Episode 8 - Sunshine Dermatology

In this episode of BJD Talks, Dr Jonny Guckian chats to Prof Richard Weller about the Sun and what it means for our patients in terms of benefits and risks. Prof Weller examines the role of UV, Nitric Oxide and Vitamin D, as well as delving into evolutionary genetics and dermatology's relationship with generalism.

Transcript

SPEAKER_01 0:18

Hello everyone, and welcome to BJD Talks. We are the official podcast of the British Journal of Dermatology. In this podcast, we look well beyond our published studies and we try to explore real-world implications of dermatology research. And we do so in an accessible, relaxed way. This podcast is designed for anyone with an interest in skin health research. So that means whether you're a dermatology professor, researcher, registrar, patient, or even just a skin enthusiast, we really hope you'll join us as we build on world-leading research through friendly chats. My name is Dr. Johnny Guccian, and I'm a dermatology registrar in Leeds in the UK. As well as that, I'm the BJD's Podcast Associate Editor. Together with our listeners, we'll dive into a huge range of issues which matter in dermatology, covering issues as broad and diverse as artificial intelligence, social media in dermatology, peer review, and patient and public involvement in research. And I'm really pleased to welcome our latest guest, Professor Richard Weller. Prof. Thank you, and welcome to uh BJD Talks.

SPEAKER_00 1:36

Um, Johnny, thanks. Great to be here. And I listened to you while walking the dog. Um so I have to say poo bag in hand usually, but but but not today. So it's it's lovely to be speaking rather than just listening.

SPEAKER_01 1:49

I'm sure there's a metaphor in in there somewhere for my my quality of hosting. Um so just for everyone listening, I first came across uh Prof. As part of a TED talk. Uh that was called Can the Sun Be Good for Your Heart? Um and our listeners can check that TED talk out online uh after listening to us, of course. Um so, Prof. I'd like to just start by um chatting about the issues that you raise in in your TED talk, just because it's quite it's quite accessible and fascinating. Uh nitric oxide and the sun. Can you tell us about your research and what this has to do with dermatology?

SPEAKER_00 2:24

Yeah, sure. So I mean the long and short of it is we found a mechanism separate from vitamin D by which sunlight has health benefits. So that's the kind of short message. I think sunshine is good for you, and it's not just vitamin D. And what I showed was that the so nitric oxide, Nobel Prize for Medicine back in 1998, went to the three people who discovered this substance, it's gas, a nitrogen and an oxygen, that dilates blood vessels, and by doing that it lowers blood pressure. And blood pressure is important because it's the leading cause of death and disease in the world today. It's overtaken smoking. And uh it turns out that the skin has large stores of storage forms of nitric oxide, and when sunlight hits the skin, it does some photochemistry and it mobilizes those stores from the skin, and the NO that's released moves into the circulation, and in the circulation it dilates blood vessels and and lowers blood pressure. So, you know, we kind of know that. I mean, what it interested me was I could remember from medical school days that you know blood pressure is seasonal. So people's blood pressure in the UK, um, blood pressure is almost six millimeters of mercury systolic lower in summer than winter. That is a big amount, that is a pharmacological amount, and it's not vitamin D that's doing it, even though measured vitamin D levels are higher in summer than winter. If you give people vitamin D supplements, it has no effect on blood pressure. And also temperature only accounts for a little bit of that fall, probably about half of it. But half of that fall in blood pressure by season correlates with UV rays. And we've got a mechanism here, it's it's nitric oxide from the skin.

SPEAKER_01 4:16

I mean that that's it's fascinating. What I find was really interesting was this is an example of how you can take the basic science related to the skin and generate meaning and solve puzzles like that. I thought that I thought that was that was really cool. One thing I find troubling at at medical school, uh, in the early days, was making this basic science meaningful. And I think this is just a prime example of of how we can apply this toology.

