Så, inden jeg blev hudlæge, startede jeg i almen medicin, som de fleste hudlæger i England gør. Derefter tog jeg til Australien, for cirka 20 år siden. Det man lærer når man tager til Australien er at asutraliere er utrolige konkurrencemennesker. Og de er ikke storsindede med deres sejr. Og det skete ofte: "I britter, I kan ikke spille cricket, rugby." Det kunne jeg acceptere.
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.
Men med hensyn til arbejde -- og hver uge er der det der hedder en journal klub, hvor man sidder ned med de andre læger og gennemgår en videnskabelig artikel relateret til medicin. Og efter den første uge, handlede det om kardiovaskulær mortalitet, et tørt emne -- om hvor mange mennesker dør af hjertelidelser, om hvad raten er. Og de var konkurrencemindede omrking dette: "I britter, jeres antal af hjertelidelser er chokerende."
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."
Og selvfølgelig havde de ret. Australiere har omkring en tredjedel færre hjertelidelser end vi har -- færre dødsfald af hjerteanfald, hjerte fejl, færre slagtilfælde -- de er generelt set et sundere slæng. Og selvfølgelig sagde de at dette var på grund af deres gode moral, deres motion, fordi de er australiere og vi er splejsede britter, og så videre.
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.
Men det er ikke kun Australien der har bedre helbred end England. Indenfor Storbritanien, er der grader af helbred -- og det er det der hedder standardiseret mortalitet, som dybest set er ens chancer for at dø. Her ser vi på data fra en artikel fra omkring 20 år siden, men det er stadig sandt i dag. Sammenlignet med ens rate for at dø 50 grader nord -- det er syden, det er London og sådanne steder -- i breddegrader, og 55 grader -- de dårlige nyheder er, at her, Glasgow. Jeg kommer fra Edinburgh. Dårligere nyt, det er selv Edinburgh.
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.
(Latter)
(Laughter)
Så hvad er det, der gør rede for dette forfærdelige sted her mellem os heroppe i det sydlige Skotland og syden? Men, vi kender til rygning, dybfrosne Mars, chips -- Glasgow kosten. Alle disse ting. Men denne graf tager hensyn til alle disse kendte risikofaktorer. Den tager hensyn til rygning, social klasse, kost, alle de kendte risikofaktorer. Tilbage er dette manglende stykke med et forhøjet dødsantal jo længere nordpå man kommer.
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.
Men, sollys, selvfølgelig, kommer ind i dette. Og vitamin D har fået en masse presseomtale, og mange mennesker er bekymret over det. Og vi har brug for D vitamin. Det er nu et krav at børn får en bestemt mængde. Min bedstemor voksede op i Glasgow, tilbage i 1920'erne og 30'erne da rakitis var et virkeligt problem og torske-levertran blev introduceret. Og det afværgede virkelig rakitis der plejede at være almindeligt i byen. Og som barn blev jeg fodret med torske-levertran af min bedstemor. Jeg husker tydeligt -- ingen glemmer torske-levertran.
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.
Men en association: Jo højere menneskers indhold af D vitamin i blodet er, jo færre hjertelidelser har der, mindre kræft. Det lader til, at der er meget data, der antyder at D vitamin er meget sundt for en. Og det er det, for at forhindre rakitis og så videre. Men hvis man giver mennesker D vitamn tilskud, ændrer man ikke den høje rate af hjertelidelser. Og beviset på at det forhindrer kræft er endnu ikke overbevisende. Så det jeg vil foreslå er at D vitamin ikke er den eneste historie i byen. Det er ikke den eneste grund der forhindrer hjertelidelser. Høje D vitamin niveauer, tror jeg, er en markør for eksponering for sollys, og eksponering for sollys, på de måder som jeg vil vise, er godt for hjertelidelser.
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.
Hvorom alt er, jeg kom tilbage fra Australien, og på trods af de åbenlyse ricisi imod mit helbred, flyttede jeg til Aberdeen. (Latter) Så, i Aberdeen startede jeg min dermatolog uddannelse. Men jeg blev også interesseret i forskning, og jeg blev især interesseret i denne substans, nitrogenmonoxid. Så disse fyre heroppe, Furchgott, Ignarro og Murad, vandt Nobel prisen i medicin tilbage i 1998. Og de var de første mennesker til at beskrive denne nye kemiske sender, nitrogenmonoxid. Det nitrogenmonoxid gør er, at det udvider blodkarene, så det sænker ens blodtryk. Det udvider også hjerte pulsårene, så det stopper hjertekrampe.
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.
Og det der var bemærkelsesværdigt ved det var at da vi før i tiden tænkte på kemiske sendere i kroppen, tænkte vi på komplicerede ting som østrogen og insulin, eller nerve transmission. Meget komplekse processer med meget komplekse kemikalier det passer ind i meget komplekse receptorer. Og her er dette utrolig simple molekule, et nitrogen og et oxygen der er sat sammen, og alligevel er disse utrolig vigtige for [utydeligt] vores lave blodtryk, for neurotransmission, for mange, mange ting, men i særdeleshed for vores kardiovaskulære helbred.
