how it was presented:
harold said: John Kwok - I hope that this is an over-hyped but very worthwhile discovery. At worse, it seems to be a bacterial lineage with a very interesting adaptation to an environmental compound that is toxic to most life. That's true even if it's just an arsenic-tolerating extremophile, and even more true if it can utilize arsenic as a substitute for phosphorus under limited conditions. Figuring out the mechanism of tolerance will be of great interest, and it could even have applications.

John Kwok · 6 December 2010

Am afraid that this may be this year's Darwinius, for anyone familiar with what has transpired with respect to a prior "sensational" scientific discovery. Both reporters and scientists need to do their homework better in the presenting and reporting of "important" scientific work (And I might add as an aside, both this incident and Darwinius are examples of poor scientific journalism, which, regrettably, Chris Mooney hasn't really come to grips with, especially in his book (co-authored with Sheril Kirshenbaum), "Unscientific America". Could be a classic case of Public Relations 101 for those reporters who need to be educated on what is really good science:
Mike Elzinga said:
harold said: It's unfortunate that all of this "Arsenic-based Invaders From Uranus" type publicity (the authors' own fault, and so is the preliminary nature of the data and the possibility of some claims that may not stand up) got started, but the discovery itself may still turn out to be of great interest.
This has been a problem with reporters for as long as I can remember. I remember I and my colleagues cringing when a reporter got wing of our research and wanted to interview someone about it. Not one person I have ever worked with in my entire career with ever wanted to talk to a reporter. It was always the case that a reporter or his editor wanted to inject some catchy phrase or “human interest” paragraph that made the whole article look ridiculous. Most scientists know their results are subject to being overturned. They would rather have the crucible of peer-review and crosschecking by other scientist take care of this process rather than have it sensationalized with ludicrous science fiction mixed in.

Mike Elzinga · 6 December 2010

John Kwok said: But NASA bears some of the blame for playing this up too:
Yup; and that is unfortunate. It is potentially interesting; but it needs follow-up study and verification by other groups. The “culture of celebrity” has no place in research.

Ntrsvic · 6 December 2010

John Harshman said: Unfortunately, Science and Nature are all too prone to publish sensational-sounding results without delving too much into their actual merit. Anyone who's ever had a paper rejected by either should feel simultaneous annoyance and schadenfreude over the reaction. I know I do.
A very current problem I am experiencing with my collaborators. They got a paper published in Science that I would no way "reach" the same conclusions that they did.

Jim Thomerson · 6 December 2010

I've been fortunate to be able to review and edit press releases about my work.

I watched the presentation on TV and thought it very poorly done. There were two reporters shown in sidebars and it was clear that neither had any idea what was going on. The station soon switched to another topic.

Torbjörn Larsson, OM · 6 December 2010

I don't get the graph scale discussion, Rosie seems to me to have it right.

Absorbance is already log so that an exponential decreasing intensity with a thicker or denser sample becomes a linear measure of same.

Then it must be wrong to compare that linear density measure on a linear scale with a semilog scale for another linear density measure (# cells/volume)!?

Doc Bill · 6 December 2010

I am wondering if how much of the results were due to accidental contamination by arsenic.
You must be a Kwok impersonator! First, the real Kwok wouldn't write something that stupid. Second, the real Kwok would quote at least two classmates from his fancy, dancy New York high school. And, third, the real Kwok would point out the importance of arsenic in Klingon cosmology. So, impostor, you didn't fool us at all. Better luck next time!

harold · 6 December 2010

John Kwok -

I'm not a microbiologist but I have spent a lot of time in clinical microbiology labs, and cultured a lot of E. coli back in the old days. I also have a pretty good background in biochemistry and molecular biology.

It will massively surprise me if the bacteria do not turn out to be adapted to a high arsenic environment. That alone is a worthwhile finding. It's possible that even this is wrong, but that's unlikely.

The claims of arsenic substituting for phosphorus have some rationale behind them. They may or may not stand up to more rigorous testing, but they weren't just made out of thin air.

