The Greatest Show on Earth (21 page)

ANALOGIES FOR DEVELOPMENT

It is surprisingly hard to find a good analogy for the development of living tissue, but you can find partial similarities to particular aspects of the process. A recipe captures something of the truth, and it is an analogy that I sometimes use, to explain why ‘blueprint’ is not appropriate. Unlike a blueprint, a recipe is irreversible. If you follow a cake recipe step by step, you’ll end up with a cake. But you can’t take a cake and reconstruct the recipe – certainly not the exact words of the recipe – whereas, as we have seen, you could take a house and reconstruct something close to the original blueprint. This is because of the one-to-one mapping between bits of house and bits of blueprint. With conspicuous exceptions such as the cherry on top, there is no one-to-one mapping between bits of cake and the words, say, or sentences of its recipe.
What other analogies to human manufacturing might there be? Sculpture is mostly way off the mark. A sculptor starts with a chunk of stone or wood and fashions it by subtraction, chipping away until the desired shape is all that remains. There is, admittedly, a somewhat sharp resemblance to one particular process in embryology called apoptosis. Apoptosis is programmed cell death, and it is involved, for example, in the development of fingers and toes. In the human embryo, the fingers and toes are all joined. In the womb, you and I had webbed feet and hands. The webbing disappeared (in most people: there are occasional exceptions) through programmed cell death. That is a bit reminiscent of the way a sculptor carves out a shape, but it is not common enough or important enough to capture how embryology normally works. Embryologists may briefly think ‘sculptor’s chisel’, but they don’t let the thought linger for long.
Some sculptors work not by subtractive carving but by taking a lump of clay, or soft wax, and kneading it into shape (which may subsequently be cast, in bronze for example). That again is not a good analogy for embryology. Nor is the craft of tailoring or dressmaking. Pre-existing cloth is cut, to shapes set out in a pre-planned pattern, then sewn together with other cut-out shapes. They are often then turned inside out to disguise the seams – and that bit, at least, is a good analogy to certain parts of embryology. But in general, embryology is no more like tailoring than it is like sculpture. Knitting might be better, in that the whole shape of a sweater, say, is built up from numerous individual stitches, like individual cells. But there are better analogies, as we shall see.
How about the assembly of a car, or other complicated machine, on a factory assembly line: is that a good analogy? Like sculpture and tailoring, assembly of pre-fabricated parts is an efficient way to make something. In a car factory, parts are pre-made, often by casting in moulds in a foundry (and there is, I think, nothing remotely like casting in embryology). Then the pre-made parts are brought together on an assembly line and screwed, riveted, welded or glued together, step by step according to a precisely drawn plan. Once again, embryology has nothing resembling a previously drawn plan. But there are resemblances to the ordered sticking together of pre-assembled parts, as when, in a car assembly plant, previously manufactured carburettors and distributor heads and fan belts and cylinder heads are brought together and joined in correct apposition.
Below are three kinds of virus. On the left is the tobacco mosaic virus (TMV), which parasitizes tobacco plants and other members of the family Solanaceae, such as tomatoes. In the middle is an adenovirus, which infects the respiratory system in many animals, including us. On the right is the T4 bacteriophage, which parasitizes bacteria. It looks like a lunar lander, and it behaves rather like one, ‘landing’ on the surface of a bacterium (which is very much larger) then lowering itself on its spidery ‘legs’, then thrusting a probe down the middle, through the bacterium’s cell wall, and injecting its DNA inside. The viral DNA then hijacks the protein-making machinery of the bacterium, which is subverted into making new viruses. The other two viruses in the picture do something similar, although they don’t look or behave like lunar landers. In all cases their genetic material hijacks the protein-making apparatus of the host cell and diverts its molecular production line to churning out viruses instead of its normal products.

