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So most folks are convinced that RNA was the first genetic material, and that it was only superseded by DNA after first double-stranded RNA formed, and then there was a chemical alteration of the sugar in the backbone (deoxyribose for ribose) and one of the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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A door into RNA world

[N.B.: This post is a little on the technical side, if you're not a biology type.  Trust me, the work is worth it, because what these people have discovered is stupendous.]

I had the experience yesterday of stumbling on an article published in Nature this week that, from the title, seemed like something that could only interest biochemistry geeks.

Then I started reading it, and I had to pick my jaw up off the floor.

Before I tell you about the paper, a little background.

Most laypeople know that genes are basically stretches of DNA, and that DNA is a double helix made of chains of smaller molecules called nitrogenous bases, of which there are four -- adenine, thymine, guanine, and cytosine.  (A, T, G, and C for short.)  Because the bases always pair the same way (A to T, C to G), it allows for DNA to replicate itself.

So far, so good.  But how do you get from a gene to a trait?  It took a long time to figure this out, and there's still work being done on how genes switch on and off during development.  But a simplified explanation goes like this:

The first step is that one gene (a piece of DNA) is copied into a similar, but not identical, chemical called RNA.  (This is called transcription.)  RNA is a single helix, so only one side of the DNA gene is copied; the other side only exists so the DNA can be replicated.  Then the RNA goes to a cellular structure called a ribosome, where the base sequence is read in threes (a group of three is a codon), and each trio instructs the ribosome to bring in a specific amino acid.  The amino acids dictated by the codon sequence are linked together into a protein, and those proteins directly generate the trait.  (This is called translation.)  Every trait is basically produced this way, whether it's something simple like skin color, or the interaction between the thousands of genes and proteins that it takes to generate a functioning human heart.

Okay, gene > RNA > protein > trait.  The sequence is so ubiquitous that it's been nicknamed The Central Dogma of Molecular Genetics.

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

But here's the problem.  When life first began, how did the process get started?

The problem isn't the building blocks; given the conditions that we're virtually certain existed on the early Earth, all of the pieces -- the bases, the sugars that make up the backbone of both DNA and RNA, the amino acids -- form spontaneously and abundantly.  They will even link up to form chains on their own.  It's likely that any Earthlike, water-containing planet has plenty of all the biochemical bits and pieces.

But how do you get from a particular RNA to a particular protein?  Remember, it's the sequence of bases in RNA that determines the sequence of amino acids in the protein, but to read the RNA sequence and assemble those amino acids requires a lot of cellular machinery -- first and foremost the ribosome.

Which is itself made of RNA.

So it seems like the first life had to pull itself up by its own bootlaces.  Put succinctly, to do transcription and translation, you need to have the mechanisms of transcription and translation already in place.

Or at least, that's what I thought until I read this paper.

Enter the team led by Felix Müller of Ludwig-Maximilians-Universität in Munich, Germany, and their paper "A Prebiotically Plausible Scenario of an RNA-Peptide World."  Here's how the paper begins, with a couple of parenthetical notes added by me:

A central commonality of all cellular life is the translational process, in which ribosomal RNA catalyses peptide [i.e. protein] formation with the help of transfer RNAs, which function as amino acid carrying adapter molecules.  Comparative genomics suggests that ribosomal translation is one of the oldest evolutionary processes, which dates back to the hypothetical RNA world [the theory that the earliest self-replicating genetic molecules were RNA, not DNA, which is generally accepted in the scientific world].  The questions of how and when RNA learned to instruct peptide synthesis is one of the grand unsolved challenges in prebiotic evolutionary research.

The immense complexity of ribosomal translation demands a stepwise evolutionary process.  From the perspective of the RNA world, at some point RNA must have gained the ability to instruct and catalyse the synthesis of, initially, just small peptides.  This initiated the transition from a pure RNA world into an RNA–peptide world.  In this RNA–peptide world, both molecular species could have co-evolved to gain increasing ‘translation’ and ‘replication’ efficiency...

