0:00:00.380,0:00:02.787 So, before I became a dermatologist, 0:00:02.787,0:00:05.339 I started in general medicine, 0:00:05.339,0:00:07.555 as most dermatologists do in Britain. 0:00:07.555,0:00:09.603 At the end of that time, I went off to Australia, 0:00:09.603,0:00:11.499 about 20 years ago. 0:00:11.499,0:00:13.620 What you learn when you go to Australia 0:00:13.620,0:00:16.346 is the Australians are very competitive. 0:00:16.346,0:00:18.403 And they are not magnanimous in victory. 0:00:18.403,0:00:20.467 And that happened a lot: 0:00:20.467,0:00:22.899 "You pommies, you can't play cricket, rugby." 0:00:22.899,0:00:25.017 I could accept that. 0:00:25.017,0:00:27.347 But moving into work -- 0:00:27.347,0:00:29.885 and we have each week what's called a journal club, 0:00:29.885,0:00:32.343 when you'd sit down with the other doctors 0:00:32.343,0:00:34.463 and you'd study a scientific paper 0:00:34.463,0:00:36.304 in relation to medicine. 0:00:36.304,0:00:39.053 And after week one, it was about cardiovascular mortality, 0:00:39.053,0:00:42.733 a dry subject -- how many people die of heart disease, 0:00:42.733,0:00:44.117 what the rates are. 0:00:44.117,0:00:46.093 And they were competitive about this: 0:00:46.093,0:00:49.189 "You pommies, your rates of heart disease are shocking." 0:00:49.189,0:00:51.085 And of course, they were right. 0:00:51.085,0:00:55.066 Australians have about a third less heart disease than we do -- 0:00:55.066,0:00:58.857 less deaths from heart attacks, heart failure, less strokes -- 0:00:58.857,0:01:00.917 they're generally a healthier bunch. 0:01:00.917,0:01:02.608 And of course they said this was because of 0:01:02.608,0:01:04.672 their fine moral standing, their exercise, 0:01:04.672,0:01:08.740 because they're Australians and we're weedy pommies, and so on. 0:01:08.740,0:01:13.771 But it's not just Australia that has better health than Britain. 0:01:13.771,0:01:17.299 Within Britain, there is a gradient of health -- 0:01:17.299,0:01:19.235 and this is what's called standardized mortality, 0:01:19.235,0:01:21.323 basically your chances of dying. 0:01:21.323,0:01:24.667 This is looking at data from the paper about 20 years ago, 0:01:24.667,0:01:26.142 but it's true today. 0:01:26.142,0:01:29.232 Comparing your rates of dying 50 degrees north -- 0:01:29.232,0:01:31.499 that's the South, that's London and places -- 0:01:31.499,0:01:34.851 by latitude, and 55 degrees -- 0:01:34.851,0:01:37.235 the bad news is that's here, Glasgow. 0:01:37.235,0:01:40.083 I'm from Edinburgh. Worse news, that's even Edinburgh. 0:01:40.083,0:01:44.207 (Laughter) 0:01:44.207,0:01:47.513 So what accounts for this horrible space here 0:01:47.513,0:01:49.717 between us up here in southern Scotland 0:01:49.717,0:01:50.727 and the South? 0:01:50.727,0:01:52.145 Now, we know about smoking, 0:01:52.145,0:01:54.847 deep-fried Mars bars, chips -- the Glasgow diet. 0:01:54.847,0:01:56.175 All of these things. 0:01:56.175,0:01:58.967 But this graph is after taking into account 0:01:58.967,0:02:01.031 all of these known risk factors. 0:02:01.031,0:02:04.800 This is after accounting for smoking, social class, diet, 0:02:04.800,0:02:06.543 all those other known risk factors. 0:02:06.543,0:02:08.767 We are left with this missing space 0:02:08.767,0:02:12.627 of increased deaths the further north you go. 0:02:12.627,0:02:15.264 Now, sunlight, of course, comes into this. 0:02:15.264,0:02:17.584 And vitamin D has had a great deal of press, 0:02:17.584,0:02:19.586 and a lot of people get concerned about it. 0:02:19.586,0:02:23.578 And we need vitamin D. It's now a requirement that children have a certain amount. 