Looking for a signature

Finding unequivocal evidence of extraterrestrial life is not as easy as science fiction makes it sound.

The problem is, we're biased toward detecting terrestrial life -- living things that have a similar chemistry to the familiar life forms here on Earth.  It's understandable; I mean, why would we not be?  While there is a great diversity of species here on our planet (something on the order of nine million extant, at an estimate), they all share the same basic biochemistry, including:

• ATP as an energy driver
• some form of sugar-fueled cellular respiration to produce that ATP
• phospholipid bilayers as cell membranes, and (for eukaryotes) for the internal membranes that compartmentalize the cell
• proteins to facilitate structure, movement, and catalysis (the latter are called enzymes)
• nucleic acids such as DNA and RNA for information storage and retrieval
• lipids for long-term energy storage

While there are obviously different twists on how exactly these things work, those features are common to just about all life on Earth.  (Interestingly, a 2010 paper claiming a microbe had been discovered in California's Mono Lake that incorporates arsenic into the backbone of its DNA instead of phosphorus was just retracted by the journal Nature -- although the retraction is controversial, and the authors are still defending their work as valid.)

The question remains unsolved, therefore, of the extent to which the genesis and evolution of life are constrained -- by which we mean that the pathways taken by biology might be expected to repeat on other Earth-like worlds.  (Or, to use Stephen Jay Gould's pithy phrase, we might find that evolution would produce similar forms again here on Earth if we were somehow able to "replay the tape of life.")  Would living things, down to the biochemical level, be at least somewhat like terrestrial life, or would they be entirely different?

To be fair to the science fiction writers, there have been instances where they've made a significant effort to consider what life "not as we know it" might look like.  Star Trek's Horta ("The Devil in the Dark"), Crystalline Entity ("Silicon Avatar"), and Tholians ("The Tholian Web") come to mind, as well as Doctor Who's Vashta Nerada ("Silence in the Library"), Boneless ("Flatline"), Not-Things ("Wild Blue Yonder"), and Midnight Entity ("Midnight").  

Even Lost in Space gave it a creditable try with the Bubble Creatures in "The Derelict."

The problem is more complex than that, though.  Since we can't actually go to other planets and search for living things -- even going to planets and moons in our own Solar System is crazy expensive and fraught with difficulties -- we're stuck with looking for biosignatures, traces (either structural or chemical) that show unequivocal evidence of being created by living things.

The sticking point is that word unequivocal.  Two good examples of this came to light in the last couple of weeks, one of them (from the standpoint of people like me who would love nothing better than to find out we're not alone in the universe) bad news, and the other one -- at least tentatively -- good news.

Let's start with the bad news first.

Back in 2005, NASA's Cassini mission spotted something exciting -- the presence of organic molecules in water-rich plumes erupted from Saturn's icy moon Enceladus.  The surmise was that these plumes were created by pressure in the moon's interior, where water might be kept liquid by tidal deformation from the huge gas giant's gravitational pull.  Now, organic doesn't mean produced by life; it's a chemistry term meaning "containing carbon and hydrogen."  (Formaldehyde, for example, is an organic compound, and has been found by its spectral signature in interstellar gas, and no one's claiming that it was made by aliens.  At least, no one I'd want to have a conversation with.)  On the other hand, lots of organic compounds are made by living things, so their presence in Enceladus's geysers certainly seemed to raise at least the possibility that underneath the ice, there might be a watery ocean that harbored life.

Well, a study led by scientists from Italy's Istituto Nazionale di Astrofisica e Planetologia Spaziale has found another possible explanation.  The organic molecules could be formed right there on the surface by radiation funneled in by Saturn's magnetic field, then blasted off the surface -- i.e., they didn't come from an interior ocean at all.  "While the identification of complex organic molecules in Enceladus's environment remains an important clue in assessing the moon's habitability, the results demonstrate that radiation-driven chemistry on the surface and in the plumes could also create these molecules," said Grace Richards, who led the study.  "Molecules considered prebiotic could plausibly form in situ through radiation processing, rather than necessarily originating from the subsurface ocean.  Although this doesn't rule out the possibility that Enceladus's ocean may be habitable, it does mean we need to be cautious in making that assumption just because of the composition of the plumes."

The second paper had more hopeful news.  It comes out of Stony Brook University, and is an analysis of some mudstones found in Jezero Crater on Mars by the Perseverance rover.  The analysis -- done long-distance, obviously -- found traces of organic material, along with ferrous sulfate and ferric sulfide.  Most interestingly, the organic material seems to have undergone post-deposition redox reactions; redox reactions are the mechanism by which all terrestrial life forms harvest energy for their life processes (cellular respiration is, basically, one long string of redox reactions).  The minerals, the researchers say, "challenge some aspects of a purely abiotic explanation" -- cautious science-speak for, "Life?  Yeah, could be."

Of course, this is not proof, and Sagan's principle that I mentioned in a post a few days ago -- "Extraordinary claims require extraordinary evidence" -- certainly applies here.  But it is fascinating, and if further inquiries support the biotic explanation for the odd chemistry of the Jezero mudstones, it'll be somewhere beyond exciting.  I've always thought it likely that life is common in the universe, but having a real, honest-to-Gallifrey extraterrestrial example would be amazing.

In any case, keep your eyes on the science news.  Despite the ridiculous budget cuts NASA is facing, they're still doing some wonderful science.  And hopefully, at some point, we'll actually find proof of aliens.  Wouldn't that be cool?

