13 November 2015

Reflections on living things.

Caenorhabditis elegans
What would be involved in a complete understanding of a single animal? It would require a full study of its behaviour at all stages of its life cycle. We'd need a complete map of its genome and an understanding of all the proteins that the genes code for, as well as an understanding of the interrelationships of these genes (epigenetics) and which genes were active across the lifespan of the organism. Also a complete wiring diagram of its nervous system and a way of correlating all behaviour to brain activity. Amongst the most closely studied of all animals the tiny nematode worm, Caenorhabditis elegans is probably closest to this ideal.

C. elegans is an unsegmented, round-worm, transparent, about 1mm in length, which normally lives in soil. It is a relatively simple organism that has digestive and reproductive systems, but no circulatory or respiration system. Most individuals are described as "female hermaphrodites" (a female that also has male gonads and can self-inseminate) while a minority are males. We know the precise number of cells that make up the body: 959 cells in the adult hermaphrodite; 1031 in the adult male. There are also about 2000 germ cells in the former and 1000 in the latter (Alberts 2002). Reproduction is clearly important!
Body plan of C elegans. 

We have a complete genome for the worm (The C. elegans Sequencing Consortium 1998) and this information is open access. The worm has a total of 100,291,840 base pairs in its genome including some 19,735 protein-coding genes. That's about 100 million bits of information, a mere 12 megabytes, but these code for roughly 20,000 different proteins. The 2000-3000 cells are of a relatively limited number of types: nerve, muscle, gonad, skin, gut lining.

The development of all the cells in the animal's body over its lifespan has been traced in detail:
"C. elegans begins life as a single cell, the fertilized egg, which gives rise, through repeated cell divisions, to 558 cells that form a small worm inside the egg shell. After hatching, further divisions result in the growth and sexual maturation of the worm as it passes through four successive larval stages separated by molts. After the final molt to the adult stage, the hermaphrodite worm begins to produce its own eggs. The entire developmental sequence, from egg to egg, takes only about three days." (Alberts 2002)
A complete wiring diagram, or connectome, for the brain of C elegans, has been mapped out (White et al. 1986). The nervous system contains 302 neurons and 7000 synapses (including sensory and motor nerves).
C elegans connectome diagram (head to the right).
Scientific America
In 2008, Stephens et al. published an article that began to characterize the behaviour of the worm in response to a temperate gradient. And this showed that more complex behaviours are the result of combinations of simpler behaviours that can be described mathematically. The results of this paper were partial, partly because they only concerned two dimensions, and the authors flagged the need for more study and especially fully three-dimensional descriptions of movement. But this seems to be an important step in understanding how the simple mechanism can produce relative complex behaviour. In turn, this will eventually make it easier to link behaviour (i.e. movement) to brain activity.

Another interesting experiment was an attempt to use the neural wiring diagram to control a lego robot (right) roughly modelled on the worm's body.
"It is claimed that the robot behaved in ways that are similar to observed C. elegans. Stimulation of the nose stopped forward motion. Touching the anterior and posterior touch sensors made the robot move forward and back accordingly. Stimulating the food sensor made the robot move forward." Black (2014)
There are some fairly obvious gaps. We need to know how to get from the genome to the adult animal. A genome is certainly interesting, but we need to know which genes are active, when in the life-cycle, and where in the body. This involves identifying all the proteins that protein-coding genes code for, and the interactions of controlling genes that switch other genes on and off (the epigenetics). We particular need to know how the expression of genes over time as proteins leads to the construction of the cells, organs, and body of the worm.

We know a good deal about the internal workings of animal cells but are nowhere near a full understanding or having the ability to make a living cell from scratch. Most of the research I've cited about is five or more years old. Progress is occurring all the time. Small gains, lead to bigger breakthroughs, that perhaps in time will accumulate and amount to a paradigm shift. If we do gain a full understanding of a complex living organism then C. elegans is a very likely candidate to be it. 


