Redefining the Chemistry of Life?

"The way I like to think about this organism is that it's an extremophile. They've discovered a new extremophile... This is an organism that they have discovered that would prefer phosphorus but can make use of arsenic if it is present... Just because life exists under extreme conditions doesn't mean that it is more likely to originate under those conditions than more moderate conditions... Whether... high temperature, high acid, high alkalinity, high salinity, or high radiation environments, all those circumstances... will actually disrupt pre-biotic chemistry needed to generate life and this would be the same situation. Just because it exists under high arsenate conditions does not mean it could originate under those conditions." ~ Dr. Fazale "Fuz" Rana

Last month there were a bunch of headlines floating around touting a discovery made by NASA astrobiology research fellow Felisa Wolfe-Simon ("Fe Lisa" or "Iron Lisa") that she and her team published in Science. A few popular headlines were "Arsenic-eating microbe may redefine chemistry of life", "Microbe Finds Arsenic Tasty; Redefines Life", or (my favorite) "Arsenic-Eating Bacteria Opens New Possibilities for Alien Life". A few of you out there have asked me about this privately and I have given some short answers, but I have wanted to write up a more detailed comment on this work for the last month. Because December was so busy, as I am sure it was for all of you, I have not gotten to it until now. Of course, that might be a good thing because I have now had the chance to read the paper and look at some peer criticism of how this was communicated to the public. But, now that I have a little time, here it goes...

Before we get into the actual paper and discovery, I would like to talk a little about the history of thought in chemistry and biology that led to this research and Dr. Wolfe-Simon's discovery. This is going to get a little bit technical but I will do my best to explain it clearly and it is necessary to talk about this discovery.

Life as we know it has six major elements that are crucial for it: carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. You might see these abbreviated as CHNOPS because they are commonly talked about as a group in reference to life. These particular elements are among the most abundant in the universe and have unique chemical properties that allow them to assemble into complex, stable molecules that can then further aggregate into complex, stable super-systems (DNA and RNA would be examples of these) to create an organism. Most scientists today believe that life must have these elements to exist. There are, however, a few that believe life could possibly be built on an alternative biochemistry. For example, it has been suggested that silicon could replace carbon or, in the case of this discovery, arsenic could replace phosphorus.

Why these particular replacements? Well that has to do with the chemistry of the elements in the Periodic Table (PT). The PT is one of the greatest achievements of science (I say that even though I am a physicist, not a chemist) and one of the reasons I say that is because of its construction. One can look at the PT and get a lot of information about the elements just by the position of those elements in the table. For example, elements in the same column have similar chemical properties. The closer they are, the more similar the chemistry. That is what is important for our purposes here. Take a look at the cutout from the PT on the left. Carbon's chemical symbol is C, silicon's is Si, and silicon is right below carbon in the PT, which shows us that there are chemically similar. Phosphorus' chemical symbol is P, arsenic's chemical symbol is As, and arsenic is right below phosphorus in the PT, which, again, tells us that they too are chemically similar. Some scientists think that the chemistry may be similar enough to represent possibilities for alternate biochemistries other than CHNOPS. Perhaps one could replace Si for C, thus the biochemistry would be SiHNOPS or perhaps As could replace P creating a CHNOAsS biochemistry. It is this kind of thinking that motivated the study.

Before we go further to the pertinent study, a few words need to be said about phosphorus and arsenic since they are the important elements for this particular discovery. In nature phosphorus primarily exists as phosphates (an ion with four oxygen atoms bound to a phosphorus atom). In this form, phosphorus plays an extremely important role in biochemistry. It is crucial to a number of biochemical functions (like regulating protein activity and the formation of the cell membrane) and biomolecules (like DNA, RNA, and metabolites). It has been generally thought that it is phosphorus' unique qualities that allow it to play an integral role in all of these functions but, as described above, arsenic is chemically very similar to phosphorus. Could arsenates (similar to phosphates) serve the above functions?

Arsenic does form into arsenates (an ion with four oxygen atoms bound to an arsenic atom) but they are toxic. Since arsenates are so similar to phosphates, organisms can incorporate them into biomolecules but since they are different from phosphates, the bonds in those biomolecules created with arsenates (instead of phosphates) will become unstable and break down, creating havoc in the metabolic system of the organism. So arsenate is similar enough to phosphate to be allowed into the cell but dissimilar enough that, once incorporated, the cell starts to break down. If this happens on a large enough scale the organism will die. So, life should not be capable of existing in an arsenate system.

This brings us to this discovery by Dr. Wolfe-Simon and her team. First, I would like to say that this is very impressive work. These scientists should be commended for this discovery and they should be proud of themselves for opening up the door to what will probably be years of fascinating research on this organism and others like it. That being said, the discovery as portrayed to the media and the general public is overblown. This newly discovered organism is not an "arsenic-based" organism, it does not find "arsenic tasty", and it is not really as "alien" as it is made out to be.