SPEAKER_00 4:40

And also, I mean, my I mean, I absolutely agree. And the other thing is we've always taken pride in the fact in Britain that uh dermatology we have regarded ourselves as a branch of internal medicine. I still strongly feel that is the case. So, you know, when I started off looking at nitric oxide, I was, in dermatological terms, a good boy. I believe sunlight was dreadful, we should live down mineshafts, and here I am, I moved to Scotland, you know. And initially, I was working up an Aberdeen, and one of the clinical pharmacologists there, Ben Benjamin, in the early days of nitric oxide, was doing fantastic research on it, and I just kind of slotted onto him. And first of all, we found that nitric oxide is released from the skin, and I got really excited by that. And I was trying to work out what it did, and having started off literally as a registrar, just doing experiments on the side, I then actually got funding to go and do research. And I set off trying to work out what NO was doing in the skin, and I went off to Germany, and I went to America, so I spent three years doing research. And I was mostly working in mouse models then, and I thought nitric oxide would be something to do with skin cancer, because nitric oxide can affect apoptosis and non-inflammatory cell death, and that's involved in you know keratinocytes escaping from mutations, and so on, and so on. And I was doing all this mouse work in America, came back to Edinburgh, and it and I was trying to repeat my mouse work in man, and I just couldn't do it. And I couldn't do it because I've been using knockout mice in America, and I was pharmacologically trying to antagonize NO release in humans in Edinburgh, so different model system, different approaches. And that pharmacological blocking of NO production does not turn off the photochemical release of NO. So I was trying to do my mouse experiments in man and I couldn't, and spent a couple of years of, you know, very stressfully no data, no publications, nothing working, you know, my god, just you know, watching the the years tick by and not producing anything. And it was literally at a meeting with colleagues over a pint in Bragenz at the NO meeting, chatting with your friends, and then Martin Feelish, this friend down in Southampton, had described this mechanism by which, this photochemical mechanism by which UV could release NO from stores. And I went, hang on, I found these stores in man. Could that be what's happening? And I then could remember from medical school days all about the seasonality of blood pressure. And also, having been a junior doctor doing internal medicine, Johnny, you're too young to remember this, but we used to have winter bed crises in the NHS. So summer was all lovely and tickety-boo, and the hospital wasn't full, and you'd go on holiday. And in winter there was a kind of unspoken agreement you didn't go on holiday because it got busy and the hospital was full. Now, this has now been replaced, I might say. We now have 12 months a year of bed crises in the NHS. Such is the price of progress. But it used to be seasonal, and it's fact this fact that there are 23% more admissions to hospital in winter with cardiovascular disease than in summer. And it ties up with this sunlight lowers blood pressure, improves blood flow. And we just we just shrug our shoulders and say people are sick in winter without thinking, well, why? You know, could we do something about this? And you know, thus thus I moved on to this.

SPEAKER_01 8:20

That's absolutely fascinating. I I I mean I'd never thought about it. That you know, you you just assume, oh yeah, it's it's cold in winter and people get sick in winter. That's that's why I I love that that symmetry. And I I enjoy the um the journey you've taken from following the standard commandments of the dermatologist of slinking around in the sun. I say this as I'm I'm recording my end from um I'm on holiday at the moment in uh back home in Derry, and we've had maybe one ray of sunlight since I've been back I've been back on the on the Atlantic coast. Um but um yeah, and to to moving literally across the world to find to find us, and then doing what you know so many of you know us kind of researchers and scientists and scholars in in uh across different fields ex experienced, which is you know getting things wrong over and over again, and then suddenly getting a eureka moment over a pint, uh um that that is uh that's it's very inspiring, and I know I'm gonna have to have my next research meeting clearly.

