The Chirality Problem

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NB: I published a follow-on article to this, which you can find here.

It was the fall of 1980. John Lennon still had a couple months to live. Young me had visions of majoring in chemical engineering at Princeton. After a hilarious and humbling first week, I settled into a seat in the former Frick lecture hall, pen and notebook in hand. Two years of high school chemistry had been easy-peasy, so this freshman chemistry class was gonna be a snap. I owned chemistry. Acids, bases, covalent bonds, molarity — all that fun stuff. Geez, I should be teaching this class… <ahem>

In due time, the jovial, middle-aged prof with the moppy hair strolled onto the dais and introduced himself. With the formalities out of the way, he began to explain that he specialized in organic chemistry. And even though this was freshman chemistry — well, prepare yourselves, because the road ahead might get a little dicey.

And then he started talking about chirality.

Chi- what??? It sounded like a Keith Jarrett album. And, really, for all I knew he could have been discussing jazz, as this stuff had nothing to do with any chemistry that I was taught as an overachieving teen. He went on to show some examples, using the technology of the day — an overhead projector, and a stack of transparencies. Aside: Most of my memories of overhead projectors consist of teachers struggling with them. I subconsciously ranked teachers by their sense of calm when rolling the overhead projector into position. You could see the sweat on some, silent obscenities slipping through pursed lips. And you just knew the class would be a train wreck.

But not this time.

It turns out that molecules have shapes. Fine, I knew that from high school. And those shapes matter — I knew that too, sort of. But in organic chemistry — the chemistry of life — those shapes take on deeper meaning. The building blocks of life are like Legos; the pieces need to fit together, else they act like deadly flotsam riding the waves of the living room floor, armed to destroy bare feet. Every complex molecule in every cell of your body has an important three-dimensional shape, which more or less determines if it will do something useful or wreck your day, like so many stray Legos near the coffee pot on a sleepy morning. In the chemistry of life, if you ain’t part of the solution, you truly are part of the problem.

This molecular shape factor has interesting consequences. Most notably for the subject at hand, some molecules can be mirror images of each other, just like, say, your hands or your feet. Your two hands are not the same. Your right hand and your left hand require different gloves, if the gloves have distinctive top and bottom. Mirror you is not quite you you. This is what chemists mean by chirality — or, somewhat anthropomorphically, “handedness”. In chemistry, two so-called “enantiomers” (left and right hands) of a chiral molecule will have the same chemical properties, but they cannot be superimposed on each other in 3-D space.

I remember shrugging and thinking “So what, Professor Jones? I mean, who really cares if they are mirror images, if they have the same chemical properties? Why are you obsessing over this? More importantly, why are we studying this in freshman chemistry, when the lectures have nothing to do with the labs? Answer that one, smart guy.”

Decades later, I’m very glad that I learned about chirality in freshman chemistry. But I wasn’t entirely wrong in wondering why that class was structured the way it was. The chaos and lack of mellifluous integration ended my interest in chemical engineering. The graduate student TA was cute though. I’ll give it that.

So you’re probably wondering why I chose the awkward and haughty term “mellifluous integration”. I could lie and say that it symbolizes the inner struggle of the people who designed the syllabus for the class, who clearly lacked mellifluous souls. That sounds credible. But the real reason is that I’ve been wanting to work “mellifluous” into my vocabulary ever since my kid’s seventh grade English teacher included it in a list of her “Super Seventy” words that the class should memorize. It took seventeen years, but I finally did it. Ha!

Anyway… It turns out that life is very picky about it’s own form of mellifluous integration. Fun fact: All of the sugar molecules in your DNA are right-handed. And all of your proteins are left-handed. “Big deal!” you exclaim — kind of like me that day in 1980 (except I was dumb enough to think it with a world-class research scientist staring at me). And I get it. Truth be told, the non-living side of nature couldn’t care less about chirality. If you buy a sample of some chiral chemical off the shelf, you will get what’s called a “racemic” (ra-see’-mick) product, which means that it contains both mirror images mixed together. This is the natural state of things. Of course, if you are a biochemist feeling all giddy about your new NIH grant funding, and you need a specific enantiomer (again, the fancy word for one particular mirror image), you can buy it, but you will pay up to ten times more. Because making non-racemic mixtures is difficult. They don’t just happen — except inside living cells, where they happen all the time.

