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.
Sebelum saya menjadi dokter kulit, saya memulai dari kedokteran umum, seperti kebanyakan dokter kulit di Inggris. Waktu itu, saya pergi ke Australia, sekitar 20 tahun lalu. Saat ke Australia, saya sadar bahwa orang Australia sangat kompetitif. Dan mereka tak murah hati soal kemenangan. Dan itu banyak terjadi: “Orang Inggris, kalian tak bisa bermain kriket, rugbi.” Saya bisa menerima itu.
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."
Tapi beralih ke pekerjaan -- dan tiap minggu kami adakan yang namanya klub jurnal, saat Anda duduk bersama dokter lain dan Anda akan mempelajari makalah ilmiah yang berkaitan dengan kedokteran. Di minggu pertama, kami membahas kematian kardiovaskular, topik biasa -- berapa banyak yang meninggal karena penyakit jantung, berapa tingkatnya. Dan mereka berkata: “Orang Inggris, tingkat penyakit jantung kalian mengejutkan.”
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.
Dan tentu saja, mereka benar. Orang Australia mempunyai penyakit jantung 1/3 lebih sedikit daripada kami -- lebih sedikit kematian atas serangan jantung, gagal jantung, lebih sedikit stroke -- umumnya mereka lebih sehat. Tentu mereka mengatakan ini karena kedudukan moral mereka baik, latihan mereka, karena mereka orang Australia, kami orang Inggris lemah, dan sebagainya.
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.
Namun bukan hanya Australia yang kesehatannya lebih baik dari Inggris. Di Inggris, ada gradien kesehatan -- dan inilah yang disebut kematian standar, pada dasarnya peluang Anda untuk mati. Data ini diambil dari artikel sekitar 20 tahun lalu, tapi datanya benar hari ini. Membandingkan tingkat kematian Anda di 50 derajat utara -- itu daerah Selatan, itu London dan tempat-tempat -- menurut garis lintang, dan 55 derajat -- berita buruknya ada di sini, Glasgow. Saya dari Edinburgh. Kabar buruknya, Edinburgh termasuk.
(Laughter)
(Tawa)
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.
Jadi apa yang menyebabkan ruang mengerikan ini di antara kita di sini di Skotlandia selatan dan daerah Selatan? Sekarang, kita tahu soal rokok, Coklat Mars goreng, keripik -- diet Glasgow. Semua hal ini. Tapi grafik ini setelah memperhitungkan semua faktor risiko yang diketahui ini. Grafik ini setelah memperhitungkan merokok, kelas sosial, diet, semua faktor risiko lain. Kita disisakan dengan ruang yang hilang dari peningkatan kematian ini semakin jauh ke utara.
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.
Sinar matahari, tentunya, berperan. Dan vitamin D mendapat banyak tekanan, dan banyak orang mencemaskannya. Kita butuh vitamin D. Kini anak-anak diwajibkan memilikinya di jumlah tertentu. Nenek saya dibesarkan di Glasgow, di tahun 1920-an dan 30-an ketika rakitis jadi masalah nyata dan minyak ikan cod dibawa masuk. Minyak ikan cod amat mencegah rakitis yang dulu umum di kota ini. Saat masih kecil, saya diberi makan minyak ikan cod oleh nenek saya. Saya jelas -- tak ada yang melupakan minyak ikan cod.
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.
Namun ada asosiasi: makin tinggi kadar vitamin D dalam darah seseorang, makin sedikit penyakit jantung yang dimiliki, makin sedikit kanker. Tampaknya ada banyak data menunjukkan vitamin D sangat baik bagi Anda. Dan ia mencegah rakitis dan sebagainya. Tapi jika Anda memberi orang suplemen vitamin D, Anda tak mengubah tingkat penyakit jantung yang tinggi itu. Dan bukti suplemen mencegah kanker belum mendukung. Saya usulkan bahwa vitamin D bukanlah satu-satunya yang penting. Ia bukan satu-satunya alasan pencegahan penyakit jantung. Kadar vitamin D yang tinggi, menurut saya, adalah penanda paparan sinar matahari, dan paparan sinar matahari, dalam metode yang akan saya tunjukkan, baik untuk penyakit jantung.
