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.
Prije no što sam postao dermatolog, započeo sam se baviti općom medicinom, poput većine dermatologa u Britaniji. Na kraju tog razdoblja, otišao sam u Australiju. Prije 20-ak godina. U Australiji naučite da su Australci vrlo kompetitivni. I nisu velikodušni u pobjedi. Puno se puta to događalo... "Vi, dotepenci britanski, ne znate igrati kriket, ragbi..." To sam mogao prihvatiti.
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."
Ali... prijeđimo na posao... Svakog tjedna okupljamo se u tzv. znanstvenom klubu, gdje mi, liječnici, međusobno razgovaramo i proučavamo znanstvene radove iz medicinskog područja. Drugog tjedna... Tema je bila smrtnost od kardiovaskularnih bolesti. Suhoparno područje! Koliko ljudi umire od srčanih bolesti, kolike su stope smrtnosti...? I u tome su bili natjecateljski raspoloženi... "Vi, dotepenci britanski, vaše stope srčanih bolesti su šokantne!
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.
I, naravno, bili su u pravu. Australci imaju oko trećinu manje srčanih bolesti od nas. Manje smrtnih slučajeva od srčanog udara, zatajenja srca, manje moždanih udara... Općenito su zdravija družina. I, naravno, rekli su da je to zbog njihovih visokih moralnih gledišta, njihovog vježbanja, jer oni su Australci, a mi smo pripiti britanski dotepenci,...
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.
Ali, nije Australija jedina zemlja u kojoj su ljudi boljeg zdravlja od Britanaca. U Velikoj Britaniji, koristimo se tzv. gradijentom zdravlja - to je ono što se naziva standardiziranom stopom smrtnosti - u osnovi, vjerojatnost da ćete umrijeti. Ovo su podaci iz istraživanja od prije 20-ak godina, ali vrijede i danas. Uspoređujući stope umiranja na 50 stupnjeva sjeverne zemljopisne širine - to je jug... London, i obližnja mjesta - s onima na 55 stupnjeva... Loša vijest je da je to ovdje - Glasgow. Ja sam iz Edinburgha. Još gora vijest - to je čak i Edinburgh.
(Laughter)
(Smijeh)
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.
Kako objasniti ovu strašnu razliku između nas ovdje gore, na jugu Škotske, i ljudi na jugu Engleske? O pušenju sve znamo, o prženim čokoladicama, čipsu, prehrani u Glasgowu.... O svim tim stvarima. Ali, ovaj prikaz uzima u obzir sve te poznate rizične čimbenike: i pušenje, i društvenu klasu, prehranu, i sve ostale poznate rizične čimbenike. No, nedostaje nam i dalje razlog povećane smrtnosti što dalje idemo prema sjeveru.
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.
Naravno, ne zaboravimo na Sunčevu svjetlost... O vitaminu D je u tisku bilo puno govora, i zainteresirano je mnogo ljudi. Nama je vitamin D potreban! Danas ga djeca moraju imati u određenoj količini. Moja je baka odrasla u Glasgowu, 1920-ih i 30-ih kada je rahitis bio istinski problem, i kad je u liječenje uvedeno bakalarevo jetreno ulje. To je doista zaustavilo rahitis, dotad uobičajen u ovom gradu. I mene je moja baka u djetinjstvu hranila bakalarevim jetrenim uljem. Jako se dobro sjećam... nitko ne zaboravlja bakalarevo jetreno ulje!
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.
Jedna asocijacija: što je viša razina vitamina D u krvi, rjeđe su srčane bolesti, rjeđi je rak. Čini se da dosta podataka ukazuje da je vitamin D vrlo dobar za sve nas. I jest, za sprečavanje rahitisa i sličnih bolesti... No, prepisujete li ljudima dodatke vitaminu D, ne smanjujete tu visoku stopu srčanih bolesti. I dokazi da oni sprečavaju nastanak raka još uvijek nisu uvjerljivi. Zato bih naglasio da vitamin D nije jedino o čemu vrijedi govoriti. On nije jedino što sprečava pojavu srčanih bolesti. Smatram da je visoka razina vitamina D pokazatelj izlaganja suncu, a izlaganje suncu, u postupcima koje ću prikazati, blagotvorno je za srčane bolesti.
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.
Kako god, vrativši se iz Australije, i unatoč očitim rizicima za moje zdravlje, preselio sam se u Aberdeen. (Smijeh) U Aberdeenu sam započeo s dermatološkom izobrazbom. Međutim, zainteresirao sam se i za istraživanje, i to osobito dušikovog oksida. Ova trojica ovdje, Furchgott, Ignarro i Murad, osvojila su Nobelovu nagradu za medicinu 1998. Oni su bili prvi koji su opisali ovaj novi kemijski prijenosnik - dušikov oksid. Dušikov oksid proširuje krvne žile snižavajući tako krvni tlak. Proširuje i srčane arterije, onemogućavajući tako anginu.
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.