The Pons-Fleishman cold fusion claims had no steps to bounce down. It was either cold fusion, or it wasn't, and it wasn't.

Here the circumstance is a bit different. It's true that the "Arsenic-eating killer tomatoes from Uranus" reports are incorrect.

I would say it is overwhelmingly likely that these are bacteria that can tolerate a fairly high environmental concentration of arsenic, which alone is of interest and a great model for further study. The entire technique of PCR, which has revolutionized molecular genetics research, was massively accelerated by study of an obscure extremophile bacterial strain.

I am pretty skeptical of the "arsenic in the DNA" claims, but some kind of ability to exploit arsenic may well be found. That would make it even more interesting.

harold · 6 December 2010

Doc Bill -

Just FYI, Stuyvessant High is an enriched PUBLIC school in NYC, where a lot of smart kids from humble backgrounds get their education. It's academically one of the best schools in the country, but it's no Andover. And there's nothing George W. Bush could have done to get into Stuyvessant. Not even if John Kwok wanted him to.

Doc Bill · 6 December 2010

Harold, my old buddy, and fellow Delta Pi Gamma president-for-life, I'm sure Kwok came from Humble, Tx, to attend Stuyvessant where he learned to drop names faster than I dropped calculus (twice).

All of which makes me suspicious of the idiotic comment attributed to my great friend and Klingon aficionado Kwok. Should I be proved wrong, however, I shall unfriend him (again) from my Facebook and teach the moron a great lesson. So there.

_Arthur · 6 December 2010

John Kwok: The entire technique of PCR, which has revolutionized molecular genetics research, was massively accelerated by study of an obscure extremophile bacterial strain.
More precisely, a particular heat-resistant enzyme produced by that bacteria. Most of the PCR work is done around 99C, which DNA survives, and, in the presence of that particular enzyme, the DNA is being actively duplicated. All other biological processes are being prevented by the boiling water temperatures.

John Kwok · 6 December 2010

Feckless human, thou art wrong:
Doc Bill said:
I am wondering if how much of the results were due to accidental contamination by arsenic.
You must be a Kwok impersonator! First, the real Kwok wouldn't write something that stupid. Second, the real Kwok would quote at least two classmates from his fancy, dancy New York high school. And, third, the real Kwok would point out the importance of arsenic in Klingon cosmology. So, impostor, you didn't fool us at all. Better luck next time!
Qap'la. I am John Kwok, and proud to be the scourge of my "buddy" Bill Dembski and his fellow Dishonesty Institute mendacious intellectual pornographers. Anyway, just to prove I am real, I'll leave with this little tantalizing glimpse as to what I am working on in my spare time (Note that this is unpublished, it shouldn't be distributed elsewhere online.): " He has psyched himself for hours, alert to Riordan’s e-mail. Should be simple, almost routine, having agreed in advance with him, some possible locales for this very meeting. Twice he has checked his Toshiba; shortly after he checked into his hotel room, and then, much later, after his trip to Chinatown. Clicking on it immediately, the Toshiba’s Microsoft Outlook in-box has a new unopened envelope, its golden yellow rectangle winking brightly. Riordan has finally e-mailed him. Good Lord, Jimmy thought. Good Lord! Five minutes before midnight in the Old Pueblo. Doesn’t Gerry Riordan ever fall asleep?" "Riordan has arranged his rendezvous with the Silicon Valley contact with the ease of a veteran hotel concierge, which Jimmy knows he’s not: The Japanese Tea Garden. Tomorrow. At 2 PM sharp. Her name shall be Kate. No last name, just Kate."

John Kwok · 6 December 2010

Trust me, though they don't like to think so, Stuy is better than Andover (Stuyvesant alums such as myself refer to the school as "Stuy".):
harold said: Doc Bill - Just FYI, Stuyvessant High is an enriched PUBLIC school in NYC, where a lot of smart kids from humble backgrounds get their education. It's academically one of the best schools in the country, but it's no Andover. And there's nothing George W. Bush could have done to get into Stuyvessant. Not even if John Kwok wanted him to.

