The glass RNA factory

A couple of months ago, I wrote about a discovery that has startling (and encouraging) implications for the search for extraterrestrial life -- that amino acids, the building blocks of proteins, are so easy to form abiotically that they are common even in interstellar dust clouds.

Well, because of my twin-brudda-from-anudda-mudda, the wonderful writer and blogger Andrew Butters, I found out that a new bit of research has shown that another piece of biochemistry -- RNA -- is equally easy to make in large quantities.

If anything, this is even more exciting to us aliens-in-space aficionados than the amino acid research was, because the model for the origins of life on Earth that is now virtually universally accepted is called "RNA world."  The idea has been around since the early 1960s, and simply put, it's that the first nucleic acid type to form in the early oceans was not DNA, but RNA.  At first this model met with considerable skepticism.  One common criticism was that the only organisms that encode their genome as RNA are certain viruses (such as the common cold, flu, rabies, mumps, measles, hepatitis, and COVID-19); all other organisms encode their genomes as DNA.  The second is that RNA has a tendency to be unstable.  It's a single helix; the shape resembles a spiral with short spokes sticking out at angles along its length, and that open shape allows it to be attacked and broken down readily by solvents (including water).

[Image licensed under the Creative Commons DataBase Center for Life Science (DBCLS), 201904 RNA, CC BY 4.0]

Two subsequent discoveries tilted biochemists toward accepting the RNA world model.  First, it was found that there are stable forms of RNA, such as transfer RNA, that are able to protect themselves from breakdown by having "hairpin loops" -- places where the helix doubles back and bonds to itself through complementary base-pairing, just like DNA has.

[Image licensed under the Creative Commons Vossman, Pre-mRNA-1ysv-tubes, CC BY-SA 3.0]

The second discovery was that RNA is autocatalytic -- pieces of RNA can actually feed back and speed up the reactions that form more RNA.  DNA doesn't do this, which was a major stumbling block to figuring out how the first self-replicating DNA formed.

So most folks are convinced that RNA was the first genetic material, and that it was only superseded by DNA after first double-stranded RNA formed, and then there was a chemical alteration of the sugar in the backbone (deoxyribose for ribose) and one of the nitrogenous bases (thymine for uracil).  But this only shoved the basic problem back one step.  Okay, RNA came before DNA; but what made the RNA?

We've known for ages, because of the stupendous Miller-Urey experiment, that making nucleotides -- the building blocks of both RNA and DNA -- is easy in the abiotic conditions that existed on the early Earth.  But how did link together into the long chains that form the structure of all functional RNA?

The new research indicates that it's amazingly simple -- all you have to do is to take the solution of nucleotides, and allow it to percolate through the pores of one of the most common rocks on Earth -- basaltic volcanic glass.

This stuff is kind of everywhere.  Not only is ninety percent of all volcanic rock on Earth made of basalt, it's also common on the two other rocky worlds we've studied -- the Moon and Mars.  "Basaltic glass was everywhere on Earth at the time," said Stephen Mojzsis, of the Budapest Research Centre for Astronomy and Earth Sciences, who co-authored the study.  "For several hundred million years after the Moon formed, frequent impacts coupled with abundant volcanism on the young planet formed molten basaltic lava, the source of the basalt glass.  Impacts also evaporated water to give dry land, providing aquifers where RNA could have formed."

Basalt also contains two ions that the team showed were critical for forming the RNA nucleotides and then linking them together -- nickel and boron.  The experiments they ran showed that all you had to do was pour the nucleotide slurry over the basaltic glass, and wait -- and voilà, in a day or two you had 100- to 200-subunit-long chains of RNA that look exactly like the kind you find in living things.

Given basalt's ubiquity on rocky planets, this makes it even more likely that there is life elsewhere in the universe, and that its biochemistry might have some striking overlap with ours.  Exciting stuff.

So it looks like the quote from the wonderful movie Contact might well turn out to be prescient.  "The universe is a pretty big place. It's bigger than anything anyone has ever dreamed of before. So if it's just us... seems like an awful waste of space."

