The Art of Genes How Organisms Make Themselves

Wait Disney cartoon version of The Sword in the Stone, the wizard Merlin has a duel of magic with a witch, Madam Mim. In the climax, the witch turns into an enormous purple dragon only to be defeated by Merlin turning into a tiny infectious germ that brings her down in a rash. Internal parasites, many of them unicellular organisms, pose a continual threat to multicellular life. Plants and animals are vulnerable to all sorts of infection and whole batteries of genes, such as those involved in the animal immune system or plant disease resistance, have evolved as a way of trying to combat this problem.

Another price paid by multicellular organisms is that they go through a vulnerable period as they develop. When a unicellular organism reproduces, its progeny can be pretty much ready straight away to survive in their environment. Multicellular organisms, however, typically need to spend extended periods as embryos developing from single cells before they get to the point that they can survive effectively as independent individuals. This has led to the evolution of various protective devices, such as surrounding the developing embryos with a hard shell or seed coat, or keeping them within the mother for as long as possible. In all these cases, new adaptations have evolved to protect the more vulnerable stages brought about by the requirements of development.

Yet another problem for multicellular life is that development itself is prone to go wrong. Development is a highly intricate process that can derail at any time. For example, cancer is caused by particular cells in the body dividing and proliferating in an uncontrolled way. In many cases this is because hidden colours, scents or sensitivities, which have a normal role to play in development, start to be active at inappropriate times or places. The very mechanisms that allow internal patterns to be elaborated become the cause of a disease when they go wrong. Unicellular individuals cannot die from cancer because there are no cells within them that can start to misbehave; the individual and the cell are one and the same.

Perhaps the most important sacrifice of all in adopting a multicellular life has to do with the length of time it takes to reproduce. One year for a dog is often compared to seven human years. If you were to make the same comparison with the bacterium E. coli, the figure would be more like a million human years. In one year, it is possible for certain bacteria to go through more generations than is covered by the span of human life on earth. This means that unicellular organisms can evolve much more rapidly in response to environmental conditions.

For all these reasons, unicellular organisms have not died out and been replaced by multicellular life. They are ever present and vastly outnumber everything else. You can find unicellular organisms everywhere, from hot acid springs to the depths of the ocean. These organisms are not inferior creatures, lower down on the scale of being, but highly successful in their own right. Multicellular and unicellular organisms are not different stages on the road to perfection, they simply represent different types of compromise, different ways of surviving and reproducing in an environment.

The history of internal painting is a story of putting old genes to new uses. We have seen how genes for hidden colours, scents and sensitivities allowed unicellular ancestors to change in time according to circumstance. As multi-cellular organisms evolved, these elements of painting were recruited to elaborate internal spatial patterns. New identities started to be specified as colours were interpreted in space as well as time. As this happened, the range of particular colours and sensitivities also expanded, allowing more elaborate patterns to be built up. Internal painting did not arise in a vacuum but through the modification of previous genes, allowing the same basic paintbox to be used in a whole variety of ways.

Chapter 18 The art of Heath Robinson

I have tried to show in this book how organisms are not simply manufactured according to a set of instructions. There is no easy way to separate instructions from the process of carrying them out, to distinguish plan from execution. Development is more like a creative process, in which each step interprets and elaborates what went before, than a process of fabrication. Nevertheless, an objection might still be raised to this viewpoint. Creativity seems somehow more subjective and difficult to pin down than fabrication. Although there may be many respects in which it is inadequate as a metaphor for development, at least fabrication has the merit of being there for everyone to see.

I now want to take a closer look at this issue. To do this, I will begin with the more traditional notion of development as a form of fabrication and try to establish where its logical foundations lie. We shall see that, contrary to what might have been expected, this view is actually on a weaker material footing than the alternative based on comparisons with creativity. Once this is appreciated, we will be able to look in a more coherent way at the fundamental relationships between different forms of making.

The dual analogy

Fabrication is not a self-contained process. To manufacture an object, somebody first has to come up with a plan for how to make it. For example, it took many years of technological innovation to come up with the detailed procedures and instructions for how cars should be made. These ideas and plans, essential for car production today, depend on a long history of human creativity and ingenuity. A similar thing may be said for all cases of fabrication, from the manufacture of washers to computers: they all depend on plans having first been created by humans. Fabrication, then, does not support itself; it is grounded in a form of human creativity.