We found that non-canonical vestige nucleosides [i.e. unusual bases which are still part of some structures made of RNA, but aren't on the list of the four standard bases], which are key components of contemporary RNAs, are able to equip RNA with the ability to self-decorate with peptides.  This creates chimeric structures, in which both chemical entities can co-evolve in a covalently connected form, generating gradually more and more sophisticated and complex RNA–peptide structures...  We... found that peptides can simultaneously grow at multiple sites on RNA on the basis of rules determined by sequence complementarity, which is the indispensable requirement for efficient peptide growth.

Which is way more dignified than what I'd have written, which is, "Holy shit, we just figured out how gene expression evolved!"

In my AP Biology classes, I ended the unit on evolution with a list of some of the questions that evolutionary theory had not yet solved, and the origins of gene expression and protein synthesis topped the list.  It looks like that one might now be checked off -- which, if my assessment is correct, should put Müller and his team in contention for this year's Nobel Prize in chemistry.

I find it so fascinating that there are still some of the Big Questions out there, and that scientists are actually making inroads into answering them.  Good science doesn't just say "it's a mystery" and forthwith stop thinking.  We're gradually chipping away at problems that were thought to be intractable -- in this case, giving us insight into how life began on Earth four billion years ago.

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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 just got 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 a few days ago.  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.

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This week's Skeptophilia book recommendation is for people who have found themselves befuddled by such bizarre stuff as Schrödinger's Cat and the Pigeonhole Paradox and the Uncertainty Principle -- which, truthfully speaking, is probably the vast majority of us.

In Six Impossible Things: The Mystery of the Quantum World, acclaimed science writer John Gribbin looks at six possible interpretations of the odd results from quantum theory.  Gribbin himself declares himself a "quantum agnostic," that he is not espousing any one of them in particular.  "They all on some level sound crazy," Gribbin says.  "But in quantum theory, 'crazy' doesn't necessarily mean 'wrong.'"

His writing is clear, lucid, and compelling, and will give you an idea what the cutting edge of modern physics is coming up with.  It'll also blow your mind -- but isn't good science always supposed to do that?

[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!]

Altering the message

It's always a little startling when something is discovered that ends up explaining... well, damn near everything.

If I exaggerate, it's not by much.  I'm referring to epigenetics, which is the modification of DNA or RNA by chemical changes that don't alter the gene sequence itself.  Usually this is accomplished by adding various "markers" to the strand that then change how it is expressed.  These alterations are at least sometimes inheritable; in 2008, a group of geneticists at Cold Spring Harbor came up with the definition of epigenetics as a "stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence," and that's pretty much the one that still is used today.

[Image is in the Public Domain]

It has led to some pretty startling discoveries.  In a paper in Nature in 2014, geneticist Moshe Szyl showed evidence that mice that were taught (using mild electric shocks) to fear an odor gave birth to offspring that feared the odor as well -- and that heightened fear response lasted for two further generations.  Szyl found that a particular olfactory gene was "demethylated" by the conditioning -- had a marker called a methyl group removed -- and this enhanced the mice's ability to detect the odor, and modified their response to it.  This led to some serious speculation that the children and grandchildren of people who had been through atrocities like the Holocaust might inherit similar enhancements, leading to significant changes in behavior.

If you think this sounds Lamarckian, you're not wrong.  It turns out there is a way to inherit acquired characteristics.  It doesn't work the way Lamarck thought it did, but there was a grain of truth in what the man said.

This comes up because of a paper in Science this week describing evidence that epigenetic marking influences everything from embryonic development to cancer susceptibility to memory formation.  In fact, one such modification -- called m6a -- can do all three depending on which RNA strand it's acting on.  The last one is the most interesting to me; a team led by Chuan He of the University of Chicago found that if you knocked out an enzyme that reads m6a in mice, they have memory defects but are otherwise normal.  They then injected a virus carrying the normal reader gene into the mice -- and the defects went away.

This sounds to me like the basis of as much of a revolution as Mendel's discovery of the gene itself, and the discovery of DNA's structure and function by Rosalind Franklin, Marshall Nirenberg, James Watson, Francis Crick, and Maurice Wilkins.  The idea that a relatively small alteration to our DNA could create inheritable changes without altering the base sequence runs so contrary to both Mendelian inheritance and the "Central Dogma of Molecular Biology" that it looks like it'll force significant revisions to every bit of genetics we thought we understood.

My guess is that they're only beginning to test the depth of this discovery.  "We just need … a lot more knowledge about these things,” He said.  "We need to stay open-minded. The field is still very young."