John Kwok · 6 December 2010

I should have said, Doc Bill, I wonder how much the results were affected by accidental contamination by arsenic. If am reading Redfield's analysis correctly, there are some serious issues as to how well the NASA researchers handled the samples so as to minimize any contamination:
Doc Bill said:
I am wondering if how much of the results were due to accidental contamination by arsenic.
You must be a Kwok impersonator! First, the real Kwok wouldn't write something that stupid. Second, the real Kwok would quote at least two classmates from his fancy, dancy New York high school. And, third, the real Kwok would point out the importance of arsenic in Klingon cosmology. So, impostor, you didn't fool us at all. Better luck next time!

Gary Hurd · 6 December 2010

Why the attempted discussion was less successful than I had hoped is that a cluster of barnacles are affixed to the PT hull. They are the "commentators" who are still in this thread pontificating about a paper they have not read, and research that they are apparently unable to understand.

Matt Young · 6 December 2010

I don't get the graph scale discussion, Rosie seems to me to have it right.
No, she does not. A commenter, AMac, explained it correctly on her blog at 9:41 today. I responded to that commenter, saying that I thought he got it exactly correct, but my comment has since disappeared. Very briefly, the optical transmittance is proportional to the concentration of cells in suspension (at least presuming that the suspension is optically thin). Optical density, or absorbance, is the logarithm of the transmittance (more precisely, the negative of the logarithm). If you want to display the logarithm of the concentration, then you have to compare it with the logarithm of the transmittance, which is precisely the optical density. Thus it was completely correct to compare optical density, which is inherently a logarithmic quantity, on a linear scale with concentration on a logarithmic scale, and there is nothing nefarious in doing so. That is roughly what I wrote in response to AMac's comment. In my mysteriously disappeared comment, I also responded to a comment by GregH to the effect that

I think your comments would have more credibility if you removed the ones that suggest what the author's motives are. It is difficult to distinguish between evil and incompetence. Just stick to the facts and leave out the personal jabs.

Specifically, I supported GregH and suggested that it was impertinent of Professor Redfield to hint that Professor Wolfe-Simon and her team used a "shabby" trick, especially considering that Professor Redfield did not understand the 2 graphs in question and indeed asked me whether it made any difference whether they measured scattered or transmitted light. Finally, I called on Professor Redfield to apologize to Professor Wolfe-Simon and her team. My comment appeared almost immediately, but sometime later I noticed it had disappeared. Accusing the authors of trickery was completely out of line, it seems to me, and I still think that Professor Redfield owes them an apology.

Matt Young · 6 December 2010

Please stop feeding the Kwok troll. I realize that he is mostly on the right side and he frequently makes sense, but anyone who publishes 3, 4, and 5 comments in a row is a troll. Please do not bait him any more; I do not think I can tolerate reading "mendacious intellectual pornographer" one more time. Indeed, just dictating the phrase is enough to make anyone neurotic.

John Kwok · 6 December 2010

You should admit that the ongoing publicity about this is so reminiscient for Darwinius as the putative "missing link" connecting lower primates with the apes, and thus, Man, when it was later shown to be merely a sister taxon to that "missing link":
Gary Hurd said: Why the attempted discussion was less successful than I had hoped is that a cluster of barnacles are affixed to the PT hull. They are the "commentators" who are still in this thread pontificating about a paper they have not read, and research that they are apparently unable to understand.
I don't have a Science subscription, but will read the article. Have read only the abstract.

John Kwok · 6 December 2010

Matt, I have been away and unable to reply for hours. My apologies if you think I have been trolling:
Matt Young said: Please stop feeding the Kwok troll. I realize that he is mostly on the right side and he frequently makes sense, but anyone who publishes 3, 4, and 5 comments in a row is a troll. Please do not bait him any more; I do not think I can tolerate reading "mendacious intellectual pornographer" one more time. Indeed, just dictating the phrase is enough to make anyone neurotic.

