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.

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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.

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