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.
Lagi pula, saya kembali dari Australia, meski risiko kesehatan saya jelas, saya pindah ke Aberdeen. (Tawa) Sekarang, di Aberdeen, saya memulai pelatihan dermatologi saya. Saya pun tertarik pada penelitian, dan khususnya pada zat ini, nitrit oksida (NO). Ketiga pria di sini, Furchgott, Ignarro dan Murad, memenangkan Hadiah Nobel untuk kedokteran pada 1998. Mereka orang pertama yang mendeskripsikan pemancar kimia baru ini, nitrit oksida. Yang dilakukan nitrit oksida adalah melebarkan pembuluh darah, jadi ia menurunkan tekanan darah Anda. Ia melebarkan arteri koroner, sehingga menghentikan angina.
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.
Yang luar biasa tentangnya yaitu dulu saat kita memikirkan pembawa pesan kimiawi di dalam tubuh, kita memikirkan hal-hal rumit seperti estrogen dan insulin, atau transmisi saraf. Proses yang sangat kompleks dengan bahan kimia kompleks berkaitan dengan reseptor yang sangat kompleks. Dan inilah molekul yang sangat sederhana ini, nitrogen dan oksigen yang saling menempel, namun ini sangat penting untuk [tidak jelas] tekanan darah rendah kita, untuk transmisi saraf, untuk banyak hal, tetapi terutama kesehatan jantung.
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?
Saya memulai penelitian, dan kami menemukan, menariknya, bahwa kulit menghasilkan nitrit oksida. Jadi itu tak hanya muncul di sistem kardiovaskular saja. Nitrit oksida muncul di kulit. Nah, setelah menemukan dan menerbitkannya, saya pikir, apa fungsinya? Tekanan darah rendah di kulit? Itu bukan hati. Apa yang dilakukannya?
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.
Saya pun ke Amerika, seperti orang lain saat akan penelitian, dan saya habiskan beberapa tahun di Pittsburgh. Ini Pittsburgh. Dan saya tertarik dengan sistem yang sangat rumit ini. Kami pikir mungkin nitrit oksida memengaruhi kematian sel, cara sel bertahan hidup, dan ketahanannya pada hal lain. Dan awalnya saya mulai bekerja dalam kultur sel, menumbuhkan sel, lalu saya memakai model tikus tak berdaya -- tikus yang tak bisa membuat gen. Kami menemukan mekanisme, yang -- NO membantu sel bertahan hidup.
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.
Lalu saya pindah kembali ke Edinburgh. Di Edinburgh, hewan percobaan kami mahasiswa kedokteran. Ia spesies yang dekat dengan manusia, dengan keunggulan dibanding tikus: Mereka gratis, tak harus dicukur, mereka memberi makan diri sendiri, dan tak ada yang jaga kantor sambil berkata, "Selamatkan mahasiswa lab kedokteran." Mereka memang model 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.
Tapi kami menemukan kami tak bisa mereproduksi pada manusia, data yang ditunjukkan pada tikus. Sepertinya kami tak bisa mematikan produksi nitrit oksida di kulit manusia. Kami oleskan krim yang memblokir enzim yang membuatnya, kami menyuntikkan sesuatu. Kami tak bisa mematikan nitrit oksida.
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?