Non-living chemical systems mostly don’t care about chirality. But chirality is non-negotiable within living systems. If you want to progress from non-life to life, you must make the leap from racemic chemistry into very picky chiral chemistry. The chasm between the two worlds is not small.

To appreciate the importance of chirality to life, let’s look just a bit closer at this whole right-handed DNA and left-handed protein thing. Life is extraordinarily complicated, but one bedrock fact of life is that it depends on proteins. And the recipe for the proteins is stored in your DNA.

NB: To be precise, proteins are strings of amino acids. It’s actually the amino acids that are left-handed. I am speaking broadly to avoid losing the core points of the discussion in a sea of details.

DNA is not a protein, and proteins are not DNA — just like your favorite recipe book is not food, and your food is not a recipe. So let’s clarify a bit:

• Proteins are large molecules with specific three-dimensional shapes, designed to do thousands of shape-specific jobs in a cell. This system is so precise that serious abnormalities result from single defects in the recipe for single proteins. Given that proteins often consist of hundreds of building blocks, this is a tall order.

• DNA is a huuuuge molecule that stores the instructions for making perfect proteins (among other things). DNA is basically an organic hard drive with an operating system pre-installed. With a couple exceptions, your body squeezes this entire “database of you” into every cell. Cells have extremely complex systems for converting the information in DNA into proteins. Amazingly, the DNA has the instructions for making those systems too (imagine that your recipe book also has recipes for making KitchenAid mixers).

Fortunately, we do not need to dive a whole lot deeper. The important takeaway is that both DNA and proteins have life-critical functions and very specific geometries. DNA is enormous and winds into a very compact form, starting with something called a double helix. You probably heard about it in high school biology; it was one of the most celebrated scientific discoveries of the mid 20th century. On the other hand, proteins are like jigsaw puzzle pieces, designed to fit specific targets. In other words, DNA and proteins are very different types of complex molecules, with very different but critical requirements for exploring three-dimensional space in the cell. If your DNA and proteins stop working, so do you.

Another fun fact: If you stretched out the DNA in just one of your cells into a single strand, it would be roughly eighty inches long. 8-0. Cell sizes vary a lot, but lets consider a decent-sized cell that is, say, 0.001 inches in diameter — one thousandth of an inch. Fitting eighty inches of DNA into a thousandth of an inch is a neat trick. Realistically, it is more difficult than that, since most of your DNA needs to fit in the nucleus of the cell, which of course is smaller than the cell it serves.

How can eighty inches of DNA fit in a space that is a hundred thousand times smaller? The answer is a lot of precise twisting and folding, which is an ongoing area of intense scientific research. We know that the folding involves multiple factors, but one very basic factor is the strict chirality of DNA. Chirality accounts for the helix structure, without which subsequent folding would be irrelevant. Without chirality, the DNA would not fit inside the cell, and it would be game over for any chance of life. Chirality also figures heavily in other properties of DNA, but let’s not get distracted. Chirality prevents chaos, and is a big reason why you are you and not goo.

Recall that the DNA contains the recipes for proteins. And proteins are large-ish molecules that also need to fold into highly complex and specific shapes to perform their own assigned functions. Proteins are like custom machines — “unitaskers”, as food pedant extraordinaire Alton Brown would put it. Brown hates unitaskers in the kitchen, understandably. But without them in the cell, well… Jack You Dead.

Man, I love that album.

