The Extended Phenotype: The Long Reach of the Gene (Popular Science) (34 page)

Spectacular as their achievements have been, is it possible that molecular biologists have hitherto, like biologists at other levels, been in something like the position of our Martian? By assuming that the cell is a place where molecular machinery whirrs for the good of the organism, they have come a long way. They may go further if they now cultivate a more cynical view and countenance the possibility that some molecules may be up to no good from the point of view of the rest. Obviously they already do this when they contemplate viruses and other invading parasites. All that is needed is to turn the same cynical eye on the cell’s ‘own’ DNA. It is because they are starting to do just this that I find the papers of Doolittle and Sapienza and Orgel and Crick so exciting, in comparison with the objections of Cavalier-Smith (1980), Dover (1980) and others, although of course the objectors may be right in the particular detailed points they make. Orgel and Crick summarize the message well:

In short, we may expect a kind of molecular struggle for existence within the DNA of the chromosomes, using the process of natural selection. There is no reason to believe that this is likely to be much simpler or more easy to predict than evolution at any other level. At bottom, the existence of selfish DNA is possible because DNA is a molecule which is replicated very easily and because selfish DNA occurs in an environment in which DNA replication is a necessity. It thus has the opportunity of subverting these essential mechanisms to its own purpose.

In what sense is selfish DNA an outlaw? It is an outlaw to the extent that organisms would be better off without it. Perhaps it wastes space and molecular raw materials, perhaps it wastefully consumes valuable running time on the duplicating and proofreading machinery. In any event we may expect that selection will tend to eliminate selfish DNA from the genome. We may distinguish two kinds of ‘anti-selfish DNA’ selection. Firstly, selection might favour positive adaptations to rid organisms of selfish DNA. For example, the already discovered proofreading principle might be extended.
Long sequences might be examined for ‘sense’ and excised if found wanting. In particular, highly repetitive DNA might be recognized by its statistical uniformity. These positive adaptations are what I had in mind in my above discussion of arms races, ‘mimicry’, etc. We are talking, here, about the evolution of anti-selfish DNA machinery which could be as elaborate and as specialized as the antipredator adaptations of insects.

There is, however, a second kind of selection that could act against selfish DNA, which is much simpler and cruder. Any organism that happened to experience a random deletion of part of its selfish DNA would, by definition, be a mutant organism. The deletion itself would be a mutation, and it would be favoured by natural selection to the extent that organisms possessing it benefited from it, presumably because they did not suffer the economic wastage of space, materials and time that selfish DNA brings. Mutant organisms would, other things being equal, reproduce at a higher rate than the loaded down ‘wild-type’ individuals, and the deletion would consequently become more common in the gene pool. Note that I am not now talking about selection in favour of the
capacity
to delete selfish DNA: that was the subject of the previous paragraph. Here we are recognizing that the deletion itself, the
absence
of the selfish DNA, is itself a replicating entity (a replicating absence!), which can be favoured by selection.

It is tempting to include under the heading of outlaws somatic mutations that cause cells to out-reproduce the non-mutant cells of a body, to the ultimate detriment of the body itself. But although there is a kind of quasi-Darwinian selection that can go on in cancer tumours, and Cairns (1975) has ingeniously drawn attention to what appear to be bodily adaptations to forestall such within-body selection, I think that to apply the outlaw concept here would not be helpful. Not, that is to say, unless the mutant genes concerned somehow manage to propagate themselves indefinitely. They could do this either by getting themselves transported in virus-like vectors, say through the air, or by somehow burrowing into the nuclear germ-line. In either of these two cases they would qualify as ‘germ-line replicators’ as defined in
Chapter 5
and the title of outlaw would be appropriate.

There has been one startling recent suggestion that genes which are beneficiaries of somatic selection might indeed burrow into the germ-line, though in this case they are not cancerous and not necessarily outlaws. I want to mention this work because it has been given publicity as a would-be resuscitator of the so-called ‘Lamarckian’ theory of evolution. Since the theoretical position adopted in this book is fairly describable as ‘extreme Weismannism’, I am bound to see any serious revival of Lamarckism as undermining my position. It is therefore necessary to discuss it.