I hope it's not the Vashta Nerada, though.  Those mofos are scary.

****************************************

Curse to cure

The always-hilarious Gary Larson, whose ability to create absurd combinations of cultural references is unparalleled, had a Far Side comic strip showing a typical office waiting room.  Sitting in one of the chairs, cross-legged and reading a magazine, is a mummy.  The secretary -- with the trademark Larson bouffant hairdo and cat's-eye glasses -- is on the phone to her boss, saying, "Mr. Bailey?  There's a gentleman here who claims an ancestor of yours once defiled his crypt, and now you're the last remaining Bailey, and... oh, something about a curse.  Shall I send him in?"

The whole "Mummy's Curse" thing usually brings to mind the "Boy King" Tutankhamen, and the claim that twenty members of the expedition that opened the tomb died not long afterward.  There are three caveats to this, however: the deaths happened over a decade, suggesting that Tut wasn't in a great hurry to get his vengeance; a statistical study showed that the average age at death of the people who did succumb to "King Tut's Revenge" was no lower than that of the background population; and there is a plausible case to be made that at least two of the deaths (Howard Carter's personal secretary, Richard Bethell, and Bethell's father Lord Westbury, both of whom were murdered) were killed by, or on the orders of, none other than Aleister Crowley.

Whether this last bit is true or not remains very much to be seen; in my opinion, the case relies on highly circumstantial evidence, and after a hundred years it's doubtful we'll ever know for certain.  What I'm pretty sure of is that a scattered bunch of deaths, over ten years or so, of men who were mostly upper middle-aged is not really that much of a mystery, and the curse is nothing more than an attempt to give an added frisson to an archaeological find that honestly is interesting enough without all the supernatural trappings.

On the other hand, consider the opening of the tomb of Casimir IV Jagiellon, King of Poland and Grand Duke of Lithuania.  Casimir is considered one of the most able Polish kings, and consolidated his territory, won many military victories, and generally was a force to be reckoned with.  He died in 1492, and was interred with much pomp and circumstance in Wawel Cathedral in Kraków.

Casimir IV Jagiellon of Poland [Image is in the Public Domain]

In 1973, a team of twelve historians and archaeologists opened his tomb.

Within weeks, ten of the twelve were dead.

So do we have a real-life example of tomb desecration?  Oh, and something about a curse?

It turns out that (unsurprisingly) there's nothing supernatural involved here, either.  No need to invoke ancient Polish witchcraft.  The unfortunate researchers succumbed to infections of Aspergillus flavus, a pathogenic fungus that secretes an especially nasty group of organic compounds called aflatoxins.  Fungal infections are notoriously hard to treat -- fungal cells are similar enough to animal cells that chemicals which will kill a fungus often don't do our own tissues any good at all.  Fungal spores are also incredibly tough and long-lived; the Aspergillus spores that killed the research team members had likely been there since the tomb was sealed, over 530 years ago.

But Aspergillus isn't all bad.  A team at the University of Pennsylvania just published a paper in Nature Chemical Biology looking at a different set of compounds the fungus produces -- and found they target and disrupt cancer cells, especially those in leukemia.

The chemicals are called ribosomally synthesized and post-translationally modified peptides.  The biochemists call them RiPPs, even though the actual acronym would be RSaPTMPs, which I have to admit would be a little hard to pronounce, so RiPPs it is.  And the scientists found that the RiPPs produced by Aspergillus flavus had as much potency against leukemia cells as cytarabine and daunorubicin, two of the go-to drugs used to treat the disease for decades.

"Nature has given us this incredible pharmacy," said Sherry Gao, senior author of the study.  "It's up to us to uncover its secrets.  As engineers, we're excited to keep exploring, learning from nature and using that knowledge to design better solutions."

Which I think you will all agree is a better approach than superstition about opening graves.

Still, it's probably best to be cautious in any tomb-raiding you're planning on doing.  Curses not withstanding, aspergillosis is nothing to mess around with.  Even if the fungus turns out to have some beneficial features, remember to wear your respirators the next time you investigate the burial sites of fifteenth-century Polish kings.

****************************************

To dye for

The history of dyes is actually way more interesting than it sounds.

People have been coloring cloth (and pottery, and cave walls, and their own bodies) for a very long time, but all colors don't turn out to be equally accessible to the palette.  Red, for example, is fairly easy, especially if you don't care if it's not screaming scarlet and has a slight brownish tint (what we'd call "brick red"), because that's the color of iron oxide, better known as rust.  Iron oxide is plentiful, and I know from messing around with pottery glazes that it's got two properties: (1) mixed with other minerals and/or heated in the absence of oxygen, it can give you a variety of other colors, from black to dark blue to green; and (2) it sticks to everything.  I have brushes I use in the glazing process that I used once or twice to apply an iron-based glaze, and now they're permanently stained red.

Other colors, however, aren't so easy.  Some of the more notoriously difficult ones are true blues and purples; our appending the word "royal" to royal blue and royal purple is an indicator of the fact that back then, only the really rich could afford blue or purple-dyed cloth.  Blue can be achieved using small amounts of cobalt, or finely powdered lapis lazuli, but neither is common and although they have other uses (cobalt in pottery pigments, lapis in paints) neither works well for dyeing cloth.  Lapis, in fact, was used to produce the finest rich blue pigment for oil paints, which got named ultramarine because the mineral was imported from what is now Afghanistan -- a place that was ultramarinus ("beyond the sea") to the people in Italy and France who were using it.