Scientists spend a lot of time studying how proteins fold, in an effort to predict such behavior. AI tools figure heavily in this work nowadays — it’s a very big deal in medical and pharmaceutical research. A huge factor in how proteins fold is — you guessed it — their chirality. A protein might consist of hundreds of building blocks (the aforementioned amino acids), and each building block must be left-handed. Slipping a right-handed amino acid into the mix turns your exquisite molecular unitasker into a crossbeam that has gone out of skew on the treadle. And nobody needs that. Or the Spanish Inquisition.

But let’s think about this. Remember that the chirality in the DNA allows the huge DNA molecule to twist and fold inside the tiny cell nucleus, in ways that would make world-class contortionists blush. But now we’re saying that the same chirality is conferred (in reverse) to proteins — whose chemistry, geometry and purpose are entirely different, and vary by protein. And yet the “handedness” conferred to the proteins also meets thousands of unique, unitasker requirements within the cell, which have their own very different folding issues. Those requirements have nothing to do with DNA storage.

In other words, the same ground-floor design feature that makes DNA storage and other features possible also just happens to transform thousands of unique proteins from toxic trash to life-enabling wonder molecules. That’s quite a coincidence. I won’t bore you with the math. The probability of this happening by accident is absurdly small — effectively zero. That is, this could not happen by chance.

Remember: Living systems aside, the chemistry of these molecules is effectively independent of their chirality. If the molecules are left to their own devices — say, in a warm little pond somewhere, as one very famous writer once suggested, long before the chirality of life was understood — the different mirror images will mix together quite peacefully. But those peaceful mixtures are lifeless goo, with no chance of forming a living system. The organic chemistry of life demands extreme organization from the outset, part of which is perfect chirality throughout disparate systems in the cell. All DNA is right-handed, and all proteins are left-handed — in you, your dog, your goldfish, and anything else that is alive. Life requires it. Life is not simply chemistry; it demands much more discipline than mere chemistry imposes.

That’s weird. But it gets much weirder.

In recent years scientists have discovered something called “Chiral-Induced Spin Selectivity”, or CISS. Pardon the mumbo jumbo, but, as we will see, it is a pretty good name.

It turns out that chirality in organic molecules is not just about geometry. CISS is a quantum effect, and the details are way beyond the scope of this layman discussion. Quantum mechanics is not exactly light reading. But I will do my best to summarize, while noting that I have not had the time to study the proposed mechanisms of CISS in depth, or read any papers on the subject. These are relatively new findings, but the scientific consensus seems to be solidifying around hard evidence.

Why is CISS important? Living systems store and use a lot of energy, and they do it with incredible efficiency that non-living systems cannot match. This extreme efficiency was a mystery for a long time. Some parts of cells’ energy transfer systems are nearly 100% efficient in converting energy from one form to another. CISS explains how this is possible. And you will not be surprised to learn that a key requirement is chirality.

A review of crucial energy transfer processes like photosynthesis and the Krebs Cycle is beyond my purpose here. We can stipulate that scientists worked out the basics of these decades ago, and the details now torment high school biology students across the land. Photosynthesis allows green plants to store the energy in sunlight in sugars; the Krebs Cycle allows organisms to extract useful energy at the cellular level from food. Both are complex chemical processes that manipulate electrons through a series of steps.

At this level of discussion, the key is to know that electrons have a property called “spin” that can be either “up” or “down”. In a non-chiral system, the movement of these up and down electrons can cause their flow to interfere with each other. Conceptually, the net effect is like friction in a mechanical system, leading to substantial energy loss. However, in the chiral systems of the cell, the CISS effect filters the electrons so that only electrons of a particular spin are permitted to flow. This reduces the “friction” to nearly zero. Spin selectivity for the win.

An interesting footnote on the Krebs Cycle in particular: Some of the key molecules involved, like citrate, are not chiral to start. However, they are described as “protochiral” because the process employs enzymes (i.e., highly optimized proteins) to add components that make them chiral. Did you catch that? Even where fate and geometry inject a symmetrical, non-chiral molecule into the process, the process has workarounds to impose chirality.

What does it all mean?

