Power, Sex, Suicide: Mitochondria and the Meaning of Life (36 page)

Several other considerations militate against the gene as the ‘unit of selection’ in bacteria. It is said that in clonal replication all the genes are passed on together, so there is no distinction between the fate of the genes and the fate of
the cell. This isn’t quite true. Bacteria swap genes, and are prey to viruses called bacteriophages which load up cassettes of selfish DNA. Yet whereas eukaryotes are stuffed with selfishly replicating ‘parasitic’ DNA (DNA sequences that replicate for their own benefit, rather than that of the organism), bacteria have small genomes and next to no parasitic DNA. As we saw in
Part 3
, bacteria lose excess DNA, including functional genes, because this speeds up their replication. If these genes are ‘selfish’, they are punished for it by being regularly thrust out into the hostile world. Perhaps it’s reasonable to think of lateral gene transfer in bacteria as a selfish rearguard action on the part of the genes themselves, but in general such lateral gene transfers only last as long as the cell needs the extra genes, and then they are lost again, along with any other genes that are not needed. I don’t doubt we could interpret all of this in terms of selfish genes, but I find such behaviour much easier to grasp in terms of the costs and benefits to the cells themselves, not the genes.

There is another sense in which it might be better to see the cell as the selfish unit, rather than its genes, at least in bacteria. This is that genes do not code for cells: they code for the machinery that makes up cells, the proteins and RNA that in turn build everything that is needed. This may seem a trivial distinction, but it is not. All cells have a highly elaborate structure, even bacterial cells, and the more we learn about them, the more we appreciate that cellular function depends on this structure; as we saw in
Part 2
, cells are emphatically
not
just a bag of enzymes. Intriguingly, there seems to be nothing in the genes that codes for the
structure
of cells. For example, membrane proteins are directed to their particular membranes by means of well-known coding sequences, but nothing stipulates how to create such a membrane from scratch, or determines where it should be built: lipids and proteins are added to existing membranes. Similarly, new mitochondria are always formed from old mitochondria—they cannot be made from scratch. The same goes for other components of the cell like centrioles (the bodies that organize the cytoskeleton).

At the fundamental level of the cell, then, nature
depends
on nurture, and vice versa. In other words, the power of the genes depends absolutely on the pre-existence of the cell itself, while the cell can only be perpetuated through the action of the genes. Accordingly, the genes are
always
passed on within a cell, such as an egg or a bacterium, never as a discrete packet. Viruses, which are a discrete packet, only come alive when they gain access to the machinery of an existing cell. The microbiologist Franklin Harold, whom we met in
Part 2
, has pondered long and deep about these matters; he put it thus some twenty years ago, and little has changed:

The genome is the sole repository of hereditary information and must ultimately determine form, subject only to limited modulation by the environment. But the inquiry into just how the genome does this leads through another set of Chinese boxes, to show the
innermost one empty…. Gene products come into a pre-existing organized matrix consisting of previous gene products, and their functional expression is channelled by the places into which they come, and by the signals they receive. Form is not explicitly spelled out in any message but is implicit in its combination with a particular structural context. At the end of the day, only cells make cells.

On balance, then, there are many reasons to see the bacterial cell as the selfish unit of evolution, rather than its genes. Perhaps, as Dawkins said, the invention of sex in the eukaryotes changed all that; but if we wish to understand the deeper currents of evolution we must look to the bacteria, which alone held dominion over the world for two billion years.

These differences in perspective help to explain why microbiologists, such as Lynn Margulis, are among the most prominent critics of the selfish gene. In fact, Margulis has become an outspoken critic of mathematical neo-Darwinism in general, going so far as to dismiss it as being reminiscent of phrenology, that Victorian obsession with cranial shape and criminality, and likely to suffer the same ignominious fate.