Dan alasannya, ternyata, setelah dua atau tiga tahun bekerja, adalah karena di kulit kita terdapat simpanan yang sangat besar bukan dari nitrit oksida, karena nitrit oksida adalah gas, dan ia dilepaskan -- dan dalam beberapa detik ia menghilang, tapi ia bisa diubah menjadi bentuk nitrit oksida ini -- nitrat, NO3; nitrit, NO2; nitrosothiol. Dan ini lebih stabil, dan kulit Anda memiliki simpanan NO yang sangat besar. Kami lalu berpikir, dengan simpanan besar itu, saya ingin tahu apakah sinar matahari bisa mengaktifkan simpanan itu dan melepaskannya dari kulit, di mana simpanan sekitar 10 kali lebih besar dari yang beredar. Bisakah matahari mengaktifkan simpanan itu ke dalam sirkulasi, dan di sana sirkulasi melakukan hal baik bagi sistem kardiovaskular Anda?
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.
Saya ahli dermatologi eksperimental, kami lakukan yang kiranya kami harus memaparkan hewan percobaan kami ke sinar matahari. Jadi yang kami lakukan ialah kami ambil sekelompok sukarelawan dan kami paparkan mereka pada sinar ultraviolet. Jadi ini semacam lampu matahari. Yang kami lakukan hati-hati adalah, vitamin D dibuat oleh sinar ultraviolet B dan kami ingin memisahkan kisah kami dari kisah vitamin D. Jadi kami gunakan ultraviolet A, yang tak menghasilkan 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.
Saat kami menempatkan orang di bawah lampu yang setara sekitar 30 menit sinar matahari musim panas di Edinburgh, yang dihasilkan ialah, kami menghasilkan peningkatan nitrit oksida yang bersirkulasi. Jadi kami tempatkan pasien dengan subjek ini di bawah UV, dan tingkat NO mereka naik, dan tekanan darah mereka turun. Tidak banyak, sebagai tingkat individu, tapi cukup pada tingkat populasi untuk menggeser tingkat penyakit jantung di seluruh populasi. Saat kami menyinari mereka sinar UV, atau saat kami hangatkan mereka ke tingkat yang sama dengan lampu, tapi tak biarkan sinarnya mengenai kulit, hal ini tak terjadi. Jadi sepertinya ini ciri sinar ultraviolet yang mengenai kulit.
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.
Kami masih mengumpulkan data. Beberapa hal bagus di sini: Tampaknya ini lebih ditandai pada orang tua. Saya tak yakin berapa banyak. Salah satu subjek di sini ibu mertua saya, dan jelas saya tak tahu usia beliau. Tapi yang pasti pada orang yang lebih tua dari istri saya, ini tampaknya menjadi efek yang lebih nyata. Yang juga harus disebutkan adalah tidak ada perubahan pada vitamin D. Ini terpisah dari vitamin D. Vitamin D baik, menghentikan rakitis, mencegah metabolisme kalsium, hal-hal penting. Tapi ini mekanisme yang terpisah dari vitamin 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.
Satu masalah saat meneliti tekanan darah ialah tubuh Anda melakukan segalanya untuk menjaga tekanan darah Anda. Jika kaki dipotong, Anda kehilangan darah, tubuh Anda akan tertekan, detak jantung meningkat, lakukan segalanya menjaga tekanan darah tetap tinggi. Itulah prinsip fisiologis yang sangat mendasar.
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.
Jadi yang kami lakukan selanjutnya adalah beralih meneliti dilatasi pembuluh darah. Kami mengukur -- sekali lagi, perhatikan tak ada ekor dan bulu, dia mahasiswa kedokteran. Di lengan, Anda bisa mengukur aliran darah di lengan dengan berapa banyak darah yang membengkak saat darah mengalir ke dalamnya. Dan yang kami tunjukkan adalah melakukan penyinaran palsu -- ini garis tebal di sini -- ini UV yang bersinar di lengan hingga menghangatkan tapi tetap menutupinya agar sinarnya tak mengenai kulit. Tak ada perubahan aliran darah, pada pelebaran pembuluh darah. Tapi penyinaran aktif, selama UV dan satu jam setelahnya, terjadi pelebaran pembuluh darah. Inilah mekanisme di mana Anda menurunkan tekanan darah, di mana Anda juga melebarkan arteri koroner, agar darah mensuplai jantung. Jadi di sini, data lebih lanjut tentang ultraviolet -- yaitu sinar matahari -- memiliki manfaat pada aliran darah dan sistem kardiovaskular.