So let’s summarize, with a little added color:

• Life requires complex chemicals, and it depends on a particular feature of some chemicals called chirality. We observe strict “handedness” in DNA, in proteins, and in crucial energy transfer systems. Where specific handedness is required (almost everywhere), exceptions cannot be tolerated. Cells do not work a little less efficiently without chiral discipline; they do not work at all. In rare situations where a non-chiral molecule is implicated, the cell produces unitasker enzymes to make the molecule chiral.

• The chirality throughout the cell descends from the chirality in DNA. Depending on who you ask, it is either an unfathomably unlikely and happy accident or an example of incredible design efficiency that this “source chirality” in the DNA also happens to meet the very specific needs of thousands of disparate, downstream biochemical processes that have nothing to do with squeezing DNA into cells.

• To create a living cell that functions anything like even the simplest forms of biological life (known or theorized), starting from non-living raw materials, it is necessary to transform racemic (mixed) raw materials into pure, single-handed components.

• There is no inorganic chemistry in nature that can, without intelligent planning and coercion, create pure, “single-handed” chemicals in the wild. A few natural processes can result in slightly biased percentages, rather than exact 50-50 racemic mixtures. But these are very special cases and do not, in any case, produce anything resembling the pure, single-handed chemicals required by life. (NB 6/24/26: This is not true. Please see my follow-on article for a more accurate discussion of current research. I apologize for the error)

• Therefore, any successful origin of life theory must identify some form of self-replicating, respirating system that either does not exploit chiral chemistry, or that is tolerant of sloppy racemic mixtures in its earliest forms. But no such system is known, nor is there any evidence that such an organism existed or could exist, let alone emerge by accident.

I can already feel the agita of some people, as they read my blasphemous doubt in the ability of nature to just whip up some life. Cool your jets. I am not anti-science — I’m about as pro-science as they come. What I oppose is science acting as a de facto religious faith. The rest of this piece will dig a little deeper into this.

A Personal Reflection

I have looked at only one issue here, namely, the chirality built into organic molecules, and its multifaceted significance to life. It wasn’t a particularly deep or rigorous dive (the Russian Judge in me gives it a 3), but it serves the purpose. But this is only one of hundreds of issues that come to bear on the purported ability of non-living chemicals to form living systems. If you believe that such a thing is possible, you believe it out of a blind faith — a faith that is increasingly oblivious to hard evidence and established mathematics of probability.

In recent years, certain friends and acquaintances have been peeling away from me, as some come to realize that I am not a materialist. I do not dwell on these things in conversations, nor do I impose my metaphysics or ethics on people. I write what I write, but in day to day life I try to meet people where they are, and enjoy friends for who they are. But it is clear that some folks have a strong intolerance for intelligent people who look at the broader pool of evidence and reach unpopular conclusions — for example, that we simply don’t know some things that opinion leaders insist are facts (or who sloppily speak in such terms). Or that life could not invent itself. These are not popular positions. A respectable, educated person is supposed to support the team, and bury such pesky doubts in appropriate closets.

A common response/tactic of these folks is to quote notable materialist scientists, often out of context, while tactfully (or not so tactfully) demeaning my own qualifications to even render an opinion. I resist the urge to respond, as the arguments are both insulting and not worth my time; they are the tired and perfunctory defense mechanisms of people who have chosen a tribe that comports with their lifestyle and worldview. I tire of listening to enthusiasts over-inflate the significance of minor scientific studies that support their views, which they do in deference to the evangelism of tribal shamans with funding and legacies to protect.

That sounds almost… religious. And that’s because it is. These tribal affiliations are deeply important to many people, sometimes more important than personal relationships. It is their metaphysical support network. Unfortunately, it becomes a house of cards when faced with mountains of inconvenient data — data that their preferred shamans provide the necessary permission and rationalization to simply ignore. Origin of life is one such arena, where the promises of materialist science remain entirely unfulfilled, and the math and physics strongly suggest that they will stay that way.

