What Mad Pursuit (4 page)

When I visited Bernal’s laboratory I was discouraged by his secretary, Miss Rimmel, an amiable dragon. “Do you realize,” she said, “that people from all over the world want to come to work with the professor? Why do you think he would take you on?” But a more serious difficulty was Mellanby, who said the MRC could not support me if I worked with Bernal. They wanted to see me doing something more biological. I decided to take A. V. Hill’s advice and try my luck at Cambridge, if someone there would have me.

I visited the physiologist Richard Keynes, who talked to me as he ate his sandwich lunch in front of his experiment. He was working on ion movement in the giant axon of the squid. I talked to the biochemist Roy Markham, who showed me an interesting result he had recently obtained with a plant virus. Typically he described it in such a cryptic manner (I was not yet familiar with the way nucleic acid absorbed ultraviolet light) that I could not at first grasp what he was telling me. Both were helpful and friendly but neither had any space to offer me. Finally I visited the Strangeways Laboratory, headed by Honor Fell, where they did tissue culture. She introduced me to Arthur Hughes. They had had a physicist at the Strangeways—D. E. Lea—but he had died recently and his room was still vacant. Would I like to work there? The MRC agreed and gave me a studentship. My family also helped me financially so that I had enough to live in lodgings and still had some money to buy books.

I stayed at the Strangeways for the better part of two years. While I was there I worked on a problem they were interested in. Hughes had discovered that chick fibroblasts in tissue culture could engulf, or phagocytose, small crumbs of magnetic ore. Inside the cell these tiny particles could be moved by an applied magnetic field. He suggested I use their movements to deduce something about the physical properties of the cytoplasm, the inside of the cell. I was not deeply interested in this problem but I realized that in a superficial way it was ideal for me, since the only scientific subjects I was fairly familiar with were magnetism and hydrodynamics. In due course this led to a pair of papers, one experimental and one theoretical, in
Experimental Cell Research
—my first published papers. But the main advantage was that the work was not too demanding and left me plenty of time for extensive reading in my new subject. It was then that I began in a very tentative way to form my ideas.

Some time during this period I was asked to give a short talk to some research workers who had come to the Strangeways for a course. I recall the occasion vividly, since I tried to describe to them what the important problems in molecular biology were. They waited expectantly, with pens and pencils poised, but as I continued they put them down. Clearly, they thought, this was not serious stuff, just useless speculation. At only one point did they make any notes, and that was when I told them something factual—that irradiation with X rays dramatically reduced the viscosity of a solution of DNA. I would dearly love to know exactly what I said on that occasion. I
think
I know what I would have said, but the memory is so overlaid with the ideas and developments of later years that I feel I can hardly trust it. Nor, as far as I know, have my notes for the talk survived. However, what I probably discussed was the importance of genes, why one needed to discover their molecular structure, how they might be made of DNA (at least in part), and that the most useful thing a gene could do would be to direct the synthesis of a protein, probably by means of an RNA intermediate.

After a year or so I went to Mellanby to report progress. I told him that I was getting results on the physical properties of cytoplasm but that I had spent much of my time in trying to educate myself. He looked rather skeptical. “What does the pancreas do?” he asked. I had only the vaguest ideas about the function of the pancreas but I managed to mumble something about it producing enzymes, hastily adding that my interests did not lie so much in organs as in molecules. He seemed temporarily satisfied.

I had visited him at a fortunate moment. On his desk lay the papers proposing the establishment of an MRC unit at the Cavendish to study the structure of proteins using the method of X-ray diffraction. It was to be headed by Max Perutz, under the general direction of Sir Lawrence Bragg. To my surprise (because I was still very junior), he asked me what I thought about it. I said I thought it was an excellent idea. I also told Mellanby that now that I had a background in biology, I would like to work on protein structure, since I felt my abilities lay more in that direction. This time he raised no objection, and the way was cleared for me to join Max Perutz and John Kendrew at the Cavendish.

I
T IS TIME to step aside from the details of my career to consider the main problem. Even a cursory look at the world of living things shows its immense variety. Though we find many different animals in zoos, they are only a tiny fraction of the animals of similar size and type. J. B. S. Haldane was once asked what the study of biology could tell one about the Almighty. “I’m really not sure,” said Haldane, “except that He must be inordinately fond of beetles.” There are thought to be at least 300, 000 species of beetles. By contrast, there are only about 10, 000 species of birds. We must also take into account all the different types of plants, to say nothing of microorganisms such as yeasts and bacteria. In addition, there are all the extinct species, of which the dinosaurs are the most dramatic example, numbering in all perhaps as many as a thousand times all those alive today.

The second property of almost all living things is their complexity and, in particular, their highly organized complexity. This so impressed our forebears that they considered it inconceivable that such intricate and well-organized mechanisms would have arisen without a designer. Had I been living 150 years ago I feel sure I would have been compelled to agree with this Argument from Design. Its most thorough and eloquent protagonist was the Reverend William Paley whose book,
Natural Theology
—
or Evidence of the Existences and Attributes of the Deity Collected from the Appearances of Nature
, was published in 1802. Imagine, he said, that crossing a heath one found on the ground a watch in good working condition. Its design and its behavior could only be explained by invoking a maker. In the same way, he argued, the intricate design of living organisms forces us to recognize that they too must have had a Designer.