While one senses that Margulis is repelled by the concept of the selfish gene, it is also true that bacteria are rather more likely to behave in a civil manner, forming communities that live together in harmony rather than ‘eating’ each other: the idea of bacteria as merely pathogenic is persistent but false. For Margulis, evolution is largely a bacterial affair, and can be explained in terms of mutual collaborations between consortia of bacteria, including endosymbioses, such as those which founded the eukaryotic cell. These consortia work well in bacteria because predatory behaviour doesn’t pay: as we saw in
Part 3
, the mechanism of respiration across the cell membrane means that large, energy-rich bacterial cells capable of physically engulfing other cells (phagocytosis) are virtually precluded by natural selection. Bacteria are obliged to compete with each other by the speed of their growth, rather than the size of their mouth. Given the reality of food shortage in bacterial ecosystems, bacteria gain more by living from each others’ excrement than they do by fighting over the same raw materials. If one bacterium lives by fermenting glucose to form lactic acid, then there is scope for another to live by oxidizing the waste lactic acid to carbon dioxide; and for another to convert the carbon dioxide into methane; and another to oxidize the methane; and so on. Bacteria live by endless recycling, which is best achieved via cooperative networks.

Perhaps it’s worth remembering that even cooperative partnerships can only persist if the partners do better within the partnership than without. Whether we measure ‘success’ by the survival of cells or the survival of their genes, we still see only the survivors—the cells or genes that
did
copy themselves most successfully. Those cells whose altruism is so extreme that they die for another are doomed to disappear without trace, just as many young war heroes fought
and died for their country, leaving behind a mourning family but no children of their own. My point is that collaboration is not necessarily altruistic. Even so, a world of mutual collaboration seems a far cry from the conventional idea, expressed by Tennyson, of ‘nature, red in tooth and claw’. Collaboration might not be altruistic, but neither is it ‘aggressive’—it doesn’t make us think of jaws dripping in blood.

This discrepancy is partly responsible for the schism that has opened between Margulis and neo-Darwinists like Dawkins. As we have seen, Dawkins’ ideas about selfish genes are equivocal when applied to bacteria (which he does not try to do). For Margulis, however, the whole tapestry of evolution is woven by the collaborations of bacteria, which form not just colonies but the very fabric of individual bodies and minds, responsible even for our consciousness, via the threadlike networks of microtubules in the brain. Indeed, Margulis pictures the entire biosphere as the construct of collaborating bacteria—Gaia, the concept that she pioneered with James Lovelock. In her most recent book,
Acquiring Genomes: A Theory of the Origins of Species
, written with her son Dorion Sagan, Margulis argues that even among plants and animals, new species are formed by means of a bacterial-style merging of genomes, rather than the gradual divergence pictured by Darwin, and accepted by virtually every other biologist. Such a theory of merging genomes might be true in some instances, but in most cases it flies in the face of a century of careful evolutionary analysis. In dismissing neo-Darwinism, Margulis deliberately provokes the majority of mainstream evolutionists.
¹
Few have the patience displayed by the late Ernst Mayr, who contributed a wise foreword to the book, in which he commended Margulis’s vision of bacterial evolution, while cautioning the reader that her ideas don’t apply to the overwhelming majority of multicellular organisms, including all 9000 species of bird, Mayr’s own particular field of expertise. The reality of sexual reproduction means that genes must compete for space on the chromosomes; and the rise of predation in the eukaryotes means that nature, at this level, really is red in tooth and claw, however much we may wish it otherwise.

Given their different perspectives, it’s ironic that the views of Dawkins and Margulis do not diverge as far as one might think when it comes to the individual. As we have seen, Dawkins wrote of the individual as a colony of collaborating genes, while Margulis thinks of an individual as a colony of collaborating
bacteria, which might be construed as a colony of collaborating bacterial genes. Both see the individual as a fundamentally collaborative entity. Here is Dawkins, for example, in his splendid book
The Ancestor’s Tale
: ‘My first book,
The Selfish Gene
, could equally have been called
The Cooperative Gene
without a word of the book itself needing to be changed… Selfishness and cooperation are two sides of a Darwinian coin. Each gene promotes its own selfish welfare, by cooperating with other genes in the sexually stirred gene pool which is the gene’s environment, to build shared bodies.’

But the ideal of collaboration does not give proper weight to the conflict between the various selfish entities that make up an individual, and in particular to the cells and mitochondria within the cells. While conflict between various selfish entities is entirely in keeping with Dawkins’s philosophy, he did not develop the idea in
The Selfish Gene
—these ideas awaited his own later book
The Extended Phenotype
, and in the 1980s and 1990s the important work of Yale biologist Leo Buss and others. Thanks to the exploration of such conflicts and their resolutions, evolutionary biologists now appreciate that colonies of cells (or genes, if you like) do not constitute true individuals, but rather form a looser association, in which individual cells may still act independently. For example, multicellular colonies like sponges often fragment into bits, each of which is able to establish a new colony. Any commonality of purpose is transitory, for the fate of individual cells is not tied to the fate of the multicellular colony.