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The recipe for life

Back in my teaching days, I was all too aware of how hard it was to generate any kind of enthusiasm for the details of biology in a bunch of teenagers.  But there were a few guaranteed oh-wow moments -- and one that I always introduced by saying, "If this doesn't blow your mind, you're not paying attention."

What I was referring to was the Miller-Urey experiment.  This phenomenal piece of research was an attempt to see if it was possible to create organic compounds abiotically -- with clear implications for the origins of life.  Back in the early twentieth century, when people started to consider seriously the possibility that life started on Earth without the intervention of a deity, the obvious question was, "How?"  So they created apparatus to take collections of inorganic compounds surmised to be abundant on the early Earth, subject them to various energy sources, and waited to see what happened.

What happened was that they basically created smog and dirty water.  No organic compounds.  In 1922, Soviet biochemist Alexander Oparin suggested that the problem might be that they were starting with the assumption that the Earth's atmosphere hadn't changed much -- and looking at (then) new information about the atmosphere of Jupiter, he suggested that perhaps, the early Earth's atmosphere had no free oxygen.  In chemistry terms, it was a reducing atmosphere.  Oxygen, after all, is a highly reactive substance, good at tearing apart organic molecules.  (There's decent evidence that the pathways of aerobic cellular respiration originally evolved as a way of detoxifying oxygen, and only secondarily gained a use at increasing the efficiency of releasing the energy in food molecules.)

It wasn't until thirty years later that anyone tested Oparin's hunch.  Stanley Miller and Harold Urey, of the University of Chicago, created an apparatus made of sealed, interconnected glass globes, and filled them with their best guess at the gases present in the atmosphere of the early Earth -- carbon monoxide, methane, hydrogen sulfide, sulfur dioxide, water vapor, various nitrogen oxides, hydrogen cyanide (HCN), and so on.  No free (diatomic) oxygen.  They then introduced an energy source -- essentially, artificial lightning -- and sat back to wait.

No one expected fast results.  After all, the Earth had millions of years to generate enough organic compounds to (presumably) self-assemble into the earliest cells.  No one was more shocked than Miller and Urey when they came in the next day to find that the water in their apparatus had turned blood red.  Three days later, it was black, like crude oil.  At that point, they couldn't contain their curiosity, and opened it up to see what was there.

All twenty amino acids, plus several amino acids not typically found in living things on Earth.  Simple sugars.  Fatty acids.  Glycerol.  DNA and RNA nucleotides.  Basically, all the building blocks it takes to make a living organism.

In three days.

A scale model of the Miller-Urey apparatus, made for me by my son, who is a professional scientific glassblower

This glop, now nicknamed the "primordial soup," is thought to have filled the early oceans.  Imagine it -- you're standing on the shore of the Precambrian sea (wearing a breathing apparatus, of course).  On land is absolutely nothing alive -- a continent full of nothing but rock and sand.  In front of you is an ocean that appears to be composed of thick, dark oil.

It'd be hard to convince yourself this was actually Earth.

Since then, scientists have re-run the experiment hundreds of times, checking to see if perhaps Miller and Urey had just happened by luck on the exact right recipe, but it turns out this experiment is remarkably insensitive to initial conditions.  As long as you have three things -- (1) the right inorganic building blocks, (2) a source of energy, and (3) no free oxygen -- you can make as much of this rather unappealing soup as you want.

So, it turns out, generating biochemicals is a piece of cake.  And a piece of research at Friedrich Schiller University and the Max Planck Institute have shown that it's even easier than that -- the reactions that create amino acids can happen out in space.