I use the word ‘scare’ because, to be painfully honest, I can think of few
things that would more devastate my world view than a demonstrated need to return to the theory of evolution that is traditionally attributed to Lamarck. It is one of the few contingencies for which I might offer to eat my hat. It is therefore all the more important to give a full and fair hearing to some claims made on behalf of Steele (1979) and Gorczynski and Steele (1980, 1981). Before Steele’s (1979) book was available in Britain,
The Sunday Times
of London (13 July 1980) printed a full-page article about his ideas and ‘astonishing experiment which seems to challenge Darwinism and resurrect Lamarck’. The BBC have given the results similar publicity, in at least two television programmes and several radio programmes: as we have already seen, ‘scientific’ journalists are constantly on the alert for anything that sounds like a challenge to Darwin. No less a scientist than Sir Peter Medawar forced us to take Steele’s work seriously by doing so himself. He was quoted as being properly cautious about the need to repeat the work, and as concluding: ‘I have no idea what the outcome will be, but I hope Steele is right’ (
The Sunday Times
).

Naturally any scientist hopes that the truth, whatever it is, will out. But a scientist is also entitled to his innermost hopes as to what that truth will turn out to be—a revolution in one’s head is bound to be a painful experience—and I confess that my own hopes did not initially coincide with Sir Peter’s! I had my doubts about whether his could really coincide with those attributed to him, until I recalled his, to me always slightly puzzling (see page 22), remark that ‘The main weakness of modern evolutionary theory is its lack of a fully worked out theory of variation, that is, of
candidature
for evolution, of the form in which genetic variants are proffered for selection. We have therefore no convincing account of evolutionary progress—of the otherwise inexplicable tendency of organisms to adopt ever more complicated solutions of the problems of remaining alive’ (Medawar 1967). Medawar is one of those who have, more recently, tried very hard, and yet failed, to replicate Steele’s findings (Brent
et al
. 1981).

To anticipate the conclusion I shall come to, I now view with equanimity, if with dwindling expectation (Brent
et al
. 1981; McLaren
et al
. 1981), the prospect of Steele’s theory being upheld, because I now realize that, in the deepest and fullest sense, it is a Darwinian theory; a variety of Darwinian theory moreover which, like the theory of jumping genes, is particularly congenial to the thesis of this book, since it stresses selection at a level other than that of the individual organism. Though pardonable, the claim that it challenges Darwinism turns out to be just a journalistic gloat, provided Darwinism is understood in the way that I think it ought to be understood. As for Steele’s theory itself, even if the facts do not uphold it, it will have done us the valuable service of forcing us to sharpen our perception of Darwinism. I am not qualified to evaluate the technical details of Steele’s experiments and those of his critics (a good evaluation is given by Howard
1981), and will concentrate on discussing the impact of his theory, should the facts eventually prove to support it.

Steele forges a threefold union of Burnet’s (1969) theory of clonal selection, Temin’s (1974) provirus theory, and his own attack on the sanctity of Weismann’s germ-line. From Burnet he gets the idea of somatic mutation leading to genetic diversity among the cells of the body. Natural selection within the body then sees to it that the body becomes populated by successful varieties of cells at the expense of unsuccessful varieties. Burnet limits the idea to a special class of cells within the immune system, and ‘success’ means success in neutralizing invading antigens, but Steele would generalize it to other cells. From Temin he gets the idea of RNA viruses serving as intercellular messengers, transcribing genes in one cell, carrying the information to another cell and reverse-transcribing it back into DNA in the second cell using reverse transcriptase.

Steele uses the Temin theory, but with an important additional emphasis on
germ-line
cells as recipients of reverse-transcribed genetic information. He wisely limits most of his discussion to the immune system, although his ambitions for his theory are larger. He cites four studies on ‘idiotypy’ in the rabbit. If injected with a foreign substance, different individual rabbits combat it by making different antibodies. Even if members of a genetically identical clone are subjected to the same antigen, each individual responds with its own unique ‘idiotype’. Now, if the rabbits really are genetically identical, the difference in their idiotypes must be due to environmental or chance differences, and should not, according to orthodoxy, be inherited. Of the four studies cited, one gave a surprising result. The idiotype of a rabbit turned out to be inherited by its children, although not shared by its clone-mates. Steele stresses the fact that in this study the parent rabbits were exposed to the antigen
before
mating to produce the offspring. In the other three studies the parents were injected with antigen
after
mating, and the offspring did not inherit their idiotypes. If idiotype were inherited as a part of an inviolate germ-plasm, it should not have made any difference whether the rabbits mated before or after injection.

