So, before I became a dermatologist, I started in general medicine, as most dermatologists do in Britain. At the end of that time, I went off to Australia, about 20 years ago. What you learn when you go to Australia is the Australians are very competitive. And they are not magnanimous in victory. And that happened a lot: "You pommies, you can't play cricket, rugby." I could accept that.
Antes de facerme dermatólogo, comecei na medicina xeral, como fan moitos dermatólogos en Gran Bretaña. Ao rematar, fun a Australia, hai case vinte anos. Cando marchas a Australia aprendes que os australianos son moi competitivos. E non son magnánimos nas vitorias. E iso pasaba moito: "Ingleses, non sabedes xogar ao cricket, rugby...". Podía aceptar iso.
But moving into work -- and we have each week what's called a journal club, when you'd sit down with the other doctors and you'd study a scientific paper in relation to medicine. And after week one, it was about cardiovascular mortality, a dry subject -- how many people die of heart disease, what the rates are. And they were competitive about this: "You pommies, your rates of heart disease are shocking."
No relacionado ao traballo, temos semanalmente un club de lectura, onde sentas cos outros médicos e estudas unha publicación científica que teña relación coa medicina. O segundo encontro foi sobre a mortalidade cardiovascular, un tema complicado. As mortes por enfermidades cardíacas, cales son as taxas. E eran competitivos sobre isto:
And of course, they were right. Australians have about a third less heart disease than we do -- less deaths from heart attacks, heart failure, less strokes -- they're generally a healthier bunch. And of course they said this was because of their fine moral standing, their exercise, because they're Australians and we're weedy pommies, and so on.
"Ingleses, as vosas taxas de cardiopatías son tremendas." E certamente tiñan razón. Os australianos teñen un terzo menos de cardiopatías ca nós --menos mortes por ataques ao corazón, por insuficiencias cardíacas ou infartos. Adoitan ser máis sans. E claro, dicían que isto era pola súa superior integridade moral porque eles son australianos e nós frouxos inglesiños.
But it's not just Australia that has better health than Britain. Within Britain, there is a gradient of health -- and this is what's called standardized mortality, basically your chances of dying. This is looking at data from the paper about 20 years ago, but it's true today. Comparing your rates of dying 50 degrees north -- that's the South, that's London and places -- by latitude, and 55 degrees -- the bad news is that's here, Glasgow. I'm from Edinburgh. Worse news, that's even Edinburgh.
Pero non é só que teñan mellor saúde ca Gran Bretaña. En Gran Bretaña hai un gradiente de saúde, isto chámase mortalidade estandarizada, é dicir, as probabilidades de morrer. Estes son datos dos xornais de hai vinte anos, mais segue sendo certo hoxe. Se comparamosas taxas de mortalidade a 50 graos norte --esa frecha sinala o sur, Londres e contorna-- e a 55º norte, a mala noticia é que Glasgow é isto de aquí. Eu son de Edimburgo. Peores novas aínda en Edimburgo.
(Laughter)
(Risos)
So what accounts for this horrible space here between us up here in southern Scotland and the South? Now, we know about smoking, deep-fried Mars bars, chips -- the Glasgow diet. All of these things. But this graph is after taking into account all of these known risk factors. This is after accounting for smoking, social class, diet, all those other known risk factors. We are left with this missing space of increased deaths the further north you go.
Entón, que é o que pasa neste terrible espazo, aquí entre nós, no sur de Escocia, e o sur? Xa sabemos o dos fumadores, as barriñas Mars fritidas, as patacas... a dieta de Glasgow. Todo iso. Mais esta gráfica xa ten en conta, todos estes factores de risco coñecidos. Isto xa ten en conta fumadores, clase social, dieta, todos eses factores de risco coñecidos. Quédanos este espazo perdido, de mortes crecentes canto máis vaias ao norte.
Now, sunlight, of course, comes into this. And vitamin D has had a great deal of press, and a lot of people get concerned about it. And we need vitamin D. It's now a requirement that children have a certain amount. My grandmother grew up in Glasgow, back in the 1920s and '30s when rickets was a real problem and cod liver oil was brought in. And that really prevented the rickets that used to be common in this city. And I as a child was fed cod liver oil by my grandmother. I distinctly -- nobody forgets cod liver oil.
A luz do sol, por suposto, inflúe. A vitamina D tivo moi mala prensa, e moita xente preocúpase por ela. E precisamos a vitamina D. Agora é unha obriga que os nenos teñan unha cantidade concreta. Miña avoa medrou en Glasgow, alá polo 1920 e os anos 30, cando o raquitismo era un gran problema e chegou o aceite de fígado de bacallau. Iso solucionou o raquitismo que era tan común nesta cidade. A min, de pequeno, miña avoa fíxome tomar este aceite.