But dyeing cloth was another matter.  One solution was, bizarrely enough, a secretion of a sea snail of the genus Murex.  These snails' hypobranchial glands produce a gunk that when purified produces a rich purple dye that is "color fast" on cloth.

How anyone thought of doing this is an open question.  Maybe they just smeared slime from various animals on cloth until they found one that worked, I dunno.

Be that as it may, the color of the dye was called φοῖνιξ (phoinix) by the ancient Greeks, and the sea traders who cornered the market on producing and selling the dye were called the Φοίνικες (Phoinikhes).  We anglicized the word to Phoenicians -- so Phoenician means, literally, "people of the purple."

The reason all of this colorful stuff comes up is a paper in Science Advances that describes how a group of chemists in Portugal successfully determined the origin of a purple to blue (depending on how it's prepared) watercolor pigment called folium that was used in medieval watercolors.  It is a gorgeous color, but all previous attempts either to replicate it or to determine its source had been unsuccessful.  The difficulty with trying to figure out things like this is that there was no standardized naming system for plants (or anything else) back then, so the name in one place could (and probably did) vary from the name in another place.  Reading manuscripts about natural dyes from that time period, about all we can figure out is "it's made by boiling this plant we found" or "it's made from special snail slime," which doesn't really tell us much in the way of details.

Samples of medieval folium on cloth [Image courtesy of Paula Nabais/NOVA University]

In the case of folium, it was known that it came from a weedy plant of some sort, but there was no certainty about which plant it was or where it grew.  But now some Portuguese chemists have identified the source of folium as the seedpods of a roadside weed in the genus Chrozophora, a little unassuming plant in the Euphorbia family that likes dry, sunny, rocky hillsides, and when you grind up the seedpods, creates a knock-your-socks-off purple dye.  The dye was then applied to cloth, and you took small bits of the cloth and soaked them in water when you were ready to use them to make a natural watercolor paint.

The scientists were able to determine the chemical structure of the dye itself, which is pretty astonishing.  But even finding the plant was a remarkable accomplishment.  "We found it, guided by biologist Adelaide Clemente, in a very beautiful territory in Portugal [called] Granja, near a very beautiful small town Monsaraz -- a magical place, still preserved in time," said study co-author Maria João Melo, in an interview with CNN.  "Nobody in the small village of Granja knew [anything] about this little plant.  It may look like a weed, yet it is so elegant with its silvery stellate hairs that combine so well with the greyish green, and what a story there is behind it."

I'm always impressed with how intrepid our forebears were at using the resources around them to their fullest, but as with the snail slime, I'm mystified as to where that knowledge came from.  Some of it was probably by happy accident -- I think fermented milk products like yogurt and cheese probably were discovered because of milk that spoiled in just the right way, for example.  But bread has always mystified me.  Who first thought, "Let's take these seeds, and grind 'em up, and add this fungus powder to it with water until it gets all bubbly and smells funny, then stick it in the fire!  That'll be delicious with jam spread on it!"

And here -- grinding up the seedpods of a random weed ended up producing one of the rarest and prettiest dyes ever discovered.  Undoubtedly the brainstorm of some medieval artist or botanist (or both) who happened to get lucky.  Makes you wonder what other plants are out there that could have odd artistic, medicinal, or culinary uses -- especially in places of enormous biodiversity like the Amazonian rainforest, where there are probably as many plant species that have not been identified as there are ones that have been.

So if you needed another good reason to preserve biodiversity, there it is.

****************************************

Dangerous reflection

Last week I ran across an article in the journal Science about our capacity for creating "mirror life," and the risks thereof.  I considered addressing the topic here, but after some thought concluded that the human race has more pressing things to worry about at the moment, such as climate change, global pandemics, terrorism, environmental collapse, and Donald Trump opening the Seventh Seal of the Apocalypse because he thought it was a can of Pepsi, so I decided against it.

Since then I've been sent the article (or various summaries and commentaries) four times, along with the questions "can you tell me more about this?" and "should I be freaking out right now?"  So I guess there's enough interest (and concern) over this that it's worth a post.

The answer to the second question, at least, is "No, not yet;" and as for the first, here goes.

The issue has to do with a property of a great many organic molecules called chirality.  Chirality is like the handedness of a pair of gloves; no matter how you flip or turn a left-handed glove, it's not going to fit on your right hand.  It's made of the same parts, but put together in such a way that it can't be rotated or translated to coincide with its opposite.  Pairs of molecules like that are called enantiomers or optical isomers (the latter because crystals made of them rotate polarized light in opposite directions).

A left-handed and right-handed enantiomer of an amino acid [Image is the Public Domain courtesy of NASA]

The key point here is that on Earth, living things generally can only synthesize and metabolize one form of chiral molecules; our amino acids are all left-handed, while our sugars (including the ones in the backbones of DNA and RNA) are right-handed.  Given a diet of food made of right-handed amino acids and left-handed sugars, we'd probably not notice a difference in taste or texture -- but since our enzymes are all evolved to deal with a particular handedness, the food wouldn't be metabolizable.

In short, we'd starve to death.