SPEAKER_00 9:15

And it's interesting. So here am I in Scotland, there are you um over in Derry. And um, so look, so it's really interesting going back to the history of this. So we have this fixation with sunlight being bad. And actually, having found these benefits to sunlight, and there's more which I hope we'll move on to, I then began to think, well, you know, where is it? Because there are no papers showing that sunlight shortens life. None whatsoever. Although we know you know that UV is a risk factor for skin cancer, that's what we focus on. That is entirely correct. And that is, you know, we have epidemiology, we have mechanism, we have the Nambo Sunblock study, you know, we have clinical trials. UV is a risk factor for skin cancer. However, I I then say to people, well, can you name any papers showing increased sunlight correlating with reduced lifespan? And there's a silence. And the answer, that silence is correct. There are none. If you ask a first-year medical student about evidence that smoking shortens life, or high blood pressure shortens life, or obesity shortens life, or poverty shortens life, or air pollution shortens life, or diet low in fruit, etc. etc. etc., there is the Framingen study, the UK Biobank study, the Nurses' Health study, the Six Diddy study, etc., etc. etc. All of those things extensively, we have correlations between increased exposure to, say, cigarettes and shorter lifespan. There is not a single paper showing that for UV. So where did all this start? And it's interesting, and you go back, and so it was kind of suspected that sunlight was a risk factor for skin cancer back in the late 19th century. You know, Una, the great German dermatologist in Hamburg, described Zemonds out, the sailor skin. He showed that sailors got what we now call skin cancers, and of course, you know, high UV off the sea, and so on and so on. So that was a suspicion. The confirmation that UV was carcinogenic was produced by George Find Lee, so an Edinburgh graduate from my own university, who in 1927 did the classic experiments published in the Lancet and at mouse models. You shine UV at mice, they get skin cancer. So that proved causally that UV precipitates skin cancer. And he then disappears. And he's not a dermatologist, never heard of again. And I thought, well, you know, who is this guy? Hundreds of citations, this Lancet paper. Whenever you write a review on UV and skin cancer, you say, Una Zeman Sao, Findy then proves it, etc. So who is this guy? And so he uh Edinburgh Graduates um worked at the Imperial Cancer Research Boards for two years doing this. He then went off to Africa and he looked at riphalli fever, he looked at malaria, he looked at yellow fever. He dealt with medical problems of empire. What happens to white-skinned Brits who leave these Northern Isles and go to Australia, who go to Africa, who go to India. And, you know, it there, in a climate for which your skin is not suited, one of the problems you get, along with yellow fever and malaria, is you get UV-induced skin cancer. And our whole approach to UV stems back to that. Now that is irrelevant to you and Dairy. It is irrelevant to me here in Edinburgh. Because it's interesting, you look at so the UV index, you know, our measure of of uh erythemally weighted UV, that the risk of UV causing DNA damage. So the number of days in Townsville where the UV index is six or above, so high or above, is 365. So every day of the year in Queensland, you have a high or higher UV index. White-skinned people living there need to take skin protection. So we measure it in Reading in the UK. So I actually just before this talk had a quick I quickly jumped onto the website, the the Environment Agency website. So it's got last year's data. So the days in southern England where the UV index is six or higher. And so, I mean, any idea? And it's going to be far less for you. Yeah, well, I'm gonna say here is probably about five. Um at the most, it probably is. It probably is. So down in Reading, down in the uh southeast of England, so less clouds, it's about sort of around th so last year there were 30 or 40 days when the UV index just ticked um above five for you know 15 minutes in the middle of the day. Uh uh in Glasgow it's much less, and in Derry it will be less. And yet we are using sunlight advice, sunscreen between 11 and 3, you know, avoid the sun, sit in the shade. Designed for subtropical Australia, it is entirely in a in my belief inappropriate. Because sunlight doesn't just have risks, it has benefits. And if you're avoiding those risks too much, particularly when it's inappropriate, you are avoiding the benefits.

SPEAKER_01 14:31

Oh, I I bet some of our listeners here following like the dermatology doctrines have having their toes curly listen to this, and I and I I I love it. I love controversy on this. You you've mentioned benefits a couple of times now. Do you want to chat a little bit about that? And tell just tell us about some of these exact benefits.

SPEAKER_00 14:48

Yeah, uh so absolutely. So that there are a vast array of diseases where we know that people with higher measured vitamin D levels are healthier in pretty much every way. I there's not many things where they're not healthier, maybe power, you know, renal calcification. But so, you know, people with high measured vitamin D's, and yet when you give people vitamin D, there are far fewer benefits proven by giving people vitamin D in clinical trials than the association studies suggest. So we know vitamin D is hugely important for Ricketts. I mean, that's so you know, a hundred years ago, Ricketts was endemic in uh cities like like Belfast and Glasgow, these kind of poor northern industrial cities. And that was just dramatically abolished by bringing cod liver oil vitamin D supplementation. And we've then got this fixation that vitamin D is a panacea. But remember, correlation is not causation. Just because vitamin D levels are higher in people with less heart disease, less strokes, less diabetes, less multiple sclerosis, less inflammatory bowel disease, less cancer, less, doesn't mean it's causative. For that, you've got to do clinical trials. And actually the clinical trials have been really disappointing. So this week, in the BMJ, published two days ago, um, there were two clinical trials published in this week's BMJ on vitamin D supplementation for COVID. So we know that people with higher measured levels of vitamin D were less likely to die of COVID. So a big trial in the UK of I think 13,000 people with high dose vitamin D, some get high dose, some get medium dose, um, and a trial in Norway where they gave cod liver oil, published three days ago, both studies negative. So although we know that people with measured vitamin D levels are less likely to suffer from COVID, giving vitamin D to them does nothing. And then a bizarre editorial in this week's BMJ that says these two studies show no benefit from vitamin D, and it concludes you should take vitamin D. Absolutely bizarre. I just read the papers, read the editorial. If you can explain it to me, please do. Because the other trial of vitamin D supplementation, so the biggest trial of vitamin D supplementation called the Vital Study has run for five years. And this is looking at lots of endpoints, not just COVID, like the two studies in this week's BMJ. So the vital study is 25,000 people randomized, half get vitamin D, half get placebo, placebo controlled, blinded, randomized, ran for five years. Looking at various endpoints, and and most of the endpoints were negative, doesn't stop you getting cancer, doesn't stop you getting cardiovascular disease, etc. If you have cancer, it reduces your risks of progressing. So once you got a cancer diagnosis, there there may be benefits to vitamin D then. Anyway, New England Journal ran the latest outcome study from the vital study in July of this year. So 30% of all Americans over the age of 60 take vitamin D. Okay, it's a three billion dollar a year industry. And the editorial in the New England Journal um eight weeks ago concludes stop taking vitamin D supplements. It's not going to prevent most of these diseases. So here we are, a BMJ editorial discussing two negative studies says take vitamin D. I don't understand it. Um the New England Journal eight weeks ago says stop taking vitamin D. So it's this this contentious, contentious area. What I'm saying is that sunlight has, via a number of mechanisms, which we can move on to discuss, uh, I think has significant health benefits. Um and vitamin D accounts for some of those benefits, but not for uh, I would say the majority of them. So vitamin D is not not the whole story. There's there's it's not the whole story, exactly.

