Friday, December 3, 2010

Friday Flora Frakking Fall edition

Too many leaves.




I marvel at deciduous trees. So much carbon wasted every year.

OMG! ARSENIC EATING MICROBES!!1!

It’s quite a roll-out: first, NASA’s astrobiology program announces a very important press conference coming in one week. There is all kinds of speculation, some of it quite fervid. Finally, the news. No Martians, no radio signals from Tau Centauri. Instead, a more mundane headline in the NY Times says “Microbe Finds Arsenic Tasty; Redefines Life.”

The actual science is interesting, though it doesn’t quite live up to the hype (surprise!). While the the hype is about “redefining life” and “stretching the possibilities for extra-terrestrial life,” the real interest lies in a demonstration of the power of selection and what down-to-earth microbes can do.


Here on earth, microbes (and humans, and every other living thing) have to grow—they take in atoms from their environment and convert that “dead” matter into a part of a cell. Every living thing uses pretty much the same ingredients: Carbon, Hydrogen, Nitrogen, Oxygen, and Phosphorus, with a sprinkle of other elements Why only those particular elements? Carbon is neat, but could it be substituted with an element from the same column on the periodic table, such as Silicon? No. Even though it shares some characteristics with carbon, it just doesn’t have the same wonderful reactive repertoire.


This has not stopped speculation about the other ingredients found in a cell; Felisa Wolfe-Simon at the NASA Astrobiology Institute and her coworkers wondered if the phosphorus found in the cell could be replaced with a similar atom on the periodic table. However, the element most similar to phosphorus on the periodic table is Arsenic.


As the headline suggests, Wolfe-Simon found—or more correctly, evolved—a microbe that can almost completely replace its phosphorus with arsenic. In this cell, arsenic behaves similarly enough to phosphorus that it grows reasonably well. However, despite the headlines, very little adjustment need be made to the definition of life. Some definitions of life hold that “life is mainly made of the elements Carbon, Hydrogen, Nitrogen, Oxygen, and Phosphorus.” So, that can be revised to read “…and Phosphorus (or Arsenic).” Ho hum.


The most interesting thing about this report was its application of selection. Natural selection is one of the driving forces behind evolution—from a varied initial population, the environment selects those individuals who are best able to survive and reproduce, and allows them to do so. The rest don’t make it. It’s very simple, but amazingly powerful. You can do this in the laboratory: start with a varied initial population, select only those individuals who have a certain trait (say, the ability to survive exposure to Arsenic), and allow only them to reproduce; the rest die.


As my mentors taught me, “you get what you select for.” If you start with a very large and very varied population, and slowly ratchet up the selection pressure, you can select for, and evolve, almost anything. In fact, something very similar to this recent study was accomplished over a decade ago, using slightly cleverer techniques.


A biology textbook might refine the above definition of life by mentioning proteins, and how they are all made of the same 20 amino acids, just in different arrangements. There is a genetic code, in which each of the 20 amino acids is specified by three nucleotides strung together in DNA. There are four different nucleotides (called A, G, C, and T), so there are 64 possible three-nucleotide combinations. 61 of these specify the 20 amino acids (there is obviously some redundancy), and three specify the end of a protein. You probably saw this table back in high school:

Starting in the 1980s, researchers (most notably Peter Schultz) tried to redefine life: they wanted to make proteins that had different, new, non-biological amino acids in them. To do this, they had to somehow persuade the cells to change the way they decoded their genetic information. Essentially, they had to convince a cell that “UAG” no longer should be decoded as “stop”, but rather as the bizarre new amino acid Propargyloxyphenylalanine. The cell, you might imagine, required some strong persuasion—and this is where selection came in.


Schultz’s group cleverly placed a gene in the cell for chloramphenicol resistance—if this gene were properly expressed, the cell could survive exposure to the antibiotic chloramphenicol. However, this gene was modified: it could only be properly expressed if “UAG” were translated as Propargyloxyphenylalanine. If UAG were used normally, as “stop”, the cell would stop making the protein, and die. That’s selection for you—and it allowed Schultz to find the very rare cell that had mutated so that it could pull of this trick. All he had to do was look for cells that survived chloramphenicol exposure.


Schultz used selection again to make sure hat he had succeeded; there was, after all, the possibility that the cell sometimes translated UAG as Propargyloxyphenylalanine, and sometimes translated UAG as some other amino acid. So, he cleverly placed another gene in the cell that encoded a weird protein called “barnase.” If the cell makes even a little bit of barnase, the barnase will kill the cell. The gene that Schultz used also had a UAG in it, but in this case, functional barnase would only be produced if UAG were translated as anything but Propargyloxyphenylalanine. Again, selection allowed Schultz to find the very rare cell that only translated UAG as Propargyloxyphenylalanine—selection killed every other cell. Again, all he had to do was look for the surviving cells.