The activity that we call “science” is not that old. The notable successes of Enlightenment-era scientists, combined with parallel developments in western philosophy, led to a hubris about what is explainable within a materialist program. This hubris led to a set of philosophical assumptions about what is real (ontology) and how we can know things (epistemology). These assumptions now constitute the strict rules of a professional game. Which is fine — all games need rules! Even if science is just a materialist game, we can all agree that it has been an awesome and productive one, when it plays on its designated field. But we should also recognize that this game requires oodles of money, which cements incentive structures toward tribal conformity.

I am happy that scientists spend a lot of time researching origin of life, and the possibility of chemical evolution. I wish them well. I enjoy reading about the latest breakthroughs, even if they are inevitably exposed as tiny mole hills rather than the hyped mountains. But science is also a victim of its own success. We are farther away — much farther away — from explaining life’s origin than when we started a century or so ago; the goal posts move nearly every day. Thanks to science, our appreciation of life’s complexity is accelerating wildly, and now grows much faster than any progress we make in explaining it. For example, nobody knew about CISS twenty five years ago — which, as we have seen, adds yet another dependency to the chirality conundrum.

Yes, we do typically expect researchers and theoreticians to hone in on answers. Fortunately, science generally self-regulates, ceasing to pursue targets deemed moot by new understanding (e.g., astronomers stopped refining epicycles, after a better theory emerged). But we should grant generous exceptions for big questions, such as origin of life and cosmology. When scientists play the game by the rules, their efforts should be respected. Keep looking. Keep proposing. Keep learning. Keep publishing. Keep respecting the rules, even if those rules are overly restrictive. It’s best for everyone that a discipline exists that looks for explanations based on physical laws. Just don’t claim that you know something that you don’t know, or can create something that you can’t create. Just be honest.

In other words, my issue is not with materialist science, per se. It does great work, and we need it. My issue is the arrogance of insisting that one particular method of inquiry is the sole arbiter of Ultimate Truth, and then force-feeding this faith-based quasi-religion through the institutions of a civilization. Our western culture and education system now demand dishonesty, and they routinely misrepresent what we actually know about big questions. They demand that people adopt the arbitrary ground rules of science as a much broader lens through which everyone must view the universe. And that’s a very big and unreasonable ask. The rules of the science game are not equipped for that task. As a result, cultural myths develop and calcify, providing materialist science permission to ignore evidence that cannot be explained. Instead of confronting it, science either denies that such evidence exists, or relegates it to a bucket labeled “No Worries, We’ll Figure It Out Someday”.

To be clear, the “we’ll figure it out someday” bucket is a valid and essential part of science. But it takes vigilance, wisdom and intellectual integrity to avoid peeing in it. Without those guard rails, the label on the bucket morphs into “My Materialist Faith”. That bucket is growing in size every day, as the evidence increasingly eats away at certain shibboleths of materialist science. Eventually, the label degenerates into “Let’s Just Ridicule the Kid Who Can’t See the Emperor’s New Clothes”.

Sadly, I think we are there. But this is inevitable when we trade truth for tribes, and the tribes enforce the hegemony of their particular brand of truthiness. For my part, I gladly accept the ridicule. Better to be ridiculed in reality than honored in a role-playing game. Unfortunately, some folks in my life, or who used to be in my life, prefer the roles to the real world. I’ll choose reality every time, wherever it might lead, and in whatever state of poverty it requires me to exist. Per Solzhenitsyn, live not by lies.

Thanks for reading.

First published 6/1/26. Last edit: 6/24/26 at 10:30 AM EDT.

NOTE: I frequently edit my writing after publishing it here. I realize that this is a curious habit, but such is the life of self-publishing on a shoestring. Pushing pieces out the door is my way of imposing deadlines and avoiding the perfection trap. Which is all to say… if you are an E-Mail subscriber, you will frequently find a slightly improved version of a piece on the substack site a few days later. Going forward, I will add an end note when a piece has been edited since its first release.