"Water plays an important role in the conventional way in which peptides are created," said Serge Krasnokutski, who co-authored the paper.  "Our quantum chemical calculations have now shown that the amino acid glycine can be formed through a chemical precursor – called an amino ketene – combining with a water molecule.  Put simply: in this case, water must be added for the first reaction step, and water must be removed for the second...  [So] instead of taking the chemical detour in which amino acids are formed, we wanted to find out whether amino ketene molecules could not be formed instead and combine directly to form peptides.  And we did this under the conditions that prevail in cosmic molecular clouds, that is to say on dust particles in a vacuum, where the corresponding chemicals are present in abundance: carbon, ammonia, and carbon monoxide."

The more we look into this, the simpler it seems to be to generate the chemicals of life -- further elucidating how the first organisms formed on Earth, and (even more excitingly) suggesting that life might be common in the cosmos.  In fact, it may not even take an Earth-like planet to be a home for life; as long as a planet is in the "Goldilocks zone" (the distance from its parent star where water can exist in liquid form), getting from there to an organic-compound-rich environment may not be much of a hurdle.

That's still a long way from intelligent life, of course; chances are, the planets with extraterrestrial life mostly have much simpler organisms.  But how exciting is that?  Setting foot on a planet covered with life -- none of which has any common ancestry with terrestrial organisms.

I can think of very little that would be more thrilling than that.

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People made fun of Donald Rumsfeld for his statement that there are "known unknowns" -- things we know we don't know -- but a far larger number of "unknown unknowns," which are all the things we aren't even aware that we don't know.

While he certainly could have phrased it a little more clearly, and understand that I'm not in any way defending Donald Rumsfeld's other actions and statements, he certainly was right in this case.  It's profoundly humbling to find out how much we don't know, even about subjects about which we consider ourselves experts.  One of the most important things we need to do is to keep in mind not only that we might have things wrong, and that additional evidence may completely overturn what we thought we knew -- and more, that there are some things so far out of our ken that we may not even know they exist.

These ideas -- the perimeter of human knowledge, and the importance of being able to learn, relearn, change directions, and accept new information -- are the topic of psychologist Adam Grant's book Think Again: The Power of Knowing What You Don't Know.  In it, he explores not only how we are all riding around with blinders on, but how to take steps toward removing them, starting with not surrounding yourself with an echo chamber of like-minded people who might not even recognize that they have things wrong.  We should hold our own beliefs up to the light of scrutiny.  As Grant puts it, we should approach issues like scientists looking for the truth, not like a campaigning politician trying to convince an audience.

It's a book that challenges us to move past our stance of "clearly I'm right about this" to the more reasoned approach of "let me see if the evidence supports this."  In this era of media spin, fake news, and propaganda, it's a critical message -- and Think Again should be on everyone's to-read list.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

The walk of life

It's remarkably difficult to decide exactly what we mean when we say something is alive.

As a biologist, this is kind of embarrassing.  After all, "biology" means "the study of life."  So in a very real sense, we're studying something when we're not even sure what it is.  Oh, sure, there are some clear-cut examples; a dog is alive, a rock is not.  But amazingly enough, when you try to pinpoint what the dog is doing that the rock is not, you get into some shaky ground -- and rules that are rife with exceptions.

How about "capable of reproducing?"  You can't just say "reproduces," because a good many organisms don't reproduce because of choice or circumstance.  And let's even throw out the timeworn exceptions of the hybrid, infertile mules and ligers as being genetic anomalies.  But what about worker ants?  Worker ants are females that had the development of functional reproductive anatomy suppressed, so they are completely infertile; but they're not genetic accidents like infertile hybrids are.  They are not even theoretically capable of reproducing, but I doubt seriously anyone would argue that they're not alive.

Then, there's "limited life span."  Living things die, usually after a length of time characteristic of the particular species.  However, the bristlecone pine (Pinus longaeva) doesn't seem to have an upper bound on its life span.  Most plants, even most trees, age out after a while -- birch trees live thirty to forty years, silver maples eighty or ninety, red oaks two hundred, white oaks as much as eight hundred -- bristlecone pines don't do that.  Unless they meet with misfortune, they just keep on living.  A bristlecone in the Inyo National Forest of California is 4,851 years old.  To put that into perspective, when the Great Pyramid at Giza was built, this tree was already three hundred years old.