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.
Jadi rasanya kami hanya akan membuat model -- Jumlah UV berbeda menghantam bagian bumi berbeda di waktu berbeda sepanjang tahun, jadi Anda sungguh bisa menghitung simpanan nitrit oksida itu -- nitrat, nitrit, nitrosothiol di kulit -- membelah demi melepaskan NO. Panjang gelombang cahaya berbeda memiliki aktivitas berbeda dalam melakukannya. Lihat panjang gelombang cahaya yang melakukannya. Lihatlah -- jika Anda tinggal di ekuator, matahari tepat di atas kepala, ia melalui sedikit atmosfer yang tipis. Di musim dingin atau musim panas, jumlah cahayanya sama. Jika Anda tinggal di sini, di musim panas matahari akan langsung turun, tetapi di musim dingin ia datang melalui sejumlah besar atmosfer, dan sebagian besar ultraviolet disingkirkan, dan rentang panjang gelombang yang menghantam bumi berbeda dari musim panas ke musim dingin. Anda bisa mengalikan data itu dengan NO yang dirilis dan Anda bisa menghitung berapa banyak nitrit oksida yang akan dilepaskan dari kulit ke dalam sirkulasi.
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.
Jika Anda berada di ekuator di sini -- yaitu dua garis ini, garis merah dan garis ungu -- jumlah nitrit oksida yang dilepaskan adalah area di bawah kurva, area di ruang ini. Jika Anda berada di khatulistiwa, Desember atau Juni, Anda mendapat NO besar-besaran dilepaskan dari kulit. Jadi Ventura berada di California selatan. Di musim panas, Anda mungkin berada di ekuator. Sangat bagus. Banyak NO dilepaskan. Ventura pertengahan musim dingin, yah, masih ada jumlah yang lumayan. Edinburgh di musim panas, area di bawah kurva cukup bagus, tapi Edinburgh di musim dingin, jumlah NO yang bisa dilepaskan hampir tak ada, jumlahnya kecil.
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.
Jadi apa yang kami pikirkan? Kami masih mengerjakan ini, kami masih mengembangkan dan memperluasnya. Kami pikir ini sangat penting. Ini mungkin menjelaskan alasan kesenjangan kesehatan utara-selatan di Inggris. Ini relevan bagi kita. Kami berpikir bahwa kulit -- kita tahu bahwa kulit punya simpanan nitrit oksida yang sangat besar dalam berbagai bentuk lainnya. Kami duga banyak yang berasal dari makanan, sayuran berdaun hijau, gula bit, selada memiliki banyak nitrit oksida yang kami pikir masuk ke kulit. Kami pikir mereka lalu disimpan di kulit, dan kami pikir sinar matahari melepaskannya di mana ia memiliki efek yang umumnya menguntungkan.
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?
Ini yang masih dikerjakan, tapi dokter kulit -- maksud saya, saya dokter kulit. Tugas saya memberitahu, “Anda punya kanker kulit, penyebabnya sinar matahari, jangan berjemur." Saya kira pesan yang jauh lebih penting ialah ada manfaat serta risiko dari sinar matahari. Ya, sinar matahari faktor risiko utama yang bisa diubah untuk kanker kulit, tapi kematian akibat penyakit jantung 100 kali lebih tinggi dibanding kematian akibat kanker kulit. Dan saya pikir kita perlu lebih waspada, dan juga menemukan rasio risiko-manfaat. Berapa banyak sinar matahari yang aman, dan bagaimana kita bisa mengatur yang terbaik bagi kesehatan secara umum?
So, thank you very much indeed. (Applause)
Jadi, terima kasih banyak. (Tepuk tangan)