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Is life itself a simulation of life?

It often happens in science that our theory of some area of reality is very precise, but the reality is too complex to work out precisely, or analytically.  This can be when we decide to use computer simulation of that reality to get at least a close approximation to the truth.  When a phenomenon is determined by a precise process, then if we increase the complexity of our simulation, and if the simulation really is simulating the underlying reality, then the more computer power we apply, the closer we get to the truth--that is, our results approach that truth asymptotically.

For example, if you want to predict the rotation of galaxies in space relative to each other, and of the stars within the galaxies, the theories of physics will do the job, in principle. But solving the equations directly the way one does in algebra or calculus is not possible with so many variables.  However, you can use a computer to simulate the movement and get a very good approximation (we've discussed this here, among other places).  Thus, at each time interval, you take the position and motion of each object you want to follow, and those measures of nearby objects, and use Newton's law of gravity to predict the position of the objects one time interval later.

If the motion you simulate doesn't match what you can observe, you suspect you've got something wrong with the theory you are using. In the case of cosmology, one such factor is known as 'dark matter'.  That can be built into models of galactic motion, to get better predictions.  In this way, simulation can tell you something you didn't already know, and because the equations can't be directly solved, simulation is an approach of choice.

In many situations, even if you think that the underlying causal process is deterministic, measurements are imperfect, and you may need to add a random 'noise' factor to each iteration of your simulation.  Each simulation will be slightly 'off' because of this, but you run the same simulation thousands of times, so the effect of the noise evens out, and the average result represents what you are trying to model.

Is life a simulation of life?
Just like other processes that we attempt to simulate, life is a complex reality.  We try to explain it with the very general theory of evolution, and we use genetics to try to explain how complex traits evolve, but there are far too many variables to predict future directions and the like analytically.   This is more than just because of biological complexity however, in part because the fundamental processes of life seem, as far as we can tell, inherently probabilistic (not just a matter of measurement error).  This adds an additional twist that makes life itself seem to be a simulation of its underlying processes.

Life evolves by parents transmitting genes to offspring.  For those genes to be transmitted to the next generation, the offspring have to live long enough, must be able to acquire mates, and must be able to reproduce. Genes vary because mutations arise.  For simplicity's sake, let's say that successful mating requires not falling victim to natural selection before offspring are produced, and that that depends on an organism's traits, and that genes are causally responsible for those traits.  In reality, there are other process to be considered, but these will illustrate our point.

Mutation and surviving natural selection seem to be probabilistic processes.  If we want to simulate life, we have to specify the probability of a mutation along some simulated genome, and the probability that a bearer of the mutation survives and reproduces.  Populations contain thousands of individuals, genomes incur thousands of mutations each generation, and reproductive success involves those same individuals.  This is far too hard to write tractable equations for in most interesting situations, unless we make almost uselessly simplifying assumptions.  So we simulate these phenomena.

How, basically, do we do this?  Here, generically and simplified, but illustrating the issues, is the typical way (and the way taken by my own elaborate simulation program, called ForSim which is freely available):

For each individual in a simulated population, each generation, we draw a random number based on an assumed mutation rate, and add the resulting number and location of mutations to the genotype of the individual.  Then for each resulting simulated genotype, we draw a random number from the probability that such a genotype reproduces, and either remove or keep the individual depending on the result.  We keep doing this for thousands of generations, and see what happens.  As an example, the box lists some of the parameter values one specifies for a program like ForSim.



Sometimes, if the simulation is accurate enough, the probability and other values we assume look like what ecologists or geneticists believe is going on in their field site or laboratory.  In the case of humans, however, we have little such data, so we make a guess at what we think might have been the case during our evolution.  Often these things are empirically estimated one at a time, but their real values affect each other in  many ways.  This is, of course, very far from the situation in physics, described above!  Still, we at least have a computer-based way to approximate our idea of evolutionary and genetic processes.

