The Blind Watchmaker (23 page)

What does ‘better’ mean? Ultimately it means more efficient at selfreplication, but what might this mean in practice? This brings us to our third ‘ingredient’. I referred to this as ‘power’, and you’ll see why in a moment. When we discussed replication as a moulding process, we saw that the last step in the process must be the new copy’s breaking free of the old mould. The time that this occupies may be influenced by a property which I shall call the ‘stickiness’ of the old mould. Suppose that in our population of replicators, which vary because of old copying errors back in their ‘ancestry’, some varieties happen to be more sticky than others. A very sticky variety clings to each new copy for an average time of more than an hour before it finally breaks free and the process can begin again. A less-sticky variety lets go of each new copy within a split second of its formation. Which of these two varieties will come to predominate in the population of replicators? There is no doubt about the answer. If this is the only property by which the two varieties differ, the sticky one is bound to become far less numerous in the population. The non-sticky one is churning out copies of non-sticky ones at thousands of times the rate that the sticky one is making copies of sticky ones. Varieties of intermediate stickiness will have intermediate rates of selfpropagation. There will be an ‘evolutionary trend’ towards reduced stickiness.

Something like this kind of elementary natural selection has been duplicated in the testtube. There is a virus called Q-beta which lives as a parasite of the gut bacterium
Escherichia coli
. Q-beta has no DNA but it does contain, indeed it largely consists of, a single strand of the related molecule RNA. RNA is capable of being replicated in a similar way to DNA.

In the normal cell, protein molecules are assembled to the specification of RNA plans. These are working copies of plans, run off from the DNA masters held in the cell’s precious archives. But it is theoretically possible to build a special machine - a protein molecule like the rest of the cellular machines - that runs off RNA copies from other RNA copies. Such a machine is called an RNAreplicase molecule. The bacterial cell itself normally has no use for these machines, and doesn’t build any. But since the replicase is just a protein molecule like any other, the versatile protein-building machines of the bacterial cell can easily turn to building them, just as the machine tools in a car factory can quickly be turned over in time of war to making munitions: all they need is to be fed the right blueprints. This is where the virus comes in.

The business part of the virus is an RNA plan. Superficially .it is indistinguishable from any of the other RNA working blueprints that are floating around, after being run off the bacterium’s DNA master. But if you read the small print of the viral RNA you will find something devilish written there. The letters spell out a plan for making RNAreplicase: for making machines that make more copies of the very same RNA plans, that make more machines that make more copies of the plans, that make more …

So the factory is hijacked by these self-interested blueprints. In a sense it was crying out to be hijacked. If you fill your factory with machines so sophisticated that they can make anything that any blueprint tells them to make, it is hardly surprising if sooner or later a blueprint arises that tells these machines to make copies of itself. The factory fills up with more and more of these rogue machines, each churning out rogue blueprints for making more machines that will make more of themselves. Finally, the unfortunate bacterium bursts and releases millions of viruses that infect new bacteria. So much for the normal life cycle of the virus in nature.

I have called RNAreplicase and RNA respectively a machine and a blueprint. So they are, in a sense (to be disputed on other grounds in a later chapter), but they are also molecules, and it is possible for human chemists to purify them, bottle them and store them on a shelf. This is what Sol Spiegelman and his colleagues did in America in the 1960s. Then they put the two molecules together in solution, and a fascinating thing happened. In the testtube, the RNA molecules acted as templates for the synthesis of copies of themselves, aided by the presence of the RNAreplicase. The machine tools and the blueprints had been extracted and put into cold storage, separately from one another. Then, as soon as they were given access to each other, and also to the small molecules needed as raw materials, in water, both got back to their old tricks even though they were no longer in a living cell but in a test tube.