Such cavalier behaviour is ruthlessly suppressed in true individuals, in whom all selfish interests are subordinated to a common purpose. Various means are employed to guarantee a common purpose, including the early sequestration of a dedicated germ-cell line, so that the great majority of cells in the body (so-called somatic cells) never pass on their own genes directly, and can only participate in the next generation voyeuristically, as it were. Such voyeurism could not possibly work if the individual cells within the body did not share identical genetic bonds—all derive from a single parent cell, the fertilized egg (the zygote), by asexual, or clonal, replication. Although their own genes are not passed on directly to the next generation, the germ-line cells do pass on exact copies of them, which is the next best thing, and ultimately little different. Even so, carrot measures are not enough: stick measures are also needed. The resolution of selfish conflicts between the cells themselves, even though they are genetically identical, can only be achieved by the imposition of a police state reminiscent of Stalinist Russia. Offenders are not prosecuted but eliminated.

The consequence of this draconian system is that natural selection ceases to pick and choose between the independent entities that make up an individual, and begins to operate at a new and higher level, now choosing between the
competing individuals themselves. Yet even within apparently robust individuals, we can still detect echoes of dissent, a reminder that the unity of an individual was hard won, and all too easily lost. One such echo of the past is cancer, and it is to this, and the lessons we can learn from it, that we turn in the next chapter.

Cancer is a chilling ghost of conflict within an individual. A single cell opts out of the body’s centralized control and proliferates like a bacterium. At a molecular level, the sequence of events is one of the most graphic illustrations of natural selection at work. Let’s consider briefly what happens.

Cancer is usually, but not always, the result of genetic mutations. A single mutation is rarely enough. Typically, a cell must accumulate eight to ten mutations in rather specific genes before it can transform into a malignant cell, whereupon the transformed cell puts its own interests before those of the body. Genetic mutations tend to accumulate at random as we grow older, but it takes a particular combination to cause cancer: mostly the mutations must be in two sets of genes known as oncogenes and tumour-suppressor genes. Both sets code for proteins that control the normal ‘cell cycle’—the way in which cells proliferate or die in response to signals from elsewhere in the body. The products of oncogenes normally signal a cell to divide in response to a particular stimulus (for example, to replace dead cells after an infection) but in cancer they get stuck in the ‘on’ position. Conversely, the products of tumour suppressor genes normally act as a brake on uncontrolled cell division: they countermand the signals for proliferation, making cells quiescent, or forcing them to commit suicide instead. In cancer, they tend to get stuck in the ‘off’ position. There are numerous checks and balances in cells, which is why it takes an average of eight to ten particular mutations before a cell transforms into a cancer cell. People with a genetic predisposition to cancer may inherit some of these mutations from their parents, leaving them with a lower threshold of ‘new’ mutations that must accumulate before the onset of cancer.

Transformed cells no longer respond normally to the body’s instructions. As they proliferate, they form into a tumour. Yet there is still a big distinction between a benign growth and a malignant tumour: many other changes still have to take place for a cancer to spread. First of all, to grow larger than a couple of millimetres across, the tumour requires sustenance. Slow absorption of nutrients across the surface of the tumour is no longer enough—the tumour cells need an internal blood supply. To acquire a blood supply, they need to produce the right chemical messengers (or growth factors) in appropriate
quantities to stimulate the growth of new blood vessels into the tumour. Further growth requires digestion of the surrounding tissues, giving the tumour space to invade: the cells need to spray potent enzymes that break down the tissue structure. Perhaps the most feared step is the leap to remote sites elsewhere in the body—
metastasis
. The properties required are opposing and specific. Cells must be slippery enough to escape the clutches of the tumour, and yet sticky enough to bind to the walls of blood vessels elsewhere in the body. They must be able to evade the attentions of the immune system during their passage through the blood or lymph system, often by ‘sheltering’ in a clump of cells that bind together despite their slipperiness. On arrival, the cells must be able to bore their way through the vessel walls, into the safe haven of the tissue behind—but then stop there. And throughout this hazardous solo journey they must retain their ability to proliferate, to found a cancerous outpost in the new continent of a different organ.