The irony is that now we understand so much about physiology, we understand a great deal of what is happening behind these extreme sports’ events, and in a way, that descends from Lavoisier and his colleagues, and in a way also that descends, as you will see at the end of the talk, from some of the philosophical issues that were raised at the time of the years of the guillotine.
The other great race of course is not the Tour de France, which is new, but the marathon. The marathon is 2000 years old and it, of course, is named after the great run from Marathon to Athens by Pheidippides, who ran there with news of a victory over the Persians on a hot summer’s day and collapsed and died of heat exhaustion, after he had shouted “We have victory!” That is what they say anyway and they are sticking to it.
The Paris Marathon is a big event, the fifth biggest in the world, and they take the same route as the Tour de France at the end, but in the opposite direction, and they go underneath the Eiffel Tower, as they do.
What marathons have done is to show us that, actually, there are differences in individual physiology, individual abilities to deal with oxygen shortage, with heat and the like, which mimic those which you can generate with drugs, and in some ways are more effective than those you can generate with drugs.
That has been known in animals for quite some time. If you climb to the height of Everest, the amount of oxygen in the air drops to a third of what it is at the bottom, and there are almost no animals who can survive on the top of Everest, apart from one, which is this thing called the bar-headed goose. There are some in Green Park, when they are not flying over the top of Everest because it is an Indian bird, and every year, they fly over Tibet at 30,000 feet and more, with absolutely no difficulty. How do they do that? No other bird could do that. They have a shift in haemoglobin. They have got special haemoglobin which can soak up more oxygen than other birds’ haemoglobin, and they also have bigger lungs and they also have more effective muscles, against their muscle fibres. So, these birds have evolved to deal with low oxygen levels, and so have other warm-blooded animals, including the people of Tibet themselves, people of the Andes, and those of the Amhara Mountains in Ethiopia and the Kalenjin Mountains in Kenya.
These are some of these people, and if you test them, it turns out that, in their different ways, these individuals are more able to deal with oxygen-shortage than are people from the lowlands. They do it in a different way. The Tibetans do it by altering the extent to which their blood vessels open, so they can move a lot more blood through the arteries. The Andeans do it with more haemoglobin. The Andeans have not been there as long as the Tibetans, or so it seems, because the Andeans still suffer from mountain sickness, and they suffer from a problem which is, if you have got so much haemoglobin, so many red cells, they can, as it were, get clogged up and cause you real problems. But one of the main winners in this year’s, or the winner of this year’s Tour de France was himself an Andean.
So, there are biological differences between these people, and it is not just in oxygen sensitivity, it is in the ability to withstand pain. This is a colleague of mine who works on pain and it turns out that people of an African background, for reasons we really do not understand, are more able to stand intense pain than people of an Hispanic, European that is, or Asian background, and there are more differences too. The heat thing that really counts – Pheidippides died in 490BC and the Sun in that day published a headline, typical headline, “Maniac killed by 25 mile run – copycats warned over marathon suicide dash”. This was actually the Sun’s attempt to produce an educational book, and it was not really, it is bad.
Here, we have got Pietri in the first Olympic Marathon. The poor guy was so exhausted, so much had heatstroke that he took the wrong turn in the stadium and went the wrong way around, and here, they are helping him to the finishing post, and of course, the medal was taken away from him, rather sadly, but he was heat-exhausted. Heat exhaustion is a major issue when it comes to marathons or any other sport. All the world marathon records have been gained in months outside July and August. The Paris Marathon and the London Marathon are in August, but nobody is going to break the records there. They only break records in May and September, when it is relatively cool. So, even a slight increase in temperature cause a big demand.