What's clear about this project is that we gain a huge amount of information through analysis, i.e. from breaking the worm down into its component parts. This many cells, of these types, arranged in this way. This many neurons connected by this many synapses. This many genes, encoding this many proteins. These kinds of internal cells structures and mechanisms. It's quite essential that we have all this information in our quest to understand the organism C. elegans. But once we have it, we need to understand how it is organised into and operates as systems. All of the parts have to fit together and operate together over time. There's no question that the genome and connectome were huge advances in our understanding of organisms. But we already see that this kind of static information represents first steps on the way to a much greater goal of understanding the dynamics of the parts functioning together as a system, and as systems within systems; or systems of systems; or networks of systems.

Understanding how the parts at the organism, cellular, and genetic levels, change over time emerges as a key goal. Life happens in time. It is particular patterns of change amongst the constituents and the whole over time that are key to our understanding that something is alive. We can use an analogy for this.

Imagine we stand at the top of the Tower of Pisa with a cannonball and a bird. We drop them at the same time. For perhaps half a second they both simply fall towards the ground (in reality, as they convert potential energy into kinetic energy, they follow a curved path through space that appears to us as acceleration towards the centre of the earth). The cannon ball continues to fall, it's path describing a parabolic curve until it hits the ground. We can describe the path it follows to ten decimal places. In Newtonian terms, it appears to accelerate at about 10 meters per second per second. Air resistance is minimal, but in a longer fall or a less aerodynamic object it becomes significant after a few seconds and the acceleration of gravity is equalled by the drag of the air so that a falling object reaches a maximum or terminal velocity. Since all non-agentive objects behave this way we usually gain an intuitive understanding of them quite early on. And at least by physical maturity, but often much earlier, we can accurately predict the path of a falling object by seeing a fragment of its path and use this to perform feats like catching balls that are thrown to us or dodging objects that might otherwise hit us. Next time you see a juggler, note that they do not look at their hands, i.e. where the ball lands, they look at the top of the arc of the ball which gives them all the information they need to catch it. This is possible because all simple objects behave similarly. All humans have always known this. We now have incredibly accurate models for the patterns and an understanding of why these patterns exist, which we call "physics". 

On the other hand, the bird behaves very differently from the canon ball. It may well fall for a very short time, but it soon stabilises its orientation to the ground, extends its wings to generate a counteracting force of lift, and begins to fly in a non-parabolic course, perhaps in a level, straight line away from the tower. It is this failure to fall that alerts us that a bird is not an object, it alerts us that the bird is not an object. The ability to move in ways that are not simply determined by the laws of motion is a defining characteristic of living things. We humans usually assume that anything which can do this has some kind of (human-like) agency for making decisions. For a creature with only 302 neurons, this projection is stretched to breaking point. For a single-celled organism, it is broken completely. Still deliberate movement in response to stimulus is characteristic of all living things.

Of course, as I previously described, there are non-living systems that defy prediction, such as a double pendulum (as I mentioned in my essay on freewill). Still, the movements of a double pendulum seem random, like raindrops falling or leaves shivering in the wind. There is nothing purposeful about them and they do not make us think that an agent might be present. 

The words organic and organism come from an Indo-European root *werg-  'to do'. Cognate words include work, erg, and orgy. In Latin, an organum is a tool or implement. In ancient Greece, orgia were religious perform-ances; just as in India karma ("work" from √kṛ 'to do') originally meant a ritual action.
The distinction between an object and an organism in terms of how they operate under the influence of gravity, one bound inexorably to it and the other free to work against it, is very similar to our intuitive understanding of the distinction between non-living and living things in general. Movement that is obviously bound by rules external to the object, or which appears random, is indicative of non-living systems. Of course, the physicist will say that all movement is bound by the laws of physics and that even the apparently random double-pendulum follows a lawful path. But by "rules" here we refer to the rules that can be intuited by an uneducated human being unconsciously observing their environment. In terms of Justin Barrett's psychology of belief, these are non-reflective beliefs in that they typically emerge unconsciously as a result of interacting with our environment (see also Why Are Karma and Rebirth [Still] Plausible [for Many People]?).