So, you get what you select for—no matter how rare or absurd. Using the power of selection, Schultz and others have evolved cells that use more than 70 different, completely non-biological amino acids in their proteins—a pretty thorough redefinition of this aspect of life. How does this relate to the Arsenic story? Selection. Wolfe-Simon selected for the ability to use Arsenic in place of phosphorus, and you get what you select for.


She started with microbes that were already pretty tolerant of arsenic. They are not from a very unusual family—they are proteobacteria, a family name as bland among bacteria as “Smith” among Americans. However, these had been recovered from Mono Lake in California, an environment with unusually high concentrations of arsenic. In the lab, the cells were grown with increasing amounts of arsenic and decreasing amounts of phosphorus. These conditions selected for the ability to replace phosphorus with arsenic, so cells that could do this would grow and reproduce. Those cells that could not (and these were the vast majority) simply died. The selection was made harsher and harsher, so that eventually cells were growing in as close to phosphorus-free conditions as could be managed. Selection found the rare cells that learned to use arsenic, and all Wolf-Simon had to do was look for the survivors. Over the course of just a few generations, Wolfe-Simon forced the evolution of an Arsenic-using bacterium (figure C).

This is a rather extraordinary claim, and as Carl Sagan noted, extraordinary claims require extraordinary evidence. So, the bulk of Wolf-Simon’s report consists of proofs that these cells are chock-full of arsenic and very low in phosphorus. It’s bizarre—virtually everything that is usually has phosphorus has arsenic. So DNA and RNA have a sugar-arsenate backbone; ATP is now Adenosine tri-Arsenate; NADH has Arsenate rather than phosphate; the membrane phospholipids are now arseno-lipids, and so on. There’s a hint of phosphorus left. (One thing that needs to be cleared up is just how much phosphorus there is left, and where it is.) These cells (figure C) are strikingly different in aspect from their immediate “wild” ancestors (figure D). The Arsenic-incorporating cells are larger and somewhat irregularly shaped. A cross-section electron micrograph shows that much of their volume is made up of storage vacuoles absent in their ancestors (figure E; note that the magnification is five times greater). These may be for storing excess arsenic, or protecting some cellular machinery from arsenic. These are not exceptionally happy cells, though: it takes them almost two days to grow and divide. One can almost hear them sighing with relief when the arsenic is taken away and replaced with phosphorus; their growth rate almost doubles.


Like any good study, this one raises lots of new (and previously undreamt-of) questions. The ancestors of these cells were isolated from an arsenic-rich environment—so, how much arsenic (if any) is there incorporated into these cells in the wild? How much actual genetic difference is there between the laboratory-grown cells and wild cells? Could one evolve arsenic-using cells from other cells in the same environment, or even cells from other environments? The cells grown on arsenic are clearly sick—could they evolve to actually prefer arsenic to phosphorus? These are all questions that would really help us understand life on earth.


I don’t think this has the hyped impact on astrobiology. For one thing, NASA’s own definition of life scrupulously avoids mentioning specific elements as being necessary for life. Furthermore, arsenic is a much less common element in the universe than phosphorus. However, this is a really neat finding, the result of clever work, and it gives us fresh opportunity to marvel at what life can do.


Liu, Chang. C, and Peter G. Schultz. (2010). Adding New Chemistry to the Genetic Code. Annual Review of Biochemistry 79: 413-44.


Felisa Wolfe-Simon, Felisa, Jodi Switzer Blum, Thomas R. Kulp, Gwyneth W. Gordon, Shelley E. Hoeft, Jennifer Pett-Ridge, John F. Stolz, Samuel M. Webb, Peter K. Weber, Paul C. W. Davies, Ariel D. Anbar, and Ronald S. Oremland (2010). A Bacterium that can Grow by Using Arsenic Instead of Phosphorus. Published on-line ahead of print: Science DOI: 10.1126/science.1197258.


We’ll leave the last word to XKCD: (click to get the punch-line.)

Wednesday, December 1, 2010

The problem is that truth is boring

I had a phone conversation with a parent the other day. He was concerned about vaccination for his daughter, and had questions about safety and long-term effects of vaccines. The nature of his questions--which were the well-intentioned questions of a concerned parent--reflected the ways that different types of information get around. It's like Mark Twain is alleged to have said, a lie travels halfway around the world while the truth is still getting its shoes on.

The questions the parent had were familiar to anyone who has paid attention to the vaccine "controversy." Is there a link between vaccines and autism? Is the mercury in vaccines going to cause brain damage? Is the aluminum in vaccines going to cause problems? There are so many vaccines--won't the immune system get tired out? Isn't the flu vaccine ineffective? Was the whole response to H1N1 completely overblown?

The answer to all of these questions is no. The undying persistence of these questions is really frustrating, and shows the sort of asymmetrical warfare that goes on between reality and wishful thinking. All you have to do is mention some poorly-supported hypothesis once, and it is established. If it appeals to people's fears or prejudices, then it is solidly rooted. The problem, though, is that the truth is boring. It can take a long explanation with lots of evidence and patient demonstration to prove the obvious--and even then, there has been some research showing that people still assign greater trust to the thing that they heard first, even if they've been shown solid evidence to the contrary.