0:02:23.578,0:02:25.810 My grandmother grew up in Glasgow, 0:02:25.810,0:02:29.396 back in the 1920s and '30s when rickets was a real problem 0:02:29.396,0:02:31.594 and cod liver oil was brought in. 0:02:31.594,0:02:35.538 And that really prevented the rickets that used to be common in this city. 0:02:35.538,0:02:39.458 And I as a child was fed cod liver oil by my grandmother. 0:02:39.458,0:02:42.482 I distinctly -- nobody forgets cod liver oil. 0:02:42.482,0:02:47.264 But an association: The higher people's blood levels of vitamin D are, 0:02:47.264,0:02:50.591 the less heart disease they have, the less cancer. 0:02:50.591,0:02:54.433 There seems to be a lot of data suggesting that vitamin D is very good for you. 0:02:54.433,0:02:56.727 And it is, to prevent rickets and so on. 0:02:56.727,0:02:59.447 But if you give people vitamin D supplements, 0:02:59.447,0:03:02.879 you don't change that high rate of heart disease. 0:03:02.879,0:03:06.607 And the evidence for it preventing cancers is not yet great. 0:03:06.607,0:03:11.464 So what I'm going to suggest is that vitamin D is not the only story in town. 0:03:11.464,0:03:14.775 It's not the only reason preventing heart disease. 0:03:14.775,0:03:19.144 High vitamin D levels, I think, are a marker for sunlight exposure, 0:03:19.144,0:03:22.359 and sunlight exposure, in methods I'm going to show, 0:03:22.359,0:03:24.798 is good for heart disease. 0:03:24.798,0:03:26.759 Anyway, I came back from Australia, 0:03:26.759,0:03:30.255 and despite the obvious risks to my health, I moved to Aberdeen. 0:03:30.255,0:03:32.807 (Laughter) 0:03:32.807,0:03:35.958 Now, in Aberdeen, I started my dermatology training. 0:03:35.958,0:03:37.903 But I also became interested in research, 0:03:37.903,0:03:41.078 and in particular I became interested in this substance, nitric oxide. 0:03:41.078,0:03:42.454 Now these three guys up here, 0:03:42.454,0:03:44.024 Furchgott, Ignarro and Murad, 0:03:44.024,0:03:47.286 won the Nobel Prize for medicine back in 1998. 0:03:47.286,0:03:49.429 And they were the first people to describe 0:03:49.429,0:03:52.774 this new chemical transmitter, nitric oxide. 0:03:52.774,0:03:55.799 What nitric oxide does is it dilates blood vessels, 0:03:55.799,0:03:57.670 so it lowers your blood pressure. 0:03:57.670,0:04:01.837 It also dilates the coronary arteries, so it stops angina. 0:04:01.837,0:04:03.223 And what was remarkable about it 0:04:03.223,0:04:07.294 was in the past when we think of chemical messengers within the body, 0:04:07.294,0:04:10.464 we thought of complicated things like estrogen and insulin, 0:04:10.464,0:04:11.934 or nerve transmission. 0:04:11.934,0:04:15.229 Very complex processes with very complex chemicals 0:04:15.229,0:04:17.517 that fit into very complex receptors. 0:04:17.517,0:04:19.878 And here's this incredibly simple molecule, 0:04:19.878,0:04:23.216 a nitrogen and an oxygen that are stuck together, 0:04:23.216,0:04:27.846 and yet these are hugely important for [unclear] our low blood pressure, 0:04:27.846,0:04:30.452 for neurotransmission, for many, many things, 0:04:30.452,0:04:33.854 but particularly cardiovascular health. 0:04:33.854,0:04:37.156 And I started doing research, and we found, very excitingly, 0:04:37.156,0:04:39.766 that the skin produces nitric oxide. 0:04:39.766,0:04:42.663 So it's not just in the cardiovascular system it arises. 0:04:42.663,0:04:44.530 It arises in the skin. 0:04:44.530,0:04:46.396 Well, having found that and published that, 0:04:46.396,0:04:48.452 I thought, well, what's it doing? 0:04:48.452,0:04:49.932 How do you have low blood pressure in your skin? 0:04:49.932,0:04:52.023 It's not the heart. What do you do? 0:04:52.023,0:04:56.094 So I went off to the States, as many people do if they're going to do research, 0:04:56.094,0:04:59.831 and I spent a few years in Pittsburgh. This is Pittsburgh. 0:04:59.831,0:05:02.444 And I was interested in these really complex systems. 