The article in Science deals with the fact that biochemists have been working to find out if it's possible to create "mirror life" -- organisms constructed of molecules with the opposite handedness as our own.  And this is what has some people concerned.  The authors write:

Driven by curiosity and plausible applications, some researchers had begun work toward creating lifeforms composed entirely of mirror-image biological molecules.  Such mirror organisms would constitute a radical departure from known life, and their creation warrants careful consideration.  The capability to create mirror life is likely at least a decade away and would require large investments and major technical advances; we thus have an opportunity to consider and preempt risks before they are realized.  Here, we draw on an in-depth analysis of current technical barriers, how they might be eroded by technological progress, and what we deem to be unprecedented and largely overlooked risks.  We call for broader discussion among the global research community, policy-makers, research funders, industry, civil society, and the public to chart an appropriate path forward.

The main concern is that if these mirror organisms were somehow to escape from the lab, we wouldn't have much of a way to fight back.  Both antibodies and antibiotics are chiral as well, and likely wouldn't recognize and bind to organisms whose cell surfaces were made of molecules with the opposite handedness.  Any of these synthetic organisms that did turn out to be pathogenic would require a whole different suite of medications, and our own bodily defenses would likely be relatively useless against them.

But.

Here's the thing.  If the scientists do succeed in creating mirror life, and it does escape, the most likely result would be... nothing.  Mirror life would itself need food, and of the proper handedness for its own enzymes; and given that everything in the environment has the same left-handed amino acids and right-handed sugars that we do, these synthetic life forms would have nothing to eat.  The only possible problem would be if the scientists created a mirror autotroph -- something capable of synthesizing its own nutrients, like cyanobacteria, algae, or plants.  Then, it could be a problem, from the standpoint that like exotic invasives, it would have no natural predators and might outcompete other organisms in its environment.

The other concern, though, is the "life finds a way" thing.  A mutation allowing one of these synthetic organisms to metabolize proteins or sugars of the opposite handedness from their own (or both of them) would be at a distinct advantage; if we created one of those, and it escaped, we might well be fucked.  The thing is, from what we know of biochemistry, that's an extremely rare adaptation.  I only know of one organism -- a rather obscure plant pathogen called Burkholderia caryophyllii -- that has an enzyme called D-threo-aldose 1-dehydrogenase that allows it to oxidize left-handed glucose.  

But unless you're a carnation, Burkholderia isn't a threat.

So that's an awful lot of ifs.  Thus my response that you don't have anything pressing to worry about from this research.

Now, mind you, I'm all for being careful, and I mean no criticisms of the scientists who are advising cautious consideration.  We have a rather abysmal track record of launching into stuff without thinking about the consequences.  But as far as whether we ordinary laypeople need to be worried about some synthetic mirror-image pathogen attacking next Tuesday and reducing us all to little quivering blobs of goo, I'd say no.

On the other hand, I'm the guy who told his AP Biology students in January of 1997 that "adult tissue cloning is at least ten years away," exactly one month before the announcement about Dolly the Sheep.  So maybe any predictions I make should be taken with a grain of salt.

****************************************

Hand-in-glove

One of the more fascinating bits of biochemistry is the odd "handedness" (technically called chirality) that a lot of biological molecules have.  Chiral molecules come in a left-handed (sinistral) and a right-handed (dextral) form that are made of exactly the same parts but put together in such a way that they're mirror-images of each other, just like a left-handed and right-handed glove.

Where it gets really interesting is that although the left-handed and right-handed forms of biologically active molecules have nearly identical properties, they aren't equivalent in function within living cells.  Nearly all naturally-occurring sugars are right-handed (that's where the name dextrose comes from); amino acids, on the other hand, are all left-handed (which is why amino acid supplements often have an "l-" in front of the name -- l-glutamate, l-tryptophan, and so on).  Having evolved with this kind of specificity has the result that if you were fed a mirror-image diet -- left-handed glucose, for example, and proteins made of right-handed amino acids -- you wouldn't be able to tell anything apart by its smell or taste, but you would proceed to starve to death because your cells would not be able to metabolize molecules with the wrong chirality.

Chirality in amino acids [Image is in the Public Domain courtesy of NASA]

Molecular chirality was used to brilliant effect by the wonderful murder mystery author Dorothy Sayers in her novel The Documents in the Case.  In the story, a man dies after eating a serving of mushrooms he'd picked.  His friends and family are stunned; he'd been a wild mushroom enthusiast for decades, and the fatal mistake he apparently made -- including a deadly ivory funnel mushroom (Clitocybe dealbata) in with a pan full of other edible kinds -- was something they believed he never would have done.

The toxic substance in ivory funnels, the alkaloid muscarine, is -- like many organic compounds -- chiral.  Naturally-occurring muscarine is all left-handed.  However, when it's synthesized artificially in the lab, you end up with a mixture of right- and left-handed molecules, in about equal numbers.  So when the contention is made that the victim hadn't mistakenly included a poisonous mushroom in with the edible ones, but had been deliberately poisoned by someone who'd added the chemical to his food, the investigators realize this is the key to solving the riddle of the man's death.

Chiral molecules have another odd property; if you shine a beam of polarized light through a crystal, right-handed ones rotate the polarization angle of the beam clockwise, and left-handed ones counterclockwise.  So when an extract from the victim's digestive tract is analyzed, and a polarized light beam shined through it splits in two -- part of the beam rotated clockwise, the other part counterclockwise -- there's no doubt he was poisoned by synthetic (mixed-chiral) muscarine, not by mistakenly eating a poisonous mushroom that would only have contained the left-handed form.