Three kinds of virus

Most of what you see in the pictures is the protein container for the genetic material, and in (‘lunar lander’) T4’s case the machinery for infecting the host. What is interesting is the way in which this protein apparatus is put together. It really is self-assembled. Each virus is assembled from several previously made protein molecules. Each protein molecule, in a way that we shall see, has previously self-assembled into a characteristic ‘tertiary structure’ under the laws of chemistry given its particular sequence of amino acids. And then, in the virus, the protein molecules join up with each other to form a so-called ‘quaternary structure’, again by following local rules. There is no global plan, no blueprint.
The protein sub-units, which link up like Lego bricks to form the quaternary structure, are called capsomeres. Notice how geometrically perfect these little constructions are. The adenovirus in the middle has exactly 252 capsomeres, drawn here as little balls, arranged in an icosahedron. The icosahedron is that Platonic perfect solid that has 20 triangular faces. The capsomeres are arranged into an icosahedron not by any kind of master plan or blueprint but simply by each one of them obeying the laws of chemical attraction locally when it bumps into others like itself. This is how crystals are formed, and, indeed, the adenovirus could be described as a very small hollow crystal. The ‘crystallization’ of viruses is an especially beautiful example of the ‘self-assembly’ that I am touting as a major principle by which living creatures are put together. The T4 ‘lunar lander’ phage also has an icosahedron for its main DNA receptacle, but its self-assembled quaternary structure is more complex, incorporating additional protein units, assembled according to different local rules, in the injection apparatus and the ‘legs’ that are attached to the icosahedron.
Returning from viruses to the embryology of larger creatures, I come to my favourite analogy among human construction techniques: origami. Origami is the art of constructive paper-folding, developed to its most advanced level in Japan. The only origami creation I know how to make is the ‘Chinese Junk’. I was taught it by my father, who learned it in a craze that swept through his boarding school during the 1920s.* One biologically realistic feature is that the ‘embryology’ of the Chinese junk passes through several intermediate ‘larval’ stages, which are in themselves pleasing creations, just as a caterpillar is a beautiful, working intermediate on the way to a butterfly, which it scarcely resembles at all. Starting with a simple square piece of paper, and simply folding it – never cutting it, never glueing it and never importing any other pieces – the procedure takes us through three recognizable ‘larval stages’: a ‘catamaran’, a ‘box with two lids’ and a ‘picture in a frame’, before culminating in the ‘adult’ Chinese junk itself. In favour of the origami analogy, when you first are taught how to make a Chinese junk, not only the junk itself but each of the three ‘larval’ stages – catamaran, cupboard, picture frame – comes as a surprise. Your hands may do the folding, but you are emphatically not following a blueprint for a Chinese junk, or for any of the larval stages. You are following a set of folding rules that seem to have no connection with the end product, until it finally emerges like a butterfly from its chrysalis. So the origami analogy captures something of the importance of ‘local rules’ as opposed to a global plan.
Also in favour of the origami analogy, folding, invagination and turning inside out are some of the favourite tricks used by embryonic tissues when making a body. The analogy works especially well for the early embryonic stages. But it has its shortcomings, and here are two obvious ones. First, human hands are needed to do the folding. Second, the developing paper ‘embryo’ doesn’t grow larger. It ends up weighing exactly as much as when it started. To acknowledge the difference, I shall sometimes refer to biological embryology as ‘inflating origami’, rather than just ‘origami’.

Chinese junk by origami, with three ‘larval stages’: ‘catamaran’, ‘box with two lids’ and ‘picture in a frame’

Actually, these two shortcomings kind of cancel each other out. The sheets of tissue that fold, invaginate and turn inside out in a developing embryo do indeed grow, and it is that very growth that provides part of the motive force which, in origami, is supplied by the human hand. If you wanted to make an origami model with a sheet of living tissue instead of dead paper, there is at least a sporting chance that, if the sheet were to grow in just the right way, not uniformly but faster in some parts of the sheet than in others, this might automatically cause the sheet to assume a certain shape – and even fold or invaginate or turn inside out in a certain way – without the need for hands to do the stretching and folding, and without the need for any global plan, but only local rules. And actually it’s more than just a sporting chance, because it really happens. Let’s call it ‘auto-origami’. How does auto-origami work in practice, in embryology? It works because what happens in the real embryo, when a sheet of tissue grows, is that cells divide. And differential growth of the different parts of the sheet of tissue is achieved by the cells, in each part of the sheet, dividing at a rate determined by local rules. So, by a roundabout route, we return to the fundamental importance of bottom-up local rules as opposed to top-down global rules. It is a whole series of (far more complicated) versions of this simple principle that actually go on in the early stages of embryonic development.
Here’s how the origami goes in the early stages of vertebrate development. The single fertilized egg cell divides to make two cells. Then the two divide to make four. And so on, with the number of cells rapidly doubling and redoubling. At this stage there is no growth, no inflation. The original volume of the fertilized egg is literally divided, as in slicing a cake, and we end up with a spherical ball of cells which is the same size as the original egg. It’s not a solid ball but a hollow one, and it is called the blastula. The next stage, gastrulation, is the subject of a famous bon mot by Lewis Wolpert: ‘It is not birth, marriage, or death, but gastrulation, which is truly the most important time in your life.’
Gastrulation is a kind of microcosmic earthquake which sweeps over the blastula’s surface and revolutionizes its entire form. The tissues of the embryo become massively reorganized. Gastrulation typically involves a denting of the hollow ball that is the blastula, so that it becomes two-layered with an opening to the outside world (see the computer simulation on p. 231). The outer layer of this ‘gastrula’ is called the ectoderm, the inner layer is the endoderm, and there are also some cells thrown into the space between the ectoderm and endoderm, which are called mesoderm. Each of these three primordial layers is destined to make major parts of the body. For example, the outer skin and nervous system come from the ectoderm; the guts and other internal organs come from the endoderm; and the mesoderm furnishes muscle and bone.