Steele’s interpretation begins with the Burnet theory. Somatic mutation generates genetic diversity in the population of immune cells. Clonal selection favours those genetic varieties of cell that satisfactorily destroy the antigen, and they become very numerous. There is more than one solution to any antigenic problem, and the end result of the selection process is different in every rabbit. Now Temin’s proviruses step in. They transcribe a random sample of the genes in the immune cells. Because cells carrying successful antibody genes outnumber the others, these successful genes are statistically most likely to be transcribed. The proviruses cart these genes off to the germ cells, burrow into the germ-line chromosomes and leave them there, presumably snipping out the incumbent occupants of the locus as they do so.
The next generation of rabbits is thereby able to benefit directly from the immunological experience of its parents, without having to experience the relevant antigens themselves, and without the painfully slow and wasteful intervention of selective organism death.

The really impressive evidence only became available after Steele’s theory was cut and dried and published, a striking and rather surprising instance of science proceeding in the way philosophers think it proceeds. Gorczynski and Steele (1980) investigated the inheritance, via the father, of immune tolerance in mice. Using an extremely high-dosage version of the classic Medawar method, they exposed baby mice to cells from another strain, thereby rendering them tolerant as adults to subsequent grafts from the same donor strain. They then bred from these tolerant males, and concluded that their tolerance was inherited by about half their children, who were not exposed as infants to the foreign antigens. Furthermore, the effect seemed to carry over to the grandchild generation.

Subject to confirmation, we have here a prima-facie case for the inheritance of acquired characteristics. Gorczynski and Steele’s brief discussion of their experiment, and of extended experiments reported more recently (Gorczynski & Steele 1981), resembles Steele’s interpretation of the rabbit work, paraphrased above. The main differences between the two cases are firstly that the rabbits could have inherited something in maternal cytoplasm while the mice could not; and secondly that the rabbits were alleged to have inherited an acquired immunity, while the mice are supposed to have inherited an acquired tolerance. These differences are probably important (Ridley 1980b; Brent
et al
. 1981), but I shall not make much of them, since I am not attempting to evaluate the experimental results themselves. I shall concentrate on the question of whether, in any case, Steele is really offering ‘a Lamarckian challenge to Darwinism’.

There are some historical points to get out of the way first. The inheritance of acquired characteristics is not the aspect of his theory that Lamarck himself emphasized and,
contra
Steele (1979, p. 6), it is not true that the idea originated with him: he simply took over the conventional wisdom of his time and grafted to it other principles like ‘striving’ and ‘use and disuse’. Steele’s viruses seem more reminiscent of Darwin’s own pangenetic ‘gemmules’ than of anything postulated by Lamarck. But I mention history just to get it out of the way. We give the name Darwinism to the theory that undirected variation in an insulated germ-line is acted upon by selection of its phenotypic consequences. We give the name Lamarckism to the theory that the germ-line is not insulated, and that environmentally imprinted improvements may directly mould it. In this sense, is Steele’s theory Lamarckian and anti-Darwinian?

By inheriting their parents’ acquired idiotypes, rabbits would undoubtedly benefit. They would begin life with a head start in the immunological battle
against plagues that their parents met, and that they themselves are likely to meet. This is a directed, adaptive change, then. But is it really imprinted by the environment? If antibody formation worked according to some kind of ‘instructive’ theory, the answer would be yes. The environment, in the shape of antigenic protein molecules, would then directly mould antibody molecules in parent rabbits. If the offspring of those rabbits turned out to inherit a predilection to make the same antibodies, we would have full-blooded Lamarckism. But the conformations of the antibody proteins would, on this theory, somehow have to be reverse-translated into nucleotide code. Steele (p. 36) is adamant that there is no suggestion of such reverse translation, only reverse
transcription
from RNA to DNA. He is
not
proposing any violation of Crick’s central dogma, although of course others are at liberty to do so (I shall return to this point in a more general context later).