The last word
Dr Richard Weller, Senior Lecturer in Dermatology, has uncovered a mechanism by which sunlight appears to produce health benefits, potentially changing the advice given by his fellow dermatologists around the world.
Research does not always travel in straight lines, but therein lies its interest. I moved to Edinburgh in 2003 from the US, where I had been studying the role of the small molecule nitric oxide (NO) in the skin’s reaction to sunlight, to see if this would give an insight into skin cancer development. The Nobel Prize for medicine in 1998 was awarded for the discovery of NO; a growing number of effects of NO were being discovered; and the synthase enzyme that makes it had been found in increased levels in skin after sun exposure.
In Pittsburgh, working with mice that lacked NO synthase, I had published some interesting cellular effects of NO, and hoped to move this research into humans on my return to Scotland.
Things did not go as I had expected. Working with Dr Megan Mowbray, a very able MD student, we found that we were unable to turn off NO release in human skin, whichever way we blocked the NO synthase.
This was depressing stuff: two years’ work had led to nothing, as we were unable to see what happened to skin in the absence of NO. We set about analysing why this was, and to our surprise, discovered that the skin contains large stores of NO, as stable oxidised forms.
In the chemical conditions of the skin, ultraviolet radiation – as found in sunlight – can convert these back to NO. There was some satisfaction that we had worked out why our experiments hadn’t worked, but, I am ashamed to admit, initially no realisation that this might be important.
At a meeting in Bregenz about six months later, I was talking with colleagues and the possibilities began to dawn on me. Maybe this mechanism might link sunlight and skin with other aspects of physiology. Working with a succession of research students, I was able to show that irradiating humans with ultraviolet A moves NO from its stores in the skin to the circulation, where it dilates blood vessels and lowers blood pressure.
High blood pressure is now the leading cause of premature death and disease in the world, so any steps that reduce it are immensely important. This UV-skin-NO pathway suggests a mechanism by which sunlight may have health benefits.
Colleagues in Australia, working with the knowledge that obesity and a tendency to diabetes are commoner in winter than summer, developed a mouse model of these conditions (known as metabolic syndrome). We showed that UV reduces metabolic syndrome in mice, that vitamin D plays no part in this, but that the UV-skin-NO pathway is again responsible. Here in Edinburgh, we have found a new NO-mediated immune regulating effect in humans, which we are about to publish. We suspect this also may account for some of the anti-inflammatory effects of sunlight.
I have had to go back and look at the epidemiology of sunlight and all-cause mortality.
The clinical half of my life as a dermatologist involves advising patients to limit sunlight exposure to prevent skin cancer. I have now had to go back and look at the epidemiology of sunlight and all-cause mortality, realising that this is a far more important outcome measure than skin cancer alone. Remarkably there are no worthwhile data showing that sunlight exposure shortens life, although it undoubtedly is a risk factor for skin cancer. Several epidemiological studies from Scandinavia now show that increased sun-seeking behaviour correlates with increased life span – even at the expense of more skin cancers.
This continues to be a fascinating research journey. The slightly controversial message has caught the public interest and I have found myself giving talks for TED, the BBC, and even the Cabaret of Dangerous Ideas at the Edinburgh Fringe Festival.
I have recently teamed up with Dr Darren Shaw at the University’s Roslin Institute to analyse the UK Biobank data and find how sunlight exposure affects all-cause mortality in the UK. I have also received funding from the British Heart Foundation to start a clinical trial on the use of daily UV as a treatment for high blood pressure. Let’s see what the official public health advice will be on sunlight 10 years from now.