Transcriber: Ellen Maloney Reviewer: Denise RQ
Thanks.
My name is Richard Weller, and I am from Edinburgh.
It's tough following that;
your heart sinks when you hear the words "academic dermatologist",
after the last couple of talks, I am sure.
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.
This is the days when sunglasses were big, and trousers were short,
about 20 years ago.
What you learn when you go to Australia is the Australians are very competitive.
Within a day of arriving,
"Oh, you Pommies, cricket, rugby, blah, blah."
And they are not magnanimous in victory, and that happened a lot.
"Ah, you Pommies, you can't play cricket, rugby."
I could accept that.
But moving into work, we have each week what is called "a journal club"
when you would sit down with the other doctors,
and you'd study a scientific paper in relation to medicine.
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!"
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 are generally a healthier bunch.
Of course, why they said this was because of their fine moral standing,
their exercise, because they are Australian,
and we are "wheezy Pommies", and so on.
But you know, it is not just Australia that has better health than Britain.
Within Britain, there is a gradient of health.
This is what is called "standardized mortality",
basically, your chances of dying.
[This is a paper looking at data] about 20 years ago, but it's true today,
comparing your rates of dying at 50 degrees north,
that is the south, that is London and places,
by latitude, and 55 degrees.
The bad news is that is here, Glasgow.
I am from Edinburgh. Worse news; that is even Edinburgh.
(Laughter)
If you live in Glasgow, you do not expect to live a long time.
(Laughter)
(Applause)
So what accounts for this horrible space here,
between us up here, in southern Scotland, and the south?
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.
Sunlight, of course, comes into this.
Vitamin D has had a great deal of press, and lots of people get concerned about it.
We need vitamin D, it is 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.
That really prevented the rickets that used to be common in this city.
I, as a child, was fed cod liver oil by my grandmother,
and nobody forgets cod liver oil.
(Laughter)
There is 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 do not change that high rate of heart disease,
and the evidence for it preventing cancers is not yet great.
What I am suggesting is that vitamin D is not the only story in town.
It's not the only reason for preventing heart disease.
High vitamin D levels, I think, are a marker for sunlight exposure.
Sunlight exposure, in methods I am going to show,
is good for heart disease.
Anyway, I came back from Australia,
and despite the obvious risks to my health, I moved to Aberdeen.
(Laughter)
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, Murad,
won the Nobel prize for medicine, back in 1998.
They were the first people to describe this new chemical transmitter;
nitric oxide,
which, I would say in relation to the last talk,
- there is a neat segue -
Viagra works via nitric oxide.
That's my only link to the last talk.
(Laughter)
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.
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 is this incredibly simple molecule,
a nitrogen and an oxygen that have stuck together.
And yet, these are hugely important for maintaining our low blood pressure,
for neurotransmission, for many, many things.
But particularly, cardiovascular health.
I started doing research,
and we found, very excitingly, that the skin produces nitric oxide.
So it is not just in the cardiovascular system this 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?
You know, it's not the heart, what do you do?
I went off to the States, as many people do if they are going to do research,
and I spent a few years in Pittsburgh.
This is Pittsburgh.
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.
I first of all started work in cell culture, growing cells.
Then I was using knockout mouse models, mice that couldn't make the gene.
We reckoned we had worked out a mechanism
by which NO was helping cells survive.
I then moved back to Edinburgh.
And in Edinburgh the experimental animal we use is the medical student.
It is a species close to humans, with [inaudible] close to humans,
with several advantages over mice;
they are free, you don't shave them, they feed themselves,
and nobody pickets your office saying, "Save the lab medical student!"
So they are really an ideal model.
But what we found, was that we could not reproduce in man
- this thing is not advancing -
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.
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.
Your skin has got really large stores of NO.
We then thought to ourselves, with these 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?
I am an experimental dermatologist, so what we did
was we thought we'd have to expose our experimental animals to sunlight.
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.
To cut a long story short and show the key data,
when we put people under a lamp,
for the equivalent of about 30 minutes of sunshine in summer in Edinburgh
- clearly not Glasgow, because there is no sunshine in Glasgow -
(Laughter)
but in Edinburgh,
what we produced was a rise in circulating nitric oxide.
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.
We are still collecting data.
A few good things here:
well, this appeared to be more marked in older people.
I am not sure exactly how much.
One of the subjects was my mother-in-law, and clearly, I do not know her age
(Laughter)
but certainly, in people older than my wife,
this appears to be a more marked effect.
The other thing I should mention was that there was no change in vitamin D.
This was separate from vitamin D.
Vitamin D is good for you - it stops rickets,
it promotes calcium metabolism, important stuff -
but this is a separate mechanism from vitamin D.
One of the problems with looking at blood pressure
is your body does everything it can to keep your blood pressure the same.
If your leg it 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.
So what we have next done,
is we have moved on to looking at blood vessel dilatation.
This is again, notice no tail and hairless, this is a medical student.
We shone UV at the arm,
and then in the arm, you can measure blood flow in the arm
by how much it swells up as blood flows into it.
What we have 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 do not 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 [heart] be supplied with [blood].
So here, further data, that ultraviolet, that sunlight,
has benefits on the blood flow and the cardiovascular system.
We thought we would just kind of model-
- different amounts of UV hit the Earth,
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 -
release a 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.
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 is the same amount of light.
If you live up here, in summer, sun is coming fairly directly down,
but in winter, it is coming through a huge amount of atmosphere,
and much of the ultraviolet is weeded out.
The range of wavelengths that hit the Earth
are different in summer to winter.
So what you can do is 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.
Now, if you are 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 are on the equator, December or June,
you have got masses of NO being released from the skin.
I first gave this talk in California at a research meeting,
in Ventura, which is in southern California.
So Ventura, in summer, you might as well be at the equator.
It's great, lots of NO is released.
Ventura in mid-winter, well, there is still a decent amount.
Edinburgh, in summer, the area beneath the curve is really good,
but Edinburgh in winter,
the amount of NO that can be released is next to nothing, tiny amounts.
So what do we think?
We are still working at this story,
we are still developing it, we are still expanding it,
we think it is very important.
We think it probably accounts
for a lot of the north-south health divide within Britain.
It is of relevance to us.
We think that the skin,
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, have a lot of these nitric oxides
that we think go to the skin.
We think they are then stored in the skin,
and we think that sunlight releases this where it has generally beneficial effects.
This is ongoing work, but I mean, dermatologists,
- I am a dermatologist -
my day job is saying to people,
"You have 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 100 times higher
than deaths from skin cancer.
I think there are benefits that we need to be more aware of,
and we need to find the risk-benefit ratio:
how much sunlight is safe?
How can we finesse this best for our general health?
Thank you very much indeed.
(Applause)