It is but a short step from this to natural selection and evolution in the laboratory. It is just a chemical version of the computer biomorphs. The experimental method is basically to lay out a long row of testtubes each containing a solution of RNAreplicase, and also of raw materials, small molecules that can be used for RNA synthesis. Each testtube contains the machine tools and the raw material, but so far it is sitting idle, doing nothing because it lacks a blueprint to work from. Now a tiny amount of RNA itself is dropped into the first testtube. The replicase apparatus immediately gets to work and manufactures lots of copies of the newly introduced RNA molecules, which spread through the testtube. Now a drop of the solution in the first testtube is removed and put into the second testtube. The process repeats itself in the second testtube and then a drop is removed and used to seed the third testtube, and so on.

Occasionally, because of random copying errors, a slightly different, mutant RNA molecule spontaneously arises. If, for any reason, the new variety is competitively superior to the old one, superior in the sense that, perhaps because of its low ‘stickiness’, it gets itself replicated faster or otherwise more effectively, the new variety will obviously spread through the testtube in which it arose, outnumbering the parental type that gave rise to it. Then, when a drop of solution is removed from that testtube to seed the next testtube, it will be the new mutant variety that does the seeding. If we examine the RNAs in a long succession of testtubes, we see what can only be called evolutionary change. Competitively superior varieties of RNA produced at the end of several testtube ‘generations’ can be bottled and named for future use. One variety for example, called V2, replicates much more rapidly than normal Q-beta RNA, probably because it is smaller. Unlike Q-beta RNA, it doesn’t have to ‘bother’ to contain the plans for making replicase. Replicase is provided free by the experimenters. V2 RNA was used as the starting point for an interesting experiment by Leslie Orgel and his colleagues in California, in which they imposed a ‘difficult’ environment.

They added to their testtubes a poison called ethidium bromide which inhibits the synthesis of RNA: it gums up the works of the machine tools. Orgel and colleagues began with a weak solution of the poison. At first, the rate of synthesis was slowed down by the poison, but after evolving through about nine testtube transfer ‘generations’, a new strain of RNA that was resistant to the poison had been selected. Rate of RNA synthesis was now comparable to that of normal V2 RNA in the absence of poison. Now Orgel and his colleagues doubled the concentration of poison. Again the rate of RNA replication dropped, but after another 10 or so testtube transfers a strain of RNA had evolved that was immune even to the higher concentration of poison. Then the concentration of the poison was doubled again. In this way, by successive doublings, they managed to evolve a strain of RNA that could self-replicate in very high concentrations of ethidium bromide, 10 times as concentrated as the poison that had inhibited the original ancestral V2 RNA. They called the new, resistant RNA V40. The evolution of V40 from V2 took about 100 testtube transfer ‘generations’ (of course, many actual RNAreplication generations go on between each testtube transfer).

Orgel has also done experiments in which no enzyme was provided. He found that RNA molecules can replicate themselves spontaneously under these conditions, albeit very slowly. They seem to need some other catalyzing substance, such as zinc. This is important because, in the early days of life when. replicators first arose, we cannot suppose that there were enzymes around to help them to replicate. There probably was zinc, though.

The complementary experiment was carried out a decade ago in the laboratory of the influential German school working on the origin of life under Manfred Eigen. These workers provided replicase and RNA building blocks in the testtube, but they did
not
seed the solution with RNA. Nevertheless, a particular large RNA molecule evolved
spontaneously in
the testtube, and the same molecule re-evolved itself again and again in subsequent independent experiments! Careful checking showed that there was no possibility of chance infection by RNA molecules. This is a remarkable result when you consider the statistical improbability of the same large molecule spontaneously arising twice. It is very much more improbable than the spontaneous typing of METHINKS IT IS LIKE A WEASEL. Like that phrase in our computer model, the particular favoured RNA molecule was built up by gradual,
cumulative
evolution.

The variety of RNA produced, repeatedly, in these experiments was of the same size and structure as the molecules that Spiegelman had produced. But whereas Spiegelman’s had evolved by ‘degeneration’ from naturally occurring, larger, Q-beta viral RNA, those of the Eigen group had built themselves up from almost nothing. This particular formula is well adapted to an environment consisting of testtubes provided with ready-made replicase. It therefore is converged upon by cumulative selection from two very different starting points. The larger, Q-beta RNA molecules are less well adapted to a testtube environment but better adapted to the environment provided by
E.coli
cells.

