Quantum spookiness is nothing compared to biology's mysteries!

The news is properly filled these days with reports of studies documenting various very mysterious aspects of the cosmos, on scales large and small.  News media feed on stories of outer space's inner secrets.  We have dark matter and dark energy that, if models of gravitational effects and other phenomena are correct, comprise the majority of the cosmos's contents. We have relativity, that shows that space and even time itself are curved.  We have ideas that there may be infinitely many universes (there are various versions of this, some called the multiverse).  We have quantum uncertainty by which a particle or wave or whatever can be everywhere at once and have multiple superposed states that are characterized in part only when we observe it.  We have space itself inflating (maybe faster than the speed of light).  And then there's entanglement, by which there seem to be instant correlated actions at unlimited distances.  And there is some idea that everything is just a manifestation of many-dimensional vibrations ('strings').

The general explanations are that these things make no 'sense' in terms of normal human experience, using just our built in sensory systems (eyes, ears, touch-sense, smell, etc.) but that mathematically observable data fit the above sorts of explanations to a huge degree of accuracy.  You cannot understand these phenomena in any real natural way but only by accustoming yourself to accept the mathematical results, the read-outs of instrumentation, and their interpretation.  Even the most thoughtful physicists routinely tell us this.

These kinds of ideas rightfully make the news, and biologists (perhaps not wanting to be left out, especially those in human-related areas) are thus led to concocting other-worldly ideas of their own, making promises of miracle precision and more or less health immortality, based on genes and the like.  There is a difference, however: unlike physicists, biologists reduce things to concepts like individual genes and their enumerable effects, treating them as basically simple, primary and independent causes.

In physics, if we could enumerate the properties of all the molecules in an object, like a baseball, comet, or a specified set of such objects, we (physicists, that is!) could write formal equations to describe their interactions with great precision.  Some of the factors might be probabilistic if we wanted to go beyond gravity and momentum and so on, to describe quantum-scale properties, but everything would follow the same set of rules for contributing to every interaction.  Physics is to a great, and perhaps ultimate extent, about replicable complexity.  A region of space or an object may be made of countless individual bits, but each bit is the same (in terms of things like gravity per unit mass and so on).  Each pair, say, of interactions of similar particles etc. follows the same rules. Every electron is alike as far as is known.  That is why physics can be expressed confidently as a manifestation of laws of nature, laws that seem to hold true everywhere in our detectable cosmos.

Of cats and Schroedinger's cat
Biology is very different.  We're clearly made of molecules and use energy just as inanimate objects do, and the laws of chemistry and physics apply 100% of the time at the molecular and physics levels. But the nature of life is essentially the product of non-replicable complexity, of uniquely interacting interactions.  Life is composed strictly of identifiable elements and forces etc at the molecular level. Yet the essence of life is descent with modification from a common origin, Darwin's key phrase, and this is all about differences.  Differences are essential when it comes to the adaptation of organisms, whether by natural selection, genetic drift, or whatever, because adaptation means change.  Without life's constituent units being different, there would be no evolution beyond purely mechanical changes like the formation of crystals.  Even if life is, in a sense the assembling of molecular structures, it is the difference in their makeups that makes us different from crystals.

Evolution and its genetic basis are often described in assertively simple terms, as if we understood them in a profound ultimate sense.  But that is a great exaggeration: the fact that some simple molecules interacted 4 billion years ago, in ways that captured energy and enabled the accretion of molecular complexity to generate today's magnificent biosphere, is every bit as mysterious, in the subjective sense of the term at least, as anything quantum mechanics or relativity can throw at us. Indeed, the essential nature of life itself is equally as non-intuitive. And that's just a start.

The evolution of complex organisms, like cats, built through developmental interactions of awe-inspiring complexity, leading to units made up of associated organ systems that communicate internally in some molecular ways (physiology) and externally in basically different (sensory) ways is as easy to say as "it's genetic!", but again as mysterious as quantum entanglement.  Organisms are the self-assembly of an assemblage of traits with interlocking function, that can be achieved in countless ways (because the genomes and environments of every individual are at least slightly different).  An important difference is that quantum entanglement may simply happen, but we--evolved bags of molecular reactions--can discover that it happens!

The poor cat in the box.  Source: "Schrödinger cat" by File:Kamee01.jpg: Martin Bahmann, Wilimedia Commons

This self-assembly is wondrous, even more so than the dual existence of Schroedinger's famous cat in a box.  That cat is alive and dead at the same time depending on whether a probilistic event has happened inside the box (see this interesting discussion), until you open the box, in which case the cat is alive or dead. This humorous illustration of quantum superposition garnered a lot of attention, though not that much by Schroedinger himself for which it was just a whimsical way to make the point about quantum strangeness.

