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