And it isn't just plants.  There's a jellyfish, Turritopsis dohrnii, that is effectively immortal -- when it reaches senescence, it begins to despecialize its cells, returning to the polyp (juvenile) stage, then redifferentiating.  There seems to be no limit to the number of times it can do this -- putting the Time Lords with their twelve regeneration cycles to considerable shame.

And don't get me started on viruses, which are an exception to the majority of the usually-accepted characteristics of life.

The upshot is that the whole topic is way more controversial than you'd think.  Even such seemingly-obvious ones as "composed of one or more cells" and "encodes genetic information as DNA or RNA" may be looking at things from an Earth-bound perspective; life on other planets might well compartmentalize their metabolic processes and store their genetic information in entirely different ways, and still be recognizably "alive."

There's one characteristic, though, that very few people whose opinions count will argue over; living things are subject to evolution by natural selection.  (Okay, the creationists will argue like hell about it, but they conspicuously fail on the "opinions counting" qualification.)  Clearly living things evolve, and it's hard to imagine a non-living thing that would do so.  This, then, would make "evolution by natural selection" not only a necessary condition for being alive, but a sufficient one.

Which would settle once and for all the questions of whether viruses are alive.  They clearly evolve, which is why one flu shot doesn't make you immune for life.

[Image licensed under the Creative Commons Myworkforwiki, Major Evolutionary Transitions digital, CC BY-SA 4.0]

Well, as I am wont to do, I've been leading you down the garden path.  Because if you have been nodding your head and saying, "Okay, that makes sense" to what I've written above...

... scientists in a research lab in Germany have just created life.

Christian Mayer, a chemist at the Center for Nanointegration, and Ulrich Schreiber, a geologist at the University of Duisberg-Essen, have long been of the opinion that life on Earth began underground, not in shallow tide pools (the more common hypothesis).  The heat and pressure in deep crevices in the Earth create conditions that would lead to the formation of vesicles -- water-filled bubbles surrounded by a lipid-bilayer membrane.  These are thought to be the earliest cells, eventually trapping bits of RNA and leading to the first true life-forms.

So Mayer and Schreiber decided to recreate these deep crevices.  They allowed the temperature in lab apparatus simulating deep-Earth characteristics to fluctuate between 40 and 80 C, and the pressure between 60 and 80 bar.  Sure enough, under those conditions, a "primordial soup" forms vesicles readily.  Like soap bubbles, they are created and destroyed rapidly, some lasting longer than others.

But unlike soap bubbles, these vesicles evolve.

For full impact, here's the relevant quote from the press release:

In their laboratory experiment, they regularly changed the pressure in the system at 20-minute intervals, thereby changing the quality of the solvent, as it also occurs in nature through tidal forces and geysers.  In the process, the vesicles were periodically destroyed and re-formed.  Thus, a total of 1,500 generations of vesicles were created and disintegrated again within two weeks. 

The researchers discovered that an increasing number of vesicles survived the generation change.  Analyses showed that these vesicles had embedded specific sequences of 10 to 12 amino acids from the pool of possible peptides into their membrane in a cluster-like manner.  Further tests, specifically carried out with one of these peptides, revealed three effects on the vesicles in question: They became thermally more stable, smaller and hence more resistant and – most importantly – the permeability of their membrane was considerably increased.

Put simply, the vesicles underwent natural selection and evolved to increase their stability and permeability.  The embedded peptides they mention are the first approach to the transmembrane channel proteins that every cell has, allowing it to transport materials across the membrane as needed.

"As we have simulated in time-lapse, functions could have been created billions of years ago that made such vesicles stable enough to come to the surface from the depths, for example with the flow of tectonic fluids or during geyser eruptions," said study co-author Ulrich Schreiber.  "Subsequently, a first metabolism with concentration gradients as an energy source could have developed.  If the ability to self-replicate is eventually acquired, then even from a biological point of view an inanimate component slowly becomes a living organism, a first cell."

