Genome Medicine
Bioinformatician Tim Hubbard on the ‘100,000 Genomes Project’, how to use genome data in diagnostics and treat...
The video is a part of the project British Scientists produced in collaboration between Serious Science and the British Council.
We’re talking in Cambridge University and perhaps the best student we ever had here was Isaac Newton, who was a student here in the 1680-s and he is famous because he achieved the first unification in physics. He realized that the force that makes the apple fall and which holds us onto the ground is the same as the force which holds the Moon in its orbit around us and holds the planets their orbits around the Sun. He showed that everything could be understood in our Solar System if objects moved under the action of a force which depended on their mass and fell off as the inverse square of the distance – if things are twice as far away the force is four times weaker – and this was a wonderful insight and this allowed him to understand the motions of the planets and why we have eclipses etc.
Newton was actually very lucky in that he seized on one of the few phenomena in nature which we can both understand and predict. We can understand gravity, we can understand the motion of the planets and we can actually predict the motion of the planets. Many things in science we can’t understand at all, but even when we can understand something, we often can’t make predictions. For instance, weather – we can understand what causes weather, but we famously can’t predict the weather more than a few days ahead because it becomes chaotic. But in the case of gravity and the planets – we can understand it and we can predict it. And since Newton’s work we’ve understood that gravity applies not just in our solar system but further beyond. Stars are in equilibrium because they are held together between two forces – the gravity which is crushing them and the pressure of their hard interiors that is holding them up. And galaxies like our Milky Way galaxy – they are in equilibrium between the orbital motion of all the stars around the central hub of the galaxy and the gravity which is pulling them in – so, it’s gravity that’s holding our galaxies together and indeed, on a bigger scale, tosses the galaxies.
Newton’s theory of gravity is extremely precise and it works very well in explaining most stars and things in the solar system and also things within the galaxy, but it’s got limits. First of all, it doesn’t explain why the law is an inverse square law, why it falls off by a factor of four if you go twice as far away. Nor does it really explain very clearly why the force of gravity is the same on everything – I mean, why should it be that the feather and the lead ball in the vacuum fall with the same speed? It doesn’t really explain that. And Also there are other limits to it which have become more apparent in the last hundred years, which is that it breaks down, if things move very fast – if things are moving at a speed close to the speed of light.
That’s why the theory that Einstein developed in 1915 – over a hundred years ago – called “General Relativity” was a huge advance on Newton’s theory of gravity. Einstein didn’t prove Newton wrong – he often said that he did, but that’s unfair, – what Einstein did was he transcended and extended Newton. He gave us a theory of gravity which agrees with Newton within Newton’s domain of relevance, but it applied for fast moving objects and it also applied when gravity was very strong. And that became very important in astronomy when we discovered objects where gravity is indeed very strong. In particular, here in Cambridge in 1968 there was a discovery of the objects called ‘neutron stars’. These are objects which are as heavy as a star – heavier that the Sun in fact – but they are only about ten kilometres across, and if you squeeze the mass of a star, they are very small, then you get a very strong gravitational field. A field so strong that if you wanted to escape from a neutron star you’d have to fire a rocket at half the speed of light. And if you are near to a neutron star then you’d find that light rays which are anyway slightly bent by a star and the Sun, would be bent a lot – so you certainly need a theory beyond Newton’s to understand a neutron star, and Einstein’s theory is important in that context.
Even more extreme are objects called black holes, where not only has the material become very dense like a neutron star, but it’s gone on collapsing. If you try to make a neutron star ten times as heavy as the Sun, for instance, you’d find that even the force of nuclei could not hold it up, it would go on contracting and it would become what we now call a black hole. A black hole is something which is collapsed so much that not even light can escape from it. It’s cut itself off from the rest of the universe, leaving, as it were, a gravitational imprint frozen in the space that’s left. So it’s a sort of dark domain in space which can suck things in, but nothing comes out of it. And we’ve known for the last forty years that these objects actually exist. They are rather hard to detect, of course, because they are by definition ‘black’, but many have been found indirectly. The first ones were found by looking for objects in binary star systems, when there was a small object orbiting around an ordinary star and its gravitational field is tugging material from the surface of the ordinary star – and, even though the black hole itself is invisible, material that’s pulled towards it and swirls down into it like a whirlpool gets very very hot and emits a lot of radiation. So astronomers observed objects that were emitting very intense radiation from a small object orbiting around an ordinary star and they inferred that that small object was a black hole and the gas swirling into it gave sporadic radiation, often not just visible light but x rays and gamma rays as well – and that way we found that there were black holes.