So, what did they discover? Well, Dr. Wolfe-Simon and her team went to Mono Lake in CA to search for bacteria that use arsenic. They chose Mono Lake because it has an extraordinarily high phosphorus and arsenic content so any bacteria found there would at least have to be able to deal with arsenic. They discovered a strain of bacteria, that they labeled GFAJ-1, which appears to be able to use arsenates and phosphates to grow. They then wanted to see if it could survive only with arsenates. In order to test this, they took GFAJ-1 from the lake (where the environment has high levels of phosphorus and arsenic) into their lab and put it in an environment with no phosphates and lots of arsenates. They did this to try to force the bacteria to use only arsenates, if it could, since phosphates were not available at all. They found that GFAJ-1 did survive and appeared to be incorporating arsenates into its biochemistry. Now, since the bacteria was formed in the lake with phosphorus and arsenic, they have not yet proven that it can completely substitute arsenates for phosphates because the bacteria still had plenty of phosphates to run critical systems. They did, however, show that it appears that at least some of the cells functions were using arsenates instead of phosphates, which was thought to be impossible. Through a process known as fractionation they found evidence that the arsenates were being used by GFAJ-1 in proteins, nucleic acids (DNA and RNA), and metabolites. The bacteria was even able to grow and reproduce under these conditions. Conventional biochemical knowledge says that GFAJ-1 should have died because the arsenates should have destabilized almost its entire metabolic system. With all this data, however, the conclusion that this bacteria appears to be able to do what was thought impossible--incorporate arsenates into its biochemistry, stabilize the arsenates (through a yet-to-be-determined mechanism), and survive--seems plausible (though it is also possible that this bacteria could simply be strongly resistant to arsenates).

Did they show that this life is "alien" or discover something that "redefines" the chemistry of life? No, they did not. Let me explain why. Assuming they are right that GFAJ-1 really is incorporating arsenates into its biochemistry: 

• First, even though the organism was able to survive under the extreme arsenate-rich and phosphate-poor environment, it was far from thriving like it did in Mono Lake where phosphate was readily available. The bacteria grew very slowly, reproduced at a proverbial snail's pace, and had a very distorted growth morphology. What is going on here is not completely clear yet, but these issues in the growth of the bacteria show that it probably has some kind of machinery in place to stabilize arsenates yet would prefer phosphates. So while the bacteria can survive in an arsenate-rich environment, it certainly prefers phosphates and will only thrive with phosphates.
• Second, there has been no long-term experiment done to see how long this bacteria can survive under these conditions. The bacteria began with phosphates since it was taken from Mono Lake. As it reproduced in the lab those phosphates were divided up to run critical systems. It is highly possible, as some critics has suggested, that colony could die off after it has spread its phosphate supply too thin. 
• Third, this finding is not proof that there is any bacteria naturally doing this. It only shows that it this bacteria seems to have a mechanism that allows it to use arsenate when it has to. It could potentially do it naturally (no one is sure how long it can) but this is certainly not proof that there are lifeforms regularly doing this.
• Fourth, the team had to create an arsenic-rich, phosphorus-poor environment. Finding a natural environment like this where biochemistry would have to be completely redefined is highly unlikely. Why? Because phosphorus is much more abundant in our universe than arsenic. In the earth's crust there is 667 times more phosphorus than arsenic. In the rest of our known universe there is 2500 times for phosphorus than arsenic. These abundances show that it is highly improbable that there would ever be a naturally occurring environment anywhere in the universe with all arsenic and no phosphorus that would cause life's chemistry to be redefined in a way similar to GFAJ-1.

What is the bottom-line? If it is not "alien" and does not "redefine" life's chemistry, what kind of organism is it? As I quoted from Dr. Rana above, it is (at best) an extremophile--organisms that can grow and survive under extreme conditions like high temperatures, high acidity, or, in this case, environments with high amounts of toxic arsenates. To get a little more specific, it could be a facultative arsenophile, which means it seems that it can use arsenic when necessary. Organisms are either obligatory or facultative. The former means they require a particular set of conditions to live. The latter means that the organism can make use of something if it is present under extreme conditions but do not prefer it. For example, e. coli is a facultative anaerobe, meaning that it would prefer an environment with oxygen but can, if necessary, survive in an oxygen-poor environment. In this case, GFAJ-1 being a facultative arsenophile means that it seems to make use of arsenic under extreme conditions. It is not an organism that has a "redefining" biochemistry, it is not an "arsenic-base" organism, it does not find "arsenic tasty;" at best it an extremophile that can possibly make use of arsenic when it is the only thing available in the environment but its preference would be phosphate.

Before I wrap this post up, I want to comment on one more thing that I quoted from Dr. Rana above. It has been suggested that this type of organism could represent an alternate way that life could emerge. Sorry, but this kind of organism does not provide a different possible pathway for life to originate. The reason why Dr. Rana says that, and I agree, is because this type of organism not only has the biochemistry of normal bacteria but has extra mechanisms that allow it to live under the harsh condition of excess arsenic. In short, it is an organism that is significantly more complex than normal bacteria that is based on phosphates alone. Arsenate is unstable, so unless you already have in place mechanisms that could stabilize the arsenates, there is no way life could form with arsenates. Origin of life in an arsenate system (vs. a phosphate system) is a significantly more complex pathway and even more improbable than the existing, phosphate-based origin of life scenarios. The same is true for all extremophiles. In fact, there have been papers written by other biologists arguing this point.

So what has Dr. Wolfe-Simon's done? She and her team have done some excellent research and made a fascinating discovery but they have not redefined anything or discovered something alien. What they have done is open the door for much more research in this area. There are still a lot of questions to be answered about this bacteria. Is GFAJ-1 really using the arsenates or just surviving as best it can in such an environment? If so, how are the arsenates stabilized? What do the molecules that incorporate arsenate look like? Could a DNA molecule with arsenate instead of phosphate be made in the lab?

By His Grace,
Taylor