Thursday, 12 July 2012

Epigenetics - new hair, new legs, new science.

Many of the most powerful and elegant ideas in science don’t address why, or how, things happen. For example, Newton realised that under perfect conditions, if you push something, like a car, it speeds up and if you push it twice as hard it speeds up twice as quickly. Now, if you push a bigger car, one with exactly twice the mass, and apply exactly as much force, the car speeds up exactly half as quickly. This relationship is so precise and so famous that it is usually just called “the Second Law of Motion” and it has a role in everything from building bridges to planning missions to Mars.

However, the laws of motion don't tell us why mass and acceleration should both be related to force in this simple way. (Not to mention why objects have mass in the first place, how an object can be accelerated by gravity without being touched, and a host of other difficult questions.) Newton himself thought that speculations about such things “have no place in experimental philosophy”. Despite this, physicists have tried to answer these more difficult questions and have made a lot of progress.

Newton might not have been interested in why or how things happen, but most of the rest of us are. The answers we come up with may not be as elegant or precise as the Second Law, but they make a real difference. So scientists spend most of their time attempting to emulate Dorothy when she pulls back the curtain to reveal the old man behind all the apparently magical goings on in Oz: “Aha! That’s what makes it all happen!”

Take genetics as an example; from its beginnings in the mid-nineteenth century there has been an increasingly powerful sense of the curtain being drawn back and the machinery of life being revealed. As a result we are all now familiar with the idea that our genes come from our parents and contain some sort of “blueprint” which determines how we are put together. This idea is clear enough. But all our cells contain exactly the same instructions, and although we start out as a ball of essentially identical cells, we do not, of course, end up that way.

Cells all develop differently, they differentiate, they become heart cells, or brain cells, or whatever type of cells, and they pass on this specialism, this memory of the sort of cell they are, to their offspring. This inheritance cannot be genetic because the genetics of every cell in the organism is identical. The mechanism that does this is outside genetics or epigenetic. If genetics is the study of the cards you are dealt, then epigenetics is the study of how the hand is played out.

Gardeners know that new plants can be generated from small cuttings. This is because the new cells produced as the cutting grows discover new roles, in fact all the roles necessary to make a whole plant. In contrast most animal cells mostly remain true to their epigenetic inheritance and so animals have only limited abilities to regenerate. However, in some amphibians cells that are near a limb amputation have their differentiation switched off. As a result embryo-like development starts over again and a new limb grows complete with bones, muscles, and nerve connections. Never mind Newton, people really want to know how this works.

In humans (and mammals in general) regeneration abilities are rare, but one or two examples are worth noting. The nerve connections that allow mammals to smell are, unusually, absolutely determined to re-grow after all sorts of injury and abuse, and they often succeed. Also there is a strain of laboratory-bred mice that can regenerate in remarkable ways; for example, large holes punched in their ears do not stay open but heal. They do not heal over with scar tissue, but with supple new cartilage and skin complete with regenerated hair follicles; thus offering hope to middle aged men everywhere.

A 2012 paper in the journal PLoS One (Tyrka et al, 2012) is one of many to take epigenetic investigations much further. It presents evidence that epigenetics may help explain why people who are affected by maltreatment, abandonment, or bereavement in childhood are at higher risk of mental illness as adults. Parts of the genetic code are, it seems, epigenetically switched off as a result of what the authors call “Disruption or lack of adequate nurturing”. Notice again, that we certainly are interested in why this link exists, not simply that it exists.

From growing new nerves and limbs, to interventions which prevent long term traumatic stress blighting the lives of millions affected by war and disaster; epigenetics promises to be a vital part of the story. It is a science in its infancy and progress may initially be sporadic and disconnected. But we really do want to know how it works.