Neurulation

The next stage in the embryo’s origami is called neurulation. The diagram on the right shows a cross-section through the middle of the back of a neurulating amphibian embryo (it could be either a frog or a salamander). The black circle is the ‘notochord’, a stiffening rod that acts as a precursor of the backbone. The notochord is diagnostic of the phylum Chordata, to which we and all vertebrates belong (although we, like most modern vertebrates, have it only when we are embryos). In neurulation, as in gastrulation, invagination is much in evidence. You remember I said that the nervous system comes from ectoderm. Well, here’s how. A section of ectoderm invaginates (progressively backwards along the body like a zip fastener), rolls itself up into a tube, and is pinched off where the sides of the tube ‘zip up’ so that it ends up running the length of the body between the outer layer and the notochord. That tube is destined to become the spinal cord, the main nerve trunk of the body. The front end of it swells up and becomes the brain. And all the rest of the nerves are derived, by subsequent cell divisions, from this primordial tube.*
I don’t want to get into the details of either gastrulation or neurulation, except to say that they are wonderful, and that the metaphor of origami holds up pretty well for both of them. I am concerned with the general principles by which embryos become more complicated through inflating origami. Below is one of the things that sheets of cells are observed to do during the course of embryonic development, for example during gastrulation. You can easily see how this invagination could be a useful move in inflating origami, and it does indeed play a major role in both gastrulation and neurulation.

Invagination in a sheet of cells

Gastrulation and neurulation are accomplished early in development and they affect the whole shape of the embryo. Invagination and other ‘inflating origami’ manœuvres achieve these stages of early embryology, and they and similar tricks are involved later in development, when specialized organs like eyes and the heart are made. But, given that there are no hands to do the folding, by what mechanical process are these dynamic movements achieved? Partly, as I have already said, by simple expansion itself. Cells multiply all through a sheet of tissue. Its area therefore increases and, having nowhere else to go, it has little choice but to buckle or invaginate. But the process is more controlled than that, and it has been deciphered by a group of scientists associated with the brilliant mathematical biologist George Oster, of the University of California at Berkeley.

MODELLING CELLS LIKE STARLINGS

Oster and his colleagues followed the same strategy we considered earlier in this chapter for a computer simulation of starlings flocking. Instead of programming the behaviour of a whole blastula, they programmed a single cell. Then they ‘cloned up’ lots of cells, all the same, and watched to see what happened when those cells got together in the computer. When I say they programmed the behaviour of a single cell, it would be better to say they programmed a mathematical model of a single cell, building into the model certain known facts about a single cell, but in simplified form. Specifically, it is known that the interiors of cells are criss-crossed by microfilaments: sort of miniature elastic bands, but with the additional property that they are capable of active contraction, like twitching muscle fibres. Indeed, the microfilaments use the same principle of contraction as muscle fibres.* The Oster model simplified the cell down to two dimensions for drawing on a computer screen, and with only half a dozen filaments, strategically placed in the cell, as you see in the diagram above. In the computer model, all the microfilaments were given certain quantitative properties with names that mean something to physicists: a ‘viscous damping coefficient’ and an ‘elastic spring constant’. Never mind exactly what these mean: they are the kinds of things physicists like to measure in a spring. Although it is probable that in a real cell many filaments would be capable of contraction, Oster and his colleagues simplified matters by endowing only one of their six filaments with this capacity. If they could get realistic results even after throwing away some of the known properties of a cell, it would presumably be possible to get at least as good results with a more complicated model that kept those properties in. Rather than allowing the one contractile filament in their model to contract at will, they built into it a property which is common in certain kinds of muscle fibre: when stretched beyond a certain critical length, the fibre would respond by contracting to a much shorter length than the normal equilibrium length.