So I tried to be patient and tactful with the concerned parent. I pointed out the origin of each of the rumors, how they were generally based on very incomplete and biased information. How, if you directly tested the question, the problem just disappeared. How the immune system can generate a virtually infinite number of immunities. How, due to poor sampling and a knowledge of history, H1N1 was initially terrifying to epidemiologists. How there's a whooping cough epidemic going on in California, and how it is totally unnecessary. How, if you were concerned about risk, you'd avoid McDonalds and driving. But I don't know if the concerned parent will vaccinate. Too often, if reality doesn't conform to bias, bias wins.

This pattern goes on too often. Just about any popular "debate" about science follows this pattern--evolution, climate change, vaccination, you name it. Rumor blurts something out, and refuting it takes patient work with lots of footnotes.

The day after my conversation, this cartoon appeared on the web, from the often amusing SMBC:

Sunday, November 28, 2010

First ski of the year

Skiing has some similarities to playing the violin. It's really easy to do it badly. And, when you do it just right, it feels so amazingly good that you are instantly hooked. You're desperate for the next fix, so you struggle and try and spend and go to all sorts of lengths in search for that perfect instant.

Today was the first ski of the year for the Real Doctor and myself. California has had a series of cold, wet storms blow through, and last night it was cold enough that it snowed down to 3,000 ft in elevation. 7,000 feet up at Donner Pass, where we ski, there was eight feet of snow and the morning temperature was in the teens. We got to the ski area around 10 in the morning, and the temperature was about 25 degrees--absolutely perfect. "Blue wax" conditions like these are rare in California, where klister is the rule for most of the season, so it was a struggle to avoid the irrational exuberance that is normal for the first ski of the year. I am only a little sore.

As they say, if you can walk, you can ski. However, you'll ski very badly. Skiing well is nothing like walking, and my muscles have been forgetting all about how to ski for the last 8 months. So most of the day was spent just trying to remember...hip forward...open up like so...weight over there, then over there...don't look at your skis, look at the trees!...and so on.

Friday, November 26, 2010

Friday Flora

The Real Doctor has been acquiring plants at an alarming rate due to a titration problem. It started with a couple of interesting orchids being purchased from Santa Barbara Orchid Estates; these few required some indoor lighting set-up. However, the indoor lighting set-up, despite being small, still had some extra space. So, more plants were purchased. However, the number of plants exceeded the room on the indoor lighting set-up. So, a larger indoor lighting set-up was purchased. (Note the persistent use of the passive voice; this absolves all concerned from any agency or blame). However, the only reasonable larger indoor lighting set-up involves three shelves illuminated by four-foot fluorescent lights. So, the capacity of the indoor lighting set-up now vastly exceeds the number of plants. Clearly, more plants must be acquired.

Fortunately, I like plants. Especially funky cacti that look like they are desperately trying to be rocks, until they let loose with blooms like this:

Ariocarpus kotschoubeyanus (Northern Mexico, S. of the Rio Grande)

Wednesday, November 24, 2010

Just in time for Thanksgiving

The turkeys have made another appearance. It's the same flock of four, and they're still clueless about how to deal with traffic. When I saw them this morning, one was paused in the middle of the road, holding up traffic. A car tried to pass at the same instant the turkey decided to finish crossing the street. The bird ended up running alongside the car for a while, confused as to why it couldn't run around the car. This agitated the three other birds, who couldn't see their pal, so they started some concerned gobbling. The incident was resolved when all four birds flew straight up, then onto the roof of a two story house.

We haven't seen them for over a month, and I was thinking that maybe they went and joined their brethren on the American River Trail, or (given their inability to figure out cars) they had shuffled off this mortal coil. However, I'm thinking they may be a permanent part of the 'hood. As neighborhood fauna, I prefer them to the cats that infest our yard.

Monday, November 22, 2010

Like Senioritis

I commiserated with K. today. Like me, she is a lecturer at the university. It's near the end of the quarter and we're both more tired than we expected to be. We have both taught our classes many times before, so we could easily phone them in. However, we both are always trying to get them to work better. We tinker with this, adjust that, experiment with the other, and so on. The bulk of the class remains the same, but so much work is spent on the fiddly improvements that it wears you out. It's kind of like Greg LeMond said about bicycling--it never gets any easier, you just go faster. Teaching's always all-consuming, you just hope that you do it better.

We both have spent a lot of time and energy to improve our courses. She has attended workshops in college teaching, and done amazing things with introductory biology at Davis. She has even written her own textbook. She teaches something like 1500 students every year. Like me, K. has been told by the university that there won't be employment for us next year.

So, we're tired, largely because of challenges we're making for ourselves. We try not to think about the end of our jobs--as soon as we do, we both find ourselves just not caring. Why should we bother? We decided that we're in danger of a sort of professional senioritis. K. is looking for something that motivates her (other than riding a horse). I'm probably in denial, keeping thoughts of an uncertain future at bay by giving myself more work to do.