Experiments such as these help us to appreciate the entirely automatic and non-deliberate nature of natural selection. The replicase ‘machines’ don’t ‘know’ why they make RNA molecules: it is just a byproduct of their shape that they do. And the RNA molecules themselves don’t work out a strategy for getting themselves duplicated. Even if they could think, there is no obvious reason why any thinking entity should be motivated to make copies of itself. If I knew how to make copies of myself, I’m not sure that I would give the project high priority in competition with all the other things I want to do: why should I? But motivation is irrelevant for molecules. It is just that the structure of the viral RNA
happens to
be such that it makes cellular machinery churn out copies of itself. And if any entity, anywhere in the universe, happens to have the property of being good at making more copies of itself, then automatically more and more copies of that entity
will
obviously come into existence. Not only that but, since they automatically form lineages and are occasionally miscopied, later versions tend to be ‘better’ at making copies of themselves than earlier versions, because of the powerful processes of cumulative selection. It is all utterly simple and automatic. It is so predictable as to be almost inevitable.

A ‘successful’ RNA molecule in a testtube is successful because of some direct, intrinsic property of itself, something analogous to the ‘stickiness’ of my hypothetical example. But properties like ‘stickiness’ are rather boring. They are elementary properties of the replicator itself, properties that have a direct effect on its probability of being replicated. What if the replicator has some effect upon something else, which affects something else, which affects something else, which … eventually, indirectly affects the replicator’s chance of being replicated? You can see that, if long chains of causes like this existed, the fundamental truism would still hold. Replicators that happen to have what it takes to get replicated would come to predominate in the world, no
matter how long and indirect
the chain of causal links by which they influence their probability of being replicated. And, by the same token, the world will come to be filled with the links in this causal chain. We shall see those links, and marvel at them.

In modern organisms we see them all the time. They are eyes and skins and bones and toes and brains and instincts. These things are the tools of DNA replication. They are caused by DNA, in the sense that differences in eyes, skins, bones, instincts,
etc.
are caused by differences in DNA. They exert an influence over the replication of the DNA that caused them, in that they affect the survival and reproduction of their bodies - which contain that same DNA, and whose fate is therefore shared by the DNA. Therefore, the DNA itself exerts an influence over its own replication, via the attributes of bodies. DNA can be said to exert power over its own future, and bodies and their organs and behaviour patterns are the instruments of that power.

When we talk about power, we are talking about consequences of replicators that affect their own future, however indirect those consequences might be. It doesn’t matter how many links there are in the chain from cause to effect. If the cause is a selfreplicating entity, the effect, be it ever so distant and indirect, can be subject to natural selection. I shall summarize the general idea by telling a particular story about beavers. In detail it is hypothetical, but it certainly cannot be far from the truth. Although nobody has done research upon the development of brain connections in the beaver, they have done this kind of research on-other animals, like worms. I am borrowing the conclusions and applying them to beavers, because beavers are more interesting and congenial to many people than worms.

A mutant gene in a beaver is just a change in one letter of the billionletter text; a change in a particular gene G. As the young beaver grows, the change is copied, together with all the other letters in the text, into all the beaver’s cells. In most of the cells the gene G is not read; other genes, relevant to the workings of the other cell types, are. G is read, however, in some cells in the developing brain. It is read and transcribed into RNA copies. The RNA working copies drift around the interior of the cells, and eventually some of them bump into protein-making machines called ribosomes. The protein-making machines read the RNA working plans, and turn out new protein molecules to their specification. These protein molecules curl up into a particular shape determined by their own aminoacid sequence, which in turn is governed by the DNA code sequence of the gene G. When G mutates, the change makes a crucial difference to the aminoacid sequence normally specified by the gene G, and hence to the coiled-up shape of the protein molecule.