SPEAKER_01 18:57

Interesting. So so if it's not vitamin D, if what what mechanisms are are are happening to Yeah, so it's an interesting one.

SPEAKER_00 19:05

And of course, the the first thing I'd say is we haven't looked. So a hundred years ago, we knew that codibroil was a dramatic thing that stops it getting rickets, and we knew from mouse models that UV causes skin cancer. So for a hundred years, I'm going to paraphrase here, but it's broadly correct, dermatologists have said live in a cave, take vitamin D supplements, and they've been so happy with that advice that they've not bothered to move on. And the other thing is we've kind of said that look, UV is our bit. We're dermatologists, we deal with UV. And we've only thought about the skin, because we're dermatologists, and I wish we could remember our internal medicine past. And so we have looked at UV with the eyes of a dermatologist and concerns about skin cancer, which of course it causes. And the benefits to UV, I would suggest the data shows, are not just the skin, although, of course, we do use it to treat inflammatory skin disease like psoriasis and eczema. That aside, I think probably a larger part of the benefits of UV, via a number of the mechanisms, are on systemic health problems. So, you know, classically we know that multiple sclerosis is a sunlight deprivation disease. Again, another big study published in JAMA last week, I think it was JAMA. Vitamin D supplements, uh no benefits on M. You know, the same story there, as in with cardiovascularities. So mechanisms are there. So look, so vitamin D is good for the ricket's bone health, may prevent progression from cancer. It's part of the benefits of sunlight, but not all of them. I think my nitric oxide pathway, and Christoph Suschik, I should mention, uh, a friend and collaborator in Germany also has worked on this. I think the NO pathway is more important than vitamin D. I think the data would suggest, and we're trying to get more of it, that may well account for the cardiovascular benefits of sunshine. And cardiovascular disease is the biggest killer in the world now. There are then probably other effects. So we know that if you look at um transcriptome data, if you look at expressed gene transcriptome data from whole blood, in so about 30% of your entire blood transcriptome has seasonal variation. And broadly speaking, in summer, anti-inflammatory genes are upregulated, and in winter pro-inflammatory genes are upregulated. Now, the the sort of thought that paper writ by Dopico in uh in Nature um about six years ago. The thought here is that you know, in winter there's lots of infectious disease flying around, you turn up your inflammatory genes ready to jump on infection. But in summer, of course, you want to turn your anti inflammatory genes to reduce that inflammatory signature, which is so unhealthy. But just no one's looked. You know, and that's the big problem. Nobody has looked. This huge great gap in evidence. Despite the fact we live with overflowing hospitals in winter, um seasonal disease, and we just shrug our shoulders and just say that's the way the world is.

SPEAKER_01 22:11

Yeah, fascinating. So it's challenging existing consensus really and and yeah, paradigms. One thing we we often do when we have guests on is chat a little bit about um what you think the the dermatologists or the dermatology researchers of of tomorrow should be focusing on, and what one specific area if you if you had to say um read about that and write about that and study it and investigate it and come up with an answer and change the world. I'm guessing you'd be saying this these specific mechanisms um are the areas to go hunting.

