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Science: Under the microscope - Yours, mortally

LETTER TO MARY SHELLEY

Lewis Wolpert
Sunday 08 February 1998 00:02 GMT
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DEAR MARY, I'm sure you have been following your recent successes. First there was Dolly, after which you were elected an FGGEC(E) Fairy Godmother of Genetics (Evil Class). Now, the latest story is that immortality is just around the corner. How satisfied you must be with your remarkable imaginative achievement. Your ideas about Dr Victor Frankenstein-style creations are everywhere.

The new claim to reach the headlines is that the so-called biological clock in all our cells that is supposed to cause ageing has been tricked into not keeping time. The idea comes from quite old experiments on connective tissue cells taken from various animals and placed in culture. The cells then grow and divide, and everyone thought that these cells would continue to divide and multiply so long as they had both space to and a good culture medium. Not so. After a certain number of divisions the cells just stopped.

The striking observation was that there is a quite good correlation between the number of divisions and lifespan. If the cells came from a mouse they would divide about 10 times, but from animals that lived longer, like humans, the number of divisions could go up to 40 or so. Moreover, if the cells were taken from a young person they would divide more than if taken from someone who is old. No wonder they thought that the biological basis of ageing had been discovered - cells had a clock that ran down with age. The latest work has enabled the cells to continue to divide indefinitely and so apparently stop the clock. This has been done by providing them with an enzyme that keeps the ends of their chromosomes in good order. A very nice piece of work, but has it anything to do with ageing?

Probably not. There is just no evidence that the limited ability of cells to divide in culture has anything to do with the normal process. For example cells, other than fibroblasts, can divide many more times. But more importantly, our mortality is much more related to many causes of wear and tear and to disease. Elephants die in old age because they lose their teeth. We rarely die of old age. We die from a wide variety of causes. About half the deaths in our population are from cardiovascular disease such as heart attacks and strokes; another quarter are from cancer and then there are many other organs whose failure leads to our demise - kidney, brain, liver, and so on. These diseases have nothing to do with the inability of cells to divide - and cancer itself is due to cells continuing to divide when they should not.

Ageing is, nevertheless, under genetic control. A newborn baby elephant has been 20 months in the womb and shows no signs of ageing, while a mouse of the same age is well into late middle age. The reason is that evolution has ensured that animals do not show signs of ageing - that is loss or deterioration of bodily functions - until they have given birth to their young and cared for them. After that time evolution loses interest and that is why so many diseases are prevalent in older age groups.

Cancer is, in general, a disease of old age. Cells are exposed to all sorts of chemical attacks and so what has happened in evolution is that animals have evolved repair systems that try to prevent accumulation of damage before reproduction is over. Life expectancy has almost doubled in this country over the last 150 years due to the unnatural improved conditions of modern civilisation.

There are some fascinating new experiments that have identified genes in flies and worms that can significantly increase their lifespan. And rats, on a very restricted diet, live much longer. But ageing is as yet poorly understood. No doubt there will be many more scary stories to come.

If ever a child is cloned I do hope that they will have the decency to name it either Victor or Victoria in honour of your great doctor. Yours, in admiration and irritation.

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