But nobody seems to give a thought beyond sympathy for the poor cat!  That's too bad, because what's really amazing is the cat itself.  That feline construct makes most of physics pale by comparison.  A cat is not just a thing, but a massively well-organized entity, a phenomenon of interactions, thanks to the incredible dance of embryonic development.  Yet even development and the lives that plants and animals (and, indeed, single-celled organisms) live, impressively elaborate as they are, pale by comparison with various aspects these organisms have of awareness, self-awareness, and consciousness.

This is worth thinking about (so to speak) when inundated by the fully justified media blitz that weird physics evokes, but then you should ask whether anything in the incomprehensibly grand physics and cosmology worlds are even close to the elusiveness and amazing reality of these properties of life and how these properties could possibly come about, how they evolved and how they develop in each individual--as particular traits, not just the result of some generic evolutionary process.

And there's even more:  If flies or cats are not 'conscious' in the way that we are, then it is perhaps as amazing that their behavior, which so seems to have aspects of those traits, could be achieved without conscious awareness.  But if that be so, then the mystery of the nature of consciousness having evolved, and the nature of its nature, are only augmented many-fold, and even farther from our intuition than quantum entanglement.

Caveat emptor
Of course, we may have evolved to perceive the world just the way the world really is (extending our native senses with sensitive instruments to do so).  Maybe what seems strange or weird is just our own misunderstanding or willingness to jump on strangeness bandwagons.  Here from Aeon Magazine is a recent and thoughtful expression of reservations about such concepts as dark matter and energy.

If quantum entanglement and superposition, or relativity's time dilation and length contraction, are inscrutable, and stump our intuition, then surely consciousness trumps those stumps.  Will anyone reading this blog live to see even a comparable level of understanding in biology to what we have in physics?

The Planck spacecraft....and physiological cosmology?

The Planck interplanetary satellite recently provided data leading to glorious images of microwave radiation in our cosmos, providing information about the fundamental nature and origins of our universe.  Here's one of those, that we grabbed from the Wikipedia article on the report:

The non-uniformity provides esthetic beauty and to physicists and cosmologists, information about what happened just after the time of conception (the Big Bang), and subsequently, in our universe.  One apparent aspect of the findings was that so-called dark matter makes up an even greater proportion of all the stuff the universe is made of than had been thought.  According to the Wikipedia page reporting the 2013 results the universe is "contains 4.9% ordinary matter, 26.8% dark matter and 68.3% dark energy."

Dark matter is rather dark to us, and beyond what we personally know much about.  But we understand that it isn't directly detectable by the scales and meters that we use to detect the regular stuff, the atoms and energy that we know about.  It supposedly neither emits nor absorbs electromagnetic energy nor has gravity of its own, but does affect ordinary mass -- but a minority, the 10% we know about!

Astrophysicists knew it was likely to be there because, unless there was some other mistake in physics theory, such as an incorrect basic physical parameter value, darkness affected the things we can see, even if we can't see the dark matter itself.  For example, the effects of gravity upon the behavior of energy (like light) and matter, that we can see, don't predict what would be errors or distortions--the differences seem to physicists to be able to be accountable if we posit a different kind of matter and energy, which since we can't directly see it is called 'dark'.

About a year ago we heard a cosmologist talking about this on the BBC (can't now remember the show or interviewee) who pointed out, rather melodramatically, that we're infused with fluxes of Darkness all the time.   But, not to worry, she said--it doesn't affect us.  But how would she know?

Could darkness shed light on life?
Now, we see (and remark--complain?--about) countless genetic studies, like GWAS mapping attempts, finding that  genome regions, only identifiable by huge studies with various problematic aspects, finding weak statistical support for tiny effects.  Even these typically only account for a usually small fraction of the overall genetic effect as estimated by the correlation of the trait among relatives.  Could there be a 'dark' explanation for such findings?

We think the BBC interviewee's point was that dark matter and energy may make up the vast bulk of the stuff of the universe, but its effects are very, very small--far too small to affect the 'light' matter we're (aware that we're) made of.  Of course, we're not physicists nor cosmologists, so we cannot make knowledgeable comments about that value judgment.  But we can ask how it can be known, if it isn't even 100% sure that there is dark matter and energy, that if it exists it can't affect us?

One might imagine that it provides an unseen 'molasses' that affects the cellular processes, the speed or nature of interactions of molecules, and so on.  Or perhaps it can somehow mimic our DNA as a form of modeling of its shape, some sort of 'dark DNA' that affects cells and their behavior and is variable in some way (like, on a micromicro scale, the lumpiness of things in space in the microwave image above) and is inherited.  It could affect our traits, be inherited (and hence generate correlation among relatives, but if it is not directly shackled to DNA it would not show up in mapping studies or, the weak evidence for genetic contributions may implicate specific DNA locations strictly as an artifact of the statistical methods used that assume location in DNA is everything that matters.

This is, of course, fanciful and we have absolutely no reason to assert such things with any confidence at all.   But the deeper point is that such unknown stuff or forces or factors could exist and could be confounding us, given that we believe that we know of all the possible factors that may contribute to our traits, their inheritance, or their evolution.