We run this for many, usually many thousand generations, and see the trait and genomic causal pattern that results (we've blogged about some of these issues here, among other posts).  This is a simulation since it seems to follow the principles we think are responsible for evolution and genetic function.  However, there is a major difference.

Unlike simulations in astronomy, life really does seem to involve random draws for probabilistic processes.  In that sense, life looks like it is, itself, a simulation of these processes.  The random draws it makes are not just practical estimates of some underlying phenomenon, but manifestation of the actual probabilistic nature of the phenomenon.

This is important, because when we simulate a process, we know that its probabilistic component can lead to different results each time through.  And yet, life itself is a one-time run of those processes. In that sense, life is a simulation but we can only guess at the underlying causal values (like mutation and survival rates) from the single set of data: what actually happened its one time through.  Of course, we can test various examples, like looking at mutation rates in bacteria or in some samples of people, but these involve many problems and are at best general estimates from samples, often artificial or simplified samples.

But wait!  Is life a simulation after all?  If not, what is life?
I don't want us to be bogged down in pure semantics here, but I think the answer is that in a very profound way, life is not a simulation in the sense we're discussing.  For the relevant variables, life is not based on an underlying theoretical process in the usual sense, of whose parameters we use random numbers to approximate in simulations.

For example, we evaluate biological data in terms of 'the' mutation rate in genomes from parent to offspring.  But in fact, we know there is no such thing as 'the' mutation rate, one that applies to each nucleotide as it is replicated from one generation to the next, and from which each actual mutation is a random draw.  The observed rate of mutation at a given location in a given sample of a given species' genomes depends among other things on the sex, the particular nucleotides surrounding the site in question (and hence all sites along the DNA string), and the nature of the mutation-detection proteins coded by that individual's genome, and mutagen levels in the environment.  In our theory, and in our simulations, we assume an average rate, and that the variation from that average will, so to speak, 'average out' in our simulations.

But I think that is fundamentally wrong. In life, every condition today is a branch-point for the future. The functional implications of a mutation here and now, depend on the local circumstances, and that is built into the production of the future local generations.  Life in fact does not 'average' over the genome and over individuals does not in fact generate what life does, but in a sense the opposite.  Each event has its own local dynamics and contingencies, but the effect of those conditions affects the rates of events in the future.  Everywhere it's different, and we have no theory about how different, especially over evolutionary time.

Indeed, one might say that the most fundamental single characteristic of life is that the variation generated here today is screened here today and not anyplace else or any time else.  In that sense, each mutation is not drawn from the same distribution.  The underlying causal properties vary everywhere and all the time.  Sometimes the difference may be slight, but we can't count on that being true and, importantly, we have no way of knowing when and to what extent it's true.

The same applies to foxes and rabbits. Every time a fox chases a rabbit, the conditions (including the genotypes of the fox and rabbit) differ. The chance aspect of whether it's caught or not are not the same each time, the success 'rate' is not drawn from a single, fixed distribution.  In reality, each chase is unique.

After the fact, we can look back at net results, and it's all too tempting to think of what we see as a steady, deterministic process with a bit of random noise thrown in.  But that's not an accurate way to think, because we don't know how inaccurate it is, when each event is to some (un-prespecified) extent unique.  Overall, life is not, in fact, drawing from an underlying distribution.  It is ad hoc by its very nature and that's what makes life different from other physical phenomena.

Life, and we who partake of it, are unique. The fact of local, contingent uniqueness is an important reason that the study of life eludes much of what makes modern physical science work.  The latter's methods and concepts assume replicable law-like underlying regularity. That's the kind of thing we attempt to model, or simulate, by treating phenomena like mutation as if they are draws from some basic underlying causal distribution. But life's underlying regularity is its irregularity.

This means that one of the best ways we have of dealing with complex phenomena of life, simulating them by computer, smoothes over the very underlying process that we want to understand.  In that sense, strangely, life appears to be a simulation but is even more elusive than that.  To a great extent, except by some very broad generalities that are often too broad to be very useful, life isn't the way we simulate it, and doesn't even simulate itself in that way.