Now if the development of an organism is a type of fabrication, a process of manufacture according to a plan, where does the plan come from in this case? The traditional answer is that it is a product of evolution. The ability of organisms to develop did not appear out of the blue, it arose gradually by natural selection over many millions of years. As with fabrication, biological development depends on a previous history, but a history of evolution rather than human ingenuity. The analogy between development and fabrication therefore leads to a second analogy: between evolution and human creativity. I shall refer to this double comparison as the dual analogy, summarised in Fig. 18.1.

Fig. 18.1 The dual analogy.

According to this view, the horizontal arrows in Fig. 18.1, which take us from creativity to fabrication (top arrow) or from evolution to development (bottom arrow), should represent parallel pathways. In other words, if there is an analogy between these various processes, then the same

should apply to the paths that connect them. To see whether this is indeed the case, I want to take a particular example of human creativity, the act of tinkering, and follow its course as compared to that of evolution.

Tinkering with the past

The anthropologist Claude Lévi-Strauss used the French equivalent of tinkering (bricolage) to describe how myths evolve. He contrasted the activity of a tinkerer to that of an engineer. Whereas an engineer carefully chooses his tools and raw materials to achieve the desired end, a tinkerer uses whatever is ready to hand. The tinkerer makes do with whatever happens to be in the work-shed to cobble various bits together:

Consider him at work and excited by his project. His first practical step is retrospective. He has to turn back to an already existent set made up of tools and materials, to consider or reconsider what it contains and, finally and above all, to engage in a sort of dialogue with it ... A particular cube of oak could be a wedge to make up for the inadequate length of a plank of pine or it could be a pedestal— which would allow the grain and polish of the old wood to show to advantage. In one case it will serve as extension, in the other as material. But the possibilities always remain limited by the particular history of each piece and by those of its features which are already determined by the use for which it was originally intended or the modifications it has undergone for other purposes.

There is a continual interaction, or dialogue, between the tinkerer and his materials, rather than the tinkerer following a clearly defined plan. As a consequence, the tinkerer is constrained by the collection of oddments, each of which may have had a previous use, rather than a set of tools and materials that have been carefully chosen with a particular outcome in mind. Lévi-Strauss used this example to point out how mythical thought is an intellectual form of 'bricolage'. Myths arise by tinkering with previous cultural elements, not by carefully planned design. François Jacob used the same imagery to describe biological evolution:

In contrast to the engineer, evolution does not produce innovations from scratch. It works on what already exists, either transforming a system to give it a new function or combining several systems to produce a more complex one. Natural selection has no analogy with any aspect of human behaviour. If one wanted to use a comparison, however, one would have to say that this process resembles not engineering but tinkering, bricolage as we say in French. While the engineer's work relies on his having the raw materials and the tools that exactly fit his project, the tinkerer manages with odds and ends. Often without even knowing what he is going to produce, he uses whatever he finds around him, old cardboard boxes, pieces of string, fragments of wood or metal, to make some kind of workable object. As pointed out by Claude Lévi-Strauss, none of the materials at the tinkerer's disposal has a precise and definite function. Each can be used in different ways.

Like tinkering, evolution is always constrained by what happens to be available. It builds on the past rather than making plans for the future. The history of internal painting, described in the previous chapter, illustrates this very well. Unicellular organisms did not evolve the elements of internal painting just so that they might be used some time later on to generate complex spatial patterns. They did not anticipate or plan their subsequent use. The later patterns arose by simply tinkering with elements that were previously on the table for other reasons. Hidden colours that

were originally an adaptation for one purpose (changing in time) were recruited to an additional use, the production of patterns in space. As multicellular organisms evolved, so the range and significance of hidden colours expanded by tinkering.