So maybe I need to change my declaration in yesterday's post that "the twentieth century was [past tense] the century of the gene."  If my intuition is right, we might be on the brink of a whole new chapter -- hell, a whole new textbook -- in our understanding of how genes work.  All of which reiterates something I've believed for years -- that if you're interested in science, you'll never run out of new discoveries to be amazed at.

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This week's Skeptophilia book recommendation is about a subject near and dear to me: sleep.

I say this not only because I like to sleep, but for two other reasons; being a chronic insomniac, I usually don't get enough sleep, and being an aficionado of neuroscience, I've always been fascinated by the role of sleep and dreaming in mental health.  And for the most up-to-date analysis of what we know about this ubiquitous activity -- found in just about every animal studied -- go no further than Matthew Walker's brilliant book Why We Sleep: Unlocking the Power of Sleep and Dreams.

Walker, who is a professor of neuroscience at the University of California - Berkeley, tells us about what we've found out, and what we still have to learn, about the sleep cycle, and (more alarmingly) the toll that sleep deprivation is taking on our culture.  It's an eye-opening read (pun intended) -- and should be required reading for anyone interested in the intricacies of our brain and behavior.

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

Hybrids, DNA, and the glow cats from hell

One of the most powerful pieces of evidence of our common ancestry with every other life form on Earth is that we all read the genetic code the same way.  The RNA codon chart, the work of such giants in the field of genetics as Marshall Nirenberg, Francis Crick, and James Watson, works equally well for every species from bacterium to petunia to wolf spider to human.  It's the basis of genetic engineering; you can take an embryo of a cat, and insert a gene from a jellyfish that in the jellyfish produces a phosphorescent protein, and with luck and skill you will end up with...

... The GlowCat from Hell.

His name is "Mr. Green Genes."  No, I am not making this up.

The cats' genetic decoding mechanisms read the DNA in exactly the same way as the jellyfish did, and therefore assemble the glow-in-the-dark protein in precisely the same way.  Put simply, every organism on Earth speaks the same genetic language.

It's why, as I was discussing with some students just last week, Mr. Spock is vastly improbable.  That a DNA-based life form could arise on another planet is entirely plausible; the building blocks of DNA, called nucleotides, are apparently rather easy to produce abiotically.  But the likelihood that the decoding protocol would have evolved precisely the same way on Vulcan as it did on Earth, and therefore result in two species that can interbreed, is about as close to impossible as anything I can think of.   So however tantalizing a plot element it was to have the tortured, half-emotional and half-stoic First Officer struggling to control his human side with logic, it's much more likely to be a simple biological impossibility.

If the extraterrestrials even turn out to be humanoid, and have the right... um... equipment to engage in some hot alien/human bow-chicka-bow-wow in the first place.

Interestingly enough, given the morning's rather odd topic of conversation, that yesterday afternoon I ran into a website that claims that not only are human and alien DNA compatible, but that we are hybrids already.  Well, at least some of us are. F rankly, it's a little hard to tell what exactly the writer is claiming:

Civilizations from parallel realities and parallel dimensions similar to our own reality have been manipulating human DNA from the beginning of our recorded history and it is highly likely that all of this activity over the decades is the visually elusive air traffic of beings involved in one singularly focused mission involving humans.  This genetic program is a part of our human history, it is here with you and I now and will continue flowing down line into humanities future.  It is time to accept the fact that we are hybridized humanoid beings with alien DNA.

The problem is, human DNA is pretty much like the DNA of any other terrestrial species, as I mentioned earlier.  There's nothing alien about it.  But this doesn't stop the owner of the website, The Hybrids Project, from claiming that we're somehow... different.  And getting more different all the time:

Hybridization of a conscious humanoid appears to be quite complex.  Evolution is not ruled out, but there is a point at which highly advanced humanoids begin to upgrade other humanoids.  The benefits of this process would, at its simplest, be the perpetuation of life, intelligence and consciousness.  This is a logical expectation within an infinite multiverse and likely a process that spans countless worlds and vast expanses of time as we know it.  Earth is but a part of the process and not the process itself.  We will come to realize that we are part of a larger galactic family and the relatives are coming to introduce themselves.