Some such transforming discovery could immediately allow many unknowns to fall into place, as the major 'revolutions' in science have done in the past.  Whether we are currently in the mode of trying to force our explanations to fit a crippled model of reality, or are correctly assuming that bigger conventional studies will eventually bring the entire truth to light, or are putting ourselves willfully in the dark by believing so rather than that the complexity of very weak but ordinary factors is the reality, are things that we cannot know.

One can play this mind game:  Of course we can't know what we don't know, but could we learn about it by questioning our very basic assumptions, asking: suppose it isn't so?  Suppose there is some other explanation for this or that fact or observed pattern: what might that be?  If we were serious about asking that question about the frayed edge of what we know that stubbornly refuses to be hemmed into the fabric of our current theory, perhaps some deep insight could result.

But the discovery of very subtle but important aspects of the physical universe should be a sobering tempering for our confidence that we already know what's what when it comes to the living universe.

A TUF nut to translate? The function of 'noncoding' RNA

One of the fundamental principles of life, which we've written about from time to time and include a lot about in our book, is chance. It's everywhere, from the randomness of which genes we inherit from each parent, to being the unlucky fish that get caught in the shark's maw as it sweeps through a school with an open mouth.

Another aspect of chance is sloppiness, which is also found everywhere. Echolocating bats are notably imprecise in their discrimination among prey, error-prone transcription of DNA into RNA is routine--it has been estimated, in fact, that perhaps 3% of a cell's energy is used to correct transcription errors.*

The environment presents us with the unpredictable, too, in the form of phenomena like hail storms or hurricanes, unusual heat or cold, volcanoes, etc., as well as the regular, predictable fluctuation of the seasons. (Of course, as Ken is a former meteorologist, he's inserting the self-defense caveat here that weather forecasting is not entirely unpredictable in the short run, though many details are, and weather may never be predictable very many days in advance--but then, for organisms other than humans, and then only recently, this is irrelevant).

Chance is so ubiquitous that being able to adapt to chance effects--within limits, of course; no amount of adaptiveness will help that fish escape being that marauding shark's dinner--is a characteristic of life that had to have evolved very early because all organisms can do it to some degree. The lineages that couldn't disappeared long ago.

Errors and chance are found at the molecular level, too.  It has been known for decades that only a small fraction of DNA is transcribed into messenger RNA and translated into proteins, and it was thought that the 98% of the genome that wasn't transcribed was 'junk', detritus from evolutionary trial and error. But recently, unexpected transcripts from non-coding DNA have been reported by a number of labs, leading to speculation about the actual role of all that 'junk DNA'. A recent paper in PLoS Biology by van Bakel et al., accompanied by a commentary, addresses this question. van Bakel et al. describe these excess transcripts this way:

Dubbed transcriptional “dark matter”, the “hidden” transcriptome, or transcripts of unknown function (TUFs), the exact nature of much of this additional transcription is unclear, but it has been presumed to comprise a combination of novel protein coding transcripts, extensions of existing transcripts, noncoding RNAs (ncRNAs), antisense transcripts, and biological or experimental background. Determining the relative contributions of each of these potential sources is important for understanding the nature and possible biological function of transcriptional dark matter.

To address the question of what these are, van Bakel et al. compared the usual method for identifying transcripts (tiling arrays) to a "single- and paired-end RNA-Seq" method, and found that the RNA-Seq method identified many fewer unexpected, or 'dark matter' transcripts (reminding us that high-powered technology can be error-prone, too). Most of the transcripts were identifably from intronic regions, suggesting that they were perhaps "fragments of pre-mRNAs", and were associated with open chromatin, that is, segments of DNA that are open for business, ready to be transcribed.

We conclude that analysis of data from tiling arrays leads to vast overestimates of the proportion of transcriptional dark matter. However, the mammalian transcriptome does contain thousands of unannotated transcripts, exons, promoters, and termination sites.

That is, they still found enough unidentified stuff to write home about, maybe 2% of the transcripts they analyzed. While that is considerably less than the dark matter that's given rise to so much speculation, it still suggests that even after 3 billion years, DNA copying enzymes make mistakes. As Richard Robinson says in the PLoS commentary,

The emerging picture of RNA polymerase is of an inherently imprecise, not to say promiscuous, copyist, one whose output includes some mistakes along with lots of valuable product. In this view, most dark matter transcripts are not signals emerging from a hidden universe within the genome, but instead simply the noise emitted by a busy machine.

If these latest results bear out, it will mean that at least some of the enthusiasm in recent years for the idea that there is a huge unknown realm of DNA functions uninvolved with direct protein expression may not be completely warranted, and that our standard ('old-fashioned'?) theory, including the error-proneness of the system, may be pretty accurate after all. 

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*Kurland, C., and J. Gallant. (1996). "Errors of heterologous protein expression." Current Opinion in Biotechnology 7(5):489-493.