But an association: The higher people's blood levels of vitamin D are, the less heart disease they have, the less cancer. There seems to be a lot of data suggesting that vitamin D is very good for you. And it is, to prevent rickets and so on. But if you give people vitamin D supplements, you don't change that high rate of heart disease. And the evidence for it preventing cancers is not yet great. So what I'm going to suggest is that vitamin D is not the only story in town. It's not the only reason preventing heart disease. High vitamin D levels, I think, are a marker for sunlight exposure, and sunlight exposure, in methods I'm going to show, is good for heart disease.
Obviamente... ninguén esquece nunca o aceite de fígado de bacallau. Unha cuestión: canto máis altos son os niveis de vitamina D na xente, menos cardiopatías e menos cancros teñen. Hai moitas estatísticas que indican que a vitamina D é boa para nós. E así é, para previr raquitismo e iso. Pero se lle dás á xente suplementos de vitamina D, non cambias esa alta taxa de cardiopatías. E as probas de que preveña o cancro aínda non son definitivas. Entón o que vou suxerir é que a vitamina D non é o único importante aquí. Non é a única razón que prevén unha cardiopatía. Niveis altos de vitamina D, penso eu, son indicadores da exposición á luz solar, e a exposición á luz solar, nos mecanismos que vou ensinar, é boa para as enfermidades do corazón.
Anyway, I came back from Australia, and despite the obvious risks to my health, I moved to Aberdeen. (Laughter) Now, in Aberdeen, I started my dermatology training. But I also became interested in research, and in particular I became interested in this substance, nitric oxide. Now these three guys up here, Furchgott, Ignarro and Murad, won the Nobel Prize for medicine back in 1998. And they were the first people to describe this new chemical transmitter, nitric oxide. What nitric oxide does is it dilates blood vessels, so it lowers your blood pressure. It also dilates the coronary arteries, so it stops angina.
En calquera caso, volvín de Australia e, a pesar dos obvios riscos para a miña saúde, mudeime a Aberdeen, (Risos) Agora, en Aberdeen, comecei a miña formación como dermatólogo. Pero tamén me interesei na investigación, e sobre todo nesta substancia, o óxido nítrico (NO). Estes tres tipos de aquí, Furchfott, Ignarro e Murad, gañaron o Premio Nobel de Medicina en 1998. Foron as primeiras persoas en describir este novo transmisor químico, o óxido nítrico. O óxido nítrico (NO) dilata os vasos sanguíneos, así baixa a túa presión sanguínea. Tamén dilata as arterias coronarias, co que detén as anxinas.
And what was remarkable about it was in the past when we think of chemical messengers within the body, we thought of complicated things like estrogen and insulin, or nerve transmission. Very complex processes with very complex chemicals that fit into very complex receptors. And here's this incredibly simple molecule, a nitrogen and an oxygen that are stuck together, and yet these are hugely important for [unclear] our low blood pressure, for neurotransmission, for many, many things, but particularly cardiovascular health.
E o que é máis impresionante del é que no pasado, cando pensabamos en mensaxeiros químicos dentro do corpo, pensabamos en cousas complicadas como estróxeno e insulina, ou a transmisión nerviosa. Procesos moi complexos con substancias químicas moi complexas que encaixan en receptores moi complexos. E velaquí esta molécula incriblemente simple, un nitróxeno e un osíxeno pegados, que son tamén moi importantes para manter baixa a presión arterial, para a neurotransmisión e para outras moitas cousas, especialmente para a saúde cardiovascular.
And I started doing research, and we found, very excitingly, that the skin produces nitric oxide. So it's not just in the cardiovascular system it arises. It arises in the skin. Well, having found that and published that, I thought, well, what's it doing? How do you have low blood pressure in your skin? It's not the heart. What do you do?
Comecei a investigar e descubrimos, de xeito moi emocionante, que a pel produce óxido nítrico. Así que non xorde só no sistema cardiovascular. Xorde na pel. Despois de descubrilo e publicalo pensei, que é o que fai? Como tes baixa presión arterial na pel? Non é o corazón. Que facemos logo?
So I went off to the States, as many people do if they're going to do research, and I spent a few years in Pittsburgh. This is Pittsburgh. And I was interested in these really complex systems. We thought that maybe nitric oxide affected cell death, and how cells survive, and their resistance to other things. And I first off started work in cell culture, growing cells, and then I was using knockout mouse models -- mice that couldn't make the gene. We worked out a mechanism, which -- NO was helping cells survive.