David · 7 December 2010

Matt (and others)-

The discussion on OD600 is a bit confused. Yes, optical density is the log of the inverse of transmittance ( OD = log(I0/I) ). But transmittance is not proportional to concentration, OD is. This is Beer's law, OD = e * l * c, where e is extinction coefficient, l is path length, and c is concentration. I refer you to the wikipedia entries on absorbance and beer's law:
http://en.wikipedia.org/wiki/Optical_density
http://en.wikipedia.org/wiki/Beer%27s_law

Now, it is true that OD600 of cells is not measuring absorbance proper, but scattering, so it only obeys beer's law when OD is low (and thus secondary scattering effects are negligible). Fortunately, this is generally true for OD600 less than 0.5 or so, right in the range of maximum sensitivity for most commercial spectrophotometers. See the following, and links therein for details:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC170707/pdf/aem00013-0282.pdf

So in most cases, including the arsenic paper, OD600 is proportional to cell density, not log cell density. As for Rosie's point, I think she's being a little harsh, for this particular point (her other criticisms are spot on, as is her point that these problems should have been caught in review). OD600 is normally presented on a linear scale (mainly b/c the dynamic range is only about a log or so), while cell density is often presented on a log scale; so the respective scales for each figure are fine. Nevertheless, Rosie is correct to point out that these two graphs cannot be compared directly, without correcting for scale.

David · 7 December 2010

Oops. amend the above:
forgot the minus sign in absorbance: OD = - log(I0/I) (where I is detected intensity, I0 is input intensity, and I/I0 is transmittance)

also, for the reference about OD of cells, "links therein" should have been references therein; the paper predates the interwebs.

harold · 7 December 2010

David -
So in most cases, including the arsenic paper, OD600 is proportional to cell density, not log cell density. As for Rosie’s point, I think she’s being a little harsh, for this particular point (her other criticisms are spot on, as is her point that these problems should have been caught in review). OD600 is normally presented on a linear scale (mainly b/c the dynamic range is only about a log or so), while cell density is often presented on a log scale; so the respective scales for each figure are fine. Nevertheless, Rosie is correct to point out that these two graphs cannot be compared directly, without correcting for scale.
It's also worth noting that the point of the OD600 measurements is part of an effort to quantify bacterial growth. It's natural for every part of a paper that draws this kind of attention to be critiqued on every aspect. It is not my impression that bacterial growth in relatively high arsenic concentration environments is highly controversial here, particularly not given the background that this strain was purified from a very high arsenic environment to begin with. Any reported results can later turn out not to stand up, but this seems unlikely to be a result that will be unreplicable. The details of growth rate in various conditions may well be modified, but the claim that they resist arsenic at all seems fairly secure. What has been controversial about this paper, and has driven the media exaggerations, has been the claims that this bacterial lineage may actually make use of arsenic, including substitution of arsenic for phosphorus in the nucleotides of DNA. As at least two people in this thread pointed out, one of them me and the other the commenter Divalent, ability to strongly exclude arsenic from cell biochemistry might seem, intuitively, to be a more likely adaptation. However, the claims about arsenic biochemistry were not made without any rationale. They were based on centrifugation fractions, and, if I recall correctly, some preliminary crystalography. Whether this startling and over-publicized result will stand up remains to be seen. This paper has generated publicity, and the publicity generated irritation, to the extent that even application of very basic techniques is being looked at with a highly critical eye, and that's reasonable. From the perspective of interested lay people, extreme focus on the OD600 may not make much sense, as that particular result is tied to the less controversial claim (bacterial growth in the presence of arsenic), not to the more controversial claim (incorporation of arsenic).

Matt Young · 7 December 2010

This is Beer's law,...
Sorry, I have to be in class all morning, till midafternoon at the earliest, but I have a feeling that Mr. David is right and I am mistaken. That does not change my view that the researchers did nothing underhanded. As for the rest of the paper, I am one of those who has not the foggiest idea and will probably agree with whoever has written in most recently.