SPEAKER_00 22:41

Yeah, absolutely right. Because you know, the types of research as epidemiology, because I've been talking here about epidemiology, you know, associations between sunlight and and and less of a number of diseases. But that's not proving it, that's just an association. I went to watch Scotland playing Australia at rugby with my son on the weekend. So, you know, who's the better rugby team, the all blacks or Scotland? Well, you know, I'm afraid to say it's it's always the all blacks. Well, if if I give New Zealand passports to the Scottish rugby team, will they play so well they beat England? Sadly they won't, and yet the association between carrying a New Zealand passport and being a really good player is phenomenal. But it's association, it's not causation. There's something about being a Kiwi that makes you a good rugby player. It's not the passport. You know, and it's and so sure, there's epidemiology. I I think there's lots of mechanisms to be looked at, and I think that gets really interesting. I have to say I've also become very interested by the whole skin colour, uh, evolutionary adaptation to different UV environments. And this is something we've started looking at because one of the bits of evidence that sunlight must have benefits is is the evolutionary story. So Parbe Svaavo, who got the Nobel Prize for Medicine uh last month, you know, he's this wonderful Swedish researcher who actually used to work with one of my collaborators at the Karolinska Padelinkfist. And he developed these techniques for looking at ancient DNA. Really exciting. And so that's technology which has become available in the last ten years or so. And the other thing that's become available in the last 10 years is we now understand the genetics of pigmentation, certainly in European groups very well, but you know, a certain amount of evidence for lots of human groups. And it has become possible, literally in the last decade, less than that, the last five years, to look at what has happened to human skin pigmentation as we have moved around the world from our African origins. I mean, Nina Jablonski is the great writer on this, wrote a wonderful review two years ago. So humans, Homo sapiens, arose in Africa about 200,000 years ago. Those of us who are not African are the descendants of people who left Africa 60,000, 70,000 years ago, and we scattered round the world. Now, what is interesting is as the different human groups have moved to high latitude, low-light environments, they have repeatedly evolved pale skin. So in East Asia, in China, the genetic variant leading to pale skin is Kit Lg. Um up here in Europe, it's SLC24A5. The SAN, right down in the in southern South Africa, the original inhabitants down there, actually even MC1R variant. But the point is repeatedly the same phenotype, pale skin, evolves by different genetic pathways. It's what's called convergent evolution. So there has to be a benefit because it doesn't just happen once by chance, it occurs multiply. So there's got to be a benefit. And what skin colour does is it mediates our interaction with UV. So I I work in Ethiopia a lot, so I've been going there most years for the last 13, 14 years, and we do not see UV-induced melanoma in Ethiopia. Despite the fact it's on the equator, it's two and a half thousand metres, you know, it's shed loads of UV. And if you look at Adawali Adams' work from the United States, black people do not get UV-induced melanoma or UV-induced SECs. So you don't get the downside with dark skin to UV. But in work I published either last year or the year before, um in one of the cardiology journals, we showed that in America, African Americans get less of a fall in blood pressure with a rise in UV than white Americans. So with dark skin, you're not getting the dangers of UV, but you're getting less of the benefits. So, you know, UV mediates our response to UV. So what are the benefits to UV? Because I don't think it's cardiovascular. Looking back in historical times, I suspect it's not cardiovascular. You know, as hunter-gatherers, as farmers, um, you know, those are those are good physical workouts. And I mean I could move on to talk about infection, but we've got data now suggesting that I think infection has been the evolutionary driver to pale skin, which I could talk about more if you'd like me to.

SPEAKER_01 27:23

Yeah, yeah, I think I think that would be great. I would jump in first and just pick you up on something you said earlier about um talking about correlation and causation and linking um the Kiwis to um you know being always being the best at at rugby. I think probably a better example is the fact that you know Ireland are actually top of the world rankings at the moment. Um and uh That's what's called chance.

SPEAKER_00 27:43

That's what's called chance, I believe.

SPEAKER_01 27:45

Yeah, if you ever saw if you ever saw me playing rugby, you'd you'd certainly know that correlation is not causation. Um uh yes, tell me more about about infections around all this.