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.
Og jeg begyndte at forske, og vi fandt ud af, meget spændende, at huden producerer nitrogenmonoxid. Så det er ikke kun i det kardiovaskulære system at det opstår. Det opstår i huden. Jamen, efter at have fundet det og udgivet det, tænkte jeg, jamen, hvad gør det? Hvordan har man et lavt blodtryk i huden? Det er ikke hjertet. Hvad gør man?
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?
Så jeg tog til staterne, som mange mennesker gør hvis de vil lave forskning, og jeg tilbragte et par år i Pittsburgh. Dette er Pittsburgh. Og jeg var interesseret i disse meget komplekse systemer. Vi tænkte at nitrogenmonoxid måske påvirkede celledød, og hvordan celler overlever, og deres modstand overfor andre ting. Og jeg begyndte - som det første - at arbejde med celle kulturer - at dyrke celler, og så brugte jeg hammerlækre musemodeller -- mus der ikke kunne lave genet. Vi udarbejdede en mekaniske, hvor -- nitrogenmonoxid hjalp cellerne med at overleve.
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.
Og så flyttede jeg tilbage til Edinburgh. Og i Edinburgh er det eksperimentelle dyr vi bruger de medicinstuderende. Det er en art tæt på mennesker, med adskillige fordele i forhold til mus: De er gratis, man barberer dem ikke, de fodrer sig selv, og ingen strejker ude foran ens kontor med, "Red de forsøgs-medicinstuderende." Så de er faktisk en ideel model.
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.
Men det vi fandt ud af var at vi i et menneske ikke kunne reproducere de data vi havde vist i mus. Det virkede som om at vi ikke kunne slukke for produktionen af nitrogenmonoxid i menneskers hud. Vi puttede creme på, der blokkerede det enzym der producerer det, vi indsprøjtede ting. Vi kunne ikke slukke for nitrogenmonoxiden.
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.
Og grunden til dette, viste det sig, efter to eller tre års arbejde, var at vi i huden har kæmpestore depoter ikke af nitrogenmonoxid, fordi nitrogenmonoxid er en gas, og den bliver udløst -- (Poof!) -- og efter få sekunder er den væk, men den kan ændres til disse former for nitrogenmonoxid -- nitrat, NO3; nitrit, NO2; nitrotioler. Og de er mere stabile, og ens hud har virkelig store depoter af nitrogenmonoxid. Og så tænkte vi for os selv, med de store depoter, gad vide om sollys aktiverer de depoter og frigør dem fra huden, hvor depoterne er omkring 10 gange så store, som det der er i cirkulation. Kunne solen aktivere de depoter til cirkulationen, og der - i cirkulationen - gøre gode ting for ens kardiovaskulære system?
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?
Jamen, jeg er eksperimentel dermatolog, så det vi gjorde var, at vi tænkte at vi skulle udsætte vores forsøgsdyr for sollys. Så det vi gjorde var, at vi tog en stak frivillige og vi udsatte dem for ultraviolet lys. Så dette er en slags sollamper. Så, det vi var forsigtige med at gøre var, D vitamin er lavet af ultraviolette B stråler og vi ville separere vores historie fra D vitamin historien. Så vi brugte ultraviolet A, som ikke laver D vitamin.
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.
Da vi satte mennesker under en lampe til det der svarede til 30 minutters sollys om sommeren i Edinburgh, det vi frembragte var, vi frembragte en stigning i den cirkulerende nitrogenmonoxid. Så vi satte patienter sammen med disse forsøgspersoner under en UV lampe, og deres nitrogenmonoxid niveauer stiger, og deres blodtryk falder. Ikke med meget, på et individuelt niveau, men nok på befolknings niveau til at flytte raterne på hjertelidelse i hele befolkningen. Og når vi skinnede UV stråler på dem, eller når vi varmede dem op til samme niveau som lamperne, men faktisk ikke lod strålerne ramme huden, skete dette ikke. Så det ser ud til at være en egenskab ved ultraviolette stråler der rammer huden.
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.
Men, vi indsamler stadig data. Et par gode ting her: Dette lod til at være mere markant hos ældre mennesker. Jeg er ikke sikker på præcis hvor meget. En af forsøgspersonerne her var min svigermor, og jeg kender selvfølgelig ikke hendes alder.(latter) Men hos mennesker, der er ældre end min kone, ser dette ud til at have en mere markant effekt. Og den anden ting jeg bør nævne er, at der ikke var nogen ændring i D vitaminet. Dette er separat fra D vitamin. Så D vitamin er godt for en -- det stopper rakitis, det forhindrer kalcium metabolisme, vigtige ting. Men dette er en separat mekanisme fra D vitaminet.