This compelling argument was shattered by Charles Darwin, who believed that the
appearance
of design is due to the process of natural selection. This idea was put forward both by Darwin and by Alfred Wallace, essentially independently. Their two papers were read before the Linnean Society on July 1, 1858, but did not immediately produce much reaction. In fact, the president of the society, in his annual review, remarked that the year that had passed had not been marked by any striking discoveries. Darwin wrote up a “short” version of his ideas (he had planned a much longer work) as
The Origin of Species.
When this was published in 1859, it immediately ran through several reprintings and did indeed produce a sensation. As well it might, because it is plain today that it outlined the essential feature of the “Secret of Life.” It needed only the discovery of genetics, originally made by Gregor Mendel in the 1860s, and, in this century, of the molecular basis of genetics, for the secret to stand before us in all its naked glory. It is all the more astonishing that today the majority of human beings are not aware of all this. Of those who are aware of it, many feel (with Ronald Reagan) that there must be a catch in it somewhere. A surprising number of highly educated people are indifferent to these discoveries, and in western society a rather vocal minority are actively hostile to evolutionary ideas.

To return to natural selection. Perhaps the first point to grasp is that a complex creature, or even a complex part of a creature, such as the eye, did not arise in one evolutionary step. Rather it evolved through a
series
of small steps. Exactly what is meant by small is not necessarily obvious since the growth of an organism is controlled by an elaborate program, written in its genes. Sometimes a small change in a key part of the program can make a rather large difference. For example, an alteration in one particular gene in
Drosophila
can produce a fruitfly with legs in the place of its antennae.

Each small step is caused by a random alteration in the genetic instructions. Many of these random alterations may do the organism no good (some may even kill it before it is born), but occasionally a particular chance alteration may give that particular organism a selective advantage. This means that in the last analysis the organism will, on average, leave more offspring than it would otherwise do. If this advantage persists in its descendents then this beneficial mutant will gradually, over many generations, spread through the population. In favorable cases every individual will come to possess the improved version of the gene. The older version will have been eliminated. Natural selection is thus a beautiful mechanism for turning rare events (strictly, favorable rare events) into common ones.

We now know—it was first pointed out by R. A. Fisher—that for this mechanism to work inheritance must be “particulate,” as first shown by Mendel, and not “blending.” In blending inheritance the properties of an offspring are a simple
blend
of those of its parents. In particulate inheritance the genes, which are what is inherited, are particles and do not blend. It turns out that this makes a crucial difference.

For example, in blending inheritance a black animal mated with a white animal would always produce offspring whose color was a blend of black and white, that is, some shade of gray. And
their
offspring, if they bred together, would always remain gray. In particulate inheritance various things can happen. For example, it could be that all the first-generation animals were indeed gray. If these were now mated together, we would obtain in the second generation,
on average
, one-quarter black animals, one-half gray animals, and one-quarter white. [This assumes that color is, in this case, a simple Mendelian character, without dominance.] The genes, being particulate, do not blend, even if their
effects
, in a single animal, blended, so that one white particle (gene) and one black particle, acting together in the same creature, produced a gray animal. This particulate inheritance
preserves
variation (we have mixed black, gray, and white animals after two generations, not just gray ones), whereas blending inheritance
reduces
variation. If inheritance were blending, the offspring of a black animal and a white animal mate, would produce gray animals indefinitely. This is obviously not the case. The fact can be seen clearly in humans: people do not become more and more alike as the generations go on. Variation is preserved.

Darwin, who was a deeply honest man and always faced up to intellectual difficulties, did not know about particulate inheritance and was consequently very disturbed by the criticisms of a Scottish engineer, Fleeming Jenkin. Jenkin pointed out that inheritance (which, without realizing it, Darwin assumed to be blending) would not allow natural selection to work effectively. As particulate inheritance had not yet been thought of, this was a very damning criticism.

What, then, are the basic requirements for natural selection to work? We obviously need something that can carry “information”—that is, the instructions. The most important requirement is that we should have a process for exact replication of this information. It is almost certain that, in any process, some mistakes will be made, but they should occur only rarely, especially if the entity to be replicated carries a lot of information. [In the case of DNA or RNA, the rate of making mistakes, per effective base pair, per generation must, in simple cases, be rather less than the reciprocal of the number of effective base pairs.]

The second requirement is that replication should produce entities that can themselves be copied by the replication process or processes. Replication should not merely be like that of a printing press, when master plates make many copies of a newspaper but each newspaper cannot, by itself, produce further copies of either the press or the newspaper. [In technical terms, replication should be geometrical, not merely arithmetical.]

The third requirement is that mistakes—mutations—should themselves be capable of being copied, so that useful variation can be preserved by natural selection.