The notion of tinkering is perhaps best captured in the art of William Heath Robinson. Heath Robinson became famous for his illustrations of various contraptions; so much so that Heath Robinson or Heath Robinsonian has become a catch-phrase for complicated and ingenious devices. Look at his drawing of a Pancake Making Machine (Fig. 18.2). The contraption has obviously been cobbled together from various bits and pieces that happened to be around. Some irons and a coal scuttle are used as a weight, and a brick on a piece of string is used to control when the weight is released. It is an obvious case of tinkering, putting all sorts of available objects to a new use. The illustrations work so well because we are familiar with the previous use of many of the objects and enjoy seeing them used in an unexpected way. Irons are normally used for pressing clothes and a coal scuttle for moving coal, not for tossing a pancake in the air.

Fig. 18.2 Pancake Making Machine (1933), Heath Robinson.

If tinkering, as a creative process, provides a good analogy for evolution, where might fabrication and development fit in? At each stage in the creation of a Heath Robinson machine, the contraption changes in some way, with some part added, rearranged or removed. Every stage therefore looks different from the next, not needing the steps to have been planned in advance. But once you have a particular Heath Robinson contraption and want to make many copies of it consistently, the best way would be to write a set of instructions on how to make it. By following the instructions we can manufacture exactly the same contraption every time. We can churn out or fabricate as many copies of the Pancake Making Machine as we want. Perhaps this, then, corresponds to the process of development. According to this view, the transformation of an egg into an adult is like following a set of instructions to manufacture the same contraption every time.

In the case of the egg, the instructions are not written down in words but in the DNA text, as genes. Evolution proceeds by creative tinkering but development is a question of consistent manufacture once evolution has produced the contraption to begin with. We have arrived back at the dual analogy: evolution as creativity, development as fabrication.

To my mind, there is a flaw in this reasoning. We have skipped too rapidly along the horizontal arrows of the dual analogy and have therefore missed out some problematic steps. The problems we jumped over trace back to Darwin's own account of evolution, and there is perhaps no better way of revealing them than by looking at how Darwin was himself misled.

A new twist on orchids

Shortly after completing his work On the Origin of Species in 1859, Charles Darwin chose to illustrate many of his ideas with orchids. In 1862, he published a volume On the Various Contrivances by which British and Foreign Orchids are Fertilised by Insects in which he described how different types of orchid flower could be understood as a series of modifications of previous types. Towards the end of the book he summarised:

Although an organ may not have been originally formed for some special purpose, if it now serves for this end, we are justified in saying that it is specially adapted for it. On the same principle, if a man were to make a machine for some special purpose, but were to use old wheels, springs and pulleys, only slightly altered, the whole machine, with all its parts, might be said to be specially contrived for its present purpose. Thus throughout nature almost every part of each living being has probably served, in a slightly modified condition, for diverse purposes, and has acted in the living machinery of many ancient and distinct specific forms.

In other words, adaptations were not invented from scratch. They evolved by tinkering, modifying what went before, just as a man might make a new machine by slightly altering some old wheels and springs that were already around. Darwin illustrated the point with many different examples taken from orchids, ranging from the way pollen is released to the overall arrangement and structure of organs in the flower. I want to highlight just one example, to show how Darwin's conception of tinkering compares to our present viewpoint.

The flowers of some orchid species, such as Malaxis paludosa (bog orchid, also known as Hammarbya paludosa) undergo a change during development that seems to be completely pointless: they twist themselves round in a full circle. To make this clearer, think of an upright main stem, with a flower at the end of a stalk coming out to the side. Now imagine twisting the flower stalk, gradually rotating the flower so that it turns upside-down, and then continuing to twist in the same direction until the flower is upright again, a turn of 360°. You end up by getting the flower back to where it started from, except that it now has a twist in its stalk. This is essentially what happens in some species of orchid to all of their flowers; they all do a little pirouette. You can see the evidence in the mature flowers by looking at their twisted stalks (Fig. 18.3).

Fig. 18.3 The orchid Malaxis paludosa showing a flower with the labellum at the top after it has twisted around by 360°. Note the twist in the flower stalk (modified from Darwin 1862).