What would be a better approach to understanding life?  The next generation will have to discover that.

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?

Unknowns, yes, but are there unknowables in biology?

The old Rumsfeld jokes about the knowns and unknowns are pretty stale by now, so we won't really indulge in beating that dead horse.  But in fact his statement made a lot of sense.  There are things we think we know (like our age), things we think we don't know but might know (like whether there will be a new message in our inbox when we sign onto email), and things we don't know but don't know we don't know (such as how many undiscovered marine species there are). Rumsfeld is the subject of ridicule not for this pronouncement per se (at least to those who think about it), because it is actually reasonable, but for other things that he is said to have done or said (or failed to say) in regard to American politics.

Explaining what we don't know is a problem!  Source: Google images

The unknowns may be problems, but they are not Big problems.  What we don't know but might know are at least within the realm of learning.  We may eventually stumble across facts we don't know but don't yet even know are there.  The job of science is to learn what we know we don't know and even to discover what we don't yet know that we don't know.  We think there is nothing 'inside' an electron or photon, but there may be if we some day realize that possibility.  Then the guts of a photon will become a known unknown.

However, there's another, even more problematic, one may say truly problematic kind of mystery: things that are actually unknowable.  They present a Really Big problem.  For example, based on our understanding of the current understanding of cosmology, there are parts of the universe that are so far away that energy (light etc.) from them simply has not, and can never, reach us.  We know that the details of this part of space are literally unknowable, but because we have reasonably rigorous physical theory we think we can at least reliably extrapolate from what we can see to the general contents (density of matter and galaxies etc.) of what we know must exist but cannot see.  That is, it's literally unknowable but theoretically known.

However, things like whether life exists out there are in principle unknowable.  But at least we know very specifically why that is so.  In the future, most of what we can see in the sky today is, according to current cosmological theories, going to become invisible as the universe expands so that the light from these visible but distant parts will no longer be able to reach us.  If there are any living descendants, they will know what was there to see and its dynamics and we will at least be able to make reasonable extrapolations of what it's like out there even though it can no longer be seen.

There are also 'multiverse' theories of various sorts (a book discussing these ideas is Our Mathematical Universe, by Mark Tegmark).  At present, the various sorts of parallel universes are simply inaccessible, even in principle, so we can't really know anything about them (or, perhaps, even whether they exist).  Not only is electromagnetic radiation not able to reach us so we can't observe, even indirectly, what was going on when that light was emitted from these objects, but our universe is self-contained relative to these other universes (if they exist).

Again, all of this is because of the kind of rigorous theory that we have, and the belief that if that theory is wrong, there is at least a correct theory to be discovered--Nature does work by fixed 'laws', and while our current understanding may have flaws the regularities we are finding are not imaginary even if they are approximations to something deeper (but comparably regular). In that sense, the theory we have tells us quite a lot about what seems likely to be the case even if unobserved. It was on such a basis that the Higgs boson was discovered (assuming the inferences from the LHC experiments are correct).

What about biology?
Biology has been rather incredibly successful in the last century and more.  The discoveries of evolution and genetics are as great as those in any other science.  But there remain plenty of unknowns about biological evolution and its genomic basis that are far deeper than questions about undiscovered species.  We know that these things are unknown, but we presume they are knowable and will be understood some day.

One example is the way that homologous chromosomes (one inherited each of a person's parents) line up with each other in the first stage of meiosis (formation of sperm and egg cells).  How do they find each other?  We know they do line up when sex cells are produced, and there are some hypotheses and bits of relevant information about the process, but we're aware of the fact that we don't yet really know how it works.

Homologous chromosomes pair up...somehow.  Wikimedia, public domain.