David · 7 December 2010

Matt-
I of course encourage you to check my claims and correct me if I'm wrong. It's also refreshing to have someone consider points rationally and adjust their views when warranted; I've probably spent too much time arguing with creationists, to be impressed with this, but so it goes.

I agree with you that there's no evidence of underhandedness here, and it's a bit unfair to claim so. However, naivete and wishful thinking probably did come in to play, and I'm not the only one to think so. Check out Carl Zimmer's article in slate:
http://www.slate.com/id/2276919/

harold-
I agree, it's a minor point, and not central to the most controversial claims. I encourage you to check out Carl's article, too, I'm mostly in agreement with many of the others mentioned there.

John Kwok · 7 December 2010

Not only that David, but Carl Zimmer has (no surprise) done his homework and shown that there are other scientists who are skeptical not only of the results, but how the NASA team's analysis was carried out:
David said: Matt- I of course encourage you to check my claims and correct me if I'm wrong. It's also refreshing to have someone consider points rationally and adjust their views when warranted; I've probably spent too much time arguing with creationists, to be impressed with this, but so it goes. I agree with you that there's no evidence of underhandedness here, and it's a bit unfair to claim so. However, naivete and wishful thinking probably did come in to play, and I'm not the only one to think so. Check out Carl Zimmer's article in slate: http://www.slate.com/id/2276919/ harold- I agree, it's a minor point, and not central to the most controversial claims. I encourage you to check out Carl's article, too, I'm mostly in agreement with many of the others mentioned there.

John Kwok · 7 December 2010

This isn't an instance where it is Redfield, and Redfield, only who is quite critical of this study:
John Kwok said: Not only that David, but Carl Zimmer has (no surprise) done his homework and shown that there are other scientists who are skeptical not only of the results, but how the NASA team's analysis was carried out:
David said: Matt- I of course encourage you to check my claims and correct me if I'm wrong. It's also refreshing to have someone consider points rationally and adjust their views when warranted; I've probably spent too much time arguing with creationists, to be impressed with this, but so it goes. I agree with you that there's no evidence of underhandedness here, and it's a bit unfair to claim so. However, naivete and wishful thinking probably did come in to play, and I'm not the only one to think so. Check out Carl Zimmer's article in slate: http://www.slate.com/id/2276919/ harold- I agree, it's a minor point, and not central to the most controversial claims. I encourage you to check out Carl's article, too, I'm mostly in agreement with many of the others mentioned there.

harold · 7 December 2010

Thanks for the link, David.

The Carl Zimmer article is pretty much right in sync with everything else I have heard.

My conclusions -

1) It's honest research but possibly hasty.

2) It's pretty damn likely that these bacteria tolerate high levels of arsenic in their environment. That's a very cool feature, one with potential applications, and one that shouldn't be dismissed if everything else doesn't pan out.

3) The claim that they incorporate it into DNA was not completely without rationale, but that claim is highly controversial and contamination rather than incorporation might be the explanation. The physical chemistry arguments about the stability of arsenic in aqueous solution are perhaps the most worrisome. Still, I will reserve judgement until others attempt to replicate this more rigorously.

4) In no way shape or form does this research have strong implications for OOL, or, likely, seriously unusual biochemistry. These are earthly bacteria with an adaptation.

qetzal · 7 December 2010

I'm late to this party, but I think Redfield makes a pretty devastating argument against As in the DNA. The expected instability of DNA containing AsO4 in place of PO4 has been noted above. But Redfield also analyzes the authors' data on the amount of As in gel purified DNA. The result is only sufficient to account for about 1 As for every 5000 base pairs. The other 9,999 backbone links are presumably standard PO4.

1 modification per 5000 bp is quite a low level. Even if it's true, it might simply be the equivalent of 'damaged DNA' that the cell hasn't (yet) repaired. It's certainly not consistent with the claim that these cells are "using" As in their DNA.

harold · 7 December 2010

quetzal -

I just happened to post this on another blog -

There are four basic possibilities with regard to incorporation of arsenic into DNA in this bacterial strain. Incidentally, although the toxicity of arsenic is multi-factorial, it is mainly due to its interference with ATP as the fundamental unit of energy exchange.

