Once again, the key is apoptosis. Oncogenes are genes that cause division and growth but, surprisingly, several of them also trigger 2 4 0 G E N O M E
cell death. In the case of one such gene, known as
When these survival signals run out, death takes over. It is as if the designer, aware of
Normal cell growth can only occur if all three are working properly.
In the words of the scientists who discovered these connections:
'Without such support, booby traps spring and the affected cell is either killed or rendered moribund - either way, it is no longer a
[cancerous] threat.'
The story of p53 and the oncogenes, like much of my book, challenges the argument that genetic research is necessarily dangerous and should be curtailed. The story also strongly challenges the view that 'reductionist' science, which takes systems apart to understand them, is flawed and futile. Oncology, the medical study of whole cancers, diligent, brilliant and massively endowed though it was, achieved terribly little by comparison with what has already been achieved in a few years by a reductionist, genetic approach.
Indeed, one of the first calls for the complete sequencing of the human genome came from the Italian Nobel prize-winner Renato Dulbecco in 1986 because, he argued, it was the only way to win the war on cancer. There is now, for the first time in human history, a real prospect of a genuine cure for cancer, the cruellest and most common killer of all in the west, and it has come from reductionist, genetic research and the understanding that this brings. Those who would damn the whole science as dangerous should remember that.9
Natural selection, once she has selected a method of solving one problem, frequently uses it to solve another. Apoptosis has other functions than the elimination of cancer cells. It is also useful in the fight against ordinary infectious disease. If a cell detects that it has been infected with a virus, it can kill itself for the good of the D E A T H 2 4 1
body as a whole (ants and bees may do this as well, for the good of their colonies). There is good evidence that some cells do indeed do exactly this. There is also, inevitably, evidence that some viruses have evolved a way of preventing this from happening. Epstein¬
Barr virus, the cause of glandular fever or mononucleosis, contains a latent membrane protein whose job seems to be to head off any tendency the infected cell shows to commit suicide. Human papil-loma virus, cause of cervical cancer, has two genes aboard whose job is to switch off
As I mentioned in the chapter on chromosome 4, Huntington's disease consists of unplanned and excessive apoptosis of brain cells which cannot then be replaced. Neurons cannot be regenerated in the adult brain - which is why some brain damage is irreversible.
This makes good evolutionary sense because unlike, say, skin cells, each neuron is an exquisitely shaped, trained and experienced opera-tor. To replace it with a naive and untrained randomly shaped neuron would be worse than useless. When a virus gets into a neuron, the neuron is not instructed to undergo apoptosis. Instead, for reasons that are not entirely clear, the virus itself sometimes induces apoptosis of the neuron. This is true in the case of fatal alphavirus encephalitis, for instance.10
Apoptosis can also be useful in preventing other kinds of mutiny than cancer, such as genetic distortion of the kind induced by selfish transposons. There is some good evidence that the germ cells in the ovary and testicle are under surveillance from follicular and Sertoli cells respectively, whose job is to detect any such selfishness and, if so, to induce apoptosis. In the ovary of a five-month-old human foetus, for example, there are nearly seven million germ cells.
By birth, there are only two million, and of those two million, just 400 or so will be ovulated during the coming lifetime. Most of the rest will be culled by apoptosis, which is ruthlessly eugenic, issuing strict orders to cells that are not perfect to commit suicide (the body is a totalitarian place).
The same principles may apply in the brain, where there is mass culling of cells during development by
any cell that does not work well is sacrificed for the good of the whole. So not only does the apoptotic cull of neurons enable learning to take place, it also improves the average quality of the cells that remain. Something similar probably happens in the immune cells, another subject
Apoptosis is a decentralised business. There is no central planning, no bodily Politburo deciding who should die and who should live.
That is the beauty of it. Like the development of the embryo, it harnesses the self-knowledge of each cell. There is only one conceptual difficulty: how apoptosis could have evolved. In passing the test of killing itself if infected, cancerous or genetically mischievous, a cell by definition dies. It cannot therefore pass on its goodness to its daughters. Known as 'the kamikaze conundrum', this problem is solved by a form of group selection: whole bodies in which apoptosis works well do better than whole bodies in which it fails to work; the former therefore pass on the right traits to the cells of their offspring. But it does mean that the apoptotic system cannot improve during a person's lifetime, because it cannot evolve by natural selection within the body. We are stuck with the cell-suicide mechanism that we inherited.11
C H R O M O S O M E 1 8
C u r e s
Our doubts are traitors,
And make us lose the good we oft might win,
By fearing to attempt.