Marchei aos Estados Unidos, como fai moita xente que quere investigar, e pasei uns poucos anos en Pittsburgh. Velaí Pittsburgh. Interesábanme estes sistemas tan complexos. Pensabamos que o óxido nítrico podía afectar á morte das células, a como sobreviven e á súa resistencia a máis cousas. Entón comecei a traballar no cultivo de células, e usei modelos de rato "knockout" --ratos con xenes desactivados-- Traballamos nun mecanismo en que o NO lles axudaba ás células a sobrevivir.
And I then moved back to Edinburgh. And in Edinburgh, the experimental animal we use is the medical student. It's a species close to human, with several advantages over mice: They're free, you don't shave them, they feed themselves, and nobody pickets your office saying, "Save the lab medical student." So they're really an ideal model.
Daquela mudeime outra vez a Edimburgo. Alí o animal de laboratorio que usamos foi o estudante de medicina É unha especie próxima ao ser humano, con moitas vantaxes sobre os ratos: son libres, non os tes que afeitar nin alimentar, e ninguén se manifesta diante do despacho dicindo "Salva ao estudante de medicina de laboratorio". Polo que son un coello de indias ideal.
But what we found was that we couldn't reproduce in man the data we had shown in mice. It seemed we couldn't turn off the production of nitric oxide in the skin of humans. We put on creams that blocked the enzyme that made it, we injected things. We couldn't turn off the nitric oxide.
Atopamos que non podiamos reproducir en persoas os datos recollidos dos ratos. Parecía que non podiamos frear a xeración do óxido nítrico na pel humana. Puxémoslles cremas para bloquear o encima que o xeraba, inxectámoslles cousas. Non podiamos parar o óxido nítrico.
And the reason for this, it turned out, after two or three years' work, was that in the skin we have huge stores not of nitric oxide, because nitric oxide is a gas, and it's released -- (Poof!) -- and in a few seconds it's away, but it can be turned into these forms of nitric oxide -- nitrate, NO3; nitrite, NO2; nitrosothiols. And these are more stable, and your skin has got really large stores of NO. And we then thought to ourselves, with those big stores, I wonder if sunlight might activate those stores and release them from the skin, where the stores are about 10 times as big as what's in the circulation. Could the sun activate those stores into the circulation, and there in the circulation do its good things for your cardiovascular system?
A razón era --descubrímolo despois de dous ou tres anos de traballo-- que na pel temos uns enormes almacéns, non de óxido nítrico, que é un gas, e logo de liberado... puf! Nuns segundos desaparece, mais pode encontrarse noutras formas: nitrato (NO3), nitrito (NO2), tionitritos. Estes son máis estables, e a túa pel ten enormes almacéns de NO. Despois pensamos, se estes almacéns, poderían ser activados pola luz solar para liberar o óxido desde a pel, onde os almacéns son dez veces máis grandes do que son na circulación. Podería o sol activar estes almacéns cara á circulación, e aí, na circulación, facer cousas boas para o sistema cardiovascular?
Well, I'm an experimental dermatologist, so what we did was we thought we'd have to expose our experimental animals to sunlight. And so what we did was we took a bunch of volunteers and we exposed them to ultraviolet light. So these are kind of sunlamps. Now, what we were careful to do was, vitamin D is made by ultraviolet B rays and we wanted to separate our story from the vitamin D story. So we used ultraviolet A, which doesn't make vitamin D.
Ben, eu son dermatólogo experimental, e o que fixemos foi pensar que debiamos expoñer os coellos de indias á luz solar. Así que collemos unha serie de voluntarios e expuxémolos á luz ultravioleta. Son unha especie de lámpadas solares. Agora ben, fomos coidadosos co seguinte, a vitamina D está feita de raios ultravioleta B e queriamos separar o noso estudo do estudo da vitamina D Así que usamos ultravioleta A, que non xera vitamina D.
When we put people under a lamp for the equivalent of about 30 minutes of sunshine in summer in Edinburgh, what we produced was, we produced a rise in circulating nitric oxide. So we put patients with these subjects under the UV, and their NO levels do go up, and their blood pressure goes down. Not by much, as an individual level, but enough at a population level to shift the rates of heart disease in a whole population. And when we shone UV at them, or when we warmed them up to the same level as the lamps, but didn't actually let the rays hit the skin, this didn't happen. So this seems to be a feature of ultraviolet rays hitting the skin.