I have to admit that we certainly could use an upgrade, given some of the behavior we like to engage in.  But the kind of thing that this website goes on to describe isn't, as far as I can tell, much of an improvement.  The alien species he describes are all a little... sketchy.  We have the Tall Grays and the Short Grays, who differ only in size and otherwise are your typical bald, skinny gray aliens with enormous black eyes.  Then there are the Tall Whites, which are bald, skinny white aliens with enormous blue eyes.  None of these, frankly, are my type.  I'm more attracted to plain old humans, thanks.

At least a bit more appealing are the Tall Blonds, the male version of which looks a little like Orlando Bloom.  But then, finally, we have the Mantid Beings, which are just horrifying.  The idea of a human/mantid hybrid would imply that there was some way for a human to have sex with what amounts to a giant grasshopper, a mental image which I really didn't need to have bouncing around in my skull.  (And about my decision to pass it along to you: "You're welcome.")

By the way, if you're curious to see what any of these things look like, I encourage you to peruse the website, which is chock-full of artists' depictions and is really highly entertaining.

Also on the website are all sorts of descriptions of abduction experiences, in which Earthlings were captured and brought on board ship and examined, probed, and worse by various members of these alien species.  The hybrid children thus produced, the website tells us, "are quite different and far more advanced than you and I and thus are currently living off world out of harm's way."  Which is pretty convenient. A ll of the kids I see on a day-to-day basis seem like regular people to me.  None of them have gray skin or black eyes or look like Orlando Bloom or a giant praying mantis.

Fortunately.

So, anyway.  As much as I love the idea of extraterrestrial life, the tales of abduction and hybridization and so on seem to me to be not only delusional, but biological impossibilities.  Much as some people don't like the idea,  Homo sapiens forms nothing more than a tiny little blip in a continuum with other terrestrial life forms -- any interesting features we have, like our (relatively) large brains, are perfectly well explained by the evolution and genetics we already understand.

Which, in some ways, is too bad.  Mr. Spock was kind of cool.  And if I'm wrong, let me just mention to any alien life forms who might be looking in my direction; I'm already spoken for.

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As will be obvious to any long-time readers of Skeptophilia, I have a positive fascination with things that are big and scary and can kill you.

It's why I tell my students, in complete seriousness, if I hadn't become a teacher I'd have been a tornado chaser.  There's something awe-inspiring about the sheer magnitude of destruction they're capable of.  Likewise earthquakes, hurricanes, wildfires...

But as sheer destructive power goes, there's nothing like the ones that are produced off-Earth.  These are the subject of Phil Plait's brilliant, funny, and highly entertaining Death From the Skies.  Plait is best known for his wonderful blog Bad Astronomy, which simultaneously skewers pseudoscience and teaches us about all sorts of fascinating stellar phenomena.  Here, he gives us the scoop on all the dangerous ones -- supernovas, asteroid collisions, gamma-ray bursters, Wolf-Rayet stars, black holes, you name it.  So if you have a morbid fascination with all the ways the universe is trying to kill you, presented in such a way that you'll be laughing as much as shivering, check out Plait's book.

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

Life out of catastrophe

After yesterday's post about mysterious explosions in distant galaxies, today I want to look at a colossal explosion that happened much, much closer to home -- and may have jump-started life on Earth.

In a paper by Steven Benner of the Foundation for Applied Molecular Evolution in Alachua, Florida, presented at a conference last fall in Atlanta, we find out that there's geological evidence that early in Earth's history, there may have been a collision with an enormous object -- by some estimates, the size of the Moon -- that drastically altered the atmosphere.  4.47 billion years ago, only sixty million years after the Earth coalesced from the ring of planetary debris where it originated, it was struck so hard by planetoid that water molecules were ripped apart into oxygen and hydrogen, and superheated metallic debris was flung into the air and generated a torrential rain of molten iron.

Artist's conception of what the collision might have looked like from space

As the atmosphere (and everything else) cooled, the highly reactive oxygen bound to the iron, forming a thick layer of iron (and other metal) oxides that explains their prevalence in the Earth's crust today.  More interesting still is that the collision left behind the hydrogen in the atmosphere.  This created what is called a reducing atmosphere -- a collection of gases with an abundance of free electrons, essentially the opposite of what we have today (an oxidizing atmosphere, where oxygen and other electronegative elements mop up any available electrons, making organic matter and other reduced compounds fall apart).