What appears to be pointless at first sight becomes a bit more comprehensible when you know another fact about orchids: the flowers of most species are upside-down! Each orchid flower has three petals, one of which is distinctively elaborated to form a lip or labellum. In the great majority of orchids, the labellum is lowermost and typically acts as a landing platform for pollinators (Fig. 18.4). However, although the labellum is at the bottom of the mature flower, it is uppermost earlier on in the flower-bud. As the flower-bud develops, it goes through a half turn, a 180°twist, so that the labellum eventually comes to lie towards the bottom even though it started at the top (the twist normally occurs in the flower stalk, which also includes the ovary).

Fig. 18.4 Generalised orchid showing the labellum in the typical lower position.

This inverted arrangement, called the resupinate position, is so common in orchids that it is thought to have been a feature of their ancestors. According to this view, the few exceptional orchid species (e.g. M. paludosa) with the labellum uppermost could have evolved later on by counteracting the inversion in some way. There are several ways to turn an upside-down flower the right way up again. One is for the bud not to twist at all but to stay in the same position throughout development. This appears to be the case in a few orchid species. Another way, as noted by Darwin for M. paludosa, is by continuing to twist beyond 180°until the flower comes back to having its labellum at the top, a full turn. In Darwin's words:

in many Orchids the ovarium (but sometimes the foot-stalk) becomes for a period twisted, causing the labellum to assume the position of a lower petal, so that insects can easily visit the

flower; but from slow changes in the form or position of the petals, or from new sorts of insects visiting the flowers, it might be advantageous to the plant that the labellum should resume its normal position on the upper side of the flower, as is actually the case with Malaxis paludosa, and some species of Catasetum, &c. This change, it is obvious, might be simply effected by the continued selection of varieties which had their ovaria less and less twisted; but if the plant only afforded varieties with the ovarium more twisted, the same end could be attained by the selection of such variations, until the flower was turned completely round on its axis. This seems to have actually occurred with Malaxis paludosa, for the labellum has acquired its present upward position by the ovarium being twisted twice as much as is usual.

If orchids were designed according to some plan, the full turn of M. paludosa makes no sense. In Darwin's view, though, adaptations were not carefully planned from scratch; they arose by continual tinkering with what was there before. Should it become advantageous for an orchid flower to have its labellum uppermost, natural selection would act on what was already available. It would modify the inverted flower to restore the upright condition in one of two ways: either by reducing the extent of twisting or by increasing the twist until the flower is the right way round again. When seen in the light of evolutionary tinkering, as a modification of what went before, the 360°turn becomes much more understandable.

There is, however, an important way in which Darwin's conception of this sort of tinkering was misleading. To appreciate this, I need to explain Darwin's views on heredity. I will then come back to his notion of how the orchid got its twist.

Darwin's hypothesis of pangenesis

As mentioned in Chapter 13, Darwin's ideas on inheritance were very different from our present day outlook based on genes. For one thing, he believed that characters acquired during the lifetime of an individual could be inherited. If, for example, you had an accident as a child and lost your thumb, then according to this notion, as a result of this accident your own children would have a greater chance of being born without a thumb. At first sight it may come as a surprise that Darwin would have believed in such an idea, as we normally associate it with his predecessor, Jean Baptiste Lamarck. Lamarck, though, not only believed in the inheritance of acquired characters, he also thought that the variation in these characters was directed according to the organism's needs. If a deer-like animal, for example, found its surroundings bare of vegetation, it might need to stretch its neck to reach the leaves higher up. Over many generations, the neck would gradually be extended more and more to satisfy this need, accounting for the evolution of giraffes. Unlike Lamarck, Darwin believed that the acquired characters were essentially random with respect to adaptation. He did not think that adaptive or beneficial variations arose preferentially over non-adaptive ones. The vagaries of the environment were simply a source of heritable variation that was then acted upon by natural selection.

But what sort of mechanism would allow characters acquired during the lifetime of an individual to be passed on to its offspring? Darwin reasoned that there had to be some way for the sex cells to monitor the state of the whole body. Otherwise, it is difficult to see how the accidental loss of a thumb, say, would be able to influence the reproductive system. Somehow, hereditary information from the maturing body tissues had to travel to the egg or sperm cells. Darwin's provisional solution to how this might occur was his hypothesis of pangenesis.