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.
Men, et af problemerne ved at se på blodtrykket er at ens krop gør alt hvad den kan for at holde ens blodtryk på det samme niveau. Hvis ens ben bliver hugget af og man mister blod, vil ens krop spænde sig, sætte pulsen op, gøre alt hvad den kan for at holde ens blodtryk oppe. Det er et absolut fundamentalt fysiologisk princip.
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.
Så det vi gjorde bagefter er at vi begyndte på at kigge på udvidelsen af blodkarene. Så vi har målt -- dette er igen, læg mærke til ingen hale og ingen hår. Dette er en medicinstuderende. I armen, kan man måle blod gennemstrømningen ved hvor meget den svulmer op, når der flyder noget blod i den. Og det vi har vist er, at lave en falsk bestråling -- det er denne tykke linje her -- den skinner UV på armen så den varmes op men holdes dækket, så strålerne ikke rammer huden. Der er ikke nogen ændring i blodgennemstrømningen, eller i udvidelsen af blodkarene. Men den aktive stråling, i løbet af UV og i en time derefter, er der en udvidelse af blodkarene. Dette er mekanismen hvormed man sænker blodtrykket, hvormed man også udvider hjerte pulsårene, for at lade blodet blive forsynet til hjertet. Så her, mere data, at ultraviolet -- det er sollys -- har fordele for blodgennemstrømningen og det kardiovaskulære system.
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.
Så vi tænkte at vi ville lave en model -- Forskellige mængder UV rammer forskellige dele af jorden på forskellige tider af året, så man kan faktisk træne de nitrogenmonoxid depoter -- nitraterne, nitriterne, nitrosotiolerne i huden -- bane sig vej for at frigive NO. Forskellige bølgelængder af lys har forskellige måder at gøre det ved. Så man kan se på bølgelængderne af lys der gør det. Og man kan se -- Så, hvis man bor på ækvator, kommer solen lige ovenover hovedet, den kommer gennem et meget tyndt lag atmosfære. I vinter eller sommer, er det den samme mængde lys. Hvis man lever heroppe, om sommeren kommer solen temmelig direkte ned, men om vinteren kommer den igennem en kæmpe mængde atmosfære, og meget af det ultraviolette bliver siet fra, og rækkeviden af bølgelængderne der rammer jorden er forskellige om vinteren og sommeren. Så det man kan gøre er, at man kan gange den data med den NO der er frigivet og man kan beregne hvor meget nitrogenmonoxid der ville blive løsladt fra huden ind i cirkulation.
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.
Men, hvis man er på ækvator her -- det er de to linjer her, den røde linje og den lila linje -- mængden af nitrogenmonoxid der bliver frigivet er området under kurven, det er området i dette mellemrum her. Så hvis man er på ækvator, december eller juni, der er masser af NO der bliver frigivet fra huden. Så Ventura ligger i det sydlige Californien. Om sommeren, man kunne lige så vel være på ækvator. Det er fedt. Der bliver frigivet masser af NO. Ventura midt om vinteren, jamen, der er stadig en pæn mængde. Edinburgh om sommeren, området under curven er temmelig godt, men i Edinburgh om vinteren, er mængden af NO der kan blive frigivet nærmest ingenting, bittesmå mængder.
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.
Så hvad mener vi? Vi arbejder stadig på denne historie, vi udvikler den stadig, vi udvider den stadig. Vi mener det er meget vigtigt. Vi mener det sandsynligvis forklarer meget af helbreds- skellet af nord og syd indenfor Storbritannien. Det er relevant for os. Vi mener at huden -- jamen, vi ved at huden har meget store depoter af nitrogenmonoxid ved disse andre forskellige former. Vi mistænker at meget af det kommer fra kosten, grønne bladrige grøntsager, rødbeder, salat har mange af disse nitrogenmonoxider som vi mener går til huden. Vi mener at de bliver opbevaret i huden, og vi mener at sollyset frigiver dette hvor det generelt set har gavnlige effekter.
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.
Og dette er løbende arbejde, men dermatologer -- Jeg mener, jeg er dermatolog. Mit almindelige arbejde er at sige til mennesker, "Du har hudkræft, det er forårsaget af sollys, gå ikke ud i solen." Jeg mener faktisk at et meget vigtigere budskab er at der er fordele lige så vel som risici ved sollys. Ja, sollys er den store justerbare risicofaktor for hudkræft, men antallet af døde af hjertelidelser er hundrede gange højere end antallet af døde af hudkræft. Og jeg mener at vi skal være mere klar over, at vi har brug for at finde risiko-gavn raten. Hvor meget sollys er sikkert, og hvordan kan vi optimere dette på den bedste måde for vores generelle helbred?
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?
Så, bestemt mange tak. (Bifald)
So, thank you very much indeed. (Applause)