SPEAKER_00 27:57

Yeah, so look, so this is the interesting one because um two papers published um two years ago. Actually, two papers that came out in the in in actually in Nature um last week, and we're just looking at the edit from that. However, before last week, I would have said that the most recent um that that the oldest human from whom we had genetic data, Cheddarman, so someone from 8,000 years ago, uh from Cheddar Gorge in Somerset, again a paper in Nature three years ago, there was a brief kind of mini-ice age, the younger Dryas, um about 9,000 years ago, when for a thousand years ice returned to Britain, Northwest Europe, and humans were driven out. And then as that melted uh 9,000 years ago, Northwest Europe was repopulated and initially from the Iberian Peninsula by what are called the Western Mesolithic hunter-gatherers. So looking at ancient DNA, you know, this year's Nobel Prize winning technology in these people, when we have bones to take this from, and then using modern uh knowledge of the genes that lead to skin pigmentation, what we find is that these Western Mesolithic hunter-gatherers had dark skin and blue eyes. And so actually, the first from 9,000 years ago until about 5,000 years ago, probably, of course, the data points are few. We only have, you know, the N numbers are low because we don't have much data from that time. And yet it does seem that up here in Northwest Europe we had dark-skinned, blue-eyed hunter-gatherers. And they were only replaced 5,000 years ago by white-skinned farmers. So the European white-skinned gene, SLC24A5, first arises 8,000 years ago in Anatolia, modern Turkey, at the time that farming develops. So it arises in the Neolithic, the first farming people. And over 3,000 years they migrate up through Europe, arriving in the British Isles, they're just become Isles, 5,000 years ago. In China, the move to pale skin with Kit LG occurs about 10,000 years ago, and that is when in China farming develops. So European farming is sheep and goats and wheat, and in China it's rice and pigs. Independently, farming develops, and at the time that farming develops in low light environments, white skin develops. So this is correlation. What could it be? So really what precipitated our thoughts here was this COVID work. Was our COVID work. So it's not just living at high latitude that seems to drive pale skin, it's living at high latitude and being a farmer. Because for 5,000 years we had dark-skinned hunter-gatherers in low light North Europe, and the same in China. So it's it's a low light environment and being a farmer. And my thoughts here are that this is probably infection. It could be diet, dietary change, but I think infection is more likely. Because when you start farming, when people started farming, that is when infectious disease became prevalent. Because most infections are zoonotic, you know, COVID comes from bats, TB comes from cows, you know, flu comes from pigs, etc. So most infectious disease is zoonotic, and when you're farming, you're suddenly close to uh animals. And of course, once you're living in communities, once you're living with other people, infectious disease can spread because you're not dispersed over the landscape as a hunter-gatherer, but you're living in communities as a farmer. And then what gives supportive evidence to this is the fact that what we found with COVID was we had actually an inverse. So I published a paper in the BJD last year, and a group from Harvard published a paper in PNAS that it grouped at just the same time. We both submitted to PNAS in the same week. They sat on our paper for six months saying it's wonderful as one of us and no no, it's a bit boring. Um and took the anyway, that's uh me feeling pretty hacked off with PNAS. Anyway, we both published. So what we showed, we did a super paper, read it, it's in the BJD. We showed that more UV inversely correlates with deaths from COVID. Lots of extensive corrections for confounders. And the uh the the paper in PNAS shows that more UV correlates with less growth of COVID. So you've got these correlations. This was then taken up by an American company, Cytokind, who I've been advising, who then ran a clinical trial of UVB phototherapy for treating patients admitted to hospital uh with COVID. And um we published it in well, I'll put a link at the end of the podcast. We published it in one of the uh American Dermatology journals. And what they they having saved 300 people admitted to hospital with COVID, 15 got daily UV, 15 got a sham control, and it was randomized and blinded. And of those that got UV, two died. Of those that got the sham, five died. And now it's not significant, but it's moving in the right direction, and we now want to spread this out further. The other thing is about deaths from COVID. Of course, the highest death rates from COVID were from dark-skinned people in Britain. Now, there's there's social confounders there, which it's hard to disentangle it. But I I, with colleagues here, we have been looking in the UK Bio Bank at redheads and non-redheads. So redheads are the palest of all, but there's no social confounders between a right redhead and a white non-redhead. And I'm not going to talk about that data in detail much because we're still working on it and we'll be publishing it. But it does support the idea that paler skin may help you have reduced infectious deaths uh in a low-light environment. So what we're doing. And and it would suggest that you know maybe what killed off these dark-skinned hunter-gatherers was infection. Because if you're more likely to die of infection because you haven't got these UV-driven mechanisms of fighting infection are less effective if you've got dark skin because you don't get the benefits of UV so much. But anyway, it's what we're working on now, and I it's I I think it's really interesting.