In George Lakoff's terms, the cannonball (a lump of iron) is probably close to most people's prototype of the category of non-living objects. The bird is certainly not in this category and is more like a prototypical living being. The bird is not bound by gravity, but can (by creating a counteracting lift force) defy gravity. Culture plays a part here. Pāḷi texts talk about the gods of rain (deve vassantecausing rain to fall, suggesting that the authors might have believed weather to be the result of agentive behaviour. English people also commonly treat the weather as the result of a mildly malevolent agent. Folk beliefs almost always allow for disembodied agents. Justin Barrett places such imagined agents in the category of "minimally counter-intuitive concepts": those that conflict with our intuitive beliefs, but only minimally, and in such a way as to be interesting and memorable.

These observations give us some insight into what we think of as a living organism versus a non-living object. The individual parts of the organism appear to conform to our non-reflective beliefs about non-living things. We take the parts not to be alive because we don't observe any violation of the non-reflective beliefs about how non-living things behave. Take any one of the 20,000 proteins from C. elegans and, for all intents and purposes, it is non-living. Organic but not of itself an organism. The parts together are capable of complex interactions that routinely violate our non-reflective beliefs about how objects behave; the parts alone are not capable of this. The basic difference between the cannon ball and the bird is in the complexity of their behaviour and the extent to which they conform to category prototypes of non-living objects and living beings.

Categories are imposed on nature by human beings (Lakoff 1990). This imposition is not arbitrary since our experience of interacting with the world is fundamental to the construction of categories. But the basic categories with which we think are based on non-reflective beliefs generated by experience and conditioning. All human beings have more or less the same sensory and motor equipment to interact with the world, but some cultures emphasise difference aspects and interpretations. In other words, the distinction living beings and non-living objects is a perceptual one that exists in our minds on the basis of non-reflective beliefs about previous experience. Indeed, many cultures have a distinction between living and non-living categories that is permeable: some non-living objects (e.g. mountains for example) are attributed with living qualities, and thus can be placed in the living category. Or take an animated cartoon, for example, which can elicit emotional responses appropriate to interacting with another person! Other cultures take living things, people, for example, and allow them to be in the non-living category (e.g. zombies, or strangers). People who live in cities very often treat the strangers around them as people-shaped objects. They are just obstructions to be navigated around, not beings to be interacted with. Unintentional interactions are often met with hostility ("watch where you're going, idiot!"). The distinctions still apply and what allows these exceptions to arise is that the features attributed to them are counter-intuitive in just the right way to make them interesting and memorable (cf. Barrett 2004).

Systems are capable of such complex behaviour that they confound our ability to distinguish living from non-living. They easily overwhelm our criteria for categorising in the same way that an animation does, by presenting us with motion that is too complex for our non-reflective, experientially derived rules for describing the behaviour of objects. Computers, for example, are not intelligent, but they are complex enough that sometimes they don't seem to fit the non-living category or to partially fit the living category. We begin to suspect an agent at work, especially as our desires are thwarted.

Life is complex. A problem with understanding life is that we don't see the underlying complexity because it is microscopic. That vast complexity could exist, at several scales deeper than what we see (cells, molecules, atoms, particles, quarks...) is counter-intuitive. That a gram of carbon might contain a number like 1023 atoms is inconceivable. For example, it is vastly more than the number of hairs on our heads (ca 100,000); or people in the world (ca 7 billion); or the seconds in the average lifespan of a human being (only about 2.5 x 106); or the stars in our galaxy (ca 100 billion, though we can only see about 10,000 with the naked eye under ideal conditions) or even all these numbers added together. 1023  is more than all the stars in all the galaxies in the universe. For most of us cells, molecules, atoms etc are just something we have to take on faith. It is true, that their existence can be demonstrated, but we'll never know it from experience.