Black holes don’t just exist as the endpoint of stars. There’s an even more dramatic way in which the black forms form and that is in the centers of galaxies. A galaxy is a big swirling disc of stars around some central hub and the density of stars and the density of gas is higher towards the centre, and we now know that right in the middle of almost all galaxies there lurks a black hole weighing billions, in some case as much as the mass of the sun. These supermassive black holes are very important because if gas folded into them then you get something which is hugely bright, far brighter than a galaxy. And these are called quasars, which were discovered by astronomers in 1960s, where something in the center of the galaxy outshone all the billions of stars in the galaxy by a factor of a hundred or so. These are now understood as massive black holes in the centers of galaxies which are capturing gas of even entire stars from their surroundings. So black holes exist in our universe, not just the stellar massive but supermassive black holes.
Now, black holes are crucially important because they exemplify Einstein’s theory in this most dramatic way. Einstein’s way gave us a new way of looking at gravity. He thought of space and time as being linked together, so that near a large mass spaces were curved, which means that light tries to follow the straightest path, but that path is a curved path and near a black hole space is, as it were, falling in. So Einstein’s theory is really very counter-intuitive because it tells us that we can’t really think of space as being fixed and flat – space is itself dynamic – and the most dynamic manifestations of space occur when two black holes merge together.
We should imagine two black holes which are in orbit around each other and they will, as Einstein’s theory predicts, emit what’s called gravitational radiation, which is a sort of ripple in space itself which moves outwards, and that will take away energy and make these two black holes get closer and closer and then they will eventually merge. And these black holes will then form one big one. And one of the most exciting developments recently in 2016 was the discovery of gravitational radiation from a merger of two black holes about a billion lights years away. What was observed was a tiny oscillation in space which was induced by this shattering event when two black holes merged – and at this distance it’s a tiny effect. It was 1/10^21 and that’s equivalent to moving by the thickness of a hair at the distance of alpha centaur, the nearest star – a very tiny effect, but very precise measurements actually revealed this just in 2016. And this is an amazing technical achievement, but it is also the most spectacular vindication we’ve had so far of Einstein’s theory. So Einstein’s theory allows us to understand the extremes, when gravity has overwhelming all the other forces of nature to make a black hole.
And Einstein’s theory also is crucial to understand the very beginning of our universe, because then space and time were very different from what they are today. And one of the challenges which awaits twenty-first century physicists is to produce the final grand unification – unification between the force of gravity and Einstein’s theory which affects very large objects like stars, and the quantum theory which affects atoms and molecules. Now, most of science gets by very well without unification, that’s because quantum theory is important for small things like the atoms in a molecule, and gravity is not very important between small things. On the other hand, astronomers need to worry about gravity when they think about the orbits of planets and stars, but the quantum fussiness, the quantum uncertainty is unimportant for things as big as a star or a galaxy or even a planet, so astronomers don’t have to worry about quantum theory when they talk about orbits. But if you imagine the beginning of the universe when everything was squeezed together to very small dimensions, then we need to worry about quantum effects and about gravity at the same time, and so we need a theory which we don’t yet have in order to understand the very beginning of the big bang and maybe whether our big bang was the only one – and that is a challenge for twenty-first century physics.
There is another thing about gravity which is very important and that is that, though it is an important force for holding us on the ground and for astronomy, it’s in a sense a weak force, in the following sense: if you take two atoms, then they have electrons and protons in them, and the electrical forces between the electrons and the protons are stronger than the gravitational force between them by a huge number, almost forty powers of ten – and that’s why chemists don’t need to worry about gravity. But the difference between gravity and electric forces is that for electric forces there are positive and negative charges and they always almost cancel out for any big objects, but gravity always, as it were, has the same charge, it adds up. And what this means is that on big objects gravity wins. Imagine you are building up solid objects – let’s imagine a sugar lump, a lump of rock – then gravity is not important in those.
Even an asteroid – gravity is not important. But for some of them as big as the planets gravity is important, and it then makes things round. And if you make a planet as big as Jupiter, then it starts to crush it, and if you try to make a planet as heavy as Jupiter you’d find that it would get smaller, not larger, and eventually if you make something more than a hundred times as massive as Jupiter, it turns into a star, and so gravity wins for very big objects. But because it’s weak you have to pile together many many atoms, in fact, 10^57 atoms, before you get something like a star. And that’s a good thing, because if gravity wasn’t so weak, then it wouldn’t be possible for us to exist as we are able to exist because we are made of complexity and layer upon layer of structure, and we contain many atoms before enough to be crushed by gravity. So if there weren’t these huge numbers of powers of ten between the force of gravity on a microscopic scale and the electric forces, then our complex universe couldn’t exist. So gravity is a crucial force for molding the universe and allowing the stars and galaxies to exist and allowing us to be held down ourselves on the Earth, but the weaker it is the better. So gravity, although the weakest force in nature, is crucial for a large scale structure.
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