SPEAKER_01 34:33

I mean, it certainly signs it, and we will share your BJD um paper whenever we share this podcast. Don't you worry. Um and you can you can you can tell me which which uh journal you you you publish that that that study in. I'd love to get to a stage in my career where I forget the journal that I've done that I published that I published a paper in. Instead, I'm just bagging my head against the wall, trying to get anyone to take some of my stuff at the moment. Fascinating. And I mean I I did not expect to be discussing evolutionary genetics in this podcast, so that this has taken a few really interesting segues. Um so thank you for that. One thing I actually wanted to talk about, it's taking another turn from these points of discussion, is something you've touched on a couple of times is about and very separate to the Sun and UV, etc. But dermatology's relationship with internal medicine, I think is is a very interesting area because uh it's been historically there was obviously kind of schisms and we've always for a long time felt very separate to medicine, but uh within my experience within medical education, with medical education research and policy, there is a wider driver for generalism at the moment. And I'd be very interested in your in your your take on that, because if we've got a postgraduate education system now where um we are pushing for more generalists to meet the needs of our society, this is is undoubtedly going to affect um the next generation of dermatologists. So do you think this is that that's an area we should be traveling in?

SPEAKER_00 35:59

Yeah, so look, so the truth of the matter is dermatologists are far less involved with general medicine than we ever used to be. And I get a little bit peeved. I hear these cries saying, oh, you know, uh people talking the talk, we're part of general medicine. I have had real problems getting my message heard. Because why is a dermatologist talking about cardiovascular disease and blood pressure and infectious disease? You know, keep in your lane. And so I just think you guys are talking the talk, you're not actually doing it. Because you know, what I what I'm doing has ended up being very much overlap. And there's a lot of interest in my work from you know, renal physicians and clinical pharmacologists and hypertension, none whatsoever from dermatologists. Of course, the problem I have is that you know, sending to these journals, going to these meetings, what's a dermatologist doing here? In the same way that the dermatology meeting, why is Richard talking about blood pressure? And you know, my papers, is this environmental science, is it cardiology, is it public health, is it photobiology, is it dermatology? You know, well, of course it's it's all of the above, and there is no logical home for this kind of thing. So, you know, I think I think people specialise earlier, you know, people whip into dermatology and stay there, and general medicine is hard, and internal medicine is hard, and it changes fast, and you need to be doing it all the time to be on top of it. And I think it is, you know, we're we're the busiest outpatient specialty, and you know, our hands are full coping with dermatology. Is it reversible? Sadly, I fear not, but I think that the kind of stuff I do, which is actually how the skin mediates our response to UV, and that mediation is driving lots of internal medicines.

SPEAKER_01 37:57

Yeah, I th I think having that link that that in some way not necessarily you know merging lanes as such, but having a link is important because you you know COVID has shown us that you you can have one area which can massively cross these lanes uh into different into different specialties, and suddenly you need the specialty you never thought you would, and you need the knowledge you never thought you would, and then without realizing it, suddenly you're doing you're a consultant dermatologist doing a uh general medicine board round, um as as many of our listeners may have may have experienced and and still be having nightmares about I mean I have to say I mean I mean I I look at the Dan Creamer and Sarah Wolstan in uh Kings Who Led Us All.

SPEAKER_00 38:39

I mean I I um shifted to think the COVID triaging wards here. I have to say, I actually really enjoyed. Um I mean, I had to decide was somebody sick and came into hospital or were they not sick? So you've got to you that you're you're working within a narrow range of what you're gonna do. But it was you know, talking the talk, walking the walks. I I I felt I couldn't not do it when they're saying that we dermatologists need to be doing this. And it was it, you know, it was a a a major event in our lives, wasn't it? And I had a a protected exposure to it that I'm I'm glad to have had.

SPEAKER_01 39:13

I bet all your patients had absolutely pristine blood pressures.

SPEAKER_00 39:17

Uh well, indeed. I I tell you the frustrating thing here, we were doing the the this work on the UV and COVID. So when COVID hit, I you know, I was thinking, gosh, well, a lot of infectious respiratory infectious use like influenza is seasonal. I wonder if COVID will be. And we've sh we've done the epidemiology, it doesn't tell us the mechanism yet. And we realized we you know you have to wait 12 months to get a seasonal picture. But read the paper. What it shows is we use the the size of America and different UV environments around it to model effects of UV. And after three months of hard work and hard number crunching, we were pretty confident that more UV correlated with S COVID, yes. And I remember being very frustrated that first summer of COVID when it was dampening down and the beaches were opening, and the government was saying, don't go to the beaches because there's other people around. And I was thinking, we've got this data which is sitting in the bloody reviewers in training of an American journal, which I will not mention. And I want to get it out there, I want it to be out there, being read, but you know, having thoughts going into it, because I think that's wrong. I think people should be outside in the sunshine. And um I might I say the I don't know who the reviewers were who reviewed us for the BJD, they were perceptive, constructively critical. I mean, really good reviewers in the BJD. John Ingram, I don't know who he produced as reviewers, they were informed, intelligent, strict, made sure it was one of these cases where the review makes the paper better. And we really, really appreciated. If those mystery reviewers are listening, we appreciated your incisive and thoughtful improving comments. Anyway, we we had this frustration about wanting to get our paper out there because we felt it was important and germane to the environment at the time. And so we sat there thinking, get out on the beaches, you know.