The reducing atmosphere, Benner says, stuck around for two hundred million years, and it was during this time that the first organic compounds were formed.  This lines up neatly with the famous Miller-Urey experiment, where biochemists Stanley Miller and Harold Urey of the University of Chicago showed back in 1952 that in the presence of reducing gases and a source of energy, organic compounds formed readily, including DNA and RNA nitrogenous bases, amino acids, and simple sugars.

Benner believes that the critical one was RNA.  RNA is (as far as we know) unique in that it can not only replicate itself, it's autocatalytic -- it can catalyze its own reactions.  This pull-yourself-up-by-your-shoelaces ability is why a lot of scientists believe that the first genetic material was RNA, not the (currently) more ubiquitous DNA.  And Benner's theory about how the reducing atmosphere was generated explains not only how the building blocks of RNA could have formed, but why the Earth's atmosphere was reducing in the first place.

Benner believes the key is a set of biochemical reactions that involves repeated wetting and drying, along with interaction of the oxygen-free atmosphere with sulfur-containing gases released from volcanic eruptions.  He has demonstrated that in these conditions, formaldehyde -- CH₂O, one of the simplest organic compounds, would form "by the metric ton."  From there, reactions with the sulfur-bearing gases produced hydroxymethanesulfonate, which reacts readily to form glyceraldehyde (a simple sugar) and the four bases of RNA, adenine, cytosine, guanine, and uracil.

Once that happens, the autocatalytic ability of RNA means you're off to the races.  As Richard Dawkins pointed out in his tour-de-force The Blind Watchmaker, if you have two things -- an imperfect replicator, and a selecting mechanism -- you can generate order from disorder in the blink of an eye.  "[M]any experiments have confirmed that once RNA chains begin to grow, they can swap RNA letters and even whole sections with other strands, building complexity, variation, and new chemical functions," said science journalist Robert F. Service, writing for Science magazine.  "[T]he impact scenario implies organic molecules, and possibly RNA and life, could have originated several hundred million years earlier than thought.  That would allow plenty of time for complex cellular life to evolve by the time it shows up in the fossil record at 3.43 billion years ago."

This research not only confirms what Miller and Urey showed in their landmark experiment 67 years ago, but lines up beautifully with what is known from studies by geologists of the earliest rocks.  As for Benner, he's ready to put aside any doubt.  When Ramon Brasser, paleogeologist at the Tokyo Institute of Technology, laid out a timeline of the early Earth in his talk at the Atlanta conference, Benner asked him when the atmosphere would have likely dropped below a temperature of 100 C, the boiling point of water.  Brasser indicated a point about fifty million years after the impact with the planetoid.

"That's it, then!" Benner said excitedly, pointing to a spot at about 4.35 billion years ago on the timeline.  "Now we know exactly when RNA emerged. It's there—give or take a few million years."

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This week's Skeptophilia book recommendation is a little on the dark side.

The Radium Girls, by Kate Moore, tells the story of how the element radium -- discovered in 1898 by Pierre and Marie Curie -- went from being the early 20th century's miracle cure, put in everything from jockstraps to toothpaste, to being recognized as a deadly poison and carcinogen.  At first, it was innocent enough, if scarily unscientific.  The stuff gives off a beautiful greenish glow in the dark; how could that be dangerous?  But then the girls who worked in the factories of Radium Luminous Materials Corporation, which processed most of the radium-laced paints and dyes that were used not only in the crazy commodities I mentioned but in glow-in-the-dark clock and watch dials, started falling ill.  Their hair fell out, their bones ached... and they died.

But capitalism being what it is, the owners of the company couldn't, or wouldn't, consider the possibility that their precious element was what was causing the problem.  It didn't help that the girls themselves were mostly poor, not to mention the fact that back then, women's voices were routinely ignored in just about every realm.  Eventually it was stopped, and radium only processed by people using significant protective equipment,  but only after the deaths of hundreds of young women.

The story is fascinating and horrifying.  Moore's prose is captivating -- and if you don't feel enraged while you're reading it, you have a heart of stone.