Cando puxemos xente baixo a lámpada durante o equivalente a 30 minutos de sol no verán en Edimburgo, o que producimos foi un crecemento na circulación de óxido nítrico. Entón, ao poñer estes suxeitos baixo a luz ultravioleta, os seus niveis de NO medraron, e a súa presión arterial diminuíu. Non moito, a nivel individual, pero abondo a nivel poboacional, como para cambiar as taxas de enfermidades cardíacas en toda a poboación. Cando lles diriximos raios ultravioleta, ou cando os quentabamos ao mesmo nivel que as propias lámpadas, impedindo que os raios acadaran a pel, iso non sucedía. Parece ser unha característica dos raios ultravioleta cando acadan a pel.
Now, we're still collecting data. A few good things here: This appeared to be more marked in older people. I'm not sure exactly how much. One of the subjects here was my mother-in-law, and clearly I do not know her age. But certainly in people older than my wife, this appears to be a more marked effect. And the other thing I should mention was there was no change in vitamin D. This is separate from vitamin D. So vitamin D is good for you -- it stops rickets, it prevents calcium metabolism, important stuff. But this is a separate mechanism from vitamin D.
Agora aínda estamos recollendo datos. Algunhas cousas boas: O efecto é máis pronunciado nas persoas maiores. Non sei canto exactamente. Aquí, un dos suxeitos foi miña sogra, de quen, obviamente, non sei a idade. Mais certamente en xente maior que a miña muller, este parece ser un efecto máis pronunciado. Outra cousa que debo mencionar é que non houbo cambios na vitamina D. Isto é independente da vitamina D. Así que a vitamina D é boa para ti: frea o raquitismo, prevén o metabolismo do calcio, etc. Mais isto é un mecanismo independente da vitamina D.
Now, one of the problems with looking at blood pressure is your body does everything it can to keep your blood pressure at the same place. If your leg is chopped off and you lose blood, your body will clamp down, increase the heart rate, do everything it can to keep your blood pressure up. That is an absolutely fundamental physiological principle.
Un problema coa presión arterial é que o corpo fai todo o que precisa, para manter estable a presión arterial. Se che cortan a perna e perdes sangue, o corpo toma medida:, incrementa o ritmo do corazón, fai todo o posible para manter a presión arterial. É un principio fisiolóxico fundamental.
So what we've next done is we've moved on to looking at blood vessel dilatation. So we've measured -- this is again, notice no tail and hairless, this is a medical student. In the arm, you can measure blood flow in the arm by how much it swells up as some blood flows into it. And what we've shown is that doing a sham irradiation -- this is the thick line here -- this is shining UV on the arm so it warms up but keeping it covered so the rays don't hit the skin. There is no change in blood flow, in dilatation of the blood vessels. But the active irradiation, during the UV and for an hour after it, there is dilation of the blood vessels. This is the mechanism by which you lower blood pressure, by which you dilate the coronary arteries also, to let the blood be supplied with the heart. So here, further data that ultraviolet -- that's sunlight -- has benefits on the blood flow and the cardiovascular system.
O que fixemos despois foi comezar a observar a dilatación dos vasos sanguíneos. Medimos --fíxense que sen cola e sen pelo, este é un estudante de medicina. (Risos) No brazo, pódese medir o fluxo sanguíneo, calculando o que este incha cando o sangue o atravesa. Demostramos que facendo unha irradiación simulada, nesta liña máis grosa, radiando raios ultravioleta no brazo para quentalo, manténdoo cuberto para que os raios non acaden a pel, non hai cambio no fluxo sanguíneo, na dilatación dos vasos sanguíneos. Pola contra, a irradiación activa, durante a radiación ultravioleta e ata unha hora despois , provoca dilatación dos vasos sanguíneos. Este é o mecanismo polo que a presión arterial baixa, polo que se dilatan as arterias coronarias, para que o corazón subministre sangue. Aquí hai máis datos sobre os raios ultravioleta (UV), a luz solar, que ten beneficios no fluxo sanguíneo e no sistema cardiovascular.
So we thought we'd just kind of model -- Different amounts of UV hit different parts of the Earth at different times of year, so you can actually work out those stores of nitric oxide -- the nitrates, nitrites, nitrosothiols in the skin -- cleave to release NO. Different wavelengths of light have different activities of doing that. So you can look at the wavelengths of light that do that. And you can look -- So, if you live on the equator, the sun comes straight overhead, it comes through a very thin bit of atmosphere. In winter or summer, it's the same amount of light. If you live up here, in summer the sun is coming fairly directly down, but in winter it's coming through a huge amount of atmosphere, and much of the ultraviolet is weeded out, and the range of wavelengths that hit the Earth are different from summer to winter. So what you can do is you can multiply those data by the NO that's released and you can calculate how much nitric oxide would be released from the skin into the circulation.