So there you are.  Mayer and Schreiber, being cautious scientists, are not saying they've created life, but the implication is there -- and even the most hesitant amongst us (not you, creationists) would have to admit that whatever you want to call it, this represents a huge step toward generating something that is unequivocally alive.

Which I find to be somewhere beyond mind-boggling.

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These days, I think we all are looking around for reasons to feel optimistic -- and they seem woefully rare.  This is why this week's Skeptophilia book recommendation of the week is Hans Rosling's wonderful Factfulness: Ten Reasons We're Wrong About the World--and Why Things Are Better Than You Think.  

Rosling looks at the fascinating bias we have toward pessimism.  Especially when one or two things seem seriously amiss with the world, we tend to assume everything's falling apart.  He gives us the statistics on questions that many of us think we know the answers to -- such as:  What percentage of the world’s population lives in poverty, and has that percentage increased or decreased in the last fifty years?  How many girls in low-income countries will finish primary school this year, and once again, is the number rising or falling?  How has the number of deaths from natural disasters changed in the past century?

In each case, Rosling considers our intuitive answers, usually based on the doom-and-gloom prognostications of the media (who, after all, have an incentive to sensationalize information because it gets watchers and sells well with a lot of sponsors).  And what we find is that things are not as horrible as a lot of us might be inclined to believe.  Sure, there are some terrible things going on now, and especially in the past few months, there's a lot to be distressed about.  But Rosling's book gives you the big picture -- which, fortunately, is not as bleak as you might think.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]

Scanning the skies for life

It will come as no surprise to regular readers of Skeptophilia that one of my dearest wishes is to live long enough to see incontrovertible proof of life on another planet.

Intelligent life would just be the icing on the cake, but I'm not counting on it, especially given how rare it is down here on Earth.  And the best of all -- having the intelligent life come here so I could have a talk with it -- is so unlikely as to be impossible, given the enormous (shall we say astronomical) distances involved.

But that doesn't mean we can't find out more about the conditions that could generate life and the likelihood of it being found elsewhere, as three pieces of research last week showed.

The first, which appeared in the journal Science Advances, is called "The Origin of RNA Precursors on Exoplanets," by a team of Cambridge University astrophysicists, Paul B. Rimmer, Jianfeng Xu, Samantha J. Thompson, Ed Gillen, John D. Sutherland, and Didier Queloz.  In it, we find out that the conditions for forming RNA nucleotides -- the fundamental building blocks of RNA, one of the two carriers of genetic information (and generally thought to be the one that formed first) -- have been narrowed down to a specific range of temperatures and luminance.  The authors write:

Given that the macromolecular building blocks of life were likely produced photochemically in the presence of ultraviolet (UV) light, we identify some general constraints on which stars produce sufficient UV for this photochemistry.  We estimate how much light is needed for the UV photochemistry by experimentally measuring the rate constant for the UV chemistry (“light chemistry”, needed for prebiotic synthesis) versus the rate constants for the biomolecular reactions that happen in the absence of the UV light (“dark chemistry”).  We make these measurements for representative photochemical reactions involving and HS−.  By balancing the rates for the light and dark chemistry, we delineate the “abiogenesis zones” around stars of different stellar types based on whether their UV fluxes are sufficient for building up this macromolecular prebiotic inventory.  We find that the light chemistry is rapid enough to build up the prebiotic inventory for stars hotter than K5 (4400 K).  We show how the abiogenesis zone overlaps with the liquid water habitable zone.  Stars cooler than K5 may also drive the formation of these building blocks if they are very active.

The good news, for exobiology aficionados like myself, is that this not only homes in on what conditions are likely to produce life -- telling us where to look -- they're conditions that are relatively common in the universe.  Which further bolsters something I've said for ages, which is that life will turn out to be plentiful out there.

