The Epigenetics Revolution

In front of him is the lever that controls movement. Forward pressure sends the machine into the future. Backward pressure, into the past. And the harder the pressure, the faster the machine travels.

Everyone nods sagely at this explanation. The only problem is that this isn’t an explanation, it’s just a description. And that’s also true of that statement about cells using the same information in different ways – it doesn’t really tell us anything, it just re-states what we already knew in a different way.

What’s much more interesting is the exploration of how cells use the same genetic information in different ways. Perhaps even more important is how the cells remember and keep on doing it. Cells in our bone marrow keep on producing blood cells, cells in our liver keep on producing liver cells. Why does this happen?

One possible and very attractive explanation is that as cells become more specialised they rearrange their genetic material, possibly losing genes they don’t require. The liver is a vital and extremely complicated organ. The website of the British Liver Trust[3] states that the liver performs over 500 functions, including processing the food that has been digested by our intestines, neutralising toxins and creating enzymes that carry out all sorts of tasks in our bodies. But one thing the liver simply never does is transport oxygen around the body. That job is carried out by our red blood cells, which are stuffed full of a particular protein, haemoglobin. Haemoglobin binds oxygen in tissues where there’s lots available, like our lungs, and then releases it when the red blood cell reaches a tissue that needs this essential chemical, such as the tiny blood vessels in the tips of our toes. The liver is never going to carry out this function, so perhaps it just gets rid of the haemoglobin gene, which it simply never uses.

It’s a perfectly reasonable suggestion – cells could simply lose genetic material they aren’t going to use. As they differentiate, cells could jettison hundreds of genes they no longer need. There could of course be a slightly less drastic variation on this – maybe the cells shut down genes they aren’t using. And maybe they do this so effectively that these genes can never ever be switched on again in that cell, i.e. the genes are irreversibly inactivated. The key experiments that examined these eminently reasonable hypotheses – loss of genes, or irreversible inactivation – involved an ugly toad and an elegant man.

Turning back the biological clock

The work has its origins in experiments performed many decades ago in England by John Gurdon, first in Oxford and subsequently Cambridge. Now Professor Sir John Gurdon, he still works in a lab in Cambridge, albeit these days in a gleaming modern building that has been named after him. He’s an engaging, unassuming and striking man who, 40 years on from his ground-breaking work, continues to publish research in a field that he essentially founded.

John Gurdon cuts an instantly recognisable figure around Cambridge. Now in his seventies, he is tall, thin and has a wonderful head of swept back blonde hair. He looks like the quintessential older English gentleman of American movies, and fittingly he went to school at Eton. There is a lovely story that John Gurdon still treasures a school report from his biology teacher at that institution which says, ‘I believe Gurdon has ideas about becoming a scientist. In present showing, this is quite ridiculous.’[4] The teacher’s comments were based on his pupil’s dislike of mindless rote learning of unconnected facts. But as we shall see, for a scientist as wonderful as John Gurdon, memory is much less important than imagination.

In 1937 the Hungarian biochemist Albert Szent-Gyorgyi won the Nobel Prize for Physiology or Medicine, his achievements including the discovery of vitamin C. In a phrase that has various subtly different translations but one consistent interpretation he defined discovery as, ‘To see what everyone else has seen but to think what nobody else has thought’[5]. It is probably the best description ever written of what truly great scientists do. And John Gurdon is truly a great scientist, and may well follow in Szent-Gyorgyi’s Nobel footsteps. In 2009 he was a co-recipient of the Lasker Prize, which is to the Nobel what the Golden Globes are so often to the Oscars. John Gurdon’s work is so wonderful that when it is first described it seems so obvious, that anyone could have done it. The questions he asked, and the ways in which he answered them, have that scientifically beautiful feature of being so elegant that they seem entirely self-evident.