Pensamos que conseguiramos un modelo, diferentes cantidades de UV acadan a Terra en diferentes momentos do ano, así pódense activar os almacéns de óxido nítrico, os nitratos, nitritos, tionitritos na pel... descompostos para liberar NO. Diferentes lonxitudes de onda da luz teñen diferentes mecanismos para facelo. Pódese ver a lonxitude de onda da luz que o fai. Pódese observar que se vives no ecuador, o sol chega xusto sobre a cabeza, atravesa unha capa fina de atmosfera. A cantidade de luz é a mesma no inverno e no verán. Se vives aquí no norte, no verán o sol chega directamente, pero no inverno atravesa unha gran cantidade de atmosfera, e moitos dos raios ultravioleta desfanse, e o rango das lonxitudes de onda que golpean a Terra é diferente no verán e no inverno. Entón podes multiplicar estes datos polo NO que se libera e podes calcular canto sería liberado pola pel na circulación.
Now, if you're on the equator here -- that's these two lines here, the red line and the purple line -- the amount of nitric oxide that's released is the area under the curve, it's the area in this space here. So if you're on the equator, December or June, you've got masses of NO being released from the skin. So Ventura is in southern California. In summer, you might as well be at the equator. It's great. Lots of NO is released. Ventura mid-winter, well, there's still a decent amount. Edinburgh in summer, the area beneath the curve is pretty good, but Edinburgh in winter, the amount of NO that can be released is next to nothing, tiny amounts.
Agora ben, se vives no ecuador, nestas dúas liñas de aquí, as liñas vermella e violeta, a cantidade de óxido nítrico que se libera é a área baixo a curva, a área neste espazo de aquí. Entón se estás no ecuador, en decembro ou en xuño, libéranse grandes cantidades de NO da pel. Na cidade de Ventura, no sur de California, o verán pode ser tal e como é no ecuador. É xenial. Libérase un montón de NO. Ventura, na metade do inverno, hai aínda unha boa cantidade. En Edimburgo, no verán, a área baixo a curva é bastante boa, mais Edimburgo no inverno, a cantidade de NO que pode ser liberada é case nula, pequenas cantidades.
So what do we think? We're still working at this story, we're still developing it, we're still expanding it. We think it's very important. We think it probably accounts for a lot of the north-south health divide within Britain, It's of relevance to us. We think that the skin -- well, we know that the skin has got very large stores of nitric oxide as these various other forms. We suspect a lot of these come from diet, green leafy vegetables, beetroot, lettuce has a lot of these nitric oxides that we think go to the skin. We think they're then stored in the skin, and we think the sunlight releases this where it has generally beneficial effects.
Entón que pensamos? Seguimos traballando no estudo, estamos desenvolvéndoo e expandíndoo. Pensamos que é moi importante. É probable que explique o gradiente de saúde entre o norte-sur do Reino Unido, É relevante para nós. Pensamos que a pel, sabemos que a pel ten grandes almacéns de óxido nítrico baixo formas diversas. Sospeitamos que isto procede da dieta, vexetais de folla verde, remolacha e leituga, teñen moitos destes óxidos de nitróxeno que pensamos que van á pel. Pensamos que están almacenados na pel, e pensamos que a luz solar os libera, onde teñen, polo xeral, efectos beneficiosos.
And this is ongoing work, but dermatologists -- I mean, I'm a dermatologist. My day job is saying to people, "You've got skin cancer, it's caused by sunlight, don't go in the sun." I actually think a far more important message is that there are benefits as well as risks to sunlight. Yes, sunlight is the major alterable risk factor for skin cancer, but deaths from heart disease are a hundred times higher than deaths from skin cancer. And I think that we need to be more aware of, and we need to find the risk-benefit ratio. How much sunlight is safe, and how can we finesse this best for our general health?
Isto é un traballo en curso, pero os dermatólogos, é dicir, eu son un dermatólogo. O meu traballo diario é dicirlle á xente: "Tes cancro de pel por culpa da luz solar, non te poñas ao sol". Penso que unha mensaxe realmente máis importante é que a luz solar produce beneficios e riscos. Si, a luz solar é o principal factor de risco modificable de cancro de pel, pero hai centos de veces máis mortes por enfermidades do corazón ca por cancro de pel. Creo que necesitamos ser máis conscientes disto, e atopar a relación de risco-beneficio. Canta luz solar é segura, e como podemos axustar mellor isto para a nosa saúde xeral?
So, thank you very much indeed. (Applause)
Moitas grazas, de verdade. (Aplausos)