0:05:02.444,0:05:06.485 We thought that maybe nitric oxide affected cell death, 0:05:06.485,0:05:08.965 and how cells survive, and their resistance to other things. 0:05:08.965,0:05:12.332 And I first off started work in cell culture, growing cells, 0:05:12.332,0:05:14.452 and then I was using knockout mouse models -- 0:05:14.452,0:05:16.189 mice that couldn't make the gene. 0:05:16.189,0:05:20.599 We worked out a mechanism, which -- NO was helping cells survive. 0:05:20.599,0:05:24.420 And I then moved back to Edinburgh. 0:05:24.420,0:05:27.202 And in Edinburgh, the experimental animal we use is the medical student. 0:05:27.202,0:05:29.260 It's a species close to human, 0:05:29.260,0:05:31.162 with several advantages over mice: 0:05:31.162,0:05:34.618 They're free, you don't shave them, they feed themselves, 0:05:34.618,0:05:36.738 and nobody pickets your office saying, 0:05:36.738,0:05:39.138 "Save the lab medical student." 0:05:39.138,0:05:42.401 So they're really an ideal model. 0:05:42.401,0:05:44.362 But what we found 0:05:44.362,0:05:48.979 was that we couldn't reproduce in man the data we had shown in mice. 0:05:48.979,0:05:52.219 It seemed we couldn't turn off the production 0:05:52.219,0:05:55.299 of nitric oxide in the skin of humans. 0:05:55.299,0:05:58.091 We put on creams that blocked the enzyme that made it, 0:05:58.091,0:06:02.475 we injected things. We couldn't turn off the nitric oxide. 0:06:02.475,0:06:05.739 And the reason for this, it turned out, after two or three years' work, 0:06:05.739,0:06:09.787 was that in the skin we have huge stores 0:06:09.787,0:06:12.875 not of nitric oxide, because nitric oxide is a gas, 0:06:12.875,0:06:16.027 and it's released -- (Poof!) -- and in a few seconds it's away, 0:06:16.027,0:06:19.251 but it can be turned into these forms of nitric oxide -- 0:06:19.251,0:06:22.883 nitrate, NO3; nitrite, NO2; nitrosothiols. 0:06:22.883,0:06:24.299 And these are more stable, 0:06:24.299,0:06:28.459 and your skin has got really large stores of NO. 0:06:28.459,0:06:31.284 And we then thought to ourselves, with those big stores, 0:06:31.284,0:06:34.595 I wonder if sunlight might activate those stores 0:06:34.595,0:06:36.339 and release them from the skin, 0:06:36.339,0:06:39.731 where the stores are about 10 times as big as what's in the circulation. 0:06:39.731,0:06:42.571 Could the sun activate those stores into the circulation, 0:06:42.571,0:06:47.811 and there in the circulation do its good things for your cardiovascular system? 0:06:47.811,0:06:50.339 Well, I'm an experimental dermatologist, 0:06:50.339,0:06:51.644 so what we did was we thought 0:06:51.644,0:06:55.171 we'd have to expose our experimental animals to sunlight. 0:06:55.171,0:06:59.251 And so what we did was we took a bunch of volunteers 0:06:59.251,0:07:01.949 and we exposed them to ultraviolet light. 0:07:01.949,0:07:03.678 So these are kind of sunlamps. 0:07:03.678,0:07:06.374 Now, what we were careful to do was, 0:07:06.374,0:07:09.334 vitamin D is made by ultraviolet B rays 0:07:09.334,0:07:13.310 and we wanted to separate our story from the vitamin D story. 0:07:13.310,0:07:17.157 So we used ultraviolet A, which doesn't make vitamin D. 0:07:17.157,0:07:19.438 When we put people under a lamp 0:07:19.438,0:07:24.514 for the equivalent of about 30 minutes of sunshine in summer in Edinburgh, 0:07:24.514,0:07:27.054 what we produced was, we produced a rise 0:07:27.054,0:07:29.046 in circulating nitric oxide. 0:07:29.046,0:07:31.894 So we put patients with these subjects under the UV, 0:07:31.894,0:07:34.310 and their NO levels do go up, 0:07:34.310,0:07:36.446 and their blood pressure goes down. 0:07:36.446,0:07:38.823 Not by much, as an individual level, 0:07:38.823,0:07:41.190 but enough at a population level 0:07:41.190,0:07:44.910 to shift the rates of heart disease in a whole population. 