[If you purchase the book from Amazon using the image/link below, part of the proceeds goes to supporting Skeptophilia!]

The master cookbook

Every year, I look forward to teaching my biology classes the basics of molecular genetics, because it's just so cool.

All organisms on the Earth contain a master recipe book -- DNA -- that contains all of the instructions necessary to create them.  Each of those recipes is deciphered, through a pair of processes called transcription and translation; the first produces a temporary copy of a single recipe (called RNA), and the second takes that RNA and uses it to build a protein of some sort.  So to extend the analogy of DNA-as-cookbook; transcription would be photocopying a single recipe, and translation would be reading that recipe and using it to make lasagna.  (The lasagna, if you don't mind my stretching the analogy to the snapping point, would be the protein.)

The problem is, as with most things in life, it's not quite that simple.

Your DNA contains a lot more than recipes used in a straightforward fashion to the building of a protein.  Between twenty and seventy percent of your DNA -- depending on whom you believe -- is junk DNA, which are essentially evolutionary leftovers.  Genes that got damaged, lost promoters (promoters are, more or less, universal "on" switches), or were moved somewhere in the genome that they couldn't be activated.  Some researchers think that junk DNA provides a sort of backhanded benefit; it gives us a larger target for mutations.  Mutations in the junk DNA have no effect, so it makes it less likely that any given mutation will kill us.

But there are other complications, too.  Some DNA (called "non-coding DNA") doesn't actually produce proteins directly, but acts to control the activity of other genes -- so it's pretty critical even though it's not specifically making your lasagna for you.  Some of these are "riboswitches" -- bits of DNA that are transcribed into RNA, but the RNA then binds to other pieces of RNA and alters the rate at which they're translated.  Another example are the telomeres, which form the ends of the chromosomes and act to protect them from degradation -- the decreasing size of telomeres is thought to play a role in aging.  A third, more mysterious example are the VNTR (variable number tandem repeat) regions, which are regions made of the same pattern of bases repeated over and over -- it's been made useful in the technique of DNA fingerprinting in forensics, but their function in the living organism is unknown.

With all of this complexity, it's been an ongoing source of contention as to exactly how many genes we have.  As you can see from the admittedly brief description I've given, it's not completely clear whether something is a functional gene in the first place, so how could you hope for an accurate count?  Estimates have run up to 6.7 million genes in the human genome -- and it certainly seems like something as sophisticated as we are must surely be the product of a huge number of individual instructions.

But the more people have looked into it -- starting with the Human Genome Project in the 1990s -- the smaller the estimate has become.  Just last week, the most recent revision was released, and it's pretty startling; a team led by Steven Salzberg at Johns Hopkins University has come up with a tally of 21,306 coding genes (ones that directly produce proteins) and 21,856 non-coding genes (bits of DNA that act to control the expression of other genes).

Which, considering that we're made up of trillions of cells interacting in countless different ways, is really a pretty small number when you come to think about it.

Salzberg is up front that these estimates could still be revised.  He, and study co-author Mihaela Petrea, write:

We aligned all human genes from NCBI's RefSeq database to the Ensembl gene set in an attempt to explain the differences, but although the total counts differ by less than 300, there are several thousand genes in each set that do not map cleanly onto the other, many of them representing genes of unknown function.  Our personal best guess for the total number of human genes is 22,333, which corresponds to the current gene total at NCBI.  We prefer this to the slightly higher Ensembl gene count both because the NCBI annotation is slightly more conservative, and because recent compelling arguments support an even lower gene total.  This number could easily shrink or grow by 1,000 genes in the near future.  However, recent analyses make it clear that even if we agree on a complete list of human genes, any particular individual might be missing some of the genes in that list.  The genome sequence is complete enough now (although it is not yet finished) that few new genes are likely to be discovered in the gaps, but it seems likely that more genes remain to be discovered by sequencing more individuals.  Additional discoveries are likely to make our best estimates for this basic fact about the human genome continue to move up and down for many years to come.

So the exact count of recipes in our DNA cookbook is still a matter of contention, but the whole thing is fascinating -- to think that such a (relatively) small number of sets of instructions could produce something as complex as we are.  As for me, this whole discussion has left me hungry, for some reason.

I think I'm going to make some lasagna.