1) The idea that they require or utilize arsenic in a way analogous to the use of phosphorous in other life ("arsenic based life form") can be dismissed out of hand; the paper makes no such claim, media reports notwithstanding, and shows that the bacteria do better on a high P low As medium.

2) The paper does suggest that, when environmental P is low, they may use As as a substitute, at least in some ways. That is a very controversial suggestion and it should be viewed with skepticism. Nevertheless, it probably warrants further study.

3) It's possible that they somehow can tolerate the incorporation of some amount of As into structural DNA or other crucial cell biochemicals, at least at low ratio to P.

4) Or they might actually be extremely effective at excluding As from biochemical reactions, and As found in the DNA fraction, as purified, might be a contaminant. "3)" and "4)" are not necessarily mutually exclusive. There could be tolerance for low level incorporation and and some contamination.

I am, of course, taking it for granted that the bacteria do tolerate high As concentration in the external environment, which I think has been show adequately enough that the onus is on those who would challenge that.

Mother Lode · 7 December 2010

"Researchers said that the bacterium was trained to grow without phosphorus..."

Uh, How exactly do you TRAIN a bacterium to grow without phosphorus? Wouldn't a random mutation that just happened to be successful for this particular environment be more likely? Or are we trying not to upset the creationist crowd?

Henry J · 7 December 2010

Uh, How exactly do you TRAIN a bacterium to grow without phosphorus?

"Sit!!!... Stay!!!... "

AMac · 7 December 2010

David has the right of it on absorbance being proportional to cell density, in his Dec. 7 1:05am comment. I regret claiming this proportionality for transmittance in Rosie's thread. (Old guy... slaps self.)

t. ikeda · 8 December 2010

I remember the great lengths some researchers had to go in order to show the some bacteria could grow without elements like iron. The task of demonstrating that their apparatus and media were free of trace iron was huge. What this paper shows is that one shouldn't skimp on the controls...

Given the short format of Science papers, one would hope the online, supplementary data provides more detail.

Aside: I noticed that John Roth and Norm Pace provide skeptical comments in the Zimmer article. That's not good.

Torbjörn Larsson, OM · 9 December 2010

Matt Young said:
I don't get the graph scale discussion, Rosie seems to me to have it right.
No, she does not. A commenter, AMac, explained it correctly on her blog at 9:41 today. I responded to that commenter, saying that I thought he got it exactly correct, but my comment has since disappeared. Very briefly, the optical transmittance is proportional to the concentration of cells in suspension (at least presuming that the suspension is optically thin).
Well yes, if it is thin. The reference I gave, and which you don't seem to have used, refers to extinction however. Precisely what David explains but, I assume, the correct optical theory. (Not into optics here, though I do remember having taken a course or two on lenses, lasers and fibers.) The rest of the comment doesn't pertain to me. Another rush job?

Torbjörn Larsson, OM · 9 December 2010

Matt Young said: Please stop feeding the Kwok troll.
And now I *know* you are rushing it, *I* didn't answer the Kwok. :-D

Matt Young · 10 December 2010

And now I *know* you are rushing it, *I* didn't answer the Kwok. :-D
No, sorry, incorrect inference. It appears to be a bug in the software: the second comment that I sent contained the "Replying to..." header, which must have been lying (or floating) around in cyberspace after the first comment. I went into the control panel but could not find any way to delete it. In any event, thank you for not feeding trolls.

harold · 10 December 2010

With regard to OD, please see my comment at the top of this page.

It is important to understand it and get it right, but it is, in this routine application, a measure of bacterial survival and growth. It is a very, very, very time-tested and routine technique. It is highly intuitive that bacteria make a broth solution "cloudy" when they reproduce in it. That part of the paper is very uncontroversial. The bacteria were isolated from an arsenic contaminated lake; anyone who claims that they don't even have a tolerance for a high arsenic environment is making an unusually obsessive criticism, and the onus is on them to demonstrate how that result is fundamentally wrong, and how there are bacteria in the lake if it is.