0:07:44.910,0:07:47.334 And when we shone UV at them, 0:07:47.334,0:07:50.996 or when we warmed them up to the same level as the lamps, 0:07:50.996,0:07:54.258 but didn't actually let the rays hit the skin, this didn't happen. 0:07:54.258,0:07:58.122 So this seems to be a feature of ultraviolet rays hitting the skin. 0:07:58.122,0:07:59.946 Now, we're still collecting data. 0:07:59.946,0:08:01.394 A few good things here: 0:08:01.394,0:08:04.541 This appeared to be more marked in older people. 0:08:04.541,0:08:06.154 I'm not sure exactly how much. 0:08:06.154,0:08:07.927 One of the subjects here was my mother-in-law, 0:08:07.927,0:08:10.879 and clearly I do not know her age. 0:08:10.879,0:08:14.311 But certainly in people older than my wife, 0:08:14.311,0:08:17.444 this appears to be a more marked effect. 0:08:17.444,0:08:18.695 And the other thing I should mention 0:08:18.695,0:08:20.751 was there was no change in vitamin D. 0:08:20.751,0:08:22.871 This is separate from vitamin D. 0:08:22.871,0:08:24.407 So vitamin D is good for you -- it stops rickets, 0:08:24.407,0:08:26.647 it prevents calcium metabolism, important stuff. 0:08:26.647,0:08:29.679 But this is a separate mechanism from vitamin D. 0:08:29.679,0:08:32.255 Now, one of the problems with looking at blood pressure 0:08:32.255,0:08:33.807 is your body does everything it can 0:08:33.807,0:08:35.390 to keep your blood pressure at the same place. 0:08:35.390,0:08:37.039 If your leg is chopped off and you lose blood, 0:08:37.039,0:08:39.944 your body will clamp down, increase the heart rate, 0:08:39.944,0:08:42.168 do everything it can to keep your blood pressure up. 0:08:42.168,0:08:45.144 That is an absolutely fundamental physiological principle. 0:08:45.144,0:08:46.951 So what we've next done 0:08:46.951,0:08:50.607 is we've moved on to looking at blood vessel dilatation. 0:08:50.607,0:08:52.104 So we've measured -- this is again, 0:08:52.104,0:08:57.432 notice no tail and hairless, this is a medical student. 0:08:57.432,0:09:00.050 In the arm, you can measure blood flow in the arm 0:09:00.050,0:09:03.282 by how much it swells up as some blood flows into it. 0:09:03.282,0:09:06.757 And what we've shown is that doing a sham irradiation -- 0:09:06.757,0:09:08.226 this is the thick line here -- 0:09:08.226,0:09:10.626 this is shining UV on the arm so it warms up 0:09:10.626,0:09:13.450 but keeping it covered so the rays don't hit the skin. 0:09:13.450,0:09:17.362 There is no change in blood flow, in dilatation of the blood vessels. 0:09:17.362,0:09:19.211 But the active irradiation, 0:09:19.211,0:09:22.563 during the UV and for an hour after it, 0:09:22.563,0:09:24.660 there is dilation of the blood vessels. 0:09:24.660,0:09:27.260 This is the mechanism by which you lower blood pressure, 0:09:27.260,0:09:29.636 by which you dilate the coronary arteries also, 0:09:29.636,0:09:31.347 to let the blood be supplied with the heart. 0:09:31.347,0:09:35.740 So here, further data that ultraviolet -- that's sunlight -- 0:09:35.740,0:09:40.619 has benefits on the blood flow and the cardiovascular system. 0:09:40.619,0:09:42.962 So we thought we'd just kind of model -- 0:09:42.962,0:09:49.211 Different amounts of UV hit different parts of the Earth at different times of year, 0:09:49.211,0:09:53.235 so you can actually work out those stores of nitric oxide -- 0:09:53.235,0:09:55.491 the nitrates, nitrites, nitrosothiols in the skin -- 0:09:55.491,0:09:58.363 cleave to release NO. 0:09:58.363,0:10:02.188 Different wavelengths of light have different activities of doing that. 0:10:02.188,0:10:04.267 So you can look at the wavelengths of light that do that. 0:10:04.267,0:10:08.252 And you can look -- So, if you live on the equator, the sun comes straight overhead, 0:10:08.252,0:10:10.068 it comes through a very thin bit of atmosphere. 