[Image licensed under the Creative Commons ESO/M. Kornmesser/Nick Risinger (skysurvey.org), Artist impression of the exoplanet 51 Pegasi b, CC BY 4.0]

The second, which appeared in Monthly Notices of the Royal Astronomical Society, suggests one way to detect that life at a distance.  In "Biological Fluorescence Induced by Stellar UV Flares, a New Temporal Biosignature," by Jack T. O'Malley-James and Lisa Kaltenegger (both of Cornell University), we find out that class-M stars -- of which the Sun is one -- not only have the right temperature ranges to foster planets with life, but their habit of generating solar flares could tip us off as to which planets hosted life.  The phenomenon of biofluourescence -- the absorption of high-energy light (such as ultraviolet) and its conversion into lower-energy light (visible light) -- could act as a protective mechanism during solar flares.  So when a star flares up, all we have to do is look for the flash of fluorescence that follows.

"On Earth, there are some undersea coral that use biofluorescence to render the Sun’s harmful ultraviolet radiation into harmless visible wavelengths, creating a beautiful radiance," said study co-author Lisa Kaltenegger, who is the director of the Carl Sagan Institute for Astrophysics.  "Maybe such life forms can exist on other worlds too, leaving us a telltale sign to spot them."

The coolest thing is that one of the stars being studied is Proxima Centauri -- the closest star to our Solar System.  So the technique O'Malley-James and Kaltenegger propose using could find life that is, so to speak, right next door.

As a cool followup to this paper, the following day a paper appeared in arXiv by a team of astrophysicists led by Stefan Dreizler of the Georg-August-Universität Göttingen that found not one but three planets in the "Goldilocks zone" of a relatively nearby star -- GJ1061.  One of the problems with figuring out which planets to study for signs of life is that the mass of the planet and its distance from the star aren't the only factors that matter; another, and one much harder to determine from Earth, is the stability of the orbit.  I still remember when I was a kid watching the generally-abysmal 1960s science fiction show Lost in Space, and was blown away when it was revealed that the planet the Robinson family was on was in a highly elliptical orbit -- so the seasons varied from blisteringly hot at the planet's perigee and freezing cold at its apogee.  (The way it played out in the show was, predictably, kind of silly, but it was a concept I'd never run into before, and at age six I was pretty damned impressed.)

But what Dreizler et al. found was that the three planets around GJ1061 were in stable orbits, meaning it was likely that they were relatively circular.  (Elliptical orbits cross each other and therefore increase the likelihood of collisions or gravitational slingshots slinging a planet into the star or out into space.)

So this gives us another likely candidate for biosignatures.

I'm pretty encouraged at all the effort that's being expended in this endeavor.  I vividly recall watching my favorite movie -- Contact -- for the first time, and being appalled at how astronomer Ellie Arroway had to fight to be taken seriously, not only because she was a woman in what then (and still is to some extent now) was a man's world, but because her area of research was the search for extraterrestrial life.  What more fascinating research is there, to find out if life on Earth is unique -- or if, as I contend, we're just one of a multitude of planets hosting life?

I can't imagine a more deeply resonant idea, nor one that would have as profound an effect on how we see ourselves and our place in the universe.  And if that's not worth researching, I don't know what is.

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This week's Skeptophilia book recommendation is a must-read for anyone interested in astronomy -- Finding Our Place in the Universe by French astrophysicist Hélène Courtois.  Courtois gives us a thrilling tour of the universe on the largest scales, particularly Laniakea, the galactic supercluster to which the Milky Way belongs, and the vast and completely empty void between Laniakea and the next supercluster.  (These voids are so empty that if the Earth were at the middle of one, there would be no astronomical objects near enough or bright enough to see without a powerful telescope, and the night sky would be completely dark.)

Courtois's book is eye-opening and engaging, and (as it was just published this year) brings the reader up to date with the latest information from astronomy.  And it will give you new appreciation when you look up at night -- and realize how little of the universe you're actually seeing.

[Note: if you purchase this book from the image/link below, part of the proceeds goes to support Skeptophilia!]