This animation (by David Bolinsky and team) gives a brilliant, but simplified, glimpse into cells from a particular point of view (response to inflammation). It is simplified mainly by making water molecules transparent - all that space you see is filled with water, salts, sugars, etc.

So life is complex but complex in ways that are non-experiential and more or less beyond imagination (the video shows a reality unlike anything ever imagined by a pre-modern society). The ordinary person bases their understanding of living things on their own non-reflective beliefs, derived from interactive experience and (cultural) imagination. Generalising from interactive experience is extremely unlikely to succeed in producing an accurate description of life except by unlikely accident. Nor does so-called "insight into reality" help us here. No account of insight, Buddhist or otherwise, ever gave us a hint that the body might be made of cells or anything like a Newtonian, let alone post-Newtonian, explanation of the world.

For example no one who insists that there is not a self or that the subject-object duality is an illusion is telling us anything at all about reality, the world, or living things. They are telling us (more) things about how generalising from our perceptions of these things results in erroneous conclusions. They explicitly want us to believe that they perceive the world not just differently, but more accurately, in a more satisfying matter. I would generously estimate that about 1% of 1% of religious practitioners gain access to this perspective (about 1 in 10,000). Not all of them are people I'd want to emulate. Some of them have some very peculiar ideas that can be traced to culturally specific theologies. A Vedantin and a Buddhist might well experience the same phenomena, say the cessation of specific aspects of selfhood, and yet each might tell us that it means different things. For one it is ātman, for the other it is anātman. So it is entirely apparent that even insight doesn't grant access to an absolute truth. If it did everyone that had that experience would express the same ideas about it, and we's have stopped arguing about it more than 2000 years ago. As yet scientists do not fully understand life either. We understand perhaps about 1%, but we currently understand life (as a process) better than any pre-modern culture ever did. No supernatural forces are required in this description. 

The arguments about features of living things, such as so-called "consciousness", suffer from exactly the same problems. Buddhists are working almost entirely from pre-modern models and generalising from individual experiential. They haven't a hope of understanding life, or consciousness, or any complex feature of life. Half the time Buddhists are just regurgitating some ancient ideology (something I trust less and less the more I find the ancients to have been confused or plain wrong in their thinking). But they may well come to some understanding of something, so what is that they do understand? It's this question that fascinates me, more than arguments over models and semantics. I only wish more Buddhists would deprecate the legacy jargon and ideology and just describe what they have experienced or at least the effect is has had on them in plain English. It would help us all to understand what is going on. 



Alberts B, Johnson A, Lewis J, et al. (2002) Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. http://www.ncbi.nlm.nih.gov/books/NBK26861/

Barrett, Justin L. (2004) Why Would Anyone Believe in God? Altamira Press.

Black, Lucy (2014) A Worm's Mind In A Lego Body. I Programmer. Sunday, 16 November 2014. http://www.i-programmer.info/news/105-artificial-intelligence/7985-a-worms-mind-in-a-lego-body.html

The C. elegans Sequencing Consortium (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282: 2012–2018. http://dx.doi.org/10.1126/science.282.5396.2012

Hillier LW, Coulson A, Murray JI, Bao Z, Sulston JE, and Waterston RH. (2005) Genomics in C. elegans: So many genes, such a little worm. Genomes Research. 2005. 15: 1651-1660 doi: 10.1101/gr.3729105

Lakoff, George. (1990). Women, Fire and Dangerous Things:  What Categories Reveal About the Mind. University of Chicago Press.

Stephens GJ,  Johnson-Kerner B, Bialek W, Ryu WS. (2008) Dimensionality and Dynamics in the Behavior of C. elegans. Computational Biology. April 25, 2008DOI: 10.1371/journal.pcbi.1000028

White JG, Southgate E, Thomson JN, Brenner S (1986) The structure of the nervous system of the nematode Caenorhabditis elegans. Phil Trans R Soc B 314: 1–340 (1986). http://dx.doi.org/10.1098/rstb.1986.0056
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