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This week's recommended read is Wait, What? And Life's Other Essential Questions by James E. Ryan.  Ryan frames the whole of critical thinking in a fascinating way.  He says we can avoid most of the pitfalls in logic by asking five questions: "What?"  "I wonder..." "Couldn't we at least...?" "How can I help?" and "What truly matters?"  Along the way, he considers examples from history, politics, and science, and encourages you to think about the deep issues -- and not to take anything for granted.

RNA attack

It's a common strategy.  If simply spouting alarmist rhetoric doesn't cause your target audience to panic sufficiently, throw in some quasi-technical nonsense to make it sound like your position actually has scientific merit.  Unfortunately, it has a way of working, as people like Vani "The Food Babe" Hari discovered when she launched her "if you can't pronounce it, you shouldn't be eating it" campaign, which if it succeeded, would rob your diet of most of its essential nutrients, leaving behind only easy-to-say stuff like "starch."

It's the old "if you can't dazzle 'em with brilliance, baffle 'em with bullshit" approach dressed up in new clothes.  It's a favorite strategy of such anti-science types as the anti-vaxxers and anti-GMOers (who in many cases are one and the same).  Witness the latter's latest sally against the scientific establishment, which revolves around the claim that if you're eating GMO food, it contains RNA (true) and this RNA can alter your own genes (false).

I learned about this bizarre statement from Sterling Ericsson's wonderful blog A Science Enthusiast, wherein we learn that the anti-GMO cadre have gone from the diffuse claim that all GMOs are bad to proposing a specific mechanism by which they do their dirty work -- they contain "engineered RNA" that then can get into your cells and interfere with your normal cellular processes.  And to the non-scientific, even the actual research can certainly sound like the stuff of science fiction; gene-modification techniques like CRISPR, switching genes on and off with RNA interference, inserting DNA from one species into another to generate organisms that express "foreign" genes as they would their own.

[image courtesy of Christopher Bock, the Max Planck Institute, and the Wikimedia Commons]

My objection to the anti-GMO stance has always been that it lies squarely in the midst of the package-deal fallacy; just as our "natural" genes have thousands of different functions, each GMO is different from all the others.  GMOs are no more all bad than genes are, and each one has to be tested for safety individually.  (And they have been, extensively.)  But the addition of the "ingesting engineered RNA" claim adds a whole new layer of pseudoscience to the anti-GMO stance.  Rather than making it stronger, it makes it weaker, and (further) shines a harsh light on exactly how unscientific the claim itself is.

Because all of the food we eat contains nucleic acids, DNA and RNA both.  If you eat lettuce, you're eating (among other things) lettuce DNA and RNA.  If you eat a hamburger, you're ingesting the genetic material from cows (and tomatoes and whatever else you like on your burger).  If you eat "Slim Jims," you're consuming DNA from... well, whatever the hell organism "Slim Jims" are made from.  I dunno.  But presumably it was some kind of living thing at some point that had its own genetic material.

And miraculously, we don't start expression lettuce, cow, tomato, or Slim Jim genes, nor do any of those interfere with our own gene expression.  The reason is that in your small intestine you have enzymes called nucleases that break down the DNA and RNA of the organisms we eat, specifically to prevent us from accidentally incorporating foreign genetic material into our cells, which could cause us to express foreign proteins (depending on what they were and where they were produced, this could certainly be deleterious).  So the DNA and RNA in our food -- which is there even in the most organic-y of organic free-range locavore diets -- never survives the passage through our digestive system intact.

That includes any "artificially engineered" DNA and RNA, because your body can't tell the difference between the genetic material that came from a healthful, natural, non-engineered peach and that which came from BT corn purchased directly from Monsanto.  It all breaks down, natural and artifical alike.  If there's a health effect from eating GMOs, it doesn't come from the DNA and RNA -- it comes from the proteins they produced within the genetically modified organism before you ate it.

And like I said, those have been tested to a fare-thee-well.  But this is not likely to persuade the anti-GMOers, for whom the naturalistic fallacy is very nearly one of the Ten Commandments.

So anyhow, be on the lookout for this.  Call it out for the nonsense it is.  As I've said many times before, you do not make your point stronger by leaning on poorly-understood science.  All you do is make it seem like the rest of your claim has little merit as well -- which in this case, seems to be the truth.