Chromosomes also are arranged in a very different 3-dimensional way during the normal life of every cell.  They form a spaghetti-like ball in the nucleus, with different parts of our 23 pairs of chromosomes very near to each other.  This 'chromosome conformation', the specific spaghetti ball, shown schematically in the figure, varies among cell types, and even within a cell as it does different things.  The reason seems to be at least in part that the juxtaposed bits of chromosomes contain DNA that is being transcribed (such as into messenger RNA to be translated into protein) in that particular cell under its particular circumstances.
Chromosomes arrange themselves systematically in the nucleus.  Source: image by Cutkosky, Tarazi, and Lieberman-Aiden from Manoharan, BioTechniques, 2011
It is easy to discuss what we don't know in evolution and genetics and we do that a lot here on MT. Often we critique current practice for claiming to know far more than is actually known, or, equally seriously, making promises to the supporting public that suggest we know things that in truth (and in private) we know very well that we don't know.  In fact, we even know why some things that we promise are either unknown or known not to be correct (for example, causation of biological and behavioral traits is far more complex than is widely claimed).

There are pragmatic reasons why our current system of science does this, which we and many others have often discussed, but here we want to ask a different sort of question:  Are there things in biology that are unknowable, even in principle, and if so how do we know that?  The answer at least in part is 'yes', though that fact is routinely conveniently ignored.

Biological causation involves genetic and environmental factors.  That is clearly known, in part because DNA is largely an inert molecule so any given bit of DNA 'does' something only in a particular context in the cell and related to whatever external factors affect the cell.  But we know that the future environmental exposures are unknown, and we know that they are unknowable.  What we will eat or do cannot be predicted even in principle, and indeed will be affected by what science learns but hasn't yet learned (if we find that some dietary factor is harmful, we will stop eating it and eat something else).  There is no way to predict such knowledge or the response to it.

What else may there be of this sort?
A human has hundreds of billions of cells, a number which changes and varies among and within each of us.  Each cell has a slightly different genotype and is exposed to slightly different aspects of the physical environment as well.   One thing we know that we cannot now know is the genotype and environment of every cell at every time.  We can make some statistical approximations, based on guessing about the countless unknowns of these details, but the numbers of variables will exceed that of stars on the universe and even in theory cannot be known with knowable precision.

Unlike much of physics, the use of statistical analytic techniques is inapt, also to an unknowable degree.  We know that not all cells are identical observational units, for example, so that aggregate statistics that are used for decision-making (e.g., significance tests) are simply guesses or gross assumptions whose accuracy is unknowable.  This is in principle because each cell, each individual is always changing.  We might call these 'numerical unknowables', because they are a matter of practicality rather than theoretical limits about the phenomena themselves.

So are there theoretical aspects of biology that in some way we know are unknowable and not just unknown?  We have no reason, based on current biological theory, to suspect the kinds of truly unknowables, analogous to cosmology's parallel universes.  One can speculate about all sorts of things, such as parallel yous, and we can make up stories about how quantum uncertainty may affect us. But these are far from having the kind of cogency found in current physics.

Our lack of comparably rigorous theory relative to what physics and chemistry enjoy leaves open the possibility that life has its own knowably unknowables. If so, we would like at least to know what those limits may be, because much of biology relates to practical prediction (e.g., causes of disease). The state of knowledge in biology, no matter how advanced it has become, is still far from adequate to address the question of the levels of knowable things that may eventually be knowable, but also what the limits to knowability are.  In a sense, unlike physics and cosmology, in biology we have no theory that tells us what we cannot know.

And unlike physics and cosmology, where some of these sorts of issues really are philosophical rather than of any practical relevance to daily life, we in biology have very strong reasons to want to know what we can know, and what we can promise....but perhaps also unlike physics, because people expect benefits from biological research, strong incentives not to acknowledge limits to our knowledge.

Rare Disease Day and the promises of personalized medicine

O ur daughter Ellen wrote the post that I republish below 3 years ago, and we've reposted it in commemoration of Rare Disease Day, Febru...