So specific chirality is ubiquitous in the natural world.  We have a particular handedness, all the way down to the molecular level.  What's a little puzzling, however, is why this tendency occurs.  Not chirality per se; that merely arises from the fact that if you bond four different atoms or groups around a central carbon atom, there are two ways you can do it, and they result in molecules that are mirror images of each other (as shown in the image above).  But why do living things all exhibit a preference for a certain handedness?  It must have evolved extremely early, because virtually all living things share the same preferences.  But what got this bias started -- especially given that left-handed and right-handed molecules are equally easy to make abiotically, and have nearly identical physical and chemical properties?

Well, a paper this week in the journal Advanced Materials may have just answered this long-standing question.  A group led by Karl-Heinz Ernst, at the Swiss Federal Laboratories for Materials Science and Technology, found that the selection for a particular handedness happened because of the interplay between the electromagnetic fields of metallic surfaces with the spin configuration of chiral molecules.

They created surfaces coated with patches of a thin layer of a magnetic metal, such as iron or cobalt, and analyzed the magnetic "islands" to determine the direction of orientation of the magnetic field of each.  They then took a solution of a chiral molecule called helicene, which had equal numbers of right and left-handed forms, and poured it over the surface.  The hypothesis was that the opposite patterns of spin of the electrons in the two different forms of helicene would allow them to bond only to a magnetic patch with a specific orientation. 

So after introducing the mixed helicene to the metal surfaces, they looked to see where the molecules adhered.

Sure enough -- depending on the direction of the magnetic field, one or the other form of helicene stuck to the metal surface.  The magnetic field was acting as a selecting agent on the spin, picking out the handedness that was compatible with the orientation of the patch.

This, of course, is only a preliminary study of a single chiral molecule in a very artificial setting.  However, it does for the first time provide a mechanism by which selective chirality could have originated.  "In certain surface-catalyzed chemical reactions," Ernst explained, "such as those that could have taken place in the chemical 'primordial soup' on the early Earth, a certain combination of electric and magnetic fields could have led to a steady accumulation of one form or another of the various biomolecules -- and thus ultimately to the handedness of life."

So a simple experiment (simple to explain, not to perform!) has taken the first step toward settling a question that chemistry Nobel laureate Vladimir Prelog called "one of the first questions of molecular theology" back in 1975.  It shows that science has the capacity for reaching back and explaining the earliest origins of biochemistry -- and how life as we know it came about.

****************************************

The biochemical zoo

The human/alien hybrid is a common trope in science fiction.  From the angst-ridden half-Vulcan Mr. Spock, to the ultra-competent and powerful half-Klingon B'Elanna Torres, to the half-Betazoid empath Deanna Troi, the idea of having two intelligent humanoid species produce children together is responsible for dozens of plot twists in Star Trek alone.

Much as I love the idea (and the show), the likelihood of a human being able to engage in any hot bow-chicka-bow-wow with an alien, and have that union produce an offspring, is damn near zero.  Even if the two in question had all the various protrusions and indentations more or less lined up, the main issue is the compatibility of the genetic material.  I mean, consider it; it's usually impossible for two ordinary terrestrial species to hybridize -- even related ones (say, a Red-tailed Hawk and a Peregrine Falcon) are far enough apart genetically that any chance mating would produce an unviable embryo.

Now consider how likely it is to have genetic compatibility between a terrestrial species and one from the fourth planet orbiting Alpha Centauri.

Any hope you might have had for a steamy tryst with an alien was smashed even further by a study that came out of a study from the Tokyo Institute of Technology, Emory University, and the German Aerospace Center.  Entitled, "One Among Millions: The Chemical Space of Nucleic Acid-Like Molecules," by Henderson James Cleaves II, Christopher Butch, Pieter Buys Burger, Jay Goodwin, and Markus Meringer, the study shows that the DNA and RNA that underlies the genetics of all life on Earth is only one of millions of possible information-encoding molecules that could be out there in the universe.

It was amazing how diverse these molecules were, even given some pretty rigid parameters.  Restricting the selection to linear polymers (so the building blocks have to have attachment points that allow for the formation of chains), and three constituent atoms -- carbon, hydrogen, and oxygen, like our own carbohydrates -- the researchers found 706,568 possible combinations (counting configurations and their mirror images, pairs of molecules that are called stereoisomers).  Adding nitrogen (so, hooking in chemicals like proteins and the DNA and RNA nitrogenous bases, the letters of the DNA and RNA alphabets) complicated matters some -- but they still got 454,442 possible configurations.

The results were a surprise even to the researchers.  "There are two kinds of nucleic acids in biology, and maybe twenty or thirty effective nucleic acid-binding nucleic acid analogs," said Henderson James Cleaves, who led the study, in an interview in SciTechDaily.  "We wanted to know if there is one more to be found...  The answer is, there seem to be many, many more than was expected."

Co-author Pieter Burger of Emory University is excited about the possible medical applications of this study.  "It is absolutely fascinating to think that by using modern computational techniques we might stumble upon new drugs when searching for alternative molecules to DNA and RNA that can store hereditary information," Burger said.  "It is cross-disciplinary studies such as this that make science challenging and fun yet impactful."