S time u vezi, značajno je da smo nekoć, sjetimo li se kemijskih glasnika u tijelu, razmišljali o kompleksnim stvarima poput estrogena i inzulina, ili o živčanom prijenosu. Vrlo složeni procesi, s vrlo složenim kemikalijama, što se uklapaju u vrlo složene receptore. A ovdje je ta nevjerojatno jednostavna molekula, spoj dušika i kisika, no iznimno važna za snižavanje krvnog tlaka, za prijenos živčanih impulsa, za mnogo toga... Naročito za zdravlje krvožilnog sustava!
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?
Započeo sam s istraživanjima, i otkrili smo - vrlo uzbudljivo! - da koža proizvodi dušikov oksid. Dakle, ne pojavljuje se on samo u krvožilnom sustavu... Pojavljuje se u koži. Pošto smo to otkrili i objavili otkriće, pomislio sam: Dobro, a na što on utječe? Kako postići nizak krvni tlak u koži? Ne radi se o srcu. Što učiniti?
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.
Otišao sam u SAD, kao i mnogi ljudi koji se kane baviti istraživanjima, i proveo sam nekoliko godina u Pittsburghu. Ovo je Pittsburgh. Zanimali su me ovi doista složeni sustavi. Pomislili smo da dušikov oksid možda utječe na umiranje stanica, i na preživljavanje stanica, i na njihovu otpornost na razne tvari. Započeo sam raditi na staničnoj kulturi, na uzgoju stanica... Potom sam koristio mišje "knockout" modele - miševe koji nisu mogli stvoriti gen... Otkrili smo mehanizam prema kojemu dušikov oksid pomaže stanicama preživjeti.
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.
Onda sam se vratio u Edinburgh... A u Edinburghu, kao "laboratorijskog miša" koristimo - studenta medicine. To je vrsta bliska ljudskoj, s nekoliko prednosti u odnosu na miševe: besplatni su, nije ih potrebno brijati, sami se hrane, i nitko ne upada u vaš ured uz riječi: "Zaštitimo laboratorijskog studenta medicine!" Dakle, oni su stvarno idealni predlošci.
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.
Međutim, otkrili smo da na čovjeku ne možemo ponoviti nalaze koje smo dobili na miševima. Čini se da nismo mogli isključiti proizvodnju dušikovog oksida u koži ljudi. Stavljali smo kreme koje onemogućavaju enzim koji ga stvara, ubrizgavali smo koješta. Nismo mogli isključiti dušikov oksid.
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?
Nakon dvije ili tri godine rada, ispostavilo se da u koži imamo ogromne zalihe - ne dušikovog oksida, jer on je plin, i pušten... puf!... nema ga za par sekundi, ali može se pretvoriti u oblike dušikovog oksida: nitrate (NO3), nitrite (NO2), nitrozotiole. Oni su stabilniji. U našoj koži postoje uistinu velike zalihe dušikovog oksida. Kad su već zalihe tolike, pitali smo se može li ih Sunčeva svjetlost aktivirati i otpustiti ih iz kože u kojoj su one i 10-ak puta veće od onih u krvotoku. Može li Sunce te zalihe potaknuti ka krvotoku, i tako blagotvorno djelovati na krvožilni sustav?
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.
Kako sam ja eksperimentalni dermatolog, pomislili smo da ćemo morati naše "pokusne kuniće" izlagati suncu. Uzeli smo stoga hrpu dobrovoljaca i izlagali ih ultraljubičastom svjetlu. To su, znači, svojevrsne solarne svjetiljke. Pritom smo vodili računa o tome da ultraljubičaste B-zrake potiču stvaranje vitamina D, a ovaj smo svoj rad željeli odvojiti od teme vitamina D. Zato smo upotrebljavali ultraljubičaste A-zrake koje ne stvaraju vitamin 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.
Kad smo ljude izložili zrakama svjetiljke onoliko koliko je istovjetno 30-minutnom ljetnom sunčanju u Edinburghu, izazvali smo porast dušikovog oksida u krvi. Onda smo uključili i pacijente i njih izlagali ultraljubičastim zrakama; količine dušikovog oksida su i kod njih rasle, a krvni tlak je padao. Na individualnoj razini ne suviše, ali na razini populacije dovoljno da utječe na učestalost srčanih bolesti u cijeloj populaciji. Kad smo ih obasjavali ultraljubičastim zrakama, ili kad smo ih zagrijavali do temperature svjetiljki, ali smo onemogućili kontakt zraka i kože, to se nije dogodilo. Dakle, čini se da samo sraz ultraljubičastih zraka i kože dovodi do takvog učinka.
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.
Naravno, još prikupljamo podatke. Nekoliko je dobrih vijesti... Čini se da je to izraženije kod starijih ljudi. Nisam siguran točno koliko. Jedna od ispitanika bila je i moja punica, i, očito, ja ne znam koliko joj je godina. Ali, sigurno kod osoba starijih od moje supruge učinak se čini izrazitijim. Moram napomenuti da nije bilo promjene u razini vitamina D. Ovo nema veze s vitaminom D. Dakle, vitamin D je dobar za vas - zaustavlja rahitis, sprečava razgradnju kalcija, važnog elementa. No, ovdje se radi o procesu različitom od onoga kod 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.