0:10:10.068,0:10:12.507 In winter or summer, it's the same amount of light. 0:10:12.507,0:10:15.020 If you live up here, in summer 0:10:15.020,0:10:17.676 the sun is coming fairly directly down, 0:10:17.676,0:10:20.983 but in winter it's coming through a huge amount of atmosphere, 0:10:20.983,0:10:24.204 and much of the ultraviolet is weeded out, 0:10:24.204,0:10:26.556 and the range of wavelengths that hit the Earth 0:10:26.556,0:10:28.884 are different from summer to winter. 0:10:28.884,0:10:30.826 So what you can do is you can multiply those data 0:10:30.826,0:10:32.819 by the NO that's released 0:10:32.819,0:10:36.003 and you can calculate how much nitric oxide 0:10:36.003,0:10:39.172 would be released from the skin into the circulation. 0:10:39.172,0:10:41.172 Now, if you're on the equator here -- 0:10:41.172,0:10:44.599 that's these two lines here, the red line and the purple line -- 0:10:44.599,0:10:48.996 the amount of nitric oxide that's released is the area under the curve, 0:10:48.996,0:10:51.027 it's the area in this space here. 0:10:51.027,0:10:53.724 So if you're on the equator, December or June, 0:10:53.724,0:10:56.980 you've got masses of NO being released from the skin. 0:10:56.980,0:10:59.444 So Ventura is in southern California. 0:10:59.444,0:11:01.660 In summer, you might as well be at the equator. 0:11:01.660,0:11:03.716 It's great. Lots of NO is released. 0:11:03.716,0:11:07.659 Ventura mid-winter, well, there's still a decent amount. 0:11:07.659,0:11:11.620 Edinburgh in summer, the area beneath the curve is pretty good, 0:11:11.620,0:11:15.835 but Edinburgh in winter, the amount of NO that can be released 0:11:15.835,0:11:19.693 is next to nothing, tiny amounts. 0:11:19.693,0:11:21.498 So what do we think? 0:11:21.498,0:11:23.090 We're still working at this story, 0:11:23.090,0:11:25.002 we're still developing it, we're still expanding it. 0:11:25.002,0:11:26.650 We think it's very important. 0:11:26.650,0:11:30.243 We think it probably accounts for a lot of the north-south health divide within Britain, 0:11:30.243,0:11:31.874 It's of relevance to us. 0:11:31.874,0:11:33.562 We think that the skin -- 0:11:33.562,0:11:36.450 well, we know that the skin has got very large stores 0:11:36.450,0:11:38.674 of nitric oxide as these various other forms. 0:11:38.674,0:11:40.547 We suspect a lot of these come from diet, 0:11:40.547,0:11:42.818 green leafy vegetables, beetroot, lettuce 0:11:42.818,0:11:46.138 has a lot of these nitric oxides that we think go to the skin. 0:11:46.138,0:11:48.282 We think they're then stored in the skin, 0:11:48.282,0:11:50.682 and we think the sunlight releases this 0:11:50.682,0:11:53.315 where it has generally beneficial effects. 0:11:53.315,0:11:55.794 And this is ongoing work, but dermatologists -- 0:11:55.794,0:11:57.514 I mean, I'm a dermatologist. 0:11:57.514,0:12:00.042 My day job is saying to people, "You've got skin cancer, 0:12:00.042,0:12:01.922 it's caused by sunlight, don't go in the sun." 0:12:01.922,0:12:04.658 I actually think a far more important message 0:12:04.658,0:12:08.082 is that there are benefits as well as risks to sunlight. 0:12:08.082,0:12:13.835 Yes, sunlight is the major alterable risk factor for skin cancer, 0:12:13.835,0:12:16.706 but deaths from heart disease are a hundred times higher 0:12:16.706,0:12:18.658 than deaths from skin cancer. 0:12:18.658,0:12:21.307 And I think that we need to be more aware of, 0:12:21.307,0:12:23.386 and we need to find the risk-benefit ratio. 0:12:23.386,0:12:24.858 How much sunlight is safe, 0:12:24.858,0:12:29.058 and how can we finesse this best for our general health? 0:12:29.058,0:12:31.238 So, thank you very much indeed. 0:12:31.238,0:12:38.135 (Applause)