Mere efforts to fine tune or correct the precise growth rate would be constructive and potentially important, but at a high level of specialized detail, and would not conflict with the observed result that the bacteria in question are unusually tolerant of environmental arsenic.

The controversy revolves around whether the bacteria are merely resistant to arsenic, or whether they can utilize it as a less good substitute for phosphorus; the authors imply the latter, but the former is likely to be more correct, and that's true even if they have and tolerate some low level incorporation of arsenic into their biochemistry when grown on high arsenic low phosphorus media. However, further testing will resolve this to a greater degree of rigor.

The ludicrous idea that they preferentially utilize or require arsenic instead of phosphorus ("arsenic based life form") is in no way, shape, or form supported by the reported results, media claims notwithstanding.

harold · 10 December 2010

I will note that these bacteria could be said to "prefer" high arsenic environments in a more mundane sense.

They grew better in low arsenic medium in the lab, but in non-lab environments like that, they would likely be out-competed by other bacteria. High arsenic gives them a relative competitive advantage.

Here are some questions I am left with - some of them may well be answered in the paper, and my apologies if they are...

1) What other bacteria are they related to? They sort of look like cocci in the electron micrographs. I don't even know if they are gram negative or gram positive.

2) I doubt that they need arsenic as a nutrient, even a trace one, but have they been grown on truly arsenic free media?

3) How did their growth rate on low arsenic, high phosphorus media compare with the growth rate of common environmental bacteria?

John Kwok · 10 December 2010

Before you consider these questions, harold, I would suggest reading Carl Zimmer's Slate piece first. In light of what I have read there, I think these questions are now moot:
harold said: I will note that these bacteria could be said to "prefer" high arsenic environments in a more mundane sense. They grew better in low arsenic medium in the lab, but in non-lab environments like that, they would likely be out-competed by other bacteria. High arsenic gives them a relative competitive advantage. Here are some questions I am left with - some of them may well be answered in the paper, and my apologies if they are... 1) What other bacteria are they related to? They sort of look like cocci in the electron micrographs. I don't even know if they are gram negative or gram positive. 2) I doubt that they need arsenic as a nutrient, even a trace one, but have they been grown on truly arsenic free media? 3) How did their growth rate on low arsenic, high phosphorus media compare with the growth rate of common environmental bacteria?

John Kwok · 10 December 2010

Typo - Meant to say, "Before you consider these questions, harold, I would suggest reading again Carl Zimmer's Slate piece. In light of what I have read there, I think these questions are now moot:"
John Kwok said: Before you consider these questions, harold, I would suggest reading Carl Zimmer's Slate piece first. In light of what I have read there, I think these questions are now moot:
harold said: I will note that these bacteria could be said to "prefer" high arsenic environments in a more mundane sense. They grew better in low arsenic medium in the lab, but in non-lab environments like that, they would likely be out-competed by other bacteria. High arsenic gives them a relative competitive advantage. Here are some questions I am left with - some of them may well be answered in the paper, and my apologies if they are... 1) What other bacteria are they related to? They sort of look like cocci in the electron micrographs. I don't even know if they are gram negative or gram positive. 2) I doubt that they need arsenic as a nutrient, even a trace one, but have they been grown on truly arsenic free media? 3) How did their growth rate on low arsenic, high phosphorus media compare with the growth rate of common environmental bacteria?

harold · 10 December 2010

I don't interpret the Zimmer summary that way.

Arsenic resistance is fairly rare and itself of interest. (This is not necessarily the only instance of it, but it is unusual and of interest.)

One could simply attach an arbitrary exaggerated claim to any discovery, and then say that the valid parts of the discovery shouldn't even be discussed because an exaggerated claim was made. However, that would be most silly.

I suppose it's true that research on the mechanism of arsenic resistance will be inappropriately inhibited by the backlash against the publicity, but that's unfortunate.

harold · 10 December 2010

And that will be my final comment on the thread, as no-one seems to have much interest in this topic beyond refuting the exaggerated media claims.