There is a final requirement that the instructions and their products should stay together [cross-feeding is to be avoided]. A useful trick is to use a bag—a cell, that is—to do this, but I will not dwell on this point.

In addition, the information needs to do something useful, or to produce other things that will do useful jobs for it, to help it to survive and to produce fertile offspring with a good chance of survival.

In addition to all this, the organism needs sources of raw material (since it has to produce copies of itself), the ability to get rid of waste products, and some sort of source of energy [Free Energy]. All these features are required, but the heart of the matter is obviously the process of exact replication.

This is not the place to explain Mendelian genetics in all its technical details. However, I shall try to provide a glimpse of the astonishing results that a simple mechanism like natural selection can produce over long periods of time. A fuller and very readable account can be found in the early chapters of Richard Dawkins’s recent book,
The Blind Watchmaker.
One may wonder at the title of the book.
Watchmaker
obviously refers to the designer that Paley invoked to explain the imaginary watch found on the heath. But why “blind”? I cannot do better than quote Dawkins’s actual words:

Dawkins gives a very pretty example to refute the idea that natural selection could not produce the complexity we see all around us in nature. The example is a very simple one, but it drives the point home. He considers a short sentence (taken from
Hamlet
):

METHINKS IT IS LIKE A WEASEL.

He first calculates how exceedingly improbable it is that anyone, typing at random (traditionally a monkey, but in his case his eleven-month-old daughter or a suitable computer program) would by chance hit on this exact sentence, with all the letters in their correct place. [The odds turn out to be about 1 in 10
⁴⁰
.] He calls this process “single-step selection.”

He next tries a different approach, which he calls “cumulative selection.” The computer chooses a
random
sequence of twenty-eight letters. It then makes several copies of this but with a certain chance of making random mistakes in the copying. It next proceeds to select the copy that most resembles the target sentence, however slightly. Using this slightly improved version, it then repeats this process of replication (with mutation) followed by selection. In the book Dawkins gives examples of some of the intermediate stages. In one case, after thirty steps, it had produced:

METHINKS IT IS LIKE A WEASEL

and after forty-three steps it had the sentence completely correct.
How many
steps it takes to do this is partly a matter of chance. In other trials it took sixty-four steps, forty-one steps, and so forth. The point is that by
cumulative
selection one can reach the target in a relatively small number of steps, whereas in
single-step
selection it would take forever.

The example is obviously oversimple, so Dawkins tried a more complex one, in which the computer grew “trees” (organisms) according to certain recursive rules (genes). The results are too complex to reproduce here. Dawkins says: “Nothing in my biologist’s intuition, nothing in my 20 years’ experience of programming computers, and nothing in my wildest dreams, prepared me for what actually emerged on the screen” (p. 59).

If you doubt the power of natural selection I urge you, to save your soul, to read Dawkins’s book. I think you will find it a revelation. Dawkins gives a nice argument to show how far the process of evolution can go in the time available to it. He points out that man, by selection, has produced an enormous variety of types of dog, such as Pekinese, bulldogs, and so on, in the space of only a few thousand years. Here “man” is the important factor in the environment, and it is his peculiar tastes that have produced (by selective breeding, not by “design”) the freaks of nature we see preserved all around us as domestic dogs. Yet the time required to do this, on the evolutionary scale of hundreds of millions of years, is extraordinarily short. So we should not be surprised at the ever greater variety of creatures that natural selection has produced on this much larger time scale.

Incidentally, Dawkins’s book contains a fair but devastating critique (pages 37-41) of the book
The Probability of God
by Hugh Montefiore, the Bishop of Birmingham. I first knew Hugh when he was Dean of Caius College, Cambridge, and I agree with Dawkins that Hugh’s book “… is a sincere and honest attempt, by a reputable and educated writer, to bring natural theology up to date.” I also agree wholeheartedly with Dawkins’s criticism of it.

At this point I must pause and ask why exactly it is that so many people find natural selection so hard to accept. Part of the difficulty is that the process is very slow, by our everyday standards, and so we rarely have any direct experience of it operating. Perhaps the type of computer game Richard Dawkins describes might help some people to see the power of the mechanism, but not everyone likes to play with computers. Another difficulty is the striking contrast between the highly organized and intricate results of the process—all the living organisms we see around us—and the randomness at the heart of it. But this contrast is misleading since the process itself is far from random, because of the selective pressure of the environment. I suspect that some people also dislike the idea that natural selection has no foresight. The process itself, in effect, does not know where to go. It is the “environment” that provides the direction, and over the long run its effects are largely unpredictable in detail. Yet organisms appear as if they had been designed to perform in an astonishingly efficient way, and the human mind therefore finds it hard to accept that there need be no Designer to achieve this. The statistical aspects of the process and the vast numbers of
possible
organisms, far too many for all but a tiny fraction of them to have existed at all, are hard to grasp. But the process clearly works. All the worries and criticisms just listed have no content when examined carefully, provided the process is understood properly. And we have examples, both from the laboratory and the field, of natural selection in action, from the molecular level to the level of organisms and populations.