While I certainly can appreciate the implications of this research from an Earth-based standpoint, I was immediately struck by its application to the search for extraterrestrial life.  As I mentioned earlier, it was already nearly impossible that humans and aliens would have cross-compatible DNA, but now it appears that alien life might well not be constrained to a DNA-based genetic code at all.  I always thought that DNA, or something very close to it, would be found in any life form we run across, whether on this planet or another; but the Cleaves et al. study suggests that there are a million or more other ways that organisms might spell out their genetic code.

So this drastically increases the likelihood of life on other planets. The tighter the parameters for life, the less likely it is -- so the discovery of a vast diversity of biochemistry opens up the field in a manner that is breathtaking.

... but the chance that the aliens will look like this is, sadly, pretty low.

This raises the problem of whether we'll recognize alien life when we see it.  The typical things you look for if you're trying to figure out if something's alive -- such as a metabolism involving the familiar organic compounds all our cells contain -- might cause us to overlook something that is alive but is being carried along by a completely different chemistry.

And what an organism with that completely different chemistry might look like -- how it would move, eat, sense its environment, reproduce, and think -- well, there'd be an embarrassment of riches.  The possibilities are far beyond even the Star Trek universe, with their fanciful aliens that look basically human but with odd facial structures and funny accents.

The whole thing boggles the mind.  And it further reinforces a conclusion I've held for a very long time; I suspect that we'll find life out there pretty much everywhere we look, and even on some planets we'd have thought completely inhospitable.  The "Goldilocks Zone" -- the region surrounding a star where orbiting planets would have conditions that are "just right" for life to form -- is looking like it might be a vaster territory than we'd ever dreamed.

****************************************

The biochemical symphony

Sometimes I run into a piece of scientific research that's so odd and charming that I just have to tell you about it.

Take, for example, the paper that appeared in ACS Nano that ties together two of my favorite things -- biology and music.  It has the imposing title, "A Self-Consistent Sonification Method to Translate Amino Acid Sequences into Musical Compositions and Application in Protein Design Using Artificial Intelligence," and was authored by Chi-Hua Yu, Zhao Qin, Francisco J. Martin-Martinez, and Markus J. Buehler, all of the Massachusetts Institute of Technology.  Their research uses a fascinating lens to study protein structure: converting the amino acid sequence and structure of a protein into music, then having an AI software study the musical pattern that results as a way of learning more about how proteins function -- and how that function might be altered.

What's cool is that the musical note that represents each amino acid isn't randomly chosen.  It's based on the amino acid's actual quantum vibrational frequency.  So when you listen to it, you're not just hearing a whimsical combination of notes based on something from nature; you're actually hearing the protein itself.

[Image licensed under the Creative Commons © Nevit Dilmen, Music 01754, CC BY-SA 3.0]

In an article about the research in MIT News, written by David L. Chandler, you can hear clips from the Yu et al. study.  I recommend the second one especially -- the one titled "An Orchestra of Amino Acids" -- which is a "sonification" of spider silk protein.  The strange, percussive rhythm is kind of mesmerizing, and if someone had told me that it was a composition by an avant-garde modern composer -- Philip Glass, perhaps, or Steve Reich -- I would have believed it without question.  But what's coolest about this is that the music actually means something beyond the sound.  The AI is now able to discern the difference between some basic protein structures, including two of the most common -- the alpha-helix (shaped like a spring) and the beta-pleated-sheet (shaped like the pleats on a kilt -- because they sound different.  This gives us a lens into protein function that we didn't have before.  "[Proteins] have their own language, and we don’t know how it works," said Markus Buehler, who co-authored the study.  "We don’t know what makes a silk protein a silk protein or what patterns reflect the functions found in an enzyme.  We don’t know the code."

But this is exactly what the AI, and the scientists running it, hope to find out.  "When you look at a molecule in a textbook, it’s static," Buehler said.  "But it’s not static at all.  It’s moving and vibrating.  Every bit of matter is a set of vibrations.  And we can use this concept as a way of describing matter."

This new approach has impressed a lot of people not only for its potential applications, but from how amazingly creative it is.  This is why it drives me nuts when people say that science isn't a creative process. They apparently have the impression that science is pure grunt work, inoculating petri dishes, looking at data from particle accelerators, analyzing rock layers.  But at its heart, the best science is about making connections between disparate ideas -- just like this research does -- and is as deeply creative as writing a symphony.

"Markus Buehler has been gifted with a most creative soul, and his explorations into the inner workings of biomolecules are advancing our understanding of the mechanical response of biological materials in a most significant manner," said Marc Meyers, professor of materials science at the University of California at San Diego, who was not involved in this work.  "The focusing of this imagination to music is a novel and intriguing direction. his is experimental music at its best.  The rhythms of life, including the pulsations of our heart, were the initial sources of repetitive sounds that engendered the marvelous world of music.  Markus has descended into the nanospace to extract the rhythms of the amino acids, the building blocks of life."

What is most amazing about this is the potential for the AI, once trained, to go in reverse -- to be given an altered musical pattern, and to predict from that what the function of a protein engineered from that music would do.  Proteins are perhaps the most fundamental pieces of living things; the majority of genes do what they do by making proteins, which then guide processes within the organism (including frequently affecting other genes).  The idea that we could use music as a lens into how our biochemistry works is kind of stunning.

So that's your science-is-so-freaking-cool moment for the day.  I peruse the science news pretty much daily, looking for intriguing new research, but this one's gonna be hard to top.  Now I think I'm going to go back to the paper and click on the sound links -- and listen to the proteins sing.

