Hic, Haec, Hype–Little Green Men or Arsenic in DNA?

Double-stranded B-DNA. Central base pairs illustrated schematically in dark blue. Alternating sugar and phosphate/arsenate backbone (sugar = pentagon, arsenic/phosphorous cyan, and oxygen atoms in red).  Illustration prepared by the author using UCSF Chimera.

I was on the treadmill watching CNN as the drama of the NASA press conference unfolded. Speculation had been going on for days about the topic. Could there possibly be life in outer space?

I have been a little skeptical about NASA ever since being involved with it on a crystallization project in the 80s, when I worked at 3M, fondly remembered by me and other old-timers as The Mining.

At that time 3M took the now unfashionable step of forming something they called the Science Research Laboratory (SRL) where we were to do basic science with high potential for industrial applications.

It was a marriage made in limbo. 3M wanted to claim that it was doing cutting edge research, and NASA wanted to demonstrate that its work was of interest and applicability to industry.

What came of this? Some work on perfectly round spheres and more perfect crystals than could be grown on earth. The junior executive running our lab got to fly to Florida for launches. Friends from as far away as Germany sent me pictures of outer space grown urea crystals that had appeared in their local papers. One sarcastically asked if this was the work of Dr. Gleason.

When the time came to put money on the table, 3M demurred. But NASA’s interest in crystallography in space did not end. About that time I went to a national crystallography meeting and there a NASA rep asked if NASA could do anything for the community, like put a diffractometer in space. This never happened. To be fair, many excellent crystallographers actually got money from NASA for crystal growth experiments both on earth and in space. To a certain extent, when this country was flush, I don’t see a problem. As the Great Alinsky put it, if you can’t get people to do the right thing for the right reason, get them to do it for the wrong.

When the presser finally arrived, there was at first disappointment because it was not about discovery of little green men or their biological equivalent. It was about a bacteria that use arsenic in place of phosphorous. To me the most startling—and possibly wrong—conclusion was that phosphorous had been incorporated into the DNA backbone as illustrated in the figure above.

Now to me DNA is one of those magic molecules. I was born in 1945 and have grown up watching its story unfold. As a young prof, before good models or computer graphic were readily available, I can remember using Oreo cookies, shoestrings, and paper plates to illustrate the DNA structure.

One of my scientific heroes, the Harvard chemist Frank Westheimer, has written about possible alternatives to phosphate esters for genetic material:

“Another compound that must be considered as a basis for a possible genetic material is arsenic acid, which is also tribasic. … In any case, arsenic esters are totally unsuitable, the hydrolysis of esters of arsenic acid is remarkably fast.” Science, 6 March, 1987

So if it is really true that the DNA backbone contains mostly arsenic this is a very interesting and exciting indeed. A little digging—references not shown—indicates that the arsenate instability is lessened at low temperatures and high (alkaline) pH. Mono lake, from which the bug was initially isolated, is very alkaline and also contains a relatively high level of arsenic. One could perhaps overcome arsenate instability by using DNA repair enzymes, but that seems a little far-fetched.

There are many other interesting questions, not the least of which is the energy source for this organism. The arsenic equivalent of ATP seems unlikely to provide the same amount of energy that is released during the breakdown of the normal phosphorylated compound. The energy released by ATP breakdown is used to drive many essential biological processes.

So many questions need to be answered, but the most important one  is: Has the DNA incorporated into its structure  large amounts of arsenate and, if so, how does it get around the hydrolysis problem?

So what if Frank Westheimer got it wrong? He actually hasn’t been proven wrong yet, but it could happen. If he were still with us, I hope that he would smile. I know Pauling would. One of the nice things about science is that even great scientists are sometimes wrong. Most  of us ordinary folks make a reasonable number of mistakes, some of them even published. I remember an undergrad showing me the first generally used Web browser, in 1989. He demonstrated how links worked and how one could move seamlessly from one site to another. My reaction was: “Why would anyone want to do that?” This still makes me smile.

Further Information:

I’ve tried to keep this from being too geeky or wonkish as Krugman would say. For those hungering after more hard science, please see the following posts. If you are really hardcore, read all of the very interesting comments.

  1. Ed Yong – Not Exactly Rocket Science

Mono Lake bacteria build their DNA using arsenic (and no, this isn’t about aliens)

2. PZ Meyers – Pharyngula

It’s not an arsenic-based life form

3. Rosie Redfield – RRResearch

Arsenic Associated Bacteria (NASA’s Claims)

4. David Dobbs – Neuron Culture

Is that Arsenic-Loving Bug – Formerly an Alien – A Dog?

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