SPEAKER_01 41:15

So Well, I think I think just on on the topic of reviewers, um, our actually our next episode of BTD Talks will be looking at peer review. Um so we we I would I would emphasize we are very grateful.

SPEAKER_00 41:27

When I mean good peer review is is fantastic, and it's um i I mean I've you know you you really remember when you've got good peer review, and that was that was one that was well reviewed by them.

SPEAKER_01 41:38

I think as a as a kind of a final point, and really kind of one of the things I was wanting to touch on when talking about the generalism and and linking with genital medicine is that you've really practiced across the various different interests you've explained, you've you've really practiced what you might describe as a kind of a holistic research approach, or at least a kind of a wider horizon scanning, really, rather than a narrow approach. What advice would you give to any early career dermatologists who are looking to follow that approach?

SPEAKER_00 42:06

Uh John, it's a really good comment because I mean epidemiology mechanism clinical trials, these three kind of separate fields, which are often treated separately, must do one or the other. You know, I started off mechanistically looking at no what's this stuff doing. The data then led me to the fact that actually maybe it's got an effect on systemic. So having started off down the mechanism route, cell culture, animal models, chemoluminescence, I then moved into human studies. So it suggested there might be a benefit to UV. So I then had to move to epidemiology. I've then done clinical trials. I've got a um, you know, I ran a clinical trial on giving UV phototherapy for hypertension, which I published last year. And again, I can't I can't remember the journal. So I published that again, another cardiology journal. And um, you know, I'm advising this company in clinical trials. But of course, as a clinician scientist, you know, you're you're never going to be in the lab doing this stuff because you're too expensive. So you are going to be coordinating people doing different approaches, and none of those bits of evidence by itself is enough. Epidemiology sets questions. Mechanism tells you about mechanism might be. Clinical trials are are really important. They show you the outcomes, but you actually need all of those bits of evidence to be able to get closer to the truth, which is what we're pursuing. You know, start with one, you know, it doesn't matter where you start in that triad, but you've got to start somewhere and get good at something. I've been lucky in my you know, I've I've got an old fashioned, I'm employed by the university. They don't specify very much what I do. I'm incredibly fortunate in that way. And I've kind of moved sideways and I've chased the data and what's interesting, but most of all I've collaborated. Because people tell me what I do and I really don't know. What are your skills? I really don't know. I don't think I've got any particular skills. I I really don't um I'm quite good at telephoning and emailing and getting people to jump onto my you know kind of wacky ideas. And I I suppose that has been my skill, but I have collaborated with really clever, able people who actually are really good at those things we've done.

SPEAKER_01 44:20

That's really helpful and you you've really quite captured a lot of what I tried to discuss across various different episodes of this of this podcast is the broad view of res of research and scholarship within dermatology, the various different uh approaches that can be taken, and you beautifully kind of laid that out, but also thrown in some um useful perils. So that's really helpful. So I think we'll finish up there. Uh honestly, I could probably sit, I feel like I could sit and chat to you about all this stuff for ages, but we what we'll do is uh for any listeners who are interested, please do have a look at Prof. Weather's TED Talk called Can the Sun Be Good for Your Heart? And we will share um some of the BJD uh research um that we mentioned earlier whenever uh we share this podcast um on social media. So in this episode we have covered a vast variety of different areas, including uh nitric oxide UV, um, but going delving deeper into uh evolutionary genetics and epidemiology. So um I know I've I've learned a lot and I'm sure that the listeners will have picked up a few really interesting key points. So thank you so much, Prof. For joining us. That is really has meant a lot.

SPEAKER_00 45:26

Johnny, thanks a lot. I really enjoyed the conversation. So uh that was that was great. I shall I shall walk the dog enthusiastically in future.

SPEAKER_01 45:37

Excellent. Um so for for our listeners, we're really busy on social media, so you can reach us via at Brj Dermatol on Twitter and at Brj Dermatology on Instagram uh or by using the hashtag bjdalks. And I'm sure that um if you've got any questions uh for profitweller, we can send send them on. Uh I'm sure you can offer some some more uh sage advice. So thank you all, and bye for now.