****************************************

Life on ice

I'm currently reading planetary scientist Sarah Stewart Johnson's wonderful book The Sirens of Mars, about the search for signs of life on Mars (and other planets in the Solar System).  What strikes me whenever I read anything on this topic is that everything we've learned supports the contention that life is common in the universe.  (Not necessarily intelligent life; as I've dealt with before, that's another discussion entirely.)  As I learned from another great book I read a while back, Michael Ray Taylor's Dark Life: Martian Nanobacteria, Rock-Eating Cave Bugs, and Other Extreme Organisms of Inner Earth and Outer Space, every place we've looked on Earth -- however seemingly inhospitable -- we've found living things.  Fissures in rocks miles underneath the Earth's surface; deep-sea hydrothermal vents under crushing pressures and sky-high temperatures; brine ponds containing water many times the salinity of seawater; alkaline and acidic hot springs; chilly, pitch-dark caves with toxic air; anaerobic, sulfur-filled mud.  Teeming with life, all of them.

Not only that, but the building blocks of life are kind of everywhere.  When Stanley Miller and Harold Urey did their mind-blowing experiment back in 1953, it was unclear whether they had just happened on the right formula; they'd included their best guesses as to the constituents of the early Earth's atmosphere, and used artificial lightning as an energy source, and in short order they had organic compounds in enormous quantities.  It turned out, though, that the results had been not so much of a happy accident as an inevitability.  As long as you have (1) a reducing atmosphere (i.e. no free oxygen), (2) inorganic sources of carbon, hydrogen, oxygen, nitrogen, phosphorus, and sulfur, and (3) some kind of an energy source, you end up synthesizing all twenty amino acids found in living things (plus some we don't use), DNA and RNA nucleotides, simple sugars, fatty acids, glycerol, and a host of other organic compounds.

In other words, every monomer you need to build an organism.  All from off-the-shelf inorganic chemicals and some kind of power source.

What became clear after Miller and Urey published their results is that the early Earth's seas -- and by extension, the seas of any planet with a reducing atmosphere and sufficient liquid water -- might be expected to be brimming with the building blocks of life.  This so-called "primordial soup" on Earth gave rise to primitive life in a relative flash, and there's no reason to expect the same wouldn't happen elsewhere.

What came as something of a shock, though, is that you don't even need warm, Earthlike conditions to generate biochemistry.  Not long ago, astrophysicists started finding the characteristic signatures of organic compounds in interstellar nebulae.  And just last week researchers at the University of Copenhagen announced that they'd discovered organic compounds in a cloud of gas, dust, and ice called Chameleon 1 -- one of the coldest, darkest places ever to be studied, located about six hundred light years away.

The Tarantula Nebula [Image courtesy of NASA, ESA, CSA, STScI, and the Webb ERO Production Team]

Detected by their spectroscopic fingerprints -- the characteristic frequencies of light they absorb from the ambient starlight -- these chemicals were located during a new study using the James Webb Space Telescope.  "With the application of observations, e.g. from ALMA [the Atacama Large Millimeter Array, which was also used in the study], it is possible for us to directly observe the dust grains themselves, and it is also possible to see the same molecules as in the gas observed in the ice," said Lars Kristensen, who co-authored the study.

"Using the combined data set gives us a unique insight into the complex interactions between gas, ice and dust in areas where stars and planets form," added Jes Jørgensen, who also co-authored.  "This way we can map the location of the molecules in the area both before and after they have been frozen out onto the dust grains and we can follow their path from the cold molecular cloud to the emerging planetary systems around young stars."

What this shows is that a great many of the compounds in the primordial soup may have formed before the coalescence of the Earth, and might already have been present when the seas formed.  "This study confirms that interstellar grains of dust are catalysts for the forming of complex molecules in the very diffuse gas in these clouds, something we see in the lab as well," said Sergio Ioppolo, another co-author.

Further evidence that biochemistry -- and almost certainly life -- is plentiful in the universe.

I wonder what life is like on other worlds.  Surely whatever it is, it's evolved into a host of forms completely different from what we have here, ones that have adapted to whatever the local conditions are.  Different sets of environmental challenges would generate new and innovative evolutionary solutions, as would a different set of one-off occurrences (such as the Chicxulub Meteorite collision that ended the supremacy of the dinosaurs and put us mammals on the pathway to pretty much running the place).  Now, take that diversity, those "endless forms most beautiful and most wonderful," as Darwin so trenchantly put it -- and multiply that by a million times.

That is what is very likely to be out there in the cosmos.

If I can be forgiven for ending a post with a quote by Carl Sagan two days in a row, the line he put in the mouth of his iconic character Ellie Arroway (from the book and the movie Contact) seems apposite: "If we're the only ones in the universe, it seems like an awful waste of space."

****************************************

Assembling aliens

There are a lot of hurdles in detecting extraterrestrial life, and that's not even counting the possibility that it might not exist.

Honestly, I don't think that last stumbling block is all that likely, and it's not just because proving we're not alone in the universe has been one of my dearest wishes since I was six years old and watching the original Lost in Space.  Since astronomer Frank Drake came up with his famous Drake equation in 1961, which breaks down the likelihood of extraterrestrial intelligence into seven individual parameters (each with its own, independent probability), the estimates of the values of those parameters have done nothing but increase.  As only one example, one of the parameters is f(p) -- the fraction of stars that have planetary systems.  When Drake first laid out his equation, astronomers had no certainty at all about f(p).  They were working off a sample size of one; we know the Solar System exists because we live in it.  But was its formation a fluke?  Were stars with planets extremely uncommon?