According to pangenesis, as the cells of the body divide and grow, they continually throw off minute granules or gemmules, which are dispersed throughout the individual. As the organism reaches the reproductive age, gemmules from all parts of the body are collected within the sex cells. By this means they can be passed on to the next generation. The essential property of Darwin's gemmules sounds rather peculiar to us now: they tend to reproduce the structures from which they were derived. That is, the gemmules throw n off by eye cells will be those involved in making eyes in the next generation; while gemmules produced by ear cells will be of a different type, those needed to make ears. That is why gemmules from all over the body need to be collected together in the sex cells if a complete organism is to be produced in the next generation. Failure to collect the eye gemmules, for instance, would lead to offspring without eyes (strictly speaking this would have to happen in both parents for complete eye loss, as both contribute the gemmules). The corollary is that if, for example, an animal were to lose its eyes through injury, then eye-making gemmules would cease to be thrown off. Fewer of these gemmules would then be collected in the sex cells, leading to a tendency for the eyeless feature to be transmitted to its offspring. The loss of eyes or thumbs are rather extreme examples of environmental accidents; most of the acquired variations that Darwin had in mind as being important for evolution were much more subtle than this. As organisms developed, each would experience slight differences in their environment that would lead to minor changes to their gemmules, and so to small heritable changes:

organisms have often been subjected to changed conditions of life at a certain stage of their development, and in consequence have been slightly modified; and the gemmules cast off from such modified parts will tend to reproduce parts modified in the same manner.

He was aware, however, of some striking exceptions that seemed to argue against his idea of pangenesis. For example, the circumcision of Jewish boys did not result in their sons inheriting the modification; although even here Darwin expressed some doubts:

With respect to Jews, I have been assured by three medic al men of the Jewish faith that circumcision, which has been practised for so many ages, has produced no inherited effect. Blumenbach, however, asserts that Jews are often born in Germany in a condition rendering circumcision difficult, so that a name is given them signifying 'born circumcised' ... But it is possible that all these cases may be accidental coincidences, for Sir J. Paget has seen five sons of a lady and one son of her sister with adherent prepuces; and one of these boys was affected in a manner 'which might be considered like that commonly produced by circumcision;' yet there was no suspicion of Jewish blood in the family of these two sisters.

How could his theory account for an operation repeated over many generations having at best only sporadic effects on the offspring? It was no good postulating that the mother provided the foreskin gemmules because she would not have had a foreskin to cast them off. Darwin's answer was that the gemmules are not only thrown off by parts of the body, they also have an innate ability to divide and multiply themselves. This means that removal of the foreskin need not completely eliminate foreskin gemmules because there might still be lots of them kicking around from earlier generations, when circumcision had not been practised. In such cases, it might take many generations to significantly alter the course of inheritance.

Back to orchids

The reason that Darwin's conception of heredity is so important to us here is that it had a profound effect on his notion of evolutionary tinkering. If acquired characters can be inherited, then evolutionary change can result from direct tinkering with the organism. The modifications you see over an evolutionary timescale can be built up from physical rearrangements of the adult parts themselves. In the case of orchids, for example, if the flower happened to twist a bit more or a bit less for some environmental reason, the seed from that flower might be expected to give plants that also showed the altered twist. In other words, new degrees of twisting acquired during the lifetime of a plant might be transmitted to its progeny. A final twist of 360ºwould result from an accumulation of twists brought about by the environment. Each extra little twist in the flower would have been acquired during the lifetime of one or more plants, and then been subject to natural selection. It is as if all the tinkering could happen at the level of the flower itself. I have given the twist of the orchid flower to illustrate this point but the same principle would apply to all other evolutionary changes: if acquired characters are inherited, all features can be thought to have evolved through direct tinkering with the organism.