There is one group of athletes who now of course dominate the world of the marathon. In 1948, there was only one African in the top 25 marathon runners. Then, as you go on, to 2012, every single one is of African origin, and 21 of those 25 all come from a small part of Kenya, which is Kalenjin – it is 21 of the top-25, and it is a fifth of the top-100. The Kalenjin represent one in 2,000 of the world population, and yet they are one-fifth of top marathon runners, and if you look at them, they have got better heat loss, through body build, they have got low oxygen genes, their basal metabolic rate, the rate at which their body ticks over, is relatively low, they tolerate higher body temperatures because they have got lower pain sensitivity. You can see that all these things have a lot to do with their success, and if you look at them, if you look at any great runner, you will find that they have got long, spindly arms and legs, which gives them more mechanical advantage and also helps them to lose heat. So, these guys are winning, and they go in for it because they get a lot of money. You can get enough to keep your family for a lifetime if you win an international marathon. So these people are highly motivated as well. That is genetic, all these, we know that genes are behind this and we are beginning to find the genes behind heat-sensitivity, behind the ability to deal with oxygen shortage and the like.
But everything has now changed in genetics, in a way of course which you have heard no doubt, because genetics, running of DNA, has in effect become free. This is the cost of reading the human genome from one end to the other – it is 3,000 million DNA letters. There are four letters, A, G, C, and T, and we have all got 3,000 million of those letters in every one of our cells. If any one of you, struck dumb by boredom through this talk, were to rush out into the main street outside here, that dreadful roundabout, and be struck by a speeding bus, or more likely a speeding bicycle I would say, and squashed flat, squashed entirely flat, the DNA in your body would stretch from the damp patch on the pavement that used to be you to the Moon and back 8,000 times. Now, that is a lot of DNA…! That is because there are trillions of cells in your body, each of which has got two metres of DNA in it.
But we can read that now, and I remember when people started talking in the year 2000 about reading off the whole of human DNA, all of us geneticists thought what a load of rubbish, what a waste of money, and of course that is because we were not involved in doing it. The US Government and the Wellcome Trust, not the British Government, the Wellcome Trust, put aside $100 million to do the job, and they basically spent most of their $100 million, but technology of reading the DNA off has expanded at the most astounding, almost unbelievable rate. The solid black line there is what is called Moore’s Law, and what that does, it accepts the fact that the price of computer chips halves and the speed of computer chips doubles, and that has been true consistently for the last 15 or 20 years, and that is pretty impressive. DNA sequencing, in the year 2000, cost $100 million; by 2006, it was down to $10 million; by 2013, it was down to $1000; this year, it is down to $100, and at this rate, it will be down to $10 before 2020. So, you will be able to read DNA, human DNA, for effectively nothing, and people are already going out – there is already a 1000 Genome Project going on in Britain to read 1000 DNA, and that has been done, 1000 seems like nothing, we are going for 10,000 now, and they are going to be taking people, like athletes and the sedentary among us, and asking, on the average, what is the genetic constitution of the athletes versus those of those who are simply sedentary, and they are going to find them.
Here is one they have found, which is an enzyme called Angiotensin Converting Enzyme. This is one of these enzymes that alters the ability to soak in oxygen. It does lots and lots of other things too, but it helps you soak in oxygen. It is important in medicine because, if you have got a feeble version of it and you are having difficulty breathing, you are considerably worse off than you would otherwise be. And, like lots of these enzymes [and] genes, it is present in different flavours in different people. In fact, about a third of the people in this room have got a version of that enzyme, the ACE-gene as it is called, which has inserted into it two copies, insertions it is called, with an extra length of DNA; about another third has got two copies, two lengths of that section of the enzyme with no insertion; and the rest of us have got one copy of the insertion. It turns out that your ability to deal with low oxygen levels, either after an asthma attack or after damaging your chest in a car accident, is strongly related to what your genotype is there.
This was work which began at UCL, a friend of mine called Hugh Montgomery, who himself is a manic, maniacal athlete. He is getting on a bit now – he is in his late-fifties, but in his youth, he was a major athlete. He was a major semi-professional alpine Himalayan climber. He was a free diver who dived down deep into water. He had his own light plane. He writes children’s books that sell hundreds of thousands of copies. In fact, he really annoys me every day but that is a different story! But Hugh’s great desire – he has been up Everest several times, but he has never done it without oxygen. He has never done the bar-headed goose experiment. So, he said up at the base – at the Everest Base Camp, there is a UCL laboratory now, where they test people who have gone up and come down and ask various questions about them, and this is what he found…
If you look at the top here, here is the ACE-gene.