No one knew.

Now, exoplanet discovery has become so routine that it barely even makes the news any more.  The first exoplanet around a main-sequence star -- 51 Pegasi b -- was discovered in 1995.  Since then, astronomers have found 5,297 exoplanets, with new ones being announced literally every week.  It seems like damn near a hundred percent of stable main-sequence stars have planetary systems, and most of them have at least one planet in the "Goldilocks zone," where the temperatures are conducive to the presence of liquid water.

Even setting aside my hopes regarding aliens, the sheer probability of their existence has, from a purely mathematical standpoint based upon the current state of our knowledge of the universe, improved significantly.

But this still leaves us with a problem: how do we find it?  The distances even to the nearest stars are insurmountable unless someone comes up with warp drive.  (Where are you, Zefrem Cochrane?)  So we're left with remote sensing -- looking for biosignatures.  The most obvious biosignature would be a radio transmission that's clearly from intelligent life, such as the one Ellie Arroway found in Contact; but it bears keeping in mind that through almost all of the Earth's 3.7-billion-odd years it's been inhabited by living creatures, it would have been entirely silent.  Alien astronomers looking from their home worlds toward the Earth would not have heard so much as a whisper.  It's only since we started using radio waves to transmit signals, a century ago, that we'd be detectable that way; and given how much transmission is now done via narrow-beam satellite and fiber optics cables rather than simple wide-range broadcast, it's entirely possible that once the technology improves Earth will go silent once again.  There may only be a short period during which a technological civilization is producing signals that are potentially detectable from a long way away.

So the question remains: how could we determine if an exoplanet had life?

I'm guessing that whatever the aliens look like, it's not this.  Unfortunately.

The tentative answer is to look for other kinds of biosignatures, and the most obvious one is chemicals that "shouldn't be there" -- in other words, that would not form naturally unless there were life there producing them through its metabolic processes.  This, too, is not a simple task.  Not only is there the technological challenge of detecting what's in a distant exoplanet's atmosphere (something we're getting a lot better at, as spectroscopy improves), there's the deeper question of how we know what should be there.  If we find an odd chemical in a planet's atmosphere, how do we know if it was made by life, or by some exotic (but abiotic) chemistry based on the planet's composition and conditions?

We've gotten caught this way before; three years ago, scientists discovered traces of a chemical called phosphine in the atmosphere of Venus, and a lot of us -- myself included -- got our hopes up that it might be a biosignature of something alive in the clouds of our hostile sister planet.  The consensus now is that it isn't -- the amounts are vanishingly small, and any phosphine on Venus is a product of its wild convection and bizarre atmospheric makeup.  So once we detect a chemical on an exoplanet, is there a way to do a Drake-equation-style estimate of its likelihood of forming abiotically?

Astrobiologist Leroy Cronin, of the University of Glasgow, has proposed an answer, based on something he calls "assembly theory."  Assembly theory, significantly, doesn't rely on any kind of analogy to terrestrial life.  Cronin and others are now trying to figure out strategies to find life as we don't know it -- living creatures that might be based upon extremely different chemistry.

What he's done is given us a purely mathematical way to index chemicals according to how many independent steps it takes to create them from simple, pre-existing building blocks.  This molecular assembly number, Cronin says, is directly proportional to its likelihood of being created by a living thing.  As a simple analogy, he shows how you would find the molecular assembly number for the word abracadabra:

1. add a + b;
2. add ab + r;
3. add abr + a;
4. add abra + c;
5. add abrac + a;
6. add abraca + d;
7. add abracad + abra (we'd already created abra in step three).

Seven steps from the primordial building blocks, so the molecular assembly number for abracadabra is seven.

Replace putting letters and letter groups together with steps in a chemical reaction chain, and you have an idea how assembly theory works.

Like the Drake equation, Cronin's method isn't proof.  Finding some complex chemical in an exoplanet's atmosphere, the gas of a nebula, or a meteorite might be suggestive of life, but almost certainly wouldn't convince the doubters without a lot more in the way of evidence.  Still, just as Frank Drake did in 1961, it's nice to have a protocol for determining the likelihood of a biosignature that doesn't depend on our unavoidable Earth-centrism.  Like with the formation of the Solar System, we're familiar with only one kind of life -- the kind all around us, that we ourselves are examples of.  Shaking the bias that all life is Earth-like is not easy.

It's understandable that the creators of Lost in Space and Star Trek visualized almost all of the aliens as basically humans with odd facial excrescences, and that's granting the difficulty of finding a way to portray non-humanoid aliens convincingly using human actors.  When they did manage to get beyond humans with rubber noses, such as in the Lost in Space episode "The Derelict" and the Star Trek episodes "The Devil in the Dark" and "Obsession," the aliens were, respectively, giant mobile bubbles, a tunneling, acid-spewing rock, and a disembodied vampiric mist cloud, all of a which at least gave a shot at trying to visualize what truly non-Earthlike life might be.

I'm hopeful that the work of Cronin and others is moving the new field of astrobiology forward from simple "what ifs" to actual rigorous algorithms for analyzing the spectroscopic data we're gathering from exoplanet atmospheres.  And maybe... just maybe... within my lifetime we'll have enough data to feel confident we've identified for certain what I've been waiting for since I was six: life on another planet.

****************************************