We now know that this is not the way inheritance works. Achange in the developed parts of an organism will not of itself be transmitted to its progeny. This is because it is variation in the genetic material, DNA, rather than in the structure of the final organism, that is passed on from one generation to another. A novel character can be inherited only in so far as it results from a mutation in DNA, because it is only variation in DNA that gets replicated each generation. This means that evolutionary tinkering cannot be understood simply by considering the final organism: we have to look at the relationship between genes (DNA) and the way the organism grows and develops. I shall try to illustrate this by taking another look at the orchid's twist. I should warn you in advance, though, that the genes involved in orchid evolution are very far from being understood (orchids have a long generation time and are avoided by most geneticists like the plague), so I shall only be able to show the sort of explanation that might now be given. Before doing this, I need to give a little more background on how orchids twist.

The twisting and turning that leads to most orchid flowers adopting an inverted (resupinate) condition, with the labellum lowermost, is thought to be a response to gravity. If, for example, you turn an orchid plant upside-down so that its main stem points downwards, the flowers that develop will fail to twist: they retain the same orientation as when they were in bud. In other words, whichever way up the plant is, the flowers always develop oriented with the labellum at the bottom. If the plant is upright, the flower has to twist by 180ºto achieve this; but if the plant is upside-down the labellum will already be in the lower position to begin with, so no twist is needed. The twisting of the flower therefore seems to reflect a mechanism that orients the flower in a consistent way with respect to gravity.

This sort of orienting response is found in many other plant species. It is just that the final orientation in most species is similar to the orientation in the bud. For example, members of the pea family (legumes), such as lupins, beans and peas, have flowers with an enlarged petal called the standard (Fig. 18.5). Like the labellum of orchids, the standard starts off uppermost in the bud, but unlike the labellum, this orientation is maintained through to maturity. Nevertheless, if a stem of a pea plant is bent or happens to be tilted, the flowers it produces will still be oriented with the standard upwards; flowers of the pea family still adjust their orientation with respect to gravity. This makes adaptive sense because it ensures that the flower is suitably oriented for visits by pollinators, even when the stem bearing the flowers happens not to be growing straight up. A

dramatic illustration of this si given by laburnum, a member of the pea family that bears its flowers on drooping (pendant) stems. Even though the flowering stem now points downwards, the flowers of laburnum resupinate— they twist through 180º, restoring the standard to the uppermost position (Fig. 18.5). Laburnums and orchids are almost inverted images of each other: laburnum flowers twist so as to keep the standard uppermost, whereas orchids twist so as to keep the labellum lowermost. For a stem growing upwards, this means that orchid flowers need to twist, but for a stem growing downwards, it is flowers of the pea family that need to twist. If most plant stems grew pointing down, as eventually happens in species with pendant stems, orchids would seem perfectly natural and untwisted, whereas members of the pea family would look peculiar in always twisting to readjust the standard to be uppermost. Incidentally, this suggests one explanation (amongst others) for why most orchids twist by 180º: perhaps the common ancestor of orchids had pendant stems and therefore evolved an orienting response while the flowers were upside-down. Later on, when orchid species evolved with upright stems, the orienting response ensured that the flowers would twist to maintain their original orientation.

Fig. 18.5 Flowers of lupin (upright stem on left) compared to laburnum (pendant stem on right). Note that in both cases the mature flowers have the same orientation, with the standard uppermost.

The precise mechanism responsible for the orientation response of flowers is not known. Nevertheless, by analogy with previous examples in this book, we can imagine how genes might be involved. Perhaps orientation response genes code for some sort of receptor protein in the cells of the flower that can respond to gravity. When the flower is oriented 'incorrectly', some receptors are stimulated, setting off a chain of events that lead to parts of the flower stall growing more than others, giving it a twist. When the flower reaches the 'correct' orientation (i.e. labellum lowermost for most orchids), the receptors are no longer stimulated in this way and the flower stops twisting any further. Of course, I am not pretending that this explanation is at all satisfactory: it begs a lot of questions, like how a receptor can detect the direction of gravity. I only present it because if you want to understand how a twist might have evolved, you need to have some idea of how genes could contribute to it.

We can now look again at the evolution of the 360ºtwist in orchids such as M. paludosa. The extra twist cannot be explained simply by tinkering with the final flower; we have to tinker with the genes involved in the orientation process. Perhaps the simplest model is that the same mechanism that normally turns the flower through 180ºis somehow reactivated once the flower is