Jedan od problema s krvnim tlakom je što tijelo čini sve što može da bi ga održalo. Ostanemo li bez noge i gubimo krv, tijelo će pooštriti kontrolu, ubrzati rad srca, učiniti sve što može kako bi održalo naš krvni tlak. To je apsolutno temeljno fiziološko načelo.
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.
Potom smo proučavali širenje krvnih žila. Mjerili smo... ovo je ponovno... vidite ćelavoga i bez repa, studenta medicine. Protok krvi u ruci moguće je izmjeriti po tome koliko ruka nabrekne uslijed dotoka krvi. Pokazali smo da lažno ozračivanje - to je ova debela crta ovdje - ovo je ultraljubičasto ozračivanje ruke, kojime ju se zagrijava, ali zrake ne dopiru do kože, jer je pokrivena. Nema promjena u protoku krvi, niti u širenju krvnih žila. Međutim, pri aktivnom ozračivanju ultraljubičastim zrakama i sat vremena nakon njega, vidljivo je proširivanje krvnih žila. Na ovaj se način može sniziti krvni tlak, čime se proširuju i srčane arterije, što srcu olakšava potiskivanje krvi u tijelo. Ovo je daljnja potvrda da ultraljubičaste zrake, tj. Sunčeva svjetlost, imaju blagotvoran učinak na protok krvi i na krvožilni sustav.
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.
Odlučili smo uobličiti u model različite količine UV-zračenja, na različitim dijelovima Zemlje, u različita doba godine. Tako je moguće izračunati zalihe dušikovog oksida - nitrate, nitrite, nitrozotiole u koži - koji cijepanjem oslobađaju dušikov oksid. Različite svjetlosne valne duljine imaju pritom različite uloge. Stoga možemo promatrati koje svjetlosne valne duljine što čine. Dakle, ako živimo na ekvatoru, Sunce je točno iznad naših glava; probija se kroz vrlo tanak sloj atmosfere. I zimi i ljeti, to je ista količina svjetla. Živimo li ovdje, ljeti sunce pada prilično izravno, ali zimi se probija kroz ogromne slojeve atmosfere, i mnogo se ultraljubičastih zraka gubi, a raspon valnih duljina koje dolaze do Zemlje se od ljeta do zime razlikuje. Dakle, možemo pomnožiti te podatke s oslobođenim dušikovim oksidom i izračunati koliko će dušikovog oksida biti iz kože otpušteno u krvotok.
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.
Nalazimo li se na ekvatoru - to su ove dvije crte ovdje, crvena i ljubičasta - količina oslobođenog dušikovog oksida odgovara površini ispod krivulje, površini u ovom području ovdje. Dakle, nađemo li se na ekvatoru, u prosincu ili u lipnju, koža će otpuštati gomile dušikovog oksida. Ventura se nalazi u južnoj Kaliforniji. Ljeti bi nam jednako bilo i na ekvatoru. Sjajno je ondje! Oslobađaju se ogromne količine dušikovog oksida. Ventura usred zime? Još je uvijek zamjetna pristojna količina. Edinburgh ljeti? Površina ispod krivulje je zadovoljavajuća. Ali, Edinburgh zimi? Količina oslobođenog dušikovog oksida gotovo je nikakva, neznatna.
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.
Dakle, što mi mislimo? Još uvijek na ovome radimo, još uvijek razvijamo model, proširujemo ga. Smatramo ovo vrlo važnim! Ovo vjerojatno uvelike objašnjava zdravstvene razlike između britanskog sjevera i juga. Ovo je i za nas važno! Mislimo da koža... Dobro, znamo da koža sadrži vrlo velike zalihe dušikovog oksida u svim tim različitim drugim oblicima. Pretpostavljamo da je za mnoge zaslužna prehrana - zeleno lisnato povrće, cikla ili zelena salata bogati su dušikovim oksidima za koje vjerujemo da odlaze u kožu. Potom se pohranjuju u koži, i mislimo da ih Sunčeva svjetlost oslobađa što, općenito, ima korisne učinke.
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?
Puno je još posla pred nama, ali dermatolozi... Želim reći, ja sam dermatolog. Moj svakodnevni posao je govoriti ljudima: "Imate rak kože; uzrokovan je suncem; ne izlazite na sunce..." A mislim da je, zapravo, daleko važnija poruka da se u sunčevoj svjetlosti kriju i blagodati, kao i opasnosti. Da, Sunčeva svjetlost je glavni promjenljiv rizični uzročnik raka kože, ali smrtnost oboljelih od srčanih bolesti stoput je veća od smrtnosti uslijed raka kože. Mislim da moramo biti oprezniji, i da trebamo naći pravu mjeru opasnosti i blagodati. Koliko se smijemo izlagati suncu, i kako ga možemo najbolje iskoristiti za svoje zdravlje?
So, thank you very much indeed. (Applause)
Hvala vam najljepša, doista! (Pljesak)